Abstracts: 2017 Annual Meeting Boston, MA
Awarded Best Poster or Video
Abstract | Abstract Title | Session | Meeting | Track 1 | Track 2 | Abstract | ||
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FRI-01 |
From a very select club to an universal and powerful European Association of Urology (EAU) |
History of Urology: History Forum | 17BOS |
Abstract: FRI-01 Sources of Funding: none Introduction After the second World war Europe was totally devised by the “iron curtain”. Eastern and Western Europe had no longer contacts and specialists in urology could no longer assist medical congresses at the other side of the curtain. Collaboration between East and West was completely impossible. Methods Nevertheless, around 1970, some individual professors in urology were allowed to cross the curtain and the idea of an European Association of Urology was in the air. At the meeting of the Association Française d’Urologie in 1972, in Paris, the European Society of Urology was founded as a very private and closed society with a selection of only 150 European urologists from Eastern and Western Europe. Results After a second preliminary meeting in Zürich and at the SIU congress in Amsterdam in 1973 the name was changed in European association of Urology and the 19 founding Fathers decided to hold the 1st congress in 1974 in Pavia (Italy). Prof. Ravasini was the first chairman and the congress was planned every 2 years._x000D_ Since 1975 the official Journal of the EAU was “European Urology” and Claude Schulman was editor till 2005._x000D_ In 1990, Frans Debruyne, chairman of the 9th EAU Congress in Amsterdam, decided that the congress should be open for all European urologists. This congress was a milestone in the history of the EAU and was attended by 1500 participants._x000D_ Since 1998 the congress was organised every year and the number of participants grew constantly with a peak of 13489 attendants in Milan (Italy) in 2008._x000D_ The EAU is now organised in 15 scientific sections and the office moved from Nijmegen to Arnhem in 1999._x000D_ Since 2004 there is an intensive collaboration between the EAU and the EBU (European Board of Urology) and both have their headquarters in Arnhem. The EAU has a scientific and educational role, the EBU has a regulatory role._x000D_ Conclusions What was only a dream and at that time perhaps an illusion to found an European group of a small selected group of urologists in 1970, developed into a big and powerful European association of Urology, open for all urologists all over the world. Funding none
Authors
Johan Mattelaer
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FRI-02 |
AGAINST ALL ODDS: THE BEGINNING OF EXPERIMENTAL RENAL PHYSIOLOGY |
History of Urology: History Forum | 17BOS |
Abstract: FRI-02 Sources of Funding: None Introduction The experimental studies of Zambercari (1670) showed that unilateral nephrectomy has no impact on the survival of animals. Borelli (1680) presented a revolutionary theory of the kidney acting as a sieve producing a filtrate of blood. However, initial physiology progress in the 18th century was weakened by two main sources of medical science, which opposed experimental studies: Morbid anatomy and Naturphilosophie. Morbid anatomy explained the disease based on clinico-anatomical observation . Naturphilosophie , a major philosophical doctrine in science, proclaimed the laws of nature form the lecturing desk . In the 19th century, function slowly became a measuring unit of physiological studies. Comhaire (1803) observed no urine production after bilateral nephrectomy. Coindet (1820)demonstrated no urine production after bilateral ligation of renal vessels. However, the first true experimental study of kidney function became possible by the progress in chemistry and young Geneva scientists: physician J.L. Prevost and pharmacist's apprentice J.B. Dumas. Methods Review of original papers 1670-1825 Results In 1820, the nature of urea, first marker of the kidney function, was fiercely debated: does it circulates in the blood or produced by the kidney? Prevost and Dumas decided to &[Prime]put an end to the vagueness of accepted ideas and replace it by positive facts&[Prime]. They chose the old model of bilateral nephrectomy but, instead of relying entirely on anatomical and autopsy findings, reinforced it by new quantitative measurement of urea in blood and urine. The experiments took place in a fortification of the Geneva guards between 2-3 AM, since vivisection was prohibited in the city. Initially the researchers confirmed that urea crystals from the blood and urine of the animals were the same . The urea was lower in the blood of control group but doubled in binephrectomised animals. It was concluded that &[Prime]the kidney is only an eliminating surface, it does not produce urea&[Prime]. The study , presented before the Geneva Society of Physics and Natural History on 11/15/1821 , &[Prime]puts an end to all alternative theories&[Prime]. _x000D_ Conclusions Prevost and Dumas pioneered quantitative experimental renal physiology at a time of triumphant anatomo-clinic and philosophical approach to medical science. Their rigorous landmark study , mostly forgotten, became a model of the future coordinated physiological research using innovative new methods of chemical control. _x000D_ Eventually,serum BUN/Cr became the main clinical test of kidney function.But the foundation for experimental renal physiology was set 196 years ago Funding None
Authors
April Szafran
David Schulsinger Yefim Sheynkin |
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FRI-03 |
Kidney or conspiracy? Was renal failure the cause of Mozart’s death? A brief review of the composer’s known illnesses and theories surrounding his death. |
History of Urology: History Forum | 17BOS |
Abstract: FRI-03 Sources of Funding: None Introduction Wolfgang Amadeus Mozart (1756 to 1791) was a child prodigy and prodigious composer whose works remain popular today. His premature death at the age of 35 provoked many theories which are still debated. I aim to outline the theories surrounding Mozart&[prime]s early death. Methods Literature review Results Mozart had bouts of ill health starting in childhood and recurring throughout his life. This is unsurprising as at the time childhood mortality was high (only Mozart and his sister survived to adulthood of 7 siblings). Mozart&[prime]s recorded medical complaints include scarlet fever and an ulcerous molar (age 7). This complaint became chronic and troubled Mozart throughout his life. Aged 9 he almost died of abdominal typhus and aged 10 he contracted smallpox. He also suffered from articular rheumatism. In his early teens he suffered frostbite on both hands and his face. In 1784 the first of several attacks of renal colic was recorded. In the later years of his life he complained of severe headaches, nosebleeds, difficulty in concentrating and depression._x000D_ _x000D_ Mozart became unwell in Prague on the 6th September 1791. His heath further declined on the 20th November with symptoms of pain and swelling in his limbs, headache, pyrexia and later vomiting and diarrhoea. The edema worsened and Mozart became bedridden and increasingly agitated. Delirium then coma followed before Mozart died on December 5th 1791._x000D_ _x000D_ His death certificate records the cause of death as &[Prime]severe miliary fever&[Prime]. A week after his death a newspaper published claims that he had been poisoned._x000D_ Since then at least 118 causes of death have been suggested including rheumatic fever, streptococcal infection, vasculitis causing renal failure, acute glomerulonephritis, trichinosis, thyrotoxic crisis, influenza , infection following a bloodletting procedure, syphilis and mercury poisoning (either an accidental side effect of treatment for syphilis or murder). Various murder and conspiracy theories have been suggested. The accused include the royal band master Antonio Salieri, Mozart&[prime]s physician and friend Gottfried van Swieten or even Mozart&[prime]s Freemason lodge. There is, however, no historical evidence to support these claims._x000D_ Conclusions Mozart&[prime]s grave has been lost so it seems unlikely that we will ever have a definitive answer to the mystery of his death. The most probable theory seems to be an acute exacerbation of chronic kidney disease causing uraemia, likely secondary to febrile illness. Funding None
Authors
Margaret Lyttle
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FRI-04 |
First Female Authors in the Journal of Urology |
History of Urology: History Forum | 17BOS |
Abstract: FRI-04 Sources of Funding: none Introduction In 1917, Alma Hiller became the first woman to publish in the Journal of Urology (JU). Her contribution was soon followed by articles from Carol Beeler and Dr. Isabel Mary Wason. Dr. Wason (1890-1972) became the first female lead author in JU. This study explores their careers and contributions, especially those of Dr. Wason. Methods We reviewed JU articles from 1917 to 1925 and identified Hiller, Beeler, and Dr. Wason as the first three women authors. We contacted librarians and archivists to obtain records of their education, academic appointments, and publications. Results In 1917, JU&[prime]s first issue featured &[Prime]The Relation of the Non-Protein Nitrogen to the Urea Nitrogen of the Blood&[Prime] by Hiller and Dr. Herman Mosenthal. Subsequently, in 1918, Beeler and Dr. HF Helmholz published &[Prime]Experimental Pyelitis in the Rabbit.&[Prime] Hiller and Beeler worked with their male co-authors as a biochemist and technician, respectively. It wasn't until 1920 that Dr. Wason published &[Prime]Report of a Case of Congenital Stenosis of Both Ureteral Orifices&[Prime] in JU, her first paper as a Pathologist._x000D_ _x000D_ Dr. Wason earned her degree in 1911 from The Western College for Women, where she stayed to complete a fellowship in Chemistry. She applied to Johns Hopkins Medical School (JHMS) in 1912. After graduating in 1917, Dr. Wason was recruited by Dr. Milton, the Yale Pathology Department Chair, to become the first woman instructor within the department (Figure 1). During her early career, she published three papers and a textbook on the pathologies of infection and nutritional deficiency, in addition to urogenital disease._x000D_ _x000D_ With her considerable body of experience, Dr. Wason moved to St. Luke&[prime]s Hospital (SLH) in Massachusetts in 1925 where she served as laboratory director. Dr. Winternitz described Dr. Wason as a &[Prime]splendid pathologist, a good bacteriologist, [with] considerable experience in clinical pathology, surgical pathology and chemical [l]ab analyses&[Prime] in letters to SLH. She stayed at SLH through 1943._x000D_ _x000D_ Figure 1: Dr. Wason with colleagues at YUSM in 1924. Conclusions During an era in which female physicians were few and far between, Dr. Wason distinguished herself as an academic Pathologist. Her relationship with the field of Urology, along with that Heller and Beeler, is of historical significance. Funding none
Authors
Kathryn A Marchetti
Ted Lee David A Bloom Julian Wan |
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FRI-05 |
M. L. GANNON: PIONEER IN UROLOGY |
History of Urology: History Forum | 17BOS |
Abstract: FRI-05 Sources of Funding: None Introduction Upon reading this abstract title did you imagine Dr Gannon as a male urologist? Dr Mary Gannon was the 2nd woman, following Dr Elisabeth Pickett, to become a board certified urologist. She was the 1st female urologist elected to the AUA (1975). Methods We interviewed Dr Gannon and researched media, text and articles pertaining to her life and women in urology. Results Mary Louise Gannon was born in 1941 in Des Moines, Iowa. She grew up on a farm and aspired to become a veterinarian but was told she could not apply to veterinary school because of her gender. This led her to say "if you aren't going to allow me to take care of animals then I'll take care of humans."_x000D_ _x000D_ She was one of 5 women admitted to her medical school class at the University of Iowa, College of Medicine (1962-1966). She became interested in urology thanks to her mentor Dr Reuben Flocks and because she enjoyed endoscopy. After completing medical school, she applied to over 30 urology residency programs as "M.L. Gannon" and was accepted to multiple programs until they learned that the "M" stood for "Mary." Ultimately, 3 urology residency programs accepted her and she chose to train at the University of Wisconsin under Dr Weir and Dr Uehling. While in residency she stated she had great support from her attendings, was well accepted by her patients, but that the greatest resistance came from her fellow residents._x000D_ _x000D_ After completing her residency she had difficulty finding a job and tells of one "interview" where after spending a day with a practicing urologist, she was told that they were not looking to hire her but had "wanted to see what a female urologist looked like." The lack of equal opportunities as a urologist led her to open her own practice in Spencer, Iowa and she practiced from 1972-1984. She stopped practicing urology in 1984 because she said she was burned out. _x000D_ _x000D_ Her passion for counseling and working with patients led her to pursue training in psychotherapy and she completed a fellowship and was board certified in addiction medicine. Her mental health background gave her significant insight into her experiences. She feels that her isolation with no significant support system and a lack of lifestyle balance were what made her journey through urology so difficult and led her to eventually leave her field._x000D_ Conclusions Dr Mary Louise Gannon is a pioneer in urology. Her story illustrates many of the hurdles women have worked to overcome in urology and highlights many current issues in our field. When asked what advice she had for women in the field today, Dr Gannon replied "First find your passion, but also remember you need to find a balance in your life. Seek out good colleagues as having a strong support group is important." Funding None
Authors
Sutchin R Patel
Sara L Best Stephen Y Nakada |
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FRI-06 |
The Light at the End of the Scope: The History of Electro Surgical Instruments Co and the Mignon Lamp |
History of Urology: History Forum | 17BOS |
Abstract: FRI-06 Sources of Funding: none Introduction Prior to the development of the mignon small light bulb, endoscopes struggled to gain traction in the medical field. The first endoscopes were expensive, cumbersome, and provided poor visualization. The mignon light bulb was a small, inexpensive interchangeable light bulb that screwed into the end of the endoscope allowing significant improvement in visualization. Methods A review of textbook chapters, peer-reviewed articles on pubmed, original product catalogues, surgical meeting catalogues, review of Electro Surgical Instruments Co (ESI) office records and company archives and original period instruments were performed on topics related to the development and impact of the mignon lamp. Results In 1879 when Edison introduced the light bulb, cystoscopy commonly used external light sources or open platinum incandescent filaments requiring extensive cooling mechanisms. The first urologic use of a modified Edison lamp came in 1883 when David Newman attached a miniature bulb to the end of a cystoscope. Three years later, German urologist Maximillian Nitze and Austrian instrument manufacturer Josef Leiter, introduced a cystoscope incorporating the new technology. Early Edison bulbs caused thermal injuries and were cost prohibitive for all but the most prominent urologists. Dr. Henry Koch, a urologist, and Charles Preston, an electrician, from Rochester, New York, modified the Edison bulb to a smaller size and amperage suitable for medical devices and the mignon lamp was born. ESI Co., founded in 1896 by Koch, Herman Behm, William Maier and Frederick Maier, marketed the mignon bulb as a &[Prime]cold&[Prime] lamp allowing contact with body tissue without the potential for burns and ulcerations. Patented in 1899, the Koch urethroscope was the first instrument to utilize the exchangeable lamps from ESI. The Device had no magnification, only a sheath French 20-33, an obturator and a light carrier with the ESI lamp fixture at the end. Through their collaboration with other notable urologists, including former AUA president Ferdinand C. Valentine, ESI created surgical instruments that allowed urologic diagnosis and treatment to reach new heights. Conclusions The mignon lamp, developed by a urologist in conjunction with ESI revolutionized endoscopy not only for urology but for many surgical disciplines. For the first time, endoscopic visualization of the bladder became accessible to the average urologist. Endoscopic illumination using mignon light bulbs was not improved upon until the advent of the quartz rod lens system by Hopkins and Stortz in the second half of the twentieth century. Funding none
Authors
Scott Quarrier
Ronald Rabinowitz |
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FRI-07 |
A Race to Imaging Revolution: Pioneers in Fiber Optics |
History of Urology: History Forum | 17BOS |
Abstract: FRI-07 Sources of Funding: None Introduction Until the 20th century, visualization beyond tortuous anatomic and mechanical contours posed a perennial hurdle for physicians and military engineers alike. The end of World War II coincided with profound discoveries in imaging through flexible glass fibers. However, discoveries in fiber optics were not widely distributed and gained little traction for practical use. Both Abraham van Heel and Harold Hopkins separately overcame this by publishing their work in Nature, enigmatically, in the same issue. We sought to discover the timeline of events preceding the publications and explain the coincidental timing. Methods PubMed, Google Scholar, HathiTrust and ProQuest were searched for sources describing van Heel and Hopkins&[prime] work on fiber optic imaging devices. Also, since both men are deceased we interviewed Jeff Hecht (City of Light: History of Fiber Optics, 1999) and reviewed his research documents, including articles translated from Dutch and correspondence with Hopkins and William Brouwer, van Heel&[prime]s assistant. Results Van Heel, professor of optics at the Technical University of Delft in the Netherlands, focused on coating individual glass fibers to maximize the light delivery and potential length of the fibers. Hopkins, a professor of optics at the Imperial College in London, used bundles of many tiny fibers to increase image resolution. Both innovations proved crucial to fiber optics&[prime] success. When Frits Zernike, another Dutch optics expert, learned of Hopkins&[prime] work while receiving his Nobel prize in physics, he shared this information with van Heel and sparked a race to publish._x000D_ Van Heel was the first of the two to publish his findings. The article appeared in De Ingenieur in June 1953, but had geographically limited readership. To address this, van Heel also sent a letter to the editor of Nature. This was received on May 21, 1953, but delayed in publishing until January 2, 1954. 82&[permil] of letters in the 5 issues centered around January 2, 1954 were published within 2 months of receipt. Van Heel&[prime]s letter appears above a longer letter documenting Hopkins&[prime] own work. Although Hopkins denied prior knowledge of van Heel&[prime]s work, Brouwer references Hopkins as the editor of van Heel&[prime]s letter and suggests his role in the delay in publication. Conclusions Harold Hopkins&[prime] pioneering work to improve the image quality of the first flexible fiberscopes is well documented. However, van Heel&[prime]s simultaneous and independent contribution of fiber coatings to increase light delivery should also be credited. When considered together, both Hopkins and van Heel&[prime]s discoveries launched modern fiber optics and changed the field of urology forever. Funding None
Authors
Kimberly A Maciolek
Sara L Best |
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FRI-08 |
The Leaky Faucet: A History of the Treatment of Male Urinary Incontinence |
History of Urology: History Forum | 17BOS |
Abstract: FRI-08 Sources of Funding: None Introduction Male urinary incontinence has been described from antiquity and various techniques have evolved to treat this disorder. Methods A literature review of PubMed articles in English pertaining to male incontinence was performed to compile a historical perspective of the treatment of male incontinence. Results Male urinary incontinence was first mentioned in Egyptian manuscripts in 1500 B.C., where papyrus leaves were used &[Prime]to remove constant running of the urine.&[Prime] In 1564, French surgeon Ambroise Pare described one of the first portable urinals for incontinent males. German surgeon Wilhem Hildanus created the first condom catheter with pig bladder in the 1600s and was also credited with creating the first penile clamp; however, it was not popularized until 1980 as the &[Prime]Cunningham clamp.&[Prime] German anatomist and surgeon Lorenz Heister introduced a perineal bulbar urethral compression belt in 1747 which provided the blueprint for air-inflated bulbar urethral compression devices such as the one designed by British physician S.A. Vincent in 1960. Meanwhile, Austrian surgeon Robert Gersuny took his experience with paraffin in plastic surgery and adapted it to urologic care to perform the first periurethral paraffin injection as bulking therapy. Americans entered the field in 1929 when urologist Frederic Foley introduced the modern catheter, which was adopted for management of retention and incontinence. Foley is credited with creation of the first artificial urinary sphincter; however, his version was worn around a surgically isolated segment of the corporal spongiosum. From 1970-73, American urologist Joseph Kaufman described multiple crural crossover procedures which provided surgically created bulbar compression for post-prostatectomy incontinence, but not before designing the first male sling with partner John L. Berry in 1958. The gold standard therapy for male incontinence did not appear until 1973 when American urologist F. Brantley Scott described the first multi-component artificial inflatable sphincter. Improvements upon minimally invasive intraurethral bulking therapy occurred rapidly with Teflon (1973), collagen (1989), autologous adipose tissue (1989) and cross-linked silicone gels (1991). Finally, stem cell therapy has emerged since 2007 to promote regeneration of functional components for adequate urethral coaptation. Conclusions Treatment for male urinary incontinence has evolved from noninvasive devices to various surgical procedures, both endoscopic and reconstructive. Artificial sphincters remain the gold-standard therapy for male urinary incontinence. Funding None
Authors
Julio Chong
Vannita Simma-Chiang |
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FRI-09 |
More Than Just Storing and Emptying: The Bladder’s Functions in the Kitchen |
History of Urology: History Forum | 17BOS |
Abstract: FRI-09 Sources of Funding: none Introduction While centuries of physicians and anatomists dating back to Hippocrates and Galen have sought to characterize the functions of the bladder, another group simultaneously found additional uses: cooks. Methods Primary and secondary sources describing the multiple uses of the bladder in food preparation were examined. Results An early description of the bladder in cooking comes from Greece in Aristophanes' The Clouds. Written in 423 B.C.E., it contains a passage in which the food placed inside a sheep's bladder for roasting spilled out when the bladder ruptured. The Romans found another use, as described in a recipe for suckling pig from the first century A.C.E. The bladder was filled with a dressing and a bird's quill was placed in the bladder neck. The bladder and quill tip were then used like a pastry bag to apply the dressing under the pig's skin for seasoning prior to baking. The bladder played a role in medieval cooking. A fifteenth-century German cookbook includes a recipe for creating a giant egg: several yolks were placed inside a small bladder, which was then placed inside a large bladder filled with egg whites, then cooked. Popular at Lent, saffron and figs substituted for yolks, while ground almonds and pike roe substituted for the whites. The bladder fulfilled multiple functions in 17th and 18th century cooking. Animal bladders, usually cow or sheep in origin, became commonplace in food storage. Fresh or rehydrated dried bladders were used to cover crockery. As the bladders dried, they created an airtight seal, preserving the contents. During this time, bladders became popular as a way to preserve flavor and moisture during cooking, similar to the modern method of sous vide. Meats, poultry, and seasonings were placed inside the bladder (ox bladders were described in the use of cooking whole chickens in 1730), which was then tied and boiled until the contents were fully cooked. The bladder was then opened and discarded. The technique is referred to as en vessie and is still used today in traditional French cooking. The bladder can also be eaten. For centuries, cow bladder has served as casing in the traditional Italian salumi mortadella di Bologna and culatello, and bladders can be used in preparing regional fare such as Scottish haggis, Slovenian ded and vratnik, or French gogue. Conclusions Although well known to the masses for storing and emptying waste, a full understanding of the bladder continues to be debated among urologists. Still, the bladder's history of culinary utility in creating and storing foods is irrefutable, proving it to be a versatile organ. Funding none
Authors
Janae Preece
Kristina Suson |
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FRI-10 |
Cran-sensitive: The berried history of the cranberry’s role in the prevention of urinary tract infections |
History of Urology: History Forum | 17BOS |
Abstract: FRI-10 Sources of Funding: none Introduction The public has long considered cranberry juice to contain properties that prevent urinary tract infections (UTI), a common enough conception that it has been explored repeatedly by scientific bodies. This work highlights the history of the medical opinion regarding the role of cranberries in UTI prevention. Methods A literature search including Pubmed and domestic periodicals was performed. Results Cranberries were first thought to have medicinal qualities by Native Americans, and their plant leaves used for urinary and gastrointestinal disorders. As early as the 1920s, the scientific community reported that cranberry consumption contributed to the acidification of urine, and over the next decade, this was found to be a result of excreted hippuric acid. Until the 1970s, acidification of the urine was considered to be the utility of cranberries in the prevention of UTIs. Studies aiming to confirm this theory showed no or only a transient effect and new theories were sought. After the discovery of the importance of bacterial adherence in the pathogenesis of UTIs, several studies in the mid- and late-1980s suggested that cranberries prevent the adhesion of bacterial organisms, specifically E. Coli, to the uroepithelial cell walls. Over the next decade, fructose and proanthocyanidins were identified as the &[Prime]active&[Prime] components that exhibit this anti-adhesion property. In the last twenty years, multiple randomized-control and quasi-randomized control studies investigated the effectiveness of cranberry juice, syrups, powders, capsules and tablets in preventing UTIs. An article published in 2000 and sponsored by Ocean Spray Cranberries, Inc. presented a multitude of studies that suggest that regular consumption of cranberry juice cocktail reduces the risk of UTIs and inhibits bacterial adherence to mucosal surfaces. Cochrane reviews in 2000, 1998, 2004, and 2008 evaluated these studies and furthered the notion that there may be a decrease in symptomatic UTIs in women with recurrent infections over a 12-month period. However, the most recent update in 2012, which included 24 studies (14 more than 2008) and 4,473 participants suggested no statistically significant benefit in any high-risk group. Most recently, a study in JAMA found no benefit among women living in nursing homes. Conclusions While a mechanism by which cranberry consumption may theoretically prevent UTIs has been proposed, and some research has suggested a benefit, a lack of strong evidence has left the most current medical opinion unable to justify proactive physician support of the practice. Funding none
Authors
Jason Rothwax
Jeffrey Stock |
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FRI-11 |
Obstructive Pyohydronephrosis and Life Saving Intervention of the Greatest Starlet of All Time- Sarah Bernhardt. |
History of Urology: History Forum | 17BOS |
Abstract: FRI-11 Sources of Funding: None Introduction The Mount Sinai Hospital in New York City, heralded some of the very first innovations in urology at the turn of the 20th century. Sarah Bernhardt was at the peak of her international reputation and was touring the U.S. when she became ill with obstructive pyohydronephrosis. Methods A review of the literature of Ms. Bernhardts life and illnesses was cross-referenced to surviving documents of the event from the Emanuel Libman Archives at the National Library of Medicine. Leo Buerger, the urologist who operated upon Ms. Bernhardt is even more apocryphal and difficult to pursue, though he was the Buerger of the Brown-Buerger cystoscope fame. Dr. Emanuel Libman proved to be the key player who actually kept hospital records recording the events of her Tuesday, April 17th 1917 surgery. Results Sarah Bernhardt is considered by many to be the first actress superstar of the modern era, bridging into the silent movie era. She may well have suffered from tuberculosis throughout her long life, but an injury to her leg resulted in an amputation, late in life and during her final U.S. tour she was often unwell. She became ill and was brought to Mount Sinai Hospital in New York City in critical condition. She had a left pyohydronephrosis with an obstructing calculus. Cystoscopy and retrograde evacuation of pus was performed first on Saturday July 14th. Buerger records that a large amount of pus washed out from left kidney. She did not do well, though and by the evening of Tuesday, July 17th it was deemed her situation was critical enough to warrant emergent open surgery. He records, Incision was made into the kidney and six ounces of foul smelling pus obtained. Large irregular calculus in the pelvis, which was removed. We also have the records of her hospital vital signs which clearly show her post-operative improvement. With no available antibiotics it is almost miraculous that she survived. She adopted Buergers only daughter, Yvonne as her godmother and became close to Germaine Schnitzer, Buergers wife. Conclusions Of the five attending physicians who cared for Ms. Bernhardt, she kept in contact with both Buerger and Libman in her final years. She was a dynamo of activity working on another silent movie in her final year, dying on March 26, 1923 in Paris. Dr. Buergers life apparently fell to pieces following this surgery, becoming a footnote only in the history of urology. Funding None
Authors
Michael Moran
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FRI-12 |
Mary Helen Schirm of Savannah, the first US patient, who underwent indicated nephrectomy |
History of Urology: History Forum | 17BOS |
Abstract: FRI-12 Sources of Funding: non Introduction Outlining history from a patient's view is a major theme in the social and cultural history of medicine. Since Porters work in the 1980th "patients view meets the clinical gaze" (Condrau 2012). Within the research on the history of urology there could be traced besides Margarethe Kleb (1820-1878), a washer women, (nephrectomy), and Theodor Baum of Cologne (1830-1886) (first indicated cystectomy) only some famous patients who had written ego-documents as Samuel Pepys (1633-1703), Chief Secretary to the Admiralty of Great Britain and his diaries or the report on Jan de Doot by Nicholaes Tulp (1593 - 1674). Other famous urologic patients were Napoleon III. (1808-1873) or Michel de Montainge (1533 -1592) whose legacy should not be lost (Moran, 2013)._x000D_ Mary Helen Schirm (1840-1871) nee Williams from Savannah (Georgia) was suffering from kidney stones for years. She had married an immigrant from Germany, Wilhelm Philip Schirm (1836-1896) from Scheuern near Nassau/Lahn, who came to the US in 1857 and served during the Civil War in the 3rd Georgia battalion of the Confedered Army. Two pregnancies of Mary were interrupted due to renal colics._x000D_ Therefore she sought urgent help. At that time giving birth to a son and heier was a major "task" of a married women. With the popularized information about first successfull nephrectomy from the department of Gustav Simon (1824-1876) from Heidelberg, about 80 km away form her husbands former home, she traveld to Germany. The operation took place on August 8th 1871 but the patient died about one month later and was buried in Obernhof/Lahn where the German relatives were living._x000D_ Methods An analysis of the local and scientific reports and primary sources on the patient, the operation and the person of Gustav Simon will be combined with a social analysis a the medical system in the last quarter of the 19th century in Germany and the US. Results The first indicated operations proved that it is possible to remove one kidney in a human being and that a patient can survive with only one kidney. However, nephrectomy slowly gained acceptance due to a lethality rate about 40% at the early years. At the turn to the 20th century operation became the major corner stone to define the new specialty of urology besides endoscopy. Conclusions The study is intended to suggest the dimensions international communication had on the differentiating specialty of urology. In its general perspective, the study tries to understand the dimension of a history of patients view in the history of urology especially in Germany, Europe and the US. Funding non
Authors
Friedrich Moll
Thorsten Halling Matthis Krischel Heiner Fangerau |
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FRI-13 |
ANATOMY OF THE PROSTATE GLAND: EVOLVING UNDERSTANDING THROUGH LAPAROSCOPIC AND ROBOTIC UROLOGICAL SURGERY |
History of Urology: History Forum | 17BOS |
Abstract: FRI-13 Sources of Funding: None Introduction The prostate gland was ill understood until the Renaissance when anatomists discovered the organ naming it "glandulous body." In 1600 the French physician du Laurens introduced the name "prostatae" (Josef et al. 2009). Modern insight into the anatomy of the gland was supplemented by McNeal&[prime]s description of the zonal anatomy of the prostate (1981), and by rapid surgical advances in surgical technology. This is a review of recent developments in understanding of the prostate through robotic and laparoscopic urological surgery. Methods A systematic literature search of PubMed, Medline, EMBASE, textbook chapters and historical archives was performed. Results The introduction of laparoscopic radical prostatectomy (LRP) allowed assessment of the prostate and its anatomical relations with heighted magnification and new visual angles. Robotic surgical systems further enhanced visualisation, with superior magnification and additional three-dimensional views. New anatomical understanding led to modifications of surgical technique aiming to preserve continence and potency. In 2002, it was noted that important relationships existed between pelvic plexus ganglions and seminal vesicles. Further fine neural plexuses along the posterior and antero-lateral surface of the prostate were described based on cadaveric studies and laparoscopic and robotic views. Later on, the technique of nerve preservation in which a plane (deep to the Santorinis plexus) between the prostatic capsule and inner prostatic fascial layer is developed at its cranial extent was described (i.e. the Veil of Aphrodite). In 2003-2004, Lunacek et al. noted that the cavernosal nerves running along the prostate become displaced further anteriorly and spread, thus forming a concave shape (like a &[prime]curtain&[prime]) of the neurovascular bundles. This led to the description of the modified &[prime]curtain dissection&[prime] in 2005. Recently interfascial dissection of the neurovascular bundles that is tension and cautery free was described. Recent advances on microdissection robotic platforms such as mini-balloon tissue dissection could render further understanding of the anatomy of the prostate (Kommu et al. J Endourol 2009). Conclusions Laparoscopic and robotic urological surgery has had a significant impact on our understanding of the prostate gland. This evolving understanding continues to redefine surgical practices towards optimised outcomes in oncological treatment, preservation of erectile function and maintenance of continence during radical prostatectomy. Funding None
Authors
Peter Macneal
Sashi Kommu Peter Rimington Harold Ellis |
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FRI-14 |
Review of the Evidence of the Female Prostate as a Functional, Sexually-Relevant Gland in Women |
History of Urology: History Forum | 17BOS |
Abstract: FRI-14 Sources of Funding: None Introduction Introduction: Throughout centuries of publications, different names and varied implications have accompanied the use of the term female prostate, an otherwise small anatomic region in women. As a result, many deny the existence and functional role of the female prostate in women’s sexual health. In reviewing past medical literature, we came across reports of the existence of the female prostate from the early days of the Kama Sutra. Scholars then discussed the homologous female prostate as a distinct organ within the female pelvis. Similarly, in 300 BC Herophiles identified the prostate gland during his human dissections and claimed this organ to be an anatomical component of both male and female reproductive anatomy. In 1672 Reignier de Graaf is credited with the first anatomical depiction of prostatic tissue surrounding the mid-urethra in women. Three centuries later Grafenberg described the role of the female urethra and surrounding prostatic tissue in orgasm. Methods Methods: A literature search was performed using the keywords "female prostate", "Skene's gland", "peri-urethral gland", and "G-spot". Over 200 publications were found based on relevance. Categories for analysis included anatomy, physiology, embryology, pathology, neural innervation, adenomatous and cancerous changes, and orgasmic potential. _x000D_ Results Results: More than 60 publications were included for review and analysis. Since 400 BCE scholars have proposed the existence of sexually sensitive homologous "female prostate" peri-urethral anterior vaginal wall tissue. Contemporary researchers have characterized “female prostate” exhibiting glandular and secretive elements identical to male prostate via immunohistochemical studies with prostate specific antigen (PSA), prostate specific acid phosphatase, androgen receptors, biochemical analyses of PSA and creatinine in female ejaculate as well as three-dimensional modelling and waxy casts. _x000D_ Conclusions Conclusion: "Female prostate" is embryologically and physiologically identical to male prostate. In some women, stimulation of "female prostate" via the anterior vaginal wall results in orgasm, analogous to stimulation of the anterior wall of the rectum resulting in orgasm in some men. The female prostate is not simply an incidental, vestigial organ; injury during surgical procedures may have clinical consequences, as peri-urethral anterior vaginal wall tissue possesses neurally-mediated sexually functional attributes. Despite skepticism, its existence is supported by extensive, reliable contemporary evidence._x000D_ Funding None
Authors
Nicole Szell
Barry Komisaruk Todd Campbell Sue Goldstein Irwin Goldstein |
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FRI-15 |
Crime and Punishment: Genitourinary Mutilation as a Legal Sentencing |
History of Urology: History Forum | 17BOS |
Abstract: FRI-15 Sources of Funding: None Introduction Genitourinary organs have played a notorious role in both crime and legal sentencing throughout history. Criminal activities including adultery, rape, and child molestation have been met with legally enforced castration and penile amputation. We aimed to provide a comprehensive review of criminal punishment as it relates to urologic structures. Methods A Pubmed and Medline review of literature concerning criminal sentencing as it relates to urologic organs was completed. Further research was then conducted using various primary resources, periodicals and encyclopedias detailing those events. Results Throughout ancient cultures, sexual mutilation was an accepted punishment for many criminal activities. Chinese law in the Dynastic era included Five Punishments, all of which involved physical mutilation. One of them, termed Gong, was a penalty for promiscuity or adultery and involved the removal of the testicles and penile shaft. Penile amputation was also utilized as punishment for licentious behavior during the Japanese Heian period. Punitive genital mutilation, however, is by no means confined to ancient history. Currently, eight states allow for chemical and/or surgical castration of incarcerated persons seeking rehabilitation for child molestation. The requirements for castration include that the criminal request surgery, that informed consent is obtained, and that castration cannot be coerced via threats or inducements. Other countries are not so enlightened as to ask permission prior to castration. Indonesia recently enacted legislation allowing for castration of men convicted of rape despite objections from the Amnesty International. Occasionally, however, the crime involves genital mutilation and the punishment is withheld. In Thailand from 1973-1990s, over 100 assaults involving penile amputation were reported with only a hand full of prosecutions for those committing the acts. Most amputations resulted from wives of husbands who were abusing them or committing adultery. Many husbands never filed charges and for those who did the Thai court system most often sided with the female defendant. Conclusions While criminal acts involving removal of genitourinary structures have been reported for centuries, it is troubling that some legally approved urologic mutilations are still prevalent in society. Despite the objections of human rights organizations, castration continues to be a legal punishment across the globe, including within the United States. Funding None
Authors
Matthew Goland-Van Ryn
David Ahlborn Jeffrey Stock |
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FRI-16 |
Radiation effect on male spermatogenesis and fertility – the science and ethical consideration of the Oregon and Washington radiation experiments on prison inmates |
History of Urology: History Forum | 17BOS |
Abstract: FRI-16 Sources of Funding: None Introduction The post-World War II era witnessed a proliferation of atomic science and an intense interest in radiation hazards to astronauts and pilots in nuclear-powered aircrafts, troops in the fields, and workers in nuclear plants. This became the context for two controversial experiments on the effects of x-ray irradiation on male fertility using human prison inmates. The objective of this study is to review the science and ethics of the medical experimentation on prisoners. _x000D_ Methods We reviewed primary scientific literature on the two radiation experiments and secondary sources from legal journals and government investigations. _x000D_ Results Between 1963 to 1973, the Atomic Energy Commission sponsored two studies on the effects of x-ray irradiation on human testicular function using healthy prison inmates at the Washington and the Oregon State Penitentiary. The studies enrolled a total of 165 prisoners who received exposure of 7.5 to 600 rad of radiation to the testes. Inmates in both control and exposure groups underwent period testicular biopsies and weekly seminal fluid examinations to determine the radiation dose that causes azoospermia or complete sterility. Both studies found a transient complete elimination of sperm production at 50 rad. However, at as high as 400 rad exposure, significant return of sperm production was invariably seen. All men were encouraged to undergo vasectomy at the end of the study to prevent possibility of defective offspring; however, eight men refused and some went on to have children with genetic defects. _x000D_ _x000D_ Both studies would have been in violation of federal regulation on permissible medical research in prison population as they exist today. Major ethical issues include coercion and exploitation of prison subjects, informed consent, and financial incentives. Prisoners were not properly counseled on risk of testicular cancer from radiation, in fact, the term cancer was deliberately avoided in the informed consent process. Conclusions The Washington and Oregon prison experiments on radiation effects on male spermatogenesis and fertility confirmed profound effect of radiation on testicular function. The result of the studies formed the basis of current limit of radiation exposure and occupation hazard regulation. These two experiments are important case studies not only for their contribution to the urologic knowledge but also for highlighting the interface between science and ethics. Funding None
Authors
Hong Truong
James Ryan Mark |
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FRI-17 |
"Walk like a man": Sex testing and female gender identity in international athletic competition |
History of Urology: History Forum | 17BOS |
Abstract: FRI-17 Sources of Funding: None Introduction During the 2016 Rio Summer Olympic Games, Caster Semenya participated in the 800m finals and won gold. Her win, while a personal accomplishment, also had historical implications. Seven years prior, questions began to be raised about her gender ultimately leading to her temporary ban from athletic competition while she underwent "sex verification testing." The sex-testing to which she was subjected had a historical precedent. This paper seeks to explore the historical narrative surrounding intersex disorders as the presented in the form of female athletic competition. Methods A literature review was conducted in PubMed which identified primary and secondary sources regarding "sex testing" and "femininity certificates." These sources were reviewed in order to evaluate the sociocultural context of sex testing among female athletes in international competition. Results Sex testing began in earnest in the 1950s with the mandatory sex testing of female athletes during the European Championships, although rumblings of questioning the ender of female athletes pre-dated the creation of this mandatory law. In the 1930s, as women became increasingly involved in athletic competition, women's bodies were scrutinized if they appeared too "male-like" or exhibited athletic exceptionalism. Early sprinters such as Dora Ratjen of Germany and Stella Walsh of Poland were driven away from the sport due to claims that they were in fact men. Once testing became official, it consisted of invasive physical examinations, heavily focused on the genitalia as women were asked to "parade nude before a panel of doctors." Often as a direct response to these athletic community's inquiries into their sexual identity, these female athletes, who were branded as male and termed "hermaphrodite" subsequently underwent surgical reassignment. While testing transitioned to include genetic and hormone testing, the results remained relatively inconclusive and significantly altered the lives of the women on whom they were conducted_x000D_ _x000D_ Conclusions Historically, dominant performances by women on the international athletic stage called into question their gender identity. Invasive sex testing was performed and many of the individuals who were investigated would be identified as intersex today. Contemporary discussions of transgender identity add a new layer of complexity to examinations of the intersection of gender and athletic competition as transgender athletes made history in the 2016 Rio Olympic Games by competing without having undergone gender reassignment surgery. Funding None
Authors
Unwanaobong Nseyo
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FRI-18 |
Changing gender and annulling marriage – a historical perspective on the early history of hypospadias. |
History of Urology: History Forum | 17BOS |
Abstract: FRI-18 Sources of Funding: None Introduction Hypospadias is one of the commonest genetic abnormalities of the male genital tract. _x000D_ It is nowadays well understood that abnormalities of the genital organs can lead to psychosocial and psychosexual complications._x000D_ This study aims to review whether this was also recognised in antiquity._x000D_ Methods Modern and historical manuscripts were reviewed using paper and online resources such as JSTOR, Google Books and archive.org. Results Hypospadias was recognised in the early classical period. Aristotle in his De generatione animalium (4th century BC) describes 'instances of boys in whom the termination of the penis has not coincided with the passage through which the residue from the bladder passes out,- on this account they sit in order to pass water, and when the testes are drawn up they seem from a distance to have both male and female generative organs.'_x000D_ _x000D_ This highlights the early recognition that hypospadias could give rise to vague genitalia and have an impact on perceived gender stereotypes such as having to sit to pass water for boys._x000D_ _x000D_ Hypospadias may have also affected early Hellenic art. Laios et al propose that the 'Phallus Vulva' vase, a piece of Greek pottery dated circa 610BC which depicts a phallus with an hole at the base of the shaft, may have be the first representation of a penoscrotal hypospadias in art. _x000D_ _x000D_ _x000D_ Social impact:_x000D_ _x000D_ Diodoros Sulcus (1st century BC) in Fragmenta Libri XXXII describes the case of a Greek woman named Kallo who although married had always declined sexual intercourse. A genital infection finally caused her to seek the services of a pharmacist who, upon incising what appeared to be labial adhesions discovered a case of penoscrotal hypospadias. _x000D_ The marriage was dissolved and Kallo elected to change her name to the male Kallon and live in a male gender role. _x000D_ _x000D_ A further maritial case arose over a millennium later in Malta and may well be the first recorded urological cause for the annulment of marriage in modern legal literature. _x000D_ A woman named Mathia living in Medina brought legal action against her husband John Azzopardi in 1542 due to his inability to perform his 'natural manly duties'._x000D_ He was examined by two physicians who rather uncharitably described his penis as: 'inept or incapable and also useless for deflorating or perforating' due to a ventral hypospadias with chordee. The marriage was annulled._x000D_ _x000D_ Conclusions _x000D_ There is evidence that even in antiquity hypospadias was recognized as a condition with a potential impact on both the personal and societal perceptions of gender roles, having sometimes devastating and life changing effects on the men affected by it_x000D_ Funding None
Authors
Alberto Coscione
Nicholas Simson Thomas Stonier Michalis Varnavas |
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FRII-01 |
Michelangelo’s Kidney: A Case Presentation of Urolithiasis |
History of Urology: History Forum | 17BOS |
Abstract: FRII-01 Sources of Funding: none Introduction Through Michelangelo’s life and artwork we gain glimpses of the Italian artist’s condition or recurrent kidney stones. Our aim was to search through literature to gain a better understanding of his symptoms and how he was treated for urolithiasis. Methods A literature search was performed using PubMed and Google on Michelangelo Buonarroti and kidney stones. Results Michelangelo Buonarroti (1475-1564) was presumed to suffer from chronic illness throughout life. He had a history of recurrent kidney stones as well as gout later in life. In 1999, Eknoyan claimed that Michelangelo’s medical condition influenced his artwork. Eknoyan pointed out the painting, God Separating Earth from Waters, was drawn in the shape of a “bisected right kidney”. Perhaps it is the artwork which stimulates further interest in Michelangelo’s medical history. _x000D_ According to some authors, Michelangelo was diagnosed with kidney stones at age 75 in 1549 and was treated by Realdo Colombo. However, there is mention of symptoms and kidney problems prior to 1549. In The Life of Michelangelo, Condivi mentions “gravel in his urine” which may have preceded kidney stones. A Week in the Life of Michelangelo relates events from 1518-1526 where the artist kept records of the food he ate during the day as he was recommended to eat light meals to prevent stones. _x000D_ Most detailed accounts of Michelangelo’s condition come from letters written to his nephew. In March 1549, he complains of difficulties with urination, fever, and pain which keeps him up at night. A few days later, in another letter he mentions being told to drink “a certain kind of water” which leads to passing of his stones along with “thick white matter”. He continues to mention this “spring water from Vitterbo” as his treatment regimen and reports feeling better. While acknowledging the treatment, Michelangelo continues to pray and thank God in each of his letters which give us a glimpse of the importance of faith in his illness. Despite treatment, Michelangelo’s health worsened and he was diagnosed with gout in 1555. The development of gout raises suspicion that he was suffering from urate stones. This could be due to a congenital medical illness or as Wolf suggested in 2005 it could be acquired from injury to his kidneys due to lead exposure from lead-based paints and wine stored in lead containers. Conclusions While the literature is inconclusive on the cause of Michelangelo’s kidney stones, it appears that compounds found in the paint he used contributed to his health conditions, which later manifested in his artwork in the form of God emerging from a bisected kidney. Funding none
Authors
Kailash Kapadia
Andrew Chen Kirk Redger Felix Cheung Howard L Adler |
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FRII-02 |
How a Urology Career Ending Hand Injury, Produced a Pioneer of Uroradiology |
History of Urology: History Forum | 17BOS |
Abstract: FRII-02 Sources of Funding: none Introduction Dr. Howard Pollack retired as a well-known pioneer of uroradiology. He originally trained as a Urologist, but a disabling accident forced him to make a career change to Radiology. Dr. Pollack capitalized on the career change and helped found the specialty of GU radiology in the USA. Methods Internet and historical archive review, as well as personal interviews with former residents and faculty Results A lifelong Philadelphian, Pollack graduated from Temple University for college and medical school, and then Episcopal Hospital, for urology residency. He initially worked as a military urologist, as Chief of Urology at the 1,100th U.S. Air Force Hospital and advisor to the Surgeon General&[prime]s office. On return to civilian life, Pollack had a prosaic career as a community urologist. In a freak accident at home, a glass injury severely injured his hands ,disabling him and ending his urologic career. Instead of surrendering to tragedy, at middle age he changed careers and retrained as a Radiologist. His true calling was radiology. He quickly became an academic specialist, by applying his urologic skills to radiology. First, as chairman and professor of radiology at Episcopal Hospital and then as founder of the division of uroradiology at the University of Pennsylvania in 1977. He codified the specialty by establishing the Uroradiology Club in 1966, The Society of Uroradiology in 1974 and The Journal of Urologic Radiology in 1979. His textbook, Clinical Urography has been the bible of uroradiology. He also helped invent the endorectal coil for prostate imaging, sonographic classification of renal masses, and developed and refined interventional procedures (six patented inventions). Dr. Pollack was also a renaissance man; an art and history buff, passionate detective novel reader, and accomplished jazz pianist, and life-long baseball fanatic and sports trivia master. He published several sports articles and was more proud of them then any academic manuscript. On retirement, he worked on a definitive guide to every sports museum and hall of fame in the USA. Ironically, he died of metastatic renal cell cancer. Conclusions Dr. Pollack&[prime]s life epitomized the saying &[Prime]I asked for health, that I may do great things. I was given infirmity, that I might do better things.&[Prime] Funding none
Authors
Steven Brandes
Stephanie Thompson Robert Goldfarb |
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FRII-03 |
Max Wilms: A Triphasic History of the Man, His Eponymous Tumor, and Its Evolving Treatment |
History of Urology: History Forum | 17BOS |
Abstract: FRII-03 Sources of Funding: None Introduction Nephroblastoma has been described for over a century. We explored the man behind the eponym, advances in tumor biology, and its how its treatment has evolved since early descriptions. Methods Literature review of Wilms and nephroblastoma. Results The Man: Born in 1867, Carolus Maximilianus Wilhemus Wilms initially pursued pathology but later secured a position with the surgeon Trendelenburg. During this time, published a three-part monograph, the first of which described mixed renal tumors. He pioneered new approaches to prostatectomy, though his interests extended far beyond urology. During his chief surgeon appointment to a World War I army corps, he became septic after performing a tracheotomy on a prisoner of war with diptheria, dying in 1918. _x000D_ The Tumor: Despite the eponym, Wilms tumor was described before his monograph. Microscopically confirmed as cancer in the 1850s, the mixed histology was not described until 1872. Wilms explored it further, identifying connective tissue, smooth and striated muscle, and epithelium, and proposed an embryologic origin in 1899; he was granted the eponym in 1900. Later pathologists identified traits, such as anaplasia, that impact outcomes and fine-tuned the triphasic elements described by Wilms into blastemal, epithelial and stromal components. Its association with multiple syndromes and occasional familial tumors primed it for genetic insights. _x000D_ Its Treatment: Jessop performed the first successful nephrectomy for nephroblastoma in 1877. Although the boy died 9 months later, he was one of the few early patients to survive nephrectomy for Wilms tumor; there was a debate among the surgical community as to whether surgery was ever appropriate because of the high mortality rate. Survival remained abysmal well into the 20th century. Operative mortality decreased after 1932, but <25% remained alive for ≥2 years. The cure rate jumped to 47% in the 1940s, an improvement attributed to early vessel ligation and post-operative radiation. Survival dramatically increased again with the advent of chemotherapy for Wilms, first reported in 1960. In America (1969) and Europe (1971), multi-center research groups formed to elucidate the best treatments. The groups diverged on the timing of surgery and chemotherapy. Now in an era with improved survival, treatment goals include minimizing morbidity and following long term sequelae._x000D_ Conclusions Max Wilms, a man of diverse interests who died a hero, happened upon a biologically fascinating tumor. Its treatment, well-described for over a century, continues to evolve as we identify ways of maximizing survival with the least morbidity. Funding None
Authors
Kristina Suson
Yegappan Lakshmanan Janae Preece |
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FRII-04 |
Little Big Man with a Short Thumb: J Bentley Squier as Urologic Giant and the Founding of the World’s First Academic Medical Center |
History of Urology: History Forum | 17BOS |
Abstract: FRII-04 Sources of Funding: None Introduction The early 20th century was a marked period of growth and expansion of the health care system that was closely followed on America's biggest stage, New York City. A major milestone was the creation of the world's first academic medical center in 1928; which combined The Squier Urological Clinic, Sloan Hospital for Women, the Vanderbilt Clinic, and Presbyterian Hospital with Columbia University. Methods University historical archives and internet search, and personal communications of former Urology faculty. Results The name J. Bentley Squier is not eponymous with any signs, symptoms, procedures or technique. Perhaps his most unique attribute was his short stature and a partially amputated thumb. Squier believed in surgical expediency and efficiency, best demonstrated by his suprapubic prostatectomy (which he championed over perineal prostatectomy); often completing the surgery ≤10 minutes; 12 minutes if with bladder stones.His small hands and partially amputated thumb were uniquely suited to a narrow pelvis and to core out the adenoma. He was quite the showman, awing audiences by emerging from the pelvis with the entire adenoma sitting atop his thumb like an apple on a stick. To create the world's first academic medical center, Squier moved his Urological clinic from Madison Avenue to a new 70 bed unit on the 10th floor of the new hospital. To do so, Squier raised $400,000 from his many devoted and wealthy patients. Squier was the Urologists to the stars; like world heavy weight boxing champ Gene Turney,and NY Times publishers Ochs and Sulzberger. The Clinic had its own operating and cystoscopy rooms, pathology and radiology departments, and library. In 1929, he established a 30-bed pediatric service in Babies Hospital. In 1935 he became Chair of Columbia&[prime]s first Urology Department. He was already an academic giant; as one of the founding fathers, President, Governor and Regent of the American College of Surgeons and President of The American Urological Society. Just like today's changing medical landscape, the 1930's were tough economic times - so the clinic targeted well-healed private patients by creating more private rooms, a $4 a day &[Prime]pay ward&[Prime], and reducing charity beds . Increasing &[Prime]fee for service&[Prime] payers kept the Clinic solvent. Squier was succeeded as Chair in 1939, leaving behind a world-renowned and profitable Urology Department. _x000D_ _x000D_ Conclusions The world of urology surrounding Squier resembles many challenges faced today: hospital mergers and acquisitions and a changing medical and economic landscape. Squier was a Urologic giant. Funding None
Authors
Robert Goldfarb
Stephanie Thompson Steven Brandes |
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FRII-05 |
Tobias Goodman and the New England Origin of Ureteroscopy. |
History of Urology: History Forum | 17BOS |
Abstract: FRII-05 Sources of Funding: none Introduction Ureteroscopy is one of the most commonly performed procedures in current urologic practice, although rigid ureteroscopy was unheard of until the very recent past. Its origins has direct New England ties. Although the first documented “ureteroscopy” is attributed to Hugh Hampton Young who performed inadvertent endoscopy of the ureter in a 2 month old child with posterior urethral valves, this 1929 report was essentially relegated to anecdote that lacked any practical application.50 years later, in a small New England town, diagnostic and therapeutic ureteroscopy were born with the first planned rigid ureteroscopy and the introduction of ureteroscopic-guided intervention. Methods A comprehensive search of Medline was undertaken to assess all published articles describing ureteroscopy prior to 1980. References of identified papers were also reviewed to identify the earliest published accounts of rigid ureteroscopy. Upon identifying the initial reported ureteroscopy, the author was interviewed to better understand the context surrounding the inception of ureteroscopy. Results The first report of planned rigid ureteroscopy was in 1977. The procedure was performed by Dr. Tobias M. Goodman at Westerly Hospital. Dr. Goodman attended Browne and Nichols school in Cambridge, MA, then matriculated to Harvard College where he was an accomplished scholar in Classic Languages. After graduating from residency at Boston Medical Center, he started solo practice in Westerly, RI. At the time, blind stone-basketing was standard practice, but he recounts unease with the imprecise nature of blind manipulation. Thirty years prior to the AUA recommendation against blind-basketing, he proposed to several patients an improved, directly visualized approach to management of ureteral pathology. With a reputation as a physician who “knew how to stay out of trouble,” his patients eagerly agreed. Using a pediatric cystoscope with a standard bridge and an 11Fr sheath, he accessed, visualized and fulgurated a distal ureteral tumor. He developed techniques for diagnostic ureteroscopy and stone extraction, publishing the first series of rigid ureteroscopy in 1977. He subsequently developed patents for a ureteroscope, a 3-way endoscopic valve and Uroshiol for treatment of bladder cancer. Since retirement, he has authored 2 non-medical books: Out of the Attic and Ancient purple. He still resides in Westerly, RI where he is a guest columnist for the Westerly Sun. Conclusions Dr Tobias Goodman is a urologic pioneer who serves as an example of the creative thinking that has allowed the dramatic progress we continue to enjoy. Funding none
Authors
Joseph Yared
Vernon Pais |
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FRII-06 |
Boston, MA: The Home of Dr. Joseph E. Murray and the First Organ Transplant |
History of Urology: History Forum | 17BOS |
Abstract: FRII-06 Sources of Funding: None Introduction Dr. Joseph E Murray was born, raised and educated in Massachusetts, where he developed a passion for science and research. Through his training and military experience, he witnessed the mysteries of graft rejection, which ultimately put him on a trajectory to become the first surgeon to perform a living donor transplant. He single-handedly transformed the world of transplant medicine into what we practice today. Methods Information on Dr. Murray was obtained from a thorough review of his published works, the William P. Didusch Center for Urologic History, the Nobel Prize organization, and testimonials from close friends and colleagues. Results Dr. Murray was born April 1, 1919 in Milford, MA. From a young age, he had a passion for science. He attended Holy Cross College where he gave up sports in order to attend science labs. Staying close to home, he attended Harvard Medical School. After completing his internship at Peter Bent Brigham Hospital, he joined the Army where he met Colonel James Barrett Brown, Chief of Plastic Surgery at Valley Forge General Hospital in Pennsylvania. Together, they treated soldier's burns and were eye witnesses to the consistent rejection of skin grafts. They observed that the closer the genetic relationship between the donor and recipient, the slower the rate of rejection of the skin grafts. After leaving the military, Dr. Murray pursued research on this concept, working for years with a renal transplant team at Brigham. Then, in 1954, Dr. Murray had the opportunity to take his bench research to the bedside when identical twin Richard Herrick was hospitalized with life threatening chronic nephritis. Amid harsh criticism and skepticism, Dr. Murray and his team prepared for the first human kidney transplant, which they successfully performed on December 24, 1954. He would go on to perform the first successful transplant in a non-identical recipient and the first cadaver transplant. Conclusions Dr. Murray was awarded the Nobel Prize in 1990 and praised for his perseverance in the field at a time when his work was heavily criticized. In addition to his professional accomplishments, he was also a loving husband of 67 years, a father to 6 children and grandfather to 18 grandchildren. The work of Dr. Murray transformed the realm of transplant medicine and continues to give the gift of life to thousands of people to this day. Funding None
Authors
Alexandra Rehfuss
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FRII-07 |
HOW CHESTER ALAN ARTHUR ‘BRIGHTENED’ FROM A POLITICAL SPOILSMAN TO A CIVIL SERVICE REFORMER |
History of Urology: History Forum | 17BOS |
Abstract: FRII-07 Sources of Funding: None Introduction The radical transformation of President Chester Alan Arthur, from a political &[Prime]spoilsman&[Prime] to civil service reformer could be linked to his fatal diagnosis of Bright&[prime]s disease (chronic kidney disease) early on in his presidency. Methods We completed a review of the literature on President Arthur&[prime]s life, with a focus on his transformation from a political &[prime]spoilsman&[Prime] to a political reformer. Did his renal parenchymal disease lead to his passing of the Pendelton Act, which legislated civil service reform? What was the reason behind his passing of radical civil service reform which combated the very system of patronage responsible for his rise to presidency? Results President Arthur became the 21st President of the United States in 1881 after James Garfield succumbed to an assassin&[prime]s bullet. Before being chosen as Garfield&[prime]s vice-president, Arthur was known as the consummate political insider during an era that was marked by political patronage or the &[prime]spoils&[prime] system. Thus, when Garfield died and Arthur assumed the presidential mantle, many considered him to have little interest in political reform. The etiology of Arthur&[prime]s transformation from insider to reformer is unclear, however, early on in his administration, Arthur learned that he had Bright&[prime]s disease, a progressive and, at that time, uniformly fatal form of renal parenchymal disease. While Arthur&[prime]s role as a political reformer could be ascribed to his impending mortality, the extent of Arthur&[prime]s uremia, which resulted from progression of his Bright&[prime]s disease, may have moderated his temperament, softened deliberations, and hastened his signing of the Pendleton Act into law. The few primary sources that are available portray a President who is mentally and physically unwell immediately before, during, and after the passage of the Pendleton Act. In other words, Arthur may have been too sick and tired to fight civil service reform and simply signed the Pendleton Act as the path of least resistance. Conclusions President Arthur&[prime]s motivation in signing The Pendleton Act remains unclear given his early history, but it is conceivable that the diagnosis and/or the effects of Bright&[prime]s disease contributed to his uncharacteristic action of signing into law such landmark legislation._x000D_ Funding None
Authors
Daniel Canter
Hailey Silverii Stephen Carriere |
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FRII-08 |
Wallwerk Meets Stone Work: The Bladder Meets the Moon in the Eyes of Franz von Paula Gruithuisen |
History of Urology: History Forum | 17BOS |
Abstract: FRII-08 Sources of Funding: None Introduction Franz von Paula Gruithuisen lived a life of inquiry. Through opportunity bore out of service to his country of Austria he forged his way into the medical ranks. Through his favored relationships with royalty he was able to reach for the stars. An unbridled mind of inquiry - we sought to tell his story, where impossible dreams transcend space. Methods Information was obtained through original works, translated to English; as well as accounts of his personal life through German and Austrian historical works. Results Franz von Paula Gruithuisen was born March 19th, 1774 in Upper Bavaria. The son a falconer from Holland and a sculptor; it is no surprise that his life would be spent looking to the skies and marveled by stone. _x000D_ He took quickly to the study of medicine and treatment of the human body while living in Landsberg (modern Germany) serving as a Barber's Apprentice. At the age of 14 he volunteered for the Austrian Army to serve as an assistant of the Field Surgeon in the Austro-Turkish War. Upon completion of his service, Prince Karl Theodor took special interest in von Paula Gruituisen bringing him into his personal employment in 1792 and eventually sponsoring his scholarship at university. He received a magnitude of awards for his works. _x000D_ In March of 1813 he published his works, "Should one abandon the long-standing hope of one day being able to remove stones in the bladder by mechanical or chemical means?" thereby laying his foundation for the transurethral destruction and removal of bladder calculi. He had postulated that stone destruction could be achieved by a variety of methods: washing of the stone with water, mechanical crushing, chemical dissolving, and galvanic pulverization. He drew heavily from his works across the natural sciences. In 1813 he tested his method by passing a straight tube into the bladder for drilling. His illustrations and instruments would serve as the scaffolding for lithotists to follow._x000D_ In 1826 King Ludwig I of Bavaria nominated Dr. Gruithuisen as an Extraordinary Professor of Astronomy, leading to von Gruithuisen forgoing his medical endeavors in order to focus on his astrological research. Gruithuisen's Crater was named in honor of his dedication to the study the moon._x000D_ Conclusions Franz von Paula Gruithuisen pioneering work in transurethral bladder stone destruction served as the ground work for generations of urologist who followed. With one foot on the earth and his eyes turned to the stars, he dreamed about what may lie beyond our world. His lifelong pursuit of investigation is one to be admired and emulated. Funding None
Authors
Joseph Mahon
Charles Welliver Mark White |
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FRII-09 |
Conservative Kidney Trauma Management and Conservative Politics: How Sir Winston Churchill's Physicians May Have Saved the Western World |
History of Urology: History Forum | 17BOS |
Abstract: FRII-09 Sources of Funding: none Introduction The exquisite leadership and unmatched resolve of Sir Winston Churchill during the Second World War are known well beyond the borders of Britain. The adversities he overcame in the 1930’s and 1940’s have been extensively explored. However, one lesser known misfortune he faced earlier in life had a profound impact upon Mr. Churchill. The details surrounding this urologic traumatic event are herein examined, specifically with respect to the management his physicians selected. These medical decisions early in Mr. Churchill’s life were important for shaping the future of the Western World and the emergence of the ‘British Bulldog’. Methods A review of the literature was performed with Google Scholar to assess secondary sources pertinent to the early life of Sir Winston Churchill. Specifically, to further examine the urologic traumatic event that took place during Churchill’s late adolescence and how this clinical situation was managed. Results In the early winter of 1892, an 18 year old Winston Churchill was on holiday at the estate of his aunt in Bournemouth, England. While accompanied by his younger brother and a young cousin, the boys took up a game of chasing the older Churchill. Churchill found himself in the middle of a bridge straddling a ravine with a boy on either side. In the spirit of the game, he climbed over the railing of the bridge and pondered, “to plunge or not to plunge, that was the question!” He chose to plunge, and the slender firs he hoped would break his 29-foot fall did little to mitigate the traumatic results. It was 3 days before he regained consciousness and several weeks before he could climb from bed. He was diagnosed with a ‘kidney rupture’ as well as a concussion and right shoulder injury. The Churchill’s family physician, Dr. Robson Roose, as well as a London surgeon, Dr. John Rose, recommended 3 months of bed rest. Churchill’s recovery was prolonged and he stated, “for a year I looked at life round a corner.” Conclusions Kidneys are the 3rd most common solid organ to be damaged following blunt trauma, and renal lacerations are a common result of rapid deceleration. These injuries need operative intervention in less than 10% of cases, but those numbers are bolstered by 21st century imaging. In late 19th century Britain, without the use of modern imaging technology, these physicians selected the appropriate conservative treatment modality. If young Winston Churchill would have met an early demise, the fight against Nazi Germany may have ultimately had a different outcome. Funding none
Authors
Alan Carnes
Zach Klaassen Michael Kemper Arthur Smith Durwood Neal |
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FRII-10 |
HM3 Lithotripter at University of Virginia: 1984-2016, End of an Era |
History of Urology: History Forum | 17BOS |
Abstract: FRII-10 Sources of Funding: None Introduction The Dornier HM3 Lithotripter is an extracorporeal shockwave lithotripsy (ESWL) machine that revolutionized treatment of urolithiasis. Over 10,000 patients have been treated by the HM3 at University of Virginia (UVA) from 1984-2016. Continued use of the HM3 is a testament to its efficacy in treating stones and the dedication of lithotripsy technicians maintaining the device. Due to exhaustion of spare parts, we can no longer maintain the machine, and it will be retired on 1 Jan 2017. To our knowledge, this is the last HM3 lithotripter at an academic center in the United States. Methods We conducted structured interviews of key personnel present during installation in 1984. Detailed records were available for the number of HM3 cases per year from 2007-2016. From 1984-2004, the number of cases were estimated based on the number of shocks administered. Shocks per case were estimated at 3,000. We reviewed literature comparing the HM3 to other lithotripters. Results Dr. Jay Y. Gillenwater acquired the HM3 for 1 million dollars in 1984. The HM3 was initially only available to a group of 4 urologists working with Dornier, although Dr. Gillenwater had contacted the company first. Despite strong resistance against UVA acquiring the lithotripter machine and funds to finance it, Dr. Gillenwater leveraged connections with congress to put pressure on the company to sell the machine. Installation was completed over a 6-month period finishing in July 1984. The first patients treated were Air Force One pilots rendered unable to fly due to stones. Initially, the HM3 had been used only on renal stones, but Gillenwater pioneered the safe and effective treatment of ureteral stones, changing FDA regulations to allow ureteral stone treatment. Case volume increased to a maximum of 19 patients per day as a result. Use of the lithotripter has declined with the advent of ureteroscopy (Figure). Randomized clinical trials and observational studies have established the HM3 as the most efficacious lithotripter ever used. Conclusions The HM3 at UVA successfully treated over 10,000 patients and continues to outperform later-generation lithotripters. It leaves a significant legacy and ends a storied period of stone treatment at UVA. Funding None
Authors
Matthew Clements
Jay Y Gillenwater Noah Schenkman |
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FRII-11 |
RARE AND UNUSUAL UROGENITAL DISEASES |
History of Urology: History Forum | 17BOS |
Abstract: FRII-11 Sources of Funding: NONE Introduction To present some aspects of rare and unusual urogenital disorders, including congenital malformations and syndromes, sometimes occurring in eminent personalities or having been described by famous scientists. Methods The review of historical sources and biographies of famous sufferers and the study of modern medical literature about all these rare urogenital diseases. Results Penile deformities such as hypospadias (the most known representative was Henry II of France (1519-1559), suffering also from chordee) and epispadias (respectively the most known was the Byzantine Emperor Heraclius, (575-641)) were recorded mainly by historians because of the infertility consequences or the bizarre urination habits (Heraclius needed protective measures to avoid getting wet). Historians also were attracted by spectacular and dramatic urological emergencies, such as Fournier gangrene, known by the case of the prominent sufferer Herod 10 BC-44 AD). _x000D_ Referring to famous researchers, François Gigot de La Peyronie (1678-1747), founder of the Royal Academy of Surgery of France, described the homonymous disorder (1743), consisting of penile deformity due to induration of the corpora cavernosa of the penis, now also called Induratio Penis Plastica (IPP) is one of the extraordinary urogenital problems together with the strongly psychologically and non- physically induced syndromes Koro (Genital Retraction Syndrome) and Castration Anxiety (the latter described by Sigmund Freud(1856-1939)). Belief that genitals have disappear and fear of damage or loss of the penis characterize them both. Much of the research has been done on the two above topics, although still relevant today._x000D_ Conclusions Rare and unusual urogenital disorders attract the attention as extraordinary events (called Mirabilia by historians), especially if occurring on famous or evil persons (as a divine punishment). Furthermore, publicity is given when the above abnormalities are described by eminent physicians. Funding NONE
Authors
ELEFTHERIA-FOTEINI POULAKOU
APOSTOLOS REMPELAKOS C TSIAMIS M CHRISOFOS |
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FRII-12 |
Urologic Disease During the American Civil War |
History of Urology: History Forum | 17BOS |
Abstract: FRII-12 Sources of Funding: none Introduction The Civil War marked a major turning point in American epidemiology and medicine. Regulations at the start of the Civil War required the senior medical officer of each hospital, post, regiment, or detachment, to make monthly reports to the Surgeon General of the sick and wounded, deaths, and discharges. Urologic infectious, benign and traumatic diagnoses were documented along with other diseases across geographic and racial divides. Using primary documents and epidemiologic data, we attempt to reconstruct the state of urologic disease among soldiers during the War. _x000D_ Methods Primary documents from the UC Davis Blaisdell Civil War Medicine Collection including the epidemiological tables of sickness and mortality from the Medical and Surgical History of the War of the Rebellion by Surgeon General Joseph K. Barnes were analyzed. A non-systematic review of Pub Med was also conducted. _x000D_ Results In addition to ushering in new paradigms for the military hospital system, trauma surgery, and anesthesia, the Civil War also brought about major improvements in the way diseases were categorized and recorded. Data from the Medical and Surgical History of the War of the Rebellion demonstrates a small but significant burden of genitourinary pathology in the troops across the Atlantic, Central and Pacific Regions. Among GU diagnoses, sexually transmitted infections including syphilis, gonorrhea and orchitis had the highest incidence, averaging 33, 43 and 6 annual cases per 1000 white troops. The incidence of GU pathology was similar between white and non-white troops, with the exception of venereal disease, which was reported more frequently in whites. Venereal disease had a higher incidence at the start and end of the war. Prostitution, which has been well documented, was a likely contributor to the spread of venereal disease. The incidence of stones, benign scrotal disease, testis tumors and urethral strictures was relatively low and stable over the course of the war; surprisingly, of all GU diagnoses, varicoceles were associated with the highest rates of discharge from service. In this pre-penicillin era, the most fatal diagnoses were syphilis and infectious nephritis and cystitis. As previously described by Herr, traumatic GU injuries were relatively uncommon, representing <1% of all battle wounds; however, about half of injuries to the bladder and kidney were fatal and these injuries were fraught with complications such as fistulae. Conclusions Urologic pathology played a small but significant role in the lives of soldiers during the Civil War._x000D_ Funding none
Authors
Patrick Fisher
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FRII-13 |
War And Peace: Leo Szilard's Nuclear Legacy |
History of Urology: History Forum | 17BOS |
Abstract: FRII-13 Sources of Funding: None. Introduction The men and women who invented the atomic bomb would be horrified at its worldwide proliferation. Foremost among those scientists was Leo Szilard (1898-1964), arguably the first physicist to conceptualize an uncontrolled nuclear chain reaction. Szilard possessed an uncanny ability to see what was coming, and in fact got out of Berlin in 1933, one day before the authorities there began restricting exit visas. Safely in London, he was puzzled by Lord Rutherford's pronouncement that the atom would never be harnessed as an energy source, and as an avid reader of science fiction, he wondered if an element could be found whose nuclei would each release 2 neutrons upon bombardment by a single neutron. Realizing the implications of this exponential reaction, he had the foresight to take out a patent on the idea, thus delaying nuclear research in Europe for years. Methods Newly arrived in the U.S., Szilard worked secretly with Enrico Fermi in Chicago to build the world's first nuclear reactor, and was instrumental in galvanizing both the American scientific community and the Roosevelt administration to mobilize hastily to produce a fission weapon before the Germans did, putting him into direct competition with his old mentor, Werner Heisenberg, who didn't like Hitler, but naturally wanted Germany to have the bomb. Results After the successful test of a plutonium implosion prototype in July 1945, Szilard reversed course 180 degrees, leading a group of renegade scientists opposed to the use of the bomb in warfare. With an Allied victory all but certain, he argued against using it on the Japanese, who did not have a nuclear weapons program. He feared the precedent of using the new technology, realizing this was a seminal moment for humanity. After the war, Szilard dedicated the rest of his life to seeking world peace and fostering better communication between nations, as well as embarking upon a second career in biophysics. The many "firsts" attributed to him also include the breeder reactor, a reactor cooling system (for which he collaborated with Albert Einstein), and the linear accelerator, which is essential in the modern delivery of radiation therapy. Conclusions Szilard's final challenge epitomized his outlook on life - diagnosed with bladder cancer at age 60 in Denver, where his wife was a professor, he got a second opinion in New York from Dr. Willet Whitmore, who recommended a radical cystectomy and ileal conduit. Always the maverick, Szilard declined Dr. Whitmore's advice and designed his own cobalt therapy, under the direction of Dr. James Nickson at Sloan-Kettering. He subsequently remained cancer-free for 4 years, until he died in his sleep from an MI. Funding None.
Authors
Lawrence Wyner
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FRII-14 |
Evolution of Social Media in Pediatric Urology: the First Live Tweet Chat on Testicular Torsion |
History of Urology: History Forum | 17BOS |
Abstract: FRII-14 Sources of Funding: None Introduction Social media is a global phenomenon altering the way in which people interact. Its uses and reach have evolved beyond mere online networking to include and impact medicine. Reports show that 70-75% of US consumers look to the Internet for healthcare advice, of which 40% rely on responses from social sites. Social media allows for rapid communication, discussion, and dissemination of information to large groups of people. It also allows physicians to bring to the forefront important healthcare issues. Pediatric urology in particular is well suited to utilize social media as a unique way to touch base with younger patients, particularly in discussing sensitive topics such as testicular torsion. _x000D_ _x000D_ There is no reliable method to identify which patients may develop testicular torsion until the onset of symptoms. If the patient is unaware of the condition, there may be a delay in presentation and intervention. The TWIST (Testicular pain suddenly; Warning or take action for pain, swelling, or redness; Immediately tell an adult; See a doctor; Time is limited) campaign began in 2013 as a regional campaign in DE, PA, and FL to promote awareness of testicular torsion. When this topic was taught at school and discussed openly in the community, these patients were found to present earlier leading to a higher likelihood of testicular salvage. With the advent of social media, this campaign led to the first live tweet chat on testicular torsion._x000D_ Methods A comprehensive literature review in PubMed was performed related to keywords "social media" and "urology". Additionally, informatics regarding the live tweet chat were also obtained. Results The first live chat on Twitter regarding testicular torsion took place on 6/15/2015. It was sponsored by Kids Health, Nemours, Urology Care Foundation, Young Men’s Health, and Men’s Health Network. Dr Rupal Gupta, medical editor at Kids Health, Dr Carlos Estrada from Boston Children’s Hospital, and Dr T. Ernesto Figueroa from Nemours/AI duPont Hospital for Children were the facilitators of the chat. The search tags included #khchat and #TesticularTorsion. It lasted one hour, and was joined by 90 people producing 660 tweets and 33,750,157 impressions on this subject. Throughout the chat, various questions were posed by Kids Health that were answered by the facilitators to provide information and generate discussion. Conclusions Social media provides an outlet to discuss significant healthcare topics and serves as a unique way to reach a younger audience. Tweet chats in particular are a successful way in pediatric urology to promote awareness of important topics. Funding None
Authors
Christina Ho
T. Ernesto Figueroa |
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FRII-15 |
‘Evolution of Innovation’: Historical perspectives on the management of Urethral stricture disease |
History of Urology: History Forum | 17BOS |
Abstract: FRII-15 Sources of Funding: none Introduction Urethral stricture is a prevalent and challenging urological condition. Management has evolved over the last century, specifically with the advent of oral mucosal grafts for urethroplasty. We review the history of urethral stricture treatment._x000D_ Methods A literature search of medical texts, journal articles and historical texts was performed pertaining to history of urethral strictures. _x000D_ Results Urethra originates from the Greek word ourein 'urinate'. Urethral stricture was first depicted in Hindoo scriptures (6th century BC). Susruta described in Ayurveda the treatment by means of graduated dilators of metal or wood. Ambrose Pare in his depictions of urethrotomy mentions 'A silver weir, sharp at the upper end, is to be passed in as far as the obstruction, then by oft thrusting it in and out, it may wear and make plain the resisting caruncles'. _x000D_ _x000D_ In 1894, Sapezho first used oral mucosa in urethroplasty. Humby revived the use in 1941. This landmark discovery revolutionized urethral surgery. Several modern innovations have since been described: staged repair (Johanson 1953), dorsal onlay (Barbagli 1996), ventral onlay (Morey, McAnnich 1996), dorsal inlay penile (Hayes and Malone1999), dorsal inlay bulbar (Asopa 2001), panurethral stricture management (Kulkarni 2000), nerve sparing and bulbospongiosus sparing bulbar reconstruction (Barbagli 2008), Enterourethroplasty (Mundy 2010), Non-transecting anastomotic urethroplasty (Mundy 2015). Over this period the perineal incision has evolved from a lamda to a midline incision._x000D_ _x000D_ Current advances include liquid mucosal grafts; tissue engineering and stem cells, which would halt the process of fibrosis and prevent stricture formation._x000D_ _x000D_ Posterior urethral injuries have traditionally been managed by anastomotic urethroplasty. Pierce 1962 performed total abdominal pubectomy. Paine & Coombs 1968 performed anastomotic urethroplasty after excision of scar by abdominal approach. 1973 Waterhouse developed abdominoperineal approach. 1976 Turner-Warwick used omental wrap for transpubic primary anastomosis. Webster & Goldwasser 1986 performed perineal anastomotic urethroplasty using inferior pubectomy. Kulkarni 2010 described etiology and management of posterior urethral injuries. _x000D_ _x000D_ Currently a progressive stepwise approach has been used for managing posterior urethral injuries. _x000D_ Conclusions Management of urethral stricture patients has evolved over the last century. The use of oral mucosal grafts is still one the greatest advancements. As we continue to better understand urethral strictures, we hope to make even greater strides over the next decade._x000D_ Funding none
Authors
Devang Desai
Pankaj Joshi Hazem Orabi Sandesh Surana Sanjay Kulkarni |
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MP01-01 |
Stent Early Encrustation (SEE) Study: Factors associated with acute calcifications |
Stone Disease: Epidemiology & Evaluation I | 17BOS |
Abstract: MP01-01 Sources of Funding: None Introduction Acute ureteral stent encrustation (USE) is a commonly encountered problem that can increase stent morbidity and make stone treatment challenging. Previous research into USE has focused on the physical and biochemical properties of ureteral stents to decrease encrustation. To date, this research has proven generally unsuccessful. To our knowledge, no detailed data exists on individual patient characteristics of early stent encrusters. We sought to characterize this population in order to identify risk factors associated with acute USE. Methods An IRB approved prospective study was designed to identify patients with early USE, defined as a calcified stent identified within 3 months of stent placement. From June 2016 to October 2016 all patients with indwelling ureteral stents were screened. Patients with stent encrustation were identified. Demographic data, past medical history, indwelling time of stent, stent size, and stent manufacturer were collected. Additionally, at the time stent removal, urine analysis, urine culture, stent culture, stone culture, encrusted stent stone analysis, and ureteral stone analysis were obtained. Results Seventy-six consecutive patients undergoing ureteroscopy and stent placement were screened. 9.2% of cases demonstrated early USE. Average age of our cohort was 46 years old (STD 5.1) and 57% of patients were female. Urinary tract stones were found in the ureter (60%) and renal pelvis (40%). Average BMI was 26.2 (STD 6.3). No patient had identifiable metabolic stone disease. All patients had normal baseline renal function (GFR>60). The median indwelling stent time was 56 days (IQR 44-69 days). 57% of patients had a positive urine culture taken at time of stent removal. In 71% of patients, the major stone composition for USE and urinary tract stones was brushite (range 60-100%). Stone and calcified stent cultures were positive in 4 of 7 patients, but were never the same organism isolated in urine culture. Only 1 patient had an encrusted stent consistent with struvite. Furthermore, Streptococcus species were isolated in 50% of encrusted stent cultures. One patient had a positive stent culture with a negative concomitant urine culture. Conclusions In our series, the most common calcification associated with acute USE was brushite stones. Additionally, stone and calcified stent cultures were positive with organisms dissimilar from those isolated in the urine. Stone and calcified stent cultures should be obtained in this group of patients, principally if stent exchange or additional procedures are required. Funding None
Authors
William T Berg
Yefim Sheynkin David Schulsinger |
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MP01-02 |
A nomogram for predicting ureteral stone passage |
Stone Disease: Epidemiology & Evaluation I | 17BOS |
Abstract: MP01-02 Sources of Funding: None Introduction Medical expulsive therapy (MET) is frequently used for patients with ureteral stones who present to the emergency department (ED). Our goal was to develop and validate a nomogram to predict the probability stone passage on MET for ureteral stones. Methods We reviewed ED visits within our health system with an ICD-9 diagnosis of urolithiasis, an associated CT scan, and discharged on MET between 2010-2013. CT's were reviewed to confirm stone size, location, and associated hydronephrosis. The primary outcome was spontaneous stone passage within 90-days of initial ED visit. Patients with no documented follow up in our system were called to collect data on stone passage. A nomogram was developed using variables chosen for clinical and statistical significance and validated internally using a bootstrapping technique. Results 1,424 ED visits met the inclusion criteria and of these, 1,146 (80.4%) had confirmed ureteral stones on CT. Patients lost to follow up and who were unreachable by phone were excluded, leaving 661 patients to build the final model. The median age was 50 years (IQR 38-59) with 419 (63.4%) males and a median stone size of 4.0 mm (IQR 3.0-5.2). A majority of patients, 422 (64%), spontaneously passed their stone while the remaining underwent a procedure. On univariable analysis, patients who passed stones tended to have smaller stones (3.6 mm vs 5.2 mm, p < 0.001), stones in the distal ureter (73% vs. 41%, p < 0.001), and significantly higher WBC counts (9.49 vs. 8.57, p < 0.001). There were no associations between age (49 vs. 50, p = 0.831) or gender (64% male vs. 62% male, p = 0.451) on stone passage. In the multivariable model, stone size (per 1 mm increase; OR 0.49, 95% CI 0.43-0.57, p < 0.001), stone location (p < 0.0001), a prior history of stone passage (OR 1.74, 95% CI 1.04 - 2.93, p = 0.036), and WBC count (per 1k/uL increase, OR 1.12, 95% CI 1.04-1.21, p = 0.001) were significantly associated with spontaneous stone passage. The model was validated internally (bootstrap-adjusted concordance index, 0.80) and demonstrated excellent calibration. Conclusions For patients presenting with ureteral stones in the ED amenable to observation, we have developed a model to predict the probability of stone passage. Early follow-up or intervention for patients with a low probability of stone passage could improve patient satisfaction and prevent costly ED returns. Funding None
Authors
Vishnu Ganesan
Michael Kattan Christopher Loftus Bryan Hinck Daniel Greene Yaw Nyame Sri Sivalingam Manoj Monga |
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MP01-03 |
Patient Centered Factors Influencing Ureteral Stone Passage |
Stone Disease: Epidemiology & Evaluation I | 17BOS |
Abstract: MP01-03 Sources of Funding: None Introduction Patients generally prefer to avoid surgery for ureteral stones. The initial management decision is a leap of faith influenced by patient and physician experiences and preferences. We explore the impact of patient centered factors on initial decision making. Methods As an element of an ongoing quality improvement program, patients presenting to a subspecialty stone clinic after discharge from Emergency Department were identified. Inclusion criteria were unilateral ureteral stone <= 10mm on computed tomography and freedom from infection. Patients completed PROMIS pain intensity and pain interference symptom surveys (PROMIS score of 60 = 1 standard deviation above US population average). Patients participated in a shared decision making process between ureteroscopy and medical expulsive therapy (MET). Patients electing MET were followed for 90 days from initial clinic encounter in standardized fashion. Results Between 6/1/2014 and 5/31/2016, 686 patients met inclusion criteria consisting of 300 with proximal and 386 with distal ureteral stones. MET was elected by 483 (70.4%) patients including 164 (55%) proximal and 319 (82%) distal stone patients. Logistic regression demonstrates that patients with proximal stones, larger stone sizes, and higher PROMIS pain intensity were associated with choosing ureteroscopy (all p<0.001, Figure 1). Amongst patients electing MET, 61 (37.2%) proximal and 45 (14.1%) distal stone patients eventually had ureteroscopic stone clearance. Logistic regression demonstrates patients with proximal and larger stones were more likely to require surgery (all p<0.001, Figure 2). Conclusions As expected, patients with larger, more proximal stones were less likely to choose and be successful with stone passage. While of prognostic utility, these factors are beyond patient and physician control. However, outpatient symptom control after discharge from Emergency Department could be improved and may be an important opportunity to increase the number of patients attempting stone passage. Funding None
Authors
Andrew Portis
Jennifer Portis Suzanne Neises |
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MP01-04 |
Innovation in Ureteral Stone Care Delivery after Emergency Department (ED) Visit: Matched Controlled Study. |
Stone Disease: Epidemiology & Evaluation I | 17BOS |
Abstract: MP01-04 Sources of Funding: none Introduction We aimed to improve the care of patients who were discharged from our ED with ureteral stones by decreasing the time to definitive surgical treatment, reducing subsequent ED re-use, and minimizing the loss of follow-up after ED acute care, using a new model of care involving collaboration between the ED and Endourology Division. Methods Starting March 1, 2015, automated email notifications were sent from our ED about all patients who were discharged from the ED with a diagnosis of ureteral stones. Among them, we determined those eligible for early surgical intervention using prospectively determined criteria (stone size ? 5mm, persistent pain, signs of infection, or renal function deterioration) and an Endourology provider contacted eligible patient by phone to offer them early surgical intervention without an intervening clinic visit. We compared patients in the initial email intervention period with a control group who were discharged from the ED prior to initiation of the email program. We matched intervention and control patients 1:1 by stone size, location, and gender. We then fitted a Cox Regression model to examine for differences in time to surgery between two groups, which was our primary endpoint. In addition, we compared the groups in terms of the loss of follow-up and ED revisits. _x000D_ Results We compiled a comparison group of total 72 patients who underwent the email intervention and standard care. The groups had comparable body mass index, previous stone history, and renal function (all p>0.20). The time to surgery was much shorter in the intervention compared to the control group (8 days vs. 29 days, respectively, p-value <0.001). The new intervention was also associated with decreased proportion of patients lost to follow up (8% vs. 42%, p-value =0.001) and returning to the ED (6% vs. 25%, p-value 0=0.02). After adjusting for baseline characteristics and surgeon, using the email intervention decreased the time to surgery by 5 times that of the control group (HR=4.9, p-value <0.0001)._x000D_ _x000D_ Conclusions An automated email notification program following by a phone call to offer early surgical intervention improved the quality of care for patients with ureteral stones by decreasing the time from ED to surgery, reducing the patient care burden on the clinic, minimizing loss of follow-up, and reducing ED revisits. Funding none
Authors
Abdulrahman Alruwaily
Sapan Ambani Steven Kronick Gary Faerber John Hollingsworth William Roberts J. Stuart Wolf, Jr. |
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MP01-05 |
Can a stone obstructing the ureter cease to cause pain? |
Stone Disease: Epidemiology & Evaluation I | 17BOS |
Abstract: MP01-05 Sources of Funding: none Introduction Follow-up imaging is recommended as follow up for patients who present to the emergency department with ureteral stones and colic, but it often omitted if patients report cessation of pain. The purpose of this study was to update a previous report of how often a patient’s ureteral colic will cease despite still having a stone obstructing the ureter. Methods Fifty-three patients evaluated in an emergency department for ureteral colic and diagnosed with an obstructing ureteral stone who subsequently had follow-up in the urology clinic were retrospective evaluated. Patients who described the cessation of pain 72 hours prior to their office visit and who had follow up imaging were included in the study. Results Fifty-three (53) patients were included in the study. Mean patient age was 49.7 years (SD 15.3), gender distribution was 36% female:64% male, and mean time between visits was 27.4 days (SD 37.5). All patients (100%) reported having no pain for at least 72 hours prior to follow-up appointment, while 12/53 patients (22.6%) still demonstrated an obstructing ureteral stone on follow up imaging. Mean stone axial diameter was not different for patients who had passed their stones versus those who had not (4.9 mm versus 5 mm, p=NS). Conclusions In this study of 53 patients,?22%?of patients with ureteral stones?whose?pain completely ceased still had obstructing stones lodged in the ureter?on follow up imaging. ?This demonstrates that in the short term, one cannot confidently assume that cessation of pain signifies stone passage. Funding none
Authors
Natalia Hernandez
Yan Song Sarah Mozafarpour Brian Eisner |
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MP01-06 |
Predictors of flank pain in patients with a non-dilated collecting system: Results from RESKU, the Registry for Stones of the Kidney and Ureter |
Stone Disease: Epidemiology & Evaluation I | 17BOS |
Abstract: MP01-06 Sources of Funding: Funding support was provided by NIH R21-DK-109433 (TC) and NIH NIDDK K12-DK-07-006 (TC). Introduction Classically, acute flank pain and renal colic in nephrolithiasis is attributed to the presence of hydronephrosis and distention of the renal capsule. Patients often present with stones and no collecting system dilation, however, creating a therapeutic dilemma for urologists. Given that the biophysical mechanisms of visceral flank pain are not well understood, we aimed to characterize predictors of renal colic among stone patients without hydronephrosis. Methods From October 2015 to May 2016, new stone patients at the University of California, San Francisco (UCSF) were prospectively enrolled into the Registry for Stones of the Kidneys and Ureter (ReSKU). This electronic medical record (EMR) based stone registry captures patient clinical and imaging data for research purposes. For this study, we identified all patients with imaging-confirmed upper tract urinary stones and absence of hydronephrosis based on ultrasound or cross-sectional computed tomography imaging. Data analysis was performed on STATA Version 14.1 to identify factors associated with flank pain. Results During the study period, 116 patients with nephrolithiasis and no hydronephrosis were identified. 62.7% (n=74) had no flank pain associated with an ipsilateral stone, while 35.6% (n=42) had flank pain with an ipsilateral stone. There were no statistically significant differences between patients with and without flank pain with respect to age (60.0±2.1 vs. 57.3±2.6 years old), gender (51 vs. 45% male), smoking history (28.2 vs. 32.4% smoker), drinking history (48.7 vs. 42.3% none), BMI (28.4±1.0 vs. 26.4±1.5), or stone burden (1.86±2.6 vs. 1.80±4.0 cm). For patients with flank pain, those with renal stones were more likely to have flank pain compared with patients with ureteral stones (78.7 vs. 21.4%, p=0.018, Pearson chi-squared test). Conclusions Stones in the renal pelvis or calyces are more likely to cause pain in patients without hydronephrosis when compared with ureteral stones. Alternate mechanisms for acute renal colic must exist beyond obstruction and renal capsule distension. Understanding these mechanisms is critical to developing effective treatments for a subgroup of difficult-to-treat patients and warrants additional study. Funding Funding support was provided by NIH R21-DK-109433 (TC) and NIH NIDDK K12-DK-07-006 (TC).
Authors
Carissa Chu
Manint Usawachintachit David T. Tzou Kazumi Taguchi Marshall Stoller Thomas Chi |
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MP01-07 |
The Added Utility of Digital Tomosynthesis to Standard Abdominal Radiography for Identification of Urinary Calculi |
Stone Disease: Epidemiology & Evaluation I | 17BOS |
Abstract: MP01-07 Sources of Funding: General Electric Introduction The current gold standard for imaging evaluation of urinary stones is non-contrast CT (NCCT), although in recent years the concerns regarding repeated radiation doses has called into question the need for this modality in all cases. For this reason, plain abdominal radiography (KUB) is used by many urologists in a diagnostic and follow-up setting. Digital tomosynthesis (DT) is a novel imaging technique that produces a number of coronal images from a single tomographic sweep, creating high quality images with less radiation than low-dose NCCT. Our aim was to evaluate the added utility of DT to KUB for the identification of urinary stones. Methods Seven fresh cadavers with an intact genitourinary system and no history of nephrolithiasis were implanted with kidney and ureteral stones of known size and composition using endoscopic methods or a small ureterotomy. After stone implantation was completed, the cadavers were imaged with KUB and DT. Three blinded readers (2 urologists and 1 radiologist with experience in evaluating KUB/KUB-DT for stone disease) evaluated all sets of radiographs. Readers initially evaluated only KUB for the presence and location of calculi and recorded their responses. Readers then were instructed to add in tomogram images to their evaluation and re-record the presence and location of calculi to assess the possible value added by tomograms without changing their initial responses based on KUB only. Reference standard was established by consensus reading with a board-certified urologist and board-certified radiologist with 7 years of experience, neither of which served as a blinded reader on this study. Accuracy of stone detection and assessment of stone location was performed using an exact and nearest neighbor match to account for potential movement of stones after implantation as well as perception differences between readers as to nomenclature of stone location. Results A total of 59 stones were identified in the seven cadavers as part of the gold standard interpretation. Using KUB only with an exact and nearest neighbor match, Reader 1 accurately identified 45.7% (27/59 stones), Reader 2 identified 47.4% (28/59) stones, and Reader 3 identified 35.6% (21/59) stones. Using KUB-DT with an exact and nearest neighbor match, there was a statistically significant improvement in accuracy of stone detection (p <0.01 for all readers) as Reader 1 accurately identified 72.9% (43/59 stones), Reader 2 identified 62.7% (37/59) stones, and Reader 3 identified 66.1% (39/59) stones. Overall this was calculated as a 57% relative increase in stone detection. Of note, the number of false positives (suspected calculi based on reader assessment that were not present on gold standard reading) on KUB and KUB-DT was similar across both reading sessions (11 and 16 respectively, for all readers combined). Conclusions Addition of digital tomosynthesis to KUB leads to significant improvement in the detection of urinary calculi when compared to KUB alone without a concomitant significant increase in false positives. Further studies will determine the true cost and radiation savings associated with the use of this technology, but it appears to be a promising imaging modality for urinary stones and a possible alternative to NCCT in some settings. Funding General Electric
Authors
Daniel Wollin
Rajan Gupta Brian Young Eugene Cone Adam Kaplan Daniele Marin Bhavik Patel Michael Ferrandino Glenn Preminger Michael Lipkin |
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MP01-08 |
Use of dedicated stone analysis software to assess urinary stone size: Towards semi-automated metrics to enhance prediction of spontaneous stone passage |
Stone Disease: Epidemiology & Evaluation I | 17BOS |
Abstract: MP01-08 Sources of Funding: Mayo Clinic Urolithiasis O'Brien Grant Introduction Computed Tomography (CT) is a clinically established modality to evaluate suspected urinary stones. The maximum stone dimension in the axial reconstruction and stone location are often used to estimate the probability of spontaneous stone passage and potential likelihood of surgical intervention. However, the measured axial dimension of urinary stones can vary considerably owing to irregular shape, obliquity to the imaging plane, non-isotropic imaging voxels, interobserver variability, and volume averaging. This limits the reproducibility of axial stone measurements and the accuracy of predictions based upon maximum axial stone dimension. The present study compared the standard measures of stone size from axial images to those obtained using dedicated stone analysis software, which determined maximal stone dimensions in all planes. Methods Non-contrast-enhanced abdominal CT scans from 211 consecutive emergency department patients performed to evaluate flank were retrospectively evaluated. Radiological reports were reviewed for a diagnosis of urolithiasis, the maximum axial stone dimension, and stone location. Corresponding 1 mm thick images were analyzed using dedicated stone analysis software to compute the maximum linear dimension in any direction and stone volume. Descriptive outcomes are reported here (mean (SD)), comparing traditional maximum axial dimension and stone volume (assuming a spherical stone) to measurements made using dedicated software that performed 3D stone segmentation. Results A total of 228 stones were identified in 143 of the 211 patients. The mean maximum dimension in any direction computed by the software algorithm was 5.0 (3.2) mm, which was significantly higher than the mean maximum dimension of 3.9 (2.9) mm contained in the radiographic reports (p=0.0002). The actual stone volume computed by the algorithm based upon the true stone dimensions and shape was 52.8 (141.5) mm3, while the stone volume calculated assuming a spherical shape was 31.06 (102.16) mm3 (p=0.0628). Conclusions Using dedicated stone analysis software, maximal stone dimension in any plane and stone volume were significantly larger than traditional measurements made in the axial plane and the associated volume. Semi-automated 3D measurements of stone size hence may be more accurate and reproducible. Further studies are needed to determine if automated 3D stone size metrics offer improved and more reliable prediction of spontaneous stone passage. Funding Mayo Clinic Urolithiasis O'Brien Grant
Authors
Scott Heiner
John Lieske Roy Marcus John Knoedler Shane Dirks Joel Fletcher Cynthia McCollough |
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MP01-09 |
Implementing Ultrasound and Kidney, Ureter, Bladder Film As First-Line Imaging Requirements for Patients with Known Urinary Calculous Disease in an Outpatient Setting |
Stone Disease: Epidemiology & Evaluation I | 17BOS |
Abstract: MP01-09 Sources of Funding: None Introduction American Urological Association guidelines recommend a combination of ultrasound (US) and kidney, ureter, bladder film (KUB) for monitoring patients with known ureteral calculous disease. We implemented a protocol of KUB and US for patients with known renal and/or ureteral calculous disease to investigate the subsequent use of computed tomography (CT) imaging and 90-day outcomes. Methods We conducted a retrospective review of patients who presented in an outpatient setting with a known ICD-9 diagnosis of renal and/or ureteral calculous disease whose evaluation involved a request for CT imaging. Included patients presented between November 1, 2013 and May 31, 2014, were non-pregnant adults (>18 years old), and had no US or KUB within 60 days of CT imaging request. CT requests were sent to a specialty benefits management company (SBM), from which the data were obtained, and a third party payer. For CT imaging to be approved, the SBM required US or KUB within 60 days prior to CT imaging request. Two cohorts were evaluated: 1) approved initial CT (iCT) request and 2) redirected CT request to initial US or KUB (iUS/KUB). Requests for the iCT cohort were approved because providers attested to prior US or KUB within 60 days, while CT imaging requests for the iUS/KUB cohort were redirected because providers did not attest to prior US or KUB within 60 days. Subsequent 90-day outcomes were analyzed including need for further CT imaging, emergency department (ED) visits, and hospitalizations. Results A total of 1307 patients were evaluated. The iUS/KUB cohort (n=447) underwent a significantly lower percentage of CT scans compared to the iCT cohort (n=860) (43.8% vs. 52.1%, p<0.005). There were no significant differences between the iUS/KUB and iCT cohorts in subsequent ED visits (7.4% vs. 6.7%, p=0.67) or hospitalizations (13.6% vs. 15.0%, p=0.51). Conclusions The use of US or KUB for outpatients with known renal and/or ureteral calculous disease was associated with reduced utilization of CT imaging without significantly affecting 90-day ED visits or hospitalizations compared with patients undergoing CT alone. These results may contribute to reducing the effective dose of radiation delivered to patients and may optimize resource utilization while maintaining similar patient outcomes. Funding None
Authors
Robert Medairos
M. Ryan Farrell Jacob Hess Deborah Lamm Christopher Buckle Christopher Coogan |
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MP01-10 |
Lean Muscle Mass is More Accurate Than Creatinine to Weight Ratio to Evaluate 24-Hour Urine Collection Adequacy: Development and validation of a regression model |
Stone Disease: Epidemiology & Evaluation I | 17BOS |
Abstract: MP01-10 Sources of Funding: Not applicable Introduction Approximately half of 24-hour urine collections in prior studies have been found to be outside the accepted cutoffs with urinary creatinine to weight ratio. Our study objective was to evaluate the relationship between measured urinary creatinine and lean body mass calculated 24-hour creatinine excretion based to improve accuracy for the evaluation of 24-hour urine collection adequacy. Methods This was a retrospective evaluation of 24-hour urine collections for 1319 unique nephrolithiasis patients. An established formula (figure 1c) previously to estimate urinary creatinine based on lean body mass was applied all patients in our cohort (Yu et al). We divided our cohort into two equal partitions (training and validation datasets) using a random number generator. Linear regression was used to quantify the relationship between the calculated and measured urinary creatinine in our training dataset. We then applied this relationship to our validation dataset. Two standard deviations from the expected value was considered an &[Prime]abnormal&[Prime] 24-hour urine collection. This regression-based approach was then compared with the standard method of verifying 24-hour urine adequacy. Results As demonstrated in Figure 1 for the validation cohort, there was a strong relationship between expected 24-hour urine creatinine based on lean body mass and the measured urinary creatinine (r2=0.7, p<0.01), which was stronger than the relationship between measured urinary creatinine and weight (r2=0.5, p<0.01). Using the traditional metric of Cr/Kg, 38% of patients in our cohort were considered to have an inadequate 24-hour urine collection (Figure 1a), and there more dispersion among inadequate specimens. Using the regression model on the validation set (Figure 1b), 15% of specimens were considered inadequate, and the majority were due to under collection. Conclusions Urinary creatinine is more strongly correlated to an individuals muscle mass rather than body weight. Our regression model demonstrated the utility of a lean body mass based 24-hour creatinine estimator that improves the ability to determine the adequacy of a 24-hour urine collection. Funding Not applicable
Authors
Natalia Leva
Thomas Sanford Ryan Hsi Krishna Ramaswamy Thomas Chi Marshall Stoller |
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MP01-11 |
CT-based diagnosis of visceral obesity is associated with low urinary pH, uric acid nephrolithiasis, and larger stone volumes |
Stone Disease: Epidemiology & Evaluation I | 17BOS |
Abstract: MP01-11 Sources of Funding: none Introduction Prior studies have demonstrated links between uric acid stone risk and low urine pH, visceral fat area (VFA) and the ratio of visceral to subcutaneous adipose tissue (VFA%). Our objective was to assess the association of CT-based visceral obesity with 24-hour urine metabolic risk factors stone composition in kidney stone formers (KSF). Methods This is a retrospective analysis of 99 kidney stone formers who had CT imaging and 24-hour urine studies at our institution. For each patient, a single axial area measurement was obtained at L3-4 in females and L2-3 in males for visceral fat area (VFA) and subcutaneous fat area (SFA). Percentage of visceral fat was calculated with the formula VFA%=[VFA/(VFA+SFA)] X 100. From established data, a VFA > 186 cm2 was considered elevated in terms of risk of nephrolithiasis. Patient demographics, serum chemistry, 24-hour urine parameters and stone composition were collected for each patient. Univariate analysis was performed to compare patients with normal and elevated VFA. Multivariate linear and logistic regression was performed to assess for variables associated with 24-hour urine parameters and stone composition. _x000D_ _x000D_ Results Compared to patients with normal VFA, patients with high VFA were older (65 vs 51 yrs, p<0.0001), more obese (BMI 33.3 vs 28, p=0.02) and were male (70.7% vs 30%, p=0.001). They also had higher prevalence of HTN (81% vs 45%, p<0.0001), DM (31% vs 12.5%, p=0.003), CAD (32.8% vs 7.5%, p=0.003). Higher VFA was associated with higher urinary sodium (175 vs 157 mmol/d, p=0.036), lower urine pH (5.724 vs 6.478, p<0.0001), higher serum uric acid (6.6 vs 5.3, p=0.002), higher prevalence of uric acid stones (15.5% vs 2.5%, p=0.031), lower bone mineral density (146 vs 168 HU, p<0.0001) and larger stone volume (256 vs 67 mm3, p=0.009). Multivariate analysis revealed higher BMI (p=0.009), coronary artery disease (p=0.027) and lower 24-hour urine pH (p=0.001) correlated with elevated VFA. 24-hour urinary citrate (p=0.031) and higher VFA (p=0.048) correlated with uric acid stone formation. Linear regression demonstrated that a higher VFA% was associated with lower 24-hour urine pH (β-coefficient -0.574, p=<0.0001) Conclusions CT-based diagnosis of elevated visceral fat area is associated with lower 24-hour urinary pH and formation of uric acid calculi. Evaluation for visceral obesity may help identify patients best suited for alkalinization and dissolution therapy. _x000D_ _x000D_ Funding none
Authors
Nishant D Patel MD
Ryan Ward MD Juan Calle MD Erick Remer MD Manoj Monga MD |
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MP01-12 |
THE ASSOCIATION OF HEMOGLOBIN A1C AND URINARY OXALATE IN STONE FORMERS |
Stone Disease: Epidemiology & Evaluation I | 17BOS |
Abstract: MP01-12 Sources of Funding: AUA Research Scholar Introduction Greater body mass index (BMI) and type 2 diabetes mellitus are associated with kidney stone risk. Increased urinary excretion of oxalate (Uox) has been correlated to increasing BMI. Our objectives were to determine if this association is linked to hemoglobin A1C levels (A1C). Methods We retrospectively reviewed 1,428 twenty-four hour urine collections gathered from a single institution from 2004-2015 from two urologists. 665 unique non cystinuric adult stoneformers (SF) with complete data including BMI, age, gender, A1C levels, and Uox were then analyzed using ANOVA, Chi-squared, and linear regression analyses. Results Average age of SF was 49.9 years. 46% of SF were female. Average BMI was 29.2 (Underweight 1.4%, Normal weight 26.5%, Overweight 35.8%, Obese 27.7%, Morbidly Obese 8.6%). Greater BMI correlated with increased Uox (mg/d) (p≤0.0001, r=0.245) and remained significant for both males (p≤0.001, r=0.30) and females (p≤0.001, r=0.195). The positive correlation between BMI and Uox was also seen in both African American and Caucasian subjects (r=0.34, p=0.02 and r=0.20, p≤0.005). A significant positive correlation between A1C and Uox was demonstrated (r=0.24, p≤ 0.009). Conclusions Among SFs, there is a positive correlation between BMI and Uox as well as A1C and Uox. These relationships may explain associations between both obesity and diabetes and the development of kidney stones. Funding AUA Research Scholar
Authors
Kyle Wood
Marc Colaco John Knight Ross Holmes Dean Assimos |
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MP01-13 |
IS THERE A SHIFT FROM INFECTIOUS STONES IN STAGHORN CALCULI? |
Stone Disease: Epidemiology & Evaluation I | 17BOS |
Abstract: MP01-13 Sources of Funding: None Introduction Historically staghorn calculi have been thought of as infectious stones, made up primarily of magnesium ammonium phosphate or (struvite) stones. The American Urological Association (AUA) guidelines for management of staghorn calculi continue to state calcium oxalate or calcium phosphate stones as unlikely causes of staghorn calculi. We reviewed our institutions incidence of infectious and metabolic composition in large staghorn calculi Methods Medical records were retrospectively reviewed for patients who underwent percutaneous nephrolithotomy (PCNL) for complete staghorn calculus from 2010 to 2015. Stone analysis and charts were reviewed for demographics, surgical complications, preoperative urine results and outcomes compared to stone type. Primary outcome of the study was to identify stone composition in infectious and non-infectious cases Results 217 PCNLs were completed at our institution between 2010-2015 for stones >2cm. 72 patients (75 kidneys) had large staghorn calculus that met our size criteria. 3 of these were excluded. Overall 28 (39%) of patients were found to have infection stones, either struvite or carbonate. 44(61%) stones were composed of metabolic based stones without any infectious composition. The primary compositions in the metabolic stone group were calcium phosphate (52%), Uric Acid (18%), calcium oxalate (18%), and cystine (12%). In patients with purely metabolic stones, 65% of patients with primarily calcium phosphate hydroxyapatite had positive pre-op urine cultures, while only 12.5% of patients with primary calcium oxalate stones had positive pre-op urine cultures. Preoperative urine cultures revealed Proteus present (4.5% vs 46.4%) for non-infectious and infectious stones. E. Coli was present in preoperative urine cultures (15.9% vs 3.5%) for non-infectious and infectious stones. Proteus was the most common bacteria in infectious stones, while E. Coli was most common with metabolic stones. Infectious stones were 3.2 times as likely to have at least a Clavien-Dindo Grade 1 complication as metabolic stones (p=0.017). Conclusions In our study more staghorn calculus were composed of metabolic stones than infectious stones. Calcium phosphate was the most common stone composition for staghorn calculi differing from historical reports of staghorn calculi being primarily infectious. Patients with calcium phosphate stones also had a high rate of positive urine cultures. More research is needed on the cause of this paradigm shift._x000D_ _x000D_ Funding None
Authors
Tyler Haden
Paige Kuhlmann Jacqueline Ross Stephen Kalkhoff Carrie Johans Alex Jones Stephen Weinstein Mark Wakefield Daniel Hoyt James Cummings Naveen Pokala |
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MP01-14 |
Do Metabolic Factors Influence the Formation and Recurrence of Bladder Calculi? |
Stone Disease: Epidemiology & Evaluation I | 17BOS |
Abstract: MP01-14 Sources of Funding: None Introduction Metabolic abnormalities are associated with an increased risk for renal calculi. However, no studies to date have investigated whether metabolic factors affect the formation or recurrence of adults with bladder calculi. We aim to characterize patients with primary bladder stones, with and without kidney stones, based on their clinical factors, 24-hour urine, and stone composition. Methods We reviewed the medical records of patients with primary bladder stones and classified them based on their history of kidney stones, metabolic factors, clinical characteristics, and stone composition. We used descriptive statistics, multivariate analysis, and one-way ANOVA to look at associations between these parameters. Results Final analysis included 50 men with mean age 64 years (range: 21 to 92). 90% of these patients had a history of concurrent kidney stones. Bladder stone only formers (N=10) were older, and had greater total stone burden, higher stone recurrence rates (40% versus 25%), more metabolic abnormalities, and significantly lower urine pH (p = 0.03) compared to the concomitant kidney stone formers (N=40). Bladder stone only formers had a higher incidence of uric acid (UA) composition compared to their counterparts (62.5% versus 31.5%). Further, UA stones in the bladder demonstrated lower pH (p = 0.02) while renal UA stones were associated with lower Cit24 (p = 0.03). Stone concordance in the concomitant kidney stone group was 55.6%. Conclusions Primary bladder stone formers had surprisingly high rates of kidney stone formation and higher incidence of recurrence than has been previously reported. Duly, bladder stone formation may pose a risk for recurrence of bladder and/or kidney stones. The metabolic profiles of both groups, regardless of whether they made only bladder stones or both bladder and kidney stones, were similar. Aggressive treatment for outlet obstruction and metabolic abnormalities may be warranted in patients who are bladder stone only or concomitant kidney stone formers. _x000D_ _x000D_ Funding None
Authors
Julie Thai
Tim Tran Egor Parkhomenko Mantu Gupta |
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MP01-15 |
Perceptions of Nephrolithiasis Promoting Factors and Preventive Measures: A Prospective Survey Analysis |
Stone Disease: Epidemiology & Evaluation I | 17BOS |
Abstract: MP01-15 Sources of Funding: none Introduction Understanding patients&[prime] knowledge of risk factors for nephrolithiasis may aid in developing prevention programs. We assessed patients&[prime] perceptions of dietary risk factors affecting kidney stone formation, and determined independent predictors of patient awareness of factors promoting stone disease. Methods A 24-question survey assessing dietary knowledge of nephrolithiasis risk factors and demographic data was administered prospectively to 1,018 urology patients. Responses were summarized with frequency and percent. Statistical comparisons were made using chi-square tests. Multiple logistic regression was used to detect significant predictors of knowledge of stone disease risk. Results The study cohort was comprised of 70% (n=711) male patients; overall, only 25% (n=259) of participants responded that diet had an effect on kidney stone development. A total of 28% (n=284) reported a prior history of stone disease; of those respondents, 43% (n=122) believed that diet does effect kidney stone formation. The majority of respondents (58.9%, n=598) reported a willingness to make lifestyle changes aimed at lowering their stone risk. Participants who reported previous nephrolithiasis education were 35 times more likely to indicate that diet affects the risk of kidney stone formation. (Odds ratio [OR] =35.15, 95% confidence interval [CI] = 5.58, 221.25, p <0.01) (Table 1). Respondents who had received prior education were 6.25 times more likely to have been counseled by a urologist than by a primary care physician (OR = 6.25, 95%, CI = 1.1, 33.3, p <0.04). Conclusions Knowledge of dietary risk factors promoting nephrolithiasis was limited among our study population. However, the majority of patients expressed a willingness to make appropriate nutritional modifications. Respondents who received prior education on stone development appeared to be aware that diet affects the risk of kidney stone formation. Patients indicated that urologists typically deliver kidney stone related education. These results suggest a need for comprehensive teaching strategies for patients regarding the modifiable risk factors for nephrolithiasis. Funding none
Authors
Mathew Q. Fakhoury
Barbara Gordon Barbara Shorter Matthew R. Cohn Elizabeth Cabezon James S. Wysock Marc A. Bjurlin |
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MP01-16 |
Metabolic syndrome increases the risk for calcium oxalate stone formation: results from a Nationwide Survey on Urolithiasis in Japan |
Stone Disease: Epidemiology & Evaluation I | 17BOS |
Abstract: MP01-16 Sources of Funding: none Introduction Recent epidemiologic studies have shown an increased prevalence of kidney stones in patients with metabolic syndrome (MetS). We have reported that the clustering of MetS traits is associated with greater severity of kidney stone disease (Am J Kidney Dis 61: 923-929, 2013). The aim of the present study is to clarify which stone composition is associated with MetS. Methods We retrospectively analyzed detailed clinical data from 30,448 patients with urolithiasis enrolled in the 6th Nationwide Survey on Urolithiasis in Japan conducted in 2005. Patients with lower urinary tract stones, struvite stones, cystine stones, other types of rare stone composition, unknown stone composition, or hyperparathyroidism and those younger than 15 years were excluded. According to the types of stone composition, the severity of kidney stone disease, assessed by the number of existing stones (single/multiple) and number of stone episodes (first time/recurrent), and abnormalities in urine constituents were examined by the number of MetS traits (obesity, hypertension, dyslipidemia, and diabetes). Results A total of 4,440 patients included in the final analyses were classified into four groups: calcium oxalate (CaOx) (n=3213), CaOx + calcium phosphate (CaP) (n=881), CaP (n=115), uric acid (UA) (n=191). The proportions of patients with recurrent and/or multiple stones significantly increased with the number of MetS traits only in patients with CaOx stone (P < 0.01, table 1). However, similar associations were not observed in patients with other stone compositions. In patients with CaOx stone, there was a significant and stepwise increase in the odds of recurrent and/or multiple stones after adjustment for age and sex. In patients with 3 or 4 MetS traits, the odds was 1.8-fold greater compared with patients with 0 traits (OR, 1.78; 95% CI, 1.29-2.42). In addition, the presence of MetS traits was associated with significantly increased odds of having hypercalciuria in patients with CaOx stone after adjustment for age and sex. Conclusions In patients with CaOx stone, MetS trait clustering is associated with greater severity of the disease and increased urinary calcium excretion. These results suggest that CaOx stone disease should be regarded as a systemic disorder linked to MetS. Funding none
Authors
Akinori Iba
Yasuo Kohjimoto Takashi Iguchi Shimpei Yamashita Satoshi Nishizawa Kazuro Kikkawa Isao Hara |
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MP01-17 |
Age, Sex, and Climate Differences in the Temperature-Dependence of Kidney Stone Presentation |
Stone Disease: Epidemiology & Evaluation I | 17BOS |
Abstract: MP01-17 Sources of Funding: NIH K23DK106428 Introduction Prior studies have demonstrated that high daily temperatures increase the risk of kidney stone presentation, men produce more sweat than women, and people with public insurance have greater exposure to ambient temperatures than those with private insurance. The objective of this study was to determine differences in the temperature dependence of kidney stone presentation by sex, age, race, climate, and insurance type. Methods We performed a time series study of 132,597 patients who presented with kidney stones to Emergency Departments in South Carolina from 1996-2015. Conditional Poisson regression and distributed lag non-linear models were used to assess the association and lagged response between daily temperature and kidney stone presentation stratified by sex, age, insurance type, race, and climate zone. Results The relative risk for a daily temperature at the 99th percentile versus 10°C was 1.72 (95% CI 1.55, 1.91) for men and 1.15 (95% CI 1.01, 1.31) for women. This difference was greatest among patients 20-65 years old. The risk of kidney stone presentation following moderately high daily temperatures was less among patients living in warmer climates. The temperature-dependence of stone presentation did not differ by race or insurance type. Conclusions The risk of kidney stone presentation following high daily temperatures was substantially greater among men than women and similar between patients with public and private insurance, which suggests that the higher risk among men is due to the sexually dimorphic effect of heat on evaporative water loss rather than greater exposure to ambient temperature. The lower risk among patients living in warmer climates suggests that prolonged heat exposure may lead to adaptive responses that mitigate the effect of high temperatures on kidney stone presentation. These differences should be considered in secondary prevention strategies to increase fluid intake and projections of the effect of climate change on nephrolithiasis prevalence. Funding NIH K23DK106428
Authors
Gregory Tasian
Ana Vicedo-Cabrera Robert Kopp Lihai Song Michelle Ross Jose Pulido Steven Warner David Goldfarb Susan Furth |
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MP01-18 |
Precipitation (and not temperature) is associated with urinary stone disease in California |
Stone Disease: Epidemiology & Evaluation I | 17BOS |
Abstract: MP01-18 Sources of Funding: none Introduction It is commonly accepted that increased temperatures are associated with increased prevalence of kidney stone disease. When examining stone mapping studies of the United States, while some regions with high annual temperatures (the southeast) have higher kidney stone prevalence, other warm regions such as the southwest do not. One major climate difference between these two regions is annual precipitation and humidity. We sought to explore the associations among, temperature, precipitation and urinary stone disease. Methods We identified all patients who underwent ureteroscopy, percutaneous nephrolithotomy, or shock wave lithotripsy using data from the Office of Statewide Health Planning and Development (OSHPD) for the state of California (2010-2012). We calculated the rate of operative stone disease for each county based on the patient’s home zipcode. We obtained climate data for each county in California from the National Oceanic and Atmospheric Administration. We compared the rate of urinary stone surgeries, adjusted for county population, mean annual temperature, total number of days over 90 degrees, and the total annual precipitation. Results A total of 63,994 unique patients underwent stone procedures in California between 2010-2012. The mean county stone surgery rate was 1.77 cases per 1000 persons (range 0.05-3.16). In the lowest quartile of rainfall (less than 21 inches per year), the average stone surgery rate was 1.5 per 1000 persons. This was significantly less than 2.2 per 1000 persons in the regions with the highest quartile of rainfall (44 inches per year) (p<0.01). In fully-adjusted models, precipitation (0.019 increase in surgeries per 1000 persons per inch, p<0.01) and higher mean temperature (0.029 increase in surgeries per 1000 persons per degree, p<0.01) were associated with an increased rate of stone surgery (Figure 1). The effect of temperature was not significant unless precipitation was controlled for. Conclusions In the state of California, temperature alone is not associated with the county-level rate of stone surgery until precipitation is included in models. Our results appear to agree with the larger trends seen through the United States where the areas of highest stone prevalence have warm humid climates, and not warm arid, climates. Funding none
Authors
Kai Dallas
Simon Conti John Leppert Christopher Elliott Mario Sofer Alan Thong |
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MP01-19 |
Recent Epidemiological and Metabolic Trends in Stone Disease: Rising Hypocitraturia and Hyperoxaluria |
Stone Disease: Epidemiology & Evaluation I | 17BOS |
Abstract: MP01-19 Sources of Funding: None Introduction Metabolic factors underlying the recent increase in stone prevalence are unknown. Herein, we evaluate metabolic risk factors in stone patients from two different decades, comparing changes in metabolic profiles of stone formers over time. Methods A retrospective review was performed of patients who underwent metabolic evaluation of urolithiasis with 24-hour urine collections at a single institution. There were 309 stone patients evaluated from 1988-1994 (group 1), and 229 patients from 2007-2010 (group 2). A comparison between both groups was performed to assess changes in demographics and metabolic profiles. Results Comparing group 1 to group 2, the male: female ratio decreased from 1.3:1 to 0.8:1, obese patients (BMI ≥ 30) increased from 22% to 35%, and patients ≥ 50 y increased from 29% to 47% (all p < .005). A greater percentage of patients had hypocitraturia in the recent cohort (46% to 60%, p = .001), with hypocitraturia significantly more frequent in obese patients (p = .005). Hyperoxaluria was also increased in group 2 compared to group 1 (23% to 30% p = .07), a finding that was significant in males (32% to 53%, p = .001). Conclusions Urolithiasis has increased in females, obese, and older patients, consistent with population based studies. We report a rising incidence of hypocitraturia and hyperoxaluria in the contemporary cohort, particularly in obese patients and in males, respectively. Further studies are needed to better characterize the metabolic changes corresponding to the increase in stone disease. Funding None
Authors
Ramy F. Youssef
Jeremy W. Martin Khashayar Sakhaee John Poindexter Simone L. Vernez Rahul Dutta Charles D. Scales Glenn M. Preminger Michael E. Lipkin |
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MP01-20 |
Shockwave lithotripsy impairs urine pH: results of the prospective Swiss Kidney Stone Cohort register |
Stone Disease: Epidemiology & Evaluation I | 17BOS |
Abstract: MP01-20 Sources of Funding: none Introduction Urolithiasis is a global health problem with a lifetime risk of up to 15 % in white men and 6 % in women and a recurrence rate of about 50 % in these patients. Over the last three decades (and since the introduction of shock wave lithotripsy [SWL]) there was a change in stone composition observable with an increasing prevalence of calcium phosphate stones. Calcium phosphate crystallization is driven by urinary calcium phosphate supersaturation which rises with elevated urine pH. A recent animal study revealed an increase in urine pH of SWL treated porcine kidneys. We therefore evaluated the effect of SWL on urine pH in the Swiss Kidney Stone Cohort (SKSC), a nationwide, multicenter, prospective register of kidney stone patients. Methods Of the first 350 patients enrolled in the SKSC register, 170 patients were eligible; 180 patients had to be excluded because of a short follow-up of <6 months, uric acid stone composition and/or incomplete data on previous stone treatment. The patients were grouped into 3 different groups according to their previous treatment: group A: SWL (n=49), group B: endourological treatment (n=67), group C: spontaneous stone passage (control group; n=54). The paired t-test and one-way ANOVA was used to compare the change of urine pH over time within and between the 3 different groups. Results 44/170 (26%) patients were female. Median patient age was 47 years (range: 20-86). Stone composition was available in 57% of patients and did not significantly differ between the three groups (p=0.8). The median urine pH at first visit (≥ 4 weeks post stone passage or intervention) was slightly higher in group A after SWL as compared to the other two groups: pH 5.7 (IQR: 5.1-6.0) in group A; pH 5.5 (IQR: 5.0 -5.9) in group B; pH 5.5 (IQR: 5.1-6.0) in group C; p=0.4. There was a significant rise in urine pH at follow-up visit (3-6 months after initial visit) in group A after SWL treatment whereas no significant change was seen in the non-SWL groups B and C (median pH difference in groups A, B and C: +0.25, -0.19 and -0.005, respectively; p<0.001). Conclusions There was an increase in urine pH in patients who had undergone SWL while this was not seen in urinary stone patients who were treated endourologically or conservatively. This suggests that SWL may cause tubule cell injury that leads to functional disturbances such as changes of urine pH. Whether this has an impact on the rate of recurrences or future stone composition (increase in calcium phosphate content) will be explored in the further follow-up of these patients. Funding none
Authors
Veronika Skuginna
Nilufar Mohebbi Daniel Fuster Min-Jeong Kim Carsten A. Wagner Grégoire Wuerzner Nasser Dhayat Olivier Bonny Beat Roth |
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MP02-01 |
Prostate photovaporization vs. transurethral resection of the prostate: a matched paired analysis comparing the BPH6 outcome. |
Benign Prostatic Hyperplasia: Surgical Therapy & New Technology I | 17BOS |
Abstract: MP02-01 Sources of Funding: None Introduction Laser therapy has gained increasing acceptance as a relatively less invasive treatment for the treatment of lower urinary tract symptoms (LUTS) secondary to benign prostatic enlargement (BPE). The potassium-titanyl-phosphate (KTP) laser, as well known as GreenLight laser (PVP) has been recently tested in a numbers of clinical studies. However, clinical outcomes have been different and not always the same. Recently, it has been tested the BPH6 score as a reliable patient reported outcome (PROM) for the evaluation of patients who underwent BPE surgery. _x000D_ In this study we aimed to compare PVP vs. TURP regarding BPH6 outcomes at 12 months of follow-up in a matched pair analysis. _x000D_ Methods From January 2014 to January 2016, we conducted a matched pair analysis on 220 patients to compare the efficacy and safety of PVP laser and bipolar TURP in terms of the composite BHP6 endpoint at 12 mo. A propensity score matching was performed to adjust for preoperative prostate volume, peak flow and international prostate symptoms score (IPSS). _x000D_ Patients with LUTS secondary to BPE and refractory to medical therapy underwent TURP of 180 W PVP. The BPH6 primary study endpoint is a composite of six elements that assess overall outcome including LUTS relief, recovery experience, erectile function, ejaculatory function, continence and safety. The final BPH6 responder endpoint is achieved if a participant meets all six of the criteria defined as follow: LUTS relief: reduction of >=30% in IPSS at 12 mo compared to baseline, Recovery experience: QoR VAS >=70 by 1 mo, reduction of <6 points for SHIM (Sexual Health Inventory For Men) compared to baseline during 12-mo follow-up, response to MSHQ-EjD (Male Sexual Health Questionnaire Short Form for assessing ejaculatory dysfunction) question 3 indicating emission of semen during 12-mo follow-up, ISI (Incontinence score index) of ?4 points at all follow-up intervals, no treatment-related adverse event greater than grade I on the Clavien-Dindo classification system at any time during the procedure or follow up. _x000D_ All data presented are given as mean ± standard deviation (SD). Statistical analysis was performed using the SPSS 19.0 statistical software package (SPSS Inc., Chicago, IL, USA). _x000D_ Results After the matched paired-analysis, a total of 123 (55 TURP and 68 PVP) were analyzed. Participants were well matched between the study arms, with no statistically significant differences of prostate volume, peak flow and IPSS. When comparing both groups, the proportion of patients achieving the BPH6 recovery endpoint by 12 mo was 45.6% in the PVP group, which was significantly better than the rate in the TURP group (18.2%) (p=0.001). In particular, PVP group showed better BPH6 outcomes vs. regarding TURP regarding recovery (82.4% vs. 58.2%; p<0.05), ejaculatory function (58.8% vs. 34.5; p<0.05) and safety (94.1% vs. 78.2%; p<0.05). The TURP group showed greater catheterization time (4.67 vs. 1.25; p<0.01) while PVP showed greater recovery experience (77.35 vs. 68.73; <0.01). Postoperative Ejaculatory dysfunctions were observed in both groups, 58.8% in TURP and 34.5% in PVP group. _x000D_ No difference regarding LUTS reduction, erectile function and continence. In both groups surgery did not cause any adverse events that required surgical intervention or revision and reintervention for failure to cure did not occurred in 12mo follow up. The multivariate logistic regression analysis, adjusted for pre-operative variables, showed that PVP was independently associated with BPH6 recovery endpoint (odds ratio= 3.77 [95%CI 1.64-8.70]; p<0.01). _x000D_ Conclusions This study sheds some light in support of PVP technology. The results prove that PVP of the prostate represents an effective and safe technique, combining minimal morbidity and significant advantages compared to TURP regarding BPH6 outcomes. In fact, this is the first study comparing those two techniques in terms of the composite BHP6 endpoint, a reliable tool that can easily applied to compare BPE surgery procedures. Funding None
Authors
Sebastiano Cimino
Giorgio Ivan Russo Salvatore Voce Fabiano Palmieri Tommaso Castelli Vincenzo Favilla Salvatore Privitera Giuseppe Morgia |
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MP02-02 |
Pure bipolar plasma vaporization of the prostate: 5-year follow-up from a prospective 3D ultrasound volumetry study |
Benign Prostatic Hyperplasia: Surgical Therapy & New Technology I | 17BOS |
Abstract: MP02-02 Sources of Funding: none Introduction Pure bipolar plasma vaporization (BPV) has been established as low-morbidity alternative to conventional transurethral resection of the prostate (TURP). Low intra- and postoperative morbidity as well as excellent functional short-term results have been reported. However, long-term outcome is still lacking. The extent of prostate tissue removal, which impacts the durability of postoperative functional improvements, is also unknown after BPV. The aim of the present study was to investigate the long-term functional outcome and associated prostate volume changes following pure BPV of the prostate. Methods A consecutive series of 75 patients treated by pure BPV in a tertiary care academic center was prospectively investigated. Prostate volume was assessed using planimetric volumetry following transrectal 3D-ultrasound of the prostate. Prostate volume and clinical parameters were recorded preoperatively and regularly after BPV (after catheter removal, 6W, 6M, 1, 3 and 5Y). Results Median (interquartile range; IQR) preoperative prostate volume was 41 ml (26.8ml), IPSS 16 (10), QoL 4 (2), Qmax 10.1ml/s (8ml/s), PVR 91ml (140ml) and PSA 2.57ng/ml (3.5ng/ml). A significant relative prostate volume reduction (RVR) of 33.3% (IQR: 22.3%; p<0.001) was already detectable at the time of catheter removal. Relative volume reduction increased significantly up to 12M (6W: 45.9% (17.4%; p<0.001), 6M: 50.5% (16.1%; p<0.001) and 12M 52.2% (17.4%; p=0.014). After 12M the RVR remained stable with 50.6% (14.3%; p=0.58) after 3Y and 52.6% (14.1%; p=0.59) after 5Y. Postoperatively, all investigated clinical parameters improved significantly and remained stable during the 5Y follow-up [5Y results (IQR): IPSS: 3 (8), QoL: 1 (1), Qmax: 16.3ml/s (13.7ml/s), PVR 20ml (46.5ml)]. Median PSA reduction after 5Y was 55% (36.2%). During the observation period 9 urethral strictures (12%) were detected of which 7 were de novo strictures. Bladder neck incisions for postoperative bladder neck stenosis were performed in 6 patients (8%). Median prostate volume in these patients was 30.6ml (18.2ml). Re-resections for re-grown adenoma were not necessary. Conclusions Low intra- and postoperative morbidity in combination with excellent functional outcome and durable prostate volume reduction confirm the role of contemporary BPV as a minimally invasive alternative to conventional TURP. However, postoperative bladder neck stenoses appeared rather frequent after BPV and might be a procedure-specific drawback. Funding none
Authors
Benedikt Kranzbühler
Oliver Gross Christian D. Fankhauser Marian S. Wettstein Nico C. Grossmann Etienne X. Keller Daniel Eberli Tullio Sulser Cédric Poyet Thomas Hermanns |
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MP02-03 |
LONG TERM OUTCOMES AFTER PHOTOVAPORIZATION OF BENIGN PROSTATIC HYPERPLASIA USING XPS GREENLIGHT® LASER : A 5-YEAR FOLLOW-UP STUDY. |
Benign Prostatic Hyperplasia: Surgical Therapy & New Technology I | 17BOS |
Abstract: MP02-03 Sources of Funding: none Introduction To evaluate for the first time long-term outcomes after Photovaporization of the prostate (PVP) with the XPS Greenlight® laser (GL-XPS) in patients with symptomatic benign prostatic hyperplasia (BPH). Methods A prospective study was performed of all patients with symptomatic BPH who underwent GL-XPS vaporization at our institution between September 2010 and September 2012. Functional outcomes with at least 48 months of follow-up were evaluated by questionnaire. Long term rate of complications and /or reoperation were assessed. Prostate Specific Antigen(PSA) level was measured at 3, 12 and 48 months of follow up. Results The response rate of the long terms questionnaire was high, 82 %. 84 patients with full data were included. Mean follow-up was 57,4±6,8 months. Mean International Prostate Symptoms Score (IPSS) decreased significantly from 19,9±6,4 preoperatively to 8,2±5,7, 6,16±5,6, and 3,94±3,4 at 1, 3 and 12 months respectively. Mean IPPS remained stable at 5,9±5,8 after 48 months. The mean PSA level has reduced significantly, from 4,5±4,31ng/mL preoperatively. to 2,00±2,13ng/mL, 2,08±2,08ng/mL and 2,66±2,27ng/mL respectively at 3, 12 and 48 months. Urinary parameters were significantly improved. Mean Qmax increased from 9,6±3,8 mL/s preoperatively to 21,8±11,3 mL/s, 23,9±11,5mL/s at 1 and 3 months respectively and remained stable at 12 months at 25,2±9,2mL/s. The satisfaction rate was high, 88% after a mean follow-up of 57,4 months. Two patients required reoperation due to recurrent BPO and two others for bladder neck contracture. Conclusions PVP with the GL-XPS is a safe and effective laser technique at improving durably IPSS in patients with symptomatic BPH. Funding none
Authors
Jehanne CALVES
Georges FOURNIER |
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MP02-04 |
Validation of Pre-operative TRUS Volume Model in Predicting Enucleation Rates for HoLEP Surgery. |
Benign Prostatic Hyperplasia: Surgical Therapy & New Technology I | 17BOS |
Abstract: MP02-04 Sources of Funding: None Introduction The use of pre-operative transrectal ultrasound (TRUS) volume to size prostates prior to holmium laser enucleation of the prostate (HoLEP) surgery supports case selection during the steep learning curve. We have previously reported the use of TRUS volume as a predictive tool for enucleation and operating room (OR) times. For the established surgeon TRUS volumes can optimize theatre utilization. We represent our predicted versus actual enucleation and OR times to generate validated charts to use as an accurate predictive tool to enhance theatre utilization. Methods 393 HoLEPs were undertaken with a 50 Watt (W) holmium laser (Auriga XL, Boston Scientific Inc., Richard Wolf Piranha Morcellator) by two HoLEP naive surgeons during their learning curve and subsequently. All patients underwent a TRUS volume pre-operatively (B-K Hawk 2102). Accurate enucleation time and total operating room (OR) time for a given TRUS volume were plotted to use as a predictive tool to enhance operating list scheduling. Using the predicted enucleation times from a original cohort of 253 cases linear regression modelling was undertaken to validate predictive enucleation & OR times with the actual enucleation times for our last 100 cases. Results Enucleation time and TRUS volume were plotted graphically for the 393 cases (blue shaded region) and compared to similar data previously plotted for our first 253 cases (red line). There was a clear improvement in enucleation and total operating room times indicating further improvement and accuracy in the predictive times for a given TRUS size as surgeon experience increases. This allows for the enhanced prediction of theatre time improving theatre utilization._x000D_ Conclusions Validation of predictive TRUS volume graphs for enucleation time during HoLEP surgery can be used as a tool to enhance theatre utilization by individual surgeons. We recommend the use of this simple tool for units setting up a HoLEP service._x000D_ Funding None
Authors
Farooq Khan
Mohamed Asad Saleemi Barney Barrass Sanjeev Taneja Asher Alam Aza Mohammed Ian Nunney |
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MP02-05 |
Comparative Analysis of Outcome Following Laser Vaporization and Laser Enucleation with Morcellation - A National Database Analysis |
Benign Prostatic Hyperplasia: Surgical Therapy & New Technology I | 17BOS |
Abstract: MP02-05 Sources of Funding: None Introduction Laser enucleation with morcellation (LEM) has gradually increased in popularity and is increasingly being performed in the United States. This database study compares early operative and post-operative outcomes following laser enucleation and laser photovaporization (LP). Methods All patients (2011-2014) that underwent LEM (CPT code 52649) or LP (CPT code 52648) were identified from the National Surgical Quality Improvement (NSQIP) Database. The two groups were compared for demographics, operative times, post-operative complications, readmission and re-operative rates. Data are represented as mean ± standard deviation (SD) or median (interquartile range). Logistic regression analysis was performed to account for confounders and a p value of <0.05 was considered significant. Results A total of 8,171 patients were identified. 14.5% (n=1187) had LEM and 84.5% (n=6984) had LP. The respective mean age group was 69.3±8.7 and 71.4±9.2 years in the LEM and LP groups. Race distribution (LEM/LP) was white (1007/5096), Black (71/338) and others (109/1150). The ASA distribution (1/2/3/4) was 47/646/466/28 in LEM and 228/3099/3356/298 in LP groups. The mean BMI was similar for the LEM and LP groups at 28.4 and 27.87, respectively. The number of cases performed during the years 2011, 2012, 2013, and 2014 were 135/291/372/389 in the LEM group and 1045/1562/2056/2321 in the LP group. A higher proportion of patients required general anesthesia ( 93.6% vs 84.3%) and were performed in an inpatient setting( 38.5% vs 17.4%) in LEM vs LP. The mean operative time was significantly longer in the LEM (106.7 vs 54.8 minutes, p=0.001) versus the LP groups. The mean length of stay after surgery was also longer (1.24 vs 0.67 days, p=0.0001) in the LEM group. The differences in the transfusion rates, urinary tract infections, re-operative and readmission rates are shown in Table 1. Conclusions Regarding patients undergoing LEM versus LP, a higher proportion of patients require inpatient admission and the operative time is significantly longer in the LEM group compared to the LP group. The transfusion rate is higher for LEM compared to LP, but readmission and re-operative rates are similar. LEM is a feasible and comparatively safe operation to LP. Funding None
Authors
Alex Jones
Carrie Johans Naveen Pokala Tyler Haden |
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MP02-06 |
Learning curves and perioperative outcomes after endoscopic enucleation of the prostate: A comparison between GreenLight 532-nm and holmium lasers |
Benign Prostatic Hyperplasia: Surgical Therapy & New Technology I | 17BOS |
Abstract: MP02-06 Sources of Funding: none Introduction Studies comparing learning curves and outcomes after HoLEP compared to other endoscopic enucleation techniques are lacking. None have assessed the learning curve of Greelight Laser enucleation of the prostate (GreenLEP). The aim of this study was to compare the learning curves and the perioperative and early functional outcomes of GreenLEP to those of HoLEP Methods Data from the first 100 consecutive cases treated by GreenLEP and HoLEP by two surgeons were prospectively collected from dedicated databases and analysed retrospectively. En-bloc GreenLEP and two-lobar HoLEP enucleations were conducted using the GreenLight HPS™ 2090 laser and Lumenis™ Holmium laser. Patients’ characteristics, perioperative outcomes and functional outcomes after 1, 3 and 6 months were compared between groups. Results Total energy delivered and operative times were significantly shorter for GreenLEP (58 vs 110 kJ, p<0.0001; 60 vs 90 min, p<0.0001). Operative time reached a plateau after 30 procedures in each group. Length of catheterization and hospital stay were significantly shorter in the HoLEP group (2 vs 1 day, p<0.0001; 2 vs 1 day, p<0.0001). Postoperative complications were comparable between GreenLEP and HoLEP (19% vs 25%; p=0.13). There was a greater increase of Qmax at 3 months and a greater IPSS decrease at 1 month for GreenLEP, whereas decreases in IPSS and IPSS-Q8 at 6 months were greater for HoLEP. Transient stress urinary incontinence was comparable between both groups (6% vs 9% at 3 months; p=0.42). Pentafecta was achieved in four consecutive patients after the 18th and the 40th procedure in the Greenlep and HoLEP group respectively. Learning curves ranged from 14–30 cases for GreenLEP and 22–40 cases for HoLEP. Conclusions Learning curves of GreenLEP and HoLEP provided roughly similar peri-operative and short-term functional outcomes. Funding none
Authors
benoit peyronnet
grégoire robert vincent comat morgan roupret fernando gomez-sancha jean-nicolas cornu vincent misrai |
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MP02-07 |
En-bloc Green Light 532nm Enucleation of Prostate (GLEP): First U.S. Experience |
Benign Prostatic Hyperplasia: Surgical Therapy & New Technology I | 17BOS |
Abstract: MP02-07 Sources of Funding: None Introduction The optimal management option for BPH/LUTS for prostates >80g is unclear. Theoretical advantages of GLEP include improved hemostasis due to the absorption spectrum of 532nm laser, better tissue handling due to the side-firing laser fiber, better visualization of the prostate capsule, and more versatility with concomitant vaporization. We study the safety and feasibility of en-bloc GLEP with prostate morcellation using a side-firing laser as a new technique for definitive management of symptomatic LUTS in patients with prostates >80g. Methods We performed a retrospective analysis of 82 consecutive patients who underwent GLEP from 9/2014 to 8/2016. Primary outcomes were AUA symptom score, maximum flow rate, and post-void residual volume. Secondary outcomes were quality of life score, IIEF-5 score, and PSA._x000D_ _x000D_ Technique: Using 26 Fr Wolf resectoscope and side-firing 2090 GreenLight laser fiber, we incise the apical mucosa, separating the prostate from the external sphincter. Using the laser energy and blunt dissection, prostate lobes are enucleated on either side of the verumontanum. Dissection is carried out circumferentially until the bladder neck is reached. Hemostasis is achieved with laser coagulation. Once the enucleated adenoma is pushed into the bladder, morcellation is completed using the Wolf Piranha morcellator._x000D_ Results Mean age was 71 years, with 47.6% of patients on anticoagulation and/or antiplatelet therapy. Mean procedure time was 140 min ±55. The mean preoperative prostate size was 145ml ±86.46, with a mean size morcellated volume of 66mL ± 54. 75% of patients were discharged home on postoperative day (POD) 1 and 75% of patients had catheters removed by POD2. Primary and secondary outcomes can be found in Table 1, with statistically significant improvement in all parameters (p<0.05) except IIEF-5, which demonstrated no change. Complication rates included 1.2% blood transfusion, 6.1% clot retention, 4.9% urinary tract infection, and 13.4% stress urinary incontinence. The majority of patients regained continence at later follow-up. There was no incidence of urethral stricture, capsular perforation, bladder or ureteral injury. Conclusions In experienced hands, GLEP is a safe and feasible option for management of large prostates. Funding None
Authors
Kai Li
Alan Yaghoubian Mahdi Zangi Bo Wu Shahin Tabatabaei |
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MP02-08 |
HoLEP in Patients with Low Risk Prostate Cancer is Safe and Effective |
Benign Prostatic Hyperplasia: Surgical Therapy & New Technology I | 17BOS |
Abstract: MP02-08 Sources of Funding: None Introduction When a man with surveillance-appropriate low risk prostate cancer (PCa) has significantly bothersome BPH in a large gland, this typically tips the scales towards either radical prostatectomy or radiation therapy. However this presumes the PCa is the more threatening of his coexisting conditions. Incidentally discovered (T1a/b) PCa following Holmium Laser Enucleation of the Prostate (HoLEP) is a well known phenomenon. However, performing HoLEP in the setting of a PCa harboring gland has been underexplored. Herein, we describe outcomes of HoLEP in a select cohort of patients with significant LUTS, and known low risk PCa._x000D_ Methods Data were collected retrospectively on patients undergoing HoLEP by a single surgeon. A select group of well informed patients with large symptomatic glands and low risk cancer were carefully counseled that HoLEP was an option to address the obstructive BPH, would unpredictably remove the cancer (all, part, or none), emphasizing they were not undergoing a cancer operation, and that HoLEP would be followed by continued surveillance. Pre- and post-operative clinical factors, and operative and hospital stay data were collected. Results In total, 7 men were included. All men had Gleason 3+3 cancer in at most 20% of at most 3 cores on biopsy. Other preop characteristics are described in Table 1. Mean tissue removed was 48.8g. No patients required transfusion or reoperation. Median length of hospital stay was 24.5 hours; median length of catheterization was 19 hours. On final pathology, 3 of 7 of patients had cancer in the specimen, all of which were Gleason 3+3. At f/u, all flow rates improved, PVR improved or remained low, and PSA significantly decreased in all patients (Table 1). No patient have developed stricture, bladder neck contracture, incontinence, or required reoperation. Median f/u time was 4 months (range 4-24 months). Notably, 2 patients had prostate MRI within 2 years of HoLEP, neither of which showed suspicion for PCa. Conclusions We have offered HoLEP judiciously to select patients on surveillance for low risk PCa and significant symptomatic BPH, a complex and increasingly common scenario, with acceptable short term outcomes. Further investigations into long-term cancer-specific outcomes, as well as strategies for continued surveillance, will be crucial in order to further evaluate and refine this new approach. Funding None
Authors
Kristian Stensland
Daniel Pelzman Christopher Robertson Jared Schober Alireza Moinzadeh David Canes Jessica Mandeville |
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MP02-09 |
Evaluation of Surgical Outcomes with Photoselective Greenlight XPS Laser Vaporization of the Prostate in High Medical Risk Men with Benign Prostatic Enlargement: A Multicenter Study |
Benign Prostatic Hyperplasia: Surgical Therapy & New Technology I | 17BOS |
Abstract: MP02-09 Sources of Funding: Boston Scientific Corporation Introduction To evaluate the safety and short-term outcomes of photoselective vaporization of the prostate using GreenLight XPS in treatment of high medical risk men. _x000D_ Methods A multicenter retrospective analysis of 941 men who underwent photoselective vaporization of the prostate between August 2010 and August 2014 was performed. Patients were considered high medical risk if they had an American Society of Anesthesiologists physical status score >= 3. Postoperative adverse events, unexpected postoperative medical provider visits after intervention, and functional urinary outcomes were examined. _x000D_ Results High medical risk men (n=273) were older (mean age 72.3 +/- 8.1 vs. 67.1 +/- 9 years, p < 0.01), had larger prostate volume (82.8 +/- 48.2 vs. 73.7 +/- 49.4 g, p < 0.01), and were more likely to be on anticoagulant and antiplatelet medications (all p < 0.01). Moreover, overall operative time (65 +/- 35.1 vs. 53.9 +/- 24.9 min), energy delivered (313.4 +/- 207 vs. 258 +/- 164 KJ), and energy density used (4.2 +/- 3.8 vs. 3.8 +/- 3 KJ/g) were greater in the high medical risk group (all p < 0.05). Although high medical risk men were more often treated in a hospital setting (p < 0.01), there were no differences in intraoperative adverse events. Both groups had sustained improvements from baseline for all urinary functional outcomes at six months. Regarding safety, the two groups had comparable 90-day Clavien-Dindo complication rates, number of urgent care visits, and number of outpatient consultations. High medical risk men, however, had more hospital readmissions within 90-day post-surgery (3.7% vs. 1.3% [p = 0.04])._x000D_ Conclusions Despite older age, comorbidities, and higher use of anticoagulants, HMR men (ASA-PS 3/4) who undergo GL-XPS experience postoperative complications similar to healthier men (ASA-PS 1/2) in short term follow-up in addition to symptom improvement. GL-XPS produces safe and effective short-term outcomes in patients with multiple comorbidities. _x000D_ Funding Boston Scientific Corporation
Authors
Emad Rajih
Abdullah Alenizi Malek Meskawi Come Tholomier Pierre-Alain Hueber Mounsif Azizi Ricardo R. Gonzalez Gregg Eure Lewis Kriteman Mahmood Hai Kevin Zorn |
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MP02-10 |
Low-power versus high-power en-bloc no-touch HoLEP: comparing feasibility, safety and efficacy |
Benign Prostatic Hyperplasia: Surgical Therapy & New Technology I | 17BOS |
Abstract: MP02-10 Sources of Funding: None Introduction HoLEP (Holmium Laser Enucleation of the Prostate) is a safe and effective procedure for BPO treatment. Six years ago we modified the traditional 3-lobe technique into the so-called en-bloc no-touch approach, characterized by the enucleation of the adenoma in one single horshoe-like piece (en-bloc), largely exploiting the vaporizing plasma bubble generated around the tip of the laser fiber at a short distance from the tissue (no-touch). After more than 250 procedures with the 100-120W holmium laser device, in 2015 we chose to apply a low-power approach to deliver less energy to the capsular plane, and possibly minimize postoperative dysuria. The aim of the present work was to assess the feasibility of the low-power approach, and to compare its outcomes in terms of safety and efficacy with those of the traditional high-power HoLEP. Methods 316 patients suffering from BPO (any prostate volume, normal PSA, Qmax <15 ml/sec, IPSS>10, PVR <300 cc) underwent en-bloc no-touch HoLEP in our Department. From January 2012 to May 2015 214 consecutive patients underwent high-power HoLEP (group 1) with the 100-120W Versapulse holmium laser (Lumenis), 2J energy setting, 50 Hz, 100W power. From June 2015 to June 2016 102 consecutive patients underwent low-power HoLEP (group 2) with the 120W Versapulse holmium laser (Lumenis) for the first 20 patients, then the 50W Auriga XL holmium laser device (Boston Scientific), both 2.2J energy setting, 18 Hz frequency, long pulse length, almost 40W power. Patients demographics and clinical data were prospectively registered. Data were correlated using the Pearson correlation test. Results Mean age (69.4 years +/- 7.5 d.s. vs. 67.7 years +/- 8 d.s.) and adenoma weight (55 g +/- 39 d.s. vs. 46 +/- 36 d.s.) were similar in both groups. Energy used in Group 2 (53 kJ +/- 23 d.s.) was 1/3 less than in Group 1 (83.5 kJ +/- 32 d.s.). Enucleation time (31 min +/- 13 vs. 27.5 +/- 15), efficiency (1.64 g/min +/- 0.8 vs. 1.7 +/- 1) and morcellation time (9 min +/- 7.6 vs. 7.7 +/- 7.1) were equivalent. Pre- and postoperative IPSS (pre: 22 +/- 2.4 d.s. vs. 22 +/- 7 d.s.; post: 6.5 +/- 5 d.s. vs. 7.8 +/- 5 d.s.), incidence of postoperative bleeding (no blood transfusions)(4.2% vs. 3%) and recatheterizations (4.2% vs. 3%) were similar. Long-lasting incontinences of variable entity (mainly mild) were similar (1.4% vs. 1.6%), as well as the incidence of postoperative dysuria (10%) at 3-month follow up. Conclusions Low-power en-bloc no-touch HoLEP is feasible, safe and effective as the high-power approach, in the hands of experienced operators, being energy consumption reduced by nearly one third. Funding None
Authors
Cesare Marco Scoffone
Manuela Ingrosso Nicola Russo Cecilia Cracco |
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MP02-11 |
Postoperative dysuria after high- and low-power en-bloc no-touch HoLEP |
Benign Prostatic Hyperplasia: Surgical Therapy & New Technology I | 17BOS |
Abstract: MP02-11 Sources of Funding: None Introduction HoLEP (Holmium Laser Enucleation of the Prostate) is a safe and effective procedure for BPO treatment. Six years ago we modified the traditional 3-lobe technique into the so-called en-bloc no-touch approach, characterized by the enucleation of the adenoma in one single horshoe-like piece, exploiting the vaporizing effects of the plasma bubble generated around the tip of the laser fiber at a short distance from the tissue. Transient storage symptoms, mostly resolving spontaneously or with medical therapies within 1-3 months, are described among the early complications in 9-59% of patients who underwent HoLEP, and have been correlated also with energy consumption. The aim of the present study was to determine whether postoperative dysuria is somehow influenced by the use of a low-power approach rather than of a high-power one. Methods 316 patients suffering from BPO (any prostate volume, normal PSA, Qmax <15 ml/sec, IPSS>10, PVR <300 cc) underwent en-bloc no-touch HoLEP in our Department. From January 2012 to May 2015 214 consecutive patients underwent high-power HoLEP (group 1) with the 100-120W Versapulse holmium laser (Lumenis), 2J energy setting, 50 Hz, 100W power. From June 2015 to June 2016 102 consecutive patients underwent low-power HoLEP (group 2) for the first 20 cases with the Versapulse holmium laser (Lumenis), then the 50W Auriga XL holmium laser device (Boston Scientific), both 2.2J energy setting, 18 Hz frequency, long pulse length, almost 40W power. Patients demographics and clinical data were prospectively registered. IPSS questionnaires were self-administered before surgery and at 3-month follow up, VAS evaluation 1 month after surgery. Results Age (range 51-87 years) and adenoma weight (range 10-200 grams) were similar in the two groups. Mean energy employed for enucleation was 83.5 kJ +/- 32 d.s. for group 1, 53.4 kJ +/- 23 d.s. for group 2 (p<0.01), with a kJ/g ratio 2 +/- 1 vs. 1.5 +/- 0.8. Mean enucleation time was equivalent (31 min +/- 13 d.s. vs. 27.5 min +/- 11 d.s.), mean enucleation efficiency too (1.64 g/min +/- 0.8 d.s. vs. 1.7 g/min +/- 1 d.s.). Pre- and postoperative IPSS were similar (pre: 22 +/- 2.4 d.s. vs. 22 +/- 7 d.s.; post: 6.5 +/- 5 d.s. vs. 7.8 +/- 5 d.s.). Postoperative dysuria had the same incidence (10%), but in group 2 mean VAS evaluation at 1-month follow up was significantly better (6.2 +/- 1.5 d.s. in group 1, 2.4 +/- 3 d.s. in group 2). Conclusions Low-power en-bloc no-touch HoLEP uses less energy than the high-power approach, with reduced kJ/g ratio and similar postoperative dysuria (10%), being intensity and duration of the storage symptoms reduced. Funding None
Authors
Cecilia Cracco
Manuela Ingrosso Nicola Russo Cesare Marco Scoffone |
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MP02-12 |
Intravesical prostatic protrusion is not the same in its shape: evaluation by preoperative cystoscopy and outcome in HoLEP |
Benign Prostatic Hyperplasia: Surgical Therapy & New Technology I | 17BOS |
Abstract: MP02-12 Sources of Funding: none Introduction Intravesical prostatic protrusion (IPP) has been known as a predictor of efficacy not only for medical treatment such as alpha 1 blocker and dutasteride, but also for holmium laser enucleation of the prostate (HoLEP). However, the IPP is considered not the same in its shape because middle lobe and/or lateral lobes can protrude into bladder. Here, we evaluated the shape of IPP by cystoscopy and analyzed the outcome. Methods We reviewed charts of patients who had undergone HoLEP in Kyoto University Hospital from January 2006 to June 2016. Among 222 cases, 157 cases were evaluable for IPSS, uroflowmetry, IPP and its shape by preoperative flexible cystoscopy in outpatient clinic. IPP was classified into 5 groups: A, no protrusion; B, middle lobe only; C, lateral lobe only; D, bilateral lobe; E, B+C or B+D. Paired match analysis with similar IPP and other parameters was performed between the group with middle lobe protrusion (B+E, n=33) and the one without it (C+D, n=33). Results Table 1 shows the number of patients, age, score of total IPSS, QOL score, Qmax and IPP in the five groups. The group A (no protrusion) had a significantly higher Qmax than other groups. Groups with middle lobe protrusion (B or E) had a better tendency in changes in total IPSS score and Qmax. Paired match analysis shown in Table 2 demonstrated that the group with middle lobe protrusion had a significantly greater improvement of total IPSS score than the one without it (-16.6 vs. -10.8. p<0.01). Among them with less than 16 mm of IPP, all of patients with middle lobe protrusion improved IPSS, while only 76.5% (13/ 16) of patients without it were improved. Conclusions Patients with middle lobe protrusion had a greater improvement of IPSS in HoLEP than those having similar length of IPP without middle lobe protrusion. IPP should be clinically divided into two groups at least. Funding none
Authors
Hiromitsu Negoro
Ktsuhiro Ito Atsuro Sawada Shusuke Akamatsu Ryoichi Saito Takashi Kobayashi Naoki Terada Toshinari Yamasaki Takahiro Inoue Tomomi Kamba Osamu Ogawa |
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MP02-13 |
Prostate Enucleation Technique: Short Term Results of Prospective Randomized Trial of Comparing Holmium Laser and Bipolar Energy for Obstructive BPH. |
Benign Prostatic Hyperplasia: Surgical Therapy & New Technology I | 17BOS |
Abstract: MP02-13 Sources of Funding: None. Introduction Techniques of Prostatic Adenoma Enucleation by variety of energy sources are commonly practiced for surgical treatment of Obstructive BPH. We compare our short term results of Holmium Laser Enucleation ( HoLEP ) and Bipolar Enucleation ( PKEP/TUEB) in a prospective Randomized trial. Methods Between August’15 and April’16, a total of 98 patients with Obtructive BPH were treated and prospectively analysed at our center. A computerized randomization schedule was used. HolEP was done in 52 and Bipolar Enucleation was done in 46 patients. All Patients were evaluated by IPSS, Maximum Flow Rates ( Qmax), Transrectal Ultrasound Guided Prostate Volume(PV), Post Void Residue(PVR) and PSA. 100 W Holmium Laser and Plasmakinetic Bipolar energy by Spatula/Button Electrode was used for enucleation by single surgeon. Primary end points were IPSS and Qmax, secondary being reduction in PVR and PSA. Intraoperative and Immediate postoperative data like OR Time, Blood Loss, Irrigation Volume, Catherization/hospitalization time were compared between two groups. Results Pre-operative Demographics in both groups were comparable including Prostate Volume, HolEP ( 58± 8.2gms) versus Bipolar Enucleation _x000D_ ( 56.5±6.8 gms) p value being >0.05. Primary and secondary end points were comparable for both groups (p>.001). Blood loss in HolEP was marginally superior to Bipolar Enucleation ( 36±8.5 ml versus 68.5±7ml respectively, p=0.123). There was no significant difference in other parameters in both groups. OR time (34.5 versus 37 minutes) Catheterisation time ( 2.8 versus 3.1 days), Irrigation Volume (16.9 L versus 17.6 L), Hospital Stay ( 3.4 versus 3.9 days). One patient had prolonged hematuria, without requiring any intervention in bipolar group and two patients in each group had SUI lasting 3-4 weeks. There was no statistically significant difference in Primary and secondary end points in both groups at 1, 3 and 6 month follow-up. Conclusions Endoscopic Enucleation is effective irrespective of Energy source. Mean Prostate volume in our study was suggestive of Medium size Obstructive BPH, where, Bipolar Enucleation of Prostate was found to be equally efficacious compared with HoLEP in Short term follow-up. However, long term follow-up results in larger Prostate Volume remains to be seen. Funding None.
Authors
Ajay Bhandarkar
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MP02-14 |
First post-void residual urine volume following holmium laser enucleation of the prostate: Predictor of de novo urinary incontinence |
Benign Prostatic Hyperplasia: Surgical Therapy & New Technology I | 17BOS |
Abstract: MP02-14 Sources of Funding: none Introduction Transient urinary incontinence may occur in up to 44% of patients after holmium laser enucleation of the prostate (HoLEP). However, there are few published data concerning the factors associated with de novo urinary incontinence (UI). The aim of this study was to investigate the associated factors of de novo UI after HoLEP. Methods Our study included 141 patients who underwent HoLEP. Enrolled patients were divided into two groups according to the presence of UI. Independent t test was used to compare between two groups. Logistic regression was performed to analyze a correlation between de novo UI and other factors such as age, prostate volume, retrieved tissue weight, operative time, and the first post-void residual (PVR) urine volume immediately after removing postoperative urethral catheter. Urethral catheter was removed after bladder instillation with a 200 ml normal saline via urethral catheter, and PVR urine volume was estimated immediately after the first postoperative self-voiding. All definitions of UI corresponded to recommendations of the International Continence Society. Results After HoLEP, 44 patients (31.2%) had de novo UI, most of which resolved within 1-6 months; 34 had stress UI, 6 had urgency UI, and 4 had mixed UI. Age and PVR urine volume were significantly higher in UI group than non-UI group (75.09 ± 6.82 vs 72.01 ± 8.04 years; P = 0.029, 81.88 ± 67.13 vs 30.15 ± 23.56 ml, P < 0.001). In a logistic linear regression analysis, only PVR urine volume was an independent predictor of de novo UI after HoLEP. The most optimal cut-off value of PVR urine volume for predicting de novo UI was defined as 39.5 ml in the receiver operating characteristics curve analysis (sensitivity, 75.0%; specificity, 74.2%; AUC, 0.815; P < 0.001). Conclusions About one-third of patients might undergo de novo UI following HoLEP, and most of them might have been resolved within 1-6 months. High PVR urine volume after removal of postoperative urethral catheter is associated with de novo UI after HoLEP, and could be used as a practical tool to predict postoperative de novo UI. Funding none
Authors
Jun Seok Kim
Dong Hoon Yoo Dong Hoon Lim Myung Ki Kim Hee Jong Jeong Eun Mi Yang Seong Woon Park Joon Hwa Noh |
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MP02-15 |
PSA-changes and micturition improvement 5-years after thulium vapoenucleation of the prostate for symptomatic benign prostatic obstruction |
Benign Prostatic Hyperplasia: Surgical Therapy & New Technology I | 17BOS |
Abstract: MP02-15 Sources of Funding: None. Introduction To assess the long-term results of thulium vapoenucleation of the prostate (ThuVEP) for the treatment of symptomatic benign prostatic obstruction (BPO) retrospectively. Methods 500 patients with symptomatic BPO were treated with ThuVEP and consecutive mechanical morcellation between January 2007 and January 2010 at our institution. Patients were reassessed 1 and 5 years after ThuVEP with International Prostate Symptom Score (IPSS), Quality of Life (QoL), maximum urinary flow rate (Qmax), post-void residual urine (PVR), PSA, and prostate volume measured by transrectal ultrasound. To assess treatment effects, patients were divided into two groups according to the prostate volume: group A (<60ml) and group B (>60ml). Patient data is presented as median (interquartile range). Results 131 patients completed the 5-year follow-up and were included in the final analysis. IPSS, QoL, Qmax, and PVR improved significantly and continued to do so during 5-year follow-up (p≤0.001). At 1-year follow-up, the median prostate volume (50 ml vs. 13 ml, p<0.001) decreased significantly with a median prostate volume reduction of 80.8% (64.3-88%). Median PSA was significantly reduced at 1-year (0.83 μl/l) and 5-year (0.72 μg/l) follow-up as compared to median preoperative PSA (3.39 μg/l) (p≤0.001). The median PSA-reduction was 77.1% (51.5-89.3%) at 5-year follow-up and significantly different between group A (70.2% (42.7-87.3)%) and group B (83.5% (70.2-91.5%)) (p≤0.006). IPSS was significantly lower at 5-year follow-up in group B compared to group A (2.5 vs. 6, p<0.001), while Qmax, QoL, PVR showed no differences at 5-year follow-up between the groups. Bladder-neck contractures (n=4) and urethral strictures (n=4) developed 3.1% of the patients each. Three patients (2.3%) were re-treated during follow-up for recurrent prostatic tissue. Conclusions ThuVEP is a durable procedure for the treatment of symptomatic BPO with regard to micturition improvement and prostate volume reduction. The reintervention rate of the ThuVEP procedure at long-term follow-up was low. Funding None.
Authors
Christopher Netsch
Benedikt Becker Ann Kathrin Orywal Thomas Herrmann Andreas Gross |
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MP02-16 |
Effects of 5?-Reductase Inhibition on Benign Prostatic Hyperplasia Treated by Photoselective Vaporization Prostatectomy with the 180 Watt GreenLight XPS Laser System: results from the GOLIATH population |
Benign Prostatic Hyperplasia: Surgical Therapy & New Technology I | 17BOS |
Abstract: MP02-16 Sources of Funding: none Introduction Objective of the study was to investigate whether the effectiveness of GreenLight XPS (GL-XPS) laser Photoselective Vaporization Prostatectomy is different in patients with or without chronic 5-Alpha-Reductase Inhibitors (5ARI) therapy._x000D_ Methods We retrospectively evaluated prospectively collected 12 months data from the multicenter GOLIATH study regarding the 136 patients with benign prostatic hyperplasia (BPH) treated by PVP with the GL-XPS Laser System. A total of 36 patients were on chronic 5ARI therapy while 100 were not. The two groups were compared with respect to lasing density defined as kilojoules of energy applied per gram of prostate volume, prostate volume and Prostate Specific Antigen (PSA) reduction from baseline, symptom score change from baseline and uroflowmetry parameters improvement._x000D_ Results The two groups were largely similar at baseline. Mean prostate volume was 51.7 and 47.5 g in the group taking 5ARI and the group not, respectively. Lasing time and energy used were also greater in that group (50.5±22.4 min vs 42.4±20.4 min; 269.2±138.9 kJ vs 219.2±124 kJ). Energy delivered per prostate volume was greater in the group taking 5ARIs but the difference was not statistically significant (5.5±3.1 kJ/g vs 4.8±2.3 kJ/g, p = 0.185). No statistically significant differences were observed postoperatively in the two groups regarding prostate volume reduction, PSA decrease, improvement in symptom score and uroflowmetry parameters (Table 1)._x000D_ Conclusions Twelve-month efficacy outcomes and lasing efficiency were not statistically significantly different between the group taking 5ARI and the group not taking pharmaceuticals. 5ARI do not reduce the ability to treat patients with the GreenLight XPS laser system._x000D_ Funding none
Authors
Aldo Brassetti
Flavia Proietti Riccardo Lombardo Cosimo De Nunzio Andrea Tubaro |
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MP02-17 |
Ejaculatory dysfunction after treatment for lower urinary tract symptoms. What do patients really think? |
Benign Prostatic Hyperplasia: Surgical Therapy & New Technology I | 17BOS |
Abstract: MP02-17 Sources of Funding: None Introduction Benign prostatic obstruction (BPO) is the main cause of lower urinary tract symptoms (LUTS) in men over 50 years of age. This condition is highly prevalent and many men will undergo medical or surgical treatment leading to ejaculatory dysfunction with a potential negative impact on quality of life (QoL). Through urological generations, patients were warned of the almost inevitable risk of ejaculatory dysfunction as consequence of the treatment without asking their opinion on this issue. Our objective was to evaluate with a survey the patient’s wishes on ejaculatory function after surgical treatment for BPO. Methods All consecutive patients with LUTS and sexually active scheduled for BPO relief surgery in a tertiary reference center were included in this prospective evaluation. All patients were offered a surgical treatment with preservation of the ejaculatory function and were informed of the risk of failure and early recurrence of LUTS with the need of medication or surgery. Once information given, patients were asked their wish about the preservation of ejaculatory function. Results A total of 489 patients were included with a mean age of 68.3 years [43.2 - 93.8]. Among them, 175 (36%) preferred to undergo a surgery with attempt to preserve the ejaculatory function. The mean age of this group (group 1) was 61.8 [43.2 - 81.2] compared to 71.9 [52.8 - 93.8] for the group preferring a complete BPO relief surgery (group 2), p<0.001. At the preoperative evaluation, the mean IPSS symptom score was significantly lower in group 1 compared to group 2 (18.3 [1 - 35] versus 21 [3 - 35], p=0.02). Regarding the IPSS QoL score, there was no difference between the two groups, 5.7 [0 - 6] in group 1 versus 4.45 [1 - 5] in group 2, p=0.2. No difference in Qmax was observed: 9.3 mL/s [1 - 31] in group 1 versus 7.77 mL/s [2 - 26] in group 2, p=0.45. There was also no difference in prostate volume performed with transrectal ultrasound, 57.5 mL [17 - 220] in group 1 versus 62.3 mL [15 - 164] in group 2, p=0.13. About medication, 41% were under alpha-blockers in group 1 versus 51% in group 2 (p=0.06), and 9% were under 5-ARI in group 1 versus 24% in group 2, p<0.001. Conclusions This survey showed that more than one third of patients with indication of surgical treatment for BPO would like to preserve antegrade ejaculation despite of the risk of failure and early recurrence of LUTS. These patients were slightly younger than the others. This issue should be taken into consideration in the decision of the urologists which may change their surgical approach to preserve this function. Funding None
Authors
Steeve Doizi
Bertrand Lukacs |
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MP02-18 |
Trends in Minimally Invasive Simple Prostatectomy For Benign Prostatic Enlargement in the United States |
Benign Prostatic Hyperplasia: Surgical Therapy & New Technology I | 17BOS |
Abstract: MP02-18 Sources of Funding: None Introduction Guidelines for the management of very large prostates among men with symptomatic benign prostatic enlargement suggest simple prostatectomy (SP) or enucleation for those over 80g. Minimally invasive (MI) approaches to SP have been pursued to decrease procedural morbidity, with robot-assisted SP (RASP) gaining in favor. The broad effect of the advent of robotics on the frequency of SP has not been assessed. We aimed to examine trends in the use of SP in the United States in the era of growing enucleation popularity. Methods Using the Premier Healthcare Database, we identified men who underwent SP (ICD-9 codes 60.3, 60.4) with a concurrent diagnosis of BPH (ICD-9: 600.x), excluding those diagnosed with prostate cancer. Using a combination of ICD-9 codes and a detailed review of the billing codes, we identified procedures as as robotic (ICD-9: 17.4x), or laparoscopic (ICD-9: 54.21). We evaluated trends across the study period (2003 to 2015) in the use of SP by surgical approach (open, laparoscopic, robotic), in addition to predictors in the use of robotic and MI (laparoscopic and robotic) SP using multivariable logistic regression models. We adjusted for potential confounders and accounted for clustering by hospitals and survey weighting to ensure nationally representative estimates. Results A total of 43,731 SPs (40,995 open, 1,348 laparoscopic, 1,388 robotic) were performed at 414 hospitals from 2003 to 2015. Figure 1 shows the decreasing trend in number and proportion of open SP and a gradual rise in robotic SP being performed (p<0.001). Predictors of robotic SP use include lower age (OR 0.97, p<0.01), white (vs. non-white, OR 1.88, p=0.01), larger hospital bedsize (OR 3.61, p<0.01), teaching hospital status (OR 4.54,p<0.001), Northeast region (vs. Midwest, OR 5.52, p=0.01) and higher annual surgeon volume (OR 1.28, p=0.001). Predictors of MI SP include white (OR 1.53, p=0.02), higher surgeon volume (OR 1.15, p=0.08) and lower hospital volume (OR 0.93, p<0.01). Conclusions Though RASP is increasing as a percentage of SPs performed, it's growth in use has not lead to an increase in SP frequency, likely owing to its morbidity profile and the growing popularity of enucleation. The increasing use of MI, particularly robotic, SP is secondary to a variety of patient, hospital and surgical characteristics. Funding None
Authors
Jeffrey Leow
Gregory Mills Steven Chang Nicolas Von Landerberg Philipp Gild Quoc-Dien Trinh Jesse Sammon |
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MP02-19 |
Minimally Invasive Prostatic Urethral Lift (PUL) Efficacious in a Large Percentage of TURP Candidates: A Multi-center German Study after Two Years |
Benign Prostatic Hyperplasia: Surgical Therapy & New Technology I | 17BOS |
Abstract: MP02-19 Sources of Funding: None. Introduction Outcomes following prosthetic urethral lift implants (UroLift) (PUL) have been reported in a number of clinical trials. This investigation follows the mid term results in patients of five German centers who were treated in a normal clinical setting outside of study limitations. Previously reported studies rigorously selected subjects with mild to moderate obstruction. We report the prospective outcomes of patients treated by PUL in lieu of TURP after education concerning the less invasive therapy. Methods In a multicenter prospective observational study in 212 patients from five German centers were included during the period of 10/2012 through 06/2014. All candidates, submitted for transurethral resection of the prostate (TURP), received information on PUL and were given the choice of procedures. The only exclusion criterion was a prominent median lobe. No patients were excluded because of high post void residual (PVR), prostate volume (PV), history of retention, or oral LUTS therapy. Maximum urinary flow (Qmax), PVR, and the International Prostate Symptom Score (IPSS) with the Quality of Life questionnaire were assessed at baseline and 3, 6, 12, 18 and 24 months after surgery. Results Of the 212 candidates submitted for TURP, 85 (patient age was 38-85y) chose PUL. A total of 3.8 (2-7) implants were delivered over 57 (35-90 min) under general or local anesthesia. 38% of our more severely obstructed patients would have been denied PUL utilizing previously reported study criteria. _x000D_ 96% reported immediate symptom relief within the first month; mean Qmax, PVR, IPSS, and QoL significantly improved (p<0.001) and was maintained or further improved within the time of follow-up. Sexual function including ejaculation was unchanged or even improved of those who reported sexual activity prior to surgery. _x000D_ Eleven patients (13%) without severe obstruction but related to their high PVR underwent retreatment: two had successful additional PUL and 9 (with PVR values of 90-280ml) underwent TURP, four of which did not significantly improve further and one remained with a suprapubic catheter. Conclusions PUL is a new and promising surgical technique which may alleviate symptomatic BPH, even in severely obstructed patients. It is an easy surgical technique and has been efficacious in candidates who would have undergone, until now, TURP or another equivalent therapy. Within the follow-up, these patients demonstrated a similar outcome to those in published studies. _x000D_ Funding None.
Authors
Karl-Dietrich Sievert
Martin Schonthaler Richard Berges Florian Miller Bjorn Volkmer Annika Herlemann Ulrich Wetterauer Bastian Amend Christian Graztke |
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MP02-20 |
Definitive management of carcinogenic surgical smoke during transurethral resection of the prostate using a closed irrigation system |
Benign Prostatic Hyperplasia: Surgical Therapy & New Technology I | 17BOS |
Abstract: MP02-20 Sources of Funding: none Introduction Surgical smoke, which is produced during surgical procedures by electronic devices, contains harmful gases. Although these gases are also produced during transurethral resection (TUR), the dangers of surgical smoke in urological procedures are not widely known. The present study analyzed the gas composition of surgical smoke during TUR of the prostate (TURP), and investigated a technique to protect against the effects of harmful gases. Methods A total of 54 TURP (in saline) cases were enrolled and divided into two groups according to the irrigation evacuation methods: (1) spontaneous irrigation with outlets opened by natural pressure (open irrigation group) or (2) continuous irrigation with closed suction to outlets by continuous evacuation (closed irrigation group). The clinical parameters were analyzed in both groups. The conditions in the operating room during TURP were evaluated by the surgical staff with face scale questionnaires. The composition of the surgical smoke produced by TURP was collected into charcoal tubes, and analyzed by gas chromatography. Results The two groups did not differ in operation time or postoperative hemoglobin values, whereas resection efficiency was better in the closed irrigation group (0.45 gram/min) than in the open irrigation group (0.38 gram/min) (p=0.002). The conditions in the operating room improved significantly by a decrease in the unpleasant smell in the closed irrigation group (3.6, by face scale) compared to that in the open irrigation group (1.1, by face scale) (p<.0001). The closed irrigation system was able to expel the gases remaining in the dome of the bladder during TURP. The surgical smoke produced during TURP contained several gases including benzene and ethylbenzene, which are known carcinogens. Conclusions The surgical smoke produced by TURP contained carcinogenic gases. The application of the closed irrigation system during TURP would significantly improve conditions in the operating room and reduce exposure of the staff to the harmful effects of the gases by clearing this occupational hazard Funding none
Authors
YOHEI OKADA
Hideki Takeshita Yutaka Uchijima Satoru Kawakami |
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MP03-01 |
Magnetic resonance imaging-guided prostate biopsies fail to outperform standard transrectal ultrasound-guided biopsy in detecting high-risk prostate cancer: A Bayesian network meta-analysis of 24 randomised controlled trials |
Prostate Cancer: Detection & Screening I | 17BOS |
Abstract: MP03-01 Sources of Funding: None Introduction The introduction of three kinds of magnetic resonance imaging-guided biopsies (MRI-GB) has changed the paradigm regarding prostate biopsies. Since whether to use MRI-GB and which technique should be preferred are still matters of controversy, we aimed to compare and rank prostate biopsy strategies. Methods We did a network meta-analysis to incorporate both direct and indirect evidence from relevant trials. We searched PubMed, the Cochrane Library Central Register of Controlled Trials, Scopus, Embase and the reference lists of relevant articles for randomised controlled trials published up to Sep 1, 2016, of different prostate biopsy strategies. The primary outcome was overall prostate cancer (PCa) detection rate. The secondary outcomes were clinically significant PCa (csPCa), clinically insignificant PCa (ciPCa) and positive core rate. We did pairwise meta-analyses by random effects model and network meta-analysis by Bayesian random effects model. We assessed the quality of evidence contributing to each network estimate using the GRADE framework. This study is registered with PROSPERO, number CRD42015026114. Results From a total of 3616 citations, 24 randomised trials with a total of 6 497 participants were included in this network meta-analysis. 11 prostate biopsy strategies published between 2000 and 2016 were considered. The quality of evidence was rated as low in most comparisons. Only for MRI-cognitive GB (Relative risk [RR] 2.66, 95% credible interval [CrI] 1.44-4.72) enough evidence existed to support superiority when compared with transrectal ultrasound(TRUS) (10-12)-GB. csPCa and ciPCa detection rate suggested no significant difference between any pair of groups for biopsy technique. In terms of positive core rate, MRI-cognitive was significantly effective than TRUS(10-12) (RR 4.32, 95% CrI 1.45-13.30), TPUS(10-12) (RR 4.55, 95% CrI 1.34-15.98) and TRUS(>12) PB (RR 4.80, 95% CrI 1.34-17.58). In the subgroup of patients ≥ 65 yr and PSA < 10 ng/ml, MRI/TRUS was significantly effective than TRUS(10-12) (RR 2.47, 95% CrI 1.30-4.75; RR 2.45, 95% CrI 1.20-5.09). Conclusions MRI-cognitive GB had better overall PCa detection rates compared with TRUS(10-12)-GB, but similar rates of csPCa and ciPCa.Nevertheless, doctors need to consider our results together with all known safety and economy information when selecting the strategy for individual patients. Head-to-head comparisons of MRI-GB techniques are limited and are needed to confirm our findings. Funding None
Authors
Shi Qiu
Lu Yang Qiang Wei |
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MP03-02 |
Combined clinical parameters and multiparametric MRI for advanced risk modeling of prostate cancer - patient-tailored risk stratification can reduce unnecessary biopsies |
Prostate Cancer: Detection & Screening I | 17BOS |
Abstract: MP03-02 Sources of Funding: None Introduction Multiparametric MRI (mpMRI) is gaining widespread acceptance in prostate cancer (PC) diagnosis and improves significant PC (sPC) detection (Gleason-score >= 3+4). Decision making based on European Randomised study of Screening for PC (ERSPC) risk-calculator (RC) parameters may overcome PSA-screening limitations. We added pre-biopsy mpMRI to ERSPC-RC parameters and developed a risk model (RM) to predict individual sPC-risk on biopsy. _x000D_ Methods We retrospectively analyzed clinical parameters of 755 men (biopsy-naive or after previous biopsy) who underwent mpMRI prior to MRI/TRUS-fusion-biopsy between 2012 and 2014 as training sample. The RM was validated in 404 consecutive patients in 2015. A stepwise multivariate regression analysis was used to determine significant sPC-predictors in the training set and to develop the RM. The accuracy was compared to ERSPC-RC3 (for biopsy-naive men) and 4 (for patients after previous biopsy) and PI-RADSv1.0 scoring using receiver operating characteristics (ROC). Discrimination and calibration of the RM, as well as net decision and reduction curve analyses were evaluated in validation set. _x000D_ Results PSA, prostate volume, digital-rectal examination and PI-RADS were significant sPC-predictors and included in the RM (Figure a). ROC area under the curve (AUC) for the RM was significantly larger (0.82 each), compared to ERSPC-RC3 (0.79, p=0.004), RC4 (0.68, p<0.001) and PI-RADS (0.74-76, p=0.015 and p=0.006)(Figure b-e). Similarly, in the validation cohort, RM`s discrimination was higher for biopsy-naive and post-biopsy men (0.84 and 0.76), compared to PI-RADS (0.76 and 0.69, p=0.002 and p=0.006) and ERSPC-RC3/4 (0.79/0.74, p=0.003/p=0.146). The calibration plot demonstrated an excellent slope (1.03)(Figure f). The RM`s benefit exceeded that of ERSPC-RCs and PI-RADS in the decision which patient to biopsy and enabled the highest reduction rate of unnecessary biopsies. _x000D_ Conclusions The novel RM, incorporating ERSPC-RC parameters and PI-RADS, performed significantly better compared to the tools alone and provides measurable benefit in making the decision to biopsy men at suspicion of PC. _x000D_ Funding None
Authors
Jan Philipp Radtke
Bonekamp David Claudia Kesch Martin Freitag Bertram Hitthaler Matthias Claudius Roethke Celine Alt Kathrin Wieczorek Wilfried Roth Stefan Duensing Dogu Teber Heinz-Peter Schlemmer Markus Hohenfellner Boris Hadaschik |
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MP03-03 |
Changes in prostate cancer detection rate of fusion vs systematic biopsy over time: a single center experience |
Prostate Cancer: Detection & Screening I | 17BOS |
Abstract: MP03-03 Sources of Funding: This research was made possible through the NIH Medical Research Scholars Program, a public-private partnership supported jointly by the NIH and generous contributions to the Foundation for the NIH by the Doris Duke Charitable Foundation (Grant #2014194), the American Association for Dental Research, the Colgate-Palmolive Company, Genentech, and other private donors. For a complete list, visit the foundation website at http://www.fnih.org. Introduction To determine the effect of learning curves and changes in fusion platform during 9 years of NCI experience with multiparametric MRI (mpMRI)/TRUS fusion biopsy. Methods A review was performed of a prospectively maintained database of patients undergoing mpMRI followed by fusion biopsy (Fbx) and systematic biopsy (Sbx) from 2007 to 2016. The patients were stratified based on the timing of first biopsy in 3 groups. Cohort 1 included patients biopsied between 7/2007 to 12/2010, accounting for learning curve at our institution. Cohort 2 included patients biopsied from 1/2011 up to the debut of UroNav (Invivo) platform in 5/2013. Cohort 3 included patients biopsied after 5/2013. Clinically significant (CS) disease was defined as Gleason 7 (3+4) or higher. Cancer detection rates (CDR) between Sbx and Fbx during different time periods were compared using McNemar test. Age and PSA standardized CDRs were calculated for comparison between 3 cohorts. Results 1528 patients were included in the study with 219, 549 and 761 patients included in 3 respective cohorts. Mean age, PSA and race distribution were similar across 3 cohorts. In cohort 1 there was no significant difference between CDR of CS disease by Fbx (24.7%) vs Sbx (21.5%), p=0.377. Fbx was significantly better than Sbx in detection of CS disease in cohort 2 and cohort 3 (31.5% vs 25.3%, p=0.001; 36.5% vs 30.2%, p<0.001, respectively). There was significant decline in the detection of low risk disease by Fbx when compared to Sbx in the same period (cohort 2: 14.2% vs 20.9%, p<0.001; cohort 3: 12.5% vs 19.5%, p<0.001). Age and PSA standardized CDR of CS cancer by Fbx increased significantly between each successive cohort (cohort 1 and 2: 5.2%, 95% CI [2.1-8.5]), 2 and 3 (5.2%, 95% CI [1.8-8.6]). While CS CDR in patients with a prior negative biopsy was not significantly different between Fbx and Sbx in cohort 1, it was significantly different in cohorts 2 and 3 (p=0.388, p>0.001, p=0.036, respectively). Conclusions Our results show that after an early learning period using Fbx, CS prostate cancer was detected at significantly higher rates with Fbx than with Sbx, and low risk disease was detected at lower rates. Advances in software allowed for even greater detection of CS disease in the last cohort. This study shows that accuracy of Fbx is dependent on multiple factors; surgeon/radiologist experience and software improvements together produce improved accuracy. Funding This research was made possible through the NIH Medical Research Scholars Program, a public-private partnership supported jointly by the NIH and generous contributions to the Foundation for the NIH by the Doris Duke Charitable Foundation (Grant #2014194), the American Association for Dental Research, the Colgate-Palmolive Company, Genentech, and other private donors. For a complete list, visit the foundation website at http://www.fnih.org.
Authors
Brian Calio
Abhinav Sidana Dordaneh Sugano Amit Jain Mahir Maruf Maria Merino Baris Turkbey Peter Choyke Bradford Wood Peter Pinto |
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MP03-04 |
Does the Inclusion of Non-Index Lesions at Biopsy Improve Our Ability to Predict Adverse Pathologic Outcomes at Radical Prostatectomy? Implications for Targeted plus Systematic Biopsy Schemes |
Prostate Cancer: Detection & Screening I | 17BOS |
Abstract: MP03-04 Sources of Funding: none Introduction Although prostate biopsies targeted only to MRI detected lesions allow for the detection of clinically significant diseases, they would not result into a complete sampling of the entire prostate. Therefore, lower grade tumors (i.e., non-index lesions) in other areas would not be detected. We hypothesized that the presence of non-index lesions might impact on the risk of adverse outcomes at radical prostatectomy (RP) Methods 761 PCa patients treated with RP between 2012 and 2016 were identified. All biopsy specimens were re-reviewed by two high-volume dedicated uro-pathologists. The index lesion was defined as the highest-grade core at biopsy. When multiple positive cores were present, the index lesion was defined as higher-grade disease or higher number of positive cores with higher-grade disease from the same location. Non-index lesions were defined as lower grade or lower number of positive cores in other areas. Multivariable logistic regression (MVA) analyses tested the impact of the non-index lesions and of the number of positive non-index lesion cores on the risk of extracapsular extension (ECE), seminal vesicle involvement (SVI), and positive surgical margins (PSM). AUC of the models without information on the presence of non-index lesions were compared with full models using the DeLong method. Results Overall, 284 (37.5%), 83 (10.9%), and 145 (19.1%) patients had ECE, SVI, and PSM at final pathology. At MVA, the presence of non-index lesions was a predictor of ECE (Odds ratio [OR]: 2.12; P=0.001), SVI (OR: 2.75; P=0.02), and PSM (OR: 2.16; P=0.01). Similarly, the number of positive cores in the non-index lesion was associated with the risk of ECE (OR: 1.09; P=0.02), SVI (OR: 1.13; P<0.001), and PSM (OR: 1.07; P=0.01). The inclusion of information on non-index lesions improved the accuracy of the model predicting PSM (AUC: 67.0 vs. 69.4%; P=0.04). No differences in the AUCs of the base model and of the model including the presence of non-index lesions were observed for ECE (78.8 vs. 78.6%; P=0.7) and SVI (81.5 vs. 82.1%; P=0.3). Conclusions The presence of non-index lesions and the number of positive cores in the non-index lesion represent predictors of ECE, SVI, and PSM. The inclusion of these parameters improves our ability to identify patients at higher risk of PSM. A systematic sample of the prostate provides useful preoperative information on the risk of adverse pathologic outcomes and should be always considered in association with targeted biopsies. Funding none
Authors
Giorgio Gandaglia
Marco Bandini Paolo Dell'Oglio Nicola Fossati Francesco Pellegrino Giuseppe Fallara Emanuele Zaffuto Carlo Andrea Bravi Luigi Nocera Rocco Damiano Massimo Freschi Rodolfo Montironi Francesco Montorsi Alberto Briganti |
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MP03-05 |
Not all mpMRI targeted biopsies are equal: the impact of the type of approach and operator expertise on the detection of clinically significant prostate cancer |
Prostate Cancer: Detection & Screening I | 17BOS |
Abstract: MP03-05 Sources of Funding: none Introduction The aim of this study was to compare the detection rate of clinically significant prostate cancer (csPCa) of different mpMRI targeted approaches and to assess the role of operator expertise on the detection of csPCa Methods 244 patients underwent mpMRI targeted biopsy (cognitive-CB or fusion-FB) between 2013 and 2016 at a single tertiary referral centre. A 1.5 T mpMRI study using an endorectal coil was performed in all men. All procedures were performed by four operators. csPCa was defined as Gleason Score at biopsy ≥7. Operator expertise was coded as progressive number of targeted biopsies performed by each physician. Multivariable logistic regression analyses (MVA) were used to assess the association between type of targeted biopsy technique (FB vs. CB) and operator expertise (modelled by natural log function) with the detection of csPCa. Covariates consisted of PSA, prostate volume, PIRADS v.2 (3 vs. >3), number of targeted cores per MRI lesion, digital rectal examination (negative vs. positive). The same analyses were performed only in patients undergoing FB, after accounting also for type of FB approach (trans-rectal vs. trans-perineal). Lowess smoother weighted function was used to graphical assess the effect of operator expertise on the probability to detect csPCa in FB group, after accounting for all confounders Results Overall, 157 (64.3%) patients underwent FB and 87 (35.7%) underwent CB. Overall csPCa detection rate was 57.9 vs. 44.8% for FB and CB, respectively (p=0.07). A significantly higher csPCa detection rate of targeted samples alone was also observed for FB as compared to CB (56.7 vs. 35.6%; p=0.002). At MVA, FB and operator expertise were significantly associated with higher probability of csPCa detection in targeted samples (OR: 2.4 and 1.7, respectively; all p≤0.03). When the same analyses were repeated in those patients undergoing FB, operator expertise remained an independent predictor of csPCa (OR: 1.9; p=0.004). A progressive increase of the probability to detect csPCa with the increasing number of performed procedures was observed (Fig. 1) Conclusions We provided evidence that FB had higher detection rate of csPCa relative to CB. Moreover, operator expertise was significantly related to the detection of csPCa Funding none
Authors
Paolo Dell'Oglio
Armando Stabile Giorgio Gandaglia Nicola Fossati Vincenzo Scattoni Giorgio Brembilla Tommaso Maga Ella Kinzikeeva Andrea Losa Franco Gaboardi Gianpiero Cardone Antonio Esposito Francesco De Cobelli Alessandro Del Maschio Francesco Montorsi Alberto Briganti |
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MP03-06 |
Diagnostic performance of multiparametric MRI in prostate cancer: per core analysis of three prospective ultrasound/MRI fusion biopsy datasets |
Prostate Cancer: Detection & Screening I | 17BOS |
Abstract: MP03-06 Sources of Funding: none Introduction The fusion of multiparametric (Mp) magnetic resonance imaging (MRI) with real time 3D ultrasound during prostate biopsy is gaining popularity. The aim of this study was to evaluate the diagnostic performance of Mp-MRI using a per-core analysis of patients who underwent prostate “fusion” biopsy Methods Baseline, clinical and pathological data of 498 consecutive patients who underwent Mp-MRI/ultrasound “fusion” biopsy of prostate were prospectively collected in three centres between October 2013 and October 2016. The UroStation™ (Koelis, France) and ultrasound system with an end-fire 3D TRUS transducer were used for the imaging fusion process. _x000D_ Diagnostic accuracy of Mp-MRI was evaluated in the whole cohort and in those patients with Gleason score >6, separately. Sensitivity (Se), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV) and accuracy (Ac) of Mp-MRI were assessed on the base of a per core analysis of histologic findings._x000D_ Results Demographic data are reported into Table 1._x000D_ Out of 498 patients, 286 had a PCa diagnosis (57.4%); 162 of them (32.5%) were Gleason score ?7. Overall, 9360 cores were taken: Se, Sp, PPV, NPV and Ac of Mp-MRI in the whole cohort were 46.5%, 81.7%, 36.6%, 87% and 75.2%, respectively. When restricting the analysis to Gleason scores >6, Se, Sp, PPV, NPV and Ac were 45.9%, 79.8%, 25.1%, 90.9% and 75.4%, respectively. In a per patient analysis, the detection rate of PI-RADS scores 3,4 and 5 were 24%, 68% and 93.6%, respectively, while for Gleason score PCa>6 the detection rate of PIRADS 3, 4 and 5 were 6%, 35.2% and 73.4%, respectively.(Table 1). In a per core analysis, the PPV of PI-RADS scores 3,4 and 5 were 8.5%, 37.8% and 73.2%, respectively, while the PPV of PI-RADS scores for Gleason score PCa>6 were 5.1%, 21.2% and 62.2%, respectively. (Table 2)_x000D_ Conclusions This study confirmed high PCa detection rates with Mp-MRI-ultrasound fusion biopsy. A meticulous analysis of 9360 biopsy cores taken showed a poor sensitivity and PPV of Mp-MRI, especially for Gleason score >6 PCa. Despite the poor discrimination of PI-RADS scores of 3 and 4, PIRADS scores 5 correctly identified PCa lesions with Gleason scores >6. Funding none
Authors
Mariaconsiglia Ferriero
Alessandro Giacobbe Rocco Papalia Devis Collura Emanuela Altobelli Riccardo Mastroianni Gabriele Tuderti Francesco Minisola Leonardo Misuraca Salvatore Guaglianone Giovanni Muto Michele Gallucci Giuseppe Simone |
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MP03-07 |
Combined clinical parameters and multiparametric MRI for prediction of side-specific extraprostatic disease - a risk-model for patient-tailored risk stratification before Radical Prostatectomy |
Prostate Cancer: Detection & Screening I | 17BOS |
Abstract: MP03-07 Sources of Funding: None Introduction Multiparametric MRI (mpMRI) improves the detection of significant prostate cancer (PC) and extraprostatic extension (EPE). We combined pre-biopsy mpMRI data and clinical parameters to develop a risk model (RM) to predict individual side-specific risk of EPE on radical prostatectomy (RP). Methods MRI and clinical parameters of 132 men who underwent mpMRI fusion-biopsy and RP were analysed as training set. The RM was validated prospectively in 132 consecutive patients. Multivariate regression analysis was used to determine EPE predictors for RM development. The calibration of the RM was analysed using a calibration plot. The accuracy was compared to digital rectal examination (DRE), ESUR MRI criteria for EPE alone and the nomogram for side-specific EPE prediction of Steuber et al., using receiver operating characteristics (ROC) in training and validation set. Differences between the ROC curves were analysed using Likelihood ratio tests. Results Primary Gleason pattern on biopsy on specific side, ESUR MRI criteria of side-specific lesion, PSA-density, clinical T-stage, lesion volume in milliliter and capsule contact length in millimeter on MRI were significant EPE-predictors and were included in the RM (Figure a). The calibration plot of the RM showed that predicted and actual probabilities were close (slope 1.12)(Figure b). ROC area under the curve (AUC) for the RM was significantly larger in both sets (0.88 and 0.84), compared to DRE (0.69, p=0.004, 0.66, p<0.001) and the risk model of Steuber et al. (0.77, p=0.009, 0.71, p=0.006). Compared to ESUR criteria (AUC 0.87 and 0.80), the AUC was only significant larger in the validation set (p=0.03) (Figure c/d). Conclusions The RM, incorporating clinical and standardized MRI parameters performed significantly better compared to a renowned risk model, ESUR MRI criteria and clinical parameters alone. Thus, it provides accurate individual risk stratification of side-specific EPE of prostate cancers prior to RP. Funding None
Authors
Jan Philipp Radtke
Boris Hadaschik Claudia Kesch Bonekamp David Martin Freitag Celine Alt Bertram Hitthaler Matthias Claudius Roethke Kathrin Wieczorek Wilfried Roth Stefan Duensing Heinz-Peter Schlemmer Markus Hohenfellner Dogu Teber |
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MP03-08 |
Impact of dynamic contrast-enhanced sequences in prostate cancer detection: biparametric versus multiparametric MRI interpreted by 5 radiology residents. |
Prostate Cancer: Detection & Screening I | 17BOS |
Abstract: MP03-08 Sources of Funding: None Introduction Dynamic contrast-enhanced imaging (DCE) is recommended by Prostate Imaging - Reporting And Data System (PI-RADS) guidelines in addition to the combination of T2-weighted imaging (T2W) and diffusion-weighted imaging (DWI) for prostate cancer (PCa) detection, but its usefulness is not well-established. We compared the performance of biparametric (T2W+DWI) and triparametric (T2W+DWI+DCE) MRI, in the diagnosis of the index lesion. Methods Fifty-seven patients (who underwent preoperative mpMRI and radical prostatectomy) and 23 controls (examined by mpMRI, with at least a 2-year follow-up excluding PCa) were retrospectively analysed. Biparametric MRI and triparametric MRI (the latter according to PI-RADSv2) were reviewed by 5 independent radiology residents, allowing a 4-week interval between the two sessions. Each reader had an 8 months dedicated MRI experience and was blinded to clinical and pathological data. A senior consultant uro-pathologist reviewed whole-mount sections (according to 2014 ISUP protocol), providing the reference standard for comparing diagnostic accuracy. The index lesion was defined as the largest PCa focus identified at the final pathology. Results No statistically significant difference in index lesion detection was observed among bi- and triparametric MRI, in a pooled analysis of the 5 readers. Sensitivity was 72% and 81% respectively (p=0.08); specificity was 78% and 79% (p=0.92); accuracy was 74% and 81% (p=0.12; Figure 1). The larger lesion had also the higher Gleason score in 53/57 patients (92,9%). Bi- triparametric MRI did not differ significantly in measuring lesion diameter (p=0.54), although histologic value was significantly higher than measures of both imaging protocols (+54% on average, p=0.01). Conclusions No significant difference in detecting and measuring prostate cancer index lesion was observed by adding DCE sequences to T2W and DWI, among MRI readers with intermediate experience. The sole use of biparametric prostate MRI can provide a good diagnostic accuracy on index lesions. Funding None
Authors
Paolo Gontero
Giorgio Calleris Giancarlo Marra Marco Oderda Jacopo Giglio Francesca Misischi Francesco Gentile Patriciu Cimpoesu Luca Molinaro Laura Bergamasco Riccardo Faletti Paolo Fonio Bruno Frea |
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MP03-09 |
MRI-based nomogram predicting the probability of diagnosing a clinically significant Prostate Cancer with MRI-US fusion biopsy |
Prostate Cancer: Detection & Screening I | 17BOS |
Abstract: MP03-09 Sources of Funding: none Introduction Identifying clinically significant prostate cancers is the main objective of prostate cancer diagnosis. The aim of this study was to develop, to internally validate and to calibrate a nomogram to predict the probability of detecting a clinically significant prostate cancer. Methods Prospectively collected data from 3 tertiary referral center series of 478 consecutive patients who underwent MRI-US fusion biopsy using the UroStation (Koelis, France) were used to build the nomogram. A logistic regression model is created to identify predictors of PCa diagnosis with MRI-US fusion biopsy. Predictive accuracy was quantified using the concordance index (CI). Internal validation with 200 bootstrap resampling and calibration plot were performed. Results Mean age was 66.3 yrs (± 7.98) and mean PSA levels were 9.8 ng/mL (± 7.98). The overall PCa detection rate was 57.4%. _x000D_ Age, PSA serum levels, PIRADS score at MRI report, number of targeted and number of systematic cores taken were included in the model (Figure 1). Predictive accuracy was 0.81. On internal validation the CI was 0.81 and predicted probability was well calibrated (Figure 2). _x000D_ Limitations include the lack of external validation and the absence of patients with races different by Caucasian in the development cohort._x000D_ Conclusions Predicting the risk of a clinically significant PCa is the goal of physicians. This nomogram provides a high accuracy in predicting the probability of diagnosing a clinically significant PCa with MRI-US fusion biopsy. The ease to use makes this nomogram a clinical tool for both patients and physicians. Funding none
Authors
Giuseppe Simone
Rocco Papalia Emanuela Altobelli Alessandro Giacobbe Luigi Benecchi Gabriele Tuderti Leonardo Misuraca Salvatore Guaglianone Devis Collura Giovanni Muto Michele Gallucci Mariaconsiglia Ferriero |
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MP03-10 |
Contemporary assessment of the predictive value of multiparametric MRI for index lesion localization in prostate cancer |
Prostate Cancer: Detection & Screening I | 17BOS |
Abstract: MP03-10 Sources of Funding: none Introduction In the setting of active surveillance and focal therapy for prostate cancer (PCa), precise localization of the index lesion is crucial to ensure good oncological outcomes. Our objective was to assess the accuracy of multiparametric MRI (mp-MRI) for index lesion localization. _x000D_ Methods We conducted a retrospective bi-centric study including 405 patients operated by radical prostatectomy from 2010 to 2015 and having been assessed preoperatively by mp-MRI in two national referral centres for PCa management._x000D_ Pre-operative mp-MRI sequences included T2-weighted, diffusion weighted, and dynamic contrast enhanced and were acquired from 1,5 (n=344) or 3 Tesla (n=61) with external phased array coils. The MRI index lesion was defined as the lesion with the highest PI-RADS score. The pathological index lesion was defined as the lesion with the greatest Gleason score. If there were multiple lesions with the same PI-RADS or Gleason score, the largest one was considered as the index lesion. A neighbouring method, dividing the prostate in 12 sectors, was applied to determine the concordance between mp-MRI findings and pathology reports for index lesion localization. Results Out of the 405 patients, 385 (95%) had an index lesion identified on the mp-MRI and 20 (5%) had a normal mp-MRI. On pathology reports, the Gleason score was 6 in 113 (28%), 7 in 252 (62%) and ≥ 8 in 40 (10%) of the patients. The index lesion diameter was greater than 10mm in 336 (83%) patients. For index lesion detection, mp-MRI had a sensitivity of 63%, a specificity of 67% and a positive predictive value of 66%. Increased sensitivity was obtained for larger tumors on mp-MRI (>10mm, 194/275; 71%) and greater biopsy Gleason score tumors (≥7, 147/202; 73%). _x000D_ In multivariate analysis, the detection of the index lesion by mp-MRI was significantly improved when the biopsy Gleason score was ≥ 7 (4+3) (p=0.001), the index lesion mp-MRI size was > 10mm (p<0.001) and the prostate weight was ≤ 50g (p=0.017). Conclusions In this contemporary assessment, mp-MRI failed to localize the index lesion in up to 40% of cases. Larger tumor sizes on mp-MRI and higher Gleason scores on biopsy cores were associated with significantly higher sensitivity of mp-MRI for index lesion localization. Funding none
Authors
Samuel Lagabrielle
Edouard Descat Yann Lebras Camille Dupin Rémi Kaboré Nicolas Grenier Jean-Marie Ferrière Henri Bensadoun Jean-Christophe Bernhard Grégoire Robert |
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MP03-11 |
Institutional Learning Curve Associated with Implementation of a MR/US Fusion Biopsy Program Using PIRADS Version 2: Factors that Influence Success |
Prostate Cancer: Detection & Screening I | 17BOS |
Abstract: MP03-11 Sources of Funding: none Introduction MR/US fusion biopsy (FB) is a promising modality for detection of clinically significant prostate cancer (csPCa), defined as Gleason >=7 in patients who have had a prior negative biopsy. The purpose of this study is to assess the learning curve with adoption of FB using PI-RADS Version 2 (v2) for detecting csPCa and to identify patient and technical factors that predict success. Methods A total of 113 consecutive patients with at least one prior negative biopsy and a multiparametric MRI (mpMRI) exam of the prostate with a PIRADS 3 or greater index lesion underwent FB at a single academic center previously naive to FB technology. Outcomes are detection rates for Gleason 6 cancer, csPCa, and any cancer. The following 22 covariates were analyzed: age, body mass index (BMI), PSA, prostate volume (MRI-estimated), prostate volume (US-estimated), PSAD (MRI-estimated), PSAD (US-estimated), time interval since the last negative SB, number of prior negative systematic biopsies, number of targeted biopsy cores of the index lesion, size of index lesion, PI-RADS v2 score, number of suspicious lesions on mpMRI, institution experience, surgeon, obesity, digital rectal exam (DRE), atypical small acinar proliferation (ASAP) on prior biopsy, high-grade prostatic intraepithelial neoplasia (HGPIN) on prior biopsy, and location of index lesion (zone, region, and sector). Multiple logistic regression with model selection was used to select covariates having significant effects on the outcome._x000D_ Results Prostate cancers were identified in 52% of cases. Among patients diagnosed with prostate cancer, 80% were clinically significant. The detection rates of csPCa using FB when a PIRADS 3, 4, or 5 index lesion was present on mpMRI were 6%, 46%, and 66%, respectively. PI-RADS v2 score had a predictive accuracy (AUC) of 0.79 for csPCa detection. Institutional experience over time, MRI-estimated prostate volume, and PI-RADS v2 score were independent predictors of success at detecting csPCa. Conclusions Since FB is a highly technical and experience-driven process, development of internal quality measures to assess the institutional learning curve and the quality of PI-RADS v2 scoring is critical with adoption of this technology. Funding none
Authors
Matthew Truong
Eric Weinberg Gary Hollenberg Marianne Borch Ji Hae Park Jacob Gantz Changyong Feng Thomas Frye Ahmed Ghazi Guan Wu Jean Joseph Hani Rashid Edward Messing |
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MP03-12 |
Accuracy of multiparametric MR Imaging with PI-RADS V2 Assessment in Detecting Infiltrations of the Neurovascular Bundles prior to Prostatectomy |
Prostate Cancer: Detection & Screening I | 17BOS |
Abstract: MP03-12 Sources of Funding: none Introduction To evaluate mpMRI-based assessments of neurovascular bundle (NVB) infiltration and to determine the value of PI-RADS V2 scores for the prediction of NVB-infiltration before prostatectomy. Methods Our institutional review board approved the study. 198 patients underwent standardized mpMRI at 3T prior to surgery, including high resolution T2w-TSE-imaging in 3 planes, T1-w-TSE, DWI with ADC map, PD-TSE and Gd-DCE with post-processing of images. Assessment for NVB-infiltration was made for each side of each prostate (n=396). Maximum PI-RADS-V2 scores were determined for the posterolateral areas adjacent to the NVB (n=396). MRI-findings were correlated to pathologic analysis as reference standard, where NVB-infiltration was defined as tumor invasion into the NVB or extraprostatic expansion (EPE) in the posterolateral area adjacent to the NVB. Results Overall T-staging accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of mpMRI were 78.3%, 644 %, 892 %, 82.4% and 76.2%, respectively. In 396 cases infiltration of the NVB was predicted with 89.4%, 75.2%, 94.0%, 80.2% and 92.1% overall accuracy, sensitivity, specificity, PPV and NPV, respectively. By correlating 365 maximum PIRADS-V2 scores to the pathology of adjacent NVBs, infiltration was demonstrated in 13 NVBs despite low likelihood of cancer presence (PI-RADS 1 or 2 scores), amounting to 14% false negative predictions. Conclusions mpMRI-based assessment of NVB-infiltration should be acknowledged when nerve sparing surgery is considered. However, areas without tumor suspicion (PI-RADS 1 or 2) might demonstrate NVB-infiltration in pathology causing false negative predictions. Funding none
Authors
Markus Sauer
Julius Weinrich Georg Salomon Pierre Tennstedt Gerhard Adam Dirk Beyersdorff |
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MP03-13 |
Multiparametric MRI cannot predict clinically significant prostate cancer outside the index lesion: implications for extended biopsy templates |
Prostate Cancer: Detection & Screening I | 17BOS |
Abstract: MP03-13 Sources of Funding: none Introduction There is growing interest on the using of prostate mpMRI for performing targeted biopsies. However, lack of consensus exists whether it is mandatory to perform concomitant systematic biopsies. The aim of this study was to assess the predictors of clinical significant prostate cancer (csPCa) outside the mpMRI detected index lesion (IL) and to assess whether MRI parameters may predict csPCa outside IL Methods 244 patients underwent mpMRI of the prostate with subsequent biopsy between 2013 and 2016 at a single tertiary referral centre. A 1.5 T mpMRI study using an endorectal coil was performed in all patients. Lesions suggesting of significant PCa visualized on mpMRI, defined as PI-RADS v.2 ≥3, were targeted with cognitive or fusion approach. Furthermore each patient was submitted to standard random biopsy during the same session. csPCa was defined as Gleason Score ≥7. Multivariable logistic regression analysis (MVA) was performed to assess the predictors of csPCa outside the IL. Covariates consisted of age at biopsy, PSA, prostate volume, digital rectal examination (negative vs. positive), PI-RADS (3 vs. >3), IL volume, number of ILs, number of random cores and previous biopsy (biopsy naive vs. previous negative biopsy vs. previous positive biopsy) Results Overall, 46 and 54% of patients were previous biopsied and biopsy naive, respectively. Median PSA, prostate volume, number of random cores, number of ILs, IL volume were 7 ng/ml, 47 cc, 12, 1, 0.70 cc, respectively. The overall detection rate of csPCa outside the IL was 34%. When patients were stratified according to the targeted biopsy results, the detection rate of csPCa outside the IL was 10 and 30% in men with a negative and positive targeted biopsy, respectively. At MVA age (OR: 1.07; p=0.01), PSA (OR: 1.12; p=0.01), prostate volume (OR: 0.98; p=0.02), positive digital rectal examination (OR 3.7; p<0.01) and previous negative biopsy (OR 0.31; p=0.01) were independent predictors of the presence of overall csPCa outside the IL (AUC: 65%). Conversely, PI-RADS, IL volume, number of ILs detected at mpMRI were not associated with overall detection of csPCa outside the IL (all p≥0.1) Conclusions mpMRI missed csPCa outside the IL in approximately a third of men. Despite the presence of clinical predictors, neither patient characteristics nor mpMRI data are able to reliably select patients candidate for targeted biopsy alone (AUC: 65%). Therefore, based on our data, systematic biopsies should be always performed in conjunction with targeted biopsy in men with suspected csPCa at mpMRI Funding none
Authors
Armando Stabile
Paolo Dell'Oglio Giorgio Gandaglia Giulia Cristel Ella Kinzikeeva Tommaso Maga Andrea Losa Antonio Esposito Gianpiero Cardone Vincenzo Scattoni Francesco De Cobelli Alessandro Del Maschio Nazareno Suardi Franco Gaboardi Francesco Montorsi Alberto Briganti |
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MP03-14 |
High accuracy of tumor-foci location in the prostate by mp MRI-based stereotactic transperineal fusion biopsy could allow precise focal therapy |
Prostate Cancer: Detection & Screening I | 17BOS |
Abstract: MP03-14 Sources of Funding: None Introduction Focal therapy of prostate cancer might be an alternative to radical prostatectomy (RP) in treating patients with low- or intermediate-risk disease. Since MRI alone might not be sufficient in tumor location, template perineal biopsy is performed. To investigate the accuracy of locating a tumor focus we compared the results of multiparametric (mp)MRI and perineal stereotactic MRI-based TRUS-guided fusion biopsy (SFB) with the histopathology of the radical prostatectomy specimen. Methods All patients who underwent a SFB in our hospital with positive findings of tumor that lead to a RP from 08/2012 to 07/2016 were included. MRI of the prostate was performed multiparametric and evaluated according to PI-RADS-classification. Lesions were marked 3-dimensionally by the radiologist. The SFB was performed using the BiopSee ©-platform. Lesion-targeted and random biopsies were taken. The cores’ positions in the prostate were recorded. Cores were embedded separately, the basal tips got marked with dye. In the histopathological report the location of tumor in the core in terms of apical, mid or base location was mentioned. Thereby tumor-foci location could be projected on the prostate in 3 dimensions. In the prostatectomy-specimen (whole mount step section) the tumor’s location was reported by the pathologist. A single investigator determined the conformity of all three results visually: good (all 3 results matching), intermediate (MRI or biopsy matching with prostatectomy’s result), and poor conformity (no match at all). Results 128 patients could be included. 103 patients (79.8 %) showed good, 17 (13.2 %) intermediate, and 8 (6.2 %) poor conformity of the tumor’s location. According to oncological criteria (PSA< 15 ng/ml, Gleason max. 7a, cT1-2a, unilateral disease) 67 patients (52%) would have been suitable for focal therapy. From these 50 (75%)would have been in good conformity, 12 (18%)in intermediate and 5(7,%) in poor conformity to the prostatectomy result. Conclusions These results show a high accuracy in locating the tumor by SFB. This could give a good base for a precise focal therapy that is not only sufficient in terms of treating all tumor cells but also in sparing surrounding structures by avoiding over-estimation of the extensions of he foci. Funding None
Authors
Julia Bohr
Anne Vogel Michaela Vanberg Michael Musch Susanne Krege Darko Kroepfl |
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MP03-15 |
The analysis of prostate biopsy in negative multiparametric magnetic resonance imaging patients |
Prostate Cancer: Detection & Screening I | 17BOS |
Abstract: MP03-15 Sources of Funding: none Introduction To evaluate the cancer detection rate in negative multiparametric magnetic resonance imaging (mp-MRI) patients who accept the first time prostate biopsy. To analyze the potential influential factors of prostate cancer diagnosis. Methods The records of men undergoing prostate biopsy were retrospectively collected between July 2011 and June 2016. The PI-RADS score was used to evaluate the prostate imaging according to the European Society of Urological Radiology (ESUR) guideline and PI-RADS 1~2 was defined as negative. Finally, 196 patients were MRI negative. All the patients accepted T1, T2 and DWI image. Part of them had DCE image.The mean diagnosis age is 66.6±9.0yrs, and the median PSA is 7.44ng/ml.All patients accepted the transrectal ultrasound guided systematic 12-coreprostate biopsy._x000D_ Statistical analysis was carried out with the SPSS 19.0 computer package. A P value<0.05 was considered statistically significant._x000D_ Results There were 196 patients enrolled, with the mean diagnosis age 66.6±9.0yrs, and the median PSA 7.44ng/ml. Of the 196 patients, there were 42(21.4%) diagnosed with prostate cancer, of which, 30 were clinically significant.The negative predictive value (NPV) was 78.6% for prostate cancer, and 84.7% for clinically significant prostate cancer.(a_image, b_image)_x000D_ Age and serum PSA were related with positive diagnosis. Patients over 70yrs was associated with a 2.4-fold higher risk for prostate cancer, which was 1.47 when patients were divided according to the PSA level of ≤4ng/ml, 4~10ng/ml, 10~20ng/ml and >20ng/ml.(c_image) Conclusions Clinical significant prostate cancer may exist in negative MRI patients in first time biopsy. The age and PSA level relate to the cancer detection rate. Funding none
Authors
Ming Liu
Zhipeng Zhang Jianye Wang |
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MP03-16 |
Utility of Multi-Parametric MRI/Ultrasound Fusion: Cognitive Not Inferior to Targeted Software-Based Prostate Biopsies |
Prostate Cancer: Detection & Screening I | 17BOS |
Abstract: MP03-16 Sources of Funding: None Introduction Prostate cancer (PCa) remains the only solid organ tumor that is diagnosed by a non-targeted sampling method. Recently, multi-parametric MRI (MP-MRI) in conjunction with an MRI- ultrasound (US) fusion guided biopsy (bx) has demonstrated improved PCa detection. Unfortunately, this technology has been limited to tertiary care centers. Therefore, we sought to compare cognitive versus targeted software to assess the ability of cognitive registration to disseminate more readily into the community. Methods Consecutive patients underwent an MRI-US fusion prostate bx for elevated PSA, abnormal DRE, active surveillance or prior negative bx with a persistently elevated PSA. All subjects underwent pre-bx MP-MRI and lesions visible on MRI were graded using the PI-RADS version 2 classification system. The UroNav bx tracking system was used to fuse the stored MR images with real-time US generating a 3D model, which was then used to sequentially perform cognitive, targeted, and standard 12 core systematic biopsies in an office setting under local anesthesia. Descriptive statistics included patient characteristics and univariate analysis was done using logistic regression analysis to detect the associations between presence of cancer, clinically significant cancer, demographic variables, and bx method. Signed rank test was used for paired comparisons amongst bx method. Results 44 patients (median age 66 yrs, median PSA 6.4) underwent an MRI-US fusion bx between July 2014 and October 2015 with an overall CDR of 59%. Cognitive CDR was 40.9% with 25% being clinical significant disease. The targeted CDR was 27.3% with 22.7% being clinically significant disease. Overall, the cognitive approach had a sensitivity of 69.2% (95% CI: 50%, 88%) whereas the targeted approach had sensitivity of 46.2% (95% CI: 26%, 67%). Furthermore, the targeted approach missed 8 cancers when compared to the cognitive approach, whereas, the cognitive approach missed 2 cancer when compared to the targeted approach. The difference in sensitivity is most pronounced when comparing standard and targeted methods (p=0.02) and approaches significance when comparing cognitive and targeted methods (p=0.11). Conclusions MRI-US fusion targeted software when compared to the cognitive platform, was not found to have higher cancer detection rate nor sensitivity. We believe this highlights the importance of the MRI itself, rather than the platform used. Funding None
Authors
Avinash Chennamsetty
Steve Kardos William Chu Justin Emtage Nora Ruel Paul Gellhaus Clayton Lau Bertram Yuh Ali Zhumkhawala Kevin Chan Jonathan Yamzon |
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MP03-17 |
MRI-based nomogram to predict the probability of Prostate Cancer diagnosis with MRI-US fusion biopsy |
Prostate Cancer: Detection & Screening I | 17BOS |
Abstract: MP03-17 Sources of Funding: none Introduction The wide diffusion of multiparametric magnetic resonance imaging (MRI) has dramatically modified the scenario of prostate cancer (PCa) diagnosis. The detection rate of MRI-ultrasound (US) fusion biopsy increased as well as the need for an extended prostate biopsy sampling with saturation biopsy decreased. The aim of this study was to develop, internally validate and calibrate a nomogram to predict the probability of detecting a prostate cancer. Methods Prospectively collected data from 3 tertiary referral center series of 475 consecutive patients who underwent MRI-US fusion biopsy using the Koelis system were used to build the nomogram. A logistic regression model is created to identify predictors of PCa diagnosis with MRI-US fusion biopsy. Predictive accuracy was quantified using the concordance index (CI). Internal validation with 200 bootstrap resampling and calibration plot were performed. Results Mean age was 66.3 yrs (±7.98) and mean PSA levels were 9.8 ng/mL(±7.98). The overall PCa detection rate was 57.4%._x000D_ Age, PSA serum levels, PIRADS score at MRI report, number of targeted and number of systematic cores taken were included in the model (Figure 1).Predictive accuracy was 0.82. On internal validation the CI was 0.81 and predicted probability was well calibrated (Figure 2)._x000D_ Limitations include the lack of external validation and the absence of patients with races different by Caucasian in the development cohort._x000D_ Conclusions This nomogram provides a high accuracy in predicting the probability of PCa diagnosis with MRI-US fusion biopsy. This is an easy to use clinical tool that physicians may use for patients counselling purposes. Funding none
Authors
Giuseppe Simone
Mariaconsiglia Ferriero Emanuela Altobelli Alessandro Giacobbe Luigi Benecchi Gabriele Tuderti Leonardo Misuraca Salvatore Guaglianone Devis Collura Giovanni Muto Michele Gallucci Rocco Papalia |
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MP03-18 |
Absence of learning curve impact may let MRI-TRUS fusion guided biopsy up for early diagnosis of prostate cancer |
Prostate Cancer: Detection & Screening I | 17BOS |
Abstract: MP03-18 Sources of Funding: none Introduction To evaluate the impact of urologist learning curve (LC) for mpMRI-TRUS fusion biopsy on clinically significant PCa (sPCa) detection rate. _x000D_ Methods Data from 291 patients who underwent mpMRI-TRUS transperineal/transrectal targeted (TB) and systematic transrectal biopsy (SB) for suspicion of PCa were prospectly collected at a single institution. For mpMRI-TRUS fusion-guided prostate biopsy, the BioJet fusion system (D&K Technologies, Germany) was used; biopsies were performed in a transrectal or transperineal setting according to the location of the primary lesion on the mpMRI. All the procedures were performed by two urologists who had already experience with TRUS guided random prostate biopsies. mpMRI studies were reported by different experienced radiologists. The cohort was divided into six groups representing consecutive times during the study period. Overall PCa detection rate (CDR) and csPCa detection rate (csCDR), defined with Epstein criteria, were reported and stratified according to progression groups. Sensitivity, specificity, negative predictive value and accuracy of MRI-TRUS TB were calculated. Linear regression analyses were performed to evaluate the learning curve of the procedure. Results Overall PCa detection rate was 42.6% (n=124) and csPCa detection rate was 28% (n=81). CDR at target biopsy was 38% (n=111). Considering CDR stratified according to PIRADS, we reported 16.7% (n=1), 21% (n=22), 50.7% (n=74) and 75% (n=27) for PIRADS 2, 3, 4 and 5 respectively(p<0.01)._x000D_ Cancer detection rate increased from 38.8% to 42.6% from group A to group F (R2=0.06). csCDR and target biopsy CDR increased from 22% to 42% (R2=0.002) and from 38.8% to 39.5% (R2=0.7) respectively. Sensitivity, specificity, NPV and accuracy of TB in detecting PCa was 79% (CI: 0.68-0.89), 73% (CI: 0.66-0.78), 93 % (0.89-0.96) and 74% (0.68-0.79) respectively. Sensitivity, specificity, NPV and overall accuracy of TB in detecting csPCa was 93% (CI: 0.86-0.98), 83% (CI :0.77-0.87), 96% (CI:0.94-0.99) and 85% (CI: 0.81-0.89) respectively. When the LC impact was assessed, overall diagnostic accuracy on PCa and csPCa of TB did not show a significant increasing trend (R2=0.5 and R2=0.09). Conclusions We failed to demonstrate a statistically significant impact of LC for PCa and csPCa detection. mpMRI-TRUS-TB seems to be an easy, reliable and feasible procedure in the hands of experienced urologists. Our findings represent a starting point for faster widespread of the technique in the urological practice. Funding none
Authors
Giuliana Lista
Giovanni Lughezzani Massimo Lazzeri Vittorio Bini Rodolfo Hurle Nicolò Buffi Pasquale Cardone Luisa Pasini Silvia Zandegiacomo DeZorzi Roberto Peschechera Giorgio Bozzini Davide Maffei Giorgio Guazzoni |
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MP03-19 |
Difference between the PZ and the TZ in Diagnostic Accuracy of Magnetic Resonance Imaging (MRI) 5-Point Likert Scoring System Evaluated by the Result of MRI/Ultrasonography Fusion Targeted Biopsy of the Prostate |
Prostate Cancer: Detection & Screening I | 17BOS |
Abstract: MP03-19 Sources of Funding: none Introduction The aim of this study was to evaluate the accuracy of magnetic resonance imaging (MRI) scoring system for prostate cancer detection in the peripheral zone (PZ) and the transition zone (TZ) using MRI/trans-rectal ultrasonography (US) fusion targeted biopsy as a reference standard. Methods We retrospectively reviewed 762 patients who underwent 3-Tesla multi-parametric (mp)-MRI and the following MRI/US fusion targeted biopsy, all of which were performed by experienced urologists (10/2012-8/2015). We excluded patients in whom MRI did not identify any suspicious lesions and radiologists who reported in less than 50 cases. Finally, 648 patients with 1255 suspicious lesions were included in this study. The mp-MRIs were reported on a 5-point Likert scale of suspicion. The UroStation® (Koelis, France) was used for the image fusion. Clinically significant cancer was defined as biopsy Gleason score ≥7. Results Median age was 64 years, pre-biopsy prostate-specific antigen (PSA) level was 6.93 ng/ml and estimated prostate volume was 52.1 ml. _x000D_ Of 1255 suspicious lesions on MRI, 62.4% (n=783) were located in the PZ and 19.5% (n=245) in the TZ. _x000D_ There was no significant difference in the proportion of 5-point suspicious grades between the PZ and the TZ (p=0.077)._x000D_ In comparison between the PZ and the TZ, there was no significant difference in overall cancer detection rate in grade 1-2 lesions (11.8% vs 15.1%, p=0.362), grade 3 lesions (26.9% vs 19.8%, p=0.163) and grade 4-5 lesions (55.4% vs 50.0%, p=0.551)._x000D_ Regarding clinically significant cancer detection rate, there was no significant difference in grade 1-2 lesions between the PZ and the TZ (3.1% vs 6.6%, p=0.087). In contrast, statistical differences were noted in grade 3 lesions (15.1% vs 5.9%, p=0.019) and grade 4-5 lesions (45.9% vs 23.7%, p=0.013) between the PZ and the TZ. _x000D_ Conclusions The diagnostic reliability of mp-MRI for detecting clinically significant cancer in the TZ was less than that in the PZ. Although grade 3 lesions in the TZ showed similar overall cancer detection rate compared to that in the PZ, clinically significant cancer detection rate of grade 3 lesions in the TZ was quite lower than that in the PZ. Improvement of radiologist's interpretation, grading system itself, or targeting technique for grade 3 lesions in the TZ should be re-considered. Funding none
Authors
Toshitaka Shin
Thomas Smyth Osamu Ukimura Nariman Ahmadi Andre Luis Abreu Daniel Freitas Carlos Fay Masakatsu Oishi Hiromitsu Mimata Inderbir Gill |
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MP03-20 |
Diagnostic Performance of Apparent Diffusion Coefficient Between the Peripheral Zone and Transitional Zone in Localized Prostate Cancer |
Prostate Cancer: Detection & Screening I | 17BOS |
Abstract: MP03-20 Sources of Funding: None Introduction Apparent diffusion coefficient (ADC) grade is increasingly reported in prostate magnetic resonance imaging (MRI). We evaluated the usefulness and limitations of ADC grade for peripheral zone (PZ) and transitional zone (TZ). Methods We reviewed the data of 455 consecutive men who underwent 3.0 Tesla diffusion-weighted MRI before radical prostatectomy from January 2015 to May 2016. The level of suspicion from the ADC map was graded using the 5-grade Likert scale. Patients with a Likert grade ≥ 3 were included in the final analysis. The MRI index lesion was defined as the lesion with highest grade or the largest lesion when multiple lesions had an identical grade. After radical prostatectomy, topographic analyses were performed on the intraprostatic location of tumor foci at each specimen. The pathologic index tumor was defined as the tumor with the highest Gleason score or largest tumor when multiple foci had an identical GS. We matched the location between MRI index lesions and pathologic index tumors. The concordance rate was compared between the PZ and TZ using chi-square tests. Results In 455 patients with prostate cancer, 350 (77%) had suspicious MRI index lesions (ADC grade ≥ 3). Of the 350 lesions, 58% were seen in the PZ and 42% in the TZ. The overall concordance rate was gradually increased from ADC grade 3 to 5 (52%, 72%, and 86%) and biopsy Gleason score 6 to ≥ 8 (68%, 77%, and 80%). The overall concordance rate in the PZ was significantly higher than in the TZ (82% vs. 67% p < 0.01). The concordance rate in the PZ was higher than in the TZ among the subgroup of patients with ADC grade 5 (91% vs. 76%, p = 0.007). However, the rate was similar among the subgroup of patients with ADC grade 3 (50% vs. 54%, p = 0.78). Conclusions ADC grade from diffusion-weighted MRI is more useful in men with PZ tumor than in those with TZ tumor. Especially, ADC grade 5 in the PZ showed higher accuracy for the detection of index tumor. Funding None
Authors
Jung Keun Lee
In Jae Lee Tae Jin Kim Hakmin Lee Jong Jin Oh Sangchul Lee Seong Jin Jeong Seok-Soo Byun Sang Eun Lee Sung Kyu Hong |
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MP04-01 |
Financial toxicity prevalence and delay in care among bladder cancer patients |
Bladder Cancer: Epidemiology & Evaluation I | 17BOS |
Abstract: MP04-01 Sources of Funding: none Introduction Bladder cancer is the sixth most common cancer in the United States, but the most expensive from diagnosis to death. Costly surveillance and treatment can lead to financial toxicity (FT), an adverse financial condition as a consequence of the treatment of a disease. The purpose of this study is to define the prevalence of FT among patients with bladder cancer and identify causes for delay in care. Methods Bladder cancer patients were identified from the University of North Carolina Health Registry/Cancer Survivorship Cohort (HR/CSC), which includes patient-reported data on FT. FT was defined at agreement with the following statement “you have to pay more for medical care than you can afford.� Demographic characteristics and factors leading to delayed care were compared using Fisher’s exact tests. Results 144 bladder cancer patients were enrolled in HR/CSC, of which 138 completed the baseline questionnaire. Median age was 66.9 years. 75% were male, 89% were white, and 66% had less than a college degree. Half of patients had a stage of cT2 or higher. Thirty-three participants overall (24%) endorsed FT. Participants with FT were more likely to be younger, black, and have less than a college degree (p<0.01). Patients with non-invasive disease were more likely to report FT than those with invasive bladder cancer (15% vs. 30%; p=0.04). Patients who endorsed FT were more likely to report delaying care (19.8% vs. 35.1%) although this did not reach statistical significance (p=0.07). Patients reporting FT were more likely to delay care due to inability to take time off work (p=0.04) and inability to afford general expenses (p=0.04). Conclusions FT is a major concern among bladder cancer patients, with nearly 25% reporting that healthcare costs are more than they could afford. Younger patients were more likely to experience FT, which may be related to Medicare eligibility at age 65, which increases affordability of care. Higher rates of FT among non-invasive disease may reflect long-term, costly surveillance. Funding none
Authors
Marianne Casilla-Lennon
Seul Ki Cho Allison Deal Gopal Narang Jeannette Bensen Pauline Filippou Benjamin McCormick Raj Pruthi Eric Wallen Michael Woods Hung-Jui (Ray) Tan Matthew Nielsen Angela Smith |
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MP04-02 |
Long term incidence of venous thromboembolic events following cystectomy: a population-based analysis. |
Bladder Cancer: Epidemiology & Evaluation I | 17BOS |
Abstract: MP04-02 Sources of Funding: Ajmera Family Chair in Urologic Oncology Introduction Cancer and immobility both contribute to the development of venous thromboembolic events (VTE), including pulmonary embolism and deep vein thrombosis. As such, patients undergoing radical cystectomy for bladder cancer are at elevated risk. We sought to assess the long-term incidence of VTE among all patients undergoing radical cystectomy in the province of Ontario. Methods We conducted a population-based cohort study to examine the incidence of VTE, a composite of pulmonary embolism and deep vein thrombosis, among all patients treated with radical cystectomy for bladder cancer between 2002 and 2014 in Ontario, Canada. We estimated the cumulative incidence of VTE and used Fine and Grey competing risk survival analysis to assess risk factors for VTE while accounting for the risk of any cause mortality. Results Among 3623 eligible patients, the 10 year cumulative incidence of VTE was 6.68% (Figure). Among those who experienced VTE, the median time from surgery was 216 days (interquartile range 52-677 days; mean 527 days). However, VTE rates peaked much earlier with a mode of 20 days. Neither preoperative (HR 0.68, 95% CI 0.39-1.18) nor postoperative chemotherapy (HR 1.32, 95% CI 0.95-1.84) were significantly associated with VTE incidence. While patients with a prior history of VTE had increased risk of VTE after cystectomy (HR 5.1, 95% CI 2.2-12.0), age, gender, comorbidity score, rurality, diversion type (continent vs ileal conduit), treatment at an academic institution, or year of treatment were not significantly associated with the risk of VTE. Conclusions Among patients undergoing cystectomy for bladder cancer, the cumulative incidence of VTE continues to rise long after the date of surgery indicating that previous studies may have underestimated these rates, but the highest rates occur at 20 days after surgery. Chemotherapy does not appear to increase the risk of VTE. Funding Ajmera Family Chair in Urologic Oncology
Authors
Christopher Wallis
Diana Magee Raj Satkunasivam Robert Nam |
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MP04-03 |
Non-Muscle Invasive Bladder Cancer is Associated With Decreased Physical Health-Related Quality of Life |
Bladder Cancer: Epidemiology & Evaluation I | 17BOS |
Abstract: MP04-03 Sources of Funding: none Introduction The effect of non-muscle invasive bladder cancer (NMIBC) on health-related quality of life (HRQOL) is poorly understood. We evaluated changes in HRQOL in patients with a new diagnosis of NMIBC compared with the general population using the Surveillance Epidemiology and End Results (SEER) Medicare Health Outcomes Survey (MHOS) database. Methods We identified 325 Medicare beneficiaries diagnosed with NMIBC between initial and 2-year follow-up using SEER-MHOS data (1998-2013). NMIBC patients who underwent cystoscopy with biopsy or transurethral resection of bladder tumor(s) for bladder cancer were propensity matched 1:5 to non-cancer controls (n=1685). Changes from baseline in the physical component score (PCS) and mental component score (MCS), which are normalized to between 0-100, where 50 represents the US population mean, were compared between NMIBC patients and non-cancer controls with χ2 testing and multivariate linear regression analysis. We secondarily assessed differences in urinary symptoms on post-diagnosis surveys with univariate and multivariate models. Results Pre-diagnosis, mean PCS (39.94 vs 39.54, p = 0.71) and mean MCS (52.03 vs 52.17, p = 0.82) scores were similar between NMIBC patients and matched non-cancer controls. Post-diagnosis, NMIBC patients had a significantly greater decrease in PCS compared with controls (-2.87 (95% CI -3.87, -1.86) vs. -1.47 (95% CI -1.93, -1.02), p = 0.02). Conversely, mean MCS change did not vary between groups (-1.79 (95% CI -2.76, -0.81) vs. -0.72 (95% CI -1.21, -0.23), p = 0.09). With respect to urinary function, NMIBC pts were more likely to have worsening of urinary leakage (38.0 % vs 18.7 %, p= < 0.01), require physician intervention for urinary symptoms (33.9 % vs 13.7 %, p= <0.01 ), and receive treatment for urine leakage (31.6 % vs 12.0 %, p= <0.01 ) compared with non-cancer controls (p = <0.01). Conclusions The diagnosis of NMIBC is associated with a significant decrease in physical HRQOL, including a significant impact on urinary symptoms and leakage. Further efforts to prospectively evaluate HRQOL in patients with NMIBC should be pursued to inform and improve patient counseling. Funding none
Authors
Wayne Brisbane
Sarah Holt Brian Winters John Gore Atreya Dash Michael Porter Jonathan Wright George Schade |
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MP04-04 |
Characterizing the costs of complications after cystectomy: Can we target the primary drivers? |
Bladder Cancer: Epidemiology & Evaluation I | 17BOS |
Abstract: MP04-04 Sources of Funding: None Introduction Radical Cystectomy (RC) is subject to substantial morbidity and patients face complication rates as high as 64% at 90-days. Understanding the costs of complications after RC is essential to improving care. We studied the financial costs of different categories of complications after RC in order to identify drivers of expenditures. Methods Using the Premier Hospital Database we identified adult patients who underwent RC for bladder cancer from over 600 hospitals across the United States between 2003-2013. Ninety-day complications were captured using ICD9 codes. Complications were categorized according to Agency for Healthcare Research and Quality Clinical Classification Software. The primary outcome was cost of complication and secondary outcomes were mortality, length of stay (LOS), and discharge disposition. A generalized liner model conforming to a gamma distribution was used to evaluate cost data. Analyses were survey weighted, and all models were adjusted for patient (age, race, obesity, marital status, payer), hospital (bed size, teaching affiliation, rural, region), and surgery characteristics (lymphadenectomy, continent diversion, robotic, operative time, transfusion, surgeon volume, hospital volume) and clustered by hospital. Results We identified 9,137 RC patients, representing a weighting population of 57,553 patients. The top four most costly complications were venous thromboembolism (VTE $17547), soft tissue ($13523), gastrointestinal (GI $8663), and infectious (non-wound, i.e. sepsis, $7930) (p<0.001 for each). Pharmacy related costs were the primary driver of VTE costs. LOS was increased in each complication by 1.7 days for infectious, 4.5 days for soft tissue, 3.5 days for GI, and 3 days for VTE (p<0.001 for each). Being married, having fewer comorbidities, larger hospitals, teaching hospitals, shorter operations, lack of transfusions, high volume hospitals, and high volume surgeons were associated with statistically significantly lower costs of complications after cystectomy. Conclusions VTE, soft tissue, and GI complications are the most expensive complications after cystectomy, and thereby highlight potential candidates for future quality improvement initiatives. Funding None
Authors
Matthew Mossanen
Ross E. Krasnow Matthew D. Ingham Mark A. Preston Quoc D. Trinh Adam S. Kibel Steven I. Chung Steven L. Chang |
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MP04-05 |
Declining Use of Continent Diversions for Bladder Cancer |
Bladder Cancer: Epidemiology & Evaluation I | 17BOS |
Abstract: MP04-05 Sources of Funding: None Introduction Radical cystectomy with urinary diversion is a standard treatment for high-risk non-invasive and muscle-invasive bladder cancer. Continent diversions (CD) may allow better quality of life and body image perceptions over ileal conduits (IC) in selected patients. Our aim is to study contemporary trends in the utilization of ICs and CDs in patients undergoing radical cystectomy. Methods Using ICD-9 codes, we identified in the National Inpatient Sample (NIS) from 2001-2012 all patients with the principal diagnosis of malignant neoplasm of bladder (188.x, 233.7) who underwent radical cystectomy (57.71) followed by either ileal conduit (56.61) or orthotopic neobladder/continent diversion (57.87). Patient sociodemographics, comorbidities and in-hospital complications, mortality, length of stay (LOS), and total cost after radical cystectomy with IC vs CD were compared. Chi square test and multivariable logistic regression were used to analyze patient and hospital characteristics. Student’s t-test and Wilcoxon rank sum test were used to evaluate continuous variables. Results Between 2001-2012, an estimated 69,049 ICs and 6,991 CDs were performed. The total number of CDs increased from 2001 to 2012 (p < 0.0001), but peaked in 2008 and subsequently declined every year thereafter. Patients of all ages received ICs at a higher rate than CDs (Table 1), including younger age groups (40-59 and 60-69). Males and Caucasians were more likely to have CD compared to females (p<0.001) and African Americans (p<0.0001), respectively. The rate of CDs was highest in the West (12.1%, p<0.001), at urban teaching centers (10.85%, p<0.001), and in large hospitals (9.71%, p<0.001). On logistic regression analysis, when accounting for age, gender, comorbidities, and hospital characteristics, ICs were associated with higher rates of overall (OR 1.06, p=0.0185) and infectious (OR 1.13, p=0.002) complications and in-hospital mortality (OR 1.87, p<0.0001). There was no difference in LOS between the two groups. Conclusions The number of CDs performed has declined since 2008. Patients of all ages, including young patients, are more likely to receive IC than CD. Gender, socioeconomic factors, and geographic location may influence diversion type. CDs are associated with comparable rates of complications and in-hospital mortality. Potential causes for declining incidence of continent diversions may include physician reimbursement, length of surgical time, and higher incidence of robotic surgery. These factors should be the subject for further study. Funding None
Authors
Nicholas Farber
Izak Faiena Viktor Dombrovskiy Alexandra Tabakin Brian Shinder Rutveej Patel Sammy Elsamra Thomas Jang Eric Singer Robert Weiss |
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MP04-06 |
Personalized decision support tool to prevent hospital readmission for patients treated with radical cystectomy |
Bladder Cancer: Epidemiology & Evaluation I | 17BOS |
Abstract: MP04-06 Sources of Funding: none Introduction To create a user-friendly, personalized decision support tool that can display the likelihood of readmission after radical cystectomy, as well as recommendations for optimal follow-up based on published data. Methods We developed the "REACT: Readmission Elimination App for Cystectomy Treatment" using Apple's Xcode. This tool uses delay-time analysis models to determine the optimal timing of office visits and phone calls in order to maximize the probability of detecting radical cystectomy patients susceptible to readmission. We calibrated and validated the tool using radical cystectomy patient data from the 2009-2010 Healthcare Cost and Utilization Project State Inpatient Databases, and our institution's bladder cancer database from 2007 to 2011, as published in J Urol. 2016 May;195(5):1362-7. Results Our decision support tool generates a forecasted probability of readmission as well as suggested follow-up frequencies. Sample screenshots from the tool are presented in the Figure. After inputting the date of hospital discharge and other patient characteristics, the app tracks the status of the patient, suggests an optimal follow-up strategy, provides patients with the ability to contact their provider by phone, and tracks future appointments. Conclusions We integrated a delay-time analysis methodology into a software tool that can run on personal computers, iPads and iPhones to improve follow-up of patients after radical cystectomy. This software generates real-time predictions of the likelihood of readmission and indicates when future follow-up should be performed, so as to identify clinical deterioration in a timely manner. Through further customization and pilot testing, this decision support tool will enable personalized follow-up to help prevent hospital readmission after radical cystectomy. Funding none
Authors
Sarah Finley
Shivani Joshi Tudor Borza Xiang Liu Ted A. Skolarus Bruce L. Jacobs Benjamin Y. Li Heather Jim Scott M. Gilbert Zhitong Xie Jonathan E. Helm Mariel S. Lavieri |
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MP04-07 |
Prognostic impact of immunohistochemical classification of bladder cancer according to luminal (Uroplakin III) and basal (Cytokeratin 5/6) markers |
Bladder Cancer: Epidemiology & Evaluation I | 17BOS |
Abstract: MP04-07 Sources of Funding: none Introduction Recent genomic studies suggest that urothelial carcinoma (UC) can be grouped into luminal and basal subtypes. Basal bladder cancers are enriched with squamous features and are associated with worse prognosis. Previously, we reported that Desmocollin2 (DSC2) is an immunohistochemical (IHC) marker of squamous differentiation (SD) in UC, that correlates significantly with advanced tumor stage and poor prognosis. Here, we examined the subtype classification of bladder cancer based on Uroplakin III (UPK3) and Cytokeratin 5/6 (CK5/6) expression. Methods Expression of UPK3, CK5/6 and DSC2 was measured by IHC in 57 cases of bladder cancer treated with cystectomy (data set-1:previously reported in IHC of DSC2), which included 39 cases of pure UC and 18 cases of UC with SD. Next, we confirmed the result in the other data set of 77 cases of muscle invasive bladder cancer treated with cystectomy from 2006 to 2015 (data set-2). Results In dataset-1, the positivity of UPK3, CK5/6 and DSC2 in pure UC was 46%, 21% and 0%, while the positivity in UC with SD was 0%, 83% and 100%, respectively. CK5/6 expression correlated with DSC2 expression, and UPK3 expression was mutually exclusive of both CK5/6 and DSC2 expression. In addition, the positivity of UPK3 and CK5/6 in papillary tumors was 43% and 14%, respectively, and in flat and non-papillary tumors was 28% and 49%, respectively. In normal urothelium, UPK3 expression was observed only in umbrella cells, while CK5/6 expression was detected only in the basal layer. The intermediate layer showed no staining with either marker. UPK3 positive cases had the most favorable cancer specific survival (CSS at 5 years; 83%), while CK5/6 positive cases had the worst prognosis (55%), and cases negative for both markers had an intermediate prognosis (68%)._x000D_ In dataset-2, the expression of UPK3 and CK5/6 in papillary UC was 57% and 4%, respectively, while expression in flat and non-papillary UC was 11% and 39%, respectively. CSS at 5 years was 95% in UPK3 positive, 49% in CK5/6 positive and 59% in marker-negative cases. _x000D_ Conclusions While genomic subtyping of UC requires clustering of large datasets derived from an entire cohort of patients, our simple IHC with two markers of luminal and basal differentiation is capable of stratifying prognosis on an individual patient basis. IHC classification of UC lends itself to easy adoption in routine clinical practice. Funding none
Authors
Tetsutaro Hayashi
Kazuhiro Sentani Shinji Kakumoto Htoo Zarni Oo Naoya Sakamoto Kazuaki Mutaguchi Kohei Kobatake Keisuke Goto Shogo Inoue Jun Teishima Peter Black Akio Matsubara |
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MP04-08 |
Why investigate asymptomatic microhematuria? Implications of applying UK national guidance |
Bladder Cancer: Epidemiology & Evaluation I | 17BOS |
Abstract: MP04-08 Sources of Funding: None Introduction The 2015 UK NICE guidance (NG12) for &[prime]urgent suspected cancer&[prime] (USC) referrals suggested that asymptomatic microhematuria (AMH) need not be seen as USC._x000D_ _x000D_ We hypothesized that declining referrals for AMH was safe, and would help to address our unacceptably long wait for the one-stop hematuria clinic (OSHC). We present the outcome of rejecting referrals for AMH entirely for one year, the first study of its kind to adopt this innovative approach. Methods Hematuria referrals to a UK cancer center (catchment population >600K) were analyzed retrospectively prior to NG12 publication from July 14 to July 15 (cohort 1) and compared to prospective data following NG12 from July 15 to July 16 (cohort 2). After NG12, referrals for AMH were declined in writing. Bladder cancer was categorized as per the European Organisation for Research and Treatment of Cancer risk stratification. Results Over the study period, 1963 patients were seen in a OSHC; 1105 prior to NG12 (cohort 1), and 858 after (cohort 2). In cohort 1, 686 had gross hematuria (GH), 159 had symptomatic microhematuria (SMH), and 260 had AMH. Cancers were diagnosed in 132 cohort 1 patients; 83% (110 patients) had urothelial malignancies, of which 107 (97%) presented with GH or SMH, and only 3 with AMH. Twenty-six patients (23%) were diagnosed with high-risk non-muscle invasive bladder cancer (HRNMIBC), 21 patients (19%) with muscle invasive bladder cancer (MIBC), and 4 (4%) with upper tract TCC (UTTCC)._x000D_ _x000D_ In cohort 2, 137 cancers were diagnosed, of which 114 (83%) were urothelial malignancies. These included 26 HRNMIBCs (23%), 24 MIBCs (21%), 3 metastatic bladder cancers (3%), and 7 UTTCCs (6%). One-hundred and fifty-three referrals for AMH were rejected in writing during cohort 2._x000D_ _x000D_ By excluding patients with AMH from cohort 1, only 3 low-risk non-muscle invasive bladder cancers would have remained undetected after implementing NG12 (in addition to 2 small renal tumors). Furthermore, after NG12, the average time from referral to first appointment fell from 35 days in July 15, to 17 days in July 16 (up to 50% reduction)._x000D_ Conclusions Prior to NICE guideline NG12 implementation, no significant cancers were detected in patients referred with AMH in our study. After NG12, and rejecting referrals with AMH entirely, patients with bladder cancer were seen and treated earlier._x000D_ _x000D_ While such a novel approach to AMH may attract criticism, this study outlines for the first time, that declining to accept such referrals in a state-funded healthcare system is an effective approach for rationalization of resources. Funding None
Authors
Adam Cox
Matthew Jefferies Mohamad Kamarizan Maureen Hunter Jim Wilson Daniel Painter Adam Carter |
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MP04-09 |
A longitudinal study of health disparity in metastatic bladder cancer using the California Cancer Registry |
Bladder Cancer: Epidemiology & Evaluation I | 17BOS |
Abstract: MP04-09 Sources of Funding: None Introduction Bladder cancer (BCa) is one of the top ten most common cancers in the world. However, very few studies have reported on health disparities involving advanced BCa. The objective of this study was to identify disparities in treatment and survival for patients with metastatic bladder cancer. Methods Patients with metastatic BCa diagnosed between 1991 and 2014 were identified through the California Cancer Registry. Included in the analysis were age at diagnosis, sex, race/ethnicity, area-based socioeconomic status (SES), first course of treatment, and survival time. Predictors of treatment were identified using logistic regression, and cause-specific survival was analyzed using Cox regression. Results A total of 3,073 cases of metastatic BCa were identified. Among these cases, 67.39% were male, and 32.61% were female. The race distribution was 74.78% non-Hispanic (NH) white, 6.25% NH black, 12.46% Hispanic and 5.96% NH Asian/Pacific Islander (Asian/PI). Among all patients presenting with metastatic bladder cancer, 45.6% received chemotherapy. Of those receiving chemotherapy, 42% underwent additional local treatment (radical cystectomy or radiotherapy). Patients over age 65, female patients and those residing in all but the wealthiest census tracts were less likely to receive chemotherapy with or without local treatment. NH black patients also were slightly less likely to be treated. Patients diagnosed between 2003 and 2014 were 32% more likely to receive chemotherapy than those diagnosed between 1991 and 2002 (p<.001). Overall and cause-specific survival for the entire cohort was 11.1% and 14.5%, respectively. A smaller proportion of NH black patients survived two years after diagnosis (6.5% versus 14.4% NH white, 18.3% Hispanic, and 15.4% Asian/PI). After adjustment for other factors, patients aged 80 and older were more likely to die from bladder cancer (HR=1.2, 95% CI=1.0-1.3) as were black patients (HR=1.2, 95% CI=1.0-1.5). Patients residing in poorer census tracts were slightly more likely to die of bladder cancer although results were not statistically significant. Patients who received no chemotherapy had more than twice the risk of death. There was no evidence that overall survival improved in the most recent time period. Conclusions Non-Hispanic blacks and patients who were not treated with chemotherapy experienced poorer survival than other groups. There had been no improvement in this heath disparity or in overall survival over the last two decades. Funding None
Authors
Kevin Pan
Amy Klapheke Rosemary Cress Stanley Yap |
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MP04-10 |
A PROSPECTIVE COHORT STUDY OF 112 ELDERLY PATIENTS WITH BLADDER CANCER: PREDICTIVE FACTORS OF EARLY DEATH AFTER A COMPREHENSIVE GERIATRIC ASSESSMENT |
Bladder Cancer: Epidemiology & Evaluation I | 17BOS |
Abstract: MP04-10 Sources of Funding: none Introduction Bladder Cancer (Bca) is significantly associated with aging. However, the correct management of BCa in the elderly remains controversial. The aim of the study is to analyse predictive factors of early death in a group of patients >70y, with Bca, at 100 days after a geriatric comprehensive assessment (CGA), in order to help in therapeutic decision making. Methods 112 patients with Bca were enrolled. This is a multicentric and prospective cohort study approved by an ethics committee. A standardized comprehensive geriatric assessment (CGA) was done before the treatment decision and different geriatric data were collected: MMSE, MNA, BMI, Grip hand grip strength, ADL, IADL, GIRSg, Gait speed, QLQC30, Charlson, G8 and Balducci classification. Characteristics of cancer, social and demographic data were also collected. During a 100-days follow up, the rate of death, treatments made and geriatric interventions were collected. Results A total of 112 patients were enrolled, including 25,9 % of women and a mean age of 82y [70-96]. 26,8% (n=30) of patients died within the 100-days follow up. 34,8%(n=39) of patients had metastatic cancers. The most common proposed treatments, by the surgeron or the oncologist, were surgery (radical cystectomy) (44,6%) and chemotherapy (41,6%). In 35,7% of cases, CGA has modified the therapeutic decision, in favor to palliative care in 57,5%._x000D_ In univariate analyzes, metastatic cancers (HR= 2,7 [ 1,3-5,5],p=0,008), cognitive deficit (MMSE<24) (HR=3;2[1,5-7],p=0,003), confusion (HR=2,2 [1,1-4,5],p=0,032), under nutrition (MNA<17) (HR=6,9 [2,1-22],p<0,001), lower gait speed (HR=5,6 [2,4-12,9],p<0,001), social isolation (HR=4,5 [2,1-9,6], p<0,001), and loss of autonomy in ADL (HR=2,7 [1,1-6,2],p=0,023) and IADL (HR=2,7 [1,1-6,5],p=0,032) had significantly more risk of dying. The predictive factors of early death, in multivariate analyzes, were the metastatic cancers (HR=3,5 [1,6-7,5], p=0,002), the lower gait speed (HR=3,1 [1,2-7,7], p=0,015), social isolation (HR= 2,6 [1,2-5,9], p=0,02)and loss of autonomy in ADL (HR=3,3 [1,2-9,2],p=0,022)._x000D_ _x000D_ Conclusions This study confirms that some geriatric data could be predictive of worse outcome. These results can help the geriatrician, the surgeon and the oncologist in decision making. But these data also encourage to propose targeted geriatric interventions to improve the patients’s prognosis, especially customize their perioperative care. Funding none
Authors
Cyrielle RAMBAUD
Marine SANCHEZ Sébastien GONFRIER Matthieu DURAND Delphine BORCHIELLINI Hervé QUINTENS Romain PRADER Rabia BOULAHSSASS Olivier GUERIN |
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MP04-11 |
Obesity may be a risk factor for ureteroenteric anastomotic strictures after radical cystectomy with urinary diversion |
Bladder Cancer: Epidemiology & Evaluation I | 17BOS |
Abstract: MP04-11 Sources of Funding: None Introduction Ureteroenteric anastomotic strictures (UAS) are a known long-term complication of radical cystectomy with urinary diversion (RCUD). Often a silent process, UAS can be associated with progressive renal function decline, and often require additional procedures. We assessed our series of RCUD to determine predictors of UAS. Methods We completed a retrospective review of consecutive patients who underwent RCUD between 2005-2015 by a single surgeon. All ureteroenteric anastomoses were performed in a freely-refluxing end-to-side fashion over an 8Fr feeding tube. Kaplan-Meier time-to-event analysis was performed to estimate the cumulative incidence of UAS, with patients censored at last follow-up or death. Univariable and multivariable logistic regression were performed to identify predictors of UAS. The final multivariable model was selected using Akaike Information Criterion to optimize model parsimony and fit. _x000D_ Results RCUD was performed in 286 bladder cancer patients, with a median age of 69.9 years (IQR 62.8-76.2) and median follow-up of 21.4 months (IQR 8.9-42.3). Urinary diversions included ileal conduit (164, 57.3%), orthotopic ileal neobladder (114, 39.9%), and continent cutaneous reservoir (8, 2.8%). _x000D_ UAS developed in 29 patients (10.1%), at a median of 6.4 months (IQR 4.4-8.8) postoperatively. The cumulative incidence of UAS was 12.5% (95% CI 8.7-17.7) at 24 months. UAS patients had higher rates of obesity (72.4% vs 28.0%, p<0.001), were younger (66.4 vs 70.3 years, p=0.003), and had a longer median follow-up (34.0 vs 20.2 months, p=0.04). There was no difference in preoperative radiation in the UAS group (3.5% vs 10.3%, p=0.2). _x000D_ On time-to-event analysis, obese (BMI ≥30) patients had a higher cumulative incidence of stricture than non-obese (25.2% vs 5.9%, p<0.001) at 24 months (Figure). On multivariate analysis, only obesity was an independent predictor of UAS (OR 6.4, 95%CI 2.6-156; p<0.001)._x000D_ Conclusions Ureteroenteric anastomotic strictures are often a silent event arising within the first year of radical cystectomy with urinary diversion. Obese patients are at a significantly increased risk of stricture development, regardless of urinary diversion type or oncologic characteristics. Funding None
Authors
Belinda Li
Robert H. Blackwell Bethany K. Burge Elizabeth L. Koehne Marcus L. Quek |
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MP04-12 |
Outcomes of nested variant of urothelial carcinoma following radical cystectomy |
Bladder Cancer: Epidemiology & Evaluation I | 17BOS |
Abstract: MP04-12 Sources of Funding: None Introduction Nested variant (NV) urothelial cell carcinoma (UCC) is a rare histological subtype of UCC with benign features. There is limited data on the outcomes and characteristics of patients with this histology (largest study with 52 patients); however, it has traditionally been viewed as a more aggressive subtype of UCC and neoadjuvant chemotherapy is not recommended. Our primary interest was to assess whether there is a difference in overall survival (OS) after radical cystectomy (RC) between patients with NV features compared to patients with pure UCC. Methods We identified 1949 patients who underwent RC between January 1995 and December 2015 and had pure UCC or NV. We utilized a univariate and multivariable Cox proportional hazards model, adjusting for gender, positive lymph node invasion status, neoadjuvant chemotherapy, age and tumor stage at cystectomy to assess whether there was a difference in OS between UCC and NV patients. To determine whether there were differences in demographics and tumor characteristics between patients with NV and those without, group comparisons were made using Fisher’s exact test for categorical variables and Wilcoxon rank?sum test for continuous variables. Lastly we utilized the Cochran?Mantel?Haenszel method stratified on histology and applied the Breslow?Day test for homogeneity to evaluate whether there were differences in response to neoadjuvant chemotherapy based on histology. Results We identified 1807 (93%) pure UC patients and 142 (7.3%) patients with nested features. Among our 1949 patients, 919 with pure UCC and 77 with NV, died from any cause. The median follow up time for survivors was 4.6 years from RC. A larger proportion of NV patients at time of RC had lymph node invasion (p=0.007) and worse pathological tumor stage (p < 0.001) than pure UCC. On univariate analysis NV was associated with poorer OS (HR 1.26; 95% C.I. 1.00, 1.60; p = 0.049); however, on multivariable analysis, the association between histology and OS is no longer significant (HR 0.96; 95% CI 0.75, 1.22; p=0.7). We did not find a significant difference in response to neoadjuvant chemotherapy between the two histological groups (p = 0.6). Conclusions NV carcinoma presents at a higher stage than pure UCC at time of RC, but does not necessarily represent a more aggressive variant. It perhaps represents a delay in diagnosis due to NV benign features. Funding None
Authors
Joel Hillelsohn
Amy Tin Dev Mally Daniel Sjoberg Guido Dalbagni |
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MP04-13 |
Cancer Surveillance after Radical Cystectomy for Urothelial Carcinoma: A Novel Risk-Adapted Strategy |
Bladder Cancer: Epidemiology & Evaluation I | 17BOS |
Abstract: MP04-13 Sources of Funding: None Introduction Current guidelines for surveillance after radical cystectomy (RC) are based on pathologic stage and do not take into account other patient specific factors. We previously reported Weibull models determining duration of cancer surveillance. We now present a novel surveillance protocol outlining the frequency and duration of follow-up based on stage specific recurrence risk and competing risks of non-cancer mortality. Methods We identified 2205 patients who underwent RC for urothelial carcinoma (UC) at the Mayo Clinic from 1980 to 2010. The risks of abdomen/pelvis and chest recurrence were estimated using accelerated failure-time (AFT) models, stratified by pathologic stage (pT0, pTa/Cis/1, pT2, pT3/4, pTanyN+). Similarly, the risks of non-cancer death according to age (<60, 60-69, 70-79, >80) and Charlson comorbidity index (CCI <1 versus ≥1) were also calculated. Surveillance intervals were calculated for each conditional 1%, 3%, and 5% recurrence risk increase up to 10 years follow-up. Specific surveillance recommendations balance estimated risk of non-cancer death with recurrence risk where allowable recurrence risk is up to the risk of non-cancer death. Results At a median follow-up of 4.7 years (IQR 1.1, 10.3), disease recurrence was diagnosed in 852 (38.6%) patients. Using AFT models for recurrence, surveillance intervals for all stage, age, and comorbidity risk groups were generated. The surveillance strategy (e.g. 1%, 3%, or 5%) for an individual patient is selected based on probability of non-cancer specific mortality as determined by age and CCI (Tables 1 and 2). For example, a patient less than 60 with CCI ≤ 1 would follow a 1% recurrence risk schedule for the full 10 years. Conversely, a patient age 60-69 with a CCI > 1 would follow a 5% schedule for the full 10 years. Conclusions Using AFT modeling we have developed a risk-adapted protocol for surveillance frequency and duration after RC taking into account both the risk of recurrence and the risk of non-cancer mortality. Funding None
Authors
Ross Mason
William Parker Stephen A. Boorjian Suzanne Merrill Prabin Thapa Igor Frank |
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MP04-14 |
Survival Differences Among Bladder Cancer Patients According to Gender: Critical Evaluation of Radical Cystectomy Use and Delay to Treatment |
Bladder Cancer: Epidemiology & Evaluation I | 17BOS |
Abstract: MP04-14 Sources of Funding: This study was conducted with the support of the Institute for Translational Sciences at the University of Texas Medical Branch, supported in part by a by a Clinical and Translational Science Award Mentored Career Development (KL2) Award (KL2TR001441) from the National Center for Advancing Translational Sciences, National Institutes of Health, Comparative Effectiveness Research on Cancer in Texas (CERCIT) (RP140020) and the National Cancer Institute (NCI) (K05 CA134923) (SBW) and in part by the fellowship from University of Texas MD Anderson Cancer Center's Halliburton Employees Foundation (JH). Introduction To provide a population-based assessment regarding utilization and timing of radical cystectomy (RC) according to gender. Methods A total of 49,974 patients aged 66 years or older diagnosed with clinical stage TI-IV N0M0 bladder cancer from January 1, 2001 to December 31, 2011 from SEER-Medicare data were analyzed. We used multivariable regression analyses to identify factors predicting the use and delay of radical cystectomy. Cox proportional hazards models were used to analyze survival outcomes. Results Of the 49,974 patients diagnosed with bladder cancer 13,015 (26.0%) were female. Women were significantly more likely to undergo RC across all stages compared to their male counterparts (Stage I: Relative Risk (RR) 1.53, 95% Confidence Interval (CI) = 1.27-1.84, p < 0.001; Stage II: RR 1.52, 95% CI = 1.37-1.70, p < 0.001; Stage III: RR 1.26, 95% CI = 1.15-1.39, p < 0.001; Stage IV: RR 1.37, 95% CI = 1.17-1.47, p < .001). Moreover, there was no significant difference in delay to RC except women with Stage IV disease were less likely to have delay to RC than men (RR 0.67, 95% CI = 0.62-0.95, p=0.017). Using propensity score matching, women had improved overall (Hazard Ratio (HR) 0.85, CI 0.82-0.88, p < 0.001), but worse cancer-specific survival (HR 1.08, CI 1.02-1.15, p = 0.008) than men, respectively. Conclusions Gender differences persist with women significantly more likely to undergo RC independent of clinical stage. However, women have significantly worse cancer?specific survival than men. Delay from diagnosis to surgery did not account for this decreased survival among women. Funding This study was conducted with the support of the Institute for Translational Sciences at the University of Texas Medical Branch, supported in part by a by a Clinical and Translational Science Award Mentored Career Development (KL2) Award (KL2TR001441) from the National Center for Advancing Translational Sciences, National Institutes of Health, Comparative Effectiveness Research on Cancer in Texas (CERCIT) (RP140020) and the National Cancer Institute (NCI) (K05 CA134923) (SBW) and in part by the fellowship from University of Texas MD Anderson Cancer Center's Halliburton Employees Foundation (JH).
Authors
Justin E. Fang
Jinhai Huo Preston Kerr Tamer Dafashy Cameron Ghaffary Leslie Ynalvez Jacques G. Baillargeon Edwin Morales Simon Kim Padraic O'Malley Yong-Fang Kuo Eduardo Orihuela Douglas S. Tyler Stephen J. Freedland Ashish M. Kamat Stephen B. Williams |
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MP04-15 |
THE PREVALENCE AND IMPACT OF PREOPERERATIVE FRAILTY: A PROSPECTIVE STUDY OF PATIENTS UNDERGOING CYSTECTOMY |
Bladder Cancer: Epidemiology & Evaluation I | 17BOS |
Abstract: MP04-15 Sources of Funding: American Cancer Society Seed Grant. Introduction Perioperative morbidity is common amongst patients undergoing radical cystectomy. Frailty (decreased functional reserve) measurement has been proposed to identify at-risk patients, but there has been limited comparative prospective analysis of different frailty measures. Methods 98 cystectomy patients at our institution from January 2015 to September 2016 were prospectively evaluated preoperatively, using the protocols for the four frailty indices: Duke Activity Status Index (DASI), Edmonton Frailty Index (EFI), Fried Frailty Index (FFI) and Schonberg Mortality Index (SMI) by a urology resident. Consensus Statement malnutrition assessment was performed by a dietitian. We examined the relationship between frailty, patient characteristics (age, neoadjuvant chemotherapy, malnutrition), and outcomes (length of stay 30-day readmission, 30-day Clavien grade > 2) were examined. Results Median DASI was 39.4 (IQR: 26.9, 58.2), median EFI was 3 (IQR: 2, 4.2), median FFI was 2 (IQR: 1, 3), and median SMI was 12 (IQR: 9.7, 15). The median age of cystectomy patients was 71 years (IQR: 62, 77). 66 of 98 (67.3%) patients underwent neoadjuvant chemotherapy while preoperative malnutrition was present in 32 of 98 (32.6%) patients. With respect to outcomes: median length of stay was 7 days (IQR: 5, 8), 30-day readmission rate was 25.8%, and the 30-day complication rate was 41.8%. The associations of variables with the four frailty indices are displayed in Table 1. Increased age was significantly associated with all four indices. Neoadjuvant chemotherapy was only associated with the FFI (p=0.04). The presence of malnutrition was associated with the EFI (p=0.02), FFI (p<0.01), and SMI (p=0.04). The SMI was only index related to postoperative outcomes, as increased SMI was associated with both 30-day complications (p=0.04) and 30-day readmission (p<0.01). Conclusions Different frailty indices appear to measure different aspects of functional status. In this prospective evaluation, frailty was associated with age, malnutrition, and complications to varying degrees. The SMI was the strongest predictor of readmission and postoperative complications in patients undergoing cystectomy. Evaluation of patients preoperatively can be used to better counsel patients about postoperative complication risk._x000D_ Funding American Cancer Society Seed Grant.
Authors
Conrad Tobert
Nathan Brooks Lewis Thomas Chermaine Hung Sarah Bell Kenneth Nepple |
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MP04-16 |
PERIOPERATIVE AND LONG TERM OUTCOMES AFTER RADICAL CYSTECTOMY IN HEMODIALYSIS PATIENTS |
Bladder Cancer: Epidemiology & Evaluation I | 17BOS |
Abstract: MP04-16 Sources of Funding: none Introduction End stage renal disease patients on hemodialysis (HD) have in increased risk of developing bladder cancer, which is more likely to present in an advanced stage. These patients also have significant risk of non-cancer related morbidity and mortality, especially from cardiovascular disease. Radical cystectomy (RC) is the standard of care for non-metastatic muscle invasive bladder cancer, but is associated with significant morbidity. Despite this high risk scenario, very little is known regarding outcomes in HD patients following RC._x000D_ Methods The US Renal Disease System database was used for this study, which is a prospective database which includes every HD patient in the United States. A retrospective review of all HD dependent patients who underwent radical RC for bladder cancer between 1989-2013 was performed. Competing risks analysis was used to estimate overall and disease specific survival. Cox regression was used to identify predictors of death. Results During the 25-year study period, a total of 1594 patients were identified for analysis, of whom 76.1% were male. The mean age was 70.4 ± 9.8 years. Mean length of stay was 16.2 ± 14.8. Concurrent nephrectomy was undertaken in 33.1% of patients. The 30-day mortality rate was 5.9%. Overall 1, 3, and 5-year survival was 58.4%, 31.4%, and 19.6% respectively. Bladder cancer specific survival at 1, 3, and 5 years was 89.3%, 82.3%, and 80.0% respectively. Predictors of overall mortality were age (HR, 1.03; 95%CI, 1.02-1.03), history of congestive heart failure (CHF) (HR, 1.19; 95%CI, 1.03-1.38), history of diabetes (HR, 1.22; 95%CI, 1.04-1.42), concurrent nephrectomy (HR, 1.09; 95%CI, 1.03-1.14), and female sex (HR, 1.15; 95%CI, 1.01-1.33). Amount of time on HD prior to RC was not predictive of mortality. _x000D_ Conclusions This represents the largest study to date evaluating outcomes following RC in HD patients. RC is associated with significant morbidity and less than 20% of patients survive 5 years. Older patients, female patients, and those with a history of CHF or diabetes are at an increased risk of mortality._x000D_ Funding none
Authors
Scott Johnson
Zachary Smith Joseph Rodriguez III Gary Steinberg |
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MP04-17 |
Blood-based biomarkers as predictors of oncologic outcomes for non-muscle-invasive urothelial bladder carcinoma |
Bladder Cancer: Epidemiology & Evaluation I | 17BOS |
Abstract: MP04-17 Sources of Funding: none Introduction Our group has previously demonstrated that blood-based tumor markers can be useful clinical outcome predictors for non-muscle invasive urothelial carcinoma of the bladder (UCB) Our aim in this study is to further evaluate the predictive value of CEA, CA 19-9 and CA 125 on disease recurrence and progression. _x000D_ Methods We prospectively included 328 consecutive patients between February 2008 and August 2014 to measure preoperative serum levels of CEA, CA 19-9 and CA 125 before first transurethral resection of the bladder (TUR). Institutional Ethical Committee approval was obtained prior to this study. Patients diagnosed with pT2 UBC were excluded (42), leaving 286 patients for analysis of recurrence or progression. After first TUR, patients were followed with routine cystoscopy, cytology and ultrasound every 6 months. All patients with non-muscle invasive (NMI) bladder cancer with high-grade disease, previous recurrence, carcinoma in situ (CIS) or T1 received induction and maintenance intravesical BCG. Results We found that CEA and CA 19-9 levels were significantly higher in patients who had either tumor recurrence and/or progression compared to those who had no UBC recurrence during follow-up (p=0.02; p=0.03). As we had found previously, however, CA 125 levels did not differ between the two groups (p=0.42). Overall, mean CEA level was 2.1 (0.2-12.8), CA 19-9 was 17.1 (0.4-189.9) and CA 125 was 12.5 (1.2-103.9). In patients who presented tumor recurrence and/or progression, mean CEA was 5.5, mean CA 19-9 was 21.0 and CA 125 was 13.8, while in the non-recurring group, mean CEA was 3.1, mean CA 19-9 was 11.1 and CA 125 was 11.3. Mean follow-up was 4.9 years. Patients were 70.3% males (201); 63.3% (181) of patients had pTa at first TUR. Concomitant carcinoma in situ was present in 25 cases (8.7%). Conclusions Biomarkers utilized in routine follow-up of other malignancies, such as CEA and CA 19-9, can also be included in UCB management, since it proved able to distinguish a higher risk group of patients that could be managed accordingly. Future studies may add these blood-based tumor markers to a predictive model and validated in a larger cohort. Although CA 125 was not significantly associated with oncologic outcome, further studies are required before excluding this potential biomarker in UBC. Funding none
Authors
Daher Chade
Andre Machado Ricardo Waksman Guilherme Garcia Paulo Esteves Sanarelly Adonias Flavio Areas Luis Botelho Mauricio Cordeiro Claudio Murta Leopoldo Ribeiro-Filho Alvaro Sarkis Shahrokh Shariat Diogo Bastos Carlos Dzik Miguel Srougi William Nahas |
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MP04-18 |
SMOKING INTENSITY AS A PREDICTOR OF SURVIVAL IN BLADDER CANCER PATIENTS: RESULTS FROM A POPULATION-BASED FLORIDA CANCER REGISTRY (1981-2009) |
Bladder Cancer: Epidemiology & Evaluation I | 17BOS |
Abstract: MP04-18 Sources of Funding: None Introduction There is limited information regarding the association between smoking intensity and survival trends among patients with bladder cancer (BC). We examined demographic and survival trends for patients diagnosed with BC stratified by smoking intensity._x000D_ Methods The Florida Cancer Data System (FCDS) linked with US census data was used to identify all smoking adult patients ?18 years residing in Florida diagnosed with BC between 1981 and 2009. Median and 5-year overall survival rates were compared between patients that smoked <1, 1-2, and >2 packs of cigarettes per day (PPD). A multivariable Cox regression model was used to determine the adjusted hazard ratio (AHR) along with 95% confidence interval (95% CI) for mortality after adjustment for age at diagnosis, sex, race, ethnicity, socioeconomic status (SES), marital status, regional lymph node positvity, treatment, grade, and stage of BC. _x000D_ Results Of the 14,077 smoking BC patients, 25%, 63%, and 12% smoked <1, 1-2, and >2 PPD, respectively. The majority of patients were males (74%), Whites (96%), living in an urban area (94%), and with a middle-high/highest SES (53%). The majority of them had localized BC (73%). Median overall survival and 5-year survival rates for the entire cohort were 4.0 years and 43.7% (95%CI: 42.7-44.7), respectively. Median overall survival for patients smoking <1, 1-2, and >2 PPD was 4.2 years, 3.9 years, and 4.1 years, respectively. The 5-year survival rates for patients smoking <1, 1-2, and >2 PPD were 45.1% (43.1-47.1), 43.1% (41.8-44.3), and 43.6% (40.9-46.3), respectively. Patients smoking 1-2 PPD ([HR] 1.11; 95% CI 1.06-1.16, p<0.001) and >2 PPD ([1.08] 1.00-1.16, p=0.042] were significantly more likely to have a higher risk of mortality compared to patients that smoked <1 PPD on multivariate analysis._x000D_ Conclusions Higher smoking intensity is associated with an increased risk of mortality among patients with BC. These data highlight the importance of smoking cessation for BC patients and underscore the need for patient education regarding the dangers of smoking. Smoking cessation efforts should be targeted to this population since even a small reduction in the amount of smoking may still have potential survival benefit. Funding None
Authors
LuÃs Felipe Sávio
Tulay Koru-Sengul Diana M Lopategui Feng Miao Nachiketh Soodana Prakash Bruno Nahar Vivek Venkatramani Sanjaya Swain Sanoj Punnen Dipen J Parekh Chad Ritch Mark L. Gonzalgo |
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MP04-19 |
Prognostic impact of serum CYFRA 21-1 among classic tumor markers in patients with non-metastatic but potentially lethal bladder cancer |
Bladder Cancer: Epidemiology & Evaluation I | 17BOS |
Abstract: MP04-19 Sources of Funding: none Introduction No serum prognosticator has been established in patients with potentially lethal bladder cancer. The aim of this study is to evaluate the prognostic impact of serum CYFRA 21-1 (CYFRA) in these patients compared with classic tumor markers. Methods Serum levels of CYFRA and other classic tumor markers: CA19-9, SCC, and C-reactive protein (CRP) were measured in 66 patients with T1G3 (n = 20) or muscle invasive bladder cancer (n = 46) without metastasis between Jan 2011 and Aug 2015. Cut-off values of the tumor markers were determined by receiver operating characteristic analyses. Prognostic values of age, gender, T stage, hydronephrosis, albumin, hemoglobin, CA19-9, SCC, CRP, and CYFRA were evaluated using multivariate analysis with a Cox proportional hazards model. Results The median (range) value of CYFRA was 2.6 (1.1-34) ng/mL. The median follow-up period was 24.3 (1.1-58.1) months. Prognostic values of age (< 73 vs. ≥ 73), T stage (< T2 vs. ≥ T2), hydronephrosis (absence vs. presence), albumin (cut-off 4.0 g/dL, median), hemoglobin (cut-off 12.7 g/dL, median), CA19-9 (cut-off 21 U/mL), SCC (cut-off 1.5 ng/mL), CRP (cut-off 0.1 mg/dL), and CYFRA (cut-off 3.5 ng/mL) were evaluated dichotomously. Multivariate analyses revealed that CYFRA (p = 0.017) was the only significant and independent predictor of cancer-specific survival. Risk of cancer-specific mortality was 4.48-fold (95% CI, 1.37-18.27; p = 0.012) higher in CYFRA-high patients than in CYFRA-low/either classic tumor marker-high patients._x000D_ _x000D_ Figure. Cancer-specific survival curves according to CYFRA and classic tumor markers status Conclusions The current results indicated that cancer-specific mortality of non-metastatic bladder cancer could be better predicted by CYFRA than other previously reported tumor markers. Further prospective analyses will be needed to confirm our results. Funding none
Authors
Akihiro Yano
Kojiro Tachibana Shunsuke Hiranuma Hironori Sugiyama Makoto Kagawa Hideki Takeshita Yohei Okada Makoto Morozumi Satoru Kawakami |
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MP04-20 |
The association between mortality and distance to treatment facility in patients with invasive bladder cancer |
Bladder Cancer: Epidemiology & Evaluation I | 17BOS |
Abstract: MP04-20 Sources of Funding: None Introduction Muscle-invasive bladder cancer (MIBC) and its treatment are associated with high morbidity and mortality. The concentration of care in tertiary centers is believed to improve patient outcomes but the potential negative impact of travel distance on quality of care and survival is unclear in MIBC as it may be associated with delay in diagnosis, decreased access to multimodal care and difficulty in managing the complications associated with care. Using data from the National Cancer Data Base (NCDB), we evaluated the association between distance to treating facility and overall mortality in patients with MIBC. Methods Data were obtained from NCDB 2004-13. We evaluated all cause mortality for patients with MIBC (T2-T4a, N0, M0), stratified by travel distance to treatment facility in 3 categories: <12.5, 12.5-49, 50-250 miles. Cox proportional hazard models were fit in the overall population, then in subgroups according to treatment facility type. A secondary analysis was done examining the interaction between distance and facility type. Results 34,729 patients with MIBC identified. The three groups included 20,234 (58.3%), 10,400 (29.9%), 4,095 (11.9%) patients living <12.5, 12.5-49, 50-250 miles from their treatment facility, respectively. Kaplan -Meier curve constructed for overall survival separated by distance (Figure 1). HRs for distance and mortality are reported in table 1. There was a trend towards decreased probability of mortality as distance to facility increased; this relationship was significant when traveling a long distance for care at an academic facility . Conclusions Lengthy travel distance to treating facility was not associated with decreased survival in patients with MIBC. In contrast, travel distance was associated with improved overall survival if the treatment facility was an academic center. Funding None
Authors
Stephen Ryan
Patrick Karabon Gregory Mills Moritz Hansen Matthew Hayn Mani Menon Quoc-Dien Trinh Firas Abdollah Jesse Sammon |
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MP05-01 |
Management and prognosis of positive surgical margins after radical prostatectomy: retrospective analysis of a contemporary cohort |
Prostate Cancer: Localized: Radiation Therapy I | 17BOS |
Abstract: MP05-01 Sources of Funding: none Introduction Positive surgical margins (PSM) after RP are a known factor associated with BCR. Radiation therapy (RT) currently represents an established option for metastasis-free patients. However, the timing of administration is not univocal._x000D_ The aim of this study is to identify factors related to the indication to adjuvant radiation therapy (aRT) vs salvage (sRT), taking a picture of the contemporary management and prognosis of patients with PSM after radical prostatectomy (RP) at an academic tertiary institution. Methods We retrospectively reviewed our perspectively-maintained database. RP has been performed with an open retropubic approach until 2010, then with a robotic transperitoneal one._x000D_ All the cases with PSM and adverse pathological features (stage ≥pT3, GS ≥8) were submitted to a multidisciplinary discussion. The indication to sRT was given if biochemical recurrence (BCR, PSA 0.2 ng/ml), preferably before PSA >0.5 ng/ml._x000D_ Logistic regression models were used to determine the factors associated with RT indication and BCR in univariate and multivariate analysis. The BCR-free survival was calculated using Kaplan-Meier method. Results Out of 789 patients, 197 had PSM (overall prevalence 25,2%), with monofocal involvement in 121 (60.8%) and multifocal in 78 (39.2%). _x000D_ An aRT was indicated in 40 patients (20.3%). Findings are summarized in table 1. Factors independently related to aRT indication were: pathological stage, number of sites of PSM and post-operative PSA. The median follow-up time was 51.1 months (IQR 30.9-69.3). Among the 157 patients for whom aRT was not indicated, 39 experienced a relapse of PSA (prevalence of BCR 24.8%, p not significant). 26 were then treated by sRT, 8 by androgen deprivation therapy, 5 underwent surveillance. Overall, a BCR was found in 46 patients (23.4%) after a median time of 24.0 months (IQR 18.0-36.0)._x000D_ At the last available control 176 patients (89.3%) had a PSA < 0.2 ng/ml (median value 0.02). Only pathological stage was significantly related to the risk of BCR. Conclusions In a real-life scenario, the indication to aRT is more restrictive than what recommended by guidelines and is driven by the amount of PSM and a detectable post-operative PSA. No differences in BCR free survival are evident in patients with PSM submitted to aRT vs sRT. Funding none
Authors
Carlotta Palumbo
Alessandro Antonelli Giacomo Galvagni Irene Mittino Maria Furlan Stefania Zamboni Simone Francavilla Marco Lattarulo Angelo Peroni Claudio Simeone |
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MP05-02 |
CRITICAL ASSESSMENT OF RADIOTHERAPY FOLLOWING RADICAL PROSTATECTOMY: TIMING OF RADIOTHERAPY, RECURRENCE AND OUTCOMES |
Prostate Cancer: Localized: Radiation Therapy I | 17BOS |
Abstract: MP05-02 Sources of Funding: none Introduction Level one evidence and current NCCN guidelines recommend adjuvant radiotherapy (ART) for patients with adverse pathologic features following radical prostatectomy. Salvage radiotherapy (SRT) administered upon detection of biochemical recurrence may be an appropriate alternative limiting overutilization of radiotherapy in the majority and cost?effective. We sought to describe our outcomes using salvage radiotherapy. Methods A total of 1,269 consecutive patients diagnosed with localized prostate cancer who underwent robot?assisted radical prostatectomy (RARP) from 2002 to 2013 were included. Biochemical recurrence was defined as 0.2 ng/mL or greater on 2 consecutive visits following surgery. Primary outcomes included BCR, prostate cancer specific mortality (PCSM), and overall mortality (OM). Cost estimates for radiotherapy administered were calculated based on 2016 Medicare reimbursement rates. Results Of the 1,269 men who underwent RARP at median follow?up of 5.0 years, 227 (17.9%) men had BCR. According to NCCN guidelines, ART was recommended to 436 (34.4%). Of these eligible patients, 273 (62.6%) had no ART with no subsequent BCR; 84% had follow?up exceeding 2 years. The remaining 163 (37.4%) men did have BCR of which 32 (2.5%) received ART concurrent with androgen deprivation therapy. The remaining had salvage therapy including 27 (2.1%) with SRT alone (Table 1). Overall and PCSM was 59 (4.7%) and 18 (1.4%), respectively. Medicare expense for ART is $37,130.85. Following NCCN guidelines would equate to an additional $10 million in radiotherapy costs in men with no subsequent BCR. Given >80% in this NCCN ART group with no evidence of disease 2+ years, the risk of further progression in the ART group is minimal (<10%). Conclusions For men with adverse pathologic features the risk of overtreatment with ART ranged from 67?85%. These outcomes are consistent with prior reports suggesting utilization of SRT may be more cost effective and have comparable outcomes to ART. These results support current clinical trials underway discerning the utility of SRT in men with adverse pathologic features. Funding none
Authors
Linda Huynh
Stephen Williams Thomas Ahlering |
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MP05-03 |
Continence after post-prostatectomy Intensity Modulated Radiation Therapy |
Prostate Cancer: Localized: Radiation Therapy I | 17BOS |
Abstract: MP05-03 Sources of Funding: none Introduction Limited data exist regarding urinary continence after post-radical prostatectomy (RP) intensity modulated radiation therapy (IMRT) and whether IMRT influences urinary continence or interfere with the recovery from RP when given early. Methods 118 men were treated with curative-intent RT after RP. Forty-three men (36%) received adjuvant RT (13%) and early salvage (23%) within the 1st year from surgery and 75 men (64%) received late salvage RT (>1year from RP). Quality of life measures were prospectively assessed using the Expanded Prostate Cancer Index Composite (EPIC-26) by patients at baseline and at follow-up times. Each group (early and late RT) was compared to a control group from our prospective collected RP cohort that did not had RT based on age at RP, BMI, pre-operative incontinence scores and post-operative incontinence scores and pad usage. The control group included 248 men with a median follow-up time of 44 months. Due to differences in stage of the RP and RT cohorts, it was not possible to control for sparing of the neurovascular bundles. Endpoints are pad usage and incontinence score. Results With a median follow-up time of 60m, in men treated with IMRT, 29 patients (25%) deteriorated in pad usage, 14 (12%) improved and 75 (63%) were stable. Deterioration in continence was correlated with poor baseline incontinence scores (p<0.001) and with pre-RT number of pad usage per day. Of the patients that scores 100 in the incontinence score, only 3% deteriorated in continence. _x000D_ In the early (<1 year) RT group, mean incontinence score improved from 57 to 72 (p<0.01) and in the late RT group, mean incontinence score deteriorated from 80 to 69 (p<0.001) and was associated with a 13% deterioration in pad-free rates (p<0.05). _x000D_ Comparison to the control group showed a 12% and 5% differences in pad-free status in the late RT group and the early RT group respectively. Comparison of the entire cohort to the control group showed a 10% higher pad free rate in the control group - 74% Vs. 64% (p<0.001) (figure 1) _x000D_ Conclusions Late salvage RT caused 12% deterioration in pad-free status._x000D_ With the limitations of our control group, comparison to the cohort group showed 10% lower pad free rates after post prostatectomy RT. _x000D_ Deterioration in continence is strongly associated with the baseline urinary function._x000D_ Funding none
Authors
Itay Sagy
Nimrod Barashi Shay Golan Scott eggener Stanley Liauw Arieh Shalhav |
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MP05-04 |
Effectiveness of combination therapy of external-beam radiation and high dose-rate brachytherapy for high-risk prostate carcinoma |
Prostate Cancer: Localized: Radiation Therapy I | 17BOS |
Abstract: MP05-04 Sources of Funding: none Introduction Our institution is a high volume center of radiotherapy for prostate cancer patients (PCaPts). We have performed either neoadjuvant androgen deprivation therapy (NADT), followed by external-beam radiation therapy (total 39 Gray) and high dose-rate brachytherapy (HDR-B, total 18 Gray) (NEH) or radical prostatectomy (RP) on high-risk PCaPts, as defined by prostate specific antigen (PSA) level (>20ng/mL), pathology of biopsy specimen (Gleason score [GS]: ≥8), and/or clinical staging (≥T3). No comparative studies have been reported for NEH and RP. In order to determine if NEH is a better therapy than RP, we compared biochemical recurrence-free survival (bRFS, i.e., post therapeutic PSA elevation) and overall survival (OS) between NEH and RP on high-risk PCaPts. Methods Between 2007 and 2012, 192 and 167 high-risk PCaPts were treated by NEH and RP, respectively. Biochemical failure (BF) for NEH was defined using Phoenix definition: any PSA increase of >2 ng/mL higher than the PSA nadir value, regardless of the PSA nadir value. Whereas BF for RP was defined as PSA values of >0.2 ng/mL. Of note, PSA of 18 RP-cases (10.8 %) did not decrease to less than 0.2 ng/mL. In these cases, the day of PSA nadir was defined as BF date. Difference between bRFS and OS were calculated using Kaplan-Meier method and log-rank tests. Results The median follow-up duration was 58.7 months. Age was significantly older in NEH group (median [interquartile range] = 71.9 [67.3-75.3] years) than in RP group (69.0 [64.9-72.3] years, p< 0.001, Mann-Whitney U test [MWU]). Initial PSA was higher in NEH (20.0 [10.1-43.6]) than RP group (15.9 [8.1-24.7] ng/dL, p<0.01, MWU). RP group had a trend of higher GS (72.1%) than NEH group (62.5%, p=0.07, chi square test). T stage was similar (NEH [66.1 %] vs RP [66.4 %], p=0.928, chi square test). The 5- and 7-year bRFS rates in NEH group (0.79 and 0.76, respectively) were significantly higher than those in RP group (0.51 and 0.41, respectively, p<0.001 each, Fig. 1A). However, in OS, no significant difference was found (p=0.838). Conclusions We retrospectively compared clinical outcomes of NEH and RP, and found that NEH might be as effective as RP for high-risk PCaPts. Currently, we are preparing prospective randomized case study comparing NEH and RP by adjusting age, GS, PSA, and T stage. Funding none
Authors
Kenjiro Suzuki
Suguru Shirotake Koshiro Nishimoto Soichi Makino Hideyuki Kondo Takashi Okabe Yota Yasumizu Kiichiro Kodaira Shingo Kato Masafumi Oyama |
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MP05-05 |
Long-term outcomes of men with stage pT3b prostate cancer diagnosed by seminal vesicle biopsy and treated by brachytherapy and external beam irradiation |
Prostate Cancer: Localized: Radiation Therapy I | 17BOS |
Abstract: MP05-05 Sources of Funding: none Introduction Men diagnosed after prostatectomy with seminal vesicle invasion often have external beam irradiation (EBRT) as adjuvant treatment. Typically, men treated with radiation do not have assessment or treatment for T3b because it is often not detected. We report our results of seminal vesicle biopsy (SVB) in men with higher risk features planning to undergo permanent seed implant (PSI) followed by EBRT. Methods Of 1981 men who treated by PSI and followed 5-22 years (mean 10), 615 (31%) with high risk features had 6 TRUS guided biopsies of the SV (3 from each side). Patients with +SVB underwent laparoscopic pelvic lymph node dissection and those with positive nodes, bone or CT scans were excluded from implantation. 3 months of hormone therapy (NHT) was followed by Pd-103 implant to the prostate (dose 100 Gy) and proximal SV and 2 months later 45 Gy of conformal or image guided EBRT to prostate and SV only. NHT was given a median of 9 months. Within 2 months after treatment CT-based dosimetry was done with radiation doses converted to the biologic effective dose (BED). Biochemical freedom from failure (BFFF) was computed by the Phoenix definition, freedom from metastasis (FFM) in men with BF by absence of a positive bone or CT scan and cause-specific survival (CSS) by freedom from death in men with clinical recurrence. Association of risk features to +SVB were compared by chi-square and linear regression (LR). Survival was computed by Kaplan-Meier estimates with comparisons by log rank and Cox hazard rates (HR). Results 53/615 (9.4%) had +SVB. Higher stage, Gleason score (GS) and PSA were associated with a positive SVB (p<0.001). LR demonstrated significance for stage (p<0.001) and GS (p=0.001). BED was higher in patients receiving a SV implant (202. Vs. 179.3 Gy2, p<0.001). BFFF, FFM and CSS was worse for +SVB (all p<0.001). 48/53 (90.6%) with +SVB had NCCN3 (high risk) status. BFFF in these men without and with a +SVB was 88.5 vs. 74.9%, 75.3 vs. 62.2% and 70.3 vs 62.2% at 5, 10 and 15 years (p=0.023). FFM was 99.3 vs. 89.6%, 96.5 vs. 84.4% and 94.9 vs. 75% (p<0.001) and for CSS was 99.6 vs. 97.8%, 96.4 vs. 82.1% and 91.3 vs. 65.7% (p<0.001). CSS by BED < 180 vs ≥ 180 Gy2 was 55.6 vs. 76.9% (p=0.406). In these high-risk patients, prostate cancer death was 40/314 (12.7%) for men with -SVB and 8/21 (38.1%) for +SVB (OR 4.22, 95%CI 1.6-10.8). Cox HR demonstrated GS (p=0.001, HR 1.9), BED (p=0.05, HR 0.991) and +SVB (p<0.001, HR 0.125) as significantly associated with CSS. Conclusions Men who have pT3b disease have inferior BFFF, FFM and CSS. Advanced stage and high GS are highly associated with a +SVB. Higher radiation dose is associated with improved CSS in the pT3b patients. Taken together these data suggest SVB should be performed in men presenting with high GS and stage when considering combination radiation therapy. When performing PSI, implantation of the SVs will increase dose and improve long-term cause-specific survival. Funding none
Authors
Nelson Stone
Richard Stock |
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MP05-06 |
Long-term survival in men with Gleason score 9-10 treated with prostate brachytherapy and external beam irradiation |
Prostate Cancer: Localized: Radiation Therapy I | 17BOS |
Abstract: MP05-06 Sources of Funding: none Introduction Very high grade prostate cancer is associated with poor outcomes. We report on the long-term outcomes of men with Gleason score (GS) 9-10 prostate cancer treated by prostate brachytherapy (PSI) and external beam irradiation (EBRT). Methods Of 1981 men who were treated by PSI and followed 5-22 years (mean 10), GS was ≤6 in 1304 (65.8%), 7 in 466 (23.5%), 8 in 142 (7.2%) and 9-10 in 69 (3.5%). Men with positive bone or CT scans were excluded from implantation. 3 months of hormone therapy (NHT) was followed by Pd-103 implant to the prostate (dose 100 Gy) and 2 months later 45 Gy of conformal or image guided EBRT. NHT was given a median of 9 months. Within 2 months after treatment CT-based dosimetry was done with radiation doses converted to the biologic effective dose (BED). Biochemical freedom from failure (BFFF) was computed by the Phoenix definition, freedom from metastasis (FFM) in men with BF by absence of a positive bone or CT scan and cause-specific survival (CSS) by freedom from death in men with clinical recurrence. Association of risk features to GS 9-10 were compared by chi-square and linear regression (LR). Survival was computed by Kaplan-Meier estimates with comparisons by log rank and Cox hazard rates (HR). Results Mean age was 65.6 years (median 66, range 39-85); mean PSA was 9.4 ng/ml (median 6.7, range 0.3-300) and mean BED 194.6 Gy (median 200, range 15-299). Median BED for GS9-10 was 199 Gy2. BFFF, FFM and CSS by GS are shown in the table. The mean survival time for the 4 GS groups was: 1) 21.5 years (95%CI 21.2-21.8), 2) 19.2 years (95%CI 18.6-19.7), 3) 18.1 years (95%CI 17.2-19.1) and 4) 13.9 years (95%CI 13.1-14.8, p<0.001). Only clinical stage was associates with CSS with 15-year survival for ≤ T2a 100%, T2b-c 40.5% and T3 0% (p=0.025). Cox HR for CSS was significant for stage (p=0.055, HR 2.0) and BED (p=0.081, HR 0.985). Conclusions PBI combined with EBRT has excellent 15-year survival in men with GS 9-10 and clinical stage ≤ T2a. While 68% of men with T3 GS9-10 are alive at 10 years, at 15-year survival was 0. These men should be considered for alternate treatment strategies, possibly with early systemic therapy. Funding none
Authors
Nelson Stone
Richard Stock |
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MP05-07 |
Prolonged hormonal therapy and external beam radiation independently increase the risk of persistent hypogonadism in men treated with prostate brachytherapy |
Prostate Cancer: Localized: Radiation Therapy I | 17BOS |
Abstract: MP05-07 Sources of Funding: none Introduction We sought to identify variables that may predict persistent hypogonadism and castration in patients with prostate cancer (PCa) treated with brachytherapy (BT). Methods A retrospective analysis was performed on a prospectively maintained database of patients receiving BT ± external beam radiation therapy (EBRT) ± hormone therapy (HT) for NCCN low, intermediate or high-risk prostate cancer at a single institution between 1990-2011 with a minimum follow-up of 5 years. Patients were categorized as receiving no HT (n=438, 41.6%), ≤ 6 months (n=317, 31.1%) or > 6 months (n=298, 28.3%) of HT. Those receiving combination HT within one year of final testosterone (T) measurement were excluded, as well as patients receiving salvage ADT at any time. 5 and 10-year freedom from persistent hypogonadism (T<280 ng/dL) and castration (T<50 ng/dL) for each group was evaluated with Kaplan-Meier estimates. Multivariable cox proportional hazards models were used to compare risk of persistent hypogonadism and castration at a median follow-up of 6.5 years (post-treatment to final T) (IQR: 4.3-9.1 years; Range: 1.0-19.2 years). Results Of 1,981 patients receiving BT for clinically localized PCa, 1,053 met inclusion criteria. The 5-year freedom from hypogonadism rates were 92.4%, 88.9% and 87.0% for patients with no HT, ≤ 6 months and > 6 months of HT, respectively (10-year rates: 66.7%, 55.3%, 40.5%); 5-year freedom from castration rates were 99.2%, 98.0% and 98.4%, respectively (10-year rates: 97.9%, 95.5%, 90.9%). In multivariable analyses, number of months of HT (continuous variable, HR=1.04, p=.030) and BT with EBRT vs. BT alone (HR=1.56, p=.010) significantly increased the risk of persistent hypogonadism. Older age (HR=1.04, p<.001) and diabetes (HR=1.43, p=.048) were also significant. Number of months of HT was the only variable which increased the risk of persistent castration (HR=1.09, p=.014). Conclusions EBRT is an independent risk factor for persistent hypogonadism among patients receiving BT for PCa. The mechanism of this finding needs to be elucidated, but may be secondary to scatter radiation during EBRT. Prolonged HT additionally increases the risk for persistent hypogonadism and castration. Funding none
Authors
Daniel Sagalovich
Kyrollis Attalla David Paulucci John Sfakianos Ketan Badani Ashutosh Tewari Richard Stock Nelson Stone |
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MP05-08 |
The impact of baseline serum testosterone on the risk of biochemical failure after definitive radiation therapy for prostate cancer: more favourable oncological outcomes in hypogonadal invididuals |
Prostate Cancer: Localized: Radiation Therapy I | 17BOS |
Abstract: MP05-08 Sources of Funding: none Introduction The exact role of pre-treatment (baseline) total serum testosterone (BST) is still controversial in patients with prostate cancer (PCa) and conflicting results are reported in the literature. We assessed the impact of BST on the risk of biochemical failure (BF) in patients with PCa and treated with definitive radiation therapy (RT). Methods The current study is a retrospective analysis of 360 prospective patients diagnosed with non-metastatic PCa between 2002 and 2014 and enrolled into seven different prospective multicentric phase II-III trials performed at our institution. All patients received definitive RT after initial diagnostic workup which included PSA and BST assessment. Patients were stratified according to hypogonadal (BST<11 nmol/L) vs. non-hypogonadal state (BST≥11 nmol/L). The ability of this BST cut-off to predict BF was assessed in Kaplan-Meier analyses, as well as in univariable and multivariable Cox regression analyses. Internal validation of our findings was performed using bootstrap resampling with 10,000 replications. Results The median (IQR) age at diagnosis was 71 years (65-74). Median (IQR) PSA was 7.7 ng/mL (5.6-12.1). Testosterone ranged from 0.7 to 28.9 nmol/L (mean: 11 nmol/L; median 10.2 nmol/L; IQR 8.3-13.0 nmol/L). The number of patients with BST < 11 nmol/L was 209 (58.0%), while a total of 151 patients had a BST ≥ 11 nmol/L (42.0%). A total of 272 patients (75.6%) had available BMI data, which ranged between 17.5 and 52.6, without significant differences between the two groups (p=0.1). ADT was administered only to 108 patients (30%), including all individuals diagnosed with PSA > 20 ng/mL. Median follow-up was 72 months. Overall, BF-free survival rates at 96 months was 79.6% (95% CI: 72.3-87.6%) in hypogonadal vs. 65.1% (95% CI: 55.3-76.7%) in non-hypogonadal individuals (p=0.042). In multivariable Cox regression analyses, BST < 11 nmol/L was associated with a significantly reduced risk of BF (HR: 0.50; CI 0.30-0.83; p = 0.007). After 10,000 bootstrap resamples, virtually the same results were recorded. Conclusions Oncologic outcomes for PCa after primary radiation therapy are affected by pre-treatment testosterone levels. Individuals with lower baseline testosterone levels experienced more favourable biochemical failure rates after adjusting for the use of ADT. As many still debate about the role of testosterone in PCa, our findings need to be validated in larger patient cohorts. Funding none
Authors
Emanuele Zaffuto
Pierre I. Karakiewicz Helen Davis Bondarenko Sami-Ramzi Leyh-Bannurah Guila Delouya Carole Lambert Jean-Paul Bahary Marie Claude Beauchemin Maroie Barkati Cynthia Ménard Markus Graefen Alberto Briganti Fred Saad Daniel Taussky |
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MP05-09 |
Risk of hospitalization following outpatient prostate brachytherapy |
Prostate Cancer: Localized: Radiation Therapy I | 17BOS |
Abstract: MP05-09 Sources of Funding: None Introduction Transrectal prostate brachytherapy is a common outpatient procedure for the treatment of clinically-localized prostate cancer. While the long-term morbidity and toxicities of prostate brachytherapy are widely published, rates of short-term complications are largely unknown. We aim to determine the incidence of acute hospital visits for treatment-related complications of outpatient prostate brachytherapy and to identify associated risk favors. Methods Patients who underwent prostate brachytherapy (CPT code 55875) for prostate cancer (ICD9 code 185) in an ambulatory surgery setting were identified in the Healthcare Cost and Utilization Project (HCUP) State Ambulatory Surgery Database for California between 2007-2011. Emergency department visits and inpatient admissions within 30 days of treatment were determined from the California HCUP State Emergency Department Database and State Inpatient Database, respectively. Risk factor analysis was performed using multivariate logistic regression. Results Over five years, 8,188 patients underwent brachytherapy for prostate cancer. Within thirty days, 576 (7.0%) patients experienced 686 hospital visits. Emergency department visits comprised the majority of the encounters (623 visits (79.8%), at a median time from surgery of 5 days (IQR 1-13). Inpatient hospitalizations occured on 158 visits (20.2%) at a median 11 (IQR 5-20) days from surgery. Common presenting diagnoses included urinary retention n=335 (42.9%), hematuria n=59 (7.6%), and urinary tract infection n=47 (6.0%)._x000D_ Logistic regression demonstrated that increasing patient age (65-75 years: OR 1.3 (95% CI 1.1-1.6); >75 years: OR 1.6 (95% CI 1.3-2.1)) and any inpatient admission within 90 days prior to surgery (OR 1.6 (95% CI 1.3-1.9) increased the risk of requiring hospital-based medical evaluation following outpatient brachytherapy. Baseline medical comorbidity (Charlson score) did not influence risk. Conclusions Emergency department visits and inpatient admissions are common following prostate brachytherapy, though at less frequent rates than previously reported. Risk of readmission is higher in elderly patients and those who have had recent inpatient hospitalizations. Funding None
Authors
Robert H. Blackwell
William S. Gange Belinda Li Jennifer L. Saluk Matthew A. Zapf Anai A. Kothari Robert C. Flanigan Paul C. Kuo Gopal N. Gupta |
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MP05-10 |
Long-term urinary symptoms following prostate brachytherapy |
Prostate Cancer: Localized: Radiation Therapy I | 17BOS |
Abstract: MP05-10 Sources of Funding: none Introduction Urinary symptoms in men who are treated with prostate brachytherapy (PSI) are known to worsen over time. We explored which patient and treatment related factors were associated with increased IPSS score in men who presented with minimal symptoms prior to treatment. Methods Of 1981 men followed a minimum 5 years (mean 10, range 5-22), 1842 (93%) had pre-implant and last IPSS. 1110 (60.3%) had minimal initial urinary symptoms (score of 0-7). There were 491 (44.2%) low risk men treated with PSI alone or with 3-6 months of neoadjuvant hormone therapy (NHT) for prostate size > 50cc, 218 (19.6%) intermediate risk men treated with PSI plus NHT, or 76 (6.8%) with external beam irradiation (45 Gy EBRT) and 325 (29.4%) high risk treated by PSI/NHT/EBRT. NHT was given a median of 9 months. Median prostate volume (PV) was 37 cc (range 2.4-188.1). Data was prospectively collected on comorbidities. Radiation dose was converted to the biological effective dose (BED). Initial IPSS was compared to last by student-t test (2 tailed). Survival estimates for minimal symptoms increasing to moderate or severe (IPSS 8-19 and 20-35) were determined by Kaplan-Meier method with comparisons by log rank and Cox Hazard Rates (HR). Results The change from pre-treatment score to last IPSS score for the minimal, moderate and severe symptoms was: 3.6 to 7.3 (p<0.001), 11.6 to 11.3 (p=0.426) and 24.1 to 16.9 (p<0.001). For those with minimal symptoms the 10 and 15 year estimates for freedom from worse symptoms were 72.9 and 39.1%, respectively. The 10 and 15 year estimates for pre-treatment and treatment related factors for freedom from increased IPSS are shown in the table. Cox HR for the significant variables were age (1.02, p=0.024), implant type (p=0.019), BED (1.005, p=0.005) and HTN (0.766, p=0.019). Diabetes, heart disease, race, stroke, PV, and atrial fibrillation were not significant. Conclusions While most symptomatic men have improved scores, a substantial number of men with low IPSS experience worsening urinary symptoms with long-term follow up after PSI. Age, implant type, radiation dose and HTN are risk factors for an increase in IPSS. Funding none
Authors
Nelson Stone
Jared Winoker Jamie Cavallo Steven Kaplan Richard Stock |
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MP05-11 |
Prostate Brachytherapy and TURP: Pre-implant Symptom Severity Has Greater Influence than Timing of TURP on Long-Term Urinary Quality of Life |
Prostate Cancer: Localized: Radiation Therapy I | 17BOS |
Abstract: MP05-11 Sources of Funding: None Introduction Numerous studies have examined urinary symptoms and incontinence risk in brachytherapy (BT) patients undergoing transurethral resection of the prostate (TURP), but there are limited data on quality of life (QOL) outcomes in this population. We aimed to evaluate the long-term impact of TURP and BT on QOL, in particular, as a function of pre-treatment symptom severity and timing of TURP in relation to implantation. Methods 1848 patients underwent BT with or without external beam radiation therapy (EBRT) for the diagnosis of prostate cancer between October 1990 and May 2011 and were followed a minimum of 5 years. In total, 160 (8.7%) patients underwent TURP before or after implant for refractory urinary symptoms or retention. International Prostate Symptom Scores (I-PSS) and QOL bother scores were recorded prior to implantation and at follow-up evaluations. Patients were subdivided by timing of TURP - pre-implant (n=85), post-implant (n=69), pre- and post-implant (n=6) - and compared to patients not receiving TURP (n=1688). Paired t-test was used to analyze changes in QOL, stratified by pretreatment I-PSS. Chi-squared test and multivariate logistic regression were used to assess clinical and treatment-related factors predictive of worse long-term QOL. Results Median follow up after implantation was 9.0 years and median time to post-implant TURP was 20.0 months. Across all groups, men with mild pretreatment I-PSS had worsening urinary QOL (p<.001), while those with severe pretreatment I-PSS improved (p=.005). This was also true for men who never had a TURP (p<.001 for mild, p<.001 for severe). Men with moderate symptoms undergoing TURP had no significant QOL change (p=.89). In men with pretreatment QOL score < 2, age over 65 years was the only predictor of poor QOL (score ≥ 3) at last follow up; EBRT, hormone therapy, and BED > 200 Gy had no influence on reported QOL in these men. Conclusions Most BT patients regressed toward the mean over time with respect to urinary QOL, irrespective of receipt or timing of TURP. Men with worse urinary QOL who underwent a post-implant TURP improved while men with a mild QOL bother score were worse after TURP. These data suggest a more conservative approach should be considered when electing a post-implant TURP unless patients have significant bother. Funding None
Authors
Jared S. Winoker
Kyle A. Blum Harry Anastos Richard G. Stock Nelson N. Stone |
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MP05-12 |
Race, Comorbidities and Long-Term Erectile Function After Prostate Brachytherapy: What Role Does Each Have on Potency Preservation |
Prostate Cancer: Localized: Radiation Therapy I | 17BOS |
Abstract: MP05-12 Sources of Funding: none Introduction Limited data is available on the influence of race on long-term potency preservation after prostate seed implant brachytherapy (PSI). We sought to identify if race and comorbidities effect long-term erectile function (EF) following PSI. Methods 1,909 patients were identified from a prospectively managed database who underwent PSI for T1-T3 localized prostate cancer from 1990 to 2011. Median follow up time was 9.2 years (range 5-22). Patients were stratified by race and treatment type (PSI alone, PSI + EBRT, PSI + neoadjuvant hormone therapy (NHT) or PSI + EBRT and NHT. EF was assessed by SHIM questionnaire grouped into 4 categories (A: 0-7, B: 8-11. C:12-16 and D: 17-25) where C and D were considered potent. EF was recorded at initial, 5 year and last visit. NHT was given a median of 6 months. Last testosterone (T) levels were recorded a median 6 years after PSI. Pre- and post-treatment variables were compared by ANOVA, chi-square and multivariable regression. Potency preservation was estimated by Kaplan-Meier method with comparisons by log rank and Cox hazard rates (HR). Results There was no difference in SHIM scores between races pre-treatment. Caucasians (CC) were older than African Americans (AA) and Hispanics (H) (p=0.002). 42.6% of CC received implant alone compared to 32.5% of AA, and 28.9% of H (p<0.001). Combination therapy was more common in AA (40.8%) and H (41.3%) compared to 25.9% for CC (p<0.001). NHT was given to 59.8% of CC, 62.6% of AA and 61.2% of H men (p=0.001). EF was preserved overall in 82.5% and 40% at 5 and 10 years. Cox HR for EF included pre-SHIM score (HR 1.69, p<0.001), age (HR 1.04, p<0.001) and NHT use (HR 1.05, p=0.011). Total radiation dose, type of implant, race, T level and HD, diabetes, hypertension were not significant. Conclusions The presence of HD, pretreatment EF, age and prolonged use of NHT negatively impact EF. Other comorbidities and race do not appear to influence long-term preservation of potency. Funding none
Authors
Kyle A. Blum
Carl A. Olsson Jared S. Winoker Jamie A. Cavallo Richard Stock Nelson N. Stone |
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MP05-13 |
The Cost of Treatment for Localized Prostate Cancer |
Prostate Cancer: Localized: Radiation Therapy I | 17BOS |
Abstract: MP05-13 Sources of Funding: Ajmera Family Chair in Urologic Oncology Introduction Treatment options for localized prostate cancer include radical prostatectomy (RP) and radiation therapy (RT). Treatment choice depends on patient age, comorbidity and preferences as well as tumor characteristics. . Initial treatment decisions can have long-term consequences that can result in complications, possible future secondary treatments and significant economic impact. We sought to compare 5-year annual treatment-related complication (TRC) costs for patients treated with RP or RT for localized prostate cancer._x000D_ Methods We performed a population-based retrospective cohort study of all men ?18 years old who underwent RP or RT (external beam or brachytherapy) for clinically localized prostate cancer in Ontario, Canada from 2002 to 2009. Costs were determined using a validated costing algorithm using linked administrative databases, to capture inpatient hospital admissions, emergency department visits, cancer clinic visits, physician billings and Ontario Drug Benefit Plan medication usage for 5 years after treatment (including costs for initial treatment). Costs for medical care unrelated to management of prostate cancer or its treatment-related complications were excluded. Costs were adjusted for inflation to 2015 Canadian dollars. We matched men treated with RP and RT 1:1 using a propensity-score including age, income quintile, co-morbidity score and year of diagnosis. Negative binomial regression was used to assess the association between treatment modality and costs. Results In total, 28,849 men underwent treatment for localized prostate cancer from 2002 – 2009 in Ontario. Men who underwent RT (n=12,675) were older, from less affluent neighborhoods and had more comorbidities than men who underwent RP (n=16,174, p<0.001). Men who underwent RT had higher total 5-year per patient treatment-related costs than men who underwent RP ($16,716/pt vs. $13,213/pt), with a mean incremental difference of $3,503/pt._x000D_ Men who underwent RT had a lower relative cost in their first year after treatment, compared to those receiving RP (RR 0.97, 95% CI 0.94 – 1.0, p=0.025). There was no difference in relative cost in year two (p=0.1). In years 3, 4 and 5, RT had a significantly higher relative cost than RP (p<0.05 for all). _x000D_ Conclusions Men who undergo RT have significantly higher 5-year total treatment-related costs compared to men who undergo RP. Relative costs are higher in the first year for patients treated with RP and increasingly higher in subsequent years for patients treated with RT. Funding Ajmera Family Chair in Urologic Oncology
Authors
Alaina Garbens
Christopher Wallis Refik Saskin Robert Nam |
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MP05-14 |
Morbidities of Radiofrequency Tracking Beacons vs Cone Beam CT (CBCT) Image-guided Radiotherapy on Prostate Cancer |
Prostate Cancer: Localized: Radiation Therapy I | 17BOS |
Abstract: MP05-14 Sources of Funding: None Introduction External beam radiation therapy is a common modality for prostate cancer, although acute and chronic side effects remain significant. Radiofrequency tracking beacons allow for real-time tracking of the prostate using 3 non-coplanar markers and intrafraction monitoring of prostate position and is one modality of image guidance that may help to decrease local radiation exposure._x000D_ _x000D_ This study retrospectively evaluated the acute and chronic morbidities of radiofrequency tracking beacons vs CBCT radiotherapy. Methods This is a IRB-approved single center retrospective review of patients who presented to St. Elizabeth Hospital for radiofrequency tracking beacons or CBCT for prostate cancer during April 2010 - December 2011. Inclusion criteria were T1/T2 prostate cancer without prior radiation, prostatectomy, or brachytherapy. A total of 191 patient charts were reviewed and 131 patients were included: 55 cone-beam and 76 beacons transponders. Short-term and long-term morbidites were recorded: short-term were defined as under two years and long-term was defined as lasting or beginning greater than two years after treatment. These toxicities were graded using the Radiation Therapy Oncology Group (RTOG) toxicity grading system. Significance was set as p<0.05 and analyzed using single variate analysis. Results There were no significant differences between age, Gleason score, starting PSA, and use of anti-androgens between the treatment_x000D_ groups. The short term morbidities of CBCT vs radiofrequency tracking beacons were_x000D_ significantly different (p<0.01) at 27.3% and 59.2%, respectively._x000D_ Nocturia (p<0.01) and hematuria (p=0.05) were significantly higher in the radiofrequency beacons. Long-term morbidities of CBCT vs tracking beacons were_x000D_ not significant (p=0.59) with values of 5.5% vs 7.9%. There were no_x000D_ significant differences in biochemical cancer recurrence._x000D_ Conclusions For short-term morbidities, beacons transponders patients experienced side effects significantly more than CBCT patients, particularly those of nocturia and hematuria._x000D_ This may be due to irritation from beacon placement and increased radiation dosage when using beacons transponders._x000D_ _x000D_ The long-term morbidities correlate with current literature as there were no significant differences in biochemical cancer recurrence and long-term morbidities between standardly used radiation modalities. This study suggests that beacons transponders do not decrease the amount of radiation associated short-term morbidities._x000D_ Funding None
Authors
Virginia Li
Carl Peterson |
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MP05-15 |
Heterogeneous outcomes in Gleason Score 7 prostate cancer patients are associated with differential biological effective dose and hormone utilization |
Prostate Cancer: Localized: Radiation Therapy I | 17BOS |
Abstract: MP05-15 Sources of Funding: None Introduction The prognostic heterogeneity in patients with Gleason Score (GS) 7 prostate cancer (PC) is owed to the more aggressive behavior of GS 4+3 vs. 3+4 disease. Modifications in the Gleason grading system were proposed to address these differences in cancer behaviors when reporting GS 7 PC, as Grade Group 3 portends a higher likelihood of systemic spread compared to Grade Group 2. Prognostic differences are recognized in patients undergoing surgical extirpation; we therefore sought to investigate differences in outcomes between Groups 2 and 3 patients treated with radiotherapy with or without hormone therapy (HT). Methods A retrospective analysis was performed on a prospectively maintained database of patients receiving brachytherapy ± external beam radiation therapy ± hormone therapy (HT) for NCCN low, intermediate or high-risk PC at a single institution between 1990-2011. Patients with a minimum follow-up of 5 years were included. Kaplan-Meier survival analyses were used to compare GS 3+4 vs 4+3 for the study endpoints of biochemical recurrence (BCR; Phoenix criteria), distant metastases, and cancer specific survival (CSS), with and without stratification by biological effective dose (BED; <150 vs. 150-200 vs. >200 Gy). Cox proportional hazards model was used to assess risk of BCR over time, adjusting for HT receipt, GS, stage, PSA, and BED. Results 472 patients were identified with GS 7 PC; 276 with GS 3+4 and 196 patients with GS 4+3. No significant differences were seen in BCR (p=0.349), distant metastasis (p=0.07), and CSS (p=0.62) in GS 3+4 vs. 4+3. Among patients with PSA > 10 ng/ml or stage > T2b, significant differences in biochemical freedom from failure (BFFF) were observed for GS 3+4 vs. 4+3 stratified by escalating BED (table 1). Neoadjuvant HT improved 10-year BFFF from 81.3% to 88.2% for GS 3+4 and from 66.3% to 87.6% for GS 4+3 (p=0.021). Cox proportional hazards model demonstrated HT receipt (HR 11.86, 95% CI 1.26 – 112.06, p=0.031) and total BED (HR 0.98, 95% CI 0.97 – 0.99, p=0.001) significantly impact time to BCR. Conclusions BCR, distant metastasis, and CSS were similar between patients in Group 2 and 3 PC treated with radiotherapy. Higher BED substantially improves BFFF in higher risk patients with PSA >10 and stage > T2b, especially in Group 3. Higher dose and neoadjuvant HT should be strongly considered in GS 7 PC with adverse features. Funding None
Authors
Kyrollis Attalla
Daniel Sagalovich Nikhil Waingankar Reza Mehrazin Richard Stock Nelson Stone |
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MP05-16 |
What is the impact of diabetes mellitus on radiation induced proctitis after radical radiotherapy for adenocarcinoma prostate? |
Prostate Cancer: Localized: Radiation Therapy I | 17BOS |
Abstract: MP05-16 Sources of Funding: Prostate Cancer UK. Introduction Long-term complications of diabetes include cardiovascular disease, retinopathy, nephropathy, and neuropathy. Diabetic patients with prostate cancer could be at a high risk of radiation-induced proctitis following radical radiotherapy. Our aims were to determine whether diabetic patients treated by radical radiotherapy for prostate cancer have higher incidence, severity, and duration of radiation proctitis. Methods 716 patients with prostate cancer were recruited. Patients were stratified into diabetic patients and non-diabetic patients. The incidence, severity, and duration of proctitis were the main outcomes. A polynomial ordered logistic regression was fitted to determine the influence of diabetes status, age, blood pressures medication, co-morbidities, Gleason score, PSA after treatment, and tumour stage on the grades of proctitis. Time to resolution per year was modelled as a negative binomial generalised linear model. Results Data exploratory analysis suggested that the only highly significant explanatory variable was the presence or absence of diabetes. Polynomial ordered logistic regression, however, showed that the presence (or not) of diabetes remained as the only significant predictor (t = -2.74; p = 0.0059) of severity of proctitis (Figure 1). A negative binomial generalised linear model showed that both grade of proctitis (z = -17.178; p < 0.001), and diabetes (z = -5.92; p < 0.001), were highly significant predictors of time to resolution. Conclusions Diabetic patients were significantly more likely to have proctitis after radical radiation therapy for prostate cancer. Diabetes was significantly associated with an induced risk of radiation induced proctitis and also with deceleration of its resolution. Funding Prostate Cancer UK.
Authors
Catherine Paterson
Abduelmenem Alashkham Stephen Hubbard Ghulam Nabi |
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MP05-17 |
Shift to Seed Stranding in Prostate Brachytherapy – Are There Consequences? |
Prostate Cancer: Localized: Radiation Therapy I | 17BOS |
Abstract: MP05-17 Sources of Funding: none Introduction Prostate brachytherapy is an effective option for the treatment of low-to-intermediate risk localized prostate cancer (CaP). Post-implant dosimetry, based on computerized tomography (CT) or magnetic resonance imaging (MRI), remains an important part of brachytherapy treatment protocols to ensure adequate prostate dosing. New techniques, including the use of strands of radionuclide seeds, have been developed in recent years with the goal of improving delivery of radiation to the prostate while maintaining efficacy and minimizing radiation to surrounding structures. In this study, we evaluate the impact of transitioning from loose seeds to stranded seeds based on dosimetry delivered to the prostate and rectal wall and post-implant PSA values._x000D_ Methods We retrospectively reviewed the charts of 225 patients who underwent Palladium-103 prostate brachytherapy seed implant for low-to-intermediate risk prostate cancer January 2003-August 2013. 91 patients underwent implantation of loose seeds (LS) between January 2003 and June 2006 and 134 patients underwent placement of stranded seeds (SS) between June 2007 and August 2013. Pre-treatment variables including gland volume, Gleason score and prostate-specific antigen (PSA) were similar between the two cohorts with the exception of age. Post-implant dosimetry quality and critical organ dosimetry were assessed by determining the minimal dose received by 90% of the prostate gland (D90), the dose covering 50% of the rectal wall (D50) and the percent volume of the prostate with a dose 200% of the prescription (V200). These values were then compared between the LS and SS cohorts. PSA levels were recorded approximately 3 months and 12 months after implantation._x000D_ Results The D90 and the mean D90 as a percentage of the prescribed dose were unchanged after transitioning to SS. The decrease in rectal wall D50 after transitioning from LS to SS was statistically significant (p<0.005). Similarly, the V200 decline from 28.1 cm 3 to 16.8 cm3 after changing to SS was also statistically significant (p<0.005). Mean PSA at 3 months after seed implantation was 1.10 ng/mL for the LS group and 1.34 ng/mL for the SS group. At one year, mean PSA was 0.60 ng/mL for the LS group and 0.69 ng/mL for the SS group. There was no statistically significant difference between the two groups in terms of post-implant PSA values. Conclusions In our patient cohort, the shift from loose to stranded seeds resulted in the same radiation dose to the prostate with no significant difference in post-treatment PSA while decreasing unnecessary radiation to surrounding organs._x000D_ Funding none
Authors
Elizabeth Malm-Buatsi
Patricia Heller Elizabeth Koehne Bradley Moore Julie M Riley Steven Westgate Mark R Wakefield |
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MP05-18 |
Prostate Fiducial Marker Placement in Patients While on Anticoagulation: Feasibility Prior to Prostate SBRT |
Prostate Cancer: Localized: Radiation Therapy I | 17BOS |
Abstract: MP05-18 Sources of Funding: None Introduction Fiducial marker placement is required in patients undergoing robotic-based Stereotactic Body Radiotherapy (SBRT) for prostate cancer in order to track the six degrees of prostate motion that occur intrafractionally, during treatment. Many patients take anti-coagulant medication due to other comorbidities. Anticoagulation therapy can cause patients to bleed during procedures and, in general practice, are often temporarily discontinued prior to invasive medical procedures to reduce that risk. Some patients may not be able to temporarily discontinue anticoagulation therapy due to an increased risk of a thromboembolic event from their comorbid medical conditions_x000D_ _x000D_ _x000D_ Methods From August 2015-October 2016 23 consecutive patients on chronic anticoagulation therapy who were not cleared to stop these medications underwent TRUS-guided fiducial marker placement for SBRT/Image Guided Radiation Therapy. The reasons for patients being on anticoagulation therapy were recent stent placement (11,) myocardial infarction (7,)atrial fibrillation (3,) and pulmonary embolus (2.)The anticoagulation consisted of Plavix (9,)Aspirin (7,)Coumadin (3,)Lovenox (2,)Eliquis (1,)Brillinta (1,)Pradaxa (1,)and Effient (1,) All patients received 4 fiducial markers placed under Transrectal ultrasound guidance (TRUS.) EMLA Cream and lidocaine gel were used to numb the perineum and rectum. 2 needles each double loaded with 2 gold fiducial markers with a spacer in between were placed transperineally into the prostate. 2 fiducial markers were placed at the right and left base and 2 fiducial markers were placed at the right and left apex. Patients had a CT scan after procedure to confirm ideal geometry of the marker placement. The needles were withdrawn as was the ultrasound transducer. Gentle pressure was applied by the nursing staff. All patients were monitored for bleeding afterwards by a registered nurse_x000D_ _x000D_ _x000D_ Results All 23 patients who were on anticoagulation and underwent fiducial marker placement were discharged home the same day of the procedure. No patient experienced significant bleeding in the peri-procedural window and no patient had any untoward cardiovascular event._x000D_ Conclusions This series suggests active anticoagulation is not an absolute contraindication to fiducial marker placement _x000D_ in patients undergoing SBRT or IGRT for prostate cancer._x000D_ Transperineal fiducial marker placement appears to be safe in patients on active anticoagulation medication. These patients should be closely monitored after the procedure for bleeding complications._x000D_ Funding None
Authors
Jonathan Haas
Aaron Katz Joshua Harris Todd Carpenter Susan Carbone Thomas Kole Steven Pristupa Matthew Witten Seth Blacksburg |
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MP05-19 |
Outcomes of treatment for localized prostate cancer in a single institution; comparison of radical prostatectomy vs radiation therapy ~Propensity Score Matching Analysis~ |
Prostate Cancer: Localized: Radiation Therapy I | 17BOS |
Abstract: MP05-19 Sources of Funding: None Introduction Radical prostatectomy (RP), intensity modulated radiation therapy (IMRT) and brachytherapy (BT) are three major definitive treatment modalities for localized prostate cancer in recent years. While a lot of technical progress are seen in this decade, patients with localized prostate cancer are often struggling with making a decision of their treatment. It might be due to luck of information in terms of comparing the outcomes among these modalities since only few reports are seen in the literature. _x000D_ We analyzed the results of three treatment modalities using propensity score in a single institution in Japan._x000D_ Methods From Jan 2004 to Dec 2015, a group of 2272 patients with clinically localized prostate cancer treated with RP (570pts), IMRT (391pts) and BT(1311pts) were identified in our institution. The records of RP(n=410) , IMRT(n=276) and BT(n=1034) patients with a minimum of 2 years of follow-up (total 1720) were reviewed. Propensity scores were calculated using multivariable logistic regression based on the covariates including patient's age, preoperative PSA, Gleason score, number of positive cores, clinical T stage. Each cohort were categorized according to NCCN risk classification and biochemical outcomes plus overall survival were examined. Biochemical failure was defined as RP: PSA >0.2ng/ml, IMRT, BT: nadir PSA level +2ng/ml. Results Median follow-up was 75 months (mo) for RP, 57 mo for IMRT and 64 mo for BT patients. After adjustment of propensity scores, a total of 300 patients (150 each) and 468 patients (234 each) were matched for RP vs IMRT cohort and RP vs BT cohort, respectively. Kaplan-Meier analysis did not show any statistically significant differences in terms of overall survival in these two cohorts (RP vs IMRT:p=0.421, RP vs BT:p=0.764). Regarding biochemical failure free survival, there was statistically significant differences in all risk group in RP vs IMRT cohort (High-risk: p=0.000, Intermediate-risk: p=0.001, Low-risk: p=0.007), while significant differences were observed in low (p=0.003), intermediate (p=0.006) risk group among RP vs BT cohort. Conclusions Our mid-term outcomes for localized prostate cancer using propensity score analysis demonstrated no significant differences in overall survival. Despite the difference of biochemical failure definition, IMRT and BT improved biochemical failure free survival compared to RP with excellent tumor control. Funding None
Authors
Narihiko Hayashi
Yumiko Yokomizo Kimito Osaka Hisashi Hasumi Kazuhide Makiyama Keiichi Kondo Noboru Nakaigawa Masahiro Yao Eiko Ito Madoka Sugiura Shoko Takano Yuki Mukai Takeo Kasuya Masataka Taguri |
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MP05-20 |
Adjuvant Radiation referral patterns in men with high-risk prostate cancer |
Prostate Cancer: Localized: Radiation Therapy I | 17BOS |
Abstract: MP05-20 Sources of Funding: none Introduction Studies have shown that adjuvant radiation therapy (ART) decreases biochemical recurrence after radical prostatectomy in men with adverse features. Guidelines recommend including these patients in a shared decision making (SDM) discussion about the risk and benefits of ART. Despite possible benefits, ART is not commonly prescribed. Our objective is to understand the relationship between adverse features and referral to Radiation Oncology (RO) in high-risk patients who had a SDM discussion with their urologist. Methods Pathologic data was prospectively collected at a single site on all radical prostatectomy specimens from 2009-2015. Patients with adverse features were selected, defined as positive surgical margins (SM), extraprostatic extension (EPE), and seminal vesicle invasion (SVI). All patients had a negative 3-month postoperative PSA. Chart review recorded ART discussion in the notes, explicit recommendation for ART, referral to RO for ART, receipt of ART, and if a patient was referred for salvage therapy. Univariable logistic regression analysis for each individual adverse feature was performed, and a second analysis for patients with 2 or more features. Results 200 patients had any adverse feature. ART was discussed in 131 (66%) and recommended to 46 (23%). Thirty-nine patients (19.5%) had a consultation with RO for ART, 24 (12%) underwent ART, and 30 (15%) were referred for salvage therapy. The likelihood of recommendation for ART was 6.7%, 14.3%, 20%, and 52% for SM, EPE, SVI, and 2 or more risk factors, respectively. Odds ratios are presented in Table 1. Conclusions To our knowledge, this is the first study to examine how adverse features influence referral for ART after a SDM discussion after prostatectomy. In our study, ART was discussed with the majority of patients but an explicit recommendation was underutilized. A single individual adverse feature negatively correlated to recommendation, whereas multiple adverse features were strongly associated with referral. Funding none
Authors
Stephen Ryan
Gregory Mills Matthew Cheney Matthew Hayn |
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MP06-01 |
Evaluation of the Relationship between the Donor and Recipient during Kidney Transplant |
Transplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery I | 17BOS |
Abstract: MP06-01 Sources of Funding: None Introduction In 2014, approximately 6,100 people in the United States underwent living donor nephrectomy. Unlike other types of organ donation, this patient population has a longer-than-average life expectancy due to strict selection criteria. Greater than 99% of patients that donated a kidney at Cedars-Sinai Medical Center donated to an immediate family member, relative, or close friend. Our study seeks to qualify and quantify functional changes in the relationship between the donor and the recipient before and after surgery as well as to identify perioperative complications and stress to determine if patients are content with their decision to donate. Methods From 2002-2012, 532 patients underwent donor nephrectomy for kidney transplant at Cedars-Sinai Medical Center. After IRB approval, a randomized subset of these patients were administered a standardized questionnaire regarding his or her experience. We assessed if each patient would undergo the donation process again, now having more intimate knowledge and appreciation of the pre- and post-operative surgical and medical course. Results Of the fifty patients who participated in our survey, 92% stated that their relationship with the recipient improved after surgery. Of the 8% that noted a deterioration in the relationship, there was a distribution of dissatisfaction with relation to the sexual relationship (n=1), recipient personality changes (n=1), or divorce (n=2). Approximately 10% of patients experienced a complication related to surgery, all of which were clavian grade I-II. Examples of these included incisional hernia (n=3, upper midline incision, BMI>30 kg/m2) and urinary tract infection (n=2). Overall, 98% of patients were extremely satisfied with the donation process and would not hesitate to participate again. Only one patient stated that he would not donate again, as he developed an unanticipated glomerulonephropathy not related to surgery that required hemodialysis. Conclusions Our research demonstrates that the act of donating a kidney overwhelmingly enhances the bond between the donor and recipient. Even donors who noted a decline in their relationship with the recipient all stated that they would still donate if faced with the same decision again. This suggests that the relationship with the recipient is of highest importance and a crucial component of pre-operative counseling that should be emphasized. Our urology group has started to incorporate this practice in our management with great success. Funding None
Authors
Christopher Dru
D. Joseph Thum Devin Patel Justin Houman Gerhard Fuchs |
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MP06-02 |
Serum sialyl hybrid typed N-glycan levels predicts early ABMR in living donor kidney transplant patients |
Transplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery I | 17BOS |
Abstract: MP06-02 Sources of Funding: This work was supported by JSPS KAKENHI grant number 15K15579 and grant number 25220206. This work was also supported by Japanese Society for Clinical Renal Transplant for an incentive scheme of clinical research grant 2014. Introduction ABMR is a diagnostic challenge in living donor kidney transplant (LKTx) medicine, and there is a need to identify predictive markers of ABMR to improve graft survival. The use of serum N-glycans as a predictive biomarker of ABMR has not yet been tested. In the present study, we performed serum N-glycomics in transplant patients and evaluated its potential as a predictive serum-based biomarker of early ABMR. Methods N-glycomics in whole serum and immunoglobulins (Igs) fraction were performed in randomly selected 16 recipients with biopsy-proven ABMR occurred within 1 month after LKTx, 40 recipients with biopsy-proven TCMR, and 141 recipients without any adverse events. The putative structure of N-glycans was analyzed by MALDI-TOF-MS analysis. Results Serum sialyl hybrid-type N-glycans (m/z 1709, 1871, and 2033) levels before LKTx and on postoperative Day 1 (POD1) was significantly lower in recipients who developed ABMR than non-ABMR group. The m/z 2033 N-glycan <1.3 μM and the presence of preformed donor-specific antibodies (DSA) on POD1 were found to yield a higher odds ratio for prediction of ABMR than did other factors according to logistic regression analysis. Receiver-operating characteristic area under the curve for m/z 2033 < 1.3 μM combined with preformed-DSA status was 0.86. Combined preformed DSA with m/z 2033 N-glycan status; thus, double-positive patients (preformed-DSA positive and m/z 2033 < 1.3 μM) or single-positive patients (preformed-DSA positive or negative and m/z 2033 > 1.3 μM or < 1.3 μM) can cover all 16 ABMR cases. These results suggest that the combined indicator holds promise for identification of patients who will not develop ABMR by means of serum samples collected on POD1. Although, N-glycan profile of immunoglobulin (Ig)s fractions compared with those of whole-serum, ABMR-related N-glycans in Igs fractions were not detected. Therefore, the ABMR-related N-glycans carrying proteins are not an Igs. Conclusions The serum m/z 2033 sialyl hybrid-type N-glycan combined with preformed DSA status may predict acute ABMR in patients undergoing LKTx. _x000D_ Funding This work was supported by JSPS KAKENHI grant number 15K15579 and grant number 25220206. This work was also supported by Japanese Society for Clinical Renal Transplant for an incentive scheme of clinical research grant 2014.
Authors
Daisuke Noro
Tohru Yoneyama Shingo Hatakeyama Yuki Tobisawa Kazuyuki Mori Yasuhiro Hashimoto Takuya Koie Masakazu Tanaka Shinichiro Nishimura Hideo Sasaki Mitsuru Saito Hiroshi Harada Tatsuya Chikaraishi Hideki Ishida Kazunari Tanabe Shigeru Satoh Chikara Ohyama |
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MP06-03 |
Robot Assisted Transplant Allograft Nephrectomy Series: A Novel Approach for a Challenging Operation |
Transplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery I | 17BOS |
Abstract: MP06-03 Sources of Funding: None Introduction Despite improvements in medical care, surgical removal of failed transplant renal allografts may be mandated by sepsis, bleeding, pain, or erythropoietin resistance. Transplant nephrectomy has historically been performed in an open fashion by transplant surgeons and carries morbidity up to 50% with mortality up to 7%. To date, there is a single reported case of robot assisted transplant allograft nephrectomy from a deceased donor kidney. We herein present our series of robotic assisted transplant nephrectomy (RTN). Methods All patients who underwent robotic allograft nephrectomy at Mayo Clinic Arizona were included. Patients were not excluded for undergoing a concurrent procedure. All RTN were performed by a single Urologist (EPC) in conjunction with a single Transplant surgeon (NNK) via a transperitoneal approach utilizing a dual console Da Vinci Robotic Si/Xi surgical system. Study design was retrospective and observational. Variables analyzed included: demographics (age, BMI, ASA), comorbidities, transplant related (time from transplant to transplant nephrectomy, living related or deceased donor transplants), operative variables (operative time, estimated blood loss and additional procedures performed) peri-operative variables (length of stay (LOS), drain duration, Foley catheter duration, and hemoglobin change), and 30-day Clavien-Dindo complications. All variables were analyzed by non-parametric tests with commercially available software (SPSS vs, 21, Chicago, Illinois Results Six patients underwent RTN between 10/31/2014 until 4/31/2016. The time from transplant to transplant nephrectomy was a median of 5.9 years (range: 0.3 - 40). The majority of transplants were from deceased donors (66%). The median operating time was 306 minutes (range: 178 – 532). Of note, in two of the six RTN cases bilateral laparoscopic native nephrectomies were performed and in a third case a robotic nephrectomy and a lymph node biopsy by plastic surgery was performed. There were no intraoperative complications or conversions to open nephrectomy. Estimated median blood loss was 150 mL (range: 100 – 400), with a transfusion rate of 16%. Drains were utilized in 84% of patients and for a median of 2 days. There were three minor complications. Conclusions In this first reported series of robotic transabdominal allograft nephrectomy we demonstrate the safety and feasibility of the use of robotic technology for transplant nephrectomy. This is a small series that includes our learning curve. Funding None
Authors
Rafael Nunez
Nicholas Jakob Sean McAdams Kelli Gross Haidar Abdul-Muhsin Nitin Katariya Erik Castle |
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MP06-04 |
Safety and efficacy of sofosbuvir-based Direct-Acting Antiviral Agents in kidney transplant recipients with hepatitis C virus infection: a systematic review and meta-analysis |
Transplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery I | 17BOS |
Abstract: MP06-04 Sources of Funding: This study was supported by the National Natural Science Foundation of China (Grant No. 81370855, 81200551, 81300627, 81200551 and 81470980), the Prostate Cancer Foundation Young Investigator Award 2013 and Foundation of Science & Technology Department of Sichuan Province (Grant No. 2013SZ0006 and 2015SZ0230). Introduction Hepatitis C Virus (HCV) infection affects more than 200 million people worldwide. The infection rate of HCV reaches approximately 1.8% to 8% in kidney transplant (KTx) recipients, which is much higher than that of normal people because of the repeated blood transfusion, dialysis, and immunosuppression. In current work, we aimed to perform a systematic review and meta-analysis to evaluate the efficacy and tolerability of sofosbuvir (SOF)-based Direct-Acting Antiviral Agents (DAAs) in KTx recipients. Methods A systematic literature search of MEDLINE, EMBASE, The Cochrane Library, Web of Science, and ClinicalTrials.gov was performed to identify clinical trials evaluating SOF-based DAAs in KTx with HCV infection published or in press from 2012 to present. Effect sizes were collected as pooled event rates (sustained viral response, SVR12 or SVR4) with corresponding 95% CIs. All statistical analyses were conducted by R 3.3.1. Results Eleven studies with a total of 360 KTx recipients were finally included. Most KTx recipients (88.1%) had HCV-1 infection. A total of 24 patients who received dual or combined organs transplants were reported. The overall rate of SVR12 reached 94% (95%CI: 88% to 97%). No significant heterogeneity was observed (p=0.92). SVR4 reached 99% (95%CI: 93% to 100%). The clearance rate of HCV RNA at the end of treatment (EOT) (12 weeks) was 94% (95%CI: 87% to 97%). The rate of rapid virological response (RVR) was 73% (95%CI: 55% to 85%; I2=58.9%, P=0.045). The SOF-based DAAs did not impact the kidney function, whereas the liver enzyme parameters (such as ALT, ATS) had decreased during. The most frequent AEs were headache 6.9% (n=25/360), asthenia 4.4% (n=15/360), and fatigue 3.3% (n=12/360). Conclusions In summary, our meta-analysis represented the first systematic review to evaluate the efficacy and safety of SOF-based DAAs in the post-KTx setting for a total of 360 patients from eleven individual studies. Data from current analysis suggest that SOF-based DAAs therapy is a highly effective treatment with an SVR12 rate (94%) and excellent tolerability, compared to prior interferon therapy for KTx recipients. Funding This study was supported by the National Natural Science Foundation of China (Grant No. 81370855, 81200551, 81300627, 81200551 and 81470980), the Prostate Cancer Foundation Young Investigator Award 2013 and Foundation of Science & Technology Department of Sichuan Province (Grant No. 2013SZ0006 and 2015SZ0230).
Authors
Ping Tan
Lu Yang Liangren Liu Qiang Wei |
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MP06-05 |
Learning curve of a new surgical procedure: Experience from a new center adopting Robotic Kidney transplant. |
Transplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery I | 17BOS |
Abstract: MP06-05 Sources of Funding: none Introduction Evaluating learning curve of a new procedure is important in order to assess the reproducibility and ease of adoption of the procedure, and also to track progress of an institution adopting the new procedure. This study reports the results and learning curves of robotic kidney transplantation (RKT) with regional hypothermia at a center that recently adopted this procedure._x000D_ Methods 33 patients underwent Vattikuti Urology Institute technique of RKT in Turkey, by surgeons routinely performing robotic surgery and kidney transplantation. Standard KT outcomes were noted with a minimum follow-up of 1 month for all, and compared to the results of an established RKT program in India, who used the same technique of RKT. CUSUM analysis was done to evaluate the learning process. Target values were based on the average values of the established RKT program. Completion of learning curve was defined as anastomosis and rewarming times plateauing within 2 standard deviations (SD) of the target value. Results All patients underwent RKT successfully. The mean console, warm ischemia, and rewarming times were 187±34.6 min, 1.89±0.5 min, and 58.0±17.8 min respectively. Arterial, venous, and ureterovesical anastomosis times were 19.3±5.9, 21.9±6.8, and 22.5±4.2 min respectively. The median hospital stay was 10 days (6-14 d), and creatinine at discharge was 1.43±5.73 mg/dl. These results differ significantly from the results of the established program with regard to anastomosis times and rewarming time (p<0.05 for all). However, there was no difference in creatinine at discharge (p>0.05) (figure 1a). There was no delayed graft function, no Clavien grade ?3 complications, lymphoceles, vascular or ureteral complications; one wound infection requiring medical management. CUSUM analysis revealed that learning curve lasted for 9 cases with regards to rewarming time, 19 cases for arterial anastomosis, 18 cases for venous anastomosis. No learning curve existed for uretrovesical anastomosis (Figure 1b). Conclusions RKT has excellent outcomes, and low complication rates at a center that recently adopted this procedure. It has a short learning curve, and is reproducible. The longer anastomosis times at the start of learning curve do not affect graft function, supporting the hypothesis that regional hypothermia is protective._x000D_ Funding none
Authors
Sohrab Arora
Volkan Tugcu Akshay Sood Mahendra Bhandari Rajesh Ahlawat Mani Menon |
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MP06-06 |
Pre-transplant antibody removal can be avoided in ABO incompatible kidney transplantation. |
Transplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery I | 17BOS |
Abstract: MP06-06 Sources of Funding: none Introduction Recently, desensitization therapy became more widely used in ABO incompatible kidney transplantation (ABOi-KTx). A body of evidence has been accumulated suggesting that anti-A, anti-B antibody titer is not necessarily a good indicator for the development of acute antibody mediated rejection (AMR) or for favorable or unfavorable patient outcome. We have omitted the pre-transplant antibody removal in selected patients since 2010 at out institution. Methods Twenty-two patients with baseline antibody titer ≤ 1:64 received ABOi-KTx without pre-transplant antibody removal between 2010 and 2015 (Group 1). Historical control group consisted of 22 patients with baseline antibody titer ≤ 1:64 who received ABOi-KTx with 2 or 3 sessions of pre-transplant antibody removal before 2009 (Group 2). All patients were treated with calcineurin inhibitor (CNI), mycophenolate mofetil (MMF), and methylprednisolone (MP) starting 4 weeks before ABOi-KTx. Two doses of rituximab (100mg) were given in both groups before ABOi-KTx. Protocol biopsies were performed 1-2 month after ABOi-KTx. Results Recipient and donor age, sex, the number of HLA mismatch were not significantly different between the 2 groups. Baseline antibody titers (IgG) were 1:17 (range 0-64) and 1:18 (range 0-64) in Group 1 and 2, respectively (P=0.81). Antibody titers at the day of ABOi-KTx were 1:10 (range 0-32) and 1:8 (range 0-32) in Group 1 and 2, respectively (P=0.43). Five year graft survival were 100 % in both groups. Serum creatinine levels at 3 years after ABOi-KTx were 1.25±0.75 and 1.46±0.43 mg/dl in Group 1 and 2, respectively (P=0.39). Biopsy proven AMR occurred in 2 patients of Group 1 (9.1%) and 3 patients of Group 2 (13.6%). AMR in these patients was abrogated with steroid pulse therapy with or without plasma exchange. There was no significant difference in protocol biopsy results of Banff 2013 criteria between the 2 groups. C4d score more than 2 was detected in 72 % in Group 1 and 75 % in Group 2 (P=0.97). IgM deposition on peritubular capillary was seen in 38.8 % in Group 1 and 60.0 % in Group 2 (P=0.25). Conclusions Pre-transplant antibody removal is not required for patients whose serum antibody titers are ≤ 1:64 in ABOi-KTx as long as desensitization therapy consisting of CNI, MMF, MP and retuximab is implemented appropriately. Funding none
Authors
Masayuki Tasaki
Yuki Nakagawa Kazuhide Saito Naofumi Imai Yumi Ito Vladimir Bilim Kota Takahashi Yoshihiko Tomita |
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MP06-07 |
CD4+IFN-γ+IL-10+ cells facilitate a prolongation of graft survival in old recipient mice treated with Rapamycin |
Transplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery I | 17BOS |
Abstract: MP06-07 Sources of Funding: S.G.T. was supported by grants from the National Institutes of Health (RO1AG039449). K.M. was supported by Osaka Medical College Educational Foundation. M.Q. (QU 420/1-1) and T.H. (HE 7457/1-1) were supported by the German Research Foundation (DFG). Introduction The elderly represent a rapidly growing population among kidney transplant recipients, however, this population remains underrepresented in clinical trials. Moreover, age-specific effects of immunosuppressive therapies in renal transplantation remain poorly understood. Methods Here, we assessed the impact of Rapamycin on alloalloimmune responses in aging using a fully MHC-mismatched (DBA/2 on B57BL/6) murine transplantation model. Results Old untreated recipients displayed prolonged skin graft survival compared to their young counterparts (median survival time 9 vs. 7 days, p=0.006). Surprisingly, treatment with Rapamycin led to a marked prolongation of graft survival specifically in old recipients (19 days vs. 12 days, p=0.004). This age-specific effect was not linked to changes in frequencies or subset composition of CD8+ and CD4+ T cells. Furthermore, anti-proliferative effects of Rapamycin on CD8+ and CD4+ T cells as assessed by in-vivo BrdU-incorporation were comparable in both young and old recipients. In contrast, systemic production of IL-10 was markedly elevated in old recipients treated with Rapamycin. This in-vivo shift in cytokine balance was linked to an emergence of IFN-γ/IL-10 double-positive regulatory type 1 cells during Th1-differentiation of old T helper cells in presence of Rapamycin, a process independent of regulatory T cells. Conclusions Our results demonstrate a novel pathway of age-dependent alloimmunity with relevance for renal transplantation. Funding S.G.T. was supported by grants from the National Institutes of Health (RO1AG039449). K.M. was supported by Osaka Medical College Educational Foundation. M.Q. (QU 420/1-1) and T.H. (HE 7457/1-1) were supported by the German Research Foundation (DFG).
Authors
Koichiro Minami
Timm Heinbokel Markus Quante Hirofumi Uehara Abdala Elkhal Haruhito Azuma Stefan G. Tullius |
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MP06-08 |
Mirabegron Improves Symptoms Associated with Small Bladder Capacity Following Kidney Transplantation |
Transplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery I | 17BOS |
Abstract: MP06-08 Sources of Funding: none Introduction As the waiting time increases for listed renal failure patients, it is becoming common to encounter patients with minimal or no urine output with small shrunken bladders at the time of transplant. Mirabegron has proven benefit in treating overactive bladder(OAB) symptoms by relaxing the bladder through beta-3-adrenergic receptors. Our aim is to evaluate the efficacy of Mirabegron following kidney transplantation on patients with small bladder capacity. Methods Kidney transplant recipients with small bladder volumes who experienced OAB symptoms and were started on Mirabegron therapy within 3 months after transplant were included in this study. Patients were excluded if they had evidence of urinary tract infection or a history of complex urologic surgeries preceding transplantation. We used the OAB-symptom score (OAB-SS; Journal of Urology, 2007), a simple self-report questionnaire evaluating OAB symptoms. The minimum OAB-SS score for inclusion was 12. Patient demographics and OAB-SS pre and post-Mirabegron were collected and compared using paired t-test analysis. Results The 36 participants were predominantly male (83%) and deceased-donor kidney transplant recipients (86%). Median age was 48 years (IQR 36.5-60). 47% of patients reported pre-transplant urinary symptoms, most commonly recurrent UTI (28%). BPH-lower urinary tract symptoms (LUTS) reported by 30% of males may contribute to the sample sex imbalance. Before Mirabegron initiation, 44% of patients had failed trials of at least one pharmacologic agent and over 20% had failed trials of at least two medications. After starting Mirabegron therapy, 86% reported a decrease in OAB-SS. Overall mean score change was -4.7 points (p<0.001). Mean score on each OAB-SS survey question also decreased significantly (p<0.001, Table 2). Conclusions Mirabegron effectively reduces severity of symptoms related to small bladder volume following renal transplantation by increasing bladder relaxation and storage capacity. Funding none
Authors
Charbel chalouhy
Jessica Moore Benjamin Philosophe |
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MP06-09 |
Local sildenafil accelerate renal regeneration after ischemia/ reperfusion injury in canine model. |
Transplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery I | 17BOS |
Abstract: MP06-09 Sources of Funding: no funding Introduction The renoprotective effect of sildenafil has been proven in animal model. Also, it is reported to enhance expression of hepatocyte proliferating antigen after hepatic ischemia/ reperfusion injury (IR) in animal model. Yet this was not studied before in renal IR. We aim to investigate the role of local sildenafil administration in enhancement of renal recoverability and regenerative capacity after renal IR in canine model. Methods Seventy two male mongrel dogs were classified into 3 groups (each consists of 24 dogs): sham (right nephrectomy without left renal ischemia), local (LC) group (right nephrectomy, left renal ischemia for 6o minutes and local perfusion of ischemic kidney with saline and heparin for 5min immediately after ischemic induction) and local Sildenafil (LS) group (as LC and local perfusion with sildenafil 0.5 mg/kg). Each group is subdivided into 4 subgroups (6dogs each) according to time of scarification (1, 3, 7 and 14 days). Serum creatinine (Scr) and diuretic renography were performed for all dogs at the day of sacrification and compared with pre-ischemic values. Histopathological examination of the kidney was performed by un-informed pathologist. Renal cortex and medulla were examined for necrosis, interstitial fibrosis and regenerative indices (RI). Regenerative indices (RI) are mitosis, solid tubules, solid sheet, hyperchromatosis and prominent nucleoli. Also, immunohistochemical examination of renal tissue was done for assay of proliferative marker ki-67. Results Renal function tests were statistically significant lower in ischemic groups (LC and LS) in comparison to sham through the study period, where LS group showed statistically significant lower serum creatinine and higher GFR at all end point times than LC group. (Figure 1) Sildenafil-treated group showed statistically significant lower renal cortical and medullary necrosis and interstitial fibrosis than control group. Regarding RI, LS group showed statistically significant higher expression of all RI than other groups (p value <0.05). Also, LS group showed statistically significant higher expression of Ki-67 than both groups at 1, 3, 7 and 14 days post renal IR injury (p Values < 0.05). (Figure 2) Conclusions Local sildenafil administration; beside its role in renal protection against IR, enhances renal regenerative capacity after release of ischemic insult. Funding no funding
Authors
Mohamed H Zahran
Nashwa Barakat Shery Khater Amira Awadalla Ahmed Mosbah Adel Nabeeh Ahmed A Shokeir |
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MP06-10 |
The Activation of Inflammation Amplifier in Kidney Transplant Graft and Urinary Biomarker for Chronic Rejection |
Transplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery I | 17BOS |
Abstract: MP06-10 Sources of Funding: none Introduction Inflammation amplifier (IA), a local chemokine inducer in non-immune cells is induced by the simultaneous activation of NF?B and STATs (IL-17, TNF?, and IL-6) and leads to a synergistic production of chemokines, growth factors, and cytokines. IA was essential for the development of inflammation in various autoimmune disease models. More recently, IA was critical for the development of chronic rejections both in murine models and human allogeneic lung transplantations (J Immunol. 189, 1928 and Int. Immunol. 25, 319). The status of IA can be a new biomarker and its regulator can be a new therapeutic target in rejected kidney allografts (KA). The objective of this study was to investigate the contribution of IA during the rejection process in KA and to identify genes regulating IA. Methods Primary human kidney cells (PHKC) were stimulated with IL-17, IL-6, TNF?, and expressions of chemokines and IL-6 were measured by RT-PCR. Among the genes highly expressed in PHKC with IA activation, we focused on a gene named Renal NFkB Enhancer-1 (RNE1). A deficiency of RNE1 suppressed chemokines and IL-6 after IA activation in PHKC, indicating that RNE1 might be a positive regulator in IA. In another experiment, urinary RNE1 in kidney transplant recipients (KTR) were measured by ELISA and clinical data (serum creatinine, CRP, urinary protein, urinary albumin, urinary NAG, and eGFR) were also compared among the KTR patient groups with normal histology, interstitial fibrosis and tubular atrophy (IF/TA), or chronic active antibody-mediated rejection (CAAMR). Results PHKC expressed excess amounts of chemokines and IL-6 after IA activation by IL-17, IL-6, and TNF?. Urinary RNE1 in KTR showed significantly higher amount in CAAMR patients (48606 ng/mgCre, n=9) compared to IF/TA (10744 ng/mgCre, n=21) and normal (6081 ng/mgCre, n=13). In contrast, serum creatinine, CRP, eGFR, U-NAG levels showed no significant difference among patient groups. Conclusions IA was activated in PHKC, and urinary RNE1 was elevated in rejected KA. These results suggested that activation of IA is involved in KA rejection, and RNE1 could be a new biomarker. Now, we are planning to examine detailed molecular mechanisms how RNE1 regulates NF-kB pathway in kidney cells and to examine if it will be a new therapeutic target for allogeneic kidney transplantations._x000D_ _x000D_ Funding none
Authors
Haruka Higuchi
Daiki Iwami Kiyohiko Hotta Nobuo Shinohara Masaaki Murakami |
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MP06-11 |
Incidental nephrolithiasis in live related kidney Donors: epidemiology, long term outcome of donor and recipient. |
Transplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery I | 17BOS |
Abstract: MP06-11 Sources of Funding: None Introduction The use of computerized tomography angiography for donor evaluation has resulted in the increased detection of incidental nephrolithiasis in living renal donor candidates. This study aims at reporting the epidemiology of asymptomatic renal stones in healthy live related potential donors as well as the management strategy and long-term outcome of kidney recipients with asymptomatic stones in donors. Methods 2200 potential donors, between 2000 and 2015 were evaluated for the presence of asymptomatic renal stones. They were subjected to abbreviated metabolic panel for stone disease along with a detailed clinical history. Donors with stones > 15 mm, significant metabolic abnormalities and presence of associated risk factors for recurrent stone disease were rejected. Finally, 36 donors with stones, proceeded for donation with stone size of 2-15 mm (group I: stone ? 4 mm, n=17; Group II: stone 5-15 mm, n=19). Patients of group I were accepted for donation with stones in situ whereas, patients of group II were treated for stones prior to donation. Records were analyzed for recipient outcome, with special attention to stone events, as well outcome of donors in terms of stone recurrence in residual kidney. Results Prevalence of asymptomatic renal stone in potential donors was 4.2 %. Mean age of the donor was 42.5±10.5 years with mean GFR of the transplanted kidney being 38±5.5 ml/min. In group I, follow up imaging revealed seven, four and one patients had residual stones (all ? 4 mm) at 1 month, 3 month and one year respectively. Similarly, in group II, five, three and one patient had residual stones (?6 mm). Except one, none of the recipients had stone related events in post transplant period. One patient of group II required ureteroscopic stone retrieval in post transplant period. The mean serum creatinine of the recipients at 3 months and one year was (1±0.25) mg/dl and (1.45±0.4) mg/d respectivelyl. With a mean follow up of 6.5 years, donors did not show any stone recurrence in the residual kidney. Conclusions Transplantation of kidneys with small, asymptomatic renal stones in situ can be safely done with adequate post-operative follow up. Donors that donated the stone-bearing kidney fared equally well in terms of recurrence of stone in residual kidney. Funding None
Authors
Sanjoy Sureka
Aneesh Srivastava Uday Singh Rakesh Kapoor M S Ansari Sandeep Kumar |
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MP06-12 |
Usefulness of Multi-Detector Computed Tomography Scanning for replacement of diethylenetriamine pentaacetic acid (DTPA) |
Transplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery I | 17BOS |
Abstract: MP06-12 Sources of Funding: none Introduction Both estimated split renal function measured by DTPA renography and kidney volume measured by MDCT can be used to predict postoperative renal function in kidney donors. We compared predicted post donation eGFR which was estimated by split renal function and renal volume with measured eGFR. Methods From January 2013 to May 2015, a total of 303 living kidney donors were analyzed. All donors underwent preoperative DTPA renography and MDCT scan. Bilateral renal cortex volume was measured by 3-dimension MDCT(Fig 1.). We estimated DTPA-eGFR(Remained split renal function(%) x preoperative eGFR) and Vol-eGFR (remained renal volume/total renal volume (%) x preoperative eGFR) and analyzed with DTPA-eGFR, Vol-eGFR and MDRD eGFR(1 week, 1 month, 3 month, and 6 month postoperatively). Also, we compared DTPA-eGFR and Vol-eGFR with ?eGFR. Results The mean value of DTPA-eGFR was 52.97±10.32 (ml/minute/1.73 m2) and Vol-eGFR was 51.26±10.26 (ml/minute/1.73 m2). Predicting dominating side was not agreed in 113/303 (37.3%). The MDRD eGFR showed a statistically significant correlation with total renal volume, DTPA-GFR and Vol-eGFR (p<0.001; Table1). ?eGFR shows significant correlation with total renal volume, DTPA-eGFR and Vol-eGFR(p<0.001). There were 101 patients who were eGFR less than 60ml/minute/1.73m2 at 6months after donor nephrectomy. Receiver operating characteristic (ROC) was performed to predict possibility of eGFR less than 60ml/minute/1.73m2 at six months with DTPA-eGFR and Vol-eGFR. DTPA-eGFR (AUC=0.858 p<0.001), and Vol-eGFR (AUC=0.878 p<0.001) could predict CKD III at 6 months (Figure1). Conclusions MDRD eGFR, Vol-eGFR, and DTPA-eGFR showed a statistically significant correlation. Moreover, Vol-eGFR and DTPA-eGFR were observed high prediction ability for CKD III at six months. In conclusion, Vol-eGFR was good predictive value for renal function recovery, and thus MDCT might substitute for DTPA renography in planning donor nephrectomy. Funding none
Authors
Hyung Ho Lee
Sook Young Kim Young Eun Yoon Sung Ku Kang Jae Yong Jeong Kwang Hyun Kim Kyung Hwa Choi Joong Shik Lee Koon Ho Rha Young Deuk Choi Sung Joon Hong Woong Kyu Han |
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MP06-13 |
Benefical effect of Hydrogen Sulfide on Renal Ischemia-Reperfusion Injury in CLAWN Miniature Swine |
Transplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery I | 17BOS |
Abstract: MP06-13 Sources of Funding: none Introduction The organ shortage is the major problem in kidney transplantation. To overcome this obstacle, kidney transplants of the marginal donor, cardiac death (DCD) and extended-criteria donors, were increasing. In this setting, the prevention of ischemia-reperfusion injury (IRI) is important for both early and long-term allograft function. Hydrogen Sulfides (H2S) have recently been reported to demonstrate both anti-inflammatory and cytoprotective effects. However, the efficacy and safety of H2S has yet to be elicited in a large animal model. We investigated whether H2S administration was effective for control of renal IRI and optimal administration method in a large animal model. Methods Female, MHC-inbred, CLAWN miniature swine (n=8) underwent renal ischemia for 120-minutes by occlusion of the left renal artery and vein. Group 1 animals (n=3) underwent renal ischemia exclusively without any additional treatment. Group 2 recipients (n=2) received 1.1 mg/kg of intravenous Na2S 10-minutes prior to kidney reperfusion, followed by an additional 1.1 mg/kg of Na2S 30-minutes post-reperfusion. Group 3 recipients (n=3) underwent selective renal artery administration of 1.1 mg/kg of Na2S 10-minutes prior to reperfusion, followed by an additional 1.1 mg/kg of Na2S 30-minutes post-reperfusion via the supra-renal aorta with concomitant occlusion of the infra-renal aorta, thus allowing for exclusive renal administration. Post-operative renal function was monitored by daily serum creatinine, analysis of circulating cytokine activity (TNF-α, IL-6 and HMGB1) to measure the inflammatory response to IRI and histological evaluation of renal biopsies obtained on post-operative days (POD) 2, 7 and 14. Results H2S administration did not result in any adverse side effects in the recipients. All animals experienced transient acute kidney injury, achieving a peak serum creatinine level by POD 3. Recipients in the untreated group had the higher post-operative serum creatinine level than selective renal H2S administration group (POD4: 4.4 vs 8.6 mg/dl, p<0.001). Pathologically, Control group still showed strongly epithelial flattering and vacuolations, congestion of PTC, and condensed tubular nuclei as a result of influence of IRI. In systemic group, the structures of renal tubule were well preserved comparatively, and those changes in selective group were obviously disappeared. Furthermore, on POD 7, specimens from selective group showed disappointment of IRI change. In selective group, the serum TNF-α and HMGB-1 level was lower than systemic group (TNF-α: 30.6 vs 85.4 pg/ml, p<0.05, HMGB-1: 2.6 vs 11.4 ng/ml, p<0.05). The mRNA expression of IL-1β was also suppressed in selective group specimen. Conclusions H2S administration performed safety and appeared to have potential cytoprotective and anti-inflammatory effects following renal IRI. This effect was most profound with selective renal artery administration. Further work investigating the benefits of H2S for organ procurement and preservation is warranted as this may allow for improved outcomes following renal transplantation. Funding none
Authors
Yuichi Ariyoshi
Mitsuhiro Sekijima Takahiro Murokawa Hisashi Sahara Motoo Araki Yasutomo Nasu Kazuhiko Yamada |
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MP06-14 |
Impact of visceral and subcutaneous adipose tissue on post donation renal function in living kidney donors |
Transplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery I | 17BOS |
Abstract: MP06-14 Sources of Funding: none Introduction It was reported that some variables were revealed remain renal function after live donor nephrectomy. This study was conducted to determine the influence of visceral and subcutaneous adipose tissue on renal function in living kidney donors. Methods Between July 2013 and February 2015, a total of 75 kidney donors who underwent living donor nephrectomy at our institution were analyzed. Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were measured at the level of the umbilicus using CT scan. The border of the intra-abdominal cavity was outlined on the CT image, the cross-sectional surface areas of the visceral fat and subcutaneous fat were calculated by a single urologist using Xelis CT software (INFINITT, Seoul, Korea)(Fig 1.). Renal function was estimated with the Modification of Diet in Renal Disease formula till six months after kidney donation. The relationship between preoperative visceral and subcutaneous adipose tissue and recovery of renal function was analyzed. Results Thirty-three donors (44%) were male, and 13 (17.3%) grafts were secured from the right side. The mean BMI was 23.5±2.6 kg/m2 and the mean preoperative eGFR was 103.0±19.6 mL/min/1.73 m2. The mean VAT was 73.0±41.6cm3; SAT was 117.5±70.2cm3, and VAT/SAT ratio was 0.7±0.5. On multivariate linear regression, preoperative eGFR, ?eGFR, and VAT/SAT ratio were independently associated with eGFR at 6th month (Table 2). A ROC curve analysis showed that preoperative eGFR, ?eGFR and VAT/SAT ratio were highly predictive of developing of CKDIII at 6th month after donor nephrectomy (AUC = 0.933, p < 0.001). Conclusions Pre-donation eGFR, ?eGFR and V/S ratio are associated with the development of delayed renal recovery (GFR <60 ml/min/1.72m2) 6th month after donation. VAT/SAT ratio was associated with the postoperative renal function in living kidney donors. Kidney donors with higher VAT/SAT ratio require close observation, given their predisposition to CKD III after donation Funding none
Authors
Hyung Ho Lee
Sook Young Kim Young Eun Yoon Sung Ku Kang Jae Yong Jeong Kwang Hyun Kim Kyung Hwa Choi Joong Shik Lee Koon Ho Rha Young Deuk Choi Sung Joon Hong Woong Kyu Han |
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MP06-15 |
Effect of CORM-3 in ischemia reperfusion injury and cisplatin-induced toxicity: differences in normal kidney cell and renal cancer cell |
Transplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery I | 17BOS |
Abstract: MP06-15 Sources of Funding: none Introduction To investigate the effect of a novel soluble carbon monoxide-releasing molecule (CORM) on cisplatin (CP) induced cytotoxicity and ischemia reperfusion injury (IRI) in vitro. Methods The effects of CORM-3 (200 µM) were compared in normal kidney epithelial cells (HK-2, LLC-PK1) and renal cancer cells (Caki1, Caki2), which were treated with CP (50~200 μM) and induced IRI. To induce IRI condition, cell plates were placed anaerobic chamber (37°C, 95% N2, 5% CO2) for 48hrs, and then cell medium was changed complete medium and incubation in 37°C humidified CO2 incubator for 6hr. The effect of CORM-3 on stimulated IRI and CP treated normal cells/RCC was the determined by measuring the cell viability (CCK assay), TNF-α mRNA induction (Q-RT PCR), protein expression of cleaved caspase 3 and oxidative stress markers including Erk1/2, JNK, P38 (western blot). Results Viability after IRI were approximately 40% compared with control. Protective effect of CORM-3 on IRI in vitro model was dose-dependent. Cell viability was 40% recovered in 200 μM CORM-3 pretreated cells compared with control cells. Confluent normal cells and cancer cells were exposed for 24h to CP (50~200 µM) alone or in combined with CORM-3 (12.5 ~200 µM). Protective effects of CORM-3 on CP-treated cells were weaker than those of IRI model. TNF-α mRNA induction occurs following stimulate IRI or CP exposed cells and expression of TNF-α mRNA levels decreased in CORM-3 pretreated cells. Also, IRI or CP-induced activated oxidative stress markers decreased in CORM-3 pretreated cells. CORM-3 reduced expression of c-caspase-3 which is an apoptotic marker. Conclusions Our data demonstrate that protective effect of CORM-3 on CP-treated and IRI model in vitro. We suggest that CO attenuates IRI and CP induced cytotoxicity by amelioration of inflammatory and oxidative stress pathways. These effects were observed in not only normal kidney cells but also renal cancer cells. Funding none
Authors
Young Eun Yoon
Hyung Ho Lee Youn Jung Lee Joong Shik Lee Kyung Hwa Choi Kwang Hyun Kim Seung Hwan Lee Won Sik Ham Koon Ho Rha Woong Kyu Han |
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MP06-16 |
Our experience in the management of Prostate Cancer in Renal Transplant Recipients |
Transplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery I | 17BOS |
Abstract: MP06-16 Sources of Funding: none Introduction Prostate cancer (PC) in renal transplant recipients (RTR) has not been widely studied and its incidence remains controversial, reported 2-5 times more than general population. The management of this disease is challenging because it is believed that RTR under immunosuppressive therapy may have increased postoperative morbidity and higher rate of tumor progression. Currently there are not guidelines or consensus about the management of this condition. The aim of the study was to analyze our experience in the management of PC in RTR. Methods Prospective and consecutive study in a single tertiary centre from 2003-2015. Inclusion of RTR diagnosed of PC by urinary symptoms, prostatic specific antigen (PSA), digital rectal examination, imaging and biopsies. PC assessment for staging and treatment was in agreement with the contemporary guidelines for the general population. Main outcome measures included demographics, characteristics and associated factors, type of treatment, complications, oncological outcomes and follow-up. Retrospective and descriptive analysis. Results During the study period 1330 renal transplants were performed, diagnosed of PC in 28 RTR (2.1%), mean age 66 years±6.6 (51-78). Type of donors were cadaveric (n=26) and live (n=2). Immunosuppressive therapy: without mTOR (n=14) and with mTOR (n=14). Mean time between renal transplantation and PC diagnosis 111 months±75 (24-270). Median PSA of 9.6ng/ml and PSA ratio 0.19. Treatment: a) Radical prostatectomy (n=20): perineal approach (n=16), laparoscopic (n=2), robotics (n=2)/ lymphadenectomy was performed in one patient; b) Radiotherapy combined with hormone therapy (n=6); c) Active surveillance (n=2). Histology: ≤pT2 (n=15), pT3a (n=4) and ≥pT3b (n=1). No graft loss due to PC treatment was reported. Complications (18%): incontinence post-prostatectomy (n=2), anastomotic stricture (n=2) and urinary fistula (n=1). Outcomes: Remission of the 85% (n=22), Biochemical recurrence after radical prostatectomy treated with salvage radiotherapy (n=4). Mortality by other causes without evidence of recurrence (n=11), loss of monitoring (n=1). Not specific mortality from cancer prostate was reported. Observed survival rates were 100% at 12 months after treatment. Mean follow-up was 61 months±37 (12-132). Conclusions This is the first largest series to analyze the management of PC in RTR from a single center in Spain. PC after renal transplantation could be managed as any non-organ transplant patient with the same range of therapeutic options. According to our experience, these patients has similar histopathologic evaluation, post-treatment complications, rate of remission and recurrence than non-transplant patients, without specific mortality from PC. Active surveillance should also be provided in RTR despite being under immunosuppressive treatment. Funding none
Authors
Alonso Narváez Barros
Lluis Riera Canals Jaime Fernández-Concha Schwalb José Suárez Novo Manel Castells Esteve Francesc Vigués Julià |
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MP06-17 |
UROTHELIAL CARCINOMA AFTER KIDNEY TRANSPLANT: A HETEROGENEUS ENTITY IN TERMS OF DIAGNOSIS, TREATMENTS AND ONCOLOGICAL OUTCOMES |
Transplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery I | 17BOS |
Abstract: MP06-17 Sources of Funding: None Introduction Cancer development after KT is increasing, and urothelial carcinoma (UCa) incidence has been estimated 3 times higher, especially focused in bladder. However, upper urinary tract (UUT) can also be affected, both in native and less commonly in graft UUT. Management of UCa after KT is demanding because of aggressiveness and potential graft involvement. The aim of the study is to assess all UCa developed after KT, as well as treatments performed and oncological outcomes Methods Retrospective analysis of 1.693 KT at our institution between 1977-October 2016. Age, sex, tumor location, TNM stage, tumor grade, presence of Cis, treatments and oncological outcomes are assessed, including median Overall Survival (mOS) and cancer-specific-survival (CSS) Results 13 patients developed 14 UCa (0.83%), 61.5% male. Median age at the moment of cancer was 62.5 years (range 40-81) and median time from KT to cancer 52.5 months (range 2-209). UCa were located in bladder (8), in native UUT (1) and in graft UUT (5). At diagnosis, only 1 patient was metastatic and 35% of the cases (5/14) had Cis associated. Regarding tumor grade, 1 was G2, 9 were G3 and 4 were G4. Pathologic stage and treatments performed for UCa after KT are detailed in Table 1. 67% patients with non-muscle-invasive bladder tumor (NMIBT) received BCG. All patients with graft UUT UCa had locally advanced tumors and were treated with graft RNU and pelvic lymphadenectomy, returning to dialysis. At present, 69.2% (9/13) are alive, and median-overall-survival (mOS) is 36 months (range 2-182). Of the total 4 deaths, 1 was cancer-related, 1 during RC postoperative course and the other 2 ESRD-related. Cancer-specific-survival (CSS) was 92% (12/13). _x000D_ Conclusions Bladder is the most common place of UCa after KT. BCG is also a part of the treatment in these patients. Graft UUT UCa was relatively high in our study comparing to literature. It is usually locally advanced and sometimes unresectable. mOS of UCa after KT is 36 months, which is lower than other uro-cancers in this population. Treatment of this cancer is challenging and can potentially involve the graft, being necessary to remove it and so returning to dialysis Funding None
Authors
Vital Hevia
Javier Lorca Victoria Gomez Sara Alvarez Victor Diez Francisco Javier Burgos |
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MP06-18 |
CT volumetry of the kidney is a cost effective alternative to MAG3 scan in predicting renal function after donor nephrectomy |
Transplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery I | 17BOS |
Abstract: MP06-18 Sources of Funding: none Introduction In selecting living kidney donor, we need to evaluate split renal function. We routinely use Tc-99m-mercapto-acetyltriglycin (MAG3). However, all transplant programs do not use MAG3 because of its high cost and radiation exposure. Computed tomography (CT) volumetry of the kidney is a new tool to evaluate split renal function. Since CT scan is used in all transplant programs for preoperative evaluation, CT volumetry adds no cost. If we can substitute CT volumetry for MAG3, donor can avoid extra radiation exposure and save some money. We examined the correlation between MAG3 and CT volume of the kidney. Moreover, we evaluate which is a better method to predict post-operative donor&[prime]s renal function (1, 3, 12 months). Methods Sixty-three patients underwent donor nephrectomy from 2009 to 2016 in our institution. Those who did not perform thin slice CT (1mm), and those with follow up less than 1 year were excluded. Thirty-four living kidney donors were included in this retrospective study. Renal volume was automatically calculated by volume analyzer software (SYNAPSE VINCENT, FUJIFILM, Tokyo, Japan). The correlation was evaluated using Bland-Altman plot. Results Median age is 60.5 years, and the rate of male is 50%. All patients underwent left side donor nephrectomy. Preserved parenchymal volume is 139.6ml, and preserved cortex volume is 102.0ml. eGFR decreased by 36.8% from 72.0 mL/min/1.73m2 at baseline to 47.8 mL/min/1.73m2 at 1 year post-donation._x000D_ A strong correlation was observed in split function measured by between MAG3 and cortex volume (R=0.92) (Fig. 2) preoperatively. Moreover, post-op eGFR was correlated with split function measured by between MAG3 and cortex volume (Fig 3). There are no significant differences in correlation between MAG3 and CT volumetry of the kidney at the each follow-up period (1, 3, 12 months) (Fig. 3). _x000D_ _x000D_ _x000D_ Conclusions CT volumetry is an alternative to MAG3 to evaluate split renal function and to predict postoperative renal function. It is cost effective and beneficial by reducing extra radiation exposure to a donor. Funding none
Authors
Yosuke Mitsui
Takuya Sadahira Motoo Araki Shingo Nishimura Koichiro Wada Yasuyuki Kobayashi Toyohiko Watanabe Yasutomo Nasu |
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MP06-19 |
LONG-TERM OUTCOME OF ADULT RENAL TRANSPLANTATION IN PATIENT WITH CONGENITAL LOWER URINARY TRACT MALFORMATIONS : A MULTICENTER STUDY. |
Transplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery I | 17BOS |
Abstract: MP06-19 Sources of Funding: None Introduction Lower urinary tract malformations managed in infancy represent a particular group of kidney transplantation since it may impair the final function of the graft. Data in literature remains sparse. The aim of this study was to report the feasibility and long-term results of renal transplantation during adulthood in patients with a congenital lower urinary tract malformation. Methods A retrospective multicenter study from 3 French renal transplant centers included 123 transplantations in 112 patients with lower urinary tract malformations (1996-2016). Graft and patient survivals and complications were analyzed. The results were stratified according to the underlying uropathy and type of initial management during childhood. Results Mean age at transplantation was 32,1 years (±11,2). Were included posterior urethral valves (n= 49), spina bifida (n=21), central neurogenic bladders (n=13), bladder exstrophy (n=14), Prune Belly (n=12), Hinman syndrome (n=6), urogenital sinus (n=4) and others (n=4). The mean follow up was 7,2years. Overall the 1, 5, 10 and 15 years patients survival was 97.4%, 93.0%, 89.4% and 80.0%. Grafts survival at 1, 5, 10, 15 and 20 years was 96.6%, 87.6%, 77.3%, 60.6% and 36.4%. Enterocystoplasty and continent urinary diversions exposed grafts to more frequent acute pyelonephritis (p=0.02). There were no differences on graft survival when transplantation was performed in enterocystoplasty or urinary diversions compared to a native bladder provided a well conducted bladder management. Conclusions Lower urinary tract malformations should be considered for renal transplantation as any other cause of end stage renal disease. Despite previous surgeries and possible bladder dysfunction, these patients should not be excluded from renal transplantation programs. Even if enterocystoplasty and continent urinary diversions exposed grafts to more frequent acute pyelonephritis, patients and graft survival rates at 10 years are similar to other kidney transplantation. Funding None
Authors
Stéphane MARCHAL
Nicolas Kalfa François IBORRA Lionel BADET Georges Karam Julien Branchereau lucas Broudeur Rodolphe Thuret |
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MP06-20 |
Randomized experimental study comparing non-oxygenated vs oxygenated hypothermic machine perfusion in a type III Non-Heart-Beating Donor pig model of autotransplantation. |
Transplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery I | 17BOS |
Abstract: MP06-20 Sources of Funding: None Introduction Hypothermic machine perfusion (HMP) reduces risk of delayed graft function (DGF) and improves graft survival. Cold reduces oxygen requirement, although metabolic rate remains around 10% and consequently hypoxia would result a source of tissue damage. Hence, the concept of supplying O2 during perfusion is growing, because it would combine active circulation of dissolved oxygen in the perfusate. Oxygenated HMP could allow ATP resynthesis._x000D_ The aim of the study was to compare HMP with or without oxygen in a pig model of kidney autotransplantation, reproducing conditions of type III non-heart-beating donor (NHBD) Methods Porcine model of type III NHBD autotransplantation approved by animal ethical committee. 6 female pigs randomized to HMP with or without O2. Left kidney retrieval after 30 min of warm ischemia time (WIT). Kidney was cold-flushed with Celsior® and preserved in LifePort® for 22 h. Afterward, nephrectomy of the remaining right kidney and the transplant of the preserved left kidney in an orthotopic manner were performed. Perfusion conditions are measured with serial perfusate gasometry and miRNAs expression, as well as hemodynamic machine parameters. Serum levels of creatinine are measured every 2 days. After sacrifice, pathology exam was carried out Results Fig. 1 shows Cr evolution, with a peak 2-3 days after transplant. Oxygenated HMP (pigs 1, 5, 6) has shown nearly significant differences in flow: 73.3 vs 46.7 (p= 0.05) and RI: 0.36 vs 0.54 (p=0.05) at the end of perfusion. Fig. 1 shows histological analysis of kidneys and miR10a expression. The increased expression of miR10a (lower DCTs) that has been linked to cell proliferation and tubular repair is correlated with the presence of severe ATN in animal 2. _x000D_ _x000D_ _x000D_ Conclusions In our preliminary results, oxygenated HMP has shown nearly significant differences in flow and RI at the end of perfusion, as well as better functional results. ATN development was linked to increased expression of miR10a that would make it a biomarker for graft outcome. Similarly, oxygenated allografts have shown lower miR10a expression correlating with less tissue damage, so they could be a useful tool for monitoring oxygen effects in kidney perfusion Funding None
Authors
Vital Hevia
Victoria Gomez Maria Laura Garcia-Bermejo Sara Alvarez Francisco Donis Victor Diez Ana Saiz Adolfo Martinez Francisco Javier Burgos |
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MP07-01 |
Genetic Outcomes of Conception in Men with Elevated Sperm Aneuploidy |
Infertility: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP07-01 Sources of Funding: AWP is a K12 scholar supported by a Male Reproductive Health Research (MRHR to DJL) Career Development Physician-Scientist Award (Grant # HD073917-01) from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Program. This work is also supported in part by the Burnett Research Fund. Introduction Sperm aneuploidy can be assessed using fluorescent in situ hybridization (FISH) and is associated with recurrent spontaneous abortion (SAB) and implantation failure. Here, we examine the relationship between elevated sperm aneuploidy on sperm FISH testing, and genetic abnormalities identified during PGS, SAB, amniocentesis, and in live births._x000D_ Methods We identified men who had previously undergone sperm FISH testing in a single academic andrology clinic. Sperm FISH examines sperm disomy, sex chromosome disomy, and aneuploidy in autosomes 13, 18, or 21, and the sex chromosomes X and Y. Severity of aneuploidy was measured using the sum of abnormal FISH components (range 0-5, with each chromosomal abnormality considered an abnormal component). Chart review and telephone survey was performed to determine genetic outcomes of conceptions of men who had sperm FISH testing. The survey inquired about any PGS results, karyotype results for SABs or amniocenteses, about the general health of offspring, and whether any offspring had trisomy 13, 18, or 21._x000D_ _x000D_ Results We interviewed 99 couples; 46 couples had 175 genetic evaluations for product of conception. Ten couples provided PGS results for 102 embryos (mean±SD female age 35.8±5.7 years). Of these, 61 embryos (59.8%) were abnormal; 44.2% had monosomy, 29.5% trisomy, 11.5% tetraploidy, 3.3% chromosomal region duplications, and 11.5% were burst embryos. In couples with >3 abnormal FISH components, 66.7% of embryos were abnormal (weighted mean female age 35.7±4.0 years), while in couples with ≤3 abnormal FISH components, 45.2% of embryos were abnormal (weighted mean female age 31.3±6.4 years) (p=0.132). Fifteen couples had karyotype analysis of the conceptus after SAB, with 2 reporting a normal karyotype, 4 reporting trisomy 21, and 9 with karyotype findings that were incompatible with life. Miscarriages occurred at a mean of 7.2±2.9 weeks of gestation. Fewer chromosomal abnormalities were observed in pregnancies continuing beyond 15 weeks; all 6 amniocenteses performed were normal. Within our cohort, 52 live births were reported. Only one child had a genetic abnormality, having trisomy 21. Maternal age at conception was 25 years and the father had 5 abnormal FISH components. No deaths or significant health issues were reported for any live births. Conclusions Elevated sperm aneuploidy has increased risk of abnormal embryos compared to couple with less elevated sperm aneuploidy. Within this cohort, only normal embryos resulted in live births. Thus, couples with abnormal sperm FISH results should be counseled on the high rate of potentially abnormal embryos. _x000D_ Funding AWP is a K12 scholar supported by a Male Reproductive Health Research (MRHR to DJL) Career Development Physician-Scientist Award (Grant # HD073917-01) from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Program. This work is also supported in part by the Burnett Research Fund.
Authors
Taylor P. Kohn
Alexander W. Pastuszak Matthew F. Cherches Kristin F. Pascoe Sohum Shah Dolores J. Lamb Larry I. Lipshultz |
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MP07-02 |
PolyA tag library preparation for new generation sequencing (NGS) in human testis fails to detect non-coding and translated RNAs important in testicular function as compared to ribosomal RNA depletion method. |
Infertility: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP07-02 Sources of Funding: P50 HD076210, U1 1U01HD074542-01, Frederick J. and Theresa Dow Wallace Fund of the New York Community Trust, the Mr. Robert S. Dow Foundation, Irena and Howard Laks Foundation_x000D_ _x000D_ This work was supported in part by the Urology Care Foundation Research Scholar Award Program and AUA New York Section Research Scholar Fund Introduction Non-coding RNAs (ncRNAs) are emerging as important but poorly understood regulators of mRNA transcription and translation. However, common library preparation techniques for RNA sequencing selects for coding mRNAs by the presence of a poly-A tail; thus, by excluding non-PolyA ncRNAs, many biologically significant transcripts may be overlooked by using this method. The objective of this study was to evaluate differences in testicular RNA identification using 2 different methods of library preparation: polyA and ribosomal RNA depletion (RibZero) using Illumina kits. Methods Total RNA was extracted from 3 human testis samples and processed using two different methods of library preparations: one based on polyA tags, and the other on depletion of ribosomal RNAs. The cDNA libraries were then sequenced at the same depth and annotated to known published databases. Identified transcripts were divided into two groups based on presence in one of the library preparation methods but not the other. Clinical and biological significance of identified genes was examined using the DAVID. Failure of detection of RibZero-only genes by RNAseq using polyA preparation was then confirmed by analyzing results of RNAseq in 64 testicular samples from normal patients, men with sertoli cell only (SCO), early and late maturation arrest and hypospermatogenesis. Results 61 genes were detected only using polyA method with no detection in RibZero group (p=0.05): 17 of them belonged to small nuclear RNAs (snRNAs), 12 were snRNAs hosting genes, 3 humanin like proteins, and 3 were miRNA hosting genes: MIR137HG, MIR17HG, MIRLET7DHG. Deletion of MIR17HG leads to Feingold syndrome in humans and animal models. 74 genes were identified exclusively in RibZero group and not identified in the polyA group. The top 4 genes identified exclusively by RibZero were TAS2R50, MAGI1-AS, HIST1H3I, HIST1H4K. HIST1H4K was then further analyzed and its expression was highly abundant and specific to pachytene spermatocytes. Important components of the miRNA processing complex: AGO1,2, and 3 were expressed at >2x higher level (p=0.03) in ribosomal RNA library depletion preparation then polyA prep. Conclusions PolyA tail RNA enrichment method fails to adequately detect at least 7% of important RNAs in the human testis. Including ribosomal depletion RNA library preparation in addition to polyA tags enrichment is an important step to more comprehensively evaluate ncRNAs and testicular function. Funding P50 HD076210, U1 1U01HD074542-01, Frederick J. and Theresa Dow Wallace Fund of the New York Community Trust, the Mr. Robert S. Dow Foundation, Irena and Howard Laks Foundation_x000D_ _x000D_ This work was supported in part by the Urology Care Foundation Research Scholar Award Program and AUA New York Section Research Scholar Fund
Authors
Ryan Flannigan
Anna Mielnik Alex Bolyakov Phil V. Bach Peter Schlegel Darius Paduch |
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MP07-03 |
Improved sperm DNA integrity in the second semen sample from men providing double ejaculates |
Infertility: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP07-03 Sources of Funding: none Introduction High sperm DNA fragmentation rates reduce pregnancy rates and are related to higher rates of pregnancy loss. Sperm DNA fragmentation rates above a DNA Fragmentation Index (DFI) of 30% is associated with lower pregnancy rates. There have been suggestions that more frequent ejaculation may reduce sperm DNA damage. Our study seeks to determine whether a second ejaculate provided on the same day has lower DNA fragmentation rates. _x000D_ Methods Men provided 2 semen samples approximately 4 hours apart for analysis. In addition to the regular semen testing, sperm DNA fragmentation rates were measured using the sperm chromatin structure assay and reported as the DNA Fragmentation Index (DFI).Data analysis was performed using a Student’s T-test . Results A total of 54 men, mean age of 38.6 +/- 5.9 (SD) years old provided double ejaculates. The DFI in the first and second ejaculates was 38.6 +/- 21.2% and 35.5 +/- 21.2% (p < 0.001). For those with DFI < 30% on the first semen sample, the mean DFI decreased from 19.8 +/- 5.8% to 17.1 +/- 5.7% (p<0.001), while for those with initial DFI > 30%, the mean DFI decreased from 51.5 +/- 17.8% to 47.1 +/- 19.3% (p<0.001). There were a range of changes in DFI, with 8/54 (15%) found to have decreases of DFI >10% in the second ejaculate. For the men with elevated but not extremely high DFIs (DFI range 30-40%) found with the first semen specimen, the DFIs were reduced to the normal DFI (DFI <30%) range in 64% (7/11) of the men with the second semen sample. _x000D_ _x000D_ As expected, semen volume was significantly lower on the second sample 2.3 +/- 1.3 mL vs 1.5 +/-0.9 mL (p<0.001) as was the total motile sperm count (TMC) decreasing from 20.5 +/- 40 to 9.6 +/- 17.1 X 106 (p=0.003). 23/54 men had initial TMCs > 5 X 106, with 6/23 declining to < 5 X 106 in the second sample. 29/54 had TMCs above zero but less that 5 X 106 for both the first and second semen sample. 2/54 (4%) had TMC = 0 with the first semen specimen, which increased to a mean of 0.9 X 106 with the second sample. _x000D_ Conclusions This is the first prospective study to identify significant improvements in sperm DFI rates in the second sample from men providing a double ejaculate. Testing men for changes in DFI rates with double ejaculates should be considered in those with high sperm DFI rates. Funding none
Authors
Tristan Juvet
Susan Lau Kirk Lo Ethan Grober Keith Jarvi |
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MP07-04 |
Abnormal hypermethylation of VDAC2 promoter is associated with male idiopathic asthenospermia |
Infertility: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP07-04 Sources of Funding: none Introduction This study aims to explore the association between the methylation status of the vdac2 gene promoter region and IAS. Methods Twenty-five patients with IAS and 27 fertile NZ were evaluated. GC-2spd cells were treated with different concentrations of 5-Aza-CdR (5, 10 and 15 ?mol/L) for 24 and 48 h. Real-time polymerase chain reaction was conducted to reveal whether or not vdac2 gene expression is regulated by methylated modification. After predicting the promoter region, dual-luciferase activity detection was used to verify vdac2 promoter activity in GC-2spd cells. Bisulphite genomic sequence was used to analyze DNA methylation of the vdac2 promoter. Results vdac2 expression was significantly increased in men treated with 15 ?mol/L 5-Aza-CdR for 48 h compared with that in the other groups (P < 0.05). Strong activity of the promoter (?2000bp to +1000bp) was detected by dual-luciferase activity detection (P < 0.05). Bisulphite genomic sequencing indicated that the percentages of uncompleted, mild and moderate methylation in normozoospermic men were 83.65% ± 5.51%, 8.73% ± 1.38% and 7.61% ± 5.68%, respectively. Moreover, the percentages of uncompleted, mild and moderate methylation in patients with IAS were 76.01% ± 6.94%, 7.14% ± 1.86% and 16.62% ± 8.27%, respectively (P = 0.005, 0.02 and 0.003, respectively). Correlation analysis showed that PR was associated with uncompleted methylation and negatively related to moderate methylation. Conclusions High methylation of the vdac2 promoter CpGs could be positively correlated with low sperm motility. Abnormal methylation of vdac may be related to idiopathic asthenospermia. Funding none
Authors
Zengjun Wang
Bianjiang Liu Shifeng Su Aiming Xu Jianzhong Zhang |
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MP07-05 |
ANALYSIS OF >23,000 IUI CYLES: CORRELATING SPERM STRICT KRUGER MORPHOLOGY WITH CYCLE PREGNANCY OUTCOMES |
Infertility: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP07-05 Sources of Funding: None. Introduction A significant number of couples initiate fertility treatment with unmedicated and medicated intrauterine insemination (IUI) cycles. Previous published studies have suggested that low strict morphology scores are correlated with cycle failure. In an extremely large cohort, we sought to analyze whether strict morphology was correlated with results, and further analyzed the confounding variable of female age in correlation with cycle outcome. Methods In this retrospective study, couples undergoing an IUI cycle from December 2000 to October 2016 were reviewed. Sperm morphology scores were determined via Kruger&[prime]s strict criteria. Male partners were segregated by percent normal sperm morphology. Females were segregated by age (A: <35, B: 35-37, C: 38-40). Females greater than age 40 were excluded from the analysis. Pregnancy rates (PR) were determined by the presence of bHCG circulation in the blood stream (positive bHCG). Student&[prime]s t-test and chi-square analysis were performed with significance set at p<0.05. Results IUI cycles (n=23,035) that met the study&[prime]s inclusion criteria were evaluated. Overall, 4,019 IUI protocols resulted in achieving a positive pregnancy outcome (PR: 17.45%). In females <35, pregnancy rates rose steadily (PR: 13.4-24.3%) as percent of normal sperm morphology increased (% Normal Sperm: 1-11%). A similar trend was observed in older female cohorts (Age: 35-37; 38-40), albeit to a lesser degree (PR: 11.4-19.1%; 9.6-19.5% respectively) than the youngest cohort. Overall, a significant decline in pregnancy rate was between all patient age cohorts (<35-40) when the percent normal sperm morphology was ≤ 4% versus > 4% (PR: 14.4% versus 19.3%)(p<0.05). Conclusions Female age and sperm morphology have an influence on IUI pregnancy potential. This study demonstrated that females <35 to 40 can successfully utilize an IUI approach, albeit their cycle’s chances of success appear to diminish in the presence of low percentages of normal sperm morphology. This study confirms the utility of strict Kruger morphology criteria in counseling couples regarding their expected success with IUI intervention. Funding None.
Authors
Jared Winoker
Joseph Lee Michael Whitehouse Alan Copperman Natan Bar-Chama |
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MP07-06 |
Study on single nucleotide polymorphisms within the novel testis-specific Haspin gene encoding a serine/threonine protein kinase in human male infertility |
Infertility: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP07-06 Sources of Funding: none Introduction It has been reported that many testis-specific functional genes are drastically expressed during spermatogenesis, and defects in their expression cause male infertility. Haspin, encoding a germ cell-specific protein kinase, was cloned from a subtracted cDNA library constructed from mouse testis. Genomic analyses revealed that mouse Haspin is an intron-less gene located within the 26th intron of the integrin alpha E (Itgae) gene on chromosome 6, which is conserved in rats and humans. It was shown that human HASPIN phosphorylates histone H3 at threonine 3 and is required for this phosphorylation event in mitotic cells. HASPIN is found at the centrosomes and spindles during mitosis, where it integrates the regulation of chromosome and spindle function during mitosis and meiosis. The present study assessed whether HASPIN is a cause of infertility in Japanese males. Methods Japanese subjects with nonobstructive infertility (n = 282) were divided into subgroups according to their degree of defective spermatogenesis: 192 (68%) of these patients had nonobstructive azoospermia, while 90 (32%) had severe oligospermia (<5 × 106 cells/ml). The control group consisted of fertile males who had fathered children born at a maternity clinic (n = 262). Their HASPIN coding sequence (CDS) was screened by the direct sequencing of PCR amplified DNA. This study was conducted with approval from the institutional review board and an independent ethics committee at Osaka University. Results Polymorphisms were found at 10 positions within the HASPIN CDS. Among those polymorphisms, there were six nt changes causing an amino acid substitution, one insertion (TCCCGACGA) leading to the addition of three amino acids (aspartic acid- aspartic acid-proline: DDP), and three silent mutations. There were no correlations among the polymorphisms in terms of their co-occurrence. Three single nucleotide polymorphisms (SNPs) (c365C > A, c560T > C, and c2205A > G) and the insertion resulting in three additional amino acids (c204-/TCCCGACGA) were identified in Japanese males for the first time. Unexpectedly, c2143G > A (rs376754182) was present only in homozygous form in the infertile group. Conclusions In this study, we found 10 polymorphisms within the HASPIN CDS. Among those, 5 were found only in the infertile group, 3 of which were nonsynonymous. These polymorphisms found only in the infertile patients may be a cause of male infertility, although significant differences in the frequencies of the genotypes were not identified. This is the first analysis of HASPIN genetic polymorphisms in male infertile population and these results will contribute significantly to future large-scale studies on the genetic background of infertility in Japanese males and on functional analyses of the role of HASPIN in cell cycle progression. Funding none
Authors
Yasushi Miyagawa
Tetsuji Soda Norichika Ueda Shinichiro Fukuhara Hiroshi Kiuchi Akira Tsujimura Hiromitsu Tanaka Norio Nonomura |
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MP07-07 |
Radical orchidectomy and fertility preservation: a need to change practice |
Infertility: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP07-07 Sources of Funding: None Introduction Testicular cancer is the most common malignancy affecting men in their fertile years. One in ten are azoospermic, when banking sperm, at initial presentation. Knowledge of patients' fertility potential and sperm count, prior to orchidectomy, may allow potential sperm retrieval from the testis removed during surgery. We assessed orchidectomy specimens to identify whether spermatogenesis was present in malignant testes, and what features affected spermatogenesis. Methods A retrospective review of 103 radical orchidectomy specimens for germ cell tumours, from 2011 to 2016, by a single expert pathologist (CH), was conducted. Tumour stage, type, volume, presence of testicular microlithiasis (TML) and the relationship to spermatogenesis (focal/widespread) were assessed and compared using Chi Square (significance p<0.0.5). Results Overall spermatogeneis was seen in 72/103 (70%), it was focal in 27/72 (38%) and it was widespread in 45/72 (62%). Neither tumour type (seminoma vs. non seminoma, p=0.87), stage (T1 vs. T3, p=0.09), nor presence of TML (p=0.12) were significantly related to spermatogenesis. The percentage volume of testis affected by tumours did significantly correlate with spermatogenesis (28.3% with sperm vs. 48.4% when no sperm found, p=0.05)._x000D_ _x000D_ _x000D_ _x000D_ Conclusions Spermatogeneis is present in the majority of testes affected by germ cell tumours (70%), and it does not appear to be related to any tumour pathology, apart from percentage tumour volume. Sperm extraction at the time of orchidectomy is a sensible approach, as testis specimens, destined for the pathology lab, would otherwise be a waste of functionally viable tissue. Given that spermatogenesis was focal in 38%, sperm retrieval is best performed with a microTESE (onco microTESE) to allow identification of these small foci. In our own experience, we have found sperm in 60% of patients with testicular tumour and azoospermia, at first presentation, using this technique. A change in focus to identify the azoospermic patient, prior to orchidecotmy, is vital to allow such an approach to be adopted. Funding None
Authors
Jemma Moody
Catherine Horsfield Malene Pedersen Kamran Ahmed Pippa Sangster Majed Shabbir |
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MP07-08 |
Characterization of lactoferrin receptor on human spermatozoa |
Infertility: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP07-08 Sources of Funding: None Introduction Lactoferrin (LF) is abundant in human seminal plasma and on sperm surfaces. However, lactoferrin receptor (LFR) on human spermatozoa has not yet been reported. Methods To study the expression, localization and characteristics of LFR on human spermatozoa, different experimental approaches were applied: LFR gene was amplified from a human testis cDNA library and recombinant LFR (rLFR) protein was produced in the expression vector Escherichia coli BL21 (DE3); human sperm membrane proteins were extracted and analysed via Western blot; the binding of LF to LFR was investigated by Far-Western blot, immunoprecipitation and autoradiography analysis and the localization of LFR on sperm surfaces was detected using immunofluorescence. Results LFR gene was amplified from a human testis cDNA library and the molecular weight of rLFR was 34 kDa. The native LFR on human spermatozoa was a 136-kDa tetramer which was anchored to the sperm head and mid-piece through glycophosphatidylinositol. LF could bind to LFR competitively in vitro. Conclusions As far as is known, this study has elucidated for the first time that LFR was expressed at the testis level, was anchored to the sperm membrane by glycophosphatidylinositol during spermatogenesis. LFR may play important roles through binding to and mediating LF. Â Funding None
Authors
Zengjun Wang
Pengqi Wang Bianjiang Liu Xiaobin Niu Shifeng Su Wei Zhang |
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MP07-09 |
Exploring RNA expression profiles of Klinefelter’s syndrome in the setting of Non-Obstructive Azoospermia |
Infertility: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP07-09 Sources of Funding: P50 HD076210, U1 1U01HD074542-01, Frederick J. and Theresa Dow Wallace Fund of the New York Community Trust, the Mr. Robert S. Dow Foundation, Irena and Howard Laks Foundation_x000D_ _x000D_ This work was supported in part by the Urology Care Foundation Research Scholar Award Program and AUA New York Section Research Scholar Fund Introduction Klinefelter syndrome (KS) is characterized by the presence of an additional X chromosome (47,XXY) and leads to sertoli cell only (SCO) histological phenotype. Age dependent progressive hyalinization observed in men with KS and SCO is not seen in 46,XY men with SCO. Hyalinization in KS is believed to play a significant role in age dependent decline in sperm recovery during microscopic testicular sperm extraction. The objective of our study was to evaluate if there are genes differentially expressed between men with KS (47,XXY) and men with 46,XY and histological pattern of SCO. Therefore, providing insight on the role that the additional X chromosome contributes to progressive testicular hyalinization in men with KS. _x000D_ _x000D_ Methods Total RNA was extracted from tissue harvested during microscopic testicular sperm extraction (mTESE) from patients with NOA and KS, and SCO as well as normal testicular tissue. RNA libraries were sequenced on an Illumina HiSeq 2000 platform. Results were mapped to the genome and transcriptome using TopHat (v2.0.8). Cufflinks was then used to quantify the number of reads. RNA Seq data was expressed as FPKMs and normalized using a TMM, JMP genomic was used to identify differentially expressed (DE) transcripts at FDR = 0.001._x000D_ _x000D_ Results Testicular tissue from 6 patients with KS 47,XXY SCO, 11 with SCO and 10 with normal spermatogenesis were harvested, processed and sequenced. Using a clustering analysis, RNA expression in SCO 47,XXY was most similar to SCO 46,XY. 10,777 genes were found to be DE between SCO and normal controls largely representing genes expressed in germ cells. However when men with SCO 47,XXY were compared to men with SCO 46,XY we identified that only 546 transcripts (5%) were differentially expressed between these two groups despite both having SCO histology. Further analysis demonstrated downregulation of CELA2A and CELA2B as well as PRSS12 in men with SCO and KS as opposed to men with SCO and normal karyotype. These genes are known to code for serine proteases involved in elastin and collagen metabolism. Elastin and Type 4 collagen are known to contribute the characteristic hyalinization of KS tubules. Therefore, loss of these genes in men with KS may explain age dependent progressive hyalinization of tubules observed commonly in KS. _x000D_ _x000D_ Conclusions Hierarchical clustering of gene transcripts demonstrates that 46,XY and 47XXY men with SCO share very similar expression profiles. Reduced expression of CELA2A, CELA2B and PRSS12 in men with KS may explain age-dependent progressive hyalinization of seminiferous tubules among these men._x000D_ Funding P50 HD076210, U1 1U01HD074542-01, Frederick J. and Theresa Dow Wallace Fund of the New York Community Trust, the Mr. Robert S. Dow Foundation, Irena and Howard Laks Foundation_x000D_ _x000D_ This work was supported in part by the Urology Care Foundation Research Scholar Award Program and AUA New York Section Research Scholar Fund
Authors
Ryan Flannigan
Alex Bolyakov Anna Mielnik Phil V. Bach Darius Paduch |
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MP07-10 |
Usefulness of a portable computer-assisted sperm analyzer system using smartphone |
Infertility: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP07-10 Sources of Funding: Scholarship donations Introduction Despite the necessity of semen analysis on diagnosis and treatment of infertile couples, male partners are hesitant to receive outpatient services for infertility claiming pressure of business and embarrassment. As a result, in many cases, only female partners seek examination and treatment, and are thus forced to bear a great psychological and physical burden. In response to this situation, we validated the usability of a portable computer-assisted sperm analyzer(CASA) system utilizing a smartphone as a camera and an analyzer, an app, and a microscopic lens integrated with a semen specimen chamber(Figure 1). Using this system patients themselves can measure sperm motility as well as sperm concentration at home(Figure 2). Methods A total of 100 semen samples obtained from volunteers who had visited our outpatient clinic because of infertility were used in automated analysis for sperm concentration and motility after obtaining written informed consent. After adjusting the system through measurement of first 13 semen samples, we compared the results of succeeding 87 samples between the system and visual observation, then calculated correlation coefficients for sperm concentration and motility between them. Measurement of first 70 samples were conducted by embryologists and next 30 samples by patients themselves. The smartphone used was an iPhone 6. Results The correlation factor between the results of the measurement with the system and those with visual observation was 0.76 for sperm density and 0.65 for sperm motility. There were no particular problems with patient use of the system. Conclusions We are confident that this portable CASA system plays a role in motivating infertile men to visit clinics, thus resulting in early diagnosis and treatment. It is also hoped that this system contributes to a decrease in the mental and physical burden for women on the infertility treatment, a shortening of the time required to achieve pregnancy and a decrease in medical expenses. Funding Scholarship donations
Authors
Kazumitsu Yamasaki
Noriko Watanabe Tatsuji Ihana Sumio Ishijima Toshihiro Fujiwara Osamu Tsutsumi Teruaki Iwamoto |
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MP07-11 |
Roles of histone H3.5 in human spermatogenesis and spermatogenic disorders |
Infertility: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP07-11 Sources of Funding: none Introduction Histone H3.5 (H3.5) is a newly identified histone variant highly expressed in the human testis. We have reported the crystal structure, instability of the H3.5 nucleosome and accumulation around transcription start sites, mainly in primary spermatocytes, but its role in human spermatogenesis remains poorly understood. Methods Testicular biopsy specimens from 30 men (mean age: 35 years) with non-obstructive azoospermia (NOA) who underwent microdissection testicular sperm extraction and 23 men with obstructive azoospermia (OA) were included. The transcriptome of the testicular homogenate using the Illumina platform were expressed as fragments per kilobase. An H3.5-specific mouse monoclonal antibody recognizing an H3.5-specific synthetic peptide was generated, and immunohistological staining for H3.5 and proliferating cell nuclear antigen (PCNA) was performed on Bouin’s solution-fixed sections. Apoptosis of germ cells was assessed by TdT-mediated digoxygenin-dUTP nick end labelling (TUNEL). Expression and localization of H3.5 were compared with patient background, germinal stage and PCNA expression. Results In normal spermatogenesis testes, the H3.5 protein was mainly localized in leptotene spermatocytes, independent of germinal stage. In NOA testes, mRNA expression of H3.5 (H3F3C) was significantly reduced compared with other H3 histone family members, and expression of H3.5 was significantly lower than that in OA. Additionally, the number of H3.5-positive germ cells was higher in hypospermatogenesis or late maturation arrest than in early maturation arrest in NOA testes (p<0.01). A significant positive correlation was observed between H3.5 and PCNA expression (p<0.05) but not TUNEL-positive cells, and expression of H3.5 was enhanced after hCG-based salvage hormonal therapy. Conclusions Different from other testis-specific histones, which are often expressed during the histone to protamine transition during meiosis, H3.5 was expressed mainly in immature germ cells. H3.5 may play roles in DNA synthesis, but not apoptosis, and its expression is regulated by gonadotropins, indicating that such epigenetic regulations are important in normal spermatogenesis and spermatogenic disorders. Funding none
Authors
Koji Shiraishi
Aya Shindo Akihito Harada Yasuyuki Ohkawa Hitoshi Kurumizaka Hiroshi Kimura Hideyasu Matsuyama |
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MP07-12 |
Damage to seminiferous tubules in patients with Sertoli cell only syndrome progresses with aging |
Infertility: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP07-12 Sources of Funding: none Introduction Atrophy of seminiferous tubules (ST) and thickening of lamina propria (LP) are the major histological findings in testes with impaired spermatogenesis, and are variably present in patients with Sertoli cell only syndrome (SCOS). However, the clinical significance of the different degrees of ST atrophy and thickening of LP is unknown. In this study, we assessed ST atrophy and thickening of LP according to age and serum hormone levels in men with SCOS. Methods A total of 2,179 seminiferous tubules of 15 patients without any known etiology such as cryptorchidism or chromosomal anomalies who were diagnosed with SCOS by testicular biopsy during microdissection testicular sperm extraction (micro-TESE) were assessed. Diameter of ST and thickness of LP were measured in cross-sections, and average values were calculated in each patient. Correlation between these histological parameters (diameter of ST and thickness of LP) and patient age or serum hormone (luteinizing hormone [LH], follicle-stimulating hormone [FSH], and total testosterone [TT]) levels were assessed using Pearson's product-moment correlation coefficient. Results The mean diameter of ST and thickness of LP were 97.2 ± 32.0 (range 19.0 – 212.5) µm and 13.3 ± 6.3 (range 2.0 – 39.0) µm, respectively. There were no significant correlations between diameter of ST or thickness of LP and serum LH or FSH levels. Diameter of ST had significant negative and positive correlations with patient age (Figure A) and serum TT levels (Figure C), respectively. Similarly, thickness of LP had significant positive and negative correlations with patient age (Figure B) and serum TT levels (Figure D), respectively. Conclusions Our results indicated that degeneration of ST in patients with SCOS progresses with aging. Immediate planning for micro-TESE is necessary for patients with azoospermia. Funding none
Authors
Shoichiro Iwatsuki
Yukihiro Umemoto Tomoki Takeda Satoshi Nozaki Hideki Takada Hiroki Kubota Yasunori Itoh Shoichi Sasaki Takahiro Yasui |
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MP07-13 |
Therapeutic effect of RIPK1 inhibitor in testicular ischemia-reperfusion |
Infertility: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP07-13 Sources of Funding: none Introduction Testicular torsion makes testis ischemic. Surgery is immediately needed to reestablish blood flow. Even if the surgery succeed, testicular atrophy is often appear and lead to spermatic dysfunction. However, the etiology is still controversial in terms of pathophysiological changes. Recently it was reported that loss of the formation in any tissue after ischemia-reperfusion (IR) was involved in necroptosis, which is one of programmed cell death series. Necrostatin-1 (Nec-1) blocks both necroptosis and indoleamine 2,3-dioxygenase (IDO). In our previous research, we elucidated that IDO inhibitor decrease inflammation in testis and epididymis. First, we investigated pathophysiological change of testicular IR researching histological and biochemical phase in this study. Subsequently to the analysis, we tried to inhibit Receptor-interacting protein kinase 1 (RIPK1) and clarify a function of necroptosis in testicular IR. Methods Twelve weeks old ICR male mice were used in this study. Their unilateral testicular artery was clamped under general anesthesia. Declamping three hours later, their testicular blood flow were resumed. After the procedure, bilateral testes were removed in time dependent manner (at day 1, 3, 5 and 7). Histological and biochemical change were evaluated by immunostaining and ELISA methods. Spermatic analysis from the epididymal cauda were evaluated by computer aided sperm analysis (CASA). In the following research, Nec-1 4 µg/g was administrated (iv) after declamping testicular blood flow. After the treatment, bilateral testes were removed in time dependent manner. Then, histological, biochemical and semen analysis were evaluated. Sham surgery was performed as control. Their experiments were duplicated at least. Results Regarding histological change, invasion of lymphocyte-predominant inflammatory cells accumulated at day 3, 5 and destruction of seminiferous structure were observed at day 5, 7. Necroptosis cell using RIPK staining was abundantly expressed. In semen analysis, significant decreased spermatic concentration was observed at day 5 and 7 compared to control (p<0.05). Significant decreased spermatic motility was observed at day 1, 3, 5 and 7 compared to control (p<0.05). Interestingly, in contralateral (unaffected side) testes, significant decreased spermatic motility was observed at day 5 and 7 compared to control (p<0.05). Some candidates were picked up as molecular marker. Significant increased E-selectin expression, which is a marker of leukocyte-endothelial cell adhesion molecule, was observed at day 1 compared to control (p<0.05). Significant increased IL-6 expression, which is a marker of inflammation, was observed at day 3 compared to control (p<0.05). Significant increased 8-OHdG expression, which is a biomarker of oxidative stress, was observed at day 7 compared to control (p<0.05). Interestingly, significant increased the highest expression of E-selectin, IL-6 and 8-OHdG were observed in contralateral testes. Same results were introduced in immunohistochemical staining. After treatment of Nec-1, testicular structure were maintained and little invasion of inflammatory cells were observed. Significant decreased germ cell death (necroptosis) in seminiferous tubules were statistically observed. Significant decreased E-selectin, IL-6 and 8-OHdG were also observed. Importantly, Spermatic motility also maintained in both treated testis and contralateral testes. Conclusions Oxidative stress via inflammation and necroptosis should induce spermatogenetic dysfunction in IR testis. First, prominent inflammation was occurred in testicular ischemia-reperfusion model and not only expression of cytokines were increased, but also in contralateral testes. Subsequently, oxidative stress highly expressed and cell death appeared. Therefore, their change of bilateral testis would be one of pathophysiology in patients with ischemic testis. To inhibit RIPK1 would be contribute to protection of testicular tissue and spermatogenesis in IR model. Funding none
Authors
Shin Ohira
Ryoei Hara Shigenobu Tone Seitetsu Kin Shinjiro Shimizu Tomohiro Fujii Yoshiyuki Miyaji Atsushi Nagai |
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MP07-14 |
Co-Incubation of Human Spermatozoa with Anti-VDAC Antibody Reduced Sperm Motility |
Infertility: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP07-14 Sources of Funding: None Introduction Voltage-dependent anion channel (VDAC), a channel protein, exists in the outer mitochondrial membrane of somatic cells and is involved in multiple physiological and pathophysiological processes. Up until now, little has been known about VDAC in male germ cells. In the present study, the relationship between VDAC and human sperm motility was explored. Methods Highly motile human spermatozoa were incubated in vitro with anti-VDAC antibody. Total sperm motility, straight line velocity (VSL), curvilinear velocity (VCL), and average path velocity (VAP) were recorded. Intracellular free calcium concentration ([Ca2+]i), pH value (pHi), and ATP content were determined. Results Co-incubation with anti-VDAC antibody reduced VSL, VCL, and VAP of spermatozoa. Co-incubation further reduced [Ca2+]i. Anti-VDAC antibody did not significantly alter total sperm motility, pHi and intracellular ATP content. Conclusions The data suggest that co-incubation with anti-VDAC antibody reduces sperm motility through inhibition of Ca2+ transmembrane flow. In this way, VDAC participates in the modulation of human sperm motility through mediating Ca2+ transmembrane transport and exchange. Funding None
Authors
Bianjiang Liu
Shifeng Su Min Tang Zengjun Wang |
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MP07-15 |
Alterations in oxidative stress parameters in the testis and epididymis in a nicotine-exposed rat model. Can nicotine-abstinence overcome the oxidative damage? |
Infertility: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP07-15 Sources of Funding: Grant-In-Aid (KAKENHI) by the Japan Society for the Promotion of Science (25-03102). Introduction Epidemiological data indicate that up to 13% of infertility is attributed to cigarette smoking. Nicotine is the most abundant alkaloid chemical in tobacco. We selected nicotine as a major addictive substance of tobacco and investigated its the effects in oxidative stress (OS) changes in epididymis and testis. Additionally we examined if abstinence from nicotine can reverse these changes. Methods Eight-week-old Wistar rats were exposed to oral administration of nicotine (15 mg/kg). One group was exposed to nicotine for 10 weeks (Nico-group) and another group was exposed to nicotine for 7 weeks followed by 3 weeks of abstinence (Abst-group). Control animals had access to fresh water. Tissue levels of malondialdehyde (MDA) and total antioxidant capacity (TAC) were evaluated both in the testis and the epididymis. Additionally, cotinine levels in the urine, serum and seminal vesicular fluid (SVF) were evaluated. Furthermore, testosterone was measured in the urine samples. Finally, immunohistochemistry was performed for OS-markers and Cytochrome P450 2A6 (CYP2A6) in epididymal tail samples. Results Nicotine treatment induced significant increases of MDA levels both in the testis and epididymis in Nico-group compared to Abst and Control groups. TAC was significantly lower in both epididymis and testis in Nico group compared to Abst and Control groups. Cotinine levels in urine, serum and SVF were significantly increased in Nico-group compared to Abst group. Control samples were negative for cotinine. Urine testosterone levels in Nico group were significantly lower compared to Control-group, while there was no significant difference between Control and Abst-group, neither between Nico and Abst groups. Immunohistochemistry revealed mildly stronger intensity for all OS-markers in Nico-group compared with Abst and Control groups. CYP2A6 which is the primary enzyme responsible for the oxidation of nicotine and cotinine was expressed and localized in the epithelial cells of the epididymis in Nico-group. Conclusions Our data demonstrate that the harmful effects of nicotine in the testis and epididymis can be reversed by abstinence. Probably treatment with an antioxidant reagent could enhance the antioxidant defenses of testis and epididymis, and further ameliorate the cigarette smoke-induced oxidative stress in both testicular and epididymal tissue. The present data can provide a helpful tool for clinicians to advice smokers, especially those who attend assisted-reproductive programs, to quit smoking. Funding Grant-In-Aid (KAKENHI) by the Japan Society for the Promotion of Science (25-03102).
Authors
Panagiota Tsounapi
Masashi Honda Fotios Dimitriadis Yusuke Kimura Shogo Shimizu Bunya Kawamoto Katsuya Hikita Motoaki Saito Nikolaos Sofikitis Atsushi Takenaka |
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MP07-16 |
Utilization Rates of Cryopreserved Sperm Based on the Indication for Storage |
Infertility: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP07-16 Sources of Funding: none Introduction The use of cryopreserved of sperm cells from human and animal semen has been a described technique since the 1950s. However, the actual utilization of available cryopreservation technology for human reproduction in sexually intimate partners has been infrequently reported. We set out to examine the utilization of cryopreserved lots of sperm cells processed for males seeking this service at a multispecialty clinic in central Texas during the interval from 1988 through 2015. _x000D_ _x000D_ Methods A retrospective chart review was undertaken of all the cryopreserved semen samples at our institution from the time period specified above. The purpose for cryopreservation and eventual utilization of the sample were recorded along with outcomes of use for insemination. The types of utilization were accumulated as proportions for different purposes. The timing for use for insemination procedures was evaluated using survival statistics. The frequency of patients arranging to destroy samples was also reported. _x000D_ Results A total of 1361 cryopreserved semen samples and 81 testicular or epididymal tissue samples were identified. Samples were cryopreserved for 4 purposes: planned intrauterine insemination (IUI), planned in vitro fertilization/intracellular injection (IVF/ICSI), fertility preservation related to cancer treatment, or prior to military deployment. See table 1. Samples cryopreserved for IUI were more likely to be used, whereas VF/ICSI samples were more likely to be destroyed. Of note, while accounting for only a small amount of the samples, those collected for deployment were more likely to be utilized, while those collected for cancer were the least likely to be used. See table 1 for utilization detail. The longest duration from cryopreservation until use was 9.6 years in the cancer cohort. The deployment samples were typically used the earliest. IVF/ICSI samples had the highest proportion of pregnancies (35%). _x000D_ _x000D_ Conclusions The overall utilization rate of cryopreserved samples in our patients was low (mean, 19.3%). Not previously reported, to our knowledge, was that deployment related samples were used second only to IUI and that usage was earlier compared to other than storage indications._x000D_ Funding none
Authors
Graham Machen
Erin Bird Monica Brown Dale Ingalsbe Milaida East Michelle Reyes Thomas Kuehl |
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MP07-17 |
Role of Oxidation Reduction Potential In Varicocele Associated Male Infertility |
Infertility: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP07-17 Sources of Funding: None Introduction Patients with varicocele tend to have poor sperm quality and are at higher risk of being infertile. Although the pathophysiology of infertility in males with varicocele has been extensively studied, the underlying mechanism remains unclear. Oxidative stress has been recognized as a possible mechanism. We therefore performed a study to determine the correlation between oxidation reduction potential (ORP) and poor semen quality in infertile men with varicocele. Methods 318 infertile men with varicocele and 51 normal healthy men were recruited as the control group. Patients with varicocele were further divided into three groups according to the clinical grade of their varicoceles (grade1-3). Semen samples were analyzed using WHO 5th edition guideline and ORP levels were measured by MiOXSYS analyzer. The results were compared by Wilcoxon rank sum test and Kruskal Wallis test and a P value < 0.05 was considered significant. Results Table 1 summarized the results of semen parameters and ORP levels between study groups. All semen parameters (concentration, total motility and normal form of sperm) were all found to be lower in patients with varicocele while the ORP levels were significantly higher in patients group. ORP levels were negatively correlated with sperm concentration, motility and morphology (Figure 1). Comparing patients by the severity of varicocele showed no significant differences (Table 2). Conclusions ORP plays a role in the pathophysiology of varicocele associated infertility. Treatment targeting on ORP reduction may potentially improve semen quality in these patients. Funding None
Authors
Mohamed Arafa
Haitham ElBardisi Ahmad Majzoub Sami AlSaid Abdel Rahman Jaber Kareim Khalafalla Siew May Wang Ashok Agarwal |
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MP07-18 |
Impacts of smoking on the glycocalyx of human spermatozoa |
Infertility: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP07-18 Sources of Funding: none Introduction About 10-15% of all infertility patients are diagnosed with idiopathic infertility. Particularly, long term smokers often suffer from a reduction of basic sperm parameters (Ramlau-Hansen, 2007). The effects of smoking on male fertility are still discussed controversially._x000D_ It was shown, that the essential binding between sperm and oviduct is based on a lectine-carbohydrate interaction (Koelle, 2012). A functional reduction of fertility could occur due to a lack of binding capacity._x000D_ Therefore, our group characterized the proteins on glycocalyx of human spermatozoa that are capable to bind sugar residues. Further it was evaluated, if smokers show a restricted sugar-binding ability compared to non-smokers._x000D_ Methods We separated two study populations (smokers, non-smokers) out of 78 fresh human ejaculate samples. A direct staining with Mitotracker DeepRed, NucBlue (DAPI) and FITC-conjugated sugar residues (sialic acid- (SA), mannose- (MA) and fucose- (FU)) was performed. We used confocal microscopy to examine the fluorescence-marked samples. The fluorescent cells were analysed quantitatively and qualitatively within the study populations._x000D_ Additionally, we extracted the sperm's proteins from smokers and control group which we applied on SDS-Page (4-12.5 %). Western Blot was used to proof the presence of LMAN2 and CatSper1 proteins on the plasma membrane surface._x000D_ Results We located proteins at the middle part of the spermatozoa's head that are capable of binding sugar residues._x000D_ The ratio of fluorescence-labelled cells to the total cell count, which correspond to the capacity of binding sugar residues, was measured. We showed a significant difference between the groups: For smokers, we counted a proportion of 0.07±0.006 (SA), 0.05±0.006 (MA), 0.05±0.005 (FU) compared to 0.15±0.01 (SA), 0.20±0.02 (MA), 0.19±0.02 (FU) for the non-smokers (p<0.05). Fluorescence intensity did not vary significantly between the groups._x000D_ Protein candidates were found in Western Blot but first experiments did not show a significant difference in the amount between smokers and non-smokers. Conclusions Our results point out, that smoking could possibly lead to a reduction of sugar binding proteins on the human sperm glycocalyx. This could be a reason for a decreased binding capacity of sperms to the female reproductive tract which could lead to a reduced fertility potential of smokers. Further work is necessary to lighten the exact molecular interaction between spermatozoa and female reproductive tract. Based on these facts it might be possible to examine new diagnostic and therapeutic approach in the future. Funding none
Authors
Rick Paschold
Susanne Bour Armin Becker Christian Stief Matthias Trottmann |
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MP07-19 |
Involvement Of Oxidation Reduction Potential In The Pathophysiology Of Male Infertility In Patients With Varicocele |
Infertility: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP07-19 Sources of Funding: None Introduction Varicocele- associated infertile men tend to have poor sperm quality. However, the underlying pathophysiology of how it leads to poor sperm quality remains unclear. Oxidative stress (OS) has been recognized to be the possible mechanism. In order to determine the role of OS in infertile men with varicocele, we investigated the relationship between oxidation reduction potential (ORP) and poor sperm quality in this group of patients. Methods A total of 56 infertile men with varicocele, 132 infertile men without varicocele and 51 healthy males were recruited. The patients with varicocele were subdivided into three groups based on the clinical grade of their varicoceles. Semen analyses were performed based on the WHO 5th edition guideline. ORP measurements were obtained using the MiOXSYS analyzer. The comparisons between different groups were analyzed by Wilcoxon rank sum test and Kruskal Wallis test and a p value of <0.05 was considered significant. Results The mean age ± standard deviation of all patients with varicocele involved in the study was 35.3 ± 7 years. The results of sperm parameters and ORP values in patients with varicocele and normal healthy men are summarized in Table 1. Sperm concentration, motility and normal morphology were lower and ORP levels higher in patients with varicocele. However, there were no significant differences in these parameters when compared with the severity of disease (grade 1-3) or within fertile patients without varicocele. Conclusions Our result showed that both sperm parameters and ORP values distinguished infertile patients with varicocele from normal healthy men. The elevated ORP levels further support the role of OS as an underlying mechanism of infertility in varicocele patients. Funding None
Authors
Ashok Agarwal
Siew May Wang Nicholas Tadros Edmund Sabanegh |
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MP07-20 |
The imapct of testicular cancer on male fertility; Abnormalities detected and aetiopathogenesis |
Infertility: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP07-20 Sources of Funding: None Introduction There is an association between testis cancer and male subfertility with a number of studies reporting that men with testis cancer may have abnormalities in their semen parameters, although the exact pathogenesis is unknown.The aim of this study was to determine the effects of testicular cancer on semen parameters in men prior to radical orchidectomy and the possible basis of these abnormalities. Methods Between 2010 and 2016, 110 men underwent sperm cryopreservation prior to radical orchidectomy. Semen parameters were measured according to 2010 WHO criteria. A multiple regression analysis was undertaken to determine the effects of age, tumour size and histopathological features including lymphovascular invasion, type of tumour and preoperative tumour markers to determine whether these factors had an effect on semen parameters. Results The median age of patients was 31 years (IQR 25-35). The median sperm concentration, motility and normal forms were 17.15 million/ml, 54.25% and 6.5% respectively. Seminomatous tumours tended to be weakly but significantly associated with better motility than other tumour types (p = 0.048), whereas tumours associated with higher AFP were significantly associated with poorer morphology (p= 0.02). Median AFP was 3 (IQR 2.6-12.5). Forty nine patients (44.5%) had OAT, 8 were azoospermic (7.3%) and 38 had oligozoospermia (34.5%)._x000D_ None of the other factors, including tumour size, Beta-HCG, LDH and stage were significantly associated with semen parameters. (table 1)_x000D_ _x000D_ _x000D_ _x000D_ Conclusions 44.5% of patients with testicular carcinoma have abnormalities in their semen parameters, with azoospermia in 7.3% of patients. There appears to be an association between higher AFP and morphology, although the pathological basis of these abnormalities needs further investigation, but seems to be unrelated to tumour size. Funding None
Authors
Khaled Almekaty
Chris Poullis Elizabeth Williamson Mohamed Zahran Gideon Blecher Tet Yap Suks Minhas |
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MP08-01 |
Active Surveillance for cystic renal masses with ≥5 years of follow-up |
Imaging/Radiology: Uroradiology I | 17BOS |
Abstract: MP08-01 Sources of Funding: None Introduction We review our large singe center experience with active surveillance (AS) for cystic renal masses (CRMs), focusing on patients with ≥ 5 years (yrs) of follow-up. Methods We queried our prospectively maintained kidney cancer database (n = 2574) to identify patients with CRMs enrolled on AS. Estimated tumor volume (ETV) at presentation was calculated using a standard formula and linear growth rate (LGR) was evaluated. Wilcoxon rank sums were used to assess for demographic differences in growth rates and crossover to delayed intervention (DI). Kaplan-Meier curves were used to evaluate pts who crossed over to DI. A sub-set analysis was performed of patients with ≥5 years follow-up and no cross-over to DI. Results Of 601 AS patients, we identified 196 patients with CRMs enrolled in AS (64.3% male, median age 64.3 yrs, and mean ETV of 39.1 cm3). The median follow-up for the CRM cohort was 59.7 months. 48 patients (24%) with cystic renal masses crossed over to DI with a median time to DI of 16.7 months (IQR 10.8 - 27.7 months). When compared to solid masses, patients with CRMs (33.9% vs. 23.3%, p < 0.016) were less likely to proceed to treatment. The majority of patients (64%) with CRMs who crossed over to DI did so within 2 years. Younger patients (57.2 vs. 64.4 yrs, p < 0.001) were more likely to crossover to DI. Mean change in ETV was 5.8 cm3/yr and mean LGR was 2.6 mm/yr. Mean change in ETV of cystic masses was slower than solid masses (5.8 vs. 11.4 cm3/yr, p <0.04). A majority of patients (95.4%) were still alive at 60 months follow-up. A subset of 37 patients with CRMs had ≥5 years of follow-up without crossing over to DI. All of the patients were alive and only one patient developed distant metastasis. Mean LGR for this sub-set was 0.1 mm/yr. Conclusions Active surveillance with or without delayed intervention is a successful strategy in well selected patients with localized cystic renal masses. Most patients who cross over into DI are likely to do so within the first 2 years on AS. Metastasis and death are rare events in a well selected group of patients. Cystic masses grow more slowly and are less likely to proceed to intervention when compared to solid masses. Funding None
Authors
Andrew McIntosh
Pranav Parikh Anthony Tokarski Eric Ross David Chen Richard Greenberg Alexander Kutikov Marc Smaldone Rosalia Viterbo Robert Uzzo |
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MP08-02 |
Nephrometry Scores are useless for experienced urologists in clinical practice. |
Imaging/Radiology: Uroradiology I | 17BOS |
Abstract: MP08-02 Sources of Funding: none Introduction Several nephrometry scores have been proposed to predict perioperative outcomes in partial nephrectomy, but for clinical uses, its been questioned as an instrument for helping in decision-making. Therefore, our objective was to compare the ability of Nephrometry scores (R.E.N.A.L., PADUA and ABC) to subjective evaluation of the image by a group of experienced urologists and a group of first-year general surgery residents in predicting surgical outcomes in patients who underwent Partial Nephrectomy. Methods Computerized Tomography or Magnetic Resonance preoperative images of 87 patients who underwent nephron sparing surgery were retrospectively analyzed and classified by experienced Radiologist using nephrometry scores (R.E.N.A.L., PADUA and ABC) and subjective classification of the image in low, medium or high complexity was done by a group of blinded urologists (3) and residents (3) with none experience in renal surgery. The most common classification in each group was chosen or in the case of 3 divergent findings, medium complexity was the selected option. The outcomes were postoperative complication, positive surgical margin, ischemia time, surgery lenght, bleeding, renal functional lost and hospital stay period. Chi-Squared test was used for analyzing qualitative outcomes and a Spermans correlation test was used for continuous variables. Results R.E.N.A.L., PADUA and ABC Score can predict surgery time (p=0.004, p= 0.003 and p<0.001) and ischemia time (p<0.001 for all). The evaluation performed by the urologists also statistically predicts surgery time (p=0.001) and ischemia time with a better correlation than the Scores (p<0.001) Table 1. The evaluation performed by the urologists was the only one capable for predicting postoperative complications (p=0.049). Regarding bleeding, positive surgical margins, hospital stay and decrease in renal function, none of the scores or subjective evaluation had statistically significant correlation. Conclusions Nephrometry scores can overcome a subjective evaluation done by a non-experienced surgeon. On the other hand, experienced urologists perform better than Nephrometry scores in predicting surgical outcomes when analyzing pre-operative imaging. Therefore, those scores have little utility in clinical decision-making. Funding none
Authors
Henrique Nonemacher
Giuliano Guglielmetti George Lins de Albuquerque Rafael Coelho Mauricio Cordeiro Arnaldo Fazoli Paulo Afonso Carvalho Tiago Magalhaes Freire kayann Kaled R el Hayek Vitor Pagotto George Lins de Albuquerque Mauricio Cordeiro Bruno Aragao Rocha Diego Parga Rodrigues Alexandre Fligelman Kanas Publio Cesar Cavalcanti Viana Willian Nahas |
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MP08-03 |
Prediction of Histological Subtypes of Small Renal Masses: Striving for a Standardized MRI Diagnostic Algorithm |
Imaging/Radiology: Uroradiology I | 17BOS |
Abstract: MP08-03 Sources of Funding: Partially funded by grant 5RO1CA154475 Introduction MRI may aid in the management of small renal masses (<=4 cm, SRM) by differentiating among histologic subtypes. However, standardized approaches to MRI interpretation and interobserver agreement data are lacking. _x000D_ _x000D_ To assess the performance of a wide spectrum of MRI features for predicting the histologic diagnosis of SRM, and determine the interobserver agreement among multiple readers._x000D_ _x000D_ Methods Retrospective HIPAA-compliant IRB-approved study including 109 patients with cT1a SMR and a pre-surgical MRI. Images were reviewed by 7 radiologists with body MRI training and 1-15 years of experience. The following characteristics were analyzed on non-contrast images: T2-weighted (T2W) signal intensity/texture, presence/absence of intravoxel or bulk fat, magnetic susceptibility, central scar, and hemorrhage. Features assessed on post-contrast images included contrast avidity, enhancement homogeneity, dynamic characteristics, and segmental enhancement inversion. Multivariate generalized linear mixed model analysis with logit link was used to identify independent subtype predictors, as confirmed by histopathology, with p < 0.05 considered significant. Pairwise weighted analysis was used to measure interobserver agreement._x000D_ Results Clear cell renal cell carcinomas (ccRCC) represented 51% of the masses, papillary RCC (pRCC) 25%, chromophobe RCC (chrRCC) 6%, oncocytoma 6%, minimal-fat angiomyolipoma (mfAML) 6%, and others 9%. Table 1 includes values for the MRI features. ccRCC was predicted by signal intensity on T2W (high vs low, OR, odds ratio: 3.2 CI 95%: [1.4, 7.1], p < 0.001) and contrast avidity (avid vs. low, OR: 4.5 [1.8, 10.8], p < 0.0001), while pRCC was predicted by contrast avidity (low vs avid, OR: 0.05 [0.02, 0.2], p < 0.0001) on multivariate analysis. Segmental enhancement inversion was an independent predictor of oncocytoma (present vs absent, OR: 16.2 [1.0, 275.4], p < 0.05). None of the features were significant predictors of chrRCC or mfAML on the multivariate analysis. _x000D_ Conclusions Our data support the use of T2W signal intensity and contrast avidity as critical steps in the implementation of standardized MRI interpretation algorithms for predicting the histological subtype of SRM. Segmental enhancement inversion can be used as a feature for the diagnosis of oncocytomas. Funding Partially funded by grant 5RO1CA154475
Authors
Fernando U. Kay
Noah E. Canvasser Yin Xi Daniella F. Pinho Daniel Costa Alberto Diaz de Leon Gaurav Khatri John R. Leyendecker Takeshi Yokoo Aaron Lay Nicholas Kavoussi Ersin Koseoglu Jeffrey A. Cadeddu Ivan Pedrosa |
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MP08-04 |
Diagnostic evaluation of microscopic hematuria in young adults: Time to rethink the American Urological Association Guideline |
Imaging/Radiology: Uroradiology I | 17BOS |
Abstract: MP08-04 Sources of Funding: None Introduction Underlying disorders associated with Microscopic hematuria (MH) vary from benign conditions to more serious causes such as urinary tract malignancies. American urological association has issued an updated guideline on asymptomatic MH in 2012, addressing this heterogeneity and emphasizing on detection of urinary tract malignancies. The recommended protocol includes cystoscopy and multiphasic computerized tomography urography (CTU) in all patients older than 35 years. Low detection rate of malignancies in patients with MH, has questioned the necessity of performing full evaluations and exposing patients to the risks of radiation, allergic contrast reactions and contrast-induced nephropathy, as well as, imposing financial burdens to the health systems. We conducted this study to evaluate the efficacy of various urologic investigations in determining etiology of MH in young adults. Methods In this multi-institutional study, we retrospectively analyzed the records of 408 patients younger than 50 years with unexplained MH who underwent cystourethroscopy between December 2008 and January 2016. Furthermore, results of upper urinary tract investigations, including CTU or intravenous urography (IVU) and ultrasonography, as well as urine cytology and cystoscopy were obtained and analyzed to assess the role of each modality in determining the etiology of MH in young adults. Results During the study period, we identified 408 patients with MH, who underwent cystourethroscopy. Mean age of patients was 38.7±7.3, ranging from 22 to 50 years. Extensive urological evaluations revealed no pathology in 363 (89.0%) patients. However, 37 (9.0%) and 8 (2.0%) patients were diagnosed with benign and malignant pathologies, respectively._x000D_ In the present study, neither urine cytology nor upper tract imaging with CTU/IVU changed the diagnosis made by ultrasonography alone. However, cystoscopy was necessary for diagnosis of low grade bladder tumor in one patient. In multivariate analysis, age and the number of RBC/HPF were significantly associated with urothelial malignancies. Conclusions Our results showed that the probability of malignant pathologies is low in young patients presenting with MH. Moreover extensive urologic workup including upper tract imaging with CTU/IVU and voided urine cytology add little, if any information to that obtained by ultrasonography. Funding None
Authors
Erfan Amini
Farhad Pishgar Mohsen Ayati Bita Foratikashani Iman Ghazi Elnaz Ayati Mohammad Reza Nowroozi Majid Ali Asgari Ramin Pourghorban Faeze Salahshour Hassan Jamshidian |
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MP08-05 |
Calculation of Bladder Volumes Using 2D and 3D Ultrasound Compared to Urodynamic Measurements in Women with Overactive Bladder |
Imaging/Radiology: Uroradiology I | 17BOS |
Abstract: MP08-05 Sources of Funding: Support provided by NIH R01DK101719, VCU Presidential Research Quest Fund, and VCU Dean's Undergraduate Research Initiative. Introduction Various methods are currently available to non-invasively quantify bladder volume. The goal of this project was to determine the most accurate method of quantifying bladder volume using 2D and 3D ultrasound techniques during urodynamics. Methods Nine female participants with OAB underwent an extended urodynamics procedure (Laborie Aquarius XT) while ultrasound images of the bladder were obtained using a 3D 6MHz transabdominal probe (GE Voluson E8). The bladder was filled with saline at a rate of 10% bladder capacity (based on an initial clinical fill) per minute while ultrasound images were captured once per minute. Bladder volume was estimated from 2D cross-sectional images in the sagittal and transverse planes assuming an ellipsoid geometry (Eqn 1, Vspheroid), assuming a shape in between an ellipsoid and a cube (Eqn 2, VBih by Bih et. al. 1998), and from the 3D ultrasound data obtained by tracing the bladder outline in six planes with GE's 4D View software (V3D, Fig. 1 panel A)._x000D_ VSpheroid= π/6 (W*H*D) Eqn. 1_x000D_ VBih=0.72*W*H*D=1.375*VSpheroid Eqn. 2_x000D_ In Equations 1 and 2, W is the width (horizontal diameter) and H is the height (vertical diameter) in the sagittal direction and D is the depth in the transverse direction (horizontal diameter)._x000D_ Results VSpheroid was significantly lower than infused volume (VH2O) when compared by a paired t-test. VBih and V3D tended to be slightly, but not statistically, larger than VH2O (Fig. 1, Fig. 1 panel B). Conclusions The bladder shape cannot be assumed to be an ellipsoid in patients with OAB. Tracing the perimeter in several 3D imaging planes better accounts for the non-uniform geometry, providing a more accurate volume measurement. Volumes estimated by VBih or by tracing the bladder in 3D were not significantly different from VH2O, demonstrating that these are the most accurate methods of non-invasive assessment of bladder volume. Funding Support provided by NIH R01DK101719, VCU Presidential Research Quest Fund, and VCU Dean's Undergraduate Research Initiative.
Authors
Anna Nagle
Rachel Bernardo Jary Varghese Adam Klausner John Speich |
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MP08-06 |
Combination of RGB and narrow band imaging for discrimination of non-muscle invasive bladder cancer |
Imaging/Radiology: Uroradiology I | 17BOS |
Abstract: MP08-06 Sources of Funding: none Introduction We evaluated the use of white light imaging (WLI) and narrow-band imaging (NBI) cystoscopy for the detection of bladder cancer. Additional objectives were to provide summary RGB data and to determine a relationship between cancer detection and tumor characteristics. Methods A prospective double blinded controlled study of NBI was conducted in 102 consecutive patients with definite or suspected bladder cancer after WLI and NBI cystoscopy by 2 urologists. Transurethral targeted biopsies were performed and the histologic outcomes were compared. We analyzed average RGB color on 3x3 pixel of the randomized 3 other points for abnormal lesions and grossly normal in bladder._x000D_ _x000D_ Results A total of 172 biopsies for suspicious lesions (WLI+/NBI+=145, WLI-/NBI+=27) were taken. The percentage of malignancies in the sites identified only by NBI was 63.0% (17 sites).Of 15 CIS sites, 53.3% was detected by only NBI. The positive predictive value of NBI and WLI were 70.3% and 67.1%, respectively. _x000D_ Bladder washing cytology positive (HR=3.87, p=0.002). grossly papillary feature (HR=6.80, p<0.001) average blue of lesion for WLI (HR=0.96, p=0.006) were significant risk factors for detection of bladder cancer during transurethral targeted biopsy. Conclusions NBI is a simple and effective method for identifying CIS without the need for dyes. RGB analysis for bladder wall would be helpful for discrimination bladder cancer. Funding none
Authors
Kwang Suk Lee
Kyo Chul Koo Do Kyung Kim Jongsoo Lee Jong Won Kim Jae Yong Jeong Sung Ku Kang Byung Ha Chung |
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MP08-07 |
Single Pulse-Per-Second Setting Significantly Reduces Fluoroscopy Time During Ureteroscopy |
Imaging/Radiology: Uroradiology I | 17BOS |
Abstract: MP08-07 Sources of Funding: none Introduction Both patients and surgeons are exposed to ionizing radiation during endourologic procedures. Modern C-arms have settings that can be modified to lower radiation exposure, including "low-dose" and pulsed fluoroscopy. Pulsed fluoroscopy rates range from a standard rate of 30 to 1 pulse-per-second (pps). We present here the only known series evaluating the effect of 1 pps on fluoroscopy time and surgeon radiation exposure. Methods A retrospective review of a single endourologist's operative records was performed over a 12 month period. Adult patients undergoing ureteroscopy were included. At the 6 month point, the switch from continuous "low-dose" to 1 pps "low-dose" fluoroscopy was made. Collected data included age, gender, body mass index (BMI), aggregate stone burden, stone multiplicity, laterality, laser and ureteral access sheath usage, operative time, fluoroscopy time, rates of failed or staged ureteroscopy and complication rates. Surgeon radiation exposure was measured using 1 dosimeter placed at the torso under the lead apron and 1 dosimeter overlying the chest outside the lead apron. Deep Dose Equivalent (DDE), Lens Dose Equivalent (LDE), and Shallow Dose Equivalent (SDE) were calculated using the EDE1 formula._x000D_ Results A total of 84 and 70 patients underwent ureteroscopy using continuous and 1 pps fluoroscopy, respectively. No significant differences were identified between the 2 groups with regards to patient age (p=0.96), sex (p=0.26), BMI (p=0.95), stone multiplicity (p=0.31), bilateral ureteroscopy (p=0.07), pre-stenting (p=0.99), staged (p=0.84) or failed ureteroscopy (p=0.99), ureteral access sheath utilization (p=0.10), or case duration (p=0.54). Patients in the 1pps cohort had a larger median stone burden (1.8cm IQR 0.9-2.8cm vs. 1.3cm IQR 0.8-2.0 cm, p=0.04). Median fluoroscopy time was reduced from 77 (IQR 54-115) to 16 seconds (IQR 13-24) using 1 pps (p<0.001). Monthly surgeon radiation exposure was reduced by an average of 64%, from 6.8±8.3 to 1.8±2.7 mRad DDE (p = 0.11), 120.6±101.4 to 49.2±66.6 mRad LDE (p=0.10), and 116.2±97.8 to 47.6±64.0 mRad SDE (p=0.11). Complications were rare without significant difference between the 2 groups. Image quality was acceptable in all cases using 1 pps fluoroscopy despite a maximal patient BMI of 82.2. The only technical compromise noted was increased motion artifact, which was easily avoided by allowing the C-arm to complete motion prior to image acquisition._x000D_ Conclusions Use of single pulse-per-second fluoroscopy significantly reduces fluoroscopy time and lowers surgeon radiation exposure by 64%._x000D_ Funding none
Authors
Todd Yecies
Anisleidy Fombona Michelle Semins |
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MP08-08 |
Reading reports Vs Reviewing images….How Important is it for Endourologists to Look at Films Prior to Decision-making? |
Imaging/Radiology: Uroradiology I | 17BOS |
Abstract: MP08-08 Sources of Funding: None Introduction The diagnosis and management of endourological conditions is highly dependent on imaging studies. Radiology reports do not always address all the issues relevant to decision-making, and on occasion can be inaccurate. To our knowledge, there is no data available in the endourological literature regarding the importance of self-viewing of images by treating physicians. We prospectively compared the diagnosis and management of endourology patients based on CT radiology reports alone vs. the viewing of images by an experienced endourologist. Methods We randomly selected 46 new patients referred to an endourology practice who came with CT radiology reports for evaluation. A diagnosis was rendered and a treatment plan was formulated based on the report and history and physical exam. Following this, during the visit, the actual images were obtained and reviewed in detail and a final diagnosis and treatment plan rendered. Comparative findings and decisions were graded according to our protocol. Results We saw changes in findings or treatment plan after reading of images in 29 patients (63.1%). Discrepant findings included wrong side in report, inaccurate stone size, missing stones, inaccurate location of stones, number of stones, degree of hydronephrosis etc. New findings included presence of AML, contralateral stones, crossing vessels, retrorenal colon, malrotated kidneys, duplicated collecting system, horseshoe kidney, scoliosis, and others. Missing information that affected treatment strategy included skin to stone distance, stone density, stone volume, and presence of encrustations on stent already in place. Grade 1 changes (defined as minor differences not affecting surgical plan) were observed in 11/29 (37.9%). Grade 2 changes (change in type of procedure) were noted in 7/29 (24.2%). Grade 3 changes (decision for observation vs. surgery) were observed in 5 (10.9%). Grade 4 changes (an additional procedure needed during surgery) were observed in 3 (6.5%). Grade 5 changes (potentially severe complication avoided, e.g. retrorenal colon in case of PCNL, change in side of surgery, crossing vessel at UPJ in patient candidate for endopyelotomy) were observed in 3 patients (6.5%). Conclusions Reviewing CT images rather than relying on a report alone results in a significant (grades 2 to 5) change in treatment plan in randomly selected endourology patients and can potentially avoid complications._x000D_ Funding None
Authors
Haresh Thummar
Ponkhraj S Shivang D N Thummar |
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MP08-09 |
Population-level Cancer Detection and Patterns of Care Following MRI-guided Prostate Biopsy |
Imaging/Radiology: Uroradiology I | 17BOS |
Abstract: MP08-09 Sources of Funding: Emory University Department of Urology Research Scholars Grant_x000D_ Winship Cancer Institute Prostate Cancer Pilot Grant Introduction The use and outcomes of MRI-guided prostate biopsy (MRI-Bx) have not been broadly characterized in a nationwide community setting. We evaluated CaP detection rates across Bx types and evaluated subsequent care patterns at a population-level among men covered by private health insurance._x000D_ Methods Using MarketScan Commercial Claims data (2009-2013), we identified men who underwent Bx without prior CaP diagnosis/treatment. We assigned approach (MRI-Bx vs TRUS-Bx vs transperineal (TP-Bx)) using CPT codes for Bx and pelvic MRI. We assigned MRI-guidance if MRI performed ≤3 months before Bx. Primary outcome was new CaP diagnosis (i.e., ICD-9 185.0). Other outcomes included treatment (yes/no) and treatment type (prostatectomy (RP) vs radiation (RT)) Multivariable logistic regression adjusted for patient and geographic covariates to estimate odds of these outcomes._x000D_ Results We identified 210,894 men who underwent 1+ Bx (MRI-Bx n=1,378; TRUS-Bx n=208,776, TP-Bx n=740). The mean age of this cohort was 57 years (standard deviation 5 years). Overall, a new CaP diagnosis was most common after TRUS-Bx (36.4%) versus MRI-Bx (28.9%) and TP-Bx (29.3%) (p<0.001). Patients with prior negative Bx were less likely to have a new CaP diagnosis (20.5% vs 37.7% Bx-naive, p<0.001). Patients with prior negative Bx who underwent MRI-Bx were not more likely to be diagnosed with CaP (OR 1.12 vs TRUS-Bx, 95% CI 0.88-1.43) (Figure). Among Bx-naive men, MRI-Bx was associated with a lower odds of CaP detection (OR 0.81 vs TRUS-Bx, 95% CI 0.71-0.93). Patients managed with MRI-Bx and diagnosed with CaP were less likely to receive treatment (OR 0.77, 95% CI 0.62-0.98). There is no association between Bx approach and type of treatment (OR 1.19 RP vs RT, 95% CI 0.90-1.58)._x000D_ Conclusions During initial adoption, use of MRI-Bx was not associated with significantly increased CaP detection among men with prior negative Bx. Furthermore, patients receiving MRI-Bx were less likely to then have treatment for PCa. These findings merit further investigation, taking tumor and provider factors, including operator experience, into account. _x000D_ Funding Emory University Department of Urology Research Scholars Grant_x000D_ Winship Cancer Institute Prostate Cancer Pilot Grant
Authors
Wen Liu
Dattatraya Patil David Howard Renee Moore Heqiong Wang Martin Sanda Christopher Filson |
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MP08-10 |
Prospective Evaluation of Cancer Detection Rates of the Prostate Imaging Reporting and Data System version 2 |
Imaging/Radiology: Uroradiology I | 17BOS |
Abstract: MP08-10 Sources of Funding: The author&[prime]s postdoctoral fellowship is funded by a research grant from the &[Prime]Dr. Mildred Scheel&[Prime] foundation (Bonn, Germany) Introduction Prostate Imaging-Reporting and Data System version 2 (PI-RADSv2) was introduced in 2015. The likelihood of harboring clinically significant prostate cancer (CS PCa) on multiparametric MRI (mpMRI) is assessed on a five-point scale. We prospectively evaluated cancer detection rates (CDRs) of PI-RADSv2 scores using the new International Society of Urological Pathology (ISUP) grading group system as the gold standard. Methods From May 2015-May 2016, 963 patients underwent prostate mpMRI including T2 weighted (T2W), diffusion weighted, apparent diffusion coefficient maps, high b value (1500-2000s/mm2) and dynamic contrast enhancement sequences. 339/963 patients underwent MRI/US fusion guided biopsy. The highest Gleason score per target lesion was given an ISUP score. Lesion-based CDRs for all PCa and CS PCa (ISUP≥2, ≥Gleason 3+4) were calculated for each PI-RADSv2 score in the entire prostate, peripheral (PZ) and transition zones (TZ). Results CDRs for all and CS PCa for each PIRADSv2 score are shown in Figure 1. PI-RADSv2 score 5 had the highest CDRs for all and CS PCa at 87% and 72%, respectively. PI-RADSv2 score 4 had unexpectedly low CDR for both all and CS PCa (39% and 22%, respectively). Specifically, in the PZ, the CDR of T2W PI-RADSv2 score 4 was significantly higher than the CDR of overall PI-RADSv2 score 4 for all PCa (48% vs. 37%, p=0.01) and CS PCa (33% vs 23%, p=0.002) (Figure 2). Conclusions CDRs increase with higher PI-RADSv2 scores. CDR of PI-RADSv2 score 4 is low due to a high false positive rate. In the PZ, T2W scores combined with DWI scores, rather than DWI scores alone may improve the CDR for PI-RADSv2 score 4 lesions. Future versions of PI-RADS should take this into account. Funding The author&[prime]s postdoctoral fellowship is funded by a research grant from the &[Prime]Dr. Mildred Scheel&[Prime] foundation (Bonn, Germany)
Authors
Sherif Mehralivand
Sandra Bednarova Joanna Shih Francesca Mertan Sonia Gaur Maria Merino Bradford Wood Peter Pinto Peter Choyke Baris Turkbey |
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MP08-11 |
Radiologist Experience Level Does Not Predict the Accuracy of Prostate MRI Interpretation for Clinically Significant Prostate Cancer: Are Consensus Reads the Answer? |
Imaging/Radiology: Uroradiology I | 17BOS |
Abstract: MP08-11 Sources of Funding: None Introduction To provide standardization as prostate MRI becomes increasingly utilized, the Prostate Imaging-Reporting and Data System (PIRADS) was developed and has been modified to its latest version (v2). Using biopsy outcome as the standard, we examined the predictive accuracy of a PIRADS 4 or 5 read for clinically significant (Gleason 7+) PCa in a blinded fashion. Methods We reviewed our prospectively maintained database of consecutive men who underwent prostate MRI prior to biopsy between September 2014 and December 2015. A proportionally representative sample (based on the original clinical PIRADS v2 interpretation) was selected for re-examination (n=32). The prostate MRIs for these patients were de-identified and were loaded by a blinded third party. Four radiologists of varying levels of experience independently interpreted all prostate MRI, blinded to all clinical information. An &[Prime]over-read&[Prime] was defined as a PIRADS 4 or 5 read with biopsy result of benign prostate or Gleason 6 PCa. An &[Prime]under-read&[Prime] was defined as a PIRADS 1-3 read with resulting biopsy result of Gleason 7+ PCa. Results The distribution of accuracy is provided in Table 1. Accurate interpretation ranged from 56% (18/32) to 75% (24/32), and the differences among the radiologists were not significant (p=0.48). The improvement of accuracy with a &[Prime]majority read&[Prime], as defined by two or more accurate radiologists&[prime] blinded interpretations, over the original clinical read trends toward significance (p=0.16). No clinical variable was predictive of an incorrect &[Prime]majority read&[Prime], including age, PSA, family history, use of 5-alpha reductase inhibitors, prostate volume, or previous biopsy history. Conclusions In a blinded assessment of radiologists at our institution, we find that the predictive accuracy of PIRADS 4 or 5 for clinically significant PCa varies among radiologists independent of experience level. A &[Prime]majority read&[Prime] performed better than the original clinical interpretation, suggesting that consensus interpretation of prostate MRI may improve predictive accuracy. Funding None
Authors
Eric Kim
Joel Vetter Anup Shetty Kathryn Fowler Aaron Mintz Cary Siegel Gerald Andriole Robert Grubb III |
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MP08-12 |
Multi-institutional evaluation of MRI and Fusion Biopsy in Confirmatory Biopsy for Active Surveillance |
Imaging/Radiology: Uroradiology I | 17BOS |
Abstract: MP08-12 Sources of Funding: None Introduction Preliminary single-institution data has suggested a benefit of prostate MRI and fusion biopsy (FBx) in evaluation of patients considered for active surveillance (AS). We aim to determine the utility of MRI/FBx for confirmation of AS candidacy and identify predictors of Gleason upgrading in a multi-institutional cohort of patients. Methods A retrospective review was completed at five tertiary referral centers to identify patients with Gleason 3+3=6 or Gleason 3+4=7 prostate cancer with PSA < 15 who underwent 3T prostate MRI and confirmatory FBx between 2012-2015. MRI regions of interest (ROI) were reported according to PIRADSv2 criteria. The primary outcome was Gleason score upgrading on targeted sampling when compared to pre-FBx standard 12-core biopsy (SBx). Univariate and multivariate analysis of variance were performed to identify clinical, imaging, and pathologic characteristics independently associated with Gleason score upgrading on fusion biopsy. Results A total of 225 patients were identified meeting inclusion criteria, of which 209 (93%) had Gleason 3+3=6 and 16 (12%) had Gleason 3+4=7 disease on SBx. Confirmatory FBx resulted in Gleason score upgrading within the targeted ROI in 90 patients (40%). Detailed patient demographics and pathologic characteristics are depicted in Table 1. FBx did not miss any high risk PCa, while identifying 10 patients (12.5%) with high risk disease missed on SBx alone. Patient age (p=0.003), pre-fusion biopsy PSA (p=0.020), initial standard 12-core Gleason score (p=0.070), prostate volume (p=0.003), and PI-RADSv2 classification (p=0.056) were found to be associated with confirmatory FBx upgrading on univariate analysis. Multivariate analysis demonstrated a significant and independent association of patient age (p=0.001), pre-fusion biopsy PSA (p=0.006), prostate volume (p=0.020), and PI-RADSv2 classification (p=0.050) with FBx upgrading. Conclusions Confirmatory FBx improves risk stratification of patients considering AS. Age, pre-FBx PSA, prostate volume, and PI-RADSv2 classification were independently associated with Gleason score upgrading on confirmatory FBx. Funding None
Authors
Christopher M. Russell
Amir H. Lebastchi Matthew Lee Scott A. Tomlins Jeffrey S. Montgomery Chandy S. Ellimoottil Jont T. Wei Matthew S. Davenport Nicole Curci Thomas P. Frye Matthew Truong Srinivas Vourganti Ardeshir Rastinehad Paras Shah Vinay Patel Arvin George |
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MP08-13 |
MR Radiomics in the Risk Stratification of Prostate Cancer |
Imaging/Radiology: Uroradiology I | 17BOS |
Abstract: MP08-13 Sources of Funding: None Introduction The current paradigm in prostate cancer risk stratification, including DRE, PSA values, and prostate biopsy, has resulted in overdiagnosis and overtreatment. A noninvasive marker is needed to more accurately differentiate between aggressive and indolent disease. This study evaluated multiparametric magnetic resonance imaging (mpMRI)-derived texture metrics as a biomarker for prostate cancer risk stratification. Methods In this IRB approved, retrospective study, we identified 66 prostate cancer lesions in patients who underwent 3T mpMRI prior to prostate biopsy. Biopsy proven Prostate cancer lesions were divided into high, intermediate, and low risk categories per National Comprehensive Cancer Network guidelines. Lesion regions of interest were manually segmented from apparent diffusion coefficient (ADC) and T2 weighted images (T2WI). Texture analysis was performed using gray-level co-occurrence matrices (GLCM), fast Fourier transfer-based spectral metrics, and ADC and T2 signal intensity. Kruskall Wallis test and analysis of variance were used to determine if there is an association between texture metrics and prostate cancer risk categories. Stepwise logistic regression was used to select the best predictors in discriminating high risk lesions from other lesions. Results Of the spectral metrics, Complexity Index on ADC and T2WI was significantly different (p<0.01) between the risk categories. ADC-derived GLCM metrics variance, contrast, homogeneity, dissimilarity, and difference of average were significantly different (p<0.01) between the risk categories. Of the texture metrics, GLCM Variance on ADC (ADC_Var) and Information Measures of Correlation 1 on T2WI (T2_ICM1) were the best metrics in discriminating high risk lesions from intermediate and low risk lesions and were selected in the final prediction model. Used alone, the areas under the receiver operator curve (AUC) for ADC_Var and T2_IMC1 were 0.77 (95%CI: 0.64-0.9) and 0.71 (95%CI: 0.59-0.82) respectively. The AUC when using both metrics together was 0.83 (95%CI: 0.72-0.94). Conclusions mpMRI-based texture analysis can differentiate high risk prostate cancer lesions from intermediate and low risk lesions, demonstrating promise as a biomarker for prostate cancer risk stratification._x000D_ _x000D_ Funding None
Authors
Frank Chen
Bino Varghese Darryl Hwang Steve Cen Mihir Desai Suzanne Palmer Monish Aron Manju Aron Inderbir Gill Gangning Liang Andre Abreu Sameer Chopra Osamu Ukimura Vinay Duddalwar |
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MP08-14 |
Development and Validation of a Nomogram for Predicting PIRADS 4-5 Lesions on Multiparametric Prostate MRI |
Imaging/Radiology: Uroradiology I | 17BOS |
Abstract: MP08-14 Sources of Funding: none Introduction Multiparametric MRI (mpMRI) of the prostate is gaining popularity for use in prostate cancer (PCa) detection in patients with a prior negative sextant biopsy as well as in low risk PCa patients on active surveillance. The presence of PIRADS 4 and PIRADS 5 lesions on mpMRI have the highest diagnostic yield for clinically significant PCa on subsequent MRI-ultrasound fusion biopsy. Counseling patients regarding the benefit of mpMRI is becoming an increasingly important aspect of urologic practice. Nomograms may be clinically useful to individualize decisions to perform mpMRI based on patient risk profiles._x000D_ Methods We identified 1023 patients who underwent mpMRI of the prostate from July 2014-October 2016 at our institution. Inclusion criteria were patients who underwent mpMRI to aid PCa detection or while on active surveillance. Using clinical variables, nomogram development was performed using 883 consecutive patients who met the inclusion criteria for the study. Clinical variables assessed included age, PSA, prostate volume, and PSA density (PSAD). Multivariable logistic regression generated a nomogram incorporating age, PSA, and prostate volume for finding PIRAD 4 or 5 lesions on mp MRI. A separate nomogram using PSAD alone was generated. Internal validation of each nomogram was performed by generating an ROC, calibration, and decision analysis curves. Results Age, PSA, prostate volume, and PSAD were all significant predictors of PIRADS 4-5 lesions on univariable analysis (all p < 0.001). Upon internal validation, a nomogram incorporating age, PSA, and prostate volume had an AUC of 0.746 (p < 0.001). A separate nomogram using PSAD alone had an AUC of 0.729 (p < 0.001). Both nomograms had excellent calibration and high net benefit on decision curve analysis across a wide range of predicted probabilities. The two nomograms performed similarly regardless of indication for mpMRI. Conclusions We developed two clinical nomograms that accurately predict the probability of finding PIRADS 4-5 lesions on mpMRI, which may be useful in counseling patients undergoing prostate cancer screening or who are on active surveillance. These nomograms pose no additional cost given that age and PSA are readily available and prostate volume obtained at previous transrectal ultrasound-guided biopsy can be used as input. Externally validation should be performed to confirm the utility of this nomogram in other cohorts. Funding none
Authors
Matthew Truong
Thomas Frye Dang Lam Ji Hae Park Bokai Wang Changyong Feng Gary Hollenberg Eric Weinberg Edward Messing |
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MP08-15 |
Multi Institutional Study on Multi-Parametric Magnetic Resonance Imaging/Ultrasound Fusion Biopsy, are we getting better? |
Imaging/Radiology: Uroradiology I | 17BOS |
Abstract: MP08-15 Sources of Funding: none Introduction The usage of multi-parametric Magnetic Resonance Imaging/Ultrasound fusion biopsy (Fbx) to aid in the diagnosis of clinically significant (CS) prostate cancer (CaP) has taken place in recent years. Our objective was to determine if the detection rate of our multi institutional experience with Fbx and standard 12 core sextant biopsy (SBx) in detecting clinically significant prostate cancer is improving over time. Methods A retrospective review of 803 patients who underwent FBx biopsy and SBx in the same setting between September 2014 and September 2016 was performed. Group 1 consisted of patients who underwent FBx and SBx in the first year of starting FBx and group 2 consisted of patients who underwent FBx and SBx in the second year of starting FBx. All patients underwent a 3-Tesla multi-parametric MRI (mpMRI) performed at 3 different institutions. mpMRI was performed using T1/T2 phases, dynamic contrast enhancement and diffusion weighted imaging. Using a 3-dimensional model fusion software [InVivo (Phillips), Gainesville (USA)], 2-5 fusion biopsies were performed on each prostate lesion. FBx was only performed on patients with at least 1 PIRADS ?3 lesion on mpMRI. Gleason score ? 7 was considered as clinically significant prostate cancer. Results 341 patients underwent an FBx and SBx between September 2014-2015 and 462 patients underwent FBx and SBx between September 2015-2016. Age, PSA, race, BMI and location where mpMRI was not significantly different between both groups, p>0.05. 109/341 patients (32%) were diagnosed with CaP in 2015 and 162/462 patients (35%) were diagnosed with CaP in group 2. 56/341 patients (16%) were diagnosed with CS CaP in group 1 and 96/462 (21%) patients were diagnosed with CS CaP based off fusion biopsy in group 2 (Table 1). Compared to SBx, FBx is likely to detect clinically CS CaP as can be seen in both years on table 1. Conclusions Our experience show that FBx may have a learning curve with lower detection rate initially which improves over time. Although FBx is better at detecting CS CaP compared to SBx, more studies are required to determine the ideal number of FBx needed to overcome this initial learning curve and where detection rate would start to plateau. Funding none
Authors
Wei Phin Tan
Thomas Hwang Mukund Gande Daniel Dalton Paul Yonover Kalyan Latchamsetty Christopher Coogan |
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MP08-16 |
Use of duplicate axial imaging in newly diagnosed prostate cancer – trends across the Pennsylvania Urologic Regional Collaborative (PURC) |
Imaging/Radiology: Uroradiology I | 17BOS |
Abstract: MP08-16 Sources of Funding: Data was provided with permission from the Pennsylvania Urology Regional Collaborative (PURC), funded by participating urology practices and the Partnership for Patient Care, a quality improvement initiative supported by the Health Care Improvement Foundation, Independence Blue Cross, and southeastern PA hospitals and health systems. Introduction NCCN prostate cancer (CaP) guidelines currently designate either CT or MRI as recommended staging modality in select patients. The versatility of MRI may provide an additional aide in surgical planning or risk-stratification for active surveillance. Potential exists for overuse, resulting in duplicate axial imaging (CT + MRI) in same patient. We sought to analyze axial imaging utilization and to quantify the incidence of duplicate axial imaging in patients with newly diagnosed CaP across a regional collaborative. Methods PURC is a prospective regional collaborative comprised of six large academic and private urology practices in Southeastern Pennsylvania launched in 2014. Demographic and clinicopathologic data for patients with newly-diagnosed CaP were abstracted. Rates of duplicate axial imaging (CT+MRI) were examined using chi-square and Spearman&[prime]s correlation statistical analyses. Results Data from 1892 patients with newly diagnosed CaP (May 2015 to Nov 2016) were abstracted. Median age was 63 [IQR 58-68], 66.1% were Caucasian and 26.2% African American. Median PSA was 6.1 [IQR 4.6-9.4] and NCCN risk category was very low, low, intermediate and high/very high in 7.4%, 22.5%, 45.0% and 25.1%, respectively. Overall, 923 patients (48.8%) underwent axial imaging. MRI alone was utilized in 659 (34.8%) and CT in 332 (17.5%). Duplicate imaging was observed in 68 patients, 7.4% of the patients with any axial imaging, 3.6% of the overall cohort. Patients with duplicate imaging differed significantly from the remainder of the cohort in clinicopathologic characteristics (higher PSA, p<0.001; higher cT stage, p=0.015; higher Grade Group, p<0.001; higher NCCN risk category, p<0.001) but not demographic characteristics (age, race, family history of CaP, Charlson comorbidity score). 48% of providers were observed to utilize duplicate axial imaging, with significant variation by individual provider from 0% to 60%. A weak correlation was observed between individual provider&[prime]s patient volume and use of duplicate imaging (Spearman&[prime]s correlation 0.313, n=56, p=0.019). Conclusions A non-trivial rate of duplicate axial imaging in patients with newly diagnosed CaP involving nearly half of participating providers was observed across PURC. Clinicopathologic factors such as higher PSA levels, clinical T stage, Grade Group and NCCN risk category were associated with higher duplicate imaging rates. Further studies are needed to assess specific indications leading to such duplication. Funding Data was provided with permission from the Pennsylvania Urology Regional Collaborative (PURC), funded by participating urology practices and the Partnership for Patient Care, a quality improvement initiative supported by the Health Care Improvement Foundation, Independence Blue Cross, and southeastern PA hospitals and health systems.
Authors
Serge Ginzburg
Adam Reese Edouard Trabulsi Tianyu Li Claudette Fonshell Bret Marlowe Thomas Guzzo Thomas Lanchoney Marc Smaldone Robert Uzzo |
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MP08-17 |
Is magnetic resonance imaging sensitive enough for partial gland high intensity focused ultrasound treatment? Comparing prostate cancer lesions between magnetic resonance imaging and prostatectomy specimens |
Imaging/Radiology: Uroradiology I | 17BOS |
Abstract: MP08-17 Sources of Funding: none Introduction Focal ablation during high intensity Focused ultrasound (HIFU) offers reduced comorbidities, but increased risk of untreated disease. Magnetic resonance imaging (MRI) is increasingly being used to select patients for focal HIFU. Our objective was to characterize how well MRI fusion biopsy identifies disease within the prostate by studying men who have underwent a MRI fusion biopsy and subsequent radical prostatectomy. Methods A prospective database was queried for a history of radical prostatectomy and MRI fusion biopsy. Men underwent a 3 Tesla multi-parametric MRI, one of two radiologists evaluated all MRI scans, and lesions were scored from 1-5 using an institution specific system. A genitourinary pathologist reviewed all prostatectomy specimens and primary and secondary lesions were reported. Differences between MRI lesions and prostatectomy tumor foci were assessed for size, Gleason score, and laterality. Means were compared using students t-test and all statistical analysis was performed using Stata 13.1. Results Fifty-eight patients underwent MRI-fusion and 12-core biopsy followed by prostatectomy with a total of 702 biopsy cores evaluated. The median (IQR) age = 66.4years (60-70), PSA = 9.3ng/mL (6-15), and number of prior biopsies = 1 (0-2). Final Gleason score was as follows: 6= 2(3%), 7= 46(79%), and 8-9= 10(17%). There were a total of 120 MRI lesions with a median (range) of 2 (1-5) marked for fusion biopsy per patient, and a mean of 2.4 fusion biopsies per lesion. A MRI lesion was found in the quadrant of the primary (largest) surgical pathologic focus in 45/58 (78%). However, of these MRI lesions only 24 (53%) had matching grade with 12 benign biopsies being upgraded to Gleason ≥7 on surgical pathology. The mean MRI lesion greatest dimension was 1.9cm compared to 2.2cm on final pathology (p=0.03). MRI lesions were similar in size to final pathology (not more than 1cm smaller) in 37/45 (82%) while 3 (7%) were 1-1.9cm smaller and 5 (11%) were ≤2cm smaller. A total of 23/58 (40%) had fusion biopsy Gleason ≤7 on a single side, and on final pathology 14 (61%) had a secondary focus of bilateral disease. Conclusions A significant number of surgical specimens contained lesions larger than predicted by MRI or had bilateral disease when only unilateral disease was seen on biopsy. When considering focal HIFU, it would be prudent to treat a larger area surrounding the dominant MRI lesion. Furthermore, follow-up biopsies of the contralateral untreated lobe are imperative. Funding none
Authors
Clinton Bahler
Clint Cary Ronald Boris Temel Tirkes Timothy Masterson Thomas Gardner Michael Koch |
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MP08-18 |
Diagnostic accuracy of the shear wave elastography for the identification of Prostate Cancer: a diagnostic meta-analysis |
Imaging/Radiology: Uroradiology I | 17BOS |
Abstract: MP08-18 Sources of Funding: This study was supported by the Prostate Cancer Foundation Young Investigator Award 2013, the National Natural Science Foundation of China (Grant No. 81300627 and 81370855) and Programs from Science and Technology Department of Sichuan Province (Grant No. 2013SZ0006 and 2014JY0219). Introduction This meta-analysis aimed to evaluate the performance of shear wave elastography in the identification of prostate cancer. Methods PubMed, Embase and the Cochrane Library were searched for relevant studies with a publication date through March 2016. The methodological quality was assessed using QUADAS tools. Data synthesis was calculated using Meta-Disc Version 1.4. Results Of the 137 studies identified, 11 were included with 1407 patients. Methodological assessment demonstrated study quality was moderate to high. The pooled sensitivity, specificity, and area under the summary receiver operating characteristic curve of SWE for detecting malignant prostatic nodules were 85 % (95% CI, 82-87%), 84 % (95% CI, 82-86%), and 92% (95% CI, 90-95%), respectively. Positive and negative predictive values were 27.7-44.7% and 98.1-99.1 %. The positive and negative likelihood ratio were 4.45 (95% CI: 2.87-6.89) and 0.18 (95% CI: 0.11-0.32). The summary diagnostic OR was 28.48 (95% CI: 12.42- 65.35). Publication bias regression test revealed no significant small-study bias. Conclusions Shear wave elastography is a highly accurate diagnostic method for the identification of prostate cancer using the histopathology as the reference standard and may help to reduce the number of core biopsies in the future. Funding This study was supported by the Prostate Cancer Foundation Young Investigator Award 2013, the National Natural Science Foundation of China (Grant No. 81300627 and 81370855) and Programs from Science and Technology Department of Sichuan Province (Grant No. 2013SZ0006 and 2014JY0219).
Authors
Xiang Tu
Lu Yang Qiang Wei |
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MP08-19 |
Prostate MRI: The Truth Lies in the Eye of the Beholder |
Imaging/Radiology: Uroradiology I | 17BOS |
Abstract: MP08-19 Sources of Funding: None Introduction Pelvic MRI can be used in the setting of prostate cancer for pre-surgical evaluation of local disease extension although limitations are debated. Less often discussed, however, is the human component; specifically, the radiologist interpreting the study. Herein, we investigate the accuracy and variability of pelvic MRI interpretation among our body radiology team versus a senior faculty member. Methods A single institution retrospective study identified 233 consecutive individuals diagnosed with prostate cancer who ultimately had a prostatectomy. All patients had pre-surgical pelvic 3T surface body coil MRI read by a fellowship trained body radiologist provided with relevant clinical information. Thereafter, a senior radiologist was selected to re-read all pelvic MRIs blinded to the initial interpretation. Both MRI readings were compared to final pathology report. Kappa (K) scores as well as sensitivity, specificity, positive predictive values (PPV), negative predictive value (NPV), and accuracy were calculated. Results When considering extraprostatic extension (EPE), there was low concordance comparing the initial versus repeat MRI interpretation (K=0.22). Additionally, when the senior radiologist re-read his own initial interpretation (n=93, blinded to initial result), concordance for EPE was greater (K=0.36) albeit similarly low. Regarding EPE, a comparison of initial MRI interpretation versus re-read by senior radiologist noted universal improvements in diagnostic characteristics include sensitivity (30.3% vs 56.1%), specificity (80.2% vs 88.6%), PPV (37.7% vs 66.1%), NPV (74.4% vs 83.6%), and accuracy (66.1% vs 79.4%). In contrast, seminal vesicle (SV) invasion interpretation was more uniform whereby initial MRI interpretation vs. re-read yielded similar sensitivity (18.2% vs 27.3%), specificity (97.2% vs 93.8%), PPV (40.0% vs 31.6%), NPV (91.9% vs 92.5%), and accuracy (89.7% vs 87.6%) (Table). Conclusions Even at an academic medical center, interobserver agreement amongst radiologists to evaluate local extent of disease on prostate MRI is relatively low. We report, however, improved characteristics when a senior member of the body radiology team reads the MRI. These findings underscore the importance of uniformity when defining criteria for EPE and SV invasion to allow for appropriate surgical planning. Funding None
Authors
Joseph C. Riney
Nabeel E. Sarwani Shehzad Siddique Jay D. Raman |
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MP08-20 |
Rapid Phenotyping of Genitourinary Anomalies in Mice Using Micro-CT |
Imaging/Radiology: Uroradiology I | 17BOS |
Abstract: MP08-20 Sources of Funding: Supported in part by 4R01DK078121-09 from the NIDDK to DJL Introduction Mouse models serve as an excellent tool for studying human disease. Yet, the small size of the mouse presents technical challenges in characterizing organ defects. The use of micro-computed tomography (micro-CT) in biomedical research has historically been limited to studying osseous structures. However, development of iodine staining techniques has allowed for improved ex vivo study of soft tissue structures. Images acquired through micro-CT allow for limitless virtual sectioning (as thin as 2 µm), a distinct advantage over traditional tissue sectioning. In this study, we demonstrate the successful use of iodine staining and micro-CT to rapidly phenotype genitourinary (GU) anomalies in mice. Methods Mice GU specimens were excised, fixed in formalin, and dehydrated in 70% ethanol. Iodine staining was performed by soaking the tissue in 0.1 N iodine (Fluka). The specimen was suspended in agar in preparation for imaging. Images were acquired using the SkyScan 1272 High-Resolution X-Ray Microtomograph (Bruker microCT, Kontich, Belgium). A 0.5 µm aluminum filter was utilized. Imaging parameters were 5 µm and 11 µm pixel size for penis and kidney specimens, respectively, and 2016 x 1344 resolution. Images were reconstructed using NRecon (Bruker microCT) and visualized using 3D Slicer v4 (slicer.org). Results Both embryonic and adult mice GU specimens were imaged. Micro-CT scan time varied with specimen size and desired resolution, but was at longest 120 minutes. Normal and pathologic GU phenotypes were characterized on three-dimensional, reconstructed images. Embryonic GU systems were examined, including a number of hydronephrotic kidneys (top left). Normal, hydronephrotic, duplex (top right), and polycystic kidneys (bottom left) were identified in adult specimens. Adult penile specimens (bottom right) were reconstructed to allow for morphometric measurements. Conclusions We demonstrate successful generation of three-dimensional, high-resolution, contrast-enhanced images of GU organs in the murine model using micro-CT. The use of micro-CT possesses a vast potential in rapid phenotyping and study of GU anomalies in the murine model._x000D_ Funding Supported in part by 4R01DK078121-09 from the NIDDK to DJL
Authors
Gene Huang
Marisol O'Neill Meade Haller Carolina Jorgez D.J. Lamb |
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MP09-01 |
Sildenafil for treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia |
Benign Prostatic Hyperplasia: Medical & Non-surgical Therapy | 17BOS |
Abstract: MP09-01 Sources of Funding: none Introduction A growing body of evidence demonstrates a relationship between lower urinary tract symptoms secondary to benign prostatic hyperplasia (LUTS/BPH) and erectile dysfunction (ED). This has led to the introduction of new combination treatments for LUTS/BPH whether accompanied by ED or not. Our aim was to evaluate and compare the therapeutic effect of sildenafil and tamsulosin either as single agents or combined on LUTS/BPH and ED. Methods We conducted a prospective randomized comparative study on 150 patients with LUTS/ BPH. They were categorized into three groups (groups A, B and C), each comprising 50 patients. These groups were comparable regarding pretreatment international prostate symptom score (IPSS) and international index of erectile function (IIEF). Group A was administered daily tamsulosin 0.4 mg as monotherapy. Group B received only sildenafil 25mg twice daily while patients of group C were given the combination of both. Parameters for comparison between pre and post treatment included IPSS, IIEF, uroflowmetry and post voiding residual volume (PVRV) at each visit (pretreatment, 4 and 16 weeks posttreatment). Results Sildenafil administered alone caused mild improvement in IPSS, flow rate and PVRV but more improvement in IIEF. Tamsulosin solely caused more improvement in IPSS, flow rate and PVRV with less improvement in IIEF score. A combination of both improved all of the parameters opposed to when each drug was used alone. Conclusions We have concluded that either tamsulosin or sidenafil as sole treatments may be used in treating mild or mild to moderate LUTS. However, more severe LUTS may benefit from a combination of both drugs. Moreover, our findings may indirectly verify the relationship between LUTS/ BPH and ED. Funding none
Authors
Ahmed M. Ragheb
Mahmoud M. Arafa Ayman S. Moussa Amr M. Massoud |
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MP09-02 |
Effects of tadalafil on storage and voiding function in patients with male lower urinary tract symptoms including benign prostatic enlargement, based on a urodynamic study |
Benign Prostatic Hyperplasia: Medical & Non-surgical Therapy | 17BOS |
Abstract: MP09-02 Sources of Funding: none Introduction Current guidelines for the treatment of benign prostatic enlargement (BPE) in several countries recommend the use of α1-blockers or PDE5 inhibitors as first treatment for male lower urinary tract symptoms (LUTS) with BPE. Tadalafil is one of the PDE5 inhibitors, and was reported to have prominent beneficial effects on subjects in some studies. However, to the best of our knowledge, the objective effects of this drug on storage and voiding function based on a urodynamic study (UDS) have not yet been reported. In this study, we investigated the effects of tadalafil on storage function and bladder outlet obstruction (BOO) based on a UDS in patients with LUTS due to BPE. Methods This open-label, single-center prospective study recruited 65 outpatients with untreated BPE. The patients received tadalafil 5 mg a day for 12 weeks. Before and 12 weeks after drug administration, International Prostate Symptom Score (IPSS), IPSS-quality of life (QOL), and Overactive Bladder Symptom Score (OABSS) were used for assessing subjective symptoms. To evaluate storage function, first desire to void (FDV), maximum cystometric capacity (MCC), and the incidence of detrusor overactivity (DO) were measured, while the maximum flow rate (Qmax), detrusor pressure at Qmax (PdetQmax), post-void residual urine (PVR), and BOO index (BOOI) were assessed as parameters of voiding function. Results A total of 60 patients with a mean age of 70.1 years and mean prostate volume of 46.7 mL were included in the analysis. Subjective symptom parameters such as IPSS, IPSS-QOL, and OABSS improved significantly at 12 weeks after treatment. In the storage phase of UDS, FDV and MCC significantly increased. Besides, out of 33 patients with DO before administration of tadalafil, 14 (42.4%) patients showed apparent improvement in DO after administration. In the voiding phase, the mean Qmax significantly increased from 7.1 to 9.0 mL/s. The mean BOOI significantly decreased from 61.6 to 47.7. Conclusions Tadalafil was effective for relieving LUTS by improving storage and voiding function as well as subjective symptoms in patients with BPE. Funding none
Authors
Yoshihisa Matsukawa
Shohei Ishida Kazuna Matsuo Yudai Miyata Hideo Narita Momokazu Gotoh |
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MP09-03 |
Combination therapy of tadalafil and tamsulosin for men with moderate to severe benign prostatic hyperplasia |
Benign Prostatic Hyperplasia: Medical & Non-surgical Therapy | 17BOS |
Abstract: MP09-03 Sources of Funding: none Introduction Benign prostatic hyperplasia (BPH) is commonly treated with alpha-blockers and 5-alpha-reductase inhibitors (5ARIs). However, tamsulosin has sexual side-effects, including ejaculatory dysfunction. Recently, tadalafil 5 mg daily has been shown to be helpful in treating lower urinary tract symptoms (LUTS). Thus, we compared tadalafil and tamsulosin with tamsulosin alone in terms of symptom improvement in males with moderate to severe BPH. Methods This 12-week study was a randomized, parallel group evaluation of clinical outcomes in males aged ≥ 50 years with symptomatic (IPSS≥12) BPH and a prostate volume ≥ 30 mL. Eligible patients received a combination of tadalafil 5 mg daily with tamsulosin 0.4 mg daily (n=30), or tamsulosin 0.4 mg daily only (n=30). The primary outcomes included the post-treatment IPSS, peak urinary flow rate, and post-void residual urine volume. The secondary outcomes were changes in scores on the IIEF, the Global Assessment Questionnaire (GAQ), and the Life Satisfaction Checklist (LSC). Results The IPSS improved similarly from baseline to 12 weeks in both groups (tadalafil+tamsulosin; -2.2 vs. tamsulosin only; -2.3; p=0.528). However, the IPSS storage subscale improved to a significantly greater extent in the tadalafil+tamsulosin group. Changes in the Q(Max) and PVR did not differ significantly between the groups. The tadalafil+tamsulosin group showed significantly greater changes in the erectile and orgasmic function domain scores of the IIEF compared to the tamsulosin-only group. In terms of the GAQ and LSC scores, the tadalafil+tamsulosin group exhibited significantly greater improvements. The adverse events profiles were consistent with those of previous reports. Conclusions Combination therapy with tadalafil and tamsulosin afforded improvements in LUTS/BPH scores similar to those seen when tamsulosin only was given. However, the combination also had obvious benefits in terms of sexual function. Tadalafil can compensate for the decreased sexual performance that is a side-effect of tamsulosin, and improve the LUTS. Funding none
Authors
Hyun Jun Park
Tae Nam Kim Jong Kil Nam Du Geon Moon Nam Cheol Park |
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MP09-04 |
Comparison between Tadalafil 5 mg vs. Serenoa Repens/selenium/lycopene for the treatment of benign prostatic lower urinary tract symptoms secondary to benign prostatic hyperplasia. A phase IV, randomized, multicenter, non-inferiority clinical study. SPRITE study. |
Benign Prostatic Hyperplasia: Medical & Non-surgical Therapy | 17BOS |
Abstract: MP09-04 Sources of Funding: None Introduction Over the last years, the disease management of lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH) have been consistently improved. In particular, tadalafil (5 mg once daily) has been licensed for the treatment of male LUTS/BPH. Recently, the PROCOMB trial demonstrated the efficacy of the combination treatment with Serenoa Repens, Lycopene (Ly), and Selenium (Se) and tamsulosin than single therapies (SeR-Ly-Se or Tamsulosin) in improving IPSS and increasing Qmax in patients with LUTS at 12 months. Although either Tadalafil 5 mg and Se-Ly-Se have been test versus tamsulosin, there are no data about the comparison between Tadalafil and Se-Ly-Se for the treatment of LUTS/BPH. For this reason, the aim of this phase IV, randomized, multicenter, non inferiority clinical study was to evaluate the efficacy and tolerability of the therapy Serenoa repens, selenium and lycopene (Profluss®) versus a Tadalafil® 5 mg for 6 months for the treatment of LUTS/BPH. Methods From April 2015 to September 2016, 439 men aged between 50 and 75, with digital rectal examination negative for prostate cancer, prostate specific antigen (PSA) < 4ng/ml, IPSS ?12, PVR <100 ml, peak flow between 4 and 15 ml/s were screened (ISRCTN73316039) from 21 Italian urological centres. After screening and eventually pharmacological wash-out, the participants were off-site central randomized with a 2:1 ratio into SeR-Se-Ly for 6 months (Group A; n= 300) or Tadalafil 5 mg for 6 months (Group B; n= 139). _x000D_ It was a non inferiority randomized clinical study. Two sided noninferiority test using one-sided of ? levle with 95% power assuming an equivalence margin of 0.5 for the IPSS and 0.8 for the peak flow, requiring 300 patients. The sample size was set at 330 (assuming a 10% drop- outs) using one-sided of a level of 0.05 with 95% power. The co-primary endpoints of the study were the changes of IPSS and peak flow after 6 months. The secondary endpoint was the reduction of post-void residual (PVR). _x000D_ One tablet of Profluss1 consisted of 320 mg of supercritical CO2 lipidic extract SeR containing 85% of fatty acids sterols, selenium (50mcg) and lycopene (5mg) and distributed by Konpharma Srl (Rome, Italy). The Treatment-related adverse events (TEAEs) were collected. _x000D_ Results A total of 303 patients concluded the study protocol, 199 in the group A and 104 in the group B. All patients were balanced at baseline and any statistical difference was found when considering age, IPSS, peak flow, prostate volume, PVR and IIEF-5. After 6 months of therapy we observed a decrease in IPSS of -3 (95%CI -4;-3) and of -3 (95%CI -3;-2) in the group A and B respectively (non inferiority test p=0.04), an increase in peak flow of 2 (95%CI 2;4) and of 2 (95% 1;3) in the group A and B respectively (non inferiority test p<0.01) and a decrease in PVR of -12 (95%CI -32;-2) and of -10 (95% -25; -5) in the group A and B respectively (non inferiority test p=0.04). We observed a total of 25 (0.08%) of TEAEs, 5 in the group A (0.02%) and 20 in the group B (0.19%)(p<0.05). Conclusions In this phase IV randomized, non-inferiority clinical trial, we demonstrated that treatment with SeR-Se-Ly was not inferior to Tadalafil 5 mg after 6 months in patients affected by LUTS/BPE and in terms of clinical efficacy and furthermore it showed less TEAEs. Funding None
Authors
Giuseppe Morgia
Giulio Reale Giuseppe Vespasiani Marina Di Mauro Rosaria M. Pareo Salvatore Voce Massimo Madonia Paolo Fedelini Pasquale Veneziano Marco Carini Giuseppe Salvia Francesco Santaniello Andrea Ginepri Marco Bitelli Carlo Terrone Marcello Gentile Antonella Giannantoni Franco Blefari Valerio Beatrici Patrizio Polledro Pasquale La Rosa Salvatore Arnone Giorgio Santelli Giorgio Ivan Russo |
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MP09-05 |
Does concomitant testosterone replacement improve the response of tadalafil 5 mg once daily in men with lower urinary tract symptoms? |
Benign Prostatic Hyperplasia: Medical & Non-surgical Therapy | 17BOS |
Abstract: MP09-05 Sources of Funding: none Introduction Recently, tadalafil was found to be effective for treating lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). Testosterone (T) regulates nitric oxide synthase and is necessary to achieve an optimum response to PDE5 inhibitors. In the present study, we determined whether T replacement in men with low T levels receiving tadalafil to treat LUTS improved the response of tadalafil on LUTS. Methods The present 12-week study was a randomized parallel study of clinical outcomes in men aged ≥ 40 years with symptomatic BPH (IPSS ≥ 12), prostate volumes ≥ 30 ml, and testosterone levels less than 300 ng/dl. Eligible patients received a combination of tadalafil 5 mg once daily and placement of a transdermal gel containing 10 g T (n=44), or tadalafil alone (n=46). The primary outcomes were post-treatment IPSS, peak urinary flow rate, and post-void residual urine volume (PVR). Secondary outcomes were changes in IIEF-EF domain scores, Global Assessment Questionnaire (GAQ) scores, and Life Satisfaction Checklist (LSC) scores. Results The extent of IPSS improvement from baseline to 12 weeks was the same in both groups (tadalafil+T - 5.2 vs. tadalafil - 5.0; p=0.634). Also, the changes in Q(max) and PVR from baseline were very similar in both groups. However, the tadalafil+T group showed a significantly greater change from baseline in the IPSS storage subscore, the IPSS-QoL score, and the IIEF-EF domain score. The tadalafil+T group showed significantly greater improvements in GAQ and LSC scores, as compared to the tadalafil-only group. The adverse event profiles of each group were similar to those of previous reports. Conclusions Tadalafil plus testosterone was superior to tadalafil alone in improving LUTS in men with BPH/LUTS and low testosterone levels. Further study is needed with more number of patients and longer duration study for support of present study. Funding none
Authors
Hyun Jun Park
Tae Nam Kim Jong Kil Nam Nam Cheol Park Du Geon Moon |
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MP09-06 |
Administration of daily 5mg tadalafil improves not only lower urinary tract symptoms but also vessel endothelial function in patients with benign prostatic hyperplasia |
Benign Prostatic Hyperplasia: Medical & Non-surgical Therapy | 17BOS |
Abstract: MP09-06 Sources of Funding: none Introduction Tadalafil is a promising phosphodiesterase (PDE) 5 inhibitor for erectile dysfunction (ED) treatment. Daily low dose (5mg) of tadalafil is also applied for the treatment of male lower urinary tract symptoms (LUTS) associated with benign prostate hyperplasia (BPH). PDE5 inhibitors induce relaxation of smooth muscle cells in urethra, prostate, bladder neck and blood vessels. The aim of this study is to investigate the efficacy of tadalafil for vessels endothelial function, besides male LUTS symptoms in patients with BPH. Methods The Institutional Review Board (IRB) had approved this clinical study, and informed consents have been obtained from 70 BPH patients._x000D_ (1) The male LUTS parameters such as international prostate symptom score (IPSS), overactive bladder symptom score (OABSS), residual urine (RU) were compared before and 1month, 3 months, 6 months, 12months after daily 5mg tadalafil treatment._x000D_ (2) In addition, erectile function and vessels endothelial function were evaluated by sexual health inventory for men (SHIM) score, brachial-ankle pulse wave velocity (baPWV) and ankle brachial index (ABI) before and 3 months, 6 months, 12months after tadalafil treatment._x000D_ Results The mean age of 70 patients were 65.7+/-11.6 years old. The prostate size was 30.2+/-22.7 ml. _x000D_ (1) All male LUTS parameters including total IPSS, OABSS and RU were significantly improved 1 to 12 months after tadalafil administration._x000D_ (2) Furthermore, SHIM score significantly improved after 3 months. baPWV is a measure of arterial stiffness and a marker of vascular damages. Generally, higher baPWV means that the vessels are less elasticity, and baPWV data increase according to aging. The results of baPWV significantly improved from 3 to 6 months (p<0.01) and the same levels at 12 months compared with baseline (Figure). ABI is an indicator of arterial sclerosis and arterial sclerosis is diagnosed when ABI is less than 0.9. In this study, ABI was not?significantly changed by tadalafil. _x000D_ Conclusions Tadalafil is effective not only for male LUTS but also ED. Furthermore, tadalafil improves baPWV data, which means higher vessels elasticity has been obtained. The major new finding of this study is that tadalafil had a potency to improve vessels endothelial dysfunction in patients with BPH. Funding none
Authors
Toshiyasu Amano
Takahiro Kishikage Tetsuya Imao |
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MP09-07 |
Evaluation of efficacy of PDE5 inhibiter by penile blood pressure for benign prostatic hyperplasia patients with lower urinary tract symptoms |
Benign Prostatic Hyperplasia: Medical & Non-surgical Therapy | 17BOS |
Abstract: MP09-07 Sources of Funding: none Introduction Tadalafil is a phosphodiesterase 5 inhibitor that affects cyclic guanosine monophosphate (cGMP). It is known to improve not only smooth muscle relaxation of the prostatic urethra and bladder, but also pelvic ischemia. In the daily clinic, tadalafil is usually prescribed for patients with lower urinary tract symptoms (LUTS), but not all patients respond to tadalafil treatment. The purpose of this study was to identify those who would be good candidates for tadalafil. This evaluation used penile blood pressure (PBP) as a feasible and reproducible method related to pelvic blood perfusion. Methods A prospective study was performed in our hospital between September 2014 and October 2016. Patients showing poor response to α1 blockers for benign prostate hyperplasia (BPH) were eligible for this study. Tadalafil was administered in exchange of the α1 blocker. Demographic data, I-PSS, I-PSS QOL, IIEF-5, uroflowmetry (UFM), post-voiding residue (PVR), prostate volume (by transabdominal ultrasound), PBP, and axial brachial index (ABI) were evaluated before and at 4 and 12 weeks after switching to tadalafil. The relationship between I-PSS scores and PBP was examined in these patients. To measure PBP, a cuff for the big toe was wrapped around the penis. This study was approved by the institutional review board. Results A total of 55 patients were eligible. Within 4 weeks after switching to tadalafil, 3 patients dropped out of the study because of adverse events and another three dropped out because of worsening LUTS. Overall, 49 patients tolerated tadalafil for the entire 12 weeks and were investigated. Median age was 74 years. 25 patients with PBP less than 110 mmHg at baseline responded better to tadalafil, with improvement of I-PSS at 12 weeks compared to those with higher PBP (p= 0.006, Figure). Lower PBP at baseline was significantly associated with improved I-PSS by tadalafil at 12 weeks on uni- and multivariate analyses (p<0.001 and p=0.001, respectively). On multivariate analysis, improved I-PSS was also related to previous anticholinergic drug use (p=0.021). Conclusions This study demonstrated that PBP could reliably identify BPH patients who could benefit from tadalafil treatment. Especially in cases with PBP <110 mmHg, we can consider changing administration to tadalafil. Funding none
Authors
Juntaro Koyama
Yoshihide Kawasaki Tomonori Sato Taro Fukushi Atsushi Kyan Yasuhiro Kaiho |
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MP09-08 |
Sleeping problems are associated with increased risk of BPH progression: Results from REDUCE |
Benign Prostatic Hyperplasia: Medical & Non-surgical Therapy | 17BOS |
Abstract: MP09-08 Sources of Funding: GlaxoSmithKline Inc. and NIH K24 CA160653 Introduction While there is a known correlation between nocturia due to BPH and sleep disturbance, it is unknown if sleep disturbances affect BPH development and symptom progression. We examined the relationship between sleep problems as measured by the Medical Outcomes Study Sleep Scale (MOSSS-6) questionnaire and BPH development and progression in the placebo arm of the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) study. Methods REDUCE was a 4-year trial testing prostate cancer chemoprevention with dutasteride in men with a PSA 2.5-10 ng/ml and a negative biopsy. At baseline, men completed the MOSSS-6 questionnaire, a 6-item scale that assesses sleep and is scored 1-100. Men were followed for 4 years and the International Prostate Symptom Scores (IPSS) was obtained at baseline and every 6 months. In men without symptomatic BPH at baseline (IPSS<8), we defined BPH development as two values of IPSS >14, any surgical procedure for BPH, or the start of a drug for BPH. In men with symptomatic BPH at baseline (IPSS≥8), BPH symptom progression was defined as ≥4 IPSS increase from baseline, any surgical procedure for BPH, or the start of a drug for BPH. In men in the placebo arm and not taking alpha blockers or 5-alpha reductase inhibitors at baseline (n=2,588), we tested the association between sleep problems as measured by the MOSSS-6 and BPH development and BPH progression using Cox models, adjusting for age, race, body mass index (BMI), smoking, digital rectal exam, prostate volume, PSA, and baseline IPSS. Results During follow-up, 209/1452 men (14%) without BPH at baseline developed BPH and 527/1136 men (46%) with BPH progressed. Median age was 62 (IQR: 58-67) and 90% were white. Median BMI was 26.8 kg/m2 (IQR: 24.7-29.1) and 15% were current smokers. Median MOSSS-6 score was 17 (IQR: 7-27). On multivariable analysis, higher MOSSS-6 scores were associated with increased risk of BPH development in men without BPH at baseline (HR 1.28, p=0.014). Among men with BPH at baseline, higher MOSSS-6 scores were associated with increased risk of BPH symptom progression (HR 1.23, p<0.001). Conclusions Among men with BPH symptoms, worse sleep scores predicted the risk of BPH symptom progression. Among asymptomatic men, worse sleep scores predicted the development of BPH. As it is often inferred that BPH leads to sleep problems, the fact that sleep problems in asymptomatic men predict BPH development suggests BPH symptoms may be a manifestation of sleep problems rather than the reverse. Whether treating sleep problems improves BPH symptoms needs to be tested. Funding GlaxoSmithKline Inc. and NIH K24 CA160653
Authors
Brandee Branche
Lauren Howard Daniel Moreira Ramiro Castro-Santamaria Gerald Andriole Martin Hopp Stephen Freedland |
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MP09-09 |
Desmopressin for Male Nocturia: A Cochrane Systematic Review and Meta-analysis |
Benign Prostatic Hyperplasia: Medical & Non-surgical Therapy | 17BOS |
Abstract: MP09-09 Sources of Funding: None Introduction Nocturia is defined as two or more voids per night. We evaluated the effects of desmopressin compared to other interventions in the treatment of nocturia in men with lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH). Methods We conducted a Cochrane review based on an a priori, protocol that included published and unpublished randomized controlled trials (RCTs) in any language. We excluded trials of children or adults with primary or secondary enuresis or underlying medical disorders. Primary outcomes were the number of nocturnal voids, quality of life (QoL), and major adverse events (AEs); secondary outcomes were duration of first sleep episode, time to first void, minor AEs, and treatment withdrawal due to AEs. We performed meta-analysis using RevMan 5.3 and rated the quality of evidence using GRADE. Results Of 271 studies identified through our search, we included 10 studies. Desmopressin was associated with a small decrease in the number of nocturnal voids (mean difference [MD] -1.1, 95% confidence interval [CI] -1.4 to -0.9; low quality evidence) and similar rates of major AEs (risk ratio [RR] 0.9, 95% CI 0.1 to 9.0; very low quality of evidence). We found no evidence for QoL. Compared to alpha-blockers, there was a similar reduction in the number of nocturnal voids (MD -0.2, 95% CI 01.2 to 0.7; very low quality evidence) and similar quality of life (MD -0.2, 95% CI -0.4 to 0.1; moderate quality of evidence). Rates of major AEs were similar (RR not estimable; low quality evidence). Conclusions Current best evidence from RCTs in men with the chief complaint of nocturia suggests that desmopressin may result in a small reduction in the number of nocturnal voids with similar major AE rates compared to placebo. We are uncertain whether it reduces the number of nocturnal voids similarly to alpha-blockers. Additional well-designed studies using active controls are needed. Funding None
Authors
Julia Han
Jae Hung Jung Caitlin Bakker Mark Ebell Philipp Dahm |
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MP09-10 |
Tamsulosin prescribing patterns based on a United States health plan claims database |
Benign Prostatic Hyperplasia: Medical & Non-surgical Therapy | 17BOS |
Abstract: MP09-10 Sources of Funding: This study was funded by Boehringer Ingelheim. Introduction Tamsulosin represented a breakthrough in the medical treatment of benign prostatic hyperplasia (BPH) due to its comparable efficacy and improved side effect profile over prior non-selective alpha 1-adrenoceptor blockers. Despite its ease of administration, prior studies suggest that urologists remain the gatekeepers for the medical management of BPH, providing higher dispensation of alpha- blockers than other medical specialties. With the changing healthcare landscape and off-label use of alpha-blockers for urolithiasis, prostatitis, and even female voiding dysfunction we evaluated current utilization trends and prescribing patterns associated with tamsulosin. Methods A retrospective analysis was performed using PharMetrics Plus, which processes pharmaceutical claims for 70 million patients from over 55 health plans in the United States. Patient and provider characteristics associated with dispensation of tamsulosin during an 18 month period between 2012 and 2013 were evaluated. Patients included in the analysis were continuously enrolled in the health plan for 12 months pre-index to 6 months post-index. Results During the period of this analysis 133,977 patients received dispensation for tamsulosin, 54.2% of whom were new users. Of the 72,583 new tamsulosin users, 59,197 (81.6%) were men and 13,386 (18.4%) were women. Interestingly, 59.2% (n=35,071) of these new male tamsulosin users did not receive a BPH diagnosis code at any time during the 18-month analysis period. Prescribing patterns, age, and comorbidities of patients initiating tamsulosin are summarized in the Table. Conclusions In this large cohort of privately insured patients, we have found some very interesting and unexpected prescribing trends for the selective alpha 1-adrenoceptor blocker, tamsulosin. Although it is FDA approved for the signs and symptoms of BPH, close to 20% of new prescriptions were for women suggesting off label uses have emerged, including management of urolithiasis, and other male and female voiding disorders. Furthermore, urologists are no longer the primary initiators of tamsulosin therapy, even for BPH. This has important implications for further research in order to fully understand the utilization of this class of pharmaceutical agents. Funding This study was funded by Boehringer Ingelheim.
Authors
Bruce Kava
Anna E. Verbeek Jan M. Wruck Marc Gittelman |
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MP09-11 |
Measuring and predicting the patient-reported goal achievement after treating male benign prostatic hyperplasia with tamsulosin monotherapy |
Benign Prostatic Hyperplasia: Medical & Non-surgical Therapy | 17BOS |
Abstract: MP09-11 Sources of Funding: This work was conducted by the UROSTAR study group and supported by Astellas Korea Introduction Since benign prostatic hyperplasia (BPH) is a chronic and refractory disease and medical therapy became a standard treatment for most BPH patients with mild to moderate lower urinary tract symptoms, adherence to and persistence with therapy are considered important factors for the success of the treatment. Monotherapy using alpha-adrenergic antagonist constitutes the largest portion of medical therapy for BPH. Therefore, we aimed to assess and predict patient-reported goal achievement after treatment of BPH patients with tamsulosin. Methods From November 2013 to October 2015, 272 patients initially diagnosed with BPH were prospectively enrolled in nine different centers. Before the treatment, subjective final goals were recorded by all patients. Every four weeks, the treatment outcomes were evaluated using international prostate symptom score (IPSS) and uroflowmetry. Patient-reported goal achievements were assessed after 12 weeks of treatment and risk factors for lower scores of goal achievement were assessed using logistic regression analysis. Results Of the enrolled patients, 179 patients completed the study and 42 patients set multiple goals (32 patients with 2 goals, 9 patients with 3 goals and 1 patient with 4 goals). The pretreatment patients’ goals included the nocturia improvement (n=63), weak urine stream improvement (n=52), frequency improvement (n=34), residual urine sense improvement (n=27), hesitancy improvement (n=22), well voiding (n=21), urgency improvement (n=11), and voiding-related discomfort improvement (n=2). Of the 179 patients, 129 patients (72.1%) reported that they achieved their primary goals after three months of medical therapy. Logistic regression analysis revealed that pretreatment quality of life (OR=8.621, 95% CI: 2.154-9.834), and improvement of quality of life (OR=6.740, 95% CI: 1.908-11.490) were independent predictors of patient-reported goal achievement after tamsulosin monotherapy. Conclusions Overall patient-reported goal achievement after medical therapy for BPH was high, and the scores of pretreatment quality of life and improvement of quality of life can be important factors to predict the achievement of treatment goals. Funding This work was conducted by the UROSTAR study group and supported by Astellas Korea
Authors
Bum Soo Kim
Jae Wook Chung Phil Hyun Song Jun Nyung Lee Yun-Sok Ha Tae Gyun Kwon Seock Hwan Choi Hyun Tae Kim Tae-Hwan Kim Sung Kwang Chung Ki Ho Kim Byung Hoon Kim Ji Yong Ha Deok Hyun Cho Gun Nam Kim Yoon Hyung Lee Jae Soo Kim Hyun-Jin Jung Hong Seok Shin Jong Hyun Yoon Jae Ho Kim Eun Sang Yoo |
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MP09-12 |
DECISION-MAKING IN MEN CONSIDERING USE OF NON-PRESCRIPTION TAMSULOSIN FOR LOWER URINARY TRACT SYMPTOMS |
Benign Prostatic Hyperplasia: Medical & Non-surgical Therapy | 17BOS |
Abstract: MP09-12 Sources of Funding: This study was funded by Boehringer-Ingelheim. The authors received no direct compensation related to the development of this abstract. AV and JW are employees of the sponsor. Introduction Tamsulosin is undergoing evaluation for non-prescription (OTC) use in men with lower urinary tract symptoms (LUTS). We aimed to assess appropriate decision-making and LUTS in men choosing to use tamsulosin in a simulated OTC setting. Methods Adult men not taking a prescription medication for benign prostatic hyperplasia (BPH) were shown a mock-up of the drug packaging and asked if the medication would be appropriate for their personal use. Criteria for appropriate “self-selection� included: 2 or more specified LUTS for at least 3 months, absence of any &[Prime]Do Not Use&[Prime] warning symptoms, and no allergy to sulfa or tamsulosin. Compliance with &[Prime]Ask a Doctor Before Use&[Prime] conditional warnings was assessed in a separate analysis. Three urologists reviewed the data of men reporting the product to be appropriate for their use who did not meet appropriate self-selection criteria. Their decision was revised to appropriate if deemed so by 2 out of 3 urologists (&[Prime]mitigated&[Prime] analysis). Results 470/619 (75.9%) eligible men self-selected use. Mean age of men self-selecting use was 61.7 years, 82 (17.4%) had low health literacy, and 365 (77.7%) reported seeing a physician at least once per year. Mean AUA-SI total, voiding, and storage subscores were 16.5, 8.1 and 8.3, respectively, and 380 (80.9%) reported LUTS duration of >1 year. The proportion of men meeting appropriate self-selection criteria on unmitigated and mitigated analyses was 92.8% (95% CI 90.0-94.9%) and 97.9% (95% CI 96.1-99.0%), respectively, with similar findings in men with low health literacy. When considering planned compliance with &[Prime]Ask a Doctor Before Use&[Prime] warnings 82.8% (95% CI 79.0-86.1%) and 96.8% (95% CI 94.8-98.2%) of men made an appropriate selection decision on unmitigated and mitigated analysis, respectively. Conclusions Men self-selecting use of tamsulosin are characterized by chronic LUTS with a voiding component, suggesting potential benefit from the medication. The decision to use tamsulosin based on indications and warnings was appropriate for most men, including those with low health literacy, which may mitigate risks associated with self-directed use. Funding This study was funded by Boehringer-Ingelheim. The authors received no direct compensation related to the development of this abstract. AV and JW are employees of the sponsor.
Authors
Joshua Cohn
Roger Dmochowski Casey Kowalik Claus Roehrborn Douglas Bierer Anna Verbeek Jan Wruck |
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MP09-13 |
Clinical Efficacy and Safety of Full Dose Antimuscarinic Agent Treatment on Unsatisfactory Improvement of Symptoms after Low Dose Antimuscarinic Treatment in Male Patients with Overactive Bladder: A Retrospective Multicenter Study |
Benign Prostatic Hyperplasia: Medical & Non-surgical Therapy | 17BOS |
Abstract: MP09-13 Sources of Funding: None Introduction This study aimed to analyze the efficacy and safety of full dose antimuscarinic treatment on male patients with overactive bladder (OAB) symptoms who showed unsatisfactory improvements after low dose antimuscarinic treatments. Methods We retrospectively reviewed the data of 567male patients aged 40 or older with OAB symptoms between January 2013 and June 2015. All patients were treated with low dose antimuscarinics at least for 4 weeks and showed unsatisfactory symptom improvements and therefore changed to full dose antimuscarinics using 10 mg of solifenacin for more than 12 weeks. International Prostate Symptom Score (IPSS) and Overactive Bladder Symptom Score (OABSS) at baseline (V0), 4 weeks (V1), and 12 weeks (V2) were analyzed. Safety of treatment was assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Results Among the total patients, one showed acute urinary retention and was excluded, leaving 566 patients in the analysis. Median age, body mass index, and prostate-specific antigen were 69.0 years, 24.2 kg/m2, and 1.24 ng/dL respectively. Mean value of total IPSS and OABSS scores significantly decreased from V0 to V2 (16.73 to 13.69, and 7.33 to 5.34, respectively, all p < 0.001). All scores of each questionnaires demonstrated significant decrease except for IPSS questionnaires number 3 and 6. Four and nine patients complained constipation and thirst respectively, and all adverse effects were graded 2 or below. Conclusions Full dose antimuscarinic therapy using solilfenacin 5mg may be safe and effective treatment for those patients who have OAB symptoms refractory to low dose antimuscarinic therapy. Funding None
Authors
Myungsun Shim
Woo Jin Bang Cheol Young Oh Yong Seong Lee Jin Seon Cho |
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MP09-14 |
Comparison of the efficacy of combination therapy with an anticholinergic agent and an α1-blocker versus a β3-adrenoceptor agonist and an α1-blocker for patients with benign prostatic enlargement complicated by overactive bladder: A randomized, prospective trial based on a urodynamic study |
Benign Prostatic Hyperplasia: Medical & Non-surgical Therapy | 17BOS |
Abstract: MP09-14 Sources of Funding: none Introduction Although several randomized studies have reported the efficacy of a combination therapy (CT) with an anticholinergic agent and an α1-blocker or β3-adrenoceptor agonist and an α1-blocker for patients with benign prostatic enlargement (BPE) complicated by overactive bladder (OAB), no study has compared the improvement of subjective and objective symptoms in patients with BPE/OAB, between the two drugs. We compared the efficacy of CT with an anticholinergic agent and an α1-blocker, and CT with β3-adrenoceptor agonist and an α1-blocker for patients with BPE/OAB, by conducting a urodynamic study (UDS). Methods This was a randomized prospective study involving 80 outpatients with untreated BPE (IPSS ≥8, IPSS- QOL ≥3, prostate volume ≥25 mL) associated with urinary urgency at least once per week, who had an OAB symptom score (OABSS) of ≥3. The patients were randomly assigned to receive CT with silodosin at 8 mg/day and fesoterodine 4 mg/day (Feso-CT group) or CT with silodosin and mirabegron 50 mg/day (Mira-CT group). Changes in parameters from baseline to 12 weeks after administration were assessed based on IPSS, IPSS-QOL, OABSS, and voiding and storage functions, as measured using a UDS. Results In the efficacy analysis, 33 patients from the Feso-CT group (mean age, 71.3 years; mean prostate volume, 47.2 mL) and 31 patients from the Mira-CT group (70.8 years, 45.9 mL) were included. Although the mean IPSS and OABSS significantly improved in both groups, the improvement in OABSS in the Feso-CT group was significantly greater than that in the Mira-CT group. With regard to the storage function assessed by UDS, the Feso-CT group demonstrated a significantly greater improvement in terms of the incidence of detrusor overactivity. Urodynamic voiding function significantly improved in both groups, without significant inter-group difference (Table). Conclusions CT with silodosin and fesoterodine or mirabegron significantly improved subjective and objective symptoms in patients with BPE and OAB. Thus, CT with fesoterodine was thought to be more effective than CT with mirabegron, with regard to storage symptoms and functions. Funding none
Authors
Yoshihisa Matsukawa
Takashi Fujita Masashi Kato Yasuhito Funahashi Tokunori Yamamoto Momokazu Gotoh |
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MP09-15 |
The continuous use of antimuscarinics after TURP in BPH patients with storage symptoms requiring antimuscarinics before surgery – a nationwide population-based study |
Benign Prostatic Hyperplasia: Medical & Non-surgical Therapy | 17BOS |
Abstract: MP09-15 Sources of Funding: none Introduction To use antimuscarinics in BPH patients with storage symptoms has become a common practice. TURP may be needed in a part of these patients and some still need to stay on antimuscarinics after surgery. This study investigates the post-operative use of antimuscarinics in BPH patients with storage symptoms requiring antimuscarinics before surgery by analyzing a nationwide health insurance database. Methods A urology dataset including 3,431,366 individuals was selected from the National Health Insurance Research Database (NHIRD) of Taiwan for the year 2006 to 2010. The claim data was used for the study. Exclusion criteria were patients with prostate cancer or bladder cancer, those with co-morbidities which might present with LUTS, and those who had underwent procedures which might cause urinary retention. We identified 2,224 patients receiving antimuscarinics within 6 months prior to TURP and have been followed for more than one year after surgery. The post-operative use of antimuscarinics was serially investigated quarterly in terms of the percentage of patients continuing antimuscarinics. Results In 2,224 patients, 519 patients (23.3%) had AUR while using antimuscarinics before TURP. The percentage of patients continuously using antimuscarinics after TURP decreased significantly from the first quarter (26.4%) to the fourth quarter (10.8%) and then plateaued. The patients who did not suffer from pre-operative AUR had higher percentage to continuously use antimuscarinics post-operatively. Significant differences were observed in the first 3 quarters post-operatively. The differences were more pronounced in patients with larger prostate resection weight (≥15gm). When identifying patients with uninterrupted follow-up on an annual basis, the trend was similar. (Fig.) Conclusions For BPH patients with storage symptoms requiring antimuscarinics, the continuous use of antimuscarinics after TURP decreased significantly from the first quarter to the fourth quarter and then plateaued. More patients continuously used antimuscarinics post-operatively in those who did not suffer from pre-operative AUR than those who did. The difference was more obvious in patients with resection weight of prostate≥15gm. Funding none
Authors
Eric Yi-Hsiu Huang
Hsiao-Jen Chung Chih-Chieh Lin Ruo-Shin Peng Yen-Hwa Chang Alex T.L. Lin Kuang-Kuo Chen |
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MP09-16 |
5-Alpha Reductase Inhibitors for Male Lower Urinary Tract Symptoms: A Cochrane Systematic Review and Meta-Analysis |
Benign Prostatic Hyperplasia: Medical & Non-surgical Therapy | 17BOS |
Abstract: MP09-16 Sources of Funding: Departmental Introduction 5-alpha reductase inhibitors (5ARIs) are being promoted as an integral part of the armamentarium to treat male LUTS attributed to benign prostatic hyperplasia (BPH). To establish the benefits and harms in the least biased manner, we conducted a rigorous Cochrane review. Methods Based on an a priori, protocol we searched the published and unpublished literature for randomized controlled trials (RCTs) in any language. Primary outcomes were: Mean change in urologic symptom scores using validated questionnaires, mean change in quality of life and the number of participants who experienced a major adverse effect; secondary outcomes included episodes of urinary retention and need for surgical intervention. We performed meta-analysis using RevMan 5.3 and rated the quality of evidence using GRADE. All steps were performed independently and in duplicate. Results Among 2604 screened records identified from multiple database, 28 unique studies ultimately met inclusion criteria. Based on 18 studies with 16,142 patients, 5ARIs resulted in a small reduction of symptom score with a mean difference (MD) of -1.5 (95% CI -1.9 to -1.1; low quality evidence) compared to placebo (Table 1). The rate of major adverse events was similar with a risk ratio (RR) of 0.9 (95 CI 0.8 to 1.1; low quality evidence). Compared to alpha blockers (ABs) based on 9 trials with 7954 participants (Table 2), symptoms scores were higher with a MD of +1.1 (95 CI 0.5 to -1.7; moderate quality evidence) and was associated possible reduction in the absolute risk of acute urinary retention (23 fewer per 1,000; 95% CI 35 fewer to 5 more; low quality evidence) and a small reduction in the need for surgical intervention (32 fewer per 1,000; 95% CI 38 fewer to 23 fewer; moderate quality evidence). Conclusions 5ARIs alone may reduce urological symptom scores and the absolute risk of acute urinary retention slightly compared to placebo. Compared to ABs, they probably reduce the need for surgical intervention slightly and may reduce the risk of acute urinary retention slightly. Funding Departmental
Authors
Herney Garcia-Perdomo
Hugo Lopez Philipp Dahm |
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MP09-17 |
5-Alpha Reductase Inhibitors for Treatment of Benign Prostatic Hyperplasia Does Not Increase the Risk of Erectile Dysfunction |
Benign Prostatic Hyperplasia: Medical & Non-surgical Therapy | 17BOS |
Abstract: MP09-17 Sources of Funding: This study was funded by a grant (5R21DK100820-02) from the United States National Institutes of Health (NIH) / National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Introduction 5-alpha reductase inhibitors (5ARIs) have been reported to increase the risk of erectile dysfunction (ED) in patients treated for benign prostatic hyperplasia (BPH); however BPH itself is an ED risk factor (potential confounding by indication). We conducted a cohort study with nested case-control analyses using the United Kingdom's Clinical Practice Research Datalink to estimate the risk of ED in men who used 5ARIs for the treatment of BPH. Methods We identified men aged 40+ with BPH who received at least one prescription for a 5ARI (finasteride or dutasteride), alpha blocker (AB), or both. Exposures were classified as 5ARI only, 5ARI+AB, and AB only. Cases were men who had a first ED diagnosis or treatment (surgery or phosphodiesterase type-5 inhibitor prescription) during follow-up. We calculated incidence rates (IRs) and adjusted incidence rate ratios (IRRs) with 95% confidence intervals (CIs). We also conducted a nested case-control analysis to control for major confounders and calculated adjusted odds ratios (ORs) with 95%CIs. Results We identified 71,849 men, among whom 5,814 were identified as new cases of ED over the 20 year study period (1992-2011). The incidence rate of ED was lowest among users of 5ARI only (15.3 per 1000 person-years) and similar among users of 5ARI+AB (19.2 per 1000 person-years) and AB only (20.1 per 1000 person years). The risk of ED was not elevated with use of 5ARI only (IRR=0.92, 95%CI 0.85-0.99) or 5ARI+AB (IRR=1.09, 95%CI 0.99-1.21) in comparison with AB only. In the nested case-control analysis, ORs were 0.94 (95%CI 0.85-1.03) for 5ARI only and 0.92 (95%CI 0.80-1.06) for 5ARI+AB, compared to AB only, and remained null regardless of number of prescriptions or exposure timing. The risk of ED increased with longer duration of BPH, independent of exposure. Conclusions In a large, 20 year, real world observational study, 5ARI therapy for BPH does not significantly increase the risk of clinically meaningful incident ED compared to AB treatment. Risk of ED increased with longer duration of BPH. Funding This study was funded by a grant (5R21DK100820-02) from the United States National Institutes of Health (NIH) / National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Authors
Katrina Hagberg
Hozefa Divan Rebecca Persson Susan Jick J. Curtis Nickel |
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MP09-18 |
Change of urinary steroid metabolites in BPH patients treated with dutasteride |
Benign Prostatic Hyperplasia: Medical & Non-surgical Therapy | 17BOS |
Abstract: MP09-18 Sources of Funding: no Introduction So far no studies have investigated whether administration of dutasteride (DUT) could affect the steroid metabolite pathway in symptomatic BPH patients. Methods Urine and blood samples, and clinical parameters such as IPSS, QoL score and prostate volume were prospectively collected before and after 0.5 mg daily DUT administration in 60 symptomatic BPH patients. Among the 60 patients, 25 discontinued DUT after treatment at 12 months and urine samples after the withdrawal of DUT treatment were also prospectively collected. Urine samples were evaluated by urinary steroid profile (USP), which could measure all 63 urinary steroid metabolites at a same time. The USP analysis was determined by gas chromatography/mass spectrometry. We evaluated the pharmacological changes in urinary metabolites in USP and their correlations with clinical parameters in BPH patients treated with DUT. Results The urinary androsterone/etiocholanolone (An/Et) ratio in the sex-steroid pathway was significantly decreased from 1.39 ± 0.62 to 0.02 ± 0.01 (p<0.01). Urinary metabolites in other steroid pathways such as 5αTHF/5βTHF in the glucocorticoid pathway and 5αTHB/βTHB in the mineralocorticoid pathway were also significantly decreased after DUT treatment. In the 25 patients who discontinued DUT treatment, the mean An/Et ratio at baseline before DUT treatment, just before withdrawal of DUT, one month, 3 months, and 6 months after withdrawal of DUT treatment were 0.01, 1.42, 0.02, 0.18, and 1.17, respectively. All other urinary metabolite ratios such 5αTHF/5βTHF and 5αTHB/βTHB were also changed in a similar manner. Prostate volume, IPSS, and QoL score just before withdrawal of DUT treatment (12 months after DUT treatment) were significantly lower than those at baseline before DUT treatment, but these parameters 3 months and 6 months after withdrawal of DUT were not significantly different from those just before withdrawal of DUT treatment. The mean PSA level at baseline before DUT treatment, just before withdrawal of DUT, and 3 months, and 6 months after withdrawal of DUT treatment were 5.6, 2.3, 3.7, and 5.2 ng/ml, respectively. Significant correlation was observed between the recovery rate of PSA level and the recovery rate of An/Et in USP before and 3 months after withdrawal of DUT (ρ=0.61, p<0.01). Conclusions The urinary 5α/5β metabolites in all steroid pathways were strongly suppressed after daily 0.5 mg DUT administration for one month. The recovery rate of PSA after withdrawal of DUT treatment might reflect the recovery rate of 5α/5β steroid metabolites. Funding no
Authors
Yota Yasumizu
Eiji Kikuchi Takahiro Maeda Masanori Hasegawa Akira Miyajima Mototsugu Oya |
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MP09-19 |
The effect of statins on the risk of receiving transurethral resection of prostate in outpatients of genitourinary clinic - a study by applying nation-wide population based database |
Benign Prostatic Hyperplasia: Medical & Non-surgical Therapy | 17BOS |
Abstract: MP09-19 Sources of Funding: None Introduction Statins were reported to reduce prostate volume and slow the clinical progression of BPH. Herein, we apply the national database to investigate whether the statins reduces the risk of receiving transurethral resection of prostate (TURP) in the outpatients of genitourinary clinic. Methods The subset of the National Health Insurance Research Database (NHIRD) of Taiwan contains data on all medical benefit claims and covers more than 98% of Taiwan populations. A urology dataset including 3,431,366 individuals was selected from NHIRD for the year 2006 to 2010. Their claim data were used for the study. We recruited the patients without past history of TURP but with the ICD-9 diagnostic code of 600.X (except 600.3) twice in 3 months, from the time of 2006 July to 2008 June. All patients with the diagnosis of prostate and bladder cancer were excluded. The medication of all statins, ?-blockers, and 5? reductase inhibitors were reviewed and must be prescribed by urologists at outpatient department for more than 3 months. TURP after taking all statins, ?-blockers, and 5? reductase inhibitors was recorded. We used a conditional logistic regression to compute the odds ratio (OR) for having previously used statins among all groups. Results Among the overall 3,431,366 individuals who visited urology outpatient clinic during 2006 to 2010, 198,486 patients were recruited without the diagnosis of dementia, cerebrovascular disease, and myocardial infarction before recruitment. Among these patients,11,145 (5.62%) taking statins and 79,411(40.01%) taking ?-blockers and/or 5? reductase inhibitors. In addition, 21,684 (10.92%) received TURP after medication. In the group of statins users, the percentage (10.47%) of receiving TURP in patients with medication of ?-blockers and/or 5? reductase inhibitors is significantly lower than that (11.84%) of patients without ?-blockers and/or 5? reductase inhibitors (p < 0.001). Conversely in the group of non-statins users, the percentage (5.14%) of receiving TURP in patients with medication of ?-blockers and/or 5? reductase inhibitors is significantly higher than that (3.08%) of patients without ?-blockers and/or 5? reductase inhibitors (p < 0.001). In the both groups of non-BPH or BPH medication users, the percentage of receiving TURP in patients with medication of statins is significantly lower than that of patients without statins (p < 0.001). The odds ratio of statins user vs. non-statins user is 0.381 (p < 0.01) Conclusions In this research, the patients with statins use have lower risk to receive TURP, even in the occasion without any BPH medication. Funding None
Authors
Chih-Chieh Lin
Hsiao-Jen Chung Yi-Hsiu Huang Alex Tong-Long Lin |
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MP100-01 |
Partial Nephrectomy versus Cryoablation or Radiofrequency Ablation for Clinical Stage T1 Renal Masses: Systematic Review and Meta-Analysis of more than 3900 Patients |
Kidney Cancer: Ablative Therapy | 17BOS |
Abstract: MP100-01 Sources of Funding: None Introduction Conflicting data exist with regard to the outcomes of ablation procedures when compared with partial nephrectomy (PN) for cT1 renal masses. _x000D_ We compared all-cause mortality (ACM), cancer-specific mortality (CSM), local recurrence (LR), distant metastases (DM), treatment-related complication rates, and post-procedure changes in estimated glomerular filtration rate (eGFR) between PN and ablation therapies._x000D_ Methods We performed systematic review of original articles published upto July 2016. We conducted a meta-analysis to evaluate ACM, CSM, LR, DM rates, treatment-related complications and changes in eGFR. Publication bias was assessed using Begg and Egger tests. Results We identified 961 papers, of which 15 fulfilled our inclusion criteria. These 15 studies represented 3974 patients who had undergone an ablative procedure (CA or RFA; n = 1455, 37%) or PN (n = 2519, 63%). ACM and CSM rates were higher for ablation than for PN (HR 2.11 [95% CI 1.54-2.87], p < 0.05; HR 3.84 [95% CI 1.66-8.88], p < 0.05 respectively). No statistically significant difference in LR rate or risk of DM was seen between ablation and PN (HR 1.32 [95% CI 0.79-2.22], p = 0.22 and HR 1.83 [95% CI 0.67-5.01], p = 0.23, respectively). Complication rates were lower for ablation than for PN (13% versus 17.6%, respectively; OR 0.49 [95% CI 0.25-0.94], p < 0.05). The overall difference in reduction of eGFR between the ablation and PN groups was -7.42 mL/min/1.73 m2 (95% CI -12.48, -2.36; p = 0.04). Conclusions In this up-to-date meta-analysis, ablation, when compared to PN was associated with higher ACM and CSM, but no differences were seen in rates of LR or DM. Ablation was associated with fewer complications and a smaller reduction in eGFR when compared with PN. Funding None
Authors
J. Ricardo Rivero
Jose De La Cerda Hanzhang Wang Ann M. Farrell Michael A. Liss Ronald Rodriguez Dharam Kaushik |
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MP100-02 |
Boiling Histotripsy Ablation of Renal Carcinoma in a Chronic Rat Model |
Kidney Cancer: Ablative Therapy | 17BOS |
Abstract: MP100-02 Sources of Funding: The Urology Care Foundation, The Focused Ultrasound Foundation, NIH K01EB015745S_x000D_ Introduction Boiling histotripsy (BH) is a focused ultrasound (US) technique that produces non-thermal mechanical ablation of targeted tissues. Our group has been developing BH as a non-invasive treatment for renal carcinoma (RCC). Previously, we have demonstrated the feasibility of BH ablation of RCC in vivo in the Eker rat RCC model. Here in we accessed the long-term effects of BH ablation and the evolution of the homogenized lesion over time._x000D_ Methods Eker rats (n=15) were monitored for de novo RCCs with serial US. When tumors were ≥6 mm, rats underwent transcutaneous BH using a 1.5 MHz transducer (10-20 ms pulses, ~30kW/cm2) under US guidance targeting ~50% of the tumor. Following treatment, rats were provided with ketoprofen analgesia and monitored for complications. Serial US (Days 0, 1, 2, 7, 14, 28 and 56) was performed to assess the evolution of treatment within the targeted tumor. Rats were survived for 7 (n=5), 14 (n=5) or 56 (n=5) days. At euthanasia, necropsy was performed to assess for collateral damage and both kidneys underwent gross and histologic assessment._x000D_ Results BH was successful in all cases producing hyperechoic bubbles within the targeted tumor which gave way to hypoechoic regions consistent with mechanical disruption. On serial post-BH US we observed an evolution of these heterogeneous hypoechoic regions within the tumor into well-circumscribed, nearly anechoic cavities by day 7. Subsequently, the cavities decreased in size and were mostly re-absorbed with apparent contour deformities on day 14, with no apparent cavity by Day 28. Histologically, day 7 tumors demonstrated sharply demarcated lesions containing homogenized cell debris that appeared to be devoid of all cellular features by day 14. Day 56 kidneys appeared completely healed. Rats appeared well post-BH with minimal pain and did not require analgesia beyond 24 hours. Hematuria was noted in 33% (n=5) of rats which resolved in all but one within 24 hours and in all by day 2. One rat required humane euthanasia on day 1 for a large perinephric hematoma. _x000D_ Conclusions BH is a promising non-invasive treatment for RCC, producing desired tumor ablation with minimal collateral damage. Treatment appears well tolerated with rapid healing. Further studies will assess long-term tumor control while optimizing pulse parameters and image guidance to improve efficacy and safety._x000D_ Funding The Urology Care Foundation, The Focused Ultrasound Foundation, NIH K01EB015745S_x000D_
Authors
Wayne Brisbane
Tatiana Khokhlova Stella Whang Kayla Gravelle Yak-Nam Wang Joo Ha Hwang Vera Khokhlova George Schade |
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MP100-03 |
Multi-Point Thermal Sensing Needles: Improved Oncological Outcomes Following Cryoablation |
Kidney Cancer: Ablative Therapy | 17BOS |
Abstract: MP100-03 Sources of Funding: None Introduction Cryoablation is a minimally invasive modality for the management of small renal cortical neoplasms. Successful ablation is dependent on achieving target temperatures (i.e. -20°C) that result in tumor cell death. However, in most cases no thermal sensing device is deployed to monitor the temperature. We investigated long-term oncological outcomes following cryoablation using Multi-Point Thermal Sensing (MTS) needles, which allow precise temperature determination at four points along the needle. Methods We reviewed 20 cryoablation procedures for renal tumors < 4 cm done between 2005 to 2009; 11 procedures were performed with MTS needles with the goal of obtaining -20°C at the tumor margin, while 9 procedures were done without MTS needles. Patient demographics, tumor characteristics, and operative data were retrieved. Follow up CT or MRI imaging was used to assess recurrence status. Results With a mean follow-up of 45 months, none of the 11 MTS patients experienced a recurrence, compared to 4 (44.4%) of the non-MTS patients (p = 0.026). Of the biopsy-confirmed renal cancers, none of the 6 in the MTS group recurred compared to 3 of 6 in the non-MTS group (p = 0.182). Age, gender, tumor size, tumor histopathology, grade, follow-up time, and skin-to-tumor distance were similar between the MTS and non-MTS groups. The MTS group had increased duration of freeze (p = 0.041), increased procedure time (p = 0.020), increased number of cryoprobes placed in order to achieve the targeted temperature (p = 0.049), and a greater ratio of cryoprobes used per cm tumor (p = 0.003). Conclusions Using MTS needles, precise target temperatures could be determined during cryoablation of renal tumors. The use of MTS needles was associated with improved oncological outcomes. Funding None
Authors
Jeremy W. Martin
Roshan Patel Zhamshid Okhunov Aashay Vyas Jaime Landman Duane Vajgrt Ralph V. Clayman |
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MP100-04 |
Percutaneous Microwave Ablation for clinical T1b Renal Cancers |
Kidney Cancer: Ablative Therapy | 17BOS |
Abstract: MP100-04 Sources of Funding: None Introduction Small renal cell carcinomas (RCC) may be treated using percutaneous microwave ablation (MW) but few data are available to evaluate treatment for tumors 4 - 7 cm in size. The purpose of this study was to evaluate safety, feasibility, and oncologic efficacy for consecutive biopsy-proven clinical T1b RCC treated with MW ablation. Methods Thirty-five biopsy-proven cT1b RCC in 34 consecutive patients (19M/15F, median age 66, IQR: 62.5 - 66.0) from May 2012 and October 2016. Patient and procedural data were collected including body mass index (BMI), comorbidities, RENAL nephrometry score. Technical success was evaluated with immediate contrast enhanced post-procedural imaging. Local tumor progression, incidence of complications, and changes in renal function were assessed at follow-up. The Kaplan-Meier method was used for survival analysis. Results Median tumor diameter and nephrometry score were 4.5 cm (IQR: 4.2 - 5.1) and 8.0 (IQR: 8.0 - 9.0), respectively. Median Charlson Co-Morbidity Index was 5.0 (IQR: 4.0 - 7.0). Clear cell RCC histology represented 33/35 (94%) tumors (1 Chromophobe and 1 Papillary Type 2 RCC). There was no significant change in eGFR (p = 0.963). There were 5 (14.7%) high-grade (Clavien-Dindo III-IV) procedure-related complications. Post-operatively one patient developed urosepsis, one developed a urinoma requiring stent placement, and one developed a retroperitoneal hematoma. The remaining two complications were related to the anesthetic. Of 25 patients with follow-up imaging available, the median duration of imaging and clinical follow-up was 17.0 months (IQR = 8.5 - 26.0) and 20.7 months (IQR = 13.9 - 27.6), respectively. Immediate technical success was achieved for 33/35 (94%) tumors. There were 2 patients with difficulty visualizing residual enhancing tumor during initial ablation that required repeat ablation. Local tumor recurrence occurred in 1 (2.8%) patient at 26.3 months. The 3 treatment failures were successfully treated with salvage microwave ablation conferring a secondary efficacy of 100%. Estimated 3-yr local progression-free survival, cancer specific survival and overall survival were 83%, 100% and 76%, respectively. Conclusions Conclusion: Percutaneous MW ablation is feasible and safe for clinical T1b RCC. Long-term follow-up is needed to establish oncologic efficacy. Funding None
Authors
Brett Johnson
Shane Wells Sara Best Michael Hartung Timothy Ziemlewicz Meghan Lubner J. Louis Hinshaw Fred Lee Stephen Y Nakada E. Jason Abel |
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MP100-05 |
Long-Term Outcome Data from 47 Treated Renal Malignancies with MRI-Guided and Monitored Laser Ablation: A Single Center Study |
Kidney Cancer: Ablative Therapy | 17BOS |
Abstract: MP100-05 Sources of Funding: None Introduction Percutaneous ablation has become a viable treatment option for localized renal malignancy. MRI guidance has shown an added value for intraprocedural confirmation of complete ablation, potentially reducing the incidence of recurrence. The aim of this study is to report the long term local control data associated with in-bore MRI-guided laser ablation of renal malignancies. Methods 34 patients (18M, 16F, age=29-88y) with 47 renal masses underwent biopsies followed by MRI-guided laser ablations. A laser fiber with 15mm diffusing tip encased in 5.5 F cooling catheter (Visualase, Texas, USA) was introduced into the target lesion. A test dose of diode laser energy (980nm, 30sec, 9W) was applied to verify location of ablation nidus. Subsequently, ablative energy dose was delivered (27W cycles of 90-240 sec) with treatment endpoint based realtime thermal monitoring of ablation. Fiber repositioning for additional ablation was conducted as needed. Results Biopsies showed 1 renal metastasis from lung cancer and 46 RCCs (23 clear, 11 papillary, 2 chromophobe, 7 oncocytic, 1 poorly differentiated, 2 not specified). Tumor sizes were 0.7-4.5 cm (17 upper, 10 lower, 19 midpole). 11 patients (30%) had a single kidney, 6 patients (18%) had prior partial nephrectomy, and 2 lesions were recurrent after cryoablation. Access to desired part of kidney was feasible in all cases. The flexible nature of laser fibers eliminated the complexity of handling bulky ablation probes. Short ablation cycles facilitated accurate temperature mapping. 9 small-moderate self-limited perinephric hematomas and 1 delayed abscess occurred. Otherwise, no complications were encountered. Median follow-up was 24 months (max = 56 months). No residual or recurrent neoplasms were identified. Conclusions Interactively guided renal ablations performed within an interventional MRI suite are safe and well-tolerated. Data indicate reliable local tumor control with 0% recurrence rate over extended follow-up durations. Efficacy is likely related to improved visualization of tumor margins and temperature sensitivity of MRI allowing refined ablation procedures tailored to tumor response rather than following standard pre-determined ablation parameters. Funding None
Authors
Sherif Nour
Kareem Elfatairy Debra Weber Melinda Lewis Viraj Master |
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MP100-06 |
Cryoablation of cT1 Renal Masses in “Healthier” Patients: Early Outcomes from Mayo Clinic |
Kidney Cancer: Ablative Therapy | 17BOS |
Abstract: MP100-06 Sources of Funding: None. Introduction Current guidelines suggest that percutaneous thermal ablation (PTA) can be utilized in those with significant comorbidity who are unable to tolerate surgery (radical or partial nephrectomy). However, the use of PTA in "healthier" patients, who are otherwise candidates for surgery, has been limited. Here, we reviewed our institutional experience in such patients electing to undergo PTA, specifically cryoablation. Methods We identified patients ≤65 years undergoing percutaneous cryoablation for solitary, non-metastatic renal masses <7cm (cT1). We further limited our cohort to patients with an ASA score of 1 or 2, and in whom pre-operative eGFR was >60. Clincopathologic characteristics and recurrence patterns (local recurrence within the kidney versus metastatic disease) were evaluated. Results Between March 2003 and December 2015, 705 patients underwent cryoablation, of whom 43 (6.1%) met inclusion criteria. Median age of this cohort was 57 years (IQR 52-62), with pre-ablation eGFR of 75.6 (IQR 69.0-86.3) (Table). 14 (32.6%), 19 (44.2%), and 10 (23.2%) patients reported zero, one, or multiple prior abdominal-pelvic surgeries, respectively. Five patients (11.6%) had a prior partial nephrectomy. The majority (40, 93.0%) of ablated masses were cT1a, with 3 (7.0%) being cT1b. Median tumor size was 2.0 cm. 27 masses (63.7%) were biopsy-proven renal cell carcinoma (RCC) and 6 (13.6%) were benign; histology was unknown in 10 (22.7%). Follow-up imaging was available for 37 patients. Median radiological follow-up was 22 months (IQR 9-42), during which time 2 patients developed metastatic disease and and 1 developed local recurrence; all events were in patients with biopsy-proven RCC. No patients died from RCC during this time period. _x000D_ Conclusions In this single institution cohort of "healthier" patients with cT1 solitary renal masses, cryoablation offered reasonable short term oncologic control. While longer follow-up data are needed to evaluate for durability, cryoablation in healthier patients, particularly those with challenging surgical anatomy or prior renal surgery, warrants further study. Funding None.
Authors
Harras Zaid
Thomas Atwell Grant Schmit Stephen Boorjian William Parker John Cheville Bradley Leibovich R. Houston Thompson |
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MP100-07 |
Comparison of Oncologic Results, Functional Outcomes and Complications after Partial Nephrectomy versus Percutaneous Radiofrequency Ablation in Small sized (4cm or less) Bosniak III or IV Cystic Renal lesions |
Kidney Cancer: Ablative Therapy | 17BOS |
Abstract: MP100-07 Sources of Funding: None Introduction Partial nephrectomy (PN) has been increasingly used for the treatment of small renal mass. However, percutaneous radiofrequency ablation (RFA) has been accepted as a minimally invasive treatment option. In this study, we evaluated the oncologic results, functional outcomes and complications after PN or percutaneous RFA for the treatment of small sized (4cm or less) Bosniak III or IV cystic renal lesions. Methods We retrospectively reviewed medical records of 135 patients who underwent PN (99) or RFA (36) for small sized (4cm or less) Bosniak III or IV cystic renal lesions between January 2009 and December 2014. After excluding patients with hereditary cystic disease or less than 12 months of follow-up, 128 (PN, 97; RFA, 31) patients remained for analysis. Pathologic characteristics, tumor violation during surgery, residual tumor, local recurrence and distant metastasis data were collected. Glomerular filtration rate (GFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations and checked preoperatively, 1 month, 6 months, and 12 months postoperatively. All complications were graded by Clavien classification system. Results The median size of Bosniak III or IV cystic renal lesions was 2.6cm. Renal cell carcinoma (RCC) accounted for 86.6% (84/97) of patients in PN group. In RFA group, histologic subtype was identified in 32.3% (10/31) of patients, but 90.0% (9/10) of patients revealed RCC. One case of tumor violation occurred in PN group and 2 cases of residual cancer were observed in RFA group. But there were no local recurrence or distance metastasis in both groups during the median follow-up of 34.0 months. Compared with PN group, patients in the RFA group showed a small decrease of percent change of CKD-EPI GFR at 1 month (-13.6% vs -6.8%, p=0.039). Perioperative complication rate in PN group was 29.9% and 22.6% in RFA group. According to Clavien classification system, Grade IIIa complications rate was 4.1% in PN group and 6.5% in RFA group. There were no grade IIIb and IV complications Conclusions The results of our study indicated that percutaneous RFA showed comparable oncologic results and complications and better early preservation of renal functions than PN. Funding None
Authors
Song Wan
Byung Kwan Park Chan Kyo Kim Young Hyo Choi Hyun Woo Chung Chung Un Lee Jun Phil Na Hwang Gyun Jeon Byong Chang Jeong Seong Il Seo Seong Soo Jeon Han Yong Choi Hyun Moo Lee |
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MP100-08 |
Mitochondrial – target Peptides antioxidants SS-20 and SS-31 as a kidney protector against high dose WST-11 Vascular Target Photodynamic therapy (VTP) |
Kidney Cancer: Ablative Therapy | 17BOS |
Abstract: MP100-08 Sources of Funding: Thompson Family Foundation Introduction WST11-VTP is a promising technology in cancer treatment. Several preclinical models demonstrated higher efficacy in ablation of prostate, urothelial and kidney tumors. Likewise others ablation procedures, some normal tissue beyond the tumor’s area can be affected causing some undesirable effects. Sveto et al showed the capacity of SS-20 and SS-31 peptides in reduce cells damage after ischemic kidney injury in rats. We examined combination of VTP and SS peptides on kidney tissue damage after high-dose VTP application Methods 28 black-6 male mice arranged in 4 different groups: VTP alone, VTP plus SS-20, VTP plus SS-31 and VTP plus SS-20 and SS-31. All mice got same high dose of VTP – 200 mW/cm / 10’ – and retro-orbital WST11. The SS peptides dose was 2mg/Kg, gave 30’ before VTP and daily for 4 days by subcutaneous injection. In the VTP plus SS-20/ SS-31 combination group, a single shot of SS-20 was used 30’ before VTP and the following daily doses were just SS-31. All VTP application was performed on left kidney after surgical approach by small flank incision and renal externalization. Urea and creatinine blood exam were realized one day before VTP, 24 hrs and 72 hrs after. All mice were euthanized on day 5 after VTP and tissues of interest were collected for histology assessment by a board certificated pathologist Results After 28 mice submitted a VTP high dose treatment, just one from VTP alone group died. A reduced kidney damage- analyzed by tubular injury score- was observed in all peptides groups compare to VTP alone, but only the SS-20/SS-31 combination showed a statistical significance ( p < 0.05) . As a single agent, SS-20 seems has a better effect in kidney protection compares to SS-31. The E-Cadherin grades were lowered in all peptides treatment groups compared to VTP only (positive effect), but do not reach significance. This may be mitigated by powering the study to include more animals in each cohort. The same fact was observed in creatinine and urea results analysis. Compare to VTP alone, all peptides groups had lower creatinine and urea values 24 hrs after VTP application, but without statistical importance. Exception for SS-31 and VTP alone groups that reached statistical difference (p=0.04) in the urea measures 24 hrs after VTP. Once again, SS-20/SS31 combination and SS-31 groups presented lowest levels of creatinine and urea on day after VTP. After 72 hrs of VTP application, creatinine and urea returned to baseline values in all groups Conclusions The use of mitochondria-target peptides, SS-20 and SS-31, can protect the kidney against high dose VTP in a mouse model. The rationale of combine this drugs before and after VTP seems a promising approach in renal preservation and side effects prevention after VTP ablation Funding Thompson Family Foundation
Authors
Ricardo Alvim
Barak Rosenzweig Alexander Somma Stephen La Rosa Kwanghee Kim Jonathan Coleman |
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MP100-09 |
Does Routine Biopsy Improve Detection of Residual RCC Post Microwave Ablation? |
Kidney Cancer: Ablative Therapy | 17BOS |
Abstract: MP100-09 Sources of Funding: None Introduction The histologic presence of residual RCC following thermal ablation without radiographic evidence of tumor is of uncertain clinical significance. The purpose of this study is to evaluate the incidence of viable RCC in patients with no radiographic recurrence following percutaneous microwave (MW) ablation. Methods Routine post-ablation biopsy was obtained approximately 9 months following ablation. Four cores were routinely sampled from the ablation bed (2 for H&E staining, 2 for NAD diaphorase testing). A pilot study included ex-vivo ablation of RCC immediately following nephrectomy to evaluate histologic effect of ablation. Results Pilot study included 10 patients who had nephrectomy for RCC. A sample containing tumor and normal renal parenchyma was evaluated histologically following ex-vivo supra-therapeutic MW ablation. Preservation of tumor histology was demonstrated in specimens evaluated after H&E processing. Fifty-six biopsy proven RCC tumors in 52 patients (37M/15F, median age: 67.5 IQR: 64 - 71.3) following percutaneous MW ablation from April 2012 through May 2016 were evaluated. Median tumor diameter and nephrometry score were 2.8 cm (IQR: 2.0 - 3.2) and 6.5 (IQR: 5.0 - 8.0). Median Charlson Co-Morbidity Index was 2.0 (IQR: 0.75 - 3.0). Clear cell histology represented 40/56 (71.4%). Median follow up was 15.3 months (IQR: 8.4 - 27.0). Median time between ablation and biopsy was 9.3 months (IQR: 9.0 - 10.3). Following ablation, ablation zone biopsy has no RCC present in 51/56 (91.1%) tumors while 5/56 (8.9%) had the appearance of histologically residual tumor. Positive versus negative post-ablation biopsies did not significantly differ in nephrometry score, age, tumor size, or histology (p > 0.05). In patients with residual tumor, 2 were treated with repeat ablation and 3 elected surveillance. No patients have subsequently developed radiologically identifiable kidney recurrence and one patient with negative renal ablation bed biopsy was treated surgically for recurrence outside kidney and is currently NED. _x000D_ Conclusions Histologically identifiable tumor was identified in 9% of routine biopsies in the absence of radiologic recurrence following microwave ablation. The clinical significance of preserved tissue histology is unclear as no patients have radiological recurrence in ablated renal tumors to date. Funding None
Authors
Brett Johnson
Amy Lim Shane Wells Sara Best Michael Hartung Meghan Lubner Timothy Ziemlewicz J. Louis Hinshaw Fred Lee Wei Huang Richard Yang Stephen Y Nakada E. Jason Abel |
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MP10-01 |
An Unequal Nation: The Risks of Incidence and Death from Bladder Cancer Across All U.S. Counties |
Bladder Cancer: Epidemiology & Evaluation II | 17BOS |
Abstract: MP10-01 Sources of Funding: None Introduction Bladder cancer (BC) continues to exact high morbidity and mortality in patients who have a history of tobacco use. Less is known about non-tobacco related factors associated with BC-related death which may be targeted to lower the incidence or course of the disease. The mortality-to-incidence ratio (MIR) is a novel measure that has utility as a valid indicator of fatality and burden of disease. We hypothesized that a pooled county-level, population-based dataset from the United States, could demonstrate smoking and non-smoking related risk factors that may be modifiable targets in a prevention strategy. Methods Surveillance Epidemiology and End Results (SEER) population-based cancer registry data; state-specific Behavioral Risk Factor Surveillance Study (BRFSS) results; health care manpower, psychosocial, and socio-economic data from the 2014-2015 Area Health Resources File (AHRF) were pooled to establish independent variables associated with the MIR of BC by county. Cancer data was suppressed to ensure confidentiality and stability of rate estimates. Independent multivariate stepwise regression models were built for either sex. Results A total of 3140 counties in the U.S. were included in the dataset, of which 666 and 265 counties had complete data for males and females, respectively. The mean (+/- sd) MIR of BC was 0.22 (0.05) and 0.26 (0.07) for males and females, respectively (range: 0.11 - 0.77). Tobacco was strongly associated with the MIR of bladder cancer in all counties. On multivariate analysis, significant non-tobacco-related factors that predicted a greater MIR of BC in males were: poverty, lack of insurance, low urologist density; in females: poverty, obesity and low urologist density. Conclusions There is an independent association with death from bladder cancer due to inadequate access to healthcare, including urologists, and risk factors such as obesity and poverty, especially in women. Our study demonstrates that bladder cancer continues to afflict the poor, especially those who smoke and who have little access to health care (Figure 1). Prevention strategies may be more effective if anti-smoking campaigns target medically (and urologically) underserved, rural, and obese populations. The MIR is a novel indicator of the effectiveness of the health system. Funding None
Authors
Michael Goltzman
Jonathan Bloom John Phillips |
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MP100-10 |
A Cost Analysis of Renal Biopsy vs Laparoscopic Cryoablation for Initial Management of Small Renal Masses |
Kidney Cancer: Ablative Therapy | 17BOS |
Abstract: MP100-10 Sources of Funding: none Introduction The evolving health care environment is placing increased emphasis on cost effectiveness. We investigate the cost of pre-procedure biopsy of renal masses vs immediate cryoablation with intraoperative biopsy for patients with small renal masses who are candidates for cryotherapy. Methods We retrospectively identified all patients who had laparoscopic cryoablation for a renal tumor by a single surgeon at an academic center between 2004 and 2013. Pathology results from intraoperative biopsies were collected. Cost analysis was performed for two treatment algorithms. Algorithms differed in the initial step in management: CT guided biopsy vs laparoscopic cryoablation with intraoperative biopsy. _x000D_ Results There were 96 patients in the study. Pathology results from intraoperative biopsies were: Cancer: 64 (66.7%), Indeterminate: 12 (12.5%), and Benign: 20 (20.8%). Cost of laparoscopic cryoablation and hospital stay is $10,600. Cost of a CT guided biopsy is $5,400. Cost of 5 years of surveillance is $37,400. On average, the five-year cost to manage a patient initially with laparoscopic cryoablation is $40,200. This compares to $43,400 for CT guided biopsy as first management. In order for CT guided biopsy to be cost effective, 52% of small renal masses deemed appropriate for cryoablation would need to be benign._x000D_ Conclusions Immediate cryoablation is slightly more cost effective than getting a pre-operative CT guided biopsy for patients considering treatment of small renal masses with laparoscopic cryoablation. The cost difference is not enough to unilaterally drive clinical decisions but shared decision making should include cost. The overwhelming cost over five years is driven by cost of surveillance imaging._x000D_ Funding none
Authors
Michael Kottwitz
Thomas Tieu Joshua Ring Bradley Schwartz |
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MP100-11 |
Percutaneous Irreversible Electroporation of Renal Tumors: Outcomes after Median 2 Year Follow-up |
Kidney Cancer: Ablative Therapy | 17BOS |
Abstract: MP100-11 Sources of Funding: none Introduction Percutaneous irreversible electroporation (IRE) is a novel minimally invasive technique to treat small renal tumors. IRE uses an electric field to create nano-pores within cellular membranes resulting in subsequent apoptosis. Because IRE is athermal, it offers potential advantages to radiofrequency (RFA) and cryoablation. We report on the longest followup outcomes of IRE renal tumor ablation. Methods We retrospectively reviewed all IRE cases completed at our institution from April 2013-June 2016. IRE was performed using the NanoKnife® commercial system and 15 cm monopolar probes (AngioDynamics, NY, USA). All procedures were performed with computed tomography (CT) guidance, under general anesthesia with paralytics, and with ablation synchronized to the cardiac cycle. A minimum of three months of follow-up with a contrast-enhanced CT scan was necessary to be included in the analysis. Results A total of 39 tumors in 38 patients underwent irreversible electroporation. Mean tumor size was 2.0 cm with a median R.E.N.A.L nephrometry score of 5. Twenty-six patients (68%) were discharged the same day of the procedure and no major (Clavien grade III or higher) intraoperative or post-operative complications occurred. Initial treatment success rate was 92%; our three failures (8%) underwent salvage radiofrequency ablation. With a median follow-up of 25.2 months, two-year local recurrence-free survival was 76% for patients with biopsy confirmed renal cell carcinoma, 84% with biopsy confirmed or a history of renal cell carcinoma, and 90% for the intent-to-treat cohort (figure 1). Conclusions Percutaneous irreversible electroporation has suboptimal short-term local disease control results compared to thermal ablation in this series of small, low complexity tumors. Larger series and longer follow-up is still needed to determine the durability of this modality for renal cell carcinoma. Funding none
Authors
Igor Sorokin
Noah Canvasser Aaron Lay Monica Morgan Asim Ozayar Jeffrey Gahan Clayton Trimmer Jeffrey Cadeddu |
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MP100-12 |
Should pathologic diagnosis be obtained prior to renal mass ablation? |
Kidney Cancer: Ablative Therapy | 17BOS |
Abstract: MP100-12 Sources of Funding: None Introduction Pathologic diagnosis of cancer in renal masses allows for optimal patient selection before treatment and appropriate follow-up after thermal ablation. However, biopsy is still often performed at the same time as ablation and pathologic findings are either non-diagnostic or benign in 7-45% of tumors in large ablation series. The objective of this study was to compare findings for renal mass biopsies obtained prior to treatment (priorbx) to biopsies obtained on the same day as ablation (samedaybx). Methods An institutional database identified consecutive patients with renal masses treated with thermal ablation from 2001-2015. Patients treated_x000D_ without biopsy (37) were excluded. Radiologic tumor and patient data were reviewed. Fischer’s exact or chi-square tests were used to evaluate differences between groups, non-diagnostic biopsy rate and the rate of ablation for benign tumors._x000D_ Results A total of 280 renal tumors were treated with ablation including 197 (70.4%) with priorbx and 83 (29.6%) with samedaybx. There was nodifference in patient or tumor characteristics between samedaybx and priorbx groups (table). Priorbx patients had longer skin-to-tumor distance median 10.5 vs. 8cm, p=0.0001._x000D_ _x000D_ Non-diagnostic biopsy findings were significantly more common in patients with samedaybx compared to priorbx, 14.5% vs. 1.5%, p<0.001. Ablation of_x000D_ oncocytoma was also more common in patients with samedaybx compared to priorbx, 15.7% vs. 3.0%, p<0.001.RCC diagnosis was obtained in only 69.9% of tumors with samedaybx compared to 95.4% of tumors with priorbx, p<0.001._x000D_ Conclusions Pre-ablation biopsy is associated with a decreased rate of treatment for benign and unidentified renal tumors and better diagnostic_x000D_ yield than same day renal biopsy. This approach has clear benefits to patients considering thermal ablation of small renal masses._x000D_ Funding None
Authors
Amy H. Lim
Shane Wells Matthew Grimes Tyler Wittmann Sara Best James Louis Hinshaw Fred T. Lee Meghan Lubner Timothy Ziemiewicz Stephen Y. Nakada E. Jason Abel |
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MP100-13 |
Irreversible Electroporation for Renal Masses Not Amenable to Thermal Ablation in Non-Surgical Candidates: Mid-term Clinical Follow-up |
Kidney Cancer: Ablative Therapy | 17BOS |
Abstract: MP100-13 Sources of Funding: none Introduction Irreversible Electroporation (IRE) is an emerging ablative modality for patients with renal tumors that are not candidates for surgery or conventional thermal ablation. This study aims to evaluate technical success, safety, and outcomes for IRE treated complicated renal tumors. Methods A single institution retrospective review of all renal tumors treated with Computed Tomography (CT) guided IRE between May 2013 and February 2016 was performed. A total of 17 patients underwent IRE with NanoKnife (AngioDynamics, Queensbury, New York) for primary or secondary renal malignancies. Technical success was defined as delivery of all planned pulses during ablation and verifying complete ablation by immediate post-procedure CT imaging. Local recurrence was defined as residual enhancement or increased tumor size following technical success. Follow?up imaging was scheduled at 1, 3, 6, 12, 18, and 24 months. Complications were defined using Clavien-Dino (CD) classification. Results IRE was performed on 18 complicated renal tumors with median RENAL score of 6.5 ( 1st quartile 6, 3rd quartile 9) and median tumor size of 2.2 cm (1st quartile 2.0, 3rd quartile 3.1). Most were clear cell renal cell carcinomas (n=13). Technical success was achieved in 17/18 tumor treatments (94.4%). One (5.6%) case was aborted due to bleeding (CD grade IIIb) requiring embolization. Minor CD grade one or two complications were present in 7/18 cases (38.9%), including post?procedural urinary retention (4/18, 22.2%), hypoglycemia (1/18, 5.6%), hematuria (1/18, 5.6%), and back pain (1/18, 5.6%). Patients lost to follow up were excluded (n=3) from follow-up analysis. Median follow?up was 392 days, 1st quartile 203, 3rd quartile 696). Two local recurrences (14.2%) occurred on days 320 and 230 post?procedure with RENAL Scores of 9 and 8, respectively. Both cases were successfully treated with cryoablation and follow up showed no residual tumor at 723 and 617 days post cryoablation, respectively. Conclusions IRE appears to be a safe and efficacious option for the treatment of renal tumors in patients that are not candidates for surgery or thermal ablation techniques. Further research is warranted with larger sample sizes and continued follow up. Funding none
Authors
Robert Medairos
Wei Phin Tan Kelsey Gallo Kalyan Latchamsetty Jordan Tasse Christopher Coogan Bulent Arslan |
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MP100-14 |
High Intensity Focused Ultrasound Kidney Ablation: Pre-Clinical Safety and Efficacy Evaluation in a Porcine Model using a 15mm Laparoscopic Probe |
Kidney Cancer: Ablative Therapy | 17BOS |
Abstract: MP100-14 Sources of Funding: This work was supported by a Young Investigator Award (S.C.). Introduction High intensity focused ultrasound (HIFU) has established itself clinically as a viable, safe, effective, and non-invasive tissue ablation modality. Previous studies have shown that HIFU delivered laparoscopically can be used to ablate kidney tumors, potentially enabling a lower morbidity treatment with faster recovery time as compared to partial nephrectomy procedures. Challenges remain, however, including ensuring full tissue necrosis and consistent energy coupling to the target volume. The objective of this study was to evaluate whether a newly developed laparoscopic HIFU probe is able to address these challenges. Methods A laparoscopic porcine kidney model was used to investigate the safety and efficacy of the new 15mm HIFU probe. Under ultrasound guidance, kidneys of 12 pigs were targeted and ablated with HIFU, creating on average 2 ablation zones per kidney of varying sizes and locations in order to quantify the probe&[prime]s ability to deliver HIFU to any location on the kidney. Efficacy was evaluated via the analysis of ablation volume histology slides, real-time ultrasound images collected during HIFU delivery, and MRI and ultrasound contrast images. Safety was evaluated by surviving a subgroup of the animals (2w). Gross-pathological data, sonication parameters, and workflow feedback was also collected during the study. Results Repeatable lesions could be created at a rate of 0.48cm3/min and average energy densities of 584cal/cm3. Histological evaluation indicated contiguous ablated volumes using these delivery parameters, extending from the transducer&[prime]s focal zone to the kidney surface, with a maximum treatment depth of 27mm. Ablated target volumes ranged from 5.1cm3 to 24.5cm3. Conclusions The results confirm the ability of the new probe to deliver HIFU in a consistent and reliable manner. Initial dose requirements for ablating tissue at various depths were also determined. Workflow feedback has resulted in additional system user interface improvements, with all of these results paving the way for a future clinical study. Funding This work was supported by a Young Investigator Award (S.C.).
Authors
Sameer Chopra
Inderbir Gill Alfredo Bove Carlos Fay Kevin King Vinay Duddalwar Toshitaka Shin Rene Arboleda Rodrigo Chaluisan Jesse Clanton Jacob Carr Christie Johnson Ben Ettinger Adam Morris Roy Carlson Narendra Sanghvi Mark Carol Ralf Seip |
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MP100-15 |
LONG TERM ONCOLOGICAL OUTCOMES FOLLOWING RADIO FREQUENCY ABLATION OF RENAL MASS |
Kidney Cancer: Ablative Therapy | 17BOS |
Abstract: MP100-15 Sources of Funding: NONE Introduction Widespread availability of cross sectional abdominal imaging increased the incidence of diagnosing low stage renal mass. Radio Frequency Ablation (RFA) is a treatment option in selected patients. Long-term outcome data is limited in the literature. We present our long-term follow up data after RFA Methods We reviewed the IRB approved RFA database at a tertiary care center. All patients were diagnosed with renal mass by contrast enhanced CT or MRI before surgery. They underwent laparoscopic RFA or computerized tomography guided RFA between November 2001 and August 2013. Patients were followed for tumor recurrence by contrast CT or MRI at 1 month, 6 months, 1 year and annually thereafter. Demographic and oncological follow up data were analyzed. Results There were 398 patients underwent 466 RFA procedures for the median tumor size of 2.3cm. Their median age was 70 years (IQR 57-76), mean pre-operative creatinine was 1.13 (± 0.41) and mean creatinine during most recent follow up visit was 1.18 (± 0.49). Median follow up time was 48 months (IQR 46-150 months). Radiographic failure (enhancement in the follow up CT/MRI) was diagnosed in 38 (9.5%) patients and 31 (82%) of them had follow up biopsy. Biopsy pathology showed renal cell cancer (RCC) in 18/31 (58%) patients (11 clear cell, 2 papillary and 5 unclassified RCC) and rest had normal renal parenchyma or non-diagnostic. Another thirteen patients developed new enhancing renal mass other than treated site during follow up. Total 36 patients (9%) required secondary treatment during follow up period (26 had repeat RFA, 7 had partial nephrectomy and 3 had radical nephrectomy). In total 33 (8.3%) patients deceased during follow up (3 due to metastatic RCC, one due to metastatic prostate cancer and others due to unrelated causes). Kaplan-Meier estimation of radiographic recurrence free survival was 90% at 5 years and 78% at 10 years. Five years cancer specific mortality was less than 1% and all-cause mortality was 8.3% following RFA._x000D_ _x000D_ Conclusions RFA for renal mass has acceptable local recurrence rate (9.5%) diagnosed with regular follow up and can be effectively treated with secondary procedures. Cancer specific mortality is low (<1%) within median follow-up time of 48 months. This provides an alternate treatment option in selected patients. Funding NONE
Authors
Hariharan Ganapathi
Emily Fell Kelly Aysswarya Manoharan Manuel Molina Raymond J Leveillee |
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MP100-16 |
Laparoscopic Renal Cryoablation using Real-time Intraoperative Thermal Monitoring: 15 year Experience |
Kidney Cancer: Ablative Therapy | 17BOS |
Abstract: MP100-16 Sources of Funding: None Introduction Review of 15 year, single surgeon experience using laparoscopic cryoablation (LCA) and real-time intraoperative thermal monitoring for the management of small renal masses. We present treatment success and perioperative outcomes. Methods We retrospectively analyzed 143 renal masses (128 patients) treated with LCA from 2001-2011, allowing for 5 year follow-up. Patients underwent retroperitoneal (RP) or transperitoneal (TP) LCA with objective thermal monitoring. After cryoneedle insertion, ≥2 thermal probes were placed within the tumor and outside the tumor margin to quantitatively assess temperatures. All tumors had ≥2 freeze cycles with a goal of achieving ≤-25°C at the periphery. Core tumor biopsies (3-6) were taken under direct vision during the first freeze cycle. _x000D_ _x000D_ Follow-up was recommended at least annually. Patient characteristics, operative details, pathology and perioperative labwork were analyzed. All cases of post-ablative radiologic persistence (lesion at ablation site) and recurrence (lesion outside of ablation site) were confirmed with biopsy or pathology from additional surgery._x000D_ Results Of 128 LCA patients (75 female, 53 male), mean age was 63 (30-83) years and BMI was 31.3kg/m2. Median ASA score was 3. Comorbidities included: hypertension (82/128), renal insufficiency (33/128), diabetes (28/128), ischemic cardiac disease (17/128) and solitary kidney (11/128)._x000D_ _x000D_ RP approach was used in 30/78 right vs 38/65 left-sided tumors with TP in the remainder. Mean tumor size was 3.0 (+/- 1.1) cm and surgical time was 211.1 (+/- 63.4) min. Two freeze cycles were performed in 97/143 tumors and mean freeze cycle duration was 11.0 (+/- 8.3) min. Mean EBL was 164.6mL and postop discharge was ≤24 hrs and ≤48 hrs in 45/133 and 84/133 of cases, respectively. Average hematocrit and eGFR change from pre- to postop was -5.1 mg/dL and 3.96 mL/min/1.73m2, respectively._x000D_ _x000D_ Intraoperative biopsy (n=143) showed malignancy in 97 (67.8%) or oncocytic neoplasm in 21 (14.7%) cases. Of the remainder, 18 were benign (12.6%) and 6 were angiomyolipoma (4.2%). One sample was lost._x000D_ _x000D_ Surgical limitations to tumor treatment were noted in only 3/143 (2.1%) tumors using our LCA technique. Of patients with biopsy-proven renal cancer or oncocytic neoplasm, 113/118 (95.8%) had no tumor persistence (mean radiologic follow-up 49.4 (+/-28.4) months (0.4-131.8 months)). Only 7/128 (5.5%) patients had recurrence._x000D_ Conclusions Using objective thermal monitoring may improve intraoperative tumor control and decrease the likelihood of oncologic persistence when compared to traditional LCA. Funding None
Authors
Dean Laganosky
Mark Henry Frances Kim Peter Nieh Viraj Master John Pattaras |
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MP100-17 |
PARTIAL NEPHRECTOMY VERSUS CRYOABLATION FOR TUMORS IN SOLITARY KIDNEYS: A PROPENSITY SCORE ANALYSIS |
Kidney Cancer: Ablative Therapy | 17BOS |
Abstract: MP100-17 Sources of Funding: none Introduction The optimal approach for a renal tumor in a solitary kidney is unknown. Our objective was to compare outcomes between partial nephrectomy (PN) and percutaneous cryoablation (PCA) for tumors in a solitary kidney. Methods Patients with a solitary kidney undergoing PN or PCA for a single localized primary renal tumor between 2005-2015 were identified using Mayo Clinic Registries. Exclusions were inherited tumor syndromes, multiple tumors, and salvage procedures. To achieve balance in baseline characteristics, inverse probability of treatment weighting (IPTW) was employed using propensity scores computed based on age, Charlson co-morbidity index, treatment year, nephrometry score, tumor size, baseline estimated glomerular filtration rate (eGFR), confirmed renal cell carcinoma (RCC) histology, and history of prior contralateral nephrectomy for RCC. Complications (Clavien scale), renal function outcomes, local recurrence, distant metastasis, and cancer-specific survival were compared between groups using logistic, linear, and Fine-and-Gray competing risks regression modeling. Results The cohort included 118 patients (PN: 64; PCA: 54) with a median follow-up of 48 months (IQR 23,80). In unadjusted analyses, PCA was associated with a decreased risk of complications (15% vs 31%; OR=0.4; 95%CI 0.2-1.0; p=0.04). However, upon accounting for baseline differences with IPTW-adjustment, there was no longer a significant difference in risk of complications (26% vs 27%; OR=1.0; 95%CI 0.4-2.2; p=0.9). Higher nephrometry score was associated with greater risk of complications for both PN (OR[per 1 point]=1.5; 95%CI 1.1-2.0; p=0.01) and PCA (OR[per 1 point]=1.7; 95%CI 1.0-2.9; p=0.04), but nephrometry score did not modify the effect of treatment modality on the risk of complications (p-interaction=0.17).Median percentage drop in eGFR from baseline to 3 months from treatment was 16% and 7% for PCA and PN, respectively (p=0.23). There were no significant differences between PCA and PN in risk of local recurrence (HR=1.0; 95%CI 0.3-3.4; p>0.9), distant metastasis (HR=0.7; 95%CI 0.2-1.9; p=0.5), or cancer-specific mortality (HR=1.4; 95%CI 0.2-8.0; p=0.7). Conclusions Both PN and PCA appear to be viable options for renal tumors in solitary kidneys. Although PCA was associated with fewer complications in unadjusted analyses, there were no significant differences between PCA and PN, regardless of tumor complexity, when adjusting for treatment selection bias. Short term oncologic outcomes appear similar although additional follow-up is needed. Funding none
Authors
Bimal Bhindi
Ross Mason Mustafa Haddad Stephen Boorjian Bradley Leibovich Thomas Atwell Grant Schmit R. Houston Thompson |
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MP100-18 |
Long-term Outcomes of Cryoablation for Biopsy-Proven RCC: Size Matters |
Kidney Cancer: Ablative Therapy | 17BOS |
Abstract: MP100-18 Sources of Funding: None Introduction Cryoablation (CA) is an alternative treatment for small renal cell carcinomas (RCC), although some prior studies lack biopsy data or long term follow-up. We sought to identify risk factors for treatment failure of biopsy-proven RCC following CA as primary treatment at a single institution. Methods Comprehensive data were reviewed for 89 patients with biopsy-proven T1 renal cancer who underwent CA as primary treatment between 2003 - 2012. The Kaplan Meier method was used to estimate recurrence-free survival (RFS) from the date of treatment to recurrence, progression, or most recent imaging. A multivariable Cox model was used to evaluate associations with survival. Results All tumors were biopsy proven RCC and 62/89 (70%) were clear cell subtype. Median tumor size was 2.6 cm (IQR 2.1 - 3.1) and median follow-up was 50.7 months (IQR 26.1 - 65.6). Overall 5-year survival was 48/57 (82%). Five-year cancer specific survival was 56/57 (98%). Five-year RFS was 89.1% overall. Of 10 CA failures, 9 (90%) tumors recurred locally and 1 progressed to metastatic disease. Mean tumor size among the successful treatment group was 2.63 cm versus 3.28 cm for the treatment failure group (p = 0.05) and all failures were clear cell subtype (p < 0.05). Secondary treatments included: repeat ablation 7/10, nephrectomy 2/10 and systemic therapy 1/10. On Cox multivariate analyses, increased risk of recurrence was associated with tumor diameter (HR = 1.751, p = 0.01). Age, BMI, creatinine, presence of solitary kidney, and history of previous ablation were not associated with recurrence. Median time until recurrence for tumors ≥3.0 cm was 9.9 months and 18.1 months for tumors <3.0 cm, (p = 0.38). Conclusions Cryotherapy provides durable treatment of RCC smaller than 4cm. Success of treatment inversely correlates to tumor size. Most treatment failures were successfully treated with repeat ablation. Funding None
Authors
Sara Best
Brett Johnson Shane Wells Meghan Lubner Timothy Ziemlewicz J. Louis Hinshaw Fred Lee Stephen Y Nakada E. Jason Abel |
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MP100-19 |
LAPAROSCOPIC VERSUS PERCUTANEOUS CRYOABLATION OF SMALL RENAL MASS: A META-ANALYSIS OF 1725 CASES |
Kidney Cancer: Ablative Therapy | 17BOS |
Abstract: MP100-19 Sources of Funding: none Introduction Objective: To compare the surgical, oncological, and functional outcomes of laparoscopic and percutaneous cryoablation for the treatment of small renal masses. Methods A systematic review of the literature was performed through March 2016 using PubMed, Scopus, and Ovid databases. Article selection proceeded according to the search strategy based on PRISMA criteria. Only studies comparing laparoscopic and percutaneous kidney cryoablation were included in the meta-analysis. Results Eleven studies were selected for the analysis including 1725 cases: 804 (46.6%) percutaneous and 921 (53.4%) laparoscopic cryoablation. Included studies were all retrospective comparative ones. Percutaneous cryoablation was performed more frequently for posterior tumors (p<0.001), whereas laparoscopy was more common for endophytic lesions (p=0.01). The length of follow-up was longer for laparoscopy (p<0.001). Percutaneous cryoablation was associated with a significantly shorter hospital stay (p<0.001). A lower likelihood of residual disease was recorded for laparoscopic (p=0.003), whereas tumor recurrence rate favored percutaneous cryoablation (p=0.02). The two procedures were similar for recurrence free survival (p= 0.08), and overall survival (p=0.51). No significant difference was found in post-operative eGFR (p=0.78). Conclusions Laparoscopic and percutaneous kidney cryoablation offer similar favorable oncological outcomes with minimal impact on renal function. The percutaneous access can offer shorter hospital stay and faster recovery, which can be appealing in an era of cost restraint. Determining which approach to use in clinical practice will depend on the available technology and specific expertise at each center. Funding none
Authors
Rodrigo R Pessoa
Riccardo Autorino Maria del Pilar Laguna Wilson R Molina Rodrigo R Donalisio da Silva Diedra Gustafson Priya N. Werahera Fernando J Kim |
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MP10-02 |
TEMPORAL TRENDS IN PERIOPERATIVE MORBIDITY FOR RADICAL CYSTECTOMY |
Bladder Cancer: Epidemiology & Evaluation II | 17BOS |
Abstract: MP10-02 Sources of Funding: none Introduction Radical cystectomy (RC) is the standard of care for invasive non-metastatic bladder cancer. Unfortunately, it is a complex procedure with more than half of patients experiencing a postoperative complication. A number of efforts to reduce perioperative morbidity have been made, including alterations in pain management, antibiotics, diet advancement, and anticoagulation. Many of these changes in management have been studied with favorable results; however, it is not clear whether complication rates following RC have improved in recent years. We sought to evaluate current temporal trends in postoperative complication rates following RC using a large national dataset. Methods Using the National Surgical Quality Improvement Program (NSQIP) participant use files from 2010-2014, we identified patients who underwent RC. Demographic information as well as 30-day complications, length of stay (LOS), readmissions, and death were compared according to year of operation using univariable and multivariable analyses. Results Over the 5-year study period, 5257 patients were identified for analysis. Age, race and comorbidity were similar across the study period. Overall, 58.0% of patients experienced a complication, which did not differ among years. A robotic approach was used in 6.1% of the entire cohort, and 16.7% of patients underwent a continent urinary diversion, both of which did not vary among years. There were no significant changes in any specific complication types over the study period. Transfusion rate varied among years with no discernible trend over the study period (range 39.9-44.9%). LOS decreased over time from 10.6 days in 2010 to 9.4 days in 2014 (p<0.01) while readmission rate increased over time from 20.1% in 2011 to 22.1% in 2014 (p<0.01). On multivariable analysis, there were no predictors of complications, readmissions, or death. Conclusions RC remains a procedure associated with high morbidity. While there were no improvements in complication rate, there is a slow decline in LOS, possibly at the expense of an increasing readmission rate. This is the first study to our knowledge to demonstrate an inverse relationship between trends in LOS and readmission after RC. Funding none
Authors
Zachary Smith
Scott Johnson Vignesh Packiam Joseph Rodriguez III Norm Smith Gary Steinberg |
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MP100-20 |
Cryotherapy and Thermal Ablation for Renal Malignancy Over 3 Centimeters - Comparative Analysis of Survival with Small Renal Masses |
Kidney Cancer: Ablative Therapy | 17BOS |
Abstract: MP100-20 Sources of Funding: None Introduction Ablative treatments achieve good oncological outcome for renal parenchymal tumors 3 centimeters (cm) or smaller. Larger renal malignancies are increasingly being treated with ablation. This comparative study determines the survival following ablation in these large renal masses. Methods Patients undergoing cryotherapy or thermal ablation (Procedure codes 13, 15, or 23) for renal tumors were identified from the Surveillance, Epidemiology, and End Result (SEER) Database from 1998-2013. Exclusion criteria included T stage not recorded, more than one primary malignancy, metastatic disease, or node positive disease. Demographics, stage, and overall (OS) and cancer specific survival (CSS) were analyzed. T1a tumors were compared to T1b or T2 tumors. Tumors 3 cm or less were compared to greater than 3 cm. Results A total of 4,886 patients were identified, and 2,340 patients met inclusion criteria. The mean age was 66.5 years, 1,943 were white, 243 were black, and 1,419 were male. The stage distribution included T1a (n=2159), T1b (n=172), and T2 (n=9). 1,186 tumors were right-sided, 1,149 were left-sided, and the remaining were bilateral or not specified. 2,326 patients had the size recorded. 1,637 patients had 3 cm or smaller tumors and 689 tumors were larger than 3 cm. The OS in T1a tumors was 84.4% at 5 years and 69.2% at 9 years. In individuals with T1b tumors, OS was 62% at 5 years and 38% at 9 years. The T2 tumors had an OS of 64.8% at 57 months. The 5 year CSS was 97.4% in the whole group, 97.9% in T1a, and 97.4% in the T1b group. The corresponding 9 year CSS was 96.9, 97.5, and 96.9%. Comparative CSS in patients with T1a tumors was 98% at 5 years and 97.5% at 9 years. In T1b or greater tumors, the 5 and 9 year survival was 90.2%. All patients that survived beyond 5 years were alive at 9 years of follow-up. On analysis by size, tumors 3 cm or less had a 98.4 5-yr and a 98.2 9-yr CSS and tumors that were greater than 3 cm had 95% 5-yr and a 93.9 9-yr survival. On univariate analysis, both T1a tumors and tumors smaller than 3 cm had significantly better survival (p=0.001). Conclusions Ablative therapies for small renal masses can achieve excellent CSS at 97% at 9 years. This study demonstrates that reasonable CSS can be achieved in masses larger than 3 cm and patients with T1b or larger tumors. Further studies are required to address the role of ablative therapies for larger renal masses. Funding None
Authors
Alex Jones
Megan Dinino Mark Wakefield Katie Murray Naveen Pokala |
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MP10-03 |
Preoperative Risk Factors Predicting Postoperative Complications in Radical Cystectomy for Bladder Cancer |
Bladder Cancer: Epidemiology & Evaluation II | 17BOS |
Abstract: MP10-03 Sources of Funding: none Introduction INTRODUCTION: Radical cystectomy is an extensive operation with complications reported in up to 30.5% of patients. High complication rates contribute to increased costs, patient morbidity and mortality. Accurate prospective predictions of patients’ risk for post?surgical complications have the potential to identify at risk patients. Risk estimators have been developed but often involve an extensive number of factors or produce expansive results that are not clinically useful. _x000D_ OBJECTIVE: Clinically available preoperative risk factors were identified as potential predictors of postoperative complications, at 30 and 90 days, in patients who underwent radical cystectomy for bladder cancer. We developed a postoperative complication risk prediction model using minimal factors obtained in the normal course of preoperative history, physical and staging. not clinically useful. Methods METHODS: 330 patients who underwent radical cystectomy for bladder cancer from January 2008 to July 2014 were included in this study. Potential preoperative risk predictors were collected from medical history, TURBT pathology, preoperative labs, proposed procedure type, and prior treatments. Postoperative complications were graded using the Clavien?Dindo scale. Multivariate logistic regression models were used to predict post?operative complications. Accuracy of prediction models was assessed using the area under the receiver operating characteristic curve. Results RESULTS: Of the potential preoperative risk factors, 5, 10 and 16 unique predictors along with two way interactions were determined to have strong association with 90 day postoperative complications, yielding an AUC of 0.69, 0.79 and 0.91 respectively. This is illustrated in Figure 1. Conclusions CONCLUSIONS: Our findings suggest routinely collected preoperative patient?level clinical variables may be useful for determining patient risk for short?term postoperative complications. The flexibility in our prediction model for the number of predictor inputs allow users to tailor the degree of risk assessment based on a patient’s baseline heath status. A simple and accessible prediction model with selective predictors may help identify at risk patients for patient education, counseling and development of risk reduction strategies. _x000D_ Funding none
Authors
Vassili Glazyrine
Stefan Graw Sida Niu Derek Jensen Devin Koestler Eugene Lee |
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MP10-04 |
EFFECT OF RADICAL CYSTECTOMY AND URINARY DIVERSION FOR BLADDER CANCER TREATMENT ON RENAL FUNCTION OVER TIME |
Bladder Cancer: Epidemiology & Evaluation II | 17BOS |
Abstract: MP10-04 Sources of Funding: University of Florida, Clinical and Translational Research Institute. Research reported in this publication was supported by the National Center For Advancing Translational Sciences of the National Institutes of Health under Award Number UL1TR001427. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Introduction We determined the effect of radical cystectomy (RC) and urinary diversion (UD) for bladder cancer treatment compared to controls on renal function over time. Methods In this retrospective study of 384 patients with bladder cancer who sought care in a tertiary health care center from 2000 to 2014, we determined the effect of RC&UD (n=172) on renal function over time using bladder cancer patients treated without RC&UD (n=212) as a comparison group. Renal function decline was defined using (a) annualized estimated glomerular filtration rate (eGFR) decline and (b) time to decrease in eGFR of 30% or more from baseline. We used propensity score regression adjustment to address confounding by indication. Unadjusted and adjusted linear mixed-effects and Cox proportional hazards models were used to assess the association between RC&UD and eGFR slope and time to decrease in eGFR of 30% or more, respectively. Results Mean age was 68±12 years; average follow-up was 17±13 months. Patients with RC&UD experienced a faster decline in renal function over time as compared to those without RC&UD (see Figure). After adjusting for age, propensity score, and other confounding variables, the difference in mean eGFR slope in patients with RC&UD, compared to those without RC&UD, was stable and remained statistically significant (p< 0.001). Patients with RC&UD had a higher risk of eGFR decline of 30% or more, compared to those without RC&UD (unadjusted HR=1.88, 95%CI: 1.35-2.63; p<0.001); this persisted despite adjustment for age but was attenuated and no longer statistically significant after adjustment for propensity score, and confounding variables (adjusted HR=1.01, 95% CI: 0.62-1.63; p=0.976). Conclusions RC&UD was independently associated with a faster decline in renal function over time, as measured by annualized eGFR decline. RC&UD was associated with higher risk of eGFR decline of 30% or more in unadjusted analysis but not in adjusted analysis. Our findings will inform future prospective studies to examine this association and investigate intervention strategies to prevent renal injury in this population. Funding University of Florida, Clinical and Translational Research Institute. Research reported in this publication was supported by the National Center For Advancing Translational Sciences of the National Institutes of Health under Award Number UL1TR001427. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Authors
Shahab Bozorgmehri
Scott Gilbert Xiaomin Lu Robert L. Cook Rebecca Beyth Muna Canales |
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MP10-05 |
IS DE NOVO UPPER TRACT UROTHELIAL CARCINOMA A DISTINCT ENTITY FROM BLADDER CARCINOMA? |
Bladder Cancer: Epidemiology & Evaluation II | 17BOS |
Abstract: MP10-05 Sources of Funding: None Introduction Upper tract urothelial carcinoma (UTUC) accounts for <5% of all urothelial cancers (UC). It is usually considered a part of the spectrum of UC, manifesting as bladder cancer (BC) primarily. Our objective was to find whether there are clinical differences between UTUC tumors that present de novo (DnUTUC) and those that present secondarily (SUTUC)(i.e.: having had a prior history of BC). Methods The SEER database was queried for all patients with UTUC from 1988-2013. Data collected consisted of demographic, clinical, pathologic and survival parameters. All parameters were compared between DnUTUC and SUTUC patients, including survival analyses. Results A total of 20,448 patients with UTUC were identified. Patients coded as MXNX or M1 were eliminated in order to determine stratum specific differences (N=9707).Table 1 demonstrates baseline demographic, pathologic and follow-up data. Approximately 72% of patients had DnUTUC, and almost 28% had a prior history of BC. Patients with DnUTUC were on average: younger, more likely to be female and more racially diverse. DnUTUC tumors tended to be larger, disproportionately high grade and stage. Interestingly, renal pelvic tumors were more prevalent as well. _x000D_ In terms of survival (Table 2), covariates associated with diminished CSS include: increasing age, tumor size, stage and grade and whether the tumor was de novo. Furthermore, variables associated with impaired OS include: (increasing age, tumor size, stage and grade). _x000D_ _x000D_ Conclusions This large cohort represents a unique opportunity to asses for differences in what is otherwise a rare condition and to our knowledge is the first to suggest that DnUTUC may represent a distinct clinical entity from BC. Although surveillance bias may explain the baseline differences in tumor characteristics, multivariate adjustment still demonstrates a distinct outcome for these patients. Further investigations including biomarker profiling between DnUTUC and SUTUC may further shed light into biological differences between these heretofore similar microscopic entities. Funding None
Authors
Hanan Goldberg
Thenappan Chandrasekar Zachary Klaassen Robert Hamilton Girish Kulkarni Neil Fleshner |
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MP10-06 |
Isolated red patches seen during endoscopic surveillance of bladder cancer – how often should we biopsy? |
Bladder Cancer: Epidemiology & Evaluation II | 17BOS |
Abstract: MP10-06 Sources of Funding: None. Introduction Red patches in the bladder are often seen during endoscopic surveillance of bladder cancer at cystoscopy, particularly in patients who have had intravesical BCG treatment. However, it is difficult to distinguish BCG artefact from malignancy, namely carcinoma in-situ (CIS) in the absence of narrow band imaging or photodynamic diagnostics. Therefore, can we safely assume that histologically benign persistent red patches biopsied previously within a certain timeframe will remain benign entities? Our objectives are to establish whether the regular biopsy of red patches seen during endoscopic surveillance for bladder cancer is worthwhile and determine a suitable time frame for repeat biopsy of prior histologically benign persistent red patches in patients on endoscopic surveillance for bladder cancer. Methods 4,805 flexible cystoscopy (FC) reports over a 12-month period (January - December 2015) were retrospectively reviewed at a UK tertiary teaching hospital and those undergoing cystoscopic surveillance for bladder cancer and found to have solitary red patches at flexible cystoscopy were included in the study. A proportion of these cases had biopsies taken which underwent histopathological analysis. Results 241 flexible cystoscopies performed on 183 patients on endoscopic surveillance for bladder cancer had red patches and of these, 120 (49.8%) had a history of intravesical BCG therapy. Eighty-five patients (35.3%) underwent biopsy of the red patch. Malignancy was found in 20 biopsies (23.5%), of which, 11 out of 20 (55%) were CIS. Sixteen of these recurrences had been biopsied previously of which 11 (68.8%) were benign at last biopsy, 6 of which in the last 12 months. The remaining four recurrences had no previous biopsy. Eleven out of sixteen (68.8%) of recurrences were found in patients who had been biopsied within the last 12 months. No cases of malignancy were identified in patients with low-risk bladder cancer. Conclusions We recommend the biopsy of all red patches found during endoscopic surveillance of patients with intermediate/high risk bladder cancer due to the significant incidence of malignant recurrence identified, particularly if no biopsy has been performed within the previous 12 months due to the high yield of malignant recurrence identified. This is independent of previous biopsy histology. Funding None.
Authors
Nkwam Nkwam
Shaun Trecarten Stefan Momcilovic Alvaro Bazo Gurminder Mann Benedict Sherwood Richard Parkinson |
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MP10-07 |
Increased Risk of Bladder Cancer in Chronic Kidney Disease Patients with Renal Transplantation |
Bladder Cancer: Epidemiology & Evaluation II | 17BOS |
Abstract: MP10-07 Sources of Funding: The study was supported in part by grants from the Shuang Ho Hospital, Taipei Medical University (102TMU-SHH-10) and Tung’s Taichung MetroHarbor Hospital (TTM-TMU-104-01). Introduction Chronic kidney disease (CKD) patients without effective treatment and follow-up usually progressed to end-stage renal disease (ESRD). Various therapeutic modalities including hemodialysis, peritoneal dialysis and renal transplantation are usually used to treat CKD patients. However, whether various therapeutic modalities can modify the risk of chronic diseases such as malignancies in CKD patients remains unclear. Therefore, the present study aims to investigate the association between therapeutic modalities of CKD patients and chronic diseases in Taiwan. Methods The National Health Insurance program was implemented since March 1995 by the National Health Insurance Administration, Ministry of Health and Welfare, with a coverage over 99% of 23 million people in Taiwan. The National Health Insurance Research Database (NHIRD) was released for research purposes. A total of 868 CKD patients who received renal transplantation (RT) and 54,243 non-CKD controls matched for age, gender and index date were recruited from the NHIRD. The CKD patients with RT was also confirmed by the registry of catastrophic illness. The cancer incidence was identified through cross-referencing with the Cancer Registry Database. Risks were estimated as hazard ratios (HRs) and their 95% confidence intervals (CIs) by using a Cox proportional hazards model. Results For CKD patients with RT, a significant higher incidence rate ratio (IRR) of all cancer sites (IRR = 3.79, 95% CI = 3.12-4.62) was found. After the adjustment for age, sex and co-morbidities, we also observed a significantly increased cancer risk of 3.87 (HR = 3.79, 95% CI = 3.16-4.73). Especially, we found that CKD patients with RT have a significant increased IRR of bladder cancer (IRR = 14.42, 95% CI = 8.09-25.67). A greatly increased bladder cancer risk (HR = 17.67, 95% CI = 9.64-32.38) was found for CKD patients with RT after the adjustment for age, sex and co-morbidities. Conclusions CKD patients have a higher risk of subsequent cancers, but the effect of therapeutic modalities such as RT on cancer risk is still unclear. Our finding is that CKD patients with RT have a significant increased risk of bladder cancer. Therefore, we should pay more attention to carry out effective treatments and implement an intensive follow-up to prevent CKD patients to progress to cancer. Funding The study was supported in part by grants from the Shuang Ho Hospital, Taipei Medical University (102TMU-SHH-10) and Tung’s Taichung MetroHarbor Hospital (TTM-TMU-104-01).
Authors
Min-Che Tung
Kuan-Chun Hsueh Kuan-Hua Huang Chiao-Ling Chen YUAN-HUNG WANG Chia-Chang Wu |
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MP10-08 |
A panel of micro-RNA signature as a tool for predicting survival of patients with urothelial carcinoma of the bladder |
Bladder Cancer: Epidemiology & Evaluation II | 17BOS |
Abstract: MP10-08 Sources of Funding: none Introduction Micro-RNA (miRNA) expression is altered in urologic malignancies, including urothelial carcinoma of the bladder (UCB). Individual miRs have been shown to modulate multiple signaling pathways that contribute to BC. To identify a panel of miRNA signature that can predict aggressive phenotype from normal non-aggressive counterpart using miRNA expression levels, and to assess the prognostic value of this specific miRNA markers in patients with UBC. Methods To determine candidate miRNAs as prognostic biomarkers for dividing aggressive type of UBC, miRNA expression was profiled in patients&[prime] samples with an aggressive phenotype or non-aggressive phenotype using 3D-Gene miRNA labeling kit (Toray, JAPAN). To create a prognostic index model, we used the panel of 9-miRNAs signature based on Cancer Genome Atlas (TCGA) data portal [TCGA Data Portal [https://tcga data.nci.nih.gov/tcga/tcgaHome2.jsp]]. MiRNA expression data and corresponding clinical data, including outcome and staging information of 84 UBC patients were obtained. The Kaplan-Meier and log-rank test were performed to quantify the survival functions in two groups. Results Deregulation of nine miRNAs (hsa-miR-99a-5p, hsa-miR-100-5p, hsa-miR-125b-5p, hsa-miR-145-5p, hsa-miR-4324, hsa-miR-34b-5p, hsa-miR-29c-3p, hsa-miR-135a-3p, hsa-miR-33b-3p) was determined in a UBC patients with aggressive phenotype compared with non-aggressive subject. To validate the prognostic power of the nine-signature miRNAs using the TCGA dataset of bladder cancer, the survival status and tumor miRNA expression of all 84 TCGA BCa patients, ranked according to the prognostic score values. Of nine miRNAs, six were associated with high risk (hsa-miR-99a-5p, hsa-miR-100-5p, hsa-miR-125b-5p, hsa-miR-4324, hsa-miR-34b-5p, and hsa-miR-135a-3p) and three were shown to be protective (hsa-miR-145-5p, hsa-miR-29c-3p, and hsa-miR-33b-3p). Patients with the high-risk miRNA signature exhibited poorer OS than patients expressing the low-risk miRNA profile (HR = 7.05, p < 0.001). Conclusions The miRNA array identified nine dysregulated miRNAs from clinical samples. This panel of nine-miRNA signature provides predictive and prognostic value of patients with UBC. Funding none
Authors
Teruo Inamoto
Kiyoshi Takahara Naokazu Ibuki Tomoaki Takai Taizo Uchimoto Kenkichi Saito Naoki Tanda Yuki Yoshikawa Koichiro Minami Hajime Hirano Hayahito Nomi Haruhito Azuma |
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MP10-09 |
Suppressed recurrent bladder cancer after androgen suppression with androgen-deprivation therapy or 5?-reductase inhibitor |
Bladder Cancer: Epidemiology & Evaluation II | 17BOS |
Abstract: MP10-09 Sources of Funding: This work was supported by the Medical Research Promotion Grant from Takeda Science Foundation, the Research Promotion Grant from Daiwa Securities Health Foundation, and the Research Promotion Grant from Smoking Research Foundation. Introduction It has been suggested that androgen-suppression therapy (AST) may inhibit the occurrence of primary bladder cancer as well as intravesical recurrence of bladder cancer. This study aimed to reveal whether intravesical recurrence is affected by an inhibition of androgen signaling among men with non-muscle invasive bladder cancer. Methods This study examined the intravesical recurrent rate among men treated with or without AST by androgen-deprivation therapy for prostate cancer or 5?-reductase inhibitor dutasteride for benign prostatic hyperplasia. Results This study included 228 men with AST (n = 32) or without AST (n = 196). During the median follow-up period of 3.6 or 3.0 years, intravesical recurrence occurred in four (12.5%) or 59 (30.1%) of men with or without AST, respectively. On multivariate analysis, multiple tumor (hazard ration, HR = 1.82, p = 0.027), large tumor (HR = 2.13, p = 0.043) and ever smoking (HR = 2.45, p = 0.020) as well as the presence of AST (HR = 0.36, p = 0.024) were independent risk factors for intravesical recurrence (Fig. A). Notably, tumor progression to muscle-invasive bladder cancer occurred in six (3.1%) men without AST, while no case progressed to muscle-invasive bladder cancer in men with AST. Conclusions Our study suggested the possibility of AST for prophylactic use of intravesical recurrence of bladder cancer. Further explorations on the prophylactic effect of AST on bladder cancer pathogenesis are warranted. Funding This work was supported by the Medical Research Promotion Grant from Takeda Science Foundation, the Research Promotion Grant from Daiwa Securities Health Foundation, and the Research Promotion Grant from Smoking Research Foundation.
Authors
Masaki Shiota
Keijiro Kiyoshima Akira Yokomizo Ario Takeuchi Eiji Kashiwagi Ryosuke Takahashi Junichi Inokuchi Katsunori Tatsugami Masatoshi Eto |
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MP10-10 |
Can urologists accurately stage and grade urothelial carcinoma by assessing endoscopic photographs of tumors? |
Bladder Cancer: Epidemiology & Evaluation II | 17BOS |
Abstract: MP10-10 Sources of Funding: None Introduction Assessment of urothelial carcinoma (UC) during cystoscopy or TURBT has a significant impact on the urologist's decision making: treatment with simple outpatient fulguration, the required depth of resection and the need of immediate post-surgical intravesical therapy all depend heavily on the urologist's ability to accurately assess pre-biopsy tumor stage and grade._x000D_ _x000D_ Methods Photographs of 50 UC were taken at the beginning of TURBT and were presented to 7 senior urologists separately, all blind to the pathological report. Each urologist was asked to rate the tumor as low grade and noninvasive (Ta low grade), high grade and noninvasive (Ta high grade) or invasive (T1 or more). Results were compared with the final pathological findings. Results The single urologist correctly predicted the tumor stage and grade in 63.5% of cases (222 of 350, average of 32 out of 50 accurate assessments). Of the 128 incorrect assessments 54 underestimated the UC and 74 overestimated it. After achieving consensus in each case it turned out that the final majority assessment was correct in 40 of 50 cases (80%). Sensitivity and specificity of the final results for the diagnosis of T1 or higher were 80% and 88.6% respectively. Sensitivity and specificity for TaLG were 83.3% and 80% respectively. Inter-rater reliability was calculated and showed fair agreement (kappa=0.27). Conclusions To our knowledge this is the first documented evaluation of urologists' ability to assess UC stage and grade using endoscopic photographs. The single urologist can usually identify stage and grade of UC but accuracy increases when multiple senior urologists examine the photos and achieve consensus. When photos of UC exist, a team of senior urologists can make an excellent decision about the type and extent of surgical treatment and plan ahead post-surgical management of the patient. Funding None
Authors
Snir Dekalo
Alexander Greenstein Gal Keren Paz Avi Beri Juza Chen Jacob Ben Chaim Mario Sofer Nicola Mabjeesh Haim Matzkin |
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MP10-11 |
Association of Perioperative Venous Thromboembolism With Long-Term Oncologic Outcomes Following Radical Cystectomy |
Bladder Cancer: Epidemiology & Evaluation II | 17BOS |
Abstract: MP10-11 Sources of Funding: None. Introduction Venous thromboembolism (VTE) has been reported to occur in 2-5% of patients undergoing radical cystectomy (RC). While VTE is an important cause of perioperative morbidity, the association of these events with long-term cancer prognosis has not been established. Herein, we evaluated the association of perioperative VTE with patients' risk of subsequent disease recurrence and mortality. Methods We reviewed 2889 patients undergoing RC between 1980-2009 at the Mayo Clinic to identify patients diagnosed with a VTE within 90 days of RC. These cases were then matched in a 1:2 fashion to control patients undergoing RC who did not develop VTE. Matching was performed on the basis of age, BMI, receipt of neoadjuvant chemotherapy, and pathologic T and N stages. Recurrence-free (RFS), cancer-specific (CSS), and overall survival (OS) were estimated utilizing the Kaplan-Meier method and compared with the log-rank test. Results A total of 132 patients with a VTE within 90 days of RC were identified, accounting for 4.6% of all patients analyzed. These cases were matched to 257 controls per criteria noted above, and were overall well-matched (Table). Of the 389 patients in this study, median follow-up after RC was 9.2 years, during which time 152 (39%) patients experienced recurrence and 306 (78%) died, including 157 (40%) who died of bladder cancer. We found no significant difference in 5-year RFS (59% versus 61%; p=0.75); CSS (57% versus 64%; p=0.13); or OS (45% versus 50%; p=0.15) between patients with versus without perioperative VTE, respectively. Conclusions We found that VTE within 90 days of RC did not significantly impact long-term cancer outcomes. While these events represent an important cause of perioperative morbidity, no interaction with oncologic control was noted, and patients may be counseled accordingly. Funding None.
Authors
Harras Zaid
Matthew Tollefson Igor Frank William Parker R. Houston Thompson Robert Tarrell Prabin Thapa John Cheville Stephen Boorjian |
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MP10-12 |
Epidemiological Trends and Socioeconomic Disparities in Bladder Cancer Survival: Analysis of California Cancer Registry |
Bladder Cancer: Epidemiology & Evaluation II | 17BOS |
Abstract: MP10-12 Sources of Funding: None Introduction Herein, we examined the California Cancer Registry (CCR) to determine bladder cancer survival disparities based on race, socioeconomic status (SES), insurance type, and tumor histopathology in California patients. Methods The CCR was queried for bladder cancer cases in California from 1988 - 2012. Survival analyses were performed to determine the prognostic significance of racial and socioeconomic factors. Disease specific survival (DSS) of patients with squamous cell carcinoma (SCC) was compared to urothelial carcinoma (UCB). Results 72,452 cases were included (75% men, 25% women). Median age was 72 (range 18 - 109). 81% were white, 3.8% black, 8.8% Hispanic, 5.2% Asian, and 1.2% others. SES was stratified by quintile. In black patients, tumors presented more frequently with non-urothelial histology, advanced stage, and high-grade and in females. Medicaid patients tended to be younger and have more advanced stage and high-grade tumors compared to those with Medicare or managed care (p < 0.0001). Kaplan-Meier analyses demonstrated significantly poorer 5-year DSS in black, low SES, Medicaid patients and in SCC compared to UCB (p < 0.0001). Multivariate analysis revealed that black race (DSS HR 1.295, 95% CI: 1.212 - 1.384), lowest SES (DSS HR 1.325, 95% CI: 1.259 - 1.395), Medicaid insurance (DSS HR 1.349, 95% CI: 1.246 - 1.460), and SCC histology (DSS HR 2.617 95% CI: 2.434 - 2.814) were all independent prognostic factors (all p < 0.0001) after controlling for stage, grade, age, and gender. Conclusions Analysis of California Cancer Registry demonstrated that black ethnicity, low SES, Medicaid insurance and squamous cell histology portend poorer disease-specific survival for bladder cancer patients in California, after adjusting for classic clinicopathological features. Funding None
Authors
Jeremy W. Martin
Nobel Nguyen Jenny Chang Rahul Dutta Simone L. Vernez Argyrios Ziogas Hoda Anton-Culver Ramy F. Youssef |
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MP10-13 |
IMPACT OF HISTOLOGIC SUBTYPE ON BLADDER CANCER OUTCOME |
Bladder Cancer: Epidemiology & Evaluation II | 17BOS |
Abstract: MP10-13 Sources of Funding: None Introduction Variant histology is increasingly recognized but its impact on outcomes is less well known compared to urothelial carcinoma (UC). We aim to evaluate the impact of variant histology on bladder cancer outcomes using the National Cancer Database (NCDB), a U.S. population-based cohort capturing approximately 70% of newly diagnosed cancer cases. Methods We identified patients with bladder cancer from 2004 to 2013 treated with radical cystectomy. We compared clinical and pathologic characteristics between those with UC and those with variant histology. Chi-square test was utilized for categorical variables and Independent Samples t-test for continuous variables. Multivariable Cox regression was used with hazard ratios (HR) and 95% confidence intervals (CI) to identify independent predictors of overall survival. Results A total of 40,918 patients were identified with male (75%) and Caucasian (90.9%) predominance. The mean age was 67 years. Median follow-up was 36.9 months (IQR 16.1-67.5). Squamous cell carcinoma (4.4%), small cell carcinoma (1.6%) and micropapillary (0.9%) were the most common variant histologic subtypes. Variant histology was found more commonly in women (35.6% vs 23.4%, p<0.05), black ethnicity(8.8% vs 5.6%, p<0.05), those with stage pT3 or T4 (67% vs 50.2%, p<0.05) and node positive disease (30.8% vs 26.9%, p<0.05). In adjusted models, squamous cell carcinoma (HR 1.3, 95% CI 1.2-1.4), small cell carcinoma (HR 1.6, 95% CI 1.5-1.8) and black ethnicity (HR 1.2, 95% CI 1.1-1.2) were independent predictors of increased mortality risk while micropapillary variant was associated with decreased risk (HR 0.8, 95% CI 0.7-1.0). After controlling for age, gender, surgical margin status, pathologic T stage, pathologic N stage and history of chemotherapy, all associations remained statistically significant (p<0.05). Conclusions Non-urothelial histology was associated with worse overall survival in patients with bladder cancer treated with radical cystectomy; however, contrary to some previous reports, micropapillary variant was associated with a lower risk of death. In addition, black ethnicity was associated with worse survival. Further investigation is needed to explore the impact of variant histology as well as other socioeconomic factors on survival after cystectomy. Funding None
Authors
Renu Eapen
Samuel Washington III Thomas Sanford Michael Leapman Maxwell Meng Sima Porten |
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MP10-14 |
Stage and survival for patients with urothelial carcinoma of the bladder in the United States (2004-2013): the effect of sociodemographics |
Bladder Cancer: Epidemiology & Evaluation II | 17BOS |
Abstract: MP10-14 Sources of Funding: none Introduction Bladder cancer is the most expensive cancer to manage from diagnosis to death. We used a nationwide cohort to evaluate sociodemographic disparities in the presentation of late stage bladder cancer and patient overall survival. Methods We analyzed all patients diagnosed with urothelial carcinoma of the bladder in the National Cancer Data Base from 2004 to 2013. A four level measure of socioeconomic status (SES) was developed by combining data on patient Zip Code median household income and high school education rates. Using multivariable logistic regression analysis, we assessed the association between SES, insurance (Private or Medicare vs no insurance or Medicaid), sex, and race (White, Black, Hispanic) with the diagnosis of late stage bladder cancer (stages III or IV). Cox proportional, Kaplan Meier, and log rank analyses were utilized to assess the association between covariates and overall survival. Results Of our final cohort of 328,569 patients, 25,046 (7.6%) were diagnosed with late stage bladder cancer. From highest to lowest SES, odds of late stage increased continuously (adjusted odds ratio [OR]: highest vs second 1.15, vs third 1.34, vs lowest 1.45). White males had the lowest odds of late stage diagnoses while Black females had the highest odds of late stage diagnoses compared to White males (adjusted OR 2.06, 95% CI 2.06, P<0.001). Females had higher rates of late state diagnoses compared to their male racial counterparts. Insurance type did not affect late stage diagnoses (adjusted p=0.05). Median overall survival for patients with late stage bladder cancer was 12 months for patients in the highest SES and 10 months for patients in the lowest SES (log rank p<0.001 and adjusted HR 1.14, 95% CI 1.08-1.21, p<0.001). Compared to patients in the highest SES, patients in the lowest SES received chemotherapy about as often (20%), were more likely to be treated at a community hospital (14% vs 9%, p<0.001), and more likely to delay radical cystectomy greater than 8 weeks following diagnosis (16% vs 12%, p<0.001). Conclusions Lower SES was associated with increased odds of late stage bladder cancer diagnoses and worse survival among patients with late stage disease. Insurance status did not alter stage at diagnosis when adjusting for SES. This implies expanding insurance coverage for patients will not completely mitigate disparities in bladder cancer outcomes. Black females are most likely to be diagnosed with late stage bladder cancer. Funding none
Authors
Adam Weiner
Joshua Meeks |
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MP10-15 |
Patterns of Recurrence in Different Histological Subtypes of Bladder Cancer Following Radical Cystectomy |
Bladder Cancer: Epidemiology & Evaluation II | 17BOS |
Abstract: MP10-15 Sources of Funding: None Introduction While recurrent disease patterns following radical cystectomy (RC) for urothelial carcinoma (UC) of the urinary bladder have been described, little is known regarding other histologic subtypes of bladder cancer. Herein, we describe recurrence patterns of different histological subtypes {adenocarcinoma (AC), squamous cell carcinoma (SCC), and UC with glandular/squamous metaplasia (UCM)} following RC. Methods We retrospectively analyzed patients who underwent RC between 1997-2004 at a Mansoura, Egypt. Patient demographics, tumor pathologic features and recurrence sites were retrieved. The association between recurrence sites and different histopathological features was evaluated. Results Of 1,238 RC patients identified, 374 (30%) {181 (48%) UC, 105 (28%) SCC, 35 (9%) AC, and 53 (14%) UCM} had recurrent disease. 180 (48%) had local recurrence, 106 (28%) had distant, and 88 (24%) had both. SCC had the highest local (62%), UC the highest distant (32%), and UCM the highest combined local and distant recurrence rates (30%) (p=0.05). High tumor stage was significantly associated with recurrence, regardless of the site (p=0.006). There were no significant associations between recurrence sites and tumor grade, lymphovascular invasion, lymph node positivity, a history of schistosomiasis infection, gender, and age (p>0.05 for all). The most common site of local recurrence was the pelvis (87%) across all histologic subtypes; for distant recurrence, the most common site (50%) was bone (Table 1). AC recurred the most in bone (62%) and less in the lung (5%), while lung metastasis accounted for 16% of SCC recurrence. Conclusions Patterns of disease recurrence vary significantly among different histopathological types and stages of bladder cancer. Tumor grade, lymphovascular invasion, lymph node positivity, schistosomiasis history, gender, and age are not associated with patterns of recurrence following RC for bladder cancer; further study is required to explain recurrence patterns. Funding None
Authors
Rahul Dutta
Jeremy Martin Simone L Vernez Ahmed Abdelhalim Ahmed Shokeir Hassan Abol-Enein Ahmed Mosbah Mohamed Ghoneim Ramy Youssef |
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MP10-16 |
Utilization of neoadjuvant chemotherapy in patients undergoing radical cystectomy for urothelial carcinoma in a contemporary tertiary care cohort |
Bladder Cancer: Epidemiology & Evaluation II | 17BOS |
Abstract: MP10-16 Sources of Funding: None Introduction Neoadjuvant chemotherapy (NC) with a cisplatin-containing regimen followed by radical cystectomy (RC) is the gold-standard treatment for muscle invasive bladder cancer (BC), supported by level 1 evidence. However, the proportion of patients receiving NC prior to RC remains low. Herein, we analyze our experience in a contemporary cohort of 145 consecutive patients treated with RC over a two-year period with an emphasis on receipt of NC. Methods We retrospectively reviewed 145 consecutive patients who underwent RC at our institution between 2012 and 2013. Demographic data, eligibility for and completion of NC, as well as reasons for forgoing NC were determined. Additionally, the time between BC diagnosis at TUR-BT and RC was calculated to determine the eligibility period for future experimental therapies. Results 32/145 (22.1%) patients underwent NC prior to RC. Of the 113 patients undergoing RC without NC, 46 (40.7%) had non-muscle invasive disease and were therefore not candidates for NC. The remaining 67 (59.3%) patients had indications for but did not complete NC. The most common reasons for forgoing NC were patient refusal due to toxicities and perceived modest benefit (31/113 patients, 27.4%), and variant histology resulting in primary RC (15/113, patients 13.3%). 9/113 patients (8%) were ineligible for NC due to poor renal function and 3/113 patients (2.7%) due to advanced age and/or poor functional status. The remainder of patients (9/113 patients, 8.0%) were excluded due to perioperative factors mandating primary RC or disease restricted to the prostatic urethra. We observed a median time from TURBT to RC of 34 days in patients not receiving NC. Conclusions Our data demonstrate that a large proportion of patients undergoing RC in the contemporary era are either ineligible for or refuse neoadjuvant chemotherapy. These data highlight the need for novel neoadjuvant therapies for invasive disease with improved toxicity/efficacy profiles. Additionally, we have defined a patient population with non-muscle invasive disease undergoing RC who would be eligible for future clinical trials utilizing the neoadjuvant setting to evaluate experimental bladder-sparing regimens. Funding None
Authors
Tanner Miest
R. Jeffery Karnes Stephen Boorjian Robert Tarrell R. Houston Thompson Matthew Tollefson Bradley Leibovich Igor Frank |
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MP10-17 |
Health related quality of life after radical cystectomy and urinary diversion. Open versus robotic assisted techniques. |
Bladder Cancer: Epidemiology & Evaluation II | 17BOS |
Abstract: MP10-17 Sources of Funding: no funding Introduction Robotic assisted radical cystectomy and intra-corporeal diversion (iRARC) has evolved with aim to improve surgical outcomes and health related quality of life (HRQOL) of patients undergoing cystectomy. Gains in perioperative outcomes including surgical complication rate and length of stay are not apparent for iRARC when measured in the randomized controlled setting although transfusion rates are reduced. The impact of iRARC on HRQOL is not fully evaluated. We compared the HRQOL outcome of open radical cystectomy (ORC) vs iRARC in patients from two high volume centers. Methods The study included 101 patients for whom RC and urinary diversion (52 ORC and 49 iRARC) was carried out between Jun 2011 and January 2015. All patients were disease free and completed at least 12 months of follow up. HRQOL was assessed using the European Organization for Research and Treatment of Cancer-QOL (EORTC-QLQ-C30) (English and validated Arabic version). Comparison of the HRQOL scales between both groups was performed using Mann-Whitney U test. Results The mean age for patients undergoing iRARC and ORC was 66.3 and 54.1 years, respectively. The median (range) postoperative follow up for iRARC and ORC groups was 27(17-60) and 43 (13-65) months, respectively. The iRARC group included 37 males and 12 females for whom intracorporeal orthotopic neobladder (ONB) (n=15) and ileal conduit (IC) (n=35) were performed. ORC included 31 males and 21 females for whom ONB and IC were performed in 41 and 11 patients, respectively. There was a significant difference in global health status (QL2) for iRARC in comparison to ORC (median (range)) [75(0-100) vs 33.3(0-100), p= 0.003] and a difference across functional scales for iRARC in comparison to ORC group (p<0.05). Also, iRARC showed statistically significant lower symptom scales in comparison to ORC groups (p<0.05). (Figure 1) Conclusions iRARC seems to provide patients with a better HRQOL compared to ORC. Large prospective studies including matched groups are still needed to assess HRQOL in these patients. However, our results suggest that HRQOL is an important outcome measure when assessing the potential benefits of iRARC and ORC._x000D_ Funding no funding
Authors
Mohamed H Zahran
Mohammed Abozaid Diaa-eddin Taha Benjamin Lamb Ashwin Sridhar Wei Shen Tan Khaled Almekaty Ahmed S El Hefnawy Bedeir Ali-El-Dein. John Kelly |
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MP10-18 |
Creation of a quality-improvement database for transurethral resection of bladder tumors |
Bladder Cancer: Epidemiology & Evaluation II | 17BOS |
Abstract: MP10-18 Sources of Funding: Use of the Northwestern Medicine Enterprise Data Warehouse was in part supported by Northwestern University Clinical and Translational Sciences Institute (NUCATS) grant UL1RR025741. Introduction Presence of muscle in transurethral resection of bladder tumor (TURBT) specimens is an important indication of quality of endoscopic resection. The presence or absence of muscle should be noted by the pathologist, and a sample is usually only considered adequate if there is muscle present. The objective of this study is to create natural language processing to evaluate the quality of TURBT specimens amongst many surgeons at a large institution. Methods The Enterprise Data Warehouse at Northwestern University was used to perform a retrospective analysis of patients undergoing TURBT over 10 years. Natural language processing was used to extract stage, grade, and muscle presence information from TURBT pathology reports. Initial construction of programming language was performed using a manually-created training set of 867 TURBTs. Outcomes included (1) rates of pathology reports mentioning the presence or absence of muscle, and (2) for pathology reports that mentioned muscle, rates of muscle presence in the surgical specimen. Since tumors that were cT2 involved muscle, these were excluded from the analysis. Logistic regression analysis was performed to determine associations with muscle being mentioned and present. Results 3042 TURBTs from 1324 patients performed by 20 surgeons were included in the database. Validation of 150 randomly-selected data points generated with our algorithm revealed accuracy of 98.7%. Muscle was mentioned in 72% of all 2918 TURBTs stage Conclusions Automated natural-language processing algorithm was used to create a TURBT database for quality improvement. Patients with T1 disease are more likely to have muscle mentioned and present in the report, and variations in muscle sampling exist amongst surgeons. This algorithm could be portable among medical systems and allow for large-scale quality initiatives between institutions. Funding Use of the Northwestern Medicine Enterprise Data Warehouse was in part supported by Northwestern University Clinical and Translational Sciences Institute (NUCATS) grant UL1RR025741. |
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MP10-19 |
Systemic therapy and overall survival trends in patients with non-urothelial histologic variants of muscle invasive bladder cancer undergoing radical cystectomy |
Bladder Cancer: Epidemiology & Evaluation II | 17BOS |
Abstract: MP10-19 Sources of Funding: none Introduction Histological variants of Urothelial carcinoma (UC) of the bladder have a poorer prognosis than histologically pure TCC, and the role of neoadjuvant chemotherapy (NAC) is unclear. Our objective was to evaluate NAC practice patterns and survival outcomes in patients with histologic variants undergoing radical cystectomy (RC) using a large national tumor registry. Methods Patients with cT2-4N0-3Mx muscle invasive bladder cancer (MIBC) who underwent RC from 2003-2014 were selected from the National Cancer Database (NCDB). Patients were categorized by histology code as pure UC or histologic variants. Adjusting for patient and clinical characteristics, generalized estimating equations were used to test the association between histology and receipt of NAC. The association between receipt of NAC and overall survival (OS) was evaluated using Kaplan Meier curves and Cox regression models. Results In 23,723 patients meeting inclusion criteria, receipt of NAC in histologic variants was less (12-15%) than in pure UC (28%), with the exception of micropapillary disease (29%) [Table 1]. Median OS was lower in variant histologies than for pure UC (11.1 - 29.2 vs. 39.0 months). Receipt of NAC was associated with improved survival compared to RC or RC+adjuvant chemotherapy in patients with pure UC (HR 0.88, p < 0.0001). There was no evidence of a survival benefit for NAC in the variant histologies, or that treatment effects differed by histology (P-val for interaction=0.87). Conclusions In the NCDB, a substantial proportion of patients (15%) with histologic variants of MIBC undergoing RC receive NAC in the absence of a proven survival benefit. Clinical trials inclusive of patients with variant histologies are necessary to elucidate the role of NAC prior to RC. Funding none
Authors
Shreyas Joshi
Elizabeth Handorf Andres Correa Benjamin ristau Michael Haifler Robert Uzzo Richard Greenberg David Chen Rosalia Viterbo Alexander Kutikov Daniel Geynisman Marc Smaldone |
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MP10-20 |
Prospective evaluation of a clinical tool for segregation of hematuria patients at risk for high-grade urothelial carcinoma |
Bladder Cancer: Epidemiology & Evaluation II | 17BOS |
Abstract: MP10-20 Sources of Funding: Pacific Edge Ltd. Introduction To-date there are no urine-based tests that provide clinical resolution of the severity or grade of urothelial carcinoma (UC) in patients presenting with primary hematuria. Such information permits timely diagnosis and specific management of hematuria patients identified with high grade and/or advanced UC disease. The objective of this study was, therefore, to develop and investigate the performance of Cxbladder Resolve, a new urine-based test offering identification and accurate segregation of patients with high-grade (HG) and/or late-stage disease at the time of initial urological investigation. _x000D_ Methods Participants in the study (N=863) were recruited from patients presenting with micro-(n=66) or macrohematuria (n=797) across centers in the U.S., New Zealand and Australia. An index incorporating 2 clinical variables and 5 gene expression biomarkers measured in urine was developed to segregate patients into 3 groups: 1. Low risk of UC; 2. Elevated risk of low grade (LG) UC; and 3. High risk of high grade (HG) UC. Results Of the 863 recruited patients, 89 (10.3%) primary cases of UC were observed including 40 LG and 49 HG. Cxbladder Resolve segregated the 863 participants into: low risk of UC (n=479; 55%), elevated risk of LG UC (n=288; 33%) and high risk of HG UC disease (n=96; 11%). (Table) Of the 40 patients with LG bladder tumors, 27 were correctly categorized as Elevated risk of low grade UC, with the remainder; 9 as High risk of HG UC, and 4 as Low risk of UC. Of the 49 patients with HG UC, 47 (96%) were correctly identified as having High risk of HG UC and the remaining 2 patients were classified as elevated risk of LG UC. No patients with HG UC were classified as low risk of UC. Overall a negative predictive value [NPV] of ?99% was observed._x000D_ Conclusions Cxbladder Resolve accurately identifies over 95% of HG UC patients with a reciprocal high NPV (99%) for low risk patients. The index has a low probability of incorrectly classifying pathologic HG UC patients as low risk. Clinical utility is demonstrated for stratifying hematuria patients into risk groups allowing for prioritization of high risk patients with aggressive disease requiring early investigative procedures. _x000D_ Funding Pacific Edge Ltd.
Authors
Jay D. Raman
Laimonis Kavaliers Paul O'Sullivan David Darling Parry Guilford Jimmie Suttie |
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MP11-01 |
Role of Chronic Inflammation in Prostate Cancer: A Study on Needle Biopsy Specimens |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Prostate & Genitalia II | 17BOS |
Abstract: MP11-01 Sources of Funding: Department of Defense grant W81XWH-15-1-0558, USPHS R21CA193080, R03CA186179 and VA Merit Review 1I01BX002494 to SG. Introduction The relationship between inflammation and prostate cancer has not been established, although chronic inflammation has frequently been identified in prostate biopsies, radical prostatectomy specimens and tissue resected for treatment of benign prostatic hyperplasia. In the peripheral zone of the prostate, sometimes adjacent to foci of high-grade PIN and cancer, certain morphologic changes are often identified, which may represent active and terminal phases of chronic inflammation. These changes are designated, respectively, proliferative inflammatory atrophy (PIA) and post atrophic hyperplasia (PAH), and their morphology is well documented in pathologic literature. In our previous studies, we have identified chronic inflammation as a putative contributor to neoplastic progression in prostate epithelial cells, and hypothesized that its adverse effects were related to an increase in Bcl2, a survival protein involved in cell survival and carcinogenesis. We hypothesize that changes in the stromal microenvironment, characterized by infiltration of immune cells, with generation of reactive oxygen and nitrogen species, can induce oxidative stress in the surrounding proliferating epithelium and cause permanent genomic alterations. Here we focused on several key proteins involved in the inflammatory process, COX2 and iNOS; cell survival, Bcl2 and GSTPπ; and evaluated expression of alpha-methylacyl coenzyme A racemase (AMACR) and basal cell-specific markers 34βE12 and/or p63 to evaluate possible neoplastic alterations in epithelial cells in an inflammatory environment. Methods We evaluated 16 prostate core needle biopsy specimens that exhibited the presence of chronic inflammation as well as PIA and PAH lesions. Immunohistochemical staining for P63/34βE12/AMACR cocktail, iNOS, COX2, GSTπ, and Bcl2 was performed in each set of biopsies. Results The integrity of the basal layer was maintained in the area of chronic inflammation with high to moderate expression of p63 in 72% of these cells. Approximately 68% of luminal cells expressed high to moderate levels of iNOS and COX-2, whereas 55% of these cells express modest levels of GSTπ and Bcl2. We found that basal cells near areas of chronic inflammation in the PIA lesions exhibit high AMACR expression and weak to no p63 expression. Loss of p63 and increased AMACR expression in the basal cells was associated with increased expression of the inflammatory markers COX2 and iNOS, as well as loss in pro-survival signal GSTP1 and Bcl2 in the adjacent luminal cells. These neoplastic alterations were observed in 6/16 (38%) of the needle biopsy specimens. Conclusions Our findings suggest that basal cells undergo alterations in a setting of chronic inflammation. This is important because basal cells are considered to be progenitor cells capable of differentiating into secretory luminal cells, but under the influence of chronic inflammation, they may instead transform into the neoplastic cells that characterize high grade prostatic intraepithelial neoplasia and prostatic adenocarcinoma. Funding Department of Defense grant W81XWH-15-1-0558, USPHS R21CA193080, R03CA186179 and VA Merit Review 1I01BX002494 to SG.
Authors
Shardul Soni
Michael Glover Qinghu Ren Gregory MacLennan Pingfu Fu Sanjay Gupta |
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MP11-02 |
Urethral Lichen Sclerosus Under the Microscope |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Prostate & Genitalia II | 17BOS |
Abstract: MP11-02 Sources of Funding: None Introduction Lichen sclerosus (LS) is an inflammatory dermatologic condition that involves squamous epithelium. Genitourinary LS (GLS), historically known as balanitis xerotica obliterans (BXO), is thought to involve the urethra, a stratified/pseudostratified columnar and urothelial lined organ. Given the poor understanding of the pathophysiology of LS and a lack of accepted definitive diagnostic criteria, we proposed to survey pathologists regarding their understanding of LS. We hypothesized that significant disagreement about GLS will exist. Methods All urologists participating in the Trauma and Urologic Reconstruction Network of Surgeons identified genitourinary (GUP) and dermatopathologists (DP) at their respective institutions who were then invited to participate in an online survey regarding their experience with diagnosing LS, LS pathophysiology and its relationship to urethral stricture disease. Statistical comparisons between responses provided by DPs and GUPs were performed using the Fischer’s exact test. Results There were 23 (12 DP, 11 GUP) pathologists that completed the survey. Overall, 90% still use BXO when describing GLS and 66% require a clinical history. The most agreed upon criteria for diagnosis were dermal collagen homogenization (85.7%), loss of the normal rete pattern (33.3%) and atrophic epidermis (28.5%) - thus no single criteria was deemed necessary for diagnosing GLS by all pathologists. Only 1 pathologist routinely graded GLS severity. The average number required findings for diagnosis was 2.1±1.09 (GUP 2.1±1.27 v DP 2.1±1.0; p = 0.96). No pathologists believed GLS had an infectious etiology (19% maybe, 42% unknown) and 19% believed GLS to be an autoimmune disorder (42% maybe, 38% unknown); 19% believed LS to be premalignant, but 52% believed it was associated with cancer; 80% believed that LS could involve the urethra (DP (92%) v GUP (67%); p = 0.272). Of those diagnosing urethral GLS, 80% of DUP believed that GLS must first involve the glans/prepuce before involving the urethra, while all GUP believed that urethral disease could exist in isolation (p=0.007)._x000D_ Conclusions There was significant disagreement in this specialized cohort of pathologists when diagnosing GLS. A logical first step appears to be improving agreement on how to best describe and classify the disease and characterize possible differences in histological changes between skin and GLS. Specialty-wide efforts to routinely collect and analyze urethral stricture specimens may aid in understanding pathophysiologies that continue to elude urologists and pathologists. _x000D_ _x000D_ _x000D_ Funding None
Authors
Brennan Tesdahl
Maria Voznesensky Nejd Alsikafi Benjamin Breyer Joshua Broghammer Jill Buckley Sean Elliott Christopher McClung Jeremy Myers Thomas Smith III Alex Vanni Bryan Voelzke Lee Zhao William Brant Bradley Erickson |
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MP11-03 |
HPV prevalence in males in the United States from penile swabs: results from NHANES |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Prostate & Genitalia II | 17BOS |
Abstract: MP11-03 Sources of Funding: none Introduction Human papilloma virus (HPV) is a common sexually transmitted infection (STI) in the US that can lead to both malignant transformation and genital warts. Recently, a vaccine has been developed against the 4 major strains of HPV. The American Committee for Immunization Practices has given a permissive recommendation for boys aged 11-26 years, but does not place it on the routine vaccination schedule. We aim to estimate the prevalence of HPV infection in males in the US population using a nationwide sample. Methods The NHANES database was queried for all men 18-59 years old during the years 2013-2014. During these years, the survey included penile swabs that were tested for HPV infection from 37 strains using PCR. Information was also obtained regarding other STIs, HPV vaccination, and circumcision status. HPV infection was further stratified into those known to cause genital warts, HPV 6 and 11 (LRHPV), and those known to be “high risk� and implicated in penile cancer, HPV 16 and 18 (HRHPV). Logistic regression was used to evaluate circumcision status with HRHPV, when excluding those that had received HPV vaccination. Results A total of 1,520 men had complete information on HPV infection and circumcision status. As seen in table 1, 45.2% of men had HPV infection from any strain. LRHPV was present in 2.9%, whereas HRHPV was present in 5.8% of men. Only 7.8% of all men, and 13.4% of men 18-29 years had received HPV vaccination. In addition, 77.8% of men had been circumcised. Circumcised men had an increased risk of HRHPV (OR 2.0, p=0.03) but no increased risk of LRHPV (OR 1.05, p=0.9). Conclusions Surprisingly, almost half of all men tested positive for HPV on penile swab in this nationwide sample. Only a small proportion of young males have received vaccination against HPV. More men were positive for HPV strains associated with penile cancer than HPV strains that cause genital warts. Interestingly, circumcised men had a two-fold increased risk of these high-risk HPV infections. Funding none
Authors
Michael Daugherty
Timothy Byler |
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MP11-04 |
Meningococcal urethritis. A pitfall in the conventional diagnostic process based on the nucleic acid amplification test in men with suspected gonococcal urethritis |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Prostate & Genitalia II | 17BOS |
Abstract: MP11-04 Sources of Funding: none Introduction Neisseria meningitidis is a Gram-negative diolococcus like Neisseria gonorrhoeae, and has been reportedly a pathogen of male urethritis. Unfortunately, in the current situation in which a nucleic acid amplification test (NAAT) is used exclusively for the diagnosis of N. gonorrhoeae, N. meningitidis is inevitably missed because the conventionally used diagnostic tests such as microscopic examination of urethral smear and NAAT are unable to distinguish these two microorganisms. The present study was conducted to reveal the prevalence of N. meningitidis as a pathogen of male urethritis using urine culture as a diagnostic test in relation to microscopic examination of urethral smear and NAAT for N. gonorrhoeae. Methods Between December 2013 and October 2016, a total of 480 male patients with suspected gonococcal urethritis based on symptoms and urethral discharge underwent microscopic examination of urethral smear stained with methylene blue. The presence of polymorphonuclear leucocytes containing dipolococci was judged to suggest gonococcal urethritis. In all patients, first-voided urine samples were tested for N. gonorrhoeae by NAAT and additionally also for culture of N. gonorrhoeae and N. meningitidis. Results As shown in the Table, among 480 patients 226 were positive for diplococci and 211 (93%) of them were also positive for N. gonorrhoeae by NAAT. Interestingly, in the remaining 15 patients with negative for N. gonorrhoeae by NAAT, 10 patients were positive for N. meningitidis as demonstrated by urine culture. Out of 254 patients with negative for diplococci, 251 (99%) were also negative for N. gonorrhoeae by NAAT. As a result, N. meningitidis was detected in 2.1% of patients with suspected gonoccocal urethritis, and 4.4% of patients with positive for diplococci by microscopic examination of urethral smear. Conclusions When diploccoci are positive on urethral smear but NAAT is negative for N. gonorrhoeae, N. meningitidis has to be considered as a possible pathogen of urethritis. It is to be stressed that N. meningitidis is not recognizable by conventionally used NAAT for N. gonorrhoeae, and meningococcal urethritis is a potential pitfall in the diagnosis and treatment of male urethritis. Funding none
Authors
Munekado Kojima
Yasufumi Yada Kazuhiko Yosihida Yosimasa Hayase |
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MP11-05 |
Therapeutic effect of indoleamine 2,3-dioxygenase inhibitor in epididymitis |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Prostate & Genitalia II | 17BOS |
Abstract: MP11-05 Sources of Funding: none Introduction Indoleamine 2, 3-dioxygenase (IDO) catalyzes the first and rate-limiting step of tryptophan catabolism and has been implicated in immune tolerance. IDO is known to be induced in various tissues during systematic bacterial infection and play a key role in immune response. In our previous research, we elucidated that epididymal IDO expression in the mouse is restricted to the caput region from segments 2 to 5 with peak of expression in segments 3 to 4. We hypothesize that IDO plays a central part of local immunological reaction in epididymis. We investigated all sorts of cytokines in epididymitis model of IDO knock out (IDO KO) mouse biochemically. Subsequently to the result of cytokines expression, we inhibited IDO in wild type (WT) mouse and clarified the function of IDO in epididymis. Methods Twelve weeks old C57BL/6J male mice (WT and IDO KO) were used in this study. Mice were injected with lipopolysaccharide (LPS) 4?g/g(weight) into epididymis on the side of the vas deferens. At 1,3,5 and 7 days after LPS injection, epididymides were removed. Histological changes were microscopically examined and evaluated. And then, cytokines were cyclopedically analyzed using cytokine assay (ELISA) for determining representative candidates. After that immunohistological changes were examined using immunostaing of representative cytokine candidates. In the following research, IDO inhibitor (1-Methyltryptophan: 1-MT 5mg/ml) was orally administrated to WT mice before LPS injection to their epididymides. At 1,3,5 and 7 days after the treatment, epididymides were removed. The role of IDO in epididymis was validated in terms of immunological reaction. Series of these experiments were duplicated at least. Results Prominent destruction of epididymal ductal structure and invasion of lymphocyte-predominant inflammatory cells were observed in epididymitis model of WT mice compared with that of IDO KO mice. Epididymal ductal structure in IDO KO mice was still maintained at day7 after LPS injection. Comprehensive cytokine assay (ELISA) showed that more than 2 folds of down-regulation of both inflammatory promoting cytokines (IL-1 alpha, IL-6) and chemokines (CCL3, CXCL1) were observed in epididymitis model of IDO KO mice compared with WT mice. On the other hand, more than 1.5 folds of up-regulation of inflammatory inhibiting cytokines (IL-4, IL-10) were observed in epididymitis model of IDO KO mice. The peak expression of IL-1 alpha, IL-6, CCL3 and CXCL1 were at day1 and that of IL-4 was at day3. The expression of IL-10 increased in time dependent manner. Same results were introduced from separate quantitative analysis and immunohistochemical staining. After treatment of IDO inhibition and LPS, IL-1 alpha, IL-6, CCL3 and CXCL1 were significantly down-regulated anytime in time series compared with WT mice using ELISA method (p<0.05). IL-4 and IL-10 were significantly up-regulated anytime in time series compared with WT mice (p<0.05). In the group of IDO inhibition, epididymal ductal structure was maintained at day7 after LPS injection and little invasion of inflammatory cells were observed anytime in time series. Conclusions IDO should be involved in epididymal immunological reaction via cytokines. To inhibit IDO would contribute to protection of epididymis tissue when inflammation occurs in epididymis. Therefore, IDO might be a novel target for the therapy of the epididymitis in addition to antibodiotics. Funding none
Authors
Shin Ohira
Ryoei Hara Shigenobu Tone Seitetsu Kin Shinjiro Shimizu Tomohiro Fujii Yoshiyuki Miyaji Atsushi Nagai |
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MP11-06 |
Expression of Inflammatory Mediators in Sensory Ganglia Innervating Lower Urinary Tract And Dysfunctional Voiding |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Prostate & Genitalia II | 17BOS |
Abstract: MP11-06 Sources of Funding: NIDDK, U54 DK112079 Introduction Dysfunctional voiding associated with chronic prostatic inflammation _x000D_ is considered to be caused by sensitization of primary sensory neurons innervating lower urinary tract. Published research implicates pro-inflammatory cytokines as major player in the neural sensitization and the progression of prostatitis. Therefore, we investigated the expression of cytokines and chemokines in dorsal root ganglia (DRG) from the lumbosacral region in rat model of non-bacterial prostatitis. Methods Intraprostatic injection of formalin (50μL) or saline (sham) was performed in three month- old male Sprague-Dawley rats to induce prostatitis(n=3). 12 hour night time urination pattern were noted a day before injection and 7 days later. Lumbosacral L6-S1 and cervical (C4) DRG were isolated from the sacrificed animals on the 7th day for multiplex analysis of 27 cytokines, chemokines and growth factors using a MILLIPLEX MAP Rat Cytokine/Chemokine Panel kit. Results are expressed as pg/mg of total protein Results The expression of IFN-γ, CXCL-10, VEGF and EGF was signficantly elevated in the L6-S1 DRG relative to the C4 DRG of either group(*p<0.05). Expression of CXC chemokines (CXCL-1, CXCL-2, CXCL-5), CC chemokines (CCL2, CCL3, CCL5), leptin, IL-2, IL-13 and IL-17A was only elevated in L6-S1 DRG relative to C4 DRG of sham group (#p<0.05). Frequent urination and reduced voided volume in the prostatitis group was also associated with substantial but insignficant increase in the production of CXCL-1 (p=0.06), CCL2 and leptin in the C4 DRG relative to that of the sham group. _x000D_ Conclusions Dysfunctional voiding secondary to prostatic inflammation was linked to the dramatic overproduction of inflammatory mediators in L6-S1 DRG capable of inducing phenotypic changes in micturition reflex pathways. Since cervical DRG is not directly innervated by the axons of afferent neurons from prostate and bladder, therefore, sustantial production of leptin, CXCL-1 and CCL2 in the cervical DRG may be humorally mediated in prostatitis to suggest a role for neurohumoral interaction in the evolution of prostatitis into a regional pain syndrome. Funding NIDDK, U54 DK112079
Authors
Pradeep Tyagi
Mahendra Kashyap Zhou Wang Naoki Yoshimura |
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MP11-07 |
Clinically isolated gram-positive prostate bacteria induce chronic pelvic pain. |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Prostate & Genitalia II | 17BOS |
Abstract: MP11-07 Sources of Funding: NIH R01DK094898, R01DK108127. Introduction Gram-positive bacterial strains comprise the most common isolates found in both healthy and CPPS patient samples. The role of these bacteria in development and maintenance of pain in CPPS is unknown Methods Gram-positive bacteria were isolated from the prostates, i. e. bacteria count was 1 log greater in the EPS or VB3 than that in the VB1 and VB2, of three CPPS patients (pain inducers, PI) and one from a healthy volunteer (non-pain inducer, NPI). The bacteria were inoculated intra-urethrally in two genetic mouse backgrounds and analyzed for their ability to induce tactile allodynia and to colonize the murine prostate. Results PI strains (Staphylococcus haemolyticus 2551, Enterococcus faecalis 427 and Staphylococcus epidermidis 7244) were capable of inducing and maintaining robust tactile allodynia responses (200% increase above baseline) for 28 days initiating at day 7 post-infection in NOD/ShiLtJ mice. Conversely the healthy subject derived strain (Staphylococcus epidermidis NPI) demonstrated no significant pain responses above baseline at any time-point examined (Days 7, 14, 21, 28). Intra-urethral inoculation of any of the four bacterial strains into C57BL/6 mice did not induce significant increases in pain responses above baseline. In vitro adherence and invasion assays revealed no significant difference between strains to invade WPMY or RWPE-1 cells. E. faecalis 427 demonstrated a reduced capacity for intracellular proliferation in WPMY but not RWPE-1 cells compared to the other strains. In vivo, colony counts were also performed on prostate tissues removed from both NOD/ShiLtJ and C57BL/6 mice at day 28 post-infection. All bacterial strains colonized equally well comparing within mouse background including NPI. Significant differences were observed however when comparing the bacterial loads of NOD/ShiLtJ and C57BL/6 mice. Conclusions Gram-positive isolates from the prostates of CPPS patients showed dramatically enhanced ability to induce tactile allodynia compared to taxonomically similar gram-positive strain isolated from a healthy control subject. Pain responses were shown to be dependent on the genetic background of the host and not on in vivo colonization differences between strains. All four strains demonstrated similar growth, invasion and proliferation responses in vitro, strongly implicating host:pathogen interactions in development of pain. Funding NIH R01DK094898, R01DK108127.
Authors
Stephen Murphy
Jonathan Anker Anthony Schaeffer Praveen Thumbikat |
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MP11-08 |
Reassesment of Non-traditional Uropathogens in Chronic Pelvic Pain Syndrome (CP/CPPS) |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Prostate & Genitalia II | 17BOS |
Abstract: MP11-08 Sources of Funding: NIH NIDDK R01DK094898, R01DK108127 Introduction Localization of traditional uropathogenic bacteria to the prostate has been reported in up to 8% of patients with CP/CPPS and in healthy controls. However, the frequency and significance of non-pathogenic bacteria have been highly variable. Methods We retrospectively reviewed prostate localization cultures done at our institution from 05/2010 to 11/2014 and the associated patient clinical information. Cultures were considered to be localized to the prostate if bacteria count was 1 log greater in the EPS or VB3 than that in the VB1 and VB2 (criteria 1), or 1 log greater than only that in the VB2 (criteria 2). Bacteria were analyzed for their ability to induce inflammation using THP1-Blue cells reporting NFkB expression. Results Using criteria 1, 14% (20 of 146) of patients with the diagnosis of CP/CPPS had localizing cultures all performed by (AJS). A total of 28 bacteria, all gram-positive, localized to their prostates. Using criteria 2, the localizing population included patients seen by other urologists and with 1 of 3 diagnoses: CP/CPPS (group 1, 37 patients), elevated PSA with no pelvic pain (group 2, 12 patients), and category II chronic bacterial prostatitis (CBP) or recurrent UTIs (group 3, 15 patients). Gram-positive bacteria comprised 100% of group 1 localizations, and 92% of group 2, while group 3 was 27% gram-negative. A high NFkB response was noted in 20%, 9%, and 42% of bacteria in groups 1, 2, and 3, respectively. While 100% of gram-negative organisms induced a high NFkB response, there was a subgroup of gram-positives (11% of E. faecalis, 13% of S. haemolyticus, 19% of S. epidermidis; 12 total) that also induced a high response. 100% and 83% of patients with bacteria in this subgroup reported pain and voiding complaints, respectively, compared to 66% and 69% of patients with low NFkB inducing gram-positive prostate bacteria. Conclusions Traditional gram-negative uropathogenic bacteria with high inflammatory response were prevalent among patients with CBP or UTIs. A subset of gram-positive bacteria from patients with CP/CPPS also showed a high inflammatory response and association with more pain and voiding complaints. A subset of traditional non-uropathogenic bacteria may contribute to inflammation and symptoms in patients with CP/CPPS. Funding NIH NIDDK R01DK094898, R01DK108127
Authors
Daniel Mazur
Jonathan Anker Stephen Murphy Anthony Schaeffer Praveen Thumbikat |
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MP11-09 |
Next-Generation Sequencing of Chronic Prostatitis: Preliminary Results of Comprehensive Species Level Description in 212 Men with Pelvic Pain |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Prostate & Genitalia II | 17BOS |
Abstract: MP11-09 Sources of Funding: None Introduction Clinical management of chronic prostatitis is difficult owing to inaccurate diagnostic tests, antimicrobial resistance, and a high rate of recurrence. Recent studies showed that routine cultures fail to identify up to 67% of pathogens, and less than 10% of patients with pelvic pain have a positive culture. Next-generation sequencing (NGS) provides a complete and accurate description of the composition of the urinary tract microbiome, and may be of value in dealing with the clinical challenge of pelvic pain and chronic prostatitis. Methods We undertook a community-based observational study of 212 men with pelvic pain and other symptoms of chronic prostatitis; most specimens were obtained after prostatic massage. Urines were analyzed using a multi-amplicon, multi-locus method on the Ion Torrent PGM instrument. NGS was used to describe the complete microbiome, including presumptive pathogens, fungi, and antimicrobial resistance genes. Results Bacteria can be detected at 20,000 genomic equivalents and across orders of magnitude in range. A significant number of bacteria were found in 75% of samples, with a mean of 2 bacteria per sample (range, 0-7). Gram-positive anaerobes were found in greatest abundance (60% of samples), including Enterococcus faecalis (30%) and Escherichia coli (25%), significantly greater than the 10% abundance of Enterococcus species previously reported with routine cultures from men with possible prostatitis. Co-infection by Enterococcus faecium and Enterococcus faecalis was common, possibly resulting in formation of a tenacious treatment-resistant biofilm. Antimicrobial resistance to beta-lactams was highest at 35% of samples. Conclusions This preliminary study showed that next-generation DNA sequencing of urine after prostatic massage identified numerous clinically-relevant bacteria that would likely have been missed using traditional urine culture methods, and showed that chronic prostatitis is often polymicrobial. The presence of significant numbers of bacteria in 75% of the patients suggests that more patients suffer from the bacterial form of chronic prostatitis than previously estimated. NGS testing may be useful in distinguishing chronic bacterial and abacterial prostatitis. Funding None
Authors
Eugene Park
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MP11-10 |
Clinical pharmacokinetics of beta-lactam antibiotics in prostate tissue, and dosing considerations for prostatitis based on site-specific pharmacodynamics |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Prostate & Genitalia II | 17BOS |
Abstract: MP11-10 Sources of Funding: None Introduction Piperacillin-tazobactam (8:1) and flomoxef have activities also against Enterobacteriaceae producing extended-spectrum beta-lactamases. These beta-lactam antibiotics are a therapeutic option for bacterial prostatitis and antibacterial prophylaxis in prostatic surgery. However, their clinical pharmacokinetics in prostate tissue and pharmacodynamics at the site of action had been unclear. This study thus examined, for the first time, the clinical pharmacokinetics of piperacillin-tazobactam and flomoxef in prostate tissue, and estimated their pharmacodynamic target attainment at this site. Methods Piperacillin-tazobactam (total dose of 2.25 g or 4.5 g) or flomoxef (0.5 g or 1 g) was intravenously administered to 101 patients with benign prostatic hypertrophy prior to TURP. Venous blood and prostate tissue samples were collected 0.5–5 h after starting a 0.5-h infusion. Drug concentrations were measured using high-performance liquid chromatography, analyzed using a three-compartment population pharmacokinetic model, and used to estimate the probability of attaining the bactericidal targets (time above the minimum inhibitory concentration [MIC] for bacteria, 50% for piperacillin and 70% for flomoxef). Results Both beta-lactams penetrated similarly into prostate tissue, independently of the dose, with mean prostate tissue/plasma ratios of 0.38–0.49 (maximum drug concentration) and 0.36–0.56 (area under drug concentration-time curve). Tazobactam showed similar pharmacokinetic profile with piperacillin. With this medium degree of penetration, the usual dosages of piperacillin-tazobactam 4.5 g three times daily and flomoxef 1 g twice daily (0.5-h infusions) achieved a favorable target-attainment probability of 91.3–94.0%, in prostate tissue, against clinical isolate populations of Escherichia coli and Klebsiella species (the two major causative bacteria in prostatitis). The prostatic pharmacodynamic-based breakpoint MIC (the highest MIC at which the target-attainment probability in prostate tissue was >90%) was 0.5 mg/L for piperacillin-tazobactam 2.25 g twice daily and 0.25 mg/L for flomoxef 1 g three times daily. Conclusions This study revealed the clinical pharmacokinetics of piperacillin-tazobactam and flomoxef in prostate tissue. The results on the site-specific pharmacodynamic target attainment should rationalize and optimize their dosages for prostatitis especially with Enterobacteriaceae producing extended-spectrum beta-lactamases. Funding None
Authors
Kogenta Nakamura
Kazuro Ikawa Ikuo Kobayashi Genya Nishikawa Keishi Kajikawa Yoshiharu Kato Masahito Watanabe Motoi Tobiume Kenji Mitsui Masahiro Narushima Kent Kanao Norifumi Morikawa Makoto Sumitomo |
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MP11-11 |
Increased Infective Complications from Transrectal Ultrasound Guided Prostate Biopsy Following Transition to Single Dose Oral Ciprofloxacin Prophylaxis |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Prostate & Genitalia II | 17BOS |
Abstract: MP11-11 Sources of Funding: none Introduction To examine the incidence of infective complications post Transrectal Ultrasound Guided Prostate Biopsy (TRUSPB), after transition to pre-operative administration of single dose oral fluoroquinolone. A protocol adopted from the American Urological Association (AUA) recommendations and in line with a Cochrane Database Systematic Review. Methods A retrospective study of patients undergoing TRUSPB at St Vincent’s Hospital Melbourne (2002-2016) was performed. In total 766 consecutive patients had TRUSPB; antibiotic prophylaxis between 2002-2014 consisted of 3 days of perioperative oral norfloxacin and intravenous 3rd generation cephalosporin or gentamicin (Group A, n = 687). From November 2014 patients routinely received only a single dose of oral 750mg ciprofloxacin pre-biopsy (Group B, n = 79). Patients were followed up for all postoperative complications requiring emergency department presentation and/or readmission within 30 days of biopsy. Results In Group A, 10 of the 687 patients (1.5%) presented with postprocedural fever (Temperature > 37.5C), requiring readmission and intravenous antibiotic treatment. In comparison to 4 of the 79 patients (5.1%) in Group B (p=0.02). Positive blood cultures were isolated in 0.9% (n=6, Group A) versus 3.8% (n=3, Group B), (p=0.02). Two patients in Group B cultured Escherichia Coli sensitive to ciprofloxacin despite receiving a single dose of pre-operative oral Ciprofloxacin. The 4 infectious readmissions in Group B had no additional pre-operative identifiable travel or medical risk factors. Conclusions Our study suggests antibiotic prophylaxis using single dose ciprofloxacin is associated with higher readmission with fever, UTI and bacteraemia. The episodes of ciprofloxacin sensitive Escherichia Coli bacteraemia in Group B suggest consideration of long course antibiotic prophylaxis should occur. Funding none
Authors
Sophie Riddell
Matthew Farag John Daffy Lih-Ming Wong |
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MP11-12 |
Antimicrobial Prophylaxis for Transrectal Ultrasound Guided Prostate Biopsy: A Prospective Cohort Trial |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Prostate & Genitalia II | 17BOS |
Abstract: MP11-12 Sources of Funding: State of Illinois Excellence in Academic Medicine (EAM) grant funded this project: STU00059558 EAM-237. Introduction We evaluated the effectiveness of targeted antimicrobial prophylaxis in men undergoing transrectal ultrasound guided prostate biopsy (TRUSP). Methods A prospective, non-randomized cohort study evaluated targeted prophylaxis to determine the rate of post-biopsy infectious complications. Rectal swab cultures plated on selective media identified ciprofloxacin-resistant and-susceptible gram-negative bacteria (CR-GNB and CS-GNB). Patients with CS-GNB received ciprofloxacin while those with CR-GNB received directed prophylaxis. Infectious complications were defined clinically and microbiologically within 30 days after TRUSP. Results Between November 1, 2012 and March 31, 2015, 510 men completed the study; 430 (84.3%) harbored CS-GNB, 80 (15.7%) CR-GNB and 76 (95%) CR-GNB were Escherichia coli. 484 (94.9%) completed the study per protocol, while 26 (5.1%) who received dual prophylaxis were evaluated in a separate intention-to-treat analysis. Of the 484, 475 (98.1%) had no infections, while 9 (1.9%) experienced clinical infections and 6 (1.2%) were culture-proven (CP). The infections included uncomplicated UTIs n=5 (1.0 %), 4 CP (0.8%); complicated UTIs n=1 (0.2%); and urosepsis, n=3 (0.6 %), 1 CP (0.2%). The 5 patients with uncomplicated UTIs were managed as outpatients, whereas the 4 with complicated UTIs or sepsis were admitted to the hospital for a mean of 2.6 days. All recovered without sequelae. No drug-related adverse events occurred. Conclusions Targeted antimicrobial prophylaxis achieved a low rate of infectious complications, limited morbidity and no sustained sequelae. These results were based on individual rectal flora cultures, suggesting that similar results can be obtained in a variety of patients, settings and over time. Funding State of Illinois Excellence in Academic Medicine (EAM) grant funded this project: STU00059558 EAM-237.
Authors
Teresa Zembower
Kelly Maxwell Robert Nadler John Cashy Marc Scheetz Chao Qi Anthony J. Schaeffer |
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MP11-13 |
Risk factor assessment for fluoroquinolone resistant E. coli (FRE) in bowel flora is not sufficiently discriminatory: the case for a pre-biopsy rectal swab in all patients. |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Prostate & Genitalia II | 17BOS |
Abstract: MP11-13 Sources of Funding: Waikato Urology Research Limited Introduction Infective complications post transrectal ultrasound guided (TRUS) prostate biopsy appear to be increasing, probably linked to a rising prevalence of FRE in the bowel flora. Several authors have suggested potential patient factors which may increase the risk of FRE carriage or sepsis post TRUS prostate biopsy . National guidelines have suggested screening only high risk patients for FRE. We sought in a prospective study to assess the prevalence of FRE in our patients and whether previously identified patient factors were related to this. Can we identify a high risk group for FRE and disregard the rest? Methods A transrectal swab, screening for FRE, was taken prior to biopsy. Antibiotic prophylaxis was 1 gram p.o. of ciprofloxacin prior to and 500mg after biopsy. Targeted antibiotics were used if a FRE was identified. Information was collected on: 1. Previous number of TRUS prostate biopsies, 2. Overseas travel within the last 6 months and if to a developing country, 3. Diarrhoea while away, 4. Overseas travel at any stage and if to a developing country, 5. Antibiotic use within the last six months, 6. Diabetes and 7. Inflammatory bowel disease. Naive Bayes, Logistic Regression, and Random Forest classifiers were used to build predictive models. A leave-one-out validation was used to generate class probabilities to quantify expected performance. Results Rectal swabs were performed in 1135 of 1216 prostate biopsies. FRE was detected in 95 (8.4%) of which 16 were extended spectrum beta lactamase (ESBL) E.coli. The prevalence of patient risk factors are shown in Table 1. Travel to a developing country within 6 months, ever, and diarrhoea while away were associated with FRE carriage (p<0.05). 327 patients had travelled to a developing country of whom 53 carried FRE. A naive classifier based on this would mean screening 30% to detect 50% of FRE carriers. Using leave-one-out the best classifier meant 80% of FRE was detected if 87% of patients were screened. Conclusions Travel to a developing country was associated with an increased risk of carrying FRE. However no model could be constructed that would allow screening of a small enough high risk group that was sufficiently useful. Based on this all patients should be screened for FRE prior to a TRUS prostate biopsy. Funding Waikato Urology Research Limited
Authors
Michael Holmes
Ray Littler Megan Lyons Lisa Smit Glen Devcich Adam Davies John leyland Chris Mansell |
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MP11-14 |
Cost effectiveness of targeted antimicrobial therapy in transrectal ultrasound-guided prostate biopsy |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Prostate & Genitalia II | 17BOS |
Abstract: MP11-14 Sources of Funding: None Introduction Prophylactic antibiotics are recommended in the American Urological Association (AUA) guidelines to reduce infectious complications following transrectal prostate biopsy (TRPB). Evidence for fluoroquinolone (FQ) prophylaxis is strong but high rates of FQ resistance worldwide have led to increased incidence of post-biopsy infections. Targeted antimicrobial prophylaxis based on rectal swab and culture can decrease rates of post-biopsy infections. To our knowledge, this will be the first study in North America to comprehensively analyze the cost utility of rectal swabs as a tool to reduce infectious complications after prostate biopsy. Methods A decision analytic model was prepared to compare costs of TRPB infectious complications (no infection, outpatient prostatitis, and inpatient prostatitis) among patients who had standard three-day ciprofloxacin prophylaxis compared to targeted three-day antimicrobials. Rates of infection were based on a recent large meta-analysis and rates of resistance were based on local institutional data. Costs were calculated based on hospital-derived data regarding average cost of inpatient stay, regional costs of common oral and intravenous antibiotics, and lab estimates of labour and material costs for investigations. These were all based on Canadian dollars (CAD). Quality-adjusted life years (QALYs) were calculated based on standard utility values for healthy middle-aged men, outpatient urinary tract infections (UTIs), and inpatient UTIs (as a surrogate for prostatitis). Several presumptions were made to produce a typical index patient of a man fifty to seventy years of age who is otherwise healthy and has no known multi-drug resistant organisms. Results Culture-guided prophylaxis resulted in reduced cost compared to standard prophylaxis ($77 CAD versus $143 CAD) and reduction in quality-adjusted life years (QALYs) by 0.00051. Increasing the cost of performing rectal swabs from $31 CAD to 95CAD causes the two arms to equalize at $141 CAD. Utilizing standard prophylaxis, compared to targeted, would result in an $83 CAD increase in cost to the patient. Conclusions The use of rectal swabs prior to prostate biopsy for targeted prophylactic antimicrobial therapy is both less costly and confers a greater quality of life compared to standard ciprofloxacin prophylaxis. Funding None
Authors
Alaya Yassein
Jean-Eric Tarride Timothy Davies |
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MP11-15 |
Predictors of Fluoroquinolone Resistance in the Rectal Vault of Men Undergoing Prostate Biopsy |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Prostate & Genitalia II | 17BOS |
Abstract: MP11-15 Sources of Funding: none Introduction Fluoroquinolone (FQ)-resistant rectal vault flora has been associated with increased infectious complications in men undergoing transrectal ultrasound guided prostate needle biopsy (TRUS-PNB). We sought to determine the patient-related factors that predict FQ-resistant rectal swabs in men with an indication for TRUS-PNB. Methods A retrospective review was performed on 5,271 consecutive patients who underwent rectal swabs before TRUS-PNB across 28 urology clinics around Chicago from January 2013 to December 2014. One microbiology lab processed all swabs, immersed them in a ciprofloxacin broth, and cultured them on MacConkey agar to isolate gram-negative rods. After incubation, FQ-resistant organisms were subcultured and underwent additional sensitivity testing. Characteristics of patients with and without FQ-resistant swabs were compared using the Kruskal Wallis and Chi-square tests. Multivariable logistic regression was performed to determine predictors of FQ resistance. Analyses were performed using R version 2.14.2 (R Foundation for Statistical Computing, Vienna, Austria). Results Of the 5,271 rectal swabs analyzed, 4,164 (79%) were FQ sensitive, and 1,107 (21.0%) were resistant. On univariable analysis, increasing age, diabetes mellitus, antibiotic use within the past 6 months, and non-Caucasian race were predictors of FQ resistance (all p < 0.05). The number of prior biopsies, indwelling foley catheter, healthcare profession, and PSA were not predictors. FQ resistance was also associated with benign biopsy histology (p < 0.01). On multivariate analysis, increasing patient age (OR=1.01/year [1.0-1.02]), use of antibiotics in the last 6 months (OR=2.75[2.06-3.67]), Black (OR=2.08 [1.72-2.54]) and Hispanic (OR=2.13 [1.72-2.64]) races remained statistically significant. Conclusions In this cohort increasing age, recent antibiotic-use, and Black and Hispanic races were independent predictors of FQ-resistance in the rectal vault. The higher likelihood of benign histology suggests that BPH or inflammation may be additional predictors and require further study. Funding none
Authors
Nathaniel Wilson
Dimitri Papagiannopoulos Nicholas O'Block Michael Abern Lester Raff Christopher Coogan Kalyan Latchamsetty |
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MP11-16 |
Indications, Utilization, and Complications Following Prostate Biopsy: a New York State Analysis |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Prostate & Genitalia II | 17BOS |
Abstract: MP11-16 Sources of Funding: None. Introduction Uptake of active surveillance and changes in prostate cancer care may affect utilization of and complications following prostate needle biopsy (PNBx). We characterized recent trends and risk factors for PNBx complications using a statewide, all-payer cohort. Methods We utilized the New York Statewide Planning and Research Cooperation System (SPARCS) to identify PNBx performed between 2011 and 2014 via transrectal (N=9472) and transperineal (N=421) approach. We characterized trends in utilization and complications using Poisson regression and Cochrane-Armitage tests. We used logistic regression to examine predictors of complications within 30 days of PNBx. Results Ambulatory utilization of PNBx decreased over time (p<0.01). The most common indication for PNBx was elevated PSA (53.2%), followed by active surveillance for cancer (26.7%), abnormal DRE (2.6%) and atypia (1.6%). _x000D_ _x000D_ _x000D_ PNBx-associated infection rates increased from 2.6% to 3.5% during the study period (p=0.02). Among repeat PNBx (n=777), complication rates were comparable to initial PNBx. On multivariable analysis, patient race, procedure year, diabetes (OR 1.96, 95%CI 1.31-2.91, p<0.01), transrectal approach (OR 3.52, 95%CI 1.29-9.64, p=0.01), and recent hospitalization (OR 2.03, 95%CI 1.43-2.89, p<0.01) were significantly associated with infections. Median total charge for infectious complications was $4,129 (interquartile range $711-$19,185). Conclusions Across New York State, post-PNBx infectious complications have increased over time. Risk factors for infectious complications such as diabetes, recent hospitalization, and the transrectal approach may help clinicians to select patients who are most likely to benefit from infection-reducing interventions such as transperineal approach and targeted prophylaxis. Funding None.
Authors
Joshua Halpern
Art Sedrakyan Brian Dinerman Wei-chun Hsu Jialin Mao Jim Hu |
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MP11-17 |
Transrectal prostate biopsy after prophylatic preparation of the rectum with povidone-iodine – A prospective randomized trial |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Prostate & Genitalia II | 17BOS |
Abstract: MP11-17 Sources of Funding: none Introduction Transrectal ultrasound (TRUS) guided prostate biopsy can lead to urinary tract infections in up to 11% and sepsis in up to 2% of patients. We evaluate whether an original way to apply peri-procedure povidone-iodine rectal preparation prior to TRUS-guided prostate needle biopsy can reduce infectious complications. Methods Between january/2014 and september/2016, 94 men in private office were prospectively randomized to rectal cleansing (an original transrectal prostate massage for about half a minute with 2,5ml of betadine100 mg/ml) (47) or no cleansing (47) before TRUS guided prostate biopsy with periprostatic local injection of lidocaine. All of the patients received prophylactic antibiotics: levofloxacine 500mg PO for 7 days, beginning the day before procedure. Patients completed a telephone interview 4 days after undergoing the biopsy and went to doctor office 2 weeks after biopsy. The primary end point was the rate of infectious complications, a composite end point of 1 or more of 1) fever greater than 38.0C, 2) urinary tract infection or 3) sepsis (standardized definition). Results Infectious complications developed in 6 cases (11%) in the non rectal preparation group: one patient had sepsis (2%) and five had fever without sepsis. In the povidone-iodine rectal preparation group we had no infectious complication (0,0%)._x000D_ Of the 94 men who underwent TRUS guided biopsy 45 (47.9%) were diagnosed with prostate cancer and 3 (3,2%) had ASAP in the result. The hospital admission rate for urological complications within 30 days of the procedure was 1%, and only for infection related reasons (sepsis). _x000D_ Conclusions The administration of quinolone-based prophylactic antibiotics and the simple use of 2,5 ml of povidone-iodine solution in a transrectal prostate massage for about half a minute provided an excellent protocol for reducing infective complications of TRUS-guided prostate biopsy. The simplicity of these method and cost effectiveness of betadine100 mg/ml were noteworthy, with statistically significant relative risk reduction of infectious complications in this study. Funding none
Authors
José Cadilhe
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MP11-18 |
EFFECTIVENESS OF SINGLE DOSE OF AMIKACIN COMPARED WITH LEVOFLOXACIN FOR PROPHYLACTIC USE IN TRANSRECTAL PROSTATE BIOPSY. |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Prostate & Genitalia II | 17BOS |
Abstract: MP11-18 Sources of Funding: None Introduction Prophylactic antibiotics are recommended prior to prostate biopsy. The main effect of antibiotic prophylaxis is a lowered incidence of postbiopsy bacteriuria. Although not all patients with bacteriuria are symptomatic, all patients who develop infectious complications following rectal biopsy are bacteriuric. Prostate biopsy performed without antibiotic prophylaxis is associated with increased rates of bacteriuria (8 to 44 percent) and bacteremia (16 to 70 percent) Major infectious complications, such as sepsis, Fournier gangrene, and urinary tract infection requiring hospital admission have been reported in patients who did not receive prophylactic antibiotics. Fluoroquinolones are the most widely used antibiotic for prophylaxis due to their broad spectrum of activity, easy oral administration, good penetration to prostate gland tissue, and long-lasting bactericidal activity. The development of resistant organisms is becoming an increasing problem and may lead to a need to alter the antibiotic régimen. The increase in the incidence of antibiotic-resistant infections following prostate biopsy is felt to be responsible for an increasing need for hospitalization after prostate biopsy ._x000D_ We developed a standard prophylactic regimen, in which security and efficacy are the priority; however the variability in costs is reduced._x000D_ Aim: _x000D_ To prospectively evaluate the efficacy of amikacin compared with levofloxacin as prophylactic measure in transrectal prostate biopsy._x000D_ Methods A prospective, observational, comparative study, which included 393 patients who had standard indication of transrectal prostate biopsy. The study was conducted with a random choice and split into two groups, demographic characteristics were similar in both groups. Group A: 205 patients who were administered a single dose of levofloxacin (500 mg) orally 60-120 minutes before the procedure; and Group B: 188 patients who were given amikacin 15 mg / kg intramuscularly 60-120 min before the procedure. All patients underwent urinalysis and urine culture before and after the procedure. We identified post biopsy complications: bacteriuria, urinary tract infection, orchitis, pyelonephritis, sepsis, all of them were evaluated, all patients with a severe condition were hospitalized. The variables were correlated using Fishers Exact Test. Results In Group A, 4.3% of patients presented a febrile UTI and 0.97% presented sepsis. In Group B, 5.3% presented febrile UTI and .53% presented sepsis. Comparing both groups, we found no relationship between the dose and the risk for complications (p=0.52). In the group analysis considering DM, a significant relationship for complication risks was not found, Group A (p=0.62) and Group B (p=0.58). The same in the analysis of overweight and obesity no significant relationship with complications was found, Group A (p=0.85) and Group B (p=0.65). Conclusions Given its efficacy and simplicity, a single dose of 500mg of levofloxacin represents an excellent prophylaxis method in transrectal prostate biopsies guided by ultrasound. However, a single dose of amikacin shows similar results as levofloxacin, thus it can significantly reduce the cost of antibacterial therapy and have a similar safety profile. Funding None
Authors
Marcela Pelayo-Nieto
Edgar Linden-Castro Iván A. Ramírez-Galindo Daniel Espinosa-Perez Grovas Roberto C. Rodriguez-Alvarado Felipe Guzmán-Hernández Jesús A. Morales-Covarrubias Edy D. Rubio-Arellano Roberto Cortez-Betancourt |
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MP11-19 |
Targeted antibiotic prophylaxis by β-lactams based on rectal swab culture is not sufficient to prevent infective complications after transrectal prostate biopsy |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Prostate & Genitalia II | 17BOS |
Abstract: MP11-19 Sources of Funding: none Introduction The targeted antibiotic prophylaxis by susceptible antibiotics based on the rectal swab culture has been reported to be effective for prevention of infective complications (IC) after transrectal ultrasonography guided prostate biopsy (TRPB). We evaluated the efficacy of the targeted antibiotic prophylaxis by β-lactams for the prevention of IC after TRPB among patients with quinolone-resistant (QR) strains. Methods From January 2010 to December 2015, a total of 337 men who underwent TRPB were included. Prior to TRPB, rectal swabs were cultured and determined the possession of QR strains. Isolated bacteria was determined QR when their minimum inhibitory concentration of levofloxacin (LVFX) was 4 μg/mL or above. Patients were divided into two study groups. Group 1 consisted of 176 patients from January 2010 to March 2013 and group 2 consisted of 161 patients from April 2013 to December 2015. For patients without the possession of QR strains, single oral 500mg of LVFX was received 2 hours before TRPB. Patients with QR strains of the group 1 received LVFX plus amikacin and those of the group 2 received intravenous β-lactams for which isolates were susceptible. All biopsies were carried out through a standard 10-core approach with local anesthesia. The patients were followed up for 2 weeks after TRPB and febrile IC were recorded. Results Overall the prevalence of QR strains was 13.4% (45/337). That of the group 1 and the group 2 was 9.7% (17/176) and 17.4% (28/161), respectively. A total of 14 patients (4.2%) had post-TRPB fever in this study. The incidence of febrile IC of the group 1 was 1.7% (3/176) and that of the group 2 was 6.8% (11/161). Forty-five patients with QR strains were complied with targeted antibiotic prophylaxis. In the group 1, only one (5.9%) out of 17 patients with QR strains had febrile IC. In the group 2, although they received β-lactam antibiotics which were susceptible to isolates from rectal swab culture, 8 (28.6%) out of 28 patients with QR strains had febrile IC. Conclusions In the group 1, few patients with both quinolone-sensitive and QR strains had febrile IC. In the group 2, the incidence of febrile IC has increased, especially among patients with QR strains who received susceptible β-lactams for prophylaxis. The targeted antibiotic prophylaxis by β-lactams alone was less effective among patients with QR strains. Facing the increase of multi-drug resistant bacteria in the rectal flora, new tactics to prevent post-TRPB febrile IC will be needed. Funding none
Authors
Yoshitsugu Nasu
Tadashi Murata Morito Sugimoto Atsushi Takamoto |
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MP11-20 |
The difficulty interpreting endotoxaemia post transrectal prostate biopsy |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Prostate & Genitalia II | 17BOS |
Abstract: MP11-20 Sources of Funding: The study protocol was approved by the NHS Integrated Research Ethics System(London UK) 10/H0722/39 and the Hospital KCH10-069 Introduction A prospective study to measure sepsis and endotoxaemia following prostate biopsy Methods 67 consecutive patients received ciprofloxacin and metronidazole prophylaxis. Blood cultures and endotoxin assay were performed at 5 and 60 min and 24 hours post biopsy. Prostate needle washings were cultured. Results 61/67 patients (91.0%) had positive cultures from needle washings. 6/67 patients (9.0%) had positive blood cultures. Endotoxin assay was performed on 66 samples at 5 min, 60 samples at 60 min, and 55 samples 24 h post biopsy. Endotoxin was detected in 62/66 (94.0%) at 5 minutes, 53/60 (88.3%) at 60 minutes and 55/60 (91.6%) at 24 hours. Conclusions This study demonstrates the translocation of gut endotoxin post TRPB. The non portal venous drainage of the prostate is an explanation for the endotoxins measured after biopsy. These findings of endotoxaemia are in keeping with the landmark studies previously performed that demonstrated endotoxin in the unprotected placebo group._x000D_ _x000D_ The Prostate, Lung, Colorectal and Ovary (PLCO) study reported a mortality rate at 120 days post TRPB of 1.3 deaths per 1,000 biopsies in the negative biopsy group. This compares with the risk reported by Gallina et al in a population-based study, with overall 120-day mortality after biopsy of 1.3% versus 0.3% in the control group._x000D_ A review of cardiac complications after pneumonia showed a significant increase in cardiac mortality. The effect of circulating inflammatory mediators such as endotoxins leading to non-ischaemic myocardial injury is proposed as one of the potential mechanisms contributing to myocardial dysfunction._x000D_ _x000D_ This study raises several issues. What is the significance of endotoxin detection in the serum samples after prostate biopsy? Is this related to the increased mortality in relation to cardiovascular dysfunction of this group?_x000D_ The WHO's Global Action Plan on Antimicrobial Resistance in 2015 emphasises that we have a duty of governance and stewardship to review the implementation of alternative surgical approaches that will allow limitation of antibiotic prophylaxis in TRPB._x000D_ While we endeavour to understand the clinical significance of the association between bacteraemia and endotoxaemia after transrectal prostate biopsy it is important that we share with the patients the worldwide risks of the procedure as we strive to make prostate biopsy safer._x000D_ Funding The study protocol was approved by the NHS Integrated Research Ethics System(London UK) 10/H0722/39 and the Hospital KCH10-069
Authors
Peter Thompson
Wei Wang Hemant Nemade Srinath Chandersekara Sharon Sheehan Elias Khalifa John Philpott - Howard Elias Khalifa |
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MP12-01 |
INCREASED URINARY EXCRETION OF GLYCOLATE AND OXALATE IN OBESE AND DIABETIC MICE MODELS |
Stone Disease: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP12-01 Sources of Funding: AUA Research Scholar Introduction Obesity and diabetes have both been shown to be risk factors for nephrolithiasis. Both diseases are associated with increased urinary excretion of oxalate (Uox). Our objective was to study endogenous production of oxalate in diabetic and obese mouse models on controlled diets. Methods Three male mouse models of obesity and diabetes (KKAy n=3, Akita n=8, ob/ob n=3) were placed on controlled ultra-low oxalate diets and compared to matched control mice. 24 hour urines were collected and analyzed. Total body fat and lean body mass were also measured in the ob/ob and control mice with DEXA scans. Statistical analysis was performed using t-test. Results KKAy, Akita, and ob/ob weighed 198%, 58%, 56% more compared to control mice, respectively. On an ultra-low oxalate diet, when compared to control, KKay, Akita, and ob/ob mice had increased 24 hour urinary oxalate (µg/mg Cr, 164%, 223%, 241% respectively, more than control mice, p<0.05). 24 hour urinary glycolate (Ugl, µg/mg Cr) levels were 234%, 174% higher in the Akita, and ob/ob mice, respectively, compared to control mice (p<0.001). The KKAy mice had the same Ugl as control mice. The ob/ob mice had decreased lean body mass compared to controls (20.1 g vs 22.6 g, p=0.04),but had increased body fat (27.7 g vs 3.6 g, p=0.0001). For ob/ob mice and control mice, increasing urinary oxalate correlated with increasing urinary glycolate (r=0.82, p=0.05). Conclusions These findings suggest that obesity may increase endogenous oxalate synthesis via pathways linked to glycolate production. Further studies are needed to determine if this is occurring in the fat compartment or whether signaling from this area upregulates endogenous oxalate synthesis. This model system may be an ideal method of assessing such responses. Funding AUA Research Scholar
Authors
Kyle Wood
John Knight Dean Assimos Ross Holmes |
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MP12-02 |
Autophagy maintains cellular homeostasis and inhibits renal crystal formation |
Stone Disease: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP12-02 Sources of Funding: none Introduction We previously reported that tubular cell damage facilitates kidney crystal formation. Although recent evidence shows that damaged cells could induce autophagosomes and autolysosomes to perform autophagy, engulfing and removing damaged organelles, the association between autophagy and kidney crystal formation remains unclear. Hence, we analyzed the role of autophagy in renal crystal formation. Methods In vitro study We exposed M1 cells derived from the cortical collecting duct of the mouse to calcium oxalate monohydrate (COM) crystals at a concentration of 20 μg/cm2 and the levels of autophagy-related proteins (LC3-B, Beclin-1, p62) were assessed using fluorescent immunostaining and western blotting. Additionally, immunostaining of the organelles was carried out to determine mitochondrial and lysosomal damage, and the COM crystal adhesion ratio to cells was measured. Furthermore, using tandem fluorescent-tagged LC3 (tfLC3) assay, we examined autophagy behavior._x000D_ In vivo study Kidney crystal formation in C57BL/6J mice was induced by daily intra-abdominal injection of 80 mg/kg-1 glyoxylic acid, and the relationship between crystal formation and the ultrastructure of autophagosomes and autolysosomes was observed using polarized light microscopy and transmission electron microscopy (TEM). Western blotting and immunostaining of autophagy-related proteins were performed, and GFP-LC3 transgenic mice were created to check autophagy in kidneys._x000D_ Results In vitro study COM exposure damaged many organelles, in response of which autophagy increased. After 8 hours, the COM crystal adhesion ratio to M1 cells had increased and tfLC3 assay showed a slight increase in autophagy._x000D_ In vivo study Remarkable accumulation of autophagosomes and autolysosomes in proximal renal tubular cells of mice without renal crystal deposits was observed. As crystal deposits increased, autophagy expression decreased (Figure 1). Similarly, western blot analysis results from GFP-LC3 mice showed crystal deposits increase as autophagy decreases. Furthermore, crystals deposits tended to decrease to promote autophagy. _x000D_ Conclusions Results indicate that autophagy removes damaged organelles and maintains cellular homeostasis in renal tubular cells. Consequently, autophagy prevents renal crystal formation. Funding none
Authors
Rei Unno
Naoko Unno Yuya Ota Teruaki Sugino Kazumi Taguchi Shuzo Hamamoto Ryosuke Ando Atsushi Okada Keiichi Tozawa Kenjiro Kohri Takahiro Yasui |
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MP12-03 |
Metformin reduce the renal stone formation in high oxalic acid rats by inhibiting the activation of NLRP3 pathway |
Stone Disease: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP12-03 Sources of Funding: none Introduction metformin is a common oral drug which has been reported to treat diabetes and other diseases. The aim of this study was to explore the role and mechanism of metformin in reducing the incidence of kidney stone. Methods SD rats were randomly divided into 4 groups: group A (normal rats group, n=8), normal rats; group B (normal rats were given intragastric administration of metformin group, n=8); group C (hyperoxaluria rats, n=8 rats) 0.5% glycol and 1% ammonium chloride in drinking water; group D (hyperoxaluria rats were given intragastric administration of metformin group, n=8) same processing as group C, while giving the daily intragastric administration of metformin. The 24 hours’ urine of rat’s were collected before nephrectomy. Tissue sections were stained with Von Kossa to observe the crystallization, expression of OPN, CD44, NLRP3, IL-1, caspase-1 were by real-time quantitative PCR and Western Blotting. Results The urinary oxalate in C and D group was significantly higher than that in A group and B group (P<0.05). Von Kossa staining showed that crystal deposition of A, B, C, D group were 0, 0, 81.25% and 93.75%, respectively. The crystal density of group C was significantly higher than that in group D (P<0.05). OPN, CD44, IL-1, caspase-1 and NLRP3’s mRNA and protein expression of C, D group was significantly higher than the other two groups (P<0.05), the C group was significantly higher than the D group (P<0.05)._x000D_ Conclusions Metformin inhibits the production of NLRP3 in rats with high oxalate, which can reduce the activation of the inflammatory bodies and thus reduce the production of kidney stones._x000D_ Key words: kidney calculi_x000D_ Funding none
Authors
Hongyang Jiang
Tao Wang Zhuo Liu Jihong Liu Shaogang Wang Zhangqun Ye |
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MP12-04 |
Two-Stage Model to Study Idiopathic Calcium Oxalate Stone Formation |
Stone Disease: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP12-04 Sources of Funding: NIH Grant T32 DK 094789 and RO1 DK 092311 Introduction Idiopathic calcium oxalate (CaOx) kidney stones grow attached to Randall&[prime]s plaques (RPs), which are calcium phosphate (CaP) deposits on renal papillary surfaces. Our goal is to develop a two stage model system consisting of 1) CaP mineralized biomimetic RPs (BRPs) formed in-vitro using classical mineralization or the polymer-induced liquid precursor (PILP) process, followed by 2) CaOx overgrowth into a stone in-vivo on BRPs implanted as foreign bodies into the urinary bladders of hyperoxaluric male rats. Methods BRPs were developed by mineralizing decellularized porcine kidney tissue (DPK) with CaP in the presence or absence of 50 µg/ml of polyaspartic acid (PA) or osteopontin (OPN). Foreign bodies were surgically implanted into the bladders of adult male rats in the following groups: non-mineralized DPK (n=8), classical mineralization (without PA or OPN (n=8)), PILP mineralization with PA (n=8), or with OPN (n=8). Half of the rats in each group were given regular water and half were given water with 0.75% ethylene glycol (EG rats) to induce hyperoxaluria. Urine was collected at days 7 and 21 for determination of pH, microscopy, and oxalate excretion. Rats were sacrificed after 4 weeks and the foreign bodies analyzed via scanning electron microscopy and x-ray diffraction. Results Decellularized porcine kidney mineralized via the PILP process in vitro showed features resembling native plaques, such as concentric spherules and collagen fibrils with intrafibrillar mineral. EG rats had higher urinary oxalate excretion and lower urine pH than rats given regular water, and formed CaOx crystals. Bladder foreign bodies from rats given regular water were mineralized with magnesium phosphate or CaP, and those given EG water were mineralized with CaOx. Both CaOx monohydrate and dihydrate crystals were detected on foreign bodies mineralized with PA in EG rats, while only CaOx monohydrate was detected in the other EG rat groups. Conclusions Mineralization through PILP process led to the production of BRPs. When exposed to hyperoxaluria, BRPs became covered with CaOx crystals, morphologically similar to human CaOx kidney stones. The difference in crystal morphology between BRPs formed using PA and the other groups demonstrates that this model system can discriminate between small differences in RP structure and additive, and may have relevance to future therapeutic models. Further studies to determine the repeatability of these findings and investigate the utility of BRPs for use in therapeutic models of CaOx stone treatment and prevention are indicated. Funding NIH Grant T32 DK 094789 and RO1 DK 092311
Authors
Allison O'Kell
Archana Lovett Benjamin Canales Laurie Gower Saeed Khan |
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MP12-05 |
Comparative Analysis of High-Throughput Sequencing Platforms for an Oxalate Metabolizing Microbiome: Implications for the Study of the Urologic Microbiome |
Stone Disease: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP12-05 Sources of Funding: none Introduction High-throughput metagenomic profiling is becoming increasingly important in the field of urology. Analyses of urinary and gut microbiomes have been performed in the study of nephrolithiasis, prostate and bladder cancer, prostatitis and urinary incontinence. Various sequencing platforms exist in the study of the microbiome and may exhibit inherent biases. The selection of DNA sequencing platform can shape our understanding of taxonomic diversity in the study of urologic microbiomes and specifically in our understanding of nephrolithiasis. We compared the output of two high-throughput sequencing platforms in the analysis of a highly efficient oxalate-degrading microbiome. Methods Four Neotoma albigula, white-throated woodrats, were fed high and low oxalate diets ranging from 0.2-12% oxalate. Fecal samples were collected from each animal. The samples were frozen at -80°C until DNA extraction. MiSeq microbial inventories were generated by amplifying and sequencing the hypervariable V4 region of the 16S rRNA gene with primers 515F and 806R. HiSeq inventories were generated by extracting 16S rRNA sequences from shotgun metagenomic data of the same DNA samples with HMMER. Sequencing was conducted at the same laboratory (Argonne National Laboratory, Chicago, IL). After consolidating the data from both platforms, a de novo picking strategy was used to classify the operational taxonomic units (OTU). Alpha and beta diversity metrics were compared across platforms and time using open source software, QIIME and R. Significance was defined at a P value of <0.05. Results There were only 10 Oxalobacteraceae OTUs identified with the MiSeq platform compared to 128 identified with HiSeq. The alpha diversity metrics were significantly different across the MiSeq and HiSeq platforms. However these metrics were different across time only for MiSeq and not HiSeq. Beta diversity metrics demonstrated a significant difference across platforms but not across time for either MiSeq or HiSeq. Conclusions Our results indicate that differences between the Illumina MiSeq and HiSeq platforms are primarily the result of MiSeq under sampling of rare taxa. The MiSeq platform underestimated the diversity of the oxalate-degrading Oxalobacteraceae and exhibited significant compositional differences with the data derived from the HiSeq platform. The limitations of the MiSeq platform must be considered in microbiome studies of urologic disease and has implications for our understanding of the oxalate metabolism in nephrolithiasis. Funding none
Authors
Anna Zampini
Aaron W. Miller Manoj Monga Denise Dearing |
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MP12-06 |
Oxalate and COM-crystals activate Toll-like receptor 4 (TLR4)-mediated NF-?B signaling pathway and proinflammatory response in human renal epithelial cells |
Stone Disease: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP12-06 Sources of Funding: NIH-DK-RO1-54084 _x000D_ Carroll W. Fiest endowed chair funds Introduction Elevated urinary oxalate and calcium levels have independently been associated with sub-sets of idiopathic stone formers. However, precise mechanisms of interplay between elevated oxalate levels and renal tubular inflammation is not fully understood. In the present studies we set out to determine effects of oxalate on expression of pro-inflammatory genes. Methods Renal epithelial cell lines (HK2 cells) were used in culture to evaluate the effects of oxalate and COM crystals. We utilized microarray analysis using Affymetrix HG_U133_plus2 gene chip. Data analysis was performed suing Data Mining Tool (DMT 3.1, Affymetrix) and GeneSpring 7.2 (Silicon Genetics). Cell Intensity files were processed into expression values for all the 55,000 probe sets (transcripts) on each array and following the respective normalization step. Differentially expressed genes were classified according to the Gene Ontology functional category (GenMAPP v2) and functional significance of differentially expressed genes was determined using Ingenuity Pathways Analysis Software (Ingenuity Systems, http://www.ingenuity.com). Cluster and Heatmap images were generated using BRB-Array tools30. Changes in gene expression were further validated by relative quantitative RTPCR. Protein expression was monitored by Western Blot analysis, immune-histochemical and immunofluorescence methods. Results Gene Set Enrichment of the Transcriptome of human renal epithelial cells upon oxalate exposure revealed that oxalate exposure was associated with positive enrichment of genes associated with immune response, immune system processes and inflammatory response. Identification of lipopolysaccharide (LPS) gene set enrichment signature prompted us to evaluate activation of Toll-like receptor 4 (TLR4) pathway as one of the key. Oxalate induced nuclear translocation of the transcription factor NF-?B and activation of p38 MAP kinase in renal epithelial cells. Moreover, inhibition of TLR4 as well as p38 MAP kinase blocked NF-?B activation. At the protein level, effects of oxalate on expression of proinflammatory cytokines and chemokine IL-6 were similar to that of LPS treatment in renal epithelial cells. Conclusions These results show for the first time that oxalate and COM crystals engage TLR4 a member of the pattern recognition receptor system. Given the roles played by TLR4, we hypothesize that elevated levels of oxalate promote renal tubular inflammation by activating TLR4 Funding NIH-DK-RO1-54084 _x000D_ Carroll W. Fiest endowed chair funds
Authors
Sweaty Koul
Quin Dong Fentian Wang Hari Koul |
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MP12-07 |
Urine kidney injury markers do not increase following gastric bypass: a multi-center cross-sectional study. |
Stone Disease: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP12-07 Sources of Funding: None Introduction Gastric bypass surgery for obesity is known to be associated with post-operative hyperoxaluria, which can lead to urolithiasis and kidney damage. The objective of this study was to determine if markers of kidney injury correlated with urinary oxalate excretion. If so, such biomarkers might be early predictors of oxalate nephropathy. Methods Patients were recruited from 4 large academic centers > 6 months following completion of gastric bypass surgery. Patients provided a spot urine sample for analysis of three markers of kidney injury: 8-iso-Prostaglandin F2α, N-acetyl-β-D-Glucosaminidase, and Neutrophil gelatinase-associated lipocalin. Patients also provided 24 hour urine samples for stone risk analysis. Results 46 study patients provided samples and the average age was 48.4 + 11.3. There were 40 women and 6 men. There was no difference in the level of any of the three inflammatory markers between the study group and the reference range generated from healthy non-hyperoxaluric subjects. Neither oxalate excretion nor supersaturation of calcium oxalate correlated with any of the injury markers There was no difference noted between those with hyperoxaluria (N=17) and those with normoxaluria (N=29) with respect to any of the injury markers (Table 1). Conclusions Though hyperoxaluria was common after bypass surgery, markers of kidney injury were not elevated after surgery. No correlation was found between urine oxalate excretion and any of the injury markers. Funding None
Authors
Bryan Hinck
Ricardo Miyaoka James Lingeman Dean Assimos Brian Matlaga Rocky Pramanik John Asplin Benjamin Cohen Manoj Monga |
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MP12-08 |
Geographical and Prevalence Trends in Urolithiasis in England: A Ten-Year Review |
Stone Disease: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP12-08 Sources of Funding: none Introduction The prevalence of kidney stones has been increasing in the US and Europe, with stone-related emergency attendances and procedures consequently increasing, producing a significant economic impact on hospital emergency and elective services. There is sparse available literature regarding recent incidence trends of urolithiasis in the UK. As implications for workforce planning, centralisation of stone services and the potential for identifying the highest ‘risk’ become increasingly relevant and we hypothesized there may be ‘hot spots’ of stone occurrence which could prompt further epidemiological research and help plan local stone services. Methods Hospital Episode Statistics (HES) datasets and Office for National Statistics Mid-year population estimates and census data were used to calculate the occurrence of Urolithiasis England from 2003-2014. Information regarding age, gender, ethnicity, Index of Multiple Deprivation (IMD) decile and local authority district of residence were obtained. Tableau software was used to visually graph our data analysis. Results The prevalence of urolithiasis in England grew by 33.7% over the study period. The LA with the greatest increase was South Cambridgeshire which showed a compound annual growth rate of 14.06% and absolute growth of 272.7%. In contrast, the prevalence of urolithiasis decreased in 46 of 326 local authorities, with Mid Suffolk showing a compound annual growth rate of -6.07% and an absolute decrease of 46.5%. Regional grouping of LA’s was also geographically mapped._x000D_ _x000D_ An increase in the absolute growth occurred in all age categories except 0-4 years. The age group 85+ shows the greatest growth throughout the study period, with absolute growth of 106.6% and an annual compound rate of growth of 7.35%. As seen in figure [1] the 75-84 age group continued to trend upwards over the study period while the 15-44 age group stabilised from 2010 between 14.23 and 15.30 per 10,000. _x000D_ Prevalence in men and women has increased from 16.6 & 7.06 per 10,000 to 20.84 & 10.74 respectively. Men showed an absolute growth of 25.1%, and women an absolute growth of 52.1%_x000D_ Conclusions Our work confirms the increasing prevalence of kidney stones in England, and demonstrates this prevalence is varied depending on area of residence and age. 'Hot spots' of stone activity exist, and scope for further epidemiological analysis exists. Funding none
Authors
holly ni raghallaigh
dene ellis andrew symes |
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MP12-09 |
Matrix protein differences between uric acid and calcium oxalate stones |
Stone Disease: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP12-09 Sources of Funding: Froedtert Foundation_x000D_ Medical College of Wisconsin Introduction In general, kidney stones are crystal aggregates held together by an organic matrix, which contains mainly proteins. Little is known about possible differences in the protein distribution between different stone types that likely are critical to stone pathogenesis. Enrichment of highly anionic and highly cationic proteins was observed in calcium oxalate (CaOx) stone matrix compared to urine, suggesting a role for protein aggregation in this stone process. In this study, stone matrix proteins have been quantitatively identified in 3 archival uric acid (UA) stones, and compared to the distribution observed in 8 calcium oxalate stones using a previously reported method. Methods Stone matrix proteins were isolated from 3 archival UA stone samples (>95% UA content) by dissolution in sequential washes with an EDTA/SDS solution at pH=8 with dithiothreitol added. The solubilized proteins were combined, then concentrated and desalted by ultradiafiltration. Proteomic analysis was performed at the Medical College of Wisconsin Innovation Center using non-labelled, quantitative mass spectrometry methods, including only proteins with 2 or more peptide matches at >85% confidence, after removing keratin and redundant proteins. Results Strong protein signals (>3,000 SC per sample) were obtained from each UA matrix protein sample identifying 342 unique proteins. Of these, 180 proteins were found in both UA and CaOx stone matrix, accounting for 81% of total protein mass of the former and 94% of the latter. Albumin and uromodulin were found in both stone types, but at lower relative abundance than these proteins are found in urine, suggesting non-selective inclusion of these highly abundant urine proteins. Important differences were that none of the 5 predominant proteins in CaOx stone matrix was prominent in UA stone matrix, and highly anionic proteins were not enriched in UA stones. Highly cationic proteins were slightly more prominent in UA stone matrix than in CaOx stone former urine, but much less than observed in CaOx stone matrix. Nuclear proteins were much less strongly represented in UA stone matrix. Conversely, immunoglobulins and complement proteins were predominantly enriched in UA stone matrix and less prominent in CaOx stones. Conclusions Stone matrix proteins exhibit distinctly different patterns in UA compared to CaOx stones, implying different underlying pathogenesis. In particular, UA stone formation appears to be more dependent on inflammatory pathways and less dependent on cell injury processes and polyanion-polycation association compared to CaOx stone formation. Funding Froedtert Foundation_x000D_ Medical College of Wisconsin
Authors
Jeffrey Wesson
Ann Kolbach-Mandel Carley Davis Neil Mandel Brian Hoffmann |
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MP12-10 |
SNP rs17383719 in the PBX1 Gene is Associated with Cystinuria |
Stone Disease: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP12-10 Sources of Funding: FAPESP 2013/17034-5 Introduction Cystinuria is a recessive disorder characterized by impaired tubular reabsorption of cystine and dibasic amino acids. Some studies in the literature have shown mutations in the SLC3A1 gene associated with type A cystinuria that follows a complete recessive inheritance in half of the cases. The other half has been related to mutations in the SLC7A9 gene considered responsible for cystinuria type B presumably inherited by an incomplete dominant manner. Considering the paucity of studies on the genetic basis of cystinuria, we performed genome-wide human SNP array, aiming to find some single nucleotide polymorphisms (SNPs) related to cystinuria development. To confirm the microarray results we performed PCR (Polymerase Chain Reaction) searching for five SNPs that we found related to the disease and two others reported in the literature. Methods DNA samples from peripheral white blood cells were extracted from eight patients with cystinuria and 10 healthy subjects with no renal calculi that composed the control group. The SNPs were genotyped using a TaqMan® SNP Genotyping Assay Kit. Results The homozygote polymorphic genotype of SNP rs17383719 in gene PBX1 was significantly more frequent among cystinuric patients (p=0.015). The occurrence of the polymorphic allele for this SNP was associated with a 3-fold increased risk of cystinuria (p=0.036). The polymorphic alleles of SNPs rs913034 and rs7096453 (SVIL) were more frequent in the control group (p=0.04 and p=0.08, respectively). We did not detect polymorphic homozygote genotype in the SNPs for SLC7A9 (rs140134166) and SLC3A1 (rs200248046) genes. Conclusions This is the first study describing genetic variations in patients with cystinuria. The most important finding was the 3-fold increased risk for the development of the disease for the SNP in the PBX1 gene. PBX1 (Pre-B-cell-leukemia transcription factor 1) is a member of a transcription factors family associated with kidney development, but there are no studies in the literature associating this gene with nephrolithiasis. We postulate that the presence of SNP may change the gene expression of PBX1 affecting the renal absorption of cystine and other amino acids predisposing to nephrolithiasis. Funding FAPESP 2013/17034-5
Authors
Sabrina Reis
Ronaldo Guimarães Nayara Viana Katia Leite Giovanni Marchini Fabio Torricelli William Nahas Miguel Srougi Eduardo Mazzucchi |
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MP12-11 |
HOW PREVALENT IS CYSTINE STONE? A PERSPECTIVE FROM GENETICS |
Stone Disease: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP12-11 Sources of Funding: none Introduction Cystine stones are caused by cystinuria, an inborn error of metabolism. The pathogenesis of cystine stones and cystinuria have been re-classified by genetic mutations. It is defined as type A if mutations are found in both SLC3A1 alleles, and type B if mutations are found in both SLC7A9 alleles. However, the prevalence of type A and type B cystine stones has not been evaluated. We aim to clarify the prevalence of type A and type B cystine stones by employing a genetic approach. Methods We have accessed the 1000 Genomes Database Phase 3 (1KG) for identification of variants in the general population. To identify pathogenic mutations, we parsed the Human Gene Mutation Database (HGMD)._x000D_ _x000D_ SLC3A1 and SLC7A9 variants procured from both databases were intersected. Homozygotes, compound heterozygotes, multiple variants in cis or trans, double homozygotes, and double heterozygotes were examined. Related individuals were excluded. Pathogenic allele frequency, carrier rate and affected rate were calculated and estimated based on Hardy-Weinberg equilibrium. Results In 1KG, non-related healthy individuals (n=2504) carry SLC3A1 and SLC7A9 variants in 1705 and 1287 loci, respectively. In HGMD, there are 110 pathogenic SLC3A1 mutations, and 85 for SLC7A9. These variants include missense mutations, nonsense mutations, insertions, deletions, and complex substitutions._x000D_ _x000D_ Among 2504 non-related, healthy individuals in 1KG, there are 26 people who carry 9 different SLC3A1 mutations, while 12 people carry 5 different SLC7A9 mutations. There were no homozygotes, compound heterozygotes, multiple variants in cis or trans, double homozygotes, or double heterozygotes._x000D_ _x000D_ Therefore, disease-causing alleles have a frequency of 0.52% for SLC3A1, and 0.24% for SLC7A9._x000D_ Type A cysteine stone has a carrier rate of 1 in 96 individuals and affected rate of 1 in 37,100 individuals._x000D_ For type B, carrier and affected rates would be 1 in 209 and 1 in 174,167, respectively. _x000D_ The combined (type A + type B) carrier rate for cysteine stones is 1 in 66, with an overall affected rate of 1 in 30,585. _x000D_ _x000D_ Conclusions The prevalence of cystine stone type A and type B estimated from a genetic approach is lower than the prevalence of observed of phenotypes (1 in 30,585 v.s. 1 in 7,000). Possible explanations include undiscovered mutations, undiscovered genes, a different inheritance model, selection advantages over the pathogenic variant, or founder effect. Further studies and investigations are required. Funding none
Authors
Chen-Han Wilfred Wu
Fernando J. Kim Trevor Wild Anne Tsai Naomi Meeks Rodrigo Donalisio Da Silva Wilson R. Molina |
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MP12-12 |
?-lipoic acid suppresses cystine stone formation in a genetic mouse model of cystinuria |
Stone Disease: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP12-12 Sources of Funding: NIH P20 DK100863 Introduction Cystinuria is a disorder characterized chronic kidney stone formation and caused by genetic mutations in the heterodimeric cystine transporter (SLC3A1 and SLC7A9) that is responsible for cystine reabsorption. Individuals afflicted with cystinuria are often treated by hyper-hydration, urine alkalization, and/or pharmacological interventions aimed at increasing cystine solubility in urine. However, these treatments are limited in their effectiveness and often have serious adverse side effects. The objective of this study is to use a mouse model of cystinuria to identify novel approaches towards the treatment of cystinuria. Methods Methods: Using longitudinal micro-computed tomography, Slc3a1-/- mouse cystine bladder stone formation was calculated at growth rate of approximately 1 mm3/day. This measure was used to evaluate interventions aimed at attenuating stone growth. A linear mixed model with random intercept was used to assess stone growth rates between treated versus control mice. Results Lipoic acid was found to be a potent inhibitor of cystine stone formation in a Slc3a1-/- mouse model of cystinuria. Treatment with lipoic acid attenuated existing cystine stone growth, and prevented stone formation in young Slc3a1-/- mice. The inhibitory effect was found to be dose-dependent, and independent of lipoic acid effects on the antioxidant response pathway. Ex vivo cystine precipitation analysis revealed that lipoic acid treatment increased cystine solubility in urine. Conclusions Treatment with the nutritional supplement lipoic acid protects against stone formation in a mouse model of cystinuria. This result identifies a novel application of lipoic acid that increases urinary cystine solubility independently of pH, and may highlight a new avenue for understanding treatment strategies for cystinuric patients. Funding NIH P20 DK100863
Authors
Tiffany Zee
Neelanjan Bose Jarcy Zee Jennifer Beck See Yang Jaspreet Parihar Min Yang Sruthi Damodar David Hall Monique O'Leary Arvind Ramanathan Roy Gerona David Killilea Thomas Chi Jay Tischfield Amrik Sahota Arnold Kahn Pankaj Kapahi Marshall Stoller |
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MP12-13 |
A Rat Model to Study the Role of Gut Bacteria in Regulation of Urinary Calcium |
Stone Disease: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP12-13 Sources of Funding: University of Florida Department of Urology Introduction Nephrolithiasis afflicts 1 in every 11 Americans, causing severe renal pain and reduction in quality of life. A majority of nephrolithiasis patients exhibit absorptive hypercalciuria (AH), a metabolic defect where intestinal absorption of dietary calcium is abnormally high. Prior genetics studies have not yielded a mechanism for this metabolic defect. Since there is a diverse microbial community in the human intestinal tract, with poorly defined effects on systemic health, we hypothesize that AH is mediated by changes in the intestinal microbial community that increase calcium absorption by intestinal epithelium. We test this by characterizing the urine chemistry and gut microbiota changes that occur in a rodent model upon administration of high doses of oral antibiotics. Methods 6 week-old male and female Sprague-Dawley rats were evenly distributed in the following groups: control (n=12), chloramphenicol-treated (n=12) and neomycin-treated (n=12). All rats underwent pre-treatment urine and stool collection. Subsequently, control rats were provided sterile water ad libitum for 7 days; chloramphenicol and neomycin-treated rats received sterile water (ad libitum) containing 0.07% of their respective antibiotics for 7 days. Rats underwent post-treatment urine and stool collection. Pre- and post-treatment urinary calcium was assessed. Alterations in intestinal microbiota were characterized using 16S rRNA Illumina paired-end sequencing, followed by custom principal components analyses. Results Gut microbial community structure was markedly different in both antibiotic treatment groups, compared to controls. Directly following antibiotic administration, neomycin-treated rats were colonized by high numbers of Sphingomonas species and showed a loss in Lactobacillus species; chloramphenicol-treated rats were highly colonized by Klebsiella species. Urinary calcium increased in both antibiotic treatment groups, and was most pronounced immediately after antibiotic administration. Conclusions Treatment with either neomycin or chloramphenicol significantly altered the gut microbiome compared to control rats. This is consistent with classical studies that suggested intestinal microbes may impact nutrient absorption, and that use of oral antibiotics may alter urinary concentrations of calcium. These data indicate that we have designed a model in which to further test the role of gut microbiota in modulating urinary calcium, and may provide a path to novel therapies for nephrolithiasis patients. Funding University of Florida Department of Urology
Authors
Ryan Chastain-Gross
Pedro Espino-Grosso Paul Dominguez-Gutierrez John Asplin Vincent Bird Saeed Khan Benjamin Canales |
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MP12-14 |
The upper urinary tract microbiome is modulated by stone type and patient age in urinary stone disease: A pilot study |
Stone Disease: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP12-14 Sources of Funding: NIH P20-DK-100863 (TC), NIH R21-DK-109433 (TC), and NIH K12-DK-07-006: Multidisciplinary K12 Urologic Research Career Development Program (TC)_x000D_ Introduction Microbiomes refer to the collective microorganisms resident in a particular environment. They are found in all exposed tissues of the human body including the gastrointestinal, respiratory and urogenital tract. Microbiomes play a critical role in the maintenance of health and development of disease. However, the upper urinary tract microbiome has not been explored. Our objective was to define the upper urinary tract microbiome for urinary stone patients and examine its association with patient characteristics. Methods After institutional IRB approval was obtained, urine and renal stone fragments were prospectively collected from nephrolithiasis patients who underwent endoscopic stone removal at our institution. Patients were excluded who had a history of antibiotic or steroid medication exposure within 6 months prior to surgery. Specimens were immediately preserved with RNAlater solution and stored at -80°C. For analysis, specimens were homogenized and underwent DNA extraction and PCR amplification. 16S ribosomal RNA sequencing with Illumina NextSeq (Illumina Inc.) targeted at the V4 hypervariable region was used for microbiome identification. Resultant microbiome colonization patterns were then expressed in operation taxonomic units. Results 6 urinary stone patients enrolled into this study consisted of 5 males and 1 female, with a mean age of 55.8±14.4 years and a mean BMI of 29.3±3.6 kg/m2. 30 from 33 patient specimens (91%) demonstrated DNA quality above the threshold for extraction and were included in the analysis. A distinct microbiome was associated with kidney specimens and mainly consisted of Proteobacteria, Firmicutes, Bacteroides, and Actinobacteria. Microbial community differences were most strongly associated with patient age (p <0.05). A significant trend of alpha diversity stratifying bladder urine and stone fragment specimens between calcium oxalate versus uric acid stone formers was also seen. _x000D_ Conclusions This pilot study confirmed the presence of microbiome communities in the upper urinary tract for nephrolithiasis patients. Differences in these microbial communities exist and are associated with patient age and stone type. Larger scale analyses are ongoing to validate these findings and verify how the microbiome plays a role in stone formation. Funding NIH P20-DK-100863 (TC), NIH R21-DK-109433 (TC), and NIH K12-DK-07-006: Multidisciplinary K12 Urologic Research Career Development Program (TC)_x000D_
Authors
Manint Usawachintachit
Douglas Fadrosh Susan Lynch Thomas Chi |
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MP12-15 |
Comparative metagenomics of the gut microbiome reveals broad scale changes after exposure to high levels of oxalate |
Stone Disease: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP12-15 Sources of Funding: NIH 1F32DK102277-01A1 _x000D_ Lerner Research Institute Seed funds Introduction The impact of a high oxalate content diet on the gastrointestinal microbiome is unknown. Our objective was to elucidate the changes to the microbial metagenome after exposure to high levels of dietary oxalate in vivo. _x000D_ Methods The metagenomic effects of oxalate on the gut microbiota was studied in the wild mammalian herbivore, Neotoma albigula, a species that regularly consumes high levels of oxalate in the wild and harbors a highly effective oxalate-degrading gut microbiota. Four animals fed a 0.2% oxalate diet for six months prior to the experiment were gradually acclimated to a 6% oxalate diet over the course of nine days. Fecal samples were collected before addition of oxalate and at the end of a five-day period on a 6% oxalate diet for shotgun metagenomic sequencing on an Illumina HiSeq platform. Assembled sequencing data were annotated, normalized with a negative binomial Wald test (DeSeq2), and the differential abundance of genes were compared between the two oxalate diets. Results Over the course of the diet trial, animals maintained an oxalate-degrading capacity of nearly 100% of the dietary oxalate consumed. Sequencing effort resulted in 390 million sequence reads across four animals and two time points, with >50,000 unique protein-coding sequences. High oxalate exposure corresponded to a significant shift in the abundance of ~1% of genes identified within the metagenome. Affected genes included several involved in building cellular components, transmembrane transportation, nutrient assimilation, and others. Conclusions Our results show that oxalate exhibits broad stimulatory and inhibitory effects on the metagenome of the gut microbiota beyond just that of the oxalate-degrading bacteria. These results can inform the development of probiotics, synbiotics, and dietary strategies designed to maximize microbial oxalate metabolism, along with diagnostic biomarkers indicative of effective or poor microbial oxalate metabolism for patients with recurrent calcium oxalate stone episodes. Funding NIH 1F32DK102277-01A1 _x000D_ Lerner Research Institute Seed funds
Authors
Aaron Miller
Anna Zampini Manoj Monga |
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MP12-16 |
Nnt gene suppresses oxidative stress and kidney crystal deposition. |
Stone Disease: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP12-16 Sources of Funding: none Introduction We reported previously that the mouse has a strong defense system against kidney crystal deposition. By investigating subtle genetic differences between mice substrains C57BL/6J(B6J) and C57BL/6N(B6N), we identified nicotinamide nucleotide transhydrogenase (Nnt) as a new kidney stone candidate gene to elucidate the possibility of inhibiting kidney stone formation. Here, we focused on this cellular disorder. Methods Eight-week-old male B6J and B6N mice (n = 15 in each group) were used in this study. Renal calcium oxalate monohydrate crystal deposition was induced with a daily intra-abdominal injection of 80 mg/kg glyoxylate for 12 days. Every 6 days, animals were euthanized and renal specimens were collected. Kidney cross-sections were observed by polarized-light optical microphotography, and crystal regions with strong birefringence were measured and expressed as percentages of the total tissue area of the renal cross-section, using NIH Image software. Total RNA was isolated from glyoxylate-treated kidneys and reverse-transcribed into double-stranded cDNA. In another study, renal specimens were fixed with methacarn and reactive oxygen species (ROS) activity was investigated using a Carbonyl Protein Immunostaining Kit®. In addition, the changes in oxidative stress in the kidney, using superoxide dismutase-1 (SOD-1) and malondialdehyde (MDA) as markers, were compared by immunostaining and western blotting. Results Numerous kidney crystal depositions in the renal tubules were detected in both B6J and B6N mice. The number of crystal depositions was greatest after 12 days of treatment, and the crystal count was 16.2-fold higher in B6J mice than in B6N mice. ROS activity in the kidney revealed strong activity throughout the kidney tissue and a slightly higher tendency in B6J. SOD-1 and MDA expression in the kidney was observed in the renal tubular epithelial cells and did not differ significantly between the B6J and B6N mice. Conclusions The decreased expression of Nnt observed in B6J mice is also present in humans. Nnt expression reduces intracellular ROS in the mitochondria. ROS is increased by decreased Nnt expression, while kidney stone formation is predicted to be promoted. Although the findings of this study showed the same tendency, it was not possible to recognize a clear difference between the sub-systems. Further analysis of the Nnt gene may facilitate elucidation of the pathogenesis of kidney stones. Funding none
Authors
Masayuki Usami
Yuya Ota Teruaki Sugino Rei Unno Kazumi Taguchi Shuzo Hamamoto Ryosuke Ando Atsushi Okada Hideki Honma Keiichi Tozawa Kenjiro Kohri Takahiro Yasui |
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MP12-17 |
Proteomic analysis of kidney stones from male and female brushite (M-BR and F-BR) and male calcium oxalate (M-CaOx) patients |
Stone Disease: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP12-17 Sources of Funding: NIH P01 DK056788 Introduction Brushite stone disease is rare, but apparently increasing in Western countries. Why some patients form their stones of brushite is unknown. We sought to identify proteins that might be involved uniquely in brushite stone formation. Methods Micro-CT characterized stone specimens from 15 patients (5 M-BR, 5 F-BR, 5 M-CaOx) were used, 2 from each patient except for 1 M-CaOx, for which enough material was available for only 1 specimen. These 29 stone specimens were ground to fine powder and protein was extracted using sonication in 8M urea and 10 mM dithiothreitol. Protein extracts were digested with trypsin and analyzed using label-free quantitative mass spectrometry via LC-MS/MS. The acquired data were searched against the UniProt protein sequence database of HUMAN using X!Tandem algorithms in the Trans-Proteomic Pipeline. Results 1,941 unique protein database entries representing 1,812 unique gene products were identified, quantified, and statistically compared. Of these, 1,004 proteins were detected and quantified in all three groups, mean abundances compared by ANOVA, and fold-differences calculated. M-CaOx stone matrix had the largest number (305) of unique protein types while M-BR and F-BR proteins were least different. Significant differences in the abundance of both commonly detected and previously unreported stone matrix proteins were observed between groups that suggest differential stone-formation mechanisms. Overall, proteins in brushite stones were more likely to be of cellular origin, while proteins in CaOx stones were more likely to be those typically found in urine. Conclusions We found a number of proteins that differed significantly between CaOx and BR stones. Most of these were membrane or cytoplasmic proteins that were higher in brushite stones than in CaOx. These proteins could simply reflect the increased cell damage that has been shown to be a part of brushite stone disease, but they are also candidates to explain the formation of this unusual mineral in this aggressive form of stone disease. Funding NIH P01 DK056788
Authors
Frank Witzmann
James Lingeman Andrew Evan Fredric Coe Elaine Worcester James Williams |
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MP12-18 |
Calcium Oxalate and Hydroxyapatite Have Opposite Effects on Human Macrophage Differentiation |
Stone Disease: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP12-18 Sources of Funding: 2016 Urology Care Foundation Research Scholar Award Introduction Hydroxyapatite (HA) is a common constituent of most idiopathic calcium oxalate (CaOx) stones. It is frequently found at the CaOx crystal nucleation site deep within a stone and acts as suitable nucleator of CaOx in vitro. Although most crystal deposits within tissue produce inflammation (brushite and calcium oxalate), renal interstitial HA deposits in idiopathic calcium oxalate stone formers do not produce inflammation but instead accumulate within the interstitium as Randall&[prime]s plaque. To further explore this lack of response, we investigated the effect of oxalate and hydroxyapatite to differentiate primary human monocyte to macrophages. Methods In hexaplet, primary human monocytes were exposed to 0.5, 1.0, 2.0, and 3.0mM of CaOx and HA crystals. GM-CSF and M-CSF were included as positive controls for M1 and M2 macrophage differentiation respectively. At day 6, macrophages were washed 3 times with PBS to remove any undifferenced monocytes, and 200ng of LPS from S. enterica serotype Minnesota Re595 was added to half of each treatment group. After 4hrs, total RNA was collected, and cytokine expression was analyzed by qPCR. Results By day 3, monocytes exposed to CaOx and HA displayed macrophage morphology. At day 6, CaOx, HA, GM-CSF, and M-CSF displayed complete macrophage morphology (Figure). CaOx differentiates macrophages displayed similar inflammatory cytokine (TNFα, IL-6, and IL-1β) expression as GM-CSF; both displayed several hundred-fold greater inflammatory cytokine expression than HA and M-CSF differentiated macrophages. Conclusions In our immunological model for stone formation, CaOx and HA display competing immunological effects. HA induces tissue healing (M2)-like macrophages whereas CaOx induces inflammatory (M1)-like macrophages. In the context of Randall's plaque, we speculate that luminal CaOx crystals induce this potent M1 inflammatory response in monocytes, which can trigger renal epithelial cell production of HA. This HA (Randall&[prime]s plaque) induces monocyte differentiation into tissue healing (M2) macrophages, blocking further M1 inflammation. This may explain the lack of significant papillary inflammation in the pathogenesis of CaOx stone formation. Funding 2016 Urology Care Foundation Research Scholar Award
Authors
Paul Dominguez-Gutierrez
Sergei Kusmartsev Benjamin Canales Saeed Khan |
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MP12-19 |
Calcium Oxalate Crystals Induce Mitochondrial Dysfunction and Heme Oxygenase?1 Expression in a Human Monocyte Derived Cell Line |
Stone Disease: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP12-19 Sources of Funding: UAB Department of Urology, K01DK106284 (TM). Introduction Monocytes and macrophages are essential for renal crystal clearance and are recruited into the renal interstitium during this process. Mitochondria are critical for monocyte function during the immune response and oxidative stress cell signaling. Heme oxygenase-1 (HO-1) and manganese superoxide dismutase (MnSOD) are inducible stress response proteins that have been shown to be involved in mitochondrial and anti?inflammatory signaling. We recently demonstrated that monocyte mitochondrial function is decreased in calcium oxalate (CaOx) stone formers when compared to healthy subjects. The objective of this study was to determine whether CaOx crystals alter mitochondrial function, cell viability, and expression of HO-1 and MnSOD in THP-1 cells, a human monocyte derived cell line. Methods To test this hypothesis, THP-1 cells were treated with CaOx crystals (0 μg, 50 μg, 100 μg, 200 μg, 500 μg, 1000 μg) for 24 hours prior to measuring mitochondrial function (Seahorse XF96 technology), cell viability (Trypan Blue), and HO-1 and MnSOD expression (Western Blotting). These experiments were repeated in triplicate. Results Exposing CaOx crystals to THP-1 cells caused a dose dependent decrease in mitochondrial function and cell viability (p < 0.05). Both HO-1 and MnSOD protein levels were significantly increased in a dose dependent fashion with CaOx crystal treatment (p < 0.05). Furthermore, HO-1 levels were upregulated to a greater extent than MnSOD levels with increased crystal exposure. Conclusions In summary, CaOx crystals appear to decrease mitochondrial function and cell viability and induce stress response proteins in THP-1 monocytes. These findings provide potential mechanisms responsible for mitochondrial dysfunction observed in monocytes from CaOx stone formers. Funding UAB Department of Urology, K01DK106284 (TM).
Authors
Vidhush K Yarlagadda
Dean G Assimos Ross P Holmes Tanecia R Mitchell |
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MP12-20 |
Optimizing RNA extraction of renal papilla biopsy tissue in kidney stone formers: a new methodology for genomic study |
Stone Disease: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP12-20 Sources of Funding: the NIH K12-DK-07-006 and P20-DK-100863, JSPS KAKENHI Grant #16K11054 Introduction Endoscopic tools have provided versatile examination and treatment for kidney stones. Desptie endourologists performing translational research in urinary stone disease using endoscopes to collect tissue, the genomic basis for lithogenesis remains unknown. One challenge is the limited tissue that can be endoscopically removed from the papilla. We investigated a new method of renal papilla biopsy and RNA extraction to establish a genomic research methodology for kidney stone disease. Methods We conducted a prospective multi-institutional study between Japan and the United States and collected renal papilla specimens from consecutive percutaneous nephrolithotomy (PCNL) and ureteroscopy (URS) cases performed for removal of upper urinary tract stones. Renal papilla tissue was extracted using ureteroscopic biopsy forceps after stone removal. The biopsied tissues were immediately stored in RNAlater® for prevention of RNA degeneration. RNA was then extracted using 3 different extraction kits. The quantity and quality of RNA were examined by NanoDropTM for comparison. The impact of biopsy on surgical complications was also compared between cases performed with and without papillary biopsy extraction. Results A total of 87 biopsies from 44 patients were performed at 5 institutions between September 2014 and August 2016. Forty-four specimens were biopsied from normal papilla tissue whereas 43 were from Randall&[prime]s plaque lesions. The mean patient age was 52.4 ± 14.8 years old, 28 patients were males and 16 females, and mean duration between specimen collection and RNA extraction was 106 ± 113 days. One third of biopsies were performed during URS. Univariate analysis showed biopsy from PCNL had larger total yield of RNA compared to URS: 1117 ng and 415 ng, respectively (p=0.023). Both univariate and multivariate analyses revealed that usage of the RNeasy Micro Kit® and BIGopsy® forceps significantly increased total yield and improved A260/230 ratio of extracted RNA (p<0.01), enabling ideal quantities and quality of RNA purified. There were no associations between specimen storage duration prior to RNA extraction and total yield or A260/230 ratio. Moreover, comparing 18 patients who received a biopsy to 113 who received a procedure with no biopsy, there were no differences in peri- and postoperative parameters, including procedure time (p=0.139), stone free rate (p=0.061), and complications (p=0.353). Conclusions We established a methodology for optimal RNA extraction of renal papilla tissue during URS and PCNL. We believe this will accelerate genomic studies for kidney stone formers. Funding the NIH K12-DK-07-006 and P20-DK-100863, JSPS KAKENHI Grant #16K11054
Authors
Kazumi Taguchi
Manint Usawachintachit David T Tzou Benjamin A Sherer Sunita Ho Shuzo Hamamoto Takahiro Yasui Marshall L Stoller Thomas Chi |
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MP13-01 |
COMPARISON OF A MEXICAN VISUAL ANALOG SCALE (GEA SCALE) VS IPSS (NTERNATIONAL PROSTATE SYMPTOM SCORE) IN THE EVALUATION OF LOWER URINARY TRACT SYMPTOMS IN A LOW SOCIO-CULTURAL LEVEL POPULATION |
Benign Prostatic Hyperplasia: Epidemiology & Evaluation | 17BOS |
Abstract: MP13-01 Sources of Funding: None Introduction _x000D_ The World Health Organization approved the International Prostate Symptom Score (IPSS) to evaluate lower urinary tract symptoms (LUTS). This scale was developed in industrialized populations. However, there are populations around the world where there may be language and comprehension barriers in interpreting the IPSS making it less reliable. The objective of this study is to compare IPSS versus a new Visual Analog Scale (Gea Scale) and establishing which is more understandable for patients_x000D_ Methods _x000D_ A transversal, descriptive and comparative study was developed in Gea Gonzalez Hospital. Men> 45 years of age with LUTS were evaluated using 2 clinical tools: IPSS and the GEA scale which was developed with the collaboration of both: a graphic designer and a phoniatrist. Both tools were applied to each patient recording sociodemographic variables, understanding, ability to respond for themselves, accuracy and response time. Statistical analysis was performed using SPSS software (version 22.0)._x000D_ Results _x000D_ 151 men with LUTS were included, with the following results: age 67 (± 11.09), seven years schooling (± 2.5), 35% unemployed, 8% native american dialect speakers (nahuatl, mazateco and otomi). 63 patients (42%) sought help to answer IPSS questions because of socio-intellectual limitations. In contrast 87% (131) of men completed the GEA Scale while only 16 (10%) asked for help and 3 (1.9%) did not complete it because of visual / intellectual barriers (x2 = 11.68, df = 1, p <0.05). The average time to complete the IPSS was 4.8 minutes compared to 2.6 minutes for the Gea Scale (Student t 19.64, df 118, p <0.05)._x000D_ Conclusions _x000D_ The use of the Gea Scale to evaluate LUTS may be a useful and innovative adjunct to evaluate LUTS in populations with cultural or academic constraints. The results reported herein suggest that the GEA scale was more useful than the IPSS both in time and qualitative responsiveness in a population of men with intellectual, linguistic, academic or sensory limitations._x000D_ Funding None
Authors
Diego Preciado Estrella
Steven Kaplan Edgar Mayorga Gómez Mauricio Cantellano Orozco Carlos Martínez Arroyo Carlos Pacheco Gahbler |
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MP13-02 |
Is Postoperative Urinary Retention an Independent Predictor of Long-Term Future Bladder Outlet Procedure in Men? |
Benign Prostatic Hyperplasia: Epidemiology & Evaluation | 17BOS |
Abstract: MP13-02 Sources of Funding: None Introduction Postoperative urinary retention (POUR) is a common complication across surgical specialties. To date, no literature has examined POUR as a predictor of long-term receipt of surgery for bladder outlet obstruction. Methods We performed a retrospective review of patients who underwent major inpatient, non-urologic surgery in California between 2008-2010. Patients were excluded for confounding urologic conditions (eg, bladder cancer, prostate cancer, prior bladder outlet procedures, etc). Patients were identified who developed POUR during their index admission, as were those who on a subsequent encounter underwent a bladder outlet procedure (BOP; transurethral resection of prostate, photoselective vaporization of prostate, suprapubic prostatectomy). Multivariate logistic regression was performed to identify predictors of subsequent bladder outlet procedure. Kaplan-Meier time-to-event analysis was performed to determine the cumulative incidence of subsequent BOP by patient groups (Group A: Age ≥ 60 years, POUR; Group B: Age ≥ 60 years, no POUR; Group C: Age < 60 years, POUR; Group D: Age < 60 years, no POUR). Results Of 769,141 eligible male patients, 8,051 (1.1%) developed POUR. Following discharge 1,855 patients (0.24%) underwent a BOP. BOP patients were significantly more likely to have experienced POUR during their index admission (6.3% vs 1.0%, p<0.001). Within 90 days, BOP was performed on 1.5% of Group A, compared to 0.2% of Group B (p<0.001). Within three years, rates of BOP were 7.0%, 2.1%, 0.8%, and 0.2% in Groups A-D, respectively (Figure). On multivariate analysis, the strongest predictors of subsequent BOP were age ≥ 60 years (OR 7.80, 95% CI 6.50-9.37) and POUR (OR 4.05, 95% CI 3.34-4.92). Conclusions In men aged ≥ 60 years, postoperative urinary retention identifies patients with an increased incidence of bladder outlet procedures within 3 months, as well as within three years. Men < 60 years have a low rate of subsequent bladder outlet procedure, regardless of postoperative urinary retention diagnosis. Funding None
Authors
Robert H Blackwell
Srikanth Vedachalam Arpeet S Shah Anai N Kothari Paul C Kuo Gopal N Gupta Thomas MT Turk |
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MP13-03 |
Association between male lower urinary tract symptoms and the imbalance of autonomic activity |
Benign Prostatic Hyperplasia: Epidemiology & Evaluation | 17BOS |
Abstract: MP13-03 Sources of Funding: none Introduction Some previous studies suggested that the associations between lower urinary tract symptoms (LUTS) and autonomic nervous function. The heart rate variability (HRV) is a noninvasive tool for measuring autonomic nervous activity and low frequency / high frequency (LF/HF) ratio is known to be a marker that mirrors the balance of sympathetic and parasympathetic nervous activities. The purpose of this study is to evaluate the changes of autonomic functions according to the LUTS treatment. Methods 108 male volunteers with LUTS defined as International prostate symptom score over 8 were screened. Electrocardiographic signals were obtained from subjects in resting state for the analysis of their HRV. HRV parameters were analyzed to evaluate autonomic functions. We divided them into two groups by LF/HF ratio 1.6 after initial measurement. After the administration of alfuzosin 10mg once a day for 12 weeks, we evaluated HRV to investigate changes of autonomic functions. Results Total 95 LUTS patients who completed this study were enrolled. 54 subjects with LF/HF ratio under or equal 1.6 were allocated to group A and 41 patients with LF/HF ratio over 1.6 were allocated to group B. There were no statistical differences in serum PSA, volume of prostate, maximal urine flow rate between two groups. There was no statistical difference in improvement of peak urine flow rate, IPSS after treatment with alfuzosin 10mg for 12 weeks. The average LF/HF ratio of group A was increased from 0.89 ± 0.40 to 1.79 ± 1.80, however it was decreased from 3.93 ± 5.47 to 1.79 ± 1.15 in group B. Conclusions LF/HF ratios of both groups were merged to similar values after treatments of male LUTS in this study. This study suggests that the imbalance of autonomic activity may be associated with LUTS and the efficacy of LUTS treatment. Funding none
Authors
Seol Ho Choo
Se Joong Kim Jong Bo Choi Sun Il Kim Hyun Soo Ahn Taewoo Kim |
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MP13-04 |
Risk factors of weak detrusor function in benign prostate hyperplasia patients: Determining a prognostic factor from urodynamic findings. |
Benign Prostatic Hyperplasia: Epidemiology & Evaluation | 17BOS |
Abstract: MP13-04 Sources of Funding: none Introduction Benign Prostate Hyperplasia (BPH) is a major cause of Lower Urinary Tract Symptoms (LUTS) in men and surgical treatment is often required. However, due to long terms of difficulty, some patients show very weak detrusor functions. The aim of this study is to determine risk factors of low detrusor function._x000D_ Methods We retrospectively reviewed 345 patients who were clinically diagnosed as BPH and videourodynamic studies (V-UDSs) was performed between 2008 and 2016. Age, prostate volume, post-voided residual urine (PRV) were evaluated. As the UDS parameters, mean bladder compliance, mean abdominal leak point pressure, Qmax, and Pdetmax were evaluated. The Schafer&[prime]s nomogram was used to evaluate the obstruction of lower urinary tract. The correlations among age, prostate volume, and V-UDSs findings were evaluated to determine the causal factor of weak detrusor function. The results of V-UDSs were compared among the groups. Spearman's rank correlation coefficient was used to evaluate the correlations. UDS findings were compared among the divided groups using unpaired t-tests. Results The mean value of prostate volume was 39ml. Mean PVR was 97ml and 102 patients had more than 100ml of PVR. During the filling phase 79 patients had detrusor overactivity (DO). 70 patients showed decrease in urinary sensation. As the result of Schafer`s nomogram, 254 patients had a stronger obstruction than grade 3 and 102 patients had a lower detrusor function than weak. Patients who had DO had a tendency of weak detrusor. Although the values of age and prostate volume did not show a correlation with UDSs findings including obstruction and weak detrusor, age and detrusor, prostate volume and obstruction showed a correlation(Fig 1). Compared by age, 78 years old was a cut off of weak detrusor (Fig 2.3). Conclusions From this study, high age and the presence of DO was a risk factor for weaker detrusor. Elderly who have DO may need surgical treatment in an early stage. Funding none
Authors
Tetsuichi Saito
Takashi Nagai Tomonori Minagawa Teruyuki Ogawa Osamu Ishizuka |
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MP13-05 |
Clinical -not cystometric- prediction of bladder outflow obstruction in elderly male patients. |
Benign Prostatic Hyperplasia: Epidemiology & Evaluation | 17BOS |
Abstract: MP13-05 Sources of Funding: none Introduction Initial management of LUTS in elderly male may be pragmatic with lifestyle management and medication. This is frequently successful however when the patients are still symptomatic and or worried about the safety of this initial treatment it might be useful to be able to estimate the likelihood of serious bladder outflow obstruction (BOO). With the hypothesis that patients with higher grade of outflow obstruction are more likely to fail conservative (& pharmaco-therapeutic) management we tested whether clinical of symptom parameters were suitable to predict moderate and high grade BOO (hgBOO) in the elderly male patients. Methods 452 elderly male patients referred with LUTS had IPSS, flowmetry (Qmax) and transrectal ultrasound prostate volume measurement (TRUS). Mean age (sd) was 64.8y (11.2) Qmax 11.8mL/s (6.6) and TRUS 41.7cm3(23.9). All patients underwent standard cystometry and pressure flow analysis. A cut off URA value of 40cmH2O was taken for hgBOO (similar=: linPURR>3) Results ROC curve showed that TRUS and Qmax were better than IPSS to diagnose hgBOO and the combination of these to into CLIPS (TRUS-3*Qmax) further increased the diagnostic power, with ROC area .76.(Note that Qmax projects negative because a higher value is 'better') Conclusions CLInical Prostate Score= (prostate volume - 3*Qmax) is a far better predictor of high grade BOO than totalIPSS-score. Funding none
Authors
Peter Rosier
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MP13-06 |
Pharmacological treatment of Lower Urinary Tract Symptoms after a Transurethral Resection of the prostate is predictive of a new surgical treatment: 10 years follow-up |
Benign Prostatic Hyperplasia: Epidemiology & Evaluation | 17BOS |
Abstract: MP13-06 Sources of Funding: none Introduction To evaluate the long-term (at least 10 years) characteristics of patients with persistent LUTS after a TURP and continue their medical therapy post-operatively. Methods A consecutive series of patients with LUTS and Benign prostatic enlargement (BPE) underwent TURP in our center in 2004-2005 and they were then followed up to 2016. Patients were assessed at baseline, 3-, 6- months post-operatively and yearly thereafter with medical history (concomitant medication, reintervention), IPSS, PSA, prostate volume, maximal urinary flow rate (Qmax), post void residual urine (PVR). Reoperation was defined as the requirement of a new TURP to relieve bothersome LUTS. Multivariate logistic regression was used to determine covariates associated with reoperation rate and the Kaplan-Meier curve assessed the time to reoperation. Results Overall 92 patients were enrolled. Mean age was 79 ± 7 years; mean PSA was 3.2 ± 2.5 ng/ml; mean TRUS volume was 57.5 ± 18.6 ml; mean Qmax was 8.7 ± 4 ml/s; mean IPPS was 23 ± 6 respectively at baseline. Mean follow-up was 140 ± 8 months (median 142 months). Overall 20/92 (21.7%) patients received medical treatment (alpha-blockers and/or 5 alpha-reductase inhibitors) after TURP. 13 patients underwent re-TURP during follow-up (reoperation rate was 14%); out of them 9/13 (69%) received medical treatment for persistent LUTS, while the remaining 4 patients received no additional pharmacological treatment (p = 0.001). Out of the 13 patients treated with re-TURP, 12 (92%) underwent surgery within 5 years of follow-up. Median time to reintervention was 26 months, interquartile range 14/46. The need of LUTS/BPE pharmacological treatment after TURP is an independent risk factor for re-intervention (Odds Ratio 13.93; 95% Confidence Interval 3.63-53.48, p= 0.000). Cumulative re-TURP free probability, according to post-operative continuing medical treatment, is showed in Figure 1. Conclusions In our study, a small number of patients (21.7%) still required pharmacological treatment for persistent LUTS. This need was a predictive factor of a re-TURP. Considering that more that 90% of re-TURP were performed during the first 5 years of follow-up, it is assumable that a follow-up longer than 5 years is not needed in such group of patients. Funding none
Authors
Cosimo De Nunzio
Alessandro Borghesi Fabrizio Presicce Riccardo Lombardo Fabiana Cancrini Luca Sarchi Andrea Tubaro |
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MP13-07 |
Finasteride Monotherapy before TURP: Significant Improvement in Early Postoperative Quality of Life |
Benign Prostatic Hyperplasia: Epidemiology & Evaluation | 17BOS |
Abstract: MP13-07 Sources of Funding: None. Introduction Introduction: Benign prostatic hyperplasia (BPH) is a common disease affecting men 50 years and older. Treatment options consist of observation, pharmacological treatment, minimally invasive surgery and traditional surgery. Alpha-blockers and 5-alpha-reductase inhibitors are the primary medications used to treat BPH. Transurethral resection of the prostate (TURP) is the gold standard of surgical management of BPH. We sought to evaluate the effect of six weeks of finasteride therapy before TURP on overall surgical outcomes and early postoperative quality of life (QoL). Methods Between June 2011 and August 2013, patients with BPH at the urology department, Minia University Hospital, were randomly assigned to one of two groups: those receiving 5 mg of Finasteride daily for six weeks (group A) and those not receiving finasteride (group B) before TURP. All patients were assessed using a modified validated Arabic version of the International Prostate Symptom Score (IPSS). Intra operative serum hemoglobin concentration and hemoglobin concentration in irrigating fluid were recorded. On the first postoperative day, serum hemoglobin concentration, corrected by postoperative hematocrit values, was evaluated. One month post-surgery, IPSS, storage and voiding subscores and QoL scores were measured. Results We recruited 115 patients, of whom 98 completed the study. Before surgery, there was no significant difference between the two groups in prostate size, IPSS, maximum urinary flow rate, post-void residual urine test results or QoL scores. Group A patients had significantly less intraoperative blood loss than group B patients (p= 0.001). One month postoperatively, there was no significant difference in IPSS results or voiding and storage subscores between the two groups. However, group A patients showed greater improvement in QoL than group B patients (p = 0.03). Conclusions Short-term finasteride therapy for 6 weeks before TURP reduced intraoperative blood loss and improved quality of life in the early postoperative period. Funding None.
Authors
Ahmed Ali
Emad Ramadan Mamdouh El-Hawy tarek fathelbab Alayman Hussein Luay Alshara Ahmed Fawzy Ehab Tawfiek |
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MP13-08 |
Surgeon behavior and surgical modality drive variation in the surgical management of BPH |
Benign Prostatic Hyperplasia: Epidemiology & Evaluation | 17BOS |
Abstract: MP13-08 Sources of Funding: none Introduction Identifying actionable variability in care is critical to standardizing treatment and controlling cost. As our institution moves toward bundled payments for benign prostatic hyperplasia (BPH) surgery, it is important to assess the relationship between clinical factors, physician preference, and cost of care. Methods Using time-driven activity-based costing of 358 complete episodes of surgical care for BPH, a variation metric of episodic cost standard deviation divided by mean cost was calculated by surgeon, surgical technique, and prostate size._x000D_ Results Mean episodic cost and standard deviation were $3,529 +/- $570, yielding an overall variation metric of 0.16. Variation metrics ranged from 0.03-0.34 among 18 surgeons (Figure 1). The variation metric for 288 bipolar transurethral resections of prostate (TURPs) was 0.16, 0.10 for 41 laser vaporization, 0.09 for 20 monopolar TURPs, and 0.08 for 9 open prostatectomies (Figure 2). Based on prostate size, the variation metric ranged from 0.17 in prostates < 40 grams, 0.16 for glands between 40-80 grams, and 0.09 for glands > 80 grams. ANOVA with Tukey pairwise comparison revealed a significantly higher (p<0.05) average episodic cost between open prostatectomy and the 3 endoscopic techniques. There was no significant difference in episode cost based on prostate size among endoscopic approaches. Conclusions Variation in the surgical management of BPH appears to be predominantly driven by surgeon behavior and, to a lesser degree, surgical approach, at our institution. Prostate size does not appear to influence variation in the surgical management of BPH. Efforts focused on clarifying the cause of variation at the surgeon-level and based on surgical technique are most likely to yield standardized, high-value care. _x000D_ Funding none
Authors
Jamal Nabhani
Vishnukamal Golla Alan Kaplan Christopher Saigal |
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MP13-09 |
Assessment of the learning curves for prostate photoselective vaporization using GreenLightTM 180-Watt-XPS laser therapy: A Multicentric study |
Benign Prostatic Hyperplasia: Epidemiology & Evaluation | 17BOS |
Abstract: MP13-09 Sources of Funding: none Introduction Photoselective Vaporization of the Prostate (PVP) has been promoted as a valuable alternative to transurethral resection of the Prostate (TURP) and is considered an appropriate and effective treatment in men with moderate to severe LUTS. However the learning curve of this technique has never been evaluated accurately. The objective of this study was to evaluate the learning curve of PVP. Methods Multicenter retrospective study was conducted in the first patients treated with PVP by three operators in 3 different centers (Group 1: 152 patients, Group 2: 112 patients, Group 3: 101 patients). The learning curve was analyzed from the progression in time of quantitative variables: operative time (min), ratios vaporisation time (min)/operative time (%) and delivered energy (Joules)/prostate volume. We also compared the rate of complications (Clavien classification). The relationships between variables were modeled using analysis of covariance (software R 2. 14.2). Results The patients’ preoperative data differed significantly between each centers in terms of age, prostate volume and IPSS. There was no significate difference in operative time between the three centers (p=0,06). During the initial 50 cases for each center, a significantly increased in vaporisation time (min)/operative time (%) was observed. 75 patients were necessary to reach the goal of 66 to 80%. (Graphic 1) A significantly increased in energy delivery was observed (this increase appeared to plateau beyond the 50th case in group 3, beyond the 75th case in group 1 and beyond the 100th case in group 2) but a significant difference was observed in terms of energy ratio = Energy delivered / prostate volume (Graphic 2) : 3.2kJ / ml [ 2.5 , 4.1kJ] ( Montreal ) vs 2.5kJ / ml [ 1.7-3.0] ( Paris ) vs 4.1kJ / ml [ 2.9-5.2] (Toulouse) (p < 0.0001). (Figure 2) No differences were observed in terms of postoperative complications (17.6% vs. 22.3% vs. 19.8%; p=0.64)_x000D_ Conclusions This is the first study to support that the outcomes obtained during PVP learning curve may be influenced by patients and surgeons’ characteristics. In this study, 100 Greenlight 180-W XPS PVP procedures were required before to reach a plateau in intraoperative parameters. Funding none
Authors
Claire Bastard
Vincent Misrai Morgan Roupret Kevin Zorn Pierre Alain Hueber Benoit Peyronnet |
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MP13-10 |
Surgical management of benign prostatic obstruction: 20-year population-level trends |
Benign Prostatic Hyperplasia: Epidemiology & Evaluation | 17BOS |
Abstract: MP13-10 Sources of Funding: University of Toronto Functional Urology Research Group Introduction Benign prostatic obstruction (BPO) due to histologic benign prostatic hyperplasia is highly prevalent among older men. Despite widespread use of medical therapy, surgical treatment remains a mainstay in the management of BPO. We sought to characterise trends in the surgical management of BPO in a single-payer healthcare system in Ontario, Canada over a 20 year period. Methods We performed an interrupted time-series analysis using segmented regression among men aged 18 years and older undergoing surgical treatment for BPO between January 1, 1994 and December 31, 2014 in Ontario, Canada. The passage of time was considered the primary exposure. The primary outcome was the proportion of all BPO surgeries performed using each of the following modalities: transurethral resection of the prostate (TURP), endoscopic laser prostatectomy, open/laparoscopic prostatectomy, and others. Secondary outcomes included trends in the age and comorbidity of patients undergoing BPO surgery. Results We identified 136,459 men who underwent BPO surgery between 1994 and 2014. Across the study interval, the annual age-adjusted rate of BPO surgery declined significantly (24 per 10,000 population in 1995 to 10 per 10,000 population in 2014). We identified two distinct epochs with respect to treatment modality. From 1994 to 2001, there were no significant changes in the distribution of BPO surgical modalities with TURP the most common throughout (97.2% in 1994 and 97.0% in 2001). In the period 2002 to 2014, there was a significant decline in the use of TURP (92.1% to 76.9%; p=0.027) with a corresponding increase in the use of endoscopic laser prostatectomy (3.5% to 21.9%; p=0.0008). We identified small but statistically significant increases in the age (p=0.0004) and comorbidity (p<0.0001) of patients undergoing BPO surgery over time. Conclusions This large, population-based study demonstrates a shift in the management of BPO with increasing use of endoscopic laser prostatectomy, beginning in 2002. However, TURP remains the most common treatment modality. We also identified shifting demographics of patients undergoing BPO surgery with a trend for patients to be older and have greater comorbid disease at the time of surgery in more recent years. Funding University of Toronto Functional Urology Research Group
Authors
Christopher Wallis
Lesley Carr Sender Herschorn Refik Saskin Sidney Radomski Armando Lorenzo Robert Nam |
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MP13-11 |
Factors that influence on lower urinary tract symptom (LUTS) related quality of life (Qol) |
Benign Prostatic Hyperplasia: Epidemiology & Evaluation | 17BOS |
Abstract: MP13-11 Sources of Funding: none Introduction American urologic association symptom Index (AUA-SI) with the quality of life (QoL) item is the most widely used questionnaire for evaluating lower urinary tract symptom (LUTS). Symptom severity does not always account for negative impact on QoL, and someone have worse Qol scores although he has only mild LUTS. In this study, we evaluated the factors affecting the LUTS related QoL score. Methods This retrospective study analyzed 29,123 men who underwent health check-ups from January 2007 to July 2011 at a single institution. Those patients who completed the AUA-SI with QoL, Beck depression inventory (BDI) and state-trait anxiety inventory (STAI) questionnaires were included in the study. Men with a history of medication for LUTS were excluded from the study. Men who submitted QoL scores of 3 or higher in spite of mild LUTS (total AUA-SI score < 8) were defined as having a relatively worse QoL. Results Mean age of 21,390 men was 48.4 ± 9.5 years. Mean total AUA-SI score was 6.4 ± 5.9 points. The QoL score was well correlated with the total AUA-SI score (r = 0.705, p < 0.001). Among all AUA-SI items, AUA-SI item 1 (incomplete emptying, r = 0.600, p < 0.001) had the strongest correlation with QoL scores. On the multivariate analysis, hypertension, total AUA-SI score, BDI score, and trait anxiety score were found to be independent factors that influenced the QoL scores. A lower age, a higher PSA, a higher AUA-SI score and a higher BDI score were risk factors for relatively worse QoL scores in spite of mild LUTS. Conclusions Among the 7 items of AUA-SI, AUA-SI item 1 has the strongest correlation with a worse LUTS related QoL. Psychological status also influences the QoL scores. Funding none
Authors
Woo Suk Choi
Hyoung Keun Park Sung Hyun Paick Hyeong Gon Kim Hwancheol Son |
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MP13-12 |
Shift Workers with Shift Work Sleep Disorder Have Increased Lower Urinary Tract Symptoms |
Benign Prostatic Hyperplasia: Epidemiology & Evaluation | 17BOS |
Abstract: MP13-12 Sources of Funding: AWP is a K12 scholar supported by a Male Reproductive Health Research (MRHR) Career Development Physician-Scientist Award (Grant # HD073917-01) from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Program. Introduction Non-standard shift workers, who regularly work hours outside a 7am-6pm workday, have an increased risk of lower urinary tract symptoms (LUTS) relative to daytime workers, and are also at increased risk for shift work sleep disorder (SWSD), a primary circadian rhythm disorder indicated by excessive daytime sleepiness associated with shiftwork. Here we examine the association between SWSD and LUTS in shift workers. Methods Men presenting to a single andrology clinic between July 2014 and September 2016 completed questionnaires that assessed work schedule, SWSD risk, and LUTS (International Prostate Symptom Score (IPSS)). The impact of non-standard shift work and SWSD on IPSS score was assessed using ANOVA and linear regression. Results Of the 2,487 men who completed the questionnaires, 766 (30.8%) reported working non-standard shifts in the past month. Of these, 282 (36.8%) were diagnosed with SWSD. Cohort characteristics are described in Table 1. When controlling for age, comorbidities (via the Charlson Comorbidity Index), and testosterone (T) levels, non-standard shift work was not associated with worse LUTS (P=0.99). However, non-standard shift workers diagnosed with SWSD had IPSS scores 3.1 points higher than non-standard shift workers without SWSD (P<0.0001). Conclusions Non-standard shift workers diagnosed with SWSD have worse LUTS than those without SWSD, suggesting that poor sleep habits, rather than shift work itself, contribute to worse LUTS. Modification of work and sleep schedules may reduce the risk for SWSD and subsequent LUTS. Funding AWP is a K12 scholar supported by a Male Reproductive Health Research (MRHR) Career Development Physician-Scientist Award (Grant # HD073917-01) from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Program.
Authors
John Sigalos
Javier Santiago Edgar Kirby Mark Hockenberry Taylor Kohn Stephen Pickett Alexander Pastuszak Larry Lipshultz |
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MP13-13 |
Does treating nocturia lead to better sleep? Results from REDUCE |
Benign Prostatic Hyperplasia: Epidemiology & Evaluation | 17BOS |
Abstract: MP13-13 Sources of Funding: none Introduction Older men commonly complain of needing to urinate frequently during the night (nocturia) leading to a lack of sleep and not feeling rested in the morning. We assessed, within the context of REDUCE, a randomized controlled trial of dutasteride use, whether treating lower urinary tract symptoms (LUTS) with dutasteride altered either nocturia or sleep complaints. Methods REDUCE was a randomized trial comparing dutasteride 0.5mg/day vs. placebo for chemoprevention of prostate cancer. At baseline, 2-years and 4-years, men completed the International Prostate Symptom Score (IPSS) survey and the MOSSS-6 questionnaire, a 6-item scale that assesses sleep and is scored 1-100. To test the differences in IPSS (and specifically nocturia) and MOSSS over the study, we used linear mixed models with predictors of treatment, visit, and the interaction between treatment and visit. Models were adjusted for baseline age, digital rectal exam findings, PSA, body mass index, race, smoking status, prostate volume, diabetes, and geographical region. Linear contrasts were used to summarize the effect of treatment on each outcome at each study visit. Subanalyses were conducted in men who were symptomatic (IPSS ≥8) and men with ≥2 nocturia episodes a night at baseline. Results There were 6915 patients with complete baseline data. Baseline characteristics were balanced between treatment arms. Dutasteride resulted in significant improvements in IPSS at 2-years (p<0.001) and 4-years (p<0.001) as well as specifically nocturia episodes at 2-years and (p=0.005) 4-years (p<0.001). In contrast, treatment with dutasteride had no effect on overall sleep function nor any specific domain of sleep including feeling rested in the morning or getting enough sleep (p>0.1 at all visits). When analyses were limited to symptomatic men (IPSS ≥8) or men with ≥2 nocturia episodes per night, results were unchanged in that dutasteride improved LUTS including nocturia but had no effect on sleep function including feeling rested in the morning or getting enough sleep. Conclusions In men who complain of nocturia resulting in not getting enough sleep, treatment of LUTS with dutasteride significantly improves LUTS but has no effect on sleep including feeling rested in the morning or getting enough sleep. These results suggest in men with nocturia who complain of poor sleep, the poor sleep is not likely to be due to LUTS but rather likely represents a primary sleep problem. Consideration should be given to referring these men to sleep experts to evaluate for sleep problems like sleep apnea or insomnia. Funding none
Authors
Stephen Freedland
Lauren Howard Shalini Jha Daniel Moreira Gina-Maria Pomann Gerald Andriole Ramiro Castro-Santamaria Martin Hopp Claus Roehrborn |
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MP13-14 |
Studying the effect of Diabetes Mellitus type 2 on prostate related parameters: A prospective single institutional study. |
Benign Prostatic Hyperplasia: Epidemiology & Evaluation | 17BOS |
Abstract: MP13-14 Sources of Funding: none Introduction Diabetes mellitus (DM) is a serious culprit of male health. A positive association exists between clinical markers of BPH and DM. The aim of this work is to examine the effects of type 2 diabetes mellitus (DM) on the variables associated with prostatic growth including serum PSA, serum testosterone and prostate volume and to correlate these variables with the duration of diabetic treatment. Methods Our study was conducted over 3 months recruiting 501 men aged 55 years old or more, of which 207 patients had type 2 DM. Exclusion criteria were active urinary tract infection, suspicious rectal examination, urologic cancers, end organ damage and recent urologic manipulations. Serum PSA and serum testosterone were measured. Prostate volume was determined by abdominal ultrasonography using ellipsoid formula. This study was approved by the ethical committee and informed consents were obtained from participating patients. Results The mean patient age was 60.21 ± 5.95 years. The mean PSA, Testosterone and prostate volume for diabetic men were 2.3 ng/ ml, 3 ng/ ml and 56 grams respectively. These were 3.5 ng/ ml, 4 ng/ ml and 51 grams respectively for non-diabetics. (p 0.001, p 0.001, p 0.03 respectively). The mean PSA density was 0.049 ± 0.043 ng/ml/cm3 in diabetics versus 0.080 ± 0.056 ng/ml/cm3 in non-diabetics (p<0.001). As high BMI in diabetic patients was a confounding factor, multiple regression analysis was done (table 1), confirming the true significant correlation of DM with the studied parameters. Conclusions Type 2 D.M is significantly associated with lower serum PSA, Testosterone and larger prostate volume. Funding none
Authors
Ahmed Elabbady
Mohamed Mohieeldin Hashad Ahmed Kotb Ali Ghanem |
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MP13-15 |
The Relationship Between Sleep Disorders and Lower Urinary Tract Symptoms: Results from the National Health and Nutrition Examination Survey (NHANES) |
Benign Prostatic Hyperplasia: Epidemiology & Evaluation | 17BOS |
Abstract: MP13-15 Sources of Funding: NorthShore University Health System Introduction It has been demonstrated that sleep disorders (SDOs) are associated with the prevalence of nocturia in men. While previous literature supports that patients with obstructive sleep apnea (OSA), insomnia, and restless leg syndrome (RLS) are at increased risk of nocturia, the risk of daytime lower urinary tract symptoms (LUTS) in these groups has not been established. We sought to investigate the frequency of LUTS in men with and without different types of SDO. Methods We examined the National Health and Nutrition Examination Survey (NHANES) database between 2006-2008. Men age 18-70 years who completed the sleep questionnaires in addition to the prostate and kidney forms were included in the study. LUTS was defined as having one more of the following symptoms: hesitancy, incomplete emptying, or nocturia (>=2). Physician-diagnosed SDOs were self reported by patients. Statistical analyses were used to compare groups of men with and without a SDO. Results Of the 6185 men who completed all of the survey questions, 437 (7.1%) men reported a SDO. The clinical characteristics of men with and without a SDO are shown in Table 1. Men with SDOs were significantly older and significantly more likely to be Caucasian, have increased BMI and report more medical co-morbidities compared to men without SDOs. There was a significantly higher proportion of men with SDOs who reported nocturia compared to those without SDOs (39% vs 27.7%; p <.0001). Additionally, these men had a significantly higher risk of LUTS (including daytime LUTS) than men without SDOs (34.4% vs 22.8%, p <.0001). Men with OSA (31.7%) were significantly more likely to report >=2 LUTS compared to men with insomnia (18.2%) or RLS (12.5%) (p=.0002). Conclusions Older age, Caucasian race, elevated BMI, and increased comorbidity score appear to be associated with an increased risk of LUTS in men with SDOs. While men with SDOs report increased nocturia, they are also more likely to experience bothersome daytime LUTS. This is particularly relevant for men with OSA compared to other SDOs. Based upon the present data, clinicians should consider assessing LUTS in men with SDOs as intervention could improve both nighttime and daytime urinary symptoms. Funding NorthShore University Health System
Authors
Richard Fantus
Brian Helfand Chi-Hsiung Wang |
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MP13-16 |
Factors that Predispose to Lower Urinary Tract Symptoms in Diabetic Men: Results From The National Health and Nutrition Examination Survey (NHANES) |
Benign Prostatic Hyperplasia: Epidemiology & Evaluation | 17BOS |
Abstract: MP13-16 Sources of Funding: NorthShore University Health System Introduction It has been well established that diabetes mellitus (DM) is a significant risk factor for lower urinary tract symptoms (LUTS). However, data suggests that only approximately 50% of diabetics report bothersome LUTS. We sought to investigate the clinical characteristics that contribute to LUTS in men with diabetes. Methods The 2001-2008 National Health and Nutrition Examination Survey (NHANES) database was examined. The records of men age 18-70 years who completed the diabetes form in addition to the prostate and kidney forms were analyzed. LUTS was defined as having one or more of the following symptoms: hesitancy, incomplete emptying, or nocturia >=2). Patients' diabetes status, clinical characteristics and laboratory values were recorded. Statistical analyses was used to compare the frequency of clinical variables among diabetics with and without LUTS. Results 19202 patients met inclusion criteria including 1157 (6%) with DM. DM patients were significantly more likely to report hesitancy (12.2% vs 9.5%, p=0.012), nocturia (50.1% vs 25.4%, p<.001) but not incomplete emptying (83.6% vs 86.5%, p=.024) compared to non-DM patients. Diabetic men with LUTS were significantly older (63.5 vs 57.5 years, p<.001), more likely to be Caucasian (45.5% vs 28.2%, p=0.002) and more likely to report more medical co-morbidities (32% vs 29.1%, p=<.001) compared to non-DM patients without LUTS. Insulin did not alter the frequency of LUTS among DM patients (p>.05). Diabetic men with retinopathy were significantly more likely to report urinary hesitancy (38.9% vs 21.8%, p<.001), but significantly less likely to report incomplete emptying (21.9% vs 78.1%, p=.004) and >=2 different LUTS (23.1% vs 76.9%, p=.013). There was a similar trend in patients with diabetic nephropathy (defined as significant proteinuria) as shown in Table 1. Conclusions Increased age, Caucasian race and more medical co-morbidities are associated with an increased risk of LUTS in men with DM. While diabetics with evidence of end organ damage report an increase in specific urinary symptoms, they report fewer total number of LUTS. This data demonstrates the importance of screening diabetics for LUTS and suggests specific LUTS may be a harbinger of clinical deterioration in these patients. Funding NorthShore University Health System
Authors
Richard Fantus
Brian Helfand Chi-Hsiung Wang Brad Erickson |
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MP13-17 |
Catheter management after transurethral resection and ablation procedures for benign prostatic hyperplasia: Appropriateness criteria obtained using the RAND/UCLA Appropriateness Method |
Benign Prostatic Hyperplasia: Epidemiology & Evaluation | 17BOS |
Abstract: MP13-17 Sources of Funding: Agency for Healthcare Research & Quality (AHRQ) Introduction Transurethral prostate surgery is commonly used for treatment of benign prostate hyperplasia (BPH). While the procedure routinely involves urethral catheter placement, no guidelines exist to inform the duration of catheter use. For these reasons, we formally assessed the appropriateness of different timings for urethral catheter removal after transurethral resection or ablation of the prostate using the RAND/UCLA Appropriateness Method. Methods An 11-member expert panel reviewed a summary of the literature on this topic. Using a standardized, multi-round rating process from March through May 2015, the panel rated clinical scenarios for urethral catheter duration as appropriate (i.e., benefits outweigh risks), inappropriate, or of uncertain appropriateness. The appropriateness of various urethral catheter durations was examined across 4 clinical scenarios. Results Forty-four articles met inclusion criteria for our study (Figure). Based on our expert panel ratings (Table), urethral catheter removal and first trial of void on postoperative day 1 was appropriate for all scenarios except clinically-significant perforations. In this case, waiting until postoperative day 3 was deemed the earliest appropriate timing. Perforation was the only appropriate indication for waiting ≥7 days after surgery for initial catheter removal and trial of void. Waiting ≥3 days to remove the catheter for patients with or without pre-existing catheter needs, or for those with difficult catheter placement in the operating room, was rated as inappropriate. Conclusions We defined clinically-relevant guidance statements for the appropriateness of urethral catheter duration after transurethral prostate surgery. Given the lack of guidelines for catheter duration and this robust expert panel approach, our findings may serve to improve the consistency and quality of care for patients undergoing transurethral surgery for BPH. Funding Agency for Healthcare Research & Quality (AHRQ)
Authors
Ted Skolarus
Casey Dauw Karen Fowler Jason Mann Steven Bernstein Jennifer Meddings |
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MP13-18 |
Impacts of apolipoprotein A-1 and alpha-fetoprotein on the development of benign prostatic hyperplasia and lower urinary tract symptoms: Results from a high-volume health check-up database |
Benign Prostatic Hyperplasia: Epidemiology & Evaluation | 17BOS |
Abstract: MP13-18 Sources of Funding: none Introduction To investigate the reference ranges for prostate volume (PV) and annual PV change rate, and to clarify the risk factors for the development of benign prostatic hyperplasia/lower urinary tract symptoms (BPH/LUTS) in healthy Korean men. Methods A total of 11,222 healthy men who received transrectal ultrasonography at our hospital for a routine health check-up were included. Those with prior biopsies or surgery for prostate disease, or with BPH medication were excluded. BPH/LUTS was defined as International Prostate Symptom Score (IPSS)≥8 points and PV ≥30 mL. Results The prostate-specific antigen (PSA) level, PSA density, PV, transitional zone volume (TV), and transitional zone index (TZI) increased significantly with age. The annual PV growth rate was 0.48 cm3/year. Body mass index, PSA, basal metabolism, fat mass, apolipoprotein A-1, high-density lipoprotein, aspartate aminotransferase, creatine, and urine pH were statistically associated with PV. PSA, fat mass, apolipoprotein A-1, creatine, and urine pH were significant predictive factors for both PV and TV. _x000D_ For men aged >40 years without prostate cancer history and treatment for BPH/LUTS, TZI (Hazzad ration (HR) =1.02, p = 0.001), total IPSS (HR = 1.04, p = 0.004) and alpha-fetoprotein (AFP) (HR = 0.86, p=0.040) were significant risk factors for the development of BPH/LUTS within 5 years._x000D_ Conclusions This study showed that the TZI, total IPPS, and AFP were the major factors for the development of BPH/LUTS within 5 years in healthy Korean men. Funding none
Authors
Kwang Suk Lee
Kyo Chul Koo Do Kyung Kim Jongsoo Lee Jong Won Kim Jae Yong Jeong Sung Ku Kang Byung Ha Chung |
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MP13-19 |
Mediators of Prostatic Inflammation: Simultaneous Multiplex analysis of Urine and Serum Specimens |
Benign Prostatic Hyperplasia: Epidemiology & Evaluation | 17BOS |
Abstract: MP13-19 Sources of Funding: NIDDK U54 DK112079 Introduction Discovery of serum biomarkers for benign prostatic hyperplasia (BPH) is strongly pursued by the MTOPSProstatic Samples Analysis (MPSA) Consortium and other groups in order to discriminate BPH-related pathologies, identify risk of progressive disease; and personalized management of BPH-related LUTS. Compared to serum, urine collected non-invasively by the patient himself has obvious advantages as a suitable matrix for BPH biomarker discovery. Besides, proximity to prostate can permit selective contribution of BPH related proteins into urine. Here, we compared the distribution of prostatic inflammation mediators in the two biofluids obtained from a rat model. Methods Non-bacterial prostatic inflammation was induced by intraprostatic injection of formalin (50μL) or saline (sham) in three month- old male Sprague-Dawley rats (n=4 in each group). 12 hour night time urination pattern were noted in metabolic cage a day before injection and 7 days later. Urine and serum collected on 7th day was frozen prior to simultaneous multiplex analysis of 27 proteins using a MILLIPLEX MAP Rat Cytokine/Chemokine Panel kit (Millipore, Billerica, MA). Results Attached figure demonstrates that EGF, GM-CSF, IFN-γ, IL-1?, IL-10, IL-18 and eotaxin were abundant in urine, while undetectable in serum. Paired analysis of urine and serum levels from sham group against the levels of prostatitis group referred to as urine-P and serum-P, respectively found that VEGF, IL-1α, IL-4, CXCL-10 and CX3CL1 were elevated in urine-P, whereas IL-5 and CCL5 were elevated in serum-P (*p<0.05). Levels of CXCL-5, IL-12p70, CCL2, CCL3, G-CSF, TNF-α and Leptin were comparable in the biofluids of both groups. Significantly decreased levels of CXCL-10 and CX3CL-1 in serum of prostatitis group (#p<0.05) is linked to their commensurate increase in urine-P, which also showed slightly elevated IL-6, IL-13 and IL-17A. Conclusions Majority of the mediators driving prostatic inflammation were abundant in urine, while several of the mediators were undetectable in serum. Whether this discordance in the biofluids is linked to the increased proteolysis of chemokines in serum or to the exclusive secretion of chemokines from prostate into urine needs to be studied. Urine is a reliable matrix for the discovery of potential non-invasive biomarkers for the routine clinical management of BPH. Funding NIDDK U54 DK112079
Authors
Pradeep Tyagi
Mahendra Kashyap Jeffrey Gingrich Zhou Wang Naoki Yoshimura |
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MP13-20 |
Thrombospondin-1 has a possibility of biomarker predicting the progression of benign prostatic hyperplasia. |
Benign Prostatic Hyperplasia: Epidemiology & Evaluation | 17BOS |
Abstract: MP13-20 Sources of Funding: none Introduction Many factors affect the pathogenesis of benign prostatic hyperplasia (BPH). Previously, we reported that interleukin-18 (IL-18) may promote stromal hyperplasia in the prostate by inducing production of thrombospondin-1 (TSP-1), as known a regulator of angiogenesis and an activator of latent transforming growth factor beta, using BPH rat model and human cultured prostatic cells. Therefore, in this study, we aimed to determine the expression levels of IL-18 and TSP-1 in human prostate tissue and assess the roles of these expressions as biomarkers to diagnose the progression of BPH. Methods Study 1: We enrolled 28 patients without malignancy who underwent transperineal prostate biopsy at our institution. We obtained prostate tissues from the transitional zone and used these samples for total RNA extraction and cDNA preparation. The expression levels of IL-18 and TSP-1 mRNAs were evaluated by quantitative real-time reverse transcription polymerase chain reaction. We evaluated the correlation between mRNA expression levels and age, total prostate volume (TPV), transitional zone volume (TZV), transitional zone index (TZI), and serum PSA levels using Pearson’s product-moment correlation coefficient. _x000D_ Study 2: Samples from 11 of the patients in Study 1 were used to measure the volume of the prostate at biopsy and at a given point in time after biopsy. We evaluated the correlation between the increase in prostate volume per month and mRNA expression._x000D_ _x000D_ Results Study 1: There were no correlations among age, serum PSA levels, and mRNA expression. TSP-1 expression was positively correlated with TPV (r = 0.696) and TZV (r = 0.629). _x000D_ Study 2: The mean observation period was 23.9 ± 13.4 months, and the mean increase in prostate volume was 10.4 ± 12.3 ml. There was a strong positive correlation between the increase in volume per month and TSP-1 expression (r = 0.663)._x000D_ Conclusions TSP-1 expression was positively correlated with prostate volume and the increase in prostate volume per month. This result suggested that TSP-1 might be a potential biomarker for predicting the development of BPH. Funding none
Authors
Takashi Hamakawa
Shoichi Sasaki Yuya Ota Naoko Unno Rika Banno Masa Takada Yasue Kubota Kenjiro Kohri Takahiro Yasui |
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MP14-01 |
The uncoupling of diagnosis and immediate treatment in very low and low risk prostate cancer: a national perspective |
Prostate Cancer: Epidemiology & Natural History II | 17BOS |
Abstract: MP14-01 Sources of Funding: none Introduction A critical means of reducing the morbidity associated with screening for prostate cancer (CaP) is uncoupling diagnosis from treatment. In some men, treatment risks may outweigh benefits. We sought to understand the current treatment landscape of men with very low or low risk (VLoLR) CaP and to determine factors associated with receiving treatment in a contemporary national cohort. _x000D_ Methods Using the National Cancer Database for the years 2010-2013, men with CaP were categorized into risk groups using NCCN criteria by PSA, Gleason score, cT stage, and number of positive cores. In men with VLoLR CaP, radical prostatectomy (RP), radiotherapy (RT), or androgen deprivation therapy (ADT) within 1 year was considered immediate treatment. Men managed with active surveillance (AS), watchful waiting (WW), or no treatment (NoTx) were also analyzed. Treatment patterns by age, comorbidities, and diagnosis year were assessed. Logistic regression modeling was used to determine factors associated with higher likelihood of receiving any treatment. Results Of 448,810 men diagnosed with CaP, 46,290 (11.9%) had very low risk and 60,122 (15.5%) had low risk CaP. In this combined VLoLR Cap cohort, overall median age was 62 with 34.6% of men being older than 65. Overall, 74.8% of men with VLoLR CaP received primary treatment within 1 year of diagnosis. Primary treatment rates declined over time while management with AS/WW/NoTx increased (Figure 1). In men >65 with VLoLR CaP, 28.9% had RP, 35.9% got RT, and 19.2% had AS/WW/NoTx. In men >75, only 5.3% received RP, 39.9% got RT, and 25.4% had AS/WW/NoTx. Age >65 (OR 0.55 95% CI 0.53-0.57), being treated at an academic center (OR 0.68, 95% CI 0.66-0.71), and progressive years after 2010 were associated with lower odds of treatment (Table 1). Conclusions Significant numbers of men with VLoLR CaP underwent primary treatment during 2010-2013, including older men, in whom there is no established benefit to treatment. However, a trend toward more conservative management is apparent. Funding none
Authors
Richard Matulewicz
John Oliver DeLancey Anuj Desai Adam Weiner Edward Schaeffer |
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MP14-02 |
The Natural History of Men on Active Surveillance with Low-Risk Prostate Cancer at a Safety-Net, County Hospital |
Prostate Cancer: Epidemiology & Natural History II | 17BOS |
Abstract: MP14-02 Sources of Funding: Alafi Foundation Introduction Health care delivery to vulnerable and uninsured patients is challenging due to social and economic barriers. For men with low-risk prostate cancer (PCa) on active surveillance (AS), patient compliance, follow up, and access to care are essential for favorable cancer outcomes. Our primary objective is to characterize demographic, disease and cancer outcomes of men on AS at a safety-net hospital and characterize those who were loss to follow-up (LTFU). _x000D_ Methods From January 2004 to November 2014, 104 men at Zuckerberg San Francisco General (ZSFG) with low-risk PCa were followed with AS. Criteria for AS has evolved over time; however, patients with diagnostic PSA 10ng/mL or less, clinical stage T1/2, biopsy Gleason grade 3+3 or 3+4, 33% or fewer positive cores and 50% or less tumor in any single core were eligible for AS. Men were longitudinally followed with a PSA and/or DRE every 3-6 months and repeat prostate biopsy every 1-2 years. Clinical staging and grading were based on a physical exam and at least a 12-core biopsy respectively. LTFU was defined as failure to contact patients with three phone calls or any urology visit recorded within 18 months from a prior visit or biopsy. A secondary chart review was performed with EPIC Systems© CareEverywhere which allows access to non-ZSFG institutions to confirm patients were truly LTFU. Results Among the 104 men on AS at ZSFG, the median age at diagnosis of PCa was 61.5 years (range: 44-81). The median follow-up time period was 29 months (0-186 months) during which 18 men were LTFU and 48 remained on surveillance. Men who remained on AS underwent a median of 7 (1-21) serum PSA measurements and an average of 2 prostate biopsies (1-5). In total, 22 (20.6%) men had definitive treatment with the median time from diagnosis to active treatment being 26 (2-87) months. Radiation therapy was more common that radical prostatectomy (12.5% versus 7.7%). There was one prostate cancer-related death and three non-cancer deaths. Kaplan-Meir curve analysis demonstrates that initial adherence to AS is poor; however as time progresses, adherence increases as those patients committed to early surveillance continue with follow-up. Conclusions AS for low-risk prostate cancer is challenging among a vulnerable population receiving care in a safety-net hospital, as rates of LTFU were high. Our findings suggest the need for an AS program to improve adherence and follow-up among vulnerable and underserved populations. Funding Alafi Foundation
Authors
E. Charles Osterberg
Nynikka Palmer Catherine Harris Gregory Murphy Sarah Blaschko Carissa Chu Matthew Cooperberg Peter Carroll Benjamin Breyer |
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MP14-03 |
Higher Cholesterol is Linked with Increased Risk of High-grade Prostate Cancer: Results from the REDUCE Study |
Prostate Cancer: Epidemiology & Natural History II | 17BOS |
Abstract: MP14-03 Sources of Funding: Supported by GlaxoSmithKline and NIH 1K24CA160653 Introduction Given the prevalence of prostate cancer (PC) and hypercholesterolemia, multiple studies have examined the link between these two conditions with mixed results. These findings may be influenced by studies showing a correlation between higher cholesterol and higher PSA, introducing a bias that may impact the rate of prostate biopsy and cancer detection thereby making high cholesterol appear to be correlated with PC risk. We tested the association between serum lipids and PC in a post-hoc analysis of the REDUCE study, in which subjects underwent study mandated biopsies regardless of PSA, mitigating any bias due to PSA. Methods REDUCE was a 4 year multi-center study testing the effect of dutasteride on PC risk in men with a PSA of 2.5-10.0 ng/mL and a negative pre-enrollment biopsy. As part of the study protocol subjects were required to undergo study-mandated biopsies. The associations between baseline serum cholesterol, low-density lipoprotein cholesterol (LDL) and high-density lipoprotein cholesterol (HDL) with overall PC risk and disease grade (Gleason 2-6 vs. 7-10) at the 2-year biopsy was examined with logistic and multinomial logistic regression, adjusted for baseline covariates. Continuous lipid levels were presented in 10 mg/dL increments to help interpret hazard ratios. We excluded men taking statins. Results 4,904 subjects not taking statins were included. Elevated serum cholesterol was associated with a higher risk of high-grade PC diagnosis on multivariable analysis (OR 1.23, p=0.008), though no association was seen between overall or low-grade PC risk (p >0.137). No association was seen between serum LDL and overall risk of PC or low- or high-grade disease (p >0.138). In contrast, elevated serum HDL was associated with a higher risk of overall PC risk (OR 1.34, p=0.028) and high-grade PC risk (OR 1.74, p=0.013) on multivariable analysis. Conclusions In post hoc analysis of REDUCE, both elevated cholesterol and elevated HDL were associated with increased high-grade PC risk. These data support the hypothesis that high cholesterol is linked with aggressive PC. Given recent data questioning the role of HDL as a cardioprotective factor (Ko et al, J Am College of Cardiology, 2016) and a meta-analysis showing drugs that increase HDL do not reduce cardiovascular risk (Keene et al, BMJ 2014), further study is needed to better understand the link between high HDL and increased PC risk. Funding Supported by GlaxoSmithKline and NIH 1K24CA160653
Authors
Juzar Jamnagerwalla
Lauren E. Howard Adriana C. Vidal Daniel M. Moreira Ramiro Castro-Santamaria Gerald L. Andriole Stephen J. Freedland |
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MP14-04 |
Cardiovascular disease characteristics of newly diagnosed prostate cancer patients: Findings from the pilot phase of RADICAL PC: A Prospective Study of Cardiovascular Disease in Men with Prostate Cancer |
Prostate Cancer: Epidemiology & Natural History II | 17BOS |
Abstract: MP14-04 Sources of Funding: PROSTATE CANCER CANADA_x000D_ Hamilton Health Sciences RFA strategic initiative Introduction Administrative registries suggest that cardiovascular (CV) disease develops frequently in men with prostate cancer (PC). Known CV risk factors, such as hypertension, dyslipidemia, and obesity may account for some of the risk, however PC-specific factors, including androgen deprivation therapy (ADT) may also play a role. The goals of RADICAL PC are to identify the incidence and major determinants of CV disease, and to evaluate whether systematic CV risk factor modification reduces adverse CV events in men with PC. We report the findings for the pilot phase of this study. Methods RADICAL PC recruits consecutive men with a new diagnosis of PC or commencing ADT for the 1st time. Those who do not see a cardiologist annually are randomized in an open manner to receive a CV risk factor intervention (aspirin, statin, blood pressure-lowering to a target systolic of 130mmHg, and standardized exercise and dietary counseling). Those not eligible for randomization are followed to provide a representative sample. At least 6000 men will be recruited and followed for an average of 3 years. Renal function, lipids, and HbA1c will be measured serially. The primary endpoint is the composite of CV death, myocardial infarction, stroke, heart failure, or arterial revascularization. Fisher’s exact test and ANOVA test were used for categorical and normally distributed continuous variables comparisons respectively. Results The characteristics of the first 421 participants, from 3 Canadian sites, are presented. Of these, 334 were newly diagnosed and 87 were receiving ADT for the 1st time, 25 had metastatic disease and 62 were undergoing radiotherapy. Of all participants, 56% have been randomized, and the remainders are undergoing passive follow up. 41% of the patients had hypertension and of the 246 participants with no known hypertension, additional 31% had blood pressure in the hypertensive range. 17% of the patients are diabetic, 55% are current or previous smokers and 81% are overweight (45%) or obese (36%). A third of the patients are on statins and a third take ASA. Patients who are commencing on ADT are older (67+/-8.4 vs. 71+/-8.3 years p<0.0001) and have higher prevalence of preexisting coronary artery disease (11% vs. 20% p=0.003) compared to those who have no indication for ADT. Conclusions Pre-established cardiovascular disease and its risk factors are very common in newly diagnosed prostate cancer patients. The baseline characteristics of patients who are planned to initiate ADT may place them in a higher CVS risk compared to the general PC patient population. Funding PROSTATE CANCER CANADA_x000D_ Hamilton Health Sciences RFA strategic initiative
Authors
Jehonathan Pinthus
Laurence Klotz Himu Lukka Philip J Devereaux Kayla Pohl Idan Roifman Vincent Fradet Robert Siemens Tamara Wallington Shayegan Bobby Edward Matsumoto Tom Corbett Wilhelmina Duivenvoorden Mahshid Dehghan Marina Mourtzakis Darryl P. Leong |
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MP14-05 |
The Association of Age with Perioperative Morbidity and Mortality Among Patients Undergoing Radical Prostatectomy |
Prostate Cancer: Epidemiology & Natural History II | 17BOS |
Abstract: MP14-05 Sources of Funding: none Introduction Older age has been considered a relative contraindication to radical prostatectomy (RP) in men who are otherwise candidates for definitive local therapy for prostate cancer. However, there are limited data regarding the association of age with perioperative outcomes following RP, which is particularly relevant given increased life expectancy in the United States. We therefore examined the association of age with perioperative outcomes among men undergoing RP to more fully inform risk-assessment and management._x000D_ Methods We identified 35,968 adult patients aged 18-89 years who underwent open or minimally invasive RP from 2010-2015 in the National Surgical Quality Improvement Program (NSQIP) database. Age was modeled as a categorical variable. Thirty-day complications and perioperative outcomes were assessed using a standardized protocol as part of the NSQIP. The associations of age with 30-day complications and perioperative outcomes were evaluated using logistic regression, adjusted for patient features._x000D_ Results Age at surgery was distributed as follows: <60 years in 12,172 (33.8%) patients, 60-69 years in 18,076 (50.3%) patients, 70-79 years in 5,480 (15.2%) patients, and 80-89 years in 240 (0.7%) patients. Median operative time was 191 (IQR 151, 191) minutes. There were statistically significant differences in several baseline characteristics across age strata, with higher American Society of Anesthesiology (ASA) class and greater prevalence of diabetes, chronic obstructive pulmonary disease, hypertension, and renal failure among older patients. Overall, 30-day complications occurred in 1,798 (5%) patients. In multivariable analyses adjusted for patient features and surgical approach, ages 70-79 and 80-89 years were statistically significantly associated with increased risks of 30-day complications (OR 1.24, p=0.01; OR 2.83, p<0.01, respectively), perioperative blood transfusion (OR 1.25, p=0.01; OR 3.89, p<0.01, respectively) and 30-day mortality (OR 2.24, p=0.05; OR 10.02, p<0.01, respectively). Only the 80-89 years age group was associated with an increased risk of readmissions (OR 1.75, p=0.03). _x000D_ Conclusions In this national, surgical cohort, older age was independently associated with increased risks of 30-day complications, perioperative blood transfusion, hospital readmissions, and 30-day mortality. However, there were no statistically significant differences among men younger than 70 years for all perioperative endpoints. These results have implications for patient counseling and decision making._x000D_ Funding none
Authors
Jorge Pereira
Gyan Pareek Dragan Golijanin Joseph Renzulli Boris Gershman |
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MP14-06 |
Risks of cytochrome P450 1B1 polymorphisms and lifestyle choices on prostate cancer |
Prostate Cancer: Epidemiology & Natural History II | 17BOS |
Abstract: MP14-06 Sources of Funding: NCI 5R21CA185003-02 Introduction Cytochrome P450 1B1 (CYP1B1) converts xenobiotics to carcinogens and polymorphic variants have been shown to increase activity levels. Lifestyle choices such as tobacco smoking and alcohol consumption are known to enhance the carcinogenesis process and in this study, how these factors may interact with CYP1B1 polymorphisms and affect prostate cancer risk was assessed. Methods Blood genomic DNA from a Caucasian population consisting of 405 healthy men and 400 prostate cancer patients were obtained. Of these, 507 were current or former smokers and 407 were alcohol drinkers. Eight polymorphic sites of the promoter region of CYP1B1 (rs2551188 G to A, rs2567206 G to A, rs2567207 A to G, rs162556 A to G, rs10175368 C to T, rs163090 T to A, rs162330 T to G, and rs162331 A to G) were analyzed in samples using Taqman genotyping assays and real-time PCR. Lifestyle factors and its influence on CYP1B1 polymorphisms toward cancer risks were also evaluated. Results Overall, both alcohol (P=0.006) and smoker (P=0.069) status were associated with prostate cancer. CYP1B1 variants were also risks for cancer at rs2551188 (P=0.043), rs2567206 (P=0.008), and rs10175368 (P=0.001). Evaluation of linkage disequilibrium show rs2551188, rs2567206, rs2567207, and rs10175368 to be linked and interestingly, the G-G-A-C haplotype (wildtype at respective sites) was significantly reduced in cancer (P=0.0282). When classified by lifestyle factors, no associations for CYP1B1 variants were found for cancer among non-smokers with rs10175368 (P=0.051) being a risk among non-drinkers. On the other hand, variants at both rs2567206 and rs10175368 showed increased cancer risk among smokers (P=0.032 and 0.002, respectively) as well as drinkers (P=0.044 and 0.019, respectively). No genotyping differences were observed when analyzing cancers by pathological grades. Conclusions These results demonstrate smoker and alcoholic drinker status to modify the risks of CYP1B1 polymorphisms for prostate cancer and this is of importance in understanding their role in the pathogenesis of this disease. Funding NCI 5R21CA185003-02
Authors
Taku Kato
Yutaka Hashimoto Shigekatsu Maekawa Marisa Shiina Mitsuho Imai-Sumida Pritha Dasgupta Priyanka Kulkarni Soichiro Yamamura Shahana Majid Sharanjot Saini Varahram Sharryari Guoren Deng Rajvir Dahiya Yuichiro Tanaka |
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MP14-07 |
Effect of hypogonadism on prostate imaging and cancer detection |
Prostate Cancer: Epidemiology & Natural History II | 17BOS |
Abstract: MP14-07 Sources of Funding: This research was supported by the Intramural Research Program of the National Cancer Institute, NIH Introduction Previous studies have demonstrated hypogonadism to be associated with higher grade prostate cancer (PCa) on prostate biopsy. However, there is a lack of literature on how hypogonadism (HG) affects prostate imaging on multiparametric MRI (mpMRI). Here, we aim to determine the impact of hypogonadism on PCa detection on MRI and subsequent detection on MRI-TRUS fusion biopsy (FBx). Methods Clinical and pathologic data from a prospectively maintained, single-institution database were analyzed for patients who underwent FBx and standard biopsy (SBx) between 2007 and 2016. Patients with total testosterone (TT) measured within 90 days of mpMRI were included in the study. Patients were excluded if they received prior radiation or androgen deprivation therapy for prostate cancer. HG was determined by a TT level below 180 ng/dL. T2, DWI, and DCE scores were calculated from mpMRI and analyzed as binary variables. Results In our cohort, 522 patients had testosterone measured within 90 days of mpMRI, of which 80 (15.3%) were deemed to be HG. Compared to normogonadal (NG) patients, HG patients had comparable age (62.0 years, IQR 8.8 vs 65.0 years, IQR 10.0; p = 0.519) and PSA (6.66 ng/ml, IQR 6.38 vs 6.86 ng/ml IQR 5.33; p=0.523). Median TT was 171 ng/dL (IQR 46) in the HG cohort, and 311 ng/dL (IQR 131) in the NG cohort (p<0.001). Imaging results were not significantly different between the HG and NG cohorts: prostate volume on MRI was 49.5 cc (IQR 40) vs. 50.0 cc (IQR 33), p=0.621; DWI was 95.0% vs 93.2% positive, p=0.542; DCE was 96.3% vs 91.4% positive, p=0.136. There was a lower detection rate of clinically significant cancer on SBx in the HG group compared to the NG group (28.8% vs 37.2%). However, FBx detection rates were similar between the HG and NG cohorts (40.4% vs 43.6%). In our cohort, 78 patients underwent radical prostatectomy. Of these, HG patients had higher rates of positive margins, lymph node invasion, seminal vesical invasion and Gleason score upgrade on pathology (22.2% vs 14.9%, 11.1% vs 7.5%, 11.1% vs 6.0%, and 22.2% vs 12.5%). Conclusions While SBx cancer detection rate (CDR) was lower in HG patients, FBx CDR was comparable in HG and NG cohorts, suggesting that FBx may provide an advantage in HG patients. In addition, HG patients seem to have higher adverse pathologic criteria in our MRI-screened cohort. Future larger, multi-institutional studies will be necessary to fully ascertain the impact of HG on PCa detection and staging by mpMRI . Funding This research was supported by the Intramural Research Program of the National Cancer Institute, NIH
Authors
Dordaneh Sugano
Abhinav Sidana Brian Calio Sonia Gaur Mahir Maruf Amit L. Jain Maria Merino Peter Choyke Baris Turkbey Bradford J. Wood Peter A. Pinto |
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MP14-08 |
A multiscale survey of inflammatory diseases and prostate oncophenotypes. |
Prostate Cancer: Epidemiology & Natural History II | 17BOS |
Abstract: MP14-08 Sources of Funding: AKT is supported by grants from Prostate Cancer Foundation and Deane Prostate Health, Icahn School of Medicine at Mount Sinai, NY. JT is supported by grants from National Cancer Institute NCI-U54-CA189201-02, National Center for Advancing Translational Sciences NCATS-UL1TR000067 and Clinical and Translational Science Award (CTSA). KKY and SSY are PCF YIs._x000D_ Introduction Prostate cancer (PCa) is the most common cancer detected in men (181,000 annual cases), and nearly 26,000 American men die each year due to PCa and related complications. Reports have shown that PCa is more aggressive when its comorbid with inflammatory diseases. However, the correlations and risks attributed to inflammatory diseases of the abdominal cavity and oncophenotypes are not known. Methods To investigate how inflammatory pathways and PCa genes induce aggressive oncophenotypes in the setting of PCa, we have compiled a multiscale survey that includes data from surgical observations, inflammatory phenotypes, clinical registries, biomarkers and mouse models. We applied an integrative informatics approach with experimental validation to understand the associations between inflammatory diseases (e.g., Crohn's disease, ulcerative colitis, collagenous colitis, indeterminate colitis, ischemic colitis, diverticulitis, hernia, etc.) and PCa. Results We found distinct patterns of shared molecular features---gene sets, pathways, and networks---and comorbidities across inflammatory disease and PCa. For example, we found that diverticulitis tend to increase inflammation in the abdominal cavity and could potentially lead to aggressive prostate oncophenotypes. To test abdominal inflammation and PCa correlation, we induced inflammation in a mouse model of hiatus hernia, which resulted in an increase in the expression of the combined markers of inflammation and PCa (TGFB, TNFA, and IL6). Evaluation of pathology stage, Gleason scores and physical attributes of previous inflammation observed during robotic prostatectomy surgery also reveals trend towards aggressive tumor characteristics with an increase in inflammation. Gene-set overlap analyses showed that several inflammatory disease and prostate cancer genes share genetic modules. Conclusions Collectively, our findings provide the first set of computational, experimental and clinical evidence to recommend clinicians to evaluate the impact of inflammatory disease induced oncophenotypes in patients with PCa. Given that 1.3 million patients undergo prostate-specific antigen (PSA)-triggered invasive trans-rectal biopsy, the present findings in combination with PSA could facilitate the identification patient subset with aggressive cancer. Stratifying patients at risk for prostate cancer who are undergoing surgical interventions of abdominal cavity for inflammation diseases could also evaluate other non-surgical or therapeutic strategies. Funding AKT is supported by grants from Prostate Cancer Foundation and Deane Prostate Health, Icahn School of Medicine at Mount Sinai, NY. JT is supported by grants from National Cancer Institute NCI-U54-CA189201-02, National Center for Advancing Translational Sciences NCATS-UL1TR000067 and Clinical and Translational Science Award (CTSA). KKY and SSY are PCF YIs._x000D_
Authors
Kamlesh K Yadav
Khader Shameer Shalini S Yadav Cordelia Elaiho Li Li James O'Connor Benjamin Glicksberg Kipp Jhonson Marcus Badgeley Benjamin Readhead Brian Kidd Andrew Kasarskis Joel Dudley Ashutosh Tewari |
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MP14-09 |
Geographic disparities in prevalence of baseline prostate inflammation and prostate cancer risk |
Prostate Cancer: Epidemiology & Natural History II | 17BOS |
Abstract: MP14-09 Sources of Funding: American Institute of Cancer Research, NIH 1K24CA160653, GlaxoSmithKline Introduction Prostate cancer incidence rates vary 25-fold worldwide. The distribution of lifestyle factors also varies by geographic region and these factors may impact prostate inflammation, which is inversely associated with prostate cancer risk in the REduction by DUtasteride of prostate Cancer Events (REDUCE) trial. Herein, we examined geographic differences in the prevalence of histological prostate inflammation and in prostate cancer risk in REDUCE, a multinational trial of men with a negative baseline prostate biopsy. Methods We conducted a retrospective analysis of data from 7,213 men with a negative baseline prostate biopsy in REDUCE from Europe (n=4,802), North America (n=1,796), South America (n=467), and Australia/New Zealand (n=148). Histological inflammation was classified as chronic (lymphocytes, macrophages) or acute (neutrophils) by central review of negative baseline prostate biopsies. Logistic regression was used to calculate odds ratios (ORs) for associations between region and prostate inflammation, and between region and prostate cancer risk at trial-mandated repeat biopsy. To avoid confounding by race, analyses were restricted to white men. Results Chronic and acute prostate inflammation was detected in 77% and 15% of men, respectively. Relative to Europeans, North Americans and Australians/New Zealanders were more likely to have acute prostate inflammation in the negative biopsy (OR 1.74; p<0.0001 and OR 2.04; p<0.0001, respectively), while South Americans were less likely to have acute inflammation (OR 0.42; p<0.0001). Among North Americans, Canadians were more likely to have acute prostate inflammation than men from the United States (OR 1.40; p=0.014). Among Europeans, the prevalence of acute inflammation was 15-38% lower in Northern, Southern and Eastern Europe, relative to Western Europe, with similar results for chronic inflammation. Regions with higher prevalence of prostate inflammation had lower prostate cancer risk at 2-year biopsy, including North America (OR 0.87; p=0.180) and Australia/New Zealand (OR 0.48; p=0.036), relative to Europe. Conversely, regions with lower prevalence of prostate inflammation had higher prostate cancer risk at 2-year biopsy, including Northern and Eastern Europe (OR 1.30; p=0.016 and OR 1.74; p<0.0001, respectively), relative to Western Europe. Conclusions Geographic disparities in the prevalence of prostate inflammation is a potential biologic mechanism contributing to global differences in prostate cancer incidence rates. Funding American Institute of Cancer Research, NIH 1K24CA160653, GlaxoSmithKline
Authors
Emma Allott
Sarah Markt Lauren Howard Adriana Vidal Daniel Moreira Ramiro Castro-Santamaria Gerald Andriole Lorelei Mucci Stephen Freedland |
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MP14-10 |
Is it Necessary to Prevent Testosterone Flare? A Systematic Review and Reassessment in the Era of the Saturation Model |
Prostate Cancer: Epidemiology & Natural History II | 17BOS |
Abstract: MP14-10 Sources of Funding: none Introduction For 30 years testosterone flare has been believed to cause rapid prostate cancer (PCa) growth, leading to disease progression, vertebral collapse with spinal cord compression, and death. Anti-androgens (AA) have been routinely offered to to prevent these risks. Given current evidence that maximal androgenic stimulation of PCa occurs at relatively low T concentrations (the saturation model), re-evaluation of the risks of T flare is indicated, as well as the need for AA treatment. _x000D_ Methods An Ovid Medline database search was conducted to identify articles related to &[Prime]disease flare&[Prime], &[Prime]PSA flare&[Prime] or &[Prime]testosterone flare&[Prime] associated with LHRH agonists. The literature review included papers published from May 1 1980 through May 1 2016 using search terms, &[Prime]LHRH&[Prime] OR &[Prime]GNRH&[Prime] AND &[Prime]agonist&[Prime] AND &[Prime]prostate&[Prime] AND &[Prime]flare&[Prime] then &[Prime]LHRH&[Prime] was replaced with &[Prime]anti-androgen&[Prime]._x000D_ Results Serum T rises by 40-100% during T flare, peaking at day 2-3 and returning to baseline by day 8, after which it declines to castrate levels by approximately 2-3 weeks. Few studies report PSA results or disease progression during this short interval of elevated T. Of 6 studies reporting PSA in patients given LHRH agonist alone, 5 showed no significant rise in PSA despite the presence of advanced disease and mean baseline PSAs above 500ng/ml. One reported a statistically significant increase that declined rapidly when T declined. Five RCT’s reported on disease flare in metastatic PCa patients treated with LHRH agonists +/- AA or compared with orchiectomy or DES. Three reported no disease flare in patients treated with LHRH agonists alone. One reported transient pain increase in the “LHRH alone� arm. The numbers of men reported with vertebral collapse was the same in men treated with LHRH-alone arm and in men treated with either orchiectomy or DES. Occasional reports of disease flare appear in observational studies, but these lack control arms to determine whether this merely reflects the natural history of advanced PCa. _x000D_ Conclusions The evidence fails to support significant adverse effects associated with T flare. Most studies show no increase in PSA or disease progression during flare. Rates of vertebral collapse were identical to castration or DES. These results are consistent with the saturation model. There seems little value in adding AA to LHRH agonists, except for men with severely reduced T levels at baseline with extensive bony metastases._x000D_ Funding none
Authors
Yonah Krakowsky
Abraham Morgentaler |
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MP14-11 |
QUANTIFYING ANXIETY AND DEPRESSION AFTER A RECENT PROSTATE CANCER DIAGNOSIS: SHOULD ROUTINE MENTAL HEALTH COUNSELING FOLLOW THE BAD NEWS? |
Prostate Cancer: Epidemiology & Natural History II | 17BOS |
Abstract: MP14-11 Sources of Funding: Urologic Oncology Research Foundation Introduction While being given a diagnosis of cancer may result in psychological distress, formal mental health counseling does not routinely follow the bad news. Whether the severity of anxiety and depression resulting from a cancer diagnosis warrants concurrent psychological counseling is poorly understood. _x000D_ _x000D_ Methods With appropriate consent, IRB approval, and a monitoring psychiatrist, we prospectively administered the validated Beck Anxiety and Beck Depression Inventories to 50 consecutive untreated, recently diagnosed prostate cancer (PCa) patients and 50 age matched control patients without cancer. Each inventory consisted of 21 items rated 0 to 3 by the patient to quantify the severity of anxiety and depression (minimal depression: 0 to 13, mild: 14 to 19, moderate: 20 to 28, severe: 29 to 63) (low anxiety: 0 to 21, moderate: 22 to 35, severe: >35). Anxiety scores >35 or depression scores > 28 were considered worthy of a mental health evaluation. Anxiety and depression levels were compared between cases and controls and correlated with tumor grade. Results Recently diagnosed PCa patients exhibited higher mean depression levels (11.1 vs. 3.7) (median: 9 vs. 3) and higher anxiety levels (14.2 vs. 2.2; median: 15 vs. 1) compared with controls (p< 0.05) but no patients exhibited severe anxiety or depression requiring a formal mental health referral. Patients with tumor grade group 3 or higher (16/50) tended to have higher mean depression scores (14.0 vs. 10.1) and anxiety scores (16.1 vs. 12.0) than those with group grade < 3 (34/50) but this was not statistically significant. Conclusions While recently diagnosed PCa patients exhibited higher anxiety and depression levels than controls, on average these were mild and no patients displayed severe levels justifying a formal mental health referral. Funding Urologic Oncology Research Foundation
Authors
Ricardo Sanchez
Cristian Bernaschina Carla Méndez-Busó Ricardo Sánchez-Ortiz |
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MP14-12 |
Patient-reported urinary bother – what is really bothering prostate cancer patients? |
Prostate Cancer: Epidemiology & Natural History II | 17BOS |
Abstract: MP14-12 Sources of Funding: This research was supported by the Transdisciplinary Research on Energetics and Cancer (TREC) Center at Washington University in St. Louis. The TREC Center is funded by the National Cancer Institute at National Institutes of Health (NIH) (U54 CA155496), (http://www.nih.gov/) Washington University and the Siteman Cancer Center (http://www.siteman.wustl.edu/). Introduction Although research on prostate cancer survivorship points to the importance of shifting our perspective from patient function to patient satisfaction measures, few studies have focused on urinary symptom bother (UB) or its relation to urinary function (UF) in prostate cancer patients undergoing radical prostatectomy (RP). This question is important because it may inform possible non-functional mechanisms for UB, and thus modifiable targets to improve patient satisfaction following RP. Therefore, we examined the degree of concordance between patient-reported UF and UB in the Prostatectomy, Incontinence and Erectile function (PIE) study. Methods PIE participants were recruited from 2011 to 2014 at Washington University School of Medicine and Brigham & Women’s Hospital. Patient-reported outcome measures (PROMs), including UF and UB, were measured by the Expanded Prostate Cancer Index Composite (EPIC-50) pre and 5 weeks post RP in 384 men. Spearman’s rank correlation coefficients were used to describe the concordance between UF and UB. Results We observed overall agreement between UF and UB (r=0.51, see Table 1). However, two distinct groups with differing function and bother were observed: 1) men with high function and bother pre-RP (17.7%), and 2) men with low function and bother 5 weeks post-RP (27.9%). The group with high baseline urinary function and high bother (17.7%) was largely explained by differences in the components assessed by the UF and UB scales. Both of these scales measure incontinence, but the UB scale additionally measures irritative/obstructive symptoms, such as seen in men with benign prostatic hyperplasia (BPH). Splitting the UB scale into two (one for incontinence and one for irritative/obstructive symptoms), or limiting the analyses to men with non-enlarged prostates who are less likely to have BPH, resulted in considerably better agreement between UF and UB (r=0.63 for non-enlarged vs r=0.48 for enlarged prostate size). Conclusions In a pre-surgical cohort of prostate cancer patients, co-existing BPH-associated irritative/obstructive symptoms may distort measurement of UB using EPIC. In natural history studies that compare pre-to post-RP outcomes, splitting incontinence-related UB and irritative/obstructive symptom-related UB may improve the utility of this PROM. Funding This research was supported by the Transdisciplinary Research on Energetics and Cancer (TREC) Center at Washington University in St. Louis. The TREC Center is funded by the National Cancer Institute at National Institutes of Health (NIH) (U54 CA155496), (http://www.nih.gov/) Washington University and the Siteman Cancer Center (http://www.siteman.wustl.edu/).
Authors
Lin Yang
Adam Kibel Graham Colditz Ratna Pakpahan Kellie Imm Sonya Izadi Robert Grubb Kathleen Wolin Siobhan Sutcliffe |
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MP14-13 |
Changes in Health-Related Quality of Life Among Older Adults with Prostate Cancer: A Case-Control Study |
Prostate Cancer: Epidemiology & Natural History II | 17BOS |
Abstract: MP14-13 Sources of Funding: none Introduction The objective of our study was to assess health-related quality of life (HRQOL) changes before and after cancer diagnosis in older adults with prostate cancer and compare changes to non-cancer controls. Methods We used the Surveillance, Epidemiology, and End Results linked to Medicare Health Outcomes Survey (SEER MHOS) dataset. The MHOS included the SF-36 from 1998-2005 and replaced it with the VR-12 from 2006-2013. Adults 65 years and older who were diagnosed with prostate cancer between two MHOS surveys from 1998-2013 were included. Cases were matched to 5 non-cancer controls using propensity score matching. Linear mixed models were used to estimate HRQOL changes over time and factors associated with changes. Results We identified 1,764 prostate cases and 8,820 non-cancer matched controls. Among cases, 1,040 had Gleason 6-7 (low/intermediate risk) and 724 Gleason 8-10 (high-risk). Compared to controls, cases (low/intermediate and high-risk) were more likely to have significant decrements in Role Physical (-2 and -1.7 points vs. -0.5 point) and General Health (-1.9 and -2.0 vs. -0.3). Compared to controls, high-risk cases had additional significant decrements in Physical Component Score (-1.4 vs. -0.4 points), Mental Component Score (-1.7 vs. -0.5 points), and Role Emotional (-1.2 vs. -0.1 points). When stratified by time since diagnosis, immediate declines were observed across HRQOL measures (Figure1). Most HRQOL measures improved over time with the exception of Role Emotional, which deteriorated. We observed no significant differences in HRQOL changes across treatment modalities. Conclusions Following diagnosis, older men with prostate cancer experienced significant declines in physical, mental and social HRQOL relative to controls. Declines were most pronounced in the first 6 months after diagnosis and among men with high-risk disease. Understanding factors associated with HRQOL declines may inform more comprehensive HRQOL management for prostate cancer patients. Funding none
Authors
Angela Smith
Byron Jaeger Laura Pinheiro Lloyd Edwards Bryce Reeve |
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MP14-14 |
Analysis of Inpatient Palliative Care Consultation for Patients with Metastatic Prostate Cancer |
Prostate Cancer: Epidemiology & Natural History II | 17BOS |
Abstract: MP14-14 Sources of Funding: St. Louis University, Division of Urology Introduction As the nation grapples to control the ballooning cost of end-of-life care, palliative consultation services have gained traction as a potential solution for a patient-centered, cost-effective approach. NCCN guidelines recommend palliative care specialists get involved early and studies have shown improvements in quality of life and lower costs, lengths of stay, and in-hospital mortality. However, studies of palliative care services in prostate cancer are lacking. Regardless, prostate cancer is thought to be particularly amenable for palliative care with its slow course and significant morbidity affecting multiple domains of life. Our objective was to characterize the use of palliative care for patients with metastatic prostate cancer and identify its associations with costs, hospital course, and discharge. Methods Using the National Inpatient Sample database from 2012-2013, we identified 99,070 patients with metastatic prostate cancer and analyzed the data from their hospital admissions using descriptive statistics, chi-squared analysis, and regression modeling. Results Palliative care services were consulted in 10.4% (10,300) of metastatic prostate cancer admissions. These admissions were associated with non-elective origin, acute complications, and reduced surgical procedures and chemotherapy. Most consultations occurred in non-profit or government-owned large urban hospitals. Costs and charges were only marginally lower (2-5%), length-of-stay was longer, and in-house mortality was significantly increased. Controlling for factors including demographics, inpatient palliative care was more closely associated with patients having DNR orders (OR: 5.25), radiation therapy (OR: 1.67), self-pay (OR: 1.99), and being discharged to home (OR: 15.25), home health (OR: 3.85), or other facilities like hospice care centers (OR: 3.90). Conclusions Palliative care consultation could improve care for patients with metastatic prostate cancer in a different manner than observed in other conditions. Longer lengths of stay and minor cost savings are unexpected, but likely reflect the nature of the disease. The lower rates of invasive procedures and higher rates of DNRs and home-health/ hospice discharges suggest some level of end-of-life planning. With our characterization of the incidence, patient factors, and settings where palliative care consultations occur we can conclude that there is room to expand palliative care's role beyond uninsured patients in large, urban teaching-hospitals. Funding St. Louis University, Division of Urology
Authors
Neil Mistry
Sameer Siddiqui |
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MP14-15 |
Increase in the incidence of advanced prostate cancer in the United States |
Prostate Cancer: Epidemiology & Natural History II | 17BOS |
Abstract: MP14-15 Sources of Funding: None Introduction Recent population-based studies have suggested that the incidence of metastatic prostate cancer in the United States has remained unchanged over the past decade. These studies have pooled lymph node metastatic cancers with localized disease, and have used a methodology that may be suboptimal for examining aggregate trends in the incidence of distant metastases. Determining if diminished screening has coincided with an increase in the incidence of metastatic prostate cancer is important, as it suggests a reversal of the trend towards decreasing metastases that followed the advent of prostate specific antigen screening. We sought to examine temporal trends in the incidence of prostate cancer with distant and/or pelvic lymph node metastasis [PLNM] at diagnosis. Methods Using the most recent release of Surveillance Epidemiology, and End Results (SEER), we examined the standardized quarterly incidence of prostate cancers with distant or nodal metastases in men over 50 years of age from 2004 to 2013 using a piecewise regression model. Incidence was stratified by age (≥75 and <75 years). Results The incidence of prostate cancer with nodal or distant metastases decreased in men ≥75 years from the first quarter of 2004 to the second quarter of 2011 (p<0.01), and increased significantly afterward (p<0.01). There was no change in the incidence of advanced disease in men less than 75. _x000D_ _x000D_ Separated into components, we found that the incidence of distant metastases in men ≥75 years, which had been downtrending from 2004 to 2011 (p<0.01), subsequently began increasing in the second quarter of 2011 (p=0.03). There was no change in the incidence of distant metastasis in men <75 years. PLNM in the absence of distant metastasis increased in men aged 50-74 years as well as those aged ≥75 years (p<0.01, respectively). _x000D_ Conclusions In older men, the incidence of advanced prostate cancer at diagnosis, which had been decreasing from 2004 to 2011, increased from the second quarter of 2011 to 2013. This was driven both by a shift in the incidence of distant metastasis, as well as a persistent rise in PLNM over the past decade. Funding None
Authors
Jonathan Shoag
Art Sedrakyan Joshua Halpern Wei-Chun Hsu Jim Hu |
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MP14-16 |
Anterior Prostate Lesions and Cancer Detected by MRI in African American Men |
Prostate Cancer: Epidemiology & Natural History II | 17BOS |
Abstract: MP14-16 Sources of Funding: none Introduction Introduction and Objective_x000D_ African American (AA) men tend to present with higher risk prostate cancer (CaP) with poorer prognosis than a non-AA cohort. It has been postulated that the burden of anterior prostate lesions (APL) may be greater and more aggressive in AA men leading to CaP evasion of detection and increased mortality. We aim to compare the rates and grade of APLs in AA and non-AA males. _x000D_ Methods A retrospective database was established including 463 men (64 AA, 399 non-AA) at an academic hospital who underwent prostate biopsy following MRI from to June 2014 to September 2016. These patients did not carry a diagnosis of CaP. Multiparametric magnetic resonance imaging (mpMRI) was used to identify lesions suspicious for CaP. A 3-Tesla MRI machine and Invivo software was utilized for fusion. Results The AA male population studied showed no significant difference in age (p=0.92), or gland volume (p=0.73). However, median prostate specific antigen (PSA) (7.9 vs. 6.3; p<0.001) and PSA density (PSAD) (.134 vs.111; p<0.03) were significantly higher in the AA population. Despite this, there were fewer AA men with anterior lesions (15/64, 23.4%) then non-AA men (112/399, 28.1%). Additionally, there was no significant difference in maximum lesion size from the AA group to the control. When these lesions were biopsied, the ratios of both APLs and total lesions shown to be Gleason 7 or higher were equivalent for both populations. Conclusions AA men were slightly less likely to have an anterior lesion mpMRI, but had equivalent total lesions and maximal lesion dimensions. Despite higher PSAD, AA men were equally likely to have clinically significant APLs and CaP in general. These findings contradict conventional hypotheses in urology and may implicate a more complex multifactorial cause for the prognostic disparity observed. Funding none
Authors
Bryan Bisanz
Michelle Van Kuiken, MD Joseph Yacoub, MD Ari Goldberg, MD, PhD Steven Shea, PhD Neelam Balasubramanian Marcus Quek, MD Gopal Gupta, MD, PhD |
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MP14-17 |
Increased Risk of Biochemical Failure After Radical Prostatectomy Among African American Men with High Risk Prostate Cancer |
Prostate Cancer: Epidemiology & Natural History II | 17BOS |
Abstract: MP14-17 Sources of Funding: none Introduction African American men demonstrate significant disparities in prostate cancer outcomes compared to men of other ethnicities. This study aims to assess the difference in biochemical recurrence between African American men and non-African American men with high risk prostate cancer treated by radical prostatectomy. Methods This is a multi-institutional observational study comprised of 1869 men with NCCN high risk prostate cancer managed primarily by radical prostatectomy at the Cleveland Clinic, Johns Hopkins University, and MD Anderson Cancer Center. In total, 233 (12.5%) men in this cohort self-identified as AA. A Cox regression model was constructed to predict the risk of biochemical recurrence (BCR) while adjusting for differences in clinical covariates between African American and non-African American men. All data is presented as median[IQR]. Results On univariate analysis, African American men demonstrated differences in median age (60.0 years [54.0-65.0] vs. 57.0 years [52.0-67.0]), initial prostate specific antigen (PSA) (8.8 ng/ml [5.2-21.5] vs. 7.1 ng/ml [4.9-13.4]), number of cores with Gleason score 8 or greater disease (1[0-3] vs. 2[1-4]), T stage (1[1-2] vs. 2[1-2]), and grade group (4[4-5] vs. 4[4-5]), compared to non-African American men (all p < 0.01). African American men in the cohort had median follow-up of 36.5 months [14.3-59.5] compared to 36.2 months [14.1-62.0] among non-African American men (p = 0.81). Overall, the BCR-free probability was 54.7% and 51.2% for African American men and 61.3% and 51.4% for non-African American men at 3- and 5- years, respectively. On Cox regression, African American ethnicity was associated with hazard ratio 1.31 (95% CI 1.05, 1.63, p = 0.02) in a model controlling for age, initial PSA, clinical stage, grade group, and number of biopsy cores with Gleason 8 or higher disease. Conclusions African American ethnicity was associated with a 31% increased risk of biochemical recurrence when adjusted comparisons were performed. Further research is needed to determine if these observed differences in the rate of BCR are modifiable among AA men with high risk disease. Funding none
Authors
Yaw Nyame
Jeffrey Tosoian Lamont Wilkins Ridwan Alam Kasra Yousefi Meera Chappidi Chandana Reddy Elizabeth Humphreys Debasish Sundi Brian Chapin Andrew J. Stephenson Eric Klein Ashley Ross |
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MP14-18 |
Alkaline Phosphatase Velocity Predicts Metastasis among Prostate Cancer Patients who Experience Biochemical Recurrence after Radical Prostatectomy |
Prostate Cancer: Epidemiology & Natural History II | 17BOS |
Abstract: MP14-18 Sources of Funding: none Introduction Most patients undergoing radical prostatectomy (RP) for treatment of prostate cancer (CaP) will not develop biochemical recurrence (BCR) or distant metastasis (dMET). Risk factors have been difficult to establish and the role of neo-adjuvant, adjuvant, and/or salvage therapy in preventing or delaying these events is not well understood. This study builds on previous work examining alkaline phosphatase velocity (APV) in predicting dMET for castrate-resistant CaP (CRPC) patients, in a large, racially diverse cohort of patients treated in an equal access military health care system. Methods This retrospective cohort study examined CaP patients enrolled in the Center for Prostate Disease Research (CPDR) multi-center national database who underwent RP and subsequently experienced BCR (n=1725). BCR was defined as a PSA ≥ 0.2 ng/mL at ≥ 8 weeks post-RP, followed by a confirmatory PSA ≥ 0.2 ng/mL. APV was computed as the slope of the linear regression line of all alkaline phosphatase (AP) values after RP and prior to dMETs. APV values in the uppermost quartile were defined as &[Prime]rapid&[Prime] and compared to those in the lower 3 quartiles combined. Salvage therapies were categorized as: hormone therapy only, external radiation therapy only, or multi-treatment. Unadjusted Kaplan Meier curves and multivariable Cox Proportional Hazards analysis were used to model time to dMET. Results Of the 1725 eligible patients, 736 (42.7%) had sufficient data to calculate APV. Those without APV data had a greater proportion of dMET and a faster time to dMET, as well as poorer pathologic features than those who had sufficient APV data. dMET was observed in 11% of patients. We observed a significantly faster time to dMET among the rapid APV group (p<0.001). In multivariable analysis, rapid APV was predictive of over a two-fold increased odds in dMET (HOR = 2.08, p = 0.0215). Conclusions In CaP patients with BCR after RP, rapid APV is a useful predictor of dMET over time. Salvage therapy did not appear to predict dMET. This study builds on previous work demonstrating APV as predictive of dMET among castrate resistant CaP (CRPC) patients. APV may be a valuable tool for prognosticating dMET in a broader patient group, at a time point upstream of CRPC, namely CaP patients who experience BCR after RP. Funding none
Authors
Carolyn Salter
Jennifer Cullen Inger Rosner Huai-Ching (Claire) Kuo Adam Metwalli |
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MP14-19 |
Predicting Metastasis in Men with Localized High Risk Prostate Cancer Undergoing Radical Prostatectomy |
Prostate Cancer: Epidemiology & Natural History II | 17BOS |
Abstract: MP14-19 Sources of Funding: None Introduction The current pre-treatment nomograms for prostate cancer were developed and validated based on a patient population that primarily consisted of men with low or intermediate risk prostate cancer. This study aims to develop a preoperative nomogram that predicts for metastasis from a contemporary cohort of men with NCCN high (HR) or very high risk (VHR) prostate cancer. Methods We identified 1,241 men from 2005 to 2015 with NCCN HR or VHR prostate cancer from two large academic medical centers primarily treated with radical prostatectomy. The cohort was divided into training (n=620) and validation (n=621) cohorts. The primary endpoint of analysis was mets. Multivariable Cox proportional hazards regression analysis was used to model characteristics and outcomes in the training cohort. Predictive accuracy was assessed using the time-dependent area under the receiver operating characteristic curve (AUC) in the validation cohort. Results 123 men (64 training and 59 validation) developed metastasis. The overall metatasis-free probability was 86.5% (95% CI 83.7%-89.4%) at 5-years. Predictive nomograms including age, ethnicity, PSA, Gleason grade, clinical stage, and the number of positive cores with Gleason 8-10 disease were developed. The AUC for the model was 0.75. In comparison, the MSKCC preoperative nomogram and CAPRA nomogram had AUCs of 0.66 and 0.67 respectively. Conclusions Individualized risk assessment is imperative for optimal decision making for both disease management and appropriate clinical trial design. The nomogram described here, created from a population composed of HR/VHR men, has greater predictive accuracy of mets up to 5 years after radical prostatectomy than those previously established on cohorts of primarily low and intermediate risk men. Thus, this nomogram may be a more suitable approach for predicting mets in men with HR or VHR disease. Funding None
Authors
Lamont Wilkins
Alam Ridwan Jeffrey J. Tosoian Yaw A. Nyame Kasra Yousefi Meera R. Chappidi Chandana A. Reddy Elizabeth B. Humphreys Debasish Sundi Brian F. Chapin Andrew J. Stephenson Eric A. Klein Ashley E. Ross |
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MP14-20 |
Predictors of Early Disease Specific Mortality Among Patients with Prostate Adenocarcinoma Bone Metastasis at Diagnosis |
Prostate Cancer: Epidemiology & Natural History II | 17BOS |
Abstract: MP14-20 Sources of Funding: None Introduction Two recent randomized trials have suggested a survival benefit for patients with high volume metastatic prostate cancer (PCa) that initially receive chemotherapy. However, there is a paucity of data at the population-level characterizing which men presenting with bone metastatic disease are at highest risk for PCa-specific mortality (PCSM). The purpose of this study was to assess the demographic and clinicopathologic factors among patients with PCa bone metastasis at diagnosis and identify predictors of PCSM. Methods Patients with prostate adenocarcinoma were identified between 2010-2013 from the SEER database (n=200,616). Among this group, 8,040 men presented with bone metastasis, forming the study cohort. Descriptive statistics were used to compare demographic and clinicopathologic variables between patients experiencing PCSM and those that were alive/died of other causes. A Fine and Gray&[prime]s sub-distribution competing risks model was performed to generate hazards ratios (HR) for the identification of predictors of PCSM. Results There were 2,497 men (31.1%) experiencing PCSM and 5,543 men (68.9%) without PCSM (n=643 dead of other causes; n=4,900 alive) over a median follow-up of 35 months (IQR: 34-37). On univariate analysis, patients suffering PCSM were older (median 72 vs 70 years of age, p<0.0001), unmarried (40.5% vs 36.7%, p=0.001), more likely to live in the Southeast US (24.6% vs 20.8%, p=0.0006), have biopsy Gleason Group (bGG) 5 disease (40.7% vs 38.6%) or have no prostate biopsy (28.1% vs 19.5%, p<0.0001), and have concomitant PCa brain (2.1% vs 0.8%, p<0.0001), liver (6.1% vs 2.4%, p<0.0001) and lung metastases at diagnosis (9.0% vs 5.7%, p<0.0001) compared to patients without PCSM. Multivariable competing risks modelling identified older age (HR 1.023, 95CI 1.019-1.027), non-black/white race (vs black HR 0.77, 95CI 0.62-0.95), unmarried status (vs married HR 1.10, 95CI 1.01-1.20), living in the Southeast US (vs Northeast US HR 1.24, 95CI 1.07-1.44), PSA (HR 1.005, 95CI 1.003-1.008), bGG 4 (vs 1 HR 1.53, 95CI 1.04-2.26), bGG 5 (vs 1 HR 2.18, 95CI 1.50-3.19), no prostate biopsy (vs bGG 1 HR 2.97, 95CI 2.02-4.37), and brain (vs no HR1.48, 95CI 1.05-2.10), liver (vs no HR 2.18, 95CI 1.79-2.65) and lung metastases at diagnosis (vs no HR 1.33, 95CI 1.13-1.56) as predictive of PCSM. Conclusions Men presenting with PCa-bone metastatic disease have aggressive tumor biology and are at risk of PCSM in <3 years. Patients with aggressive prostate bGG disease presenting with bone and concomitant visceral metastasis (particularly liver metastasis) should be considered for early, aggressive systemic therapy and/or clinical trials. Funding None
Authors
Zachary Klaassen
Thenappan Chandrasekar Hanan Goldberg Robert J. Hamilton Neil E. Fleshner Girish S. Kulkarni |
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MP15-01 |
Can the use of narrow-band imaging (NBI) reduce persistent bladder cancer rate during white-light classic trans-urethral resection of tumor (WLcTURBT)? A preliminary single-center experience in a large case series. |
Bladder Cancer: Non-invasive I | 17BOS |
Abstract: MP15-01 Sources of Funding: none Introduction Transurethral resection of bladder tumors is the mainstay approach in bladder cancer diagnosis and treatment. Nevertheless, persistent tumor lesion is present in 33-76% of patients after WLcTURBT and a tumor stage change is reported in about 40% of patients. The aim of this study was to evaluate the probability to detect persistent high-risk bladder cancer using NBI after an initial WLcTURBT Methods From June 2010 to April 2012, 797 patients (423 males and 374 females) affected by primary, recurrent or suspicious bladder lesions, underwent WLcTURBT. We performed NBI resection of every lesion margins and bed of resection during the same surgery session. Each fragment was separately analyzed. A logistic regression model was used to evaluate the correlation between persistent bladder tumor during repeat NBI resection and bladder cancer risk factors (stage, dimension and focality). The statistical analysis were conducted using Statistical Package for Social Science version 19 Results Overall, 512 patients were diagnosed with bladder cancer. We identified 1572 bladder lesions of which 1066 (67.8%) were bladder neoplasms after WLcTURBT. Bladder tumors features are showed in table 1. We found 195 (18.2%) persistent pT1 or pCIS tumors after NBI resection (p< 0.05). Of those, 119 lesions (11.1%) were already high-risk tumors (pT1 or pCIS) after the initial WLcTURBT. In 140 lesions (13.1%) we found residual pT1 tumors (49 on margins and 91 on bed of resection) and 55 lesions (5.1%) showed residual pCIS tumors (52 on margins and 3 on bed of resection). We observed a disease down-staging in 76 lesions (7.1%) who were diagnosed with pTa tumor after the initial WLcTURBT. Of those, 50 tumors resulted pT1 bladder cancer after repeat NBI resection and 26 pTa tumors were finally diagnosed with pCIS bladder cancer. Tumor focality was correlated with significant (p< 0.05) high-risk tumor persistence on lesion margins Conclusions Bladder tumor persistence is significantly related to the endoscopic resection. NBI-TURBT represents a usefull procedure to detect residual high-risk tumors otherwise unidentifiable during WLcTURBT. Residual tumor rate in our study is 18%. Further studies are necessary to power this result Funding none
Authors
Cristina Falavolti
Barbara Cristina Gentile Gabriella Mirabile Paola Tariciotti Luca Albanesi Giorgio Rizzo Maurizio Buscarini |
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MP15-02 |
BLUE LIGHT CYSTOSCOPY FOR DIAGNOSIS OF UROTHELIAL BLADDER CANCER: RESULTS FROM A PROSPECTIVE MULTICENTER REGISTRY |
Bladder Cancer: Non-invasive I | 17BOS |
Abstract: MP15-02 Sources of Funding: None Introduction Blue Light Cystoscopy (BLC) using hexaminolevulinate (Cysview) improves the detection of non-muscle invasive bladder cancer (NMIBC). We report on our experience from the multi-center prospective BLC with Cysview Registry and its utility in different scenarios._x000D_ Methods Under IRB approval, we prospectively enrolled consecutive patients undergoing transurethral resection of bladder lesions into the registry at 9 different centers. Patients who refused catheter insertion (8), had pure upper tract or prostatic urethral lesions (7) or were lost to follow-up (10) were excluded from the study._x000D_ Results Between April 2014 and Oct 2016, 1325 separate lesions were identified from 517 BLC procedures on 426 patients (mean age 72 years, 84% male). 68 patients (16%) underwent repeat use (2-5). Using final pathology as the reference standard, the sensitivity of WL, BL and the combination for any malignant lesion was 75%, 90% and 98.5% respectively. The addition of BL to standard WLC increased the detection rate by 12% for any papillary lesions and 44% for CIS (Table 1). Within the WL negative group, an additional 170 lesions in 105 (25%) patients were detected exclusively with the addition of BL. In multifocal disease, in addition to WL-detected lesions, BLC resulted in upstaging in 54 (13 %) patients, resulting in a change in management. Overall false-positive (FP) rate was 26% for WL and 32% for BL. 164 (39%) patients received BCG at least 6 weeks prior to BLC, with a positive predictive value (PPV) of BLC-detected malignancy being 55% (FP=35%). 82 biopsies were taken from margins of a previous resection site (with more than 6 weeks interval), wherein the PPV of BLC was 51% for malignancy (FP=33%) (figure 2). Among the positive/suspicious cytology patients who had no lesions on WL (144 total), BL was able to detect an extra 57 malignant lesions in 36 patients (sensitivity 92%). There was one mild dermatologic hypersensitivity reaction noted (0.2%). 40 (12%) patients eventually underwent cystectomy, 4 (10%) of whom exclusively because of lesions detected by BLC. _x000D_ Conclusions BLC significantly increases detection rates of CIS and papillary lesions over WLC alone and can result in upstaging or upgrading in about 13% of patients. Recent BCG therapy does not appear to impact BLC accuracy. Repeat use of Cysview for BLC is safe. Funding None
Authors
Soroush T Bazargani
Hooman Djaladat Anne Schuckman Badrinath Konety Trinity J Bivalacqua Jeff Holzbeierlein Brian Willard Jennifer Taylor Joseph Liao Kamal Pohar James Tierney siamak Daneshmand |
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MP15-03 |
Who could be eliminated for random biopsies after BCG therapy in patients with bladder carcinoma in situ? |
Bladder Cancer: Non-invasive I | 17BOS |
Abstract: MP15-03 Sources of Funding: none Introduction So far few studies have investigated the predictors for identifying the presence of malignant lesions in random biopsies for the assessment of the therapeutic effect of BCG instillation against bladder carcinoma in situ (CIS) in patients with non-muscle invasive bladder cancer (NMIBC). Methods We retrospectively identified 144 patients who were initially diagnosed with bladder CIS with or without papillary lesions and treated with BCG therapy between 1995 and 2015 at our 2 institutions. Among them, 80 patients (55.6%) received random biopsies after BCG therapy in order to evaluate the therapeutic effect of the BCG therapy (RBx group) and 64 (44.4%) did not receive the random biopsies (no-RBx group). Velvet-like, reddish areas or irregular mucosa indistinguishable from inflammation were recognized as positive findings on cystoscopy 1 month after BCG therapy. We evaluated the association between parameters such as cytology results just after BCG therapy as well as the cystoscopic findings and malignant lesions on the final random biopsy specimens. Results Overall, median patient age was 70.5 years and the median follow-up period was 4.5 years. No significant differences in clinicopathological characteristics were observed between patients in the RBx group and those in the no-RBx group. The 5-year recurrence-free survival rate in the RBx group was 40.3±6.6%, which was not different from that in the no-RBx group (44.5± 8.3%, p=0.386). In the RBx group, 25% (20/80 patients) had malignant lesions on the final random biopsy specimens. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the cytology results just after completion of BCG therapy, the cystoscopic findings, and their combinations are shown in the Table below. Among the 27 patients who had negative cytology and cystoscopic findings, none had malignant lesions in the final random biopsy (NPV=100%). Conclusions The combination of negative cytology just after completion of BCG therapy and negative cystoscopic findings could eliminate unnecessary random biopsy after BCG therapy in bladder CIS patients. Funding none
Authors
KIMIHARU TAKAMATSU
Eiji Kikuchi Koichiro Ogihara Nozomi Hayakawa Kazuhiro Matsumoto Ryuichi Mizuno Akira Miyajima Masafumi Oyama Mototsugu Oya |
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MP15-04 |
New predictive scoring model for recurrence incorporating bladder neck involvement in patients with non-muscle-invasive bladder cancer |
Bladder Cancer: Non-invasive I | 17BOS |
Abstract: MP15-04 Sources of Funding: none Introduction We previously reported that bladder neck involvement (BNI) was an independent risk factor for progression to muscle invasion in primary non-muscle-invasive bladder cancer (NMIBC) and we developed a new predictive scoring model for progression incorporating BNI (Fujii et al., Eur Urol 1998; Kobayashi and Fujii et al., Urol Oncol 2014). In the present study, we investigated the impact of BNI on recurrence in NMIBC, and developed a new predictive scoring model for recurrence incorporating BNI and assessed its predictive ability. Methods We enrolled a total of 589 Japanese patients who underwent transurethral resection for bladder tumors at a single center from 2001 to 2016, and who were pathologically diagnosed with Ta and T1 NMIBC. Exclusion criteria were: carcinoma in situ and patients with tumors located in the prostatic urethra. Multivariate Cox proportional hazards regression models using the Prentice-Williams-Peterson gap time model were generated to identify the independent predictors for recurrence. The predictive ability of our model was assessed using Harrell&[prime]s concordance index (c-index) and was compared with that of the EORTC and CUETO scoring models. Results Over a median follow-up period of 3.1 years, 258 patients (43.8%) experienced a total number of 475 recurrences, and the disease progressed in 37 patients (6.3%). The recurrence probability at 3 years was 49.7%. In 106 patients (18.0%) with current and prior history of BNI, subsequent recurrence probability at 3 years was 67.2%. Multivariate analysis revealed that history of BNI (HR 1.60, P < 0.001) along with histologic grade 2-3 (HR 1.53, P = 0.020), multiple tumors of four or more (HR 1.37, P = 0.016) and male (HR 1.30, P = 0.043) were independent predictors of recurrence. Our scoring model of assigning 1 point to each risk variable represented higher c-index of 0.59 than the EORTC (0.57) and CUETO (0.50) models. Dividing patients into 3 groups according to their scores (0-1/2/3-4), recurrence rates increased as the score (P <0.001). Conclusions This study showed that current and prior history of BNI is a significant risk factor for recurrence in NMIBC. Our scoring model incorporating BNI is an easy means of estimating recurrence risk and can be used to determine the appropriate management for individual patients. Funding none
Authors
Yuma Waseda
Masaharu Inoue Masaya Ito Toshiki Kijima Soichiro Yoshida Minato Yokoyama Junichiro Ishioka Yoh Matsuoka Kazutaka Saito Kazunori Kihara Yasuhisa Fujii |
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MP15-05 |
Guideline-adherence to adequate treatment for T1 non-muscle-invasive bladder cancer: evidence from a German multicenter observation |
Bladder Cancer: Non-invasive I | 17BOS |
Abstract: MP15-05 Sources of Funding: None Introduction Patients with pT1 bladder cancer (BCa) are at high-risk of recurrence and progression and thus need proper treatment. We aimed to mirror contemporary guideline-adherence in the context of pT1 BCa treatment in a German multicenter study. Methods 111 patients with first-time diagnosis of pT1 BCa were treated at four centers. Guideline-adherence was defined as 2nd resection, instillation therapy, and quarterly cystoscopic follow-up. Patient characteristics (age, sex, and comorbidities), treatment information (treating facility, photodynamic diagnosis, early Mitomycin C (MMC) instillation), and pathological tumor parameters were assessed. First, we summarized our cohort by descriptive analyses. Second, we plotted the proportions of patients with guideline-adherence within selected subgroups and compared the distribution between the subgroups by using chi-squared tests. Third, we created a multivariable model to identify independent predictors of guideline-adherence. Results Most patients were male (78%) and median age was 75 years (range: 39-94 years). 44% had multifocal tumors, early Mitomycin C instillation was performed in 33%, repeat resection was performed in 78% of which 50% then had pT0 stage. Of 62% who underwent instillation therapy, 59% received BCG, while 41% received MMC or other agents. Quarterly cystoscopic follow-up was performed in 82%._x000D_ Overall, guideline-adherence was met in 57%. Patients aged below the median met all three adherence metrics more often compared to their counterparts above the median (66.7% vs. 46.3%; P=0.030). Similarly, men more frequently met adherence metrics compared to women (62.1% vs. 37.5%; P=0.038). More patients with multifocal tumors met all of the three adherence metrics (69.4% vs. 48.0%; P=0.050), as compared to those with unifocal lesions._x000D_ In univariable analyses, age, male sex, tumor multifocality, and early MMC instillation, were associated with guideline-adherence. In multivariable analyses, age (odds ratio [OR]=0.95; 95% confidence interval [CI]=0.91-0.99; P=0.013) and tumor multifocality (OR=2.48; 95% CI=1.01-6.11; P=0.048) held true as independent predictors of guideline-adherent treatment. Conclusions We found non-adherence in more than 1/3 of patients and treatment disparities among different age groups and according to tumor focality. While the underlying reasons are likely multifactorial, efforts should be put into evaluating this issue in larger samples and into trying to eradicate disadvantages in these patients at highest risk of recurrence. Funding None
Authors
Malte W. Vetterlein
Julia Roschinski Philipp Gild Ousman Doh Wolfgang Höppner Hendrik Isbarn Walter Wagner Guido Sauter Armin Soave Margit Fisch Michael Rink |
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MP15-06 |
Assessment of quality of care in non-muscle invasive bladder cancer: Uptake of re-resection for high grade or T1 bladder tumors in California |
Bladder Cancer: Non-invasive I | 17BOS |
Abstract: MP15-06 Sources of Funding: UC Davis academic senate Introduction Non-muscle invasive bladder cancer (NMIBC) is in need of markers of quality care and is a disease where quality improvement initiatives have significant potential to improve patient outcomes. Current guidelines support re-resection for all patients diagnosed with high grade (HG) or T1 tumors, yet no current studies have evaluated practice patterns and uptake of re-resection at the population-level. We sought to characterize rates of utilization and assess predictors of uptake of this practice as an initial step in developing quality improvement initiatives in NMIBC._x000D_ Methods Incident cases of HG or T1 NMIBC diagnosed between 2005 and 2012 were identified from the California Cancer Registry and linked to hospital records of the Office of Statewide Health Planning and Development. Tumor, patient, and hospital characteristics were included in the analysis. Incidence rates of re-resection were reported and defined as a second TURBT occurring between 14-42 days of initial resection. Multivariable logistic regression analysis was utilized to assess predictors of undergoing re-resection. Inverse propensity weighting and multivariable Cox proportional hazards regression models were utilized to assess predictors of recurrence and survival (overall and cancer-specific). _x000D_ Results The final cohort consisted of 8,468 patients with HG or T1 NMIBC diagnosed in California between 2005 and 2012. The overall incidence rate of re-resection was 8.9%, with increases observed over time: 5.2% (2005-2006) to 11.8% (2011-2012). The strongest predictors of undergoing re-resection in multivariable analysis were HG disease (OR 2.99, CI 2.46 - 3.63), tumors >5cm (OR 1.72, 1.23 - 2.39), and year of diagnosis (OR 1.28, 1.20 - 1.38 at 2 year increments). Increasing age was associated with decreased likelihood of re-resection (OR 0.74, 0.69 - 0.80 at 10 year increments). Independent predictors of recurrence included HGT1 tumor (HR 1.28, 1.10 - 1.49). Re-resection was not associated with better overall survival (HR 0.80, 0.62 – 1.05) or bladder cancer specific survival (HR 0.83, 0.54 - 1.27). _x000D_ Conclusions Rates of re-resection for HG or T1 tumors remain unacceptably low for this accepted standard practice and have demonstrated only modest improvement in recent years. Such underutilization represents a reminder of the need for better mechanisms to translate guideline recommendations into clinical practice in bladder cancer. There remains significant room for improvement in managing this disease and improving patient outcomes._x000D_ Funding UC Davis academic senate
Authors
Stanley Yap
Ann Brunson Yvonne Chan Rosemary Cress Theresa Keegan Ralph deVere White Ted Wun |
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MP15-07 |
Variations in Management of Non-Muscle Invasive Micropapillary Urothelial Carcinoma of the Bladder |
Bladder Cancer: Non-invasive I | 17BOS |
Abstract: MP15-07 Sources of Funding: None Introduction Micropapillary urothelial carcinoma is a rare and aggressive histologic variant of bladder cancer. Treatment guidelines recommend forgoing bacillus Calmette-Guerin (BCG) therapy in favor of early radical cystectomy for non-muscle invasive micropapillary bladder cancer (NMI-MPBC) due to high rates of disease progression. We hypothesize that management of NMI-MPBC will vary across centers. Methods Patients with MPBC were identified from the National Cancer Database (2003-2013). Treatment trends and rates of pathological upstaging were identified. Bivariate and multivariate analyses were performed to assess differences in outcomes by treatment approach. Results 777 patients were diagnosed with MPBC during the study period with 270 identified to have non-muscle invasive disease on presentation. BCG therapy was administered as initial therapy in 25.1% of NMI-MPBC patients and in 14.3% of non-micropapillary UC patients (p<0.001). _x000D_ _x000D_ Cystectomy was performed as primary therapy for NMI disease in 19.6% of MPBC and in 2.3% of non-micropapillary patients (p<0.001). Of the patients who underwent primary cystectomy, upstaging from NMI disease to T2-T4 disease was seen in 33.3% of the MPBC patients compared to 11.1% in patients with non-micropapillary disease (p<0.001). Upstaging to pathologic N1-3 disease was observed in 33.3% of MPBC patients compared to 11.1% non-micropapillary patients (p<0.001). _x000D_ _x000D_ Cystectomy as primary therapy for NMI-MPBC was more likely to be performed at academic (29.6%) compared to community cancer centers (11.3%) (p<0.001). On Cox regression analysis, adjusting for patient age, sex, race, comorbidities, and disease stage, care at academic cancer centers was associated with increased odds of having cystectomy as primary therapy compared to community cancer centers (OR = 3.11, 95% CI 1.53-6.29)._x000D_ _x000D_ Primary BCG therapy was not utilized any more frequently between academic (26.2%) and community cancer centers (23.7%) (p=0.64). _x000D_ _x000D_ _x000D_ Conclusions The micropapillary variant of urothelial carcinoma is associated with increased odds of disease upstaging and node-positive disease. BCG is overutilized as primary treatment in this population. NMI-MPBC patients treated at academic centers were more likely to receive radical surgery as primary treatment compared to patients at community cancer centers. _x000D_ Funding None
Authors
Kyle Scarberry
Yu Zheng Shree Agrawal John Francis Kelly Scarberry Albert Kim Itunu Arojo Simon Kim |
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MP15-08 |
High grade non-invasive recurrence following induction BCG for pT1/CIS urothelial carcinoma of bladder, is it an indication for cystectomy? |
Bladder Cancer: Non-invasive I | 17BOS |
Abstract: MP15-08 Sources of Funding: None Introduction For most patients with pT1 and Carcinoma in situ (CIS) urothelial carcinoma of the bladder (UCB), intravesical induction Bacillus Calmette Guérin (IND-BCG) is considered the gold standard treatment. However the criteria to abandon BCG therapy (i.e. BCG failure) in cases of recurrent but non-progressive UC can be vague. _x000D_ In this study we aim to assess a large cohort of CIS and pT1 UCB patients treated with intravesical IND-BCG and report on the outcomes according to the grade and stage of recurrences following IND-BCG._x000D_ Methods The data is from a single academic institution which is the only referral site for all BCG therapies for a large metropolitan area. Patients with initial diagnosis of pT1 and CIS received induction course of intravesical BCG. Post induction cystoscopy was carried out for all patients, and follow up was three monthly for the first two years, and at least biannually thereafter. Results From 2001 to 2014, 261 patients received IND-BCG for pT1/CIS. Post BCG status were as follows: 132 (51%) pT0, 48 (18%) CIS, 31 (12%) pT1, 32 (12%) pTaHG and 10 (4%) pTaLG. _x000D_ Of the patients who were pT0 post-BCG, 74% remained disease free at a median of 8 mo. 19% developed high-grade recurrences including 4% with muscle invasive UC (MIUC) at a median of 16 mo (12-27) from diagnosis. Of patients with residual CIS, 60% responded to further BCG, with progression to invasive disease in 13%. _x000D_ Of residual pTaHG patients, 53% became pT0 and 9% eventually had cystectomy at 32.4 mo for disease progression to CIS or ?pT1. 10 patients had pTa-LG recurrence and one required cystectomy. _x000D_ Only 36% of residual pT1 patients became pT0 with 29% developing invasive disease. 39% of pT1 compared to 17% of the CIS required cystectomy at a median of 17.5 mo (p=0.036). _x000D_ pT0 rates were significantly higher for CIS patients compared to pT1 (60% vs. 36%, 0.047), but similar between CIS and pTaHG. _x000D_ _x000D_ Conclusions Non-invasive recurrence of high grade UC following BCG may respond to further intravesical therapy however response is less likely in recurrent pT1 UC. Following BCG recurrent non-invasive high Funding None
Authors
Manmeet Saluja
Daljit Kaur Jonathan Masters Andrew Williams Michael Rice Kamran Zargar-Shoshtari |
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MP15-09 |
Using Grade of Tumor Recurrence after BCG Therapy to Guide further Therapy |
Bladder Cancer: Non-invasive I | 17BOS |
Abstract: MP15-09 Sources of Funding: Cancer Center Support Grant Introduction Patients who have a tumor recurrence after treatment with intravsical BCG are considered as high risk for additional recurrence or disease progression. We have previously shown that low grade (LG) papillary recurrence found at the 3 month post-BCG evaluation is highly predictive of future outcome; here we further elucidate whether this prognostic impact holds true at any time during or after intravesical BCG treatment. Methods After IRB approval, we studied a group of 155 patients with intermediate to high risk, NMIBC undergoing TURBT and subsequent intravesical BCG treatment according to the SWOG protocol. Patients with recurrences after BCG were identified. Baseline demographics and clinical characteristics prior to BCG were compared. Cystectomy-free (CFS), metastasis-free (MFS), cancer specific (CSS) and overall survivals (OS) between the groups were compared using the Log-rank test. Statistical significance was set at p<0.05. Results A total of 17 patients with LG and 53 patients with HG recurrences were identified with median follow-up intervals of 68.9 and 60 months, respectively. The two groups were comparable for baseline clinico-pathologic features except that more patients with HG recurrences started with higher stage (32.7% Ta, 65.4% T1 and 1.9% CIS vs. 70.6% Ta, 29.4% T1 and 0% TIS, p=0.018) and grade (60% HG and 40% LG vs. 98% HG and 2% LG, p<0.001) on TURBT prior to BCG treatment. As expected, more patients with HG recurrence underwent cystectomy (54.7% vs. 17.6%, p=0.011) (Fig. 1a) while those with LG recurrences continued on BCG after recurrence in 82.4% of the cases. This management paradigm yielded similar MFS, CSS, and OS (Fig. 1b, c, d). Conclusions Patients with LG recurrence after BCG treatment have excellent outcomes and can continue with bladder sparing therapy. Patients with HG recurrence after BCG treatment are more likely to undergo radical salvage cystectomy. With appropriately selected therapy, metastatic disease can be prevented, leading to similar CSS and OS as seen for those with LG recurrence. Funding Cancer Center Support Grant
Authors
Roger Li
Michael J. Metcalfe J.E. Ferguson 3rd Siddartha Gorantla Neema Navai Jay B. Shah H. Barton Grossman Colin P. Dinney Ashish M. Kamat |
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MP15-10 |
Immunologic Response to a Therapeutic Cancer Vaccine (PANVAC): Initial Results from A Randomized Phase 2 Clinical Trial |
Bladder Cancer: Non-invasive I | 17BOS |
Abstract: MP15-10 Sources of Funding: NIH intramural funding Introduction Patients who have recurrences of superficial urothelial carcinoma after BCG have limited therapeutic options. We are conducting a randomized phase II clinical trial in which patients who have recurrence after prior BCG undergo either repeat induction BCG or BCG combined with a cancer vaccine (PANVAC). In this study, we report our analysis of the initial immunologic response for the patients enrolled thus far. Methods The immunologic responses of all patients enrolled thus far were assessed. Three tumor-specific antigens (Brachyury, CEA, and MUC1) were assessed using an overlapping 15-mer peptide pool spanning the entire length of each of the peptides. HLA was used as a negative control and CEFII was used as a positive control. The tumor associated antigen (TAA) response was evaluated at an early time point (1 month after therapy initiation/1 week after 2nd vaccine administration) and at a later time point (3-4 months after therapy initiation/1 week after 4th vaccine administration). A positive response was defined as antigen levels above 250 (absolute number of cells producing cytokine) after subtracting for background. Results There were a total of 16 patients enrolled thus far: Eight patients were randomized to the BCG-only arm and eight patients were randomized to the BCG+PANVC arm. The median number of BCG instillations prior to enrollment in both groups was 6 (range 5-19). 25% of patients also had intravesical chemotherapy prior to enrollment (2 patient had Mitomycin C, 2 patients had Valrubicin). There was a higher rate of all responses in the BCG+PANVAC (mean TAA value 734) arm than in the BCG alone arm (mean TAA value 434) (p<0.01), and a higher rate of responses attributable to the brachyury antigen (p=0.03). There was also a higher rate of response when CEA and MUC1 were evaluated together. The CD8 response appeared to be greater than the CD4 response for patient in the PANVAC arm but not in the BCG only arm. _x000D_ Conclusions BCG + PANVAC appears to induce an immunological response that is greater than BCG alone in many patients. The impact of this immunological response on patient outcomes will continue to be assessed as the trial matures. _x000D_ Funding NIH intramural funding
Authors
Thomas Sanford
Renee Donahue Caroline Jochems Rebecca Dolan Sonia Bellfield Megan Anderson Eric Singer Robert Weiss Sammy Elsamra Thomas Jang Sam Brancato Daniel Su Yvonne Wall James Gulley Jeffrey Schlom Piyush Agarwal |
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MP15-11 |
Bladder Preservation In Elderly Patients Having Non-Muscle Invasive High Grade Recurrent Ta, T1 Urothelial Carcinoma With Gemcitabine, Paclitaxel, Doxorubicin And Radiotherapy: Survival And Quality Of Life. |
Bladder Cancer: Non-invasive I | 17BOS |
Abstract: MP15-11 Sources of Funding: none Introduction INTRODUCTION: Non-muscle invasive carcinoma of the bladder (NMICB) of high grade Ta, T1 tumor that recurred after Intavesical BCG, had a high incidence of tumor progression. Elderly patient are often refuse radical cystectomy (RC) and urinary diversion, to keep their body image and quality of life._x000D_ OBJECTIVES: To estimate the response rate of gemcitabine, paclitaxel, doxorubicin combined with radiotherapy aiming at bladder preservation in elderly patients ?75 years old with recurrent high grade T1 urothelial carcinoma (UC). We conducted a prospective study to evaluate the multimodality treatment for bladder preservation in elderly patients. Overall survival, disease free survival, and quality of life were estimated and correlated with a matched arm of (RC)._x000D_ Methods METHODS: In a prospective study, we included 105 elderly patients with NMICB, 57 patients had high grade T1 tumor, 48 patients with high grade Ta, both TA and T1 were NMICB, patients were recurrent after complete course of intavesical BCG, patients asked for bladder preservation. The multimodality treatment arm was compared with matched arm of 60 patients treatment with RC. Follow up was up to 3 - 4years. Overall survival (OS) and disease free survival (DFS) was calculated using Kaplan-Mayer and Cox proportional hazards model and compared to a second arm of 30 patients with similar criteria that had RC. Inclusion criteria in both arms were non-metastatic NMICB, no prior chemotherapy, glomerular filtration rate <60?mL/min. Gemcitabine (900?mg/m(2)), paclitaxel (135?mg/m(2)), and doxorubicin (40?mg/m(2)) were administered on day 1 of each 14-day cycle. Pegfilgrastim was given with every cycle on either day 1 or day. low dose radiotherapy were given following chemotherapy. Results RESULTS: Median age was 77 years (range 75-84). All patients had complete responses. Grade 3 and 4 nonhematologic toxicities were fatigue and mucositis (14% each). There were 12 episodes of neutropenic fever, no treatment-related deaths. Median overall survival was 28.5 months Conclusions CONCLUSION: Results of combination of gemcitabine, paclitaxel, and doxorubicin as first-line chemotherapy combination with radiotherapy for elderly patients with recurrent high grade Ta, T1 NMICB of UC in elderly patients ?75 years old. Were compatible with RC. Bladder preservation with first line chemoradiothery would be considered as an alternative to RC in elderly patients as it offers better quality of life Funding none
Authors
Mohamed Wishahi
Hossam Elganzoury Amr Elkhouly |
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MP15-12 |
Phase Ib Trial of ALT-803, an IL-15 Superagonist, Plus Bacillus Calmette Guerin (BCG) for the Treatment of BCG-Naïve Patients with Non-Muscle-Invasive Bladder Cancer (NMIBC). |
Bladder Cancer: Non-invasive I | 17BOS |
Abstract: MP15-12 Sources of Funding: Supported in part through NIH/NCI SBIR Phase I & II grants (CA156740: Wong) Introduction The current standard of care (SOC) treatment for patients with high risk NMIBC is a transurethral resection of the bladder tumor or biopsy followed by a 6-week induction course of intravesical BCG treatment and supplementary maintenance instillations approximately every 3 months thereafter (Lamm DL et al, 2000). While clinical response is significantly improved with BCG treatment, 50% of patients are still expected to suffer recurrent disease within the first 12 months (Sfakianos JP, et al 2014). Thus, the pursuit of novel agents to prevent progression and recurrence of NMIBC remains critical. This phase Ib clinical trial evaluates the safety and tolerability of ALT-803, an IL-15 superagonist, plus BCG in BCG-naive NMIBC patients. Methods A dose escalation 3+3 design was employed to evaluate intravesical ALT-803 plus 50 mg BCG in BCG-naive patients with Ta, T1 or Tis stage NMIBC. Patients received intravesical ALT-803 in conjunction with BCG weekly for 6 consecutive weeks (induction phase) and then encouraged (but not required) to receive maintenance BCG alone as per standard practices. Patients then had a routine cystoscopy and voided urinary cytology every 3 months for 2 years to determine confirmatory response assessment. Negative cystoscopy, VUC and/or biopsy yielded a complete response (CR). No cohort (100, 200 or 400 ?g/instillation ALT-803) experienced any dose limiting toxicities. Results To date, 100% patients (9/9) are disease-free (CR) at 12 months and continue to be followed for recurrence for up to 2 years. Adverse events (AEs) consistent with SOC BCG treatment such as hematuria and urinary tract pain were reported in all cohorts. One patient in 400 ?g ALT-803 instillation cohort developed a urinary tract infection requiring delay of intravesical treatment by 1 week. No grade 3/4 toxicities were noted and no DLTs were observed in any patients._x000D_ _x000D_ Conclusions Intravesical ALT-803 plus BCG treatment is safe and well tolerated in BCG-naive patients with NMIBC. All patients are disease-free, 12 months after treatment with BCG and ALT-803. Corollary immune studies are pending and further evaluation in expansion cohorts of a randomized phase II trial is currently underway. Clinical trial information: NCT02138734 Funding Supported in part through NIH/NCI SBIR Phase I & II grants (CA156740: Wong)
Authors
Charles J. Rosser, MD
Jeffrey Nix, MD Lydia Ferguson, PhD Hing C. Wong, PhD |
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MP15-13 |
A PHASE I TRIAL FOR THE USE OF INTRAVESICAL CABAZITAXEL, GEMCITABINE, AND CISPLATIN (CGC) IN THE TREATMENT OF BCG-REFRACTORY NON-MUSCLE INVASIVE UROTHELIAL CARCINOMA OF THE BLADDER |
Bladder Cancer: Non-invasive I | 17BOS |
Abstract: MP15-13 Sources of Funding: none Introduction Intravesical therapy is the first line treatment for non-muscle invasive bladder cancer (NMIBC) however response rates are not durable and response rates to second-line intravesical therapy are 20 percent or less in this population. The next step in management includes radical cystectomy with urinary diversion however many patients do not undergo cystectomy due to comorbid diseases or because of patient refusal. A preclinical murine intravesical trial using gemcitabine, cisplatin and a taxane found the combination therapy to be superior to single-agents alone. Thus there is a strong rationale for a multimodal combination intravesical regimen of these agents. Methods Patients with BCG refractory or recurrent high-risk (high-grade Ta or high/low grade T1 or CIS with any grade) non-muscle invasive bladder cancer who refused or were ineligible for radical cystectomy were enrolled. All patients underwent a pre-treatment transurethral resection of bladder tumor and then received a 6-week regimen of multi-agent intravesical chemotherapy. All patients received the same dose of gemcitabine (2000mg) while the dose of cisplatin and cabazitaxel were escalated as shown in table 1. Toxicity was categorized according to Common Terminology Criteria for Adverse Events v4. After treatment, patient response is assessed via random biopsy and urine cytology. Complete responders (negative biopsy and cytology at six weeks after induction) are eligible for 1 year of monthly maintenance therapy at the doses they received during the trial. Results Median age of the 9 patients was 74 years (table 1) and the median number of prior intravesical therapies was 4 (range 2-5). All patients completed 6 weeks of induction CGC. Any local toxicity was found in 7 patients with 5 experiencing at least 1 grade 1 toxicity and 4 experiencing at least 1 grade 2 toxicity. Seven of eight patients were complete responders. Conclusions Cabazitaxel, gemcitabine and cisplatin appears to be a well-tolerated intravesical salvage chemotherapy regimen for the treatment of BCG-refractory non-muscle invasive bladder cancer. Funding none
Authors
Guarionex DeCastro
Wilson Sui Jamie Pak Cory Abate-Shen Shing Lee Christopher Anderson Dara Holder James McKiernan |
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MP15-14 |
Neutrophil lymphocyte ratio predicts progression of non muscle invasive bladder cancer – prospective study one year follow up |
Bladder Cancer: Non-invasive I | 17BOS |
Abstract: MP15-14 Sources of Funding: none Introduction Non muscle invasive bladder cancer is a recurrent and progressive disease; currently we are unable to forecast recurrence in the individual patient. Recently we developed a mathematical model that found NLR as a good prognostic tool. The model was tested retrospectively in an additional study and found accurate too. The aim of the current study is to assess its accuracy to forecast recurrence prospectively in patients with NMIBC Methods All patients admitted to bladder tumor resection (TURBT) and agreed to participate in the study had blood drawn for blood count 24 hours prior to surgery. Patients with non-muscle invasive tumor were recruited and prospectively followed. Patients had urine cytology and cystoscopy every 3 months for 2 years following resection. Time to recurrence and recurrence free of tumor were recorded. Statistical analysis was done with X2 test for categorical parameters and T test for serial parameters. Logistic regression was performed to forecast prognosis. Results 123 patients were recruited, mean age was 71 years, all patients had at least 1 year follow up. Twenty nine patients (23.6%) experienced biopsy proven tumor recurrence. The mean time for recurrence was 7.38 months._x000D_ Neutrophil to Lymphocyte rate > 2 showed direct statistically significant correlation with tumor recurrence (p=0.038), tumor stage showed the same correlation (p=0.048). The specificity of our recurrence forecasting model was 96.8%. EORTC score did not demonstrate significance between the recurrent and non-recurrent groups._x000D_ Conclusions Our mathematical model that found NLR as a prognostic tool in patients with NMIBC was tested for the first time prospectively. The model demonstrated its ability to forecast recurrence more accurately then tumor stage grade and EORT score in the individual patient with NMIBC._x000D_ The main limitation of this work is the relatively low number of patients._x000D_ _x000D_ Funding none
Authors
Itamar Getzler
Zaher Bahouth Ofer Nativ Jacob Rubinstein Sarel Halachmi |
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MP15-15 |
Urine sample derived CK20- and IGF2-expression as biomarker for the detection of bladder cancer |
Bladder Cancer: Non-invasive I | 17BOS |
Abstract: MP15-15 Sources of Funding: Supported by European Regional Development Fund. Introduction Cytokeratin 20 (CK20) and Insulin-like growth factor 2 (IGF2) were previously proposed to be elevated in patients with bladder cancer (BCa). A two cohort design validation study was used to assess the relevance for BCa detection of both markers in urine samples. The results were compared to voided urine cytology (VUC). Methods RNA isolation was carried out using 5 ml spontaneous urine samples of 196 and 97* histologically positive BCa patients for the test and validation* cohort, respectively. Additionally patients with benign urological diseases, nephrolithiasis and unconfirmed BCa suspicion as well as healthy control subjects were included for a total of 103/50* control subjects in the test and validation* cohort. Urinary mRNA levels were determined by qPCR and the results were normalized as molecule ratio to RPLP0. Receiver operating characteristic curves and corresponding AUC values were used to evaluate the diagnostic performance of both markers. Optimal cut-off values were determined by Youden Index. Results Urinary mRNA levels were significantly elevated 3.4/11*-fold for CK20 and 188/64*-fold for IGF2 in BCa patients compared to controls in the test and validation* cohort, respectively. IGF2 performed slightly better with an AUC of 0.83 for both cohorts compared to CK20 with an AUC of 0.78 and 0.82* for the test and validation* cohort, respectively. Combined analysis of IGF2 and CK20 with at least one positive marker resulted in a sensitivity (0.78/0.90*) and specificity (0.88/0.84*) similar to that of VUC. The sensitivity of VUC in combination with IGF2 and CK20 was considerably increased (0.95/0.93*) while specificity was slightly reduced (0.72/0.84*) compared to VUC alone in the test and validation* cohort. Conclusions Expressions of IGF2 and CK20 correlated significantly with BCa with a diagnostic performance similar to VUC. Combined analysis of voided urine cytology together with expression levels of CK20 and IGF2 clearly enhances overall test performance. Therefore, its relevance for BCa diagnosis should be evaluated in a larger cohort. Funding Supported by European Regional Development Fund.
Authors
Karsten Salomo
Doreen Huebner Manja U. Boehme Alexander Herr Ulrike Heberling Oliver W. Hakenberg Daniela Jahn Marc-Oliver Grimm Astrid Enkelmann Daniel Steinbach Susanne Fuessel Manfred P. Wirth |
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MP15-16 |
The Association of Age with Perioperative and Clinicopathologic Outcomes Following Radical Cystectomy for Non-Muscle Invasive Bladder Cancer |
Bladder Cancer: Non-invasive I | 17BOS |
Abstract: MP15-16 Sources of Funding: None Introduction Radical cystectomy (RC) remains underutilized in patients with non-muscle invasive bladder cancer (NMIBC), particularly elderly patients, despite data demonstrating inferior survival for patients with NMIBC who experience disease progression. We evaluated the association of age with perioperative and oncologic outcomes after RC for NMIBC. Methods Multi-institutional review of patients with NMIBC managed with RC between 2000-2013. Patients were stratified by age: <70 versus ≥70. Associations of age with receipt of perioperative blood transfusion (PBT), prolonged operative time (≥75th%; pORT) and length of stay (≥75th%; pLOS), pathology at RC, and 30/90 day complications were assessed using multivariable logistic regression. Recurrence-free (RFS), cancer-specific (CSS), and overall survival (OS) were evaluated using the Kaplan-Meier method, multivariable Cox proportional hazards regression models, and competing risks models. Results A total of 489 patients were identified, of whom 263 (55.8%) were <70 and 226 (46.2%) were ≥70. On multivariable analysis, age ≥70 was not significantly associated with patients’ risk of receipt of a PBT, pORT, pathologic stage pT2-4 or pN+, 30 day or 90 day grade III+ complications (all p>0.05). pLOS was more likely in older patients (OR 1.77; 95%CI 1.09-2.85; p=0.02). Estimated 5-yr RFS, CSS, and OS in patients <70 versus ≥70 was 70% vs 62% (p=0.14), 84% vs 77% (p=0.06), and 74% vs 54% (p<0.01). On multivariable Cox regression analyses, age ≥70 was not independently associated with RFS (HR 1.10; 95% CI 0.79-1.52; p=0.57) or CSS (HR 1.22; 95% CI 0.82-1.82; p=0.32), but remained associated with decreased OS (HR 1.91; 95% CI 1.50-2.45; p<0.01). Moreover, among all patients and as stratified by age, pathologic upstaging was associated with worse RFS, CSS, and OS on both multivariable Cox proportional hazards regression and in competing risk (of non-cancer death) models (Table). Conclusions Older patients with NMIBC had similar risks of pathologic upstaging at RC, and patients upstaged at surgery had inferior cancer outcomes across age strata. Meanwhile, advanced age was not associated with increased risks of PBT, pORT, or perioperative complications. These data support the use of RC for select older patients with high-risk NMIBC. Funding None
Authors
William Parker
Woodson Smelser Igor Frank Jeffrey Holzbeierlein Prabin Thapa Tomas Griebling R. Jeffrey Karnes R. Houston Thompson Matthew Tollefson Eugene Lee Stephen Boorjian |
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MP15-17 |
Beyond Supplementation: The role of Vitamin D in Non-Muscle Invasive Bladder Cancer |
Bladder Cancer: Non-invasive I | 17BOS |
Abstract: MP15-17 Sources of Funding: None Introduction The Vitamin D Receptor (VDR) gene has been found to regulate the expression of cathelicidin, an antimicrobial peptide which represent a significant portion of the body's immune response against mycobacterium tuberculosis. VDR is also associated with macrophage phagocytosis, which is a key driver of the cell-mediated immunological response stimulated by Bacillus-Calmette Guerin (BCG). Various VDR single nucleotide polymorphisms (SNP) have been found to be associated with increased susceptibility to pulmonary tuberculosis. Hence, we hypothesize that this group of patients may similarly be unable to mount an immune response during the administration of intravesical BCG. In this study, we evaluated the predictive role of 3 VDR SNPs in the context of Asian patients with non-muscle invasive bladder cancer (NMIBC) recurrence and BCG immunotherapy outcome. Methods Peripheral blood DNA was prospectively obtained from 140 evaluable EORTC intermediate to high risk NMIBC patients, who underwent post-transurethral resection intravesical regimes of BCG or BCG with interferon alpha. 3 VDR SNPs commonly implicated in susceptibility to tuberculosis infections were evaluated using high resolution melt (HRM) analysis. Results were confirm with sequence analysis. Kaplan-Meier together with Log-Rank test and Cox regression methods were used to analyze the data._x000D_ _x000D_ _x000D_ Results Genotype frequencies were similar between the NMIBC patients and controls in accordance to the Hardy Weinberg equilibrium. Mean follow-up time was 91.9 months. Overall mean time to recurrence and progression was 25.8 months and 47.0 months respectively. Kaplan-Meier analysis indicate that individuals carrying the VDR genotype rs1544410 A/G were significantly associated with lower recurrence-free survival rates after BCG therapy (p=0.007). The VDR rs1544410 “A� allele frequency was found to be higher in patients with bladder cancer recurrences (p=0.01). 100.0% of patients with the VDR genotype rs731236 C/C had carcinoma in situ of the bladder, compared to 20.5% of the patients with the genotype T/T and 12.5% of the patients with the genotype T/C (?2 (2)= 8.31, p=0.016). No association of VDR genotypes with progression-free survival was found. Conclusions Our findings suggest that polymorphisms in the VDR gene correlate with response to BCG therapy in NMIBC patients and further work should be performed to evaluate their utility as predictive markers of response to BCG immunotherapy. Funding None
Authors
Ziting Wang
Yew Koon Lim Ratha Mahendran Esuvaranathan Kesavan Edmund Chiong |
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MP15-18 |
Safety and Tolerability Analysis of Hyperthermic Intravesical Mitomycin to Mitomycin alone in HIVEC I and HIVEC II: An Analysis of 307 Patients |
Bladder Cancer: Non-invasive I | 17BOS |
Abstract: MP15-18 Sources of Funding: Combat Medical Introduction The Combat BRS system is a novel hyperthermia delivering device which allows temperature controlled delivery and re-circulation of HM via a urethral catheter using an external heat source. HIVEC I and II are two randomized control trials to determine if HM is superior to MMC alone in intermediate risk non-muscle invasive bladder cancer (NMIBC). We report safety and tolerability outcomes comparing the two treatment arms. Methods HIVEC I and II are multi-centre, open-labeled randomized controlled trials recruiting patients from 25 Spanish and UK centers. The HIVEC I randomizes patients to either MMC, HM for 30 mins and HM for 60 mins (HM 60). Patients receive 4 once weekly treatments followed by 3 one monthly treatments. HIVEC II randomizes patients to MMC or HM 60 where both treatment arms receive 6 weekly treatments. Both trials use 40 mg MMC diluted in either 50 ml (HIVEC I) or 40 ml (HIVEC II) of sterile water. We compared all HIVEC I and II patients who were randomized to MMC (n=154) or HM 60 (n=153). _x000D_ _x000D_ HM was delivered by heating MMC to 43°C. Adverse events (AE) were reviewed by the independent data monitoring committee. HIVEC I and II were registered with EudraCT (2013-002628-18) and ISRCTN (23639415) respectively. _x000D_ Results 307 patients were included for analysis. 88.9% and 94.8% of HM and MMC patients respectively completed inductive therapy. Reasons for stopping therapy in 17 HM patients include: MMC allergy (n= 11), urinary symptoms (n=2), pain (n=1), haematuria (n=1), pneumonia (n=1) and in 8 MMC patients include: MMC allergy (n=7) and angina (n=1). AE which led to early termination of treatment were Grade II. There was no significant difference in patients with AE between HM (n=78, 51%) and MMC (n=66, 42.9%) (p=0.154). Most AE were Grade ?II (HM: 97.7%, MMC: 98.5%). There was no Grade >III related AE._x000D_ _x000D_ There was no difference in pain (HM: 13.1% vs MMC: 8.4, p=0.190), dysuria (HM: 5.2% vs MMC: 6.5%, p=0.617), urgency (HM: 11.8% vs MMC: 3.9%, p=0.067), incontinence (HM: 3.3% vs MMC: 0.6%, p=0.097) and rash/ allergic reaction (HM: 7.8% vs MMC: 5.2%, p=0.327). HM treated patients were significantly more likely to develop urinary frequency (HM: 15.0% vs MMC: 5.8%, p=0.008), haematuria (HM: 11.8% vs MMC: 3.9%, p=0.010) and bladder spasm (HM: 6.5% vs MMC: 0.6%, p=0.006). _x000D_ Conclusions HM delivered using the Combat BRS system is safe and well tolerated. The majority of AE in the HM arm were low grade with urinary frequency and haematuria more common in HM in comparison to MMC treated patients. HM represents a safe and well tolerated intravesical treatment for NMIBC. Funding Combat Medical
Authors
Wei Shen Tan
Juan Palou John Kelly HIVEC I and HIVEC II Clinical Trials Group |
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MP15-19 |
Improved Recurrence Free Survival in NMIBC Patients Taking Metformin Demonstrates Dose Dependence |
Bladder Cancer: Non-invasive I | 17BOS |
Abstract: MP15-19 Sources of Funding: none Introduction Previous literature has suggested that metformin may affect recurrence of non-muscle invasive bladder cancer (NMIBC), but data could be confounded by differences in cohorts. The purpose of this study was to evaluate the association of metformin among common prognostic factors for bladder cancer recurrence in a multivariate model and evaluate whether Metformin demonstrates a dose dependent effect. Methods An institutional database identified 503 unique patients treated with transurethral resection (TUR) for NMIBC. These patients were followed longitudinally and had an additional 682 recurrences and subsequent TURs. A total of 1185 TURs were performed on these 503 patients. 144 cases of NMIBC, in 60 unique patients, met inclusion criteria and were taking Metformin at the time of TUR. Cox proportional hazards models were used to evaluate associations with recurrence-free survival (RFS). Results Median time to recurrence was 15 months (IQR 6.18-35.6). Median age was 70.6 years. On univariate analysis, factors associated with statistically significant improved RFS included: metformin use at TUR (p=0.01, HR 0.61, 95% CI 0.42-0.89), metformin dose ≥2000 mg (p=0.03, HR 0.50, 95% CI 0.28-0.90), age, multifocality, tumor size, perioperative Mitomycin-C, bacillus Calmette-Guerin therapy, and intravesical chemotherapy. _x000D_ _x000D_ Multivariate analysis demonstrated improved RFS when comparing diabetic patients on metformin at TUR to diabetic patients not on metformin (p=0.0002, HR 0.51, 95% CI 0.36-0.72) and improved RFS even when comparing diabetic patients on metformin to non-diabetic patients not on metformin (p=0.0001, HR 0.60, 95% CI 0.46-0.77). A separate multivariate analysis, demonstrated improved RFS when comparing patients taking ≥2000 mg of metformin to patients taking <2000 mg at the time of TUR (p=0.0054, HR 0.39, CI 0.20-0.76). The 5-year RFS rate was 42.3% for diabetic patients on metformin, 35.1% for non-diabetics not on metformin, and 9.7% for diabetic patients not treated with metformin (p=0.0001). Conclusions Metformin use at the time of TUR is associated with improved 5 year RFS in a multivariate model. Metformin dose ≥2000 mg is independently associated with improved RFS. Funding none
Authors
Timothy Rushmer
Shiva Damodaran E. Jason Abel Shi Fangfang Kyle Richards David Jarrard Tracy Downs |
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MP15-20 |
MCM-2 cell based assay is a sensitive and specific test for risk stratification of bladder cancer patients. |
Bladder Cancer: Non-invasive I | 17BOS |
Abstract: MP15-20 Sources of Funding: Cytosystems Ltd., Aberdeen, Scotland, UK Introduction Cystoscopy remains the gold standard in the investigation of haematuria and follow up of patients diagnosed with the urothelial carcinoma (UC) of the bladder. There has been extensive research into identifying urinary markers with the aim of improving diagnostic accuracy. Minichromosome maintenance 2 protein (MCM2) is a marker of cell proliferation and ectopic expression is a characteristic feature of malignancy and pre-malignancy._x000D_ Here we evaluate diagnostic accuracy of MCM2 in diagnosis and surveillance of UC._x000D_ Methods A feasibility study was conducted on 176 patients and healthy volunteers from 3 centres in the UK from Cystoscopic Surveillance (CS) and Gross Haematuria (GH) clinics. The verification set comprised 149 volunteers. _x000D_ SurePath platform was used to process the urine cytology samples. Immunocytochemical analysis of MCM2 was performed as a marker for presence of UC. Feasibility data sets were used to determine MCM2 threshold for GH and CS counts using the optimised Youden’s Index (J) and optimal sensitivity, establishing conditions such that there was a zero false negative rate. Cut-off values were used to determine sensitivity, specificity, PPV and NPV._x000D_ Results Using optimised J-approach, the feasibility sets for GH and CS samples yielded cut-offs of 130 and 81 MCM2 stained cells per slide respectively._x000D_ The zero false negative approach yielded cut-offs of 44 and 13 MCM2 stained cells for GH and CS patients respectively._x000D_ Optimised J cut-off yielded sensitivities of 81% in CS group in feasibility and 92.3% in validation with specificities of 80.3 and 94.1% respectively. Corresponding NPV and PPVs ranged from 94.2-96% and 73.9-75.0%._x000D_ GH sensitivity by optimised J was 87.5 in feasibility and 70.8% in validation sets. Specificities were 92.6 and 95.8% respectively. NPVs were 97.7 and 76.7%, PPVs were 77.8 and 94.4%._x000D_ Using zero false negative level for cut-off yielded sensitivities close to 100% across all sets, albeit with a concomitant loss of specificity._x000D_ Conclusions MCM2 is a reliable non-invasive test, potentially useful in diagnosis of primary and recurrent UC. MCM2 may be used to stratify cases where there is no likelihood of disease i.e. zero false negatives, thus avoiding invasive intervention. In this setting false positives are acceptable as the intervention occurs anyway: the stratification aims to reduce intervention for a large subset of true negatives, resulting in huge health economic benefits plus reduction to morbidity and discomfort associated with flexible cystoscopy. Funding Cytosystems Ltd., Aberdeen, Scotland, UK
Authors
Kasra Saeb-Parsy
Peter Caie Durgesh Rana Nadira Narine Bensita Mary Viju Jose Thottakam Sushant Dhanvhijay Andrew Ball Alexander Wilson David Harrison |
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MP16-01 |
Clinical implications of sunitinib and N-desethyl-sunitinib plasma concentrations for treatment outcome in metastatic renal cell carcinoma patients |
Kidney Cancer: Advanced (including Drug Therapy) II | 17BOS |
Abstract: MP16-01 Sources of Funding: none Introduction Therapeutic drug monitoring (TDM) has been recognized as a useful tool for optimizing the dosages of many drugs, even in molecular-targeted therapeutics. In this study, we examined the associations between the pharmacokinetics of sunitinib (SU) and its metabolite N-desethyl-sunitinib (DSU) and adverse events (AEs) and clinical outcomes in patients with metastatic renal cell carcinoma (mRCC). Methods The pharmacokinetics of SU and DSU were examined in 26 patients (20 male and 6 female patients) with mRCC. Plasma SU and DSU levels were measured using high-performance liquid chromatography, and a pharmacokinetic study was performed on day 7 in the first cycle of SU. The associations between SU/DSU pharmacokinetics and the occurrence of AEs, best response rate, progression-free survival (PFS), time to treatment failure (TTF), and overall survival (OS) were investigated. Results All patients were treated with 37.5 mg/day SU at the day of pharmacokinetics. The mean trough levels of SU and DSU were 76.7 and 16.8 ng/mL respectively. Occurrence of hand-foot syndrome and thrombocytopenia (P = 0.002 and 0.024 respectively by Mann-Whitney test) was associated with high trough levels of SU. Low trough levels of DSU were significantly associated with drug discontinuation due to disease progression and were associated with worse tumor response (P = 0.035 and 0.042 respectively by Mann-Whitney test, Figure 1). Patients with DSU trough levels of or higher than 15.0 ng/mL showed a tendency toward increased PFS, TTF, and OS than those with trough levels lower than 15.0 ng/mL (Figure 2). SU trough levels were not associated with prognosis. Conclusions TDM of SU and DSU in patients with mRCC may be useful to determine adequate dosages and prevent severe AEs. Further studies are required to establish the usefulness of TDM of SU and DSU for ensuring long-term clinical efficacy in patients with mRCC. Funding none
Authors
Kazuyuki Numakura
Nobuhiro Fujiyama Makoto Takahashi Hiroshi Tsuruta Atsushi Maeno Mitsuru Saito Takamitsu Inoue Shintaro Narita Mingguo Huang Shigeru Satoh Takenori Niioka Masatomo Miura Tomonori Habuchi |
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MP16-02 |
Influence of genetic polymorphisms on the pharmacokinetics of sunitinib in patients with metastatic renal cell carcinoma |
Kidney Cancer: Advanced (including Drug Therapy) II | 17BOS |
Abstract: MP16-02 Sources of Funding: none Introduction Sunitinib (SU) is an oral multi-targeted tyrosine kinase inhibitor (TKI) for renal cell carcinoma (RCC). Because of severe adverse events (AEs) associated with its use, patients have to either reduce the dose or cease taking SU. Single-nucleotide polymorphisms (SNPs) from the ABCB1, ABCG2, CYP3A4, and CYP3A5 genes were reported to have an effect on individual pharmacokinetic variation in oral bioavailability of other TKIs. The aim of this study was to determine whether there exists an association between these SNPs with individual variation in sunitinib plasma concentration. Methods From April 2006 to July 2015, we administrated SU to 80 metastatic RCC (mRCC) patients at Akita University. Of these patients, the pharmacokinetics of SU and its metabolite, N-desethyl sunitinib (DSU), were examined in 25 cases (19 males and 6 females). Plasma SU and DSU levels were measured using high-performance liquid chromatography, and a pharmacokinetic study was performed on day 7 of the first cycle. We tested for association between SU and DSU pharmacokinetics with SNP genotype and allele frequencies. Results All patients were treated with 37.5 mg/day of SU on the day of pharmacokinetic assessment, and had mean trough levels of 76.7 ng/mL and 16.8 ng/mL for SU and DSU, respectively. The ABCB1 1236 TT genotype was associated with high SU trough levels compared to that found in patients with a #T or ## genotype (95.9 ng/mL versus 61.6 ng/mL, respectively; P = 0.030). In addition, the ABCB1 2677 G allele was associated with high DSU trough levels compared to that seen with the 2677 # allele (12.7 ng/mL versus 18.8 ng/mL, respectively; P = 0.047) (Table 1). Conclusions Our study found that the ABCB1 1236 TT genotype and the 2677 G allele were associated with increased trough levels of SU and DSU, respectively. Based on our findings, the pharmacokinetics of SU and DSU may be informative indicators to determine effective dosage and prevent manifestation of severe AEs in patients with mRCC. Further evaluation of ABCB1 genotypes and sunitinib dosage is warranted. Funding none
Authors
Kazuyuki Numakura
Nobuhiro Fujiyama Makoto Takahashi Hiroshi Tsuruta Atsushi Maeno Mitsuru Saito Takamitsu Inoue Shintaro Narita Mingguo Huang Shigeru Satoh Takenori Niioka Masatomo Miura Tomonori Habuchi |
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MP16-03 |
Utility of inflammatory markers in prognosis for patients with renal cell carcinoma and vena cava tumor thrombus |
Kidney Cancer: Advanced (including Drug Therapy) II | 17BOS |
Abstract: MP16-03 Sources of Funding: None Introduction Nephrectomy and inferior vena cava (IVC) thrombectomy for renal cell carcinoma (RCC) with IVC involvement is associated with significant morbidity and mortality, making accurate prognosis valuable. Systemic inflammatory markers have shown to be prognostic in malignancy. We assess preoperative C-reactive protein (CRP), albumin, and the modified Glasgow Prognostic Score (mGPS), which combines both assays, for prognostic utility in RCC with IVC thrombus. Methods From 2006-2016, one surgeon performed 149 cases of radical nephrectomy and IVC tumor thrombectomy. Only those with clear cell RCC and available laboratory data were included. Patients were assigned an mGPS score 0-2 based on preoperative lab values (0=CRP ≤ 10 mg/L, 1=CRP > 10 mg/L, and 2=CRP > 10 mg/L and albumin < 3.5 g/dL). Other factors included in the analysis were age, gender, race, body mass index, 2009 AJCC pathologic T and M stages, necrosis, and nuclear grade. Also examined were well-established prognostic scoring systems, the University of California Los Angeles Integrated Staging System and the Mayo Clinic Stage, Size, Grade, and Necrosis scoring system. Log-rank and multivariable regression analysis examined overall survival (OS). Results Of 117 clear cell RCC patients with IVC thrombus, the mortality rate was 38.4% over a median follow-up period of 12.6 months (interquartile range 4.8-32.4 months). Patients with albumin < 3.5 g/dL represented 62.7% of the population and those with CRP > 10 mg/L represented 67.7%. Those with mGPS scores 0, 1, and 2 represented 32.3%, 14.4%, and 53.54%, respectively. CRP > 10 mg/L (HR 4.94, 95% 1.7-14.2, p<0.001), albumin < 3.5 g/dL (HR 2.16, 95% 1.1-4.3, p=0.024), and mGPS=2 (HR 5.56, 95% 1.9-16.1, p=0.002) correlated with OS. After adjusting for other factors, only mGPS=2 (HR 4.25, 95% 1.4-13.3; p=0.01) was an independent predictor of OS. A secondary analysis of only non-metastatic patients maintained significance. Conclusions For patients with RCC and IVC involvement, elevated CRP and low albumin correlate with OS. Combining albumin with CRP in the modified Glasgow Prognostic Score independently predicts OS. The mGPS could serve as a useful clinical adjunct with regard to follow-up counseling and clinical trial design. Funding None
Authors
Adam Lorentz
Manik Gupta Matthew Broggi Andrew Leung Dattatraya Patil Viraj Master |
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MP16-04 |
MEAN HOUNSFIELD UNITS ON UNENHANCED CT PREDICTS RESPONSE TO EVEROLIMUS IN TUBEROUS SCLEROSIS COMPLEX ASSOCIATED ANGIOMYOLIPOMAS |
Kidney Cancer: Advanced (including Drug Therapy) II | 17BOS |
Abstract: MP16-04 Sources of Funding: Novartis Pharmaceuticals Introduction Everolimus, a mammalian target of rapamycin (mTOR) inhibitor, has been used for tuberous sclerosis complex associated angiomyolipoma (TSC-AML). However, we lack tools to accurately predict response in individual patients. Methods In this single-center phase 2 nonrandomized open label trial, eighteen patients with forty-three measurable AMLs associated tuberous sclerosis complex were treated with oral everolimus (10mg/d). AML volume and computed tomography (CT) parameters were measured at baseline, 12, 24, 48 and 96 weeks. Receiver operating characteristic curve (ROC) method was used to calculate the sensitivity, specificity and diagnostic accuracy. All analyses used a significance level of 0.05 and were generated in SPSS19.0 software. Results Target AML response, volume reductions over 50% relative to baseline defined by RECIST criteria, were 65.85%(27/41), 67.50%(27/40) and 68.42%(26/38) at weeks 12, 24 and 48, respectively. Mean HU on unenhanced CT and the longest diameter (DL) at baseline significantly correlated with percentage change of target AML at different indicated time. The AUC for mean hounsfield units (HU) on unenhanced CT were 0.99, 1.00 and 0.94 at weeks 12, 24 and 48, respectively, while the AUC for DL of 0.71, 0.78 and 0.91 at weeks 12, 24 and 48, respectively. Representative scans from two different status of mean HU target AML treated with everolimus are shown in Figure 1. A threshold of -24.50 HU for predicting AML response showed 92.86% sensitivity and 96.30% specificity at 12 weeks (likelihood ratio=25.07), 100.0% sensitivity and 96.30% specificity at 24 weeks (likelihood ratio=27.00), while 91.67% sensitivity and 96.15% specificity at 48 weeks (likelihood ratio=23.83), respectively (Figure 2). Conclusions Mean HU on unenhanced CT of target AML at baseline predicts response to everolimus and it may be useful to select treatment. Funding Novartis Pharmaceuticals
Authors
Yi Cai
Hanzhong Li Yushi Zhang |
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MP16-05 |
Early tumor shrinkage under second-line targeted therapy for metastatic renal cell carcinoma as a predictor of overall survival: a retrospective multiinstitutional study in Japan |
Kidney Cancer: Advanced (including Drug Therapy) II | 17BOS |
Abstract: MP16-05 Sources of Funding: None Introduction It remains the standard approach for assessing the prognosis of mRCC patients treated with molecular-targeted agents to use the MSKCC and IMDC risk classifications, while the significant prognostic impact of the objective tumor response to these novel agents in mRCC patients has recently been documented in various studies. We also reported that the overall survival (OS) in patients with mRCC was closely correlated with the degree of tumor shrinkage at 12 weeks after the introduction of first-line targeted agents (Target Oncol 2016; 11: 175-82). Of these, however, there was no study focusing on data from mRCC patients treated with second-line targeted agents outside clinical trials. The objective of this study was to evaluate the impact of early tumor shrinkage (ETS) induced by a second-line targeted agent on OS in mRCC patients. Methods This study retrospectively included 271 consecutive Japanese patients with mRCC who received second-line targeted therapy for at least 3 months. ETS was defined as the degree of tumor shrinkage at the first post-baseline radiological evaluation conducted 4 to 8 weeks after initiating second-line targeted therapy. Results Of the 271 patients, 26 had ETS from -100 to -50%, 70 from -49 to -25%, 84 from -24 to 0%, and the remaining 91 failed to achieve a reduction in the tumor size. The median OS following the initiation of second-line targeted therapy stratified according to ETS was 45.8, 30.9, 22.1 and 14.2 months, respectively. Univariate analysis identified prior nephrectomy, the MSKCC risk classification, C-reactive protein (CRP) level, number of metastatic organs, sarcomatoid feature, introduced second-line agent and ETS induced by a second-line agent as parameters significantly associated with OS, of which, only the MSKCC classification, CRP level and ETS appeared to have independent impacts on OS on multivariate analysis. Conclusions Collectively, these findings suggest that ETS at the first post-baseline assessment under treatment with a second-line targeted agent could serve as a useful parameter with an independent impact on OS in mRCC patients receiving second-line targeted therapy; therefore, it is highly recommended to select second-line targeted agents that make it possible to induce prompt tumor remission to further improve the prognosis of patients with mRCC following the failure of first-line targeted therapy. Funding None
Authors
Keita Tamura
Hideaki Miyake Seiichiro Ozono |
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MP16-06 |
EARLY RESPONSE AT FOUR WEEKS OF C-REACTIVE PROTEIN PREDICTS SURVIVAL IN PATIENTS WITH METASTATIC RENAL CELL CARCINOMA TREATED WITH TYROSINE KINASE INHIBITORS |
Kidney Cancer: Advanced (including Drug Therapy) II | 17BOS |
Abstract: MP16-06 Sources of Funding: none Introduction C-reactive protein (CRP) is a potential biomarker for renal cell carcinoma (RCC) (Saito K, Nat Rev Urol, 2011). The dynamic change of CRP levels, CRP kinetics, is associated with survival of patients with metastatic RCC (mRCC) in the cytokine era. We previously reported that early CRP response could predict overall survival (OS) for mRCC patients treated with tyrosine kinase inhibitors (TKI) in EAU congress 2016. In this study, we further explored whether the early CRP response could predict progression-free survival (PFS) and response rates (RR) with more number of cases. Methods A total of 103 patients (80 men and 23 women) were treated with TKI for mRCC from 2008 to 2013 at our institutions. Overall, 43 and 60 patients were treated with sunitinib and sorafenib, respectively. Fifty patients (49%) had received prior immunotherapy, and 69 patients (67%) had undergone nephrectomy previously. Baseline CRP elevation was defined as a level of 10 mg/L or more. Patients were divided into three groups according to their early CRP kinetics: patients whose baseline CRP levels were <10 mg/L (non-elevated group), patients whose baseline CRP levels were 10 mg/L or more and had decreased by more than 20% 4 weeks after the initiation of TKI (early CRP responder), and the remaining patients (non-early CRP responder). The endpoints were OS, PFS and RR. Results The median follow up period was 21 months (range 1 to 79 months). Baseline CRP levels were elevated in 41 patients (40%). Among these 41 patients, 19 (18%) were early CRP responder. The 1-year OS and PFS rates for the entire cohort were 69% and 40%, respectively. The 1-year OS rates of non-elevated group, early CRP responder, and non-early CRP responder were 79%, 62%, and 36% (p < 0.001). The 1-year PFS rates of these three groups were 50%, 23%, and 10% (p < 0.001). In multivariate analysis, the early CRP kinetics assessment was a significant independent factor for OS and PFS. Though there were no significant differences in the objective response rates between these three groups (p = 0.56), significantly more patients had progressive disease in the non-early CRP responder (p = 0.02). Conclusions Early CRP response at 4 weeks is predictive of survival for patients with mRCC treated with TKI. Funding none
Authors
Yosuke Yasuda
Kazutaka Saito Naoko Kawamura Sho Uehara Takeshi Yuasa Minato Yokoyama Junichiro Ishioka Yoh Matsuoka Shinya Yamamoto Shunji Takahashi Tetsuo Okuno Junji Yonese Kazunori Kihara Yasuhisa Fujii |
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MP16-07 |
Usefulness of inflammatory marker dynamics one month after the first-line targeted therapy initiation for PFS prediction in patients with metastatic clear cell renal cell carcinoma |
Kidney Cancer: Advanced (including Drug Therapy) II | 17BOS |
Abstract: MP16-07 Sources of Funding: None Introduction Progression-free survival (PFS) of first-line targeted therapy (TT) greatly influences on the survival of patients with metastatic renal cell carcinoma (RCC). If we can predict disease progression early after an administration of first-line TT, we may be able to choose appropriate targeted agent (TA) for individual patients. In the present study, we evaluated whether post-treatment inflammatory marker and LDH levels had adoptive impacts on PFS prediction in addition to conventional prognostic factors. Methods In this multi-institutional study 325 patients with metastatic RCC were enrolled from 8 institutions. Of these patients 215 patients whose tumors were diagnosed as clear cell type and in whom first-line TAs could be continued for more than 1 month, were selected (median follow-up period: 20.6 mo). Pretreatment clinical factors, pathological factors, and laboratory data 1 month after TA administration including inflammatory markers [neutrophil count, neutrophil-to-lymphocyte rate (NLR) and C-reactive protein (CRP)] and lactate dehydrogenase (LDH), were reviewed. To identify predictors for PFS, univariate and multivariate analyses were done by cox proportional hazards model. Results Six TAs were used as first-line TT. Tyrosine kinase inhibitors were used for 205 patients and mTOR inhibitors for 10 patients. Nephrectomy was done for 184 patients and percutaneous needle biopsy was done for the diagnosis in 31 patients. MSKCC risk criteria was favorable in 62 patients, intermediate in 122, poor in 17, not determined in 14. The 1-year PFS rate was 47%. Univariate analysis showed that female patients, Karnofsky performance status (KPS) <80%, sarcomatoid differentiation, time from diagnosis to systemic treatment <12 months, anemia, thrombocytosis, pretreatment neutrophil count >upper limits of normal (ULN), pretreatment LDH >1.5 x ULN, LDH 1 month after TT (LDH-1M) >1.5 x ULN, pretreatment NLR >3.7, NLR 1 month after TT (NLR-1M) >3.0, pretreatment CRP >3.0 mg/dL, and CRP 1 month after TT (CRP-1M) >1.5 mg/dL, were significantly associated with PFS. In contrast, LDH decline 1M after TT, decline in neutrophil count 1M after TT, CRP decline 1M after TT, and NLR decline 1M after TT, were not significant factor even in univariate analyses. In multivariate analysis, female, KPS <80%, time from diagnosis to systemic treatment <12M, pretreatment CRP >3.0, and NLR-1M >3.0 were independent predictors for PFS. When all patients were stratified to 3 groups by these 5 factors (0 risk vs. 1 or 2 risks vs. 3 risks or more), there were significant differences in PFS rates between the groups (p<0.0001). The median time to progression was 27.6 months in 0 risk, 10.0 months in 1 or 2 risks, and 2.8 months in 3 or more risks. Furthermore, when we looked at overall survival (OS), there were also significant differences in OS rates between the groups (p<0.0001). The median OS was 58.5 months in 0 risk, 33.5 months in 1 or 2 risks, and 7.6 months in 3 or more risks. Conclusions Integration of NLR-1M >3.0 to pretreatment factors may lead to the establishment of effective predictive models for disease progression in patients with metastatic clear cell RCC who receive targeted argents. The absolute value of NLR appeared to be more important for PFS prediction compared to the NLR decline 1 month after targeted therapy. Funding None
Authors
Keiichi Ito
Ayako Masunaga Nobuyuki Tanaka Ryuichi Mizuno Suguru Shirotake Yota Yasumizu Yujiro Ito Yasumasa Miyazaki Masayuki Hagiwara Kent Kanao Shuji Mikami Tetsuo Monma Ken Nakagawa Tsuyoshi Masuda Masafumi Oyama Tomohiko Asano Mototsugu Oya |
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MP16-08 |
Contribution of genetic polymorphisms related to axitinib pharmacokinetics to the clinical safety and efficacy in patients with advanced renal cell carcinoma |
Kidney Cancer: Advanced (including Drug Therapy) II | 17BOS |
Abstract: MP16-08 Sources of Funding: none Introduction Axitinib is approved for use in a second-line therapy for metastatic renal cell carcinoma (mRCC). The predictions of adverse events and efficacy may contribute to the development of personalized medicine. In this study, axitinib pharmacokinetics were analyzed, and the relationships between genetic polymorphisms, the frequency of adverse events, objective responses, and survival were evaluated. Methods A total of 53 patients with mRCC treated with axitinib were analyzed. ?High-performance liquid chromatography was used to measure the serum axitinib levels. AUC0–12 (ng?h/mL) was calculated using the serum levels at 0, 2, 4, 8, and 12 h following administration (C0, C2, C4, C8, C12, respectively; ng/mL) on day 7 of the treatment. The genetic polymorphisms related to the drug pharmacokinetics, including SLCO1B1, SLCO1B3, SLCO2B1, ABCB1, ABCG2, CYP2C19, CYP3A5, and UGT1A1, were analyzed using PCR-RELP. Results The axitinib trough levels (C0) were significantly correlated with AUC0–12 of axitinib. The mean C0 and AUC0–12 values in patients with UGT1A1 polymorphism of a poor metabolizer (*6/*6, *6/*28, and *28/*28) were significantly higher than in those with UGT1A1 polymorphism of an extensive metabolizer (*1/*1, *1/*6, *1/*28, *27/*28; p = 0.045 and P =0.035, respectively). The mean AUC0–12 value in patients with SLCO1B1 *15 was significantly higher than that in those without (p = 0.038). The incidence of hand-foot syndrome ? G2, hypothyroidism ? G2, increased aspartate aminotransferase ? G1, and increased alanine aminotransferase ? G1 in patients with C0 ? 10 ng/mL were significantly higher than that in those with C0 < 10 ng/mL (p = 0.013, P = 0.005, P = 0.037, and P = 0.005). The overall survival in patients with C0 ? 5 ng/mL?was significantly better than that in those with C0 < 5 ng/mL (p = 0.022). Conclusions The UGT1A1 and SLCO1B1 were significantly associated with serum axitinib levels. Axitinib trough levels predict therapeutic response in patients with mRCC. The optimal trough level of axitinib may be 5 to 10 ng/mL to achieve an effective treatment without severe adverse events. Funding none
Authors
Ryoma Igarashi
Norihiko Tsuchiya Takamitsu Inoue Nobuhiro Fujiyama Kazuyuki Numakura Hiroshi Tsuruta Hideaki Kagaya Atsushi Maeno Mitsuru Saito Shintaro Narita Takenori Nioka Masatomo Miura Shigeru Sato Tomonori Habuchi |
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MP16-09 |
Reexamining the Role of Extended Lymphadenectomy for the Management of Renal Malignancy in the Targeted Therapy Era |
Kidney Cancer: Advanced (including Drug Therapy) II | 17BOS |
Abstract: MP16-09 Sources of Funding: None Introduction The potential benefit of extended lymphadenectomy (eLND) for advanced renal malignancy remains controversial. We aimed to assess contemporary survival outcomes associated with eLND performed for kidney cancer patients. Methods Using Surveillance, Epidemiology, End Results (SEER) data, we identified patients with non-metastatic renal cancer (2004-2013) treated with nephrectomy with 1+ lymph nodes removed. Our primary exposure was extended lymphadenectomy, defined by 10+ lymph nodes removed. Outcomes of interest included 5- and 9-year cancer-specific (CSS) and overall survival (OS). Other covariates of interest included patient age, sex, race/ethnicity, marital status, year of diagnosis, tumor stage, tumor grade, nodal stage and tumor histology. Kaplan-Meier analyses and Cox proportional hazard models were generated to compare survival outcomes based on covariates and primary exposure of interest. Patients with missing tumor data were excluded from regression analyses. Results Among 66,013 kidney cancer patients treated with extirpative surgery, 7,523 (11.4%) had 1+ lymph nodes removed. The median lymph node count was 2 (IQR 1-6). Of this group, 1,031 (13.7%) patients had an eLND. Use of eLND was associated with advanced tumor stage and higher tumor grade (both p<0.001). Nine-year CSS and OS for eLND patients was 66.5% (vs 69.1% non-eLND, p=0.01) and 58.5% (vs 56.3% non-eLND, p=0.29), respectively. Among node-positive patients, 5-year CSS and OS with eLND were 40.0% (vs 34.3% non-eLND, p=0.55) and 33.1% (vs 28.4% non-eLND, p=0.73), respectively. After adjusting for confounding factors, Cox proportional hazard models estimated a significant OS benefit associated with eLND (adjusted hazard ratio (HR) 0.86, 95% Confidence Interval (CI) 0.74 - 0.99, p=0.04). Differences in CSS did not reach statistical significance overall (HR 0.88, 95% CI 0.74 - 1.03, p=0.11), but a CSS advantage was seen among node-positive patients (HR 0.70, 95% CI 0.52 - 0.97, p=0.03). Conclusions Extended lymphadenectomy may provide a survival benefit among patients with advanced renal cell carcinoma. Funding None
Authors
Dean Laganosky
Christopher Filson Dattatraya Patil Viraj Master |
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MP16-10 |
The impact of kinetics of biomarkers on the prediction of overall survival in patients with metastatic renal cell carcinoma treated with a tyrosine kinase inhibitor. |
Kidney Cancer: Advanced (including Drug Therapy) II | 17BOS |
Abstract: MP16-10 Sources of Funding: none Introduction Our present study aimed to investigate the impact of kinetics of biomarkers on the prediction of overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC) treated with a tyrosine kinase inhibitor (TKI). Methods Biomarkers including C-reactive protein (CRP), neutrophil count (Neu), neutrophil-lymphocyte ratio (NLR), platelet count (Plt), hemoglobin (Hb), serum lactate dehydrogenase (LDH), and serum albumin (Alb) in 118 cases of molecular targeted therapy for mRCC were measured before the first-line targeted agents started to be prescribed and at the first CT scan during treatment. All cases were classified into higher and lower biomarker groups in accordance with their data when treatments started. All groups were further classified into two subgroups on the basis of the kinetics of all biomarkers after first-line targeted therapy: decreased and non-decreased biomarker subgroups for the higher biomarker groups, or increased and non-increased biomarker subgroups for the lower biomarker groups. All cases were also classified in accordance with their other clinical backgrounds, and the overall survival (OS) of each subgroup was analyzed. Results The patients had a median age of 65 years old; and 102 and 16 were diagnosed as having a clear and non-clear cell histology, respectively. In the first-line therapy, 74, 42, and 2 cases were treated with sunitinib, sorafenib, and pazopanib, respectively. The median observation period was 23.4 months. Cases with CRP higher than 0,5mg/dl, Neu higher than the upper limit of normal (ULN), NLR higher than 2.5, Plt higher than ULN, anemia, and hypoalbuminemia had significantly worse OS than other cases (p<0.0001, p=0.0008, p<0.0001, p<0.0001, p=0.0094, and p<0.0001, respectively). Multivariate analysis revealed that pretreated CRP (hazard ratio (HR): 2.093, p=0.0179) and NLR (HR: 2.099, p=0.0431) were independent predictive factors of OS. In the higher CRP group and higher Neu group, the decreased CRP subgroup (1 year, 85.0%) and the decreased Neu subgroup (1 year, 73.9%) had significantly better OS than the non-decreased CRP subgroup (1-year, 37.2%, p<0.0001) and non-decreased Neu subgroup (1-year, 45.5%, p=0.0445). Multivariate analyses in the higher CRP group revealed that decrease of CRP was an independent predictive factor for OS (HR: 0.176, p=0.0008). Conclusions Decrease of CRP and pretreatment CRP can be novel predictive factors for OS in mRCC patients treated with molecular targeted therapy. Funding none
Authors
Jun Teishima
Shinya Ohara Kousuke Sadahide Shinsuke Fujii Hiroyuki Kitano Shunsuke Shinmei Keisuke Hieda Shogo Inoue Tetsutaro Hayashi Koji Mita Akio Matsubara |
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MP16-11 |
Japanese Phase I/II study of multipeptide-based cancer vaccine IMA901 after single-dose cyclophosphamide in Japanese patients with advanced renal cell cancer |
Kidney Cancer: Advanced (including Drug Therapy) II | 17BOS |
Abstract: MP16-11 Sources of Funding: none Introduction IMA901 is the first therapeutic vaccine for renal cell cancer (RCC) consisting of multiple tumor-associated peptides (TUMAPs) confirmed?to be naturally presented in human cancer tissue. We reported the effectiveness of the vaccine in phase 1 and 2 trial in Europe and US (IMA901-202 study) (Walter S, et al. Nat Med. 2012; 18: 1254-61). A randomized phase 3 study to determine the clinical benefit of treatment with IMA901 is ongoing in Europe and US. The objective of our study was to assess the safety and tolerability of IMA901 vaccination for the Japanese metastatic RCC patients. Methods In this phase 1 and 2 study in Japan (IMA901-IJ1), we treated a total of 10 Japanese patients with advanced RCC with human leukocyte antigen A (HLA-A)*02 + subjects in 2011-2012. Each of the vaccinations consisted of an i.d. injection of GM-CSF (75 ?g) followed within 15-30 minutes by an i.d. injection of IMA901 (413 ?g of each peptide). The vaccine therapy was a monotherapy, i.e., no other anti-tumor therapies were concomitantly administered during the study course. No treatment with either anti-cancer agents or immunosuppressants was allowed within 4 weeks before entering the trial. Patients were to receive 7 vaccinations in the first 5 weeks of treatment (induction period) followed by 10 further vaccinations at 3 weeks intervals for up to 30 weeks (maintenance period). The primary endpoint was safety and tolerability. The secondary endpoints were PFS, OS, immunogenicity. Results No treatment-related serious adverse events (SAEs) or deaths were observed during the study period. At follow-up at 4 months, all cases were assessed for treatment response. 10% of patients had partial response (PR), 50% with stable disease (SD), 40% of patients had progressive disease (PD). Median PFS was 5.5 months and median OS was 18.0 months. Among all patients analyzed for T-cell response, five showed vaccine-induced (VI) T-cell responses? against at least one HLA class I-restricted TUMAP and two patients with responses to multiple TUMAPs (Figure 1). The T-cell response rate in this study was similar to our previous study in Europe and US. Interestingly, two of the immune responders were of HLA-A*0206 phenotype, a HLA suballele rarely occurring in Europe and US but common in Japan. Conclusions This study showed safety and tolerability of IMA901 vaccination and immune responses in Japanese RCC patients. _x000D_ Funding none
Authors
Fumiya Hongo
Natsuki Takaha Takashi Ueda Kimihiro Yano Satoshi Tamada Schoor Oliver Singh-Jasuja Harpreet Tatsuya Nakatani Tsuneharu Miki Osamu Ukimura |
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MP16-12 |
Selective internal radiation therapy (SIRT) with yttrium-90 (Y-90) resin microspheres in patients with primary renal cell carcinoma (RCC): impact on renal function and quality of life in the RESIRT study |
Kidney Cancer: Advanced (including Drug Therapy) II | 17BOS |
Abstract: MP16-12 Sources of Funding: Sirtex Medical Limited Introduction Endpoints for RCC continue to evolve with increased emphasis on patient-reported outcomes alongside efficacy and safety. SIRT is a procedure used for unresectable liver tumors that may bring benefits in primary RCC patients (pts) unsuitable for nephrectomy. RESIRT is the first study to evaluate SIRT for primary RCC aiming to assess safety as a primary objective. Secondary objectives included quality of life (QoL). Methods RCC pts not amenable for or who declined conventional therapy were eligible. A single transfemoral microcatheter administration of Y-90 resin microspheres (Sirtex, Australia) was delivered super-selectively via the renal artery to the tumor at intended radiation doses of 75, 100, 150, 200, 300 Gray and a procedural endpoint of imminent stasis in a dose-escalation design. Pts were assessed for 12 months (mo) after SIRT. The primary endpoint was safety/toxicity 30 days post-SIRT. Secondary endpoints included safety/toxicity at other time points, renal function and QoL assessed by the RCC QoL Symptom Index with scores ranging from 0 (worst) to 100 (best)._x000D_ Results 21 pts were recruited: mean age 75.0 years (± 9.3); 8 (38%) had metastases and 12 (57%) had chronic kidney disease stage 3; 7 (33%) had prior total contralateral nephrectomy, 1 (5%) received pazopanib and 1 (5%) progressed after cryotherapy to the target organ. Median follow-up was 12.0 mo (95% CI 11.9-12.1); 14 pts completed 12 mo follow-up, 5 died before study completion (all mRCC at study entry), 1 withdrew and 1 is still in follow-up. The intended Y-90 doses were delivered without any dose-limiting toxicity. 18 (86%) pts reported adverse events (AEs) of any causality within 30 days of SIRT and 4 (19%) reported serious AEs (SAEs), none of which was SIRT related. Over 12 mo, 10 (47.6%) pts reported grade ≥3 AEs and 10 (47.6%) pts experienced SAEs but none of these was SIRT related. Mean creatinine clearance was 76.1 mL/min at baseline and 68.9 mL/min at 12 mo. Mean serum creatinine levels and blood urea levels were stable during the study period. The mean (±SD) QoL score was 74.6 (±15.8) at baseline and 74.8 (±13.4) at 12 mo. The mean change from baseline was 1.7 (±12.5) at day 30 (p=0.565) and -4.1 (±14.7) at 12 mo (p=0.319). Conclusions This pilot study demonstrated good tolerability of SIRT using Y-90 resin microspheres for RCC at all dose levels including imminent stasis with no major impact on renal function or QoL over 12 months. Funding Sirtex Medical Limited
Authors
Peter Aslan
William Clark Manish Patel Justin Vass David N. Cade Suresh Janeendra de Silva Paul L. de Souza |
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MP16-13 |
Clinical benefit of presurgical axitinib therapy in renal cell carcinoma patients with thrombus extending to inferior vena cava |
Kidney Cancer: Advanced (including Drug Therapy) II | 17BOS |
Abstract: MP16-13 Sources of Funding: None Introduction We aimed to investigate clinical and pathological antitumor effects of presurgical axitinib for renal cell carcinoma (RCC) extending into inferior vena cava (IVC). Methods From March 1995 to June 2016, we treated consecutive 38 RCC patients with IVC thrombus in our hospital. Patients were divided into those receiving radical nephrectomy alone (control) and those receiving presurgical axitinib before planned radical nephrectomy (Neo-Axi). Patients’ background, clinicopathological parameters, and prognosis were compared between the control and Neo-Axi groups. In the Neo-Axi group, tumor responses were evaluated by RECIST v1.1 before and after axitinib including renal tumor and IVC thrombus. Fibrosis within IVC thrombus was evaluated by Azan staining, and interstitial fibrosis (IF) rates were compared between the control and Neo-Axi groups. Results The number of patients in the control and Neo-Axi groups were 30 and 8, respectively. There were no significantly differences in age, sex, thrombus level, metastatic disease, MSKCC risk classification between the control and Neo-Axi group. Axitinib-related adverse events were grade 3 hypertensions (n=3) and diarrhea (n=1). Median tumor responses in renal tumor and IVC thrombus were 22.3% and 41.1%, respectively. Median regression IVC thrombus was 15.5 mm. Median operation time and blood loss between the control and Neo-Axi group were significantly different (318 vs. 204 minutes, 2450 vs. 450 grams, respectively). One patient experienced perioperative death due to lung thrombosis in the control group. Pathological complete response (pT0) was obtained in one patient (12.5%) in the Neo-Axi group. Median interstitial fibrosis rate of IVC thrombus was significantly higher in the Neo-Axi group compared with the control group (8.7% and 3.4%, respectively, P=0.0021). Progression free survival between the control and Neo-Axi group were 13 and 33 months, respectively (P=0.060). Overall survival between the control and Neo-Axi group were 41 months and undefined, respectively (P=0.071). Conclusions Presurgical axitinib therapy enhanced tumor reduction accompanied by fibrosis, and may contribute surgical risk reduction. Presurgical axitinib therapy might be feasible option for RCC with IVC thrombus. Funding None
Authors
Yoshimi Tanaka
Yasuhiro Hashimoto Shingo Hatakeyama Shogo Hosogoe Toshikazu Tanaka Masaaki Oikawa Kazuhisa Hagiwara Takuma Narita Daisuke Noro Yuki Tobisawa Hayato Yamamoto Tohru Yoneyama Takahiro Yoneyama Takuya Koie Chikara Ohyama |
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MP16-14 |
Clinical implication of metastasectomy in metachronous metastatic renal cell carcinoma in the era of targeted therapy |
Kidney Cancer: Advanced (including Drug Therapy) II | 17BOS |
Abstract: MP16-14 Sources of Funding: none Introduction To assess the clinical implication of complete and incomplete metastasectomy in the patients having metachronous metastatic RCC (mRCC). Methods We retrospectively reviewed metachronous mRCC treated at our institute between January 2005 and December 2015. Metachronous mRCC was defined as those diagnosed of metastatic disease >3month after initial nephrectomy. Patients were classified into three groups; A. targeted therapy for metachronouc mRCC without additional surgical treatment. B. complete metastasectomy and adjuvant targeted therapy. C. incomplete metastasectomy and adjuvant targeted therapy. Cox proportional hazard regression analysis was performed to determine if complete and incomplete metastasectomy prolongs overall survival (OS) for the metachronous mRCC. Results Total of 101 patients were enrolled and followed up for 41.9 months in this study. 22 patients (21.8%) underwent complete metastasectomy, while 17 patients (16.8%) underwent incomplete metastasectomy. Most commonly performed metastasectomy was lung wedge resection (n=14, 13.9%), followed by bone excision (n=9, 8.9%), and local recur resection (n=6, 5.9%). Overall, incomplete metastasectomy and complete metastasectomy prolonged OS (HR 0.608, 0.318, p=0.042, respectively). Complete and incomplete lung wedge resection both prolonged overall survival significantly (p<0.05). Metastasectomy for bone and retroperitoneum recurred mass both did not show survival benefit (p=0.590 and 0.133, respectively). For the other metastasis, we labeled them as soft tissue metastasis, and soft tissue metastasectomy prolonged OS (p=0.036). Incomplete metastasectomy for soft tissue prolonged OS (p=0.016) Conclusions Metastasectomy could prolong OS in metachronous mRCC. Except for metastasectomy for bone and retroperitoneum recurred mass, incomplete metastasectomy also could play a role as OS prolongation. Funding none
Authors
Jong Won Kim
Jongsoo Lee Jae Yong Jeong Sung Ku Kang Jang Hee Han Seung Hwan Lee Won Sik Ham Koon Ho Rha Young Deuk Choi Sung Joon Hong Young Eun Yoon Woong Kyu Han |
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MP16-15 |
Natural history of surgically treated local recurrence after nephrectomy |
Kidney Cancer: Advanced (including Drug Therapy) II | 17BOS |
Abstract: MP16-15 Sources of Funding: none Introduction Local recurrence (LR) without distant metastases after renal cancer (RC) treatment is relatively rare. In this context, little is known regarding the natural history after salvage surgery for LR. Methods We conducted a retrospective analysis on a cohort of 62 consecutive patients presenting with local recurrence after primary surgical treatment for RC at two academic institutions. In 25 cases (40.3%), patients presenting concomitant visceral and/or bone metastases were excluded. LR was defined as the presence of a pathologically confirmed recurrence of RC in the soft/tissue renal fossa after radical (RN) or at the level of the resection bed after partial nephrectomy (PN), respectively. All patients were treated with the complete surgical resection of the LR. Kaplan-Meier analysis was applied to assess rates of systemic progression (SP; defined as the evidence of distant metastases during the follow-up), disease-free survival (DFS; defined as the absence of either distant or local recurrence) and cancer specific mortality (CSM) after surgical resection of LR Results Overall, 37 patients had exclusive LR (59.6%). Of those, 21 (55.6%) vs. 16 (44.4%) patients were diagnosed with an LR after RN vs. PN, respectively. Median [mean (Q1-Q3)] time to LR was 18 [29.9 (8-42)] months after RN/PN. At initial treatment (PN or RN), pathologic T stage (pT) was pT1, pT2, pT3 and pT4 in 14 (38.2%) 8 (18.9%), 14 (38.2%) and 1 (2.9%) patients. Fuhrman grade resulted low (1-2) vs. high (3-4) in 21 (59.4%) vs. 16 (40.7%) patients._x000D_ At LR diagnosis, 28 (75.7%) patients were treated with LR resection only, while 9 (24.3%) received also systemic targeted therapy after LR resection. At 1 and 3 years after LR surgery, SP rates were 20% and 45% vs. 7% and 23% in RN vs. PN cases, respectively. Overall, at 1, 3 and 5 years after LR surgery, DFS was 93%, 85% and 67%. CSM resulted 10%, 20% and 25%, respectively. There was no significant difference in terms of SP, DFS and CSM between patients surgically treated for LR after RN or PN (all p>0.05). Conclusions Despite a surgical treatment of LR after either PN or RN, a systemic progression can be expected. However, given the encouraging results in terms of DFS and CSM, such management could be justified in clinical practice. Funding none
Authors
Paolo Capogrosso
Eric Barret Igor Nunes-Silva Rafael Sanchez-Salas François Rozet Alessandro Larcher Ettore Di Trapani Alberto Briganti Andrea Salonia Francesco Montorsi Roberto Bertini Umberto Capitanio Xavier Cathelineau |
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MP16-16 |
Is there any difference in prognosis between synchronous and metachronous brain metastasis from metastatic renal cell carcinoma? |
Kidney Cancer: Advanced (including Drug Therapy) II | 17BOS |
Abstract: MP16-16 Sources of Funding: none Introduction The prognosis of renal cell carcinoma (RCC) brain metastasis (BM) is relatively poor. We evaluated the oncological outcomes of synchronous and metachronous BM of metastatic RCC according to local or systemic therapy. Methods Metastatic RCC patients (n=93) with synchronous and metachronous BM were retrospectively identified. We analyzed patients and tumor characteristics, treatment method, prognostic factors, BM progression and overall survival (OS). Synchronous BM was compared with metachronous BM using multivariable Cox regression. Results 76 patients (81.7%) received local therapy (stereotactic radiosurgery [60.0%], radiation therapy [23.5%], neurosurgery [10.1%]) and 54 patients (58.1%) were treated with systemic medical therapy. Median OS after diagnosis of BM were 9.2 months. In multivariable analysis, sarcomatoid component (hazard ratio [HR] 2.807, 95% confidence interval [CI] 1.088-7.239, p=0.0328) and multiple BM (HR 3.177 95% CI 1.561-6.469, p=0.0014) were significant factors for BM progression. MSKCC poor risk (HR 3.672, 95% CI 1.441-9.36, p=0.0064), sarcomatoid component (HR 4.264, 95% CI 2.062-8.820, p=0.0001) and multiple BM (HR 2.838, 95% CI 1.690-4.767, p=0.0001) were prognostic factors for worse OS. In addition, local treatment (HR 0.436, 95% CI 0.237-0.802, p=0.0076) and systemic treatment (HR 0.322, 95% CI 0.190-0.548, p<0.0001) were also independent factors for better OS. Although the OS from initial RCC diagnosis in metachronous BM patients was longer than synchronous BM patients, there was no difference between synchronous and metachronous in BM progression and OS after diagnosis of brain metastasis. Conclusions MSKCC poor risk, sarcomatoid component of histology, and multiple BM were poor prognostic factors for OS. Systemic or local treatment improved OS, but the type of synchronous and metachronous BM did not influence BM progression and OS. Funding none
Authors
Se Young Choi
Jeman Ryu Jae Hyeon Han Wonchul Lee Han Kyu Chae Sangjun Yoo Dalsan You In Gab Jeong Cheryn Song Bumsik Hong Jun Hyuk Hong Hanjong Ahn Choung-Soo Kim |
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MP16-17 |
Outcomes in over 4,000 Patients with Renal Cell Carcinoma from the Latin American Renal Cancer Group (LARCG): A focus on metastatic disease |
Kidney Cancer: Advanced (including Drug Therapy) II | 17BOS |
Abstract: MP16-17 Sources of Funding: None Introduction Over the past several years, a major international study collaboration has occurred among centers of excellence caring for kidney cancer termed the Latin American Renal Cancer Group (LARCG). The aim of the present study is to assess the impact of clinical and pathologic variables on cancer specific survival (CSS) and overall survival (OS). Methods Analysis of data from 28 centers from 8 countries, revealed 4,060 patients with renal cell carcinoma (RCC) who underwent nephrectomy from 1990 to 2015, 530 of which (14.5%) had metastasis at clinical presentation. These are the focus of the present study. Median follow-up was six months (0-162). Of 455 patients with survival data, 203 died (44.6%), 184 (90.6%) of RCC. Results The median age of patients with metastatic RCC (mRCC) was 61 (23-71) years, 68% of patients were male and 32% female (2:1 ratio). The organs most frequently affected with metastasis were lungs (45.5%), bone (21.5%), lymph nodes (10.6%), liver (8.7%), adrenal (4%) and brain (2.2%). On univariate analysis, there were associations between 5-year OS and CSS and presence of ECOG-PS ≥1 (p=0.005 and p=0.007, respectively), ASA 3 classification (p<0.0001, for both), pT 3-4 (p=0.019 and p=0.009 respectively), pN1 (p=0.001 and p<0.0001), Fuhrman grades ≥3 (p=0.010 and p=0.008 respectively), Necrosis (p=0.024 and p=0.016), perirenal fat invasion (p<0.0001, for both), Hemoglobin <11 (p=0.001 and p=0.002), multiple metastases (p=0.002 and p=0.001), two or more involved organs (p=0.002 and p=0.005, respectively), bone vs pulmonary metastasis (p=0.017 and p=0.024), vertebral metastasis (p=0.035, for both), and more than five lungs metastases (p=0.003 for both). On multivariate analysis, the independent prognostic factor of 5-year OS was the ASA (p=0.020). Both OS and CSS were influenced by perirenal fat invasion (p=0.001 for both), and two or more metastatic organ sites (p<0.0001 and p=0.003 respectively). Conclusions This study of the impact of clinical and pathologic variables on survival in mRCC in Latin America was possible thanks to the collaborative work done by the LARCG. The presence of two or more sites of metastasis and the presence of perirenal fat invasion within the primary tumor predict shorter OS and CSS. ASA Classification was an independent predictor of OS. Funding None
Authors
Diego Abreu
Guillermo Gueglio Patricio Garcia Walter da Costa Daniel Beltrame Alvaro Zuñiga Luis Meza Ruben Bengió Carlos Scorticati Ricardo Castillejos Francisco Rodriguez Ana Maria Autran Carmen Gonzalez Miguel Sanchez Jose Gadu Alejandro Nolazco Pablo Marinez Carlos Ameri Hamilton Zampolli Raul Langenhin Diego Muguruza Marcos Tobias Machado Antonio Lima Pompeo Pablo Mingote Nicolas Ginéstar Matías López Boris Camacho Juan Yandian Jorge Clavijo Roberto Puente Sergio de Miceu Lucas Nogueira Carlos Corradi Marcelo Torrico Martin Varela Omar Clark Luis Montes de Oca Sebastian Savignano Ricardo Decia Fernando Secin Agustin Rovegno Gustavo Guimarães Sidney Glina Joan Palau Gustavo Carvalhal Philippe Spiess Stenio Zequi Marston Linehan |
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MP16-18 |
Treatment of kidney tumors with radiofrequency ablation (RFA) combined with systemic PD-1 inhibition results in both primary tumor control and prevention of lung metastasis in a preclinical animal model |
Kidney Cancer: Advanced (including Drug Therapy) II | 17BOS |
Abstract: MP16-18 Sources of Funding: This work was supported by Jiangsu Graduate Student Innovation Grant (No.KYZZ15_0066) and Excellent Doctoral Dissertations Cultivation Fund from Southeast University. Introduction Novel antibodies against immune checkpoint proteins, which led to unleash anti-tumor T cell responses, results in durable long-lasting responses but only in a fraction of patients. RFA of tumors can enhance systemic antitumor immunity through a series of mechanisms. Nevertheless, antitumor immunity induced by RFA is mostly weak and not sufficient enough to eradicate metastatic tumors completely or prevent disease progression durably. We hypothesized that these two different treatment strategies could act synergistically. The purpose of this study is to evaluate whether the combination of RFA and anti-PD-1 antibody could result in both primary tumor control and prevention of lung metastasis in a murine model bearing renal adenocarcinoma. Methods Balb/c mice were injected with Renca cells into their left kidney to establish the orthotopical model of renal cancer. One week later, the mice were injected intravenously with Renca cells, which afterwards would spread into various organs particularly into the lung. Then, the mice were treated with IgG alone, anti-PD-1 monoclonal antibodies (mAbs), surgical resection/RFA of the kidney tumor, or surgical resection / RFA + anti-PD-1. anti-PD-1 mAbs were administered by intravenous injection (i.v) every other day for three times. The antitumor effect of the treatment was evaluated by counting the numbers of the tumors in the lung, weighing the lungs and observing the survival time, and the immunological responses were assessed using peripheral blood immune parameters and analyzing the infiltration of CD+4 or CD+8 T cells into the tumors. Results Treatment of mice bearing kidney tumors with RFA and anti-PD-1 mAbs resulted in significantly greater growth suppression of primary kidney tumors and prolonged survival compared with mice treated with the other modalities. ELISA analysis showed that mice treated with RFA and i.v anti-PD-1 mAbs had higher level of IFN-γ, TNF-α in the peripheral blood after treatment compared with the other groups. In the combination therapy group, growth of lung metastases was prevented with fewer numbers of lung metastases and lighter weight of lung. The combined therapy of RFA and anti-PD-1 antibodies significantly increased T-cell infiltration, especially the effector T cells, which upregulated the effector T cells to regulatory T cells ratio. Conclusions The combination of RFA and anti-PD-1 mAbs resulted in stronger antitumor immunity and prolonged survival in this preÂclinical model of advanced RCC. Funding This work was supported by Jiangsu Graduate Student Innovation Grant (No.KYZZ15_0066) and Excellent Doctoral Dissertations Cultivation Fund from Southeast University.
Authors
Xiaofeng Chang
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MP16-19 |
Neoadjuvant and Adjuvant Chemotherapy following Nephroureterectomy: changes in utilization and outcomes |
Kidney Cancer: Advanced (including Drug Therapy) II | 17BOS |
Abstract: MP16-19 Sources of Funding: none Introduction Nephroureterectomy is the mainstay therapy for high-grade upper tract urothelial carcinoma (UTUC). As the survival remains poor for high-grade UTUC following nephroureterectomy, a number of ongoing studies are investigating the utility of neoadjuvant chemotherapy (NAC) in this disease. While awaiting these results, our objective is to examine the utilization of NAC, impact on outcomes following surgery and overall survival in a national hospital-based analysis. Methods We identified subjects diagnosed with urothelial carcinoma of the kidney or ureter from the National Cancer Database during 2004-2014, who underwent nephroureterectomy. These subjects were then stratified on the basis of receipt of NAC, and univariable and multivariable analysis was performed to identify patient and provider factors associated with use of NAC. Thirty-day mortality and readmission were assessed by chi-squared analysis. Adjusted Cox-regression was used to evaluate overall survival. Results We identified 26,309 subjects who underwent nephroureterectomy for UTUC, and 421 (1.6%) received NAC. Median follow-up was 33 months (interquartile range 14-62). Utilization of NAC significantly increased over the study period (OR=1.3 year over year, p<0.001). Younger patients (OR=0.97 per year, p<0.001) and those with metastatic disease (lymph node OR=2.0 and metastasis positive OR=1.6, p<0.001) were more likely to receive NAC in their treatment regimens. NAC was more likely to be given at academic centers (OR =3.1 p<0.001); however, hospital UTUC volume was not associated with NAC use. Patient demographics such as race, income, and level of education were not associated NAC utilization. NAC was associated with better perioperative outcomes (30-day mortality 2.2% vs. 1.6%, p=0.7 and 30-day readmission 3.9% vs. 3.1%, p=0.02). Hazard ratios adjusting for age, pathologic stage, lymph node and metastasis status demonstrated that NAC was associated with survival [HR 0.82 (95% CI0.69-0.98) p=0.029]. Conclusions In our observational, hospital-based study, NAC is associated with improved survival without adversely affecting perioperative outcomes in those with high grade UTUC. Although use is increasing over time and greater at academic medical centers, it remains low overall. Prospective studies are needed to confirm these findings and identify optimal characteristics associated with improved outcomes. Funding none
Authors
Adrien Bernstein
Ron Golan Brian Dinerman Michael Cosiano Khushabu Kasabwala Jim C. Hu |
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MP16-20 |
Litmus Test or Destination Systemic Therapy? Referral for Cytoreductive Nephrectomy after Initial Systemic Therapy in Metastatic Kidney Cancer |
Kidney Cancer: Advanced (including Drug Therapy) II | 17BOS |
Abstract: MP16-20 Sources of Funding: AMA Foundation Introduction With numerous new agents for metastatic kidney cancer (mRCC) since 2005, there is no randomized data supporting sequencing cytoreductive nephrectomy (CN) and newer systemic therapies (ST). Increased disease control with ST engenders concern that CN may shorten life or delay therapy. Thus, in all the best prognostic candidates, initial ST as a &[Prime]litmus&[Prime] test may be advocated prior to CN. We evaluated use of CN after initial ST, hypothesizing receipt of deferred CN to be associated with increased survival time, markers of increased performance status, less rapid disease and socioeconomic status. Methods The National Cancer Database was screened for adult patients with biopsy-proven mRCC treated with initial systemic therapy between 2006-2013. Covariates included demographic, oncologic, hospital-level and geographic variables. Unadjusted and multivariable logistic regression was performed, identifying factors associated with CN after initial ST. _x000D_ Results Of 14,651 patients treated with initial ST for mRCC, 709 (4.8%, median OS 19 months, IQR 9-35) underwent delayed CN compared with 13,942 (95.2%, median OS 5 months, IQR 2-13) treated with ST alone. On multivariable analysis, survival ≥3 months was highly associated with receipt of CN (OR 10.6, 95% CI 5.5, 20.5). However, of 9,796 surviving ≥3 months, only 689 (7%) underwent CN. Factors associated with lower odds of CN included older age, greater comorbidity, higher clinical stage (T and N), and unfavorable metastatic sites (i.e., brain, bone, liver) with all p<0.001. Educational attainment was associated with receipt of CN, but hospital characteristics and travel burden were not._x000D_ _x000D_ Conclusions Conclusions: Effectiveness of CN in the modern mRCC era is uncertain. Initial ST is typically for those with poor prognosis. Yet, after an initial litmus test, re-evaluation of risk rarely leads to CN. Socioeconomic factors may affect CN decision-making, a potential disparity that merits further investigation. Funding AMA Foundation
Authors
Liam C. Macleod
Atreya Dash George R. Schade Anobel Y. Odisho Scott S. Tykodi John L. Gore |
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MP17-01 |
Inflammasome Activation leads to IL-18 Expression in Prostatic Inflammation Associated With BPH |
Benign Prostatic Hyperplasia: Basic Research & Pathophysiology | 17BOS |
Abstract: MP17-01 Sources of Funding: NIDDK,U54 DK112079 Introduction Large clinical studies have implicated prostatic inflammation as a major player in the progression of benign prostatic hyperplasia (BPH). However, the molecular mechanisms that contribute to the inflammation in BPH remain unexplored. Animal studies on prostatic inflammation demonstrated a role for inflammasome in interleukin-18 (IL-18) expression. The role of inflammasome in BPH is unclear, but the expression of IL-18 was reported in biopsy of BPH patients. Here, we investigated the expression of a major inflammasome component called nucleotide-binding oligomerization domain-like receptor with pyrin domain protein 1 (NLRP) 1 and its downstream cytokine IL-18 in prostate specimens of BPH patients._x000D_ Methods Slides containing the cryosections of prostatectomy specimens of Caucasian BPH patients (40-79 years) negative for cancer (n=4) were acquired from the health sciences tissue bank at the University of Pittsburgh following the IRB# 0506140. Intra-prostatic inflammatory infiltration was assessed by H&E staining. Immunofluorscence of inflammasome and IL-18 was assessed using primary antibodies for NALP1 (1:200); and IL-18 (1:50) at 4°C for 12h followed by 2 h incubation at 25°C with secondary donkey antibody tagged to Alexa Fluor 488 or Alexa Flour 594 (1: 200). Banked urine specimens from controls and BPH patients were analyzed for IL-18 levels. Results BPH specimens remarkable for hyperplastic nodules of glands (Fig.1A) and absence of inflammation failed to show the co-localization of red and green immunoreactivity for IL-18 and NLRP1 inflammasome, respectively (Fig.1C).BPH specimens marked by stromal enlargement and infiltration of inflammatory cells (&[larr], Fig.1B) also showed the co-localization of red and green immunoreactivity for IL-18 and NLRP1 inflammasome against the blue DAPI background (red arrowhead in Fig.1D) IL-18 levels were elevated in banked urine specimens of BPH patients._x000D_ Conclusions Co-localized immunoreactivity of NLRP1, and its downstream product IL-18 supports the assembly and activation of inflammasome in BPH specimens positive for infiltration of inflammatory cells. Recapitulation of findings from the animal model demonstrate that inflammasome plays a major role in the prostatic inflammation associated with BPH and therefore inflammasome targeted therapies can be an option for BPH management. Funding NIDDK,U54 DK112079
Authors
Pradeep Tyagi
Mahendra Kashyap Jeffrey Gingrich Zhou Wang Naoki Yoshimura |
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MP17-02 |
TNFα antagonists reduce incidence of BPH in patients with autoimmune inflammatory conditions |
Benign Prostatic Hyperplasia: Basic Research & Pathophysiology | 17BOS |
Abstract: MP17-02 Sources of Funding: NIDDK Introduction Advanced benign prostatic hyperplasia (BPH) exhibits a profile of gene expression similar to that seen in autoimmune inflammatory (AI) conditions such as rheumatoid arthritis (RA). Here we tested first, whether diagnoses of BPH and an AI condition are at an increased likelihood of occurring in the same patient and second, whether patients treated for an AI condition had an altered incidence of subsequent BPH. Subsequent analysis focused on the effects of specific therapies. Methods We extracted deidentified patient data from an electronic data warehouse covering men over the age of 40 presenting at NorthShore clinics over a period of three years (1/1/09-12/31/11). The cohort included 101,383 men with no history of AI and 10,769 men with a diagnosis of one or more AI conditions. These groups were subdivided into men with and without a diagnosis of BPH, type of AI condition, and whether the AI condition occurred before or after the diagnosis of BPH. Rates were compared between groups using chi-square test. The effects of specific AI therapies on BPH were examined. Results In the control group 20,586 (20.3%) were diagnosed with BPH. Of the men with an AI diagnosis, 3,294 (30.6%) were also diagnosed with BPH, demonstrating a significant positive association (p<0.01). However when men were treated for an AI condition their chance of a subsequent BPH diagnosis dropped significantly, and overall was slightly, but significantly, lower than the control baseline at 19.4% (p<0.01). Some conditions (notably, RA, Crohns disease and ulcerative colitis) are associated with significantly higher rates of BPH while others (e.g. Celiac disease and Multiple sclerosis) show no significant difference. Treatments for some conditions e.g., psoriasis and RA resulted in large drops in subsequent BPH diagnosis. Analysis of the treatments provided to the AI patients revealed that most of the effect of BPH reduction was associated with the use of TNFα-antagonist therapies with minor contributions from other treatments such as low dose methotrexate use. Conclusions This study reveals clear associations between BPH and AI diagnoses and is strongly suggestive that some medical approaches applied to AI disorders may affect the pathogenesis and progression of BPH. Differences in the coincidence and treatment effects of therapies for various conditions may reflect the individual disease and drug characteristics and bears further examination. These data elucidate new pathways that can be examined to determine whether they can be applied to BPH. Funding NIDDK
Authors
Brittany Lapan
Omar Franco Jaclyn Pruitt Jacqueline Petkewicz Brian Helfand Charles Brendler Chi-Hsiung Wang Simon Hayward |
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MP17-03 |
Inflammation-induced prostatic enlargement and proliferation of prostate epithelial cells is reduced by growth hormone-releasing hormone (GHRH) antagonists through the inhibition of epithelial-to-mesenchymal transition |
Benign Prostatic Hyperplasia: Basic Research & Pathophysiology | 17BOS |
Abstract: MP17-03 Sources of Funding: Urology Care Foundation, SESAUA and Miami VA Medical Center Introduction The pathogenesis of benign prostatic hyperplasia (BPH) has been associated with various factors including hormonal imbalance, inflammation-induced cell proliferation and epithelial-to-mesenchymal transition. We have previously demonstrated that prostatic GHRH and its receptors are upregulated in a rat testosterone-induced BPH model and GHRH antagonists suppress the levels of proinflammatory cytokines. Based on these findings, we investigated the role of GHRH in inflammation-induced proliferation of prostate epithelial cells in vitro and prostate enlargement in experimental autoimmune prostatitis. Methods Autoimmune inflammation in the prostates of Balb/c mice was induced by subcutaneous injections of rat male tissue homogenate. Changes in prostate volume were measured with the VEVO® 1100 ultrasound imaging system. Human BPH-1 and primary prostate epithelial cells were used in matrigel-embedded 3D cultures and average sphere diameters were evaluated. Chronic inflammation was mimicked by treating cells with THP-1 macrophage-conditioned medium or Il-17A, whereas EMT was triggered with TGF-?1 or TGF-?2 peptides. The role of secreted GHRH in inflammation-induced proliferation was determined by using GHRH antagonists developed in our lab. Changes in the protein levels were determined by western blot. Results Experimental autoimmune prostatitis increased the volume of the ventral prostate by 92% at week 8 compared to control (p<0.001). A 1-month daily treatment with GHRH antagonists caused a significant, 48% reduction in prostate volume. Macrophage-conditioned medium induced a 26% increase (p<0.001) in the average diameter of cells and elevation in the expression of mesenchymal markers. The mRNA and protein expression of GHRH were significantly increased by macrophage-conditioned medium. GHRH antagonist reduced inflammation- and TGF-?2-induced increase in diameter by 64% (p<0.01) and by 67% (p<0.001), respectively, and reduced the expression of n-cadherin. The stimulatory effect of TGF-?2 was abolished when GHRH receptor expression was silenced by stable transfection of shRNA. IL-17A stimulation of the growth of primary epithelial cells were also significantly reduced by GHRH antagonists. Conclusions Our results indicate that GHRH is a key factor in prostatic inflammation-induced prostate enlargement and EMT and suggest that GHRH antagonists have beneficial effects in chronic prostatitis and BPH. Funding Urology Care Foundation, SESAUA and Miami VA Medical Center
Authors
Petra Popovics
Andrew Schally Luis Salgueiro Krisztina Kovacs Ferenc Rick |
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MP17-04 |
Complement activation mechanism activated by autoantigen recognition during growth of benign prostatic hyperplasia |
Benign Prostatic Hyperplasia: Basic Research & Pathophysiology | 17BOS |
Abstract: MP17-04 Sources of Funding: none Introduction The association between the pathogenesis of benign prostatic hyperplasia (BPH) and inflammation has recently received attention. We previously showed that not only the inflammation response pathway, but also the classical complement pathway is activated in BPH tissue from model rats with stroma-dominant BPH. The classical complement pathway is activated by autoantigens that recognize immune complexes and it is responsible for various diseases via a mechanism that amplifies inflammation. We postulated that immune complexes amplify inflammation through complement activation, which leads to prostatic proliferation. Therefore, we expressed complement factors, analyzed their functions, and identified autoantigens to understand the pathogenic mechanism of BPH. Methods Fetal urogenital sinus (UGS) isolated from male 20-day-old rat embryos was implanted into the ventral prostate of pubertal male rats to create rat models of BPH. Complement factors were expressed and functionally analyzed in BPH tissues, and then serum concentrations of IgG and the expression of complement factors in BPH tissues were assessed. We immunoprecipitated BPH protein using an anti-IgG antibody to identify antigens, and analyzed the protein by mass spectrometry after SDS-PAGE separation. The expression of complement factors in human BPH tissue was also analyzed. Results The expression of complement factors C1q, C3, MBL, factor B, and MAC was significantly up-regulated in tissues from BPH rats compared with those from normal rats (p<0.01). The classical complement pathway was initially activated, followed by an alternative complement pathway activated in BPH. These complement factors were also up-regulated mostly in stromal areas of human BPH. The serum IgG concentration was significantly increased (398.1 ng/mL, p<0.01) in rat BPH and IgG was deposited in stromal areas of the BPH. Mass spectrometry of IgG binding protein identified annexin, Hsp90, and β-actin as antigens of immunocomplexes. Conclusions We clarified that the immune system is responsible for the development of BPH. Complement pathway activation by immunocomplexes recognizing annexin, Hsp90, and β-actin as autoantigens might be responsible for the pathogenesis of BPH. Funding none
Authors
Junya Hata
Kanako Matsuoka Yuichi Sato Hidenori Akaihata Masao Kataoka Soichiro Ogawa Nobuhiro Haga Kei Ishibashi Ken Aikawa Yoshiyuki Kojima |
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MP17-05 |
Toxoplasma gondii infects the prostate and induces microglandular hyperplasia in a mouse model of prostatic hyperplasia |
Benign Prostatic Hyperplasia: Basic Research & Pathophysiology | 17BOS |
Abstract: MP17-05 Sources of Funding: NIH-NIDDK Introduction Inflammation is the most prevalent and widespread histological finding in the human prostate, and associates with the development and progression of benign prostatic hyperplasia. Several factors have been hypothesized to cause inflammation, yet the role each plays in the etiology of prostatic inflammation remains unclear. This study investigated a role for the common protozoan parasite Toxoplasma gondii in prostatic inflammation and established a novel mouse model. Methods Male mice were infected intraperitoneally with green fluorescent protein (GFP)-expressing T. gondii parasites and prostatic infection was confirmed with parasite specific staining and GFP localization. The resulting prostatic inflammation was scored on severity and focality of infiltrating leukocytes and epithelial hyperplasia. We characterized inflammatory cells with flow cytometry and the resulting epithelial proliferation with bromodeoxyuridine (BrdU) incorporation. In addition, human sera from T. gondii IgG seropositive and seronegative male patients were tested for total prostate specific antigen (PSA) concentrations by ELISA. Results We found that T. gondii infects the mouse prostate during systemic infection and can establish parasite cysts that persist for at least 60 days. T. gondii infection induces a substantial and chronic inflammatory reaction in the mouse prostate characterized by monocytic and lymphocytic inflammatory infiltrate. T. gondii-induced inflammation results in reactive hyperplasia, involving basal and luminal epithelial proliferation, and the exhibition of microglandular hyperplasia in 60 day inflamed mouse prostates. Finally, T. gondii seropositive men have 5.08 times the odds of having an elevated PSA level (>4.0 ng/ml) than age-matched seronegative men. Conclusions We found that T. gondii infects the mouse prostate during systemic infection and can establish parasite cysts that persist for at least 60 days. T. gondii infection induces a substantial and chronic inflammatory reaction in the mouse prostate characterized by monocytic and lymphocytic inflammatory infiltrate. T. gondii-induced inflammation results in reactive hyperplasia, involving basal and luminal epithelial proliferation, and the exhibition of microglandular hyperplasia in 60 day inflamed mouse prostates. Finally, T. gondii seropositive men have 5.08 times the odds of having an elevated PSA level (>4.0 ng/ml) than age-matched seronegative men. Funding NIH-NIDDK
Authors
Darrelle Colinot
Tamila Garbuz Maarten Bosland William Sullivan Gustavo Arrizabalaga Travis Jerde |
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MP17-06 |
Thyroid Hormones and Benign Prostatic Hyperplasia |
Benign Prostatic Hyperplasia: Basic Research & Pathophysiology | 17BOS |
Abstract: MP17-06 Sources of Funding: none Introduction Thyroid hormones play an important role in cell differentiation, growth, and metabolism. Several investigators have documented the role of thyroid hormones in the development of prostate cancer. However, to date there are only limited data available regarding thyroid hormone levels in benign prostatic hyperplasia (BPH). Methods A total of 5708 men aged 40 to 59 years who had participated in a health examination were included in the study. Lower urinary tract symptoms (LUTS)/BPH were assessed by international prostate symptom score (IPSS), prostate volume, maximal flow rate (Qmax), and a full metabolic workup. Serum levels of thyroid-stimulating hormone (TSH) and free thyroxine (T4) were measured using chemiluminescence immunoassay by commercial kits. We divided participants into quartiles based on their TSH and free T4 levels: first quartile, Q1; second quartile, Q2; third quartile, Q3; and fourth quartile, Q4. We then investigated their relationship using the chi-squared test, the Cochran-Armitage trend test, logistic regression analyses, and a propensity score matched case-control study. Results The mean age of the study group was 51.1 ± 5.2 years, and the mean free T4 and median TSH were 1.05 ± 0.14 and 1.44 (0.96-2.13)ng/mL, respectively. In addition, the ratio of metabolic syndrome and low testosterone (<3.5 ng/mL) were 41.9% and 11.8%, respectively. There was a significant increase in the percentage of men with IPSS>7, Qmax<10 mL/sec, and prostate volume ≥30 mL, with increase of free T4 quartile (IPSS>7(%): Q1:57.2, Q2:56.7, Q3:60.3, Q4:62.5, P=.001; Qmax<10 mL/sec(%): Q1:3.5, Q2:3.2, Q3:4.1, Q4:4.8, P=.038; total prostate volume ≥30 mL(%): Q1:15.2, Q2:16.4, Q3:18.0, Q4:19.3, P=.002). After adjusting for age, body mass index, testosterone, and metabolic syndrome, the odds ratio for prostate volume ≥30 mL of free T4 Q3 and free T4 Q4 were significantly higher than free T4 Q1 [odds ratio; 5-95 percentile interval), P value; Q1:.000 (references); Q2:1.140(.911-1.361), P=.291; Q3:1.260 (1.030-1.541), P=.025; Q4:1.367(1.122-1.665), P=.002]. After adjusting for age, body mass index, testosterone, metabolic syndrome, and prostate volume, the odds ratio for IPSS>7 of free T4 Q4 were significantly higher than that of free T4 Q1 (odds ratio (5-95 percentile interval), P value; Q1:.000 (references); Q2:.969 (.836-1.123), P=.677; Q3:1.123 (.965-1.308), P=.133; Q4:1.221 (1.049-1.420), P=.010). However, the odds ratio for Qmax<10 mL/sec was not significantly different between free T4 quartile groups after adjusting confounding factors. In propensity score matched analysis (matched for age, metabolic syndrome, testosterone, and body mass index at a 1:1 ratio), 1362 cases (Q4 of free T4) and 1362 control subjects (Q1, Q2, and Q3 of free T4) were included for comparison. The ratio of prostate volume ≥30 mL (15.1% vs. 19.3%, P = .004) and mean prostate volume (23.7±6.7 vs. 24.6±7.3 mL, P=.001) was higher in the case group than in the control group. Qmax and IPSS were not different between case and control groups. TSH was not significantly related to IPSS, Qmax, and total prostate volume in univariate and multivariate analyses. Conclusions Prostate volume, IPSS, and Qmax are significantly related to free T4, and prostate volume is significantly and independently related to total prostate volume in this study. We found a potential role of thyroid hormone in developing BPH. Funding none
Authors
Jun Ho Lee
Young Bin Kim Gyeong Eun Min Dong-Gi Lee |
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MP17-07 |
Androgenic to Estrogenic Switch in Prostate Gland as a Result of Epigenetic Silencing of Steroid 5-? Reductase 2 |
Benign Prostatic Hyperplasia: Basic Research & Pathophysiology | 17BOS |
Abstract: MP17-07 Sources of Funding: NIH/R01 DK091353 Introduction The steroid 5-[alpha] reductase type 2 (SRD5A2) is critical for prostatic development and growth. One-third of men are resistant to 5ARI therapies. We previously showed that expression of SRD5A2 is not static. Here we wished to identify whether absence of prostatic SRD5A2, when androgenic pathways are blocked, leads to modification of alternate hormonal pathways. Methods Prostatic samples were obtained from patients with symptomatic BPH undergoing transurethral resection of prostate (TURP) surgery. Methylation of SRD5A2 promoter was assessed using Methylated CpG Island Recovery Assay (MIRA). RNA was extracted for whole-transcriptome profiling analysis by Illumina Human BeadChip Arrays. Prostatic protein expression of SRD5A2, androgen receptor (AR), estrogen receptor (ER) subunits, and aromatase were determined in a panel of six BPH patients by Western blot, immunohistochemistry (IHC), and ELISA assays. Prostatic levels of testosterone (T), dihydrotestosterone (DHT), estradiol (E) were measured by HPLC-MS. In in vitro study, primary prostatic stroma cells and epithelial cell line, BPH-1, were cultured and treated with TNF-[alpha] and IL-6, and mRNA levels were determined by qPCR. Results In prostate specimens that were methylated at the SRD5A2 promoter locus, estrogen response genes were identified as one of the most significantly upregulated gene family members as determined by gene expression analysis. The levels of T, E and aromatase were significantly upregulated, while DHT was significantly decreased. Absence of SRD5A2 significantly upregulated the phosphorylation of ER? (pER?), but did not significantly affect the levels of total ER?, total ER? or pER?. In primary prostatic stromal cells, administration of TNF-?, but not IL-6, suppressed the level of SRD5A2 and upregulated aromatase activity and ER? expression. However, treatment of prostatic epithelial cells with TNF-? or IL-6 did not change the androgenic or estrogenic signalling, suggesting that stromal cells regulate the androgenic to estrogenic switch when SRD5A2 is absent. Conclusions Our study demonstrates for the first time that there is an androgenic to estrogenic switch when SRD5A2 is absent in the prostate gland. Somatic epigenetic silencing of SRD5A2 changes the prostatic hormonal milieu, and may modulate prostatic homeostasis and growth. Targeting the aromatase-estrogen-ER axis may serve as an effective treatment strategy in BPH patients who lack SRD5A2 expression. Funding NIH/R01 DK091353
Authors
Zongwei Wang
Libing Hu Rongbin Ge Keyan Salari Seth Bechis Shulin Wu Cyrus Rassoulian Jonathan Pham Shahin Tabetabaei Chin-Lee Wu Douglas Strand Aria Olumi |
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MP17-08 |
The identification of estrogen receptor gene networks in benign prostatic hyperplasia |
Benign Prostatic Hyperplasia: Basic Research & Pathophysiology | 17BOS |
Abstract: MP17-08 Sources of Funding: 5K12DK100022_x000D_ U54DK104310_x000D_ R01DK093690 Introduction Benign prostatic hyperplasia (BPH) is a disease that develops in aging men as the ratio of 17β-estradiol (E2) to testosterone (T) increases. Little is known about the role of estrogens and estrogen-regulated genes in BPH. Estrogens bind and activate estrogen receptors (ER), ERα and ERβ, to form homo- and heterodimers. These ERs play opposing roles within the prostate; ERα is pro-proliferative and ERβ is anti-proliferative. While ER activation and gene networks have been extensively studied in other organs, little is known in the prostate. The objective of this is study was to identify genes regulated by E2 and selective estrogen receptor modulators (SERMs). Methods RNA-seq was performed on BPH1 cells treated with E2 (binds ERα and ERβ), SERMs that bind ERβ (3β-diol, DPN, and WAY20070) and ERα (PPT) to identify genes specifically regulated by either ERα or ERβ. Sequences were mapped and assembled using TopHat, HTSeq, and edgeR. Genes reported were greater than 2-fold change over vehicle control with p-value < 0.05. CRISPR/Cas9 was used to knockout ERα and/or ERβ in BPH-1 cells to further validate ER-specific gene regulation as well as ER dimerization using Bioluminescence resonance energy transfer techniques. Results RNA-seq analysis of BPH1 cells treated with ER agonists revealed both overlapping and distinct gene expression profiles for each compound. By examining the overlap of genes induced or repressed by both the natural and synthetic compounds specific for each receptor, we have identified 144 ERα-specific, 222 ERβ-specific, and 42 ERα/ERβ-heterodimer genes. Luciferase assays in the CRISPR knockout cells confirm the receptor specificity of the synthetic compounds used in this study. Additionally, dimerization studies confirm the contribution of ERα and/or ERβ to the regulation of gene expression. Conclusions Using E2 and SERMs, we were able to identify and validate ERα- and ERβ-regulated genes in benign prostate cells. Further studies assessing these estrogen-regulated genes will provide a basis for biomarkers in the study of BPH/LUTD. Furthermore, given the opposing roles of ERα and ERβ, these genes will allow us to further assess the function of ER in disease promotion in patients and animal models as well as monitor the efficacy of therapeutic SERMs in the treatment of BPH/LUTS. Funding 5K12DK100022_x000D_ U54DK104310_x000D_ R01DK093690
Authors
Teresa Liu
Jalissa Wynder Taryn James Jill Macoska William Ricke |
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MP17-09 |
CXCL12-CXCR4 Axis Activation Promotes COP II Vesicle-Mediated Secretion of Collagen by Prostate Myofibroblasts |
Benign Prostatic Hyperplasia: Basic Research & Pathophysiology | 17BOS |
Abstract: MP17-09 Sources of Funding: NIH/NIDDK 1U54 DK104310 (Ricke, PI; Macoska, Co-PI); NIH/NIDDK 1R21DK098304 (Macoska , PI) Introduction Factors that promote lower urinary tract voiding dysfunction (LUTD) in aging men include excessive prostatic proliferation and muscle contraction. Recent studies suggest that tissue fibrosis, e.g., peri-urethral collagen accumulation, may also contribute to LUTD. Our group recently reported that activation of the CXCL12/CXCR4 axis and downstream MEK/ERK activation, as well as canonical TGFβ/TGFβR axis activation and downstream Smad3 activation, promote prostate fibroblast to myofibroblast phenoconversion and collagen production. Based on this finding, we hypothesized that downstream MEK/ERK and Smad signaling would converge at the transcriptional level to promote the activation of genes encoding pro-fibrotic proteins. To test this, RNA sequencing analysis was performed on prostate fibroblasts treated with CXCL12 or TGFβ. Methods Prostate fibroblasts were treated with 4ng/ml TGFβ or 100pM CXCL12 for 12 hrs (RNA) or 24, 48 and 72 hrs (protein). Total RNA was purified and subjected to qRT-PCR or RNASeq. Sequence data was pipelined through the Bowtie/TopHat/Cufflinks/CummeRbund (Tuxedo) packages. Pathview v1.10.1 and Cytoscape were used to perform Kegg pathway and network analysis, respectively. Immunoblot analysis was performed using whole protein lysates or concentrated conditioned media. Results RNASeq analysis showed that prostate fibroblasts treated with CXCL12 up-regulated the transcript levels of genes that encoded members of the Cullin-RING 3 (CRL3) ubiquitin ligase family of proteins. These proteins form COPII vesicles that transport procollagen from the endoplasmic reticulum to the cell membrane and extracellular space. Western blot analysis showed that CXCL12-treated cells up-regulated CRL3 proteins and secreted higher levels of procollagen compared to vehicle and TGFβ-treated cells. Procollagen secretion was ablated upon treatment with AMD3100, a CXCR4 antagonist, demonstrating that the observed increased collagen secretion was specifically coupled to CXCL12/CXCR4 axis activation. Conclusions The results of these studies are consistent with our hypothesis and present a major new discovery: Activation of the CXCL12/CXCR4 axis promotes fibrosis by increasing both the expression and secretion of collagen. Funding NIH/NIDDK 1U54 DK104310 (Ricke, PI; Macoska, Co-PI); NIH/NIDDK 1R21DK098304 (Macoska , PI)
Authors
Susan Patalano-Salsman
Jose A. Rodriguez-Nieves Diego Almanza Amy Avery Andrew Judell-Halfpenney Todd Riley Jill Macoska |
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MP17-10 |
E-cadherin downregulation is associated with increased luminal epithelial permeability in benign prostate hyperplasia |
Benign Prostatic Hyperplasia: Basic Research & Pathophysiology | 17BOS |
Abstract: MP17-10 Sources of Funding: 1U54 DK112079 and 1R56 DK107492 Introduction Prostate specific antigen (PSA), which is expressed by luminal epithelial cells in prostate was recently shown in the stromal compartment of BPH. Since the stromal compartment does not express PSA, epithelial barrier integrity in BPH nodules might be compromised through loss of cell junctions, resulting in the leakage of PSA and other secreted proteins into the stromal compartment and subsequently promoting BPH pathogenesis. E-cadherin, an important cell junction regulator, is found to be down-regulated in epithelial cells in clinical BPH specimens. Whether E-cadherin downregulation affects epithelial barrier permeability is unknown. This research is aimed at examining epithelial barrier permeability change in BPH and exploring the potential role of E-cadherin in prostatic luminal epithelial permeability. Methods Explants derived from BPH patients were used to study epithelial barrier permeability in BPH nodules and its normal adjacent tissues by FITC-dextran assay. Normal prostate luminal epithelial cell line BHPrE1 was utilized to perform in vitro studies. Two independent siRNAs were used to knockdown E-cadherin expression. Permeability of BHPrE1 cell monolayers in trans-well inserts was evaluated by trans-epithelium electrical resistant (TER) assay and FITC-dextran trans-well assay. Cell viability was checked by cell counting assay and MTT assay. Expression of E-cadherin and tight junction proteins following siRNAs treatment were determined by reverse transcription-polymerase chain reaction (RT-PCR) and western-blot (WB). Results FITC-dextran assay detected an increased epithelial barrier permeability in BPH tissues but not in the adjacent normal prostate in explants derived from BPH patients. Knockdown of E-cadherin in BHPrE1 cells decreased TER and increased FITC-dextran diffusion, indicating that E-cadherin knockdown disrupted epithelial barrier and increased monolayer permeability. E-cadherin knockdown had no impact on cell viability. E-cadherin knockdown also did not affect the expression of tight junction proteins ZO-1, ZO-2 and ZO-3. Conclusions Epithelial barrier permeability was increased in BPH and loss of E-cadherin is potentially an important underlying mechanism. Our results suggest blocking E-cadherin loss could be a potential approach to prevent or treat BPH. Funding 1U54 DK112079 and 1R56 DK107492
Authors
Feng Li
Laura E Pascal Anil Parwani Rajiv Dhir Joel B Nelson Peng Guo Dalin He Zhou Wang |
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MP17-11 |
Contributions of prostate volume and fibrosis to bladder outlet obstruction |
Benign Prostatic Hyperplasia: Basic Research & Pathophysiology | 17BOS |
Abstract: MP17-11 Sources of Funding: VA Merit Award: 1010 BX003454-01 Introduction It has been proposed that prostatic fibrosis contributes to bladder outlet obstruction in men with BPH/LUTS. We used preoperative urodynamics and CT imaging to evaluate the contributions of prostatic enlargement and fibrosis to obstruction in a cohort of men who underwent surgery for BPH/LUTS. Prostate volume and radiodensity were determined from the preoperative CT scan. Hounsfield units (HU), a quantitative measure of radiodensity on CT scans used frequently as a surrogate marker for liver and lung fibrosis, was used as a surrogate marker for prostate fibrosis. Methods We identified 34 men (mean age of 66 yrs, range 48-93 yrs) with complete pre-operative urodynamic evaluation for whom non-contrast axial pelvic CT scan images were available. Prostate volume was calculated using the formula for ellipsoid volume (L x W x H x 0.52). Mean prostate HU was determined by averaging the HU of ellipsoid selections of the proximal, middle, and distal prostate. The bladder outlet obstructive index (BOOI) was calculated from the formula PdetQmax - 2Qmax and used to classify patients as obstructed (BOOI ≥ 40), equivocal (BOOI 20-40), or unobstructed (BOOI < 20). Ten men aged 20-40 years who underwent non-contrast axial CT scanning for flank pain were used as controls. Results Mean BOOI was 56 (22 obstructed, 7 equivocal and 5 unobstructed). Mean prostate volume was significantly greater in patients with BPH/LUTS (mean 62 cc; range 19-217 cc) than in controls (mean 24 cc; range 14-33 cc) (<0.0001). _x000D_ Linear regression analysis revealed a significant positive relationship between volume and BOOI (p-value = 0.04) in patients with BPH/LUTS. Mean prostate HU was significantly higher in men with BPH/LUTS (mean 37 HU, standard deviation 6 HU, range 28-49 HU) compared to controls (mean 41 HU, standard deviation 5 HU, range 35-51 HU) (p=0.04) but linear regression analysis revealed no significant positive relationship between HU and BOOI (p = 0.32)._x000D_ Conclusions Our studies affirm that prostate volume is significantly associated with urodynamic evidence of obstruction among men with BPH/LUTS. Prostatic radiodensity was significantly higher in men with BPH/LUTS compared to young healthy controls, but we found no significant association bettween prostate radiodensity and urodynamic evidence of obstruction in men with BPH/LUTS. Funding VA Merit Award: 1010 BX003454-01
Authors
Matthew D Grimes
Will Lyon Sijian Wang Lori M Gettle Wade A Bushman |
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MP17-12 |
Th2 Cytokines Promote Myofibroblast Phenoconversion and Prostatic Fibrosis |
Benign Prostatic Hyperplasia: Basic Research & Pathophysiology | 17BOS |
Abstract: MP17-12 Sources of Funding: Supported by NIH/NIDDK grant 1P20DK090870?03 (JAM) and 1U54DK104310 (JAM). Introduction A growing number of recent studies associate lower urinary tract dysfunction (LUTD) with concurrent tissue fibrosis. Other studies have described profuse inflammatory infiltrate of benign prostatic hyperplasia (BPH) tissues, and that Th2 cytokines, particularly IL-4 and IL-13, are produced and secreted by infiltrating T-cells in these tissues. Because Th2 cytokines have been shown to mediate tissue fibrosis in the lung and liver, we hypothesized that Th2 cytokines secreted by inflammatory infiltrate may promote collagen accumulation and fibrosis in the prostate. Methods N1 immortalized and primary prostate fibroblasts and lung fibroblasts (the later included as positive controls) were grown in serum free defined media supplemented with vehicle, TGFbeta, IL-4, and IL-13 alone or in combination with or without IL-4 or IL-13 inhibitors. Cells were evaluated by immunofluorescence for alphaSMA and collagen expression in situ, by immunoblot for IL-4Ralpha and IL-13R1alpha expression, by WST assay for cell proliferation, by ELISA for protein expression, or by Sircol assay for collagen production. Results Prostate and lung fibroblasts expressed the IL-4Ralpha and IL-13R1alpha receptor proteins. N1 and primary prostate and lung fibroblasts underwent myofibroblast phenoconversion and significantly up-regulated collagen 1 and αSMA protein expression in response to IL-4 or IL-13 treatment. These effects were ablated through co-treatment with IL-4 and IL-13 receptors antibodies. Low concentrations of IL-4 and IL-13 significantly up-regulated N1 and primary prostate cell proliferation. Prostate fibroblasts treated with IL-4 or IL-13 significantly and almost equivalently up-regulated IL-13 protein expression, suggesting the establishment of an autocrine IL-13 expression loop. Treatment with IL-4 alone up-regulated IL-4, but not IL-13, protein expression. Neither IL-4 nor IL-13 affected TGFbeta expression levels. Conclusions The results of these studies show that IL-4 and IL-13 promote myofibroblast phenoconversion and collagen accumulation, and thus support a role for IL-4/IL-13 promotion of prostatic fibrosis associated with LUTD. A major new discovery reported here is that Th2 cytokines, particularly IL-13, can establish autocrine expression loops in prostate fibroblasts that may promote continual myofibroblast phenoconversion in the lower urinary tract. These findings support the investigation of small molecules or antibodies that target Th2 IL-4/IL13 activities for the prevention or treatment of lower urinary tract fibrosis. Funding Supported by NIH/NIDDK grant 1P20DK090870?03 (JAM) and 1U54DK104310 (JAM).
Authors
Mehrnaz Gharaee-Kermani
Jill Macoska |
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MP17-13 |
Magnetic Resonance Imaging Studies of an Experimental Mouse Model of Lower Urinary Tract Symptoms Associated with Benign Prostatic Hyperplasia |
Benign Prostatic Hyperplasia: Basic Research & Pathophysiology | 17BOS |
Abstract: MP17-13 Sources of Funding: EMM is supported by an F31 (F31DK111131). DVG is supported by an R01 (CA178431). Introduction Benign prostatic hyperplasia (BPH) is one of the most common prostatic disorders affecting aging men, causing progressive lower urinary tract symptoms (LUTS) such as bladder outlet obstruction (BOO). While ultrasound imaging is the current standard of care in monitoring human BPH, magnetic resonance imaging (MRI) offers enhanced image resolution. BPH may result from hormone-mediated aberrant proliferation of prostate progenitor cells. Lack of sufficient in vivo models has made this hypothesis difficult to test directly. The objective of this study was to evaluate a recently published murine model of BOO/BPH via longitudinal MR imaging and immunohistochemistry to further understand the underpinning mechanisms of BPH/BOO pathophysiology. Methods We adapted a recently published model of prostatic enlargement in order to investigate proliferating cell populations. Briefly, post-pubescent male mice were castrated and surgically implanted with subcutaneous implants to slowly release either testosterone (T) only or testosterone and estradiol (E). Mice were evaluated using MRI at 2-4 week intervals post-castration and then sacrificed accordingly. MR imaging was used to determine prostatic, urethral, and genitourinary blood volumes. Immunohistochemistry (IHC) was used to determine proliferating cell populations and prostate lineage changes. Results We observed a significant increase, approximately 2-fold, in the prostatic volume of mice treated with T+E as compared to T controls (p = 0.01) with a concomitant decrease in urethral volume (p = 0.01). T+E mice also had significantly higher genitourinary blood volumes (p = 0.01), indicating more genitourinary vascularization. We found no significant difference in number of CK8+ luminal cells, CK5+ basal cells, or Ki67+ epithelial cells. Conclusions Using MRI and IHC, we demonstrate that long-term treatment of mice with testosterone and estradiol induces an increase in prostatic volume with a concomitant decrease in urethral volume. Despite prostatic enlargement, we did not document an increase in proliferating prostatic epithelial cells or inflammatory infiltrate. Refining murine models is essential to understanding human BPH etiology and pathology. These data are critical to development of novel strategies that target progenitor cell populations in BPH, an unmet therapeutic need. Funding EMM is supported by an F31 (F31DK111131). DVG is supported by an R01 (CA178431).
Authors
Erin McAuley
Devkumar Mustafi Brian Simons Rebecca Valek Marta Zamora Erica Markiewicz Sophia Lamperis Greg Karczmar Aytekin Oto Donald Vander Griend |
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MP17-14 |
DEPLETION OF PERIPHERAL SEROTONIN SYNTHESIS INDUCES BENIGN PROSTATIC GROWTH IN MICE: MORE EVIDENCE FOR THE NEW “NEUROENDOCRINE THEORY” IN BPH ETIOLOGY |
Benign Prostatic Hyperplasia: Basic Research & Pathophysiology | 17BOS |
Abstract: MP17-14 Sources of Funding: Surgical Sciences Research Domain, Life and Health Sciences Research Institute, ICVS/3B’s - PT Government Associate Laboratory Introduction Ageing and testosterone cause almost inexorably benign prostatic hyperplasia (BPH) in Human males, however the etiology of BPH is unknown. Serotonin (5-HT) is produced by neuroendocrine prostatic cells and is present in high concentration in normal prostatic transition zone. In BPH neuroendocrine cells and 5-HT are significantly decreased comparatively to normal prostatic transition zone. Previously, we have demonstrated in several in vitro models that 5-HT inhibitis non-malignant prostatic growth through androgen receptor down-regulation and we suggested a new Neuroendocrine Theory for BPH etiology. Here, we investigated in vivo the effects of peripheral inhibition of 5-HT synthesis on mice prostate gland. Methods peripheral 5-HT synthesis is critical dependent of the presence of TPH1, so we used transgenic mice depleted from TPH1 (Tph1-/-) to study the in vivo effect of peripheral serotonin depletion. Male wild-type and Tph1-/- mice were sacrificed at different time points: 7, 12, 16 and 20 weeks-old. For pharmacological studies, wild-type and Tph1-/- mice with 19 week-old were treated with daily intraperitoneal injections of 0,9% saline or 5-HT (100 mg/Kg) during 10 consecutive days._x000D_ Prostate gland mass was determined and proceeded for histology, western blotting, immunofluorescence and qRT-PCR of AR expression._x000D_ Results We showed that Tph1 knockout mice depleted from peripheral 5-HT have significant higher prostate mass comparatively to wild-type (p < 0,001) and 5-HT treatment of Tph1 knockout mice restores prostate mass to levels of wild-type (p < 0,001) (figure A and B). We demonstrated also that the benign prostatic growth in Tph1 knockout mice is associated with up-regulation of AR and 5-HT treatment restores de expression of AR (p<0,05)(Figure C and D)._x000D_ Conclusions In vivo, 5-HT depletion induces benign prostatic growth in mice trough AR up-regulation. 5-HT depletion in transition zone of aging human male could be the etiologic factor for BPH etiology. Funding Surgical Sciences Research Domain, Life and Health Sciences Research Institute, ICVS/3B’s - PT Government Associate Laboratory
Authors
Paulo Mota
Emanuel Carvalho-Dias Alice Miranda Olga Martinho Cristina Nogueira-Silva Natalia Alenina Michael Bader Riccardo Autorino Estevão Lima Jorge Correia-Pinto |
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MP17-15 |
Long-term leptin treatment results in a reduction in prostatic epithelial hyperplasia in the ObOb mouse model |
Benign Prostatic Hyperplasia: Basic Research & Pathophysiology | 17BOS |
Abstract: MP17-15 Sources of Funding: 1R01 DK103483-01 Introduction Benign prostatic hyperplasia (BPH) is a major public health problem with high morbidity and associated cost. BPH arises in the context well recognized comorbidities including metabolic syndrome (MetS), obesity and diabetes. Animal models do not reflect all aspects of the human disease. Recently, an animal model, leptin-deficient obese ObOb mice has been reported that mimics the features of MetS and prostatic hyperplasia. However, details of the linkage between MetS/obesity and prostatic hyperplasia remain unknown in this model. To assess the relationship between MetS/obesity and prostatic hyperplasia in ObOb mice, we evaluated the morphological phenotype of control and leptin-treated ObOb mice prostate. Methods We started with 10-week-old male ObOb and strain-matched control mice. Three groups were examined: lean C57/Bl/6J (strain-matched control), non-treated ObOb, and leptin-treated ObOb mice. Leptin was delivered using a subcutaneous Alzet micro-osmotic pump. Leptin was delivered 5 μg/day for the initial 12 weeks of the study, and at 10 μg/day for the final 12 weeks. The liver, pancreas, spleen, skin, femoral muscle, subcutaneous fat, visceral fat, periprostatic fat, brown fat, and urogenital organs were harvested for analysis. Results In ObOb mice, total body weight and liver weight were reduced 25%-35% by leptin treatment. Leptin supplementation dramatically reduced body weight during the first month, but weight then increased slowly. Non-fasting serum blood glucose levels were normal range (≤ 250mg/dl) in all ObOb mice, but a glucose tolerance test revealed significantly longer recoveries in non-treated vs. leptin-treated ObOb mice. Compared to non-treated ObOb mice, liver weight of leptin-treated ObOb mice is significant lighter but still heavier than lean C57/Bl/6J mice. Anterior, ventral, and dorsolateral prostate glands in non-treated ObOb mice exhibited epithelial hyperplasia compared to lean C57/Bl/6J mice. In the leptin-treated mice, the number of hyperplastic prostate glands in each lobe was significant lower than in non-treated ObOb mice. Conclusions Our results demonstrated that long-term leptin treatment results in a reduction in prostatic epithelial hyperplasia in the ObOb mouse model. Full characterization of this animal model may elucidate molecular mechanisms linking MetS/obesity and prostatic hyperplasia. Funding 1R01 DK103483-01
Authors
Takeshi Sasaki
Omar Franco LaTayia Aaron Rodrigo Javier Yana Filipovich Susan Crawford Simon Hayward |
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MP17-16 |
Metformin inhibits benign prostatic epithelial cells through suppression of Insulin-like growth factor 1 receptor |
Benign Prostatic Hyperplasia: Basic Research & Pathophysiology | 17BOS |
Abstract: MP17-16 Sources of Funding: NIH/R01 DK091353 Introduction Benign prostatic hyperplasia (BPH) is the most common, proliferative abnormality of the prostate affecting elderly men throughout the world. Epidemiologic studies have shown that diabetes significantly increases the risk of developing lower urinary symptoms, some of which may be related to bladder outlet obstruction. It is unclear whether anti-diabetic medications may prevent progression of lower urinary tract symptoms. We have previously found that stromally expressed insulin-like growth factor 1 (IGF-1) promotes benign prostatic epithelial (BPE) cell proliferation through paracrine mechanisms. Here, we seek to understand if metformin, a first line medication for the treatment of type-2 diabetes, inhibits the proliferation of BPE cells through reducing the expression of IGF-1 receptor (IGF-1R) and the adjustment of the cell cycle. Methods BPE cell lines (BPH-1 and P69) and a stromal cell line (3T3) were cultured and tested in this study. Cell proliferation and the cell cycle were analyzed by MTS assay and flow cytometry, respectively. The expression of IGF-1 receptor was determined by western-blot and immunocytochemistry. The levels of IGF-1 secretion in a culture medium were measured by ELISA. Results Metformin (0.5-10mM, 6-48h) significantly inhibited the proliferation of BPH-1 and P69 cells in a dose-dependent and time-dependent manner without inducing apoptosis. Treatment with metformin for 24 hours lowered the G2/M cell population by 43.24% in P69 cells and 24.22% in BPH-1 cells. On the other hand, IGF-1 (100ng/ml, 24h) stimulated the cell proliferation (increased by 28.81% in P69 cells and 20.95% in BPH-1 cells) and significantly enhanced the expression of IGF-1R in BPE cells. Metformin (5mM) abrogated the proliferative effect of IGF-1 on BPE cells. In 3T3 cells, the secretion of IGF-1 was drastically inhibited by metformin from 574.31pg/ml to 197.61pg/ml. A conditioned medium of 3T3 cells promoted the proliferation and expression of IGF-1R in BPH-1 and P69 cells. Similarly, metformin abrogated the ability of a 3T3 conditioned medium to promote proliferation of BPE cells. Conclusions Our study demonstrates that metformin inhibits the proliferation of BPE cells by suppressing the expression of IGF-1R. Metformin may have a protective role in prostatic proliferation by inhibition of IGF-1R. Funding NIH/R01 DK091353
Authors
Zongwei Wang
Xingyuan Xiao Rongbin Ge Jijun Li Cameron Johnson Cyrus Rassoulian Aria Olumi |
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MP17-17 |
Effect of Agent Orange Exposure on the Development of Benign Prostatic Enlargement |
Benign Prostatic Hyperplasia: Basic Research & Pathophysiology | 17BOS |
Abstract: MP17-17 Sources of Funding: Veterans Administration Introduction Agent Orange exposure (AOe) has been demonstrated to be associated with an increased risk of prostate cancer (CaP). However, it is unknown whether AOe also increases the development of benign prostatic enlargement (BPE). The objective of this study was to determine the association between AOe and BPE by evaluating prostate volume in a US Veteran Cohort. Methods Risk factors including clinic-demographic and laboratory data from veterans who had undergone a initial prostate biopsy that was negative for cancer detection were collected. The primary outcome was the calculated prostate volume as determined by transrectal US. Prostate volume of AOe veterans relative to unexposed veterans was compared using univariate and multivariate logistic regression. Patient age, AOe, maximum PSA prior to biopsy, and BMI were included in the multivariate analysis. Results Of 1821 veterans undergoing an initial negative prostate biopsy 7% (129) had documented AOe. Age, BMI and maximum PSA were all significantly correlated with increasing prostate volume (p=<0.01 for each). On univariate and multivariate analysis there was no significant association between AOe and prostate volume as measured by US. Conclusions These results indicate AOe is not associated with an increase in prostate volume in a US veteran cohort undergoing an initial negative prostate biopsy. Despite its relationship with malignant growth of the prostate, AOe does not appear to be associated with BPE. Funding Veterans Administration
Authors
Daniel Sackman
Wesley Stoller Laura Peters Jackilen Shannon Mark Garzotto |
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MP17-18 |
Peri-prostatic Fat (PPF) Secretome in BPH Progression |
Benign Prostatic Hyperplasia: Basic Research & Pathophysiology | 17BOS |
Abstract: MP17-18 Sources of Funding: None Introduction Periprostatic fat (PPF) is a well-vascularized adipose tissue that encloses the prostate containing resident adipose tissue macrophages (ATM) that are mobilized and recruited to areas with high tissue remodeling. PPF can secrete a wide range of adipokines involved in physiologic and pathologic processes. It is well established that the unbalanced production of pro-inflammatory adipokines is a key component to the development of the metabolic syndrome, a risk factor for lower urinary tract symptoms (LUTS) and BPH progression. However, the link between PPF and BPH pathogenesis has not been previously addressed. In this study, we hypothesize that during BPH progression, PPF secretes a pro-inflammatory cytokine profile leading to chronic activation of NF-&[kappa]B signaling pathway Methods PPF was collected from patients undergoing prostatectomy. The thickness of PPF was determined (distance between the pubic symphysis and prostate) in 205 patients using MRI and classified based on their BMI (lean vs. obese). The composition of PPF was characterized histopathologically with emphasis on the immune/inflammatory infiltrates. To determine the factors secreted by PPF, a short in vitro culture was used to generated conditioned medium and adipocytokine array analysis performed. Proliferation of benign prostate epithelial and stromal cells exposed to PPF-CM was assessed. Upon exposure to PPF-CM, activation of the NF-&[kappa]B pathway was determined by western blot analysis. In vivo experiments were performed xenografting PPF and human prostate tissues under the kidney capsule of SCID mice to determine the effects of PPF on prostate histology and recruitment of inflammatory cells Results Histological analysis of human PPF samples showed an increased ratio of multilocular/unilocular phenotype composed mainly of macrophages and mononuclear infiltrates in obese individuals compared to the unilocular pattern and lack of inflammatory infiltrates in lean patients. Obese patients showed a significantly increased PPF thickness (more than double) compared to lean patients. Interestingly MRI showed that PPF only partially surrounds the prostate in lean patients, while fat tissue almost completely encased the prostate in obese individuals. Adipokine array assays from PPF-CM samples show the expression of a profile of pro-inflammatory factors. Addition of androgens modulated the secretion of IL11, TGFβ1, IL16 and SDF1α, among oth Conclusions Our preliminary studies suggest a potential role for the PPF pro-inflammatory secretome in BPH pathogenesis Funding None
Authors
Omar Franco
Rodrigo Javier Mathew Brady Susan Crawford Simon Hayward |
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MP17-19 |
The Expression and Functional Activities of Smooth Muscle Myosin and Non-Muscle Myosin Isoforms in Rat Prostate |
Benign Prostatic Hyperplasia: Basic Research & Pathophysiology | 17BOS |
Abstract: MP17-19 Sources of Funding: Xinhua Zhang is supported by National Natural Science Foundation of China (N.81270843 and N.81160086) Introduction Benign prostatic hyperplasia (BPH) is a common disease in aging male, which mainly caused by increased prostatic smooth muscle (SM) tone and volume. Lowering SM tone with α-blockers are one of the most effective treatment for BPH. SM and non-muscle (NM) myosin play important roles mediating SM tone and cell proliferation. But it was less studied in the prostate. Methods Rat prostate and cultured primary human prostate SM and epithelial cells were used. In vitro organ bath studies were performed to explore contractility of rat prostate, corpus cavernosum, bladder and aorta. SMM isoforms were determined with competitive RT-PCR. SM myosin heavy chain (MHC) and NM MHC isoforms (NMHC-A, NMHC-B and NMHC-C) were further analyzed with Western Blot and immunofluorescence. Results SM MHC was abundantly displayed in rat prostate, predominantly in the outer stroma layer. Prostatic SM generated significant force in response to KCl depolarization and phenylephrine (PE)-mediated stimulation in a dose-dependent manner with an intermediate tonicity between bladder typical phasic and aorta tonic contractility. And time to 50% PE mediated maximum contraction of prostate (13.2±2.6 S) was between that of bladder (5.7±1.2 S) and aorta (24.2±2.4 S). Correlated with this kind of intermediate tonicity, rat prostate mainly expressed LC17a and SM1 but with relatively equal expression of SM-B at the mRNA level. Meanwhile, isoforms of NMHC-A, B, C were also abundantly detected in the prostate with SMM present only in SM cells, NMHC-A and NMHC-B both present in SM and endothelial cells, and NMHC-C expressed only in the SM cells. Furthermore, NM expression in rat prostate was more than 2-fold higher than that of rat bladder, while SMM expression was found to be similar. Additionally, SMM specific inhibitor Blebbistatin could potently relax PE pre-contracted prostate SM, comparable to the effect of sodium nitroprusside (nitric oxide donor) and H-1152 (a specific, strong and membrane-permeable inhibitor of Rho-kinase) Conclusions Our novel data demonstrated the expression and functional activities of SMM and NM isoforms in the rat prostate. It is suggested that the isoforms of SMM and NM could play important roles in BPH development. Funding Xinhua Zhang is supported by National Natural Science Foundation of China (N.81270843 and N.81160086)
Authors
Ping Chen
Jing Yin Yuming Guo Xinghuan Wang Michael E DiSanto Xinhua Zhang |
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MP17-20 |
Phosphodiesterase type 5 (PDE5) in the human prostate: relation to key enzymes of the nitric oxide/cyclic GMP signaling |
Benign Prostatic Hyperplasia: Basic Research & Pathophysiology | 17BOS |
Abstract: MP17-20 Sources of Funding: none Introduction The significance of the nitric oxide (NO)/cyclic GMP pathway in the control of prostate smooth musculature actually serves as a rationale for the clinical development of the phosphodiesterase type 5 (PDE5, cyclic GMP PDE) inhibitor tadalafil to treat lower urinary tract symptomatology (LUTS) secondary to benign prostatic hyperplasia (BPH). However, the potential relevance of the nitric oxide (NO)/cyclic GMP signaling in the human prostate is still discussed controversly. For example, it has been speculated that the clinical efficacy of PDE5 inhibitors in patients with LUTS/BPH can be explained by the effects of this class of drugs on the urinary bladder rather than the prostate (Chapple C.R., Roehrborn C.G., Eur. Urol. 49: 651-659, 2006). This prompted us to evaluate in the human prostate the expression of key proteins of the NO pathway, namely the neuronal nitric oxide synthase (nNOS), cyclic GMP, and cyclic GMP-binding protein kinase type I (isoforms alpha und beta = cGKIα, cGKIβ), in relation to the PDE5. Methods Slices (10 µm) of specimens taken from the transition zone (TZ) of the human prostate were exposed to antibodies directed against cyclic GMP, PDE5A, nNOS, cGKIα or cGKIβ, followed by the application of fluorochrome-labeled secondary antibodies. Visualization was commenced by means of laser fluorescence microscopy. Results In the smooth muscle (SM) portion of the TZ, immunosignals specific for the PDE5 were found co-localized with cyclic GMP, cGKIα and cGKIβ, as well as with the cyclic cAMP-binding protein kinase A (cAK). SM bundles were seen innervated by slender varicose nerve fibers characterized by the expression of nNOS. Some of these nerves also presented staining related to the neuropeptide VIP (vasoactive intestinal polypeptide). Conclusions The results are in support of the hypothesis of a role of the cyclic GMP signaling in the control of the TZ of the prostate and also give hints that the cyclic GMP- and cyclic AMP-dependent signal transduction may synergistically work together. Funding none
Authors
Stefan Ueckert
Andreas Bannowsky Markus Kuczyk Petter Hedlund |
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MP18-01 |
Identification of Prostate Specific Antigen and Prostate Specific Antigen Density Thresholds at which Fusion-Guided Biopsy Outperforms Systematic Biopsy |
Imaging/Radiology: Uroradiology III | 17BOS |
Abstract: MP18-01 Sources of Funding: The author&[prime]s postdoctoral fellowship is funded by a research grant from the &[Prime]Dr. Mildred Scheel&[Prime] foundation (Bonn, Germany). Introduction Transrectal ultrasound/magnetic resonance imaging fusion-guided biopsy (FB) of the prostate improves detection of clinically significant prostate cancer (CS PCa) compared to standard 12-core systematic biopsy (SB). However, it is still unclear which patient population benefits from FB rather than SB alone. Our goal was to determine prostate specific antigen (PSA) and PSA density (PSAD) thresholds at which FB outperforms SB. Methods 1226 patients underwent prostate multiparametric MRI (mpMRI) including T2 weighted, diffusion weighted, apparent diffusion coefficient maps, high b value (1500-2000s/mm2) and dynamic contrast enhancement sequences from May 2015 to August 2016. Lesions were assigned suspicion scores according to the Prostate Imaging-Reporting and Data System version 2 (PI-RADSv2). PI-RADSv2 lesions scored ≥ 3 were routinely biopsied. 362/1226 patients underwent FB and SB in the same session. The highest Gleason scores detected by FB and SB were determined on a patient level. Patients who were upgraded to CS PCa (≥Gleason score of 3+4) by FB over SB and vice versa were identified. By calculating cumulative PSA and PSAD curves, exact thresholds for PSA and PSAD were determined at which FB upgraded more patients to CS PCa compared to SB. Results 167/362 patients were diagnosed with CS PCa. 55 patients were upgraded by FB, 35 were upgraded by SB, and both modalities diagnosed CS PCa in 77 patients. Thresholds of 6.15ng/ml for PSA and 0.14 for PSAD were determined (Figure 1). Conclusions Patients with a PSA ≥ 6.15ng/ml or a PSAD ≥ 0.14 appear to benefit more from mpMRI and subsequent FB if suspicious lesions are detected on mpMRI than patients with values below these thresholds. Funding The author&[prime]s postdoctoral fellowship is funded by a research grant from the &[Prime]Dr. Mildred Scheel&[Prime] foundation (Bonn, Germany).
Authors
Sherif Mehralivand
Sandra Bednarova Francesca Mertan Sonia Gaur Maria Merino Bradford Wood Peter Pinto Peter Choyke Baris Turkbey |
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MP18-02 |
Evaluation of MRI/ultrasound-fusion biopsy in patients with low-risk prostate cancer under active surveillance |
Imaging/Radiology: Uroradiology III | 17BOS |
Abstract: MP18-02 Sources of Funding: none Introduction Multiparametric magnet resonance imaging (mpMRI) of the prostate plays an increasingly important role during active surveillance (AS) protocols in patients with low-risk prostate cancer (PCa). We evaluated transperineal MRI/ultrasound-fusion biopsy (fusPbx) in combination with transrectal sysPbx in patients undergoing control biopsy in AS protocols. Methods 81 patients fulfilling the following criteria for low-risk PCa (Gleason Score (GS) ≤6, ≤2 positive cores, ≤50% PCa/core, cT1 or cT2a; PSA ≤10ng/mL) undergoing control-biopsy were investigated. Before biopsy, mpMRI was performed in all patients and tumour-suspicious lesions were evaluated according PI-RADS. All patients underwent a transperineal fusPbx (mean 4 cores/lesion) and, additionally, a transrectal sysPbx (mean 12 cores) during the same session. Cancer detection rate and the rate of tumour progression defined as evidence of GS≥7(3+4) were evaluated in both biopsy modalities. Results Median age was 68yrs, median PSA-level was 6.8 ng/mL, median prostate volume was 43mL._x000D_ In total, 154 lesions were detected whereas 117 (76%) were classified according PI-RADS. In the mean, 1.9 lesions were detected per patient. The overall cancer detection rate was 77% (62/81). 41 patients (51%) showed a tumour progression to GS ≥7 (3+4). The detection rate was 57% (46/81) in fusPbx and 62% (50/81) in sysPbx (p=0.57); the detection rate of GS≥7 (3+4) was 42% (34/81) in fusPbx and 37% (30/81) in sysPbx (p=0.65). FusPbx alone would have missed 20% (8/41) of GS≥7(3+4) and sysPbx alone would have missed 27% (11/41) of GS ≥7(3+4). Regarding the detection rate of GS≥7(3+4), the combination of both biopsy modalities was superior to fusPbx (p=0.016) and sysPbx (p=0.013) alone. The detection of GS≥7(3+4) in lesions with PI-RADS 2/3/4/5 was 24% (5/21), 37% (13/35), 35% (12/34) and 56% (15/27), respectively. Lesions classified as PI-RADS≥4 showed significantly more PCa with a GS≥7 (3+4) than lesions classified as PI-RADS≤3 (38% vs. 14%; p<0.005)._x000D_ Conclusions FusPbx is associated with a higher detection rate of PCa with GS ≥7(3+4). Especially the combination of both biopsy modalities outperforms fusPbx and sysPbx alone. Therefore, mpMRI with consecutive targeted biopsy in combination with sysPbx should be recommended for control biopsy in patients with low-risk PCa undergoing control-biopsy for AS protocols. Funding none
Authors
Angelika Borkowetz
Ivan Platzek Marieta Toma Theresa Renner Martin Baunacke Michael Froehner Stefan Zastrow Manfred Wirth |
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MP18-03 |
Transperineal MR/US Fusion-Guided Prostate Biopsy Maintains a High Degree of Cancer Detection Regardless of Targeted Lesion Volume |
Imaging/Radiology: Uroradiology III | 17BOS |
Abstract: MP18-03 Sources of Funding: None Introduction The advent of multiparametric magnetic resonance imaging (mpMRI) and fusion biopsy platforms have improved the diagnostic accuracy of prostate biopsies otherwise limited in standard ultrasound (US)-guided techniques. Electromagnetically (EM) tracked transperineal MR/US fusion guided prostate biopsy (tpFBx) (Invivo, Gainesville, FL) is a novel fusion biopsy system for targeting suspicious lesions on mpMRI of the prostate. In the largest series to date to critically evaluate the EM-tracked (tpFBx) system, we sought to determine if there is a difference in the ability of the biopsy platform to detect cancer based on target lesion size. Methods A total of 52 men who had undergone mpMRI of the prostate to identify regions suspicious for prostate cancer (PCa) were included. Images were interpreted using Prostate Imaging Reporting and Data System version 2 (PI-RADS v2). A total of 75 suspicious lesions were identified, all of which were sampled by EM-tracked tpFBx. Lesions were subdivided on the basis of volume (L x W x H x π/6): > 0.2 cc, 0.2 - 0.5 cc, 0.5 - 1.0 cc, > 1.0 cc. Epstein criteria for clinically significant (CS) PCa was used (tumor volume > 0.5 cc and/or Gleason Score (GS) > 6). Fisher's exact test was used to compare the targeted lesion volume groups with respect to CDR, CDR of CS PCa, and GS risk stratification. Results The CDR per lesion was 56.0% (42/75). Median age was 67.8 years and median prostate specific antigen at biopsy was 7.3 ng/ml. There was no difference in CDR across the groups after stratifying by GS risk level (Low, Intermediate, or High) (p=.23). The ability to target suspicious lesions and detect cancer was unaffected by volume of the lesion (p=.11). A subgroup analysis of lesions < 0.2 cc (n=22) and 0.2 cc to 0.5 cc (n=24) showed no statistical difference with regards to CS-PCa detection (p=.74). Conclusions The tpFBx platform does not demonstrate degradation in performance of cancer detection when targeting prostate lesions of varying volumes. This was true for all diagnosed cancers and after stratifying by GS risk. Though the size of the series is limited, these results support the diagnostic value of mpMRI in conjunction with this novel tpFBx system to accurately target suspicious areas and identify CS disease regardless of lesion size and should be evaluated further. Funding None
Authors
Harry Anastos
Jared S. Winoker Pratik A. Shukla Kyle A. Blum Cynthia J. Knauer Ashutosh K. Tewari Sara C. Lewis Bachir Taouli Ardeshir R. Rastinehad |
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MP18-04 |
Role of PI-RADS version 2 for Prediction of Upgrading after Radical Prostatectomy in Patients with Prostate Biopsy Gleason Score 6 |
Imaging/Radiology: Uroradiology III | 17BOS |
Abstract: MP18-04 Sources of Funding: none Introduction Accurate prediction of Gleason score (GS) after radical prostatectomy (RP) is important to determine treatment plans. However, 20-60% of patients with biopsy GS 6 are upgraded to GS 7 or more postoperatively. In this study, we evaluated whether Prostate Imaging Report and Data System version 2 (PI-RADSv2) has a role to predict upgrading after RP for patients with biopsy GS 6 Methods We retrospectively reviewed 443 patients who underwent magnetic resonance imaging (MRI) and RP for prostate cancer with biopsy GS 6 between January 2011 and December 2013. Preoperative clinical parameters (prostate specific antigen [PSA], prostate volume, PSA density, number of positive core and maximum percentage of cancer per core), PI-RADS v2 score and pathologic GS were examined. Multivariate logistic regression was used to analyze predictive factors of upgrading after RP. Receiver operating characteristic (ROC) curves were used to analyze the predictive accuracies of multivariate logistic regression models and areas under the curves (AUCs) of ROC curves were compared. Results Of 443 patients with biopsy GS 6, GS upgrading was identified in 297 (67.0%) patients (GS7, n=273 and GS8-10, n=24) following RP. PI-RADS v2 score 1-3, and 4-5 were identified in 157 (25.4%) and 286 (64.6%) patients, and upgrading rate after RP were 54.1% and 74.1%, respectively (p < 0.001). On multivariate analysis, PSA density > 0.16 ng/ml2, number of positive core ? 2, maximum % cancer/core >20% and PI-RADS v2 score 4-5 were predictive factors of upgrading following RP (all p < 0.05). When predictive accuracies of multivariate models were compared using AUC from ROC curves, model 2 (PI-RADS v2 score 4-5 along with model 1) was found to have significantly higher accuracy then model 1(PSA density > 0.16 ng/ml2, number of positive core ? 2 and maximum % cancer/core >20%) (0.729 vs 0.703, p = 0.041) Conclusions PSA density > 0.16 ng/ml2 , number of positive core ? 2 and maximum percentage of tumor length in a core > 20% are independent predictors of GS upgrading as preoperative variables. PI-RADSv2 4-5 confer an increased risk for GS upgrading that it may be used as a preoperative image tool to establish treatment decision. Funding none
Authors
Song Wan
Chan Kyo Kim Young Hyo Choi Hyun Woo Chung Chung Un Lee Jun Phil Na Hwang Gyun Jeon Byong Chang Jeong Seong Il Seo Seong Soo Jeon Han Yong Choi Hyun Moo Lee |
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MP18-05 |
Prostatic Arterial Variants: Lessons Learned from Interventional Radiology |
Imaging/Radiology: Uroradiology III | 17BOS |
Abstract: MP18-05 Sources of Funding: none Introduction Major urologic reference texts describe the prostatic artery originating from the Inferior Vesical artery. The advent of prostate artery embolization (PAE) has led interventional radiologists to identify variable anatomy. Our objective is to describe the variable origins of the prostatic artery (PA) identified during initial experience with PAE. Methods Prostatic arteries were identified from both computerized tomographic (CT) and catheter angiography. Two operators independently evaluated the anatomy of each pelvic half. The origin of each prostatic artery was categorized as follows: Common Anterior Gluteo-pudendal Trunk, Inferior Gluteal, Inferior Vesical, Internal Pudendal, Obturator, and Superior Vesical arteries (Figure 1). Cross-pelvic collateralization was also assessed. Results Thirty six arteries were evaluated in 26 pelvic halves in 13 patients. Sixty two percent (n=8/13) had independent ipsilateral PAs on one or both sides of the hemipelvis. Symmetric origins were noted in only 23% (n=3). The most common PAs origin was the Internal Pudendal artery (36%, n=13/36), followed by the Obturator artery (31% n=11/36) (Figure 2). The Inferior Vesical artery was the least common origin (3% (n=1/36) of the cohort. Eight patients underwent PAE, and 5 (38%, n=5/13) showed collateral flow between the right and left prostatic arterial supplies. Conclusions PAE challenges established concepts of prostate arterial supply by demonstrating high variability. In this study, we confirm the significant heterogeneity of prostatic arterial origins, with the most common published origin being the least common configuration we encountered. Additionally, collateralization underscores the complexity of prostatic arterial supply. Current technology demonstrates that descriptions in urology texts may be overly simplistic. Updated understanding of PA anatomy is essential for PAE, but may also have urological implications related to procedural efficacy or even potency given the predominance of arteries originating from the Internal Pudendal artery. Funding none
Authors
Jessica Jackson
George Rueb Andre Uflacker Ziv Haskal Noah Schenkman |
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MP18-06 |
Limitations of abdominal imaging for detection of lymph node metastases prior to prostatectomy |
Imaging/Radiology: Uroradiology III | 17BOS |
Abstract: MP18-06 Sources of Funding: Blue Cross Blue Shield of Michigan Introduction Cross-sectional imaging is performed during staging of high-risk prostate cancer to identify lymph node (LN) metastases. We investigated the performance and utilization rates of pre-robot-assisted radical prostatectomy (RARP) CT and MRI to identify LN metastases. Methods Using the MUSIC registry, we identified all patients undergoing RARP (3/2012 to 9/2016), grouping them by imaging prior to surgery (CT, MRI, none). Primary outcome was detection of LN metastases at RARP. In general, imaging studies were considered positive if LN>8mm in short axis were identified. Results Prior to 6489 RARP, 1783 patients underwent CT (27%), 282 underwent MRI (4.3%), and 4424 had no pretreatment abdominal imaging (68%). Pre-treatment factors were significantly different in these 3 populations (Table 1). For example, D&[prime]Amico high-risk patients represented 57.5%, 25.3%, and 8.3% of the CT, MRI, and no imaging cohorts, respectively (p<0.001). Predominant pattern 4 disease was present in 58%, 40%, and 23% and stage pT3/T4 cancer represented 48%, 36%, and 24% of the CT, MRI, and no imaging groups, respectively (both p<0.001). Among patients with Gleason 8-10 disease at final pathology, 30% were not imaged before RARP. Overall, 225 patients (3.5%) had pathologic LN involvement, including 0% low, 2% intermediate, and 9.4% high-risk patients. Suspicion for LN involvement was identified on 2.8% of CT (n=50) and was associated with higher Gleason score (sGS 9/10: 53%) and pT stage (pT3b/T4: 44%). Interestingly, many more patients with pN+ disease at RARP had a negative CT (n=123, 7.1%) than a positive CT (n=12, 24%), yielding a sensitivity of 8.9%, specificity of 97.7%, NPV of 93% and PPV of 24%. Conclusions Overall, 32% of patients (and 75% of those with high-risk cancer) underwent CT or MRI prior to RARP. Suspicion for LN metastases on CT was predictive of higher risk disease, but was a poor predictor of presence of LN metastases (positive predictive value: 24%). These data have implications for patients with and without suspicion of LN metastasis on CT. Patients with suspicious LNs might be managed as having disseminated disease and not be offered definitive local treatment. Conversely, patients with &[prime]negative&[prime] or no imaging may not receive PLND despite metastatic LNs in 2% and 9.4% of those with intermediate- and high-risk cancer at RARP. Funding Blue Cross Blue Shield of Michigan
Authors
Henry Peabody
Ji Qi Tae Kim James Montie Christopher Brede Jeffrey Montgomery Brian Lane Michigan Urological Surgery Improvement Collaborative |
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MP18-07 |
The accuracy and validation of multiparametric magnetic resonance imaging (mpMRI) using PI-RADS v2 in disease upgrading on re-biopsy among patients with low-risk prostate cancer on active surveillance (AS) – A Brazilian perspective. |
Imaging/Radiology: Uroradiology III | 17BOS |
Abstract: MP18-07 Sources of Funding: The authors have no funding, or financial relationships. Introduction The current selection criteria to AS is critical, it becomes even more relevant in Latin America, given the higher proportion of high risk cancers._x000D_ The objective of this study is to analyze the accuracy of mpMRI using PI-RADS v2 in predicting the risk of upgrading on re-biopsy (UR) in men with low-risk PCa on AS. Methods In this Institutional Review Board approved prospective study, patients with low-grade PCa selected for AS at our institution underwent mpMRI at least 6 weeks after the baseline 12-core random prostate biopsy (BSB), from March 2014 to March 2016. One blinded abdominal radiologist evaluated the exams regarding presence of dominant lesion and assigned the PI-RADS v2 score. MRI-target TRUS guided re-biopsies were done in all patients within 6-12 months after the BSB. Standardized 12-core biopsy was performed and additional cores were taken from suspicious areas on mpMRI. Results One hundred and nine patients were included, 93 (85.3%) patients had a dominant lesion on MRI. mpMRI were classified as PI-RADS 1, 2 or 3 in 67 (61.5%) patients, and as PI-RADS 4 or 5 in 42 (38.5%) patients. UR occurred in 42 (38.5%) patients. Out of these, 39 (92.8%) had radical prostatectomy, 6 (15.4%) T2a, 24 (61.5%) T2b, and 9 (23.1%) T3a. The proportion of UR among PI-RADS categories is shown in table 1. The diagnostic performance of mpMRI for PCa upgrading after re-biopsy was summarized in table 2. Patients assigned as PI-RADS 4 or 5 presented a significantly higher risk for UR compared with patients with PI-RADS 1, 2 or 3 (73.8% vs 16.4%, p<0.001). Logistic regression analyses demonstrated that PI-RADS 4 or 5 remained a significant predictor of UR (OR: 37.366, p<0.0001). Conclusions We demonstrated in our population that mpMRI using PI-RADS v2 is a significant predictor for upgrading on re-biopsy in patients on AS and could be used to guide TRUS biopsy, increasing the accuracy of current clinical criteria for AS._x000D_ Funding The authors have no funding, or financial relationships.
Authors
Públio Viana
Natally Horvat Rodrigo Pessoa Thiana Rodrigues Giuliano Guglielmetti Rafael Coelho Rubens Park Herbert Alberto Vargas Willian Nahas |
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MP18-08 |
Comparison of Fluciclovine (18F) PET-CT and MRI in Detection of Recurrent Prostate Cancer |
Imaging/Radiology: Uroradiology III | 17BOS |
Abstract: MP18-08 Sources of Funding: National Institutes of Health_x000D_ Blue Earth Diagnostics Limited supplied fluciclovine cassettes for the study. Introduction To compare the diagnostic performance of PET-CT using the synthetic amino acid radiotracer fluciclovine with multiparametric magnetic resonance imaging (mpMRI) in recurrent prostate cancer. Methods 24 patients with biochemical failure after non-prostatectomy definitive therapy underwent fluciclovine PET-CT and mpMRI (T2, DWI and DCE) within 29 days with blinded interpretation by expert readers. Reference standard was established via histology and clinical follow-up. Diagnostic performance was calculated for each of 2 readers for PET-CT (P1 and P2) and 2 other readers for MRI (M1 and M2). For the purpose of this analysis, equivocal interpretations were analyzed as negative. Results In the prostate, 22 patients underwent biopsy with 13 malignant and 9 benign (2 not biopsied). Accuracy for PET was 63.6% for both readers. Accuracy for mpMR was 45.5% and 40.9% for readers M1 and M2, respectively. Overall, fluciclovine PET had higher sensitivity for both readers while mpMR had higher specificity (Figure 1a)._x000D_ _x000D_ 17 patients met the reference standard for extraprostatic disease detection. 7 of these were confirmed by histology and 10 by clinical follow-up. Accuracy for PET was 88.24% for both readers. Accuracy for mpMR was 52.94% and 70.79% for readers M1 and M2, respectively. Overall, fluciclovine PET had higher sensitivity and specificity compared to mpMR (Figure 1b)._x000D_ _x000D_ Inter-reader agreement for fluciclovine PET was 91.6% in the prostate and 87.5% for extraprostatic disease detection. For mpMRI, inter-reader agreement was 37.5% and 75% respectively for prostate and extraprostatic disease detection. Conclusions Although fluciclovine PET-CT had higher sensitivity in the prostate, MRI had higher specificity for disease detection. However for extraprostatic disease, fluciclovine had higher sensitivity and specificity. Inter-reader agreement was better with fluciclovine PET-CT compared with mpMR. Funding National Institutes of Health_x000D_ Blue Earth Diagnostics Limited supplied fluciclovine cassettes for the study.
Authors
Oladunni Akin-Akintayo
Funmilayo Tade Pardeep Mittal Courtney Moreno Peter Nieh Peter Rossi Halkar Raghuveer Baowei Fei Mark Goodman David Schuster |
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MP18-09 |
Influence of Ga-PSMA PET/CT on clinical decision making in the treatment of patients with prostate cancer. |
Imaging/Radiology: Uroradiology III | 17BOS |
Abstract: MP18-09 Sources of Funding: None Introduction Positron emission tomography (PET) with Ga-Prostate Specific Membrane Antigen (PSMA) is a new imagiological technique to stage patients with prostate cancer. _x000D_ We aim to present the results of our preliminary analysis of 101 consecutive patients who performed this exam in our institution, exploring its utility in primary staging and re-staging after primary local treatment and its influence on clinical decision making. _x000D_ Methods From October 2015 to September 2016, 101 consecutive patients underwent Ga-PSMA PET/CT to stage patients before primary local treatment or, to detect recurrent or progressive disease after local treatment with curative intent in case of biochemical failure or persisting high PSA levels. _x000D_ All the exams were performed and read by nuclear medicine doctors. After the exam, in a multidisciplinary meeting, urologists, oncologists and radioncologists decided the treatment strategy in management of the patient. The exam was judged "influent" if its results, positive or negative, supported or determined a modification in clinical strategy._x000D_ _x000D_ _x000D_ Results Patients´characteristics are presented in table 1. _x000D_ Globally, Ga-PSMA PET/CT detected at least one hypermetabolic lesion in 66/101 patients (65.3%).Detection rates were 23.3%, 33.3%, %, 41.2% and 91.1% for PSA-levels between 0.2-0.5, 0.5-1, >1-2 and >2, respectively. _x000D_ Before the PET PSMA, 19 patients performed a pelvic MRI, 16 patients performed a bone scintigraphy, 7 patients a CT and 5 patients a PET-Choline exam. _x000D_ The concordance rate for positive results of Ga-PSMA PET/CT was 80% for pelvic MRI, 57.2% for bone scintigraphy, 66.7% for CT and 25% for PET-Choline exam. _x000D_ The main treatment influences of Ga-PSMA PET/CT on clinical decisions are presented in graphic 1. Decision-making was critically affected by PET-PSMA results in 81/101 (81.1%) patients. Conclusions We report our preliminary experience with Ga-PSMA PET/CT in primary staging and re-staging after primary local treatment. This exam influenced our clinical decisions in 81.2% of patients. Funding None
Authors
Carlos Ferreira
Liliana Violante Rui Freitas Isaac Braga Victor Silva Sanches Magalhães Francisco Lobo António Morais Hugo Duarte Jorge Oliveira |
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MP18-10 |
Comparison of planar scintigraphy and single-photon emission computed tomography /computed tomography (SPECT/CT) in preoperative imaging of sentinel lymph nodes in penile cancer patients |
Imaging/Radiology: Uroradiology III | 17BOS |
Abstract: MP18-10 Sources of Funding: None Introduction The aim of this study was to evaluate the diagnostic value of SPECT/CT and planar lymphoscintigraphy in preoperative imaging of sentinel lymph nodes in penile cancer patients with non-palpable inguinal lymph nodes. Methods Radio-labelling of sentinel nodes was performed by intradermal and peritumoral injection of 150MBq Tc-99 m-labelled nanocolloids according to the two day protocol. Image acquisition of planar scintigraphies was carried out by a twin head gamma camera (Siemens, ECAM and Symbia S) and indirect body contouring. Additionally, we subsequently performed SPECT/CT of the abdomen und inguinal regions using a twin-head hybrid camera system (Siemens Symbia T and Symbia Intevo). Imaging data of both modalities were prospectively evaluated by two experienced physicians in consensus reading in 52 groins of 26 patients with this tumor entity. Results A total of 71 SLNs in 37 groins were identified by planar scintigraphy. Non-visualization was observed in 15 (28.8%) inguinal basins using planar scans. 82 SLNs in 42 groins were detected by SPECT/CT (non-visualization in 10 (19.2%) groins). SPECT/CT revealed 8 inguinal hotspots as shown by planar imaging in 7 groins as false positive. 19 inguinal SLNs in 16 groins were missed on planar imaging and could be detected by SPECT/CT only. In contrast to 2D planar scintigraphy, SPECT/CT allowed to determine the precise anatomical localization of the SLNs in all 42 groins. Conclusions SPECT/CT is capable of detecting SLNs missed by planar imaging, it reduces the number of false positive findings and shows the morphological location of SLNs more accurately. If available, SPECT/CT should be used for preoperative SLN imaging in penile cancer patients with non-palpable inguinal lymph node status. Funding None
Authors
Carsten Maik Naumann
Moritz Franz Hamann Christian Colberg Klaus-Peter Jünemann Daniar Osmonov Ulf Lützen |
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MP18-11 |
Exploring the clinical uptake and use of PSMA PET MRI hybrid imaging in prostate cancer patients at an academic center in Australia |
Imaging/Radiology: Uroradiology III | 17BOS |
Abstract: MP18-11 Sources of Funding: None Introduction Positron emission tomography (PET) using prostate specific membrane antigen (PSMA) detects prostate cancer lesions with a higher sensitivity and specificity when compared to standard imaging. Hybrid PET Magnetic Resonance Imaging (MRI) has now been introduced to provide potentially improved characterization of lesions with added PET avidity. We evaluate the utilization of this novel imaging modality at the Princess Alexandra Hospital (PAH) and assess our initial outcomes. Methods A retrospective review of all PSMA PET MRI scans undertaken at the PAH since the introduction of the technology was performed. Imaging data was collected alongside baseline clinical data, PSA, previous histology, previous treatments, indication of scans, requesting clinicians and clinical outcomes. Results A total of 187 PSMA PET MRI scans were performed at the PAH from April 2015 to October 2016. The median age of imaged patients was 68, with a median PSA of 6ng/ml and Gleason score of 7 at the time of scan. 153 scans were positive for PSMA avid disease (81.8%). Scans were requested in the setting of biochemical recurrence (n=94), preoperative staging (n=77), evaluation of treatment response (n=11) and diagnostic purposes (n=5). Urologists requested PSMA PET MRI most frequently with 111 scans, of which 58.6% requested for preoperative staging. Radiation oncologists requested 69 scans with 75.4% of these in the biochemical recurrence setting. Only 7 scans were requested by medical oncologists. Amongst patients with biochemical recurrence the lowest PSA of a positive scan was 0.02 ng/ml. In this group 43 patients had prior surgery with 19 positive scans (44%). 51 patients were treated with ADT and or EBRT and 46 had positive scans (90.2%). 29 patients had tissue samples to validate PSMA PET MRI. 26 patients (89.7%) had adenocarcinoma on histology correlating with avid lesions on PSMA PET. Conclusions PSMA PET MRI has had rapid uptake in use since introduction at the PAH. Urologists and radiation oncologists appear to utilize this imaging modality most; Urologists for a preoperative “one stop shopâ€� staging study and radiation oncologists in biochemical recurrence. From this data is also appears that a positive PSMA PET/MRI is highly suggestive of prostate cancer, with a specificity of 89.7%. Hybrid PET/MRI may be used to stage men locally and systemically with one scan, with lower radiation and at PSA ≤1 ng/ml. This modality has the potential to significantly improve prostate cancer staging and allow early identification of recurrent disease. Funding None
Authors
Andre Joshi
Cheryl Nicholson Handoo Rhee Ian McKenzie Janelle Munns Greg Malone Eric Chung Malcolm Lawson Peter Heathcote John Preston Simon Wood Sonja Gustafson Ken Miles Ian Vela |
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MP18-12 |
Diffusion Weighted Imaging: Differentiation of Clear Cell from Papillary Renal Cell Carcinoma |
Imaging/Radiology: Uroradiology III | 17BOS |
Abstract: MP18-12 Sources of Funding: none Introduction Due to the differences in tumor behavior and prognosis, discriminating different subtypes of renal cell carcinoma (RCC) is important. The purpose of this study was to investigate the role of diffusion weighted imaging (DWI) derived apparent diffusion coefficient (ADC) maps in differentiating clear cell renal carcinoma (ccRCC) from papillary subtype (pRCC). Methods ADC maps from 97 renal cell carcinoma lesions (20 papillary and 77 clear cell type) from 42 patients were segmented for volumetric and pixel based histogram analysis. Mean, standard deviation, skewness and kurtosis and different quantiles of the histogram were calculated for the segmented lesions. The standard of reference for diagnosis of different types of RCC was histopathology of surgical specimens. Receiver operating characteristic (ROC) analysis was performed for each of the extracted features. Results Amongst all the above mentioned features, the analysis of the quantiles yielded the highest sensitivity and specificity for differentiation of the two subtypes. The ADC range was between 258 to 3407 and 246 to 3686 mm2/sec for pRCC and ccRCC, respectively. Quantile 30 by ADC threshold of 1500 resulted in 96% sensitivity and 84% specificity that provided the highest sensitivity and specificity among the all features. Area under the curve (AUC) was 0.95. Conclusions Volumetric pixel based analysis of the ADC maps is an objective method that can accurately differentiate pRCC from ccRCC. _x000D_ _x000D_ Funding none
Authors
Seyedeh Mojdeh Mimromen
Moozhan Nikpanah Rabindra Gautam Adam Metwalli Amir Pourmorteza William Linehan Ashkan Malayeri |
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MP18-13 |
Texture Analysis of enhancing, non-lipid containing solid renal masses: Differentiation of Malignant from Benign Renal Tumors. |
Imaging/Radiology: Uroradiology III | 17BOS |
Abstract: MP18-13 Sources of Funding: This project has received funding from the Whittier Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Foundation. Introduction Contrast Enhanced Computed Tomography (CECT) is the most common modality of imaging a renal mass. While metrics including pixel enhancement have been described for differentiation of various types of tumors, we describe an additional technique of texture analysis. Methods In this Institutional Review Board (IRB) approved, Health Insurance Portability and Accountability Act (HIPAA) compliant, retrospective study, we identified 136 patients with solid, non-lipid containing enhancing renal tumors based on post-surgical pathology examination (94 Malignant, 42 Benign). Here, we test the feasibility using textural biomarkers, to objectively quantify and differentiate the textural heterogeneity of malignant subtypes, here, clear cell renal carcinoma, papillary renal carcinoma, and chromophobe from, benign subtypes, here, oncocytoma and lipid poor angiomyolipoma, using standard-of-care contrast-enhanced computed tomography (CECT) images. Results Three sets of stepwise logistic regression were used to select the best predictor among all candidate predictors from 2D GLCM, 3D GLCM and spectral (Table 1). The discrimination power gain from spectral metrics in addition to 2D and 3D GLCM combined was assessed using a one-degree freedom chi square test when comparing the area under the curve between the full model and the model without spectral metrics. _x000D_ The full model with 2D, 3D GLCM and spectral predictors yielded an AUC of 0.92 (95% CI: 0.87-0.96), while the model with 2D and 3D only already reached almost the same AUC. The difference between the two model was less than 0.01 (p=0.89) (Figure 1)._x000D_ Conclusions CECT-based texture metrics can differentiate between malignant- and benign-renal tumors, with 2D and 3D GLCM metrics providing the most information for segregating malignant from benign renal tumors. In combination with other metrics such as contrast enhancement, shape metrics etc., texture metrics, have the potential to improve patient management and help stratify renal tumors using prostate CECT._x000D_ _x000D_ Funding This project has received funding from the Whittier Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Foundation.
Authors
Bino Varghese
Vinay Duddalwar Frank Chen Darryl Hwang Steven Cen Bhushan Desai Gangning Liang Mihir Desai Sameer Chopra Manju Aron Monish Aron Inderbir Gill |
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MP18-14 |
Multiple radiofrequency ablation zones on kidney function |
Imaging/Radiology: Uroradiology III | 17BOS |
Abstract: MP18-14 Sources of Funding: This research was made possible through the National Institutes of Health (NIH) Medical Research Scholars Program, a public-private partnership supported jointly by the NIH and generous contributions to the Foundation for the NIH from the Doris Duke Charitable Foundation, The American Association for Dental Research, the Colgate-Palmolive Company, Genentech and alumni of student research programs and other individual supporters via contributions to the Foundation for the National Institutes of Health. Introduction Radiofrequency ablation (RFA) has become an acceptable nephron-sparing treatment for small renal masses. It is sometimes considered for patients with high likelihood of repeat interventions, such as those with multifocal lesions from hereditary syndromes. Available long-term renal functional outcomes for patients with multiple lesions are limited predominantly to the surgical approach, and little is known about the effect of multiple tumor ablations in single procedure. Our aim is to compare the long–term renal functional changes for patients who had a single lesion vs. of multiple lesions treated with RFA. Methods Our institution review board approved study registry was queried for patients treated using RFA with single or multiple ablation zones. This series was limited to first ablative procedures, and follow-up was censored to time of next surgical or interventional procedures. Clinical features and renal functional outcomes as measured by change in eGFR and rate of eGFR<45 were compared between groups._x000D_ Results Overall, 63 patients met inclusion criteria and had 89.7 median months of follow-up. Of these 46 (73.0%) underwent single vs 17 (27.0%) underwent multiple tumor ablation during a single procedure. Patients who had multiple tumors ablated were had greater total tumor volume (median volume 14.5cm3 vs 9.2cm3, p < 0.001), were more likely to have been treated laparoscopically (47.1% vs 13.0%), but had similar age, gender distribution, BMI, baseline eGFR, overall survival, and length of follow-up. The rate of hereditary syndrome diagnosis between the multiple vs single ablation groups were significantly different (p<0.001): Von Hippel-Lindau (76.4% vs 84.7%), familial oncocytoma (5.9% vs 2.2%), hereditary papillary renal cancer (11.8% vs 2.2%), Birt-Hogg-Dube (11.8% vs 2.2). Multiple and single tumor ablations were associated with a similar median change in eGFR (mL/min/1.73 m2 ) at 1 year (-6.60 vs. -1.65, p=0.306), and at last follow-up (-22.0 vs. 18.9 p=0.676), as well as freedom from GFR<45 at last follow-up (5.9% vs. 4.3%, p=0.618). Conclusions In this series, multiple and single tumor ablations were associated with similar renal functional outcomes. These data suggest that multiple tumors can be safely ablated in patients with multifocal disease. Funding This research was made possible through the National Institutes of Health (NIH) Medical Research Scholars Program, a public-private partnership supported jointly by the NIH and generous contributions to the Foundation for the NIH from the Doris Duke Charitable Foundation, The American Association for Dental Research, the Colgate-Palmolive Company, Genentech and alumni of student research programs and other individual supporters via contributions to the Foundation for the National Institutes of Health.
Authors
Julie An
Shawna Boyle Venkatesh Krishnasamy Adam Metwalli W. Marston Linehan Bradford Wood |
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MP18-15 |
New classification of hydronephrosis on FDG-PET/CT predicts postoperative renal function and pathological outcomes in patients with upper urinary tract urothelial carcinoma |
Imaging/Radiology: Uroradiology III | 17BOS |
Abstract: MP18-15 Sources of Funding: none Introduction Fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) is useful for detecting of primary lesion and metastasis in patients with upper urinary tract urothelial carcinoma (UTUC). However, there is no study about ipsilateral hydronephrosis on FDG-PET/CT in patients with UTUC. We aimed to evaluate the value of our classification of hydronephrosis on FDG-PET/CT to predict postoperative renal function and pathological outcomes. Methods We retrospectively reviewed patients treated with nephroureterectomy (NU) for UTUC at our institution from 2010 to 2016. Among them, 71 patients were examined by FDG-PET/CT before NU. Patients treated with ureteral stent or nephrostomy at the time of FDG-PET/CT scan were excluded, leaving 64 patients for analysis. We classified the hydronephrosis on FDG-PET/CT based on the renal FDG excretion as follows: type0 : no hydronephrosis ; type1 : hydronephrosis with FDG accumulation ; type2 : hydronephrosis without FDG accumulation. Estimated glomerular filtration rate (eGFR [ml/min/1.73m2]) was calculated before the treatment and at early (within 1 month) and late (3-6 months) time points after NU. The change of eGFR was calculated at early time point after NU compared to pretreatment eGFR. The renal dysfunction event, defined as new-onset stage3 chronic kidney disease (CKD) or worsening of CKD stage, was evaluated at late time point after NU compared to pretreatment eGFR. SPSS was used for statistical analysis. Results The patients of type 0, 1, 2 were 30 (47%), 18 (28%) and 16 (25%), respectively. The median change of eGFR in type 0, 1, 2 was -23.9, -19.4 and 2.4 ml/min/1.73m2, respectively. The renal dysfunction event rate was the lowest in type2 group (86, 63 vs 19%). On multivariate analysis, classification of hydronephrosis and preoperative eGFR were associated with renal dysfunction event (p<0.05). Furthermore, type2 hydronephrosis was significantly associated with pahological grade3, LVI+ , ≥pT2 (muscle invasive cancer) and pN+ (p<0.05). On multivariate analysis, type2 hydronephrosis was associated with muscle invasive UTUC (p<0.05). Conclusions We classified the hydronephrosis based on renal FDG excretion. The classification of pretreatment hydronephrosis on FDG-PET/CT is simple and useful for predicting postoperative renal function and worse pathological outcomes in patients with UTUC. Funding none
Authors
Seiji Asai
Ousuke Arai Terutaka Noda Tetsuya Fukumoto Noriyoshi Miura Yutaka Yanagihara Yuki Miyauchi Masao Miyagawa Tadahiko Kikugawa Takashi Saika |
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MP18-16 |
The Importance of Urologist Estimation of Stone Burden: Results from the Registry for Stones of the Kidney and Ureter (ReSKU™) |
Imaging/Radiology: Uroradiology III | 17BOS |
Abstract: MP18-16 Sources of Funding: Funding support was provided by the NIH P20-DK-100863 (TC, MLS) and NIH R21-DK-109433 (TC) Introduction A discrepancy often exists between urologists&[prime] and radiologists&[prime] estimation of a patient&[prime]s true stone burden. Current AUA guidelines recommend treatment based on stone size thresholds and therefore accurate stone measurements are critical in directing patients to the most appropriate surgery. With an increasing trend towards determining quality of care based on the amount of stone removed, accurate stone burden estimation is essential to defining operative success. This study aimed to compare the number, size, and location of stones recorded by urologists and radiologists, and determine what discrepancies exist and how these differences could impact stone management. Methods From October 2015 to August 2016, 371 new stone patients at University of California, San Francisco were prospectively enrolled into the Registry for Stones of the Kidney and Ureter (ReSKUTM). Treating urologists personally reviewed all computed tomography (CT) imaging, recording stone number, location, and total stone burden. Stone burden was based on the largest aggregate linear dimension from axial and coronal views. A blinded, retrospective review of the corresponding radiologic reports for these patients was then performed, comparing how often these key attributes were mentioned. A report was categorized as unclear for each characteristic when it failed to specifically mention the number, location or total stone burden. Results A total of 219 patients had both CT images and a report available for review. With regard to stone number, 57/219 (26%) of reports were considered unclear. Radiologists reported significantly smaller stone burden than urologists for both single stones (8.8 ± 9.2 mm vs 10.7 ± 11.8 mm, p <0.001) and multiple stones (12.7 ± 10.0 mm vs 21.3 ± 20.3 mm, p <0.001, paired-sample t test). Of 300 stone-containing renal units, 90 (30%) had a radiology description that was either unclear or based on size discrepancy could have resulted in a potential change in surgical management (Table 2). Conclusions There is a statistically significant difference in the estimation of stone size between urologist and radiologist interpretation of CT scans. To optimize appropriate surgical selection and allow for quality outcomes measurements, urologists should perform their own imaging interpretation. Funding Funding support was provided by the NIH P20-DK-100863 (TC, MLS) and NIH R21-DK-109433 (TC)
Authors
David T. Tzou
Dylan Isaacson Manint Usawachintachit Kazumi Taguchi Benjamin A. Sherer Marshall L. Stoller Thomas Chi |
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MP18-17 |
Automated Comprehensive Stone Profile is Just One Click Away |
Imaging/Radiology: Uroradiology III | 17BOS |
Abstract: MP18-17 Sources of Funding: None Introduction Stone treatment decisions are guided by stone size and stone density. We have previously shown that automated stone volume measurements are more precise than manual size measurements. We tested a novel dedicated renal stone software program that provides a comprehensive radiographic stone profile with a single click._x000D_ Methods Urinary stones identified on CT scans were measured by a single reader to obtain the longest length on axial images and coronal images. A region of interest (ROI) was drawn inside of the stone to obtain minimum, maximum, average and standard deviation densities. The same stones were then assessed with an automated comprehensive radiographic stone profile software. This software produces the minimum and maximum linear diameter; minimum, maximum, and average stone density as well as stone volume. Maximum linear diameter, maximum density and average densities were compared between the manual measurements and the automated software data to obtain the percent difference between the measurements. The longer of either the axial or coronal manual measurements was used to compare with the maximum linear diameter from the stone profile software. Results 17 patients were identified who had a total of 42 CT scans with 85 unique stones. Patients had an average of 2.5 scans with an average of 5 stones. Stone sizes ranged from 1.9 mm to 21 mm in length with a mean of 8 mm. The average density measurement was 451 (21-1492). Volume obtained from the stone profile software averaged 182 mm3 (2.8-2668 mm3). The maximum diameter between the manual and software differed by an average of 19.1% (0-54.8%). Maximum density differed by an average of 11% (0-66.6%) and average density differed by an average of 24% (0-78%). Conclusions Automated comprehensive radiographic stone profiling can be accomplished with a single click and closely approximates manual measurements which can be laborious, requiring the reader to measure length on 2 different CT scan reconstructions and carefully place a region of interest around the stone. Automated stone profiling was able to assess stones as small as 1.9mm as well as stones with complex geometry. Stone volume was obtained in true maximum length, and density information thus facilitating rapid and accurate “one click measurements� for clinical decision making. Funding None
Authors
John Roger Bell
Perry J Pickhardt Stephen Y Nakada |
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MP18-18 |
Three-dimensional vs. two-dimensional shear-wave elastography of the testes – preliminary study on a healthy collective |
Imaging/Radiology: Uroradiology III | 17BOS |
Abstract: MP18-18 Sources of Funding: none Introduction Shear wave elastography (SWE) is a newer technique for the determination of tissue elasticity. The measured velocity of generated shear waves (SWV) has been shown to correlate positively with tissue stiffness. SWE is integrated into many modern ultrasound systems and has been used in different organ systems. Two-dimensional SWE (2D SWE) of the testes has been found to be a useful tool in recent studies on healthy volunteers. Three-dimensional SWE (3D SWE) is the latest development and is made possible by generation of a multiplanar 3D map via volumetric acquisition using a special ultrasound transducer. This technique allows the assessment of tissue elasticity in a fully accessible 3D organ map._x000D_ The aim of this preliminary study was to both evaluate the feasibility of 3D SWE and to compare 2D and 3D SWE standard values in the testes of healthy subjects._x000D_ Methods We examined the testes of healthy male volunteers (n=32) with a mean age of 51.06 ± 17.75 years (range 25-77 years) by B-mode ultrasound, 2D and 3D SWE techniques. Volunteers with a history of testicular pathologies were excluded. For all imaging procedures the SL15-4 linear transducer (bandwidth 4-15 MHz) as well as the SLV16-4 volumetric probe (bandwidth 4-16 MHz) of the Aixplorer®? ultrasound device (SuperSonic Imagine, Aix-en-Provence, France) were used. Seven regions of interest (ROI, Q-Box®?) within the testes were evaluated for SWV using both procedures. SWV values were described in m/s. Furthermore, we calculated testicular volume using both techniques and the formula for ellipsoid forms (LxWxHx0.523). Results were statistically evaluated using univariate analysis. Results Mean SWV values were 1.05 m/s for the 2D SWE and 1.12 m/s for the 3D SWE._x000D_ Comparisons of local areas delivered no statistically significant differences (p=0.11 to p=0.66), except for one ROI in the central portion of the coronal plane (p=0.03). Testicular volume was significanty higher by a mean of 1.72 ml when measured with 3D SWE (p=0.001). _x000D_ Conclusions In the assessment of testicular tissue 3D SWE proved to be a feasible diagnostic tool, while delivering similar values compared to the 2D method. It provided the examiner with a fully accessible three-dimensional map in a multiplanar view. Using 3D ultrasound a more precise testicular imaging, especially if combined with the display of tissue stiffness in SWE, is available and therefore could improve the diagnostic work-up of scrotal masses and male infertility. Further studies for a better understanding in the context of various testicular pathologies will be required. Funding none
Authors
Julian Marcon
Matthias Trottmann Johannes Ruebenthaler Melvin D'Anastasi Christian G. Stief Maximilian F. Reiser Dirk Andre Clevert |
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MP18-19 |
ASSESSING THE RELATIONSHIP BETWEEN CNS DISEASE BURDEN, URINARY SYMPTOMS AND URODYNAMIC FINDINGS IN PATIENTS WITH MULTIPLE SCLEROSIS UTILIZING MRI SEGMENTATION POST-PROCESSING |
Imaging/Radiology: Uroradiology III | 17BOS |
Abstract: MP18-19 Sources of Funding: none Introduction Recent advances in MRI techniques allow more accurate determination of disease load in Multiple Sclerosis (MS) patients. This study was undertaken to assess the relationship between disease burden, lower urinary tract symptoms (LUTS) and urodynamic (UD) findings. Methods An initial cohort of 30 patients was selected from a database of 613 MS patients prospectively enrolled in our institutional NGB database. Patients with complete data sets (UD testing, Urogenital Distress Inventory (UDI-6) scores, and complete demographic information) were selected for initial analysis. Routine brain MRI images (T2-weighted fluid attenuated inversion recovery - FLAIR) were segmented by a neuroradiologist utilizing a level tracing supervised semi-automated tool with generation of masks containing an overall count (OC) of abnormal appearing voxels (Figure 1). Volume of disease burden (VDB in cm3) was obtained by multiplying OC by voxel dimensions. Results The mean age was 57, 80% were female. Mean time since diagnosis was 17 years, 66.7% had relapsing remitting MS. Mean MCC was 395.4 ml (45-776 ml). Overall, 43.3 % had a PVR > 100 ml, 53.5% had DO, 30% had DOI 53.5% had detrusor sphincter dyssynergia (DSD), and 10% had altered compliance. Mean UDI-6 score was 9. The MRI mean disease burden was 24 cm3 (range 0.82 - 119.01). Patients with low disease burden (<10cc) had DO 85.7% of the time (6/7 patients) versus those with high disease volume (>10cc) who had DO 43.5% of the time (10/23 patients), p=0.050. Those with low disease burden had lower DO amplitude (29.5 vs. 51.1 cm H2O, p=0.61). Altered compliance was not found in patients with low disease burden. No significant differences in PVR, DSD, or questionnaire scores were noted based on total disease burden. After review of 176 discrete CNS areas, there were 12 with multiple UDS and QOL parameters that approached significance involving regions such as the pons, midbrain, and brainstem. Conclusions Volume and location of CNS burden in MS may be useful in predicting some aspects of LUT dysfunction. Current efforts are under way to expand the patient cohort and focus on the areas of interest identified in this study to refine the relationship between CNS lesions and voiding abnormalities in MS patients. Funding none
Authors
Jessica Eastman
Catherine Harris Alana Christie Ryan Hutchinson Ben Wagner Joseph A. Maldjian Marco Pinho Gary E. Lemack |
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MP18-20 |
Assessment of T0 Response Rate Following Neoadjuvant Chemotherapy for Bladder Cancer Utilizing a Computerized Volume Analysis System |
Imaging/Radiology: Uroradiology III | 17BOS |
Abstract: MP18-20 Sources of Funding: None Introduction Neoadjuvant chemotherapy (NAC) for bladder cancer is underutilized in partdue to concern for disease progression during chemotherapy. In an effort to quantify lesion response during NAC, we describe the utilization of a computerized system for segmenting bladder lesions on contrast enhanced pelvic CT scans. The accuracy of this modality is then demonstrated through a comparison of the computerized estimation of lesion volume change and pT0 status with an experienced radiologists assessment and RECIST criteria. _x000D_ _x000D_ Methods Pre and posttreatment CT scans were reviewed in 82 patients receiving NAC for bladder cancer prior to cystectomy. Patient information and disease outcomes at the time of cystectomy were abstracted. Estimations of the response to treatment were obtained through either (1) the computerized volume analysis system utilizing 3D CT segmentation of bladder lesions, or (2) using RECIST criteria as characterized by one of two independent board certified radiologists. Receiver operating characteristic (ROC) curves were generated to identify sensitivity and specificity of detecting pT0 (complete response) at the time of cystectomy and an area under the curve (AUC) was calculated. Results There were 67 men and 15 women with a mean age of 64 years (64.0± 10.6, age range 37 to 84 years of age). All patients had clinical stage T2- T4, N0 tumors, and received 3 to 6 cycles of a platinum based chemotherapy. A total of 27% of patients had pT0 disease at time of cystectomy. The AUC for correct prediction of pT0 at the time of cystectomy was 0.77 ±0.05 for the computer assisted technique compared to 0.75 ±0.05 and 0.70 ±0.06 when two separate radiologists predicted pT0 disease using RECIST criteria (Figure 1). Conclusions The utilization of a computerized segmentation system for the assessment of change in tumor volume and subsequent pT0 disease following cystectomy is equivalent to that performed by experienced radiologists. Furthermore, the accurate assessment of timely treatment response during NAC may have important implications in determining duration of chemotherapy and in the utilization of bladder preservation protocols. Funding None
Authors
Amir H. Lebastchi
Christopher M. Russel Kenny H. Cha Lubomir Hadjiyski Haeng-Ping Chan Rich Cohan Elaine Caoili Ajjai Alva Alon Z. Weizer |
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MP19-01 |
High-resolution gut microbiome profiling reveals species-level and gene content differences between kidney stone formers and controls |
Stone Disease: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP19-01 Sources of Funding: NIH R21 DK108097-01A1 Introduction Kidney stone disease (KSD) is a common urological disorder in the United States with a prevalence of 11% and 7% in men and women, respectively. Several factors are known to increase an individual's risk for KSD including obesity, diabetes, metabolic syndrome and poor nutrition; interestingly, each of these factors has a well-documented association with the human gut microbiome both in terms of taxonomic composition and metabolic capacity. In this study we applied high-resolution gut microbiome analysis to identify significant shifts in bacterial species composition and associated functional gene content between kidney stone formers and non-stone forming controls. Methods 16S rRNA amplicon sequences generated by the Illumina MiSeq platform were filtered for quality and contaminants, and subsequently analyzed using the Resphera Insight algorithm for high-resolution taxonomic assignment. Species abundances were then assessed for significant enrichment or depletion in stone formers relative to controls utilizing the negative binomial test followed by False Discovery Rate p-value adjustment. Functional gene content was also assessed with PICRUSt. Results A total of 23 patients with KSD and six non-stone-forming controls maintained an average of 3,893 sequences per sample. Species-level profiling with Resphera Insight revealed significantly different levels of several species including 90% reductions of Prevotella buccalis and Prevotella corporis in the KSD group (adj.P<0.01). We also observe relative increases of Bacteroides and Clostridia species in KSD patients including a 27-fold increase in Bacteroides acidifaciens (adj.P=1e-6), and a 40-fold increase in Clostridium ramosum (adj.P=6e-12). Functional characterization identified KEGG pathways enriched in KSD relative to controls, including primary and secondary bile acid synthesis (P=0.001), a 3-fold increase in steroid hormone synthesis (P=0.007), as well as fructose metabolism, galactose metabolism and glycosaminoglycan degradation. Conclusions KSD patients maintain significantly higher levels of specific Bacteroides and Clostridia species and significantly lower Prevotella species as compared to controls. Enrichments in multiple categories of metabolism were also identified. The gut microbiome may interact with kidney stone formation and identification of pathways and species level bacteria may allow for directed studies that will in the future build upon these findings. Funding NIH R21 DK108097-01A1
Authors
James White
Kelvin Davies Joshua Stern |
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MP19-02 |
Salivary Neutrophil Gelatinase-Associated Lipocalin (NGAL) and Cortisol measurement in acute Renal Colic |
Stone Disease: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP19-02 Sources of Funding: NONE Introduction _x000D_ Introduction _x000D_ _x000D_ In acute ureteral stone obstruction the decision to treat is sometimes missing a forecaster for a better outcome. Neutrophil Gelatinase-Associated Lipocalin (NGAL) levels are predictive biomarker of Acute Kidney Injury (AKI) with correlation to complication and survival in major surgery. NGAL is particularly expressed during the first 24 hours in the proximal tubules. Cortisol levels in saliva found to be a reliable parameter for stress. Salivary levels of NGAL during renal colic were not evaluated so far._x000D_ OBJECTIVE_x000D_ To measure salivary NGAL and Cortisol levels in patients presented to the Emergency Room (ER) with acute renal colic_x000D_ Methods Prospective controlled study of all patients who presented to ER with acute renal colic and diagnosed with single ureteric stone obstruction by non-contrast computed tomography (NCCT). Saliva, urine and blood samples were collected in patients and control group during the first morning of admission. Salivent system was used to collect the salivary samples for Human Lipocalin-2/NGAL Quantikine ELISA Kit test and for Cortisol. A questionnaire was used to evaluate patient's repose, and clinical data were collected. _x000D_ _x000D_ _x000D_ Results 44 patients in the study group, 13 in the control group, mean age 48±13 years, BMI 28±6, mean stone size 6±4 mm , mean VAS scored of 7±2 ,mean creatinine levels of 1.3±0.3 mgr/dl ,mean WBC 10,900±3,100 count per field ,CRP 29±55 .23 (53%) of patient underwent urgent intervention. Serum (199±154 vs 81±24, p < 0.001) and, predominantly Salivary (474±185 vs 328±134; p < 0.05) NGAL levels were significantly elevated in patients with acute renal colic in comparison to controls. Cortisol level on the contrary did not demonstrate any increase during acute phase of renal colic, suggestive a delay response or suppression mechanism._x000D_ _x000D_ Conclusions Salivary and blood NGAL sampling is feasible during acute phase of renal colic. High levels of salivary NGAL are observed in a single sampling during acute ureteral stone obstruction and may advance clinical decision making. Cortisol levels fail to increased suggestive of some suppression mechanism. Funding NONE
Authors
Ashraf Tamimi
Eyal Kord Yishai Rapaport Ramziya Abu hamad Shai Efrati Amnon Zisman Yoram Siegel |
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MP19-03 |
CT-based diagnosis of low vertebral bone mineral density is associated with 24-hour urine abnormalities and larger kidney stone volumes |
Stone Disease: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP19-03 Sources of Funding: None Introduction Recent studies have demonstrated associations between nephrolithiasis and systemic conditions, including low bone mineral density (BMD), which may be correlated to hypercalciuria in these kidney stone formers (KSF). Traditionally, low bone mineral density is diagnosed with dual-energy x-ray absorptiometry. Our objective was to evaluate the association of CT-based vertebral bone mineral density with 24-hour urine parameters in KSF Methods This is a retrospective analysis of 99 kidney stone formers who had CT imaging and 24-hour urine studies at our institution. For each patient, BMD was estimated by placing an oval region of interest on an area of vertebral body trabecular bone at the L1 level and CT attenuation measured in Hounsfield units (HU). From established data, a threshold for a balanced sensitivity (73.9%) and specificity (70.6%) of 160 HU was chosen to distinguish normal from low BMD. Patient demographics, serum chemistry, and 24-hour urine parameters were collected for each patient. Univariate and multivariate logistic regression analysis was performed to compare patients with low and normal BMD. Multivariate linear regression was performed to assess for variables associated with 24-hour urine parameters. _x000D_ _x000D_ Results Compared to patients with normal BMD, patients with low BMD were older (67 vs 50 yrs, p<0.0001), were male (69% vs 34%, p=0.001), had HTN (81.8% vs 24.7%, p<0.0001), underwent percutaneous nephrolithotomy (20% vs 0%, p=0.003), had higher 24-hour urine calcium (219 vs 147, p<0.0001), increased visceral fat area (251 vs 179 cm2, p=0.003) and had larger stone volume (259 vs 78.4 mm3, p=0.009). Multivariate analysis revealed older age (p=0.004) and elevated urine calcium (p=0.0002) correlated with low BMD. Linear regression demonstrated that lower BMD was associated with higher urine calcium (-coefficient 0.247, p=0.020) and lower urinary citrate (-coefficient 0.331, p=0.009). Conclusions CT-based diagnosis of low mineral bone density is associated with derangement in 24-hour urine calcium and citrate in kidney stone formers, as well as larger stone volumes. _x000D_ Funding None
Authors
Nishant D Patel MD
Ryan Ward MD Juan Calle MD Erick Remer MD Manoj Monga MD |
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MP19-04 |
The Relationship between vascular calcification and Kidney Stone Formers in a Hospital-based case control study |
Stone Disease: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP19-04 Sources of Funding: None Introduction Kidney stones are associated with systemic diseases, including cardiovascular disease and loss of bone mineral density (BMD). It has been suggested that vascular calcification (VC) may be part of this pathophysiology. Recent published data in a small, uniform cohort suggested that kidney stone formers (KSFs) had higher levels of VC then controls. We sought to clarify these findings in an ethnically diverse large case control study of KSFs and non-stone former controls. Methods Retrospective study of 672 KSFs and 253 non-stone former controls seen between 2004 and 2013 was conducted. Control patients were identified as patients without a history of kidney stones that had a non-contrast CT scan. VC was measured as Abdominal Aortic Calcification (AAC) between L1 and L4 vertebras on non-contrast CT images. Measurements were translated to a score via the use of a severity factor. BMD was measured at the L1 level. Osteoporosis was defined as ≤135 HU. Statistical analysis was performed using Student t-tests, Wilcoxon sign-rank test, Chi-square tests, and logistic regression models. Results AAC was present in 46% of KSFs and 54% of controls (p=0.02) with a lower median in KSFs compared to controls, 22.5 (5.64-129.20) vs. 105.3 (23.85-202.74), respectively (p<0.001). KSFs with AAC between 0 and 49.6 had 81% (p<0.001) increased risk of stones in a logistic regression model. Hispanic stone formers had lower AAC in comparison to non-Hispanics (15.3 vs. 25.6; p=0.04), and whites had a 2.32-fold increased risk of stones compared with others. AAC severity inversely correlated with BMD (r= -0.3; p<0.001), and KSFs had 50% increased risk of osteoporosis than controls (p=0.06). Interestingly, most KSFs (82%) and controls (93%) with osteoporosis had AAC present while 26% of those with normal BMD had AAC. Urinary calcium positively correlated with AAC (r= 0.14; p=0.014) and negatively with BMD (r= -0.16; p=0.008). Conclusions In contradistinction to previous reports, both AAC prevalence and AAC severity is greater in controls than KSFs. Interestingly, Hispanic stone formers had lower AAC severity, and whites had a higher risk of forming stones. Additionally, osteoporosis was highly prevalent alongside AAC. Though controls with osteoporosis had higher AAC severity, KSFs had increased risk of osteoporosis. Furthermore, the data regarding urinary calcium adds to the evidence that hypercalciuria is a predictive factor of BMD loss in KSFs. Our study of an ethnically diverse population strengthens the relationship between stones and AAC. Funding None
Authors
Aneesh K Pirlamarla
Ilir Agalliu Joseph DiVito Joshua M Stern |
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MP19-05 |
Computerized Simulation of Fluid Dynamics Within The Renal Collecting System And Their Association With Nephrolithiasis |
Stone Disease: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP19-05 Sources of Funding: None Introduction The role of renal collecting system anatomy as it pertains to passage of stone material has been well studied, especially in the post-intervention setting. Current understanding of anatomic factors in the genesis of calculi is more limited, however. Here, we undertake the first computational fluid dynamic simulation of the renal collecting system in a known stone forming individual in order to correlate urine stagnation with calculogenesis. Methods In this IRB exempt study, a CT urogram was 3D reconstructed from a patient with renal calculi attached to papillae. Computational fluid dynamics were performed to simulate flow within the collecting system assuming a urine production of 0.5 mL/s with "open" inlet conditions. The non-contrast phase of the CT scan was then compared to the simulated model in order to correlate simulated flowrate with stone location. Results A 48-year-old first time stone former was identified with three renal calculi attached to papilla in three separate lower pole calyces. 3-D reconstruction identified stones in calyces which were labeled "5+6" (compound calyx), "8", and "9". Flow simulation produced relative volumetric flow rates for each calyx as follows: "3" - 29.38% of total, "7" - 20.10%, "1+10+2" - 16.76%, "8" - 16.61%, "9" - 8.75%, "5+6" - 7.85%, and "4" 0.55% . Conclusions The location of renal calculi appear to correlate with calyces with low flow rates. We offer this as supporting evidence to the idea that intrarenal anatomy plays a role in crystal retention and growth. Further work is required to perform more realistic urologic physiologic simulations. Funding None
Authors
Scott Wiener
Alexandros Mathioudakis Phillip Smith Marco Molina Xinyu Zhao Erica Lambert |
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MP19-06 |
Calcium oxalate dihydrate as a marker of hypercalciuria in stone patients: A meta-analysis and exploration of the difficulties in proper stone analysis |
Stone Disease: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP19-06 Sources of Funding: NIH P01 DK56788_x000D_ Japanese-Swedish Research Foundation Introduction The mineral in calcium oxalate stones occurs in two forms: calcium oxalate dihydrate (COD) and calcium oxalate monohydrate (COM). The clinical significance of these two forms is not well established, but some studies have suggested that high calcium excretion correlates with the formation of COD stones. Our purpose was to use meta-analysis to evaluate the possibility that in a kidney stone COD may be indicative of hypercalciuria, and to explain why the natural conversion of COD to COM complicates the experimental study of this hypothesis. Methods Published reports available in Pubmed or Web of Knowledge were examined for simultaneous determination of COM/COD content in stones and measurements of urine calcium. Examples of urinary stones composed of COD, COM, and COD converting to COM were scanned by micro computed tomographic imaging (micro CT) to examine microscopic structure. Results Only 5 studies reported both COD and COM content in stones along with numerical values for urine calcium. Meta-analysis of these studies suggests a strong positive correlation between COD majority content of a stone and high levels of urinary calcium excretion (p<0.001). Additional published studies showed categorical evidence (hypercalciuria versus normal) for the same correlation. Micro CT examination of stones revealed how stones that are formed as COD can convert to COM; this argues for the probable value of assessing stone morphology, in addition to stone composition, as an aid in identifying patients who are likely to have hypercalciuria. Conclusions High urinary excretion of calcium correlates with calcium oxalate stones being composed of COD, rather than COM. Such a correlation likely also extends to stones that were formed as COD and converted over time to COM, so the addition of a simple recognition of COD surface crystal morphology to stone analysis would add additional predictive value for hypercalciuria in stone patients. Funding NIH P01 DK56788_x000D_ Japanese-Swedish Research Foundation
Authors
Maria Pless
Palle Osther James Lingeman James Williams |
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MP19-07 |
Autofluorescence of Randall&[prime]s plaque precursors |
Stone Disease: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP19-07 Sources of Funding: NIH NIDDK P20DK100863 (MLS); R21 DK109912 (SPH, MLS); NIH NIDCR R01DE022032 (SPH) Introduction Randall&[prime]s plaques at the renal papillary tips are known sites of stone propagation, yet the inciting events leading to Randall&[prime]s plaque are poorly understood. Noncollagneous proteins (NCPs) including osteopontin have been identified in the sites of biomineralization and may be critical in the early formation of Randall&[prime]s plaques. In contrast to traditional bright-field and polarized microscopy, fluorescence microscopy has the potential to localize and map these proteinaceous regions. This study was undertaken to localize osteogenic noncollagenous proteins in renal papilla as a potential nidus toward stone pathogenesis. Methods Whole human renal papillae including tissue proximal to the fornix with grossly visible Randall&[prime]s plaque were harvested en bloc after nephrectomy. Papillary tissues were processed in a routine fashion and longitudinal histologic sections were characterized using bright field (BF), polarized light (PM), fluorescence (FM), and scanning electron microscopy (SEM) techniques (see Figure) before and after decalcification using EDTA solution. Immunolocalization of NCPs including osteopontin was performed via immunogold labeling of ultrathin sections. Results Mineralized tubules (average diameter 18µm) revealed strong auto-fluorescence in blue, green, and red spectra. After decalcification of the same sections, birefringence visible under polarized light (PM) microscopy disappeared. However, the auto-fluorescence potentially associated with NCPs remained intact. Correlative light and electron microscopy (CLEM) and ultrastructural analyses revealed the mineralized tubular structure in renal papilla is rich in osteopontin (gold particles in Figure). Conclusions Localization of precursors to Randall&[prime]s plaque was detected by auto-fluorescence. NCPs appear to closely associate with tubules of diameter of 18 µm consistent with vascular elements in renal papilla, and may be intimately associated with stone formation. Funding NIH NIDDK P20DK100863 (MLS); R21 DK109912 (SPH, MLS); NIH NIDCR R01DE022032 (SPH)
Authors
Ling Chen
Ryan Hsi Benjamin Sherer Marshall Stoller Sunita Ho |
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MP19-08 |
VALIDATION OF A RENAL PAPILLARY GRADING SYSTEM FOR PATIENTS WITH NEPHROLITHIASIS |
Stone Disease: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP19-08 Sources of Funding: None Introduction A renal papillary grading scale (PGS) was recently introduced to standardize the description of papillary pathology during endoscopy. Application of this system to patients with variable stone compositions has yet to be described. Idiopathic calcium oxalate (CaOxSF) and calcium phosphate stone formers (CaPSF) are known to have unique papillary appearances but there is currently no tool to reliably quantify these differences. We tested the hypothesis that the PGS could reliably distinguish these two stone forming phenotypes. Methods 5-10 second video clips of individual papillae were created from previously recorded endoscopic stone removal procedures performed on metabolically confirmed CaOxSF and CaPSFs. Clips were graded 3 times each by 4 blinded investigators (3 urologists, 1 basic scientist) in a random order and with rotated orientations (108 videos/grader). The PGS measured papillary pathology across 4 domains including ductal plugging, pitting, loss of contour, and Randall's plaque. Features were graded (0-2) on severity of expression. Sum totals were calculated to account for total papillary pathology (range 0-8). Weighted Kappa (&[kappa]) scores were calculated to assess intra- and inter-observer reliability. Papillary scores between stone type were compared. Results Intra-observer reliability was substantial to near perfect on all domains (&[kappa] ranging from 0.75-0.99). Inter-observer reliability was near perfect for ductal plugging (&[kappa]=0.84), substantial for Randall's plaque (&[kappa]=0.68), moderate for pitting (&[kappa]=0.56), and fair for loss of contour (&[kappa] =0.40). All domains had highly significant score differences (p<0.001) between the CaOx and CaP groups. CaOxSFs had higher amounts of Randall's plaque while CaPSFs had a higher degree of ductal plugging (p<0.01) (Figures 1, 2). Conclusions Papillary appearance can be reliably measured and differs between CaOxSFs and CaPSFs using the PGS. Incorporation of this tool at the time of endoscopy has potential to improve the ability to classify patients with nephrolithiasis. Funding None
Authors
Michael S. Borofsky
Hazem M. Elmansy Nadya E. York Casey A. Dauw James C. Williams, Jr. Elaine M. Worcester Daniel L. Gillen James E. Lingeman |
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MP19-09 |
Daily hydrogen sulfide therapy during prolonged ureteric obstruction enables early renal recovery following decompression |
Stone Disease: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP19-09 Sources of Funding: Canadian Institute of Health Research_x000D_ Introduction Renal injury acquired during prolonged ureteral obstruction (UO) can lead to permanent renal dysfunction. Treatments aimed at mitigating renal injury during UO are limited. Hydrogen sulfide (H2S), an endogenous gasotransmitter, has been shown to ameliorate tissue injury. We have previously demonstrated that daily H2S treatment can reduce the histopathological markers of renal injury following 30 days of unilateral ureteral obstruction (UUO). The current study employs UUO followed by reimplantation to investigate the effects of daily H2S on renal function following the relief of obstruction. Methods The left ureter of male Lewis rats were ligated at the ureterovesical junction. Starting on post-operative day (POD) 1 and every day for 13 days, rats received either daily intraperitoneal (IP) injection of phosphate buffered saline (PBS) vehicle or 200µmol/kg of GYY4137 (slow-releasing H2S donor) in PBS. On POD 14, the ligature was removed and the left ureter was reimplanted into the bladder, and a right nephrectomy performed so that the rat is solely dependent on the left kidney. Urine and serum samples were collected to monitor renal function. On POD 30, the left kidney was removed and tissue sections were stained with hematoxylin and eosin (H&E) to measure cortical thickness. Results 67% of control rats, compared to 100% of H2S-treated rats, lived until POD 30. Histological analysis showed a significant decrease in cortical thickness (P<0.0001) in control rats when compared to Sham rats, which was significantly rescued upon treatment with H2S (P<0.0001). Serum creatinine (SCr) in control rats, but not H2S-treated rats, was significantly increased when compared to Sham animals on POD 3 and 7 (P<0.05). Following reimplantation (PODs 17, 21, 24 and 30), SCr in both control and treatment groups were significantly elevated when compared to Sham. Interestingly, H2S treatment drastically decreased SCr levels when compared to control animals on all PODs after reimplantation. Proteinuria continued to be higher in both control and treatment groups following reimplantation compared to Sham (P<0.05), however, H2S treatment group showed markedly reduced proteinuria compared to the control group. Conclusions We show, for the first time, that daily H2S therapy rescues renal function and preserves renal architecture following UO. H2S may one day become a clinically viable pre-emptive therapy against renal injury associated with UO and contribute to improved renal function in patients with UO. Funding Canadian Institute of Health Research_x000D_
Authors
Shouzhe Lin
Dameng Lian Weihua Liu Aaron Haig Ian Lobb Ahmed Hijazi Matthew Whiteman Alp Sener |
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MP19-10 |
Identification of new urinary risk markers for urinary stone patients using logistic model and multinomial-logit model |
Stone Disease: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP19-10 Sources of Funding: None Introduction The risk assessment of urinary stone disease so far has been conducted mainly on urinary biochemistry, but it has not been fully utilized for prevention of recurrence. We have clarified that inflammation is involved in the formation process of calcium oxalate (CaOx) stones. In this study, we tried to extract new stone risk factors by statistically analyzing urinary biochemistry and urine inflammation related factors._x000D_ _x000D_ Methods The subjects were male (20-79 years old) who visited Nagoya City University Hospital, excluding patients with history of abnormal urinalysis, history of tumor and collagen disease, patients taking immunosuppressants and steroids, and divided into two groups, normal group (48 cases) without history of stone and stone group who experienced CaOx stone (22 cases of the first time group, 40 cases of recurrence). Results Comparison between the normal group and the first time group revealed that the areas under the curve (AUC) of ROC of IL-1a and IL-4 as independent factors were significantly high (1.00 and 0.87 (P <0.01 in each case), respectively), which suggested that the two factors were specific to first time patients. In the comparison between the normal group and the stone group, the AUC value increased to 0.87, 0.86 by combining IL-1a or IL-4 with GM-CSF and IL-1b (both P <0.01) respectively, and the values were not as high as the discrimination between the normal and the first time groups. In the comparison of the three groups (normal, first time and recurrence group), discrimination ability by multinomial logit model using IL-4, GM-CSF, IL-1b and IL-10 including urinary Mg was the highest (prediction accuracy: 82.6%). Conclusions IL-4, IL-1a, GM-CSF, IL-1b and IL-10 were identified as urinary inflammation related factors that can accurately distinguish normal subjects and urinary stone patients. These factors are related to the activity of macrophages and neutrophils and it was suggested that combining with urinary biochemistry data could be an index to more clearly evaluate the risk of urinary stone formation. Funding None
Authors
Atsushi Okada
Teruaki Sugino Rei Unno Kazumi Taguchi Shuzo Hamamoto Ryosuke Ando Keiichi Tozawa Takahiro Yasui |
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MP19-11 |
Systemic Biomineralization in Kidney Stone Formers |
Stone Disease: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP19-11 Sources of Funding: None Introduction Emerging data has revealed that patients with nephrolithiasis are at increased risk for atherosclerosis, coronary artery disease, and stroke. While nephrolithiasis occurs within a broad spectrum of human pathologic biomineralization, the overall association of nephrolithiasis with mineralization processes at non-renal, non-osseous sites is poorly understood. The objective of this study is to characterize the overall burden of systemic biomineralization in known kidney stone formers (SFs) compared to non stone formers (NSFs). Methods The presence and quantity of biomineralization at 9 non-renal anatomic locations (listed in results) was determined by a blinded, retrospective review of clinical non-contrast computed tomography (CT) scans of the abdomen/pelvis in known SFs (n = 71, mean age 52.3) and were compared to an age-matched control group of NSFs (renal transplant donors, n=86, mean age 51.6). Each anatomic site of interest was assigned a mineralization score based on calculated CT volume of visible calcification (0 = none)( 1 = less than 0.5cm^3) ( 2 = 0.5cm3 to 1.0cm^3)( 3 = greater than 1.0cm^3). Patients were also evaluated for age, gender, BMI, comorbidities, and stone type. Results The average systemic mineralization score was significantly higher in stone formers (4.14) compared to controls (2.16). SFs were more likely than NSFs to have mineral densities in the heart (19.7% vs 3.4%), aorta (46.5% vs 23.2%), iliac arteries (38.0% vs 14.0%),spleen/splenic artery (8.95% vs 4.7%), mesentery (15.5% vs 4.7%), uterus (48.34% vs 46.7%), prostate (62.2% vs 24.0%), and pancreas (8.45% vs 0.0%). The presence of pelvic phleboliths was similar in both groups (62.0% vs 62.8%). Site-specific mineralization scores were higher in SFs at all anatomic sites (Fig 1). SFs also had higher degree of obesity (BMI 29.73 vs 27.8) and higher rates of comorbidities including diabetes, hypertension, and hyperlipidemia. Conclusions SFs have increased mineralization at many anatomic sites compared to NSFs. Understanding nephrolithiasis within the context of systemic biomineralization may help to better elucidate underlying mechanisms of nephrolithiasis and other pathologic biomineralization processes. Funding None
Authors
Benjamin Sherer
Sunita Ho Marshall Stoller |
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MP19-12 |
Papillary ductal plugging as a mechanism for early stone retention in brushite stone disease |
Stone Disease: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP19-12 Sources of Funding: NIH P01 DK056788 Introduction Mechanisms of early stone retention within the kidney are understudied and poorly understood. To date, attachment via Randall's plaque is the only widely accepted theory in this regard, best described in some idiopathic calcium oxalate stone formers. Brushite stone formers are known to have distinct papillary morphology relative to idiopathic calcium oxalate stone formers. As such, we sought to determine whether stone attachment mechanisms in such patients may be similarly unique. Methods Patients undergoing percutaneous and or ureteroscopic procedures for stone removal were consented for endoscopic renal papillary examination and individual stone collection. Each removed stone was processed using micro computed tomographic imaging in order to assess three dimensional microstructure and search for recurring structural features indicative of novel mechanisms of early growth and attachment to renal tissue._x000D_ Results Twenty eight unbroken brushite stones were removed and analyzed from nine patients. Video confirmation of attachment was available for 13/28 stones (46%) with the remainder believed to have recently dislodged naturally or in response to manipulation during the procedure. 3D assessment failed to show evidence of Randall's plaque associated with any stone. Conversely, each brushite stone demonstrated microstructural evidence of having grown attached to a ductal plug formed of apatite. Conclusions Three dimensional analysis of small brushite stones suggests overgrowth on ductal apatite plugs as a mechanism of early stone growth and retention. Such findings represent initial supporting evidence for a novel mechanism of stone formation that has previously been hypothesized but never verified. Funding NIH P01 DK056788
Authors
James Williams
Michael Borofsky Andrew Evan Fredric Coe Elaine Worcester James Lingeman |
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MP19-13 |
Simultaneous Ultrasonic Propulsion with Burst-Wave Lithotripsy To Improve Stone Breakage in An Artificial Kidney Model |
Stone Disease: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP19-13 Sources of Funding: Work supported by NIH NIDDK grants DK043881 and DK104854, the National Space Biomedical research Institute through NASA NCC 9-58, and resources from the VA Puget Sound Health Care System. Introduction Burst Wave Lithotripsy (BWL) is a developing alternative to shockwave lithotripsy for non-invasive nephrolithiasis treatment. Ultrasonic propulsion (UP) utilizes ultrasound pulses to push stones or fragments within the collecting system. Using low intensity pulses, UP may augment the effects of BWL by ejecting fragments off the primary stone, reorienting the stone to allow BWL exposure at different angles, and displacing surrounding dust fragments that shield the stone. Therefore, we hypothesized that BWL combined with concurrent UP pulses would improve stone breakage compared to BWL alone. Methods Two types of artificial stones (1.calcite and 2.Begostone) and human calcium oxalate monohydrate (COM) stones, measuring 5-8 mm, were individually tested in a polyvinyl chloride tissue phantom. The phantom with stone was placed in a water bath and aligned with a 335 kHz BWL transducer and 2.5 MHz ultrasonic propulsion-capable imaging probe. Each stone was exposed to 5-10 min of treatment (5 min for calcite, 10 min for Begostone or COM). We performed trials applying BWL alone, BWL followed by UP, and BWL with interleaved UP. UP rate was varied from 1-60 pulses/min, while BWL settings remained constant. Stone breakage success was defined by the percentage of stone broken into fragments smaller than 2 mm. Results Stone breakage success for calcite stones was 63% greater when treated with BWL and UP at 3 pulses/min (BWL alone 24±19%, BWL with UP 39±24%). Begostones treated with a similar protocol had 4.5-fold greater stone breakage success (BWL 6±4% and BWL with 6 pulses/min UP 27±8%), but was only 1.8-fold greater when UP was performed for 10 minutes after the BWL session (BWL followed by 6 pulses/min UP 11±2% breakage). Begostones treated with BWL and UP had greater breakage when propulsion pulses were applied at a faster rate, with stone breakage of 6±1%, 22±3%, and 35±5% at 0(no propulsion), 6, and 60 pulses/min, respectively. COM stones treated with the same protocol of increasing pulses/min broke at 17±11%, 25±26% (p=0.13), and 36±28% (p=0.01), respectively. UP alone did not cause fragmentation. Conclusions BWL performed with UP improves lithotripsy in an artificial kidney model with both human and artificial stone types, compared to BWL alone. This improvement is most effective when pushes are interleaved with BWL treatment, rather than performed separately, and when more propulsion pushes are applied. Funding Work supported by NIH NIDDK grants DK043881 and DK104854, the National Space Biomedical research Institute through NASA NCC 9-58, and resources from the VA Puget Sound Health Care System.
Authors
Justin Ahn
Theresa Zwaschka Bryan Cunitz Michael Bailey Barbrina Dunmire Mathew Sorensen Jonathan Harper Adam Maxwell |
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MP19-14 |
MECHANISTIC EVIDENCE THAT PAPILLARY PITS OCCUR SECONDARY TO DISLODGEMENT OF RANDALL’S PLAQUE ATTACHED STONES |
Stone Disease: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP19-14 Sources of Funding: NIH DK056788 Introduction Renal papillary characteristics among stone formers are suspected to have associations with stone forming pathophysiologies. Papillary pitting (surface erosion) is one of the most common abnormalities encountered and is a component of both recently described papillary classification systems. To date, the mechanism by which pitting occurs is unclear. One hypothesis is that pits are sites where stones overgrowing Randall's plaque (RP) became dislodged. We sought to examine this hypothesis using stone micro CT and high definition renal endoscopy. Methods Patients undergoing endoscopic stone removal had their procedures recorded and stones analyzed using micro CT. Patients with stones showing evidence of RP attachment were identified in a manner blinded to patient data. Corresponding surgical videos were reviewed independently by 2 urologists to characterize the RP/renal stone interface and look for papillary pitting. Results RP attachments were identified on micro CT in 28 patients (Figure 1). 7.3 RP stones were removed per patient, the majority of whom were recurrent stone formers (93%) with history of prior stone treatment (75%) (Table 1). A majority of patients were categorized as idiopathic calcium oxalate stone formers (78.5%) and metabolic abnormalities on 24 hour urine chemistry were common (86.4%). Pits were identified prior to any stone manipulation on at least one papilla in all cases including 7 who had had no prior procedures (Figure 2). Conclusions Stones growing over RP likely pull a piece of tissue away from the papilla when dislodged, leaving visible papillary pits. Identification of pits and incorporation into endoscopic characterization systems for stone formers may help improve patient classification. Funding NIH DK056788
Authors
Michael S. Borofsky
James C. Williams, Jr. Elaine M. Worcester Casey A. Dauw Nadya E. York Andrew P. Evan James E. Lingeman |
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MP19-15 |
The relationship between hyperuricemia and uric-acid stone for renal function deterioration: a population-based analysis |
Stone Disease: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP19-15 Sources of Funding: none Introduction Although both hyperuricemia and uric-acid (UA) stone are potential risk factors for Chronic Kidney Disease (CKD), it remains unclear which factor has much more worse effects on renal function. We accessed the influence of hyperuricemia on impaired renal function in patients with UA stone components in comparison with community-dwelling population. Methods Between 2010 and 2014, we treated 1793 consecutive patients with urolithiasis in our hospital, and identified stone components available 473 patients. Of those, 123 patients with UA stone were included in the present study. Age, sex, and serum UA concentration adjusted control subjects were selected from 3089 community-dwelling population in each group by propensity-score matching (2 :1). Subjects were divided into two groups; hyperuricemia or non-hyperuricemia groups according to the serum UA concentrations (UA-low: < 7.0or UA-high: ?7.0 mg/mL). We compared renal function between the UA stone and control subjects in each group. The renal function was evaluated as estimated glomerular filtration rate (eGFR). The independent risk factor for impaired renal function were investigated by multivariate logistic regression analysis. Results We selected pair-matched 166 control subjects and 83 UA stone patients for serum UA-low group. Similarly, 68 control subjects and 34 UA stone patients for serum UA-high group. _x000D_ UA stone patients had significantly lower in eGFR (P<0.01) compared with control subjects regardless of serum UA concentrations. Multivariate logistic regression analysis revealed that age, past-history of cardiovascular disease, serum UA, and stone former were significant factors for stage 3 CKD. UA stone component had 3-fold chance to develop stage 3 CKD than serum UA concentration._x000D_ Conclusions Uric acid stone components may strongly influence on renal function deterioration than hyperuricemia. Funding none
Authors
Toshikazu Tanaka
Shingo Hatakeyama Yuriko Terayama Fumitada Saitoh Hisao Saitoh Yasuhiro Hashimoto Takuya Koie Chikara Ohyama |
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MP19-16 |
Renal Papillary Plugging in Calcium Stone Formers May Arise via Random and Independent Crystallization Events |
Stone Disease: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP19-16 Sources of Funding: none Introduction The causes of renal papillary abnormalities observed endoscopically within a single kidney are incompletely known. One testable theory is that plugging, and perhaps Randall's plaque (RP), are random and independent events of crystallization whose risk is increased by local supersaturations. If so, their occurrence in the papillae of a kidney must follow the Gaussian distribution. Using scores from a previously introduced and validated papillary grading system, we sought to test if this is true. Methods We reduced papillary grading scores from patients who had undergone unilateral ureteroscopic stone treatment to &[Prime]present&[Prime] or &[Prime]absent&[Prime] for each variable in the grading system - pitting, plugging, loss of contour, and RP. From this we calculated the proportion of graded papillae in a given kidney involved. Probability density functions were generated and Shapiro-Wilks (SW) and Anderson-Darling AD) tests of normality were applied. Results Our cohort included 42 patients (42 kidneys), all of whom had calcium stones - 28 calcium oxalate and 14 calcium phosphate - on subsequent analysis. The mean number of papilla graded per kidney was 5.97 (95% CI 5.40-6.55). The mean proportion of papillae with plugging was 51.7% (±4.3), pitting was 20.1% (±3.0), loss of contour was 22.7% (±3.6), and RP was 33.7% (±4.0). Probability density functions are shown in Figure 1. Unlike pitting, loss of contour, and RP, plugging is uniquely normally distributed (SW and AD tests p>0.01). Conclusions Unlike pitting, loss of contour, and RP, plugging is uniquely normally distributed (SW and AD tests p>0.01), supporting that plugging is a random and independent process in individual papillae and plaque, pitting, and contour changes cannot be. Funding none
Authors
Melanie Adamsky
Andrew Cohen Glenn Gerber Elaine Worcester Frederic Coe |
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MP19-17 |
Renal Papillary Mapping and Quantification of Randall’s Plaque in Pediatric Calcium Oxalate Stone Formers |
Stone Disease: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP19-17 Sources of Funding: none Introduction Randall's plaque (RP) with attached stones is recognized as a primary mechanism for stone formation in adult calcium oxalate stone formers (CaOx SF). The role of RP in pediatric stone pathogenesis is unknown, with no reported studies to date. The purpose of this study is to investigate renal papillary abnormalities and quantify RP in pediatric CaOx SF. Methods 8 pediatric CaOx SF underwent ureteroscopy for symptomatic urolithiasis. The collecting system was mapped using a digital ureteroscope. Video for each patient was then reviewed using a retrograde pyelogram to confirm the location of each papilla. A single investigator (NLM) reviewed the video to quantify RP and other papillary abnormalities such as pitting and Bellini duct plugs. Each papilla was graded as having mild (<10%), moderate (10-50% ), or severe (>50% ) amount of RP. Patient history was recorded. Results An average of 9 papillae were mapped per patient. RP was present in 100% of patients and in 88.8% (64/72) of all papillae examined. When present, RP was uniformly distributed throughout the kidney without preferential distribution to a region or pole. The amount of RP on the papillae was graded as mild in 60%, moderate in 20.8%, and severe in 8.3% (Table 1). Other papillary abnormalities were rare in pediatric SF with Bellini duct plugging in 9.7% and pitting in 15.2% papillae. No correlation was found between the amount of plaque and age at first stone or number of prior stones (p= 0.84). Attached stones were rare (1/8 patients). The two patients with severe RP had a small amount of calcium phosphate in their stone analysis. Conclusions RP is common in pediatric CaOx SF, while pitting and Bellini duct plugging are not. Compared to adult CaOx SF where up to 75% of stones are found attached to RP, attached stones were rare. The significance of these findings in pediatric stone pathogenesis remains uncertain in this early report, however ongoing research to include correlation with 24 hr urine data and stone recurrence is currently underway. Funding none
Authors
Annie Darves-Bornoz
John Thomas Tracy Marien Gabriel Fiscus Douglass Clayton Nicole Miller |
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MP19-18 |
Variability in Renal Papillary Pitting Scores Exceeds that of Randall&[prime]s Plaque: Evidence for the Pathogenesis of Calcium Stone Formation |
Stone Disease: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP19-18 Sources of Funding: none Introduction An emerging hypothesis regarding calcium stones (CS) pathogenesis involves formation on Randall&[prime]s plaques (RP) with subsequent shedding of this complex into the urinary space leaving behind a pit. If RP are uniform in production, pitting creates disorder if stone complexes shed randomly. Pitting variability should exceed that of RP in kidneys with low RP variability (complex formed but not shed) but not when RP variability is higher (disordered by complex shedding). We aimed to test this hypothesis. Methods We identified a cohort of stone formers whose renal papillae were scored ureteroscopically using a previously described grading system that quantifies the degree of RP, pitting, plugging, and contour on each papillum. We included stone formers with at least three papillae graded. Standard deviations (SD) of pitting and RP scores were used as a measure of variability. A general linear model (GLM) with backward stepwise selection was created to identify factors associated with variability and then used to calculate adjusted variability, which was compared between RP and pitting. Results Of the 57 patients, stone composition was 57.9% calcium oxalate, 35.1% calcium phosphate, and 7.0% unknown. Mean number of papillae graded was 5.1 per kidney (±0.31). The GLM identified pitting mean and stone type as factors affecting the pitting variability, and stone type, RP mean, and gender as factors affecting RP variability. After adjusting for these factors, pitting and RP variability were compared by plotting these values and their regression line against a line of identity (Figure 1). Variability in pitting exceeds that of RP for almost all (10/12) patients in kidneys with low levels of RP variability (left of regression line), versus 6/14 for kidneys with high RP variability (X2 = 4.473, p=0.034). Conclusions These findings support the hypothesis that RP formation is a uniform process that becomes disordered by stone shedding - a stochastic process. This further supports the thought that pathogenesis of CS involves formation on RP and subsequent shedding off the papillae into the urinary space, leaving behind a pitting defect in the papillum. Funding none
Authors
Melanie Adamsky
Andrew Cohen Glenn Gerber Elaine Worcester Frederic Coe |
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MP19-19 |
Patients with calcium stones and Randall’s plaque excrete distinct populations of micro RNA-containing urinary extracellular vesicles |
Stone Disease: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP19-19 Sources of Funding: NIDDK U54 DK100227 Introduction Randall’s plaques (RP) appear to be an important precursor of urinary stone disease. However, RP cannot be noninvasively detected. Furthermore, the biologic processes that mediate growth of RP remain unclear. This study was designed to identify specific micro RNA (miRNAs) changes within urinary extracellular vesicles (EVs) based on stone forming status, and the amount of intrarenal RP. Methods A total of 40 subjects were included in this study. First time (incident) stone formers and population controls were recruited from the community (n=10 each). RP were assessed via endoscopic digital imaging with quantitative analysis in consecutive idiopathic calcium oxalate stone formers undergoing percutaneous surgery for stone removal. Subjects with high amounts of RP (HP; > 5% papillary surface area coverage; n=10) were age (+/- 5 yrs) and sex matched to a group with low amounts of RP (LP; < 5% papillary surface area coverage; n=10). Small non-coding miRNAs within urinary EVs were quantitated by XRNA Exosome RNA-Seq Library Kit (System Biosciences, Palo Alto, CA). Differentially expressed miRNAs with a p-value of 0.05 or lower were chosen for pathway analysis and miRNA target prediction comparing LP versus HP, and population controls versus stone formers. Results When controls were compared to stone formers, a total of 10 miRNA were increased (6 to 10-fold), while 5 miRNA were decreased (2 to 5-fold). When LP were compared to HP stone formers, 3 miRNA were increased (6.5 to 10-fold) while 7 miRNA were decreased (6-9 fold). The upregulated miRNAs contribute in calcification, cell proliferation, acute kidney injury, renal fibrosis, pro-apoptotic and pro-inflammatory pathways whereas down-regulated miRNAs contribute anti-apoptotic and anti-inflammatory processes, prevent renal fibrosis, ischemic injury, and progression of chronic kidney disease. Conclusions Stone formers and those with high amounts of RP excrete distinct populations of miRNAs within urinary EVs. These miRNAs may serve as novel biomarkers to indicate the presence of RP. These miRNAs may also provide new insights into early renal cellular processes in the progression of stone pathogenesis and RP and new tools for the screening, diagnosis, risk stratification and monitoring of pharmacological therapy for persons with idiopathic stone disease. Further studies to validate and extend these observations are needed. Funding NIDDK U54 DK100227
Authors
John Lieske
Xiangling Wang Robin Chirackal John Knoedler Amy Krambeck Felicity Enders Andrew Rule Pritha Chanana Muthuvel Jayachandran |
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MP19-20 |
A pilot study comparing virtual and real consultation(out patient) for stone patients Future of Endourology stone clinic |
Stone Disease: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP19-20 Sources of Funding: none Introduction Healthcare professionals are among the last, if not the last, service providers to not use Internet technology to communicate with the people they serve. As much as patients are able to communicate with their doctors, and physicians, medical professionals will also be able to transmit data between each other; overall helping the patients' well-being. Many a times, its very difficult for patients to come from far places for stone clinic for consultation wasting a lot of time. With increased use of mobile phones, Internet and with increased skill of fast communication through handy available cell phone to almost everyone. Uncomplicated stone patients do not need detail clinical examination most of the time. Can we use these advantages in current era in providing health care at every corner of world without compromising quality of care? We could not find literature to address this issue. Aim of our study was to assess feasibility, reproducibility and accuracy of e-consultation in stone clinic and compare with standard consultation defining good practice and inform its implementation in relation to clinician-patient consultations via whatsapp and similar virtual media. Methods We included 30 uncomplicated stone patients who presented to endourology clinic during Jan 2016 to June 2016 according our inclusion criteria. First we did e-consultation using whatsapp and other virtual media and assessed clinical history, biochemical profile and imaging with images and communicated through media and made a provisional diagnosis and decided management plan. Then we did real consultation as standard practice and decided management plan. We compared diagnosis and management plans in this both consultations virtual and real. We graded in five grades according to difference in diagnosis and management plan.We assessed 5 point likert score also for virtual and real consultation._x000D_ Grade Description_x000D_ 1 Minor differences not affecting surgical plan_x000D_ 2 Difference that change in type of procedure_x000D_ 3 Difference that change decision for observation vs. surgery_x000D_ 4 Difference that leads to an additional procedure needed during surgery_x000D_ 5 Difference that result in potentially severe complication _x000D_ Results There was no significant difference in diagnosis or management plan in virtual Vs real consultation. There was grade 1 change in 2 patients, grade 2 and 3 change in one patient.Five point likert scale score difference was not significantly difference. Conclusions Based on this pilot study, virtual consultation (e-consultation) for kidney stone patients is feasible and accurate in selected group of patients without compromising quality of care. And may be a future of endourology clinic. However, large number of study is required to define its role in future._x000D_ Funding none
Authors
Haresh Thummar
Shivang D N Thummar Nelson Z |
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MP20-01 |
VALIDATION OF THE AMERICAN JOIN COMMITTEE ON CANCER (AJCC) 8TH EDITION PROSTATE CANCER STAGING SYSTEM |
Prostate Cancer: Staging I | 17BOS |
Abstract: MP20-01 Sources of Funding: none Introduction In the recently published 8th edition update of the AJCC staging system for prostate cancer (PCa), pT2a/b/c sub-classifications were consolidated as pT2. Also, serum prostate-specific antigen (PSA) ≥20ng/ml or Grade Group (GG) 5 now classify patients as Stage III disease. We sought to validate these changes in a large institutional registry with long-term follow-up. Methods Men who underwent radical prostatectomy without prior therapy at Mayo Clinic between 1987-2011 were identified. The prognostic significance of a single pT2 designation was compared to previous stratification as unilateral (pT2a-b) versus bilateral (pT2c). Further, 7th edition Stage II patients were then re-categorized based on the presence or absence of PSA ≥20ng/ml and GG 5. Biochemical recurrence-free (BCR) survival, systemic progression-free survival (sPFS), and cancer-specific survival (CSS) were evaluated using Kaplan Meier analyses and multivariable Cox regression models, adjusting for age, Gleason score, preoperative PSA, and surgical margin status. Results The overall cohort included 17,846 men with a median follow-up of 11 years (IQR 7,16), during which time 5021 experienced BCR, 1246 progressed systemically, and 641 died from PCa. Among pT2 patients, sub-stratification was not independently associated with BCR-free survival (HR=1.0; 95%CI 0.9-1.1; p=0.69), sPFS (HR=1.0; 95%CI 0.8-1.3; p=0.68), or CSS (HR=0.9; 95%CI 0.6-1.2; p=0.41). Meanwhile, patients previously classified with Stage II disease who had a preoperative PSA ≥20ng/ml (now Stage III) had a 15-year CSS that was significantly worse than Stage group II patients with PSA < 20ng/ml (88% vs 94%; p<0.001), but similar to 7th edition Stage III patients (88% vs 86%; p=0.12). On the other hand, Stage II patients now classified as Stage III based on GG 5 had a 15 year CSS that was significantly worse than both 7th edition Stage II patients with GG 1-4 (48% vs 68%; p<0.001) and 7th edition Stage III patients (48% vs 60%; p<0.001). Results for BCR-free survival and sPFS were similar. Conclusions We validate the new AJCC pT2 staging classification. Moreover, our data support the designation of patients with a PSA ≥20ng/ml as Stage III disease. Interestingly, while upstaging GG5 patients from Stage II to III is an improvement, these patients have even worse outcomes than 7th edition Stage III patients, emphasizing the particular prognostic significance of the new GG and the importance of including GG in staging classification. Funding none
Authors
Bimal Bhindi
R. Jeffrey Karnes Laureano Rangel Ross Mason Matthey Gettman Igor Frank Matthew Tollefson R. Houston Thompson Stephen Boorjian |
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MP20-02 |
Novel Risk Stratification Grouping Using Standard Clinical and Biopsy Information for Patients Undergoing Radical Prostatectomy: Results from SEARCH |
Prostate Cancer: Staging I | 17BOS |
Abstract: MP20-02 Sources of Funding: Department of Veterans Affairs and NIH K24 CA160653 Introduction Prostate cancer is a heterogeneous disease, and risk stratification systems have been proposed to guide treatment decisions and inform patient prognosis. However, significant heterogeneity remains, especially among those with high risk disease, and thus improved stratification is needed. Methods Data on 3335 men, including 605 high risk, undergoing radical prostatectomy without adjuvant treatment were collected in the SEARCH database. Patients were grouped into five categories: low risk (biopsy Gleason 2-6, T1a-T2a, and PSA <10ng/ml), favorable intermediate risk (FIR), unfavorable intermediate risk (UIR), standard high risk (SHR), very high risk (VHR). Intermediate risk patients by NCCN guidelines (T2b or T2c, biopsy Gleason 7, or PSA 10-20ng/ml) were UIR if they had biopsy Gleason 4+3, ≥50% positive biopsy cores, or multiple intermediate-risk factors (T2b or T2c, biopsy Gleason 7, or PSA 10-20ng/ml), and FIR otherwise. High risk patients by NCCN guidelines (biopsy Gleason score 8-10, T3-T4, or PSA ≥20ng/ml) were VHR if they had primary Gleason 5, >50% positive biopsy cores, T3b-T4 or multiple high-risk factors (biopsy Gleason score 8-10, T3-T4, or PSA ≥20ng/ml), and SHR otherwise. Cox models were used to test the association between risk group and time to biochemical recurrence (BCR) and distant metastases (DM). Competing risks was used to test the association between risk group and prostate cancer-specific mortality (PCSM). Models were adjusted for age, race, year, and surgical center. Results Median follow-up was 78 mo. Men with VHR disease had increased risk of BCR (p<0.001), DM (P=0.004), and PCSM (P=0.011) in comparison to SHR, but there were no differences in BCR, DM, or PCSM between SHR and UIR patients (p>0.4). FIR men had increased risk of BCR (HR 1.34, p=0.006) and DM (HR 2.42, p=0.035) compared to low risk men, but there was no difference in PCSM (p=0.17). Therefore, we propose a novel risk grouping: Group 1 (low risk), Group 2 (FIR), Group 3 (UIR and SHR), and Group 4 (VHR). These groups have markedly different outcomes, with 10 year DM rates of 0.7%, 2.8%, 6.9%, and 16.3% (p<0.001) for Groups 1-4 respectively, and 10 year PCSM of 0.3%, 1.9%, 3.3%, and 10.9% (P<0.001). The c-index of this grouping was 0.80 for DM vs. 0.76 for D'Amico risk groups. Conclusions Patients classified as VHR have increased rates of PSA relapse, DM, and PCSM in comparison to SHR patients, whereas UIR and SHR patients have similar prognosis. Novel therapeutic strategies are needed for patients with VHR, likely involving multimodality therapy. Funding Department of Veterans Affairs and NIH K24 CA160653
Authors
Zachary Zumsteg
Zinan Chen Lauren Howard Christopher Amling William Aronson Matthew Cooperberg Christopher Kane Martha Terris Daniel Spratt Howard Sandler Stephen Freedland |
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MP20-03 |
Population-based validation of the 2014 ISUP Gleason grading grouping in patients treated with radical prostatectomy, brachytherapy, external beam radiation or no local treatment |
Prostate Cancer: Staging I | 17BOS |
Abstract: MP20-03 Sources of Funding: none Introduction To validate the 2014 ISUP Gleason grading grouping (GGG) in patients undergoing radical prostatectomy (RP), brachytherapy (BT), external beam radiation (EBRT) or no local treatment (NLT). Methods Using the Surveillance Epidemiology and End results (SEER)-database, we identified 242 531 patients diagnosed with nonmetastatic PCa between 2004 and 2009. Patients were grouped according to local treatment type (RP, BT, EBRT) or NLT. Biopsy and/or pathological Gleason score was categorized either in ≤6, 7 and 8-10 or according to the new grading system into GGG I (≤6), II (3+4), III (4+3), IV (8) and V (9-10). Primary endpoint was prostate cancer specific mortality (PCSM). Univariable Kaplan-Meier plots graphically depict PCSM-free survival (PCSM-FS) according to the different GGG. Multivariable Cox regression analyses adjusted for age, clinical/pathological tumor stage and lymph node status were used to compare the different GGG in each treatment cohort. The discriminant ability was assessed using the area under the Receiver Operating Characteristics (ROC) curve. Results Median follow-up was 76 months (IQR: 59 - 94). For all local treatment types and NLT, PCSM-FS rates differed significantly between the five strata of the 2014 ISUP GGG. All five GGG strata independently predicted PCSM. Relative to GGG II, GGG III exhibited a 1.5- to 2-fold higher PCSM rate. Similarly, across all local treatment types and NLT, GGG V patients exhibited a 2-fold higher PCSM rate than GGG IV patients. The multivariable discriminant ability of the 2014 ISUP GGG was between 0.4% to 1.1% better than the old Gleason stratification. Conclusions This large population-based cohort validates the ability of the new GGG to predict PCSM. The new GGG offers a modesty more accurate ability to predict PCSM-FS across all different local treatment types and NLT. Funding none
Authors
Helen Davis Bondarenko
Raisa Sinaida Pompe Emanuele Zaffuto Zhe Tian Jonas Schiffmann Sami-Ramzi Leyh-Bannurah Kevin Zorn Marc Zanaty Shahrokh F. Shariat Markus Graefen Derya Tilki Pierre I. Karakiewicz |
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MP20-04 |
Decipher Prostate Cancer Classifier Does Not Correlate With Clinicopathologic Prostate Cancer Classifiers in African American Men |
Prostate Cancer: Staging I | 17BOS |
Abstract: MP20-04 Sources of Funding: None Introduction In the post-USPSTF era, the decision to identify and treat prostate cancer (PCa) remains controversial. The Decipher Prostate Cancer Classifier (DPCC) is a genomic test that independently predicts the risk of metastasis and prostate cancer specific mortality (PCSM). The studies used to validate the outcomes of the DPCC were comprised of mostly Caucasian men. Given the increased risk of PCSM in African American (AA) men, we sought to identify the utility of DPCC in an exclusively AA cohort and compare the results to previously well-established risk classification systems. Methods Using an IRB-approved single institution database, we identified 72 AA men who had undergone radical prostatectomy between December 2008 and April 2016 for whom the DPCC was retrospectively ordered. Clinicopathologic variables were then used to risk stratify the patients based on the D'Amico and CAPRA-S risk classification systems. Comparisons were made to the DPCC risk scores based on low, intermediate, and high risk using a Chi-square analysis. Results In this AA cohort, there was no association between DPCC risk scores and CAPRA-S scores (p = 0.24). There was a relationship trend between DPCC risk scores and D'Amico risk categories, but this finding was not statistically significant (p = 0.08). Among those with a low CAPRA-S and D'Amico risk, DPCC re-classified 28.6% and 12.5% of these men into a high risk category, respectively. Conversely, among men with combined intermediate and high CAPRA-S and D'Amico risk, 43.1% and 39.3% were re-classified as low risk based on DPCC, respectively. Conclusions In this exclusive AA cohort, DPCC risk groups do not correlate with the CAPRA-S or D'Amico risk classification systems, which calls into question the clinical validity of these tools when counseling AA men. Prospective studies are needed to determine the true correlation of DPCC risk and cancer outcomes in this high risk subpopulation to better inform management decisions. Funding None
Authors
Jordan Alger
Rohit Patil Anna Chichura Filipe La Fuente Carvalho Jonathan Hwang Lambros Stamatakis |
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MP20-05 |
A diagnostic biopsy-based Genomic Prostate Score as an independent predictor of prostate cancer death and metastasis in men with localized prostate cancer |
Prostate Cancer: Staging I | 17BOS |
Abstract: MP20-05 Sources of Funding: This study funded by Genomic Health Inc. Introduction Prostate cancer (PCa) aggressiveness can be gauged by both short- and long-term outcomes including adverse surgical pathology, biochemical recurrence, development of metastases, and PCD. A 17-gene biopsy-based RT-PCR assay, which provides a Genomic Prostate Score (GPS) result (scale 0-100), is validated as an independent predictor of adverse pathology and biochemical recurrence after radical prostatectomy (RP). We sought to validate GPS further as a predictor of prostate cancer death (PCD) and metastasis in a large cohort of men with long term follow-up. Methods A retrospective cohort study using a stratified sampling design was performed within Kaiser Permanente Northern California (KPNC). Of 6,184 men in the full cohort, all men with PCD and available tissue were included along with men sampled from the non-PCD men at a ratio of approximately 1:3. PCD was determined by review of Cancer Registry and KPNC mortality files; metastases were confirmed by review of imaging, biopsy or clinical data. Central review of diagnostic biopsies was performed by one uropathologist (JSH). RNA from archival diagnostic biopsies was assayed to generate GPS results. We assessed the association between GPS and metastasis and PCD as co-primary endpoints in pre-specified univariable and multivariable statistical analyses, based on Cox proportional hazards models accounting for sampling weights. Results The final study population consisted of 279 men treated with RP for clinically low, intermediate and high-risk PCa between 1995 and 2010 (median follow-up 9.8 years). This cohort included 64 PCD, 79 metastases, and 195 non-PCD cases. Valid GPS results were obtained for 259 men (93%). In univariable analysis GPS was strongly associated with PCD - HR/20 GPS units = 3.23 (p <0.001), and metastasis - HR/20 units = 2.75 (p <0.001). The association between GPS and both endpoints remained significant in multivariable analysis after adjusting for NCCN: 1) PCD: HR/20 units = 2.69; 2) metastasis: HR/20 units = 2.34 (p<0.001 for each). GPS was also significantly associated with both endpoints adjusting for AUA and CAPRA with similar HR (p<0.001 for each). No patient with low or intermediate risk disease and a GPS result < 20 developed metastases or PCD. Conclusions GPS is a strong independent predictor of late outcomes – PCD and metastases - in RP-treated men with clinically localized PCa, and may provide improved risk stratification for men with low, intermediate and high-risk disease. Funding This study funded by Genomic Health Inc.
Authors
Stephen Van Den Eeden
Nan Zhang Jun Shan Charles Quesenberry Jeong Han Athanasios Tsiatis Ruixiao Lu Jeffrey Lawrence Phillip Febbo Joseph Presti |
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MP20-06 |
Extent of baseline prostate atrophy is associated with lower incidence of low- and high-grade prostate cancer on repeat biopsy |
Prostate Cancer: Staging I | 17BOS |
Abstract: MP20-06 Sources of Funding: none Introduction Although prostate atrophy (PA) is a common histological finding in prostate biopsy specimens its clinical significance remains unclear. Recent data suggests that PA in a prostate biopsy negative for prostate cancer (PCa) confers a decreased risk of subsequent PCa detection. However, the extent of PA varies from patient to patient. Therefore, we sought to evaluate whether baseline PA extent is associated with PCa incidence at 2-year repeat prostate biopsy in a clinical trial with systematic biopsies. Methods We performed a retrospective analysis of 3,165 men 50-75 years-old with prostate-specific antigen (PSA) between 2.5-10ng/mL and a prior negative biopsy in the placebo arm of the Reduction by Dutasteride of PCa Events (REDUCE) trial who underwent a 2-year repeat biopsy after a negative baseline biopsy for PCa. PA extent was defined as the percentage of cores with atrophic changes. The association of baseline PA with positive 2-year biopsies was evaluated with logistic regression in uni- and multivariable analysis, controlling for baseline covariates. Results PA involving none, 1-25%, 26-50%, 51-75% and >75% of the baseline cores was observed in 966 (30.5%), 1189 (37.6%), 677 (21.4%), 209 (6.6%), 124 (3.9%) cases, respectively. More extensive PA was associated with older age, lower prostate-specific antigen, larger prostate volume and higher prevalence of acute and chronic inflammations (all P<0.05). Compared to subjects without PA, those with 1-25%, 26-50%, 51-75% and >75% core involvement had an odds-ratio for PCa of 0.65 (95%CI=0.52-0.81), 0.60 (95%CI=0.46-0.78), 0.56 (95%CI=0.37-0.86) and 0.35 (95%CI=0.19-0.67), respectively (Table). In multivariable analysis, the extent of PA was independently associated with lower PCa risk (P<0.001). More extensive PA was associated with lower incidence of both low- (Gleason 2-6) and high-grade (Gleason 7-10) PCa (both P<0.01). Conclusions In a cohort of men undergoing repeat prostate biopsy 2 year after a negative baseline biopsy for PCa, the extent of baseline PA is independently associated with lower PCa risk in a dose-dependent fashion. Funding none
Authors
Daniel MO Freitas
Gerald Andriole Ramiro Castro-Santamaria Stephen J. Freedland Daniel M. Moreira |
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MP20-07 |
Association of atrophy in baseline prostate biopsy and lower prostate cancer grade in radical prostatectomy specimens |
Prostate Cancer: Staging I | 17BOS |
Abstract: MP20-07 Sources of Funding: None Introduction Prostate atrophy (PA) is a common histological finding in prostate biopsy specimens. It is known to mimic prostate cancer (PCa) on imaging and histology. Recent data suggest PA in a negative biopsy is associated with lower risk of PCa detection in subsequent biopsies, and lower risk of high-grade PCa in men who are eventually diagnosed with PCa. However, the association of PA in prostate biopsies with PCa grade in radical prostatectomy (RP) specimens has not been studied in earnest. Therefore, the objective of this study is to evaluate whether the presence of PA in a baseline prostate biopsies negative for PCa is associated with PCa grade in the surgical specimen among patients eventually diagnosed with PCa undergoing RP. Methods We performed a retrospective analysis of 137 men, 50-75 years old with prostate-specific antigen (PSA) between 2.5-10 ng/ml and a prior negative biopsy in the placebo arm of the Reduction by Dutasteride of PCa Events (REDUCE) trial, who were diagnosed with PCa in a prostate biopsy and underwent RP during the study interval. All biopsy slides were read central and systematically graded for PA was defined as absent or present. PCa grade was defined as low-grade (Gleason 2-6) or high-grade (Gleason 7-10). The association of baseline PA with PCa grade in the surgical specimen was evaluated with logistic regression in uni- and multivariable analysis, controlling for baseline patient characteristics. Results Among 137 men diagnosed with PC who underwent an RP in REDUCE, 64 (46.7%) had PA in the baseline prostate biopsy. The presence of PA was not associated with baseline patient characteristics (age, body-mass index, PSA levels, prostate volume, race, family history of PCa or digital rectal exam, all P>0.05, Table). The presence of baseline PA was associated with lower risk of high-grade PCa (OR=0.40, 95%CI=0.20-0.80, P=0.010) in the surgical specimen. Results were unchanged in multivariable analysis (OR=0.46, 95%CI=0.22-0.96, P=0.039). Conclusions In a cohort of men with negative baseline biopsy who were eventually found to have PCa in a repeat prostate biopsy and underwent RP, the presence of baseline PA was independently associated with lower risk of high-grade PCa in the surgical specimen. PA seems to be associated with lower PCa risk and aggressiveness. Funding None
Authors
Daniel MO Freitas
Gerald Andriole Ramiro Castro-Santamaria Stephen J. Freedland Daniel M. Moreira |
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MP20-08 |
Prostate cancer loci with negative multiparametric MRI for prostate cancer: correlation with prostatectomy specimens |
Prostate Cancer: Staging I | 17BOS |
Abstract: MP20-08 Sources of Funding: None Introduction Precise localization of tumor locus is critically important for successful focal therapy in prostate cancer. The accuracy of multiparametric MRI (mpMRI) for prostate cancer localization is still unknown. Methods We retrospectively analyzed 176 prostate cancer patients who underwent preoperative 3.0T multiparametric MRI (mpMRI) followed by radical prostatectomy (RP) without neoadjuvant androgen deprivation. Images of mpMRI was evaluated by a single radiologist based on PI-RADS version 2. PI-RADS score 4 or greater was considered positive. Tumor distribution was evaluated on radical prostatectomy specimen sliced at 5-mm thick and tumor volume was estimated based on planimetry. Results Of the 176 study patients, 79 (45%) had negative mpMRI. Patients with negative mpMRI had smaller index tumor compared with those with positive mpMRI with a marginal significance (1.79 ± 0.25 vs 20.5 ± 0.22 cc., p = 0.05, Figure and Table). They were also more likely to have clinically insignificant cancer (Gleason score ≤6 and tumor volume <0.5 cc.) compared with those with positive mpMRI (Tables). However, the sensitivity and specificity for clinically significant prostate cancer was only 60% and 57%, respectively, indicating that mpMRI missed 40% of clinically significant cancer. Conclusions Although negative mpMRI is associated with favorable pathological findings in prostate cancer patients who underwent radical prostatectomy, mpMRI could not safely exclude clinically significant index tumor. Further improvement in the accuracy for tumor localization is warranted for the possible application of mpMRI to plan focal therapy. Funding None
Authors
Katsuhiro Ito
Takashi Kobayashi Akihiro Furuta Yuki Teramoto Naoki Terada Shusuke Akamatsu Toshinari Yamasaki Takahiro Inoue Osamu Ogawa |
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MP20-09 |
Evaluating MRI fusion biopsy vs systematic ultrasound guided biopsy in predicting high grade cancer at time of radical prostatectomy |
Prostate Cancer: Staging I | 17BOS |
Abstract: MP20-09 Sources of Funding: none Introduction There is much enthusiasm for multi-parametric MRI (mpMRI)-ultrasound fusion biopsy in those with an elevated PSA, a prior negative biopsy or those on active surveillance. However, the predictive value of MRI – targeted biopsy in predicting final cancer grade has not been well addressed. The uncertainties of both over staging and under staging using MRI fusion targeted biopsy have not been well addressed. _x000D_ We aimed to evaluate the accuracy of cancer risk estimation with MRI fusion biopsy; traditional sextant and anterior (14 cores) ultrasound guided biopsy or the combination, using whole-mount histopathology at time of prostatectomy. _x000D_ Methods We retrospectively analyzed 114 patients who had radical prostatectomy in 2014-2016. All patients had undergone systematic ultrasound guided biopsy and mpMRI fusion biopsy. We compared Gleason Score (GS ≥7) upgrading or downgrading between MRI fusion and systematic ultrasound guided biopsy to that of the final Gleason score evaluated by whole-mount histopathological analysis. Logistic regression was used to evaluate association to adverse pathological outcome for each biopsy approach. Results Of 114 patients, GS ≥7 cancer grade found on MRI fusion biopsy matched final pathology in 46% of the cases while it was overestimated in 15% of patients and underestimated in 39%. Cancer found on traditional systematic biopsy matched final pathology in 56% of patients while it overestimated grade in 26% and underestimated grade in 17% of patients with GS≥7. The highest Gleason score from combined MRI fusion and systematic biopsy only underestimated 11% of patients but overestimated grade in 33% of patients who had GS≥7 on their final pathology. In the logistic regression model, having a GS ≥ 3+4 detected on MRI fusion biopsy was associated with higher odds (OR: 3.5 95% CI 1.3-9.3, p <0.01) of higher stage cancer (≥pT3a) at RP. The association persisted when the model was adjusted for clinical CAPRA score. This study was limited by its retrospective nature. Conclusions Risk of over - staging using MRI fusion biopsy is low compared to systematic biopsy. However, MRI fusion biopsy alone could significantly underestimate those with clinically significant disease. Using MRI fusion biopsy alone to detect high grade cancer may not be adequate in this contemporary cohort. This data may have important implications for guiding treatment decisions._x000D_ _x000D_ Funding none
Authors
Hao Nguyen
Katsuto Shinohara Janet Cowan Antonio Westphalen Matthew Cooperberg Jeff Simko Peter Carroll |
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MP20-10 |
The accuracy of Magnetic Resonance Imaging (mpMRI) guided transperineal fusion prostate biopsies (TPFB) to evaluate lesions on prostate mpMRI using prostatectomy specimens as a validation tool. |
Prostate Cancer: Staging I | 17BOS |
Abstract: MP20-10 Sources of Funding: none Introduction Prostate mpMRI guided biopsies improve detection of Gleason score ?7cancer (PCa). The objective of the current study is to assess diagnostic reliability in comparison to definitive histological diagnosis. We present a retrospective analysis of our detection accuracy of PCa by mpMRI and TPFB in comparison to histological specimens from Robotic-Assisted Radical Prostatectomy (RARP). Methods 1002 men have had TPFB at Cambridge University Hospitals Trust between March 2012 and April 2016. 93 have subsequently undergone RARP for PCa. mpMRI was performed on all 93 patients and reported according to PIRADSvs2. 79/93 (84.9%) patients had ?1 mpMRI lesions with Likert score > 2 (Likert 3=11; Likert 4=27; Likert 5=41). TPFB was performed on each patient. 2-4 samples were taken from the target zone identified on mpMRI (TB) and 18-24 samples systematically taken according to Ginsburg protocol (SB). 14/93 had a negative mpMRI but were diagnosed with PCa following SB. Samples were retrospectively compared to RARP histology. Data was examined for overall detection rate of PCa and histological analysis of each Likert group (5,4,3), TB, SB and RARP samples according to Gleason score. Results determined diagnostic accuracy of biopsy samples in comparison to definitive histological diagnosis. Results 67/79 (84.1%) patients had TB positive for PCa, with a second lesion positive in 17/79 cases. Gleason score of TB and SB was equivalent in 29 (36.7%). Gleason score was higher in TB and SB in 15 (19%) and 35 (44%) cases, respectively. TB was benign in 14 patients. Gleason score at biopsy and RARP were equivalent in 49 (52.7%) cases but higher in RARP and biopsy in 10 and 34 cases, respectively. TB was PCa positive in 38/41 (92.7%) Likert 5 lesions. 2/3 remaining patients had PCa positive SB in an identical region to TB. 21/27 (77.8%) Likert 4 lesions had TB positive PCa, 3/6 remaining cases had PCa positive SB in an identical region to TB. TB was positive in 9/11 (81.8%) of Likert 3 lesions with SB negative in the remaining 2 patients. The correlation between mpMRI-TPFB-RARP was positive for 97.6% Likert 5, 88.9% Likert 4 and 85.7% Likert 3 lesions. mpMRI identified a suspicious lesion confirmed on RARP in 74 patients (93.7%). 2/5 patients with a negative correlation had a second MRI lesion that corresponded to RARP. Conclusions The results of our analysis demonstrate the accuracy of mpMRI and the reliability of TB taken during TPFB in confirming PCa when compared to SB and definitive histological diagnosis. Funding none
Authors
Alberto Macchi
Thomas Lloyd Hansen Nienke Lisa Whittington Vincent Gnanapragasam Brendan Koo Saeb-Parsy Kasra Nadeem Shaida Anne Warren Ola Bratt Nimish Shah Tristan Barrett Christof Kastner |
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MP20-11 |
ACCURACY OF MULTI?PARAMETRIC MAGNETIC RESONANCE IMAGING FOR DETECTION OF PROSTATE CANCER EXTRACAPSULAR EXTENSION AND RELATION TO ITS HISTOLOGIC EXTENT |
Prostate Cancer: Staging I | 17BOS |
Abstract: MP20-11 Sources of Funding: none Introduction Clinical assessment of extracapsular extension (ECE) in prostate cancer may have a significant impact on treatment decision and/or surgical planning. Multi-parametric magnetic resonance imaging (MP-MRI) has emerged as a potential tool to predict the presence of ECE with variable results. Our objective was to define the accuracy of MP-MRI for detection of ECE in relation to its radial and circumferential extent. Methods We prospectively enrolled 70 patients to undergo prostate MP-MRI prior to radical prostatectomy. All MRIs were performed with a 3T scanner using an endorectal coil and T2, diffusion weighted imaging (DWI), and dynamic contrast enhanced (DCE) sequences were used. An expert genitourinary radiologist reviewed each MP-MRI and assigned a score of diagnostic certainty between 1-3 (1-absent, 2-suspicious, 3-definite) regarding the presence of ECE on each sequence (T2, DWI, and DCE, in that order). Prostatectomy whole-mount specimens were reviewed by a genitourinary pathologist and the radial and circumferential extent of ECE was measured. The accuracy of each MRI sequence was determined, as well as its association between circumferential and radial extent of ECE. Results 70 enrolled patients underwent MP-MRI of the prostate followed by radical prostatectomy. Mean preoperative PSA was 8.4 ng/dL and 50 patients (71%) had Gleason 7 or higher on final pathology. Sensitivity and specificity of MP-MRI for suspicious or definite ECE was 92.9% and 63.4%, respectively. Sensitivity and specificity of definite ECE was 78.6% and 68.3%. Area under the curve for T2, DWI, and ECE sequences was 0.79, 0.76, 0.78, respectively. Radial extent of ECE was not associated with its detection on any sequences. Circumferential extent of ECE was positively associated with suspicious or definite detection on DCE imaging (p=0.04). Conclusions Preoperative 3T MP-MRI of the prostate with endorectal coil interpreted by a 3-point scale is highly sensitive for predicting ECE. The radial extent of ECE is not associated with its detection on MP-MRI, however the circumferential extent is associated with its detection on DCE sequences. Funding none
Authors
Melanie Adamsky
Scott Johnson Vignesh Packiam Alexander Gallan Tatjana Antic Arieh Shalhav Aytekin Oto |
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MP20-12 |
Predictive value of tumor contact length on magnetic resonance imaging for extracapsular extension of prostate cancer |
Prostate Cancer: Staging I | 17BOS |
Abstract: MP20-12 Sources of Funding: none Introduction Tumor contact length (TCL) is defined as the amount of prostate cancer in contact with the prostatic capsule. We evaluated the ability of magnetic resonance imaging (MRI) determined tumor contact length to predict pathological extracapsular extension (pECE) compared to existing predictors of pECE. Methods We retrospectively analyzed the records of 128 consecutive patients with MRI/ultrasound fusion targeted, biopsy proven prostate cancer who underwent robotic-assisted radical prostatectomy from April 2013 to July 2016. Median patient age was 67 years and median prostate specific antigen was 7.11 ng/ml. Clinical stage was cT1 in 71 cases (55%) and cT2 in 53 (41%). Postoperative pathological analysis confirmed pT2 in 90 patients (70%) and pT3 in 38 (30%). We evaluated 1) in the radical prostatectomy specimen the correlation of pECE with pathological cancer volume, pathological TCL and Gleason score, 2) the correlation between pECE and MRI determined TCL, and 3) the ability of preoperative variables to predict pECE. Results Logistic regression analysis revealed that pathological TCL correlated better with pECE than the predictive power of pathological cancer volume (0.822 vs 0.659). The Spearman correlation between pathological and MRI determined TCL was r = 0.873 (p <0.0001). ROC AUC analysis revealed that m MRI determined TCL outperformed cancer core involvement on targeted biopsy and the Partin tables to predict pECE (0.84 vs 0.70 and 0.57, respectively). The best TCL thresholds for predicting pECE was 13.5 mm (sensitivity 71%, specificity 80%) and the predictability of pECE outperformed comparing with conventional MRI criteria (MRI-TCL: odds ratio of 10.0, p<0.0001, and MRI criteria: odds ratio of 1.15, p=0.8670). Conclusions MRI determined TCL could be a promising quantitative predictor of pECE. The best TCL threshold of 13.5mm might predict pECE with higher accuracy, although PI-RADSv2 reported tumor-capsule interface of greater than 1.0 cm as cut-off value for staging of pECE. Funding none
Authors
Kazumi Kamoi
Koji Okihara Fumiya Hongo Yasuyuki Naitoh Atsuko Iwata Motohiro Kanazawa So Ushijima Osamu Ukimura |
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MP20-13 |
Validation of a modified Gleason grading system in a Canadian cohort |
Prostate Cancer: Staging I | 17BOS |
Abstract: MP20-13 Sources of Funding: none Introduction Commonly used Gleason score grading of prostate cancer presents various deficiencies. Recently a new 5 Grade Group system has been developed sub-stratifying standard Biopsy Gleason scores 6, 3+4, 4+3, 8 and 9-10 into 5 distinct, prognostic Groups 1-5. We sought to replicate this new grading system for surgical Gleason score on a large contemporary Canadian cohort._x000D_ _x000D_ Methods Analysis was realized on pathologic specimens of a prospectively maintained Canadian database of men who underwent robot-assisted radical prostatectomy (RARP) between 2006 and 2016 at two major academic centers in Montreal. Outcome was based on biochemical recurrence (BCR) defined as a rising PSA>0.2ng/mL. The log-rank test assessed univariable differences in BCR by the novel Gleason score groups from prostate biopsy. Separate univariable and multivariable Cox proportional hazards used four possible categorizations of Gleason scores. Results Of the 617 patients eligible for analysis, 102, 398, 57, 34, 26 were classified as group 1,2,3,4,5 respectively. With a mean follow-up of 28 months, significant differences in BCR rates between both Gleason 3 + 4 versus 4 + 3 (p<0.001) were observed. There were no statistical difference in BCR rates between Gleason 8 versus 9-10 (p= 0.342). The hazard ratios relative to Gleason score 6 were 1.531 95% CI (0.588; 3.987), 5.146 (1.754; 15.098), 8.157 (2.783; 23.911), and 11.7 (3.585; 30.804) for Gleason scores 3 + 4, 4 + 3, 8, and 9–10, respectively. _x000D_ Conclusions The present study demonstrates the importance of the separation of the two Gleason categories 3+4 versus 4+3 in the new system. Further studies are warranted to implement the updated system for more accurate prognostications, and to improve patient counseling of cancer grading. Funding none
Authors
Marc Zanaty
Mansour Alnazari Mila Mansour Pierre Karakiewicz Emanuele Zaffuto Raisa Pompe Roger Valdivieso Assaad Elhakim Kevin Zorn |
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MP20-14 |
Anatomical evaluation of sentinel lymph nodes for prostate cancer using indocyanine green during laparoscopic radical prostatectomy |
Prostate Cancer: Staging I | 17BOS |
Abstract: MP20-14 Sources of Funding: none Introduction The exact anatomical location of the sentinel lymph nodes (SLNs) for prostate cancer has not ascertained clinically, but could be useful both for diagnosing lymph node metastasis and simplifying the procedure of extended pelvic lymph node dissection (ePLND). The aim of this study was to evaluate the suitability of SLNs detection by intraoperative fluorescence imaging with indocyanine green (ICG) during laparoscopic radical prostatectomy (LRP) and to determine the position of the SLNs. Methods A consecutive series of 50 patients with intermediate and high risk localized prostate cancer who underwent LRP between January 2014 and September 2016 was analyzed. ICG was injected into the prostate via transrectal ultrasound guidance 30 minutes before surgery. Intraoperative fluorescence imaging was performed using the Olympus near-infrared camera system. LRP was performed, starting with SLNs dissection and ePLND followed by prostatectomy. Results Median patient age was 70 years (range 61-76) and median PSA was 8.9 ng/ml (range 5.0-62.1). In addition, 24 cases (48%) were intermediate risk, 26 (52%) were high risk .SLNs were identified in 47 patients (94%). Two hundred ninety-four SLNs were removed (median 5 SLNs per patient, range 0-16), and overall 1013 nodes (median 16 nodes per patient, range 6-33) were removed during ePLND. The incidences of lymph node metastasis were 12% (6/50). Although the false negative rate was 0% and the sensitivity was 100% on a per-patient basis, pathological examination revealed a total of 22 metastatic nodes, of which 63% (14/22) were ICG stained. Importantly, 11 positive nodes which were all ICG stained were located below the bifurcation of the common iliac arteries in 5 of the 6 patients. Approximately 90 % of these positive SLNs (10/11) were located at two predominant sites along the characteristic lymphatic pathways. One was the junctional lymph nodes (45.5%, 5/11) which were located at the junction between internal and external iliac vessels, and the other was the distal internal iliac lymph nodes (45.5%, 5/11) which were located along the inferior vesical artery. Conclusions Intraoperative fluorescence imaging with ICG is feasible for detecting SLNs for prostate cancer. Our anatomical evaluation indicated that most of the positive SLNs are located at the junctional or the distal internal iliac lymph nodes. Although further investigation is needed, the possibility of ePLND overlook lymph node metastasis may be overcome by identifying these SLNs. Funding none
Authors
Jun Miki
Takafumi Yanagisawa Minoru Nakazono Taisuke Yamazaki Sotaro Kayano Taro Igarashi Seiro Tanaka Takahiro Kimura Hiroyuki Takahashi Takashi Yorozu Koichi Kishimoto Shin Egawa |
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MP20-15 |
THE ACCURACY OF 68Gallium-PSMA PET/CT IN PRIMARY LYMPH NODE STAGING FOR HIGH RISK PROSTATE CANCER |
Prostate Cancer: Staging I | 17BOS |
Abstract: MP20-15 Sources of Funding: This work was supported by the Scientific Research Projects Coordination Unit of Istanbul University, under project number 3264. Introduction PSMA/PET CT is a novel molecular imaging for accurate staging of prostate cancer. Its role has been mostly investigated in post-treatment setting. We assessed the diagnostic accuracy of 68Gallium-PSMA PET to predict LN metastases in primary N-staging in high and_x000D_ very high-risk non-metastatic prostate cancer in comparison with morphologic imaging. Methods This was a multi-centric trial of the Society of Urologic Oncology in Turkey in conjunction with Nuclear Medicine Department at Cerrahpasa School of Medicine, Istanbul University. Patients were accrued from 8 centers. High and very high-risk patients_x000D_ scheduled to undergo surgical treatment with extended LN dissection between July 2014 and October 2015 were included. Morphological imaging was with either MRI/CT. PSMA PET-CT was performed and evaluated at a single center. Sensitivity, specificity and accuracy_x000D_ were calculated for the detection of lymphatic metastases for PSMA PET/CT and morphological imaging. Kappa values were calculated for pathological and radiological incidence of LN metastases. Results Data on 51 eligible patients are presented. Sensitivity, specificity and accuracy of PSMA PET to detect LN metastases in primary setting were 53%, 86%, and 76% and increased to 67%, 88% and 81% in a sub-group with ?15 LN removed. Kappa values for correlation of imaging and pathology was 0.41 for PSMA PET and 0.18 for morphological_x000D_ imaging. Conclusions PSMA/PET CT is superior to morphological imaging for the detection of metastatic LNs in primary prostate cancer setting. Surgical dissection remains to be the gold standard for precise lymphatic staging. Funding This work was supported by the Scientific Research Projects Coordination Unit of Istanbul University, under project number 3264.
Authors
Can Obek
Tunkut Doganca Emre Demirci Meltem Ocak Ali Riza Kural Asif Yildirim Ugur Yucetas Cetin Demirdag Sarper M. Erdogan Levent Kabasakal |
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MP20-16 |
A more extended lymph node dissection template at radical prostatectomy detects metastases in the common iliac regions and in the fossa of Marcille |
Prostate Cancer: Staging I | 17BOS |
Abstract: MP20-16 Sources of Funding: none Introduction A 2008 mapping study showed that primary lymphatic landing sites of the prostate are also found medially to the internal iliac vessels, in the fossa of Marcille and along the common iliac vessels up to the ureter crossing. We then expanded our PLND template accordingly (Graphic). We assessed the effects of the template revision on pathologic and complication outcomes. Methods 753 pts underwent RP and extended PLND from 2000 to 2008 (485 pts [64%]; historical cohort) and from 2010 to 2015 (268 [36%]; contemporary cohort) at a referral center. Descriptive statistics and a logistic regression model were used. Subanalysis of patients with ?2 metastases was performed because these patients are the ones who may most benefit from removal of LN metastases. Results Median number of LN removed in the historical cohort was 25 (IQR 19-33) and in the contemporary cohort 34 (27-43; p <0.0001). _x000D_ Among 80 N+ pts (16%) in the historical cohort, the sole location of metastasis was external iliac/obturator region in 23/80 (29%) and internal iliac in 18/80 (23%), while 39/80 (49%) had metastases in both locations. Among 72 N+ pts (27%) in the contemporary cohort, the sole location of metastasis was external iliac/obturator region in 17 (24%) patients, internal iliac region in 24 (33%), and common iliac region in 1 (1%), while 30 (42%) had metastases in more than one location. While 5 patients had LN metastases in the fossa of Marcille, the latter was never the exclusive location. However, among pts with ?2 metastases in the contemporary cohort, 3 pts had one or both metastases in the common iliac regions or in the fossa of Marcille only. _x000D_ The adjusted risk to harbor nodal metastases was higher in the contemporary cohort, albeit not significantly (OR 1.19, 95% CI 0.77-1.84; p=0.4). Complications such as lymphoceles, thrombosis and neuropraxia were no more frequent with a more extended template. _x000D_ Conclusions A more extended PLND template detects LN metastases in the common iliac regions and in the fossa of Marcille and is associated with an overall non-significant higher risk of harboring LN metastases. Funding none
Authors
Lydia Maderthaner
Marc-Alain Furrer George N. Thalmann Urs E. Studer Daniel P. Nguyen |
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MP20-17 |
The Impact of Node Positive Disease Following Radical Prostatectomy on Survival: A Contemporary Population-Based Cohort |
Prostate Cancer: Staging I | 17BOS |
Abstract: MP20-17 Sources of Funding: none Introduction With the professional guidelines pulling back on the utility and frequency of prostate cancer screening, there is concern there will be a stage shift with an increase in lymph node metastases. Against this backdrop, the objective of our contemporary, population-based study was to examine outcomes associated with pelvic lymph node metastases. Methods We identified 161,079 radical prostatectomies during 2004-2014 using the Surveillance, Epidemiology, and End Results (SEER). Propensity score matching was used to adjust for confounding. Time to event analysis were used to compare all-cause mortality as well prostate cancer-specific mortality for those with (pN+) and without (pN-) pelvic lymph node metastases. Results From the total, we identified 3,697 radical prostatectomy pN+ (2.3%). Older age, higher grade and higher tumor stage were associated with pN+ (p<0.01, respectively). After propensity matching, pN+ disease was associated with higher all-cause mortality (28.5 vs 10.8 deaths per 1,000 person years, p<0.001) as well as higher prostate cancer-specific mortality (17.5 vs 3.5 deaths per 1,000 person years, p<0.01), with a median follow-up of 3.6 years (Figure 1). A higher number of positive lymph nodes was strongly associated with worse overall survival and prostate cancer-specific survival (Figure 2). Conclusions In light of our SEER studies demonstrating a recent increase in prostate cancer metastatic disease, it is worth noting that men with pN+ have significantly poorer outcomes. The effect on mortality was further increased by the number of positive lymph nodes. The outcomes from our study may guide men concerning adjuvant therapies and clinical trials. Funding none
Authors
Ron Golan
Adrien Bernstein Wei-Chun Hsu Brian Dinerman Michael Cosiano Jonathan E. Shoag Art Sedrakyan Jim C. Hu |
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MP20-18 |
Outcomes of Very-High-Risk Prostate Cancer: Validation Study from 3 Institutions over 10 years |
Prostate Cancer: Staging I | 17BOS |
Abstract: MP20-18 Sources of Funding: none Introduction Among men with localized high-risk prostate cancer (PCa), patients who met very-high-risk (VHR) criteria were shown to experience inferior outcomes after radical prostatectomy (RP) in a previous single institution study. Using a multi-institutional dataset, here we compared pathologic and oncologic outcomes between men with high-risk and VHR PCa who underwent RP between 2005-2015. Methods High-risk PCa was defined as biopsy Gleason pattern 8-10, PSA >20 ng/ml, or clinical stage T3-4. VHR PCa was defined according to pre-treatment criteria: primary Gleason pattern 5 on biopsy; or ? 5 cores containing Gleason sum 8-10; or multiple high-risk features. Pathologic outcomes by risk classification were compared using Chi-squared testing, and oncologic outcomes (biochemical recurrence - BCR, metastasis - METS, cancer specific mortality - CSM, and overall mortality - OM) were assessed using Cox proportional hazards models. Multivariable models included age, race, institution, and neoadjuvant androgen deprivation therapy as covariates. Results Among 1776 high-risk patients, 547 (30.8%) met VHR criteria. As compared to the high-risk cohort, VHR men had inferior pathologic outcomes. Positive margins: 38% vs 25%. Stage pT3b-4: 46% vs 17%. Stage pN1: 41% vs 15%. (P<0.001 for all comparisons). Over a median follow-up of 3 years, VHR PCa patients also had higher adjusted hazard ratios for BCR (2.32), METS (3.87), CSM (4.14), and OM (2.66). (P<0.001 for all comparisons). Conclusions In a multi-institutional experience of 1776 men who underwent treatment for high-risk PCa over a 10-year period, VHR cancer was strongly associated with adverse pathologic and oncologic outcomes as compared to high-risk disease. These findings serve to validate the prognostic significance of VHR PCa as a distinct entity from high-risk PCa, suggesting that VHR criteria should be considered during patient counseling and as a potential risk stratification tool in clinical trials. Funding none
Authors
Debasish Sundi
Jeffrey Tosoian Yaw Nyame Mary Achim Ridwan Alam Chandana Reddy Lamont Wilkins Amol Narang Andrew Stephenson John Davis Edward Schaeffer Ashley Ross Eric Klein Brian Chapin |
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MP20-19 |
What are the best cut-points for PSA doubling time in men with non-metastatic castration-resistant prostate cancer? |
Prostate Cancer: Staging I | 17BOS |
Abstract: MP20-19 Sources of Funding: Supported by the NIH/NCI under Award Number P50CA09231 and NIH K24 CA160653 Introduction Prostate-specific antigen doubling time (PSADT) is a useful marker for assessing disease aggressiveness at multiple stages of prostate cancer. However, in men with non-metastatic castration resistant prostate cancer (M0 CRPC), there are no commonly used PSADT cut-points for risk stratification. We examined whether PSADT correlates with metastases, all-cause mortality (ACM), and prostate cancer-specific mortality (PCSM) and identified PSADT cut-points that can be used clinically for risk stratification in men with M0 CRPC. Methods We collected data on 441 men with M0 CRPC in 2000-2015 at five Veterans Affairs hospitals. Cox models were used to test the association between log-transformed PSADT and development of metastasis, ACM, and PCSM. To identify cut-points, we categorized PSADT into groups of every 3 months (<3, 3-5.9, 6-8.9, 9-11.9, 12-14.9, 15-17.9, 18-20.9, 21-23.9, 24-119.9, 120) and then combined groups with similar hazard ratios. We tested the association between PSADT cut-points and each outcome using Cox models and compared survival using Kaplan-Meier estimates. Results Median age was 77 months (IQR: 70-83) and 160 (36%) men were black. Median PSADT was 13.3 months (IQR: 6.4-94.3) and median follow-up was 28.3 months (IQR: 14.7-49.1). As a continuous variable, PSADT was associated with metastases, ACM, and PCSM (HR 1.40-1.68, all p<0.001). We identified the PSADT cut-points <3, 3-8.9, 9-14.9, ≥15 months. As a categorical variable, PSADT was associated with metastases, ACM, and PCSM (all p<0.001). Men with a PSADT <3 months had a median 9 months to metastases, 16 months to PCSM, and 15 months to ACM. In contrast, men with a PSADT ≥15 months, had a median time to metastases of 50 months, 67 months to PCSM, and 46 months to ACM. Conclusions We found PSADT was a strong predictor of metastases, ACM, and PCSM in patients with M0 CRPC. As with patients at earlier disease stages, <3, 3-8.9, 9-14.9, and ≥15 are reasonable PSADT cut-points for risk stratification in men with M0 CRPC. These cut-points can be used for selecting high-risk men for clinical trials. Funding Supported by the NIH/NCI under Award Number P50CA09231 and NIH K24 CA160653
Authors
Lauren Howard
Daniel Moreira Amanda De Hoedt William Aronson Christopher Kane Christopher Amling Matthew Cooperberg Martha Terris Stephen Freedland |
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MP20-20 |
Identification of Disseminated Tumor Cells in the Bone Marrow with Disease-Specific Markers at Radical Prostatectomy |
Prostate Cancer: Staging I | 17BOS |
Abstract: MP20-20 Sources of Funding: This work is supported by NCI grant nos. U54CA143803, CA163124, CA093900, CA143055 to K.J.P as well as the Prostate Cancer Foundation, the Patrick C. Walsh Fund, and a gift from the Stutt family. E.E.vdT is supported by the Cure for Cancer Foundation. H.J.C. is supported by the Urology Care Foundation's Resident Research Award. Introduction Detection of microscopic disseminated disease in prostate cancer has largely been attempted with the study of circulating tumor cells (CTCs). Little is known about the character and clinical significance of disseminated tumor cells (DTCs) that have reached the bone marrow (BM), and prior study has relied on epithelial markers. Yet, it is now known that such markers are also expressed on normal erythroid precursor cells in the BM, thus we developed an assay for prostate-specific DTC identification. Methods BM aspirates from 12 men with localized and 2 men with metastatic prostate cancer were collected at time of radical prostatectomy (RP) or clinic visit respectively, and processed with the AccuCyte system (RareCyte, Inc., Seattle, WA). Slides were immunostained with DAPI (nuclear), anti-pan-cytokeratin (epithelial), anti-CD45/CD66b/CD11b/CD14/CD34 (white blood cell), and HOXB13 and NKX3.1 (prostate-specific). DTCs were required to have positive prostate channel staining and no white blood cell signal. The DTC count was adjusted for the starting volume of BM and the number of slides stained and spread over. Results DTCs were present in 83% (10/12) of patients at time of RP, with range 0 to 3592 cells/4 mL sample (average 375, median of 39.5). Two patients with metastatic prostate cancer had 52 and 105 DTCs/4mL BM (Table 1). Notably, only 4% of all DTCs were epithelial marker positive (CK+), and only 50% (6/12) of patients had any CK+ DTCs (Fig. 1). Conclusions The RareCyte system is a promising selection-free system for DTCs detection that does not rely on epithelial markers. Here we report on a novel assay to distinguish DTCs from other cells in the bone marrow using the presumed prostate-specific markers HOXB13 and NKX3.1. The majority of prostate-specific marker positive DTCs did not express the epithelial marker CK. Analyses of the association of DTC count with clinicopathologic variables are ongoing. Funding This work is supported by NCI grant nos. U54CA143803, CA163124, CA093900, CA143055 to K.J.P as well as the Prostate Cancer Foundation, the Patrick C. Walsh Fund, and a gift from the Stutt family. E.E.vdT is supported by the Cure for Cancer Foundation. H.J.C. is supported by the Urology Care Foundation's Resident Research Award.
Authors
Emma van der Toom
Stephanie Glavaris Michael Gorin James Verdone Kenneth Pienta Heather Chalfin |
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MP21-01 |
Long-term Survival Outcomes with Intravesical Nanoparticle Albumin-bound Paclitaxel for Recurrent Non-muscle Invasive Bladder Cancer after Previous Bacillus Calmette-Guérin Therapy |
Bladder Cancer: Invasive I | 17BOS |
Abstract: MP21-01 Sources of Funding: none Introduction Response rates to salvage intravesical therapies for Bacillus Calmette-Guerin (BCG) - refractory non-muscle-invasive bladder cancer (NMIBC) range from 10 to 30%. We previously reported the results of a phase II trial of salvage intravesical nanoparticle albumin-bound (nab)-paclitaxel, which demonstrated minimal toxicity and a 36% response rate. We now present an update on this cohort with long-term follow-up. Methods This was an investigator initiated, single-center, single-arm, phase II trial investigating the use of intravesical nab-paclitaxel in patients with recurrent Tis, Ta, and T1 urothelial carcinoma who failed at least one prior induction course of intravesical BCG. Patients received 500mg/100mL of nab-paclitaxel administered as 6 weekly intravesical instillations. At 6 weeks after the final instillation, response was evaluated by cystoscopy with biopsy, cytology, and cross-sectional imaging and any positive element constituted a recurrence. All complete responders (CR) were started on full-dose monthly maintenance for 6 months. Overall survival (OS), recurrence-free survival (RFS), cystectomy-free survival (CFS), and cancer-specific survival (CSS) were assessed via Kaplan-Meier analysis. Results A total of 28 patients were enrolled with a median follow-up of 41 months (range 5-76). There were 22 men and 6 women with a median age of 79 (range 36 - 93) and the median number of prior intravesical therapies was 2. Twenty-one of 28 (75%) were BCG refractory at enrollment. Ten of the 28 (36%) patients achieved CR at cystoscopy 6 weeks after their last nab-paclitaxel instillation. Six of the 28 patients remain cancer free, with RFS of 18%. 5-year OS was 56% and 5-year CSS was 91%. Radical cystectomy was performed in 11/28 (39%) patients, of whom only 2/11 (18%) had pT2 or greater disease. Conclusions With a median follow up of 41 months, 18% of this cohort of high risk BCG unresponsive NMIBC patients treated with nab-paclitaxel were disease free. Cystectomy free survival was 61% and bladder cancer-specific mortality was 9%. Nab-paclitaxel is a reasonable treatment option in this high risk population. Funding none
Authors
Dennis J. Robins
Wilson Sui Justin T. Matulay G. Joel DeCastro Christopher B. Anderson James M. McKiernan |
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MP21-02 |
The long term outcomes from early re-resection in patients with high-risk non-muscle invasive bladder cancer |
Bladder Cancer: Invasive I | 17BOS |
Abstract: MP21-02 Sources of Funding: none Introduction Around one third of bladder cancers (BCs) are high-grade non-muscle invasive tumors (HGNMI). Current guidelines advocate early re-resection for these cancers, although the benefits are unclear and the uniform need has been questioned. Here we compare the outcomes in patients with and without re-resection using a large single-centre cohort._x000D_ Methods We identified all patients with new HGNMI BC treated between 1994-2009 in Sheffield. We annotated these with hospital, pharmacy and cancer registry records. Primary outcomes were disease specific and overall survival. Secondary outcomes were the findings at re-resection, rates of muscle invasion and radical treatment. Statistical tests were two-tailed and significance defined as p<0.05._x000D_ _x000D_ Results We identified 932 eligible patients, including 229 (25%) who underwent re-resection within 12 weeks and 234 (25%) 3-6 months after diagnosis. Patients with and without re-resection were broadly similar for clinicopathological criteria. Re-resection was normal in 91 (20%) and contained BC in 138 (30%) patients. Of these, 15(10.8%) cancers were low grade, 85(61.6%) high-grade NMI and 38 muscle invasive (28%). During follow up, patients with re-resection were more frequently diagnosed with muscle invasion (126 (27%) vs. 49 (11%), Chi sq. p<0.001) and more commonly underwent radical treatment (127 (27%) vs. 35 (8%), p<0.001) than those without re-resection. In total, 528 (57%) patients died during follow up. Patients with re-resection had a significantly higher disease-specific (179 (78%) vs. 518 (76%), log rank p=0.05) and overall survival (119 (53%) vs. 251 (37%), log rank p<0.001) than those without re-resection._x000D_ Conclusions We found that patients undergoing early re-resection were more likely to be diagnosed with muscle invasion, more likely to undergo radical treatment and had a higher disease-specific and overall survival. The differences were greatest in patients with lamina propria invasion at diagnosis. Limitations of our work include retrospective design and potential selection bias. Funding none
Authors
Patrick Gordon
Jim Catto |
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MP21-03 |
DEFINITIVE TREATMENT OF BLADDER CANCER IN OCTOGENARIANS: BALANCING INCREASED PERIOPERATIVE MORTALITY WITH SUPERIOR OVERALL SURVIVAL |
Bladder Cancer: Invasive I | 17BOS |
Abstract: MP21-03 Sources of Funding: None Introduction Radical cystectomy (RC) is the gold standard treatment for muscle invasive bladder cancer (MIBC), but is sometimes avoided in the elderly due to concern for increased morbidity. We sought to quantify the perioperative risks of RC among octogenarians and analyze the survival benefit of available treatment modalities in a national database. Methods Using the National Cancer Database, we identified patients with non-metastatic MIBC from 2004 to 2013. Patients were stratified by age less than 80 and age 80-89. We assessed trends in management, perioperative mortality, and overall survival. Analysis was performed using chi-square test, multivariate regression, and Cox regression. Results A total of 54,201 patients with non-metastatic MIBC were identified, of whom 15,581 (28.8%) were ages 80-89. Compared to younger patients, octogenarians were less likely to undergo RC (18.0% vs. 47.9%, p<0.01) and more likely to be treated with combination chemotherapy and radiation (13.7% vs. 10.1%, p<0.01). On multivariate analysis controlling for Charlson comorbidity index (CCI), race, and facility type, age greater than 80 was independently associated with decreased odds of undergoing RC (OR 0.25, p<0.01). Octogenarians treated with RC have a higher 30-day (5.7% vs. 2.2%, p<0.01) and 90-day mortality (14.5% vs. 6.1%, p<0.01) than younger patients. On multivariate analysis controlling for race, CCI, and facility type, age over 80 is independently associated with 30- and 90-day mortality (OR 2.9 and 2.6, p<0.01). On Cox multivariate analysis controlling for age, race, CCI, stage, tumor size, payer status, grade and facility type, overall survival was highest among octogenarians treated with RC, and sequentially worse for those treated with combination chemoradiation, radiation, and chemotherapy (HR 0.54 vs 0.60 vs 0.75 vs 0.77, respectively; p<0.01; Table 1), compared to TURBT alone. Conclusions Despite the survival benefit of RC in MIBC, octogenarians are less likely to undergo RC than younger patients. RC in octogenarians confers a higher 30- and 90-day mortality, but is associated with improved overall survival. Quantifying these risks and benefits improves counseling for octogenarians on optimal management strategies. Funding None
Authors
William R Boysen
Vignesh Packiam Joseph Rodriguez Melanie Adamsky Norm Smith Gary D Steinberg |
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MP21-04 |
The efficacy of trimodal chemoradiotherapy as a bladder-preserving strategy for muscle invasive bladder cancer |
Bladder Cancer: Invasive I | 17BOS |
Abstract: MP21-04 Sources of Funding: none Introduction To evaluate the bladder preservation strategy used at our institution for muscle-invasive bladder cancer (MIBC) in patients undergoing chemoradiotherapy. Methods In 71 patients with MIBC, transurethral resection of the bladder tumor was performed before treatment to confirm pathological stage ?T2. Fifty patients received cisplatin-radiation (CDDP-R) therapy and 21 received gemcitabine plus cisplatin-radiation (GC-R) therapy. Extensive transurethral resection of bladder tumors was performed after chemoradiotherapy to evaluate the pathological response to treatment. We used propensity score-match analysis to compare the oncological outcomes of patients treated by chemoradiotherapy to those of patients treated by open radical cystectomy (ORC). Results The 2- and 5-year progression-free survival (PFS), bladder-intact survival (BIS), cancer-specific survival (CSS), and overall survival rates after treatment were 71.6% and 66.1%, 68.9% and 56.1%, 85.1% and 72.5%, and 83.3% and 66.6%, respectively. The complete response (CR) after chemoradiotherapy could be a good predictor of PFS, BIS, and CSS (OR = 0.31, p < 0.05; OR = 0.22, p < 0.01; OR = 0.11, p < 0.005, respectively) and clinical stage T2 could be a significant predictor of good BIS and CSS (OR = 0.28, p < 0.05 and, OR = 0.21, p < 0.05, respectively). The response to GC-R was significantly better than that to CDDP-R (CR: 81% vs. 29.4%), with tolerable adverse events. According to our propensity score-match analysis, the 2- and 5-year overall survival rates after chemoradiotherapy were 89.2 and 78.9%, respectively, and those after ORC were 82.3 and 69.6%, respectively, indicating comparable survival benefit of chemoradiotherapy to that of ORC. Conclusions Bladder preservation by chemoradiotherapy for MIBC is as effective as radical cystectomy. GC-R treatment might be more effective with better cancer control than CDDP-R. Funding none
Authors
Kazuhiro Nagao
Takahiko Hara Jun Nishijima Junichi Mori Kosuke Shimizu Nakanori Fujii Keita Kobayashi Yoshihisa Kawai Ryo Inoue Yoshiaki Yamamoto Hiroaki Matsumoto Hideyasu Matsuyama |
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MP21-05 |
Multimodal bladder preservation technique for muscle invasive bladder cancer: results from a prospective trial |
Bladder Cancer: Invasive I | 17BOS |
Abstract: MP21-05 Sources of Funding: none Introduction Over the last decades, several studies, including our group have shown that the use of tri-modal therapy consisting of transurethral bladder resection followed by concomitant chemotherapy and radiation therapy results in comparable outcomes to radical cystectomy, considered the gold standard for muscle invasive bladder cancer (MIBC). We present our oncologic outcomes for tetra-modal bladder preservation technique, which include tri-modal therapy followed by selective intra-arterial infusion of chemotherapeutics. Methods We performed an analysis of our prospectively maintained IRB approved database of multimodal bladder preservation technique. Our tetra-modality therapy consisted of complete resection of the tumor, chemotherapy and radiation therapy followed by dual balloon occluded intra-arterial infusion of chemotherapeutics - OMC regimen. We included all cases from August 2009 until December 2015 with at least 6 months of follow up. We evaluated oncologic outcomes based on T-stage, grade, lymph node status, age, sex, and presence of hydronephrosis. All data was analyzed using SPSS ver15. Results Four-hundred ten MIBC patients were enrolled in the study (median age 67 years, 78.8% male, ECOG performance status 0/1/2 100.0%, T-stage II/III/IV 67.1%;23.1%; 9.8%). The mean 8-year OS was 75.1 months (95% CI; 70.5-79.7) for cT II versus 77.1 months (95% CI; 67.7-86.5) for cT III, and 41.8 months (31.7-52.0) for cT IV. Univariate analysis for 8-year OS showed that patients&[prime] deaths were associated with age (p = 0.036) T-stage (p < 0.001), positive node (p = 0.002), and presence of hydronephrosis (p < 0.001). On multivariable logistic regression analysis adjusted for gender, age, T-stage, positive node, hydronephrosis, and tumor grade, age (p=0.006, HR:1.04, 95%CI: 1.01-1.07), T-stage (p=0.002, HR:1.80, 95%CI: 1.25-2.95), N-stage (p=0.010, HR:1.36, 95%CI: 1.08-1.73), and presence of hydronephrosis (p=0.012, HR:2.28, 95%CI: 1.20-4.35) remained as predictors for worse prognosis. Conclusions Our tetra-modality OMC-regimen significantly improves the chance of bladder preservation. Carefully selected cT II/ III patients without hydronephrosis are good candidates for bladder preservation. Funding none
Authors
Teruo Inamoto
Kiyoshi Takahara Naokazu Ibuki Tomoaki Takai Taizo Uchimoto Kenkichi Saito Naoki Tanda Yuki Yoshikawa Koichiro Minami Hajime Hirano Hayahito Nomi Haruhito Azuma Kiyohito Yamamoto Taijyu Shinbo Kazuhiro Yamamoto Yoshifumi Narumi |
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MP21-06 |
RADICAL CYSTECTOMY AFTER PRIOR PARTIAL CYSTECTOMY FOR UROTHELIAL CARCINOMA: PERIOPERATIVE AND ONCOLOGIC OUTCOMES |
Bladder Cancer: Invasive I | 17BOS |
Abstract: MP21-06 Sources of Funding: None Introduction While partial cystectomy (PC) represents an option for select patients with urothelial carcinoma (UC), approximately 20% of patients treated with PC have been reported to ultimately require radical cystectomy (RC) for disease recurrence. The outcomes for these patients have not been well described to date. We therefore evaluated perioperative and oncologic outcomes of patients undergoing RC after PC for UC. Methods We identified 61 patients who underwent RC at our institution after prior PC for UC between 1980-2010. These patients were then matched 1:3 to patients undergoing primary RC based on age, pathologic T and N stage, and decade of surgery. Perioperative outcomes were compared between the two groups using descriptive statistics. Cancer-specific (CSS) and overall survival (OS) were evaluated using the Kaplan-Meier method and conditional Cox proportional hazards regression models. Results Median age at the time of RC was 67 yrs in both groups (IQR 62, 75), while 47/61 (77%) RC after PC and 151/181 (83.4%) primary RC patients were male. Median time from PC to RC was 1.5 years (IQR 0.6, 4.4). Median Charlson comorbidity index was 2 for both groups (IQR 2, 8). Estimated blood loss was significantly higher among patients undergoing RC after PC compared to primary RC (median 1000 cc vs 700 cc; p=0.001), although there was no difference in operative time (median 322 min vs 292 min; p=0.17) or length of stay (median 10 vs 11 days; p=0.27). Similarly, there was no difference in either minor (Clavien 1-2) (49.2% vs 44.8%; p=0.71) or major (Clavien 3-5) (9.8% vs 8.3%; p=0.55) perioperative complications between the RC after PC and the RC alone groups. Median follow-up after RC was 6.0 years (IQR 1.5, 15.6), during which time 204 patients died, including 95 who died of UC. Five-year CSS was significantly worse for patients who underwent RC after PC versus primary RC (58% vs 67%; p=0.02; HR 1.8; 95% CI 1.1, 3.0), while no significant difference in 5-year OS was noted (51% vs 54%; p=0.42; HR 1.2; 95% CI 0.8, 1.7). Conclusions Patients who underwent RC for recurrent UC after prior PC had similar perioperative outcomes to stage-matched patients undergoing primary RC. However, such patients were noted to be at a higher risk of subsequently dying from bladder cancer. These data may be used in counseling patients considering PC as initial treatment for invasive UC, as well as for consideration of adjuvant therapy after RC following PC. Funding None
Authors
Ross Mason
Igor Frank Bimal Bhindi Matthew K. Tollefson R. Houston Thompson R. Jeffrey Karnes Robert Tarrell Stephen A. Boorjian |
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MP21-07 |
Selection effects may explain smoking-related outcome differences after radical cystectomy |
Bladder Cancer: Invasive I | 17BOS |
Abstract: MP21-07 Sources of Funding: none Introduction The impact of smoking on mortality in patients with bladder cancer is subject to controversies. Methods We investigated 1000 patients who consecutively underwent radical cystectomy between 1993 and 2013. Proportional hazard models for competing risks were used to study combined effects of variables on bladder cancer and competing mortality. Results The median follow-up in the survivors was 6.6 years; 331 patients had died from bladder cancer, 178 from non-cancer or unknown (n=6) causes and 54 from a second cancer. Compared with non-smokers, current smokers were more frequently male (35.7% versus 12.0%, p<0.0001), younger (63.5 versus 70.5 years, p<0.0001), had a lower body mass index (26.2 versus 27.1 kg/m2, p<0.0001) and suffered less frequently from cardiac insufficiency (12.7% versus 19.3%, p=0.0129). In current smokers there was a trend towards lower bladder cancer and higher competing mortality compared with non-smokers. In the multivariable analysis, current smoking was no predictor of bladder cancer mortality (hazard ratio, HR, in the full model 0.76, p=0.0687) but of competing mortality (HR in the optimal model 1.62, p=0.0044). Conclusions This study did not confirm adverse bladder cancer-related outcome in current smokers after radical cystectomy. With a younger mean age and a male predominance, current smokers showed a trend towards lower bladder cancer mortality that was eventually neutralized by increased competing mortality illustrating that selection effects may explain some smoking-related outcome differences after radical cystectomy. Funding none
Authors
Michael Froehner
Rainer Koch Matthias Hübler Ulrike Heberling Vladimir Novotny Stefan Zastrow Manfred P. Wirth |
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MP21-08 |
The use of antibiotic prophylaxis in patients undergoing radical cystectomy for bladder cancer |
Bladder Cancer: Invasive I | 17BOS |
Abstract: MP21-08 Sources of Funding: none Introduction Approximately 20-40% of patients after radical cystectomy (RC) suffer from perioperative urinary tract infection (UTI). Guidelines for antimicrobial prophylaxis, such as the AUA Best Practice Statement, are hampered by a lack of RC-specific research and generally based on colorectal surgery literature. Methods We analyzed RC registries between 2009-2015 from three different urological centers._x000D_ Baseline variables included i. a. ASA score, TNM-classification and type of urinary diversion. We recorded the presence of urologic devices before RC, neo-adjuvant chemotherapy, previous radiotherapy, prolonged steroids therapy before RC, microbiological urine and blood cultures. UTI was diagnosed according to EAU/ESIU definitions._x000D_ Primary objective was to analyze the type and length of antibiotic therapy (AB), the percentage and severity of UTIs after RC, the responsible bacteria and their AB sensitivity. We recorded the frequency of CT-scans and invasive procedures after RC and 30-days-readmission rate. _x000D_ Results We analyzed 217 cases of RC. Median length of hospital stay was 13 days (IQR 11-20.5) with 9.2% of the patients still in hospital after 30 days. 30-days-readmission rate was 16.1%. The most frequent AB was a combination of metronidazole (98.2%) with a cephalosporin (89.9%). The median of days of AB administration after RC was 7 days (IQR 5-14). After cessation of the first AB therapy, additional antibiotics were used in 51.6% of the patients. _x000D_ The overall number of UTIs was 42 (19.4%): 9.7% pyelonephritis, 7.8% urosepsis, 1.8% uroseptic shock. Enterococcus spp. was the most frequently isolated bacteria in urine (25.7%) and in blood (42.9%). Enterococcus showed, as awaited, a cephalosporin (100%) and gentamicine (90%) resistance but also a 100% resistance to ciprofloxacin. _x000D_ In univariate logistic regression analysis, age (odds ratio (OR)=0.94; p=0.001), continent derivation (OR=4.36; p<0.001), neoadjuvant chemotherapy (OR=3.07; p=0.044) and the presence of any urologic device before surgery (OR=0.36; p=0.013) were correlated with UTI. In multivariate logistic regression analysis only continent derivation was associated to UTI after surgery (OR=3.16; p=0.010)._x000D_ Conclusions The UTI rate after RC was 19.4% and in 9.6% of the cases UTI was urosepsis. Continent diversion was the only independent factor associated with a higher risk of UTI but perioperative AB therapy length was not. Enterococci spp. are involved in early infection and not routinely covered by the most common used AB prophylaxes. Funding none
Authors
Maximilian Haider
Roman Mayr Hans-Martin Fritsche Christian Ladurner Armin Pycha Evi Comploj Francis Lemire Louis Lacombe Yves Fradet Michele Lodde |
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MP21-09 |
Prolonged length of stay not associated with decreased hospital readmissions following uncomplicated hospitalization after radical cystectomy |
Bladder Cancer: Invasive I | 17BOS |
Abstract: MP21-09 Sources of Funding: None Introduction Clinical decision making regarding timing of discharge can vary widely for patients treated with radical cystectomy. Some patients may be kept in-house longer to diminish perceived risk of missed complications and subsequent readmission. We sought to evaluate the relationship between length of stay (LOS) and 30-day readmissions in patients who underwent radical cystectomy and did not experience in-hospital complications. Methods We used data from the American College of Surgeons National Surgical Quality Improvement Program to identify bladder cancer patients who underwent radical cystectomy (2011-2014), and excluded patients who experienced in-hospital complications. Our primary outcome of interest was 30-day readmission, and main exposure was LOS in days (<6, 6-10, >10 days). Other factors of interest included race, gender, major complications after discharge, body mass index, and operative time (stratified by quartiles). Multivariable logistic regression was performed to estimate adjusted odds ratios for 30-day readmission. Results Among 3,325 radical cystectomy patients who had an uncomplicated hospital stay, 718 (21.6%) were readmitted within 30 days after surgery. The median initial LOS was 7.0 days (interquartile range 6.0-9.0 days). A majority were discharged either between 6-10 days (42.1%) or >10 days after surgery (21.3%). Readmission was more common among patients who had post-discharge complications (35.1% vs 11.9% no complications, p<0.001) and increased operative time (29.7% top quartile vs 15.9% lowest quartile, p<0.001). Though readmitted patients had a shorter initial LOS on average (mean 7.8±3.0 vs 8.4±4.8 days no readmission, p=0.003), there was no significant relationship after adjusting for other factors (20.6% 0-6 days vs 19.5% 10+ days, adjusted OR 1.03, 95% 0.79-1.35, Figure). A subset analysis examining only surgery-related readmissions demonstrated similar findings. Conclusions If no in-hospital complications occur following radical cystectomy, applying arbitrary minimum thresholds for length of stay may not decrease the risk of hospital readmission. Funding None
Authors
Kirven Gilbert
Adam Lorentz Dattatraya Patil Mehrdad Alemozaffar Christopher Filson |
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MP21-10 |
Clinical feature in dialysis patient with urothelial carcinoma after complete urinary tract exenteration |
Bladder Cancer: Invasive I | 17BOS |
Abstract: MP21-10 Sources of Funding: None Introduction To survey long-term outcomes of dialysis patients with urothelial cancers undergone complete urinary tract exenteration (bilateral nephroureterectomy and cystectomy) Methods We retrospectively reviewed our patients with urinary tract urothelial cancer. A total of 42 dialysis patients who received complete urinary tract exenteration were enrolloed in our study. Seventeen patients received one-stage complete urinary tract exenteration and twenty-five patients who had multi-stage surgery. We review the demographic, clinical, surgical, and pathological data to determine what clinical and pathologic variables affected the survival between two groups. Results Baseline demographics were comparable in both groups. There was no significant difference in age, American Society of Anesthesiologists class, Charlson index or body mass index between the 2 groups. There were no statistically different in terms of estimated blood loss (1280 vs. 1440 ml) and total hospital stay (31 vs. 21 days). In comparsion to the multi- stage surgery, one- stage surgery was associated with a high complication rate (58.8% (10/17) vs. 8%( 2/25) ). Twenty two patients were still alive at the end of the study and 20 patients had died. The median survival after confirmation of complete urinary tract exenteration status was 27.5 months. The overall survival was not different between two groups. Charlson comorbidity index was a mandatory indicator to predict long term survival outcome. Conclusions In dialysis patients with urothelial cancers undergone complete urinary tract exenteration, one stage complete urinary tract exenteration had high periopearative complication rate. Charlson comorbidity index was a mandatory indicator to predict long term survival outcome. Funding None
Authors
Ze-Hong Lu
Chien-Hui Ou Wen-Horng Yang |
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MP21-11 |
Increased Utilization of Advanced Imaging Technology and Its Economic Impact for Patients Diagnosed with Bladder Cancer in the United States |
Bladder Cancer: Invasive I | 17BOS |
Abstract: MP21-11 Sources of Funding: This study was conducted with the support of the Institute for Translational Sciences at the University of Texas Medical Branch, supported in part by a Clinical and Translational Science Award Mentored Career Development (KL2) Award (KL2TR001441) from the National Center for Advancing Translational Sciences, National Institutes of Health (NIH), Comparative Effectiveness Research on Cancer in Texas (CERCIT) (RP140020) and the National Cancer Institute (NCI) (K05 CA134923) (SBW). This study was funded in part by the NIH Bladder SPORE (5P50CA091846-03) (AMK). This work was supported in part by the Duncan Family Institute and a fellowship from The University of Texas MD Anderson Cancer Center's Halliburton Employees Foundation (Huo). We thank Dr. Gary Deyter from the Department of Health Services Research at The University of Texas MD Anderson Cancer Center for reviewing and editing the manuscript. This study used the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. The interpretation and reporting of these data are the sole responsibility of the authors. The authors acknowledge the efforts of the Applied Research Program, NCI; the Office of Research, Development and Information, CMS; Information Management Services (IMS), Inc.; and the SEER program tumor registries in the creation of the SEER database. Introduction This study examined utilization patterns and predictors for use of positron emission tomography–computed tomography (PET/CT), magnetic resonance imaging (MRI), and computed tomography (CT) among Medicare beneficiaries diagnosed with bladder cancer. Methods We used the Surveillance, Epidemiology and End Results (SEER)-Medicare linked databases to analyze claims data for 36,855 patients aged 60-90 years diagnosed with bladder cancer from 2004 to 2011. The Cochran-Armitage test for trend was used to determine whether significant changes in the proportion of patients receiving advanced imaging after cancer diagnosis occurred during the time interval; trends in the usage of the imaging modality types were assessed. Multivariable logistic regression modeling was conducted to analyze potential demographic and clinical predictors associated with receipt of advanced imaging. The costs of imaging were measured using Medicare payments. Results While the overall trend of imaging use remained essentially unchanged over the study period, there was a significant decrease in the proportion of patients who received conventional imaging modalities (MRI and CT; P < .05) and a significant increase in the proportion of patients receiving the more advanced imaging modality (PET/CT; P < .0001). On multivariable analysis, receipt of PET/CT was significantly higher in female patients, Non-Hispanics, residents in West Census region, patients with higher grade tumors, those diagnosed with advanced stage disease, hydronephrosis, and those that received radical cystectomy and chemotherapy. In the cost analysis, the estimated national excess medical spending for advanced imaging was $6.1 million. Conclusions The sharp increase of advanced imaging (PET/CT) and substantial costs associated with this rapid adoption as we have documented suggests that further efforts should be made to evaluate the clinical and economic benefits of PET/CT imaging and to elucidate its appropriateness of use among bladder cancer patients. Funding This study was conducted with the support of the Institute for Translational Sciences at the University of Texas Medical Branch, supported in part by a Clinical and Translational Science Award Mentored Career Development (KL2) Award (KL2TR001441) from the National Center for Advancing Translational Sciences, National Institutes of Health (NIH), Comparative Effectiveness Research on Cancer in Texas (CERCIT) (RP140020) and the National Cancer Institute (NCI) (K05 CA134923) (SBW). This study was funded in part by the NIH Bladder SPORE (5P50CA091846-03) (AMK). This work was supported in part by the Duncan Family Institute and a fellowship from The University of Texas MD Anderson Cancer Center's Halliburton Employees Foundation (Huo). We thank Dr. Gary Deyter from the Department of Health Services Research at The University of Texas MD Anderson Cancer Center for reviewing and editing the manuscript. This study used the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. The interpretation and reporting of these data are the sole responsibility of the authors. The authors acknowledge the efforts of the Applied Research Program, NCI; the Office of Research, Development and Information, CMS; Information Management Services (IMS), Inc.; and the SEER program tumor registries in the creation of the SEER database.
Authors
Christopher Kosarek
Jinhai Huo Jacques Baillargeon Yong-Fang Kuo Justin Fang Cameron Ghaffary Preston Kerr Stephen Kim Eduardo Orihuela Douglas Tyler Sharon Giordano Stephen Freedland Ashish Kamat Stephen Williams |
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MP21-12 |
Health related quality of life following radical cystectomy: Comparative Analysis from the Medical Health Outcomes Study |
Bladder Cancer: Invasive I | 17BOS |
Abstract: MP21-12 Sources of Funding: Howard J Cohen Foundation Introduction Health related quality of life (HRQOL) after radical cystectomy and ileal conduit (RC-IC) is not well quantified at the population level. Given the large extirpative nature of the surgery combined with stoma creation, this is a life-changing event for patients. We evaluated post-RC-IC HRQOL in patients with bladder cancer (BC) compared with non-cancer controls and colorectal cancer (CRC) patients undergoing proctocolectomy with colostomy using SEER-Medical Health Outcomes Survey (MHOS) data._x000D_ Methods SEER-MHOS data (1998-2013) was used to identify patients with BC and CRC diagnoses and survey data available post diagnoses. 196 BC patients undergoing RC-IC were propensity score matched 1:5 to non-cancer controls (N=980) and compared with 154 CRC patients undergoing proctocolectomy with colostomy. Differences in mental and physical composite scores (MCS and PCS, respectively) were compared between groups. MCS and PCS scores are normalized on a 0-100 scale where 50 represents US population mean. _x000D_ Results RC-IC patients, compared with matched controls, had significantly lower PCS (35.9 vs. 40.2, p<0.001), physical functioning (52.6 vs. 62.4, p<0.001), role physical (41.2 vs. 54.0, p<0.001), social functioning (69.7 vs. 76.3, p=0.006), vitality (51.1 vs. 56.3, p=0.005), and general health (51.8 vs. 62.0, p<0.001). MCS and mental health subscale scores did not differ between groups. Comparing RC-IC patients with CRC patients, female gender (26 vs. 38%, p=0.01) and inflammatory bowel disease (6% vs. 14%, p=0.005) were more common in CRC patients. MCS, PCS, and HRQOL subscales did not differ between RC-IC and CRC patients. Among a subset of RC-IC patients with both pre and post-surgical data (N=46), PCS (p=0.002), physical functioning (p=0.04), social functioning (p=0.02), and general health (p<0.001) declined significantly._x000D_ Conclusions RC-IC patients have worsened HRQOL than non-cancer controls. However, HRQOL of RC-IC patients was similar to that of CRC patients undergoing proctocolectomy with colostomy. Further longitudinal study is needed to better quantify HRQOL in RC-IC._x000D_ Funding Howard J Cohen Foundation
Authors
Brian Winters
George Schade Sarah Holt Atreya Dash John Gore Jonathan Wright |
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MP21-13 |
Does Quality of Care Impact Outcomes in Patients with Locally Advanced Bladder Cancer After Robot-Assisted Radical Cystectomy? |
Bladder Cancer: Invasive I | 17BOS |
Abstract: MP21-13 Sources of Funding: Roswell Park Alliance Foundation Introduction Lack of tactile feedback and potential higher risk of positive margins may advocate against the use of Robot-assisted Radical Cystectomy (RARC) for Locally advanced disease (LAD). We evaluated the quality of RARC in patients with LAD and compared it to organ-confined disease (OCD) Methods Retrospective review of 421 consecutive RARCs between 2005 and 2015 was performed. Patients with LAD (>=pT3 and/or N+) were compared with OCD (<=pT2/N0). Validated Quality Cystectomy Score (QCS) based on 4 sets of quality metrics was used to compare surgical performance in both groups: [I- Preoperative (Administration of Neoadjuvant Chemotherapy); II- Operative (Overall operative time (< 6.5 hours) and estimated blood loss less <500 ml); III- Pathologic (Negative Soft Tissue Surgical Margins and Lymph Node Yield>20); and IV- Peri-operative (No high grade complications, Readmission or Mortality within 30-d)]. Star Scores were assigned according to the number of criteria achieved. Kaplan Meier method was used to compute recurrence free (RFS), cancer-specific (CSS) and overall survival (OS) rates. Cox proportional hazards model were fit to evaluate predictors of survival. Results 52% had LAD. They had fewer neobladders (3% vs 12%, p<0.001), received adjuvant chemotherapy more frequently (34% vs 4%, p<0.001), and experienced higher mortality within 90 d of RARC (8% vs 1%, p=0.001). LAD patients showed more positive surgical margins (18% vs 2%, p<0.001) and developed recurrences more frequently (41% vs 13%, p<0.001). There was no significant difference in complications or readmissions. Patients with OCD exhibited better 3-year RFS, DSS and OS (85% vs 47%, 96% vs 65% and 81% vs 28%, respectively) (Figure 1). 91% of OCD patients achieved >=3 stars in comparison to 81% in LAD (Table 1). For OCD, patients who achieved star score of 3 or 4 remained stable (approximately 90%), while for LAD, it improved from 72% to 93% between 2005 and 2015. Conclusions Despite receiving comparable quality of surgical care, patients with LAD exhibited worse RFS, DSS and OS. Funding Roswell Park Alliance Foundation
Authors
Youssef Ahmed
Ahmed Hussein Paul May Basel Ahmed Amir Khan John Binkowski Justen Kozlowski Khurshid Guru |
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MP21-14 |
Management of Uretero-Enteric Strictures after Robot-Assisted Radical Cystectomy |
Bladder Cancer: Invasive I | 17BOS |
Abstract: MP21-14 Sources of Funding: Roswell Park Alliance foundation Introduction When conservative management for uretero-enteric strictures (UES) following robot-assisted radical cystectomy (RARC) fails, the gold standard is open revision, which may be associated with higher morbidity and technical complexity. We sought to investigate the predictors of successful endoscopic management for UES after RARC. Methods We retrospectively reviewed our RARC database and identified patients who developed UES. All patients were initially managed with an endoscopic/percutaneous approach. Successful management was defined as absence of significant urinary tract obstruction on postoperative imaging. Data was reviewed for demographics operative approach, and perioperative outcomes. A logistic regression model was fit to evaluate predictors for successful endoscopic management. Results Our database included 418 patients. UES were identified in 51 (12%) patients. Median time to UES following RARC was 5 months (IQR 2-12). Median time to primary management was 22 (IQR 4-54) days after diagnosis. Sixteen patients had a robot-assisted (RA) repair and 6 had open (Table 1). Thirty three patients had successful management of UES after an average of 2 procedures (endoscopic 13; robot-assisted revision 15; and open revision 5) (Figure 1). Only female gender (OR 0.13, 95% CI 0.03-0.56, p=0.007) and BMI (OR 0.88, 95% CI 0.77-0.99, p=0.05) were significant predictors of successful endoscopic management. Conclusions None of the stricture characteristics or the cancer stage predicted successful endoscopic management of UES after RARC. Only patient-related factors (male gender and lower BMI) were associated with successful endoscopic management. Funding Roswell Park Alliance foundation
Authors
Youssef Ahmed
Ahmed Hussein Paul May Basim Ahmad Taimoor Ali Prasanna Kumar Khurshid Guru |
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MP21-15 |
Fistulous complications following radical cystectomy for bladder cancer: analysis of a large modern cohort |
Bladder Cancer: Invasive I | 17BOS |
Abstract: MP21-15 Sources of Funding: none Introduction Radical cystectomy (RC) and urinary diversion carries a significant risk of postoperative morbidity, including fistula formation. We identified patients who underwent RC for bladder cancer at our institution who experienced fistulous complications and analyzed the risk factors for formation as well as their management and outcomes. Methods We performed a retrospective review of our institutional database and identified patients who underwent RC for bladder cancer between January 2007 and December 2015. Patients who experienced any fistulous complication were compared to those without such complication. Further chart review was carried out on all fistula patients to assess management strategies and outcomes. Those who were successfully conservatively managed were compared to those requiring surgical repair. Univariable and multivariable analyses were performed on associations with fistula formation and failure of conservative management. Results Of the 1041 patients, 31 (3.0%) experienced fistula formation. Mean time from RC to fistula presentation was 3.4 months (range 0.1-13.6). There was no difference in age, sex, race, body mass index, Charlson comorbidity score, type of urinary diversion, pathological stage, chemotherapy exposure, or radiation exposure between the two groups (all p>0.05). Of the 31 fistula patients, there were 14 (45.2%) orthotopic neobladders, 13 (41.9%) ileal conduits, and 4 (12.9%) continent catheterizable pouches. The most common types of fistulae were entero-diversion (17, 54.8%), entero-cutaneous (9, 29.0%), and diversion-cutaneous (4, 12.9%). Five (16.1%) patients experienced multiple fistulae. Conservative management was successful in 13 (41.9%) of patients, and surgical repair was required in 18 (58.1%). Of those requiring surgical repair, success was achieved in a single operation in 17 (94.4%). There were no malignant fistulae. On univariable analysis, age (p=0.002) and Charlson comorbidity score (p=0.029) were the only factors predictive of patients failing conservative management and requiring surgical repair, however, neither were significant on multivariable analysis (p=0.151 and p=0.286). Conclusions Fistulous complications are rare after RC. They generally occur within the first few months after RC, and are most commonly between the urinary diversion and small bowel. There are no clearly identifiable risk factors for fistula formation, nor for those who fail conservative management. However, surgical repair of fistulae is generally met with a high success rate in a single operation. Funding none
Authors
Zachary Smith
Riley McGinnis VIraj Maniar Gary Steinberg Norm Smith |
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MP21-16 |
The Association Between Blood Type and Risk of Venous Thromboembolism Following Radical Cystectomy |
Bladder Cancer: Invasive I | 17BOS |
Abstract: MP21-16 Sources of Funding: None. Introduction Venous thromboembolism (VTE) is a serious complication following radical cystectomy (RC). Several risk factors have been identified including high BMI, immobility and advanced cancer. Hematologic studies have recently found ABO blood type as a genetic risk factor for VTE. We attempted to elucidate the relationship between ABO blood type and risk of VTE post RC. Methods 1409 patients with urothelial bladder cancer who underwent RC (intent-to-cure) between 2003 and 2015 were identified. All these patients received VTE prophylaxis that included oral Coumadin (2003-2009), subcutaneous heparin (2009-2015), and post-discharge 4-week lovenox (2013-2015). 1341 patients had their blood type available. VTE including DVT and PE within 90 days of surgery were recorded. We evaluated the association of blood type with risk of postoperative VTE using logistic regression model. Results A total of 595 (44.4%) patients were blood type O and 746 (55.6%) were non-O (A, B and AB). 1063 (79.3%) patients were male. 191 (14.2%) patients received adjuvant while 257 (19.2%) received neoadjuvant chemotherapy. 905 patients received an orthotopic urinary diversion (67.4%). No significant differences were noted between those with O vs. non-O blood type regarding patient age (median 70 yrs vs. 70, P=0.2), BMI (median 27.4 vs. 26.9, P=0.3), Charlson comorbidity index (P=0.7), hospital stay following RC (median 8 days vs. 8, P=0.6), tumor stage (organ confined (OC) vs. extravesicular (EV)) (65.3% vs. 61.7% OC) (P=0.5) or pN+ status (21.8% vs. 23.2%, P=0.5). Venous thromboembolic events within 90 days of surgery were recorded in 90 patients (6.7%) (43% DVT-only, 57% PE+/- DVT). On multivariate analysis controlling for age, BMI, neoadjuvant chemotherapy, and pathologic stage, non-O blood type was associated with a nearly two-fold increased risk of VTE (odds ratio [OR] = 1.94, 95% CI: 1.215-3.098, P=0.004). No significant difference was observed in the rates of VTE between the 3 prophylactic eras. Conclusions Non-O blood type was found to be independently associated with a significantly increased risk of VTE among patients undergoing radical cystectomy. Patients with non-O blood type may benefit from counseling and more comprehensive perioperative prophylaxis. _x000D_ Funding None.
Authors
Kayvan Kazerouni
Soroush T. Bazargani Gus Miranda Jie Cai Siamak Daneshmand Hooman Djaladat |
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MP21-17 |
Comparison of different lymph node staging schemes for predicting survival in patients following radical cystectomy for muscle-invasive bladder cancer |
Bladder Cancer: Invasive I | 17BOS |
Abstract: MP21-17 Sources of Funding: None Introduction Prior studies reported a novel prognostic indicator - log odds of positive lymph nodes (LODDS) might be superior to the number of lymph node metastases (LNMs) and positive lymph node density (LND) for prediction of prognosis in several gastrointestinal malignancies. Our aim was to, for the first time, evaluate the prognostic significance of LODDS in muscle-invasive bladder cancer (MIBC) and compare the performance to LNM and LND. Methods Patients with non-metastatic MIBC (T2-4N0-3M0) who underwent radical cystectomy (RC) were identified from the Surveillance, Epidemiology, and End Results (SEER) database. The primary outcome was cancer-specific survival (CSS). Univariable and multivariable Cox regression models with LNM, LND, or LODDS were analyzed. Multivariable models controlled for age, race, sex, grade, and T-stage. The prognostic performance of the models was assessed with Harrell&[prime]s concordance index (C-index) and Akaike&[prime]s Information Criterion (AIC). Results We identified 3,882 patients, 2,712 (69.9%) without LNM and 1,170 (20.1%) with LNM. Multivariable Cox models showed that increased LNM (HR = 1.057, 95% CI = 1.047-1.067, P < 0.001), increased LND (HR = 4.627, 95% CI = 3.836-5.582, P < 0.001), and increased LODDS (HR = 1.328, 95% CI = 1.286-1.373, P < 0.001) were all associated with decreased CSS. In multivariable regression the LODDS (C-index = 0.715; AIC = 21,239) was superior to LNM (C-index = 0.697; AIC = 21,410) and LND (C-index = 0.712; AIC =21,295). All the performance outcomes in each model before and after stratified with number of LNs removed are shown in Table 1. Scatter plots created to evaluate the relationship between LNM, LND, and LODDS are shown in Figure 1. For patients with LND scores of 0 or 1, LND can be stratified by LODDS. Conclusions LODDS appears to be a promising predictor of CSS in patients with MIBC following RC, especially those with an insufficient number of LNs removed. It could serve as an important adjunction to the traditional TNM and LND classification. Funding None
Authors
Leilei Xia
Jose Pulido Jeremy Bonzo Benjamin Taylor Thomas Guzzo |
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MP21-18 |
Post-therapeutic recovery of skeletal muscle mass predicts favorable prognosis in advanced urothelial carcinoma patients receiving 1st-line platinum-based chemotherapy |
Bladder Cancer: Invasive I | 17BOS |
Abstract: MP21-18 Sources of Funding: None Introduction Sarcopenia, loss of skeletal muscle mass (SMM), develops as a consequence of cancer-mediated systemic inflammation and cachexia. We recently reported that sarcopenia is an adverse prognostic factor in advanced urothelial carcinoma (aUC) patients (PLoS One 2015). Given that SMM can vary depending on disease status and patient conditions during treatments, changes in SMM may predict prognosis of patients. Here, we investigated the prognostic role of post-therapeutic recovery of SMM (PRS) in aUC patients receiving 1st-line platinum-based chemotherapy (Cx). Methods This retrospective study included 72 consecutive aUC patients (inoperable cT4 and/or metastases to lymph nodes/distant organs) receiving 1st-line platinum-based Cx (64, cisplatin-based; 8, carboplatin-based) at a single cancer center from 2004 to 2016. Variables collected were age, sex, performance status, body mass index (BMI) before Cx, changes in BMI after Cx, primary site, lymph node/distant metastasis, hemoglobin, white blood cell count, creatinine, albumin, alkaline phosphatase, lactate dehydrogenase, corrected calcium, C-reactive protein, and response to Cx according to RECIST v1.1. Skeletal muscle index (SMI) was calculated by skeletal muscle areas at L3 normalized for height on CT images taken at ≤1M before the initiation of and immediately after 2 cycles of Cx. Patients were considered to show PRS when SMI after Cx surpassed that before Cx. We assessed variables associated with progression-free survival (PFS) and overall survival (OS) using the Cox proportional hazards model. Results Of the 72 patients, 15 (21%) showed PRS. During follow-up (median 13M), 60 developed progression (3Y PFS rate 13%) and 55 died (3Y OS rate 16%). PRS was associated with Cx response with a marginal significance (p = 0.069). On multivariate analysis, PRS was an independent predictor for PFS (HR 0.33, p = 0.002) along with distant metastasis (HR 1.84, p = 0.032) and good Cx response (HR 0.44, p = 0.002). PRS was also an independent predictor for OS (HR 0.21, p < 0.001). The 3Y PFS and OS rates for patients with and without PRS were 49% vs. 4% and 57% vs. 5%, respectively (both p < 0.001). Conclusions PRS predicts favorable prognosis in aUC patients receiving 1st-line platinum-based Cx. Funding None
Authors
Hiroshi Fukushima
Yasukazu Nakanishi Madoka Kataoka Ken-ichi Tobisu Fumitaka Koga |
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MP21-19 |
Relationship between Postoperative Weight Loss Following Radical Cystectomy and oncological Outcomes |
Bladder Cancer: Invasive I | 17BOS |
Abstract: MP21-19 Sources of Funding: none Introduction Significant weight loss after surgery is reported to correlate with an increase in post-operative morbidity and mortality. However, there is limited evidence regarding the prevalence of weight loss in patients undergoing radical cystectomy (RC) for bladder cancer. We evaluated post-operative weight loss following RC and ileal neobladder construction, and examined possible association with overall survival outcomes. Methods Single institution retrospective observational analysis was performed of patients who underwent RC for muscle invasive bladder cancer, in whom pre- and postoperative weights were documented at regular intervals. Preoperative weight and post-operative weight at 1 week, and 1 month were examined, as well as demographic clinical information. We evaluated weight loss at 1 month, post-operative complications, and relationship between weight loss and prognosis. Overall survival in patients with significant weight loss (=<10% vs. >10%) was estimated using the Kaplan-Meier methods and compared with the log rank test. Risk factors for poor overall survival were determined by multivariate cox regression analysis. Results Between March 1996 and Dec 2013, we performed RC in 348 patients and 204 received orthotopic ileal neobladder construction. Of those, a total of 192 patients met the search criteria Weight loss greater than 10% at 1 month was used as the threshold to distinguish patients who had significant weight loss. Patients with significant weight loss had more high-grade complications (? Clavien grade 3) within 1 month (16%% vs 2%, P=0.014), and were significantly poor overall survival (P=0.004). Multivariate analysis showed positive lymph node (HR: 3.2, P=0.009) and postoperative weight loss greater than 10% at 1 month (HR: 3.9, P=0.003) were selected as independent risk factor for overall survival. Conclusions Patients experience 5% of weight loss following RC. Patients who experienced > 10% weight loss from baseline at 1 month had increased high-grade complications and experienced poor prognosis. Although the limitations of this study design prevent further understanding of cause and effect, perioperative nutritional optimization may prevent significant weight loss and/or improve outcomes. Funding none
Authors
Shingo Hatakeyama
Naoki Fujita Osamu Soma Teppei Matsumoto Takahiro Yoneyama Yasuhiro Hashimoto Takuya Koie Chikara Ohyama |
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MP21-20 |
The Impact of Plasmacytoid Variant Histology on Survival of Patients with Urothelial Carcinoma of Bladder after Radical Cystectomy |
Bladder Cancer: Invasive I | 17BOS |
Abstract: MP21-20 Sources of Funding: Supported in part by the Sidney Kimmel Center for Prostate and Urologic Cancers, funds from T32 CA082088, and P30 CA008748. Introduction To compare clinical outcomes of patients with any component of plasmacytoid variant(PCV) of urothelial carcinoma with that of patients with pure urothelial carcinoma (UC) treated with radical cystectomy (RC). Methods We identified 98 patients who had pathologically confirmed PCV on transurethral resection or RC and 1312 patients with pure UC and no variant history who underwent RC at our institution between January 1995 and December 2014. Univariable and multivariable Cox regression and Cox proportional hazards regression to determine if PCV histology was associated with overall survival (OS). Results Patients with PCV were younger (p=0.012), more likely to have advanced tumor stage (pT3/pT4, p=0.002), positive lymph nodes (p=0.038), and receive neoadjuvant chemotherapy than those with pure UC (45% versus 21%, p<0.0001). Rate of positive soft tissue surgical margins was over five times greater in the PCV group compared with the pure UC group (22% versus 4%, respectively, p<0.0001). Median OS for the pure UC group vs the PCV group were 8 and 3.8 years, respectively. On univariable analysis, PCV histology was associated with an increased risk of overall mortality (HR=1.34; 95% CI 1.02–1.78; p=0.039). However, on multivariable analysis adjusted for age, gender, neoadjuvant chemotherapy received, lymph node status, and pathologic stage, the association between PCV and OS was no longer significant (HR=1.13; 95% CI 0.84–1.51; p=0.4). Conclusions Patients with PCV features have higher disease burden at RC compared with those with pure UC. However, PCV was not an independent predictor of survival after RC on multivariable analysis, suggesting that PCV histology cannot be used as a prognostic factor. Funding Supported in part by the Sidney Kimmel Center for Prostate and Urologic Cancers, funds from T32 CA082088, and P30 CA008748.
Authors
Qiang Li
Melissa Assel Eugene Pietzak Daniel Sjoberg Harry Herr Machele Donat Eugene Cha Bernard Bochner Guido Dalbagni |
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MP22-01 |
Perioperative morbidity, oncological outcomes and predictors of pT3a upstaging for patients undergoing partial nephrectomy for cT1 tumors |
Kidney Cancer: Epidemiology & Evaluation/Staging I | 17BOS |
Abstract: MP22-01 Sources of Funding: None Introduction The question of whether upstaged and nonupstaged tumors have different outcomes continue to be discussed in the literature. Few published studies address this question, with a wide range of results. The aim of this study was to evaluate perioperative morbidity, oncological outcome and predictors of pT3a upstaging after partial nephrectomy(PN)._x000D_ Methods Retrospective study of 1042 patients who underwent PN for cT1 renal cell carcinoma between 2007 and 2015. A total of 113 cT1 patients were upstaged to pT3a, while 929 were staged pT1. Demographic, perioperative and pathological variables were reviewed. We compared the clinico-pathological characteristics, perioperative morbidity and oncological outcomes between pT3a and pT1 groups. Multivariate regression evaluates variables associated with T3a upstaging. Progression-free survival (PFS) and overall survival analyses were performed. Results pT3a tumors had a higher R.E.N.A.L score, higher hilar location, higher grade, and higher positive surgical margins. Patients with pT3a had a higher estimated blood loss, transfusion rate, ischemia time, overall complications, while there were no difference in median e-GFR decline and major (Grade III-V) complications. Five-year PFS was 78.5% for pT3a group, vs 94.6% for pT1 group (Log rank p <0.01). Male gender (OR 2.2, p<0.01), and R.E.N.A.L score (OR 2.3, p=0.01) were preoperative predictors of upstaging. Conclusions Perioperative morbidity is acceptable in pT3 tumors, however upstaged patients had a worse oncological outcomes. cT1/pT3a tumors are associated with adverse clinico-pathological features. Preoperative risk predictors of upstaging were, higher R.E.N.A.L score and male gender. Funding None
Authors
Pascal Mouracade
Onder Kara Julien Dagenais Matthew Maurice Ryan Nelson Ercan Malkoc Jaya Sai Chavali Jihad Kaouk |
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MP22-02 |
Synergistic prognostic impact of elevated de ritis ratio and RENAL score for prediction of survival outcomes in renal cell carcinoma after surgical treatment |
Kidney Cancer: Epidemiology & Evaluation/Staging I | 17BOS |
Abstract: MP22-02 Sources of Funding: Stephen Weissman Kidney Cancer Research Fund_x000D_ NIH grants UL1TR000100 and UL1TR001442 Introduction Renal Cell Carcinoma (RCC) is a metabolically driven neoplasm. Inflammatory markers and morphometric measures have been suggested to be predictive for prognosis. We investigated the impact of a novel combination of preoperative tumor morphology (RENAL score) and a laboratory based inflammatory marker (DeRitis Ratio, AST/ALT) on survival outcomes in localized RCC. Methods Single center, retrospective analysis of 524 patients with RCC (312 PN, 212 RN, mean follow up 35.8 months) from 2003-2015. A priori, we assigned a positive marker score of 1 if RENAL >8 or DeRitis >1.5. Patients were stratified by increasing positive markers (0=RENAL ≤8 and DeRitis ≤1.5, 1=RENAL >8 or DeRitis >1.5, 2=RENAL >8 and DeRitis>1.5). Primary outcome was overall survival (OS). Cox models and Kaplan-Meier curves were utilized. Results 524 patients, 68% male, mean age 64.8 ± 12.6 years, mean BMI 29.1 ± 6.5, mean DeRitis 1.1 ± 0.4. With regards to tumor characteristics, mean clinical tumor size was 4.8 ± 3.3cm and median RENAL score was 8 (IQR 6-10). For clinical staging, 74% were cT1, 19% cT2, and 6% were >T2. On Cox model for OS, RENAL >8 (HR 1.95, p=0.003) and DeRitis >1.5 (HR 3.74, p<0.001) were significantly associated with worsened survival. On Cox model output for OS and marker score, we found 1 marker (HR 1.83, p=0.011) and 2 markers (HR 7.68, p<0.001) were significantly associated with worsened survival (figure). Conclusions Novel combination of a morphological score (RENAL) and an inflammatory marker (DeRitis ratio) was associated with worsened OS in RCC after surgical treatment. Our findings point towards development and validation of a prognostic index to assist in risk stratification and follow up protocols for RCC. Funding Stephen Weissman Kidney Cancer Research Fund_x000D_ NIH grants UL1TR000100 and UL1TR001442
Authors
Aaron Bloch
Zachary Hamilton Charles Field Katherine Fero Sean Berquist Abd?elrahma Hassan Brittney Cotta Daniel Han Richmond Owusu Sunil Patel Fang Wan James Proudfoot Ithaar Derweesh |
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MP22-03 |
OFFICE-BASED ULTRASOUND GUIDED PERCUTANEOUS RENAL MASS BIOPSY |
Kidney Cancer: Epidemiology & Evaluation/Staging I | 17BOS |
Abstract: MP22-03 Sources of Funding: none Introduction We prospectively evaluated the feasibility, safety and efficacy of office-based, ultrasound-guided percutaneous renal biopsy (USPRB) of renal cortical neoplasms (RCN). Methods Patients with RCN were carefully selected based on tumor location to undergo office-based USPRB. Patients were instructed to apply EMLA cream to a defined area of the flank two hours before the procedure. Procedures were performed in a prone position. After the flank was prepared and draped, facilitated ultrasound targeting (FUT) technology was used to visualize the tumor. After injection of 1% lidocaine, an 18G biopsy needle was inserted through a needle guide on the transducer probe and advanced toward the RCN under US guidance; 3 to 5 cores were taken. US evaluation was then repeated one hour later to assess for hematoma prior to discharge home. We assessed patient pain on a ten-point scale (0 = no pain, 10 = severe pain) before and immediately after the procedure, and at the time of the follow-up, typically one week later. Patient demographics, tumor characteristics, complications, and histopathological diagnosis were recorded. Results A total of 40 patients with a mean age of 67 yrs. (range 43-89 yrs.) underwent renal biopsy. There were 21 (53.5%) males and 19 (46.5%) females. The mean tumor size was 3.6cm (range 1.6 - 6.3). The mean R.E.N.A.L. nephrometry score was 6 (4-12). Thirty two (80%) of the 40 biopsies were diagnostic. Diagnostic biopsies included 21 (52.5%) renal cell cancer and 11 (27.5%) patients with benign histopathology (7 oncocytomas and 4 angiomyolipomas). The patients with benign histopathology elected active surveillance. There were no complications during or after the biopsy procedure. None of the patients reported pain before the procedure. Median pain score immediately after the procedure was 1/10(0-3) and 0/10(0-5) at one hour after the procedure and 0 at three-week follow-up (p=0.657, 0=1.433). Based on histopathology (benign and indolent RCC sub-type), surgical intervention was averted in 42.5% of patients. Among the 8 patients with a non-diagnostic biopsy, all underwent a repeat CT guided biopsy. Of these, 4 were RCC subtypes and 1 remained non-diagnostic. Conclusions Urologist performed office-based, US guided renal biopsy of selected renal cortical neoplasms is feasible, safe and precludes surgical therapy in one fourth of patients. Funding none
Authors
Zhamshid Okhunov
Thomas Lee Victor Huynh Ralph V. Clayman Louis Kavoussi Jaime Landman |
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MP22-04 |
Racial disparities in the treatment and survival of metastatic renal cell carcinoma |
Kidney Cancer: Epidemiology & Evaluation/Staging I | 17BOS |
Abstract: MP22-04 Sources of Funding: none Introduction The treatment of patient with metastatic renal cell carcinoma (mRCC) has evolved significantly over the past decade. Access to newer systemic agents and cytoreductive nephrectomy (CN) may differ according to sociodemographic factors. We sought to evaluate racial disparities in the treatment of mRCC and if there is any difference in survival according to race. Methods We used the National Cancer Data Base (NCDB) to identify patients with mRCC at diagnosis between 1998 and 2012. Study period was dichotomized: the immunotherapy era (1998-2005) and the TT era (2006-2012). Race was categorized as non-Hispanic White (NHW), African American (AA), Hispanics and others. Multivariable logistic regression analyses predicting the receipt of CN, systemic therapy (ST) and metastatecomy (MTSX) adjusted for measured confounders were performed. Kaplan-Meier and Cox regression analyses were used to evaluate the difference in overall survival (OS) between races adjusting for patient and system characteristics. Results During the study period, we identified 50,764 patients with mRCC, of which 41,995 (83%), 5,238 (10%), 3,246 (6%) and 285 (1%) were NHW, AA, Hispanic or other race, respectively. NHW patients were more often older (p<0.001), had less comorbidities (p<0.001), were more often covered by private insurance (p<0.001) and less often treated in an academic center (p<0.001). On multivariable regression, compared to NHW, all races had lower odds of receiving CN (Odds Ratio [OR]= 0.54, 0.77, 0.45 for AA, Hispanics or other, respectively, all p<0.01). AA and Hispanic patients were less likely to receive MTSX (OR=0.65 and 0.80, p<0.001 and 0.04, respectively) and the gap was accentuated in the TT era. AA and Hispanics were less likely to receive ST (OR=0.72 and 0.82, respectively, both p<0.01). In adjusted OS analysis, AA had significantly worse OS compared to NHW (Hazard Ratio [HR]=1.25 95%CI 1.15-1.36, p<0.001). Conclusions Racial disparities in receipt of care for patients with mRCC exist and these differences are more pronounced in the TT era. These inequalities may explain why AA patients have worse survival than their NHW counterparts._x000D_ Funding none
Authors
Christian P. Meyer
Nawar Hanna Nicolas von Landenberg Philipp Gild Felix K.H. Chun Margit Fisch Mani Menon Steve L. Chang Philip Cheng Maxine Sun Quoc-Dien Trinh |
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MP22-05 |
Role of biopsy in management of large, locally advanced, and metastatic renal masses |
Kidney Cancer: Epidemiology & Evaluation/Staging I | 17BOS |
Abstract: MP22-05 Sources of Funding: none Introduction Few studies have evaluated the role of biopsy for large or high stage kidney tumors. The purpose of this study was to determine if pre-treatment biopsy changed management in patients with ≥cT2 renal masses. Methods Clinical and pathologic data were reviewed from patients who presented with ≥cT2 renal masses from 2010-2016. Routine biopsy technique included multiquadrant sampling of different regions within the tumor. Results From 2010-2016, 277 patients with ≥cT2 renal masses were identified; median tumor size was 8.8 cm (IQR 7.4-11 cm). Percutaneous biopsy was obtained prior to treatment in 150 (54.1%) patients and 127 (45.8%) patients were treated surgically without biopsy. Non-RCC tumors were identified in 21 (14%) of patients in the biopsy cohort and in 16 (12.6%) in the non-biopsy cohort (including angiomyolipoma, sarcomas, metastatic tumors, squamous cell carcinoma, cystic nephroma, Wilms&[prime] tumor, diffuse B-cell lymphoma, mixed epithelial and stromal tumor, Xanthogranulamatous Pyelonephritis and complex cysts). _x000D_ _x000D_ In non-RCC patients who received biopsy, 12 (57.1%) deferred upfront nephrectomy including those treated with neoadjuvant chemotherapy or radiation. For patients with metastatic RCC, 11 patients had sarcomatoid features identified on biopsy. Nine patients deferred upfront cytoreductive nephrectomy for systemic therapy or clinical trial. Six patients without metastatic disease had sarcomatoid features identified on biopsy. In 5/6 patients, more aggressive surgery including bilateral RPLND, was performed _x000D_ _x000D_ Overall, in 130 patients who were surgical candidates, the information gained from biopsy diagnosis changed management from standard upfront nephrectomy in 28 (22%) patients. These patients included 13 patients with non-RCC tumors, 9 patients with mRCC and sarcomatoid features who deferred cytoreductive nephrectomy, and 5 patients with non-metastatic RCC with sarcomatoid features who received more aggressive surgery. No Clavien 2 or greater complications were identified in patients following percutaneous biopsy. _x000D_ Conclusions Percutaneous biopsy changed management for 1 in 5 of patients with ≥cT2 renal masses by identifying non-RCC renal tumors and RCC with sarcomatoid features. Funding none
Authors
Amy H. Lim
Jennifer E. Heckman Timothy Ziemiewicz Sara Best Shane Wells Meghan Lubner James Louis Hinshaw Fred T. Lee Stephen Y. Nakada E. Jason Abel |
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MP22-06 |
The Impact of Quality Variation on Patients Undergoing Surgery for Renal Cell Carcinoma: A National Cancer Database Study |
Kidney Cancer: Epidemiology & Evaluation/Staging I | 17BOS |
Abstract: MP22-06 Sources of Funding: Princess Margaret Hospital Foundation Introduction Due to a paucity of real-world data benchmarking provider performance, it remains unclear whether all patients undergoing surgery for renal cell carcinoma (RCC) receive equivalent care. Consequently, the impact of quality variations on patient outcomes also remains elusive. Herein, we report the development and application of novel case-mix adjusted quality indicators (QIs) to benchmark nationwide hospital performance for RCC surgical care. Methods RCC patients undergoing surgery between 2004 and 2014 were identified from the National Cancer Database (NCDB). Hospital-level quality of care was assessed according to 2 disease-specific process QIs and 3 outcome QIs, selected based on Delphi consensus and literature review. Inter-hospital case-mix variation was adjusted for by multivariate modeling. For each hospital and given QI we calculated an observed to expected ratio, benchmarking hospital performance against the national average and identifying outlier hospitals providing sub-standard care. A composite measure of hospital quality, the renal cancer quality score (RC-QS), was subsequently derived and associations between RC-QS and surgical volume, academic affiliation and patient mortality were determined. Results Over 1100 hospitals were benchmarked for quality, with widespread hospital-level variation in performance observed across each QI. For a given QI, 9-35% of hospitals were identified as providing sub-standard care. Hospitals identified applying sub-standard care had lower referral volumes and were less academic as compared to higher quality hospitals (p < 0.001). Higher RC-QS was independently associated with lower 30-day, 90-day and overall mortality (OR [CI]: 0.95 [0.92-0.98], OR 0.94 [0.92-0.97], HR 0.97 [0.96-0.98] per unit increase, respectively). Conclusions Widespread variations in the quality of RCC surgery exist on a hospital-level. These variations can be captured by the RC-QS, a RCC specific composite measure of quality readily determined from the NCDB. Hospitals with good performance on the RC-QS are associated with improved patient outcomes, including mortality benefit. This data supports the use of the RC-QS as a national quality benchmarking tool for RCC surgery that provides audit level feedback to hospitals and policymakers for quality improvement. Funding Princess Margaret Hospital Foundation
Authors
Keith Lawson
Olli Saarela Robert Abouassaly Simon Kim Rodney Breau Antonio Finelli |
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MP22-07 |
Correlation of CAD Peak Lesion Enhancement with Quantitative Tumor Angiogenesis to Non-Invasively Assess Furhman Grades I-IV in Patients with Clear Cell Renal Cell Carcinoma |
Kidney Cancer: Epidemiology & Evaluation/Staging I | 17BOS |
Abstract: MP22-07 Sources of Funding: None Introduction To assess if Computer Aided Detection (CAD) of peak lesion attenuation discriminates among Fuhrman Grades I-IV and correlates with an increase in tumor angiogenesis in clear cell RCC (ccRCC) on four-phase MDCT. Methods We reviewed a cohort of patients with ccRCC and preoperative multiphasic multidetector CT imaged with a 4-phase renal mass protocol (unenhanced, corticomedullary (C), nephrographic (N), and excretory (E)). A whole lesion 3D contour was obtained in all phases with proprietary software. The CAD algorithm determined a 0.5cm diameter region of peak enhancement ≤300HU within the 3D lesion contour. For assessment of quantitative angiogenesis, immunohistochemical staining for CD34 to determine microvessel density (MVD) was performed. T-tests were used to compare peak multiphasic enhancement and microvessel density among Fuhrman grades I-IV. P values less than 0.05 were considered to be significant. Results 107 patients (71(64%) men and 40(35%) women) with 111 unique ccRCC lesions (16 (14%) Fuhrman grade I, 64 (58%) Fuhrman grade II, 23 (21%) Fuhrman Grade III, 8 (7%) Fuhrman grade IV) were analyzed. In the C phase, CAD peak lesion enhancement discriminated grade I from II (150 HU vs. 185 HU, p=0.006), I from III (150 HU vs. 178 HU, p=0.054), I from IV (150 HU vs 229HU, p<0.001). This directly correlated with an increase in quantitative angiogenesis (MVD): I from II (2134 mm2 vs. 4710 mm2, p=0.004), I from III (2134 mm2 vs. 5162 mm, p=0.001), I from IV (2134 mm2 vs 6076 mm2, p=0.057). Conclusions CAD peak lesion enhancement discriminates Fuhrman grades 1-IV on multiphasic CT and correlates with an increase in tumor angiogenesis. This may be helpful to triage patients to active surveillance, interventional therapy or, if validated, may be useful to monitor results with anti-angiogenic therapy. Funding None
Authors
Heidi Coy
Jonathan Young Michael Douek Matthew Brown Anthony Sisk James Sayre Steven Raman |
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MP22-08 |
ESTIMATED GLOMERULAR FILTRATION RATE: DO WE MEASURE THE REAL RENAL FUNCTION OR ARE WE STILL GROPING IN THE DARK? |
Kidney Cancer: Epidemiology & Evaluation/Staging I | 17BOS |
Abstract: MP22-08 Sources of Funding: NONE Introduction An accurate assessment of renal function is mandatory in the majority or urological and oncological patients to prevent renal impairment and cancer non-related deaths. Nowadays, the large part of clinicians apply CKD-EPI/MDRD formulas or 24h creatinine clearance to determine the glomerular filtration rate (GFR) before and after renal surgery (for cancer, donation, stones and pyelouretheral junction stenosis) and in metastatic patients for establish the right oncological treatment. Unfortunately, estimated GFR (eGFR) displays a wide error in reflecting real kidney function with measured GFR (mGFR) and this may lead to important consequences in the correct evaluation of patients. Methods A retrospective and prospective study based on 200 pts composed by 150 pts with uro-oncological cancer or renal functional diseases (UOCRD) and 50 kidney donors (KD) was performed in two different centers to compare eGFR formula with renal scintigraphy (N=150) or iohexol clearance (N=50). The agreement between eGFR and mGFR was evaluated using total deviation index (TDI) and concordance correlation coefficient (CCC). Results The agreement between formulas and mGFR was poor. The TDI for MDRD was 83% and for CKD-EPI was 76%, indicating that 90% of the estimations for both formulas were included within a margin of error from mGFR of about ± 76 to 80%. CCC for MDRD was 0.74 and for CKD-EPI was 0.78, indicating poor concordance between eGFR and mGFR. UOCRD population, using eGFR formulas (CKD-EPI/MDRD), was composed by 28%-21% of CKD stage I pts (eGFR > 90 ml/min), 38 %-41% CKD stage II, 7%-13% CKD stage IIIa, 16%-15% CKD stage IIIb, 9%-8% CKD stage IV, 2%-2% CKD stage V. Using Renal Scintigraphy measurements, we revealed these different proportions: 37% CKD I, 26% CKD II, 17% CKD IIIa, 15 % CKD IIIb, 9% CKD IV, 0% CKD V. Moreover, the discrepancy between mGFR with renal scintigraphy and eGFR with formulas was of 57% in CKD I, 23% in CKD II, 72% in CKD IIIa, 47% in CKD IIIb, 50% in CKD IV, 100% in CKD V stage. KD population presented eGFR > 90 ml/min with formulas for each pts; after iohexol measurement, 5 patients displayed mGFR lower than 70 ml/min Conclusions CKD-EPI and MDRD formulas may over or underestimate mGFR in more than 50% of pts, generating false evaluations in the clinical management and drug therapies for oncological, urological and kidney donor patients. We suggest to use a gold standard technique of mGFR (eg renal scintigraphy, iohexol measurement) in selected cases when GFR is crucial to determine the surgical/therapeutic approach. Funding NONE
Authors
FRANCESCO TREVISANI
UMBERTO CAPITANIO ALESSANDRO LARCHER LUIGI GIANOLLI ALESSANDRA CINQUE ARIANNA BETTIGA RICCARDO VAGO LINA BUA CRISTINA CARENZI FABIO BENIGNI FABIO MUTTIN ROBERTO BERTINI ANDREA SALONIA ALBERTO BRIGANTI NATALIA NEGRIN ANA GONZALES RINNE ARMANDO TORRES SERGIO LOUIS LIMA ESTEBAN PORRINI FRANCESCO MONTORSI |
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MP22-09 |
Diagnostic needle biopsies in renal masses: patient and physician perspectives |
Kidney Cancer: Epidemiology & Evaluation/Staging I | 17BOS |
Abstract: MP22-09 Sources of Funding: None Introduction The utility of renal mass biopsies (RMB) in the diagnosis and management of kidney tumors remains debatable. We assessed the patients and urologists preferences in this regard. Methods Seventy-three patients diagnosed with renal tumors and 59 board-certified urologists were asked to participate in an interview-based study. Decision analysis was quantified using the standard gamble method to determine the minimal accepted accuracy (MAA) at which RMB would be favored as part of the diagnostic process. Clinical and demographic data with potential to affect participants preferences were analyzed. Results At the time of study interview, 56 patients (77%) were referred for kidney surgery and 17 (23%) opted for surveillance. Overall, 59% of the patients were willing to accept some level of inaccuracy (1-20%), whereas 41% would refute a biopsy irrespective of their designated treatment. Anxiety associated with the possibility of missing cancer was the primary determinant (70%) for declining RMB among patients referred for surgery while fear of biopsy-associated complications was the primary reason (58%) to decline RMB among those undergoing surveillance. Having an academic degree was associated with acceptance of a lower accuracy threshold (p=0.03). Of the 59 participating urologists, 39% were reluctant to recommend RMB, primarily because of its inexorable non-diagnostic rate. Conclusions Most patients and urologists would favor a RMB to facilitate their definitive treatment decision. Diagnostic accuracy of 95% was acceptable by the majority of study participants. The utility of RMB as part of the diagnostic algorithm for renal tumors should be discussed with patients, emphasizing its potential benefits and limitations. Funding None
Authors
Shay Golan
Paz Lotan Shlomi Tapiero Jack Baniel Andrei Nadu Ofer Yossepowitch |
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MP22-10 |
Comparative analysis of preoperative inflammatory markers for oncologic and renal functional outcomes after surgical treatment of renal cell carcinoma |
Kidney Cancer: Epidemiology & Evaluation/Staging I | 17BOS |
Abstract: MP22-10 Sources of Funding: Stephen Weissman Kidney Cancer Research Fund. NIH grants UL1TR000100 and UL1TR001442. Introduction Neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), De Ritis Ratio (AST/ALT), and C-reactive protein (CRP) are inflammatory markers with varying predictive ability of treatment outcomes in malignancy. We sought to evaluate the utility of these markers for oncologic and renal functional outcomes in patients who have undergone partial or radical nephrectomy for suspected renal cell carcinoma (RCC). Methods Single center, retrospective analysis 945 patients from 2003-2016 (494 PN, 451 RN, mean follow up 41.9 months). Primary outcome was de novo estimated Glomerular Filtration Rate (GFR<45 ml/min/1.73m2) at last follow up Secondary outcomes included overall survival (OS) and recurrence. Kaplan Meier (KM) and multivariate analysis (MVA) were utilized to evaluate association of preoperative markers (NLR, PLR, De Ritis Ratio, CRP) with outcomes. Predetermined cutoffs of NLR >3, PLR >185, De Ritis >1.5, and CRP >3 were used. Results MVA for GFR <45 noted De Ritis ratio (HR 1.99, p<0.01), hypertension (HR 1.69, p=0.02), and coronary artery disease (HR 1.81, p<0.01). Cox model results using predetermined cutoffs for GFR<45 was significant for NLR (HR 2.09, p<0.01), PLR (1.88, p=0.01), and De Ritis (2.24, p<0.01). MVA for worsened OS noted CRP (HR 1.26, p<0.01) and RN (HR 6.99, p<0.01). Cox model results using predetermined cutoffs for OS was significant for NLR (HR 2.24, p=0.049), De Ritis (HR 3.92, p<0.01), and CRP (HR 4.0, p<0.01). Preoperative markers were not associated with recurrence on MVA. Conclusions De Ritis ratio and comorbid conditions are independent predictors of GFR <45, while CRP and RN are predictive of worsened OS. Using predetermined cutoffs of NLR >3, PLR >185, De Ritis >1.5, and CRP >3 shows significant associations for NLR, PLR, and De Ritis for GFR <45 and NLR, De Ritis, and CRP for worsened OS. Our data suggest a focus on these markers for development of prognostic models. Further investigation is requisite to validate our findings. Funding Stephen Weissman Kidney Cancer Research Fund. NIH grants UL1TR000100 and UL1TR001442.
Authors
Charles Field
Zachary Hamilton Aaron Bloch Katherine Fero Daniel Han Richmond Owusu James Proudfoot Ithaar Derweesh |
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MP22-11 |
Performance of Multiparametric Magnetic Resonance Imaging to Identify Clear Cell Renal Cell Carcinoma in cT1a Renal Masses |
Kidney Cancer: Epidemiology & Evaluation/Staging I | 17BOS |
Abstract: MP22-11 Sources of Funding: Partially funded by grant 5RO1CA154475 Introduction Detection of small renal masses (SRM) is increasing with the use of cross-sectional imaging, although many incidental lesions have negligible metastatic potential. Among common malignant masses, clear cell renal cell carcinoma (ccRCC) is the most prevalent and aggressive subtype, and a method to identify such histology would aid in risk stratification. Our goal was to evaluate a likelihood scale for multiparametric magnetic resonance imaging (mpMRI) in the diagnosis of clear cell histology. Methods Patients with cT1a masses who underwent mpMRI (T2-, chemical shift T1-, and contrast-enhanced T1-weighted imaging) and partial or radical nephrectomy from December 2011 to July 2015 were retrospectively reviewed. Seven radiologists with different levels of experience and blinded to final pathology independently reviewed studies based on a predefined algorithm, and applied a clear cell likelihood score (ccLS, 1-5): 1) definitely not, 2) probably not, 3) equivocal, 4) probably, and 5) definitely. Receiver operating characteristic (ROC) analysis determined the accuracy of ccRCC versus 'all other' histologies, and inter-observer agreement was calculated with a weighted &[kappa] statistic. Results In total, 110 patients with 121 cT1a renal masses were identified. Mean tumor size was 2.4cm and 50% were ccRCC. Figure 1 summarizes classification of the entire cohort. Defining ccRCC as ccLS 4-5 lesions demonstrated overall mean accuracy of 79%, sensitivity of 78%, specificity of 80%, positive predictive value (PPV) of 80%, and negative predictive value (NPV) of 80%. Including ccLS 3 lesions changed the mean accuracy to 77%, sensitivity to 95%, specificity to 58%, PPV to 70%, and NPV to 93%. ROC analysis calculated an area under the curve (AUC) range from 0.82-0.92 for the seven radiologists, and inter-observer agreement was moderate to good with a mean &[kappa] of 0.53. Of ccLS 4-5, 4.5% and 1.7% were false positive oncocytoma and angiomyolipoma, respectively, while 6% of ccRCC was false negative ccLS 1-2. Conclusions mpMRI can reasonably identify ccRCC histology in cT1a renal masses, and may reduce the number of patients who undergo routine biopsy of SRM. Standardization of imaging protocols and reporting criteria are needed to improve inter-observer reliability, and prospective studies are required to validate these findings. Funding Partially funded by grant 5RO1CA154475
Authors
Noah Canvasser
Fernando Kay Yin Xi Daniella Pinho Daniel Costa Alberto Diaz de Leon Gaurav Khatri John Leyendecker Takeshi Yokoo Aaron Lay Nicholas Kavoussi Ersin Koseoglu Jeffrey Cadeddu Ivan Pedrosa |
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MP22-12 |
Postoperative Outcome of Cystic Renal Cell Carcinoma Defined on Preoperative Imaging: A Retrospective Study |
Kidney Cancer: Epidemiology & Evaluation/Staging I | 17BOS |
Abstract: MP22-12 Sources of Funding: none Introduction To evaluate postoperative outcome of cystic renal cell carcinoma (RCC) defined on preoperative computed tomography (CT), and to find the optimal cut-off of cystic cystic proportion in association with patients’ prognosis. Methods In this institutional review board-approved study with waiver of informed consent, a total of 1315 patients who received surgery for single RCC with pre-operative CT were enrolled. The cystic proportion of RCC was determined on CT. The optimal cut-off of cystic proportion was explored regarding cancer-specific survival. The RCCs were categorized as cystic or non-cystic RCCs according to conventional (i.e. cystic proportion ? 75%) and the optimal cut-off, and then post-operative outcomes were compared between the two groups. Multivariate Cox regression analysis was performed to determine the independent predictor for cancer-specific survival. Results Of the 1315 lesions, 107 (8.1%) were identified as cystic RCCs according to a conventional cut-off. Postoperative outcome of cystic RCC was significantly better than that of non-cystic RCC (P<0.001). Neither metastasis nor recurrence in patients with cystic RCC was developed after surgery. In association with cancer-specific survival rate, the optimal cut-off of cystic proportion was 45%, and 197 (15.0%) were defined as cystic RCCs accordingly. On Cox regression analysis, cystic proportion ? 45% in RCC was an independent predictor of favorable outcome regarding cancer-specific survival (hazard ratio 0.34, P = 0.03). Conclusions Cystic RCC defined on preoperative CT is associated with low metastatic potential and favorable outcomes after surgery. Particularly, cystic proportion ? 45% is an independent prognostic factor for favorable survival. Funding none
Authors
Taesoo Choi
Jun Phil Na CHUNG UN LEE Hyunwoo Chung SEUNGHEE YUM Hyun Hwan Sung Hwang Gyun Jeon Seong Il Seo Seong Soo Jeon Hyun Moo Lee Han Yong Choi Chan Kyo Kim Byong Chang Jeong |
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MP22-13 |
Clinical and Pathologic Characteristics of Early Onset Renal Cell Carcinoma |
Kidney Cancer: Epidemiology & Evaluation/Staging I | 17BOS |
Abstract: MP22-13 Sources of Funding: none Introduction Based on studies from the SEER database, renal cell carcinoma (RCC) is considered early onset in adults ≤ 46 years of age. Limited data exists regarding patients with early onset RCC. Our objective was to investigate the clinical and pathologic characteristics within this unique subset of patients with RCC. Methods We retrospectively reviewed our surgical pathology database from 2011-2016 for patients with RCC. The clinical and pathologic characteristics of patients ≤ 46 years were compared to the overall population. Results We identified 98/604 (16%) cases of RCC in patients ≤ 46 years. The median age of patients with early onset RCC compared to our control group was 38.6 (range 19-46) vs. 64.4 (range 47-89) years, respectively. Early onset RCC patients included Caucasians (55%), African Americans (40%), Latino (4%), and Asian (1%). Histologic subtypes, included clear cell (54%), papillary (29%), unclassified (7%), chromophobe (5%), clear cell papillary (3%), multilocular cystic neoplasm (1%), and carcinoid (1%). 20/28 (71%) of early onset papillary RCCs occurred in African Americans. Risk factors for RCC included hypertension (47%), smoking (22%), obesity (12%), diabetes mellitus (9%), and chronic kidney disease (CKD) or end-stage renal disease (ESRD) (16.3%). Known genetic syndromes prior to diagnosis were identified in 7/98 (7%) patients (1 Von Hippel Lindau, 2 Familial Adenomatous Polyposis, 1 Marfan, 1 Tuberous Sclerosis, 1 Birt-Hogg-Dube). There was no significant difference between the two groups in terms of tumor size, focality, margin status, presence of necrosis, or sarcomatoid features. Non-Caucasians were more likely to develop early onset RCC (OR 1.98; p=0.001). Patients with early onset RCC were more likely to receive a radical nephrectomy (OR 1.98; p=0.001), have lower grade tumors (OR 0.69; p=0.033) and present with organ confined disease (p=0.008). Conclusions Despite having more indolent tumor characteristics and organ confined disease, early onset RCC patients were more likely to undergo a radical nephrectomy. In addition, a high percentage of these patients had either concurrent, or risk factors for developing, CKD/ESRD. These findings suggest that this population is potentially being over treated and should undergo nephron sparing surgery if surgically feasible. Funding none
Authors
Win Shun Lai
Tyler Clemmensen Ava Saidian Soroush Rais-Bahrami Jennifer Gordetsky |
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MP22-14 |
Preoperative haematological parameters as predictors of long-term survival in renal cell carcinoma |
Kidney Cancer: Epidemiology & Evaluation/Staging I | 17BOS |
Abstract: MP22-14 Sources of Funding: None Introduction The impact of cancer-related inflammation pathway as a proxy of aggressiveness is well known in several cancers. In the field of renal cell carcinoma (RCC), it has been already proposed the effect of pre-treatment neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio (LMR) and platelet-lymphocyte ratio (PLR) on survival after nephrectomy. No data is available as regards the potential impact of platelet to haemoglobin ratio (PHR). We aimed to systematically test and compare the prognostic effect of all those preoperative haematological parameters on long-term survival in renal cancer patients. Methods We evaluated 870 patients diagnosed with cM0 RCC and treated with partial or radical nephrectomy at a single institution. Routine laboratory measurements were performed preoperatively the day before surgery. Univariable and multivariable Cox proportional hazards regression models were used to predict cancer specific mortality (CSM) and overall mortality (OM). Covariates included age at surgery, gender, pathological T and N stage, Fuhrman grade, lymph vascular invasion, tumor size, Charlson Comorbidity Index, presence of symptoms and tumour necrosis. Results Median age was 63 years (range 21-89 years). Overall, preoperative median NLR, LMR, PLR and PHR were respectively 2.23 (range 0.3 - 75.2), 3.5 (range 0.2 - 24), 121 (range 16.26 - 946) and 15.88Â (range 1.79 - 79.21). Median follow-up was 72 months (range 10 - 90). At univariate analysis NLR (HR 1.30, p=0.01, AUC 66%), and PHR (HR 1.07, p<0.001, AUC 77%) were associated with higher risk of CSM; conversely, LMR (HR 0.30, p<0.001, AUC 62%) and PLR (HR 0.92, p<0.001, AUC 60%) were inversely associated with CSM. Considering OM, NLR (HR 2.06, p<0.001, AUC 60%) and PHR (HR 1.07, p<0.001, AUC 66%) were directly associated; conversely, LMR (HR 0.38, p<0.001, AUC 63%) was inversely associated with OM. No correlation was found between PLR and OM. At multivariate analyses, NLR (HR 1.59, p<0.001), PHR (HR 1.1, p<0.001) and LMR (HR 0.25, p<0.001) resulted independent predictors of OM. With respect to CSM, NLR (HR 1.77, p<0.001), PHR (HR 1.11, p<0.001) LMR (HR 0.15, p<0.001) and PLR (HR 0.31, p<0.001) resulted independent predictors. Conclusions We validated the role of cancer-related inflammation pathway in predicting CSM and OM according to different haematological parameters. Based on previous investigation supporting the prognostic role of anaemia and thrombocytosis, we tested the effect of PHR that emerged the most accurate predictor of CSM. Funding None
Authors
Giovanni La Croce
Fabio Muttin Alessandro Larcher Paolo Dell’Oglio Alessandro Nini Francesco Ripa Ettore Di Trapani Cristina Carenzi Federico Dehò Vincenzo Mirone Patrizio Rigatti Francesco Montorsi Roberto Bertini Umberto Capitanio |
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MP22-15 |
Renal Mass Size and Synchronous Metastatic Disease in Renal Cell Carcinoma: an Analysis of the National Cancer Database |
Kidney Cancer: Epidemiology & Evaluation/Staging I | 17BOS |
Abstract: MP22-15 Sources of Funding: none Introduction Introduction: The likelihood of metastatic disease with small renal masses (SRM) (≤3cm) is controversial. We sought to determine the risk of synchronous disease at the time of renal cell carcinoma (RCC) diagnosis. Methods Years 2004?2013 of the National Cancer Database (NCDB) were used to identify Renal Parenchymal Neoplasms. Patients were stratified by renal mass size in 1cm increments, starting at 1cm. Both clinical and pathologic nodal and metastatic disease were included. Additional variables including age, gender, race, tumor histology, grade, and treatment were analyzed. Logistic regression was performed to measure the association between tumor size and synchronous metastatic disease. Results Between 2004 and 2013, there were 328,467 cases with 45,510 (13.9%) presenting with synchronous metastases. 2.9% of patients with a SRM presented with metastatic disease (nodal or distant). Among patients with a tumor 1-2cm, 2-3cm, and 3.1-4.0cm the incidence of M1 disease at diagnosis was 2.8%, 2.7%, and 5.1%, respectively. In the cohort, 22,488 (6.8%) had pathologic metastatic disease, while 37,799 (11.5%) had clinical metastatic disease (Fig 1). Metastatic sites included lung (17.6%), bone (13.2%), liver (6.1%), and brain (3.6%). Patients with metastatic disease were more likely to be male (16.3% vs 13.6%, p<0.0001) and have a left renal mass (15.0% vs 13.4%, p<0.0001). On multivariate analysis, each 1cm size increment was associated with a corresponding increase in risk of metastatic disease. Compared to a 1.1?2.0cm mass, those with a mass >10cm were significantly more likely to have metastatic disease (OR: 19.8, p<0.0001). Increasing age (OR: 1.006), male gender (OR: 1.14), left side tumor (OR: 1.13) and poorly differentiated or anaplastic tumor grade (OR: 3.3 & 7.7 respectively) were also independently associated with increased odds of metastatic disease (all p<0.0001). Conclusions Renal mass size is associated with the presence of synchronous disease. In SRM, metastatic disease is present in approximately 3% of cases. This information may be used for risk stratification and patient counseling. Funding none
Authors
Mary E. Westerman
Vidit Sharma Bimal Bhindi Stephen A. Boorjian R. Houston Thompson Bradley C. Leibovich Matthew K. Tollefson |
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MP22-16 |
Cytoreductive partial nephrectomy for small primary tumors improves overall survival in metastatic kidney cancer |
Kidney Cancer: Epidemiology & Evaluation/Staging I | 17BOS |
Abstract: MP22-16 Sources of Funding: H&H Lee Surgical Resident Research Scholarship Introduction Cytoreductive radical nephrectomy (RN) improves survival in select patients with metastatic renal cell carcinoma (mRCC). For smaller primary tumors, however, it is unknown whether cytoreductive partial nephrectomy (PN) compromises oncologic efficacy. Our objective was first to evaluate whether the size of the primary tumor is associated with overall survival (OS) in mRCC. Second, we sought to evaluate whether PN had equivalent OS compared with RN in patients with small primary tumors. Methods We queried the National Cancer Database from 2004-2013 and identified patients who underwent cytoreductive PN or RN for mRCC. Tumor size was categorized as T1a, T1b, and T2a. Rates of cytoreductive PN were analyzed over time. Descriptive statistics were used to compare patient demographics and tumor characteristics by surgical procedure (PN vs. RN) and tumor size. Kaplan-Meier survival analysis was used to compare OS. Multivariable Cox proportional hazards models were used to determine the effect of surgery type on OS._x000D_ Results A total of 4,464 patients met our inclusion criteria, with 94.4% undergoing a RN and 5.6% undergoing a PN. Rates of cytoreductive PN increased over time from 3.2% in 2004 to 9.4% in 2013. One-year OS was 71.3%, 69.2%, and 61.7% in patients with T1a, T1b, and T2a primary tumors, respectively (log rank test: p<0.001). In a multivariable model controlling for age, Charlson-Deyo score, histology, receipt of systemic treatment, metastasis location, and surgical procedure, T2a was a predictor of worse OS (HR 1.2, 95% CI 1.07-1.33). OS was then evaluated in patients who received a PN vs. RN in the entire cohort, as well as within each primary tumor T-stage (Figure 1). Patients who underwent PN had significantly improved OS, which was significant for T1a and T1b tumors (p<0.01) but not for larger T2a tumors (p=0.74). This was maintained in a Cox multivariable model. Conclusions In patients with mRCC undergoing cytoreductive nephrectomy, primary tumor size affects OS. PN was associated with longer OS in select groups of patients with small primary tumors. Further studies are needed to establish patient selection criteria in order to optimize the surgical care of patients with mRCC. Funding H&H Lee Surgical Resident Research Scholarship
Authors
Andrew Lenis
Amir Salmasi Izak Faiena Nicholas Donin Alexandra Drakaki Arie Belldegrun Allan Pantuck Karim Chamie |
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MP22-17 |
The metastatic potential of renal tumors: influence of histologic subtypes on definition of small renal masses, risk stratification, and future active surveillance protocols |
Kidney Cancer: Epidemiology & Evaluation/Staging I | 17BOS |
Abstract: MP22-17 Sources of Funding: none Introduction The influence of histology in metastatic potential is often overlooked when discussing the management options of small renal masses (SRM), with size or growth rate often serving as the triggers for the intervention. We aim to re-examine the definition of a SRM by evaluating the metastatic potential of renal masses incorporating tumor size and histology to create metastatic risk tables. Methods SEER-18 registries database was queried for all cases of clear cell, papillary, and chromophobe RCC diagnosed between 2004 and 2012. There were 55,478 cases identified that included 43,783, 8,587, and 3,208 cases of clear cell, papillary and chromophobe, respectively. Tumors were stratified using 1 cm increments to determine the metastatic potential by calculating the metastatic rate at presentation for different size intervals in histologic categories. Results For all three histologies, tumors 5 cm or less had a rate of metastatic RCC at presentation of less than 4%. The metastatic potential was highest for clear cell, followed by papillary and then chromophobe tumors. Setting a cutoff of no more than 3% for metastatic potential to be called a SRM, makes clear cell carcinoma and papillary carcinoma a SRM up to 4 cm, while the chromophobe RCC would be considered a SRM up to 7 cm. Conclusions While clinical staging and tumor size have been the key determinants in decision-making of patients with solid renal tumors, the histology-specific risks of metastatic potential are different for each mass. The definition of a SRM should be based on the metastatic potential and not on tumor size alone. This information could be helpful for counseling and managing patients with SRMs, as well as modifying active-surveillance protocols. Funding none
Authors
Michael Daugherty
Dillon Sedaghatpour Oleg Shapiro Srinivas Vourganti Alexander Kutikov Gennady Bratslavsky |
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MP22-18 |
Contemporary incidence and epidemiologic trends of brain metastases at renal cell carcinoma diagnosis |
Kidney Cancer: Epidemiology & Evaluation/Staging I | 17BOS |
Abstract: MP22-18 Sources of Funding: none Introduction The incidence of brain metastases in patients with renal cell carcinoma (RCC) is hypothesized to have increased in the last two decades. Our objective was to provide an overview of recent incidence trends in patients with primary renal cell carcinoma (RCC) and brain metastases at diagnosis using a nationally representative cancer cohort originating from the United States. Secondary objectives include developing a tool for prediction of brain metastases at diagnosis and to assess their oncological outcomes, and externally validating it in second database._x000D_ Methods All patients with a primary diagnostic confirmation of RCC within the Surveillance, Epidemiology, and End Results (SEER, 2010-2013) database and the National Cancer Database (NCDB, 2010-2012) were abstracted. The incidence proportions (%IP) and 95% confidence intervals (CI) of brain metastases were calculated overall and according to patient, sociodemographic, and disease characteristics. A 1000-bootstrap corrected multivariable logistic regression models was developed for prediction of brain metastases at diagnosis using the SEER cohort (development). Backward variable selection was conducted to identify the most parsimonious model. Model performance was evaluated via measures of predictive accuracy in the NCDB cohort (validation). Results The overall %IP of brain metastases at RCC diagnosis was 1.51% (95% CI: 1.39-1.64) in the SEER and 1.37% (95% CI: 1.29-1.45%) in the NCDB. The odds of harbouring brain metastases at RCC diagnosis varied significantly according to sociodemographic and clinical characteristics. Following backward variable selection within the SEER database, only histology, tumor size, and cN stages were retained in the final model. Predictive accuracy was adequate in the external validation cohort (C-statistic: 0.778). Median time to any death was 6.37 months in patients with brain metastases. After adjusting for confounders, patients with brain metastases were more likely to succumb to any death than those without brain metastases at diagnosis (hazard ratio: 1.87, 95% CI: 1.71-2.05, P<0.001). Conclusions The incidence of brain metastases in patients with RCC is increasing. The oncological outcomes of such patients remain poor and their treatment management variable. A clinical risk model including cN-stage, histology and tumor size can predict the presence of brain metastases at diagnosis and may justify baseline imaging in asymptomatic but high-risk patients. Funding none
Authors
Nicolas von Landenberg
Philipp Gild Maxine Sun Guillermo DeVelasco Priscilla K Brastianos Mani Menon Joachim Noldus Paul L. Nguyen Quoc-Dien Trinh Toni K. Choueiri |
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MP22-19 |
Allogeneic Blood Transfusion is Associated with Increased Mortality and Infectious Complications After Nephroureterectomy |
Kidney Cancer: Epidemiology & Evaluation/Staging I | 17BOS |
Abstract: MP22-19 Sources of Funding: None Introduction Allogeneic blood transfusions (ABT) may have an immunosuppressive effect on patients via transfusion-related immunomodulation, particularly in patients undergoing cancer surgery. Prior studies have demonstrated strong causality data among patients with colorectal, lung, and hepatobiliary cancers, however the existing data remains mixed in renal malignancies. We examined whether ABT’s increase the risk of mortality and complications (including perioperative infections) after open and minimally invasive nephroureterectomy. Methods We used the National Surgical Quality Improvement Program (2010 to 2013) to study the use of ABT as well as identify the rate of post-operative mortality and complications. Subgroup analysis of infectious complications assessed surgical site infection, pneumonia, abscess, urinary tract infection, and sepsis. We examined the association between ABT and mortality, any perioperative complications, and infectious complications after controlling for potential confounders (ASA status, age, race, diabetes, and operative time). Results We identified 1,691 nephroureterectomies (534 open, 1157 minimally invasive) performed during the study period. The rate of ABT was 23.6% for open and 8.64% for minimally invasive (13.4% overall). Patients who received an ABT had an increased risk of mortality (5.39% vs 1.09%, p < 0.001), any perioperative complication (30.53% vs 9.97%, p < 0.001), and infectious complications (13.72% vs 4.64%, p < 0.001). After adjusting for potential confounders, ABT remained an independent predictor for all complications, infectious complications, and mortality (p < 0.001). Conclusions This analysis supports the concept that ABTs are independently associated with an increased risk of perioperative complications, particularly infectious ones. Urologists should use evidence-based “restrictive� transfusion thresholds to minimize perioperative morbidity and mortality ABTs when performing nephroureterectomy. Funding None
Authors
Michael Lam
Nicholas Chakiriyan Ann Martinez-Acevedo Christopher Amling Jen-Jane Liu |
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MP22-20 |
Abnormal Lab Values in Patients Undergoing Surgery for Localized Renal Cell Carcinoma: Prevalence and Effect on Postoperative Complications |
Kidney Cancer: Epidemiology & Evaluation/Staging I | 17BOS |
Abstract: MP22-20 Sources of Funding: None Introduction Paraneoplastic syndromes are present in about 20% of renal cell carcinoma (RCC) cases and are associated with poor oncologic outcomes. These data, however, are based on single institution studies and it is unknown if abnormal preoperative lab values are associated with postoperative complication rates. We sought to characterize abnormal lab values suggestive of paraneoplastic syndromes in patients undergoing surgery for RCC and evaluate their association with postoperative complications. Methods Using the National Surgical Quality Improvement Program (NSQIP) database, we identified all patients having surgery for RCC from 2005-2014. We queried Participant User Files with ICD-9 codes for RCC (189.00) and CPT codes for partial or radical nephrectomy (50220, 50225, 50230, 50240, 50543, 50545, 50546) selecting localized disease. We identified abnormal preoperative lab values consistent with paraneoplastic syndromes and categorized renal function by chronic kidney disease (CKD) stage. Normal lab reference ranges were defined using data from the National Library of Medicine where ranges delimit 2 standard deviations (SD) of the mean value. We used logistic regression to test if abnormal preoperative lab values were associated with postoperative complications, including postoperative transfusion, readmission and death. We extended the normal range of lab values to 3SD of the mean for a sensitivity analysis. Results A total of 12,986 patients were identified. At least 1 lab abnormality suggestive of a paraneoplastic syndrome was identified in 46% of patients (Table 1) and CKD stage >3 was found in 27% of patients. On multivariate analysis, the presence of a preoperative lab abnormality was associated with an increased odds of postoperative transfusion (OR [95% CI]: 2.84 [2.47-3.25], p<0.01), readmission (1.31 [1.09-1.58], p<0.01) and death (2.42 [1.25-4.70], p<0.01) controlling for patient and surgical factors. When we extended the range of normal to 3SD, 29% had abnormal labs and our conclusions were unchanged. Conclusions About one half of patients presenting for surgery for RCC have abnormal lab values suggestive of paraneoplastic syndromes. These patients may be at increased risk of postoperative events including bleeding, readmission, and death. Funding None
Authors
Michael J Lipsky
Christopher B Anderson |
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MP23-01 |
Human urine-derived stem cells lessen inflammation and fibrosis within kidney tissue in a rodent model of aging-related renal insufficiency |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Kidney & Bladder II | 17BOS |
Abstract: MP23-01 Sources of Funding: Wake Forest University Health Sciences, Internal funding via Pilot Award from the Hypertension & Vascular Research Center_x000D_ _x000D_ Introduction Kidney function declines with age; older adults have renal function only 50-60% that of healthy young people. Most older patients have some degree of impaired renal function after renal surgery. Cell-based therapy is a promising alternative method to restore renal function in the treatment of chronic renal insufficiency. The goal of this study is to determine whether human urine-derived stem cells (USCs) can prompt renal tissue remolding in a rodent model of age-related kidney insufficiency. Methods Urine samples were obtained from healthy men (n=6, 28-35 years old). USCs were isolated and expanded at passage 5. Eighteen male SD rats (50-62 week old) with renal insufficiency (increased levels of urine protein and serum creatinine) were divided into 3 groups (G). G1, animals received 5 intravenous cell implantations of 2 x106 cells/0.2 ml serum-free medium /rat/time period weekly; G2, as in G1 but intraperitoneally delivered; G3, as in G1 but serum-free medium alone. Healthy male SD rats at the same age were controls. Results Cultured USCs secreted >20 kinds of trophic factors, including high levels of matrix metallopeptidase 9, which is involved in extracellular matrix degradation. Histologic and immunocytochemical staining showed that ED1 (inflammatory marker), alpha-smooth muscle actin (myofibroblast marker), and collagen deposition were significantly less within the medulla or cortex in rats with renal insufficiency vs. controls. G1 and G2 rats showed significantly inhibited inflammation and fibrosis in interstitial tissue, and reduced collagen deposits around renal vessels and the basement membrane of renal tubule and glomerular tissue, compared to G3. Conclusions Renal fibrosis is potentially reversible and therapeutic use of USCs can reverse specifically targeted decrease of influx of inflammatory macrophages, interstitial fibrosis formation and collagen deposition through their paracrine effects. Implantation of USCs has potential in the prevention and treatment of renal insufficiency. _x000D_ Funding Wake Forest University Health Sciences, Internal funding via Pilot Award from the Hypertension & Vascular Research Center_x000D_ _x000D_
Authors
Ting Long
Yaodong Jiang Hua Shi Liren Zhong Deying Zhang Wei Li Yong Zhang Dong Chen Yan Jiao Debra Diz Yuanyuan Zhang |
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MP23-02 |
A Step Towards Clinical Application of Acellular Matrix: A Clue from Macrophage Polarization |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Kidney & Bladder II | 17BOS |
Abstract: MP23-02 Sources of Funding: GOFARR Laboratory Introduction The outcome of tissue engineered organ transplants depends on the capacity of the biomaterial to promote a pro-healing response once implanted in vivo. Multiple studies, including ours, have demonstrated the possibility of using the extracellular matrix (ECM) of animal organs as a platform for tissue engineering and more recently, discarded human organs have also been proposed as a scaffold source. It is known that natural matrices present diverse immune properties when compared to artificial biomaterials. However, how these properties compare between diseased and healthy ECM and artificial scaffolds has not yet been defined. Methods We used decellularized renal ECM derived from WT mice and from mice affected by Alport Syndrome as a model of renal failure with extensive fibrosis, at different time-points of disease progression. We characterized the morphology and composition of these ECMs and compared their in vitro effects on macrophage activation with that of synthetic scaffolds commonly used in the clinic (collagen type I and poly-L-(lactic) acid, PLLA). Results We showed that ECM derived from Alport kidneys differed in fibrous protein deposition (col I, col IV?1,2 and fibronectin) and cytokine content (Resistin, TIM-1/ KIM-1, DPPIV/CD26 and Reg3G) when compared to ECM derived from WT kidneys. Yet, both WT and Alport renal ECM induced macrophage differentiation mainly towards a reparative (M2) phenotype (reduced CD80), while artificial biomaterials towards an inflammatory (M1) phenotype. Anti-inflammatory properties of natural ECMs were lost when homogenized, hence three-dimensional structure of ECM seems crucial for generating an anti-inflammatory response. Conclusions Together, these data support the notion that natural ECM, even if derived from diseased kidneys promote a M2 protolerogenic macrophage polarization, thus providing novel insights on the applicability of ECM obtained from discarded organs as ideal scaffold for tissue engineering. Funding GOFARR Laboratory
Authors
Astgik Petrosyan
Stefano Da Sacco Nikita Tripuraneni Ursula Kreuser Maria Lavarreda-Pearce Riccardo Tamburrini Roger E. De Filippo Orlando Giuseppe Paolo Cravedi Laura Perin |
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MP23-03 |
Urine Based Rapid Molecular Diagnosis of Zika Virus |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Kidney & Bladder II | 17BOS |
Abstract: MP23-03 Sources of Funding: This study was funded in part by the Maureen and Ronald Hirsch family philanthropic contribution. Introduction Infection with Zika virus (ZIKV) is of growing concern since it is suspected with causing brain defects in newborns including microcephaly, and having potential and severe neurological and autoimmune complications. ZIKV is anticipated to spread globally within the next year, therefore a rapid and ideally non-invasive diagnostic test is urgently needed. Studies have suggested that ZIKV detection in urine is more sensitive and has a longer window of detection as ZIKV may be shed in the urine. The objective of this study was to develop a urine diagnostic test that could be completed under 30 minutes. Methods Urine samples spiked with ZIKV or related other related arboviruses including Dengue fever were tested using conventional real time PCR. Samples were also tested using a new methodology we developed that utilized reverse transcription loop mediated isothermal amplification (RT-LAMP). These techniques were also validated using samples from ZIKV infected patients and mosquitoes. Results RT-LAMP could specifically detect ZIKV in ZIKV positive samples. This could be done in under 30 minutes and did not require timely RNA extraction from the urine, unlike real time PCR. Conclusions Here we describe a technique by which ZIKV can be rapidly detected in a non-invasive urine sample. This may allow for easy monitoring of potentially exposed individuals, especially pregnant women, couples wanting to conceive, or individuals with suspicious symptoms. Funding This study was funded in part by the Maureen and Ronald Hirsch family philanthropic contribution.
Authors
Laura Lamb
Sarah Bartolone Michael Conway Maya Tree Olivia Lossia Gary Dunbar Julien Rossignol Christopher Smith Michael Chancellor |
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MP23-04 |
Colorimetric, pH-Responsive Membranes Allow for Immediate, Real-Time and Reversible Urine Monitoring in a Multipart System for Detection of Changes Secondary to Urease-Producing Bacteria |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Kidney & Bladder II | 17BOS |
Abstract: MP23-04 Sources of Funding: This work is supported by the University of Florida Research Opportunity Seed Fund. Introduction Within 4 weeks, 90% of long-term catheterized patients will develop bacteriuria, and 50% will experience encrustation and marked elevation of urine pH. Urease-producing bacteria have been linked to elevated urine pH, catheter-associated urinary tract infection (CAUTI), encrustation, and struvite renal calculi. We propose a method to monitor alkalinization of urine as part of a multimodal system which could play a role in prevention of catheter encrustation. Reversibility of the colorimetric membrane acts as a form of biofeedback to allow for modification of oral intake with acidifying agents and control urine pH to prevent encrustation. Methods To create a pH-sensitive, reversible colorimetric porous membrane with immediate detection of alkaline urine, high molecular weight polymer was solvated in organic solvent. A quaternary ammonium salt and indicator dye were then added for pH sensitivity and electrostatic retention of the dye. Addition of plasticizer followed to modify the membrane mechanical properties. This solvated mixture was stored under 4°C refrigeration until casting. Results The solvated membrane blend was drop cast onto the inside of catheter tubing for demonstration. Basic solution (pH 7.5 / NaOH) was passed through and a distinct and visible change of color to green (see Figure 1) was observed upon exposure. Dilute acidic solution was then passed through (pH 4 / H2CO3) and there was a rapid reversal (< 5 seconds) to original yellow color. The urinary pH range from 4.0 to 9.0 can be monitored by this system. Conclusions The clear colorimetric indication afforded by this membrane provides a robust system for the reversible detection of real-time changes in urine pH. As a component of a multipart system, this provides rapid biofeedback that allows for informed and directed intervention. This system may also assist in the detection of elevated urine pH secondary to urease-producing bacteria responsible for encrustation and recurrent struvite kidney stone formation. Funding This work is supported by the University of Florida Research Opportunity Seed Fund.
Authors
Cory French
Madeline Fuchs Hammad Huda Neal Patel Brandey Andersen Kirk Ziegler Victoria Bird |
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MP23-05 |
Using FemTouchTM in the treatment of women with recurrent Urinary Tract Infections: First experience in the United Kingdom |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Kidney & Bladder II | 17BOS |
Abstract: MP23-05 Sources of Funding: None Introduction Urinary tract infections (UTI) are one of the most prevalent conditions worldwide, with incidence increasing with age. Oestrogen decrease in post-menopausal women lowers levels of Lactobacillus within the vaginal microenvironment, a key factor in synthesising lactic acid and the creation of the acidic vaginal defence. These women often require long-term antibiotics. However with the rising incidence of bacterial resistance, there is a need to find alternative therapies._x000D_ _x000D_ FemTouch is a thermal ablative laser, which when applied to the vagina, induces a histologically proven rejuvenation of the lining to a pre-menopausal state, similar to oestrogen therapy. FemTouch is used by gynaecologists to treat atrophic vaginitis and is favourable in women unsuitable for oestrogen therapy. _x000D_ _x000D_ We present the first experience in the United Kingdom (UK) of using FemTouch to treat recurrent UTIs in a preliminary cohort of women. Methods 9 postmenopausal women with recurrent UTIs received 3 courses of FemTouch (Lumenis, Israel) at monthly intervals. Total follow up for 6 months assessed rates of UTI, changes in vaginal pH and assessment of vaginal health using subjective measures of vaginal fluid/moisture, firmness and elasticity. _x000D_ _x000D_ No patients received concurrent antibiotic or hormonal therapy during the treatment or follow up period. Results Pre-treatment, the patients averaged one UTI every 6 weeks. To date only one patient has had a recurrence of UTI after treatment. _x000D_ _x000D_ The average vaginal pH, displayed in table 1, improved with treatment. All patients described marked improvements in menopausal vaginal symptoms, as shown by their average vaginal health scores in table 2._x000D_ _x000D_ All patients described the pain of the procedure as 1/10 on average throughout. Conclusions Our preliminary results show that FemTouch is both effective and well tolerated in the treatment of recurrent UTIs in postmenopausal UK women, suggesting FemTouch may be a viable alternative to antibiotic prophylaxis. In addition, laser treatment made a big difference to patients general vaginal health, restoring it in the patients view to a pre-menopausal state._x000D_ _x000D_ There seems to be enough merit to establish a national multi-centre trial to evaluate the efficacy of FemTouch in larger groups of patients for a longer follow up period. Funding None
Authors
BOB YANG
Steve Foley |
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MP23-06 |
A Randomized, Controlled Trial of Active vs. Passive Voiding Trials |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Kidney & Bladder II | 17BOS |
Abstract: MP23-06 Sources of Funding: None Introduction There are national quality initiatives to prevent catheter-associated urinary tract infections (CAUTI) due to morbidity and cost. Differences between active and passive voiding trials have not been previously studied in the general hospitalized population. Active voiding trials entail filling the bladder with saline before catheter removal. Passive voiding trials involve the bladder filling with urine naturally after catheter removal. We assessed the effects of active vs passive voiding trials on time to hospital discharge and the rates of urinary tract infection (UTI) and urinary retention (UR). Methods In a single-center, single-blind, randomized, controlled trial, patients who had urethral catheter removal were randomized to a standardized active voiding trial or passive voiding trial. Patients undergoing urethral or bladder surgery were excluded. The outcomes of interest were the patient's time to hospital discharge after the catheter removal and the rates of UTI (defined by the National Surgical Quality Improvement Program criteria) and UR within 2 weeks of catheter removal. Logistic regression was used to identify risk factors for urinary retention. Results We enrolled 274 patients. Table 1 shows the differences in outcomes between active and passive voiding trials._x000D_ _x000D_ BPH (OR 5.3, p=0.007); neurological disease (OR 3.1, p=0.03); and admission to a neurosurgical ward (OR 3.6, p=0.009) were associated with increased urinary retention. Conclusions Patients in the active group had 64% fewer urinary tract infections than patients in the passive voiding trial group. Although patients in the active group voided nearly 3 hours sooner than patients in the passive group, there was no difference between the groups in time to hospital discharge. There was no difference in the rate of UR between the groups. BPH, neurological disease, and admission to a neurosurgical ward increased the odds of urinary retention. Funding None
Authors
James Mills
Nathan Shaw Helen Hougen Hannah Agard Robert Case Timothy McMurry Noah Schenkman Tracey Krupski |
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MP23-07 |
International comparison of causative bacteria and antimicrobial susceptibilities of urinary tract infections between developed and developing countries |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Kidney & Bladder II | 17BOS |
Abstract: MP23-07 Sources of Funding: none Introduction Causative bacteria in urinary tract infection (UTI) are generally influenced by the trend of antibiotic use and especially emergences of antibiotic resistant strains are emphasized by inappropriate antibiotic use. The use of antibiotic including infection control such as intervention for antimicrobial stewardship are varied among countries and regions; however thin kind of study spreading to several countries or regions for comparison are lacked. Under this situation, the objective of this study is to investigate the comparison of UTI-causative bacteria between developed country and developing country to clarify their frequency and the susceptibilities to the representative antimicrobial agents owing to the different uses of antibiotics. Methods For over 2 or 11-month, 1704 samples from the UTI patients were retrospectively analyzed (1260 ones from Kobe University Hospital, Japan and 544 ones from Soetomo Hospital, Surabaya, Indonesia). Isolated bacteria were identified, and their antibiotic susceptibilities were determined. The statistical analyses were performed for compassion of those data from both countries under the classification of pediatric UTI and adult UTI. Results Escherichia coli was the most common etiological agent of UTI (24.2% in Japan and 39.3% in Indonesia). Enterococcus faecalis was more often isolated in Japan (14.1%), but not in Indonesia (5.3%). Klebsiella spp. was more frequently isolated in Indonesian pediatrics (20.3%) compared to Indonesian adults (13.6%) and in Japan (6.5%). E. coli, as the most prevalent cause of UTI, was substantially resistant to ampicillin and 1st and 3rd cepharosporines in Indonesian adults but not in japan. In many cases, Indonesian isolates tended to have lower susceptibilities rates than Japanese ones. Extended-spectrum β-lactamase producing gram-negative bacteria were 5.7% in japan, 39% in Indonesian adults, and 39% in Indonesian pediatrics. Conclusions The results show that the antimicrobial resistance patterns of the causes of UTI are highly variable among countries and continuous surveillance of trends in resistance patterns of uropathogens is important for future revision of the use of antimicrobial agents. Funding none
Authors
Katsumi Shigemura
Koichi Kitagawa Kuntaman Kuntaman Toshiro Shirakawa Masato Fujisawa |
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MP23-08 |
Risk factors for recurrent urinary tract infection in urinary stone patients with acute obstructive pyelonephritis within 1 year |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Kidney & Bladder II | 17BOS |
Abstract: MP23-08 Sources of Funding: none Introduction To access the risk factor for recurrent urinary tract infection (UTI) in urinary stone patients with acute obstructive pyelonephritis (OPN). Methods We retrospectively reviewed the medical records of 52 patients who had urinary tract stone with acute OPN from 2010-2015. After treatment, patients who admitted to the department of urology or nephrology via emergency room within 1 year were included. Multivariate analysis were performed to identify the risk factors. Results Mean age of patients was 62.2±14.6 years and mean follow-up duration was 26.0±20.39 months. E-coli was dominating organism (68.1%, 15/22) in initial urine culture. After infection control and stone management, 23 patients showed recurrent UTI during follow-up. Of them, 43.5% (10/23) patients were re-admitted because of UTI within 1 month after initial treatment. Patients were divided to two groups (recurrent UTI group (n=23), non-recurrent UTI group (n=29). Between groups, significant differences were found in diabetes history (47.8% vs. 17.2%, p=0.018), stone location (kidney, recurrent group 63.0% vs. non-recurrent group 24.0%, p=0.031) and initial positive urine culture (55.6% vs. 28.0%, p=0.016, table 1). In multivariate analysis, initial urine culture (positive, p=0.040, 95% confidence interval (CI), 1.130-224.117) was identified as independent risk factor for recurrent UTI. Of recurrent UTI group, 14(60.9%) patients showed positive urine cultures which were newly diagnosed or different with initial urine culture. In multivariate analysis, acute renal insufficiency at initial laboratory test (p=0.019, 95% CI 1.375-36.157) and stone location (kidney, p=0.022, 95% CI, 1.345-46.926) were significant factors associated with newly diagnosis positive urine culture (table 2). Conclusions Initial positive urine culture was significant risk factor for recurrent UTI in urinary stone patients with acute OPN. And caution is also needed in patients with acute renal insufficiency or renal stone during follow up Funding none
Authors
Sin Woo Lee
Sol Yoon Deok Ha Seo Chunwoo Lee Seong Uk Jeh See Min Choi Sung Chul Kam Jeong Seok Hwa Ky Hyun Chung Jae Seog Hyun |
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MP23-09 |
Practice patterns across specialties in the treatment of women with recurrent UTIs in an academic healthcare system |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Kidney & Bladder II | 17BOS |
Abstract: MP23-09 Sources of Funding: None Introduction Recurrent urinary tract infections (UTIs) are a common problem managed by a variety of medical specialties. Several treatment strategies exist and no evidence-based pathway of care has been established. The objective of this investigation is to better understand the practice patterns for managing patients with recurrent UTIs in a tertiary care healthcare system. Methods A 17-question electronic survey regarding the management of recurrent UTIs in women was distributed to 210 providers in the Internal Medicine (IM), Family Medicine (FM), Ob-Gyn (OBG), and Urology departments. Recurrent UTIs was defined as ?3 in 1 year. Results A total of 68 (32.3%) providers completed the survey. Sixty percent (39/65) of providers report treating patients with recurrent UTIs with an extended course of antibiotics. Additionally, 35% (23/65) of providers treat despite lack of symptoms and 37% (24/65) of providers utilize suppressive antibiotics. OBG and Urologists utilize suppressive antibiotics more than IM and FM at 50%. Of those providing suppressive antibiotics, 79% (19/24) chose nitrofurantoin. Providers refer to specialists after trying a median of 3 courses of antibiotics (IQR 3-4). Referral to Urologists was most common for concomitant stones (88%, 51/58) or hydronephrosis (78%, 45/58), whereas referral to Infectious Disease (ID) was most common for bacterial resistance (75%, 51/68) or multiple patient allergies (48.5%, 33/68). Overall, 91.2% (62/68) of providers felt a protocol for evaluating and managing recurrent UTIs would be useful. Conclusions Practice patterns for managing recurrent UTIs in female patients vary across and within specialties within the same healthcare system. There is limited data to suggest extended courses of antibiotics are effective for recurrent UTIs and may potentially contribute to increasing susceptibility to infection, yet this strategy is commonly employed in our healthcare system. Although referral patterns differ between Urologists and ID specialists, multiple antibiotics are employed prior to referral. The majority of providers believe a written protocol would improve patient care, reducing variability and improving quality. Funding None
Authors
Matthew Sterling
Eliza Lamin Alexander Skokan Alan Wein Ariana Smith |
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MP23-10 |
Laparoscopic versus open nephrectomy for xanthogranulomatous pyelonephritis: a contemporary series |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Kidney & Bladder II | 17BOS |
Abstract: MP23-10 Sources of Funding: None Introduction Xanthrogranulomatous pyelonephritis (XGP) has historically been managed with open nephrectomy. In the era of minimally invasive surgery, a small number of reports have evaluated the use of a laparoscopic approach in XGP, with variable results. We evaluated our experience with XGP over the last 15 years. This represents the largest series to date of laparoscopic nephrectomy for XGP. Methods Retrospective review of all nephrectomy and partial nephrectomy specimens from May 2001 to August 2016 disclosed 31 patients with pathologically confirmed XGP. 28 patients underwent total nephrectomy (18 laparoscopic, 1 robotic, 9 open) and 3 patients underwent partial nephrectomy (2 robotic, 1 open). Conversion to open was performed in 3 of the laparoscopic cases. The probability of undergoing laparoscopic nephrectomy significantly increased over time (p=0.063). Results There were no differences in overall complication rate (38.9% vs. 53.8%, p=0.48), Clavien I and II complications (22.2% vs. 30.8%, p=0.689), Clavien III and IV complications (16.7% vs. 23.1%, p=0.67), readmissions (22.2% vs. 23.1%, p=1.0), or mean operative time (191 vs 209, p=0.31). Blood loss (350 vs. 775, p= 0.009) and intraoperative transfusion rate (11.1% vs. 53.8%, p =0.017) were significantly higher in the open group. There were no perioperative mortalities in either group. The mean hospital length of stay was 8 days for the open group and 3.2 in the laparoscopic group (p<0.001). Median follow-up was 47 days. Patients with preoperative glomerular filtration rate of <60, blood loss >1 liter, or hospital stay >9 days were more likely to suffer a major complication or require readmission. Conclusions Although early reported experience with laparoscopic nephrectomy for XGP was not favorable, our larger and more contemporary series demonstrates it can be performed safely, with less blood loss and shorter hospital stays. Complication rates and readmission rates are high regardless of approach. Funding None
Authors
Justin Benabdallah
Joel Vetter Ramakrishna Venkatesh R. Sherburne Figenshau |
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MP23-11 |
SURGICAL SITE INFECTION AFTER RADICAL CYSTECTOMY – INCIDENCE AND RISK FACTORS |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Kidney & Bladder II | 17BOS |
Abstract: MP23-11 Sources of Funding: None Introduction Radical cystectomy with urinary diversion is the primary treatment for muscle invasive bladder cancer. The prevalence of postoperative complications, including surgical site infections (SSI), remains high. Complying with the enhanced recovery after surgery preoperative clinical pathway recommendations, we have modified our traditional preoperative cystectomy pathway, abandoning bowel preparation and changing the antibiotics regimen (supplanting intravenous ampicillin, gentamycin and metronidazole for a single dose of intravenous ceftriaxone). Concurrently, an increased rate of SSI was observed. _x000D_ We thus sought to analyze our contemporary SSI rate after radical cystectomy and analyze its associated risk factors._x000D_ Methods We queried our prospectively assembled radical cystectomy database to retrieve 287 patients operated between 2004 and .2014. Patients' medical records were reviewed for SSI as defined by the CDC guidelines published in 1999, namely, wound infection within the first postoperative month associated with either a) purulent discharge (with or without a positive wound culture), or b) pain, local erythema and swelling requiring wound drainage. Putative predictors of SSI were assessed by univariate and multivariate analyses. Results Of the 287 patients, 62 (22%) were diagnosed and treated with SSI, 48 (77%) of whom had a positive wound culture. In 32 patients (67%) the isolated pathogen was resistant to the administered perioperative antibiotic. Table 1 represents the univariate and multivariate analyses evaluating risk factors for SSI. Older age, presence of diabetes, treatment with neoadjuvant chemotherapy and surgery duration did not increase the probability of SSI, whereas higher BMI, ileal conduit (versus orthotopic) diversion and contemporary surgery during the recent years were associated with higher SSI prevalence. Conclusions Overall, a fifth of the patients undergoing radical cystectomy in our center developed SSI. These findings might reflect the increasing number of morbid and complex patients undergoing radical cystectomy in our center during recent years. Funding None
Authors
Hanan Goldberg
Chen Shenhar Roy Mano Jack Baniel Daniel Kedar David Margel Ofer Yosseopowitch |
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MP23-12 |
Endometriosis – urinary tract involvement and predictive factors for major surgery |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Kidney & Bladder II | 17BOS |
Abstract: MP23-12 Sources of Funding: none Introduction Endometriosis affects 5-15% of premenopausal females. Urinary tract endometriosis (UTE) is present in about 1- 2% of all women with endometriosis._x000D_ Objective: To assess the severity and surgical treatment of deep infiltrating endometriosis (DIE) with involvement of the urinary tract (UT) as well as the existence of predictive factors for major surgery in patients with UTE._x000D_ Methods Retrospective analysis of 656 women undergoing surgery for endometriosis, between January 2005 and August 2016, in a large academic centre. The authors identified a group of 28 (4.3%) patients, with a mean age of 38 ± 6.9 years (27-50) at diagnosis, who underwent minor surgery (percutaneous nephrostomy [PCN] or any kind of endoscopic surgery) or major surgery (open or laparoscopic procedures) for UTE. Mode of presentation, surgeries performed, post-operative data and complication rates were analysed. Results Only 4 patients (14.3%) were asymptomatic and the most frequent symptom was lumbar pain (n = 14, 50%). The mean lesions size was 2.8 ± 1.7 cm (0.5-5) and affected the ureter in 13 (46.4%), the bladder in 11 (39.3%) and both structures in 4 (14.3%) patients. The left ureter was the most involved (n=10, 35.7%). Hydronephrosis was detected in 18 (64.3%) patients and 12 (42.9%) had renal function impairment (7 [25%] had partial loss, and 5 [17.9%] total loss of renal function). Patients with ureteric involvement were more likely to lose renal function (p = 0.034). Concerning minor surgeries, 12 (42.9%) patients underwent TURB, 9 (32.1%) double-J stenting or PCN, and 4 (14.3%) ureteroscopy. The major surgeries were distal ureterectomy in 9 (32.1%), nephrectomy in 3 (10.7%) and excision of endometriomas by laparotomy/laparoscopy in 4 (14.3%) cases. Each patient had in average 1.79 ± 1.3 (1-6) surgeries, and 11 (39.3%) had more than one surgery. The total hospitalization time was 6.3 ± 7.4 days (1-32). Patients with ureteric involvement underwent major surgeries more often (p = 0.025) and had longer hospital stay (8.2 vs 3.1 days, p = 0.05). With a mean follow-up of 36.3 months, no patient with bladder involvement had recurrence, 3 (10.7%) showed ureteral re-estenosis (Clavien-Dindo grade IIIb), 1 (3.6%) remained with lumbar pain and 1 (3.6%) had double-J stent calcification. Conclusions Despite being a histologically benign pathology, DIE can have serious consequences in the UT, often leading to multiple procedures and may result in total loss of kidney function. Surgery is highly successful in most cases and patients with ureteric involvement are more likely to undergo major surgery and have longer hospitalization. Funding none
Authors
Maria José Freire
Paulo Jorge Dinis Rita Medeiros LuÃs Sousa Fernanda Ã�guas Arnaldo Figueiredo |
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MP23-13 |
Transfusion-dependent gross hematuria requiring surgical management: are outcomes worse among patients with previous pelvic radiation? |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Kidney & Bladder II | 17BOS |
Abstract: MP23-13 Sources of Funding: none Introduction Gross hematuria requiring blood transfusion is uncommon, and few studies have evaluated management or long term outcomes after initial surgical treatment. Here, we characterize patients undergoing surgical management of transfusion dependent hematuria and evaluate post-surgical outcomes. We hypothesized that patients who had received prior pelvic radiation would have worse postoperative outcomes. Methods Following IRB approval, comprehensive clinical information was collected and analyzed for patients with hematuria requiring blood transfusion and inpatient surgical management from 2000-2015. Results Seventy patients requiring surgery for transfusion dependent hematuria were identified, including 30 (42.9%) who had received prior pelvic radiation. Hematuria was due to radiation cystitis in 20 (28.6%), post operative bleeding in 12 (17.1%), traumatic catheterization in 10 (14.3%), benign prostatic bleeding in 6 (8.57%), bladder cancer in 5 (7.14%), prostate cancer in 5 (7.14%), hemorrhagic cystitis in 4 (5.71%), and other causes in 8 (11.4%) patients._x000D_ _x000D_ All 70 patients underwent cystoscopy with clot evacuation and fulguration. Concomitant operations performed included formalin instillation in 7, TURBT in 8, suprapubic tube placement in 4, and ligation of the bulbar arteries in 1 patient(s). _x000D_ _x000D_ Radiated patients were on average 9.3 years older than their non-radiated counterparts (p=0.01). Otherwise no significant differences were identified in baseline characteristics or with regards to LOS, 90 day readmission rate, or likelihood of indwelling catheterization at discharge (Table). _x000D_ _x000D_ At median follow up of 10.9 (IQR 3.7-26.5) months, radiated patients required on average 1.9 additional surgical procedures compared to 1.4 without prior radiation (p=0.21). Previously radiated patients were more likely to require long term urinary diversion compared to non-radiated patients, 9 (31.0%) versus 3 (8.3%) patients (p=0.02)._x000D_ Conclusions Pelvic radiation is a common etiology for transfusion dependent hematuria. While initial post-operative outcomes were similar, one third of patients with transfusion dependent hematuria and prior radiation required urinary diversion for long term management. Funding none
Authors
Matthew D Grimes
Brady L Miller Tyler Wittmann Sarah E McAchran David F Jarrard Wade A Bushman Daniel H Williams Tracy M Downs Kyle A Richards Sara L Best E. Jason Abel |
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MP23-14 |
En-Bloc Stapling of the Renal Hilum during Laparoscopic Nephrectomy for Benign Inflammatory and Infectious Renal Pathology: A Multi-institutional Analysis of Safety and Efficacy |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Kidney & Bladder II | 17BOS |
Abstract: MP23-14 Sources of Funding: none Introduction During laparoscopic nephrectomy (LN), the renal artery and vein are traditionally dissected and ligated separately due to concern for increased risk of arteriovenous fistula (AVF) formation with en-bloc stapling of the renal hilum (EBSH). As the majority of data supporting this claim arises following nephrectomy for infectious and inflammatory conditions, we sought to evaluate the safety and efficacy of EBSH during LN for benign infectious and inflammatory renal conditions. Methods We performed a retrospective review of patients with benign inflammatory and infectious renal pathology undergoing LN using EBSH between 2008 and 2014 at three academic medical centers. Data analyzed included pathology, operative time, estimated blood loss (EBL), and perioperative or postoperative complications. Evaluation of AVF formation was assessed by postoperative imaging studies, physical exam (absence of abdominal bruit or palpable thrill), or evaluation of new onset diastolic hypertension. Results 67 patients (mean age 55 +/- 16.2) underwent LN for a total of 71 renal units. EBSH was used in all cases (38 left renal units, 33 right renal units). Mean operative time was 174 min (range 84 to 373 min). Mean EBL was 150ml (range 20 ml to 2000 ml). One (1.8%) laparoscopic case was converted to open nephrectomy. The predominant pathology was obstruction in 23 (34.3%) and chronic infection in 23 patients (34.3%). Eleven (16.4%) patients had ESRD and 9 (13.4%) were on dialysis at the time of LN, with 4 (6.0%) patients going on to receive renal transplantation. No patients developed clinical or radiographic evidence of AVF at a mean follow-up of 14 months. Conclusions Ligation of the entire renal hilum with en-bloc stapling during LN is safe and effective. No patients in our cohort developed any significant immediate or intermediate term surgical complications or development of AVF as a result of en-bloc ligation. This study offers the largest cohort of en-bloc stapling in benign infectious and inflammatory kidneys to date, with no resulting radiographic or clinical diagnoses of AVF. Funding none
Authors
Alyssa Greiman
Alexander Chow Melanie Adamsky Christopher Coogan Scott Eggener Arieh Shalhav Kalyan Latchamsetty Sandip Prasad |
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MP23-15 |
Early Discharge Following Decompression for Sepsis and an Obstructing Stone? A Multi-Institutional Study to Identify Predictors of Antibiotic Sensitivity |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Kidney & Bladder II | 17BOS |
Abstract: MP23-15 Sources of Funding: none Introduction Patients presenting with sepsis and an obstructing stone undergo urgent urinary tract decompression. Following this, patients are hospitalized for hemodynamic support and broad spectrum antibiotics. Urine culture results are used to tailor outpatient antibiotic therapy. At times patients achieve early clinical stability but remain hospitalized while awaiting antibiotic sensitivities. We sought to identify predictors of antibiotic resistance that may allow clinicians to select candidates for discharge on empiric oral antibiotics prior to culture results being available. Methods All patients that underwent emergent urinary tract decompression for sepsis and an obstructing ureteral stone over the last 2 years at the two above institutions were included. Clinical factors, including urine culture sensitivities and patient demographics were recorded. Student’s t-test and the chi-squared test were used to identify statistical difference. Results 134 patients were identified that met inclusion criteria. Eighty-four patients (62.7%) had urine cultures with antibiotic resistance. Comparison was made between patients with pan-sensitive and resistant urine cultures (Table 1). Patients with resistant cultures were more likely to have had previous urologic surgery (44.7% vs. 22.0%, p = 0.008) - the most notable difference was in patients that had had previous ureteroscopy (38.9% vs. 8.0%, p = 0.0002). Those with resistant cultures were more likely to require postoperative ICU-level care (27.1% vs. 12.0%, p = 0.039), have bacteremia (48.2% vs. 24.0%, p = 0.005) and a longer length of stay (5.4 vs. 3.4 days, p = 0.026). Resistance patterns were noted to be similar between the two institutions (Table 2). Conclusions Patients that have had previous urologic surgery, especially ureteroscopy, appear to be poor candidates for early discharge on empiric antibiotics prior to the completion of urine culture results due to a higher likelihood of having antibiotic resistance. These results were noted to be consistent at both institutions participating in this study. _x000D_ Funding none
Authors
Timothy Tran
Madeline Cancian Egor Parkhomenko Gyan Pareek Mantu Gupta |
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MP23-16 |
Targeted antibiotic prophylaxis can prevent febrile urinary tract infection after removal of ureteral stents in radical cystectomy patients with intestinal urinary diversion. |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Kidney & Bladder II | 17BOS |
Abstract: MP23-16 Sources of Funding: none Introduction Radical cystectomy with intestinal urinary diversion has the high incidence of post-operative infective complication. Some patients encountered febrile urinary tract infection (UTI) after removal of the ureteral stents. We started targeted antibiotic prophylaxis, which was chosen appropriate susceptible antibiotics based on urine culture. We evaluated the efficacy of the targeted antibiotic prophylaxis for prevention of febrile UTI after removal of the ureteral stents. Methods From January 2009 to April 2016, a total of 54 patients who underwent radical cystectomy with intestinal urinary diversion were included. In the first half of the study period (January 2009 to December 2011) included 21 patients, ureteral stents were removed without administration of antibiotic agent. In the last half (January 2012 to April 2016) included 33 patients, targeted antibiotic prophylaxis was done. Prior to removal ureteral stents on post-operative day 7, urine obtained from ureteral stents was cultured and determined the susceptibility of isolated bacteria. Patient received antibiotics for which the isolates were susceptible before the stent removal. Patients were followed up for 2 weeks and febrile UTI were recorded. We compared the incidence of febrile UTI between two study periods. Results Overall the incidence of febrile UTI after stent removal was 22.2% (12/54). In the first half of the study period, the incidence of febrile UTI was 47.6% (10/21) and that of in the last half was 6.1% (2/33). The incidence of febrile UTI was significantly decreased in the last half period (Fisher&[prime]s test, p=0.006). _x000D_ Urine cultures positive for bacteria were found in 29 out of 33 patients in the last half period and 33 strains of 11 bacteria species were isolated. The predominant bacteria were E.coli in 5 patients, S. aureus in 4 patients, K.peumoniae in 4 patients and E.cloacae in 4 patients. Five strains (15.2%) of methicillin resistant Staphyococci, 2 strains (6.1%) of extended spectrum β-lactamase producing bacteria and 14 strains (42.4%) of fluoroquinolone-resistant bacteria were isolated._x000D_ Conclusions The susceptibility test had an advantage of appropriate antibiotics choice, because 29 out of 33 patients had urine cultures positive for bacteria and miscellaneous and drug-resistant strains were isolated. This targeted antibiotic choice based on urine culture is more effective prophylaxis in radical cystectomy patients. Funding none
Authors
Yoshitsugu Nasu
Tadashi Murata Morito Sugimoto Atsushi Takamoto Noriaki Ono |
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MP23-17 |
The Characteristics and Progression of Bacterial Biofilms on Urinary Catheters |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Kidney & Bladder II | 17BOS |
Abstract: MP23-17 Sources of Funding: Stony Brook School of Medicine (AN, GTW); NIH NRSA F30 (GTW). Introduction The majority of hospital-acquired urinary tract infections (UTIs) are catheter-associated UTIs (CAUTIs), which are associated with increased morbidity and mortality in patients, with 13,000 attributed deaths annually. CAUTIs are also associated with increased length of hospital stays and 0.4-0.5 billion USD in annual healthcare costs, as well as unnecessary antimicrobial use. The formation of biofilms (groups of bacterial cells that adhere to one another and to a fixed surface) on catheters is critical to the development and persistence of CAUTI, as biofilms function as both barriers to antibiotics and reservoirs of microbes. We sought to determine the natural history of biofilm formation on urinary catheters. In particular, we were interested in the starting location(s) of biofilm formation, and whether biofilms predominated proximally or distally on catheters, their timing and manner of progression, and whether catheter biofilm formation was predominantly extraluminal or intraluminal. Methods Foley catheters (n=19) were collected from outpatient and inpatient clinics at a large university medical center from post-surgical patients at 1 to 28 days indwelling time. Each catheter was sectioned and stained, and biofilms were quantitated using spectrophotometry. Results Short-term catheters (indwelling <1 week) displayed predominant biofilm formation at the proximal (bladder-exposed) end, whereas long-term catheters (indwelling 3-4 weeks) displayed significant biofilm formation throughout all segments. Biofilm growth on short-term catheters was predominantly extra-luminal, whereas long-term catheters demonstrated significant extra- and intra-luminal biofilm staining. Conclusions The results of this preliminary study inform approaches to developing novel strategies to prevent and eradicate bacterial biofilms from urinary catheters. For example, this study suggests that catheter-coating techniques targeting the extraluminal surface of the proximal end of the urinary catheter may contribute to a delay of biofilm formation, and reduce the overall risk of CAUTI. Efforts are under way to further investigate biofilm progression with larger sample sizes, and to determine how a reduction in biofilm formation and progression may contribute to reduced CAUTI risk. Funding Stony Brook School of Medicine (AN, GTW); NIH NRSA F30 (GTW).
Authors
Anh Nguyen
Glenn Werneburg Jason Kim Annie Rohan David Thanassi |
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MP23-18 |
Synergistic Photodynamic Therapy for Catheter-Associated Urinary Tract Infection in Rats |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Kidney & Bladder II | 17BOS |
Abstract: MP23-18 Sources of Funding: R21/R33AI121700 (Synergistic Photodynamic Therapy for Urinary Tract Infections)_x000D_ Introduction The rise of multi-drug resistant strains of uropathogenic bacteria is increasing the number of catheter-associated urinary tract infections (CAUTIs), which affect more than one million people per year in the U.S., that are untreatable with current antibiotics. The increase of antibiotic resistance necessitates the need for new antimicrobial treatments that will be effective against multidrug-resistant strains and will not themselves induce resistance. The aim of our study is to demonstrate the feasibility of in vivo treatment of urinary tract infections in rats using photodynamic inactivation (PDI); a method of treatment which uses non-toxic dyes, called photosensitizers, excited with harmless visible light to react with ambient oxygen to produce reactive oxygen species that selectively destroy infecting bacteria while preserving host tissue._x000D_ _x000D_ _x000D_ Methods One mL of stable luciferase (lux)-expressing UPEC was inoculated into the bladder of anesthetized female rats via 20 guage angiocatheter placed in the urethra. The progression of the infection and treatment was monitored non-invasively in real time using bioluminescence imaging. The bladder infections in 10 rats were treated by installation of MB [100uM] and KI [100mM] solution after wthich the bladder was illuminated using an optic fiber with 660 nm laser light for 30mins. Serial daily imaging was conducted to document the duration of infection. This was compared to a control group of rats who were infected with UPEC but not treated as well as a group of UPEC infected rats treated only with MB. Results Synergistic UPEC killing effect of PDI (MB + KI) was observed in the PDI treatment group, which demonstrated faster resolution of infection when compared to the control group and MB only group. Conclusions As both MB and KI are approved for use in the human bladder, an ideal application of this technology would be the treatment of CAUTI in chronically catheterized patients by illuminating MB and KI solution using a laser-coupled catheter with embedded fiber optic light guide called a “photonic Foley catheter.� Our study demonstrates the feasibility of in vivo PDI as a novel approach to treatment of urinary tract infections, which merits further investigation._x000D_ Funding R21/R33AI121700 (Synergistic Photodynamic Therapy for Urinary Tract Infections)_x000D_
Authors
Anton Wintner
Yingying Huang Jeffrey Gelfand Francis McGovern Michael Hamblin |
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MP23-19 |
Fibrinogen deposits on urinary catheters in a time-dependent matter and co-localizes with E. faecalis in patients with positive E. faecalis urine cultures |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Kidney & Bladder II | 17BOS |
Abstract: MP23-19 Sources of Funding: 1F32DK104516-01 (ALF-M), and National Institute of Allergy and Infectious Diseases and National Institute of Diabetes and Digestive and Kidney Diseases Grants R01-DK051406, R01-AI108749-01 and P50-DK0645400 (ALF-M, JNW, HLS, JSP, MGC, SJH). Introduction There is mounting evidence that fibrinogen deposition on urinary catheters is a key step in the pathogenesis of catheter-associated urinary tract infection (CAUTI). The aim of this study was to investigate whether fibrinogen and Enterococcus faecalis co-localize on catheters acquired from patients with post-operative urine cultures positive for E. faecalis. Methods Urinary catheters from a series of 50 patients undergoing elective urologic procedures were collected post-operatively and analyzed via immunofluorescence to detect deposited fibrinogen. Pearson correlation was performed to measure the correlation between fibrinogen deposition and dwell time. Additional catheters and urine cultures were collected at time of catheter removal. Catheters from patients with positive Enterococcus cultures were probed for fibrinogen and Enterococcus via immunofluorescence. Results A total of 50 adult patients undergoing urinary catheterization as standard of care were prospectively identified at our institution. Fibrinogen concentration quantified as mg/catheter using a standard curve was highly correlated with catheter dwell time (r=0.63; p<0.0001) (Figure 1). E. faecalis was capable of binding to fibrinogen on these catheters ex vivo._x000D_ _x000D_ Five additional catheters were obtained from patients with E. faecalis-positive post-operative urine cultures. Fibrinogen was present at all time points (18 hours, 1 day, 1 day, 8 days, 9 days) and co-localized with E. faecalis (Figure 2) in vivo. Conclusions We have previously shown that fibrinogen deposits on urinary catheters, and that E. faecalis is capable of binding to these catheters ex vivo. In this study, we demonstrate that E. faecalis co-localizes with fibrinogen in catheterized patients with urine cultures positive for E. faecalis. This data strengthens the clinical association of fibrinogen deposition with CAUTI and suggests that targeting the binding of E. faecalis with fibrinogen may help reduce the rate of Enterococcus CAUTI. Funding 1F32DK104516-01 (ALF-M), and National Institute of Allergy and Infectious Diseases and National Institute of Diabetes and Digestive and Kidney Diseases Grants R01-DK051406, R01-AI108749-01 and P50-DK0645400 (ALF-M, JNW, HLS, JSP, MGC, SJH).
Authors
Tyler M. Bauman
Aaron M. Potretzke Ana L. Flores-Mireles Jennifer N. Walker Alyssa M. Park Henry L. Schreiber IV Jerome S. Pinkner Michael G. Caparon Scott J. Hultgren Alana Desai |
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MP23-20 |
NLRP3/IL-1β mediates Denervation During Bladder Outlet Obstruction in Rats |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Kidney & Bladder II | 17BOS |
Abstract: MP23-20 Sources of Funding: NIDDK: R01DK103534 (PI - Purves) Introduction Bladder outlet obstruction (BOO) is a common condition resulting from benign prostatic hyperplasia, neurologic pathology, organ prolapse, etc. Long-term, obstruction is well-established to evoke denervation in the bladder which causes the detrusor to become hypocontractile, leading to inefficient bladder emptying and consequent infections, continence issues or even renal failure. Recently, considerable attention has been paid to a role for inflammation in bladder deterioration during BOO and we have shown a central role for the NLRP3 inflammasome in triggering this inflammation. In the present study we explore a possible connection between this NLRP3-induced inflammation and bladder denervation. Methods Rats were divided into 5 groups: 1) Control, 2) SHAM operated, 3) BOO+Vehicle, 4) BOO+Glyburide (Gly, NLRP3 inhibitor; 10 mg/kg, p.o.), 5) BOO+Anakinra (Ana, IL-1 receptor antagonist; 25 mg/kg, i.p.). BOO is constructed in female rats by inserting a 1 mm outer diameter transurethral catheter, tying a silk ligature around the urethra and removing the catheter. Medications were administered pre-operatively and once daily. At 12 days animals were sacrificed and the bladders processed for histological analysis. Transverse sections were stained for PGP9.5 expression (pan-neuronal marker) using standard immunohistochemistry techniques. Entire sections were scanned and the area of individual neurons designated as well as total bladder area (exclusive of the urothelia and lumen). The number of neurons and respective areas were used to calculate nerve density. Results Denervation in the bladder wall during BOO was highly significant, as measured by nerve density. This effect was attenuated by either preventing NLRP3 activation with Gly or blocking the action of IL-1β at its receptor by treatment with Ana, clearly indicating a role for NLRP3/IL-1β in bladder denervation during BOO. The effect was also apparent with the total number of nerves despite considerable changes in bladder wall area (increased in BOO, maintained by Gly or Ana). Conclusions NLRP3/IL-1β-induced inflammation contributes to bladder denervation during BOO and blocking this pathway, either by preventing NLRP3 activation or inhibiting the action of IL-1β, diminishes nerve loss. Funding NIDDK: R01DK103534 (PI - Purves)
Authors
Robin Lütolf
Huixia Jin Francis Monty Hughes J Todd Purves |
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MP24-01 |
A Multi-institutional Experience with Robotic Ureteroplasty with Buccal Mucosa Graft |
Trauma/Reconstruction/Diversion: Ureter (including Pyeloplasty) and Bladder Reconstruction (including fistula), Augmentation, Substitution, Diversion I | 17BOS |
Abstract: MP24-01 Sources of Funding: None Introduction Buccal mucosa is well-suited for grafting in the urinary tract as it is compatible with a wet environment, has a thick epithelium that facilitates tissue handling, and has a highly vascular lamina propria that promotes imbibition and inosculation. Despite this, the use of buccal mucosa grafts in ureteral reconstruction has been limited. We report our multi-institutional experience with robotic ureteroplasty with buccal mucosa graft. Methods We retrospectively reviewed 25 patients who underwent robotic ureteroplasty with buccal mucosa graft by three primary surgeons at three institutions between October 2013 and October 2016. Indication for the procedure was a proximal or mid ureteral stricture not amenable to primary anastomosis secondary to length of stricture or extensive fibrosis. On follow-up, patients were assessed for: clinical success, the absence of symptoms from ureteral pathology; and radiological success, the absence of ureteral obstruction on imaging, which included renal scan, CT urogram, and/or ultrasound. Results In 21/25 (84.0%) cases, the diseased ureter was incised and a buccal mucosa graft was onlayed over the defect. In 4/25 (16.0%) cases, the diseased ureter was transected, a plate of healthy ureter was brought together, and buccal mucosa graft was used to perform an augmented ureteroplasty. Eighteen of 25 (72.0%) patients had proximal and 9/27 (28.0%) patients had mid ureteral strictures. Ten of 25 (40.0%) patients had previously undergone a failed ureteral reconstruction. The median length of stricture was 4.0 cm (range 2.0-8.0 cm), and length of buccal mucosa graft harvested was 4.0 cm (range 2.5-8.0 cm). The buccal mucosa graft was onlayed ventrally in 21/25 (84.0%) and dorsally in 4/25 (16.0%) patients. The anastomosis was reinforced with peri-renal fat in 1/25 (4.0%), omentum and appendix in 1/25 (4.0%), and only omentum in 23/25 (92.0%) cases. The median operative time was 203 min (range 136-397 min), estimated blood loss was 100 ml (range 25-420 ml), and length of stay was 2 days (range 1-15 days). There were no intraoperative complications. At a median follow-up of 8 months (range 0-32 months), 23/25 (92.0%) cases were clinically and radiologically successful. Conclusions Robotic ureteroplasty with buccal mucosa graft is an effective technique for managing complex proximal and mid ureteral strictures with excellent short-medium term outcomes. Funding None
Authors
Ziho Lee
Aaron Weinberg Mark Ferretti Benjamin Waldorf Eric Cho Daniel Eun Lee Zhao Michael Stifelman |
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MP24-02 |
Robotic Neocystostostomy wtih ureteral substitution with Robotic Boari Flap, Feasibilty and Outcome |
Trauma/Reconstruction/Diversion: Ureter (including Pyeloplasty) and Bladder Reconstruction (including fistula), Augmentation, Substitution, Diversion I | 17BOS |
Abstract: MP24-02 Sources of Funding: N/A Introduction Ureteroneocystostomy with creation of Boari flap represents a good option to substitute for the loss of the distal ureter in both benign and malignant conditions. Traditionally the procedure is performed through a large midline or Gibson incision. Utilizing the robotic daVinci surgical sytem made it feasible to achieve the objectives of the procedure with minimally invasive approach. We aim to report on our first series of robotic assisted ureteral substitution with Boari flap. Methods Between September 2009 and May, 2016, the de Vinci Si robotic system was used to reconstruct 11 distal ureters for 3 benign and 8 malignant conditions, in our institute. We utilized the 5 W shaped trocar placement in 8 cases and added sixth trocar for assistance in 3 cases. The remaining ureteral end was spatulated and reimplanted end to end to the Boari flap. Utilizing the daVinci robotic sytem we implanted 6 right ureters and 5 left ureters into the robotically created Boari Flap. Negative margin was insured in all the malignant cases. Results The average patient age was 67 years (ranging from 34-79). We had 5 males and 6 females patients. All cases were completed robotically with no conversion, the patients were followed for an average of 32 months (ranging from 3 months to 64 months). The ureters were patent in all of the 3 (% 27) patients who had benign ureteral stricture. However, two patients (%18) who had lower ureteral TCC developed ureterovesical anastomosis stricture. . Both of the strictures were due to high grade TCC on the initial and final pathology after nephroureterectomy with excision of the flap. One patient with history of high grade TCC of the lower ureter developed multifocal high grade TCC in the renal pelvis on the same side 3 years later. Conclusions Robotic reconstruction of the lower ureter with Boari flap is feasible and has an acceptable oncologic outcome. High grade TCC of the lower ureter is predictor of recurrence at the anastomosis. Longer follow up is needed especially in cases of malignancy. Funding N/A
Authors
Mohamad Salkini
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MP24-03 |
Robotic-assisted ureteral reimplantation with psoas hitch: experience in 21 patients |
Trauma/Reconstruction/Diversion: Ureter (including Pyeloplasty) and Bladder Reconstruction (including fistula), Augmentation, Substitution, Diversion I | 17BOS |
Abstract: MP24-03 Sources of Funding: none Introduction Robot-assisted surgery represents a feasible and less challenging minimally-invasive option for complex urological reconstructive procedures, including ureteral reimplantation with psoas hitch. Published experience in this field is still limited. We report our 10-year experience of this technique from a tertiary care center. Methods All patients that underwent ureteral reimplantation with psoas hitch technique between 2006 and 2016 at our institution were included in this study. The robotic system was used in 4-arm configuration with the addition of 2 assistant ports. The transperitoneal approach and tunneled nonrefluxing ureteral anastomosis was performed in all patients. The psoas hitch was performed using a 1-0 suture. The perioperative complications were described according to Clavien-Dindo classification. Results 21 patients (11 men and 10 women) underwent robot-assisted ureteral reimplantation with psoas hitch technique. The median age was 66 years (IQR 41,73), body mass index 24 kg/m² (IQR 23,28) and Charlson Comorbidity Index 1 (IQR 0,2). In 2 (9,5%) patients the procedure was performed for bilateral pathology. 11 (52,4%) patients were symptomatic; of these 7 (33,3%) had pain, 2 (9,5%) hematuria and 2 (9,5%) pyelonephritis. 17 (81,0%) patients had hydronephrosis at the diagnosis. Indication for surgery was distal ureteral tumor in 7 (33,3%) patients, iatrogenic ureteral injury in 7 (33,3%), external ureteral compression in 4 (19,1%), vesicoureteral reflux in 2 (9,5%) and 1 (4,8%) patient had distal ureteral fibrosis of unknown origin. 13 (61,9%) patients had previous surgery near the distal ureter. Median operative time was 150 minutes (IQR 120,180). Mean blood loss was 30 mL (IQR 30,50). The all grade complication rate was 28,6%; five grade 1 (two prolonged pain, two transient paresthesia of the thigh and one urinary tract infection) and one grade 3 complication (bleeding required surgical revision) occurred. Median hospital stay was 5 days (IQR 4,7) and catheter time 7 days (IQR 6,10). Ureteral stent was placed in 13 patients and left in place for a median time of 30 days (IQR 20,42). After a median follow-up of 15 months (IQR 15,23) all patients were asymptomatic with no signs of hydronephrosis. Most of the patients improved renal function and none of them had a significant postoperative worsening of it. Conclusions This series represents the largest single-institution experience with robot-assisted ureteral reimplantation with psoas hitch technique and long follow-up. It represents a safe and effective technique with excellent outcomes and limited morbidity. Funding none
Authors
Vincent De Coninck
Paolo Umari Nicola Fossati Ruben De Groote Marijn Goossens Peter Schatteman Geert De Naeyer Frederiek D'Hondt Alex Mottrie |
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MP24-04 |
Expanding role of robotic surgery in reconstructive urology |
Trauma/Reconstruction/Diversion: Ureter (including Pyeloplasty) and Bladder Reconstruction (including fistula), Augmentation, Substitution, Diversion I | 17BOS |
Abstract: MP24-04 Sources of Funding: None Introduction As robotic surgery becomes more widely used, its applications are rapidly being expanded into areas of urology beyond oncology. The objective of this study is to review the institutional experience in robotic surgery in reconstructive urology. Methods Charts were retrospectively reviewed and patient demographic, surgical, and follow-up data were collected based on a single surgeon experience with robotic surgery in reconstructive urology from 2012-2016. Descriptive statistics were used to analyze this patient population. Results A total of 39 operations on 38 patients from a single surgeon were identified - 20 robotic pyeloplasties, 9 robotic ureteral reimplantations, 3 robotic uretero-ureterostomies, 3 robotic ileal conduits, 2 robotic ileal conduit revisions and 3 robotic vesicovaginal fistula repairs. Of the robotic pyeloplasties, 16 were dismembered while 4 were Y-V plasties. A crossing vessel was identified in 50% of cases. Indication for surgery included flank pain in 90% of patients, worsening kidney function in 20%, and infection in 10%. Median LOS was 1 day. Median follow-up was 7.5 months. All patients experienced resolution of symptoms, improvement in diuretic half time and stable or improved renal function on post-operative imaging. Of the robotic ureteral reimplants, 3 required psoas hitch and 3 required Boari flap. Median LOS was 1.5 days. Median follow-up was 8 months. All patients with adequate follow-up showed resolution of hydronephrosis, improvement in diuretic half-time and stable or improved renal function on post-operative imaging. All robotic uretero-ureterostomies were performed end to end. Indications included mid-ureteral stricture, iatrogenic mid-ureteral injury, and retrocaval ureter. Median LOS was 2 days. Median follow-up was 8 months, and all patients showed resolution of hydronephrosis, improvement in diuretic half-time and stable or improved renal function on post-operative imaging. All robotic ileal conduits and revisions were performed intracorporeally. Indications included urethrocutaneous fistula, neurogenic bladder, stricture of previous cutaneous ureterostomies after cystectomy, and anastamotic ureteral strictures. All robotic vesicovaginal fistula repairs were performed using sigmoid fat interposition, with one durable success. Conclusions Robotic surgery in the field of reconstructive urology is feasible and can be performed with good results. This is especially true of ureteral reconstruction, where all patients in this experience had good outcomes, with generally brief length of stay. Funding None
Authors
Michael W. Kemper
Alan Carnes Shenelle Wilson Rabii Madi |
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MP24-05 |
Upper urinary tract decompression using ileal ureter replacement in comparison to endoureteral thermoexpandable Stent [Memokath 051] |
Trauma/Reconstruction/Diversion: Ureter (including Pyeloplasty) and Bladder Reconstruction (including fistula), Augmentation, Substitution, Diversion I | 17BOS |
Abstract: MP24-05 Sources of Funding: none Introduction To assess the long-term outcomes and complications of Ileal Ureter Replacement (IUR) compared to the use of Memokath 051 for ureteral reconstruction. Methods In the last 10 years, two groups of patients with ureteral strictures (benign or malignant) have been followed up retrospectively. The first group consists of 17 patients, mean age of 59 years, presented with ureteral obstruction and treated with a thermoexpandable stent Memokath as a minimally-invasive procedure. Whereas the second group of 27 patients, mean age of 55 years received an IUR as alternative treatment method. Patients were followed for a mean period of 42 months. Assessment included examination of serum creatinine, renal ultrasound, retrograde pyelography and isotopic renography. Results In the first group (17 pat., 27 renal units): upper tract decompression was succeed in 6 renal units only (35%), in which 3 patients had initially no obstruction and the other 3 developed a temporary obstruction. 11 Patients developed a permanent obstruction (65%), 8 of those patients received another minimally-invasive treatment like percutaneous nephrostomy, DJ stent or reinsertion of Memokath stent. 3 patients underwent open surgery. 7 patients developed urinary tract infections (41%). Obstruction with deterioration of renal function secondary to dislocation of the stent developed in 5 patients (8 renal units - 29%). Early total obstruction due to insufficient dilatation effect of the stent took place in 1 patient. Other complications included: gross hematuria, irritative voiding, urinary retention as well as ureteroenteric fistula in 1 patient (3.7% of the renal units). _x000D_ In the second group, upper tract decompression was achieved in 24 (88.8%) patients; a secondary nephrectomy was performed in 2 patients. 1 patient underwent resection of the ileal interponate because of leakage of the pyelo-ureteral and uretero-vesical anastomosis due to malvascularization (advanced PAD). Secondary complications occurred in 4 (14.8%) patients: n = 2 urinary tract infections, n = 1 pelvic vein thrombosis, n = 1 wound infection. Renal function remained stable in all patients, and metabolic acidosis was not observed. Conclusions The IUR is an effective reconstructive measure of the upper urinary tract with a low complication rate and good long-term functional results. The IUR should be preferred to the Memokath, which is an alternative niche solution. Funding none
Authors
Ilgar Akbarov
Mustafa Al-Mahmid David Pfister Axel Heidenreich |
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MP24-06 |
Multicentre study regarding the outcomes of pyeloplasty and the role of follow up imaging. |
Trauma/Reconstruction/Diversion: Ureter (including Pyeloplasty) and Bladder Reconstruction (including fistula), Augmentation, Substitution, Diversion I | 17BOS |
Abstract: MP24-06 Sources of Funding: none Introduction Our aims were to assess the impact of waiting times on the split renal function after pyeloplasty and to determine the value of repeated MAG3 renograms after the procedure. We also compared the outcomes of pyeloplasty in those with split function >30% compared to those with poorly functioning kidney (split function ≤30%)_x000D_ _x000D_ Methods Retrospective analysis of all cases that underwent primary pyeloplasty in four centres in the UK from 2008 to 2015. We excluded those < 16 years old, single kidney, bilateral UPJO and other congenital renal abnormalities. We also excluded patients that did not have FU imaging. A change of >5% split function on renogram was considered significant. Logistic regression analysis was used to determine the impact of waiting times on split renal function after pyeloplasty Results 175 pts were included. The mean age was 41.2 years with a mean length of FU of 573 days. The mean pre-op split renal function (available in 161 cases) was 39.4% (SD 10.5). 35 pts had split function ≤30%. The mean waiting time from presentation to operation was 207 days (SD 277). The mean interval between pyeloplasty and 1st post-op renogram was 118 days (SD 73). The second post-op renogram was performed at a mean interval of 355 days (SD 193) following the 1st scan _x000D_ 89 pts had split function documented in one pre-op and two post-op renograms. Seventy-two cases (81%) showed stable or improved function on their first post-op renogram (58 stable, 14 improved) and the second post-op renogram showed renal function remained stable or improved in 68 (95%). In the remaining 4 pts, the split function only marginally deteriorated (average reduction of -7%). Of the 17 cases with worsening renal function on the 1st post-op renogram, the split function continued to deteriorate in only 2 cases. Both of which remained obstructed on the both 1st and 2nd post-op renograms. _x000D_ Pts that had worsening split function post-op had a longer waiting time for their procedure (the majority of those that waited over 200 days had poor functional outcomes, p= 0.01) _x000D_ Pain was the most common presenting symptom (80% of cases). 79.2% of these pts had improved symptoms post-op. Those with split function of ≤30% showed higher levels of pain post op (26.7%) compared to those with better function (20.8%) but this was not statistically significant (p=0.6)_x000D_ Conclusions Longer waiting times from presentation to definitive treatment appear to have a significant negative impact on split renal function post-pyeloplasty. The majority of patients received functional and symptomatic improvement post-pyeloplasty but there was no significant difference in outcome between those with split renal function of ≤30% compared those with better renal function. Those with favourable results on the 1st post-operative renogram (no obstruction with stable or improved function), may not require further imaging Funding none
Authors
Marcelino Yazbek Hanna
Muhammad Elmussareh Conor Devlin Peter Smith Ata Jaffer Catriona Shenton Naeem Desai Richard Napier-Hemy Anthony Browning Andrew Myatt Bachar Zelhof |
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MP24-07 |
Laparoscopic dismembered pyeloplasty in a horseshoe kidney |
Trauma/Reconstruction/Diversion: Ureter (including Pyeloplasty) and Bladder Reconstruction (including fistula), Augmentation, Substitution, Diversion I | 17BOS |
Abstract: MP24-07 Sources of Funding: None Introduction Horseshoe kidneys are frequently associated with other congenital anomalies and ureteropelvic junction obstruction. Laparoscopic pyeloplasty have been successful in treating horseshoe kidneys with acceptable functional results, although study subjects are limited. We report our experience with laparoscopic management of ureteropelvic junction obstruction (UPJO) in horseshoe kidneys. Methods Between November 2008 and August 2016, 10 patients with symptomatic UPJO of horseshoe kidneys were underwent laparoscopic pyeloplasty. All patients presented a primary UPJO with dilatation of renal calyx system with an enlarged renal pelvis. The mean age was 32 years (range 20 to 48), and of the 6 women and 4 men, 7 (70%) presented UPJO on the left side and 3 on the left side. All patients were subject to a preoperative evaluation including renal ultrasonography, diurethic renography and intravenous urography or CT scan that revealed the presence of severe hydronephrosis. 5 (50%) had aberrant vessels. We used four ports during laparoscopic pyeloplasty. In all cases we performed dismembered pyeloplasty. After laparoscopic pyeloplasty patients were initially evaluated by ultrasonography, then diuretic scintiscan at 4 to 6 months, and followed by yearly clinical and sonographic exams. Results All patients were treated laparoscopically, and no open conversions were needed. The mean operative time was 150 minutes (range 90-180 min). The mean estimated blood loss was negligible in all patients. The mean hospital stay was 3,5 days (2 - 6 d.). No intraoperative complications have occurred. A persistent UPJO was detected at first follow-up visit in one patient and was treated by transurethral endopyelotomy. A mean follow-up period was 18 months (range 8 – 84) and demonstrated a 90.0 % success rate after the initial operation. Conclusions Laparoscopic dismembered pyeloplasty in patients with UPJO of horseshoe kidneys is a safe and effective procedure with a high overall success rate, less morbidity and lower complication rates. Funding None
Authors
Boris Komyakov
Bakhman Guliev Alexander Shipilov |
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MP24-08 |
Secondary laparoscopic pyeloplasty after failed open repair of ureteropelvic junction obstruction: Case- matched multi-institutional study |
Trauma/Reconstruction/Diversion: Ureter (including Pyeloplasty) and Bladder Reconstruction (including fistula), Augmentation, Substitution, Diversion I | 17BOS |
Abstract: MP24-08 Sources of Funding: none Introduction Laparoscopic pyeloplasty (LP) after failed open repair of uretreopelvic junction obstruction (UPJO), although a challenging reconstructive endeavor, is increasingly reported. We retrospectively review our experience and midterm results of LP for patients who have failed open pyeloplasty in comparison with those who had primary LP Methods Preoperative, intaroperative and postoperative data of 32 patients who had transperitoneal dismemebered LP after failed open pyeloplasty were reviewed. All procedures were performed by two experienced laparoscopists during the period from March 2009 to June 2013. Surgical outcomes were compared to those in 72 patients who underwent primary LP carried out by the same surgeons during the same study period. Results The study group consisted of 14 men and 18 women with the mean age of 29± 6 years. Mean operative time was 186± 57 and 123± 22 minutes in the secondary and primary LP groups, respectively. Mean hospital stay was 4.7 ± 2.3 and 4.3 ± 2.1 days in the two groups, respectively. Mean follow-up was 36 ± 11.2 months (range 24-72 months). The overall success rate for secondary LP was 90.6% compared to 94.4% in the primary LP group. There was no conversion to open surgery in both groups. Intraoperative and postoperative complications in secondary and primary LP were 9.4 and 12.5% versus 0 and 5.6% in both groups, respectively. Conclusions LP is a safe and viable treatment option for secondary uretreopelvic junction obstruction with a success rate similar to that of primary repair but with longer operative time and higher complication rate. A good experience in laparoscopic reconstructive procedures is a prerequisite for optimal results. Funding none
Authors
Aly Abdel-Karim
Ahmed Hammady Ahmed Moussa Ahmed Fahmy Wael Gamal Elnesr Rashed Mohamed Mostafa |
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MP24-09 |
Single Institutional Experience with Lighted Ureteral Stents for Minimally Invasive Colorectal Surgery |
Trauma/Reconstruction/Diversion: Ureter (including Pyeloplasty) and Bladder Reconstruction (including fistula), Augmentation, Substitution, Diversion I | 17BOS |
Abstract: MP24-09 Sources of Funding: None Introduction Iatrogenic ureteral injury is a rare (0.38%) but serious complication after colorectal surgery. Lighted ureteral stents (LUS) have been used to aid in the visual identification of the ureters during minimally invasive approaches. We aim to investigate the technical challenges, complications, and cost of LUS placement at our institution. Methods A retrospective review was performed on all laparoscopic and robotic colorectal procedures at our institution between March 2011 and October 2016 where LUS were requested. Illuminated single lumen ureteral stents were placed and removed at the end of each procedure. Technical challenges with LUS placement and postoperative complications such as ureteral injury, hematuria and acute kidney injury (AKI) were evaluated. Statistical analysis was performed using SPSS v24. Results LUS were placed during 120 laparoscopic or robotic-assisted bowel resections. Technical challenges were encountered in 15% of cases (n=18), requiring dilatation of the urethra (n=4) or ureter(n=5), or placement of a non-illuminated stent (n=8). Mean operative time for complicated vs uncomplicated LUS placement was 26.4 minutes (STD=14.69) and 14.2 minutes (STD=9.35) respectively (p<0.001). Estimated cost of complicated vs uncomplicated stent placement was $1472.33 (STD=555.13) and $954.15 (STD=265.58) respectively (p=0.001). Estimated cost of bilateral vs unilateral LUS placement was $1209.90 (STD=321.65) and $865.34 (STD=378.01) respectively (p<0.001).Postoperative AKI was encountered in 9% of cases (n=11). Of these, 72% (n=8) received bilateral LUS, 18% (n=2) received unilateral LUS, and 9% (n=1) received an open-ended ureteral stent due to inability to place a LUS (p=0.095). In total, 52 cases received bilateral LUS and 15% of these (n=8) developed postoperative AKI. All AKI episodes were self-limited except in one patient who received bilateral LUS and developed postoperative oliguria, worsening creatinine, and mild hydronephrosis, requiring bilateral indwelling ureteral stent placement. 3% of patients (n=4) developed postoperative hematuria that resolved without intervention. There was one ureteral injury despite bilateral LUS, which was identified intraoperatively and repaired robotically via ureteroureterostomy. Conclusions We found that complications associated with LUS placement are rare and mostly self-limited. While illuminated stents may improve intraoperative identification of the ureters, further investigation is needed to determine their effectiveness in the prevention of ureteral injury. Funding None
Authors
Justina Tam
Wai Lee Daniel Grajower Andrew Chen Patrick Pfizenmayer Wanye Waltzer Jason Kim |
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MP24-10 |
Upper versus lower ureteral reconstruction: What are the Differences? |
Trauma/Reconstruction/Diversion: Ureter (including Pyeloplasty) and Bladder Reconstruction (including fistula), Augmentation, Substitution, Diversion I | 17BOS |
Abstract: MP24-10 Sources of Funding: none Introduction The purpose of this study was to analyze and compare upper to lower ureteral reconstruction (UR) for ureteral stricture in a large cohort of patients. Methods A retrospective analysis was performed in patients undergoing upper and lower UR for iatrogenic injury, complications of cancer surgery, and radiation, or retroperitoneal fibrosis. Distinction between upper and lower US was above and bellow the iliac vessels, respectively. Success was defined as ureteral patency on CTIVP, Mag-3 studies, symptoms resolution, and stabilization in renal function. A descriptive and a linear regression analysis were conducted to evaluate variables associated with recurrent stricture. Results A total of 128 patients were included of which 18 underwent bilateral UR. Iatrogenic injury following pelvic surgery was the most common etiology of US, followed by radiation (26.3%) and idiopathic retroperitoneal fibrosis. There was no significant difference between groups for age (p=0.23), gender (p=0.36), length of stricture (p=0.14), prior radiation exposure (p=0.52) and estimated glomerular filtration rate (p= 0.10). Time to surgery, number of prior attempts at reconstruction and number of patients diverted prior to final reconstruction were significantly higher for patient with upper US (p value = 0.02, 0.01 and 0.004, respectively). A total of 51% (74/146) of strictures treated were in the upper ureter and required complex reconstruction procedures. Median hospital stay was 7 days (range 1-56) and length of follow-up was 120 days (32 – 2824). Short-term complications developed in 52 (34.4%). With respect to lower UR (n=72), the procedures performed were reimplant (33/72), VPH (22/72), ureterolysis (9/72), ileal ureter (IU - 5/72), transureteroureterostomy (TUU - 2/72) and ureteroureterostomy (UU - 1/72). Success rates were 100%, 100%, 100%, 80%, 50% and 100%, respectively. With respect to upper UR (n=74), the procedures performed were IU (42/74), ureterolysis (12/74), UU (8/74), vertical flap pyeloplasty (5/74), VPH (4/74), Boari flap (2/74), and TUU (1/74). Success rates were 95%, 83.3%, 100%, 80%, 50%, 50%, 0%, respectively. The overall success rate was 88%. Boari Flap, TUU and radiation exposure were associated with inferior outcomes after UR, with p values of 0.03, 0.006 and 0.01, respectively. Conclusions Upper US required more complex procedures, associated with higher incidence of complications and a lower success rate when compared to lower US. Excellent anatomical and function outcomes are expected after the treatment of both upper and lower ureteral strictures. Funding none
Authors
Rodrigo R Pessoa
Lisa M Parrillo Paul D Maroni Ty T Higuchi Brian J Flynn |
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MP24-11 |
Mitrofanoff appendico-vesicostomy as a solution of delaying end stage renal failure in children: indications and results |
Trauma/Reconstruction/Diversion: Ureter (including Pyeloplasty) and Bladder Reconstruction (including fistula), Augmentation, Substitution, Diversion I | 17BOS |
Abstract: MP24-11 Sources of Funding: none Introduction to present the indications as well as the short and long term results of the Mitrofanoff appendico-vesicostomy (MAV) in children suffering of mild or moderate renal insufficiency. Methods Between January 1992 and April 2016, 51 children (27 boys and 24 girls) underwent a Mitrofanoff appendico-vesicostomy as external continent urinary diversion. we exclude at once those presented at end stage renal failure and required renal transplantation. The remaining (45) were aged between 5 and 15 years (mean 10.27); all of them underwent MAV in their right iliac fossa. Etiologies were dominated by neuropathic bladder (41 cases) ,mainly due to spina bifida defect with myelo-meningocele ; a posterior urethral valves causing altered bladder (2 cases) and complicated bladder exstrophy (2 cases). Diagnosis was established at advanced stage in all patients with mild renal failure (11) or moderate renal insufficiency in (34) with mean creatinine clearance of( 41 ml/min/1.73m2). Results The average follow-up was approximately 135 months (ranging from 12 to 256 months). All children became continent, 43 (95% ) after a single intervention. Minor complications consisted mainly on difficulties in intermittent catheterization (11.2%), they were treated merely by external stoma refection. The renal function deteriorated to severe renal failure (1 case), 6 years after surgery, then the patient underwent renal transplantation in his left iliac fossa; it remained stable at better levels with no need to dialysis, in 33 cases (average creatinine clearance of 58 ml/min/1.73m2), with mean follow up of 9 years ; it returned to normal (11 cases) .In addition, intermittent self-catheterization was well accepted by all children and their families ,with complete readaptation to daily activities with good quality of life . Conclusions The Mitrofanoff appendico-vesicostomy operation is usually associated to good results in children who suffer of some form of renal insufficiency . It ensures better continence status and a satisfactory educational rehabilitation. Our results demonstrate that it could also stabilize damaged renal function for quite a long time before renal replacement programmes if it was associated to mild or moderate renal failure. Funding none
Authors
Mohamed Nabil MHIRI
Mohamed Amine Mseddi Mohamed Fourati Anis Masmoudi Mehdi Bouassida Mourad Hadj Slimen Nouri Rebaï |
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MP24-12 |
A modified ileo conduit tecnique to avoid ureteroenteric stricture. |
Trauma/Reconstruction/Diversion: Ureter (including Pyeloplasty) and Bladder Reconstruction (including fistula), Augmentation, Substitution, Diversion I | 17BOS |
Abstract: MP24-12 Sources of Funding: none Introduction Despite the popularity of continent urinary diversion and neobladder recostruction, radical cistectomy with ileal conduit urinary diversion remains the most commonly performed curative surgical treatment option for invasive bladder cancer. Commonly, the ileal conduit is created using a 15-20 cm ileum length. The distal left ureter passage under mesosigmoid previous its extensive dissection, in order to allow a tension-free ureteroileal anastomosis, often leads to a compromised blood supply to the left ureter, resulting in a higher incidence of delayed ischemic damage of the distal ureter, wich is the most common cause of ureteroenteric stricture. In literature, ileoureteral stricture rate reported is 1,7-14%, being more common on the left side. Of some interest is the fact that no significant diferrence is been reported in strictures occurrance rate between Bricker anastomosis type and Wallace type. The strictures resulting from urinary diversion are difficult to treat, have a high risk of recurrence and may lead to renal function deterioration. We presented our results with a modified ileal conduit tecnique (MICT) and left ileoureteral anastomosis aimed to prevent uretero-ileal anastomosis stricture. Methods We prepared an ileal tract of 20 cm medium lenght. The proximal end of the ileal conduit tract was brought on the left side through the mesosigmoid and was fixed to the parietal peritoneum, to avoid an extensive dissection and mobilization of the left ureter and to perform a tension free anastomosis. On the right side, we performed a classical Bricker ureteroileal anastomosis, while on the left side the ureter was sutured directly to the end of ileal conduit, according to our modified ureteroileal anastomosis in Y shape ileal neobladder. Between 2001 and 2010, 98 consecutive patients underwent to radical cistectomy with ileal conduit diversion with Bricker anastomotic tecnique; from 2011 to 2015, 46 consecutine patients underwent to new tecnique. Results The MICT was easily performed in all cases, leading to neither intraoperative nor postoperative complications, without increasing intraoperative time. The ileoureteral stricture rate was 9.1% (8/98 patients, 1/8 patients with bilateral stricture) in the traditional tecnique; no patient had ureteral stricture with the modified tecnique. Conclusions Our preliminary experience with the MICT are very encouraging; further randomized studies with a larger series are needed to confirm our results. Funding none
Authors
Mauro Mari
Alesandra Ambu Stefano Guercio Francesco Mangione Maria Teresa Carchedi Susanna Grande Maurizio Bellina |
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MP24-13 |
Managing pregnancy in patients following complex urological reconstruction |
Trauma/Reconstruction/Diversion: Ureter (including Pyeloplasty) and Bladder Reconstruction (including fistula), Augmentation, Substitution, Diversion I | 17BOS |
Abstract: MP24-13 Sources of Funding: none Introduction Many patients following complex urological reconstruction can achieve pregnancy within a normal life. This study aimed to evaluate antenatal and intrapartum management, and outcomes of pregnancy following urinary tract reconstruction. _x000D_ Methods A retrospective review of data collected prospectively between 2010 and 2015 identified 34 pregnancies in 29 patients (median age 31.2 years, range 17 - 46). Primary abnormality included exstrophy-epispadias (9/29), spinal dysraphism (4/29), sacral agenesis (2/29), Fowler's syndrome (1/29), neuroblastoma (2/29), bladder cancer (1/29), congenital incontinence / small bladder /short urethra (8/29), congenital vesico-ureteric reflux (1/29) and urogenital sinus (1/29). Previous urological reconstruction included augmentation cystoplasty (15), ileal conduit (1), Mitrofanoff channel (15), ureteric reimplantation (4), colposuspension (2), artificial urinary sphincter (2) and antegrade continence enema channel (1). 5 patients had a solitary kidney. _x000D_ Results There were 35 (1 set of twins) live-births comprising 17 girls and 18 boys. Mean gestation at delivery was 36 weeks (33 - 38) and mean birthweight was 2.78 kg (1.79-3.50). The majority were delivered by elective Caesarean section (94.1%, 32/34) performed jointly by a urologist and obstetrician. Two women sustained bladder injury during surgery with no long-term complications. Another two women developed vesicocutaneous fistulas which resolved spontaneously (6.25%, 2/32). One woman required early (37 weeks) Caesarean section due to worsening hydronephrosis. Pregnancy-related urological complications included UTI requiring hospital admission (11.8%, 4/34) and upper tract obstruction requiring nephrostomy (20.6%, 7/34). Three women had difficulty with the Mitrofanoff, requiring indwelling catheters. No woman had significant deterioration in renal function._x000D_ Conclusions Pregnancy can be safely managed with preservation of renal function in women with previous urinary tract reconstruction. These women are prone to complications and require shared care and careful monitoring throughout pregnancy to diagnose and manage complications proactively. Patients should be made aware of the impact of pregnancy and the high rate of pregnancy related complications. Although some of these women could potentially achieve a vaginal birth, we favour planned Caesarean section, jointly performed by an obstetrician and urologist, in patients with complex urinary tract reconstruction, in order to avoid the potential maternal and fetal risks of a complex emergency Caesarean section. _x000D_ Funding none
Authors
Simon Rajendran
Neha Sihra Patrick O'Brien Dan Wood |
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MP24-14 |
No Stoma, One, or Two? Setting Expectations for Patients with Rectourethral Fistula |
Trauma/Reconstruction/Diversion: Ureter (including Pyeloplasty) and Bladder Reconstruction (including fistula), Augmentation, Substitution, Diversion I | 17BOS |
Abstract: MP24-14 Sources of Funding: none Introduction Rectourethral fistula (RUF) is a rare and challenging condition to manage. We report our experience to aid the management of patients who are candidates for repair with no resultant diversion (no stoma), either urinary or fecal diversion (1 stoma), or double diversion (2 stomas). Methods We identified patients presenting with RUF between 2005 and 2015. Demographics, follow up, RUF and surgical details, outcomes including diversion status, complications, resolution, recurrence, or persistence of RUF were collected through retrospective chart review. Suprapubic tube was considered a form of urinary diversion. Univariable and multivariable logistic regression models were used for statistical analyses. Results We identified 110 patients with RUF, 7 were lost to follow up early and excluded from our analyses. Median age was 63 (IQR 59-70) years. Mean follow up was 31 (IQR 6-42) months. 85 (83%) patients had RUF following PCa treatment (28 surgery alone, 10 surgery + radiation, 16 XRT + brachytherapy, 31 either type of radiation alone). In addition to these treatments, 30 had undergone secondary treatments (prostate cryotherapy, HIFU, TUNA, urethral or rectal instrumentation). The remainder were related to colorectal malignancy (9), inflammatory bowel disease (3), and other (6). 29 patients had prior failed RUF repair._x000D_ At last follow up, 53% of all 103 patients had no stoma. 17% and 12% had fecal and urinary diversion respectively, and 17% had 2 stomas. 78% had resolution while 8% had recurrence and 15% had persistence of RUF. _x000D_ 82 (80%) patients had undergone surgery for RUF repair at our institution (63 transperineal, 8 transanal, 6 abdominal, 5 cystectomy with diversion). 60% had no stoma, 15% and 17% had fecal or urinary diversion, 9% had 2 stomas. 25% of these 82 patients had complications (7 recurrences, 1 bowel anastomotic leak, 3 bowel obstruction, 1 cutaneous fistula, 1 ureteral injury, 6 infection, 2 deaths due to sepsis). Of the 75 patients with 1 or no stoma, 69 (92%) had resolution of RUF. Secondary treatments (as listed above) are associated with lower likelihood of &[Prime]no stoma&[Prime] (OR 0.28, p = 0.049)._x000D_ Conclusions Although the rate of RUF resolution is high, patients should be counseled on the possibility of permanent diversion and carefully selected for the optimal surgical management. In our overall series, 53% patients had no stoma, 39% had 1 stoma, and 17% had 2 stomas at 31-month follow up. Those with secondary treatments are less likely to have no stoma. Careful evaluation of the rectal repair is necessary prior to takedown of fecal diversion, as most complications occurred after this maneuver. Funding none
Authors
Amanda Chi
Shree Agrawal John M Lacy Hadley M Wood Kenneth W Angermeier |
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MP24-15 |
MANAGEMENT OF PUBIC OSTEOMYELITIS FOLLOWING PELVIC RADIATION WITH SIMULTANEOUS PUBIC DEBRIDEMENT AND URINARY DIVERSION |
Trauma/Reconstruction/Diversion: Ureter (including Pyeloplasty) and Bladder Reconstruction (including fistula), Augmentation, Substitution, Diversion I | 17BOS |
Abstract: MP24-15 Sources of Funding: None Introduction Pubic osteomyelitis (PO) is an uncommon but challenging complication of pelvic radiation for urologic and gynecologic malignancies. Some cases of PO result from urethral strictures requiring endoscopic management. Others occur spontaneously. We describe here our experience with urinary fistula complicated by PO. Methods We retrospectively reviewed patients with fistula and PO who underwent pubic debridement and simple cystectomy with urinary diversion from 2014-2016. PO was diagnosed by history, physical exam, C-reactive protein (CRP) and imaging (CT or MRI). We analyzed patient demographics, treatment history, management, and outcomes. Results Eight patients met study criteria (7 males, 1 female). All had a history of radiation for pelvic malignancy (7 prostate cancer, 1 cervical cancer). All but one patient had history of tobacco use. The median time between radiation and PO diagnosis was 9.5 years (range 1-15 years). Six had undergone interventions for urethral stricture disease, ranging between 1 to 3 procedures. All had a history of pelvic pain, urinary tract infection, and elevated CRP prior to the diagnosis of PO. Most underwent MRI for diagnosis of PO (5 MRI, 3 CT). Average CRP was 14.1 (range 4-24). All had pubic symphysis resection and bone cultures obtained during surgery. The most common organism was Staphylococcus aureus. Seven patients underwent ileal conduit urinary diversion and 1 patient had a transverse colon conduit. The average length of stay was 11.5 days. Two patients were admitted within 30 days of discharge. Complications consisted of one post-operative death due to pulmonary embolism, and 2 patients required drain placement for pelvic abscesses. No patient had recurrent PO. Average follow-up was 8 months (range 3-21 months). Conclusions Patients with fistula and PO can be definitively managed by combined pubic debridement, simple cystectomy and urinary diversion. Funding None
Authors
Daniel Shapiro
David Goodspeed Wade Bushman |
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MP24-16 |
Urosymphyseal fistulation - What’s in a name? |
Trauma/Reconstruction/Diversion: Ureter (including Pyeloplasty) and Bladder Reconstruction (including fistula), Augmentation, Substitution, Diversion I | 17BOS |
Abstract: MP24-16 Sources of Funding: none Introduction Urosymphyseal fistulation is a recently described condition which is also referred to in the literature as osteitis pubis or pubic osteomyelitis. The morbidity of this is considerable particularly the pain it generates, which is often uncontrollable and unbearable. The name of the condition reflects our understanding of the nature and cause of the problem and in view of the discrepancy in terminology we have assessed the clinical, biochemical, microbiological and histological evidence in our own group of patients to determine the nature of the condition. Methods There were 37 patients treated in our centre in the last five years (2012 - 2016 inclusive). We have complete data in 27 of these. Blood studies, imaging and microbiological investigations were performed preoperatively; microbiology and histology specimens were taken at the time of surgery; and there was further imaging and blood studies postoperatively. Results The only imaging investigation that was 100% reliable was MRI scanning. The white blood cell count was normal in 6 patients and the average elevation was to 12.3 x103/μL. The CRP was elevated in every patient up to a level of a mean of 26.5mg/L. There appeared to be no specific correlation between the CRP and the symptoms. Urine culture was positive in only 12 patients (44.4%) with an even spread between coliforms, pseudomonas spp. and candida spp.. The tissue culture was positive in 11 (40.7%) of the patients and did not necessarily match the urine culture. Histological assessment showed chronic inflammation in both the symphysis and the adjacent bone in 9 patients. There were external beam radiotherapy-related changes in all of these. There were chronic inflammatory changes in the symphysis alone in 18 patients. There was no evidence of osteomyelitis in any patient. Conclusions Essentially the characteristic intraoperative finding was of a thick-walled fluid containing cavity within the pubic symphysis which was sometimes related to inflammatory changes in the surrounding bone and sometimes to post-irradiation changes in the bone but never to any acute inflammatory change. Correlating the symptoms, the clinical findings, the surgical findings and the haematological and microbiological findings suggest that the fundamental problem is the urine leak and direct fistulation into (and sometimes through) the pubic symphysis. The more extensive the leak the worse the pain. The urinary and tissue microbiology did not correlate with each other or with the symptoms. _x000D_ _x000D_ The correct terminology for this condition, we believe, is Urosymphyseal Fistulae. _x000D_ Funding none
Authors
Simon Bugeja
Stella Ivaz Stacey Frost Mariya Dragova Daniela E Andrich Anthony R Mundy |
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MP24-17 |
Natural history, Prevalence, Predictors & Outcomes of Parastomal Hernia after Robot-Assisted Radical Cystectomy |
Trauma/Reconstruction/Diversion: Ureter (including Pyeloplasty) and Bladder Reconstruction (including fistula), Augmentation, Substitution, Diversion I | 17BOS |
Abstract: MP24-17 Sources of Funding: Roswell Park Alliance Foundation Introduction Parastomal hernia (PH) is a frequent complication of urinary diversion after radical cystectomy. We investigated the prevalence, predictors and outcomes of PH. Clinical and radiologic evidence of PH was also investigated. Methods Retrospective review of 446 patients who underwent RARC at our institution from 2005 was conducted. Data was reviewed for demographics, clinical findings, imaging results and other perioperative outcomes. Radiologic PH was defined as protrusion of abdominal content through the stoma defect in the abdominal wall. PH was further described in terms of symptoms and their management. Kaplan Meier method was used to depict time to developing PH and logistic regression to evaluate predictors of PH. Results 384 patients who underwent RARC and IC were included in the analysis. Mean age was 70 years with median follow up of 18 months (IQR 6.8-34-.7). 74 (19%) patients had radiological evidence of PH, 24 (32%) were symptomatic and 8 (11%) underwent treatment. Median time to develop PH was 13 months (IQR 8.8-22). PH occurred at a rate of 10%, 33% and 36% at 1, 3 and 5 years respectively (Fig 1). Median time to symptoms was 24 months after RARC (IQR 7-39.6) and (8 months after radiological diagnosis. Patients with PH had significantly higher BMI (30 vs 28, p=0.009), longer overall operative time (347 vs 388 min, p=0.01), urinary diversion time (128 vs 108 p=0.03) and higher blood loss (400 vs 250, p=0.01). The incidence of PH was studied based on incorporation of intra-corporeal diversion in the program (Fig 2). On Multivariable analysis operative time was the only variable associated with higher incidence of PH (OR 1.25, 95% CI 1.02-1.04,p<0.001). Conclusions PH is a common complication following RARC (20%). Approximately one-third will develop symptoms and 10% will require surgical treatment. Risk for developing PH plateaus after the 3rd year. Longer operative time was associated with higher incidence of PH. Funding Roswell Park Alliance Foundation
Authors
Youssef Ahmed
Ahmed Hussein Paul May Basim Ahmad Taimoor Ali Khurshid Guru |
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MP24-18 |
Detrusor bioengineering using compressed collagen, adipose-derived stem cells and smooth muscle cells |
Trauma/Reconstruction/Diversion: Ureter (including Pyeloplasty) and Bladder Reconstruction (including fistula), Augmentation, Substitution, Diversion I | 17BOS |
Abstract: MP24-18 Sources of Funding: Fromm Fellowship_x000D_ Helmut Horten Foundation Introduction Conditions impairing bladder function in children and adults often need urinary diversion or augmentation cystoplasty as when untreated they may cause severe bladder dysfunction and kidney failure. Currently, the gold standard therapy of end-stage bladder disease refractory to conservative management is enterocystoplasty, which despite providing functional improvement is associated with significant long-term complications. Therefore, there is a strong clinical need for alternative therapies for these reconstructive procedures. The aim of this study is to develop functional smooth muscle tissue for the detrusor muscle repair combining various cell types in hydrogel scaffolds. Methods Rat bladder smooth muscle (SMC) and adipose-derived stem cells (ADSC) were isolated, expanded and characterized using flow cytometry. ADSC were pre-differentiated into SMC-like cells (pADSC). Cells were combined in ratios 1:1, 1:2 and 1:3 (SMC:pADSC) and embedded in compressed collagen (CC). After 1, 2 and 3 weeks, cells in CC scaffolds, direct and indirect 2D co-cultures were analyzed for viability, proliferation, morphology, SMC-marker expression and functionality. Results Cell growth conditions have been optimized and cells have shown high viability and good proliferation in the CC scaffolds. Interconnected microtissues and cell layers have developed all over the CC already after 1 week of co-culture. At 1 and 2 week timepoints cells in CC showed strong expression of the SMC markers calponin, MyH11 and smoothelin. Direct cell co-culture resulted in significantly increased cellular proliferation. Microtissues consisted of a SMC-core surrounded by pADSC. Indirect co-culture resulted in an increased pADSC survival and ratio-dependent increase in SMC-proliferation. pADSC proliferation rate also improved, but remained unaffected by the cell ratio, with 1:1 showing the most consistent results. SMC-marker expression normalized between the different ratios after 2 weeks of co-culture and reached almost the SMC monoculture expression levels. The 1:1 co-culture contracted significantly better than the other ratios after 24h. Conclusions We have shown that a SMC–pADSC co-culture results in an improved cell survival, proliferation, microtissue and cell layer formation without any significant changes in phenotype and functionality. The combination of SMC and pADSC with CC may help to engineer functional detrusor muscle tissue by solving the major issues of tissue engineering, namely poor cell survival, proliferation, phenotype instability and functionality. Funding Fromm Fellowship_x000D_ Helmut Horten Foundation
Authors
Jakub Smolar
Maya Horst Daniel Eberli |
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MP24-19 |
Transvesical Ventral Buccal Mucosa Graft Inlay Cystoplasty for Reconstruction of Refractory Bladder Neck Contractures after Benign Prostatic Hyperplasia Surgery: Surgical Technique and Preliminary Results |
Trauma/Reconstruction/Diversion: Ureter (including Pyeloplasty) and Bladder Reconstruction (including fistula), Augmentation, Substitution, Diversion I | 17BOS |
Abstract: MP24-19 Sources of Funding: None Introduction The treatment of bladder neck contracture (BNC) after BPH surgery is challenging and may even require open reconstructive surgery in patients that whish to avoid chronic catheterization or suprapubic urinary diversion. The aim of this study is to introduce a novel surgical technique for the reconstruction of refractory BNC using buccal mucosal graft (BMG) inlay through a transvesical approach. Methods We performed a retrospective analysis of patients that underwent open reconstructive surgery for refractory BNC after BPH surgery from 2010-2016 by a single surgeon (BJF). Steps of the procedure: transvesical ventral wedge resection of the fibrotic bladder neck contracture and spread fixation of appropriately sized BMG inlay. The patients were followed for post-operative complications and stricture recurrence with uroflowemtry, PVR, cystoscopy and outcome questionnaires. Outcome measures included length of follow-up, surgical technique, operative time, hospital stay, complications, and subsequent need for catheterization Results A total of 13 patients presented refractory BNC of which 11 were suitable for reconstruction and 2 required urinary diversion. Eleven patients underwent reconstruction underwent transvesical ventral buccal mucosa graft inlay cystoplasty. Prior BPH surgery included transurethral resection of the prostate (64%), plasma vaporization of prostate (27%), and open prostatectomy (9.1%). Urinary retention (82%) was the most common presenting symptom and 73% of patients were using a catheter (Foley, suprapubic, self-catheterization) pre-operatively. An average of 2.3 endoscopic procedures were performed before BNC reconstruction. Overall, BNC diameter was 9.1 Fr. The average BMG size was 11.3 cm2, operative time was 298 minutes, and hospital stay was 3.3 days. Post-operatively, four patients had transient urinary retention and two had epididymorchytis. At a mean follow-up of 1.2 (0-5.1) years, only one patient had chronic retention and was considered a failure and remains dependent on self-catheterization. Conclusions BNC after BPH surgery is challenging surgical issue. Transvesical ventral BMG inlay cystoplasty is a feasible option that effectively treats refractory BNC. This graft augmentation technique using buccal mucosa graft provide good outcomes with low morbidity for patients that failed multiple endoscopic treatments Funding None
Authors
Rodrigo Donalisio da Silva
Jeffrey M. Marks Fernando J. Kim Brian J. Flynn |
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MP24-20 |
Early Ambulation Decreases Hospital Length of Stay in Renal Trauma: A Randomized, Prospective Study |
Trauma/Reconstruction/Diversion: Ureter (including Pyeloplasty) and Bladder Reconstruction (including fistula), Augmentation, Substitution, Diversion I | 17BOS |
Abstract: MP24-20 Sources of Funding: none Introduction Non-operative management (NOM) is the standard of care for blunt renal trauma. Observation for blunt renal trauma has been widely adopted with practitioner dependent duration of bed rest. A paucity of data exists regarding the effect of bed rest on outcomes and on hospital length of stay (LOS). Urologists commonly offer either bed rest for four to five days or until the resolution of gross hematuria._x000D_ Given the system-wide emphasis on reducing LOS, we sought to prospectively determine if early ambulation leads to shorter hospital stays and its safety for patients with grade 2-4 blunt renal trauma._x000D_ Methods After obtaining IRB approval and consent from patients with Grade 2-4 renal laceration, patients were randomized to either four days of strict bed rest or strict bed rest until resolution of hematuria. Primary end-point was hospital LOS while intervention performed, complications, and rate of re-bleed was also collected. The study was closed due to failure to accrue._x000D_ Results From Aug 2012 - Sep 2015, 12 patients were randomized into one of the two groups. The bed rest group consisted of four patients while the early ambulation group consisted of eight. Median age overall was 23.5, with 22.99 in the bed rest and 25.61 in the early ambulation group (p=0.8). Overall, 3 were female (25%) and 9 were male (75%). The cohort consisted of one Grade 2 (8.3%), eight Grade 3 (66.7%), and three Grade 4 (25.0%) renal lacerations. _x000D_ Median time to ambulation was 2 days, with 5 and 1.5 days for bed rest and early groups, respectively (p<0.01). Median LOS was 4.0 days with 6.0 days and 3.0 days for the bed rest and early groups, respectively (p<0.05)._x000D_ No re-bleeds were documented in either group and no interventions were required for the early ambulation group. Two patients in the bed rest arm required angiography without other intervention and one required a blood transfusion. One patient acquired a catheter associated urinary tract infection._x000D_ Conclusions Strict bed rest protocols are associated with higher morbidity due to prolonged immobilization and the subsequent increase in LOS exposure iatrogenic morbidity and cost. Albiet a small sample size, our data illustrate Level 1 evidence that early ambulation yields decreased hospital LOS without causing adverse side effects. _x000D_ Funding none
Authors
Ilija Aleksic
Igor Sorokin Himanshu Aggarwal Adam Walker Paul Feustel Ronald Kaufman |
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MP25-01 |
CURVATURE CORRECTION TECHNIQUES FOR RESIDUAL CURVATURE AFTER PENILE PROSTHESIS PLACMENT: FROM PERSONAL OPINION TO OBJECTIVE DATA |
Sexual Function/Dysfunction: Surgical Therapy I | 17BOS |
Abstract: MP25-01 Sources of Funding: Boston Scientific Introduction Residual curvature after placement of a penile prosthesis (PP) is a common occurrence with many different opinions on how to &[Prime]handle&[Prime] the needed straightening and no objective, multicenter data. We present for the first time a large, prospective, multicenter study that incorporated evaluating what intraoperative management techniques were utilized, how effective and need for adjunctive methods these straightening maneuvers are intra-operatively. Methods A total of 313 [of a total of 1297 (24.1&[permil])] PP patients who underwent residual curvature correction techniques from the PROPPER database were included in this analysis. We evaluated 4 curvature correction techniques, up to 3 techniques used per patient, the starting and ending residual curvature for each technique, how much each technique required an additional straightening maneuver, and penile length before and after the procedure. Results Wilson / Delk remodeling was the most common first curvature correction technique used (264/313) 84&[permil]: followed by tunical incision (19/313) 6&[permil]; incision and grafting (17/313) 5.4&[permil]; and plication (11/313) 3.5&[permil]. However, the 2 least utilized first techniques required the lowest need for a second curvature correction technique with incision and grafting needing no additional techniques and only one plication (1/11) 9&[permil] requiring an additional Wilson / Delk remodeling. Meanwhile (14/19) 73.7&[permil] of the tunical incisions required an additional Wilson / Delk remodeling. See table for Wilson / Delk remodeling results. Conclusions Residual curvature requiring curvature correction technique after implantation of a PP is a common problem facing prosthetic surgeons. While Wilson / Delk remodeling and tunical incision are the most common first techniques utilized, incision and grafting and plication appear to require little need for a second maneuver. Funding Boston Scientific
Authors
Gerard Henry
Ed Karpman Anthony Bella Nelson Bennett Brian Christine LeRoy Jones Bryan Kansas Mohit Khera Tobias Kohler Eugene Rhee Will Brant |
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MP25-02 |
Exploring The Predictors Of Low Satisfaction After Penile Prosthesis Implantation |
Sexual Function/Dysfunction: Surgical Therapy I | 17BOS |
Abstract: MP25-02 Sources of Funding: none Introduction Despite reportedly high satisfaction with penile implant (PI) surgery, some patients remain dissatisfied. Complications such as infection, mechanical malfunction and erosion remain significant concerns and are major contributors to patient dissatisfaction and regret. We aimed to explore outcomes and complications after PI surgery and to search for predictors of patient satisfaction. Methods All patients who underwent PI surgery were included in the analysis. Comorbidity, demographic and implant information were recorded. Complications recorded included: minor (requiring no re-operation) such as, penile edema, hematoma, superficial wound breakdown; major (requiring hospitalization or re-operation) such as device infection, erosion, mechanical malfunction. Patient satisfaction was defined using a single question posed to the patient 6 months after surgery with a 5-point Likert scale (1 dissatisfied, 2 somewhat dissatisfied, 3 neutral, 4 somewhat satisfied, 5 satisfied). Descriptive statistics were used to define complication rates and multivariable analysis (MVA) was performed to define predictors of high (satisfaction score ?4), including degree of complication, Peyronie’s disease (PD), diabetes (DM), number of vascular comorbidities, BMI >30 and patient age. Results 901 patients were analyzed. Mean age 56.6±10.6 years. Mean BMI 30.2±5.1. Comorbidity profile was: diabetes 75%, dyslipidemia 44%, hypertension 33%, cigarette smoker 32%, PD 34%. 76% had a malleable implant and 24% an inflatable implant. 31% had a minor complication and 9% a major complication. 93% had high satisfaction (?4). Patients with any complication had a reduced rate of high satisfaction compared to those without (88% vs 98%; p<0.001) and likewise with a major complication (64% vs 98%; p<0.001). On MVA, BMI >30, number of vascular risk factors, type of implant and DM were not predictive of high satisfaction. Only the absence of a major complication was a significant predictor of high satisfaction (OR 20, 95% CI 9-50, p <0.001). The presence of PD was almost statistically significant. Conclusions A high percentage of men are satisfied after penile implant surgery. Only the presence of a major complication is robustly linked to a lower likelihood of achieving high satisfaction. Funding none
Authors
Mohamad Habous
Osama Abdelwahab Osama Laban Raanan Tal Saad Mahmoud Alaa Tealab Saleh Binsaleh John Mulhall |
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MP25-03 |
New Data Regarding Penile Length Preservation After IPP Implantation |
Sexual Function/Dysfunction: Surgical Therapy I | 17BOS |
Abstract: MP25-03 Sources of Funding: none Introduction The inflatable penile prosthesis (IPP) is the gold standard for the treatment of erectile dysfunction refractory to medical management. Loss of penile length after IPP implantation is a concern for many patients with ED who choose surgical treatment. Evidence of preservation of penile length in the postoperative setting would enhance functional outcomes and could remove a potential barrier to intervention. The purpose of the study was to evaluate the effectiveness of the Coloplast (Minneapolis, MN) Titan® cylinders in maintaining penile length post-IPP implantation in patients treated for ED._x000D_ Methods A single-armed, multi-center, multi-surgeon, prospective study was conducted with 117 patients. These surgeries were performed via both an infrapubic and a penoscrotal approach. Each penis was measured via flaccid stretch using a Furlow device from the dorsal penile base (pressed against pubic bone) to the tip of the glans. The corpora were engorged intra-operatively with an artificial saline erection (ASE). Corporal cylinders were selected based on measured corporal length without upsizing. Erect measurements were taken during both the ASE and after inflating the implanted device, in both instances from the same positions as preoperatively. Statistical difference and correlation coefficients between the preoperative penile stretch test (PST), intra-operative artificial saline erection (ASE) and erect prosthetic length (EPL) were calculated. Results The mean patient age was 65.42 +/- 7.8 years. The average preoperative penile stretch was 15.03 cm, artificial erection 14.76 cm, and average erect prosthetic length was 15.28 cm. The differences between all three of these measurements reached statistical significance based on the 95% confidence intervals. On average the EPL was 0.25 cm greater than the PST. Conclusions Preoperative penile length was preserved and exceeded in our series, which challenges the conventional wisdom that loss of penile length is a foregone conclusion after IPP placement. This suggests that chronic hypoxia due to lack of neurovascular inputs, or scarring from Peyronie’s disease, radiation, previous surgery, or medical conditions, are the main culprits of loss of penile length as males age. We recommend early intervention in patients that fail conservative therapy for erectile dysfunction to preserve maximal length. Funding none
Authors
Jared J Wallen
HI Ayoub OL Westney MS Gross PE Perito |
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MP25-04 |
Cost-Effectiveness of IPP versus Injection Treatment in Patients who Fail Oral Medication |
Sexual Function/Dysfunction: Surgical Therapy I | 17BOS |
Abstract: MP25-04 Sources of Funding: None Introduction Erectile dysfunction is reported in up to 50% of men 40 years old and older, with the real number likely higher due to negative reporting bias. Although first line medication options have increased in the last few decades, approximately 30-35% of men still fail oral medications. Furthermore, healthy men are reporting average sexually active life expectancies up to 70 years old. We analyzed the cost-effectiveness of intracorporeal injection (ICI) therapy versus inflatable penile prostheses (IPP) management for patients who fail Viagra therapy. Methods We performed a cost effective analysis using published complication and efficacy data, Medicare reimbursement costs, and commercial cost data. We compared the cost of IPP treatment including rate of infection, mechanical failure and re-operation with ICI treatment over a 15-year time-span, which is the average life of an IPP. Results Compared with ICI, IPP was more cost-effective although the overall cost (ICI $15,570 vs IPP $13,571) and health utility (ICI 0.93 vs IPP 0.92) was comparable in both groups. One-way sensitivity analysis showed that injections became cheaper, while maintaining similar efficacy at a cost less than $17.22 per injection. Similarly, when the frequency of monthly sexual intercourse fell below 3.5 times per month, ICI became the less costly option. Conclusions The average sexual lifespan of a healthy man in his 50s is estimated at 15 years and increasing. The price of injections and the rate of monthly injections were significant factors driving costs. Our study shows that IPP is the less costly approach for men overall. However, for men who successfully respond to less costly injection formulations and are happy with a lower frequency of monthly sexual intercourse, ICI may be a less costly option with similar successful outcomes. Funding None
Authors
Nancy Wang
Remy Lamberts Catherine Harris |
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MP25-05 |
A survey on Korean urologist’s practice pattern in surgical management of premature ejaculation |
Sexual Function/Dysfunction: Surgical Therapy I | 17BOS |
Abstract: MP25-05 Sources of Funding: none Introduction Current guidelines of ISSM for premature ejaculation(PE) does not recommend selective dorsal nerve neurotomy(SDN) or hyaluronic acid gel glans penis augmentation(HA-GPA) with concern of permanent loss of sexual function. However, in Korea many urologists have performed surgical management in PE as one of the treatment modality. This study conducted an e-mail based survey to analyze Korean urologist&[prime]s practice pattern and clinical outcomes of surgical treatment in PE. Methods A specially designed questionnaire was mailed to all registered members of The Association of Korean Urologist and The Korean Society for Sexual Medicine and Andrology from March 2016 to July 2016. A questionnaire consisted of 5 components: responder demographics, diagnosis of PE, the management of PE, practice pattern of SDN and HA-GPA. Results Total 54 urologists replied at the end of the survey. Their mean age was 50.1(37-64) years and the mean period after acquiring urology certification was 19.0 (6-34) years. 42 (77.2%) Urologists managed PE patients with surgical therapy such as SDN and HA-GPA. 47(87.0%) and 36 (66.7%) urologist had prior experience of SDN and HA-GPA, respectively. They reported that they had performed total 10,732 cases of SDN, 4,344 cases of HA-GPA and 1,905 cases of autologous fat glans augmentation up to date. They experienced 401(3.7%) cases of pain or paresthesia on glans and 120 (1.1%) case of erectile dysfunction after SDN. On the other hand, they reported only 36 (0.8%) cases of pain or paresthesia on glans and no case of erectile dysfunction after HA-GPA. Others complications of three surgical modalities were summarized in Table 1. Conclusions In this survey, the reported incidence of permanent loss of sexual function after surgical treatment of PE was rare, unlike ISSM&[prime]s concern. Especially, the reported paresthesia and hypoesthesia after HA-GPA were extremely rare and no case of erectile dysfunction was reported in this survey. These survey results warrant well design multi-center study is needed to clarify the relation between the HA-GPA and loss of sexual function to reconsider the current ISSM guideline in treatment of PE. Funding none
Authors
Sun Tae Ahn
Hyeong Guk Jeong Ji Yun Chae Jong Wook Kim Je jong Kim Du Geon Moon |
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MP25-06 |
Preservation of ejaculation function with nerve sparing in patients undergoing retroperitoneal lymph node dissection. |
Sexual Function/Dysfunction: Surgical Therapy I | 17BOS |
Abstract: MP25-06 Sources of Funding: none Introduction Preservation of periaortic nerve plexus during retroperitoneal dissection (RPLND) is considered a key to maintaining ejaculation function in patients with testicular cancer. Nerve-sparing techniques are often employed during primary RPLND. However, in patients undergoing RPLND after chemotherapy the rates of nerve sparing and its impact is not very clear. We sought to evaluate our experience with nerve sparing in patients undergoing RPLND for testicular cancer._x000D_ Methods On retrospective review of our database (2006-2015), 73 patients were included in the study. Patient demographics, clinical, pathological, and patient reported ejaculation function information was obtained. Non-parametric tests were used for analysis. Results Median age of the cohort was 29 years (IQR 23-66). Non-seminoma histology was noted in 65% patients with 43% patients noted to have lympho-vascular invasion. A total of 51% patients had post-orchiectomy elevated tumor markers and 59% underwent chemotherapy. Post-chemotherapy elevated tumor markers were noted in 11% patients and 27% patients had residual mass. On RPLND, 23% patients noted to have germ cell tumor and 14% noted to have teratoma in the excised nodes/mass. Bilateral template RPLND was performed in 74% of the patients. In patients with primary RPLND, nerve sparing was performed in 83% of the patients and in patient with post-chemo RPLND; nerve sparing was performed in 54% of the patients. In patients with primary RPLND with nerve sparing 82% (CI 57-94) had ejaculation function and in patients with post chemo RPLND 76% (CI 51-90) patients had ejaculation function (p=0.67) Conclusions Preservation of periaortic nerves is feasible both in patients undergoing primary as well as post-chemotherapy RPLND with maintenance of high rate of ejaculation function. There is no significant difference in preservation of ejaculation function between primary and post chemotherapy RPLND groups when optimal surgical technique is used to preserve the periaortic nerves. _x000D_ Funding none
Authors
Sudhir Isharwal
Sij Hemal Shree Agrawal Eric Klein Andrew Stephenson |
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MP25-07 |
Outcomes of Inflatable Penile Prosthesis in Patients Exposed to Pelvic Radiation |
Sexual Function/Dysfunction: Surgical Therapy I | 17BOS |
Abstract: MP25-07 Sources of Funding: None Introduction The prevalence of moderate to severe erectile dysfunction (ED) in the general population is 25%. This is compounded by exposure to pelvic radiation with some series estimating ED to be 22% to 84%, with higher numbers seen in patients who have undergone prior pelvic surgery such as for prostate cancer. Inflatable penile prosthesis (IPP) offers patients a definitive treatment option in patients refractory to medical therapy. We present our contemporary experience in placing a three-piece IPP for medication-refractory ED in patients with a history of pelvic radiation. _x000D_ Methods From 2010-2016, using an IRB-approved database we completed a retrospective review of 450 patients who underwent primary placement of an IPP (AMS 700CXM, American Medical Systems Inc, Minnetonka, MN, USA) Of those patients, 46 patients had been exposed to pelvic radiation, either external beam or brachytherapy. Some of these patients also had radical prostatectomy (12) or other pelvic surgery performed either primarily or in a salvage setting. A three-piece IPP was implanted via an infrapubic (96%) or penoscrotal approach (4%) and the reservoir placed in the space of Retzius (35%) or in the retroperitoneum via a separate incision (65%) depending on their previous surgical history. 20 patients had artificial urinary sphincters (AUS) placed during a different setting. Patient demographics and postoperative outcomes including prosthetic infection were examined._x000D_ Results No intraoperative complications were observed in patients with exposure to pelvic radiation who underwent placement of an IPP. After a mean follow-up of 753 days (35 - 2,454 days), there were no IPP infections observed. One patient had an erosion of their AUS which required explantation. A total of 6 patients (13.0%) required revisional surgery, with 3 pump revisions, 1 reservoir revision, and 2 cylinder replacements (aneurysm or upsizing). When compared to all patients who underwent IPP placement during that same study period we found no increased risk of infection in these patients. Conclusions Despite improvements in the delivery of radiation to the pelvis, erectile dysfunction is still a major cause of patient dissatisfaction. The IPP offers patients a definitive treatment option and excellent patient and partner satisfaction. In the hands of experienced surgeons, there is no increased risk of complications associated with placing these devices in this patient population. Funding None
Authors
Jeffrey Loh-Doyle
Zein Nakhoda Wesley Yip Nima Nassiri Stuart Boyd |
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MP25-08 |
Outcomes of Inflatable Penile Prosthesis After Radical Cystoprostatectomy and Urinary Diversion |
Sexual Function/Dysfunction: Surgical Therapy I | 17BOS |
Abstract: MP25-08 Sources of Funding: None Introduction After radical cystoprostatectomy (RC), post-operative erectile dysfunction can have a significant impact on a patient's quality-of-life. Inflatable penile prosthesis (IPP) offers patients a definitive treatment option when refractory to medical therapies. To date, there is no series describing the outcomes of three-piece IPP in patients with urinary diversions. Due to the obliteration of the space of Retzius and hostile anatomy of these patients a careful surgical approach is necessary for successful outcomes. We present a description of our technique in placing a three-piece IPP for post-operative erectile dysfunction in patients with a history of RC with orthotopic neobladder (NB), ileal conduit, or continent cutaneous diversion (CCD)._x000D_ Methods From 2007 - 2016, using an IRB-approved database we completed a retrospective review of patients who underwent primary placement of an IPP. We identified 61 patients (54 NB, 4 ileal conduit, 3 CCD) with urinary diversion who underwent subsequent placement of a three-piece IPP (AMS 700CXM, American Medical Systems Inc, Minnetonka, MN, USA). All 61 patients underwent RC in their treatment of carcinoma (55 bladder, 6 prostate). The device was implanted via an infrapubic approach and the reservoir placed in the lateral retroperitoneal space via a separate incision two finger-breadths medial to the anterior superior iliac spine. Patient demographics and postoperative outcomes including prosthetic infection were examined and statistical analysis was performed. _x000D_ Results There were no high-grade intraoperative complications. Median follow-up was 16.8 months (2-76 months). Three patients (4.9%) developed an infection of their prosthesis that required explantation. Two of those patients underwent successful IPP reimplantation. 5 patients (8.1%) required revision surgery (4 pump relocations, 1 corporal aneurysm repair). We did not find statistically significant associations between infection and comorbidities, age, exposure to chemotherapy, or type of urinary diversion. Conclusions Despite advances in neurovascular sparing techniques, sexual dissatisfaction is common in patients after RC. Patients are often refractory to medical therapy. The IPP offers patients a definitive treatment option and excellent patient and partner satisfaction. In the hands of experienced surgeons, the three-piece IPP can be placed successfully in patients with all form of urinary diversion. Funding None
Authors
Jeffrey Loh-Doyle
Mukul Patil Hari Sawkar Stuart Boyd |
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MP25-09 |
Use of 3D printing to prototype a custom shape memory alloy penile prosthesis |
Sexual Function/Dysfunction: Surgical Therapy I | 17BOS |
Abstract: MP25-09 Sources of Funding: Partial Funding through Boston Scientific Introduction Three-dimensional (3D) printing or additive printing is a new technology that allows for construction of complex shapes and designs outside the constraints of traditional manufacturing techniques. Traditional 3D printing was limited to thermosensitive plastics that have limited medical applications. Herein, we describe the application of a novel process that allows for 3D printing of shape memory alloys (SMA). Using our previously described concept of a SMA penile prosthesis for the treatment of erectile dysfunction, we sought to construct an intracavernosal cylinder using 3D printing technology. Methods A computer-aided design (Solidworks) 3D construct of the exoskeleton for our SMA penile prosthesis was fed into a computer-controlled 3D Bio Plotter (EnvisionTec, Germany). A novel custom printing ink consisting of pre-alloyed nickel-titanium (Ni-Ti) powder suspended in a Poly Lactic-co-Glycolic Acid (PLGA) and tri-solvent mixture was serially added in a precise 3D pattern to produce a green body reflecting the CAD geometry. Subsequently, the green body was sintered at a temperature of 1200 C, just 20-30 C below the melting point of NiTi, for 5 hours to produce the final product. This was then evaluated for its mechanical properties compared to our Ni-Ti extruded tube. Results A 1:4 scale version of the exoskeleton of our novel SMA penile prosthesis was constructed using 3D printing technology from Ni-Ti powder suspended in a PLGA/solvent mixture. Total printing time was 20 minutes (figure 1). After sintering, there was a ~30% volume reduction, which was homogenous in 3 directions. Mechanical properties were evaluated and found to be comparable to non-3D printed prototypes and SMA properties maintained. Conclusions 3D printing is a viable option for construction of SMA devices, including penile prostheses. The 3D-printed SMA prototype maintained its unique biomechanical properties. This technology opens up the possibility of more complex structures and customization without the constraints of traditional manufacturing techniques. Funding Partial Funding through Boston Scientific
Authors
Brian Le
Kevin McVary Alberto Colombo |
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MP25-10 |
Characteristics and Infection Risk in Patients Undergoing Multiple Inflatable Penile Prostheses |
Sexual Function/Dysfunction: Surgical Therapy I | 17BOS |
Abstract: MP25-10 Sources of Funding: None Introduction Inflatable penile prosthesis (IPP) remains the gold standard for refractory erectile dysfunction (ED). Despite ongoing improvements, infectious complications remain a significant concern in IPP revision surgery. We therefore sought to evaluate the impact of number of IPPs and IPP surgeries on subsequent infection rates. Methods A retrospective analysis was performed of all men presenting to a tertiary referral center for consideration of IPP revision or salvage surgery between 2013 & 2015. Demographic and clinical features were reviewed, including number of prior IPPs, reason for evaluation, and rate, number, and timing of IPP infections. Statistical analyses were performed to evaluate associations between number of IPP related surgeries and device placements and resultant infectious complications. Results A total of 44 men (median age 69; range 50, 88) were identified with at least one prior IPP. The most common reason for presentation was malfunction (52%, 23/44), followed by infection with device removal (23%, 10/44). Prior surgeries were performed at various facilities, representing a geographically diverse surgical cohort. Overall, the risk of subsequent device infection at revision surgery was strongly correlated and increased linearly based on the number of prior IPPs: 1 prior IPP (6.8%; 3/44), 2 prior (18.2%; 4/22), 3 prior (33.3%; 4/12), 4 prior (50%; 4/8), and 5 prior (100%; 2/2) (R2=0.90, p=0.01). Similarly, rates of infection positively correlated with number of prior IPP-related surgeries performed (R2=0.97, p<0.01). Freedom from an episode of IPP infection decreased with number of IPP devices and procedures performed. The median time to development of infection after most recent IPP surgery was 2 months (IQR 1-3.3 months). No clinical or demographic differences were identified between the infection and non-infection cohorts, including age, DM status, tobacco usage, Charleston Comorbidity Index score, prior prostatectomy, prior hernia repair, or Peyronie&[prime]s disease. Conclusions Infection rates of revision/salvage IPP surgery increase with each subsequent IPP placement or following IPP-related surgeries. The majority of patients experience at least one infection by their 4th device. This data could provide relevant information necessary for appropriate patient counseling. Funding None
Authors
Brian Montgomery
Matthew Ziegelmann Landon Trost |
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MP25-11 |
The Rise of Outpatient Penile Prosthesis Surgery: A Cross-Sectional Analysis of National Trends |
Sexual Function/Dysfunction: Surgical Therapy I | 17BOS |
Abstract: MP25-11 Sources of Funding: none Introduction With rising healthcare cost, there is an effort by providers to adopt strategies that decrease cost of care and optimize utilization of available resources. One approach is to decrease post-operative hospitalization. There is a paucity of data on penile prosthetic surgeries in the outpatient setting. The purpose of this study is to analyze national trends in inflatable penile prosthesis (IPP) surgery, examining factors that impact selection of surgery setting. Methods Using Boston Scientific Corporation database, we analyzed data for AMS 700 surgeries performed in the US over a 10-year period. IPP surgeries analyzed included virgin implantation, revision or removal. The surgical and available patient information were utilized to examine potential factors associated with surgical setting. Standard statistical analysis was performed and p-value < 0.05 was deemed statistically significant. Results 40,488 IPP surgeries were examined from 2005 to 2015. 75.0% were virgin implants, 22.2% revisions and 2.8% were removal of devices (1.7% for malfunction, 1.1% for infection). The most common etiologies of erectile dysfunction (ED) were organic (30.2%), prostatectomy (23.1%), Diabetes mellitus (17.0%) and vascular disease (15.2%). The Southeast region performed the highest proportion of IPP surgeries (46.7%) followed by Midwest (21.5%), Southwest (12.7%), West (11.9%) and Northeast (7.1%) regions. The overwhelming surgical approach was penoscrotal (75.9%). Over the 10-year period, there was significant increase in the proportion of IPP surgeries performed in the outpatient setting compared to in-patient (from 54.3% in 2005 to 83.2% in 2015, p<0.001, Fig.1). There was no difference in choice of surgery setting for revision or virgin IPP placement or removal for malfunction (p=0.60). However, surgery for infection occurred more frequently in the inpatient setting (1.5% vs 0.9%, p<0.001). Conclusions Outpatient IPP surgeries have increased significantly over the 10-year period. With the exception of surgery for infections, both complexity of surgery and patient comorbidities did not lead to differences in surgical setting. Outpatient IPP surgeries have the potential to decrease the cost of surgical management of ED. Future studies are needed to examine the outcomes of surgeries performed in both setting. Funding none
Authors
Richmond Owusu
Karen Seybold Dongfeng Qi Guanghui Liu Tung-Chin Hsieh |
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MP25-12 |
Diabetes is a Risk Factor for IPP Infection: Analysis of a Large Statewide Database |
Sexual Function/Dysfunction: Surgical Therapy I | 17BOS |
Abstract: MP25-12 Sources of Funding: None Introduction Although diabetes mellitus (DM) is often discussed as a risk factor for inflatable penile prosthesis (IPP) infection, the link between DM diagnosis and IPP infection remains controversial. High quality population-based data linking DM to an increased risk of IPP infection have not been published. We sought to evaluate the association of DM with IPP infection in a large public New York State database. Methods The New York Statewide Planning and Research Cooperative System (SPARCS) database was queried for men who underwent initial IPP insertion from 1995 to 2014. Diabetic patients were identified using ICD-9-CM codes. Patients presenting for first operation with diagnosis or CPT codes suggestive of prior IPP surgery were excluded. Chi-squared analyses were performed to compare infection rates in diabetics and non-diabetics within the pre- and post-antibiotic impregnated eras. Multivariate Cox proportional hazards models were constructed to evaluate whether or not DM was independently associated with IPP infection in the time periods before (1995-2003) and after (2004-2014) the widespread availability of antibiotic impregnated penile prostheses. Results 14,969 patients underwent initial IPP insertion during the study period. The overall infection rate was 343/14,969 (2.3%). Infections occurred at a median 3.9 months after implant (IQR: 1.0-25.0 months). In the pre-antibiotic impregnated IPP era, infection rates in diabetic and non-diabetic men were 5.2% (78/1,497) and 3.2% (139/4,360), respectively (p<0.001). In the contemporary era of antibiotic impregnated IPPs, infection rates in diabetic and non-diabetic men were 2.0% (55/2,803) and 1.1% (71/6,309), respectively (p=0.002). On multivariate analysis controlling for age, comorbidity index, and annual surgeon volume, DM was an independent predictor of IPP infection in both the pre- (HR 1.43, 95% CI 1.08-1.88, p=0.013) and post-antibiotic impregnated (HR 1.69, 95% CI 1.19-2.41, p=0.004) eras. Conclusions Our analysis strongly supports the notion that DM is a risk factor for IPP infection. In the contemporary era of antibiotic-impregnated devices, IPP recipients with DM are at 1.7-fold increased risk of infection compared with non-diabetic men. This has important implications for patient selection and counseling, and raises the question of whether this increased risk can be mitigated by optimization of glycemic control prior to surgery. Funding None
Authors
Michael J Lipsky
Ron Golan Ifeanyi Onyeji Ricardo Munarriz James A Kashanian Doron S Stember Peter J Stahl |
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MP25-13 |
Prospective Analysis of Accessory Pudendal Artery Transection on Potency during Robot-Assisted Radical Prostatectomy (RARP) |
Sexual Function/Dysfunction: Surgical Therapy I | 17BOS |
Abstract: MP25-13 Sources of Funding: none Introduction Preservation of erectile function (EF) following robot assisted radical prostatectomy (RARP) is essential. The impact on EF after vascular injury to accessory pudendal arteries (APA) remains to be determined. To compare recovery of EF following transection of APAs in men undergoing RARP versus men with normal vascular anatomy. Methods Retrospective cohort analysis of 880 consecutive men undergoing RARP (2007-2014). Intraoperative mapping identified 231 men with APAs which were transected during stapling of the dorsal vein. Median follow-up was 15 months. EF recovery in men without accessory arteries were compared to men with transected APAs. EF was assessed as a continuous outcome using IIEF-5 or fullness scores; and as a dichotomous outcome with IIEF-5 ≥ 15; affirmative answers to: erections are firm enough for penetration and are satisfactory or percent rigidity≥75%. Associations between preoperative characteristics and EF outcomes were tested using general linear models and logistic regression methods. Results There were no differences in baseline demographics/ clinical characteristics in men with or without APAs, Table 1. It is important to note that the presence of any APAs did not influence preoperative IIEF-5, p≥0.80. Multivariate analyses demonstrated that age and baseline IIEF-5 strongly correlated with recovery of erections and potency. However, transected APAs had no effect on recovery of potency (Table 2), IIEF-5 scores, or fullness of erections. In subgroup analysis of men 65 years or older with existing ED, there was no effect on EF recovery with transected APAs. Limitations include retrospective analysis and non-randomization to deduce cause and effect. Conclusions APA transection had no measurable effect on recovery of EF or potency regardless of age, preoperative ED or numbers of APAs transected. While surgical preservation of APAs is optimal, the role of unsuccessful APA preservation in the recovery of EF is uncertain. In analyzing a robust patient cohort, we found that sacrifice of APAs during RARP does not lessen recovery of sexual function. Funding none
Authors
Stephan Williams
Kathyrn Osann Blanca Morales Linda Huynh Douglas Skarecky Thomas Ahlering |
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MP25-14 |
Surgery for Infected Penile Prostheses in New York State: Practice Patterns, Outcomes and Impact of Surgeon Factors |
Sexual Function/Dysfunction: Surgical Therapy I | 17BOS |
Abstract: MP25-14 Sources of Funding: None Introduction We sought to describe practice patterns and outcomes of surgery performed for treatment of inflatable penile prosthesis (IPP) infections in New York State, and to investigate the impact of surgeon factors on management strategies. Methods The New York Statewide Planning and Research Cooperative System database was queried for men who underwent IPP insertion from 1995 to 2014. Operations for IPP infections were identified by diagnostic and procedural codes and characterized as explant or salvage; salvage procedures were divided by device reimplanted (semi-rigid vs IPP). Chi-squared and logistic regression analyses were used to identify surgeon factors associated with undergoing salvage versus explant. Results 14,969 men underwent IPP insertion. Of these, 343 (2.3%) had surgery for IPP infection at a median 3.9 months. Patterns of IPP infection management and outcomes are depicted in Figure 1. Salvage procedures were used in 21% of cases (72/343). There were no infections after salvage with semi-rigid implants, whereas the infection rate after salvage with IPP was 25% (13/52) (p=0.01). Ultimately, 85% of those who underwent salvage surgery and only 19.6% of those treated by explant ended up with a penile prosthesis (p<0.001). The initial implanter performed the operation for infected IPP in 233 cases (68%). The rate of salvage was higher after 2004 once antibiotic impregnated IPPs were in widespread use (27% vs 18%, p=0.04), when reoperation was performed by the initial implanter (26% vs 11%, p=0.004), and when reoperation was performed by a high volume implanter (p<0.001). On multivariate analysis, salvage was less common when the operation for infection was not performed by the original implanter (OR 0.42, p=0.04) or was performed by a low volume implanter (≤2/year vs >20/year, OR 0.21, p=0.01). Conclusions Men treated for infected IPPs with salvage procedures are far more likely to end up with a prosthesis than those treated with explant. Despite these favorable functional outcomes, salvage of infected IPPs is an underutilized strategy. We identified surgeon factors that may partially explain this suboptimal practice pattern. Proactive referral of patients with IPP infections to their original surgeons or to experienced implanters could improve functional outcomes for affected patients. Funding None
Authors
Michael J Lipsky
Ron Golan Ifeanyi Onyeji Ricardo Munarriz James A Kashanian Doron S Stember Peter J Stahl |
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MP25-15 |
FACTORS ASSOCIATED WITH INFLATABLE PENILE PROSTHESIS (IPP) EXPLANTATION: EVALUATING THE ROLE FOR POSTOPERATIVE ORAL ANTIBIOTICS ADMINISTRATION |
Sexual Function/Dysfunction: Surgical Therapy I | 17BOS |
Abstract: MP25-15 Sources of Funding: University of Chicago Institute for Translational Medicine Introduction Prescribing oral antibiotics following IPP implantation is common practice; however, the impact of oral antibiotics on device infection and explantation is unknown. We sought to identify risk factors associated with device explantation in a prospective national database focusing on the role of outpatient oral antibiotics. Methods Using MarketScan, we identified men who underwent IPP placement from 2003-2014 and their associated clinical and demographic data. The primary endpoint was subsequent device explantation as determined by IPP removal CPT codes. Multivariate analysis assessed the effect of comorbidity and outpatient oral antibiotics on device explantation. Results 10,847 men underwent IPP placement, with 228 (2.1%) undergoing subsequent explantation at a median of 42 days postoperatively (IQR 27-58). Postoperative oral antibiotics were prescribed following 6528 cases (60.6%). Patients with diabetes, higher Charlson comorbidity index (CCI) and history of prior IPP incurred higher rates of explantation, whereas rates did not differ in men receiving postoperative oral antibiotics (Table 1). On multivariate analysis, diabetes, CCI greater than 2 and prior IPP placement were all associated with increased odds of explantation (p<0.05). Postoperative oral antibiotics did not decrease the odds of explantation and trended towards harm (OR 1.27, 95% CI 0.96-1.68). Among the subset of patients with preoperative intravenous antibiotic data (3008), a regimen consistent with AUA guidelines was administered in 2006 (66.7%). Rate of explantation was lower in patients who received an AUA-recommended antibiotic regimen, although the difference was not significant (1.4 vs 2.3%, p=0.07). However, significantly lower explant rates were experienced by men receiving an aminoglycoside (1.4 vs 2.6%, p=0.04). Conclusions This review of a prospectively maintained national database did not demonstrate a benefit for postoperative oral antibiotics following IPP. Although this may be related to unmeasured risk factors prompting use of oral antibiotics, it suggests that routine use may be unnecessary and potentially detrimental. In contrast, perioperative intravenous aminoglycoside use is one modifiable factor that may reduce the risk of explantation. Funding University of Chicago Institute for Translational Medicine
Authors
William R Boysen
Melanie A Adamsky Andrew J Cohen Joseph Rodriguez Sandra Ham Roger Dmochowski Sarah F Faris Gregory T Bales Joshua A Cohn |
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MP25-16 |
PENILE REVASCULARIZATION SURGERY IN PATIENTS WITH DIABETIC ERECTILE DYSFUNCTION : LONG TERM RESUTS |
Sexual Function/Dysfunction: Surgical Therapy I | 17BOS |
Abstract: MP25-16 Sources of Funding: none Introduction To determine the overall long-term success of penile revascularization surgery in the treatment of vasculogenic erectile dysfunction and also to investigate the effect of risk factors on the results of a modified Furlow-Fisher technique.We completed our revascularization surgery results in our 50 erectile dysfunction patients having no risk factors except diabetes with a long term follow-up. Methods Between 2004 and 2015,225 patients with a mean age of 47.2(range:23–73) years underwent penile revascularization surgery.Among them, 50 patients were diagnosed as having diabetes mellitus and completed the mean 60,94±1,34 months follow-up.All the patients were routinely interviewed in the Departments of internal Medicine,Neurology,Psychiatry,and Anaesthesiology.Preoperative urological evaluation was performed with penile colour Doppler ultrasonography,corpus cavernosum electromyography(CC-EMG) and cavernosometry.At least five points of increase in the IIEF-5 score during the latest patient visit in the postoperative period compared with the preoperative period was regarded as improvement(surgical success). Results The mean total IIEF score was 28.1±5.7 before surgery,and it was 42.2±6.3 at the end of the follow-up(P<0.05).The mean IIEF-5 score was 8.3±2.2 before surgery,and it was 17.7±2.1 at the end of the follow-up(P<0.05).Before surgery, the mean Erectile Function-domain score was 11.6±3.4,and it was 21.7±6.1 at the end of the follow-up(P<0.05).According to the IIEF-15,32 patients achieved a no-ED threshold value of >26.According to the IIEF-5, the surgery was again successful in 35 of 50 diabetic patients(70%). Conclusions We suggest that penile revascularization surgery could be an alternative choice before penile prosthesis implantation in those patients having no risk factors except diabetes which is under control. Funding none
Authors
Onder Kayigil
Emrah Okulu Fatih Akdemir |
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MP25-17 |
Association of Radiation Doses with Development of Erectile Dysfunction in Patients with Localized Prostate Cancer Treated with Permanent Prostate Brachytherapy |
Sexual Function/Dysfunction: Surgical Therapy I | 17BOS |
Abstract: MP25-17 Sources of Funding: none_x000D_ Introduction We conducted a longitudinal prospective study to evaluate the effect of radiation doses on the development of brachytherapy-induced erectile dysfunction by using the International Index of Erectile Function-15 (IIEF-15)._x000D_ _x000D_ Methods From September 2004 to May 2010, we identified 48 patients whose erectile function (EF) score was 11 or greater and who did not receive any supplemental therapy. Iodine-125 seed was used and was conducted by peripheral loading. Dosimetric parameters were collected as follows; mean dose to 90% of prostate volume (total D90), percentage of prostate volume receiving at least 100% dose (total V100), and 150% dose (total V150). We also defined prostate apex as a 10 mm range from the distal edge of the prostate, and constructed a 3D model of the prostate and rectum for evaluating the radiation dose and exposed area (Figure). We prospectively collected IIEF-15 questionnaires after PB for at least 2 years after treatment. We defined an EF domain score change to less than 10 as worsened EF severity. Results Mean patient age was 65.5±7.0 years with a median follow-up time of 34 months. Mean clinical target volume was 26.7±6.53 cc, and the mean outcomes of the dosimetric parameters were: total D90; 175.6±21.8 Gy, total V100; 95.3±3.53%, total V150; 70.6±11.4%, apex V100; 95.3±6.10%, and apex V150; 68.7±18.3%, respectively. Total IIEF-15 score was 49.9±12.0 before PB, but decreased to 34.7±20.3 12 months after PB (p<0.05). Among the 48 patients, 32 (75.0%) had a deterioration of their EF score 12 months after PB. Mean age in the worsened EF severity group was 63.9 years, which was significantly lower than that in their counterparts (67.8 years, p=0.029). Furthermore, 47.9% and 58.3% of patients in the worsened EF severity group had significantly more total V100 ≥95% and apex V150 ≥70%, respectively, as compared to those in their counterparts (12.5%, p=0.024 and 18.3%, p=0.003, respectively). On multivariate analysis, an age ≥70 and apex V150 ≥70% were independent predictors of deteriorated EF severity 12 months after PB (p=0.024, HR=7.91, p=0.007, HR=7.75, respectively). Conclusions An excessive dose of radiation to the apex area of the prostate as well as advanced age may have an influence on worsening potency preservation after PB. Funding none_x000D_
Authors
Keisuke Shigeta
Eiji Kikuchi Masashi Mastushima Toshiyuki Ando Takeo Kosaka Ryuichi Mizuno Akira MIyajima Tomoaki Tanaka Toshio Ohashi Mototsugu Oya |
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MP25-18 |
Outcomes of Men Undergoing Glanulopexy for Managing SST Deformity with Penile Prostheses |
Sexual Function/Dysfunction: Surgical Therapy I | 17BOS |
Abstract: MP25-18 Sources of Funding: None Introduction Glanular hypermobility (GH) or supersonic transporter (SST) deformity is relatively common during penile prosthesis (PP) implantation and negatively impacts PP utilization and longevity. However, management strategies are limited with minimal data available on surgical outcomes. Therefore, we sought to describe outcomes of men undergoing glanulopexy for management of GH/SST. Methods A glanulopexy was performed in men with GH/SST identified at the time of or following PP placement. A modified version of the technique previously described by Mulhall and colleagues was utilized, whereby a stitch is passed into the glans and secured to the corporal tunica (Figure 1). Patients were prospectively followed to evaluate longitudinal outcomes. Results From 2014-2015, a total of 15 patients underwent glanulopexy for GH/SST. Ten (67%) were performed at the time of PP, while five (33%) were placed as a separate procedure. Vicryl suture was used in five (33%) patients and Ethibond in 10 (67%). Three patients (50%) who received Vicryl sutures required repeat glanulopexy for recurrent deformity, prompting a change to Ethibond in all patients. At a median follow-up of thirteen-months, all patients demonstrated appropriate glanular positioning without diminished sensation. Five patients (33%) underwent PP removal including three for infection, one of which was likely related to the glanulopexy suture itself. The remaining two had their devices removed due to dissatisfaction, which was felt to be unrelated to the glanulopexy. Conclusions Glanulopexy with permanent suture successfully corrects severe GH or SST in men with IPP without reduced penile sensation. To our knowledge, this represents the largest reported series of glanulopexy outcomes reported in the literature. Further study with external validation is warranted to establish the optimal role for the procedure. Funding None
Authors
Matthew Ziegelmann
Landon Trost |
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MP25-19 |
Survey on the Contemporary Management of Intraoperative Urethral Injuries during Penile Prosthesis Implantation |
Sexual Function/Dysfunction: Surgical Therapy I | 17BOS |
Abstract: MP25-19 Sources of Funding: None Introduction Intraoperative urethral injury is an uncommon event during the placement of an inflatable penile prosthesis (IPP) with an estimated incidence of up to 3%. The conventional teaching is to perform primary repair, place a transurethral catheter, and abort the procedure. Recently, alternative management strategies have been proposed with continuation of the implant following urethral injury. The objective of this study is to evaluate surgeon management of urethral injury during IPP and determine if fellowship training influences practice. Methods An online survey was sent to the society listservs of the Genitourinary Reconstructive Surgeons (GURS) and The Sexual Medicine Society of North America (SMSNA). Physicians were queried on their fellowship training, experience with IPP and urethroplasty, IPP surgical approach, and management of urethral injuries during IPP implantation. The response data was analyzed using SAS 9.4 (SAS Institute Inc., Cary, NC). Chi-squared test and Fisher's exact test were used to determine associations between variables. Results There were a total of 131 survey responses. Of the responders, 41.2% were GURS fellowship trained, 19.1% were SMSNA trained, 30.5% were non-fellowship trained, and 9.2% trained in other fellowships. 25.4% of participants perform >50 IPPs per year, while 37.7% perform 20-50 and 36.9% perform fewer than 20 per year. Urethral injury during IPP implantation was uncommon, with 26.2% reporting 0 injuries, 58.5% reporting 1-3 injuries, and 15.4% reporting >3 career injuries. Injuries were most commonly encountered during corporal dilation (71.1%), compared to corporal exposure (12.5%), or penile straightening maneuvers (7.0%). There was no statistically significant difference with aborting or continuing implantation among GURS, SMSNA, and/or non-fellowship trained surgeons. Of all responders, 55% abort the procedure after distal urethral injury, while 45% continue the procedure with unilateral or bilateral insertion of cylinders. For those who chose to abort the procedure, the next implant was attempted in <6 weeks in 9.3%, 6-12 weeks in 45.7%, and >12 weeks in 41.1%. Patient factors that increased likelihood of aborting procedure in the case of urethral injury included immunosuppression, spinal cord injury, and clean intermittent catheterization-dependence. Conclusions Urethral injury during IPP implantation is a rare but established risk of the procedure. Fellowship training does not appear to have an effect on intraoperative management of this injury. Funding None
Authors
Stephanie J. Sexton
Michael A. Granieri Aaron C. Lentz |
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MP25-20 |
Evaluating the efficacy and safety of magnetic induction activation of shape memory penile prosthesis through animal tissue |
Sexual Function/Dysfunction: Surgical Therapy I | 17BOS |
Abstract: MP25-20 Sources of Funding: Partial funding through a grant from Boston Scientific. Introduction We previously developed a novel shape memory alloy prosthesis using a lasercut Nitinol extruded tube that expands and becomes rigid when activated to simulate an erection. We also described how it is possible to activate it using magnetic induction (MI). To better understand the thermal safety and efficacy of this approach in tissue, we tested MI activation using an in vitro animal tissue model. Methods We used a commercially available magnetic inductor with a power of 1000W and a custom made 2mm copper coil of 3 turns of 4cm diameter. The prosthesis or nitinol tube was inserted down the length of a pork-product sausage. Two thermocouples were placed to measure temperature changes: (1) on the exoskeleton, and (2) 2 mm away in the tissue. The sausage with the embedded prosthesis was positioned in the middle of the coil and the miniductor activated. Temperature tracings were recorded overtime. As a control, the same setup was placed on a laboratory hot plate with temperature set at 43C. Results With the hot plate, the tissue and prosthesis gradually rose in temperature together from 23C to 43C over 300 secs with conduction of heat. Using magnetic induction to the Nitinol tube, the prosthesis temperature rose from 23C to 43C in 20 secs, with only a 2C change in tissue temperature. With the lasercut prosthesis 43C was reached in 400 secs with a 4-5C rise in surrounding tissue. With magnetic induction tissue temperature never rose above 5C from baseline. In all cases, the activated device simulated previously described erection parameters. Conclusions Magnetic induction effectively penetrates animal tissue and allows for potentially faster heat transfer and activation of a novel shape-memory penile prosthesis. There is no evidence of any thermal damage to local tissues from this process of activation. Further design optimization can enhance the magnetic induction process. Funding Partial funding through a grant from Boston Scientific.
Authors
Alberto Colombo
Kevin McVary Brian Le |
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MP26-01 |
Concordant miRNA and mRNA expression profiles in bladders of obstructed humans and mice |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP26-01 Sources of Funding: SNSF Grant 320030_156161/1, Velux Foundation Grant 895, R01 DK077195-07 Introduction Bladder outlet obstruction (BOO) leads to lower urinary tract symptoms (LUTS) and urodynamic changes. Previously we identified microRNA (miRNA) and mRNA expression profiles associated with different states of BOO-induced LUTD in human patients. Animal models of experimentally-induced partial BOO are widely used to study bladder wall remodeling. Here we determined the expression profiles of miRNAs and selected mRNAs in pBOO mice and compared the observed changes to human patients. Methods All experiments were performed using 10-to-12-week-old male mice that underwent microsurgical creation of pBOO and sham-operated control animals. Bladders were harvested 2, 4, 6 and 8 weeks after pBOO and total RNA isolated. Muscle contractility was assessed in parallel cohorts at 1, 2, 4 and 6 weeks. Expression profiles of 598 miRNAs were established using NanoString nCounter Analysis System mouse miRNA assay kit. Levels of selected mouse mRNAs were determined by QPCR. Bladder dome biopsies were collected from controls and patients with urodynamically established BOO and miRNA and mRNA expression profiles determined by Next Generation Sequencing (NGS) analysis. Results Similar to human patients&[prime] results, we observed a down-regulation of smooth muscle-associated miRNAs mmu-miR-1, mmu-miR-143, mmu-miR-145, mmu-miR-486 and mmu-miR-133a in pBOO mouse bladders. Pro-fibrotic mmu-miR-142-3p and mmu-miR-21 were up-regulated, and anti-fibrotic mmu-miR-29c down-regulated. Surprisingly, the expression levels of other miRNAs including miR-22, -26b, -10a and -342-3p, which were strongly regulated in human BOO patients, did not change in the mouse model. Pathway analysis in human BOO patients identified TNF-alpha as the top upstream regulator, and revealed signalling molecules, including MYC, FOS, CTGF, PIK3R5, which were strongly induced in different urodynamic states of BOO. In pBOO mice there was evidence of hypertrophic changes (MYBL2, MYH11 and MYC up-regulation) at 2 weeks pBOO, and CTGF was significantly increased at 4 and 6 weeks post-obstruction. Contrary to human data, we observed no regulation of TNF-responsive genes in the mouse model. Conclusions Experimentally-induced pBOO in mice led to significant gene expression changes, including alteration of pro-fibrotic mRNAs and miRNAs resembling human BOO patients. Lack of evidence of TNF-alpha-induced miRNA and mRNA regulation might indicate a different pathophysiological mechanism of organ remodelling in pBOO model compared to human disease. Funding SNSF Grant 320030_156161/1, Velux Foundation Grant 895, R01 DK077195-07
Authors
Katia Monastyrskaya
Ivonne Koeck Evalynn Vasquez Ali Hashemi Gheinani Ulrich Baumgartner Bryan Sack Stefan Lukianov Fiona C. Burkhard Rosalyn M. Adam |
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MP26-02 |
Differential responsiveness to neurostimulation across the bladder filling cycle in rodents |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP26-02 Sources of Funding: Medtronic Inc., Minneapolis, Minnesota Introduction Sacral neurostimulation (SNS) has most commonly been used as a continuous treatment for urge incontinence,but preclinical and clinical evidence suggest that non-continuous or discrete stimulation periods may also be efficacious. We used our rat model to investigate whether continuous SNS is required for increasing bladder capacity or if therapy temporally targeted to specific phases of the bladder filling cycle show similar responses. Methods Urethane anesthetized female Sprague-Dawley rats (n=24) received jugular and transvesical catheters. L6/S1 nerve trunks were isolated bilaterally and fine-wire bipolar electrodes were placed on each and insulated with parafilm and mineral oil. The wounds were closed with suture. Bladder catheters were connected to infusion pumps and pressure transducers. True bladder capacity (TBC) was determined using stable single fill cystometrograms following control continuous cystometry (0.1 ml/min) and prior to every stimulation period. In the first series, we tested the responses to SNS durations that were calculated to cover the initial 25%, 50%, 75%, and 100% of the control filling cycle duration (n=10; all stimulations were initiated at the start of bladder filling). In the second series, we measured responses to SNS over 25% or 50% of the bladder fill cycle, but initiated SNS at 0, 25, 50 or 75% of filling (for 25%) or at 0 or 50% of calculated filling (for 50%). For this test the 25% fills were randomly delivered. Data were analyzed by Friedman Test and Dunn's Multiple Comparisons Test. Results In the first series, we observed significant increases in TBC only when SNS was applied for 75 or 100% of the fill cycle duration (30 and 35% increases over controls, resp., p<0.05). In the second series, we observed significant increases in TBC only to SNS delivered beginning at 75 and 100% of total fill (25% duration SNS) and beginning at 50% fill (50% duration SNS; 32 and 43%, resp., p<0.001). Pre-SNS TBC control values did not change in either series. Conclusions These data demonstrate that SNS applications timed to occur within the latter phases of bladder filling (e.g. the final 25 or 50% of the bladder fill cycle) appear to be most important for increasing bladder capacity. A clinical strategy utilizing this principle may improve battery life and reduce frequency of reoperation for battery replacement. The results also suggest important physiological differences across the bladder filling phase that should be further explored. Temporal targeting of therapies to these phases of bladder filling may allow improved efficacy or reduced side effects. Funding Medtronic Inc., Minneapolis, Minnesota
Authors
Bradley A. Potts
Danielle J. Degoski Jillene M. Brooks Andrew C. Peterson Dwight E. Nelson Thaddeus S. Brink Matthew O. Fraser |
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MP26-03 |
BioTextile Graft Devices for Synthetic, Autograft, Allograft and Xenograft Replacement: A Biomimetic Study of a Novel Electrochemical Aligned Collagen-Based Graft Manufacturing Method. |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP26-03 Sources of Funding: Southwest Research Institute®; Armed Forces Institute of Regenerative Medicine; Biotextiles Introduction We hypothesize that biotextile graft devices of fabricated collagen-based nanoparticles share similar properties to autografts in promoting functional tissue repair and regeneration not typically seen with xenografts, allografts or synthetic mesh. The specific aim of this project was to prepare and evaluate electrochemically aligned (ECA) collagen-based biotextile graft substitutes for use in urinary incontinence sling and pelvic reconstructive surgery. Methods Lyophilized graft sheets of fabricated biotextiles from dialyzed collagen were created by controlled molecular assembly using planar ECA that moves proteins in a pH gradient produced by the electrolysis of water. In-vitro testing of ECA collagen-based grafts consisted of fracture stress determination, moisture vapor transmission rate (MVTR), oxygen permeability, live/dead assay of seeded stem cells, and inverted fluorescence and scanning electron microscopy (SEM). Results ECA collagen-based manufactured sheets of grafts are transparent and thin. These pure collagen grafts had a layered structure with nearly 30mm collagen fibril diameter, a fracture stress 8.23 times greater than heat-gelation controls, a high MVTR and excellent oxygen permeability. Stem cells proliferated well and were almost confluent on the collagen graft after 72 hours (see figure A: Fluorescence imaging reveals cytoskeleton and nuclei of stem cells extending along the fiber direction due to the alignment of collagen fibers). Conclusions Our proprietary ECA process produces transparent but densely packed, robust, fascial-like collagen structures in large, thin sheet formats designed to include other biological relevant nanoparticles. Based on characterization of the ECA matrix by biomimetic analyses, this novel collagen-based biotextile may serve as a promising pelvic fascial substitute material for slings and reconstructive surgery. These findings support further experimentation of adding other nano-particles and cross-linking manufacturing steps to further enhance the balance between additional biomechanical and biocompatibility features. Funding Southwest Research Institute®; Armed Forces Institute of Regenerative Medicine; Biotextiles
Authors
XingGuo Cheng
Nicole Edwards Brad Gill David Staskin Raymond Rackley |
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MP26-04 |
Impact of Dai-ken-chu-tou on urinary frequency induced by cold stress in rats |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP26-04 Sources of Funding: none Introduction Cold stress produced by sudden change or continuous exposure to low temperature exacerbates lower urinary tract symptoms (LUTS), such as urinary urgency, frequency, and nocturia. Stimulation of C-fibers and TRPM8 channels have been reported as mechanisms of cold stress related LUTS. Dai-ken-chu-tou, a chinese herbal medicine has been traditionally used for improvement of bowel conditions. In basic research, dai-ken-chu-tou has been reported to influence intestinal tracts by decreasing adrenomeduline and decreasing the stimulation of the pathway of TRPV1 and TRPA1, which are also important pathways with bladder function. We examined whether dai-ken-chu-tou improves cold stress related LUTS in rats. Methods A total of 22 Sprague-Dawley rats at postnatal week 10 were used in the experiments. The animals sere randomly divided into 2 gtoups, which were kept with Dai-ken-chu-tou-including food (2700mg/kg) or normal food for 4 weeks. After 4 weeks, cystometography (CMG) was performed under awake condition. CMG was first performed in room temperature (RT) for 20 minuets. Rats were then put into low temperature (LT) for 40 minutes. After LT, rats were put into RT for 20 minutes. After CMG, the whole bladder was removed and real time PCR was performed. Results Results of the CMG are shown in Fig 1. Basal pressure and micturition pressure did not show a difference between control rats and Dai-ken-chu-tou rats, but change rate with cold stress in voiding interval and micturition volume did show a significant difference. Results of real time PCR are shown in Fig 2. Significant decrease of P2X3, TRPV1, and TRPM8 in the bladder was seen in Dai-ken-chu-tou rats. Conclusions Dai-ken-chu-tou improved cold stress related frequency in rats. Down regulation of P2X3, TRPV1 and TRPM8 may have a relation with the improvement in cold stress related frequency in rats. Funding none
Authors
Tetsuichi Saito
Tetsuya Imamura Tomonori Minagawa Takashi Nagai Teruyuki Ogawa Osamu Ishizuka |
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MP26-05 |
Relaxing effect of phosphodiesterase inhibitors and β3-adrenoceptor agonist in an experimental model of detrusor overactivity |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP26-05 Sources of Funding: none Introduction Overactivity bladder syndrome has classically been treated with antimuscarinics. Frequent adverse systemic effects have led to the search for new therapeutic options. β3-adrenoceptor (β3-AR) agonists relax the detrusor smooth muscle (DSM) by the adenylyl cyclase pathway, increasing cAMP. Rolipram, a selective type 4 phosphodiesterase inhibitor (PDE4i), elevates cAMP levels by supressing hydrolysis. Phosphodiesterase type 5 inhibitors (PDE5i), such as tadalafil, relax DSM by the nitric oxide (NO)/cGMP pathway. It has been hypothesized that the inhibition of phophodiesterases could potentiate the relaxing effect of β3-AR agonists. The main objective of this study is to evaluate in vitro the effects of the combination of a β3-AR agonist with two different phophodiesterase (PDE) inhibitors (PDE4i and PDE5i) in an experimental model of detrusor overactivity. Methods The experiments were performed on bladder strips of mice treated with L-NAME for 30 days. Chronic L-NAME administration leads to detrusor overactivity by NO deprivation. The following drugs were used: BRL 37344 (β3-AR agonist), tadalafil (PDE5i) and rolipram (PDE4i). After potassium-induced contraction, strips isolated from mice were exposed to increasing concentrations of each drug. In another series of experiments, prior to contraction, strips were incubated with either tadalafil or rolipram and then increasing concentrations of BRL 37344 were added. Results Cumulative concentration-response curves were constructed. Rolipram showed the best relaxation when compared to the other drugs (Figure 1). Rolipram increased the relaxing response of BRL 37344 in almost all concentrations, but no synergistic effect with tadalafil was observed (Figure 2). Conclusions PDE inhibitors associated with the already proven effective β3-AR agonists may represent a new approach for patients with storage symptons. The relaxing effect of the β3-AR agonist was potentiated by PDE4i but not by PDE5i, suggesting cAMP plays an important role in DSM relaxation. Funding none
Authors
Bruno Lima Linhares
Lúcio F. Gonzaga-Silva Rommel P. Regadas Lucas B. Marinho João B. G. Cerqueira Manoel O. Moraes Filho Cláudia F. Santos Nilberto R. F. Nascimento Ricardo Reges |
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MP26-06 |
Non-human primate (NHP) model of urinary incontinence and erectile dysfunction after radical prostatectomy |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP26-06 Sources of Funding: R01 DK083688 Introduction Prevention of urinary incontinence (UI) and erectile dysfunction (ED) during healing following radical prostatectomy is poorly understood. A reproducible animal model that mimics human anatomy such as intrapelvic bladder, similar genitourinary system, an upright posture with ability to simulate the radical prostatectomy was the first step. Second, was to develop a reproducible, subjectively and objectively quantifiable, model of UI and ED after open radical prostatectomy (ORP) using Cynomologus monkeys at the age equivalent to middle aged men. _x000D_ Methods Ten monkeys were used; two for the anatomical study & feasibility of doing ORP and eight underwent ORP. Animals were sacrificed at 6 months follow up. UI was evaluated through, observed voiding behavior, & urodynamics performed before, 3 and 6 months after ORP. At 3 and 6 months postop, phenazopyridine was added to their juice to demonstrate observed urinary leakage. Erectile Function was assessed before, 3 and 6 months after ORP by intra-cavernosal (IC) pressure measurement after IC papaverine injection. Sexual behavior was video-monitored at the same time points. The following parameters were analyzed: mounting, thrusting and erection. CT scan was done at 3 and 6 months postop to evaluate urethral anastomosis. After being sacrificed specimens were collected for histology._x000D_ Results At 3 (N=8) and 6 (N=4) months after ORP all monkeys had UI and ED. There was a statistically significant decrease in abdominal leak point pressure (Table 1) at 3 & 6 months follow up, and a decline in the IC pressure after IC injection (Graph 1). Animals were not able to achieve erection when placed with a female partner. CT scan showed intact bladder-urethral anastomosis and Mason trichrome staining demonstrated peri-urethral fibrosis._x000D_ _x000D_ Conclusions This is the first reported long-term NHP model of UI and ED after open radical prostatectomy. This model can help in developing new strategies for prevention and treatment with novel approaches. _x000D_ _x000D_ Funding R01 DK083688
Authors
Joao Zambon
Manish Patel Ashok Hemal Gopal Badlani Ashley Dean Shannon Lankford Koudy Williams |
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MP26-07 |
INTRAVESICAL ONABOTULINUMTOXIN-A INJECTIONS DECREASE BOTH NERVE GROWTH FACTOR AND BRAIN DERIVED NEUROTROPHIC FACTOR LEVELS IN BLADDER TISSUE AND URINE IN PATIENTS WITH IDIOPATHIC AND NEUROGENIC DETRUSOR OVERACTIVITY |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP26-07 Sources of Funding: allergan Introduction The aim of this study was to investigate the impact of intravesical injections of BTX-A on neurotrophin activity in patients with idiopathic and neurogenic detrusor overactivity. Bladder tissue and urine NGF and BDNF levels were assayed and clinical and urodynamic data also collated. Methods A total of 20 patients (11 Multiple Sclerosis(MS), 9 with Idiopathic Detrusor Overactivity(IDO)) had clinical evaluation with ICIQ-OAB, ICIQ-LUTSqol, and 3-day bladder diary at baseline (Visit0), 2-weeks post BTX-A (Visit1), and at return of symptoms (Visit2). Patients received 100Units (IDO) and 200Units (MS) respectively. Urodynamic assessment was also made to confirm detrusor overactivity both before BTX-A and after return of symptoms (from 6-12months post injection). Urine samples and flexible cystoscopic bladder biopsies were collected at these time intervals. BTX-A was injected under local anaesthesia in the outpatients department. Local NHS Ethical committee approval was obtained prior to initiating the study. Neurotrophin levels were measured in urine and tissue homogenate by enzyme-linked immunosorbent assay (Abcam). Results For all patients combined, across the three time points, visitO, visit1, and visit2, ICIQ-OAB scores improved at visit1 and returned to baseline by visit2, from 39.6, 13.3, and 41.3 respectively and similarly with ICIQ-LUTSqol from 193.1, 98.2 and 191.5. Similarly bladder Diary reported daily frequency episodes changed from 10.8, 6.3, 8.9, and daily urge leakage episodes changed from 6.2, 0.8, to 3 respectively over visits 1,2 and 3. At these time points urinary BDNF/Creat and NGF/Creat levels also correlated with the observed clinical changes from 0.28, 0.19 and 0.29 and 0.2, 0.15, to 0.17 respectively. At the same time points decreases were also seen in BDNF and NGF bladder tissue content from 16.3, 9.14 and 11.07, and 0.41, 0.26 and 0.57 pg/g respectively. The neurotrophin levels in both tissue and urine followed the trend of clinical symptom and bladder diary parameters with an improvement 2-weeks after BTX-A from baseline and then return to near baseline levels once clinical efficacy had disappeared. Conclusions This study is the first of its kind to correlate the activity of neurotrophin markers in both tissue and urine simultaneously in patients with demonstrated detrusor overactivity before BTX-A injection, 2-weeks after, and on return of clinical symptoms._x000D_ Treatment of detrusor overactivity with BTX-A injections, reduces neurotrophin activity in both tissue and urine in concordance with clinical efficacy. This is seen to reverse once clinical efficacy is worn off. Funding allergan
Authors
Jai Seth
Javed Burki Juliana Ochulor Rizwan Hamid |
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MP26-08 |
Tadalafil shows the inhibitory role in urothelial signal transduction via TRP channels |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP26-08 Sources of Funding: none Introduction Phosphodiesterase 5 (PDE5) inhibitor, tadalafil, improves lower urinary tract symptoms suggestive of benign prostatic hyperplasia. The mechanism is believed to smooth muscle relaxation, increased blood perfusion and modulation of sensory stimuli via increased activity of the NO/cGMP/protein kinase G pathway. However study for tadalafil in urothelium is few, here we investigated the distribution of PDE5, as well as the molecular mechanism for tadalafil in signal transduction focusing on transient receptor potential (TRP) channels and ATP release of bladder urothelium. Methods All experiments were performed by using10-12 week old male Sprague-Dawley rats and C57BL/6 mice. PDE5 expressions were detected by immunochemistry and western blotting in rat bladder tissues and primary bladder urothelial cell cultures. Ca2+ influx was evaluated by in vitro calcium imaging system under exposure to isotonic (340mOsm), hypotonic (200mOsm), cannabidiol (CAD, TRPV2-selective agonist) (10?M), GSK1016790A (GSK, TRPV4-selective agonist) (30nM), ATP (P2X and Y agonist) (5?M) and PIP2 (TRPM7 agonist) (4?M) stimuli respectively with or without tadalafil (10?M). ATP concentration induced by stretch was measured in mouse bladder with or without tadalafil (100 ?M) by using the luciferase reagent. Results Immunochemistry and western blotting demonstrated abundant expression of PDE5 in rat bladder urothelium (Fig.1) as well as primary rat urothelial cell cultures. Ca2+ influx responded to hypotonic stimuli was significantly inhibited by pretreatment of tadalafil in primary rat bladder urothelial cell cultures. (Control (C): 13.1% v.s. tadalafil (T): 4.9%) (Fig.2). Ca2+ influx evoked by GSK (C: 74.7% v.s. T: 68.8%) or CAD (C: 52.2% v.s. T: 25.9%) was significantly inhibited by pretreatment of tadalafil. While Ca2+ influx caused by the stimulation of ATP (C: 49.6% v.s. T: 49.0%) could not be attenuated. PIP2 at the concentration of 4?M did not evoke Ca2+ influx. ATP release in the tadalafil pretreated-bladder was significantly smaller than control bladder. Conclusions Tadalafil attenuated Ca2+ influx via TRPV4 and TRPV2 channels and inhibited ATP release in bladder urothelium. Tadalafil could act an inhibitory role in urothelial signal transduction. Funding none
Authors
Xiao Dong
Hiroshi Nakagomi Tatsuya Miyamoto Tatsuya Ihara Satoru Kira Norifumi Sawada Takahiko Mitsui Masayuki Takeda |
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MP26-09 |
Involvement of toll-like receptor 4 in nonbacterial bladder inflammation and frequent urination via inflammasome pathways in spontaneously hypertensive rats |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP26-09 Sources of Funding: none Introduction Although several studies have suggested that chronic bladder inflammation associated with oxidative stress contribute to overactive bladder (OAB), the underlying pathophysiological mechanism is unclear. Recently, the toll-like receptor (TLR) 4 has been reported to play a role in triggering chronic inflammatory conditions through activation of NLRP3 inflammasome pathways followed by production of IL1β and IL18. Although oxidative stress is one of factors that activate TLR4, it is not known whether changes in the expression of TLR4 are involved in the development of OAB caused by chronic inflammation. We therefore investigated an alteration of histopathology and expression of TLR4 and NLRP3 inflammasome-related molecules in the bladder using spontaneously hypertensive rats (SHRs) as an OAB model. Methods Twenty-weeks-old male SHRs and Wistar Kyoto rats (control) were used. After voiding function was analyzed by using metabolic cages, the bladder was excised for analysis of histopathology and mRNA expression. Hematoxylin eosin and Masson&[prime]s trichrome stain were performed to analyze bladder inflammatory condition and fibrosis. Immunohistostaining for NLRP3, TLR4 was also performed. Expression levels of NLRP3, IL1β, IL-18, IL6, IL8 and TGFβ mRNA in the bladder were investigated by real-time PCR. Statistical analysis was performed using Mann-Whitney U test. P value less than 0.05 was considered statistically significant. Results In voiding function analyses, single urine volume was significantly decreased and voiding frequency was significantly increased in SHRs compared to control rats. In histological evaluation, suburothelial fibrosis was shown in SHRs compared to controls. Furthermore, immunohistostaining showed localized expression of NLRP3 and TLR4 in the bladder urothelium in both groups. In RT-qPCR analyses, mRNA expression levels of NLRP3, TLR4, IL1β, IL-18, IL6, IL8 and TGFβ were significantly increased in SHRs in the bladder compared to controls. Conclusions These results suggest that activation of TLR4 associated with oxidative stress is implicated in bladder chronic inflammation, which leads to frequent urination through NLRP3 inflammasome pathways. Therefore, further clarification of interactions between TLR4 and inflammasome pathways may offer new therapeutic targets for OAB associated with chronic inflammation. Funding none
Authors
Shinsuke Mizoguchi
Kenichi Mori Naoyuki Yamanaka Fuminori Sato Naoki Yoshimura Hiromitsu Mimata |
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MP26-10 |
Neurogenic Detrusor Underactivity: Should we Target the Bladder? |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP26-10 Sources of Funding: None Introduction Pelvic surgery induced detrusor underactivity (DU) remains a poorly understood condition. Preganglionic pelvic nerve crush injury (PNI) in the rat has been described as a model for neurogenic DU. In this study we investigate temporal changes in detrusor contractility, detrusor fibrosis and denervation of the pelvic plexus as potential players in the pathophysiology of DU. Methods Male Sprague-Dawley rats (10-12w) underwent PNI 3x15s or sham surgery. One, three and nine weeks after surgery, functional and molecular assessments were planned. Detrusor contractility was examined in vitro in organ bath studies. Contractile responses tot KCl 120mM, cumulative doses of carbachol, non-cumulative doses of α,β-methylene ATP (mATP) and electrical field stimulation (EFS) were recorded. Gene expression was assessed by RT-qPCR. The genes evaluated in the bladder and major pelvic ganglion (MPG) were: vesicular acetylcholine transporter (VAchT), tyrosine hydroxylase (TH), protein gene product 9.5 (PGP9.5); and in the bladder: M2 and M3 muscarinic receptors, P2X1 purinergic receptor, collagen 1 and 3 and smoothelin. Statistical analyses were performed by one-way ANOVA with Tukey-Kramer post test. Results No changes were observed in contractile responses to KCl 120mM. One week after PNI, a 82% upregulation of collagen 1 was observed with a 77% reduction at 9 weeks (p<0,0001). Smoothelin expression was reduced by 45% 1 week after PNI with recovery at 9 weeks (p<0,0001), all compared to sham. _x000D_ Compared to sham, maximum contractile responses to carbachol and mATP were preserved at 3 and 9 weeks following PNI. Relative expression of M3 was increased at 3 (+59%) and 9 weeks (+46%) compared to sham (p=0,0002), but no differences were seen in M2 and P2X1 expression. _x000D_ Functional detrusor denervation was objectified by EFS: at 32 Hz contractile responses were reduced at 1 week (-40%), 3 weeks (-23%) and 9 weeks (-24%) after PNI compared to sham (p<0,0001). In the bladder, VAchT expression was 4 times less at 9 weeks (p=0,03), whereas TH expression was 76% lower 1 week following PNI with partial recovery at 9 weeks (p=0,0067), all compared to sham. Similarly, TH expression was 57% less in the MPG 1 week after PNI compared to sham with recovery at 9 weeks (p<0,0001). In the MPG, the expression of PGP9.5 was reduced following PNI compared to sham (p=0,002). _x000D_ Conclusions Functional and molecular denervation of the bladder and MPG is observed in our rat model for neurogenic DU. However, the detrusor remains contractile to parasympathetic stimulation. Therefore, research should focus on optimizing neural regeneration of the pelvic plexus. Funding None
Authors
Karel Dewulf
Emmanuel Weyne Yves Deruyver Rita Van Bree Godelieve Verbist Dirk De Ridder Maarten Albersen Wouter Everaerts |
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MP26-11 |
Therapeutic outcomes of Insulin-like growth factor-1 Released from Alginate-gelatin Microbeads on Stress Urinary Incontinence in Rats with Simulated Childbirth Injury |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP26-11 Sources of Funding: NIH NIDDK R56 DK100669-01A1 Introduction Insulin-like growth factor-1 (IGF-1) treatment has been reported to accelerate recovery from stress urinary incontinence (SUI) induced by simulated childbirth injury in rats. However, a local sustained delivery method is ideal for further clinical applications to avoid side effects of IGF-1. The goal of this study was to determine the effects of controlled release of IGF1 from alginate-gelatin microbeads (IGF1-A-G-beads) on sphincter tissue repair in a rat model of stress urinary incontinence (SUI). Methods Forty-four female Sprague-Dawley rats were divided into 4 equal groups: sham vaginal distension (VD) + saline, VD + saline, VD + empty A-G-beads, & VD + IGF1-A-G-beads). All rats received periurethral injections of A-G-beads immediately after VD. Leak point pressure (LPP) testing and external urethral sphincter (EUS) electromyography (EMG) were performed 1 week later. Urethral tissue and anterior vagina were dissected en bloc for further analysis via histology and immunofluorescence. Quantitative data was analyzed using ANOVA on Ranks followed by a Tukey posthoc test with p < 0.05 indicating a statistically significant difference between groups. Data is presented as mean +/- standard error of the mean. Results LPP was significantly decreased 1 week after VD treated with saline only (23.9 ± 1.3 cmH2O) compared to sham VD (44.4 ± 3.4 cmH2O). LPP was also significantly decreased in the VD + empty A-G-beads group (21.7 ± 0.8 cmH2O) compared to sham VD, demonstrating that the microbeads themselves do not create a bulking or obstructive effect in the urethra. In contrast, rats with VD treated with IGF1-A-G-beads (28.4 ± 1.2 cmH2O) was significantly greater than LPP of rats with VD treated with empty A-G-beads and had LPP partway between and not significantly different from either the sham VD or the VD + saline groups, demonstrating initiation of a reparative effect 1 week after VD. The increase in EUS EMG amplitude with LPP testing was significantly reduced after VD treated with saline or empty A-G-beads compared to sham VD. VD rats treated with IGF1-A-G-beads had EUS EMG amplitude response to LPP testing partway between and not significantly different from either the sham VD or VD + saline groups. Histological analysis demonstrated well-developed, well-organized skeletal muscle fibers in the external urethral sphincter in the VD + IGF1-A-G-beads group, similar to that of sham VD rats. In contrast, substantial muscle fiber attenuation and disorganization was observed in VD rats treated with saline or empty A-G-beads. Conclusions IGF1-A-G-beads improved recovery in a rat model of SUI, suggesting that these microspheres could provide a local sustained delivery method for IGF-1. Funding NIH NIDDK R56 DK100669-01A1
Authors
Hao Yan
Liren Zhong Yaodong Jiang Jian Yang Dan Li Lin Xiaoyi Yuan Mei Kuang Anna Rietsch Emmanuel Opara Margot Damaser Yuanyuan Zhang |
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MP26-12 |
Motor Unit Number Estimation of the Puborectalis Muscle |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP26-12 Sources of Funding: This study was supported by NIH DK082644, Society of Urodynamics Female Pelvic Medicine and Urogenital Reconstruction, and the University of Houston. Introduction Motor unit number estimation (MUNE) techniques estimate the number of functioning motor units (MUs) in a muscle, and serve as a biomarker for neuromuscular and muscular atrophy. Application of current MUNE techniques to the pelvic floor is impractical because of the need for either multiple stimulations or invasive needle electrodes. The objective is to propose a novel MUNE technique applicable to pelvic floor muscles, by combining a high-density surface EMG (HD-sEMG) decomposition approach with pudendal nerve stimulation, negating the need for invasive needles or multiple stimulations. Methods All procedures were approved by UH IRB. The pudendal nerve was stimulated transrectally with a St. Mark&[prime]s electrode mounted on the operator&[prime]s glove. HD-sEMG recordings were acquired from the puborectalis muscle with a vaginal EMG probe (Figure 1b) during supramaximal stimulation and three maximal voluntary contractions of pelvic floor muscles. Firstly, single motor unit action potentials (SMUPs) were decomposed from EMG recordings during muscle contraction using our recently developed K-Means Clustering Convolution Kernel Compensation (KmCKC) Algorithm. All SMUPs were grouped into left or right side by visually checking their innervation zone locations following an established procedure. Next, mean SMUPs were derived for both sides by averaging all HD-sEMG profiles of grouped SMUPs. Last, MUNE was calculated as the weighted average of compound muscle action potential (CMAP) size to mean SMUP size ratios for both sides. Results Left and right branches of the pudendal nerve were simulated. Four SMUPs were decomposed from HD-sEMG signals (left: 3 and right: 1). MUNE for the left and right sides were 22.8 and 27.0, respectively. Conclusions This pilot study proves the feasibility of a novel MUNE technique for muscles in the pelvic floor region. The KmCKC algorithm enables a non-invasive collection of SMUPs, negating the need for repeated electrical stimulation or invasive needle electrodes. Results from more subjects will be available from our ongoing subject recruitment. Funding This study was supported by NIH DK082644, Society of Urodynamics Female Pelvic Medicine and Urogenital Reconstruction, and the University of Houston.
Authors
Nicholas Dias
Yun Peng Jinbao He Charles Popeney Yingchun Zhang |
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MP26-13 |
PHYSIOLOGIC FACTORS THAT DETERMINE VOLUNTARY DETRUSOR CONTRACTION DURATION IN MALES |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP26-13 Sources of Funding: None Introduction Little is known about contribution of detrusor contraction duration (DCD) for voiding function in males and initial findings have been contradictory. Our objective was to analyze physiologic factors that influence male DCD to better understand its role. _x000D_ Methods We retrospectively reviewed urodynamic studies in 148 male patients (2010-2016). 120 patients had measurable voluntary DCD. Independent variables analyzed included voided volume (VV), post void residual (PVR), detrusor pressure at maximum flow (PdetQmax), bladder compliance (BC), maximum flow rate (Qmax), bladder outlet obstruction index (BOOI), and bladder contractility index (BCI). BOOI (PdetQmax - 2 Qmax) was categorized into non-obstructed (BOOI < 20), equivocal (20 ≤ BOOI ≤ 40), and obstructed (BOOI > 40). BCI (PdetQmax + 5 Qmax) was categorized into weak contraction (BCI < 100), normal contraction (100 ≤ BCI ≤ 150), and strong contraction (BCI > 150). Multiple regression analysis determined which variables were related to DCD. Variables dependent upon each other were not analyzed together (i.e. either PdetQmax and Qmax, or BOOI and BCI). _x000D_ Results Of 120 patients, mean age was 63.4 ± 17 years and mean DCD was 103.6 ± 66.9 sec. Results from multiple regression analysis (DCD as the outcome) are shown in Table 1. Increased Qmax (p<0.05), PdetQmax (p<0.01), and VV (p<0.001) were associated with increased DCD. Regression 1 shows that when Qmax increases by 1 mL/s, DCD decreases by 2.59 ± 1.19 sec, on average. Increase in PdetQmax by 1 cm H2O increases DCD by 0.40 ± 0.15 sec. Increase in 1 mL VV increases DCD by 0.20 ± 0.04 sec. When performing multiple regression analysis using BOOI, BCI, VV, and bladder compliance, only BOOI (obstructed vs non-obstructed, p<0.002) and VV (p<0.001) were significantly associated with prolonged DCD. _x000D_ Conclusions This is one of the first studies to examine association between DCD and other voiding parameters. In men, longer DCD appears to be influenced by higher PdetQmax, VV, and lower Qmax. Men with outlet obstruction have prolonged DCD compared to men without. Contraction strength did not influence DCD. Further studies are needed to determine clinical significance of these physiologic relationships and utility of DCD._x000D_ Funding None
Authors
Henry Tran
Arindam RoyChoudhury Carrie Mlynarczyk Marissa Theofanides Gina Badalato Matthew Rutman Doreen Chung |
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MP26-14 |
A CADAVER MODEL DESCRIBING A NOVEL RETROGRADE APPROACH FOR PERCUTANEOUS PLACEMENT OF AN IMPLANTABLE TIBIAL NERVE STIMULATION LEAD |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP26-14 Sources of Funding: none Introduction To aid and clarify the approach for percutaneous lead placement for permanent implantation of tibial nerve stimulation lead electrode. Methods A cadaver model was developed to guide delivery of permanently implanted tibial nerve leads using bony landmarks, ultrasound and fluoroscopic imaging in below the knee cadaver legs. The tibial artery was identified proximally and a guide wire placed. The tibial nerve leads were placed percutaneously with a standard lead introducer. Both antegrade (proximal to distal) and retrograde approaches (distal to proximal) were explored. Both approaches were evaluated real time with ultrasound (transverse and longitudinal) and fluoroscopy (lateral and anterior-posterior). Then the cadaver legs were dissected and lead placement was evaluated with respect to depth and orientation to the nerve. Results Ultrasound identified the wire in the artery in both transverse and longitudinal planes, and the nerve posterior. Flouroscopy, lateral and anterior-posterior, was effective in identifing the vector of lead placement, whether crossing the tibial nerve vs. placement more parallel to the nerve. The antegrade approach was modified by migrating more proximally up the lower leg, to try to achieve a more parallel vector of lead placment with the nerve. However, antegrade approaches were always crossing the tibial nerve and went deep to the nerve, with only 1-2 electrodes in close proximity to the nerve. The retrograde approach, starting at the level of the medial malleolus, about 1 finger breadth behind (in general about 1/3 the distance from the medial malleolus to Achilles tendon) was easy and effective in placing the lead parallel to the nerve with 3-4 electrodes in close proximity to the nerve. Conclusions We report a novel, safe retrograde method of percutaneous lead placement parallel to the tibial nerve, avoiding key vascular structures. The retrograde approach, starting posterior to the medial malleolus, was easier and reproducibly placed a more parallel lead that may optimize tibial nerve stimulation. Ultrasound was effective in localizing the tibial artery to aid orientation and depth of placement of the stimulation lead and maximize safety. This minimally invasive retrograde percutaneous approach can place a chronic tibial nerve stimulation lead in the physicians office under local anesthesia. Funding none
Authors
Larry Sirls
Kenneth Peters |
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MP26-15 |
Interpret Uroflowmetry Scientifically: Grade and Pattern |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP26-15 Sources of Funding: None Introduction Low inter-rater's agreement has made uroflowmetry, one of the most important diagnostic tools, more art than science. We presented a novel grade and pattern system to interpret uroflowmetry scientifically. Methods Totally 1240 uroflowmetry curves from healthy children and 300 curves from pediatric patients with LUTS were reviewed by two independent experts in urodynamics. Then this model was used to teach 6 young urologists and revised according to their responses. Finally, 6 objective parameters are used to assign grade and pattern of each uroflowmetry curve: bladder volume (BV), main curve percentage (MCP), number of deep drops, Qmax, rising angle (the angle between Qmax and time to Qmax), and flow index (Qmax/ &[root]bladder volume). Results Table summarizes the definitions of grade 1 and 3 curves. Grade 1 curves are regarded as normal and imply no bladder outlet obstruction, Grade 2 curves are equivocal, and Grade 3 curves are highly suggestive of lower urinary tract dysfunction. Grade 2 curves are those not fit for grade 1 or 3. Grade 1.1, 1.2, 1.3, 2 and 3 curves were noted in 305 (24.6%), 24 (1.9%), 816 (65.8%), 65 (5.2%) and 30 (2.4%), respectively. Grade 3 plateau or staccato curves were not observed. Conclusions Based on 6 objective parameters a novel grade and pattern of uroflowmetry is developed to interpret it scientifically and to increase inter-rater's agreement in the future. Funding None
Authors
Stephan Shei-Dei Yang
Shang-Jen Chang |
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MP26-16 |
Succinate in Voiding Dysfunction Associated with Metabolic Syndrome |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP26-16 Sources of Funding: None Introduction Disruption in energy homeostasis, the main factor driving metabolic syndrome, may also be responsible for the development of its associated bladder dysfunction. Succinate, an intermediate of the citric acid cycle, along with its receptor, GPR91, have been implicated in different aspects of metabolic syndrome, and it is possible that their role could extend to the bladder. Our goal is to show that succinate can alter bladder function in a model of bladder overactivity associated with metabolic syndrome. Methods Intraperitoneal injections of saline or succinate were administered daily for a period of 4 weeks to Sprague-Dawley (SD) rats and Dahl/SS rats, a model of metabolic syndrome with hypertension. Succinate levels were measured in the plasma and urine. Conscious cystometry was then performed. On the next day, bladders were collected for organ bath experiments and quantitative PCR for GPR91. Bladder detrusor strips were stimulated with potassium chloride (KCl), carbachol, and electrical field stimulation (EFS). One-way ANOVA with Bonferroni post-hoc test was used to measure differences between all groups. P<0.05 was considered significant. Results Dahl rats have lower plasma succinate levels compared to SD rats. 24-hour urine levels of succinate were increased in succinate-treated rats in both SD and Dahl groups. SD succinate-treated rats had significantly lower levels of GPR91 in the bladder compared to SD control rats. This was not observed in Dahl rats. Dahl rats had shorter intercontraction intervals, smaller bladder capacities and lower micturition volumes than SD rats. Chronic administration of succinate lowered these parameters, albeit not significant. Organ bath data showed that the contractile responses to KCl, carbachol and EFS were significantly increased in detrusor strips from Dahl control rats compared to those from the other three groups. Conclusions Models of metabolic syndrome have obvious differences in bladder function compared with control rats. Chronic administration of succinate, as observed in vitro, alters detrusor contractility of Dahl rats. The absence of down-regulation of GPR91 in the Dahl bladder treated with succinate could explain the alterations in detrusor contractility observed only in this group. Increased urinary succinate levels may contribute to the development of bladder dysfunction. Funding None
Authors
Monica Velasquez Flores
Abubakr Mossa Philippe Cammisotto Lysanne Campeau |
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MP26-17 |
Urinary level of Monocyte Chemotactic Protein-1 (MCP-1) predicts the severity of symptom in patient with Overactive Bladder (OAB): Pilot Prospective study. |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP26-17 Sources of Funding: none Introduction This study aims to express urinary MCP-1 level in OAB patients before and after treatments, and to correlate the level of MCP-1 with severity of symptoms. Methods This was a prospective, single-blind study including 26 OAB patients (either newly diagnosed or off medications for 2 weeks). Each patient received after the first visit different OAB treatments (anticholinergic, B3 agonist and or neuromodulations). Two midstream urine samples were collected and tested for MCP-1 using ELISA; one before and the second after 12 weeks of treatments. Symptomatic responses to therapy were evaluated using different validated OAB questionnaires [Patient Perception Bladder Condition (PPBC) & Overactive Bladder Quality (OAB-q)]. MCP-1 level were normalized to the levels of creatinine. Descriptive statistics were performed to examine MCP-1 level before and after different using Wilconxon test. Post-treatment MCP1- levels compared to 12 healthy subjects as control using Mann-Whitney U test. Results The mean age of enrolled 26 patients was 69.3yrs. Females accounted for 62.5% of patients. In simple correlation, the degrees of symptoms was significantly associated with the pre-treatment level of MCP-1 (coefficient=.844, p<.000 in PPBC and coefficient=.869, p<.000 in OABq, Figure 1). Mulivariate analysis using linear regression model including age, gender and MCP-1 demonstrated that MCP-1 was significantly associated with OABq (p=.02) and PPBC (p=.03). Twelve weeks after treatment, MCP-1 level was dropped significantly (p<.000), and it was similar with control group (p=0.376, Table). After treatment, the symptom improved significantly both in OAB-q and PPBC (Figure 2). Conclusions Based on a strong association with the degree of symptom, urinary MPC-1 can be used to identify patients and monitor the progression of OAB. Funding none
Authors
Bilal Farhan
Ahmed Ahmed Kheira Bettir Ko Young Hwii Frank Zaldivair Gamal Ghoniem |
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MP26-18 |
Time-dependent bladder and urethral dysfunctions in aging rats |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP26-18 Sources of Funding: This work was supported by a Grant-in-Aid for Scientific Research (15K01376 and 15K01377) Introduction Age-related symptoms such as urinary retention, poor urine flow, and/or incontinence have been attributed to detrusor underactivity (DU). Our recent data showed that in continuous cystometry, bladder contractility did not diminish but post-void residual urine volume was higher in aging rats than in young rats. Thus, the assumption that bladder and urethral dysfunction occur simultaneously in aging rats seems reasonable. Therefore, we investigated this possibility by measuring time-dependent changes of bladder and urethral functions in rats. Methods Female Sprague-Dawley rats (young rats aged 3 months and rats aged 12 and 24 months) were used. 1) Continuous cystometry was performed under awake condition in each group. 2) Urethral activity was evaluated by simultaneous recordings of intravesical pressure under isovolumetric conditions and urethral perfusion pressure (UPP) under urethane anesthesia in 3-month-old and 12-month-old rats. 3) Masson's trichrome staining in the bladder was performed in each group. Results 1) Cystometric evaluations revealed that the intercontraction intervals in the 24-month-old rats were prolonged (p < 0.01) when compared with those in the 3-month-old or 12-month-old rats. In the 24-month-old rats, residual urine volume was significantly higher than in the 3-month-old or 12-month-old rats, and non-voiding contractions were prominent. However, the amplitude of bladder contraction did not differ among the three groups. 2) UPP relaxation (baseline UPP minus nadir UPP) was more significantly diminished (64%) in the 12-month-old rats than in the 3-month-old rats (p < 0.05). The mean rate and amplitude of high-frequency oscillation (HFO) of urethral striated muscle were also significantly lower (12% and 41%, respectively) in the 12-month-old rats than in the 3-month-old rats. 3) In the bladders of the 24-month-old rats, increases in smooth muscle cell hypertrophy and fibrous tissue were observed. Conclusions 1) Our aging model that focused on bladder function showed increased intercontraction intervals and non-voiding bladder contractions with increased residual urine volume, suggesting detrusor hyperactivity with impaired contractility bladder activity. 2) Our aging model that focused on urethral function indicates urethral dysfunction, as evident from the reduction in HFO activity of the urethral striated muscle and the urethral relaxation. Thus, age-associated bladder and urethral dysfunction seem likely to occur simultaneously, which leads to DU with a vicious cycle. Funding This work was supported by a Grant-in-Aid for Scientific Research (15K01376 and 15K01377)
Authors
Takuma Oshiro
Minoru Miyazato Asuka Ashikari Seiich Saito |
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MP26-19 |
Downregulation of monoamine oxidase A may contribute to development of detrusor hyper contractility in urinary bladder with partial bladder outlet obstruction in rats |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP26-19 Sources of Funding: Asahi Kasei Pharma Co. Introduction In a previous study, 5-hydroxytryptamine (5-HT) was found to induce hyper contraction in urinary bladder strips in rats with partial bladder outlet obstruction (pBOO) and 5-HT was suggested to be a trigger of hyper contractility of the detrusor [Sakai T. et al. 2013]. To clarify whether 5-HT contributes to the development of detrusor overactivity and whether 5-HT turnover is involved in overactivity in vivo, we investigated the expression and activity of monoamine oxidase A (MAO-A), a 5-HT-metabolizing enzyme, in the urinary bladder in pBOO rats. Methods Forty-one Female Sprague Dawley rats (aged 8-11 weeks) were used; 12 rats for histology, and 29 rats for western blotting and MAO activity assay. pBOO was induced as described previously [Sakai T. et al. 2013]. At 3, 7, and 14 days after pBOO induction, animals were anesthetized, and urinary bladders were isolated and fixed for histology, or were stored at -80°C until use for western blotting and MAO activity assay to measure expression levels of MAO-A and activity of MAO, respectively. The distribution of MAO-A in the bladder was examined by immunohistochemistry. MAO activity was measured by MAO-Gloâ„¢ Assay. All values were expressed as means ± SEM. Statistical differences were determined by unpaired t-test using SAS System ver. 9.2 and EXSUS ver. 7.7.1. P values of <0.05 were considered significant. Results Expression levels of MAO-A/GAPDH decreased to 46.2 ± 2.7% on day 7 in rat bladders with pBOO (P<0.01) as compared to those in sham rats (Fig). MAO activity in rat urinary bladders also decreased to 48.9 ± 2.9% on day 7 pBOO (P<0.01) as compared to sham rats. The decrease in MAO activity persisted on day 14 (P<0.01). On immunohistochemistry, MAO-A-positive cells were predominantly observed in the detrusor layer in sham rat bladders. In pBOO rats, in contrast, the intensity of the MAO-A-positive signal decreased overall as compared to sham rats. Conclusions We demonstrated that the levels of MAO-A and activity of MAO decreased in the urinary bladder from pBOO rats as compared with sham rats. These results suggest that downregulation of 5-HT degradation leads to detrusor hypercontractility and/or facilitates hyper-contraction induced by 5-HT in the urinary bladder in pBOO rats. Funding Asahi Kasei Pharma Co.
Authors
Mai Michishita
Tsuyoshi Hattori Kazuo Yano Ken-ichi Tomita Ken-ichi Kasahara |
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MP26-20 |
Effects of decreased estrogen on lower urinary tract function and assessment of purinergic system changes in the guinea pig bladder |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP26-20 Sources of Funding: None Introduction Decreased serum estrogen is known to cause lower urinary tract symptoms. Adenosine triphosphate (ATP) is considered to be a bioactive substance that modulates bladder function. The purpose of this study was to assess changes in purinergic regulation systems in the bladder wall, including ATP released from the urothelium, using an ovariectomy model. Methods Twenty female guinea pigs (weight: 450-550 g) were divided into an ovariectomy group (OVX; n=10), which received bilateral ovariectomy to induce surgical menopause, and a sham operation group (Sham; n=10). All animals were housed in metabolic cages for 24 hours at 4 weeks after the operation. An intact strip, which contains the whole bladder layer, was stimulated by purinergic agents (e.g., ATP, α,β-methylene ATP, ADP), carbachol (CCh; 10-8 M to 10-5 M), and by electrical field stimulation (EFS; 1-40 Hz, duration 0.5 msec). Mucosal strips including urothelium were prepared by dissection between the suburothelial and detrusor layers. The concentration of ATP perfusing through the strips was measured using a luciferine-luciferase assay. Results The serum β-estradiol level was significantly lower in the OVX group, and uterine weight was less in the OVX group (OVX 227.4, Sham 1475 mg, p<0.001). In the OVX group, 24-hour urination frequency increased, and the mean voided urine volume decreased. 10 mN of passive stretch of mucosal strips increased the ATP concentration in both groups, and the rate of increase was significantly higher in the OVX group (226.5%) than in the Sham group (127.6%). Since the response to CCh in intact strips was significantly smaller in the OVX group (pEC50; 6.21) than in the Sham group (6.36), the contractile response to ATP was higher in the OVX group (10-3 M: Sham 787.0, OVX 986.6 mN/g). Contractile responses to 10-4 M ADP and 10-5 M α,β-methylene ATP were also larger in the OVX group. Although the total contractile response to EFS was similar in both groups, atropine-resistant contraction was increased in the OVX group (24 Hz: Sham 39.2, OVX 58.7% normalized by Tmax). Moreover, the correlation coefficient between the tension of intact strips stimulated by EFS and ATP release from them was larger in the OVX group than in the Sham group (4 Hz: r2= Sham 0.342, OVX 0.578). Conclusions Detrusor contractility to CCh decreased in the OVX group, though the purinergic system for bladder contraction and ATP release were upregulated in the OVX group. It appeared that the purinergic system compensated for bladder contractility. Increasing ATP release from the mucosa may upregulate bladder sensation. Funding None
Authors
Nobuhiro Kushida
Junya Yoshida Hidenori Akaihata Kei Ishibashi Yoshiyuki Kojima |
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MP27-01 |
Characteristics of patients with persistent lower urinary tract symptoms after HoLEP in BPH |
Benign Prostatic Hyperplasia: Surgical Therapy & New Technology II | 17BOS |
Abstract: MP27-01 Sources of Funding: none Introduction Holmium laser enucleation of the prostate (HoLEP) in BPH is widely used and the effects are known to be equivalent or better than traditional TUR-P with low incidence of complications. However, some patients who underwent HoLEP still have the lower urinary tract symptoms(LUTS) after surgery. We evaluated the characteristics of patients who visited our clinics due to persistent LUTS and required additional medications after HoLEP in BPH patients. Methods The medical records of the patients who underwent HoLEP from March of 2011 to June of 2015 were reviewed retrospectively. The analysis was performed in patients who have been followed for more than 6 months after surgery. The patients were divided into 2 groups. Group A is the patients with persistent obstructive symptoms and group B is with irritation symptoms. Age, prostate specific antigen, International prostate symptom score (IPSS), prostate volume, transition zone volume of prostate, peak flow rate, maximum cystometric capacity, post voided residual volume, resected weights, operation time were analyzed. Results Among the 482 patients who underwent the HoLEP, the numbers of patients who required the medicine for lower urinary tract symptoms were 138 (28.6%). Among the patients, 53 patients (40.2%) were enrolled in Group A and 85 patients (59.8%) were enrolled in Group B. The mean age, total IPSS, PSA, total prostate volume, peak flow rate, maximum cystometric capacity, post voided residual volume, and operation time between two groups were statistically insignificant. However, transition zone volume and resected weights were significantly different between group A and B. (p=0.017, p=0.010 respectively) Conclusions More than 25 % of the patients were still taking the medicines for lower urinary tract symptoms after HoLEP. Among the patients who required the medicine, 60% of patients have complained of irritation symptoms. Bigger transition zone with resection weights were correlated with remaining of postoperative irritation symptoms. Funding none
Authors
Kang Sup Kim
Yong Sun Choi Hong Jin Suh Hyun Woo Kim Joon Chul Kim Donh Hwan Lee |
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MP27-02 |
Efficacy and safety of Holmium laser enucleation of prostate (HoLEP) in patients with underlying neurologic disease |
Benign Prostatic Hyperplasia: Surgical Therapy & New Technology II | 17BOS |
Abstract: MP27-02 Sources of Funding: None Introduction Neurologic disease can cause the neurogenic bladder which can compromise the treatment outcome of HoLEP in patients with benign prostatic hyperplasia (BPH). Moreover, anticoagulants are frequently administered in those patients. We compared the efficacy and safety outcomes of HoLEP in BPH patients with or without neurologic disease. Methods We retrospectively reviewed the medical records, and preoperative urodynamic study (UDS) results of BPH patients who underwent HoLEP between June 2009 and December 2015. Results Of the 317 patients who received the HoLEP, 26 (8.2%) patients had underlying neurologic diseases. Neurologic disease group was more frequently administered anticoagulants than non-neurologic group (69.2 vs. 18.6%; p <0.001). However, neurologic disease group demonstrated similar patient characteristics and pre-operative urologic findings with non-neurologic disease group as shown in the Table. Two groups demonstrated similar operation time (non-neurologic disease group vs. neurologic disease group; 116.2 vs. 107.8 min, p=0.291), transfusion rate (0.3 vs. 0.0%, p=0.765), hospital stay (6.1 vs. 5.6 days, p=0.245), catheter duration (3.3 vs. 3.5 days, p=0.593), re-catheterization rate (5.2 vs. 0.0%, p=0.236). At median follow-up of 6 months, two groups demonstrated similar outcome parameters such as Qmax (19.6 vs. 16.6 mL/sec, p=0.088), PVR (27.9 vs. 35.2 mL, p=0.467), IPSS-emptying (3.1 vs. 3.6, p=0.645), IPSS-storage (4.3 vs. 3.3, p=0.219), and IPSS-QoL (1.6 vs. 2.0, p=0.470). Rates of complications such as incontinence (6.7 vs. 9.1%, p=0.671), urinary tract infection (0.8 vs. 0.0%, p=0.667), urethral stricture (1.7 vs. 4.5%, p=0.347) were not also different between two groups. Conclusions Efficacy and safety outcomes of HoLEP in patients with underlying neurologic diseases did not compromise compared to those of patient without neurologic diseases. HoLEP can be a good treatment option for BPH patients with underlying neurologic disease. Funding None
Authors
Myong Kim
Myung-Soo Choo Tai Young Ahn |
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MP27-03 |
Prediction of urge urinary incontinence (UUI) after holmium laser enucleation of prostate (HoLEP): revisiting the urodynamic detrusor overactivity (DO) |
Benign Prostatic Hyperplasia: Surgical Therapy & New Technology II | 17BOS |
Abstract: MP27-03 Sources of Funding: None Introduction Recent recommendation of international continence society (ICS, 2002) suggested the qualification of urodynamic DO as according to their pattern (phasic or terminal) or causes (neurogenic or idiopathic). However, quantification of DO has not been suggested. It is well known that there are some discordances between urodynamic DO and actual storage symptoms such as UUI. We assessed whether the quantification of urodynamic DO can improve the prediction of post-operative UUI following the HoLEP in patients with benign prostatic hyperplasia. Methods We prospectively measured the filling volume at DO (Vol_DO), detrusor pressure at DO (PdetDO), and presence or absence of DO incontinence, in addition to the ICS recommendations for urodynamic study (UDS) in 105 patients who underwent HoLEP between May 2010 and September 2015. Results Mean age (±SD) and prostate volume were 71.1 (±7.0) years and 63.7 (±24.2) mL. Of the 105 patients, 10 (9.5%) patients experienced the UUI at post-operative 3 months. The UUI-positive group demonstrated higher international prostate symptom score (IPSS)-storage (11.4 vs. 7.5, p=0.004) than the UUI-negative group. However, other parameters such as age, prostate size, preoperative uroflometry findings, IPSS-emptying, and IPSS-QoL were not significantly different between two groups (p range, 0.062-0.797). On UDS findings, UUI-positive group showed higher PdetDO than UUI-negative group (100.4 vs. 54.7 cmH2O, p=0.008). However, rates of DO presence and DO_vol were not significantly different between two groups (p-value, 0.423 and 0.788). DO incontinence is more frequent in UUI-positive group than in UUI-negative group, but failed to reach the statistical significance (80.0 vs. 52.6%, p=0.098). Spline curve analysis results suggested the optimal cut-off value of PdetDO for increased risk of UUI as 108.0 cmH2O (Figure). Our multivariate analysis revealed that pre-operative IPSS-storage (OR=1.696, p=0.036) and PdetDO (≥108.0 cmH2O; OR=15.546, p=0.044) were independent predictive factors for UUI after HoLEP. Conclusions Quantification of urodynamic DO improved the prediction of UUI after HoLEP Funding None
Authors
Myong Kim
Tai Young Ahn Myung-Soo Choo |
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MP27-04 |
Giving Underactive Bladders A Second Chance: Holmium Laser Enucleation Of The Prostate For Management Of Lower Urinary Tract Symptoms In Patients With Detrusor Underactivity. |
Benign Prostatic Hyperplasia: Surgical Therapy & New Technology II | 17BOS |
Abstract: MP27-04 Sources of Funding: None. Introduction Lower urinary tract symptoms (LUTS) in men are classically attributed to bladder outlet obstruction (BOO). However, LUTS may also exist in the presence of detrusor underactivity (DU). Evaluation of the voiding phase in patients with BOO demonstrates high bladder pressures and low flow rates. In contrast, low bladder pressures and low flow rates are characteristic of patients with DU. Holmium laser enucleation of the prostate (HoLEP) has been shown to be a safe, durable and effective surgical treatment for BOO secondary to benign prostatic enlargement (BPE) in prostates of any size. In our early experience, we have identified a population of patients with DU and BPE who have benefitted from HoLEP. We compared patients with BOO to those with DU to determine if outcomes after HoLEP are comparable. Methods Our HoLEP database was retrospectively reviewed, identifying 84 patients with preoperative (preop) urodynamic studies (UDS) who underwent HoLEP with or without bladder neck incision (+/- BNI). Of these patients, 24 had UDS consistent with DU; defined as max flow rate (Qmax) < 15 ml per second and detrusor pressure (Pdet) < 40 cm water. The remaining 60 patients had BOO (Qmax < 15 and Pdet ≥ 40). International Prostate Symptom Score and Sexual Health Inventory for Men questionnaires were administered preop and at each postoperative (postop) visit. All surgeries were performed by a single surgeon, supervising residents, from December 2014 to September 2016. Results There were no differences (p > 0.05) in patient demographics, catheter dependence, preop questionnaires and incontinence, enucleation/morcellation time, tissue volume removed and length of hospital stay between the two groups. Patients with DU had higher preop post void residual (PVR) (p = 0.017) and lower Qmax (p = 0.007). There were no differences in postop questionnaires and incontinence at 6 weeks, 6 months (mo) and 12 mo. PVRs were higher in DU patients at 6 weeks (p = 0.012), but not at 6 and 12 mos. All patients were able to void after HoLEP. One patient with DU was self catheterizing once nightly at 6 mo follow up. Conclusions The standard treatment for patients with DU and urinary retention is catheterization (clean intermittent or chronic indwelling). Typically, these patients are not offered surgery. For patients who can Valsalva and stand to void, HoLEP +/- BNI may improve quality of life and allow them to be catheter free. These findings may also support expanding the indications for HoLEP. Funding None.
Authors
Garrett Smith
Dongliang Wang Jessica E. Paonessa |
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MP27-05 |
Prospective study comparing safety and efficacy of HoLEP for recurrent BPH after initial TURP |
Benign Prostatic Hyperplasia: Surgical Therapy & New Technology II | 17BOS |
Abstract: MP27-05 Sources of Funding: none Introduction To prospectively evaluate safety and efficacy of Holmium laser enucleation of prostate (HoLEP) in patients with symptomatic prostate recurrence after prior transurethral resection of prostate (TURP). We also studied indication of secondary prostatectomy after prior TURP. Methods We prospectively evaluated 43 patients with past history of TURP who underwent HoLEP between June 2003 & May 2016 (study group). The technique of enucleation was modified based on the morphology of recurrent adenoma. 100 W holmium laser machine with 550 micron laser fiber was used. Patient’s demographics, intra and postoperative data was entered in IBM SPSS Statistics 24 software and compared with 43 randomly selected patients who underwent HoLEP without prior TURP at our institute (control group). Each control group patient was the one who underwent HoLEP immediately after the study group patient in the sequence of HoLEP patients at our institute. Results Patients demographics are shown in table 1. Study group patients predominantly presented with gross recurrent hematuria (58.1 %; 25/43) and had less AUA symptom score and better uroflowmetry rates than control group. The average interval between past TURP and HoLEP was 4.22 years (range- 1 month to 16 years). Table 2 & 3 reveals that the intraoperative parameters and postoperative outcome were comparable in both groups. Conclusions Recurrent hematuria is a commonest indication of secondary prostatectomy after primary TURP. HoLEP is a safe and effective in patients needing secondary prostatectomy after TURP and has outcome similar to those patients undergoing naïve procedure. Funding none
Authors
Hemendra Shah
Rashmi Shah |
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MP27-06 |
Does a partial prostate resection improve voiding symptoms while shortening the learning curve for HOLEP? |
Benign Prostatic Hyperplasia: Surgical Therapy & New Technology II | 17BOS |
Abstract: MP27-06 Sources of Funding: None Introduction Holmium laser enucleation of the prostate (HOLEP) is an ideal option for very large prostate glands that would otherwise be managed by simple prostatectomy. However, a steep learning curve has limited widespread adoption of this procedure. Early in our experience we staged very large glands by removing the median lobe when necessary with enucleation of only one lateral lobe to reduce excessive OR times. These patients were followed to determine if a partial HOLEP adequately reduced obstructing voiding symptoms and whether additional procedures to complete the enucleation were necessary. Methods We performed a retrospective review of 84 patients with bladder outlet obstruction who underwent a HOLEP with a single surgeon between 1/2013-10/2016. We specifically evaluated whether the improved symptoms maintained over time or whether obstructive symptoms re-developed requiring another intervention. Results Median age was 72 years. Median size of prostate on transrectal ultrasound was 93gm (48-200gm). 14 patients underwent a partial HOLEP, and all were within the first 40 cases. Of these, 6 patients were content with their symptoms with significant improvement of uroflow parameters and IPSS scores (p<0.03) at last date of follow up. Eight patients of the 14 patients had persistent symptoms or developed new symptoms such that they required another intervention. One patient developed gross hematuria from the remaining lobe, one patient developed a bladder stone, and the remaining 6 complained of returning obstructive voiding symptoms requiring a completion resection. Conclusions While performing a partial HOLEP may maintain lower OR times and assist with the learning curve, the majority of patients will require another surgery within 2 years due to recurrent symptoms or complications such as bleeding and bladder stones._x000D_ A complete HOLEP should be performed whenever possible to optimize patient outcomes. _x000D_ Funding None
Authors
Saum Ghodoussipour
Adit Shah Eli Thompson Anirban Mitra Matthew Dunn |
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MP27-07 |
Can we predict the learning curve for holmium laser enucleation of the prostate (HoLEP) by using simultaneous parameter of enucleation-morcellation? |
Benign Prostatic Hyperplasia: Surgical Therapy & New Technology II | 17BOS |
Abstract: MP27-07 Sources of Funding: None Introduction Holmium laser enucleation of the prostate (HoLEP) is a minimally invasive laser therapy for benign prostatic hyperplasia. However, a steep operative learning curve may be the main drawback to use of HoLEP. The enucleation ratio or efficacy were known as one of the parameters for estimating the learning curve. But this parameter is only focused on time of enucleation not considering morcellation, even though operators spend time of enucleation and morcellation simultaneously during HoLEP surgery. The aim of this study was to evaluate a various method to assess the learning curve of HoLEP of a single surgeon. Methods Ninety-two consecutive cases performed by the single surgeon were enrolled. Intraoperative measures, including enucleation time, enucleation ratio (enucleated weight/transitional zone volume), enucleation efficacy (enucleated weight / enucleation time), consumed energy, morcellation time, morcellation efficacy (enucleated weight / morcellation time) and enucleation-morcellation efficacy (enucleated weight/enucleation and morcellation time) were analyzed. Perioperative morbidity, length of hospital stay and length of urinary drainage were also investigated. In addition, functional outcomes such as Qmax, post-void residual volume, IPSS and QoL scores at 3 and 6months were also investigated. Results The mean age of the patients was 72.9 years (49-86) with a mean prostate volume of 59.2 cc (34-180) on transrectal ultrasonography. Within all procedures, mean total operative time was 86.5 minutes (45-260 minutes) with a mean enucleated weight of 42.2 g (25-120 g). Mean enucleation time, consumed energy, morcellation time and enucleation ratio were 48.9 ± 12.1 min, 67.5 ± 22.8 kJ, 22.4 ± 14.5 min and 0.64 ± 0.32 g/mL, respectively. In terms of efficiency, enucleation efficacy, morcellation efficacy and enucleation-morcellation efficacy were 0.42 ± 0.37 g/min, 4.24 ± 1.26 g/min and 0.24 ± 0.11 g/min, respectively. Perioperative complications were observed in 12 of 92 (13.0%). Of these, 10 were urinary tract infection and 2 was urethral stricture. Considering the learning curve, the plateau of enucleation efficacy was reached after 38 cases. However, considering enucleation and morcellation time simultaneously, enucleation-morcellation efficacy has an increasing trend even after 38 cases and has remained roughly constant after 55 cases. Based on these criteria, we divided cases into two groups. Enucleation efficiency was significantly higher after 38 cases. Morcellation efficiency was also higher in the second group, however, the difference was not significant. Enucleation-morcellation efficiency was significantly higher after 55 cases. Perioperative morbidities, hospital length of stay, urinary drainage length and functional outcomes at 3 and 6months were not significantly different between the groups based on these criteria. Conclusions Although the learning curve did not interfere with functional results, our results demonstrated that even after 38 cases, surgical skill advances are still needed. Of these factors, morcellation time is as important as enucleation time in the whole surgical procedure. Enucleation-morcellation efficacy might be considered a better parameter for estimating the operative learning curve of HoLEP rather than enucleation efficacy alone. Funding None
Authors
Sung Tae Cho
Don Kyoung Choi Ohseong Kwon Young Goo Lee Ki Kyung Kim Kyungtae Ko |
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MP27-08 |
Assessment of the learning curves for intravesical adenoma morcellation using ?Piranha&[copy] device during endoscopic enucleation? |
Benign Prostatic Hyperplasia: Surgical Therapy & New Technology II | 17BOS |
Abstract: MP27-08 Sources of Funding: None Introduction Morcellation of intravesical adenoma (MIA) is an important part of the endo- scopic enucleation procedure. The aim of this study was to analyse the learning curve of the MIA during endoscopic enucleation of the prostate.? Methods We conducted a prospective study of the first 90 patients treated by endoscopic enu- cleation of the prostate by a single surgeon without previous experience of MIA. The population was divided into 3 consecutive groups of 30 patients. MIA was performed with the morcella- tor Pinranha (Wolf®) and disposable blades (Vmax&[copy]). The criteria selected to assess the progress of MIA over time were: duration of MIA (min), the intraoperative complications encountered during MIA and weight morcelleted tissue. The efficacy of MIA was assessed with the ratio weight specimen/MIA duration (min/g) over time. Results The three groups were comparable in terms of age, ASA score of prostate volume. A significant decrease in the duration of MIA was found between groups 1 and 2 (12 versus 5.5 min, P < 0.0001), to reach a plateau in the group 3 (3 min). A significant increase in the efficiency of MIA was found between group 1 and 2 (5.5 versus 11 g/min, P < 0.0001), to reach a plateau in the group 3 (20 g/min) (Figure 1). Bladder injuries were limited (7.7%), superficial and encountered in the early learning phase. Conclusions In our experience, the MIA required a learning curve estimated between 30 and 60 procedures. Funding None
Authors
Benjamin PRADERE
Benoit PEYRONNET Benoit Bordier Julien Guillotreau Kevin Zorn Vincent Misraï |
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MP27-09 |
Predictors of postoperative bacteriuria after Holmium Laser Enucleation of the Prostate (HoLEP) |
Benign Prostatic Hyperplasia: Surgical Therapy & New Technology II | 17BOS |
Abstract: MP27-09 Sources of Funding: none Introduction Transient non-bothersome, irritative bladder symptoms are not uncommon following HoLEP, and thus urine culture (UCx) is obtained to differentiate between expected transient irritative symptoms and urinary tract infection (UTI)._x000D_ Our aim is to evaluate the predictors and risk factors of postoperative bacteriuria at 6 weeks post HoLEP in an attempt to decrease the postoperative routine UCx analysis._x000D_ _x000D_ Methods After IRB approval, a retrospective chart review of 100 patients who had HoLEP between August 2015 and June 2016. It is a protocol at our institution that UCx analysis is performed at the 6 weeks postoperatively. All patients had urine cultures’ results preoperatively and 6 weeks postoperatively. Patients’ demographics, Preoperative, operative and postoperative characteristics data were obtained and analyzed. Statistical analysis was performed using USPSS and included means with standard deviation, Chi-square test, and Independent T-test when appropriate. Results A total of 100 patients were identified, 18 patients in group (A) who had positive postoperative UCx at 6 weeks after HoLEP versus 82 patients in group (B) who had negative postoperative UCx. Patients’ demographics were comparable with no statistical significance between both cohorts. 11 (61.1%) vs 22 (26.2%) patients had preoperative positive UCx in groups (A) and (B), respectively, (p=0.052). A preoperative history of UTI was noted in 7 (38.8%) vs. 28 (34.1%) patients in groups (A) and (B), respectively, (P= 0). Preoperative Urine retention was present 3 vs. 12 in groups (A) and (B) with a mean length of catheterization (LOC) of 60 vs. 75.58 days, respectively, (p= 0.708). Mean preoperative PVR was 116.45 vs. 145.48 mls in groups (A) and (B), respectively, (p= 0.463). Mean preoperative BPH impact index was 5.85 vs. 5.1 in groups (A) and (B), respectively, (p= 0.439). Mean preoperative AUA score is 22.2 vs. 24.48 in groups (A) and (B), respectively, (P= 0.383). Mean OR specimen weight was 68.6 vs. 51.5 gms in groups (A) and (B), respectively, (p= 0.294). Enucleation and morcellation times were comparable with no statistical significance. Postoperative LOC was 1.6 vs. 1.9 in groups (A) and (B), respectively, (p=0.323). Mean postoperative PVR at 6 weeks was 77.5 vs. 45.7 mls in groups (A) and (B), respectively, (p= 0.014). Mean AUA score mean at 6 weeks was comparable at 5.66 vs. 8.2 in groups (A) and (B), respectively, (p= 0.153). Conclusions The sole predictor of postoperative bacteriuria is the elevated PVR; we recommend obtaining routine UCx for patients who presents with PVR above 50 ml. Funding none
Authors
Amr Elmekresh
Victor Villarreal II Jordyn Farewell Karen Doersch Marawan El Tayeb |
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MP27-10 |
Role of Debulking Procedures in Men with Prostates less than 40 grams. |
Benign Prostatic Hyperplasia: Surgical Therapy & New Technology II | 17BOS |
Abstract: MP27-10 Sources of Funding: None Introduction There is a dearth of evidence showing a long-term benefit of performing debulking procedure in small volume prostates (<40grams), with no evidence in using 180-W XPS-greenlight system in this population. Our objective was to characterize the long term clinical and symptomatic benefit of the 180-W XPS-Greenlight laser in patients with small volume prostates. Methods A retrospective analysis of 58 patients who underwent 180-W XPS-laser PVP vaporization of the prostate between 2012 and 2016 at three tertiary medical centers. We included all comers with prostates less than 40 grams with clinical evidence of bladder outlet obstruction. Results The average age of men who underwent PVP of the prostate was 67.8±10.9 years old, with an average BMI of 29.7±3.9. The average prostate volume was 29±6.7mL, five patients were found to have a significant intravesicular median lobe. Three patients had pre-operative retention requiring catheterization, 45 patients were using an alpha blocker and 41 were using a 5-alpha reductase inhibitor. The average operative time was 45.1±22.1 minutes, laser time of 20.9± 13 minutes, and energy of 146±96.8 kilojoules. All patients were discharged from the hospital within 48 hours of the procedure, five patients were discharged with a catheter. The median follow up time was 6 months (IQR 3-22.5), there were 12 complications within 30 days, including 2 patients with persistent retention, 4 patients had urinary tract infections, 4 patients had severe urgency requiring medications, one patient had intermittent hematuria and 1 patient had a paraphimosis. There was no incidence of stricture or bladder neck up to four years of follow up. The IPSS score improved from was 22.8±7 at baseline 0.7±7 (p<0.01) and 6.31±4.4 (p<0.01) at 30 and 180 days, respectively. The maximal flow rate improved from 7.7±4.6 ml/sec at baseline to 17.25±9.3 mL/sec (p<0.01) and 19.14±7.19 (p<0.001) at 30 and 180 days, respectively, while the PVR improved from 216±271 mL pre-operatively to 32.8±45.3 (p<0.01) and 26.23±46 (p<0.01) at 30 and 180 days, respectively. The PSA drop from 1.97±1.76 ng/mL pre-operatively to 0.74±0.63 ng/mL 180 days, respectively. Conclusions Photovaporzation of prostates smaller than 40 grams with the 180-W XPS-laser has been shown to have a durable improvement in symptomatic and clinical parameters. Funding None
Authors
Ramy Goueli
Lesa Deonarine Dominique Thomas Kristina Navrazhina Kelsey Lawson Malek Meskawi Marc Zanaty Vincent Misrai Roger Valdivieso Pierre-Alain Hueber Kevin Zorn Alexis Te Bilal Chughtai |
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MP27-11 |
Complications and functional outcomes of high-risk patient with cardiovascular disease necessitating ACO treated with the 532nm-Laser Photo-vaporization Greenlight XPS 180W |
Benign Prostatic Hyperplasia: Surgical Therapy & New Technology II | 17BOS |
Abstract: MP27-11 Sources of Funding: none Introduction According to AUA guidelines Greenlight PVP 532-nm laser vaporization of the prostate should be considered in patients receiving anticoagulant medication or with a high cardiovascular risk. We sought to examine the functional and complications outcomes of high risk patients with cardiovascular disease necessitating maintenance of anticoagulation therapy (ACO). Methods Retrospective analysis of prospectively maintained institutional database was performed. Men were stratified according to ACO treatment status defined as the usage of anti-vitamin K, Heparin, direct thrombin inhibitor or and anti-Xa. Complications at 30 and 90 days according to Clavien classification and functional outcomes (IPSS, Qmax and PVR) were analyzed up to 5-years follow-up. Results A total of 39 (10%) patients were on ACO including 8 patients with prosthetic cardiac valve, 26 patients with malignant arrhythmias and 27 with coronary cardiac disease._x000D_ _x000D_ ACO patients were older (75 vs 67 years, p<0.01) and with more systemic disease defined by ASA score. Men with ACO were more likely to fail first trial of void, had significant longer catheterization time 1.7 vs 1 days and longer hospitalization 2.5 vs 0.5 days respectively (p<0.01 for all). ACO men had also higher 30 days readmission rate of 16% and higher rate of hematuria observed in almost 1/3 of the cases. Functional outcomes were significantly improved and equivalent to non ACO patients at all endpoints including at 5-year._x000D_ Conclusions This is the first study to look at safety and functional outcomes of patients with cardiovascular disease requiring ACO with 5 years follow-up. PVP provide significant and durable treatment for symptomatic BPH in these high-risk ACO patient. However treatment comes with an increased risk of bleeding related complication implying longer catheterization and hospitalization that should be discussed during pre-operative patient counseling. Funding none
Authors
Roger Valdivieso
Pierre-Alain Hueber Malek Meskawi Marc Zanaty Kelsey Lawson Mounsif Azizi Benjamin Pradere Kevin Zorn Vincent Misrai |
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MP27-12 |
Greenlight Laser (XPS) 180W photoselective vaporization (PVP) vs. plasma kinetic vaporization of the prostate (PKVP) for treatment of small to moderate sized benign prostatic hyperplasia. A randomized controlled trial |
Benign Prostatic Hyperplasia: Surgical Therapy & New Technology II | 17BOS |
Abstract: MP27-12 Sources of Funding: none Introduction As per Goliath trial, Greenlight laser (XPS) Photoselective Vaporization of the prostate (GL.PVP) is non-inferior to TURP in reduction of LUTs secondary to BPH with all advantages of laser. Plasma Kinetic vaporization of the prostate (PKVP) is a potential contender to the evolving Greenlight PVP._x000D_ _x000D_ In this study, non-inferiority of PKVP compared to GL.PVP, in reduction of LUTS secondary to BPH, was tested in a randomized trial._x000D_ Methods Between November 2014 and October 2015, 120 patients with complicated BPH (size 30-80 cc) were randomized to GL.PVP and PKVP._x000D_ Patients were assessed postoperatively using I-PSS, QOL, Qmax and PVR (at 1, 4, and 12 months), IIEF-15 and PSA (at 4 and 12 months). _x000D_ Non-inferiority of I-PSS at 1 year was evaluated using a 1-sided test at 5% level of significance. The statistical significance of other comparators was assessed at the (2-sided) 5% level._x000D_ Results At time of analysis 58 GL.PVP and 61 PKVP procedures were included._x000D_ Patients` demographics, prostate size , indications of intervention and perioperative parameters were comparable between both groups apart from more perioperative irrigant fluid use in GL.PVP (P =0.014)._x000D_ More postoperative dysuria was reported after PKVP, dysuria visual analogue scale 4(0-10) vs. 6(0-10), P=0.005 in GL.PVP and PKVP respectively. _x000D_ Urinary outcome measures revealed significant comparable improvement in both groups at different follow up points either in the net value or in the percentage improvement from baseline measure. At 1 year, median IPSS was 6 (1:25) vs 5 (1:18) P=0.7, median QoL was 1 (0:5) vs 1 (1:5) P=0.84, mean Q max was 22±9.4 vs 20±8.5 ml/sec P=0.42, median PVR was 20 (0:97) vs 25 (0:109) ml P=0.14, in GL.PVP and PKVP respectively. _x000D_ Median postoperative change in PSA was 63.5% (-54:95) following GL.PVP vs 31.6% (-66:30) after PKVP, P=0.027_x000D_ Both groups showed comparable perioperative and late postoperative complication and re-intervention rate during the first year._x000D_ Among sexually active men (25%), there was significant reduction of IIEF-15 score following PKVP in comparison to GL.PVP _x000D_ Conclusions PKVP is a safe and effective modality in treating patients with LUTS secondary to small to moderate sized BPH. In terms of symptoms control, it was not inferior to GL.PVP at 1 year. Long-term durability of the outcome is critical considering the difference in postoperative PSA reduction. Impact on the sexual function should be considered for further evaluation in a larger cohort of sexually active men. Funding none
Authors
Fady K. Ghobrial
Ahmed M. Elshal Mahmoud Laymon Nasr El-Tabey Ahmed Shoma Adel Nabeeh Ahmed Shokeir |
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MP27-13 |
Randomized Study of Greenlight XPS Laser vs Bipolar Vaporization Electrode (BiVAP) Saline Vaporization of the Prostate in Men with Symptomatic Benign Prostatic Hyperplasia (BPH) |
Benign Prostatic Hyperplasia: Surgical Therapy & New Technology II | 17BOS |
Abstract: MP27-13 Sources of Funding: Boston Scientific, Richard Wolf Introduction Bipolar transurethral vaporization the prostate (B-TUVP) and Greenlight XPS Laser photovaporization (PVP) have emerged as standard therapies for BPH. While these two modalities have been evaluated extensively, data is lacking in direct comparison of PVP versus Bipolar Vaporization Electrode (BiVAP) or &[Prime]button TUVP&[Prime], whose unique geometric form enables high energy concentration for faster, more effective tissue vaporization than the conventional loop. We compared 12-month outcomes of Greenlight PVP and BiVAP for treatment of symptomatic BPH. Methods We conducted a single-site prospective, randomized study of Greenlight XPS PVP vs BiVAP in men age ≥ 18 years with symptomatic BPH defined by American Urological Association (AUA) symptom score ≥ 15, maximum urinary flow rate (QMax) < 15mL/sec, and prostate volume ≥ 30g. Exclusion criteria included prior surgical treatment for BPH, post-void residual (PVR) > 300mL, and prostate-specific antigen (PSA) ≥ 4 ng/mL. Eligible men were randomized in a 1:1 ratio. Men were followed at 1, 3, 6, and 12 months post-operatively for assessment of the primary outcomes, AUA symptom score and QMax. Chi-square and t-tests were utilized where applicable. Results Baseline characteristics for PVP vs BiVAP were similar with regard to age, race, Qmax, PVR, AUA Symptom score, and prostate volume (59.2 ± 28.8 vs 56.1 ± 22.8 g, p=0.62). There was no difference in peri-operative outcomes including mean length of procedure (48.4 ± 30.6 vs 49.8 ± 23.7 mins, p=0.83), length of stay (100% vs 100% discharged within 24 hrs, p=1.00), and length of catheterization (76.7% vs 71.4% catheter removal within 24 hrs, p=0.78). At 12 months, mean improvement in AUA symptom score was slightly greater for PVP vs BiVAP, approaching but not reaching statistical significance (-14.7 ± 9.0 vs -10.5 ± 8.6, p=0.10). At 12 months, there were no differences in mean Qmax, PVR, or prostate volume between the groups (all p > 0.05). Conclusions Both Greenlight PVP and BiVAP TURP are safe and effective treatments for men with symptomatic BPH desiring surgery. Selection of operative approach should be driven by unique patient characteristics and surgeon experience. Funding Boston Scientific, Richard Wolf
Authors
Jonathan Fainberg
Joshua Halpern Edward Zoltan Ivan Colon Brent Yanke Ivan Grunberger |
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MP27-14 |
Combined Bipolar vaporization and Resection versus vaporization alone in treatment of BPH: A randomized prospective trial |
Benign Prostatic Hyperplasia: Surgical Therapy & New Technology II | 17BOS |
Abstract: MP27-14 Sources of Funding: none Introduction : Bipolar TURP by resection loop and vaporization button are commonly used nowadays for treatment of BPH because it causes less intraoperative bleeding, and avoids free water absorption. However, bipolar vaporization may be associated with increased operative time and postoperative morbidity. By adding resection we can minimize operative time and clean prostatic fossa from prostatic tissue shreds making prostatic fossa more smooth and regular. We compare results of combined Bipolar TURP using the resection loop and vaporization versus vaporization alone for BPH to determine the relative safety and efficacy of both technique. Methods 77 patients with BPH were included in this study and randomized to operation either by Olympus (Gyrus) Bipolar loop TURP and Olympus (Gyrus) Bipolar button vaporization (Group 1) 40 patients or Olympus (Gyrus) Bipolar button vaporization alone( Group 2) 37 patients . Inclusion criteria were; BPH with qmax <10ml/sec, IPSS score>18 and prostate volume >40 gm. All patients were evaluated preoperatively and at 1, 3 and 9 months postoperatively by IPSS, uroflowmetry and prostate ultrasound. Clavien complications and operative time were recorded._x000D_ _x000D_ Results This study included 40 patients in Group1 (combined Bipolar Vaporization And Resection) and 37 patients in Group 2. (Bipolar Vaporization alone).There was no significant difference as regard age ( 51 + 9.9 and 52.5 + 8.2) , hospital stay (1-2 days) or catheterization period (1-2 days) in both groups. Preoperative prostate volume (58 g v 55 g p=0.51) and IPSS (20 v 22 p=0.38) was equivalent. Significant increase in operative time was noticed in Group 2 (79± 15 minutes range 45-105 p <0.001) , versus (mean 59 ± 10 minutes range 35-75 minutes ,smale non-significant difference in blood loss occurred in both Groups (0.8% compared to 0.9% drop in hemoglobin, p<0.55) but increased postoperative urinary frequency (75% in G2 vs 45% in G1 ( p <0.001), hematuria with clots as long as 3 weeks after surgery (18% vs 2%, p <0.001s p=0.22), :) and postoperative urethral stricture (4% vs 0%). There was No significant difference in Q max improvement Qmax (20 cc/s vs 18 cc/ s ) or postoperative prostate volume (32 vs 31 g p=0.31) and IPSS (6 v 5 p=0.22) equivalently Conclusions Combined Bipolar vaporization and resection of the prostate, is superior to Bipolar Vaporization alone as regard operative time and postoperative morbidity without compromising its efficacy and safety. Funding none
Authors
Osama Abdelwahab
Tarek Soliman Hammoda Sherif Mohamed Habous |
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MP27-15 |
Readmission following transurethral prostatectomy for treatment of benign prostate hyperplasia in the post TURP era; Does the technique differ? |
Benign Prostatic Hyperplasia: Surgical Therapy & New Technology II | 17BOS |
Abstract: MP27-15 Sources of Funding: None Introduction Despite being frequently described as the gold standard treatment of benign prostate hyperplasia (BPH), transurethral resection of the prostate (TURP) has been recently challenged by other techniques as endoscopic enucleation, vaporization and incision of the prostate. Furthermore, TURP itself has been evolved by introduction of TURP in saline. The aim of our study was to determine independent predictors for procedure-related readmission (PRR) following transurethral interventions for BPH in a contemporary series. Methods The electronic files of our PIS were reviewed for all transurethral BPH interventions that were performed between 2005 and 2014. Patients with at least one depictable follow up were included. Files were reviewed for all perioperative and follow up data. PRR was reviewed for cause, management and time to primary intervention with assessment of readmission free survival (RFS) among different groups. Results Out of 3423 reviewed procedures 3020 were included for analysis. PRR was 262 (8.7%), 38 (1.3%) and 10 (0.3%) once, twice and three times following primary intervention respectively._x000D_ Causes of PRR and their management were summarized in table 1. _x000D_ Mean RFS (95%CI) was 102 (95:109), 117 (111:122), 73 (70:76) and 46.7 (44.7:48) months following incision, resection, enucleation and vaporization (P0.016) respectively._x000D_ Regardless energy used, on Cox regression analysis, RFS was independently predicted by surgical technique (HR 1.36, 95%CI 1.5:1.7, P0.02) and level of surgeon`s experience (HR 1.37, 95%CI 1.07:1.7, P0.01)._x000D_ The least depictable follow-up was 20 months. For prostate size less than 40ml; 20-month RFS was 97%, 89%, 93% and 87% following incision, resection, enucleation and vaporization (P0.01) respectively. Among cases with prostate size from 40 to 80ml; 20-month RFS was 80%, 97%, 95% and 89.8% following incision, resection, enucleation and vaporization (P0.02) respectively. Among cases with prostate size more than 80ml; 20-month RFS was 85%, 95% and 84% following resection, enucleation and vaporization (P0.04) respectively. Conclusions Regardless the kind of energy used, surgical technique dictates the need for readmission. Prostate incision achieves the best RFS for small sized prostate. While prostate resection or enucleation accomplish comparable high RFS in moderate sized prostate. When treating large sized prostate, least PRR seems to be with enucleation. Funding None
Authors
Ahmed M Elshal
hossam nabeeh mohamed soltan Ahmed elsherbiny mohamed nageeb Ahmed Elhussein abolazm Fady K Ghobrial mohamed abdel_basset Abdelwahab Hashem mahmoud laymon Ahmed M Mansour El_housseiny Ibrahiem |
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MP27-16 |
SURGEON-SPECIFIC VARIATION FOR OUTCOMES AFTER BENIGN PROSTATIC HYPERPLASIA SURGERY |
Benign Prostatic Hyperplasia: Surgical Therapy & New Technology II | 17BOS |
Abstract: MP27-16 Sources of Funding: None Introduction Successful benign prostatic hyperplasia (BPH) surgery has been previously linked to various patient and technical factors. Although proficiency of the surgeon is assumed to contribute to successful surgical outcomes, this link has not been explored in BPH surgery. We examined our institutional experience to determine if surgeon-specific variation exists for outcomes after BPH surgery. Methods From January 2008 to December 2015, we identified 184 patients who received BPH surgery from seven attending surgeons. Measures to define successful BPH surgery included postoperative AUA symptom score of less than 8 (AUA symptom score success) and no BPH medications (medication success) at 4 months postoperatively. Multivariate logistic regression was performed (controlling for preoperative patient characteristics, medications taken, tests performed, surgical technique, operative time, and surgeon) in order to identify predictors of AUA symptom score and medication success. P-values less than 0.05 were considered significant. Results All surgeons performed a similar number of cases during the observed time period (n=22, 19, 22, 20, 24, 29, and 48; for surgeons 1, 2, 3, 4, 5, 6, and 7, respectively). The unadjusted percentage of patients who achieved a successful outcome is summarized in Figure 1, by surgeon. On multivariate logistic regression, controlling for all measured variables, surgeon was a significant predictor of AUA symptom score success (largest difference was for surgeon 6 versus surgeon 1; OR = 11.2, 95% CI 2.3 to 53.9, p <0.01). The only other significant predictor for AUA symptom score success was preoperative post-void residual (OR=3.1, p=0.03). Additionally, surgeon was a significant predictor of medication success (largest difference was for surgeon 6 versus surgeon 1; OR = 20.7, 95% CI 3.9 to 108, p <0.01). The only other significant predictor for medication success was patient comorbidity (OR=0.38, p=0.05). Conclusions Although successful BPH surgery is dependent on various patient and technical factors, the surgeon performing BPH surgery was the strongest predictor of outcomes at our institution. More specific metrics to rate surgeon quality are needed to better understand the underlying cause of significant surgeon-to-surgeon variation. Funding None
Authors
John Weaver
Eric Kim Joel Vetter Niraj Badhiwala Seth Strope |
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MP27-17 |
3 Year Results of a Prospective Multi-Center Study on Local Anesthesia for the Prostatic Urethral Lift (PUL) |
Benign Prostatic Hyperplasia: Surgical Therapy & New Technology II | 17BOS |
Abstract: MP27-17 Sources of Funding: NeoTract, Inc. Introduction The Prostatic Urethral Lift (PUL) is a minimally invasive procedure for lower urinary tract symptoms (LUTS) that may be conducted in the office setting. In order to characterize procedure tolerance under local anesthesia, peri-operative recovery, and long-term outcomes, PUL was studied in a multi-center, prospective, non-randomized trial. Methods At 7 US centers, 51 men with International Prostate Symptom Score (IPSS)>12, peak flow rate ? 12mL/s, and prostate volume < 80cc were treated with PUL wherein UroLift® implants were transurethrally placed into the lateral lobes to enlarge the urethral lumen. Patient experience was measured via validated instruments including pelvic pain visual analog scale (VAS), Quality of Recovery VAS (QoR), Patient General Impression Index (PGI-I), Work Productivity and Activity Impairment Questionnaire (WPAI). Results All procedures were well tolerated under local anesthesia. Symptom relief was significant by 1 month (IPSS 48%, QoL 44%) and sustained through 3 years (IPSS 42%, QoL 50%). 80% of patients were catheter free after PUL and the average for all patients was less than one day. There was no de novo, sustained occurrence of ejaculatory or erectile dysfunction. By one month, 86% of subjects achieved high quality recovery per QoR, 90% reported improvement through PGI-I, 96% had returned to pre-operative activity, 100% of employed subjects had returned to work. Average erectile function scores did not change, and both ejaculatory function and bother were improved (p<0.001). Conclusions The PUL procedure is well tolerated under local anesthesia, rarely requires postoperative catheterization, and is associated with high quality recovery experiences. In addition, the results of this study indicate that PUL provides durable symptom relief to patients, as IPSS and quality of life scores remain significantly improved at 3 years. PUL offers patients a minimally invasive option for rapid, sustained LUTS relief and preserved sexual function. Funding NeoTract, Inc.
Authors
Steven Gange
Neal Shore Sheldon Freedman William Moseley Sean Heron Ronald Tutrone Thomas Brown Jack Barkin |
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MP27-18 |
Crossover Study on the Prostatic Urethral Lift (PUL): 4 Year Results |
Benign Prostatic Hyperplasia: Surgical Therapy & New Technology II | 17BOS |
Abstract: MP27-18 Sources of Funding: NeoTract, Inc. Introduction PUL is a unique, non-thermal approach to treating lower urinary tract symptoms (LUTS) in men with benign prostatic hyperplasia. We present the 4-year data from a sham to Prostatic Urethral Lift (PUL) crossover study in which each patient served as his own control. Methods 53 patients underwent control sham procedure as part of a blinded, controlled study. After 3 months, these men with symptomatic LUTS were treated with crossover PUL that involved placing UroLift® implants into the obstructing lateral lobes of the prostate. They were followed for 4 years with validated tools such as International Prostate Symptom Score (IPSS), quality of life score (QoL), BPH Impact Index (BPH II), peak flow rate, sexual function scores, and adverse event reporting. Results Average IPSS improved after sham but returned to near baseline after 3 months, while peak flow rate (Qmax) remained mildly elevated (Fig 1). At 4 years after crossover PUL, average scores for IPSS, QoL, and BPHII remained improved 45%, 49%, and 44% from baseline, respectively (p<0.001). Average peak flow rate increase of at least 50% over baseline was demonstrated at 4 years (p=0.01). On average, patients returned to normal activity within 7 days. Related adverse effects were typically transient and mild to moderate in severity. There were no reported instances of de novo, sustained erectile or ejaculatory dysfunction. Conclusions Similar to other publications, the 4 year results of the crossover study indicate the PUL procedure can result in rapid and durable improvement in symptoms, quality of life, and peak flow rate. Subjects report minimal adverse effects and return to normal quickly. Sexual function appears to be preserved. This study offers a unique perspective on the effectiveness of PUL, as the sham response is quantified for each patient. PUL is demonstrated to have a significant, non-placebo response that is durable to four years. Funding NeoTract, Inc.
Authors
Henry Woo
Jack Barkin Damien Bolton Prem Rashid Anthony Cantwell William Bogache Stephen Richardson Ronald Tutrone James Fagelson Peter Chin |
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MP27-19 |
Pooled Data from Commercial Cases Using the UroLift ® Device |
Benign Prostatic Hyperplasia: Surgical Therapy & New Technology II | 17BOS |
Abstract: MP27-19 Sources of Funding: None Introduction Treatment options for men suffering from lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH) include watchful waiting, medications, ablative surgeries, and the Prostatic Urethral Lift (PUL) procedure. We present real-world data from commercial PUL cases using the UroLift ® System. Methods PUL involves placing small, permanent, metallic implants (UroLift® System, NeoTract, Inc., Pleasanton, CA) into the prostate under transurethral cystoscopic guidance. The implant is affixed into prostate tissue to lift the lateral lobes away from the urethra and remove obstruction. 197 patients are included in a retrospective analysis on commercial PUL cases performed at multiple centers in Australia and North America. 8% of patients were in urinary retention at the time of the procedure. Post-operative assessments included LUTS relief via International Prostate Symptom Score (IPSS), quality of life (QOL), and peak urinary flow rate (Qmax). Peak flow rates were included in the analysis if the voided volume was at least 75 mL. Results Average age was 67 years, range 40-101. Average prostate size was 54.1 cc, range 19-160 cc. Average number of implants was 3.8, range 2-10. LUTS relief was significant, with IPSS demonstrating 29-42% average improvement during the follow up periods (Table 1, p values < 0.0001). Quality of life response was dramatic, with 61% improvement at 1 year (baseline: 4.3, 1 year: 1.7, p value < 0.0001). Peak flow rate improvement was mild throughout. Conclusions In clinical studies, the PUL procedure has been shown to be associated with stable and significant symptom relief. We present results from the largest body of commercial data pooled to date and provide insight into real-world application of the minimally invasive PUL therapy. In every day application, PUL offers symptom relief through at least 12 months of follow up. Funding None
Authors
Paul Cozzi
Lance Walsh Douglas Grier Andrew Hirsh Gregg Eure |
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MP27-20 |
Convective Radiofrequency Water Vapor Energy Prostate Ablation (Rez?m ®) Effectively Treats Urinary Retention |
Benign Prostatic Hyperplasia: Surgical Therapy & New Technology II | 17BOS |
Abstract: MP27-20 Sources of Funding: None Introduction New minimally invasive surgical therapies (MIST) for lower urinary tract symptoms due to benign prostatic hyperplasia (LUTS/BPH) such as prostatic urethral lift and convective radiofrequency water vapor energy prostate ablation (WaVE) have shown promising intermediate-term results in improving voiding symptoms. However, the initial trials excluded men in urinary retention; thus the ability of these new technologies to achieve catheter independence has not been evaluated. This study investigated outcomes of patients with urinary retention at baseline treated with WaVE. Methods Patients in urinary retention who underwent WaVE were retrospectively identified. Urinary retention was defined as dependence on an indwelling catheter or performance of clean intermittent catheterization (CIC) for bladder emptying. Age, duration of catheter dependence, prostate size, baseline IPSS and PVR, and number of treatments per procedure were recorded. For subjects with successful trials without catheter (TWOC), time to catheter independence and post-procedure PVR and IPSS were recorded. Baseline characteristics between subjects with successful TWOC and unsuccessful TWOC were compared using Mann Whitney U test and T-test for continuous variables and Chi-square test and Fisher&[prime]s exact test for non-continuous variables. Results 30 patients were identified with urinary retention who underwent WaVE. 22 subjects had an indwelling catheter, 8 subjects performed clean intermittent catheterization (CIC). Mean age was 76 years. Relevant baseline measures included (mean): duration of catheter dependence (6.9mo), prostate size (64.3 ml), PVR (538 mL), and number of treatments per procedure (6.4). 28/30 subjects had middle lobe treatment (1 treatment per procedure). 23 of 30 subjects (77%) achieved successful TWOC post-procedure. Mean time to catheter independence was 29 days post-procedure with mean post-procedure PVR 84 mL and post-procedure IPSS 9. There were no differences between subjects with or without successful TWOC in age, duration of catheter dependence, prostate size, baseline PVR, baseline IPSS, number of treatments per procedure, or treatment of median lobe. Conclusions WaVE can effectively treat patients with urinary retention and successfully render patients catheter independent, including patients with a median lobe. Longer-term follow up is necessary to evaluate the durability of this technology. Funding None
Authors
Nikhil Gupta
Bradley Holland Kristin Delfino Danuta Dynda J. Randolf Beahrs Lennart Wagrell Ahmed El-Zawahry Tobias Köhler Kevin McVary |
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MP28-01 |
A 17-GENE PANEL FOR PREDICTION OF ADVERSE PATHOLOGY AT RADICAL PROSTATECTOMY: PROSPECTIVE VALIDATION |
Prostate Cancer: Markers I | 17BOS |
Abstract: MP28-01 Sources of Funding: Genomic Health, Inc. Introduction Adverse pathology (AP, defined as pathological Gleason grade > 4+3 and/or >pT3) is a strong predictor of biochemical recurrence, metastasis, and cancer specific mortality in men with prostate cancer (PCa). A 17 gene tissue-based RTPCR assay (Oncotype Dx® Genomic Prostate Score™, GPS) has been validated as a predictor of AP in multiple retrospective cohorts. In this study, we aim to prospectively validate GPS as a predictor of AP in men with clinically low-risk PCa treated with radical prostatectomy (RP). Methods A pre-specified analysis from a 1200-patient prospective study was performed on patients who elected RP as initial PCa management. The primary endpoint was AP. Descriptive statistics are reported on demographic and clino-pathological characteristics. Binary logistic regression was performed to determine the association between GPS and AP. The odds ratio (OR) per 20 GPS units and 95% confidence interval (CI) were calculated. All analyses were conducted using SAS 9.4. Results Of 1200 patients enrolled from 21 sites in the study, RP was selected as initial management by 150 patients; 122 (81%) had complete surgical pathology data available. Median age was 63 yrs. (range 50-79), with 38% > 65 yrs. In this cohort, 11 (9%), 39 (32%), and 72 (59%) had NCCN Very Low-, Low-, and Intermediate-Risk disease. Biological risk (GPS+NCCN) differed from NCCN risk in 28 cases (23%). At surgery, 41 (34%) of patients had AP. Among NCCN VL, Low-Risk and Intermediate-Risk men, 1 (10%), 11 (28%), and 29 (40%) had AP at RP. Combining GPS and NCCN led to redistribution of VL, Low-Risk, and Intermediate-Risk groups and modified rates of AP at RP (Table 1). GPS was a significant predictor of AP (OR per 20 GPS units: 2.4; 95% CI: [1.3, 4.4]; p= 0.004) and remained significant after adjusting for NCCN (OR per 20 units: 2.2; 95% CI: [1.2-4.1]; p=0.01). Conclusions We report the first prospective validation of a biopsy-based genomic marker in prostate cancer. GPS is a strong predictor of AP in contemporary PCa patients. Patients with GPS+NCCN intermediate-risk categorization have twice the rate of AP as those with GPS+NCCN very low/low risk. GPS refines risk stratification and may help inform decision-making for patients with clinically low risk PCa. Funding Genomic Health, Inc.
Authors
Scott Eggener
Tim Richardson Steven Rosenberg Evan Goldfischer Ruixiao Lu Allan Shindel John Bennett Lawrence Karsh Howard Korman Phillip Febbo Bela Denes |
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MP28-02 |
Physiological Evidence of DNA Damage by Carcinogens Known to be Present in Charred and Processed Meats (PhIP DNA Adducts), in a Small Cohort of Prostate Cancer Patients. |
Prostate Cancer: Markers I | 17BOS |
Abstract: MP28-02 Sources of Funding: National Cancer Institute and National Institutes of Health Introduction Epidemiologic studies have reported an association between frequent consumption of well-done cooked meats and prostate cancer (PC) risk. Charred red meat and cooked processed meats are known to contain heterocyclic aromatic amine (HAA) carcinogens, such as 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) the most mass abundant HAA, and are linked to PC development in a rodent model. However, unambiguous physiochemical markers of DNA damage from these meat-derived carcinogens have not been identified in human samples to support the paradigm of HAA induced human prostate carcinogenesis. Methods Thirty-five men with biopsy proven intermediate to high-risk PC underwent radical prostatectomy at University of Minnesota from Dec 2015-Aug 2016. After prostatectomy, both tumor bearing tissue and non-tumor bearing adjacent fresh tissue was analyzed for DNA adducts using a highly sensitive nano-LC-Orbitrap mass spectrometry method. We also analyzed formalin fixed paraffin embedded (FFPE) tissues from each patient. Results Median age of the men with PC was 65 (range 45-78). Pathology demonstrated the following Gleason Scores (GS) and pathologic staging: GS= 6 in 1 patient (2.8%), GS=7 in 28 patients (80%) and GS=8-10 in 6 patients (17%) and 16 men (46%) were stage 2 and 19 men were stage 3 (54%). The PhIP DNA adduct was identified in 11 out of 35 patients, at levels ranging from 2 to 120 adducts per 109 nucleotides. PhIP DNA adducts also were recovered quantitatively from FFPE tissues. Conclusions Our data provide support to the epidemiological observations implicating PhIP as a DNA damaging agent that may contribute to the etiology of PC in humans. FFPE tissues can be used as a tissue source in DNA-adduct biomarker research using our mass spectrometry method. Funding National Cancer Institute and National Institutes of Health
Authors
Christopher Weight
Shun Xiao Jingshu Guo Byeong Hwa Yun Badrinath Konety Peter Villalta Resha Tejpaul Suprita Krishna Paari Murugan Robert Turesky |
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MP28-03 |
Alteration of metastatic behavior by shRNA mediated knockdown (KD) of CHD1 in human prostate xenograft tumors and clinical outcome of patients with CHD1 deletion |
Prostate Cancer: Markers I | 17BOS |
Abstract: MP28-03 Sources of Funding: none Introduction Chromodomain helicase DNA-binding protein 1 (CHD1) is a frequently deleted gene in prostate cancer (PCa). Our previous work demonstrated accelerated tumor growth as well as increased spontaneous lung metastasis of CHD1 depleted PC3 cells in a xenograft mouse model. In order to provide additional evidence for the role of CHD1 deletion in PCa metastasis and progression, we performed accompanying in vitro and in vivo experiments using ARCaP-M cells after shRNA-mediated KD of CHD1 and evaluated clinical outcomes of patients with CHD1 deletion after radical prostatectomy (RP). Methods ARCaP-M cells were stably transfected with shRNA against CHD1 by lentiviral transduction. The control cells were transfected with non-targeting shRNA. The resulting CHD1 status was assessed by western blot. In vivo, both cell lines were subcutaneously xenografted into immunodeficient pfp-/-/rag2-/- mice. At a tumor size of about 0.5 g, mice were sacrificed and primary tumors as well as right lungs were weighed and processed for histopathological analysis. DNA from the blood, left lungs, livers, brains and bone marrow were isolated for quantification of DTC and CTC by Alu-qPCR. MicroRNA (miRNA) expression in the mouse blood and mRNA expression in primary tumors were analyzed by microarray. To estimate the clinical impact of CHD1 deletion, we carried out FISH analysis in 6883 clinical PCa specimens and analyzed the pathologic and clinical follow-up of patients related to CHD1 deletion. Results We detected a stronger expression of CHD1 in ARCaP-M than previously reported for PC3 cells. KD of CHD1 resulted in effective down-regulation of CHD1 protein levels in ARCaP-M. After comparable growth periods in vivo, xenograft primary tumors with CHD1-KD were not significantly larger than control tumors. However, we observed increased levels of CTC in the mouse blood as well as a higher metastatic cell load in the lungs, livers and brains in the CHD1-depleted group, while the level of DTCs in the bone marrow was not changed and below the analytical limit of detection. Moreover, miRNA microarray analysis identified 24 miRNAs differentially expressed in CHD1-depleted mouse serum. In clinical multivariate analysis, CHD1 deletion was significantly linked to early PSA recurrence (p= 0.027), early metastasis (p= 0.001) and cancer specific mortality (p= 0.025) after RP. Overall survival was not affected by CHD1 status (p=0.41). We also observed more frequent metastases in the CHD1 deleted group (8% vs. 3,3 %, p<0.001), apart from the previous reported higher Gleason score (p<0.001) and advanced tumor stages of CHD1 deleted PCa specimens (p=0.005). Conclusions KD of CHD1 increases metastatic potential in two xenograft models of human PCa and leads to significant regulation of several miRNAs which could be involved in spontaneous dissemination of PCa cells. Moreover, multivariate analysis of oncological outcomes confirmed the significant association of CHD deletion with early BCR, early and more frequent metastasis as well as cancer specific mortality after surgery. This translational study demonstrates that CHD1 deletion predicts both histopathological tumor characteristics and disease progression by metastasis as well as cancer specific mortality after surgery and thereby supports the role of CHD1 deregulation for PCa progression. Funding none
Authors
Su Jung Oh
Derya Tilki Christiane Matuszcak Pierre Tennstedt Simon Baumgart Steven A. Johnsen Hüseyin Sirma Ronald Simon Tobias Lange |
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MP28-04 |
Sensitivity of [-2]proPSA (p2PSA) measurements for prediction of biochemical recurrence (BCR) in men after radical prostatectomy: a 3-years prospective cohort study |
Prostate Cancer: Markers I | 17BOS |
Abstract: MP28-04 Sources of Funding: Beckman Coulter Introduction Although radical prostatectomy (RP) offers a high overall cancer control rate, even in appropriately selected men, up to a third will experience failure (biochemical recurrence: BCR). PSA has been particularly considered valuable for the detection of BCR defined as a PSA concentration of at least 0.2 ng/ml. Recently, the will to detect the earliest sign of recurrence have led to the development of ultrasensitive PSAs (uPSA), but the usefulness of ultrasensitive assays has not been established. As [-2]proPSA (p2PSA), introduced in clinical practice with its derivate PHI (prostate health index), is normally expressed in pg/mL, it could be more sensible than PSA and uPSA for detecting early BCR after RP. In this study we test the hypothesis that p2PSA (index test) may detect BCR earlier than reference standard test (tPSA) in patients who underwent RP for localised prostate cancer (PCa)._x000D_ Methods The current study is an observational, prospective, cohort study in a contemporary series of consecutive patients subjected to RP for clinically localized PCa from January 2013 to June 2013. Biochemical follow-up consisted of a blood sample for reference standard test (PSA) and index test (p2PSA), after 3-6-12-18-24-30-36 months. The blood samples were processed with the UniCel DxI800 Immunoassay System analyzer (Beckman Coulter Inc., Brea, CA, USA) and managed according to the criteria described by Semjonow et al using the Hybritech calibration. BCR was defined as a confirmatory PSA concentration of 0.2 ng/ml or greater. A value of 0.8 pg/ml was considered the Limit of Detection (LoD) for p2PSA after RP as previously described. The primary outcome was to investigate the sensitivity of both tests for BCR, while the secondary end point was to determine whether or not results are consisting with different pathological outcome. Descriptive statistical analysis were complemented by Cox proportional hazards models, McNemar test and Kaplan-Meier curves for BCR-free survival by PSA and p2PSA cut-offs Results Over 145 eligible patients, 134 men were enrolled and were followed-up for 3 years. The frequencies of positive subjects, identified with p2PSA cut-off, were significantly higher in all the follow-ups than frequencies of positive subjects identified with PSA cut-off (p<0.0001). Overall we observed 18 BCR according to PSA. Five patients showed a contemporary increase of PSA and p2PSA, while 9 men presented a p2PSA increase earlier than PSA (mean time 4.9±3.1 months vs. 18.8±7.3 respectively). In 4 patients the increase of PSA was not associated with a p2PSA > 0.8 pg/ml. The analysis of Kaplan-Meier curves for BCR-free survival showed a significant lower time for p2PSA (16.7 mo; 95%CI: 14.1-19.2) respect to PSA (35.6 mo; 95%CI: 34.0-33.2). When subjects were stratified according to stage/grade and margins (positive vs. negative), patients with pT2c-GS3+4/4+3-R1 and pT3a-R0/1 could be considered the target categories, which would benefit more from the p2PSA LoD. Conclusions The current findings confirm that p2PSA could be more sensitive than tPSA in detecting early BCR at a mid term-follow-up (3 years). This is a confirmation of a previous paper of ours with a shorter follow-up (18 months). Further studies with a longer follow-up and larger population remain mandatory before considering p2PSA for clinical practice purposes Funding Beckman Coulter
Authors
Massimo Lazzeri
Giovanni Lughezzani NicolòMaria Buffi Giuliana Lista Paolo Casale Rodolfo Hurle Alberto Saita Silvia Zandegiacomo Luisa Pasini Alessio Benetti Roberto Peschechera Pasquale Cardone Ferruccio Ceriotti Marina Pontillo Vittorio Bini Giorgio Guazzoni |
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MP28-05 |
A combination of new protein biomarkers reduces unneeded prostate biopsies and improves the detection of prostate cancer: findings of a recent study |
Prostate Cancer: Markers I | 17BOS |
Abstract: MP28-05 Sources of Funding: None Introduction Increased prostate volume due to benign disease leads to many false-positive PSA results and consequently to negative prostate biopsies. Previous research indicated that cancer-related protein biomarkers discovered by a genetic-guided approach using a Pten knock-out mouse model could improve prostate cancer diagnosis. The objective of this study was to evaluate if the protein biomarkers are capable of distinguishing benign disease from prostate cancer in men with enlarged prostates. Methods We conducted a retrospective study of men with a total PSA of 2.0-10 ng/ml, negative DRE and enlarged prostate volume (?35 ml). Serum samples were collected from men before undergoing prostate biopsy at the Martini-Klinik Hamburg, Germany. All samples were taken between 2011 and 2016 following written patient consent. Serum concentration of CTSD, ICAM1, THBS1, OLFM4, TIMP1, and HYOU1 was measured using immunoassays. In addition, total and free PSA were analyzed to calculate %fPSA using the ADVIA Centaur immunoassay system. Results Of the 474 men included in this study, 236 men had a negative biopsy and 238 were diagnosed with prostate cancer. %fPSA discriminated among biopsy-positive and negative patients with an AUC = 0.650 (P <0.001; 95% CI = 0.600-0.699). Logistic regression analysis revealed that the combination of the two proteins CTSD and THBS1 yielded an AUC = 0.834 (P <0.001; 95% CI = 0.797-0.871); and when combined with %fPSA, it resulted in an even higher AUC = 0.845 (P <0.001; 95% CI = 0.810-0.880). At 90% sensitivity for prostate cancer, the specificity of the combination including CTSD, THBS1 and %fPSA was 60% indicating that 141 of 236 negative biopsies could have been avoided (see Figure 1). Independent training on samples collected before March 2013 and testing on the samples thereafter also resulted in a high AUC =0.872 (P <0.001; 95% CI = 0.826-0.918) showing reproducibility of the method. Conclusions In patients with elevated PSA, negative DRE and enlarged prostate, the method presented is significantly more accurate than %fPSA alone in determining the absence of prostate cancer. The implementation of the method in clinical practice has the potential to significantly lower the rate of prostate biopsies which are negative for cancer by more than 50%. Funding None
Authors
Pierre Tennstedt
Thomas Steuber Annalisa Macagno Bruno Golding Ralph Schiess Silke Gillessen |
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MP28-06 |
A Novel Serum Based Multiplexed 21 Autoantibody Assay to Predict High-grade Prostate Cancer at Initial Biopsy |
Prostate Cancer: Markers I | 17BOS |
Abstract: MP28-06 Sources of Funding: Armune BioScience, Inc. Introduction Autoantibodies against peptides derived from prostate-cancer tissue have demonstrated utility in prostate cancer detection (New England Journal of Medicine: 2005;353:1224-35). Indeed, a commercially available test for prostate cancer detection, APIFINY®, measures 8 such markers. We assessed the performance of a novel serum based multiplexed autoantibody assay using all 8 APIFINY® markers along with an extended set up 13 new markers (21 markers total) plus standard of care (SOC) (PSA and age) vs. SOC alone for discriminating prostate cancer risk on biopsy as well as detecting high-grade prostate cancer on biopsy (Gleason Score (GS) 7 or greater). Methods We compared the autoantibody assay with biopsy outcomes in 268 patients at risk of prostate cancer from two academic and one community clinical sites in the United States undergoing prostate biopsy. Eligible participants included cancer-free men, 40 years or older, scheduled for an initial or repeat prostate biopsy. Results Among the 268 men (median age 62.4 yrs; median PSA 5.4 ng/mL), the autoantibody assay plus SOC showed better discrimination between prostate cancer from no cancer (AUC 0.73, 95%CI 0.67-0.79) vs. SOC alone (AUC 0.55, 95%CI 0.49-0.62) (P < 0.0001). Discrimination was high for separating GS7 or greater from GS6 and patients negative on biopsy (AUC 0.74, 95% CI 0.68-0.80) compared to SOC alone (AUC 0.61, 95% CI 0.54-0.68) (p < 0.001). Finally, for discrimination between GS7 or greater from GS 6 among patients who had positive biopsies, the autoantibody assay + SOC (AUC 0.83, 95% CI 0.76-0.90) was better than SOC alone (AUC 0.71, 95% CI 0.63-0.80) (p = 0.001). A test developed with these biomarkers detected GS 6 or higher with 95.0% sensitivity and 25.2% specificity. For detected GS7 or higher test with 95% sensitivity, and 24.4% of unnecessary biopsies would have been avoided, missing only 4.9% of patients with GS7 disease. Conclusions This expanded serum based multiplexed autoantibody assay can accurately identify patients with prostate cancer and can identify patients with high grade disease better than the current SOC (age and PSA). Funding Armune BioScience, Inc.
Authors
Stephen Freedland
Sharat Singh Kristopher Kapphahn Lauren Howard Jeanne Ohrnberger Jason Hafron |
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MP28-07 |
An automated-microcapillary electrophoresis-based immunoassay system may improve diagnostic accuracy of prostate cancer and be a good indicator of Gleason score |
Prostate Cancer: Markers I | 17BOS |
Abstract: MP28-07 Sources of Funding: none Introduction Lack of specificity in PSA test for early detection of prostate cancer (PCa) is one of the major issues all over the world. Therefore, the development of novel assay system with improved specificity is urgently needed. We identified PCa-associated aberrant glycosylation of PSA (S2,3PSA) and developed an automated-microcapillary electrophoresis-based immunoassay system (μTAS method). Furthermore, we successfully applied this assay system for clinical setting. Methods S2,3PSA was clearly differentiated by the lectin reactivity to recognize aberrant glycosylation on free PSA (fPSA) and calculate the ratio (%) in the microfluidic separation channel with fPSA antibody-label conjugates. We measured %S2,3PSA by utilizing μTAS method with extremely shortened assay time (9 min) and evaluated the cutoff values in biopsy proven patient samples (103 with PCa and 50 with non-PCa ) including PSA less than 20.0 ng/ml. Receiver operating characteristic (ROC) curves were used to evaluate diagnostic accuracy for %S2,3PSA in comparison with other methods. Results %S2,3PSA of PCa was significantly higher than those of non-PCa (p < 0.0001) and the appropriate cutoff value was determined to be 40% of S2,3PSA ratio in terms of diagnostic accuracy. The area under the curve (AUC) for the detection of PCa with %S2,3PSA ratio was 0.851, which was significantly more effective than that with total PSA (AUC; 0.658). And also, good correlation in this assay with Gleason score after radical prostatectomy (pGS) was suggested for the discrimination of high risk PCa. Especially, high-risk PCa patients with GS≥4+3 could be separated by the S2,3PSA percentage cut off of 50%, achieving a high performance (AUC; 0.921). Conclusions Although the present study is still preliminary, these results suggest that the newly developed serum %S2,3PSA test may contribute improved diagnostic accuracy having good correlation with prostatectomy Gleason score. Additional validation studies are warranted. Funding none
Authors
Tomokazu Ishikawa
Tohru Yoneyama Yuki Tobisawa Shingo Hatakeyama Tatsuo Kurosawa Kenji Nakamura Takuya Koie Yasuhiro Hashimoto Chikara Ohyama |
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MP28-08 |
Refusal of prostate-specific antigen testing in the united states |
Prostate Cancer: Markers I | 17BOS |
Abstract: MP28-08 Sources of Funding: none Introduction Prostate-specific antigen (PSA)-based prostate cancer screening is a controversial practice. Most evidence point towards many individuals subjected to the test without discussion on the potential harms of overdiagnosis and overtreatment. However, little is known about the opposite phenomenon: patients offered the PSA test who refused. Methods We analyzed male participants from the 2001 to 2008 cycles of the National Health and Nutrition Examination Survey (NHANES) ?40 years, without a history of prostate cancer, recent prostate manipulation, or hormonal therapy use (n=6,032). All men were given an opportunity to undergo or refuse PSA testing after a standardized explanation about prostate cancer screening with a physician. A multivariate logistic regression was conducted after adjusting for survey weights to identify independent socio-demographic and clinical predictors for opting out of PSA testing. Results 6,032 men met inclusion criteria. Overall, 95% of the study cohort elected to undergo PSA testing. The odds of declining PSA testing was significantly higher in men 80 years of age (OR: 1.74; p=0.01), men of Black race (OR: 2.53; p<0.001), divorced/separated men (OR: 1.58; p=0.048), men with less than a high school education (OR: 1.72; p=0.02), and men with a pre-existing non-prostate malignancy (OR: 2.67; p<0.001). Conclusions Between 2001 and 2008, the majority of men who were offered prostate cancer screening underwent PSA testing. Interestingly, Black men, a subgroup generally presenting with more aggressive prostate cancer, were more likely to refuse PSA testing. Funding none
Authors
Philipp Gild
Nicolas von Landenberg Nawar Hanna Ye Wang Steven L Chang Mani Menon Felix K.H. Chun Margit Fisch Quoc-Dien Trinh |
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MP28-09 |
High serum dehydroepiandrosterone examined by ultrasensitive liquid-chromatography tandem mass spectrometry as a predictor of benign prostate or Gleason score ≤7 cancer in men with prostate-specific antigen levels below 10 ng/mL |
Prostate Cancer: Markers I | 17BOS |
Abstract: MP28-09 Sources of Funding: None Introduction We investigated the correlation between serum dehydroepiandrosterone (DHEA) levels and Gleason scores at biopsy. Methods We analyzed data of 203 men with a total PSA below 10 ng/ml who underwent initial systematic prostate needle biopsy for suspected prostate cancer. Peripheral blood DHEA concentrations were determined by liquid chromatography with two serially linked mass spectrometers (LC-MS/MS). Blood levels of DEHA was compared with pathological findings by multivariate analyses. Results Median values of patients&[prime] age, PSA and prostate volume measured by ultrasound were 68 years, 5.5 ng/mL, and 31.2 mL, respectively. Benign prostate was diagnosed in 118 patients (58.1%) and prostate cancer was diagnosed in 85 (41.9%) patients, including 31 (15.3%) patients with a Gleason score of 6, 36 (17.7%) patients with a Gleason score of 7, and 18 (8.9%) patients with a Gleason score of 8-10. Median values of DHEA in blood was 1654.7 pg/mL. In multivariate analysis, PSA (p=0.009), prostate volume (p=0.022), and serum DHEA (p=0.041) were significant predictors of benign prostate or prostate cancer with a Gleason score of ≤7. The DHEA cutoff point to predict benign prostate or cancer with a Gleason score ≤7 was established at 2179 pg/mL, with sensitivity, specificity, positive predictive value, and negative predictive value of 33.0%, 100%, 100%, and 12.7%, respectively. The area under the receiver operating characteristics curve (AUROC) for predicting benign prostate or cancer with a Gleason score ≤7 of the base model (age, PSA, and prostate volume) was 0.74. The AUROC of the base model plus DHEA was 0.81. Addition of DHEA to the base model significantly improved AUROC compared to base model._x000D_ Conclusions We confirmed that high DHEA blood levels can predict benign prostate or prostate cancer with a Gleason score ≤7 in men with PSA levels below 10 ng/mL. Serum DHEA could help to distinguish the patients with more indolent disease, which would be useful for selecting suitable patients for active surveillance form those with more aggressive disease. Funding None
Authors
Yasuhide Miyoshi
Hiroji Uemura Kazuhiro Suzuki Yasuhiro Shibata Seijiro Homma Masaoki Harada Yoshinobu Kubota Yutaro Hayashi |
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MP28-10 |
Panel of 6 microRNAs for minimally invasive diagnosis of prostate cancer |
Prostate Cancer: Markers I | 17BOS |
Abstract: MP28-10 Sources of Funding: none Introduction Routine screening of prostate cancer (PC) based on serum prostate-specific antigen detection and digital rectal examination has modest positive and negative predictive value. The aim of represented study was to identify a panel of plasma microRNAs (miRNAs) for minimally invasive diagnosis of PC. Methods During 2014-2015, 245 patients participated in the cross-sectional study. The Group 1 consisted of 188 patients with histologically confirmed PC. The Group 2 consisted of 57 patients including healthy individuals and patients with benign prostatic hyperplasia, urinary system diseases or anomalies, bladder or renal cancer. Plasma miRNAs profiles was studied with aid of GeneChip® miRNA 4.0 Arrays (Affymetrix, USA) comprising probe set for 2,578 human mature miRNAs. All miRNAs with the 3rd quartile of Bi-weight Average Signal (log2) less than 1,49 were excluded from the analysis just as miRNAs with signal correlating with hemoglobin level as hemolysis sign (p-value < 0.05 for Spearman rank correlation coefficient). SVM-based approach was used for development of a diagnostic classifier based on circulating miRNAs. Exhaustive analysis was performed for pairs and triplets of miRNAs with sensitivity, specificity and AUC calculation. Experiment have been conducted in accordance with the principles of the Declaration of Helsinki of World Medical Association. Results Diagnostic significance was demonstrated even for pairs of miRNAs. In particular best pair consisting of hsa-miR-155-5p and hsa-miR-619-5p allowed achieving 80.7% sensitivity at 69.2% specificity (AUC 0.817). Triplets of miRNAs showed better accuracy, e.g. for triplet hsa-miR-155-5p, hsa-miR-619-5p, and hsa-miR-6777-5p sensitivity was 78.9% while specificity was 80.8% (AUC 0.850). The best triplet hsa-miR-6085, hsa-miR-6511b-5p, and hsa-miR-6886-5p allowed achieving 81.3% sensitivity at 80.8% specificity (AUC 0.860). For diagnostic panel consisting of all 6 miRNAs sensitivity reached 83.7% at specificity 84.6% (AUC 0.913). Conclusions These results show high diagnostic potential of the panel of 6 circulating miRNAs (hsa-miR-155-5p, hsa-miR-619-5p, hsa-miR-6777-5p, hsa-miR-6085, hsa-miR-6511b-5p, and hsa-miR-6886-5p) for minimally invasive diagnosis of prostate cancer which may improve the diagnostic accuracy of modern PC screening. Funding none
Authors
Boris Alekseev
Evgeniy Knyazev Maksim Shkurnikov Dmitriy Mikhailenko Alexandr Zotikov Kirill Nyushko Alexandr Tonevitskiy Andrey Kaprin |
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MP28-11 |
Impact of the 17-gene Panel On Active Surveillance Persistence in Contemporary Urologic Practices: an Interim Analysis in an Observational Cohort |
Prostate Cancer: Markers I | 17BOS |
Abstract: MP28-11 Sources of Funding: Genomic Health Introduction The 17 gene assay (Oncotype Dx Genomic Prostate Score, GPS) is a validated, biopsy-based commercial gene expression assay that, combined with clinical features, provides an individual estimate of disease aggressiveness at the time of PCa diagnosis. We report interim study results on the impact of GPS on the management of clinically low risk PCa patients in community-based urology practices. Methods 1,200 patients were prospectively enrolled from 26 sites. For this interim analysis, we report 1 year outcomes in the first 297 patients with valid GPS results. The primary endpoints were GPS’ impact on initial management and persistence on active surveillance (AS) at 1 year post-diagnosis in patients who chose to pursue AS. Rates of AS utilization and persistence in GPS tested patients were compared with a group of 247 patients who did not have genomic testing managed in the same practices (baseline cohort). Descriptive statistics were reported. Analyses were conducted using SAS 9.4. Results One-year results were available in 258/297 tested patients (26% NCCN VL, 43% Low and 31% Intermediate). Both utilization and persistence on AS were higher in the GPS-tested cohort (62% vs 40% AS adoption and 89% vs 86% AS persistence) at 1 year. Higher utilization and persistence on AS resulted in a 21% absolute increase in the proportion of men on AS at 1 year post-diagnosis in the GPS tested cohort compared to and baseline (Figure 1). Net increases of patients on AS at 1 year were seen across age groups (59% vs. 41% in >=65yrs, and 51% vs. 29% in <65 yrs), and racial groups (51% vs. 39% in African American, and 55% vs. 33% in all other racial groups). Conclusions Patients, especially younger men, and physicians who received GPS were more likely to pursue AS for initial management than untested patients. Overall utilization of AS was 62% higher in GPS tested vs. untested patients at 1 year post-diagnosis. The individual risk refinement provided by genomic testing demonstrates the impact of the GPS in identifying appropriate patients and supporting more AS decisions in clinically low risk PCa. Funding Genomic Health
Authors
Gregg Eure
Raymond Germany Robert Given Richard Glowacki Tim Richardson Evan Goldfischer Ruixiao Lu Alan Shindel John Bennett Phil Febbo Bela Denes |
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MP28-12 |
Impact of Lymphovascular Invasion on Lymph Node Metastasis for T3 Patients Undergoing Radical Prostatectomy in Consideration of Resection Margin Status |
Prostate Cancer: Markers I | 17BOS |
Abstract: MP28-12 Sources of Funding: none Introduction To assess an association between the increased risk of biochemical recurrence and lymphovascular invasion in T3 margin positive or negative patients and its association with lymph node metastasis. Methods 1634 patients who underwent radical prostatectomy from 2005 to 2014 were selected. Patients with bone or distant organ metastasis at the time of operation were excluded. Survival analysis was performed to assess biochemical recurrence, bone metastasis and mortality risks by Kaplan-Meier analysis and multivariate Cox proportional hazard regression. Odds of lymph node metastasis were evaluated by Logistic regression. Results LVI was detected in 118 (7.4%) patients. The median follow-up duration was 33.1 months. In the Kaplan-Meier analysis, lymphovascular invasion was associated with significantly shorter biochemical recurrence free survival (39.3 vs. 82.5 months, p<0.001), bone metastasis-free survival (134.4 vs. 156.7 months, p=0.001) and cancer specific survival (122.7 vs. 152.6 months, p=0.034). When stratified by T stage and resection margin status, lymphovascular invasion resulted in significantly shorter biochemical recurrence-free duration in T3 patients with and without positive surgical margin (p=0.008, 0.005, respectively). In the multivariate Cox regression model lymphovascular invasion resulted in 1.4-fold risk increase (95% CI 1.05-1.75, p=0.031).Lymphovascular invasion was revealed to be strongly associated with lymph node metastasis in the multivariate Logistic regression (OR 4.26, 95% CI 2.07-8.79, p<0.001). Conclusions Lymphovascular invasion increased the risk of early recurrence in T3 patients regardless of margin status, by accelerating the metastasis. Funding none
Authors
Yong Jin Kang
Won Sik Jang Myung Soo Kim Won Sik Jung Cheol Yong Yoon In Rae Cho Young Deuk Choi |
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MP28-13 |
Prognostic Utility of Biopsy-Derived Cell Cycle Progression Score in Patients with NCCN Low-Risk Prostate Cancer Undergoing Radical Prostatectomy: Implications for Treatment Guidance |
Prostate Cancer: Markers I | 17BOS |
Abstract: MP28-13 Sources of Funding: none Introduction Previous studies have demonstrated that the cell cycle progression (CCP) score measured in prostate biopsy specimens was predictive of several clinical outcomes. However, it is currently unclear whether the CCP score improves clinical risk stratification within Gleason score (GS) 6 cancers and the subset of patients with National Comprehensive Cancer Network (NCCN) low-risk disease. Therefore, our objective was to determine the prognostic utility of the CCP score in men with NCCN low-risk disease who underwent radical prostatectomy (RP). Methods Patients who underwent RP for GS ≤6 prostate cancer at three institutions (Martini Clinic [MC], Durham Veterans Affairs Medical Center [DVA], and Intermountain Healthcare [IHC]) were identified. The CCP score was obtained from diagnostic (DVA, IHC) or simulated biopsies (MC). Primary outcome was biochemical recurrence (BCR, PSA≥0.2 ng/ml) after RP. Prognostic utility of the CCP score was assessed using Kaplan-Meier analysis and multivariable Cox proportional hazards models in the subset of men meeting NCCN low-risk criteria and the overall cohort (all GS ≤6 prostate cancer patients). Results Among the 236 patients identified, 80% (188/236) met NCCN low-risk criteria. Five-year BCR-free survival for the low (<0), intermediate (0-1), and high (>1) CCP score groups was 89.2%, 80.4%, 64.7%, respectively in the low-risk cohort (log-rank p=0.027), and 85.9%, 79.1%, 63.1% respectively in the overall cohort (log-rank p=0.041). In multivariable models adjusting for clinical and pathological variables with the CAPRA score, the CCP score was an independent predictor of BCR in the low-risk (HR=1.77 per unit score, 95%CI [1.21, 2.58], p=0.003) and overall cohorts (HR=1.41 per unit score, 95%CI [1.02, 1.96], p=0.039). Conclusions In a cohort of NCCN low-risk patients, the CCP score improved clinical risk stratification of patients at increased risk of BCR. This suggests the CCP score could help improve the assessment of candidacy for active surveillance and guide optimal treatment selection in patients with NCCN low-risk prostate cancer. Funding none
Authors
Jeffrey Tosoian
Meera Chappidi Jay Bishoff Stephen Freedland Julia Reid Michael Brawer Steven Stone Thorsten Schlomm Ashley Ross |
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MP28-14 |
Decreased Expression of Male Specific Histone Demethylase “KDM5D” is Prognostic for Development of Castration-Resistant Prostate Cancer |
Prostate Cancer: Markers I | 17BOS |
Abstract: MP28-14 Sources of Funding: This work was supported by the Louis B. Mayer Foundation. Introduction We previously showed that decreased expression of the Lysine-Specific Demethylase &[prime]KDM5D&[prime] encoded on the Y chromosome was associated with docetaxel resistance (Komura et al, 2016, PNAS). We hypothesize that loss of KDM5D may significantly affect the epigenetic landscape in prostate cancer cells and facilitate the development of CRPC. Methods To elucidate biological function of KDM5D, we performed RNAseq analysis in hormone sensitive LNCaP cells (KDM5D positive) and corresponding LNCaP-104R2 CRPC cells (KDM5D negative). Individual genes which were found as potential targets of KDM5D were further explored in a publically available clinical database. Results We found 143 overlapping genes, which are upregulated by knockdown of KDM5D in LNCaP and down regulated by overexpression of KDM5D in 104R2 and 28 genes, which were down regulated by KDM5D knockdown in LNCaP and up-regulated by KDM5D overexpression in 104R2. Gene ontology (GO) analyses with FDR<0.05 from the 143 genes identified mitotic and cell cycle related genes as most commonly upregulated by loss of KDM5D (Figure 1). To validate the results, we explored the Taylor&[prime]s prostate cancer cohort with cBioportal. Of 8643 genes negatively correlated with KDM5D expression level (Pearson Correlation Coefficient < -0.3), 69 genes were identified in both our data and the Taylor&[prime]s cohort. Upregulation of these genes in CRPC was further confirmed in 2 publicly available datasets (PAD).2 (Figure 2). Finally in a PAD from a Mayo Clinic&[prime]s cohort (Illumina DASL Cancer Panel microarray) which included 8 genes out of the 69 genes, noted shorter cancer-specific mortality in pts with higher expression of those genes was demonstrated in all 8 genes. Conclusions Loss of KDM5D is associated with upregulation of mitotic and cell-cycle related genes which may lead to development of CRPC and serve as prognostic factor for its development. Funding This work was supported by the Louis B. Mayer Foundation.
Authors
Kazumasa Komura
Seong Ho Jeong Haruhito Azuma Gwo-Shu Lee Christopher Sweeney Philip Kantoff |
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MP28-15 |
Modified Glasgow Prognostic Score as an Independent Predictor of Survival in Patients with Metastatic Hormone-Sensitive Prostate Cancer |
Prostate Cancer: Markers I | 17BOS |
Abstract: MP28-15 Sources of Funding: none Introduction The modified Glasgow prognostic score (mGPS) has shown prognostic significance in many malignancies. However, its prognostic value in metastatic hormone-sensitive prostate cancer (mHSPC) remains unclear. Thus, we aimed to evaluate the prognostic value of mGPS in mHSPC patients. Methods From January 2004 to February 2014, 1209 patients were newly diagnosed with prostate cancer at our institute. The subjects were 93 patients with metastatic lesions at diagnosis. The mGPS was estimated based on C-reactive protein (CRP) and albumin levels (score: 2, CRP>1.0 mg/dL and albumin<3.5 gd/L; score 1, CRP>1.0 mg/dL; score 0, CRP>1.0 mg/dL). The impact of mGPS on time to castration-resistant prostate cancer (TTCRPC), progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS) was analyzed using the Kaplan-Meier method and Cox proportional hazard model. Results The patients&[prime] median age was 74 years; and median prostate-specific antigen (PSA) level, 124.3 ng/ml. The Gleason score was 5 or 6 in 8 patients (9%), 7 in 20 (22%), and 8-10 in 65 (70%). We noted node and bone metastases in 54 (58%) and 45 patients (48%), respectively. Four patients had visceral metastases at diagnosis. The mGPS was 0 in 71 (76%), 1 in 16 (17%), and 2 in 6 (6%) mHSPC patients. Patients with higher mGPS had significantly inferior PFS, CSS, and OS (median PFS: 58.0, 22.5, and 21.4 months for scores of 0, 1, and 2, respectively, p<0.0074; CSS: 82.3, 47.1, and 13.6 months, respectively, p<0.0001; and OS: 75.6, 43.7, and 10.3 months, respectively, p<0.0001). In the multivariate analysis, higher mGPS was an independent predictive factor of shorter PFS (p=0.027), CSS (p=0.0022), and OS (p=0.0003). Conclusions Our study demonstrates the prognostic value of the mGPS in mHSPC patients. Funding none
Authors
Junpei Iizuka
Yasunobu Hashimoto Tsunenori Kondo Toshio Takagi Keisuke Hata Taichi Kanzawa Daigo Okada Kazuhiko Yoshida Kazunari Tanabe |
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MP28-16 |
Prostatic tissue androgen levels as prognostic factor for men with metastatic castration-resistant prostate cancer |
Prostate Cancer: Markers I | 17BOS |
Abstract: MP28-16 Sources of Funding: Grant/research funding from AstraZeneca and Takeda Pharmaceutical Company Introduction Previously, we reported that prostatic tissue androgen levels (tissue testosterone / tissue dihydrotestosterone ratio (tissue T/DHT ratio)) in prostate biopsy could predict time to castration-resistant prostate cancer (CRPC) in men with castration-sensitive prostate cancer (Andrology 2013). In this study, we investigated that if tissue T/DHT ratio in prostate biopsy specimens could predict survival for men with mCRPC. Methods We identified consecutive 34 patients with mCRPC. All patients had undergone prostate needle biopsy after failed to CRPC. We analyzed prostatic tissue androgen levels using liquid chromatography-tandem mass spectrometry (LC-MS/MS). We analyzed the correlations between prostate cancer-specific survival (PCSS) and clinicopathological characteristics, including baseline prostate-specific antigen (PSA) levels, time to CRPC, previous use of docetaxel, previous use of abiraterone or enzalutamide, and tissue T/DHT ratio. Statistical analyses were assessed using Cox proportional hazards regression models. Results The median age was 74 years and the median follow-up duration was 7.4 months. The median baseline PSA value was 20.1 ng/ml and median T/DHT ratio was 1.5. The median time to CRPC was 14 months. The number of previous use of docetaxel and previous use of abiraterone or enzalutamide were 19 (55.9%) and 6 (26.5%), respectively. In multivariate analysis, time to CRPC (time to CRPC<14 months; HR7.1, 95%CI1.63-38.1, p=0.022) and tissue T/DHT ratio (T/DHT ratio>1.5; HR5.2, 95%CI1.1-23.6, p=0.035) were significant risk factors for PCSS. Conclusions Time to CRPC and tissue T/DHT ratio were significant risk factors for PCSS. Tissue T/DHT ratio would be helpful in predicting survival and might be valuable for counseling for men with mCRPC. Funding Grant/research funding from AstraZeneca and Takeda Pharmaceutical Company
Authors
Yasuhide Miyoshi
Takashi Kawahara Mari Ohtaka Sohgo Tsutsumi Koichi Uemura Masato Yasui Shuko Yoneyama Yumiko Yokomizo Narihiko Hayashi Hiroji Uemura |
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MP28-17 |
Immunohistochemical Staining of ERG and SOX9 as Potential Biomarkers of Docetaxel Response in Patients with Metastatic Castration-Resistant Prostate Cancer |
Prostate Cancer: Markers I | 17BOS |
Abstract: MP28-17 Sources of Funding: None Introduction Docetaxel-based chemotherapy is recommended as first-line standard of care for metastatic castration-resistant prostate cancer (mCRPC). However, most of the patients developed treatment resistance and experienced treatment-related toxicity. Therefore, we constructed tissue microarrays using prostate biopsy samples and carried out immunohistochemistry (IHC) analyses to evaluate the clinical utility of ERG and SOX9 as potential biomarkers of docetaxel response in mCRPC patients. Methods We reviewed 71 patients diagnosed with mCRPC and treated with docetaxel (75mg/m2 intravenously, every 3 weeks) between 2001 and 2013. We evaluated the prostate specific antigen (PSA) response rate, PSA progression-free survival (PSA-PFS), clinical/radiologic PFS (C/R-PFS) and the overall survival (OS) based on the recommendations of the Prostate Cancer Working Group 2. The intensities of ERG and SOX9 expression in tumor cells were scored using a four-tiered grading system. A sample with more than 5% of total stained area scoring 2+ or 3+ in intensity was considered to be positive. Kaplan-Meier survival curves were constructed to illustrate the PSA-PFS, C/R-PFS and OS. Multivariate Cox proportional hazard models were utilized to estimate associations between the PSA-PFS, C/R-PFS, OS and risk factors of interest. Results ERG and SOX9 were found in 13 (18.3%) and 62 (87.3%) patients, respectively. ERG-positive had lower PSA response rates than negative (15.4% vs 62.1%, p = 0.004), and SOX9 showed a same trend (46.8% vs 100.0%, p = 0.003). ERG positivity correlated with a lower PSA-PFS (3.2 mos vs 7.4 mos, p < 0.001), C/R-PFS (3.8 mos vs 9.0 mos, p < 0.001) and OS (10.8 mos vs 21.4 mos, p < 0.001). SOX9 positivity also showed a lower PSA-PFS, C/R-PFS and OS (p =0.006, p =0.012 and p =0.023, respectively). On multivariate analysis, ERG positivity was a significant risk factor for a lower PSA-PFS (p < 0.001, hazard ratio (HR): 6.00, 95% confidence interval (CI): 2.96-12.16), C/R-PFS (p < 0.001, HR: 5.50, 95% CI: 2.68-11.29) and OS (p = 0.001, HR: 3.31, 95% CI: 1.66-6.64). In addition, SOX9 was also a significant risk factor for a decreased PSA-PFS (p = 0.018, HR: 2.75, 95% CI: 1.19-6.32), C/R-PFS (p = 0.025, HR: 2.44, 95% CI: 1.12-5.30) and OS (p = 0.047, HR: 4.30, 95% CI: 1.02-18.16). Conclusions IHC-detected ERG and SOX9 expression is significantly associated with lower PSA-PFS, C/R-PFS and OS in patients with mCRPC treated with docetaxel. They could be used as potential biomarkers for prediction to docetaxel treatment in mCRPC patients. Funding None
Authors
Song Wan
Ghee Young Kwon Jeong Hoon Kim Joung Eun Lim Young Hyo Choi Hyun Woo Chung Chung Un Lee Jun Phil Na Hwang Gyun Jeon Byong Chang Jeong Seong Il Seo Seong Soo Jeon Han Yong Choi Hyun Moo Lee |
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MP28-18 |
Implementation of prostate biopsy tissue print technologies for molecular biomarker studies |
Prostate Cancer: Markers I | 17BOS |
Abstract: MP28-18 Sources of Funding: NCI Innovative Molecular Analysis Technologies Program, NCI Early Detection Research Network, DOD Prostate Cancer Research Program Introduction With the introduction of multiple tissue-based biomarker tests for prostate cancer (PCa) the allocation of formalin fixed paraffin embedded (FFPE) biopsy tissues has become challenging. This is especially true for patients managed by active surveillance or non-surgical treatment where no radical prostatectomy specimen is available. Our goal is to develop and fully implement tissue print technologies that allow us to obtain high quality RNA and DNA from prostate biopsy cores without compromising the tissue for histopathology and other FFPE based testing. Methods Biopsy tissue prints (nitrocellulose blots) were obtained from each core during the transfer of the tissue from the cutting needle to the fixation jar and each print was immediately snap-frozen. Tissue prints were processed by a central laboratory to obtain purified RNA and DNA for QC, molecular marker discovery and targeted biomarker assays. Results At our Boston site (private office practice) we have prospectively collected 444 sets of biopsy tissue prints (>5300 cores) from study subjects undergoing standard diagnostic biopsy. Biopsy tissue print collection has also been implemented at two sites in Birmingham (an academic medical center and a private office practice) to support biomarker studies in African American patients and in patients undergoing mpMRI-US fusion guided biopsy. To date we have prospectively collected 273 sets of tissue prints (>2400 cores) from our Birmingham sites. We routinely harvest 50,000-200,000 cells/print. From cores with >50% high grade PCa the yield/print mean, median (SD) for DNA is 1611 ng, 942 ng (1191) and for RNA is 550 ng, 481 ng (506); from cores with no PCa the yield/print for DNA is 1020 ng, 926 ng (744) and for RNA is 351 ng, 250 ng (418). Prostate biopsy tissue print RNA and DNA is snap-frozen quality and has been successfully utilized for gene expression profiling, genotyping, DNA methylation and sequencing analyses. Conclusions Tissue print technologies provide a practical approach to biopsy-based biomarker analyses that preserves the tissue core for pathology diagnosis and other FFPE based testing. For research studies, prospective collection of biopsy tissue prints is feasible in both academic and private practice settings. Because tissue prints provide high quality RNA and DNA suitable for a wide range of molecular biomarker tests, the technology may also be useful in situations where there is insufficient FFPE biopsy tissue to satisfy clinical molecular testing requirements. Funding NCI Innovative Molecular Analysis Technologies Program, NCI Early Detection Research Network, DOD Prostate Cancer Research Program
Authors
Sandra Gaston
Peter Kolettis James Bryant Soroush Rais-Bahrami Jeffrey Nix Mark DeGuenther Michael Kearney George Adams William Grizzle Gary Kearney |
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MP28-19 |
Evaluating the Prognostic Utility of the CCP Score for Predicting Prostate Cancer Aggressiveness in African American Men |
Prostate Cancer: Markers I | 17BOS |
Abstract: MP28-19 Sources of Funding: none Introduction The cell cycle progression score (CCP score, based on measuring the expression levels of CCP genes) has proven to be a robust predictor of prostate cancer outcomes in various clinical settings and patient populations. However data regarding the ability to predict outcomes in African American (AA) men are sparse. Here, we evaluate the utility of the CCP score generated from diagnostic biopsy to predict BCR and metastatic disease in a large cohort of treated patients at an academic teaching institution that is highly enriched with AA patient population. Methods Patients were diagnosed with clinically localized adenocarcinoma of the prostate and treated at the Ochsner Clinic (New Orleans, LA) between January 2006 and December 2011 who had available FFPE biopsy tissue. The final cohort consisted of 694 men with both a passing CCP score and complete clinical information for calculation of CAPRA. Thirty-eight (38) percent of the cohort was AA. Study outcomes included time from disease diagnosis to either metastatic disease (N = 33, 5%), or time to BCR (N = 94, 17%) after primary treatment (EBRT or RP). Median follow-up time for patients who did not experience an event or death before the study end was 6 years. Association with outcomes was evaluated by CoxPH survival analysis and likelihood ratio tests. Results The CCP score distribution was not different by race (p = 0.66) and had an overall mean of 0.42 (IQR = -0.20, 1.00). The primary pre-planned analysis called for evaluating the association of CCP score with outcome after adjusting for CAPRA and race. In this multivariable analysis the CCP score strongly predicted both BCR [HR per unit score = 1.50, 95%CI (1.22, 1.86), p = 0.00029] and metastatic disease [HR per unit score = 2.02, 95%CI (1.48, 2.77), p = 4.2 x 10-5]. Race was not significantly associated with either outcome (p=0.51 for BCR; p=0.28 for metastatic disease). Further, there was no interaction between CCP score and race (p = 0.21), indicating that a unit increase in the score confers the same relative increase in risk to either Caucasian or African American patients. There was also no interaction between CCP score and treatment type (p = 0.34). Conclusions The CCP score provides significant prognostic information to AA patients that cannot be obtained from clinicopathologic variables. Therefore, the score is a useful tool to help differentiate risk among AA men and enables more informed clinical management of their disease. Funding none
Authors
Stephen Bardot
Julia Reid Maria Latsis Margaret Variano Shams Halat Daniel Canter Zaina Sangale Michael Brawer Steven Stone |
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MP28-20 |
Expression of HMGB1 in prostate cancer: Clinical and Biological correlations |
Prostate Cancer: Markers I | 17BOS |
Abstract: MP28-20 Sources of Funding: None Introduction The high mobility group box1 (HMGB1), which is the important nuclear factor, has been noted to play a critical role of biological processes such as DNA repair, transcription and extracellular response. Increased expression of HMGB1 has been observed in several solid cancers and known to be associated with poor prognosis. However, there have been little studies of the role of HMGB1 in prostate cancer (PCa) development and progression. Therefore, in this study, we aimed to investigate 1) the role of HMGB1 on cellular proliferation, apoptosis, migration, and invasion, 2) the underlying biological mechanisms of HMGB1 in PCa, and 3) the expression pattern of HMGB1 in PCa patients with different stage and grade and its prognostic importance. Methods After transient transfection of PC3 and DU-145 cells with HMGB1 siRNA, diverse experiments were performed to evaluate the changes in proliferation, apoptosis, migration and invasion. To determine whether HMGB1 affects the NF-?B pathway, subcellular localizations of p65 and phosphorylated p65 were assessed by western blot analysis. Using the Cancer Genome Atlas (TCGA) datasets, we determined the impact of HMGB1 on overall survival in PCa. We further validated the prognostic importance of HMGB1 by immunofluorescence staining in 131 PCa patients from the Korean Prostate Bank. Results Inhibition of HMGB1 expression significantly reduced cell proliferation and increased cell cycle arrest in the sub-Go phase of PC3 and DU-145 cells. It also inhibited the migration and invasive capacity of PCa cells. Western blot analysis showed that inhibition of HMGB1 reduced p65 and phosphorylated p65 protein levels in nuclear fractions of PCa cells. In The Cancer Genome Atlas data set (n = 498), HMGB1 was altered in 61 of 498 patients (12%). Overall survival was shorter in the high HMGB1 expression group (medians: 115.0 months vs. not reached; P = 0.0296). In the Korean Prostate Bank cohort, the positive areas of HMGB1 differed in patients with BPH, and low-, intermediate-, high-risk, and metastatic PCa (4.6, 11.9, 18.6, 19.7, and 23.4%, p?0.001). During the median follow-up of 32 months, increased expression of HMGB1 was associated with a significant decrease in biochemical recurrence free survival on Kaplan-Meier analysis. Conclusions Our findings demonstrate an important role of HMGB1 and novel relationship between HMGB1 and NF-?B pathway in PCa. Therapy targeting HMGB-associated pathways may represent a novel therapeutic avenue for PCa. Funding None
Authors
Yong Hyun Park
Ae Ryang Jung Jin Bong Choi U-Syn Ha Sung-Hoo Hong Sae Woong Kim Ji Youl Lee |
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MP29-01 |
Analyses of urine markers in patients with interstitial cystitis before and after fulguration or hydrodistention |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Interstitial Cystitis II | 17BOS |
Abstract: MP29-01 Sources of Funding: None Introduction There are few studies to investigate time-dependent changes in urine markers before and after fulguration or hydrodistention for the treatment of interstitial cystitis (IC) with or without Hunner lesions (HL), respectively. Thus we measured forty-one urine markers in HL type IC (HIC) or non-HL type IC (NHIC) patients before and after the treatment. Methods Urine specimens and bladder tissues were collected from 10 NHIC patients before hydrodistention, 10 HIC patients before fulguration and 10 age and gender-matched controls before surgical treatments including transurethral resection of the prostate (n=3) or tension-free vaginal tape operations (n=7). Urine specimens were also collected in IC patients six and twelve months after the treatment. Multiplex analyses of 41 cytokines, chemokines and growth factors were performed with a MIPPLIPLEX immunoassay kit. All participants completed the O’Leary-Sant score including symptom indexes (OSSI) and problem indexes (OSPI), and visual analog scale (VAS) pain score. In addition, the expression of interleukin-1 receptor antagonist (IL-1Ra) in the bladder was evaluated using an immunohistochemistry. Results Before the treatment, vascular endothelial growth factor (VEGF) and IL-1α were significantly increased in HIC and NHIC patients compared with controls, and CXCL8 and CXCL10 were significantly increased in HIC patients compared with controls although there were no significant differences in 41 urine markers between HIC and NHIC patients. IL-1Ra mainly expressed in the bladder epithelium was significantly decreased in HIC patients compared with NHIC patients or controls. Urine IL-1Ra was significantly increased in HIC and NHIC patients twelve months after the treatment compared with pretreatment values whereas there were no significant changes in other urine markers before and after the treatment. OSSI, OSPI and VAS scores were significantly decreased in HIC and NHC patients six and twelve months after the treatment compared with pretreatment scores, and significantly correlated positively with urine IL-1Ra levels in NHIC patients, but not in HIC patients. Conclusions The increases in angiogenesis-associated proteins such as VEGF and CXCL10 and inflammatory cytokines including IL-1α may be important for the development of IC. IL-1Ra acting as an anti-inflammatory cytokine against IL-1 was mainly expressed in the urothelium and may be positively correlated with the bladder pain symptom. In addition, the increase in urine IL-1Ra induced by hydrodistention or fulguration may contribute to the alleviation of IC symptoms. Funding None
Authors
Akira Furuta
Tokunori Yamamoto Yusuke Koike Yasuyuki Suzuki Momokazu Gotoh Shin Egawa Naoki Yoshimura |
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MP29-02 |
NEUROMETER MEASUREMENT OF CURRENT PERCEPTION (CPT) AND PAIN TOLERANCE THRESHOLDS (PTT) IN PATIENTS WITH PAINFUL BLADDER SYNDROME BEFORE AND AFTER TREATMENT WITH CYCLOSPORINE |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Interstitial Cystitis II | 17BOS |
Abstract: MP29-02 Sources of Funding: none Introduction The mechanism of action of cyclosporine (CyA) to treat bladder pain syndrome/interstitial cystitis (BPS/IC) has not been clearly elucidated. It is thought that CyA may act directly on pain sensing nerves. Therefore, we sought to determine CyA effect on various nerve fibers by measuring current perception (CPT) and pain tolerance thresholds (PTT) using the neurometer at baseline and after treatment with CyA. Additionally, we sought to compare responders versus non responders, as well as those with and without Hunner&[prime]s ulcers. Methods A total of 26 patients were enrolled in this NIH funded study. CPT and PTT were obtained at the index finger and suprapubic site. Neurometer measurements were taken at 5 Hz (unmyelinated C), 250 Hz (myelinated A-delta), and 2000 Hz (myelinated A-beta fibers). Specifically, C fibers sense a broad range of painful stimuli. Descriptive results were presented as means with standard deviations and medians with interquartile range (IQR) for continuous variables. Comparison between groups was made using paired Wilcoxon rank sum test for continuous variables with a p value of 0.05 considered significant. All analyses were done using the statistical software package R (version 3.3.0). Results Of the 26 patients, 14 were women, 7 patients had pretreatment Hunner&[prime]s ulcers, and 11 patients were considered responders (improvement in Global Response Assessment or >30% improvement in IC Symptom Index). When comparing all patients at baseline to 3-months, there was a significant decrease in PTT at 5 Hz (median of 375 vs. 250, p=0.05), meaning pain tolerance decreased during treatment with cyclosporine. However, one month after cyclosporine treatment was completed, there was no difference from baseline (median of 375 vs. 325, p=0.27). When responders only were evaluated, there was a significant decrease in PTT at 5 Hz from baseline to 3 months (median 450 vs. 262.5, p=0.037) as well from baseline to 4 months (median 450 vs. 275, p=0.015). There was no difference of CPT and PTT measurements in responders compared to non-responders or in those with or without Hunner&[prime]s ulcers. Conclusions While not predictive of response to CyA or baseline phenotype, a change in PTT was seen in those who responded to treatment. As pain tolerance threshold decreased in patients successfully treated with CyA, the mechanism of action and effect of CyA may be beyond its immunosuppressant effect. Funding none
Authors
Marisa Clifton
Courtenay Moore Daniel Shoskes |
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MP29-03 |
Childhood stressful events induce chronic bladder pain in adulthood through a TRPV1 dependent mechanism. |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Interstitial Cystitis II | 17BOS |
Abstract: MP29-03 Sources of Funding: PFD Research Foundation and ICA IC/PBS Research Grant._x000D_ Ana Charrua is supported by Fundacao para a Ciencia e Tecnologia (FCT) fellowship SFRH/BPD/68716/2010. Introduction Stressful events occurring in childhood seems to have a role BPS/IC development in adulthood. We investigate if the maternal deprivation model (MDM) is an appropriate animal model to study such link, by characterizing bladder changes. Methods MDM was induced from P2 to P15, for 1h, on female C57BL/6. Pups were separated from mother and from littermates. Non separated female pups were used as controls. _x000D_ At P156, mechanical pain threshold were analysed at P156, by applying Von Frey filaments at the abdomen. At P157, animals were anaesthetised and cystometry was performed. Afterwards, bladders were harvested, fixed, sectioned and stained with HE (to analyse urothelium integrity) and with Toluidine blue (to analysed mast cell). _x000D_ The MDM was repeated on female TRPV1 knockout (KO) mice to investigate the role of TRPV1 nociceptors in this model. Results WT lower abdominal pain threshold was 0.08±0.01g. MDM WT decreased their threshold to 0.02±0.01 (P=0.0002). TRPV1 KO and MDM TRPV1 KO mice had a similar lower abdominal pain threshold (0.13±0.18g and 0.28±0.14g, respectively; P=0.2). _x000D_ WT had 0.48±0.15 bladder contractions/minute. MDM WT bladder frequency increased to 1.05±0.35 bladder contractions/minute (P=0.04). TRPV1 KO and MDM TRPV1 KO bladder frequency was 0.50±0.12 bladder contractions/minute and 0.50±0.08 bladder contractions/minute, respectively._x000D_ The bladder of WT and TRPV1 KO had normal urothelium (0% of disrupted urothelium). MDM WT had 7±7% of disrupted urothelium. MDM TRPV1 KO urothelium was similar to the one observed in WT female (0% of disrupted urothelium)._x000D_ Mastocytosis was not observed in any of MDM animals. Conclusions MDM mimics bladder dysfunction observed in BPS/IC, as MDM WT felt pain, had bladder hyperactivity and mild urothelial disruption. TRPV1-expressing fibres seem to have a role in the development of bladder changes has MDM TRPV1 KO mice did not present the changes observed in MDM WT. Therefore, we conclude that MDM model may be useful to investigate the consequences of childhood stressful events, in particular mechanism leading to the development of chronic bladder pain in adulthood. Funding PFD Research Foundation and ICA IC/PBS Research Grant._x000D_ Ana Charrua is supported by Fundacao para a Ciencia e Tecnologia (FCT) fellowship SFRH/BPD/68716/2010.
Authors
Rita Matos
Francisco Cruz Ana Charrua |
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MP29-04 |
Comparison of five different animal models to establish the best interstitial cystitis rat model similar to human disease |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Interstitial Cystitis II | 17BOS |
Abstract: MP29-04 Sources of Funding: This work was supported by Basic Research Program through the National Research Foundation (NRF) of Korea funded by the Ministry of Science, ICT & Future Planning under Grant (NRF-2015R1C1A1A01053509). Introduction Interstitial cystitis (IC) is a chronic bladder disorder characterized by urinary frequency, urgency and pelvic pain in the absence of bacterial infection or identifiable pathology. To date, there is no reliably effective therapy for IC, and no generally accepted animal model to test novel therapies was established. We therefore analyzed and compared the characterization of five different promising rat models to establish the best interstitial cystitis animal model. Methods Five IC models were generated in 8-week-old female Sprague-Dawley rats via transurethral instillation of 0.1M HCl (HCl) or 3% acetic acid (AA), intraperitoneal injection of cyclophosphamide (CYP) or lipopolysaccharide (LPS), or subcutaneous injection of uroplakin II (UPK). Phosphate-buffered saline was transurethrally infused for the control group (PBS). After generating IC models, conscious cystometry was performed at day 3, 7, and 14. All rats were euthanized at day 14 and the bladders were removed for histological, immunohistochemical analysis and real-time quantitative polymerase chain reaction (PCR). Results In cystometric analysis, all experimental groups, including HCl, AA, CYP, LPS, and UPK, showed significantly decreased intercontraction intervals compared with control group at day 3, but only LPS and UPK group exhibited urinary frequency compared to control and other experimental groups at day 14. Histological analysis revealed that markedly increased infiltration of Toluidine blue-stained mast cells and significantly increased tissue fibrosis in LPS and UPK groups compared to the other groups. PCR analysis showed significantly elevated expression of interleukin-1b, -6, -17a, myeloperoxidase, monocyte chemotactic protein-1, toll-like receptors 2 and 4 in UPK group compared with the other groups. Conclusions Rat models generated by infusion of HCl, AA, CYP, LPS and UPK displayed urinary frequency up to 7 days and appropriate histologic changes similar to human interstitial cystitis. However, our study demonstrated that injection of UPK can be the best method to establish the interstitial cystitis rat model, considering longer continuation of bladder overactivity and higher expression of inflammatory factors. Funding This work was supported by Basic Research Program through the National Research Foundation (NRF) of Korea funded by the Ministry of Science, ICT & Future Planning under Grant (NRF-2015R1C1A1A01053509).
Authors
Bum Soo Kim
Jae Wook Chung Phil Hyun Song So Young Chun Yeon Yong Kim Hyo Jung Lee Jun Nyung Lee Yun-Sok Ha Eun Sang Yoo Tae Gyun Kwon Seock Hwan Choi Hyun Tae Kim Tae-Hwan Kim Sung Kwang Chung |
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MP29-05 |
Pain relief after triamcinolone infiltration in patients with bladder pain syndrome with Hunner's Ulcers |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Interstitial Cystitis II | 17BOS |
Abstract: MP29-05 Sources of Funding: None Introduction Bladder pain syndrome (BPS) is a chronic condition with severe implications in quality of life and no definitive treatment. Our aim was to assess pain relief after triamcinolone infiltration (TI) in patients with BPS with Hunner&[prime]s Ulcers (HU). Methods Retrospective study of those consecutive patients with BPS and HU treated with TI at the Hospital Clinic of Barcelona between 2015 - 2016. TI was offered as a sole treatment when there was no evidence of other pelvic pathologies or infection and more conservative treatments had failed. _x000D_ _x000D_ We collected data about previous treatments for BPS and presence of urinary symptoms. A pelvic floor muscle palpation was performed to detect myofascial pain. _x000D_ _x000D_ TIs were performed with a 16Ch flexible cystoscope as an outpatient procedure. Triamcinolone doses were 40mg in 1ml, diluted with 9mls of 5% sugar solution. Every HU was treated with 3-5 injections of 1ml of the dilution, depending on the HU extension. _x000D_ _x000D_ Pain was assessed according to a Visual Analogue Scale (VAS) (0: no pain; 10: very severe pain) before and after treatment. We considered response to treatment a VAS improvement ≥ 4. Outcomes were compared with T-Student test for paired samples. Ethical approval was obtained from Hospital Clinic Ethical Board._x000D_ Results Twenty-seven procedures were performed in 20 patients, 19 women and 1 man, followed-up for a median of 7 months (range 1-15). Median age was 75 years (52-86). _x000D_ _x000D_ Table 1 shows patients&[prime] characteristics._x000D_ _x000D_ Table 2 shows response to TI and comparison of VAS before and after TI. _x000D_ _x000D_ Three (15%) patients required retreatment due to non response and 5 (25%) patients for pain recurrence at a median of 4 months (3.5-8). Seven out of 10 patients who were followed up for 8 months or more required at least one retreatment. Conclusions Triamcinolone infiltration in HU in patients with BPS is associated with significant pain reduction. However, most patients will require retreatment during follow-up Funding None
Authors
Laura Mateu Arrom
Laura Izquierdo AgustÃn Franco Nathan Lawrentschuk LluÃs Peri Meritxell Costa Antonio Alcaraz |
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MP29-06 |
Therapeutic exploitation of the Schistosoma haematobium homolog of interleukin-4-inducing principle of Schistosoma mansoni eggs for chemotherapy-induced hemorrhagic cystitis and bladder hypersensitivity |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Interstitial Cystitis II | 17BOS |
Abstract: MP29-06 Sources of Funding: None Introduction Ifosfamide-induced hemorrhagic cystitis and bladder hypersensitivity can be difficult to manage when mesna fails to prevent them. Bladder hypersensitivity associated with various forms of cystitis may be refractory to multiple treatment modalities. Prior work suggests interleukin-4 (IL4) alleviates ifosfamide-induced hemorrhagic cystitis and resiniferatoxin (capsaicin receptor agonist)-induced bladder pain. IL4-inducing principle of Schistosoma mansoni eggs (IPSE) is a host modulatory protein that binds immunoglobulins on leukocytes thereby inducing IL4 production and translocates into host nuclei to alter gene transcription. We sought to determine if the S. haematobium homolog of IPSE (H-IPSE) would reduce ifosfamide- and resiniferatoxin-induced bladder pathology. Methods We cloned and expressed H-IPSE and a nuclear localization sequence (NLS)-deficient mutant H-IPSE (H-IPSE[NLS]). H-IPSE IgE binding was measured by ELISA. H-IPSE activation of IgE-bearing basophils was assayed using RSATL8 basophilic reporter cells. Cellular uptake and NLS-dependent nuclear translocation of H-IPSE and H-IPSE(NLS) were confirmed using HTB9 urothelial cells and fluorescence microscopy. We administered IL4, H-IPSE, H-IPSE+anti-IL4 antibody, H-IPSE(NLS), or H-IPSE(NLS)+anti-IL4 antibody to mice prior to ifosfamide (with and without mesna) or resiniferatoxin. Negative controls were administered saline only. Positive controls were administered ifosfamide only. Previously published metrics for pain and urinary frequency were interpreted in blinded fashion. Bladder histology was interpreted in blinded fashion. Bladder hemoglobin was quantified using Drabkin&[prime]s assay. Bladder gene expression was assessed via real-time PCR. Results H-IPSE bound IgE in vitro and activated IgE-bearing RSATL8 cells. Nuclear translocation of H-IPSE but not H-IPSE(NLS) was confirmed. H-IPSE was superior to mesna and IL4 in suppressing ifosfamide-induced bladder hemorrhage (IL4-dependent). H-IPSE was comparable to mesna in dampening ifosfamide-triggered pain behaviors (NLS-dependent) and urinary frequency (NLS-dependent). H-IPSE reduced resiniferatoxin-mediated freezing behaviors (IL4- and NLS-dependent). H-IPSE reduced mRNA expression of proinflammatory mediators and increased expression of uroplakin mRNA. Conclusions Our work suggests a uropathogen-derived host modulatory protein has therapeutic effects in bladder disease models. Funding None
Authors
Evaristus Mbanefo
Loc Le Luke Pennington Theodore Jardetzky Abdulaziz Alouffi Franco Falcone Michael Hsieh |
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MP29-07 |
Development of the Ulcerative Interstitial Cystitis Risk Score (ICUS): A Urine-based Multiple Protein Assay to Predict Ulcerative Interstitial Cystitis |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Interstitial Cystitis II | 17BOS |
Abstract: MP29-07 Sources of Funding: We would like to thank the Taubman family for their generous support of interstitial cystitis research including this project. Introduction Interstitial cystitis/bladder pain syndrome (IC/BPS) is a multifactorial syndrome of severe pelvic and genitalia pain and compromised urinary function. A fraction of IC patients who are the most severe present with Hunner's ulcers or patches on their bladder walls, termed ulcerative IC (UIC). UIC is diagnosed by cystoscopy, however this is a painful and expensive procedure. The objective of this study was to determine if a calculated Interstitial Cystitis Ulcerative Risk Score (ICUS) based on non-invasive urinary cytokines could discriminate UIC patients from controls and non-ulcerative IC patients. Methods A national crowdsourcing effort targeting IC/BPS patients resulted in 442 urine samples consisting of 153 IC patients (146 female, 7 male), 155 female controls, and 134 male controls were collected. Controls were age-matched. This consisted of 52 UIC patients (48 females, 4 male). Urinary cytokine levels were determined using Luminex assay. A predictive classification model was generated from this data using the scikit-learn machine learning library and the Python programming language. It provides a probability of ulcerative IC when the algorithm is supplied with the levels of three different proteins found in the urine. Results A defined ICUS Score of 0 to 1 was calculated to predict UIC, or a bladder permeability defect etiology (Figure 1). If the ICUS is ≥ 0.5, then there is an 87% chance that the patient has ulcerative IC. If the ICUS is <0.5, there is an 87% chance that the patient does not have ulcerative IC. The three protein levels combined provide a much better prediction model versus any of the individual protein levels alone. Conclusions The ICUS Score quantifies UIC risk, indicative of a bladder permeability defect etiology, in a subset of IC patients. This provides a new clinical tool to improve diagnosing patients with suspected IC symptoms. Funding We would like to thank the Taubman family for their generous support of interstitial cystitis research including this project.
Authors
Laura Lamb
Joseph Janicki Sarah Bartolone Interstitial Cystitis Association Bernadette Zwaans Kenneth Peters Michael Chancellor |
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MP29-08 |
Small Fiber Polyneuropathy – A Big Clue to Etiology and Management of Chronic Pelvic Pain (CPP) |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Interstitial Cystitis II | 17BOS |
Abstract: MP29-08 Sources of Funding: None Introduction We report prevalence of small fiber polyneuropathy (SFPN) in patients with refractory CPP and concurrent pain diagnoses. Studies show that patients with CPP have an average 2.4 pain comorbidities such as irritable bowel syndrome (IBS), interstitial cystitis (IC), and fibromyalgia (FM) [5, 8, 12]. The lack of a common etiology complicates treatment options. SFPN is emerging as a major contributor to unexplained multi-symptom syndromes involving chronic widespread pain and is often present in patients with IBS and FM [1, 7]. SFPN diagnosis can be confirmed via skin biopsy: decreased epidermal nerve fiber density is demonstrated on immunofluorescence. The reported "minimum prevalence" of SFPN is 53/100,000 [11]. In our practice a significant proportion of refractory CPP patients had biopsies consistent with SFPN, a finding that has not been reported in the literature. We propose that SFPN is a unifying underlying treatable mechanism for pain in the refractory CPP patient._x000D_ _x000D_ Objective: To demonstrate the prevalence of SFPN in patients with refractory CPP and/multiple pain syndromes by diagnostic skin biopsy. Methods We evaluated refractory CPP patients for SFPN: epidermal nerve fiber density in 3mm punch biopsies of the lower extremity was evaluated by immunofluorescence. The sensitivity and specificity of the test are 78-92% and 65-90%, respectively. Results 17 (61%) of 28 patients were positive for SFPN. Comorbid conditions were high in our population including migraine (39%), IBS (36%), endometriosis (21%), FM (32%), IC (14%), GERD (50%), vulvodynia (7%), lower back pain (32%), and other types of chronic pain syndrome (35%). Duration of pain was not different between the SFPN (+) and (-) groups (8.36 years SD=9.92 versus 6.03 years SD=3.14); p=0.42 based on sample t-test for unequal variances. Number of prior visits for pain and age also did not differ (16.4 prior visits versus 15.2 and average age 43 versus 47 for SFPN (+) versus (-)). Conclusions The prevalence of SFPN in specialty referral patients with refractory CPP is remarkably high versus published population data. Consideration of SFPN shifts the focus from a syndrome complex to a unifying treatable disorder. Making the diagnosis of SFPN may result in treatments not usually offered to CPP patients such IVIG or other immunomodulatory therapies [3]. Identifying SFPN should be a priority in this population. Funding None
Authors
Annie Chen
Charles E. Argoff Elise De |
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MP29-09 |
Role of spinal microglia in colon-to-bladder neural crosstalk in a rat model of colitis |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Interstitial Cystitis II | 17BOS |
Abstract: MP29-09 Sources of Funding: DOD W81XWH-12-1-0565; NIH DK088836 Introduction We investigated whether spinal cord microglia are involved in colon-to-bladder neural crosstalk in a rat model of colitis. Methods Adult female SD rats were divided into A) control, B) colitis, and C) colitis + minocycline groups. Experimental colitis was induced by instilling 50% trinitrobenzene sulfonic acid into the distal colon in groups B and C; vehicle was administered in group A. Minocycline (200 mg/day), a microglial inhibitor, was continuously infused into the intrathecal space in group C; groups A and B were given the vehicle. On day 7: _x000D_ (1) an awake cystometrogram (CMG) was performed; _x000D_ (2) nociceptive licking and freezing behavior induced by intravesical instillation of resiniferatoxin was observed;_x000D_ (3) the distal colon was stained with hematoxylin-eosin (HE);_x000D_ (4) immunofluorescence staining for CD 11b, a microglial marker, was performed on the L6 spinal cord;_x000D_ (5) reverse transcription polymerase chain reaction for mRNA was performed on the L6 spinal cord;_x000D_ (6) the bladder was stained with toluidine blue._x000D_ Results (1) CMG in group B showed significantly (p < 0.01) shorter intercontraction intervals (ICI) than in group A. Group C showed significantly (p < 0.01) longer ICI than group B._x000D_ (2) There were no significant differences in licking events among the 3 groups. However, the number of freezing events was significantly (p < 0.01) greater in group B than in group A. Group C showed significantly (p < 0.05) fewer freezing events than group B._x000D_ (3) HE staining showed substantial inflammation in the distal colon in groups B and C compared with that in group A. _x000D_ (4) The number of CD 11b-positive cells significantly differed among groups in the following order: group B > group C > group A._x000D_ (5) The mRNA expressions of interleukin-1β, chemokine ligand 3, and brain-derived neurotrophic factor in the L6 spinal cord were significantly (p<0.05) increased in group B compared with those in group A. However, group C showed significantly (p<0.05) less mRNA expression of these molecules than group B._x000D_ (6) Toluidine blue staining in group B showed significantly (p<0.01) more total and degranulated mast cells in the bladder than group A. Group C showed significantly (p<0.05) fewer total and degranulated mast cells in the bladder than group B. _x000D_ Conclusions Spinal microglia probably play an important role in colitis-induced bladder overactivity and enhanced bladder pain sensitivity in colitic rats. Funding DOD W81XWH-12-1-0565; NIH DK088836
Authors
Tsuyoshi Majima
Yasuhito Funahashi Naoki Kawamorita Yoshihisa Matsukawa Tokunori Yamamoto Naoki Yoshimura Momokazu Gotoh |
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MP29-10 |
ALTERATIONS IN THE URINARY FUNGAL MYCOBIOME IN PATIENTS WITH BLADDER PAIN AND URINARY URGENCY |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Interstitial Cystitis II | 17BOS |
Abstract: MP29-10 Sources of Funding: Funded by a Urology Care Foundation Grant (ALA) and the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Network (1U01DK103260; JTA, JK, MRF) Introduction To investigate the influence of host-microbe interactions on lower urinary tract symptoms, we characterized changes in urinary fungal communities (the “mycobiome�) associated with urinary urgency and bladder pain. While alterations in the urinary bacterial microbiome are found in interstitial cystitis/bladder pain syndrome (IC/PBS) and overactive bladder (OAB), urinary fungal populations have remained completely uncharacterized, despite recent evidence implicating fungi in association with flare in chronic pelvic pain syndromes. Methods Catheterized urine specimens were obtained from IC/PBS (n=12), OAB (n=17), and asymptomatic patients (n=14). After centrifugation, DNA was extracted from the cellular pellet. Following deep sequencing of the ITS1 fungal ribosomal gene, fungal taxa were identified by comparison to multiple fungal sequence databases. Using validated questionnaire data [the Genitourinary Pain Index (GUPI), OAB Questionnaire (OABq) and O’Leary-Sant Indices (ICSI/ICPI)], subjects were separated into tertiles based on symptomatic scores. Fungal community representation for each tertile was then examined while blinding for diagnosis. Results Comparison of microbial communities between the subjects with the lowest and highest scores on the GUPI, OABq, and ICSI/ICPI revealed decreased fungal diversity for patients with more severe symptoms, regardless of symptom type. Individual symptoms were associated with distinctive species profiles, regardless of diagnosis (Figure). Patients with severe bladder pain exhibited altered Malassezia spp. composition, while fear of leakage was inversely correlated with detectable Wickerhamomyces spp. Conclusions The urinary mycobiome is altered in lower urinary tract symptoms, with loss of diversity correlating positively with symptom severity. Specific fungal community patterns correlated independently with painful bladder and urinary urgency symptoms. These results suggest the intriguing possibility that particular microbial patterns may be associated with specific symptoms, not necessarily diagnoses, which has important implications for future studies of the urinary tract microbiome and the development of diagnostic and treatment algorithms in LUTS. Funding Funded by a Urology Care Foundation Grant (ALA) and the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Network (1U01DK103260; JTA, JK, MRF)
Authors
A. Lenore Ackerman
Jennifer Anger Jie Tang Karyn Eilber Jayoung Kim Michael Freeman David Underhill MAPP Research Network |
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MP29-11 |
Overactive Bladder and co-occurring Interstitial Cystitis/Bladder Pain Syndrome: The role of central sensitization in clinical presentation. |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Interstitial Cystitis II | 17BOS |
Abstract: MP29-11 Sources of Funding: This study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under award number K23DK103910, the Society of Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction Foundation research fund, the National Center for Advancing Translational Sciences under CTSA award number UL1TR000445, and by the Vanderbilt Office of Clinical and Translational Scientist Development. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of Vanderbilt University, the National Center for Advancing Translational Sciences, the National Institutes of Health or the Society of Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction. Introduction Many clinical characteristics overlap between Overactive Bladder (OAB) and Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) suggesting possible common pathophysiologic mechanisms. Central sensitization, which is an induced state of spinal hypersensitivity and well-recognized mechanism of centrally amplified pain perception, may be such a mechanism. Psychosocial and pain characteristics are important aspects of central sensitization disorders, but are often overlooked in women with OAB. Our aim was to examine whether these characteristics differ among OAB patients with a self-reported history of IC/BPS, OAB alone, and controls. Methods We enrolled 39 adult women initiating third-line OAB therapy and 25 healthy controls to complete clinical and psychosocial assessment. We identified a subset of women with OAB who self-identified as having a history of IC/BPS (n=13). Using Fischers exact test and linear regression, we then compared differences in bladder symptoms, psychosocial functioning, and pain sensitivity across these three groups (OAB = 26, OAB & IC/BPS = 13, and control = 25). Results Women with OAB with or without IC/BPS reported significantly greater urinary symptoms and psychosocial and pain burden than controls (Tables 1 and 2). The subset of women with IC/BPS demonstrated significantly increased symptom severity, higher rates of co-morbid somatic conditions, emotional distress, and poorer quality of life when compared to other groups. This group also reported a greater degree of widespread pain and symptoms attributable to central sensitization than those with OAB alone. Conclusions In this group of women undergoing third-line therapy for OAB, a personal history of IC/BPS was associated with worsened psychosocial, bladder, and pain function compared to those with OAB or controls. However, women with OAB alone also demonstrated similar characteristics, supporting the hypothesis that central sensitization may play a role in both conditions. Funding This study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under award number K23DK103910, the Society of Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction Foundation research fund, the National Center for Advancing Translational Sciences under CTSA award number UL1TR000445, and by the Vanderbilt Office of Clinical and Translational Scientist Development. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of Vanderbilt University, the National Center for Advancing Translational Sciences, the National Institutes of Health or the Society of Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction.
Authors
Lindsey McKernan
Joshua Cohn Stephen Bruehl Roger Dmochowski W. Stuart Reynolds |
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MP29-12 |
USE OF A BODY PAIN MAP TO CHARACTERIZE UROLOGIC CHRONIC PELVIC PAIN SYNDROME – A MAPP RESEARCH NETWORK STUDY |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Interstitial Cystitis II | 17BOS |
Abstract: MP29-12 Sources of Funding: NIH/NIDDK MAPP (Multi-Disciplinary Approach to the Study of Chronic Pelvic Pain) Research Network Introduction Patients with urologic chronic pelvic pain syndromes (UCPPS, interstitial cystitis/painful bladder syndrome and chronic prostatitis/chronic pelvic pain syndrome) suffer pelvic pain and pain in other body areas. The distribution of this pain in the body and its association with other factors has not been systematically studied. We characterized the location and distribution of pain among men and women with a body map and compared urinary symptoms, non-urological factors, and psychosocial measures between UCPPS patients who reported &[Prime]pelvic pain only,&[Prime] &[Prime]pelvic pain and beyond,&[Prime] and &[Prime]widespread body pain.&[Prime] Methods 233 women and 191 men with UCPPS enrolled in a multi-center, one-year observational study completed a battery of measures at study entry, including a body map to report the location and distribution of their pain during the past week. Participants were categorized as having &[Prime]pelvic pain only&[Prime] if they reported pain in the abdomen and pelvis only, or &[Prime]pelvic pain and beyond&[Prime] if they reported pain outside the abdomen and pelvis. Those who reported &[Prime]pelvic pain and beyond&[Prime] were sub-grouped into the numbers of broader body regions affected by pain (1-2 regions versus 3-7 regions or &[Prime]widespread body pain&[Prime]). _x000D_ Results 25% reported pelvic pain only. 38% reported widespread body pain outside the abdomen and pelvis. As we moved from 0 region (&[Prime]pelvic pain only&[Prime]) to 1-2 regions to ≥3 body regions outside the abdomen/pelvis (&[Prime]widespread body pain&[Prime]), there is an increase in non-urologic pain (p<0.0001), more sleep disturbance (PROMIS, p=0.035), worse quality of life (SF-12 physical component: p=0.021; SF-12 mental component: p=0.001), more depression (HADS-D, p=0.005), higher anxiety (HADS-A, p=0.011), higher psychological stress (PSS, p=0.005), and higher negative affect scores (PANAS, p=0.0004), using Jonchkheere&[prime]s trend test to test for 3-group gradient. Women (but not in men) with widespread pain also reported more fatigue (PROMIS, p<0.0001) than those with pelvic pain only. For both men and women, there was no difference between the three groups in terms of their urinary symptoms (e.g., severity of pelvic pain, urinary frequency, urgency ratings, Interstitial Cystitis Symptom and Problem Indexes, Genitourinary Pain Index, pain composite score, and urinary composite score). Conclusions Among MAPP participants, three out of four men and women with urologic chronic pelvic pain syndromes (UCPPS) also report pain outside the abdomen and pelvis. Widespread body pain was associated with worse quality of life and psychosocial impacts but not worse urinary symptoms. Funding NIH/NIDDK MAPP (Multi-Disciplinary Approach to the Study of Chronic Pelvic Pain) Research Network
Authors
H. Henry Lai
Thomas Jemielita Catherine S. Bradley Bruce Naliboff Robert Gereau IV David A. Williams Karl Kreder J. Quentin Clemens Larissa V. Rodriguez John N. Krieger John T. Farrar Nancy Robinson J. Richard Landis |
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MP29-13 |
Histamine intolerance and microbiota changes in patients with Painful Bladder Syndrome / Interstitial Cystitis |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Interstitial Cystitis II | 17BOS |
Abstract: MP29-13 Sources of Funding: none Introduction The cause of Painful Bladder Syndrome / Interstitial Cystitis is currently unknown.Histamine seems to play a major role in IC as neurogenic inflammation is one of the hypothesis of IC.Antihistamines are part of the guideline recommendations, foods high in histamine (e.g. Shorter-Moldwin Food Sensitivity Questionnaire) aggravate IC symptoms._x000D_ Objective: Within this retrospective study the role of histamine overload in the gut and vagina is highlighted._x000D_ Methods Between September 2012 and October 2016 a total of 80 women (range 19 to 75 years, mean age 47) were surveyed.Histamine in fecal samples was measured with a commercially available ELISA kit (LDN Labor Diagnostika Nord GmbH &Co. KG, Nordhorn, Germany).The results were compared to an age-matched cohort of 57 healthy women.Additionally, vaginal swabs were analysed for histamine producing bacteria of the Enterococcus and Enterobacteriaceae family. Furthermore a complete gut microbiota analysis was done in all women._x000D_ Results Stool results:_x000D_ In 55 of the 80 analysed women elevated histamine levels were found in fecal samples compared to a control-group of 57 healthy women.Moreover in most of the patients the protective anaerobic indicator microbiota (mainly lactobacilli and bifidobacteria) was also diminished._x000D_ Vaginal swab results:_x000D_ In 39 out of the 55 women with the elevated histamine level the presence of Enterococcus ssp. and / or Enterobacteriaceae in vaginal swabs was also detected. In 12 women only the presence of Enterococcus ssp. and / or Enterobacteriaceae was found. 4 women did neither show elevated histamine levels nor the presence of histamine producing bacteria in vaginal swabs._x000D_ _x000D_ Conclusions There are paralleles between IC and histamine intolerance: 1% of the population affected, 80% female and middle aged, symptom improvement in pregnancy because of a 500 fold higher level of the diamine oxidase (histamine eliminating enzyme).Histamine intolerance is a poorly described disease which can present with a variety of symptoms also found as comorbidities in IC patients like e.g. migraine, irritable bowel syndrome and urticaria.Histamine can increase intestinal permeability causing a leaky gut which prompts the body to initiate immune reactions causing autoimmune diseases and can also lead to pain through a toll-like receptor (TLR)-4 inflammatory response.That TLR-4 plays a role in pain has recently been demonstrated in IC patients by the MAPP research group.Moreover histamine alone as shown in mice can also cause pelvic pain. Funding none
Authors
Elke Hessdorfer
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MP29-14 |
Bladder capacity is a biomarker for a bladder-centric versus systemic manifestation in interstitial cystitis/bladder pain syndrome (IC/BPS) |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Interstitial Cystitis II | 17BOS |
Abstract: MP29-14 Sources of Funding: R21DK106554 Introduction IC/BPS is a diagnosis of exclusion for which there is no specific cystoscopic or pathological marker. The symptom heterogeneity and the myriad comorbid medical conditions in this population add confusion to the clinical picture. We recently reported that a subset of IC/BPS patients with BC < 400 ml display a molecular profile that is consistent with an inflammatory disease phenotype. This study aims to correlate the bladder capacity (BC) measured by hydrodistension with urinary and gynecological symptoms, non-urological chronic diseases, cystoscopy & histopathology._x000D_ Methods This is a retrospective chart review of women diagnosed with IC/BPS between 2011 and 2015 at one tertiary referral institution (IRB#00018552) who underwent bladder hydrodistention per the AUA guideline algorithm. Assessments for each patient included history, physical examination, OLeary/Sant Voiding & Pain Indices (ICPI & ICSI), and the Pelvic Pain Urgency and Frequency Questionnaire (PUF). After hydrodistension, bladder biopsies were collected and analyzed for pathology. Inflammation severity was characterized according to the degree of submucosal lymphocyte and monocyte infiltration, basement membrane thickness, submucosal edema, vascular ectasia, and fibrosis._x000D_ Results This study, which included data from 145 consecutively consented IC/BPS patients found a significant inverse correlation between BC and scores on three gold standard IC/BPS metrics: ICPI (p=0.0014), ICSI (p=0.0022) and PUF (p=0.0009), as well as with urinary frequency (p=0.0025) and age (p=0.014). A significant positive correlation was seen between BC and depression (p=0.0059), and BC and IBS (p=0.022). These data are demonstrated in Table 1. Cystoscopy and hystopathology data are demonstrated in Graph 1. Conclusions Patients with lower BC had more severe disease characterized either by clinical symptoms, cystoscopy and pathology. Our data suggest that low BC is a biomarker for a bladder-centric manifestation of IC/BPS._x000D_ Funding R21DK106554
Authors
Joao Zambon
Steve J Walker Gopal Badlani Catherine Matthews Heather Bowman Robert Evans |
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MP29-15 |
Biopsychosocial Predictors of Suicidality in Patients with Interstitial Cystitis/Bladder Pain Syndrome |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Interstitial Cystitis II | 17BOS |
Abstract: MP29-15 Sources of Funding: NONE Introduction Suicide is a significant problem in the general and chronic pain population. Although two studies have examined the prevalence and predictors of suicidal ideation in people suffering from Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS), these studies are limited by their sample selection, assessment of suicidal thinking and behaviour or risk, and the lack of any direct assessment of variables in current theories of suicide. _x000D_ _x000D_ The current study examines the prevalence of suicide risk and the significance of various demographic and biopsychosocial factors that are theoretically implicated in the prediction of suicide risk in an IC/BPS sample. Methods Female patients currently suffering from IC/BPS (N=813) were recruited from online support groups and complete an online questionnaire containing measures of demographic, pain, symptoms, and psychosocial variables. Results The sample was split into groups of suicide risk, based on an adult general population cut-off score of ?7 for the SBQ-R, creating a not at risk group (n = 503, M = 3.96, SD = 1.11) and an at risk group (n = 310, M = 9.73, SD = 2.65). This data split showed that 310 participants, or 38.1% of the sample, were at risk for suicide. Alternatively, using the more conservative cut-off score of ?8 (based on an adult inpatient population), 233 participants, or 28.7%, were at risk for suicide (see Figure 1). In regression analyses testing empirically/theoretically implicated contributors to suicidal behaviour, exposure to suicide, pain catastrophizing, psychache, hopelessness and perceived burdensomeness were found to significantly predict suicide risk. Further, regressions for low, moderate and severe pain patients groups showed that hopelessness was the strongest predictor of suicide risk in low pain patient group; psychache in the moderate pain group: and perceived burdensomeness in severe pain group. Conclusions The high prevalence of suicidality presented in this study denotes the imperative of recognizing suicidality within the IC/BPS population. Further, the identified psychosocial risk factors will be useful in improving screening and to anchor potential treatment targets for suicidality in IC/BPS. Funding NONE
Authors
Dean Tripp
J Curtis Nickel Joel Dueck Abigale Muere Haley Yurgan Madelaine Gierc |
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MP29-16 |
Improving the Utility of Clinical Phenotyping in Interstitial Cystitis/Painful Bladder Syndrome: From UPOINT to INPUT |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Interstitial Cystitis II | 17BOS |
Abstract: MP29-16 Sources of Funding: None Introduction The phenotyping system UPOINT has proven effective in classifying patients with Urologic Pelvic Pain Syndromes in a clinically meaningful way and to guide therapy. While highly successful in men with chronic pelvic pain syndrome (CPPS), UPOINT is more limited in patients with Interstitial Cystitis/Painful Bladder Syndrome (IC/PBS) since by definition all patients have the Urinary and Organ specific phenotype. Furthermore, AUA guidelines recommend a sequential tiered approach to therapy rather than the multimodal UPOINT scheme. We sought to modify UPOINT to be more practical and efficacious for IC/PBS Methods We developed a new phenotype by removing the Urinary and Organ specific domains from UPOINT and adding a Hunner's Ulcers (U) domain, since these patients benefit from phenotype specific therapies (fulguration, cyclosporine). This yields "INPUT": Infection, Neurologic/Systemic, Psychosocial, Ulcers and Tenderness of Muscles. We applied this system retrospectively to our previously validated upointmd.com IC/PBS database. Symptoms were measured by the Genitourinary Pain Index (GUPI) (valid for men and women). The database was searched for patients with complete data to assess the INPUT domains and include GUPI. Men were included if they reported pain relieved by voiding and/or presence of Hunner's ulcers. Groups were compared with ANOVA, Mann-Whitney, t test or Chi squared when appropriate and correlated with Spearman r Results There were 239 patients, 154 female (64%) with age range 18-79 (mean 41.8). Incidence of domains was Infection 11%, Neurologic/Systemic 51%, Psychosocial 81%, Ulcers 18% and Tenderness 85%. Mean total domains was 2.46 (range 0-5) and 65% had 2 or 3 positive domains while only 5% had none. There was a stepwise increase in GUPI score with increasing number of positive INPUT domains (ANOVA for differences between groups p<0.0001, Correlation by Spearman r=0.355 p<0.0001). Presence of Hunner's ulcers increased mean symptom score (25.7 vs 29.7, p=0.004) and indeed each of the domains significantly increased total GUPI score except for Infection. Conclusions The INPUT phenotype in IC/PBS appears to replicate the validity and potential clinical utility of UPOINT in CPPS. Patients have a diversity of phenotypes and more positive domains correlate with more severe symptoms. Since 95% of patients have at least 1 positive domain it may benefit patients to receive multimodal therapy up front for these extra domains (eg. pelvic floor physical therapy, fulguration of ulcers) rather than relying on a sequential tiered approach. Funding None
Authors
Alice Crane
Jessica Lloyd Daniel Shoskes |
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MP29-17 |
Mast Cell Subtypes: Implications for the Pathogenesis of Interstitial Cystitis |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Interstitial Cystitis II | 17BOS |
Abstract: MP29-17 Sources of Funding: None Introduction Painful bladder syndrome/interstitial cystitis (PBS/IC) is a chronic inflammatory disorder of the urinary bladder. _x000D_ _x000D_ Although its pathogenesis is largely unknown, there is evidence that it is related to mast cell (MC) proliferation and activation in a subset of patients. _x000D_ _x000D_ The objective of this study was to compare the difference in MC subtype, density, and distribution, between normal and PBS/IC bladder tissue._x000D_ _x000D_ Methods Full-thickness bladder tissue was collected from patients with PBS/IC (n=14), and from patients with normal histological findings (n=4). _x000D_ Samples were paraffin-embedded, and sectioned for immunohistochemistry. _x000D_ _x000D_ Mast cell subtypes were identified using a mast cell tryptase antibody (AA1), and anti-mast cell chymase antibody (CC1). _x000D_ _x000D_ Slides were photographed at a standard magnification, and positively stained mast cells were quantified using ImageJ software._x000D_ Results The distribution of AA1 positive mast cells within the layers of the bladder wall of PBS/IC and control individuals is shown in figure 1._x000D_ _x000D_ The distribution of mast cell subtypes within the layers of the bladder wall of PBS/IC individuals is shown in figure 2._x000D_ _x000D_ These results showed a significant difference in the density of MCs between each layer of the bladder wall in PBS/IC tissue (p<0.05)._x000D_ _x000D_ It was also shown that PBS/IC tissue contains a higher number of MCs compared to controls, with the largest difference in density between the two groups found in the lamina propria layer. _x000D_ _x000D_ There is also a significant difference in the density of MC subtype (p<0.05). Conclusions These findings suggest that MC numbers are significantly increased in PBS/IC bladder tissue, with a significant difference in subtype and density within the layers of the bladder. _x000D_ _x000D_ This may provide new insight into the role of MCs in PBS/IC, further our understanding of the pathogenesis of the disease, and develop treatment strategies._x000D_ Funding None
Authors
Brian Birch
Shabana Malik Bashir Lwaleed |
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MP29-18 |
Botulinum Toxin A bladder injection in the treatment of Bladder Pain Syndrome/IC: Trying to standardize the technique |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Interstitial Cystitis II | 17BOS |
Abstract: MP29-18 Sources of Funding: None Introduction Bladder Pain Syndrome/Interstitial cystitis (BPS) is a very complex entity with no clear etiology. Intravesical Botulinum Toxin is accepted as a 4th line treatment in BPS. The injection procedure is not standardized yet. _x000D_ _x000D_ The aim of the present study is to evaluate the efficacy of Botulinum Toxin A (BoNT A) intravesical injections in patients with BPS after a standarized injection procedure._x000D_ Secondarily, we evaluate the complications, duration of response, and the effect of adding hydrodistension (HD) during the procedure. _x000D_ Methods Fourty one patients with BPS treated between January 2008 to march 2015 were retrospectively evaluated. All patients received 200 UI of BoNT A injected under cystoscopic control: 100 UI in the trigone plus 100 UI in the detrusor. In 26 patients HD was also performed. Three days voiding chart, Visual Analogue Scale (VAS) for pain, Global Response Assessment (GRA) and urodynamic parameters were evaluated at baseline and after treatment. Results After a mean follow-up of 36 months, 25 patients (61%) reported subjective improvement (-3 points in VAS) lasting during 7 months as an average (range 3-18). Eight patients (20%) reported total relief of pain (VAS = 0). Daytime and nighttime urinary frequencies were reduced, reaching statistically significance only at night (from 7 to 4 times p < 0.001). Functional bladder capacity measured by voiding chart increased significantly (from 73 to 115 ml p < 0.003). Mean voided volume at uroflowmetry increased significantly (from 100 to 191 ml p < 0.001). Four patients reported incomplete bladder emptying, however there were no significant increase in postvoid residual volume. The comparison between HD and nonHD groups of patients did not show a significant difference in objective parameters. However, the HD group showed a significantly better GRA (7 versus 4 p <0.02). Conclusions The proposed procedure of BoNT A injection (100UI trigone + 100 UI detrusor plus HDT) was effective and safe in treating refractory BPS in our study improving significantly the nighttime frequency, voided volume in voiding chart and uroflowmetry, and relieving totally the pain in 20% of cases. HD provides a better subjective response without increasing morbidity._x000D_ Funding None
Authors
Cristina Gutiérrez
Carlos Errando Nicolas Nervo Pedro Araño Humberto Villavicencio |
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MP29-19 |
CHARACTERIZATION OF UROLOGIC AND NON-UROLOGIC FEATURES OF INTERSTITAIL CYSTITIS PATIENTS WITH HUNNER LESIONS |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Interstitial Cystitis II | 17BOS |
Abstract: MP29-19 Sources of Funding: None Introduction It has been hypothesized that IC/BPS (Interstitial cystitis/bladder pain syndrome) patients with Hunner lesions inside the bladder represent a different phenotype than IC/BPS patients without Hunner lesions. Here we compared the urologic symptoms (urgency, frequency, nocturia, urologic pain, bladder hypersensitivity, sexual function) and non-urologic features (severity and distribution of systemic pain, co-morbid functional pain syndromes, anxiety, depression) between IC/BPS patients with and without Hunner lesions visible on regular cystoscopy without hydrodistention. Methods A battery of questionnaires were given to IC/BPS patients from our clinical practice to assess their urologic and non-urologic features (Interstitial Cystitis Symptom and Problem Indexes (ICSI, ICPI), Pelvic Pain and Urgency/Frequency (PFU) Questionnaire, numeric ratings of pain, urgency, frequency, RICE Questionnaire, AUA Symptom Index , Body Pain Map, Brief Pain Inventory (BPI), Poly-Symptomatic Poly-Syndromic Questionnaire (PSPS-Q), and history of co-morbid functional pain syndromes). Among them, 123 patients underwent cystoscopy. Results 23% (28 patients) had classic Hunner lesions visible inside the bladder on regular cystoscopy without hydrodistention. 77% (95 patients) did not have Hunner lesions. When the two IC/BPS sub-groups were compared (with versus without Hunner lesions), IC/BPS patients with Hunner lesions were about a decade older (mean age 53±17 versus 42±15, p=0.002), more likely to report nocturia/night time frequency (p=0.016), and less likely to report anxiety (22% versus 43%, p=0.049) and irritable bowel syndrome (7% versus 34%, p=0.007) compared to IC/BPS patients without Hunner lesions. There was no statistical difference in their composite scores (ICSI, ICPI, PFU, AUASI), severity and bother of urologic pain, bladder hypersensitivity features (eg, increase in pain with bladder filling, decrease in pain with bladder emptying), daytime frequency, urgency, sexual function, severity and distribution of systemic pain, fibromyalgia, chronic fatigue syndrome, migraine headache, vulvodynia, and depression. Conclusions A significant percentage (23%) of IC/BPS patients demonstrate classic Hunner lesions inside the bladder during cystoscopy without hydrodistention. IC/BPS patients with Hunner lesions did not exhibit urologic and non-urologic features that would easily distinguish them from those without Hunner lesions. Cystoscopy is needed to identify these patients. Funding None
Authors
H. Henry Lai
Frederick Moh Joel Vetter |
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MP29-20 |
Treatment Effectiveness in Interstitial Cystitis/Bladder Pain Syndrome: Do patient perceptions align with efficacy based guidelines? |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Interstitial Cystitis II | 17BOS |
Abstract: MP29-20 Sources of Funding: Canadian Institute of Health Research Introduction Evidence from clinical treatment trials in interstitial cystitis/bladder pain syndrome (IC/BPS) are employed to develop treatment guidelines. Do patients&[prime] perceptions of success or failure of those specific therapies align with that of available clinical trial data? Methods 1628 adult females with a self-reported diagnosis of IC completed a web based survey in which patients described their perceived outcomes with the therapies they were exposed to. Previously published literature used in part to develop IC/BPS guidelines provided the clinical trial data outcomes. Patient reported outcomes were compared to available clinical trial outcomes and published treatment guidelines. Results Based on patient perceived outcomes (benefit:risk ratio), the most effective treatments were opioids, phenazopyridine, and alkalizing agents with amitriptyline and antihistamines reported as moderately effective. The only surgical procedure with any effectiveness was electrocautery of Hunner&[prime]s lesions. In order of efficacy reported in the literature, the therapies for IC/BPS with predicted superior outcomes should be: cyclosporine A, amitriptyline, hyperbaric oxygen, pentosan polysulfate plus subcutaneous heparin, botulinum toxin A plus hydrodistension, and L-arginine. While some of the guideline recommendations aligned with patient reported effectiveness data, there was a general disconnect between guidelines and effectiveness reported in clinical practice. Conclusions There is a disconnect between real world patient perceived effectiveness of IC/BPS treatments compared to the efficacy reported from clinical trial data and subsequent guidelines developed from this efficacy data. Optimal therapy must include the best evidence from clinical research but should also include real life clinical practice implementation and effectiveness. Funding Canadian Institute of Health Research
Authors
Avril Lusty
Elizabeth Kavaler Kay Zakariasen Victoria Tolls J. Curtis Nickel |
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MP30-01 |
Penis Transplantation: First U.S. Experience |
Transplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery II | 17BOS |
Abstract: MP30-01 Sources of Funding: Massachusetts General Hospital Introduction Penis transplantation represents a new paradigm in restoring anatomic appearance, urine conduit, and sexual function following genitourinary tissue loss. Genitourinary injuries and diseases that result in partial or complete penile loss have devastating functional and emotional consequences for patients leading to significant mental health sequelae, including depression and suicide. To date, only two penis transplants have been performed worldwide. We describe the 6 month follow up of the first successful penis transplant in the United States in a patient with a history of subtotal penectomy for penile cancer. Methods Following Institutional Review Board approval, extensive medical, surgical, and radiological evaluations of the patient were performed. His candidacy was reviewed by an multidisciplinary team of surgeons, physicians, psychiatrists, social workers, and nurse coordinators. After an appropriate donor was identified by United Network for Organ Donation, allograft procurement and recipient preparation took place concurrently. Anastomoses of the urethra, corpora, cavernosal and dorsal arteries, dorsal vein, and dorsal nerves were performed as well as inclusion of a donor skin pedicle as the composite allograft. Immunosuppression consisted of antithymocyte globulin induction, mycophenolate mofetil, and methylprednisolone, and tacrolimus. Results Postoperatively, the allograft had an excellent capillary refill and strong Doppler signals. Operative interventions on postoperative days 2 and 13 were required for hematoma evacuation and debridement of maturing skin eschar. At 3 weeks, no anastomotic leaks were detected on peri-catheter urethrogram and the catheter was removed. The patient developed one episode of steroid-resistant rejection (Banff III) which required a repeat course of methylprednisolone and antithymocyte globulin. At 6 months, the patient has recovered partial sensation of the penile shaft and has spontaneous penile tumescence. Our patient reports increased overall health satisfaction, dramatic improvement of self-image, and optimism for the future. Conclusions We have shown that it is feasible to perform penile transplantation with excellent results. Furthermore, this experience demonstrates that penile transplantation can be successfully performed with conventional immunosuppression. We propose that our penile transplantation pilot experience with encouraging short-term results represents a proof of concept that establishes a new and emerging field in reconstructive transplantation. Funding Massachusetts General Hospital
Authors
Dicken Ko
Kai Li Harry Salinas Ilse Schol Branko Bojovic Kyle Eberlin Jonathan Winograd Jeffrey Lee Garry Choy Raymond Liu Ivy Rosales Michael Grant Francis McGovern Adam Feldman Cigdem (Cori) Tanrikut Robert Colvin Curtis Cetrulo, Jr. |
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MP30-02 |
Survival of kidney transplants from uncontrolled DCD donors under normothermic preservation: are they as good as DBD kidneys? |
Transplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery II | 17BOS |
Abstract: MP30-02 Sources of Funding: None. Introduction Kidney transplantation is the best treatment for end-stage chronic kidney disease, with multiple advantages over dialysis. Because of the large quantity of people awaiting a kidney transplant there is an important organ shortage, which has led to investigate new sources of grafts. Donation after cardiac death (DCD) has emerged in the last two decades to increase the donor pool, classically composed by donation after brain death (DBD). Uncontrolled DCD is popular in not many countries, because of ethical issues among others; moreover, these kidneys have a higher ischemic risk due to longer cold ischemia time. In this series, we compare the survival of uncontrolled DCD transplants related to DBD transplants. Methods We carried out a retrospective review of 300 kidney transplants (150 uncontrolled DCD with normothermic perfusion and 150 DBD) performed in our centre between 2007 and 2012 on recipients under 60 years old. We collected preoperative features, surgical technique, graft characteristics (cold ischemia time...) and postoperative events. We estimated crude survival and death-censored and primary non function-censored survival with Kaplan Meier curves, using Stata v12.0 for Windows. Results Both groups were comparable regarding baseline characteristics, with a median follow-up of 53.6 months (interquartile range 35.3-70.5), and a median age of 43 years for donors and 46 for recipients. Crude survival (Figure 1) at 1, 5 and 10 years was 93.3%, 90.9% and 88.5% for DBD kidneys and 91.1%, 83.6% and 81.6% for uncontrolled DCD grafts, with no statistically significant difference (p=0,100). Primary non function and death censored survival (Figure 2) at 1, 5 and 10 years was 95.6%, 93% and 88.7% for DBD grafts and 97%, 88.9% and 86.9% for DCD grafts. Conclusions Uncontrolled DCD kidneys under normothermic preservation have similar survival as DBD grafts. Hence, they can be considered as a valuable source to increase the donor pool so as to minimize the current organ shortage. Funding None.
Authors
Félix Guerrero Ramos
Teresa Cavero Escribano Angel Tejido Sánchez Alfredo Rodríguez Antolín Manuel Pamplona Casamayor José Medina Polo Federico de la Rosa Kehrmann José Manuel Duarte Ojeda Felipe Villacampa Aubá Amado Andrés Belmonte Juan Passas Martínez |
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MP30-03 |
ROBOTIC KIDNEY TRANSPLANTATION: EUROPEAN ONE-YEAR DATA |
Transplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery II | 17BOS |
Abstract: MP30-03 Sources of Funding: none Introduction Kidney transplantation (KT) is the preferred treatment for patients with end-stage renal disease. In order to reduce the morbidity of the open surgery, a robotic assisted approach has been recently introduced. According to the literature, the robotic surgery allows the performance of KT under optimal operative conditions while maintaining the safety and the functional results of the open approach. We present the one-year results from the ERUS Robotic Kidney Transplantation Group common prospective recruitment database of Robotic assisted kidney transplantats (RAKT) on 69 cases. Methods An ERUS RAKT group was created in July 2015 with the intent of generating prospective data on robotic kidney transplantation. A common prospective recruitment database of RAKT performed at 8 different European Centers was therefore created in July 2015. Functional and surgical data were analyzed and herein reported. Results The patients demographic characteristics were as follows: 29 adult females and 40 males with mean age 42 years old (range: 25-64), mean BMI 26 kg/m2 (range: 22-33), and mean pre-transplantation serum creatinine 484 umol/L (range: 98-919) with a mean GFR: 10.4 ml/min per 1.73 m2 (range: 3-29). There were no vascular and ureteral anomalies in the cases included. The mean ASA score were 2. Overall surgical time was 324 min (range: 220-430) with vascular suture time of 42 min (range: 32-48), and estimated blood loss < 80 ml. Overall ischemia time (including warm ischemia, cold ischemia and rewarming time) was 98.9 min (range: 84-140). The average rewarming time was 55 min (range 51-58). Two patients were converted to open transplantation. No major surgical intra- operative complications were observed. There were two cases (3%) of transplantectomy for a massive arterial thrombosis on POD 2. One case of intraperitoneal hematoma occurred on POD 1, and was successfully managed laparoscopically. The mean post-operative serum creatinine level was 204 umol/L (range: 81-479) on post-operative day (POD) 7. Post-operative pain, evaluated with Visual Analog Scale (VAS) score, was optimal. The mean hospital stay was 6 ± 1 days (range 4-8 days). The mean time of ureteral catheter was 15 days (range: 14-16) after the surgery. There were five cases (7%) of delayed graft function although at 1 month follow up. Furthermore, no arterial nor ureteral strictures occurred. Conclusions This is the first European study on RAKT. RAKT with regional hypothermia appears to be a safe and reproducible surgical procedure in a properly selected group of patient. The potential advantages of RAKT are related to the quality of the vascular anastomosis, the possible lower complication rate and the shorter recovery of the recipients. The success rate in this group is comparable to conventional open KT. Funding none
Authors
Alberto Breda
Angelo Territo Lluis Guasa Volkan Tugcu Karel Decaestecker Michael Stoeckle Paolo Fornara Jonathan Olsburgh Giampaolo Siena Nicolas Doumerc |
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MP30-04 |
Induction of delayed renal allograft tolerance with clinical available reagents in non-human primates |
Transplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery II | 17BOS |
Abstract: MP30-04 Sources of Funding: NIH/NIAID U19AI102405-01 Introduction We have previously reported successful induction of renal allograft tolerance following a period of conventional immunosuppression (Delayed tolerance) using a nonmyeloablative conditioning with anti-CD154 and anti-CD8 mAbs or LFA3-Ig in MHC-mismatched kidney transplantation (KTx). However, since these reagents are not currently clinically available, the protocol needs to be revised to apply this approach to clinical deceased donor transplantation. In this study, we tested clinically available reagents, CTLA4Ig(belatacept) and rabbit-ATG(Thymoglobulin), for induction of delayed tolerance. Methods KTx was performed with a triple drug immunosuppression (I.S.) (tacrolimus, mycophenolate mofetil and predonisone) in MHC mismatched cynomolgus monkeys. Four months after KTx, recipients received donor bone marrow transplant (BMT) with a nonmyeloablative conditioning regimen that consisted of low dose TBI, thymic irradiation, belatacept, Thymoglobulin and a one month course of CyA. Results The first monkey received the regimen with Thymoglobulin (20mg/kg×3) and belatacept (20mg/kg ×4). Although the recipient developed mixed chimerism (MC), he died due to lethal CMV on day 19 after BMT. Another recipient received a reduced dose of Thymoglobulin (10mg/kg×2) but increased dose of belatacept (20mg/kg ×6). The recipient developed MC but died due to lymphoma on day 49. All four recipients that received Thymoglobulin (10mg/kg×2) and belatacept (20mg/kg ×4) developed MC without infectious complications or lymphoma and 3/4 achieved long-term renal allograft survival without I.S. (>300 days). The last recipient in this group did not develop rejection but died on day 108 due to ischemic kidney injury caused by hypotension during the renal allograft biopsy. Conclusions Induction of delayed renal allograft tolerance is achieved in nonhuman primates by a nonmyeloablative conditioning with belatacept and Thymoglobulin. This protocol for delayed tolerance is directly applicable to clinical deceased donor kidney transplantation. Funding NIH/NIAID U19AI102405-01
Authors
Kiyohiko Hotta
Tetsu Oura Abbas Dehnadi Gilles Benichou A. Benedict Cosimi Tatsuo Kawai |
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MP30-05 |
Optimizing Waiting Duration for Renal Transplants in the Setting of Renal Malignancy: Is Two Years Too Long to Wait? |
Transplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery II | 17BOS |
Abstract: MP30-05 Sources of Funding: None Introduction For potential renal transplant recipients, waiting duration is a significant, modifiable risk factor affecting survival. For patients with end-stage renal disease (ESRD) also affected by cancer, a waiting period is commonly imposed prior to transplant. However, no evidence based universal recommendations currently exist to guide clinicians. We aim to improve decision making by evaluating the impact of waiting duration on cancer-specific mortality (CSM), non-cancer-specific mortality (NCSM), and overall survival (OS) in kidney cancer patients awaiting renal transplant. Methods The United States Renal Data System (USRDS) was used to identify patients with a known cause of ESRD from the period 1983 to 2007. Evaluation of OS was performed with Kaplan-Meier estimates and Cox Proportional Hazards models. Fine-Gray competing risk models were used to assess CSM and NCSM. Results Of 1,374,175 patients with known causes of ESRD, 228,984 (16.7%) received a transplant. Transplant recipients with renal malignancy associated ESRD (RM-ESRD) had longer waiting durations than those with other known causes of ESRD (2.4 vs. 1.3 years, p<0.0001). RM-ESRD patients who had shorter waiting durations (0-2 years) had better overall survival than those who waited longer (2+ years) (10-year OS 69.0% vs. 46.7% respectively, p<0.0001); with similar CSM (10-year CSM of 10.3% vs. 10.2% respectively, p<0.883), while NCSM was worse for those with longer waiting durations (10-year NCSM of 20.7% vs. 44.3% respectively, p<0.0001). RM-ESRD with shorter wait time to transplantation had similar OS to other causes of ESRD, while those who waited longer had worse OS due to worse NCSM (see figure). On Cox modeling, cause of ESRD was not a significant predictor (p=0.07), while longer waiting duration remained significant (p<0.0001). Conclusions We found that longer waiting durations were associated with worse outcomes for patients with RM-ESRD. We found that CSM was not affected by waiting duration, while NCSM significantly improved with shorter wait time. These findings suggest that the overall survival of potential transplant recipients with RM-ESRD may be improved by reducing waiting duration. Further prospective trials evaluating this are warranted. Funding None
Authors
Kevin Nguyen
Jamil Syed Brian Shuch Srinivas Vourganti |
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MP30-06 |
Social Economic Status and Demographic Data of Non-Directed Living Kidney Donors |
Transplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery II | 17BOS |
Abstract: MP30-06 Sources of Funding: none Introduction The rise of non-directed kidney donation in the United States is a valuable source of high quality organs. Compared to developing countries, where there has been controversy over undereducated and compensated donors, donors in the United States are widely considered to be well informed on the issues surrounding their choice to give a kidney altruistically. However, there is very little known about the socioeconomic status and other characteristics of non-directed donors (NDDs). We aim to describe this population. Methods We collected donor characteristics from the National Kidney Registry (NKR) between 2008 and 2015. NKR is a network that has performed approximately 2000 exchange kidney transplants from >70 member centers across the United States. As we did not have direct donor level SES data, we were able to calculate a SES index, created and validated by the Agency for Healthcare Research and Quality (AHRQ), by geocoding the donor's zip code and linking it to 7 publicly available SES variables found in the 2011 US Census data (i.e. percentage of households with more than one person per room, median value of owner occupied values, percentage of people below the federal poverty line, median household income, percent of people above age 25 with at least four years of college, percent of people above 25 with less than a 12th grade education, and percentage of persons age 16 or old who are unemployed and seeking work). Results 267 predominantly female (58%) NDDs with an average age of 45.6 years old (range 21-72) were included in the study. The mean SES index score was 55.6 (SD=3.2), which corresponds to the 77th percentile of 1.5 million MediCare beneficiaries as reported by AHRQ in 2008. See table for demographic information. The average distance between donor and recipient was 954.0 miles and the time in transit for the organs ranged from 0-19 hours with an average of 6.8 hours (SD=3.2). The average NDD waited 4.5 months (SD=5.2) to donate. Conclusions The finding that NDDs are in the upper end of the economic spectrum is important in the context of efforts to increase living kidney donation. Additional NDDs may be further realized by removing financial disincentives such as travel expenses or lost wages. Funding none
Authors
Avi Baskin
Lorna Kwan Amy Waterman Sarah Connor Marc Melcher Jeffrey Veale |
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MP30-07 |
Bladder augmentation in kidney transplant patients: comparison between types of lower urinary reconstruction. |
Transplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery II | 17BOS |
Abstract: MP30-07 Sources of Funding: none Introduction The aim of this study was to assess the results of kidney transplant(KT) in patients with bladder augmentation (BA) and compare results between enterocistoplasty and ureterocistoplasty. Methods Betwenn 1988 and 2015, 64 patients with BA underwent KT ( 3 after KT), due to significant lower urinary tract dysfunction. . Ten second and 1 third KT were performed, comprising 75 KT in 64 patients The bowel segments used in the augmentation included ileum in 45(70.3%) patients, ileocecal in 3(4.7%) patients and sigmoid in 4(6.3%) patients. The ureter was used in 12 (18.8%) patients. Redo BA was performed in 4 patients after ureterocistoplasty (1 redo ureterocistoplasty, 3 redo ileocistoplasty); 2 redo BA were performed before the first KT. Mean age at first KT in Group 1(enterocistoplasty, n=48) and Group 2(ureterocistoplasty, n=12) was 24.28 and 15.06 years, respectively. Mean age at BA in Group 1 and 2 was 19.06 and 11.87 years, respectively. Redo KT was performed in 6 (11.3%) and 6 (50%) patients in Group 1 and 2, respectively. KT from deceased donor in Group 1 and 2 was 39.6% and 44.4%, respectively. KT from living donor in Group 1 and 2 was 60.4% and 55.6%, respectively. Results Mean follow-up after first BA was 188,8±118,9 (17-522) months and 140,5±71,5 (16-224) months in Group 1 and 2, respectively . In group 1, overall patient survival after 10 years was 78.78% and actuarial graft survival at 1,3,5,7 and 10 years was 94.3%,92.2%,83.1%,70.1 and 63.1%, respectively. In group 2, overall patient survival after 10 years was 90.9% and actuarial graft survival at 1,3,5,7 and 10 years was 88.5%,76.7%,76.7%,68.2 and 34.1%, respectively. Forty (83.3%) and 8(66.7%) patients in Group 1 and 2 were in clean intermittent catheterism (CIC), respectively. Symptomatic or febrile urinary tract infection occurred at least 1 episode in 81.3% and 83.3% in group 1 and 2, respectively. Conclusions Both enterocistoplasty and ureterocistoplasty are safe and effective methods of restoring lower urinary tract function in patients with end stage renal disease and a small, noncompliant bladder. CIC is safe in both groups. Graft survival rates are similar until 9 years, with a tendency of poor results after 10 years in ureterocistoplasty patients. Funding none
Authors
Kleiton Yamaçake
Affonso Piovesan Renato Falci Gustavo Messi Ioannis Antonopoulos Elias David-Neto Hideki Kanashiro Rafael Locali Gustavo Ebaid William Nahas |
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MP30-08 |
Does Marijuana Intake Affect Outcomes in Living Renal Donors and Their Recipients? |
Transplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery II | 17BOS |
Abstract: MP30-08 Sources of Funding: None Introduction There is a current shortage of kidneys available for transplantation. Based on United Network for Organ Sharing recommendations that exclude substance abusers from donation, many transplant institutions refuse live kidney donors who have a history of marijuana use; however, there is no evidence pertaining specifically to the donor or recipient outcomes. This is the first study to investigate the effect of marijuana use by live kidney donors upon outcomes in both donors and recipients. Methods A retrospective chart review for living kidney donors and their recipients between January 2000 and May 2016 was performed, stratifying patients based upon prior donor marijuana usage. Demographics and intra-operative variables were reported and compared for all groups. Outcomes compared included absolute and percent creatinine change and percent glomerular filtration rate (GFR) change in both donors and recipients, stratified by duration of marijuana usage. Baseline values for recipients were calculated based on their 1 week post-op creatinine values. Statistical analysis was performed using the t-test for numerical variables and the chi-square test for categorical variables with p<0.05 considered significant. Results Of total of 294 renal donor charts reviewed in this study,31 were marijuana using donors and 263 were non-marijuana using donors. There was no difference in donor preoperative, perioperative, or postoperative outcomes based upon marijuana use (p>0.05 for all comparisons). However, there was a trend toward better preservation of donor GFR at 1 month for marijuana using donors vs. non-marijuana using donors (-33.3% vs. -38.6%; p=0.07) respectively. Marijuana kidney recipients and non-marijuana kidney recipients were similar in creatinine change and percent creatinine change at all time periods. At 1 month, marijuana kidney recipients showed a lower percent change in GFR compared to non-marijuana kidney recipients (+0.9% vs. +20.4%; p=0.035) respectively. However, for all other time points (6 months, 1 year, and 5 years), there was no difference in percent GFR change between marijuana kidney recipients and non-marijuana kidney recipients (p>0.05 for all comparisons). Conclusions There was no difference in renal function between marijuana using donors and non-marijuana using donors and no long-term differences in renal function between non marijuana kidney recipients and marijuana kidney recipients. Considering individuals with a history of marijuana use for live kidney donation could increase the donor pool and yield acceptable outcomes. Funding None
Authors
David Ruckle
Mohamed Keheila Benjamin West Braden Mattison Jerry Thomas Samuel Abourbih Michael De Vera Arputharaj Kore Pedro Baron D. Duane Baldwin |
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MP30-09 |
Treatment Modality for Small Renal Masses may Affect Time to Eligibility for Renal Transplant Candidates |
Transplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery II | 17BOS |
Abstract: MP30-09 Sources of Funding: None Introduction There is no standardized approach to the treatment of small renal masses (SRM) in renal transplant candidates. Time on dialysis is associated with worse graft survival and overall mortality. Therefore, we conducted a study to evaluate whether treatment modality of SRM impacts time to eligibility for renal transplantation. Methods We queried transplant centers in the United States via an online survey. The survey was designed to analyze practice patterns to treat SRM and specifically focused on treatment modality and wait time required to become eligible for renal transplantation. Surveys were sent to 212 transplant centers in the US. Results We received responses from 53 (25%) US Transplant Centers, representing all 11 United Network for Organ Sharing regions. _x000D_ _x000D_ The time between definitive treatment for cT1a renal cell carcinoma and renal transplantation differed by treatment type. Responders were more likely to allow immediate transplantation after radical nephrectomy (77.4%), as opposed to partial nephrectomy (58.1%) and focal ablation (45.2%). The rest of the respondents indicated that they would observe between 2-4 years before transplantation. No respondents indicated that they would wait beyond 4 years._x000D_ _x000D_ 68.3% indicated the time interval was also dependent on tumor size; 56.9% < 1cm, 45.2% < 2cm, 11.3% < 3cm, and 9.7% < 4cm for those that indicated a threshold size._x000D_ _x000D_ In univariable analysis, respondents from institutions with experience of over 100 cases per year (OR=7.69, p=.006), with greater than 2 transplant surgeons (OR=6.83, p=.005) and with over 40 years of renal transplant experience (OR=5.06, p=.028) were more likely to proceed with immediate transplantation after definitive treatment. _x000D_ Conclusions Time to become eligible for transplant in patients with SRM was affected by treatment modality. Eligibility time was shortest for radical nephrectomy and longest for focal ablation. Tumor size and the experience of the transplant program also affected eligibility time._x000D_ _x000D_ Funding None
Authors
Alp Tuna Beksac
David Paulucci John Sfakianos Susan Lerner Jorge Pereira Ketan Badani |
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MP30-10 |
Global Kidney Exchange: Striving for Trifecta Outcomes in management of Kidney Failure |
Transplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery II | 17BOS |
Abstract: MP30-10 Sources of Funding: Alliance for Paired Donation_x000D_ Rejuvenate HealthCare, Inc Introduction While organ shortage is the major limitation to kidney transplantation in the developed world, in resource poor countries, financial barriers prevent kidney transplantation much more often—even when willing living kidney donors are available. Global Kidney Exchange (GKE) is a unique approach that allows mutual benefit between patients-donor pairs in rich and poor nations who face barriers to transplantation. Methods We propose that the cost difference between dialysis and transplantation in some countries would allow the exchange of kidneys between developed world patient/donor pairs with immunological barriers and developing-world patient/donor pairs with financial barriers to transplantation. Results Through the GKE 3 BT-O donors (2 from the Philippines and 1 from Mexico) were identified. Three Non-simultaneous extended altruistic donors (NEAD) chain were identified with each US BT-A non-directed donor (NDD) with no match in a regional kidney paired donation (KPD) pool. A US NDD or bridge donor donated to a foreign recipient creating a chain of kidney transplants. So far a total of 27 kidney transplants have been generated, with each chain producing 12, 9 and 6 transplants respectively. The blood type of the 27 GKE recipients were BT-0 in 14, BT-A in 9, and BT-B in 4. Of the 27 GKE recipients, 10 had a PRA of 0-20%, 11 had a PRA of 21-79%, and 6 had a PRA of >80%. Two of the chains remain open at this time with bridge donors awaiting donation, with the potential to extend the number of total transplants. The transplant cost for each foreign recipient was paid for by Philanthropy. An additional, $50,000 was reserved for subsequent immunosuppression for follow-up of the foreign donor/recipient pair. The cost saving from transplanting 24 U.S patients compared with the cost of dialysis will exceed $7.3 million over a 5 year period. At most recent follow-up all patients have excellent renal function. Conclusions GKE is an innovative approach that achieves the trifecta (cost reduction, quality of life improvement, and assess to kidney transplant) in the management of all patients with End-stage renal disease by providing increased opportunities for transplantation for all blood types and levels of sensitization Funding Alliance for Paired Donation_x000D_ Rejuvenate HealthCare, Inc
Authors
Obi Ekwenna
Ty Dunn Susan Rees Jeffrey Rogers Christian Kuhr Alvin Roth Laurie Reece Kimberly Krawiec Samay Jain David Fumo Christian Marsh Alejandro Cicero Jonathan Kopke Miguel Tan Puneet Sindhwani Siegfredo Paloyo Michael Rees |
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MP30-11 |
Choosing the Larger Kidney on CT Volumetry - A Study on the Early Post-Donation Kidney Function of Living Donors |
Transplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery II | 17BOS |
Abstract: MP30-11 Sources of Funding: None Introduction Computer Tomography based volume measurements (CT Volumetry) in living kidney donor imaging have been shown to correlate well with nuclear based split renal function, potentially facilitating more thoughtful selection of the side for donor nephrectomy. However, the impact of removing the relatively larger volume kidney on post donor nephrectomy renal function has not been widely studied. We compared the 6 month post-donation renal function of patients who gave their larger kidneys (on CT scan), with that of patients who did otherwise. _x000D_ Methods A clinical chart review of 103 consecutive patients (Mean Age 45.28 ±12.7, Males, n=49) who underwent uncomplicated donor nephrectomy from 2010 to 2015 was performed. All patients' bilateral kidney volumes were measured based on their preoperative CT scans. Estimated glomerular filtration rate (eGFR) was determined using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation - before and 6 months after surgery. Patients were divided into two groups and compared. Group 1 (n=29) consisted of patients who underwent donor nephrectomy of the side larger than the remaining side by 5% or more of the total kidney volume. Results Patients in Group 1 and 2 (n=74) were not significantly different (P=NS) respectively in terms of age (43.9 vs. 46.4), BMI (22.9 vs. 25.3) gender and racial distribution (58.6 vs. 51.4% Female and 59 vs. 59% Chinese). Both patient groups had equivalent proportion of controlled hypertension and hyperlipidaemia. Surgical approach, arterial number and side were not significantly different. Although total kidney volumes were equivalent between group 1 and 2 (264.8±65.4 vs. 283.6±55.9mls, P=NS), Group 1 had significantly smaller right kidney volumes (111.2±24.7 vs. 142.2±27.3mls, P=0.04). Of note, the kidney removed in 2 of 29 patients in Group 1 was 10% greater by split renal function in terms of volume than the remaining side. EGFR pre-operatively (113.6±20.0 vs.105.8.0±22.4mL/min/1.73m 2 ) and at 6 months (66.3±13.2 vs. 65.9±15.6mL/min/1.73m 2 ) were not significantly different between the two groups. Despite this, patients in group 1 had a significantly greater absolute (53.9±3.3 vs. 42.0±14.6 mL/min/1.73m 2 ,) P=0.01)and relative decline (44.7% vs. 37.1% P=0.01)in eGFR at 6 months compared to group 2. Conclusions At a threshold split renal function difference by kidney volume of 5% between the 2 sides, removal of the larger kidney for living kidney donation will result in a significantly greater early decline in an individual's renal function than kidney donors whose larger or equivalent kidney is preserved. Funding None
Authors
Lynnette Tan
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MP30-12 |
Preemptive kidney transplantation recipients are not as mentally satisfied as non-preemptive patients |
Transplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery II | 17BOS |
Abstract: MP30-12 Sources of Funding: none Introduction Preemptive kidney transplantation (KTx) is recognized as the ideal therapy to avoid dialysis. However, it is not clear whether preemptive KTx recipients experience an improvement in quality of life (QOL) after KTx that exceeds that of non-preemptive KTx recipients, since preemptive KTx recipients have not experienced the heavy burden of dialysis. The aim of this study was to evaluate the changes in QOL for preemptive and non-preemptive KTx recipients following transplantation. Methods Patients included in this study underwent living kidney transplantation at our hospital between April 2011 and August 2015. All recipients with functioning transplants for more than 12 months after KTx were included in the study. QOL was assessed by the Short Form 36 (SF-36) preoperatively and 3 and 12 months postoperatively. Categorical variables were compared with the chi-square test, and continuous variables were compared with the Mann–Whitney U test or Tukey’s test. A value of P < 0.05 was considered to be significant. Results Fourteen preemptive and 22 non-preemptive recipients were enrolled. The preemptive group included 3 women (21.4%) and 11 men (78.6%), and there was no significant difference in the proportion of men and women between the groups. The average baseline scores were similar between the preemptive and non-preemptive groups. In the non-preemptive group, the general health, social functioning, and vitality scores were higher than baseline at 12 months (38.4 vs 48.4, 42.2 vs 50.9, 45.5 vs 55.1, respectively; P < 0.05). In contrast, in the preemptive group, only the vitality score was better at 3 months (44.6 vs 56.0, P < 0.05). The mental component score showed significant improvement at 12 months (48.6 vs 56.1, < 0.05) in the non-preemptive group. However, it was not significantly changed in the preemptive group (50.5 vs 51.1, p = 0.9898). Conclusions Post-Tx improvement in QOL is more evident in the non-preemptive group. Preemptive KTx recipients are not as mentally satisfied as non-preemptive patients following KTx. Funding none
Authors
Yuichi Ariyoshi
Motoo Araki Yosuke Mitsui Koichiro Wada Toyohiko Watanabe Yasutomo Nasu |
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MP30-13 |
MTH score – A novel scoring system to risk stratify renal transplant cases and to improve outcomes post renal transplant |
Transplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery II | 17BOS |
Abstract: MP30-13 Sources of Funding: none Introduction ESRD is a highly prevalent cause of morbidity and mortality. Kidney transplantation is the optimal treatment of ESRD in terms of morbidity, mortality and quality of life. Maximum incidence of graft dysfunction in the first year post transplant. We wanted to study the pre and post transplant factors that can affect post transplant outcome and graft survival .We wanted to make a scoring system to predict outcomes post transplant. Methods 450 cases of live donor renal transplant were studied in a period of 2 years . all recipients were followed for 1 year and their mean serum creatinine was considered to compare the outcomes post transplant . We studied the pre-transplant & post-transplant factors like donor age , donor sex , ratio of donor kidney weight to recipient body weight , recipient age , donor to recipient sex , cold ischemia time , time for diuresis , number of blood transfusions to recipient , amount of steroids taken by recipient in first 3 months after transplant , number of acute rejection episodes , number of renal arteries , hepatitis C virus infection of recipient . using these factors we made 3 score charts (pre transplant,post transplant & combined MTH score) by giving points in ascending order starting from 1 to each subgroup of the factors affecting transplant outcome . Maximum points were given to the category in the subgroup which has the best impact on the transplant outcome. We classified patients into low (score >30), intermediate risk (score 21-30) and high risk (score 11-20) . Independent t test or Mann Witney U test (*) was used as test of significance to identify the mean difference between two groups. ANOVA (Analysis of Variance) or Kruskal Wallis test (**) was the test of significance to identify the mean difference between more than two groups. p value <0.05 was considered as statistically significant. Results Overall 89.76% recipients had a serum creatinine of less than 2 at the end of one year_x000D_ 54.54 % recipients in MTH high risk group had serum creatinine < 2 at the end of 1 year._x000D_ 96.72 % recipients in MTH low risk group had serum creatinine < 2 at the end of 1 year _x000D_ 27.27% recipients in MTH high risk group were restarted on HD in the first year post renal transplant_x000D_ Conclusions 1.MTH score can help risk stratify renal transplant cases_x000D_ 2.The MTH score can help predict the outcomes in renal transplant _x000D_ 3.MTH score can be a guide for future scoring systems in transplant _x000D_ 4.Modifying the risk factors can help high risk cases to fall into low risk category and may improve post transplant graft survival rates in the first year ._x000D_ Funding none
Authors
aditya yelikar
sachin joseph |
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MP30-14 |
Survival outcomes from DCD renal transplant are comparable to DBD transplants from kidneys procured from donors over 50 years of age: UNOS/OPTN analysis |
Transplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery II | 17BOS |
Abstract: MP30-14 Sources of Funding: none Introduction There is hesitancy when utilizing DCD grafts of older age. We assess the long-term graft/ patient survival outcomes in donation after cardiac death ( DCD) and donation after brain death (DBD) transplants from kidneys procured from donors > 50 years of age. Methods Utilizing the UNOS/OPTN database, we analyzed 14288 deceased donor kidney transplants (1833 DCD and 13533 DBD) from donors > 50 years between 2005-2013. Analysis of graft and patient survival was with multivariate regression analysis and Cox models with single imputation by dummy variable method to manage missing data. Results Donor and recipient demographics between DCD and DBD recipients were similar including donor age, BMI, history of diabetes, and smoking. However, KDRI Rao was 1.5 (1.06-3.31) in DCD and 1.6 in DBD (1.6 (0.96-4.1), which was significant (p<0.001). Death censored graft survival in patients receiving grafts from donors >50 years at 1 and 5 years was 90 and 76% in DCD group vs 92% and 77% in DBD (p = NS). Furthermore, patient survival was 90 and 70% in DCD vs. 91 and 72% in DBD ( p = NS). _x000D_ _x000D_ When analyzing patients receiving grafts >60 years of age, graft survival was similar between DCD and DBD groups, but patient survival was inferior in the DCD group (p<0.05). Conclusions Results of renal transplantation with grafts >50 years are similar between DCD and DBD recipients, but caution should be taken when utilizing grafts >60 years. Funding none
Authors
Patrick Luke
Hemant Sharma Jingwen Chen Alp Sener |
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MP30-15 |
Visceral obesity in living kidney Asian donors significantly impacts on renal function after donor nephrectomy |
Transplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery II | 17BOS |
Abstract: MP30-15 Sources of Funding: None Introduction Obesity is a known risk factor for kidney donors to develop chronic kidney disease. The Framingham heart study suggested that visceral adipose tissue (VAT) confers a more adverse metabolic profile compared with subcutaneous adipose tissue (SAT). Asians tend to have a higher VAT composition and it is unclear if their kidney function is affected differently. We hypothesized that living kidney Asian donors who have visceral obesity are at higher risk of renal function deterioration 1 year after donation. Methods Between 2011 and 2014, we retrospectively evaluated data from 73 consecutive patients (52% male; mean age 44.9±11.7years) before they underwent donor nephrectomy and at their 1 year routine follow up. VAT and SAT were measured at the level of the umbilicus on preoperative computerized tomography (CT). Visceral obesity (VO) was defined as a VAT >100cm2 and patients were then further examined in 2 subgroups: VAT>100 and <100cm2. Estimated glomerular filtration rate (eGFR, mL/min per 1.73m2) was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation preoperatively and 1 year postoperatively. Results Both subgroups demonstrated similar kidney function (P=NS) preoperatively. At the 1 year follow up, patients with VO experienced a more significant decline of renal function (109±9 to 89±8 mL/min per 1.73m2), compared to those without VO (111±12 to 96±11 mL/min per 1.73m2, P =0.013). VO was associated with a body mass index (BMI) >25 kg/m2 (P <0.001), male gender (P <0.001) and older age at the time of donor nephrectomy (48.0 vs 39.5 years, P =0.01). The presence of hypertension or hyperlipidemia preoperatively, choice of surgical approach, and post-operative complication rates, did not differ significantly between the subgroups. Conclusions Visceral obesity as defined by VAT >100cm2 at the level of the umbilicus on cross-sectional imaging, significantly impacts on renal function after donor nephrectomy. We suggest that adiposity markers, as measured by cross-sectional CT imaging, be incorporated into routine pre-operative kidney donor workup. Funding None
Authors
Xiang Wen Gregory Pek
Lee Ying Clara Ngoh Boon Wee Teo Anantharaman Vathsala Yen Seow Benjamin Goh Hsiang Rong Clement Yong Lata Nee Mani Raman Ho Yee Tiong |
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MP30-16 |
Longer Functional Warm Ischemic Times Do Not Impact Donation After Cardiac Death Renal Allograft Outcomes |
Transplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery II | 17BOS |
Abstract: MP30-16 Sources of Funding: None Introduction Donation after circulatory death (DCD) renal transplants are associated with long-term outcomes comparable to that of donation after neurological donor death (NDD) transplants, but the effect of longer functional warm ischemia time during withdrawal is unknown. Nevertheless, a hard cutoff of 2 hours warm ischemic time has been used to exclude the use of DCD donors. Methods We retrospectively analyzed the impact of mean arterial pressure (mAp) <55 during donation for different time points (30, 45, 60, and 90mins) on delayed graft function time (DGF), creatinine clearance (CrCl) at 1 year and overall graft survival. A total of 190 single donations after DCD renal transplants were performed at our institution between July 2006 and June 2016. Outcome variables such as CrCl, hospital stay, readmission rate, DGF and overall graft loss and rejection were compared between groups using the Student t-test and the Pearson chi-square test. A linear regression model was also used for independent prognostication. Results Mean age of recipients and donors were 54.7 and 44 years old respectively and 13% of the population were expanded criteria donors. Patients were followed for a median of 39 months (range 1 - 122 months). The mAp<55 was not associated with DGF (X2=0.06, p=0.81), patient death (X2=0.81, p=0.34), graft failure (X2=0.40, p=0.53), cell mediated (X2=0.84, p=0.36) or antibody-mediated rejection (X2=1.25, p=0.26) of the graft. Independent multivariate regression model looking at mAp<55 as an independent predictor of Cr Cl at 7 days (p=0.10), 1 month (p=0.20), 3 month (p=0.09) or 1 year (p=0.63) and patient survival (p=0.82), graft survival (p=0.17), length of stay (p=0.35), length of readmission (p=0.24) did not show any significance. However higher CrCl at 7 days (R2=0.16, F(3, 105)=6.99, p <0.05) was an independent predictor of total warm ischemia time. Conclusions The duration of actual and functional warm ischemic time was not associated with DGF, patient death, graft failure or rejection nor for patient or graft survival. The CrCl at 1 week was an independent prognosticator of actual warm ischemic time but not for functional warm ischemic time. Utilization of selected DCD donors with warm ischemic times > 2 hr should be considered. Funding None
Authors
Heena Singh
Melissa Huynh Corinne Weernick Alp Sener Patrick Luke |
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MP30-17 |
Compared incidence of postoperative complications in a series of 150 uncontrolled DCD versus 150 DBD kidney transplants |
Transplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery II | 17BOS |
Abstract: MP30-17 Sources of Funding: None. Introduction Kidney transplant (KT) is the best treatment for end-stage chronic kidney disease, with higher survival rates, better quality of life and lower economic burden than dialysis. Due to the large amount of people awaiting a KT there is a great organ shortage, which has led to investigate new sources of grafts. Donation after cardiac death (DCD) has emerged in the last two decades to increase the donor pool, classically composed by donation after brain death (DBD). Uncontrolled DCD (uDCD) is popular in scarce countries; these kidneys have a higher ischemic risk due to longer cold ischemia time, which can be related to a higher rate of postoperative complications, especially affecting the urinary reconstruction. Our aim is to compare the incidence of postoperative complications of uDCD transplants (with normothermic preservation prior to organ procurement) versus DBD transplants. Methods We carried out a retrospective review of 300 KT (150 uDCD with normothermic perfusion and 150 DBD) performed in our centre between 2007 and 2012 on recipients under 60 years old. We collected preoperative features, surgical technique, graft characteristics and postoperative complications. These complications were also stratified according to time of onset (early -during the first 90 postoperative days- versus late -after the 90th postoperative day-) and severity (based on Clavien-Dindo classification). Data were analysed using Stata v12.0 for Windows. Results Baseline characteristics were comparable, with a median follow-up of 53.6 months. Total postoperative complication rate was 77.7%. Comparative incidence of complications is presented in Table 1 and stratification is in Table 2. Conclusions Uncontrolled DCD kidneys under normothermic preservation have a rate of postoperative complications comparable to that of DBD kidneys, with no differences in time of onset or severity. We therefore believe that postoperative complications are not an obstacle when it comes to use DCD kidneys as a source of grafts to fight against organ shortage. Funding None.
Authors
Félix Guerrero Ramos
Teresa Cavero Escribano Alfredo Rodríguez Antolín Manuel Pamplona Casamayor José Medina Polo Angel Tejido Sánchez Federico de la Rosa Kehrmann José Manuel Duarte Ojeda Felipe Villacampa Aubá Amado Andrés Belmonte Juan Passas Martínez |
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MP30-18 |
Racial disparities in renal transplantation |
Transplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery II | 17BOS |
Abstract: MP30-18 Sources of Funding: None Introduction African American (AA) patients have increased rates of end-stage renal disease compared to Caucasian American (CA) patients, and despite making up 13% of the American population, AAs comprise over 30% of the kidney transplantation list. This study seeks to better define our institutional experience in renal transplantation for AA patients in order to identify methods to reduce previously published racial disparities in access to and outcomes after renal transplantation. _x000D_ Methods We retrospectively reviewed the most recent fifteen years of kidney transplants at our institution. Clinical and demographic characteristics were collected from the electronic medical record. Kaplan Meier curves were generated for patient and graft survival, stratified by race and by living versus deceased donor transplantation._x000D_ Results A total of 1840 kidney transplants were performed at our institution from 2000-2016, including 1393 CA patients and 447 AA patients. 944 of the transplants were from living donors (LD) and 846 were from deceased donors (DD). Among the 1393 transplants for CAs, 818 (59%) were from LDs, whereas among the 447 AA transplants, only 126 were LD transplants (28%, p<0.001). _x000D_ _x000D_ There was no difference in patient survival between AA and CA recipients of deceased donor recipients or living donor recipients. Graft survival was longer in CA recipients of DD transplants (mean number, p<0.0001) but there was no significance in the graft survival difference between AA and CA recipients of LD transplants (Figure 1). _x000D_ Conclusions Living donation confers a graft and overall survival advantage compared to DD, and this is true among both AA and CA patients. At our institution there is no significant difference in graft or patient survival between AA and CA patients after living donation, though after deceased donation CAs have improved graft and patient survival. Furthermore, there is a striking difference in utilization of LD transplant between AA and CA patients. This demonstrates the need for further study of why AA patients are severely underrepresented in LD transplants, and improved education and communication regarding living donation among the AA community. _x000D_ Funding None
Authors
Benjamin Abelson
Colette Harris Jamie Mitchell Songhua Lin Charles Modlin |
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MP30-19 |
1 year follow-up: Percutaneous renal hilar blockade to predict success of auto kidney transplantation for loin pain hematuria syndrome |
Transplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery II | 17BOS |
Abstract: MP30-19 Sources of Funding: none Introduction Previous reports describe renal auto-transplantation (RAT) as a possible therapy for loin pain hematuria syndrome (LPHS) with reported successful pain relief ranging between 25-65%. We propose a percutaneous renal hilar blockade (RHB) can help predict when a LPHS patient should be referred for RAT. Herein we describe our one year follow up of this study. Methods A pre-procedure pain assessment was performed using a 0-10 numeric pain rating scale. Percutaneous hilar block was then performed with the patient in the prone position on the CT gantry. A post-procedure pain assessment was then performed. If their pain score was reduced >50% immediately after the RHB then they were referred for RAT. Before surgery and one year after surgery a quality of life survey was given to each RAT patient. The survey questions collected information related to demographics, medical history, and the patients’ current medical state. In addition to this survey, the patients were also asked to fill out the Beck Depression Inventory Scale, an internationally recognized instrument for assessing the presence and severity of depression symptoms._x000D_ Results During a three-year period 24 patients were diagnosed with LPHS by our urologist and were referred for RHB. Of the 24 patients that received RHB, 20 had relief of pain with a >50% reduction in pain scores. Pre-RHB average pain score was 7/10 with post-RHB score being 0.7/10 in patients that had >50% reduction in pain score. 13 of the patients who responded then proceeded to RAT, 3 responded but were denied by insurance; 4 responded, but did not receive RAT because they are still in work up; 4 did not respond to the block and were referred to a pain clinic. Of the 13 patients that received RAT, 6 patients have had at least one year follow up after RAT. All 6 patients underwent a successful RAT and currently have a functioning graft (Table). Their 1 year f/u post RAT assessment of pain level was an average of 2.3 down from an average 7 for a 67% reduction at 1 year. Conclusions Successful RAT for LPHS relies on the appropriate diagnosis. RHB should be considered as a tool to define LPHS patients appropriate for RAT. Funding none
Authors
Jeffrey Campsen
Mitchell Bassett Ryan O'hara Alec Rosales Robin Kim Rulon Hardman Blake Hamilton |
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MP30-20 |
Suprarenal Vena Cava Resection Without Reconstruction |
Transplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery II | 17BOS |
Abstract: MP30-20 Sources of Funding: None Introduction Inferior vena cava (IVC) resection is sometimes required for complete extirpation of retroperitoneal tumors. Most often this resection is limited to the inferior vena cava below the level of the renal veins due to fears of poor renal function following resection. Additionally, when the inferior vena cava is resected superior to the renal veins, a graft is often used to re-establish venous flow. We report our series of patients who underwent suprarenal IVC resection below the hepatic veins without graft replacement Methods With IRB approval we retrospectively identified all patients who underwent suprarenal IVC resection between 2010-2016. Demographic, intraoperative, functional, pathologic, and outcome data were compiled. Results A total of 16 patients were identified during the study period. Patient demographics, pathology, and functional outcomes can be seen in Table 1. Fourteen of the 16 patients had renal cell carcinoma while one patient had testicular carcinoma and one patient had adrenocortical carcinoma. None of the patients underwent concomitant vena cava reconstruction. Overall, renal function was preserved in all patients and no patient required dialysis. Four patients had a symptomatic DVT following surgery and 3 patients had persistent lower extremity edema at three months. There was one death within 30 days. _x000D_ Conclusions Suprarenal IVC resection is safe, feasible, and does not necessarily require routine vena cava reconstruction. There was 1 mortality within 30 days and renal function was preserved in all patients. Funding None
Authors
Cory Hugen
Jeffrey Loh-Doyle Anne Schuckman Hooman Djaladat Siamak Daneshmand |
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MP31-01 |
Long-term Safety and Efficacy of SER120 1.5 mcg in Patients With Nocturia: Results From a 2-year Open-label Extension Study |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Non-neurogenic Voiding Dysfunction I | 17BOS |
Abstract: MP31-01 Sources of Funding: Allergan plc and Serenity Pharmaceuticals LLC Introduction Two randomized, placebo-controlled phase 3 trials (DB3 and DB4) demonstrated the efficacy/safety of SER120 1.5 mcg, a very low-dose desmopressin nasal spray formulation in patients with nocturia. An open-label extension (OLE) trial of the DB3 study examined the long-term safety and efficacy of SER120 1.5 mcg over a 2-year period. Methods The DB3 study enrolled patients ≥50 years of age with ≥2 nocturic episodes/night for at least 6 months. Patients could enroll in the OLE study and receive treatment with SER120 at a lower dose and escalate to the 1.5 mcg dose for up to 126 weeks if they (1) completed the DB3 study or (2) did not participate in the DB3 study but met the DB3 study screening criteria. Patients returned for study visits every 2-8 weeks for assessments. Safety and efficacy assessments were conducted in the intent-to-treat (ITT) population (N=393) and included the incidence of low serum sodium levels, mean serum sodium levels, adverse events (AEs), duration of treatment exposure, and mean change from baseline in nocturic episodes/night. Results Of the 393 patients in the ITT population, 358 received the SER120 1.5 mcg dose. At baseline, mean age was 65.7 years, and mean nocturic episodes/night was 3.3. A total of 217, 129, and 42 patients, respectively, had at least 12 months, 18 months and 24 months of exposure to the SER120 1.5 mcg dose. Significant decreases from baseline were observed in the mean nocturic episodes/night as early as week 2 (-1.3), which were sustained up to week 54 (-1.9), week 78 (-1.9), and week 110 (-2.0) (P<.0001 for all timepoints). During the 2-year treatment period, the most commonly reported AEs were nasal discomfort (24.9%), sneezing (10.2%), and rhinorrhea (9.9%), which were mostly mild or moderate in intensity. The mean serum sodium concentration at baseline was 139.7 mmol/L and remained within the normal limits over the entire treatment period. None of the patients reported hyponatremia (serum sodium levels ≤125 mmol/L) at the SER120 1.5 mcg dose for the duration of the study. Conclusions SER120 1.5 mcg was well tolerated over the long-term, with no new safety signals observed during the OLE period. A total of 217 patients reached at least 1 year of exposure with the SER120 1.5 mcg dose. Long-term treatment with SER120 1.5 mcg resulted in significant and durable improvements in nocturic episodes/night which were sustained over 2 years. Funding Allergan plc and Serenity Pharmaceuticals LLC
Authors
Scott MacDiarmid
JP Nicandro Maria Cheng Steven Abrams Seymour Fein Alan Wein |
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MP31-02 |
MicroRNA-132 Induces Bladder Hypertrophy and Bladder Overactivity Via Downregulation of Acetylcholinesterase |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Non-neurogenic Voiding Dysfunction I | 17BOS |
Abstract: MP31-02 Sources of Funding: NIH DK088836 Introduction MicroRNAs (miRs) are involved in the post-transcriptional regulation of gene expression, and there is growing evidence for their pathological role in overactive bladder (OAB). We recently reported on the perturbed expression of miR-132 in acetic acid induced bladder overactivity (BO). Here, we investigate the functional significance of miR-132 overexpression in bladder and its effect on acetylcholinesterase (AChE) and other target genes in absence of acetic acid exposure. Methods Under isoflurane anesthesia, adult female Sprague-Dawley rats were either given bladder wall injection of either 10µg of plasmid vector pLV-[hsa-mir-132] or reporter plasmid encoding luciferase gene complexed with protamine and liposomes in a volume of 80µl. Bladder wall injection was performed at 4 separate sites (20 µL at each anterior, posterior and bilateral) with a 30-gauge needle. 7 days after transfection, transurethral open cystometry under urethane anesthesia ( 1g/kg s.c) was performed and harvested bladder was weighed prior to bladder strip contractility, histology and quantitative real time PCR analysis for AChE, Nerve growth factor (NGF), connexin-43 (Cx-43), monocyte chemoattractant protein (MCP-1) and soluble intracellular adhesion molecule (sICAM-1). Results Bladder wall transfection of miR-132 plasmid upregulated the miR-132 expression and evoked BO in absence of acetic acid. The intercontractile interval of 22.28± 1.49 min noted in luciferase transfected group was significantly reduced to 10.5± 0.8 min, while bladder weight was raised from 118.4± 1.12mg to 146.8 ±7.66mg and so was the contractile response of strips to KCl and electric field after transfection of miR-132 plasmid(*p<0.01, n=5). These changes in miR-132 group were associated with a 3 fold downregulation of AChE, 5 fold upregulation of NGF and MCP-1, while a 2 fold upregulation of Cx 43 and sICAM-1. Conclusions Observed BO and bladder hypertrophy following exogenous overexpression of miR-132 demonstrate the pathological role of miR-132 in OAB. The miR-132 mediated downregulation of AChE and upregulation of Cx43 explain the enhanced detrusor strip contractility. Upregulation of NGF and chemokines by miR-132 support it as a putative mediator of communication between neural and immune cells of bladder and therefore a suitable OAB drug target. Funding NIH DK088836
Authors
Mahendra Kashyap
Christopher Chermansky Naoki Yoshimura Pradeep Tyagi |
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MP31-03 |
THE RELATIONSHIP BETWEEN THE URINARY MICROBIOME AND CENTRAL SENSITIZATION IN WOMEN WITH OVERACTIVE BLADDER |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Non-neurogenic Voiding Dysfunction I | 17BOS |
Abstract: MP31-03 Sources of Funding: NIDDK of the NIH award number K23DK103910; SUFU Foundation research fund; NCATS under CTSA award number UL1TR000445; the Vanderbilt Office of Clinical and Translational Scientist Development Introduction Differences in pain perception and urinary microbiota have been linked to the presence of lower urinary tract symptoms (LUTS) and their severity. We aimed to characterize the relationship between the urinary microbiome and the presence or absence of overactive bladder (OAB) and elevated central sensitization (CS). Methods Women undergoing third-line therapy for OAB and healthy controls were recruited to undergo clinical assessment, quantitative sensory testing, and urine sample collection. Temporal summation to evoked, thermal cutaneous pain was performed with a Medoc Thermal Sensory Analyzer at .4 Hz, a frequency known to elicit C-fiber mediated wind-up in the dorsal horn of the spinal cord. Subjects were asked to rate their pain (0 – 100 VAS) during each of a sequence of 10 brief (.5 second) heat pulses to 49°C. Temporal summation was defined as the difference in pain rating between the maximum and first pain ratings. An individual with a difference in pain ratings or a first pain rating greater than 1 SD above controls after normalization was designated as demonstrating CS. Mid-stream urine samples collected from each patient were subjected to metagenomic sequencing targeting the V3-V4 region of the 16S-rRNA gene. Relative bacterial abundances were compared using the QIIME and the Wald test statistic in the MGLM package among women with and without OAB and CS. Results 23 patients comprised the study cohort. 6/10 (60%) subjects with OAB demonstrated CS, 2/8 (25%) subjects demonstrating CS did not have OAB. Bacterial abundance differed significantly between patients with and without OAB (Wald test statistic 316, p<0.01) and CS (Wald test statistic 80, p<0.01). Relative bacterial abundances were similar in patients with OAB and CS (Table). Relative to those without OAB and CS, Enterobacteriaceae, Chitinophagaceae and Burkholderiaceae were more abundant in subjects with OAB and CS and Lactobacillaceae and Prevotellaceae less abundant. Conclusions C-fiber activation related to elevated CS and alterations in the urinary microbiome may represent a combined mechanism of action for the development of refractory LUTS in some patients that warrants further study. Funding NIDDK of the NIH award number K23DK103910; SUFU Foundation research fund; NCATS under CTSA award number UL1TR000445; the Vanderbilt Office of Clinical and Translational Scientist Development
Authors
Joshua Cohn
Elizabeth Timbrook Brown Yan Guo Casey Kowalik Melissa Kaufman Roger Dmochowski Stephen Bruehl Charles Robb Flynn W. Stuart Reynolds |
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MP31-04 |
The Power of Crowdsourcing: Novel Method for Discovery of Urine Biomarkers |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Non-neurogenic Voiding Dysfunction I | 17BOS |
Abstract: MP31-04 Sources of Funding: We would like to thank the Taubman family for their generous support of interstitial cystitis research including this project. Introduction Interstitial cystitis/bladder pain syndrome (IC/BPS) has significant unmet medical needs including the lack of an objective laboratory test, such as a urine based biomarker. National collection of adequate patient samples for IC/BPS including normal controls can be challenging. We developed a novel research model that can engage multiple stakeholders and allow fast and broad participation for biomarker development. Methods In January 2016, a national crowdsourced research project engaging the entire IC/BPS community was conducted by Beaumont Health researchers in collaboration with the Interstitial Cystitis Association (ICA). This study had Institutional Review Board approval. Announcement of this study through social media was disseminated by the ICA. YouTube videos describing the scope of the project and participant requirements were posted (https://youtu.be/3BlnZdCq5vw and https://youtu.be/GL9T7ISyImk). Questionnaires were completed online through HIPAA compliant Survey Monkey. Special urine containers with preservatives developed to maintain protein and nucleic acid integrity in urine at ambient temperature were sent to consented participants with prepaid return shipping. Results Public participation was overwhelming and enrollment was closed within two weeks. Overall, men and women of all age groups submitted samples from 46 US states (Figure 1). Total samples received is illustrated in Figure 2. Multiplex analysis discovered three proteins that were highly statistically significant different between IC with ulcer vs IC without ulcer and normal control. Conclusions Crowdsourced research toward biomarker development was shown to be feasible and successful in advancing IC/BPS research. Patients with ulcerative IC/BPS have a different profile of urine proteins than normal and non-ulcerative IC patients. A validated Interstitial Cystitis Ulcer Score (ICUS) has been developed from this crowdsourced research project involving multiple stakeholders in interstitial cystitis. Funding We would like to thank the Taubman family for their generous support of interstitial cystitis research including this project.
Authors
Michael Chancellor
Sarah Bartolone Interstitial Cystitis Association Joseph Janicki Bernadette Zwaans Abdrew Verneecke Kenneth Peters Laura Lamb |
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MP31-05 |
Impact of brain-type natriuretic peptide, a representative biomarker for cardiac load, on nocturia in men. |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Non-neurogenic Voiding Dysfunction I | 17BOS |
Abstract: MP31-05 Sources of Funding: none Introduction Congestive heart failure (CHF) has been assumed to be one of the causes of nocturia. The relationship between nocturia and the extent of cardiac load, however, has not been fully examined. Brain-type natriuretic peptide (BNP) is a diuretic and vasodilatory hormone that is secreted in response to the left ventricular load and reported to be associated with the severity of CHF. Moreover, BNP can reflect the cardiac load before cardiac symptoms develop (Adnan Nadir et al., J Am Coll Cardiol HF 2015). In this study, we aimed to investigate the influence of the cardiac load evaluated by BNP on nocturia. Methods This retrospective study included 431 men whose BNP levels were evaluated before prostate biopsy between 2014 and 2016. We assessed the frequency of nocturnal voiding by International Prostate Symptom Score (IPSS). Nocturia was defined as voiding at night two or more times. The association of BNP and other clinical variables with nocturia was examined using multivariate logistic regression analyses. The other variables were age, prostate-specific antigen (PSA), prostate volume, body mass index, the presence of prostate cancer, estimated glomerular ?ltration rate (eGFR), hypertension, diabetes, sleep disorder, and the use of any ?-blocker or muscarinic antagonist. We also assessed the correlation between BNP and each item in the IPSS subgroups. Results Median age, BNP, and PSA were 69 years, 19.8 pg/ml and 8.7 ng/ml, respectively. Median time of nocturnal voiding was 1 and nocturia was observed in 191 men (44.3%). Presence or absence of prostate cancer was not associated with nocturia or BNP levels. Median BNP in men with nocturia was 26.5 pg/ml whereas that in men without nocturia was 13.7 pg/ml (p < 0.01). Median BNP in each frequency group of nocturnal voiding was 13.1 ng/ml in 0 times (n = 65), 14.2 ng/ml in 1 time (n = 175), 23.9 ng/ml in 2 times (n = 118), 37.1 ng/ml in 3 times (n = 52), and 37.9 ng/ml in 4 or more times (n = 21) (p < 0.01). Univariate analyses demonstrated that age, PSA, prostate volume, eGFR, use of any ?-blocker, hypertension, diabetes, sleep disorder, and BNP were correlated with nocturia. In multivariate analyses, BNP (p < 0.01) was an independent risk factor of nocturia, as well as age (p < 0.01), prostate volume (p < 0.01), and diabetes (p = 0.04). There were no correlations between BNP and each item in the IPSS subgroups other than nocturia. Conclusions BNP, a representative biomarker for cardiac load, is associated with nocturia in men. Funding none
Authors
Keita Izumi
Masaya Ito Masaharu Inoue Toshiki Kijima Soichiro Yoshida Minato Yokoyama Junichiro Ishioka Yoh Matsuoka Kazutaka Saito Kazunori Kihara Yasuhisa Fujii |
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MP31-06 |
Utility of Bladder Diaries Containing Frequency Volume Charts |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Non-neurogenic Voiding Dysfunction I | 17BOS |
Abstract: MP31-06 Sources of Funding: Institute for Bladder and Prostate Research Introduction For research purposes, most authorities agree that it is necessary to measure the time and amount of each void for at least a 24 hour period using a frequency volume chart (FVC). However in clinical practice, the FVC is often omitted. Certain diagnoses - polyuria (P), oliguria (O), nocturnal polyuria (NP), and small/large bladder capacity (SBC, LBC) - can only be diagnosed by a FVC. The purpose of this study is to estimate the prevalence of these conditions based on the FVC. Methods This is a retrospective multicenter observational study of consecutive patients evaluated for lower urinary tract symptoms (LUTS) who completed a 24h bladder diary. When multiple diaries were completed, the earliest was used. There were no other exclusions. A contemporaneous uroflow voided volume (UVV) was collected for each patient after they were instructed to drink until their bladder felt full. The following data was recorded for each patient: maximum voided volume (MVV), 24 hour voided volume (24HV), and nocturnal polyuria index (NPi). Corresponding diagnoses were derived as follows: O (24HV < 1L); normal (24HV=1-3 L); P (24HV > 3 L); NP (NPi > .33); SBC (MVV <150 mL); LBC (MVV > 600 mL). Spearman correlation was calculated between UVV and MVV. Results There were 643 patients, 407 male and 236 female. Prevalence of FVC-derived conditions in this population is seen in table 1. The correlation between UVV and MVV is seen in the plot. The MVV was an average of 116 mL greater than the UVV. Conclusions P, O, NP, LBC and SBC are not uncommon in patients with LUTS; nearly a third of patients had either O or P and 20% had NP. Whether or not these data possess external validity, they demonstrate that without measurement of voided volumes during a FVC it is difficult or impossible to diagnose these conditions. Further, there is only a weak correlation between UVV measurements and MVV obtained by FVC, so one should be cautious about interpreting the results of a single uroflow. Funding Institute for Bladder and Prostate Research
Authors
Jerry G Blaivas
Lucas J Policastro Zahava M Hirsch Amy L O'Boyle David Chaikin |
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MP31-07 |
Urinary stem cell factor may become the diagnosable biomarker of overactive bladder in women |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Non-neurogenic Voiding Dysfunction I | 17BOS |
Abstract: MP31-07 Sources of Funding: none Introduction C-kit, as known a receptor tyrosine kinase protein and a receptor of stem cell factor (SCF), not only acts as a marker of interstitial cells of Cajal, but also plays a significant role in the control of bladder spontaneous activity. And it could be an interesting target for the clinical treatment of overactive bladder (OAB). Although SCF binding to c-kit is associated with various biologic phases, the distribution and role of SCF in the urinary bladder remain unknown. Thus, we speculated that c-kit and its ligand SCF could play an important role in the control of bladder function. The objective of this study was to investigate whether SCF affects the biological behaviour of OAB. Methods Differentiation between OAB and control was based on symptoms and a questionnaire of Overactive Bladder Symptom Score (OABSS). Urinary SCF levels were measured in patients with OAB and in control subjects by enzyme-linked immunosorbent assay (ELISA). The urinary SCF levels were compared among controls and OAB groups, and also between OAB patients ?75 years and <75 years. Results A total of 93 women with OAB and 71 controls were enrolled. The mean age was 74.1± 13.0 years for the OAB groups and 67.1± 15.6 years for the control group. The average urinary SCF/creatinine levels in OAB patients was 1.589 ± 2.837, and in the control group was 0.558 ± 0.773 (p<0.001) (Fig.1). Analysis of urinary SCF/Cr levels among OAB group and controls by age showed no significant differences. Conclusions Urinary SCF levels were significantly higher in women with OAB. The urinary SCF level was not associated with ageing in OAB patients and controls. These results suggested that the SCF/C-kit pathway has a potential of contribution to the onset of OAB, and urinary stem cell factor might become the evaluable biomarker of OAB in women, objectively. Funding none
Authors
Takashi Hamakawa
Yasue Kubota Yuya Ota Naoko Unno Rika Banno Masa Takada Shoichi Sasaki Kenjiro Kohri Takahiro Yasui |
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MP31-08 |
Is osteoporosis an independent risk factor for urinary incontinence? Results from the National Health and Nutrition Examination Survey |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Non-neurogenic Voiding Dysfunction I | 17BOS |
Abstract: MP31-08 Sources of Funding: None Introduction A higher prevalence of urinary incontinence has been reported in women with low bone mineral density (BMD). However, there are conflicting reports in the literature regarding whether stress or urgency incontinence predominates in this population. We examined the National Health and Nutrition Examination Survey (NHANES) to investigate the association of osteoporosis and different types of urinary incontinence. Methods A retrospective review of all female subjects in the NHANES database between 2009-2010 was performed. Bone mineral density data was reviewed, along with the subjects' responses to questions regarding stress and urgency urinary incontinence. Osteoporosis is defined as BMD of 2.5 SD below the mean peak bone mass of young, healthy adults. Analysis took into account the hidden variance and the weighting methodology pertinent to analysis of NHANES. A variety of clinical confounders, such as age, ethnicity, smoking, number of vaginal deliveries and body mass index were also collected. Descriptive statistics were calculated and a multivariable logistic regression was performed to assess the association of BMD with urinary incontinence. Results Overall, 95,886,461 individuals were included with a diverse racial background including 64.2% non-Hispanic white, 12.7 % non-Hispanic black and 9.8% Mexican American. The mean age was 47.03 (SE=0.4). The prevalence of osteoporosis was 0.4% and 3.2% among non-Hispanic black and non-Hispanic white individuals, respectively. Stress urinary incontinence (SUI) and urgency urinary incontinence (UUI) were present in 33.6% and 35.5% of osteoporotic women, respectively. After adjusting for potential covariates, osteoporosis was found to be significantly associated with SUI (OR 1.5, confidence interval 1.1-2.3). No significant independent association was found between osteoporosis and UUI. Conclusions In the large, administrative NHANES dataset, we identified an independent association of osteoporosis with SUI in a diverse cohort of women. As connective tissue weakness is considered an underlying etiology for both osteoporosis and SUI, this study may serve as a guide for future investigation of the basic underlying mechanism. Funding None
Authors
Sarah Mozafarpour
Jessica Lloyd Farsad Afshinnia Libing Hu Howard Goldman |
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MP31-09 |
Association between postoperative urethral and vesical anatomical features on MRI and lower tract urinary symptoms after radical prostatectomy. |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Non-neurogenic Voiding Dysfunction I | 17BOS |
Abstract: MP31-09 Sources of Funding: none Introduction To elucidate the etiology of lower urinary tract symptoms (LUTS) after radical prostatectomy (RP), the present study investigated association between postoperative urethral and vesical anatomical features on magnetic resonance imaging (MRI) and LUTS. Methods Fifty-three consecutive patients undergoing RP also underwent pre- and postoperative MRI. Preoperative MRI only evaluated preoperative membranous urethral length (MUL). Postoperative MRI evaluated postoperative MUL, posterior-urethral vesical angle, depth of the urethrovesical junction (UVJ), and urinary pooling inside the urethra and bladder neck configuration (Figure 1 and 2). At the same time as postoperative MRI, International Prostate Symptom Score (IPSS), quality of life (QOL) index, continence grade, and uroflowmetry was investigated. Associations between pre- or postoperative MRI variables and questionnaire results or uroflowmetry were analyzed to examine the relationship between morphology of the urethral and vesical anatomical features and LUTS. Results Pre- and postoperative MRI variables were not significantly associated with parameters of IPSS total score and uroflowmetry. Urinary pooling inside the urethra was significantly associated with the urgency score in IPSS (p=0.006). Postoperative MUL (p<0.001), depth of UVJ (p=0.002) and urinary pooling inside the urethra (p=0.04) were significantly associated with continence grade. Conclusions Urinary pooling inside the urethra might induce urgency, and postoperative MUL and depth of UVJ were related to urinary incontinence. Avoiding damage to the continence nerve to prevent inflow of urine into the urethra, preserving the MUL, and developing procedures to prevent declines in the bladder neck during surgery are therefore recommended._x000D_ _x000D_ Funding none
Authors
Nobuhiro Haga
Tomohiko Yanagida Ken Aikawa Yoshiyuki Kojima |
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MP31-10 |
HEALTH LITERACY, COGNITION AND URINARY INCONTINENCE AMONG GERIATRIC INPATIENTS DISCHARGED TO SKILLED NURSING FACILITIES |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Non-neurogenic Voiding Dysfunction I | 17BOS |
Abstract: MP31-10 Sources of Funding: Department of Health and Human Services Centers for Medicare & Medicaid Services Grant #1C1CMS331006 Introduction The etiology of and disease burden associated with incontinence in the elderly is multifactorial. We aimed to investigate the association between health literacy and cognition and urinary incontinence in a geriatric inpatient population transitioning to a skilled nursing facility (SNF). Methods Health literacy, depression and cognition were assessed via the Brief Health Literacy Screen (BHLS), Geriatric Depression Scale 5-item (GDS) and Brief Interview for Mental Status (BIMS), respectively. Multivariate logistic regression controlling for demographic and clinical factors was performed to determine the association between BHLS score and incontinence by: 1) nursing report of urinary incontinence during hospitalization and 2) patient self-reported “bladder accidents� in the post-enrollment study interview. Results 1556 hospitalized patients aged 65 and older met inclusion criteria, of whom 922 (59.3%) were women and 1480 had available BHLS scores. 464/1556 (29.8%) patients had urinary incontinence by nursing report and 515 (33.1%) by patient report. On average, incontinent patients by nursing report were older (p<0.001) and had higher GDS scores (p<0.001), fewer years of education (p=0.034) and lower BHLS (8.8 vs. 10.9, p<0.001) and BIMS scores (12.2 vs. 13.6, p<0.001) relative to continent patients. On multivariate analysis, nursing-reported incontinence was significantly associated with lower BHLS (i.e. poorer health literacy) (OR 0.93, 95% CI 0.89-0.99) and BIMS (i.e. poorer cognition) (OR 0.90, 95% CI 0.83-0.97) total scores and need for assistance with toileting (OR 7.08, 95% CI 2.16-23.21). Patient-reported incontinence was significantly associated with female sex (OR 1.62, 95% CI 1.19-2.21), increased GDS score (i.e. greater likelihood of depression) (OR 1.22, 95% CI 1.10-1.36) and need for assistance with toileting (OR 2.46, 95% CI 1.26-4.79). Nursing and patient-reported incontinence were discordant in 25.8% of patients. Conclusions Poorer health literacy and cognition are independently associated with an increased likelihood of nursing-reported urinary incontinence among geriatric inpatients transitioning to a SNF. Practitioners should consider routine assessment of health literacy and cognition in frail patients at risk for urinary incontinence and consider that both patient and nursing assessment may be required to capture the diagnosis. Funding Department of Health and Human Services Centers for Medicare & Medicaid Services Grant #1C1CMS331006
Authors
Joshua Cohn
Avantika Shah Sandra Simmons Kathryn Goggins Sunil Kripalani Roger Dmochowski John Schnelle W. Stuart Reynolds |
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MP31-11 |
Novel Oral Therapy for Interstitial Cystitis/Painful bladder syndrome |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Non-neurogenic Voiding Dysfunction I | 17BOS |
Abstract: MP31-11 Sources of Funding: A Stanford institutional grant, SPARK, was awarded for completing this research Introduction Interstitial cystitis (IC) is a chronic disease, characterized by varying degrees of painful and frequent urination, which likely occurs due to a variety of etiologic factors acting through multiple pathogenic mechanisms. Although this chronic and painful condition affects up to 1% of women, there are few effective treatments. One hypothesized pathophysiologic mechanism involves thinning and dysfunction of the bladder endothelium and glycosaminoglycan (GAG) layer, leading to altered bladder epithelial permeability, migration of urinary solutes into the bladder interstitium and ultimately bladder pain and reduced bladder capacity. Pioglitazone has been shown in previous murine studies to increase bladder mucosal cell proliferation when given systemically. For patients with IC, where decreased mucosal cell proliferation is a likely etiologic factor in the disease process, this effect may prove therapeutic. Methods Using a previously described animal model for IC, 6-week-old female Sprague-Dawley rats were treated with biweekly cyclophosphamide injections (35mg/kg) to induce cystitis. Animals were divided into 4 groups (n=6): IC plus daily sham saline gavage (IC), IC plus daily pioglitazone gavage (150mg/kg) (IC+P), normal rats with daily pioglitazone (PIO), and normal rats with neither IC nor pioglitazone (CTRL). At the end of four weeks, urinary frequency was measured via counting spots on filter paper, and bladder capacity was measured cystometrically. Histologic examination was also performed, after embedding the excised bladders in paraffin, staining with haematoxylin and eosin (H&E), PAS and with Mason’s trichrome stain. Slides were reviewed in a blinded fashion by a pathologist for inflammation, bladder wall thickness, collagen deposition, and local tissue structure. Results On voiding paper tests, average voids per hour were: IC rats 10 +/- 2.44 , IC+P 4 +/-1.87, PIO 6 +/- 1.41, and CTRL voided 6 times/hour+/- 1.52. Comparison between IC and IC+P groups using students T-test showed a significant difference in voids/hour (P<.01). On cytometry, bladder volumes were significantly higher in IC+P versus IC (0.945 +/-0.122 ml vs 0.588 +/-0.165 ml s., P=.01) Control capacities averaged 0.82 +/- 0.20 ml and PIO capacities were similar at 0.94 +/-0.19ml. On histology, a diminished glycosaminoglycan layer was appreciated on cystitis bladders, and this effect was mitigated, though not resolved, in the treatment group. Conclusions Pioglitazone improved bladder function in rats with cyclophosphamide-induced cystitis with respect to both observed urinary frequency and measured cystometric capacity. Pioglitazone and other PPAR-gamma agonists, due to their propensity to cause bladder mucosal proliferation, may prove to be useful for treating interstitial cystitis, and deserve further study. Funding A Stanford institutional grant, SPARK, was awarded for completing this research
Authors
Amandeep Mahal
Amy Dobberfuhl Craig Comiter |
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MP31-12 |
Prevalence and predictive factors of de novo detrusor underactivity after robot-assisted radical prostatectomy |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Non-neurogenic Voiding Dysfunction I | 17BOS |
Abstract: MP31-12 Sources of Funding: none Introduction Radical prostatectomy (RP) damages the anatomical and functional structure of bladder and consequently induces postoperative not only urinary incontinence but also impaired detrusor contractility. The reported prevalence of detrusor underactivity (DU) after retropubic RP (RRP) ranges from 25% to 34%, but the incidence and predictive factors of de novo DU after RRP has remained unknown. This prospective study compares urodynamic parameters and detrusor function in patients before and one month after undergoing robot-assisted RP (RARP) and determines the prevalence and predictive factors of de novo DU arising in patients during the early postoperative period after RARP. Methods Urodynamic parameters were compared before and one month after RARP in 63 patients (mean age, 66.8 ± 4.7 years). DU was defined as a maximum flow rate (Qmax) of ≤ 15 mL/s and detrusor pressure at Qmax (PdetQmax) ≤ 25 cmH20 during attempted voiding. The incidence of pre- and post-operative DU was initially assessed and then predictive factors of postoperative DU were determined using univariate and multivariate logistic regression analyses. The factors comprised patient characteristics (age, body mass index, prostate volume, etc.), operative factors (surgical duration, estimated blood loss, nerve-sparing, etc.) and pre-operative urodynamic study (UDS) parameters (maximum bladder capacity, bladder compliance, detrusor overactivity, Qmax, PdetQmax, bladder contractile index (BCI), etc.). Results Preoperative and postoperative DU at one month after RARP were detected in one (1.6%) and 24 (37.5%) patients, respectively. Univariate analysis selected preoperative Qmax (p = 0.02), PdetQmax (p = 0.04) and BCI (p < 0.01) as predictors of postoperative DU (univariate odds ratios; 0.83, 0.97 and 0.94, respectively). Multivariate analyses of factors identified as significant in univariate analyses associated only preoperative BCI with postoperative DU (p < 0.01; multivariate odds ratio: 0.94). A cutoff value of 101.3 offered the optimal accuracy in receiver operating characteristics analysis. Patient characteristics and operative factors were not significantly associated with postoperative DU in both univariate and multivariate analyses. Conclusions A comparatively high prevalence of de novo DU was observed in patients at 1 month after RARP bladder, which may have been due to bladder denervation during surgery. Preoperative BCI is the most important factor for predicting early postoperative DU after RARP. Funding none
Authors
Junya Hata
Kanako Matsuoka Yuichi Sato Hidenori Akaihata Masao Kataoka Soichiro Ogawa Nobuhiro Haga Kei Ishibashi Ken Aikawa Yoshiyuki Kojima |
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MP31-13 |
Does 3-Volt Motor Provocation during Sacral Neuromodulation Improve Clinical Outcome for OBS and Urinary Retention? |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Non-neurogenic Voiding Dysfunction I | 17BOS |
Abstract: MP31-13 Sources of Funding: None Introduction Will attainment of 3-volts motor provocation [MP] during Stage 1 sacral neuromodulation [SNM] tine lead placement result in a better clinical outcome with overactive bladder symptoms [OBS] or urinary retention [UR] symptoms in women? _x000D_ Methods We conducted an observational, retrospective quadruple cohort review of 339 female patients who between January 2002 and January 2014 underwent Stage 1 and Stage 2 SNM; Group A [174 women with MP 3-volts], Group B [110 women with MP ?4-volts] both with medically recalcitrant overactive bladder symptoms, Group C [33 women with MP 3-volts], Group D [22 women MP ?4- volts] both the latter with non-obstructive urinary retention. Success rate was defined as a ?50% improvement in voiding parameters, Urinary Distress Inventory-6 [UDI-6], Incontinence Impact Questionnaire-7 [IIQ-7] and a PVR <100 mls. All study participants were fully ambulatory, with an anesthetic risk score of 3 or less [range 0-5], and had no neurological disease or had received chemotherapy/ radiation therapy. All four cohorts did not differ in clinical and demographic information. Patients had pre-and post-operative values obtained from 72-hour voiding diaries for frequency, urgency, urgency incontinence, nocturia, reprogramming sessions, post-void residual urine, Likert scores, UDI-6 and IIQ-7 scores._x000D_ _x000D_ Results Mean follow-up in months were Group A, 116.3±30.3 and Group B, 112±34.6 [p<0.354], Group C, 150.5±20.4 and Group D, 145.8±17.2 [p<0.38]. Patients with one or leads at 3-volts performed statistically better with improvements to Stage 1 to Stage 2 Conversion Rate-Group A, 93.5 % versus Group B, 72.3% [p<0.001] and Group C, 94% versus Group D, 70% [p<0.001]. Success rate at follow-up. Group A, 82.1% versus Group B, 63% [p<0.001], Group C, 85% versus Group D 72.9% [p=0.32, too small sample for significance]. Most voiding parameters, Likert and UDI-6, IIQ-7 scores and reduced reprogramming sessions were statistically significantly improved for Group’s A and C versus Group B and D with a range of p<0.02 to p<0.001. Amongst Group A and C the attainment of multiple leads at 3, 2, or 1 volts imparted no statistically significant improvement regarding all voiding parameters._x000D_ Conclusions Our straight-forward surgical technical modification to motor provocation at 3 volts may impart a statistically significant improvement in the long-term to most voiding, Likert, UDI-6 and IIQ-7 scoring parameters for both OBS and UR. Controlled trials should be recommended to confirm our results. _x000D_ Funding None
Authors
serge Marinkovic
Joseph Ford |
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MP31-14 |
Imbalance between matrix etalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) contributes to increased fibrosis of bladder in long-term diabetic rats |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Non-neurogenic Voiding Dysfunction I | 17BOS |
Abstract: MP31-14 Sources of Funding: NIH NIDDK 1R01 DK110567-01 Introduction Diabetes induces time-dependent structural and functional alterations in the urinary bladder. We have reported the actual collagen component did not change significantly in bladder of rats in the early stage of diabetes (>9 weeks after diabetes induction), but decreased as a percentage of the total tissue. This change may be related to the increased bladder compliance in rats with diabetes. However, no data is available in the long-term effects of diabetes on bladder structure. This study aimed to characterize bladder morphology in long-term diabetic rats, and to determine the potential mechanisms. Methods Streptozotocin was used to induce diabetes in 8 weeks old male Sprague-Dawley rats, while age-matched control rats received vehicle (citrate buffer) only. Forty-four weeks after diabetes induction, bladders were harvested for morphological and molecular biological analysis. The bladder was sectioned at the equatorial midline. Masson&[prime]s Trichrome staining was performed. The stained slides were scanned, and the images were analyzed with Image-Pro Plus 5.1 image analysis software. The expression of collagen I, elastin, transforming growth factor beta-1 (TGF-β1), matrix metalloproteinase-1 (MMP-1), and tissue inhibitor of metalloproteinase-1 (TIMP-1) in bladder was examined by immunoblotting. For comparison between control and diabetic group, two-tailed t-test was used. A P-value less than 0.05 was considered statistically significant. Results Masson&[prime]s Trichrome staining and morphometrical analysis revealed increased deposition of collagen in lamina propria and among detrusor muscle fibers in diabetic rats, compared with controls. The results from the immunoblotting demonstrated significantly higher collagen I but lower elastin expression in diabetic bladders compared with that in controls. Diabetic rats displayed a marked increase in the protein expression of TGF-β1. This was associated with imbalance of the extracellular matrix turnover markers in diabetic bladders, evidenced by downregulation of MMP-1, along with upregulation of TIMP-1. Conclusions Our study demonstrated that long-term diabetes can induce increased fibrosis in bladder in rats, likely due to the upregulation of TGF-β1 and dysregulation of MMP-1/TIMP-1 system. These changes may contribute to the bladder dysfunction in the late stage of diabetes. Funding NIH NIDDK 1R01 DK110567-01
Authors
Rania Elrashidy
Zhenqun Xu Firouz Daneshgari Guiming Liu |
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MP31-15 |
A new approach to measuring detrusor contraction pattern change after radical prostatectomy |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Non-neurogenic Voiding Dysfunction I | 17BOS |
Abstract: MP31-15 Sources of Funding: none Introduction Pressure flow studies (PFS) have been regarded as the gold standard for evaluating bladder function. We previously reported that radical prostatectomy (RP) restore the detrusor contractility of prostate cancer patients. However, precise changes of detrusor contraction pattern remain to be completely elucidated. The most widely used measurement of bladder contractility is the Watts factor (WF). WF was calculated throughout bladder emptying and plotted as a function of the volume of liquid in the bladder at each moment in time. Impaired bladder contraction represent not only decreased the peak of WF, but also poorly sustained contractions. From this point of view, the maximum height of the resulting curve (Wmax) and its pattern should be discussed separately. In the present study, we focused on the detrusor contraction pattern using pressure flow study parameters. Methods In the present study, we calculated the percentage of when reach the peak of WF (Wmax%) and Area under the curve of throughout the voiding cycle (WF-AUC) (figure). WF curves allow detrusor contraction power to be visualized throughout the entire duration of micturition. Wmax% and WF-AUC could represent the pattern of detrusor contractility. _x000D_ Thirty seven patients with clinically localized prostate cancer who were urodynamically evaluated pre and post RP. The urodynamic parameters included the maximum flow rate (Qmax), postvoid residual volume (PVR), Wmax, Wmax% and WF-AUC were examined._x000D_ Results Qmax increased significantly after RP (13.0&[rarr]17.3 ml/min, P<0.01). PVR significantly decreased (49.6&[rarr]31.4 ml, P<0.05). Although Wmax did not changed significantly (10.5&[rarr]11.0 W/m2), Wmax% and WF-AUC was increased significantly (51.6&[rarr]80.1, P<0.01 and 7714.0&[rarr]12115.8, P<0.05). Wmax is a measure of detrusor contraction strength at a single point in time, whereas Wmax% and WF-AUC can confirm the improvement of detrusor contraction throughout micturition to assess overall detrusor contractility. Conclusions Our study confirmed that RP change the detrusor contractility pattern of prostate cancer patients. The measurement of Wmax% and WF-AUC provides new approach to the bladder contraction sustainability. Funding none
Authors
Takeya Kitta
Yukiko Kanno Mifuka Ouchi Kimihiko Moriya Satoru Maruyama Takashige Abe Nobuo Shinohara |
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MP31-16 |
CONCOMITANT OVERACTIVE BLADDER MEDICATION USAGE AFTER SACRAL NEUROMODULATION IMPLANT |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Non-neurogenic Voiding Dysfunction I | 17BOS |
Abstract: MP31-16 Sources of Funding: This study was sponsored by Medtronic Introduction This analysis aims to describe the use of concomitant overactive bladder (OAB) medications following implant of the sacral neuromodulation (SNM) InterStim® system. Subjects with bothersome symptoms of OAB including urinary urge incontinence (UI) or urgency-frequency (UF), who had not exhausted all medication options (failed at least 1 anticholinergic medication and had at least 1 medication not tried) were included in the InSite study. Methods Subjects were restricted from taking OAB medications for the first 6 months post-implant. Concomitant use of OAB medications was allowed after 6 months. At each visit, data were collected on OAB medications used since previous visit. The number of implanted subjects who used any concomitant OAB medication post-implant is summarized by medication type. Baseline characteristics were compared between implanted subjects with and without concomitant OAB medication use during any time between implant and 5-years follow-up. Logistic regression was used to assess the effect of concomitant OAB medication use on 5-year therapeutic success in UI and UF subjects respectively. Results Of 272 subjects that were implanted, 91% were female and the mean age was 57 years. A total of 73 subjects used any concomitant OAB medications between 6 months and 5 years post implant; the most commonly used medications were mirabegron, oxybutynin, and solifenacin. At baseline, subjects qualified more frequently as both UI and UF in the group with concomitant OAB medication use vs. the group with no concomitant OAB medication (54% vs. 44%, p=0.0479), and subjects with concomitant OAB medication use were older (mean age of 60.5 vs 55.6, p=0.0163). When assessing the effect of concomitant OAB medications use on therapeutic response with baseline characteristics and test stimulation response adjusted, UI subjects were less likely to have 5-year therapeutic success if they had concomitant OAB medication use compared to those who didn't (Odds Ratio=0.28, 95% Confidence Interval 0.10-0.80, p=0.0171). No relationship between concomitant OAB medication use and UF therapeutic response was observed. Conclusions This result shows that a small portion of subjects implanted with InterStim use concomitant OAB medications post implant. However, the presence of OAB medications after implant does not improve long term therapeutic success. In UI subjects, the association between concomitant OAB medication use and poorer long term therapeutic success might indicate that a subset of subjects with symptoms remain refractory even with addition of OAB medications. Funding This study was sponsored by Medtronic
Authors
Karen Noblett
Jeffrey Mangel Craig Comiter Samuel Zylstra Erin T. Bird Tomas L. Griebling Daniel Culkin Suzette E. Sutherland Kellie Berg Fangyu Kan Steven Siegel |
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MP31-17 |
Sex specific response of GABAB receptor inhibition during tibial and pudendal neuromodulation of bladder overactivity in cats |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Non-neurogenic Voiding Dysfunction I | 17BOS |
Abstract: MP31-17 Sources of Funding: National Institutes of Diabetes, Digestive and Kidney Diseases under Grants DK-094905, DK-102427, and DK-091253. Introduction Tibial and pudendal nerve stimulation (TNS and PNS) have been shown to be effective in the management of overactive bladder (OAB). Substantial questions about their mechanisms of action remain. In prior studies, baclofen (GABAB receptor agonist) has been shown to induce both spinal and supraspinal inhibition of micturition. We hypothesized that tibial or pudendal neuromodulation activates GABAB to inhibit bladder overactivity. CGP52432 (a GABAB receptor antagonist) was administered to cats after inducing bladder overactivity to evaluate its ability to extinguish the inhibition of TNS and PNS. Methods OAB was induced by performing serial cystometrograms (CMGs) with 0.5% acetic acid. The pudendal or tibial nerves (10 cats in each group divided equally within groups by sex) were isolated and stimulated (5Hz, 0.2ms) at 2 and 4 times threshold (2T or 4T) to produce an anal or hindlimb reflex respectively. CMGs during TNS and PNS were repeated to determine a new control capacity. Increasing doses of CGP52432 were then administered intravenously. CMGs were repeated at 2T and 4T to evaluate the ability of GABAB blockade to extinguish the increase in bladder capacity produced by TNS and PNS. Results TNS and PNS inhibited bladder overactivity induced by AA irritation and significantly (p<0.05) increased bladder capacity. TNS increased capacity to 173.8±16.2% and 198.5±24.1% of control capacity at 2T and 4T and PNS increased capacity to 217±18.8% and 221.3±22.3%. CGP52432 at doses of 0.1- 1.0 mg/kg completely (p<0.05) removed the inhibition induced by 2T and 4T TNS in female cats but not males (Figure 1). In contrast, PNS inhibition of bladder overactivity was not abolished by CGP52432 in either female or male cats (Figure 2). Conclusions There is a sex specific response to GABAB receptors inhibition in tibial but not pudendal neuromodulation of OAB. This data supports a GABAB receptor dependent mechanism for tibial neuromodulation of bladder overactivity in female animals. Funding National Institutes of Diabetes, Digestive and Kidney Diseases under Grants DK-094905, DK-102427, and DK-091253.
Authors
Thomas Fuller
Xuewen Jiang Utsav Bansal Vladamir Lamm Bing Shen Jicheng Wang James Roppolo William DeGroat Changfeng Tai |
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MP31-18 |
Spinal Cord Stimulation Attenuates Visceral Pain-Related Visceromotor Reflexes in Rodents with Cyclophosphamide-Induced Cystitis |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Non-neurogenic Voiding Dysfunction I | 17BOS |
Abstract: MP31-18 Sources of Funding: Supported by NIH (R01 DK106181) to HH Chang. Introduction Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic inflammation that results in recurring pain in the bladder and the surrounding pelvic region caused by abnormal excitability of micturition reflexes. Spinal cord stimulation (SCS) is currently in clinical use for the attenuation of neuropathic pain, and has been identified for amelioration of pain in a rodent model of colorectal distention. This study aimed to investigate the potential effect of SCS on attenuation of visceral pain-related visceromotor reflexes (VMR) in rodents with cyclophosphamide-induced cystitis. Methods Female Sprague-Dawley rats underwent intraperitoneal injection of cyclophosphamide (CYP, n=8) or saline (controls, n=4). 48 hours after CYP or saline injections, all rats underwent surgical preparations under urethane anesthesia. Stimulation wires were placed on the dorsal surface of the spinal segments of L2 and L3 for SCS. A PE-50 tubing was inserted into the bladder to obtain the intravesical pressure (IVP). Two wires are placed in the left external abdominal oblique muscle to record VMR. Before and after SCS (40 Hz, 0.2 ms for 25 min), VMR and maximum intravesical pressure (IVPmax) were obtained during continuous bladder infusion and isotonic bladder distention (IBD). Results During continuous bladder infusion (Fig 1A), the ratio of VMR threshold/IVPmax was significantly decreased in CYP rats indicating early VMR appearance compared to controls. SCS significantly increased the ratio indicating the delayed VMR appearance. During IBD with urethral occlusion, SCS delayed the latency of VMR appearance in CYP rats below the voiding thresholds at 10 and 20 cmH2O. SCS also significantly decreased VMR area under the curve (AUC) in CYP rats (Figs 1B-C). Conclusions SCS attenuated visceral pain-related VMR in rats with CYP-induced cystitis suggesting a role for SCS in modulating visceral nociception and hyperalgesia. SCS appears to be a potential treatment of IC/PBS. Funding Supported by NIH (R01 DK106181) to HH Chang.
Authors
Jih-Chao Yeh
David A Ginsberg Larissa V Rodriguez Huiyi Harriet Chang |
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MP31-19 |
SYMPTOMATIC OVERLAP IN OVERACTIVE BLADDER AND INTERSTITIAL CYSTITIS/PAINFUL BLADDER SYNDROME |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Non-neurogenic Voiding Dysfunction I | 17BOS |
Abstract: MP31-19 Sources of Funding: none Introduction While bladder hypersensitivity syndromes (BHS), such as overactive bladder (OAB) and interstitial cystitis/painful bladder syndrome (IC/PBS), classically exhibit the predominant symptoms of urgency and bladder pain, respectively, there is considerable symptom overlap between the conditions. Given this finding, we sought to define the fundamental features of each syndrome and refine diagnostic criteria through retrospective comparison of self-reported symptoms in female patients with a range of clinical presentations and symptom severities. Methods We performed univariate analysis comparing responses to the Genitourinary Pain Index (GUPI), OAB Questionnaire (OABq) and O’Leary-Sant Indices (ICSI/ICPI) between 26 asymptomatic, 42 IC/PBS, and 27 OAB patients. Only five specific questions differed significantly between the IC/PBS and OAB groups, which assessed either urgency incontinence or bladder pain with filling. We used these questions to generate a novel composite scoring system with urgency incontinence (UI) and bladder pain (BP) domains to differentiate these populations. Results While all validated questionnaires could distinguish between controls and BHS, no composite symptom scores differed significantly between the IC/PBS and OAB patients (Figure 1A). Only the GUPI Pain Domain was significantly different between OAB and IC/PBS patients, but was not useful for diagnostic evaluation, resulting in a Positive Predictive Value (PPV) of only 56-60% for a range of cutoffs. Our composite score gave a PPV of 100% and Negative Predictive Value (NPV) of 85% for a diagnosis of IC/PBS, as well as a PPV of 90% and NPV of 53% for a diagnosis of OAB (Figure 1B). These results are reflective of the prevalence of significant bladder pain (35%) in OAB patients and the presence of incontinence in IC/PBS patients. Conclusions The significant overlap of urinary tract symptoms between OAB and IC/PBS suggests common pathological elements. Future studies aimed at assessing the diagnostic value of novel classification schemes that address symptoms rather than specific diagnoses may improve patient prognosis. Regardless, these data suggest a new paradigm for how we approach BHS. Funding none
Authors
A. Lenore Ackerman
H. Henry Lai Karyn Eilber Jennifer Anger |
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MP31-20 |
Correlation between symptom severity and bother in patients with lower urinary tract symptoms |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Non-neurogenic Voiding Dysfunction I | 17BOS |
Abstract: MP31-20 Sources of Funding: Institute for Bladder and Prostate Research Introduction In the absence of bother, most treatment algorithms for lower urinary tract symptoms (LUTS) recommend reassurance and follow-up. The assumptions behind this recommendation are that 1) if the symptoms are not bothersome, the underlying condition is not serious enough to warrant further investigation, and 2) the worse the symptoms, the greater a patient will be bothered by those symptoms. The aim of this study is to evaluate these hypotheses. Methods This is an IRB approved retrospective multicenter study of consecutive men and women referred for LUTS who completed the LUTS symptom score (LUTSS) and/or AUA symptom score (AUASS) questionnaires. For those with more than one entry, the earliest score was used. Contemporaneous uroflow (Q), post-void residual (PVR), Patient Global Impression of Improvement (PGII), and clinical diagnosis were gathered when available. When more than one Q or PVR was available, the best one - greatest Q and lowest PVR - was used. Voided volumes <150 mL were excluded. Spearman correlations were calculated on the LUTSS bother score. Results 1179 patients completed the LUTSS; correlations are seen in table 1. The overall correlation between total LUTSS and bother was moderate (plot 1). It was considerably lower among those who rated their improvement &[Prime]worse&[Prime] than &[Prime]about the same&[Prime] (r=0.24 vs 0.67). Among specific symptom subscores, the correlation between the relevant subscore and bother was fairly low (r=0.34-0.61). No correlation was found between Q or PVR versus bother or versus total LUTSS. Conclusions The correlation between patient bother, symptom severity and the severity of the underlying LUT condition is inexact. Additionally, there is no correlation between Q, PVR and symptom severity. Some patients with little bother and few symptoms have serious underlying conditions; others are bothered severely by what appear to be minor symptoms. Funding Institute for Bladder and Prostate Research
Authors
Jerry G Blaivas
Lucas J Policastro Zahava M Hirsch Amy L O'Boyle David Chaikin |
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MP32-01 |
Prostate Biopsy Payments to Ambulatory Surgery Centers Stable as Physician Reimbursement Falls: Summary of Medicare Reimbursement 2012 – 2014 |
General & Epidemiological Trends & Socioeconomics: Value of Care: Cost and Outcomes Measures II | 17BOS |
Abstract: MP32-01 Sources of Funding: Emory Urology Research Scholars Grant; Winship Cancer Institute Prostate Cancer Pilot Grant Introduction Since the United States Preventative Services Task Force recommended against routine prostate-specific antigen screening in 2012, the incidence of prostate biopsies has dropped substantially. In addition, Medicare decreased reimbursement for ultrasound-guidance for biopsies (Common Procedural Terminology (CPT) code 76942) in 2014. In that context, we examined how Medicare reimbursement for ultrasound-guided prostate biopsies allocated to physicians and ambulatory surgery centers (ASC) changed from 2012 through 2014. Methods Using publically available Medicare Provider Utilization and Payment Data (2012-2014), we assessed use of and Medicare payments for transrectal ultrasound-guided prostate biopsy (i.e., CPT codes 55700, 76842, 76972) for men with fee-for-service Medicare Part B coverage. We report average and total payments for (a) providers and (b) ASCs and trends from 2012 through 2014. Results From 2012-2014, we identified 359,698 biopsies performed for men with Part B fee-for-service Medicare coverage. Medicare expenditures were $134.5 million ($111.4 million to physicians, 82.8%; $23.1 million to ASCs, 17.2%). Between 2012 and 2014, Medicare payments for prostate biopsies declined by $20.3 million for physicians and only $0.4 million for ASCs. The decline in payments to physicians was due to a 20.4% decline in volume combined with a decline in the median reimbursement per procedure ($405 in 2012 to $273 in 2014, p<0.001). The slight decline in payments to ASCs reflected a 7.6% decline in volume that was offset by significant increases in median payments over time ($451 in 2012 to $463 in 2014, p=0.01). Overall, the share of biopsies performed at ASCs increased from 13.5% to 15.3%, and the overall proportion of payments to ASCs increased from 14.6% to 22.4% over that same time span (Figure). Conclusions Policy changes related to prostate cancer screening and procedure-based Medicare reimbursement resulted in drastic decreases in reimbursement for prostate biopsies performed by providers, but not ASCs. These policies may have unintended consequences of diverting typically office-based procedures to more-costly ASCs. Funding Emory Urology Research Scholars Grant; Winship Cancer Institute Prostate Cancer Pilot Grant
Authors
Mark Henry
David Howard Dattatraya Patil Benjamin Davies Christopher Filson |
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MP32-02 |
Telemedicine Utilization in Pediatric Urology and Beyond |
General & Epidemiological Trends & Socioeconomics: Value of Care: Cost and Outcomes Measures II | 17BOS |
Abstract: MP32-02 Sources of Funding: None Introduction Limited research is available evaluating utilization of telemedicine (TM) in pediatric urology. The Pediatric Health Information System (PHIS) database is comprised of claims data from 49 of the largest children’s hospitals in America, providing an opportunity for analysis of the current utilization of TM in pediatric urology. Methods Clinical Transaction ClassificationTM (CTC) is a proprietary system used by PHIS to categorize hospital billing for clinical, imaging, laboratory, pharmacy, supply, and other services in which Clinical Service Code 599120 is designated for TM. The PHIS database was queried for all patients 18 years of age and younger with CTC 599120 occurring between 2009-2016 for all clinical services using TM including pediatric urology. Variables collected include patient age group, patient ethnicity, clinic subspecialty, principal diagnosis, primary source of payment, and location of clinic. The number of telemedicine episodes observed for our institution and clinic subspecialty in the PHIS database also were compared to our internal chart audit. Results Six hospitals in the United States utilized TM in a total of 670 visits with a single hospital comprising 430 (64%) of those visits. Primary diagnoses varied, with only 70/670 (10.4%) episodes comprised of urologic diagnoses such as pyelonephritis, hydronephrosis, urinary calculus, renal cyst, vesicoureteral reflux, neurogenic bladder, urinary tract infection, renal agenesis, bladder exstrophy, gross/microscopic hematuria and others. The majority of encounters 400 (60%) were performed for neonates (<30 days) with none of the other age groups comprising > 15% of the encounters. The majority of visits were performed in Caucasian patients (429, 66%) relative to other ethnicities. Medicaid was the most common primary payment method in 472 encounters (71%). Although no TM encounters were entered into the PHIS database for our institution and service code, our internal audit demonstrated 63 total encounters for our service alone. Conclusions Telemedicine appears to be an underutilized tool in pediatric urology and pediatric medicine. Incorrect application of appropriate billing codes may underestimate the actual use of telemedicine in pediatric medicine based upon our institutional experience. Further research is needed to better understand the lack of utilization of telemedicine in pediatric urology as a means to improve on the delivery of healthcare. Funding None
Authors
Stephen Canon
Ismael Zamilpa Ashay Patel Mary Marquette |
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MP32-03 |
THE DIRECT AND INDIRECT COSTS DUE TO WORK LOSS ASSOCIATED WITH OVERACTIVE BLADDER IN THE UNITED STATES |
General & Epidemiological Trends & Socioeconomics: Value of Care: Cost and Outcomes Measures II | 17BOS |
Abstract: MP32-03 Sources of Funding: Astellas Pharma, Inc paid Truven Health Analytics, an IBM Company, to carry out this research. Introduction The impact of overactive bladder (OAB) on costs due to time lost from work is not well known. The objective of this study was to quantify the direct healthcare costs and indirect costs due to work loss associated with OAB in the United States (US). Methods Adults ≥18 years of age with an OAB diagnosis or OAB prescription therapy between 1/1/2008 and 12/31/2013 were identified from the MarketScan® administrative claims databases (index date = qualifying claim date). Patients were required to have ≥12 months of pre- and ≥1 month of post-index continuous enrollment. Data on work loss due to absence and short-term disability (STD) were available for subsets of the overall study population. Each OAB cohort was propensity score-matched to an equivalent number of non-OAB controls. Estimates of total per-patient per-month (PPPM) direct healthcare costs, as well as estimates of indirect costs attributable to absence and STD were modeled using ordinary least squares regression. The level of statistical significance for all tests was set at 0.05. Results 110,059 OAB patients were identified, 9.8% of whom had work absence data and 49.3% had STD data. Average adjusted PPPM healthcare costs were significantly higher among OAB patients than non-OAB matched controls ($3,003.42 vs. $1,122.80, p<0.0001). Similarly, among patients with STD eligibility, those with OAB incurred significantly higher PPPM indirect costs attributable to STD compared to non-OAB controls ($114.23 vs. $98.31, p=0.0192) when adjusted within the framework of a two-part model. PPPM indirect costs of work loss due to absence did not differ significantly between patients with OAB and non-OAB matched control patients ($1,412.27 vs. $1,350.56, p=0.4398). Conclusions Patients with OAB incurred 2.5 times the healthcare costs of patients without OAB. OAB patients incurred more work loss and costs due to STD than non-OAB controls. Indirect costs attributable to workplace absence, however, did not differ for OAB patients and non-OAB controls. Funding Astellas Pharma, Inc paid Truven Health Analytics, an IBM Company, to carry out this research.
Authors
Emily Durden
David Walker Stephani Gray Robert Fowler Paul Juneau Katherine Gooch |
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MP32-04 |
Medicare ACO Enrollment and Appropriateness of Prostate Cancer Screening |
General & Epidemiological Trends & Socioeconomics: Value of Care: Cost and Outcomes Measures II | 17BOS |
Abstract: MP32-04 Sources of Funding: American Cancer Society (MSRG-15-103-01-CHPHS to MJR), AUA/Urology Care Foundation Rising Stars in Urology Research Program Introduction While Accountable Care Organizations (ACOs) continue to proliferate, there remain few empiric data that specifically investigate the effect of ACO enrollment on the cancer diagnosis, treatment, and survivorship. To this end, we characterize the relationship between Medicare Shared Savings Program (MSSP) enrollment and appropriateness of prostate cancer screening. Methods We built a cohort of aged Medicare beneficiaries from 2010 through 2013 comprising 17,779,120 person-years and 9,201,163 person-years before and after ACO enrollment, respectively. We characterized our exposure of interest, ACO enrollment, by identifying all MSSP-enrolled primary care providers and recapitulating published attribution strategies, and identified our outcome, PSA screening, through relevant Medicare claims. Using claims from 2006, we fit a model for 5-year overall survival and isolated the highest and lowest quintiles of predicted survival. We then performed differences-in-differences analysis specifically evaluating the interaction between ACO enrollment and the period following ACO intervention (ACO X Post) within the highest and lowest quintiles of predicted survival to characterize between-group differences in change in prostate cancer screening attributable to ACO enrollment across the spectrum of health. Results Medicare beneficiaries in the highest and lowest quintiles of predicted survival attributed to MSSP ACO-enrolled PCPs were 4.3% and 1.8% more likely to undergo PSA screening than those attributed to non-ACO primary care providers prior to deployment of the MSSP (p<0.0001 for both). MSSP enrollment was associated with excess reduction in the rate of prostate cancer screening among both appropriate candidates (highest quintile of survival) and inappropriate candidates (lowest quintile of predicted survival), with observed difference-in-difference of 0.86% and 0.67%, respectively (Figure). Conclusions ACO enrollment increases the magnitude of observed reductions in prostate cancer screening among both appropriate and inappropriate candidates for early detection. Developing and deploying incentives to target screening to appropriate candidates and withholding screening from those unlikely to benefit will be necessary to optimize early cancer detection in the era of payment innovation. Funding American Cancer Society (MSRG-15-103-01-CHPHS to MJR), AUA/Urology Care Foundation Rising Stars in Urology Research Program
Authors
Matthew Resnick
Robert Gambrel Amy Graves Mark Tyson Daniel Lee Melinda Buntin David Penson |
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MP32-05 |
Medicare ACO Enrollment and the Prevalence of Prostate Cancer Screening |
General & Epidemiological Trends & Socioeconomics: Value of Care: Cost and Outcomes Measures II | 17BOS |
Abstract: MP32-05 Sources of Funding: American Cancer Society (MSRG-15-103-01-CHPHS to MJR), AUA/Urology Care Foundation Rising Stars in Urology Research Program Introduction While Accountable Care Organizations (ACOs) continue to rapidly proliferate, there remain few empiric data that specifically evaluate the effect of ACO enrollment on the cancer diagnosis, treatment, and survivorship. To this end, we characterize the effect of early Medicare Shared Savings (MSSP) Program enrollment on the prevalence of prostate cancer screening. Methods We built a cohort of aged Medicare beneficiaries from 2010 through 2013 comprising 17,779,120 person-years and 9,201,163 person-years before and after ACO enrollment, respectively. We characterized our exposure of interest, MSSP ACO enrollment, by identifying all MSSP-enrolled primary care providers and recapitulating published attribution strategies, and identified our outcome of interest, PSA screening, through relevant Medicare claims. We subsequently performed differences-in-differences analysis specifically evaluating the interaction between ACO enrollment and the period following ACO intervention to characterize the effect of MSSP ACO enrollment on the prevalence of prostate cancer screening. Results Medicare beneficiaries attributed to MSSP ACO-enrolled primary care providers were 2.5% more likely to undergo PSA screening than those attributed to non-ACO primary care providers prior to deployment of the MSSP (p<0.0001). We observed significant reductions in the prevalence of PSA screening throughout the study period among both ACO and non-ACO groups. Nonetheless, the rate of decline in the ACO group outpaced that of the non-ACO group, with an observed difference-in-difference of 0.742% (p<0.0001). Conclusions ACO enrollment appears to significantly mediate observed reductions in the prevalence of PSA screening among Medicare beneficiaries, although the absolute magnitude of this effect is relatively small. Characterizing the potential additive effects of guideline modifications and payment reforms will be essential to predict the future landscape of prostate cancer epidemiology. Funding American Cancer Society (MSRG-15-103-01-CHPHS to MJR), AUA/Urology Care Foundation Rising Stars in Urology Research Program
Authors
Matthew Resnick
Robert Gambrel Amy Graves Mark Tyson Daniel Lee Melinda Buntin David Penson |
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MP32-06 |
Variations in Accrual and Race/Ethnicity Reporting in Urology and Non-urology Related Cancer Trials. |
General & Epidemiological Trends & Socioeconomics: Value of Care: Cost and Outcomes Measures II | 17BOS |
Abstract: MP32-06 Sources of Funding: 1. The Center for Healthy African American Men through Partnerships (CHAAMPS). NIH grant no. U54MD008620. _x000D_ _x000D_ 2. University of Minnesota Program in Health Disparities Research (PHDR)_x000D_ _x000D_ 3. Masonic Cancer Center Introduction We sought to compare if accrual difficulties are unique to urologic cancer trials compared to other solid organ tumor trials. We also sought to assess the extent to which race/ethnicity is reported in both urologic and non-urologic cancer trials. Methods We analyzed online data for all phase III/IV trials from clinicaltrials.gov and the ISRCTN registry for prostate, bladder, kidney, colorectal, breast, and lung cancer. All closed therapeutic and non-therapeutic trials between 2000-2016 were included. For the selected trials, information about accrual sufficiency, age group, allocation, funding, gender, intervention model and type, masking, organ site, primary purpose, race/ethnicity reporting, trial duration, and trial phase were collected. Accrual sufficiency and race/ethnicity reporting by cancer type was determined. Chi squared and logistic regression analyses were used to determine factors associated with accrual sufficiency and minority enrollment. Results 326/658 (49%) clinical trials identified met our selection criteria. Data from 234/326 (71.8%) of the trials were cross-verified using peer-reviewed publications. Accrual sufficiency overall was 62%, with kidney cancer reporting the highest (79%) and bladder cancer trials reporting the lowest (50%) accruals. 57% of the trials reported race and ethnicity in their analysis with lung cancer trials reporting the highest (68%) and bladder cancer trials reporting the lowest (30%). Non-urologic (77%) trials reported higher race/ethnicity reporting than urologic (23%) trials (p<0.01). Factors associated with accrual sufficiency included funding source (p=0.01) and gender (p=0.03). Government funded trials involving women were associated with better accrual. Factor associated with minority enrollment include trial phase (p=0.03). Factors associated with reporting of African-American enrollment include allocation (p=0.03), funding source (p<0.01), and intervention model (p=0.04). Government funded trials, non-randomized trials, and cross over trials were associated with higher levels of reported African American enrollment. Conclusions Clinical trial accrual is low, raising questions about the statistical validity of results from trials with incomplete accrual. Overall race/ethnicity reporting in trials remains low, specifically in urologic trials. Government funded trials appear to perform better on both these aspects. This makes it difficult to generalize results from large trials to minority populations, especially using data from industry-sponsored trials. Funding 1. The Center for Healthy African American Men through Partnerships (CHAAMPS). NIH grant no. U54MD008620. _x000D_ _x000D_ 2. University of Minnesota Program in Health Disparities Research (PHDR)_x000D_ _x000D_ 3. Masonic Cancer Center
Authors
Koushik Paul
Chap Le Badrinath Konety |
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MP32-07 |
Association between hospital accountable care organization status and readmission following cystectomy and other major surgery |
General & Epidemiological Trends & Socioeconomics: Value of Care: Cost and Outcomes Measures II | 17BOS |
Abstract: MP32-07 Sources of Funding: This work was supported by the American Cancer Society (RSG 12-323-01-CPHPS), the National Cancer Institute (R01 CA168691, R01 CA174768, T32 CA180984) and the National Institute on Aging (R01 AG048071). Introduction Readmissions after surgery lead to low value care (worse outcomes and increased costs). Accountable care organizations (ACO) are doubly incentivized to reduce readmissions through receipt of shared savings bonuses by meeting benchmarks and avoidance of penalties from readmission reduction policies. Our objective was to determine the effect of Medicare Shared Savings Program (MSSP) ACOs on readmission rates after major surgery with a focus on cystectomy. Methods We linked a 20% Medicare sample to Leavitt Partners ACO Data and performed a retrospective cohort study of patients undergoing major surgery (cystectomy, abdominal aortic aneurysm (AAA) repair, colectomy, total knee replacement, total hip replacement, lung resection) from 2010 to 2014. We stratified hospitals by MSSP ACO participation and calculated hospital level adjusted readmission and mortality rates using multivariable logistic regression models accounting for clustering within hospitals and procedures. We then performed a difference-in-differences analysis to determine the impact of ACO participation on readmission after major surgery, procedure specific readmissions and mortality rates. We compared outcomes in the pre-implementation and post-implementation periods. Results We identified 388,003 patients of whom 61,938 (16%) underwent surgery in an ACO hospital. Overall, 60% were treated in the pre-implementation period. We noted significant secular trends in the non-ACO group from pre- to post-implementation in overall readmission rate (11.0% relative decrease, p<0.001) and mortality (11.1% relative decrease, p<0.001). ACO participation had a significant effect on readmission rate, accounting for an added 7.4% relative decrease, but no effect on mortality rate (Figure A, C; difference-in-differences estimator p=0.024, p=0.25, respectively). Trends for cystectomy were not significant for readmission (Figure B) or mortality in either group. Conclusions The overall readmission and mortality rates after major surgery decreased significantly between 2010 and 2014. ACOs accounted for an additional 7.4% reduction in overall readmission rates. Our findings demonstrate a synergistic effect of ACO participation and national readmission policy on readmissions after major surgery. Funding This work was supported by the American Cancer Society (RSG 12-323-01-CPHPS), the National Cancer Institute (R01 CA168691, R01 CA174768, T32 CA180984) and the National Institute on Aging (R01 AG048071).
Authors
Tudor Borza
Mary K. Oerline Ted A. Skolarus Bruce L. Jacobs Amy N. Luckebaugh Matthew Lee Rita Jen John M. Hollingsworth Vahakn B. Shahinian Brent K. Hollenbeck |
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MP32-08 |
Accountable care organizations and the use of prostate cancer screening |
General & Epidemiological Trends & Socioeconomics: Value of Care: Cost and Outcomes Measures II | 17BOS |
Abstract: MP32-08 Sources of Funding: none Introduction Accountable Care Organizations (ACOs) were established under the Affordable Care Act as a new payment model intended to impose greater responsibility on all stakeholders for cost control and quality improvement. Preventive services are an ideal target to monitor the effectiveness of new health care delivery models. We sought to examine and compare the prevalence of breast cancer screening (BCa-S), and prostate cancer screening (PCa-S) between ACO and traditional Medicare beneficiaries. We hypothesized that the use of BCa-S is higher among beneficiaries attributed to an ACO, whereas the use of PCa-S, a non-recommended test, would be unaffected by ACO assignment. Methods Using a random 20% sample of Medicare beneficiaries, we assessed BCa-S in those aged <75, (evidence-based cancer screening), and PCa-S in those <75 (non-recommended cancer screening) between January 1, 2013 and December 31, 2013 with appropriate exclusion criteria. ACO coverage was ascertained from the quarterly assignment in the Shared Savings Program ACO Beneficiary-level file. Results Following propensity-score weighting, our final cohorts of ACO and traditional Medicare beneficiaries included, 52,987/526,063 women for BCa-S, and 86,936/814,221 men for PCa-S, respectively. The prevalence of screening in ACO vs. traditional Medicare were 35.0% vs. 25.2% for BCa-S, and 54.6% vs. 41.7% for PCa-S (all p<.001). Conclusions The ACO model appears to have a salutary effect on preventive service utilization. Our findings vis-a-vis PCa-S among ACOs are likely a reflection of improved health care access rather than vetted screening practices. There is hope that such nonrecommended screening will decrease if more ACOs are required to move towards a "two-sided" risk shared savings and loss model. Funding none
Authors
Christian P. Meyer
Anna Krasnova Jesse D. Sammon Philipp Gild Nicolas von Landenberg Stuart R. Lipsitz Joel S. Weissman Felix K.H. Chun Margit Fisch Maxine Sun Quoc-Dien Trinh |
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MP32-09 |
Patients receiving value-based care for BPH surgery do not experience worse clinical outcomes |
General & Epidemiological Trends & Socioeconomics: Value of Care: Cost and Outcomes Measures II | 17BOS |
Abstract: MP32-09 Sources of Funding: AUA Data Grant and the Urology Care Foundation Research Scholar Award Program Introduction Recent policy changes encourage a transition toward value-based care. In 2014, we implemented value-based care redesign for patients undergoing surgery for uncomplicated BPH. We defined an optimal care pathway using outcomes and cost data, guideline recommendations, and patient input. Our pathway includes TURP or plasma vaporization without preoperative cystoscopy or urodynamics. In this study, we ask whether patients treated under a value-based care pathway experience worse outcomes. Methods We reviewed records of men undergoing an episode of BPH care between April 2014 and December 2015. Only those with UCLA HMO, ACO, or those having established PPO primary care at UCLA were included. Men with coexisting complicating urological conditions were excluded. The 5 outcomes examined were 1-year reoperation, 90-day readmission, emergency department visit within 30 days, >3 clinic visits within 30 days, BPH prescription filled >30 days after surgery. Potential confounding variables included age, gland size, diabetes, neurologic disease, and preoperative catheter status. We used multivariable logistic regression to test the effect of surgery type and the use of preoperative invasive testing. Results There were 225 men with complete data. Fifty-seven men (23%) had diabetes and 73 (29%) used indwelling or intermittent catheter prior to surgery. TURP or plasma vaporizaton was performed in 187 (74%) patients and 145 (58%) underwent preoperative invasive testing (cystoscopy or urodynamics). Patients receiving preoperative invasive testing were more likely to have >3 clinic visits within 30 days (OR 3.7, p=0.005); analyses entering cystoscopy and urodynamics as individual variables shows this attributable to cystoscopy (OR 3.1, p=0.004). There were no other differences in outcomes among those receiving value-based care. Men with neurologic disease and those undergoing laser vaporization were more likely to fill a BPH medication prescription after surgery (OR 2.8, p=0.009 and OR 2.5, p=0.04, respectively). Men >70 were more likely to visit the emergency department (OR 4.7, p=0.004). Conclusions Men with uncomplicated BPH receiving value-based surgical care were more likely to avoid certain negative outcomes. While these data validate our a priori hypothesis, we continue to measure clinical outcomes using near real time data extraction and analysis. Iterative evaluation of processes and outcomes are crucial in implementing value-based care models. A limitation is lack of IPSS data. Further studies may elucidate whether these findings apply in other settings. Funding AUA Data Grant and the Urology Care Foundation Research Scholar Award Program
Authors
Alan L Kaplan
Vishnukamal Golla Catherine M. Crespi Jamal Nabhani Mark S. Litwin Christopher Saigal |
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MP32-10 |
Variations in the patient experience at an academic urology department: how survey results drive likelihood to recommend metrics |
General & Epidemiological Trends & Socioeconomics: Value of Care: Cost and Outcomes Measures II | 17BOS |
Abstract: MP32-10 Sources of Funding: none Introduction Results from patient experience surveys are an important metric of quality and patient centered care. CMS is also publicly reporting these scores and has tied them to hospital and physician reimbursement as part of its Quality Payment Program. Improvements in patient satisfaction have also been correlated with improved adherence and health outcomes for patients. Understanding the many factors that drive positive survey responses will help focus efforts for improving patient satisfaction and care. Methods De-identified patient surveys results collected by a third-party company after outpatient clinic visits over a 4 year period were assessed. Our outcome of interest was a "top" score on any survey question, which was defined as the highest/best possible positive response. Overall scores and individual question scores were assessed. Likelihood to recommend (LTR) scores at the department and individual surgeon level were also analyzed. The association between individual question response and LTR responses were assessed using regression analyses. Results Included were 39,662 individual question responses (3,428 unique patient surveys) corresponding to 11 surgeons collected from 2013-2016. The overall percentage of "top" score responses for all questions was 79.3%. Physician level results and variation are listed in Table 1. Overall, 81.8% and 80.5% of responses were "top" for LTR doctor and LTR practice, respectively (Table 2). Of the 10 unique questions asked, 4 had significant individual associations with a "top" LTR doctor response and 2 for LTR practice (Table 2) indicating greater likelihood of a LTR response if these criteria were fulfilled according to the patient. Conclusions There is moderate physician-level variation among patient survey responses. Certain factors, such as "time spent with doctor" and "confidence in the doctor", align more strongly than others with a "top" LTR response. Focusing attention on improving these aspects of care may improve survey response scores and patient satisfaction. Funding none
Authors
Richard Matulewicz
Kalen Rimar Kent Perry Edward Schaeffer |
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MP32-11 |
The impact of the Choosing Wisely campaign on low value urologic practises |
General & Epidemiological Trends & Socioeconomics: Value of Care: Cost and Outcomes Measures II | 17BOS |
Abstract: MP32-11 Sources of Funding: AUA Data Services Grant 2015 Introduction The Choosing Wisely campaign was developed to reduce low value care practices. Specific (and overlapping) recommendations were released by both the American Urologic Association (in 2013), and the Canadian Urologic Association (CUA, in 2014), however the ability of this campaign to change physician behavior is unknown. The objective of this study was to determine if there was an increase in testosterone testing prior to supplementation, and a decrease in the use of Bone Scans in the evaluation of low risk prostate cancer patients, in accordance with the recommendations. Methods Several valid and reliable administrative data sources from Ontario, Canada were used. First, a cohort of men ≥66 years of age who received their first prescription for testosterone supplementation between April 2008 to March 2016 were identified. The primary outcome was the proportion of men undergoing a serum testosterone level in the 90 days prior to their prescription. Second, a cohort of men with a new diagnosis of prostate cancer between April 2008 and July 2015 were identified. The primary outcome was the proportion of men undergoing a Bone Scan 90 days after prostate cancer diagnosis. Piece-wise linear regression was used to evaluate for a significant change after the intervention date of November 2014 (date of CUA Choosing Wisely Campaign). Medians and interquartile range (IQR) are reported. Results We identified 11,496 men who had their initial prescription for testosterone filled during the specified time period. The median age was 71 (IQR 68-76), and the majority of prescriptions were provided by family physicians (66%). At the beginning of the study period, serum testosterone measured in an estimated 43% of men, and this increased in the pre-intervention time period by 0.2% per month; there was no significant change in this trend after Nov 2014 (p=0.27)._x000D_ _x000D_ We identified 60,209 men with a new diagnosis of prostate cancer. The median age was 67 (IQR 61-74), and approximately 2/3 were stage 1 or 2. At the beginning of the study period, bone scans were performed in an estimated 18% of men undergoing active surveillance, and this decreased by 0.05% per month in the pre-intervention time period; there was no significant change in this trend after Nov 2014 (p=0.07). _x000D_ Conclusions In Ontario, there was no evidence of a significant change in two practice patterns that were subject of the Choosing Wisely Urology recommendations. Further mechanisms for translating these and future recommendations into behavior change may be necessary. Funding AUA Data Services Grant 2015
Authors
Blayne Welk
Jennifer Winick-Ng Andrew McClure Girish Kulkarni Michael Ordon |
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MP32-12 |
Harnessing full text pathology data from the electronic health record to advance bladder cancer care – Development of a Natural Language Processing system to generate longitudinal pathology data |
General & Epidemiological Trends & Socioeconomics: Value of Care: Cost and Outcomes Measures II | 17BOS |
Abstract: MP32-12 Sources of Funding: Dept of Veterans Affairs VISN 1 Career Development Award; Conquer Cancer Foundation Career Development Award; DHMC Dept of Surgery internal Career Development Award Introduction Population-based studies to advance bladder cancer care require longitudinal pathology data that allow measurement of disease recurrence and progression. The prime data source for population-based studies has been SEER-Medicare, but SEER data is limited because pathologic information is only abstracted at time of diagnosis. We set out to obtain longitudinal pathology data by developing a natural language processing (NLP) engine to automate abstraction of important details from full text pathology reports. Methods We selected a national random sample of 600 bladder pathology reports from the Department of Veterans Affairs (VA) Corporate Data Warehouse. These reports were independently annotated by two reviewers with discrepancies resolved by a third to develop a gold standard. We used Cohen&[prime]s kappa to evaluate inter-rater reliability for histology, invasion (presence versus absence and depth), grade, and statements regarding presence of muscularis propria and of carcinoma in situ. Next, we iteratively trained, developed, and tested the NLP engine&[prime]s ability to abstract these variables from the reports. We assessed NLP performance by calculating accuracy, precision (positive predictive value), and recall (sensitivity). Results Inter-rater reliability was excellent between the two reviewers (kappa ranging from 0.82 to 0.90). NLP achieved the highest accuracy for presence of carcinoma in situ (0.98), with accuracy for histology, invasion, grade, and presence of muscularis propria ranging from 0.82 to 0.93 (Table). The most challenging variable was depth of invasion, due to the high variability in the language used to describe findings. Nevertheless, we achieved acceptable accuracy (0.82) and precision (0.79; table). Conclusions We developed an NLP engine to accurately abstract important pathologic details from full text bladder cancer pathology reports. This engine now allows for abstraction of data from tens of thousands of bladder cancer pathology reports, enabling us to develop a population-based cohort of patients with longitudinal pathology data. The resulting unique dataset will be used to examine the extent to which bladder cancer care impacts recurrence and progression of disease. Funding Dept of Veterans Affairs VISN 1 Career Development Award; Conquer Cancer Foundation Career Development Award; DHMC Dept of Surgery internal Career Development Award
Authors
Florian Schroeck
Olga Patterson Patrick Alba Scott DuVall Brenda Sirovich Douglas Robertson John Seigne Philip Goodney |
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MP32-13 |
COMPLIANCE WITH NON-MUSCLE INVASIVE BLADDER CANCER (NMIBC) GUIDELINES: AN UPDATED POPULATION-BASED ASSESSMENT OF CARE DELIVERY |
General & Epidemiological Trends & Socioeconomics: Value of Care: Cost and Outcomes Measures II | 17BOS |
Abstract: MP32-13 Sources of Funding: AUA Data Grant Introduction American Urological Association (AUA) guidelines for NMIBC management were released in 1999 and updated in 2007 and 2016. Chamie et al identified suboptimal compliance with guidelines from 1992-2002. The purpose of this study was to update this analysis and identify if dissemination of guidelines has improved urologic care delivery. In addition, we sought to develop pilot data to drive a future state-wide quality improvement initiative._x000D_ Methods We identified 865 Iowans in Surveillance, Epidemiology, and End Results (SEER)-Medicare (1992-2009) with a diagnosis of high-grade NMIBC who survived 2 years and were not treated with cystectomy or radiation therapy. Patients were assessed for compliance with guideline-based utilization of perioperative Mitomycin C, instillations, cystoscopy, cytology, and Bacillus Calmette-Guerin (BCG) during 2 years of follow-up. Results During the 2-year follow-up period, the appropriate utilization of mitomycin C perioperatively showed significant improvement, increasing from 2.5% to 28.2% between 1992-1997 to 2004-2009 (p<0.01). Individual patients received an average of 6.22 (SD: 6.46) BCG instillations, 4.89 (SD: 1.78) cystoscopies, and 1.77 (SD: 2.13) cytologies. These averages did not increase over the study period. Compliance analysis (Table 1) showed only 40% of patients received at least 1 cystoscopy, 1 cytology, and 1 BCG instillation. Significant predictors of compliance included tumor stage (Tis vs. Ta; OR: 3.0, CI 95% 1.8-5.0; p<0.01) and care at an academic cancer center (vs. non-academic; OR: 9.31, CI 95% 5.6-15.5; p<0.01). Age, gender, marital status, T1 vs. Ta and Charlson comorbidity index were not associated with compliance (all p > 0.05). Conclusions With respect to process measures of high-quality NMIBC care, the delivery of perioperative mitomycin improved over time while other care did not improve. The lack of improvement and the variability in care delivery imply that further efforts are needed to improve the dissemination and implementation of guideline-based care. Improving compliance via state-wide quality improvement initiatives, including education and outreach, represents a target for NMIBC quality improvement. Funding AUA Data Grant
Authors
Conrad Tobert
Bradley Erickson Bradley McDowell Thomas Gruca Mary Charlton Sarah Bell Kenneth Nepple |
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MP32-14 |
A Cost-Effectiveness Analysis Of Artificial Urinary Sphincter Versus AdVance Male Sling In Post Prostatectomy Stress Urinary Incontinence: A Canadian Perspective |
General & Epidemiological Trends & Socioeconomics: Value of Care: Cost and Outcomes Measures II | 17BOS |
Abstract: MP32-14 Sources of Funding: None Introduction The artificial urinary sphincter (AUS) remains the &[Prime]gold standard&[Prime] for the treatment of post prostatectomy stress urinary incontinence (PPSUI). However, in recent years, minimally invasive, less expensive sling device (AdVance) are offered as potential alternative treatments. We sought to investigate the long-term cost-utility of the AUS compared with Transobturator Retroluminal Repositioning Sling (AdVance) in the treatment of severe PPSUI. Methods A Markov model with Monte-Carlo simulation was developed to estimate the incremental cost-effectiveness ratio (ICER) of AUS vs. AdVance sling from a provincial payer perspective over a 10-year period. Probability estimates, success rates, healthcare resources and utilities were obtained from published literature when available or by expert opinion. Cost data included in this model were obtained from provincial health care insurance system and hospital data in 2016-Canadian Dollars. Results AUS Implantation had a 10-year mean total cost of $12299 (SD±3509) for 8.53 quality-adjusted life years (QALYs). On the other hand, AdVance sling had a mean total cost of $20675 (SD±12435) for 7.98 QALYs. The cost-utility analysis over a 10-year period showed that AUS becomes cost-effective when compared to AdVance sling starting the 4th year in the treatment period. The incremental cost savings of AUS over 10-year period was $8376 with an added effectiveness of 0.55 QALYs. Consequently, the AUS implementation is the dominant strategy over the AdVance sling over a 5- and 10-year time-horizon. Conclusions Although the initial cost of sling is attractive, superior long-term outcomes are demonstrated with durable high success rate of AUS in men with severe PPSUI. Hence, the AUS implementation strategy over a 10-year period time is estimated to be more economical to our health care system. More studies are needed to define utility values for health states experienced by males with PPSUI. This will enhance our ability to develop more accurate cost-utility models. Funding None
Authors
Samer Shamout
Sara Nazha Alice Dragomir Noemie Prevost Lysanne Campeau |
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MP32-15 |
Care Pathway Variation and Surgical Cost Measurement for Percutaneous Nephrolithotomy with Time-Driven Activity-Based Costing |
General & Epidemiological Trends & Socioeconomics: Value of Care: Cost and Outcomes Measures II | 17BOS |
Abstract: MP32-15 Sources of Funding: None Introduction The majority of health care cost data are based on charges or reimbursements, but these approaches fail to accurately represent the money hospitals actually spend to provide services. Time-driven activity-based costing (TDABC) provides a methodology to better understand true costs of providing a health care service and the variations in cost based on variance in timing. We applied TDABC analysis to a percutaneous nephrolithotomy (PCNL) care pathway. Methods The care pathway for PCNL was defined as the time from patient arrival to the preoperative area to discharge from post anesthesia care unit (PACU) to the hospital floor. Process maps were created with perioperative stakeholders to define the activities involved in PCNL. Stop-watch timing was performed for eleven PCNL cases. The cost rate for attending urologists was calculated using publicly available salaries and estimated capacity, additional cost rates were estimated using a ratio of the averaged salaries for each staff position. Results The activities demonstrating the greatest time variance were PACU recovery, preoperative holding, and stone clearance (214±100.3, 99±67.2 and 36±28.2 minutes respectively). The activities with the least variation were anesthesia extubation, nephrostomy tube placement and patient repositioning (13±3.9, 9±4.3, 16±6.3 minutes respectively). Total cost including disposables and overhead for the average PCNL was $5319. Preoperative care accounted for $470 (7%), intraoperative care accounted for $4351 (84%) and post-operative care accounted for $353 (9%) of the total. Thirty-seven percent of cost was attributable to disposables. Theoretical modeling with an attending performing all perioperative activities (rather than a resident) increased the human resource cost by 31%. Removing the highest time outliers from each activity reduced the cost by 21%. Conclusions Although utilizing the operative room is the most cost intensive activity for PCNL, variation exists during different phases of care. Opportunities for standardization to reduce cost is greatest in the pre- and post-operative areas. The TDABC methodology allows for estimation of true costs for PCNL and modeling of care pathway variation in order to understand health care costs and target areas for increased care value._x000D_ Funding None
Authors
Ian Metzler
Dylan Issac Manint Usawachintachit Matthew Hudnall Kazumi Taguchi David Tzou Tom Chi |
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MP32-16 |
COST IMPACT ANALYSIS OF ENHANCED RECOVERY AFTER SURGERY PROTOCOL IMPLEMENTATION IN A RADICAL CYSTECTOMY COHORT OF PATIENTS |
General & Epidemiological Trends & Socioeconomics: Value of Care: Cost and Outcomes Measures II | 17BOS |
Abstract: MP32-16 Sources of Funding: none Introduction Although an increasing body of evidence for patients undergoing radical cystectomy (RC) supports the clinical effectiveness of enhanced recovery after surgery (ERAS) programs, there is little literature regarding its cost benefit for RC. The present study aim was to analyze the implementation costs of ERAS for RC program at a tertiary, referral center. Methods A dedicated ERAS protocol was implemented in our department in July 2015. The subsequent year all consecutive patients were treated according to this protocol (ERAS group). They were compared in terms of real in-hospital charges per surgical episode with a separate pre-ERAS cohort. Mean costs per patient were compared with Wilcoxon-rank sum test and t-test, with p-value < 0.05 considered statistically significant. Results A total of 257 consecutive patients were evaluated of which 112 were ERAS patients. The median age was 70 years with no difference between the groups (p = 0.13). Median length of stay was 6 days (p = 0.748). Table 1 lists itemized in-hospital charges. The mean total charges per patient were $63,364 vs. 65,151 in the ERAS vs. pre-ERAS groups, respectively (p = 0.412). The variances between the two groups were statistically significantly different (p < 0.001). ERAS patients incurred higher medication costs ($3,505 vs. 2,796, p = 0.013). Pre-ERAS patients incurred higher supplies, treatment and miscellaneous charges (all, p < 0.05). Only 11 ERAS patients required intensive care vs. 31 pre-ERAS (p = 0.017) with no difference in cost per patient (p= 0.101). Conclusions Fewer patients in the ERAS group required intensive care. ERAS implementation did not increase overall health costs for cystectomy patients when compared to standard care. The ERAS group showed a decrease in cost variance likely due to standardization of care. ERAS elicited savings in supplies, treatment and miscellaneous costs. Funding none
Authors
Juan Chipollini
Dominic Tang Karim Hussein Sephalie Patel Rosemarie Garcia Getting Michael Poch |
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MP32-17 |
The Impact of Social Media Presence on Online Consumer Ratings and Surgical Volume among California Urologists |
General & Epidemiological Trends & Socioeconomics: Value of Care: Cost and Outcomes Measures II | 17BOS |
Abstract: MP32-17 Sources of Funding: none Introduction Urologists are increasingly using various forms of social media to promote their professional practice and attract patients. Concurrently, most patients are using consumer ratings to help select providers. We sought to determine whether social media presence is associated with higher online consumer rating scores and surgical volume among California urologists. Methods We sampled 195 California urologists rated on the ProPublica Surgeon Scorecard website. We obtained information on professional use of online social media (Facebook, Instagram, Twitter, Blog, YouTube) from 2012-2016 and defined social media presence as a binary variable (yes/no) for use of an individual platform or for use of any platform. We collected data on online consumer ratings across websites (Yelp, Healthgrades, Vitals, RateMD, UCompareHealthcare) and calculated the mean consumer rating score across all websites as an average weighted by number of reviews. We then gathered data on surgical volume for radical prostatectomy and transurethral resection of prostate (TURP) from ProPublica. We used multivariable linear regression to determine the impact of social media presence on consumer ratings and surgical volume. Results Among our sample of 195 urologists, 62 (32%) were active on some form of social media (53 YouTube, 15 Facebook, 14 Twitter, 10 Blog, 6 Instagram). In multivariable analysis, social media presence on any platform was associated with slightly higher mean consumer rating score (β coefficient 0.3, 95% CI 0.01-0.5, p=0.045). However, in models assessing the impact of individual social media platforms, only YouTube was associated with higher consumer rating score (β coefficient 0.3, 95% CI 0.0-0.5, p=0.04). In multivariable analysis, social media presence on any platform was significantly associated with prostatectomy volume (β 35.7, 95% CI 3.2-68.1, p=0.03) but not TURP. Prostatectomy volumes were most strongly associated with presence on Twitter (β coefficient 66.1, 95% CI -66.8-39.5, p=0.01) and YouTube (β coefficient 31.0, 95% CI -1.4-63.4, p=0.06). Conclusions Urologists' use of social media, especially YouTube, is associated with a modest increase in consumer ratings. Social media presence, particularly on Twitter and YouTube, is strongly associated with prostatectomy volume but not TURP. Although the majority of urologists are not currently active on social media, patients may be more inclined to endorse and choose sub-specialist urologists who post videos of their surgical technique and are actively involved in Twitter. Funding none
Authors
Justin Houman
James Weinberger Ashley Caron Joe Thum Devin Patel Timothy J. Daskivich |
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MP32-18 |
Erroneous Interpretation of Online Surgical Scorecard May Harm Patients by Increasing Willingness to Pay Out-of-Pocket Expenses for a Vanishingly Low Chance of Lowering the Postoperative Complication Risk |
General & Epidemiological Trends & Socioeconomics: Value of Care: Cost and Outcomes Measures II | 17BOS |
Abstract: MP32-18 Sources of Funding: none Introduction Several websites present estimated complication rates for individual surgeons in both the United States and Great Britain. It remains unclear how the general population may interpret these complication rates and how these sites may influence the willingness to pay out-of-pocket expenses for out-of-network surgeons. Methods We invited attendees of the 2016 Minnesota State Fair who met entry criteria, i.e. adults >18 years old, English speakers who were able to use a tablet computer, to complete our survey. Participants were presented with various screen shots from online surgeon rating websites. Participants were then asked to interpret these graphics and report complication rates or estimate the risk of complications in future operations. Some graphics displayed complications rates for one surgeon alone, while others compared/ranked multiple surgeons side-by-side. Participants were then asked to make hypothetical health care decisions, including willingness to pay out-of-pocket expenses, based on their interpretation of the graphics. Results 392 participants completed the survey from a broad geographic distribution from the upper Midwest (179 unique zip codes). Median age was 49 (Interquartile range 28-61), the female:male ratio was 3:2, 57% had completed a college or graduate degree and 85% were Caucasian vs. 15% ethnic minorities. When respondents were asked to compare/rank multiple surgeons, a large subset of respondents (n=136, 35%) drastically overestimated complication rates for some surgeons by 10 fold or more and were classified as misinterpreters. Misinterpreters were more likely to be willing to pay out of pocket expenses for a perceived &[prime]better surgeon&[prime] (odds ratio 3.4 95% CI 2.1-5.4), and were willing on average to pay $6101 for a 1 in 252 chance of lowering their risk of a postoperative complication. Misinterpreters were less likely to have graduated from college 45.6% vs. 62.5% who more accurately interpreted the data (p=0.0013). Conclusions Online surgeon rating websites that compare surgeons are often misinterpreted, particularly by those who did not graduate from college. Misinterpretation of the data may lead to patient harm by compelling patients to pay thousands of dollars of out-of-pocket expenses for an exceedingly low probability of benefit. Funding none
Authors
Christopher J Weight
Brett J Watson Lucas Labine Jacob A Albersheim-Carter Matthew T Rasmussen Daniel L Plack Badrinath R Konety |
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MP32-19 |
Cost Analysis for Initial Evaluation of Hematuria: Impact of Tele-Urology Clinics |
General & Epidemiological Trends & Socioeconomics: Value of Care: Cost and Outcomes Measures II | 17BOS |
Abstract: MP32-19 Sources of Funding: _x000D_ none Introduction The current healthcare climate demands high-quality efficient care delivered at a low cost. This study compares costs associated with tele-urology versus conventional face-to-face clinic visits for the initial outpatient evaluation of patients with hematuria. Methods We evaluated costs associated with hematuria evaluations among patients evaluated either through a tele-urology encounter by phone or in-person face-to-face clinic visit. This analysis included three main domains of costs: transportation, clinic operations (administrative, nursing and provider-related), and patient time. Transportation cost was based on data from the Veteran Transportation Services (travel distance, time, and reimbursement schedules), standard federal transportation reimbursement costs ($0.541/mile). When needed, wheelchair-dependent special mode transportation costs $130 plus $4.25/mile. Clinic operation staff cost (inclusive of 25% fringe benefits) was calculated based on hourly salary of nursing and clerical staff ($34.87 and $29.88, respectively). The total time spent by the patient for a face-to-face clinic included time for travel, parking, walking (to and from clinic), check-in and check-out, nurse's evaluation, urological evaluation by provider, laboratory time and waiting time (waiting for check-in, check-out, tests, nurse evaluation and provider evaluation). Cost of patient time was based on the Federal minimum wage of $7.25/hour. Provider time (40min) and Lab time (30min) were excluded from the comparative cost analysis since these tasks were deemed similar for both encounters. Results A total of 400 initial hematuria evaluations was studied; 300 tele-urology and 100 standard face-to-face clinic visits (controls). The distributions of micro- and gross hematuria were similar in both groups (~70:30, p=0.67). Both groups had a similar median age (63 vs 62 years, p=0.48) and similar median travel distance and time (58 vs 54 miles, p=0.19; 94 vs 82 minutes, p=0.09, respectively). The average time expended by the patient was significantly greater for face-to-face encounter compared to tele-urology (266 vs. 70 minutes, p<0.001). Exclusive of provider cost, transportation was the primary driver of cost ($83.47/encounter), followed by patient time ($32.87/encounter) and non-provider clinic staff cost ($18.68/encounter). Exclusive of provider cost, the average cost per encounter was $135.02 for face-to-face clinic and $10.95 for tele-urology (p>0.001). The cost saving associated with each tele-hematuria encounter totaled $124.07, with VA saving of $75.04 (60.5%) and patient saving of $49.03 (39.5%). Conclusions Tele-urology offers cost savings of ~$124 per encounter for the initial evaluation of hematuria compared to conventional face-to-face clinic. With 1.5 million hematuria encounters in the US annually, a nationwide implementation of tele-urology for hematuria evaluation would offer an annual cost saving in excess of $180 million. Funding _x000D_ none
Authors
Vitaly Zholudev
Dean Laganosky Ilan Safir Maggie Dear Jennifer Lindelow Brooks Goodgame James Baumgardner Dominick Vior Ralph Gary Donald Finnerty Filson Christopher Muta Issa |
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MP32-20 |
UROLOGIST PRACTICE STRUCTURE AND VALUE OF PROSTATE CANCER CARE |
General & Epidemiological Trends & Socioeconomics: Value of Care: Cost and Outcomes Measures II | 17BOS |
Abstract: MP32-20 Sources of Funding: This work was supported by research funding from the NCI (R01 CA168691) to BKH and VBS. FRS is supported by the Department of Veterans Affairs, Veterans Health Administration, VISN1 Career Development Award. Introduction Current health care reforms focused on optimizing value, higher quality of care delivered at a lower cost, are particularly relevant for prostate cancer due to its high cost in the context of wide variations in its treatment. We examined the potential impact of urologist practice structure on the value of prostate cancer care. Methods Using a 20% sample of national Medicare claims and data from the Surveillance, Epidemiology and End-Results (SEER)-Medicare linked registry, we examined spending (Medicare cohort) and quality (SEER-Medicare cohort) of prostate cancer treatment according to urologist practice type (single-specialty vs. MSG), size and ownership of an intensity modulated radiation therapy (IMRT) vault. Mixed models were used to adjust for patient differences. Results We identified 28,164 men with newly diagnosed prostate cancer treated by 6,381 urologists during our study interval (SEER cohort: 22,412 men and 2,199 urologists). We observed excess spending of $2,416 per beneficiary for large group practices compared to MSGs, and $2,770 in excess spending per beneficiary for practices with IMRT ownership compared to non-owning practices (p<0.001, Table). Adherence to all eligible quality measures was modestly better among MSGs compared to single specialty groups (20.0% adherence versus 18.2%, p=0.01) whereas there was no significant difference by ownership of IMRT (17.1% adherence in owners versus 18.9% non-owners, p=0.09). Conclusions Practices within MSGs demonstrate the lowest, whereas practices with IMRT ownership demonstrate the highest spending for prostate cancer care. Differences in quality were modest and of uncertain clinical importance, with substantial room for improvement, regardless of practice structure. Funding This work was supported by research funding from the NCI (R01 CA168691) to BKH and VBS. FRS is supported by the Department of Veterans Affairs, Veterans Health Administration, VISN1 Career Development Award.
Authors
Lindsey Herrel
Brent Hollenbeck Samuel Kaufman Phyllis Yan Tudor Borza Ted Skolarus Florian Schroeck Vahakn Shahinian |
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MP33-01 |
Similar high-grade prostate cancer detection by sextant biopsy, 12-core TRUS biopsy and MRI-targeted biopsy in the 5th screening round of the ERSPC Rotterdam |
Prostate Cancer: Detection & Screening III | 17BOS |
Abstract: MP33-01 Sources of Funding: none Introduction In a clinical setting, 12-core TRUS biopsy (12-TRUS-Bx) instead of sextant biopsy (6-TRUS-Bx) increases the low-grade (LG; Gleason 3+3) and high-grade (HG; Gleason >=3+4) prostate cancer (PCa) detection. MRI +/- target biopsy (TBx) detects less LG PCa and tends to detect more HG PCa, especially after previous negative biopsy. In this study we compare the performance of 6-TRUS-Bx vs 12-TRUS-Bx vs MRI +/- TBx in a pre-screened population-based cohort. Methods Men in the 5th screening round of the ERSPC Rotterdam (2013 – 2016) with PSA >=3.0 ng/ml received 6-TRUS-Bx or were included in the MRI side study. Men in the side study received MRI, blinded 12-TRUS-Bx and afterwards fusion target biopsy of PI-RADS >=3 lesions if present. The PCa detection rates of the 6-TRUS-Bx vs 12-TRUS-Bx vs MRI +/- TBx strategy were compared after stratification for previous biopsy. Results A total of 177 men received 6-TRUS-Bx; 158 men received MRI with 12-TRUS-Bx +/- TBx. Mean age and mean PSA were resp. 73.2 yrs (SD 1.1) and 5.1 ng/ml (SD 2.8). A total of 78/177 (44%) men who received 6-TRUS-Bx and 74/158 (47%) men who received 12-TRUS-Bx +/- TBx were biopsy naive. The rate of men with a non-suspicious MRI in the side study was 110/158 (70%)._x000D_ The HG PCa detection rates of 6-TRUS-Bx (17%), 12-TRUS-Bx (20%) and MRI +/- TBx (19%) in previously screened but biopsy naive men were comparable. The LG PCa detection rate in biopsy naive men of MRI +/- TBx (7%) was significantly lower as compared to 6-TRUS-Bx (23%) and 12-TRUS-Bx (34%). _x000D_ The HG PCa detection rates of 6-TRUS-Bx (5%), 12-TRUS-Bx (5%) and MRI +/- TBx (4%) in previously screened and biopsied (>=1 times) men were comparable. The LG PCa detection rate in previously biopsied men of 12-TRUS-Bx (24%) was significantly higher as compared to 6-TRUS-Bx (12%) and MRI +/- TBx (7%)._x000D_ Conclusions In population-based screening with multiple visits the HG PCa detection rates of 6-TRUS-Bx, 12-TRUS-Bx and MRI +/- TBx are comparable, both in biopsy naive and previously biopsied men. Only 5% of previously biopsied men harbor HG PCa at repeat biopsy, confirming the need of better risk-stratification. An MRI +/- TBx screening strategy has the potential to reduce biopsy procedures (70%) and overdiagnosis of LG PCa. Funding none
Authors
Arnout Alberts
Ivo Schoots Frank-Jan Drost Leonard Bokhorst Geert van Leenders Roy Dwarkasing Jelle Barentsz Fritz Schröder Chris Bangma Monique Roobol |
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MP33-02 |
DISADVANTAGED SOCIOECONOMIC STATUS IS STRONGLY ASSOCIATED WITH METASTATIC PROSTATE CANCER |
Prostate Cancer: Detection & Screening III | 17BOS |
Abstract: MP33-02 Sources of Funding: None Introduction Since the USPSTF recommendations against PSA screening in 2008 and 2012, there is renewed interest in focusing screening efforts towards at-risk populations in order to identify clinically significant disease. As such, defining characteristics associated with patients ultimately developing metastatic disease is valuable. Other than the well recognized association between African American race and aggressive prostate cancer (PCa), patient demographics are underexplored. We used a large hospital-based database to describe socioeconomic characteristics at diagnosis of metastatic prostate cancer. Methods The National Cancer Database (NCDB) was used to examine PCa diagnoses from 2004-2014. To minimize reporting bias, only hospitals contributing at least one case per year for the entire decade were included. Cases with clinical M1 disease were defined as metastatic. No changes to the diagnostic criteria of M1 disease were made during this time. A robust multivariate regression model was created to assess the relationship of M1 disease with included covariates: year of diagnosis, age, race, income, regional insurance and education status, Charlson-Deyo index, and PSA at diagnosis. Results A total of 1,235,869 cases of incident PCa were included, of which 49,586 (4.01%) were metastatic. The NCDB captured a declining proportion of total PCa cases in the US (cancer.org) year over year, from 68% in 2004 to 38% in 2014. Patients with no insurance or medicaid had the highest odds of bearing metastatic disease (OR 3.35 and 4.33, respectively) compared to private insurance (p < 0.001). Other factors associated with metastasis include African American race (OR 1.31, p < 0.001), more recent year of diagnosis (OR 1.12 per year vs 2004, p < 0.001), income <$38,000 (OR 1.12, compared to income >$63,000, p < 0.001) and PSA >20 at diagnosis (OR 9.37, compared to PSA < 4, p < 0.001). Conclusions Our data support well known associations of high PSA and African American race with metastatic prostate cancer. Of interest, disadvantaged socioeconomic status (low income, no insurance, medicaid) is associated with metastatic disease at initial diagnosis. In addition to patient education and selective screening, efforts must be made to address upstream issues impacting early detection in disadvantaged patients who may have suboptimal access to care. Funding None
Authors
Jared P. Schober
Kristian D. Stensland Alireza Moinzadeh Karim Hamawy David Canes |
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MP33-03 |
USPSTF FALLOUT: IS DISEASE BURDEN AT DIAGNOSIS OF METASTATIC DISEASE RISING? |
Prostate Cancer: Detection & Screening III | 17BOS |
Abstract: MP33-03 Sources of Funding: None Introduction The impact of the USPSTF on PSA screening behavior would not be expected to impact metastatic disease rates (mPCa) for several years. However a delay in diagnosis for men with prevalent mPCa might be measurable in the near term. Since PSA is a rough surrogate for disease burden, we sought to determine if the PSA at the time of diagnosis of mPCa is rising in the National Cancer Database (NCDB). Methods The NCDB was used to examine prostate cancer diagnoses from 2004-2014. To minimize reporting bias, only hospitals contributing at least one case per year for the entire decade were included. Cases with cM1 disease were defined as metastatic. PSA at initial cancer diagnosis was divided into 4 groups: 0.2-3.9, 4.0-10.0, 10.1-20, and >20 ng/ml. The ratio of mPCa compared to total PCa diagnoses were compared for each year. Descriptive statistics and a multivariate logistic regression were performed in Stata. Results The proportion of mPCa present at initial diagnosis increased over the 10-year period for every PSA group. The most significant proportional increase was observed in patients with PSA >20, from 8.5% (2004) to 22.9% (2014). The most significant rate of increase was observed after 2007 (Figure 1). On multivariate regression, PSA category was independently associated with the presence of metastatic disease at initial diagnosis (p<0.001). The percentage of patients with mPCa at initial diagnosis who had a PSA >20 was 54% in 2004 vs. 72% in 2014. Patients with a PSA <4 had a higher rate of metastatic disease at diagnosis when compared to the PSA 4-10 group. Those with PSA <4 experienced a proportional increase in mPCa from 0.92% (2004) to 2.65% (2014). _x000D_ Conclusions As expected, the presence of mPCa increases with increasing PSA, but the new finding of disproportionately more men with PSA >20 at diagnosis of mPCa in recent years is notable. We hypothesize this may represent higher disease burden at diagnosis as a near term result of USPSTF recommendations. Secondary observation of a proportionate increase in overall mPCa in the NCDB must be interpreted with caution, given that this is a registry rather than a population based dataset. Further studies are needed to elucidate if these trends equate to a greater burden of disease at diagnosis of mPCa, and whether screening behavior is causative._x000D_ _x000D_ _x000D_ Funding None
Authors
Jared P. Schober
Kristian D. Stensland Karim Hamawy Alireza Moinzadeh David Canes |
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MP33-04 |
A EIGHT-YEAR SCREENING PROGRAM IN HIGH RISK FAMILIES. NUMBER OF AFFECTED RELATIVES AND EARLY ONSET ARE ASSOCIATED WITH A HIGH RISK DETECTION. |
Prostate Cancer: Detection & Screening III | 17BOS |
Abstract: MP33-04 Sources of Funding: Programme Hospitalier de Recherche Clinique, Ligue Nationale contre le Cancer (Comité du Finistère). Introduction Familial prostate cancer (PCa) accounts for 20-25% of all cases and targeted screening is recommended in first degree relatives (FDR) of PCa patients. We aimed to support its interest by demonstrating higher risk and earlier onset in these families. Methods we obtained a serum PSA testing yearly, in a 8-year screening program, in 660 FDR (brothers or sons) aged 40-70 of PCa patients treated, between 1994-1997 in three french centers. We report here the screening results in group aged 50-70. The familial PCa status of the screening candidates, was divided in: hereditary (HR) status (3+PCa:10,6%), familial without obvious hereditary pattern (FNH) (2PCa:19%) or sporadic (1PCa:70%). Prostatic biopsies (PBx) were performed when PSA >4ng/mL, until 2002, while when PSA >2.5ng/mL thereafter. Results 315 men (mean age 58y) had the first year assessment (Table). PSA level was >4ng/ml, at least for one of the 8 assessments, for 163 men: 1) PBx diagnosed 34 PCa, 2) were negative in 43 cases, 3) were not performed in 90 cases: control of PSA < 2.5ng/ml 12/90 (13%), patient refusal 16/90 (18%), not necessary according to the FDR urologist 18/90 (20%). Positive predictive value (PPV) of PSA >4ng/ mL was high 34/77 (45%). In addition, 313 men had PSA levels >2.5 and ?4ng/mL : PBx 1) diagnosed 25 CaP, 2) were negative in 20 cases, 3) were not done in 113 cases (36%) as not indicated at that time (before 2002); PPV in this PSA range was high 25/45 (56%) ; 7 PCa (12%) were discovered in 7 FDR for PSA <2.5ng/mL in the year before diagnosis. Moreover the proportion of men with PSA >4ng/ml was significantly higher in relatives with familial PCa status (2+PCa vs. 1PCa) and in early onset PCa families (?65y vs. >65y): 30,5% vs 40% (p=0.05) and 59% vs 22% (p<0.001) respectively. In the same way PCa detection was significantly increased in relatives with familial PCa status (2+PCa vs. 1PCa) and in early onset PCa families (? 65y vs. >65y): 21% vs 8,5% (p<0.001) and 17,4% vs 9,9% (p=0,031) respectively. Conclusions Our results confirm prospectively the high risk of PCa in FDR, particularly for relatives with familial CaP status (2+PCa) and in early onset families (? 65y). Those findings suggest, targeted screening in families with HR status but also with FNH status and in sporadic families with early onset. Funding Programme Hospitalier de Recherche Clinique, Ligue Nationale contre le Cancer (Comité du Finistère).
Authors
PIERRE CALLEROT
MARIE-PIERRE MOINEAU ISABELLE CUSSENOT FRANCOISE BASCHET JOEL L'HER LAURENT DOUCET LUC CORMIER PHILIPPE MANGIN OLIVIER CUSSENOT GEORGES FOURNIER ANTOINE VALERI |
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MP33-05 |
Radical prostatectomy outcomes from a validated urine exosome gene expression assay which predicts high-grade (GS7) prostate cancer suggests utility for men enrolled in Active Surveillance. |
Prostate Cancer: Detection & Screening III | 17BOS |
Abstract: MP33-05 Sources of Funding: None Introduction _x000D_ With over-diagnosis and over-treatment of indolent prostate cancer, non-invasive screening tools that predict low-grade (? Gleason score 6, GS 6) from high-grade (?GS 7) prostate cancer (PCa) will play a significant role in the treatment decision process. Recently, we demonstrated that a urine exosome gene expression assay (ExoDx Prostate (IntelliScore) (EPI)) was able to discriminate high-grade (?GS 7) from low-grade (GS 6) and benign disease biopsy outcomes, thereby improving the identification of men with higher-grade PCa, potentially reducing the number of unnecessary biopsies. In a parallel study, we had also shown that EPI scores were associated with pathologic stage (PS) and radical prostatectomy Gleason score (RP-GS). We now sought to expand these results and further examine outcomes from men enrolled in the biopsy validation trial who had selected surgery. _x000D_ Methods _x000D_ 430 patients from a previous RP cohort study were re-evaluated using urine EPI scores and ISUP 2014 criteria with respect to RP-GS, PS and cancer volume. Specifically, urine EPI scores from men with biopsy ISUP 1 (i.e. potential candidates for Active Surveillance), were examined along with various clinical variables (including PSA, age, race, family history) for predicting RP upgrading. Additionally, RP outcomes were evaluated from men enrolled in the 519-validation cohort. Preliminary assessment using Spearman and Pearson correlation along with AUC was used to evaluate performance._x000D_ Results In the 430 RP cohort: 16% ISUP1, 45% ISUP2 (GS3+4),and 37% ? ISUP3 (GS4+3); 85% PSA <10ng/mL and 32% upgrading upon RP. Higher pre-RP urine EPI scores were associated with higher RP-ISUP groups, RP-PS and RP tumor volume (p-value<0.001). In patients from the 519-validation cohort who had a biopsy ISUP1 and chose RP, one third were upgraded and once again higher pre-RP urine EPI scores were significantly associated with a higher RP-ISUP group and higher RP-PS (p-value<0.001). Pre-RP PSA was not able to discriminate RP ISUP upgrading. Conclusions The EPI test is a noninvasive, first-catch non-DRE gene expression array that accurately discriminates low-grade from high-grade PCa in ISUP and traditional Gleason score based grading systems. Improved discrimination for predicting higher ISUP groups suggests a potential role in longitudinal monitoring of patients enrolled in Active Surveillance and warrants further validation. Funding None
Authors
Michael Donovan
Phillipp Torkler Mikkel Noerholm Johan Skog James McKiernan |
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MP33-06 |
Combined Urine and Plasma Biomarkers are Highly Accurate for Predicting High Grade Prostate Cancer |
Prostate Cancer: Detection & Screening III | 17BOS |
Abstract: MP33-06 Sources of Funding: None Introduction Distinguishing between low-grade and high-grade prostate cancer (PCa) as detected by biopsy results is very important, not only for diagnosis, but also for monitoring patients on active surveillance. However, biopsy results may underestimate the actual grade of the PCa when prostatectomy is performed. _x000D_ We developed an algorithm to predict the presence of high-grade PCa on biopsy using cell-free RNA (cfRNA) levels of UAP1, PDLIM5, IMPDH2, HSPD1, PCA3, PSA, TMPRSS2, AR, PTEN, and ERG genes in both urine and peripheral blood plasma. We show that this algorithm is highly reliable in predicting high grade (Gleason ≥ 3+4) PCa based on biopsy results in 489 patients. We also show in a prospective study that this algorithm is very reliable in an additional 300 patients who underwent prostatectomy. Methods Levels of cfRNA in urine and plasma from 489 patients were quantified using real-time PCR. Patients were selected randomly based on clinical suspicion of the presence of PCa. In addition, urine and blood samples from 300 patients were collected and tested prior to performing prostatectomy. Results Biopsy results from the first group showed Gleason 3+3 PCa in 103 patients (21%) and Gleason ≥3+4 PCa in 147 patients (30%). Patients with Gleason ≥4+3 were 55 (11%). Patients with Gleason 3+3 were grouped with non-cancer patients and considered as one group._x000D_ We used a simple algorithm incorporating prostate size, age, serum PSA along with 5 biomarkers to divide patients into two separate groups as low-risk and high-risk. Then each group was further refined and separated using a second algorithm implementing the rest of the biomarkers along with prior history of prostate biopsy. This resulted in high accuracy in predicting the presence of high-grade PCa with sensitivity between 97% and 86% and a specificity between 36% and 57%, dependent on which cut-off point was used. Sensitivity for predicting PCa Gleason ≥4+3 was between 99% and 96% and specificity between 37% and 59%. Diagnosis of Gleason ≥3+4 was missed in 1% to 3% of tested patients and of Gleason ≥4+3 in 0.2% to 1%. Testing the additional 300 samples with prostatectomy data demonstrated accurate prediction of cancer missing only 2.6% to 7% of Gleason ≥3+4 and 1 to 3% of ≥4+3, dependent on which cut-off point is used. _x000D_ Conclusions Taking advantage of urine and plasma biomarkers as well as serum PSA and prostate size and prior history of biopsy, we were able to predict high grade prostate cancer with negative predictive value (NPV) of 97% to 90% for Gleason ≥3+4 and between 99% to 98% for Gleason ≥4+3. Furthermore, this test was further proved to be highly sensitive as confirmed by prostatectomy data. Funding None
Authors
Maher Albitar, MD
Wanlong Ma, BS Lars Lund, MD Babak Shahbaba, PhD Edward Uchio, MD Soren Feddersen, PhD Donald Moylan, MD Kirk Wojno, MD Neal Shore, MD |
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MP33-07 |
Characterizing Local Recurrence after Radical Prostatectomy using MR-Targeted Biopsy |
Prostate Cancer: Detection & Screening III | 17BOS |
Abstract: MP33-07 Sources of Funding: None Introduction In patients with biochemical recurrence (BCR) after radical prostatectomy (RP), MRI is being increasingly utilized as the modality to visualize local recurrence. We aim to identify the role of MR-targeted biopsy to detect local recurrence in patients with rising PSA after RP. In addition, we evaluated clinical and pathologic characteristics to predict local recurrence using MR-targeted biopsy. Methods In a retrospective study, we identified men with rising PSA who underwent MR-targeted biopsy for local recurrence between June 2012 and June 2016. We collected data on RP pathology, pre-RP PSA, and MRI-assessed suspicion for prostate cancer scored on a standardized 5-point scale. The detection rate of prostate cancer was estimated for different MRI levels of suspicion and all patients underwent an MR-targeted biopsy. In addition, using Wilcoxon rank sum test, and Fisher’s exact test, we investigated whether RP pathologic characteristics were predictive of prostate cancer on biopsy. Results A total of 54 post-RP patients underwent MR-targeted biopsy for rising PSA. 25 (46%) patients had a positive biopsy identifying prostate cancer and 29 (54%) had a negative biopsy. In Table 1, MRI lesion score was the only clinical variable that was significantly associated (p=0.010) with improved detection of prostate cancer on biopsy. Additionally, subsequent increases in the MRI lesion score resulted in improved detection rates of prostate cancer. RP pathology features were not associated with biopsy outcomes (all p?077). Conclusions MRI-targeted biopsy can identify local recurrence in men with rising PSA after RP. The MRI lesion score is significantly associated with an increased detection rate of prostate cancer on MR-targeted biopsy, and is the only factor associated with biopsy outcomes. Our results suggest that there may be a subset of men with low MRI scores who may be precluded from biopsy, but our sample size is small and requires larger studies for confirmation. Funding None
Authors
Shawn Mendonca
John Graham Daniel Sjoberg Melissa Assel Jonathan Coleman Behfar Ehdaie |
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MP33-08 |
Baseline PSA in Older Males Predicts Prostate Cancer Mortality and Metastatic Disease |
Prostate Cancer: Detection & Screening III | 17BOS |
Abstract: MP33-08 Sources of Funding: none Introduction Prostate specific antigen (PSA) in midlife predicts increased risk of lethal prostate cancer (CaP). However, many men do not initiate CaP screening until later in life. Our aim was to determine if baseline PSA predicts lethal or metastatic CaP in an observational study of a US cohort. Methods Subjects were identified from the Prostate Lung Ovarian and Cancer (PLCO) trial. Men 60 years or older with a prior PSA in the control arm were excluded. Men were categorized by baseline PSA (at or below the 50th percentile, above the 50th percentile, 75th percentile and 90th percentile). Cox hazard ratios were used to compare subsequent risk of metastatic and lethal CaP, controlling for age, race, marital status, level of education, income, body mass index, and smoking. Results We identified 10,855 men 60 years or older without PSA screening prior to enrollment in the PLCO screening arm. Median age at first PSA was 65 (interquartile range 62-68). Median baseline PSA was 0.7, 1.6, 3.5 and 5.8 in those at or below the 50th percentile, above the 50th percentile, 75th percentile and 90th percentile, respectively. In this cohort, there were 39 deaths attributable to CaP and 147 cases of metastatic CaP. The rate of metastatic CaP and lethal CaP increased with increasing baseline PSA. Those below the 50th percentile had a 0.18% and 0.26% incidence of lethal and metastatic CaP respectively. Comparatively, those in the 90th percentile reported a 3.1% and 4.7% incidence of lethal and metastatic CaP respectively (p<0.001 between 50th and 90th percentiles). On Cox regression, higher percentile baseline PSA was associated with a significantly higher risk of metastatic and lethal prostate cancer [highest vs. lower percentile group: Hazard Ratio (HR)=27.8 (95% Confidence Interval (CI)14.9-52.1); HR=16.3, (95% CI 7.6-35) p<0.001, respectively]. Conclusions Baseline PSA testing for men aged 60 and over is strongly associated with metastatic CaP at diagnosis and lethal CaP. Men with low baseline PSA, very infrequently develop lethal CaP. These findings should help guide the frequency and intensity of individualized PSA screening Funding none
Authors
Adrien Bernstein
Ron Golan Brian Dinerman Aaron Bernie Jim C. Hu |
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MP33-09 |
Clinical Utility of Pseudouridine as a Diagnostic Marker to Detect Prostate Cancer |
Prostate Cancer: Detection & Screening III | 17BOS |
Abstract: MP33-09 Sources of Funding: Deane Prostate Health, Icahn School of Medicine at Mount Sinai. Both Shalini S Yadav and Kamlesh K Yadav are supported by the Prostate Cancer Foundation Young Investigator Awards. Introduction Given the present controversy surrounding PSA testing there have been renewed efforts to identify novel blood, urine, and genetic biomarkers for PCa. Using immunodetection-based methods, we previously observed elevated levels of pseudouridine (&[Psi]), an isomer of uridine, in AR-negative PCa cell lines and proposed &[Psi]’s use as a potential marker of aggressiveness. To this end, we analyzed several prostate cancer tissue micro arrays (TMAs) by immunohistochemistry (IHC) to assess the correlation between &[Psi] expression and disease diagnosis. We also designed an enzyme-linked immunosorbent assay (ELISA) capable of high-throughput quantification of &[Psi]RNA from blood, urine and tumor patient samples. Methods Paraffin-embedded TMAs (104 cores/92 cases total) with adjacent normal prostate tissue, including TNM, clinical stage and pathology grade, were purchased from US Biomax. An optimized protocol for IHC was performed and cell scoring and intensity staining for each core were visually assessed in collaboration with a Mount Sinai pathologist. Isolated total RNA was bound to Covalink plates (Thermo) according to manufacturer’s protocol and was incubated with anti- &[Psi] antibody. Biotinylated and streptavidin-HRP antibodies were used for signal amplification, while TMB was used for color development. Absorbance is proportional to levels of &[Psi] (in ng), and a standard curve generated from &[Psi]-oligonucleotides is used to calculate &[psi] in patient samples._x000D_ _x000D_ Results Immunohistochemical analysis demonstrated a correlation between Gleason grade and proportional/intensity staining of &[Psi]. In representative cores, nearly 80% of tumor glands in Gleason 3+3 cores exhibited 2+ staining while &[Psi]-expression is 3+ in 100% of the tumor cells in Gleason 5+4 cores. Blood RNA isolated from patients with Gleason 7+ tumors contained on average 2.08 and 6.1-folds greater quantities of &[Psi] compared to Gleason 6 and 7 tumors, respectively (n = 2 per group). Conclusions Our results establish a clear relationship between &[Psi] expression and clinical advancement of disease. Further studies with larger patient cohorts as well as additional studies to elucidate the biological role of &[Psi] would give valuable insight into how its expression could influence the onset or progression prostate cancer. Funding Deane Prostate Health, Icahn School of Medicine at Mount Sinai. Both Shalini S Yadav and Kamlesh K Yadav are supported by the Prostate Cancer Foundation Young Investigator Awards.
Authors
Jennifer Stockert
Shalini S Yadav Ashutosh Tewari Kamlesh K Yadav |
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MP33-10 |
Evaluation of the Clinical Utility of an Epigenetic Assay to Reduce Unnecessary Repeat Prostate Biopsies |
Prostate Cancer: Detection & Screening III | 17BOS |
Abstract: MP33-10 Sources of Funding: MDxHealth, Inc. Introduction Background: _x000D_ Management of men at risk of prostate cancer (PCa), but with a cancer-negative index biopsy, remains a challenge. PCa diagnosis involves an invasive biopsy procedure that is subject to significant sampling errors, possible negative quality-of-life implications for the patient and high additional costs to the healthcare system. An epigenetic assay assessing PCa-associated DNA-methylation of GSTP1, RASSF1, and APC in histologically negative biopsies has previously been clinically validated to improve the negative predictive value (NPV) relative to standard of care (SOC), yielding a NPV of 90% for all PCa and 96% for high-grade PCa (Gleason Score 7 or higher). Examination of the repeat biopsy rate associated with the outcome of this epigenetic assay would provide further evidence of its clinical utility for improving urologists' management of previously biopsied patients._x000D_ _x000D_ Objective: _x000D_ The primary goal of this study was to determine the rate of repeat biopsy in relation to the epigenetic assay and how this impacted the management of patients. Methods Practicing urologists used the epigenetic assay to evaluate 986 men (680 in the case group and 306 in the control group) with a previous negative biopsy. Men in the Case group had an epigenetic assay-negative result and were prospectively followed for a minimum of 12 months from the date of epigenetic profiling. The Control group was managed under SOC. Results The two groups were balanced in terms of patient characteristics, except for median age, which was lower in the Case group compared to the Control group (62 vs. 66 years, p<0.001). Use of the epigenetic assay resulted in significantly fewer first repeat biopsies in the Case group compared to the Control group (7.8% vs. 15.4%, respectively; p=0.004). There were also significantly fewer second repeat biopsies in the Case group compared to the Control group (12.1% vs. 26.1%, respectively; p<0.001) and significantly lower PCa detection upon repeat biopsy after a negative epigenetic assay result in the Case group compared to the Control group (0.6% vs. 4.9%, respectively; p<0.001). Conclusions In this real-world prospective study, the use of the epigenetic assay resulted in a significant reduction in the rate of excess repeat prostate biopsies. Funding MDxHealth, Inc.
Authors
Leander Van Neste
Jack Groskopf Wim Van Crienke |
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MP33-11 |
Genetic risk score can distinguish risk of prostate cancer among family members with similar degrees of relationship |
Prostate Cancer: Detection & Screening III | 17BOS |
Abstract: MP33-11 Sources of Funding: none Introduction Family history is a well-established risk factor for prostate cancer (PCa). However, family history information assigns equivalent risk to all relatives based upon the degree of relationship. Recent genetic studies have identified single nucleotide polymorphisms (SNPs) that can be used to calculate a genetic risk score (GRS) to determine an individual&[prime]s PCa risk. We sought to determine whether GRS can better estimate PCa risk among individuals with a family history of PCa. Methods Patients evaluated at a tertiary referral clinic with a family history of PCa were recruited for this study and were genotyped for 26 SNPs previously associated with PCa. The degree of familial risk (F) was calculated for each subject based on PCa among his relatives (e.g. F value of 0.5= 1 first-degree relative with PCa or 2 second-degree relatives with PCa). A GRS value was also calculated for each subject using 26 SNPs. Analyses comparing the distribution of GRS values among affected and unaffected family members with varying F values were performed. Results Subjects from 811 families with at least two affected members were included. The median GRS was significantly higher among family members with PCa (median 1.31; range 0.21-11.64) compared to unaffected family members (median 1.03; range 0.18-6.32; p=9.69e-8). There was a wide distribution of GRS values among members of each F group (Table). Higher GRS values were significantly associated with increased PCa risk among all F groups (p<0.05). For example, among subjects with F values of 1-1.49, PCa patients had a high mean GRS (1.64) than non-PCa subjects (1.12), P=0.0015. Multivariate models to assess the associations between age, GRS, F value and PCa diagnosis demonstrate that higher GRS (P=1.36e-7) and higher F values (P=2.64e-9) were independently associated with increased PCa risk. Conclusions GRS is an objective measurement that allows for differentiation of PCa risk among family members with similar degrees of familial risk of PCa. While prospective validation studies are required, this information can help guide relatives in regards to the time of initiation and frequency of PCa screening. Funding none
Authors
Brian Helfand
Haitao Chen Rong Na Carly Conran William Catalona Jianfeng Xu |
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MP33-12 |
Development of a Prostate Cancer Gene Expression Panel to Address Racial Differences of Molecular Alterations in Prostate Cancer |
Prostate Cancer: Detection & Screening III | 17BOS |
Abstract: MP33-12 Sources of Funding: Work is supported by NCI/EDRN ACN12011-001-0 and NCI RO1 CA162383-05 grants to SS Introduction Prostate cancer (CaP) affects 1 in 7 men in their life time. One of the major risk factors for the development of CaP is race/ethnicity. African American (AA) men have significantly higher incidence and mortality from CaP compared to Caucasian American (CA) men. Emerging data including ours have described significantly lower frequencies of alterations in common CaP driver genes (ERG and PTEN) in AA men as compared to CA men. We have also noted that genes commonly overexpressed in CaP (ERG, AMACR, PCA3), and currently used as diagnostic markers, exhibit much lower frequency and more heterogeneity in AA men. The goal of this study was to define a CaP marker panel that is overexpressed equally well in AA and CA CaP. Methods Three platforms (RNASeq, NanoString and qRT-PCR) were used for evaluation of CaP associated gene expression in CA and AA patients (N=144). Candidate genes with robust tumor overexpression (over 4-fold) in CaP in paired normal and tumor specimens from AA and CA patients were selected from Nanostring and RNASeq data for validation by qRT-PCR (TaqMan) in laser microdissected (LCM) tumor and benign cells of frozen tissue sections (50 CA and 35 AA). An assay protocol (gene specific RT and pre-amplification followed by TaqMan PCR) was set up for noninvasive early detection of candidate genes in regular patient urine (non-DRE) using urinary exosomal RNA. Results As expected tumor transcriptomes of CA patients consistently revealed elevated expression of PCA3 and AMACR. However, these genes had variable overexpression in AA cohort. The top genes that were similarly over expressed in tumors of AA and CA patients were validated by qRT-PCR in LCM tumor and normal epithelial cells (N=85). At least one gene of a six gene signature (DLX1, HOXC4, NKX2-3, COL10A1, HOXC6 and PSGR) was overexpressed in tumor cells of all AA and CA cases, providing a consistent ethnicity informed tumor expression signature, which was further validated in silico in TCGA RNASeq data. Urinary exosome based assay was developed and optimized for PSGR, DLX1, HOXC4, NKX2-3, as well as PCA3 and ERG. Sensitivity and specificity in a feasibility cohort (N=40) with optimal cutoff for the urine marker panel was 71% and 61%, respectively. Evaluation of the assay performance in CA and AA patients in a prospective independent cohort of 100 patients is in progress. Conclusions A CaP tissue based gene expression marker panel has been defined with potential diagnostic utility for both CA and AA men in the context of urinary exosomes. Funding Work is supported by NCI/EDRN ACN12011-001-0 and NCI RO1 CA162383-05 grants to SS
Authors
Indu Kohaar
Lakshmi Ravindranath Sreedatta Banerjee Yongmei Chen Amina Ali Jacob Kagan Sudhir Srivastava Albert Dobi David McLeod Inger Rosner Shiv Srivastava Gyorgy Petrovics |
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MP33-13 |
The Diagnostic Value of Digital Rectal Examination for Prostate Cancer: An analysis of over 20,000 Biopsies |
Prostate Cancer: Detection & Screening III | 17BOS |
Abstract: MP33-13 Sources of Funding: none Introduction In the United States a majority of prostate cancers are detected by an abnormal prostate specific antigen (PSA) level. In 2012 the U.S. Preventive Services Task Force recommended against the routine use of PSA based screening for prostate cancer, but did not fully address screening via digital rectal exam (DRE). The American Urologic Association recommends "informed decision with a doctor" starting at age 40 with baseline PSA and digital rectal exam._x000D_ DRE is known to detect some prostate cancers that are missed by PSA screening. The use of DRE is controversial as there is a high inter-observer variability and is subjective in nature. An abnormal DRE is a risk factor for high grade disease. With the USPTF recommendations many primary care physicians are not including digital rectal exam as part of their routine physical diagnosis. We sought to evaluate the clinical relevance of DRE in todays practice. _x000D_ Methods Based on systematic title literature search of articles including "digital rectal exam" and "prostate cancer" in pubmed, 204 studies could be identified in which the diagnostic value of DRE was studied. Only studies in which an unselected population which used biopsy as the reference standard of presence of disease were included. Biopsy prompts included abnormal DRE, elevated PSA and abnormal transrectal ultrasound. Only studies in which it was possible to calculate the true positive, true negative, false positive and false negative rates were included. Twenty-two articles met the above criteria. Statistical pooling was based on a random effects model. Results Total sample size was 20,434 patients undergoing biopsy. Pooling of the studies revealed a high negative predictive value (.76). A modest sensitivity (.58) and specificity (.58) was observed. The positive predictive value (.38) was low. Heterogeneity between the studies was high. Conclusions The DRE appears to be a test with a high negative predictive value. When DRE is normal the chance of missing cancer is approximately 24%. When a patient has an abnormal DRE the chance of diagnosing prostate cancer is about 38%. This is higher than the predictive value of an elevated PSA between 4-10ng/dl. With that in mind and the fact that DRE exerts little or no cost to the system, this study suggests that DRE still has utility in patient care when evaluating for their risk for prostate cancer. Funding none
Authors
Lorenzo DiGiorgio
Nitin Patel Vladislav Bargman Robert Weiss |
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MP33-14 |
The Role of Chronic Prostatic Inflammation in Prostate Carcinogenesis: a Retrospective Follow-up Study |
Prostate Cancer: Detection & Screening III | 17BOS |
Abstract: MP33-14 Sources of Funding: None. Introduction Chronic inflammation is a well-known contributor to several human cancers. The aim of this study was to investigate the role of chronic prostatic inflammation in prostatic carcinogenesis, with a specific focus on high grade cancers. Methods A retrospective search was performed to identify prostate biopsy cases accessioned in our institution between 01/01/2007 and 12/31/2009. Pathology reports of each case were reviewed. We reviewed the slides of all patients with benign initial prostate biopsies, followed by at least one set of prostate biopsies longer than one year after the initial biopsies. The presence and extent of chronic inflammation and other pathological findings were assessed and recorded. We defined chronic inflammation as involvement of 1% or more of the surface area of the prostatic tissue by a chronic inflammatory cell infiltrate. We also recorded the presence or absence of postatrophic hyperplasia (PAH) and inflamed atrophy (IA), a lesion defined by the presence of clusters of atrophic glands surrounded by a prominent and readily identifiable lymphocytic infiltrate. Cases in which prostatic adenocarcinoma was subsequently diagnosed were evaluated for Gleason pattern and score. Results Among 1006 patients who underwent prostate biopsies, a total of 244 cases with available slides were diagnosed initially as benign prostatic tissue, of which two patient subsets were identified, including 206 patients with and 38 patients without chronic inflammation in the initial biopsy. Post-atrophic hyperplasia (PAH) and inflamed atrophy (IA) were more frequently identified in patients with chronic inflammation. In follow up biopsies performed at least 1 year following the initial benign biopsies, 75 patients (36%) with chronic inflammation were found to have adenocarcinoma, whereas cancer was found in only 6 patients (16%) without chronic inflammation in the initial biopsies. Of those who were found to have cancer after the initial biopsies showing only chronic inflammation, 46% had a Gleason 3 + 3 pattern (grade group 1), 20% had a Gleason 3 + 4 pattern (grade group 2), and 13% had a Gleason 4 + 3 pattern (grade group 3). Significantly, high grade cancers with Gleason score of 8 or higher (grade groups 4 or 5) were identified in 21% (16 of 75) of patients with chronic inflammation in the initial benign biopsies, whereas no patient without chronic inflammation in the initial benign biopsies were found to have cancer with a Gleason score of 8 or higher (grade groups 4 or 5). Conclusions Our retrospective follow up study suggests a strong association between chronic prostatic inflammation and the development of prostatic adenocarcinoma. Funding None.
Authors
Liwei Jia
Shawn Silver Gregory MacLennan |
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MP33-15 |
Gender Disparity: Overlooking Hereditary Prostate Cancer and Implications for Urology Practice |
Prostate Cancer: Detection & Screening III | 17BOS |
Abstract: MP33-15 Sources of Funding: none Introduction Men and women are equally likely to carry mutations in hereditary cancer genes and both have elevated cancer risks. Prostate cancer (PC) has been associated with germline mutations in several genes, especially BRCA2; which has also been associated with more aggressive disease with significantly lower cause-specific survival. The National Comprehensive Cancer Network (NCCN) guidelines for hereditary breast and ovarian cancer (HBOC) recommend genetic testing for men with a personal and/or family history of high Gleason score prostate cancer with family history of breast, ovarian, and/or pancreatic cancer. Despite this, over 95% of patients who have hereditary cancer multi-gene panel testing (MGPT) are women. We sought to describe results of MGPT in men with PC compared to women with breast cancer (BC). Methods Test results were reviewed for PC patients and female BC patients who had MGPT (Jun 2013 - May 2016) for up to 49 genes. Clinical history was obtained from test request forms. Results Of 654 PC probands tested, 100 mutations were identified across 18 genes; 7 individuals had 2 mutations, 93 individuals had 1 mutation. 14.2% (93/654) of PC probands tested positive, compared to only 8.6% of women with BC (6,215/71,728; p=2.5e-5). Most mutations in PC patients were in BRCA (40.9%), followed by ATM (20.4%), CHEK2 (15.0%) and Lynch syndrome-associated genes (9.7%). Of 100 total mutations, 94% were in genes that would impact management recommendations for them and/or their relatives. _x000D_ _x000D_ The median time from PC diagnosis to MGPT was 6 years, compared to 1 year for female BC. Nearly 57% (53/93) of mutation-positive men had multiple primary cancers, 79.2% of which had PC first. Of BRCA positives with multiple primaries (n=21), over 90% developed PC followed by subsequent cancers, yet testing was not initiated until another cancer developed._x000D_ Conclusions MGPT identified germline mutations at significantly higher rates in this cohort of men with PC compared to women with BC. Furthermore, 59.1% (55/93) of mutation-positive PC probands had a mutation in BRCA and/or ATM, making them possibly eligible for a PARP-inhibitor clinical trial. Unfortunately, time from PC diagnosis to MGPT was several years longer than women, allowing many to develop subsequent cancers that may have been prevented or detected earlier with knowledge of the germline mutation. Revisions to NCCN guidelines do increasingly recognize the contribution of PC to HBOC; however, increased awareness among clinicians is needed to identify otherwise unrecognized male mutation carriers for appropriate cancer risk management. Funding none
Authors
Lauren Bowling
Carin Espenschied Michelle Jackson Bryan Mak Holly Laduca |
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MP33-16 |
Patient Selection for Multiparametric Prostate MRI: Identifying Clinical Predictors for Actionable PIRADS Lesions on Imaging |
Prostate Cancer: Detection & Screening III | 17BOS |
Abstract: MP33-16 Sources of Funding: None Introduction Despite a favorable sensitivity profile for high grade and large volume disease, indiscriminate use of multiparametric prostate MRI (mpMRI) adds prohibitory cost with uncertain benefit. Our study aims to identify clinical predictors of suspicious lesions on imaging to improve patient selection for mpMRI. Methods We performed a retrospective review of 839 patients undergoing mpMRI for elevated PSA between March 2012 and October 2014. mpMRI was performed on 3T magnet with pelvic phased array and endorectal coils. Baseline clinical and biochemical patient characteristics were analyzed with univariable and multivariable logistic regression to identify predictors of a positive MRI (PIRADS score 3-5). Using these variables, we constructed a nomogram to predict a positive MRI. Results Among 839 patients without prior history of prostate cancer, MRI was positive in 272 (32.4%) patients. Increasing age (P=0.001), abnormal digital rectal exam (P=0.002), prior negative biopsy (P<0.001), increasing pre-MRI PSA (P<0.001), lower prostate volume (P<0.001), and PSA velocity (P=0.044) were significant predictors of a positive MRI in univariable analysis. On multivariable analysis, age (P=0.048), positive digital rectal exam (P=0.017), prior negative biopsy (P=0.061), pre-MRI PSA (P<0.001), and prostate volume (P<0.001) remained independent predictors (Table). A nomogram predicting probability of a positive mpMRI based on these variables demonstrated good calibration and a concordance index of 0.7 (Figure). Conclusions Many of the clinical variables traditionally associated with increased PCa risk are also independently associated with a positive mpMRI. A nomogram including these variables can help identify men who are more likely to benefit from a prostate mpMRI while reducing cost by limiting the number of negative studies. Funding None
Authors
Vinay Patel
Paras Shah Daniel Moreira Arvin George Geoffrey Gaunay Jose Vilaro Manish Vira Simon Hall |
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MP33-17 |
Potential role of a novel urinary biomarker-based risk score to select patients for multiparametric MRI for prostate cancer detection. |
Prostate Cancer: Detection & Screening III | 17BOS |
Abstract: MP33-17 Sources of Funding: MDxHealth Introduction Prostate cancer (PCa) diagnostics would greatly benefit from more accurate, non-invasive techniques for the detection of clinically significant disease, leading to a reduction of over-diagnosis and over-treatment. Multiparametric MRI (mpMRI) is being used increasingly and has proven to be a valuable addition to the PCa diagnostic pathway. A novel biomarker-based risk score (SelectMDx) assessing urinary HOXC6 and DLX1 mRNA expression levels combined with traditional clinical risk factors, was recently developed to predict high-grade PCa (Gleason score >/=7) upon prostate biopsy and to reduce the number of unnecessary biopsies. The aim of this study was to investigate the correlation between the risk score and mpMRI outcomes. Methods The patients in this retrospective observational cohort were previously included in the validation study of the SelectMDx risk score, in which urine was collected after digital rectal examination (DRE) from men undergoing prostate biopsies based on an elevated serum PSA level (>/=3.0 ng/ml) and/or suspicious DRE. A subset of patients underwent an mpMRI after prostate biopsies were performed (n=174). The indications for performing MRI were based on persistent clinical suspicion of PCa after negative prostate biopsies or staging after PCa was found upon biopsy. Results 102 of 174 patients (59%) had PCa detected upon prostate biopsy, of which 54 (53%) had high-grade disease and a significantly higher SelectMDx risk score (p<0.001). The median SelectMDx risk score was also significantly higher in patients who had a suspicious lesion on MRI (p<0.001). For 81 mpMRI's the PIRADS classification was reported and there was a positive correlation observed between the risk score and the PIRADS classification (Figure 1). A Kruskal-Wallis test indicated a statistically significant difference in SelectMDx risk scores between the different PIRADS groups (p<0.001). Conclusions The novel urinary biomarker-based risk score is a promising tool in PCa detection. This study showed promising results regarding the correlation between the SelectMDx risk score with MRI outcomes. This risk score could potentially guide clinicians in selecting patients at risk for significant PCa for mpMRI. Funding MDxHealth
Authors
Rianne J Hendriks
Leander Van Neste Mulders Marloes Jack A Schalken Inge M Van Oort |
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MP33-18 |
Over Half of Contemporary Clinical Gleason 8 on Prostate Biopsy are Downgraded at Radical Prostatectomy |
Prostate Cancer: Detection & Screening III | 17BOS |
Abstract: MP33-18 Sources of Funding: none Introduction Accurate biopsy Gleason scoring is critical for the proper treatment of prostate cancer (PC). Here, we present an alarming discrepancy between PC diagnosed as high-risk pathology on biopsy and their actual pathology after radical prostatectomy (RP). Methods We retrospectively reviewed 1034 men who underwent open RP by a single surgeon between 2004 and 2015. 112 men were diagnosed with Gleason 8 pathology on prostate biopsy. We excluded 5 patients whose RPs were aborted and 4 whose neoadjuvant treatments prevented proper Gleason scoring. Biopsy and RP pathology were compared in aggregate and over one-year time intervals. Chi-squared test, Fisher's exact test, Student's t-test, and Wilcoxon Rank-Sum test were used for statistical analysis. Results 61.1% (63/103) of clinical Gleason 8 diagnoses were downgraded on surgical pathology after RP, with 60 specimens being downgraded to Gleason 7 (Gleason 4+3 n=39; Gleason 3+4 n=21). There were significant in-group differences among the one-year cohorts (p<0.02), with increased pathology downgrading over time that includes an 84.2% (32/38) downgrade rate from 2012-2015. Pathology downgrading is significantly associated with lower PSA at biopsy (median 6.9 vs 9.4 ng/ml, p<0.01), decreased tumor percentage (median 12 vs 15%, p<0.03), and lower percentage of positive margins (47.6 vs 66.7%, p<0.04). It is borderline associated with lower percentage of seminal vesicle invasion (11.1 vs 25.6%, p<0.06) and extracapsular extension (49.2 vs 69.2%, p<0.08). Neoadjuvant treatment (14/103), race, age, and clinical staging were not significantly associated with pathology downgrading. Conclusions The large, increasing percentage of pathology downgrading implies a high rate of over-diagnosis of Gleason 8 scores on biopsy, potentially leading to suboptimal treatment strategies and much patient distress. Our study adds great urgency to the efforts refining PC diagnostic techniques. Funding none
Authors
Tracy Han
Ilhan Gokhan Ghalib Jibara Robert Qi Judd Moul |
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MP33-19 |
An exome-wide association study replicated for prostate cancer in Korean population |
Prostate Cancer: Detection & Screening III | 17BOS |
Abstract: MP33-19 Sources of Funding: None Introduction To date, more than 300 susceptibility loci associated with prostate cancer (PCa) have been identified mainly from studies of European ancestry populations with much less contributions from Asian populations. As there was a genetic difference according to ethnic groups, we performed the first Korean population based exome wide association study for PCa in this study. Methods Our study was performed in a two-stage design._x000D_ Stage I – 1,001 PCa patients using a custom HumanExome BeadChip v1.0 (Illumina Inc) containing 242,186 SNPs. After quality control, genotype data from 988 PCa patients were compared with 2,641 normal controls from community cohort (KARE). _x000D_ Stage II – 5 exome-wide significant lead SNPs (P < 1.0 × 10-4) from the Stage I were selected to genotype and replicated in independent cohort (514 PCa and 548 control). Genotyping of these SNPs was performed using the Fluidigm 192.24 Dynamic Array TM IFC and Biomark HD systems. To construct a genetic risk score (GRS), the cumulative number of risk alleles was calculated using an additive model. Then, we obtained estimates of the area under the receiver-operating characteristic curve (AUC) to evaluate its discriminative ability._x000D_ Results Stage I – we detected 5 lead variants (p < 8.30E-07) – rs1512268 (8p21, NKX3-1), rs1016343 (8q24, PRNCR1), rs7837688 (8q24, CASC8), rs7501939 (17q12, HNF1B) and rs2735839 (19q13, KLK3) (figure 1)_x000D_ Stage II – mean GRS score was 4.23 ± 1.44 for the controls and 4.78 ± 1.43 for the cases. The GRS was associated with increased PCa risk (GRS 6 : OR=1.85, GRS 7 : OR=2.11 in reference of GRS 4) (figure 2). The trend of increase in PCa risk according to the increase in GRS is very strong (p<0.0001, test for trend). The predictive accuracy of GRS was 0.605 (95%CI 0.573-0.637). _x000D_ Conclusions We detect 5 risk variants for PCa in Korean population, confirmed in many previously reported findings and build the GRS to predict PCa more effectively. Our findings suggest that similarities than difference in genetic susceptibilities might be more important aspect across populations Funding None
Authors
Jong Jin Oh
Tae Jin Kim In Jae Lee Byund Do Song Dong Hwan Lee Yeon Soo Jung Hak Min Lee Sung Kyu Hong Sangchul Lee Jin-Nyoung Ho Sungroh Yoon Soo Ji Lee Joohon Sung Seok-Soo Byun |
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MP33-20 |
The SmartTarget Biopsy Trial: A Prospective Paired Blinded Trial with Randomisation to Compare Visual-Estimation and Image-Fusion Targeted Prostate Biopsies |
Prostate Cancer: Detection & Screening III | 17BOS |
Abstract: MP33-20 Sources of Funding: This trial was funded by the Wellcome Trust and the Department of Health UK - Health Innovation Challenge Fund Introduction Multi-parametric MRI targeted prostate biopsies can improve detection of clinically significant prostate cancer and decrease the diagnosis of clinically insignificant cancers. There is debate whether visual estimated targeting is sufficient or whether image-fusion software is required. We conducted an ethics committee approved, prospective, blinded, paired validating clinical trial of visual estimated targeted biopsies compared to non-rigid MR/US image-fusion using an academically developed fusion system (SmartTarget®)._x000D_ Methods 141 men requiring targeted transperineal biopsies for accurate risk stratification were enrolled following written informed consent (August2014-September2016). Entry required prior trans-rectal ultrasound biopsy, a discrete lesion on mpMRI (PIRADS 3-5) and no previous prostate cancer treatment. _x000D_ All men underwent a targeted transperineal biopsy of a single lesion using visual estimation (3 cores) and image-fusion (3 cores). Two different urologists independently conducted the targeting strategies with each urologist assigned a strategy and order by randomised. Only one urologist was permitted to be present for each biopsy strategy and did not communicate with the other about any aspect of the procedure (blinded). 14 urologists of varying levels of experience participated. All were competent in transperineal targeting. _x000D_ UCL definition 2 clinically significant prostate cancer was used as the target condition for the primary outcome (>/= G3+4 and or MCCL >/= 4mm). _x000D_ Results 129 men completed both biopsy strategies. Median age (IQR) was 65 years (58-70) and median PSA was 8.5ng/ml (5.6-12.1). 94 (72.8%) had clinically significant prostate cancer; 81/94 (86.2%) were identified on visual estimation targeting and 81/94 (86.2%) on image-fusion targeting. Fusion biopsy and visual estimation targeting each identified clinically significant cancers that the other missed, 13 and 13 respectively. We found no statistically significant difference between visual estimation and image-fusion (McNemar, p=1.00)._x000D_ Conclusions Our prospective, paired blinded trial demonstrates that there is no overall difference in detection of clinically significant prostate cancer between visual estimation and image-fusion targeted biopsies. Our results suggest that both techniques should be used together for optimal cancer detection. _x000D_ Funding This trial was funded by the Wellcome Trust and the Department of Health UK - Health Innovation Challenge Fund
Authors
Ian Donaldson
Sami Hamid Dean Barratt Yipeng Hu Rachel Rodell Barbara Villarini Ester Bonmati Paul Martin David Hawkes Neil McCartan Ingrid Potyka Norman Williams Chris Brew-Graves Caroline Moore Mark Emberton Hashim Ahmed |
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MP34-01 |
Molecular subtypes of muscle invasive bladder cancer are related to benefit from neoadjuvant chemotherapy: Development of a single sample patient assay |
Bladder Cancer: Invasive II | 17BOS |
Abstract: MP34-01 Sources of Funding: RS: Salary funded by the Swiss National Foundation. GenomeDx funded gene_x000D_ expression analysis. PB: AUA Foundation/Astellas Rising Stars in Urology Award. BvR: _x000D_ The EAU - European Urological Scolarship Programme. MSvdH: Veni grant, Netherlands_x000D_ Organisation for Scientific Research Introduction Different methods for molecular subtyping of muscle-invasive bladder cancer (MIBC) have been described. Our goal was to investigate the impact of molecular subtypes in the context of neoadjuvant cisplatin-based chemotherapy (NAC) and to develop a single sample model for clinical use. Methods Pre-NAC transurethral resection (TUR) specimens of 305 patients were profiled with the HumanExon microarray from Affymetrix. The original models (UNC, MDA, TCGA, Lund) for molecular subtyping were used to generate the subtype calls for these samples. Based on the biological and clinical significance, we developed a single sample genomic subtyping classifier (GSC) to predict modified consensus subtypes (claudin-low, basal, luminal-infiltrated and luminal). Overall survival (OS) according to subtype was analyzed and compared to OS in 376 non-NAC cases from three publicly available datasets. Results The subtype calls in our NAC dataset were similar to previously published ratios and biological functions confirmed the concordance between the different subtyping methods (e.g. UNC luminal, MDA luminal, TCGA cluster I). Our GSC predicted the four consensus molecular subtypes with high accuracy (AUC >0.85). Extravesical extension of residual primary tumor (pT3/4) after NAC was observed more frequently in claudin-low and luminal-infiltrated subtypes. GSC was not significantly associated with major pathologic response (i.e., ypT<2N0). Patients with luminal tumors had the best outcome in both datasets with 3-year OS rates of 77% and 75%, respectively. The prognosis of patients with luminal-infiltrated tumors was inferior to that of luminal tumors and did not improve with NAC. Patients with claudin-low tumors had poor OS irrespective of treatment regimen. Patients with GSC basal tumors had a 3-year OS rate of 49.2% (p<0.001) in the non-NAC cohort compared to 77.8% (p<0.001) in the NAC cohort._x000D_ Conclusions The benefit of NAC varies between molecular subtypes. The poor OS of claudin-low tumors even after NAC implies that these tumors are resistant to cisplatin-based chemotherapy, and these patients should be included in protocols investigating alternative treatment options like immunotherapy. The prognosis of patients with basal tumors improved the most when treated with NAC compared to surgery alone. Our findings require validation prior to clinical implementation._x000D_ Funding RS: Salary funded by the Swiss National Foundation. GenomeDx funded gene_x000D_ expression analysis. PB: AUA Foundation/Astellas Rising Stars in Urology Award. BvR: _x000D_ The EAU - European Urological Scolarship Programme. MSvdH: Veni grant, Netherlands_x000D_ Organisation for Scientific Research
Authors
Roland Seiler
Hussam Al Deen Ashab Nicholas Erho Bas W.G. van Rhijn Brian Winters James Douglas Kim Van Kessel Elisabeth E. Fransen van de Putte Matthew Sommerlad Qiqi Wang Voleak Choeurng Ewan A. Gibb Beatrix Palmer-Aronsten Lucia L. Lam Christine Buerki Elai Davicioni Gottfrid Sjödahl Jordan Kardos Katherine A. Hoadley Seth P. Lerner David J. McConkey Woonyoung Choi William Y. Kim Bernhard Kiss George N. Thalmann Tilman Todenhöfer Simon J. Crabb Scott North Ellen C. Zwarthoff Joost L. Boormans Jonathan Wright Marc Dall'Era Michiel S. van der Heijden Peter C. Black |
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MP34-02 |
Practice Patterns and Survival for Patients with Metastatic Urothelial Carcinoma of the Bladder: Does Real World Practice Parallel Clinical Trial Outcomes? |
Bladder Cancer: Invasive II | 17BOS |
Abstract: MP34-02 Sources of Funding: None Introduction Current projections of survival for patients with metastatic urothelial carcinoma of the bladder (TanyNanyM1; mUCB) are based largely on data from patients treated in clinical trials. As patients enrolled in trials are highly-selected, the degree to which these outcomes reflect real-world experience is unknown. We sought to describe practice patterns and survival for patients with mUCB in a large national cancer registry. Methods We reviewed the National Cancer Database to identify patients diagnosed with mUCB at presentation between 2004-2012. Sites of metastases were classified as non-regional lymph node (NRLN) only versus any non-nodal (visceral) metastatic disease (VM). Overall survival (OS) was assessed using the Kaplan-Meier method and compared with the log-rank test. Results mUCB was present at diagnosis in 3,374 patients. Median age was 71 (IQR 62, 79); 70% were male. The majority (n=2,486; 82%) were diagnosed with VM. Median OS was 5.5 months (95% CI 5.1-5.9), with an estimated 1 and 3-year OS of 27% and 7%, respectively. Patients with VM disease had a significantly inferior OS compared to patients with NRLN (median 5 vs 11 mo; p<0.01). In total, 1,325 (39%) patients with mUCB received treatment, including chemotherapy (30%), multimodal therapy (5%), surgery (3%), and radiation (1%). Median OS varied significantly (p<0.01) across treatments: multimodal (12.6 mo), chemotherapy (10.6 mo), radiation (6.9 mo), and surgery (5.4 mo). OS among patients receiving palliative therapy only (n=935; 28%) was 4.8 mo, and was 2.0 mo for those patients who did not receive treatment (n=1,114; 33%). The longest median OS (13.8 mo; 95% CI 12.9-15.9) was noted among the cohort with NRLN who received chemotherapy (5%), while patients with VM treated with chemotherapy (23%) had a median OS of 9.9 mo (IQR 9.3, 10.7) (Figure). Conclusions In our analysis of national practice, we found that patients with mUCB have a poor OS, with a median survival less than six months and only 27% surviving 1 year from diagnosis. Notably, over half of mUCB patients did not receive treatment or received palliative therapy only. Patients receiving chemotherapy for NRLN had an OS approaching that reported from clinical trials, although such patients represented just 5% of the overall mUCB cohort. Funding None
Authors
William Parker
Lance Pagliaro Brian Costello Igor Frank Elizabeth Habermann Matthew Tollefson R. Houston Thompson R. Jeffrey Karnes Harras Zaid Jeffrey Holzbeierlein Stephen Boorjian |
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MP34-03 |
ONCOLOGIC OUTCOMES FOR PATIENTS WITH RESIDUAL CANCER AT CYSTECTOMY FOLLOWING PREOPERATIVE CHEMOTHERAPY: A PATHOLOGIC STAGE-MATCHED COMPARATIVE ANALYSIS |
Bladder Cancer: Invasive II | 17BOS |
Abstract: MP34-03 Sources of Funding: None Introduction While neoadjuvant chemotherapy prior to radical cystectomy (RC) has been demonstrated to improve survival compared to RC alone for urothelial carcinoma of the bladder (UCB), the bulk of this survival benefit has been attributed to patients who achieve ypT0 status at RC. The implications of having residual UCB (rUCB) at RC after preoperative chemotherapy (POC) are less clear. As such, we evaluated survival for patients with and without rUCB at RC after POC compared with pathologic stage-matched RC patients who did not receive POC. Methods Patients undergoing RC for UCB between 1980-2010 at Mayo Clinic were identified. All RC pathology was re-reviewed by a single genitourinary pathologist. Patients who received POC for T2-T4 and/or N1-3 M0 UCB were matched 1:2 to patients not exposed to prior chemotherapy based on pT and pN-stage, soft tissue surgical margin status, and year of RC. Kaplan Meier and Cox regression analyses were used to evaluate the associations between POC and cancer-specific (CSS) and overall survival (OS), stratified by presence or absence of rUCB at RC. Results We matched 111 patients who underwent POC + RC to 222 RC-alone patients. Median age was 68 yrs (IQR 60,74); 59 (18%) were female. Median follow-up was 7.2 yrs (IQR 6,16), during which time a total of 248 patients died, with 148 dying from UCB. In patients without rUCB at RC, there was no difference in 5-yr CSS (86% vs. 90%, p=0.85) or OS (82% vs. 84%, p=0.46) between patients who did versus did not receive POC. Moreover, on multivariable analysis, chemotherapy exposure was not significantly associated with CSS (HR=1.0; 95%CI 0.3-3.1; p=0.9) or OS (HR=0.9; 95%CI 0.4-1.9; p=0.8) in this subgroup. Conversely, among patients with rUCB at RC, receipt of POC was associated with significantly worse 5-yr CSS (32% vs. 56%, p<0.001) and OS (25% vs. 48%, p<0.001). Moreover, on multivariable analysis, chemotherapy exposure remained independently associated with adverse CSS (HR=2.2; 95%CI 1.6-3.1; p<0.001) and OS (HR=2.0; 95%CI 1.5-2.7; p<0.001) among the patients with rUCB. Conclusions While patients who achieve a complete response to POC have excellent survival outcomes, patients with residual UCB at RC after POC have a worse prognosis compared to stage-matched RC patients not exposed to chemotherapy. Such patients should be considered for enrollment in novel adjuvant therapy trials, while continued investigation of which patients are most likely to achieve ypT0 status remains warranted. Funding None
Authors
Bimal Bhindi
Igor Frank William Parker Ross Mason Robert Tarrell Prabin Thapa John Cheville Brian Costello Lance Pagliaro R. Jeffrey Karnes R. Houston Thompson Matthew Tollefson Stephen Boorjian |
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MP34-04 |
Post-chemotherapy PD-L1 expression correlates with clinical outcomes in Japanese bladder cancer patients treated with total cystectomy. |
Bladder Cancer: Invasive II | 17BOS |
Abstract: MP34-04 Sources of Funding: none Introduction Programmed cell death ligand-1 (PD-L1) is a key target molecule of immunotherapy that is frequently overexpressed in bladder cancer. In the present study, we examined whether PD-L1 expression is associated with clinical outcomes in bladder cancer patients. _x000D_ Methods We enrolled 102 bladder cancer patients treated with cystectomy at the Aomori Prefectural Hospital between April 2004 and May 2014. We conducted an immunohistochemical examination of PD-L1 expression using the SP142 assay. PD-L1 expression was scored at three diagnostic levels (0/1/2). _x000D_ Results Of the 102 patients, 82 were men (81.0%) and 20 were women (19.0%) (mean age, 60 years, range, 43-84 years). Sixty-six patients (64.8%) had previously undergone neoadjuvant chemotherapy [neoadjuvant (+) group]. During the mean_x000D_ observation period of 54.5 months, 42 patients had recurring disease (41.1%) and 34 died (33.3%). The five-year cause-specific survival rate (CSS) was 66.6%; the five-year disease-free survival rate (DFS) was 59.7%. In the neoadjuvant (+) group, the 5-year DFS rate was 65.0% for PD-L1 (-) patients and 31.7% for PD-L1 (+) patients. In the neoadjuvant (+) groups, the 5-year CSS rate was 69.6% for PD-L1 (-) patients and 48.1% for PD-L1 (+) patients. Differences in CSS and DFS rates between PD-L1 (-) and PD-L1 (+) patients in both treatment groups were statistically significant (log-rank p = 0.006 and 0.039, respectively.) _x000D_ Conclusions Despite the small study size, our data suggest that post-chemotherapy PD-L1 expression is associated with poor prognosis in patients who had previously undergone cystectomy after neoadjuvant chemotherapy._x000D_ Funding none
Authors
Yasuhiro Hashimoto
Hiromi Murasawa Hiromichi Iwamura Atsushi Imai Shingo Hatakeyama Takahiro Yoneyama Takuya Koie Chikara Ohyama Ikuya Iwabuchi Masaru Ogasawara Toshiaki Kawaguchi |
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MP34-05 |
The prognostic significance of TNM staging in bladder cancer after neoadjuvant chemotherapy can be enhanced with tumor regression grading |
Bladder Cancer: Invasive II | 17BOS |
Abstract: MP34-05 Sources of Funding: none Introduction Classification of response to neoadjuvant chemotherapy (NAC) in muscle-invasive bladder cancer (MIBC) is based primarily on TNM stage at cystectomy. We recently described post-NAC tumor regression grades (TRG) as an alternative method of risk stratification. Here we aim to validate our findings in an independent cohort and to integrate TRG with TNM staging. Methods Fifty-five patients with MIBC received at least 3 cycles of cisplatin-based NAC and underwent cystectomy. As previously described (Fleischmann et al. Am J Surg Pathol 2014) TRG was assessed in cystectomy specimens by two independent investigators blinded to patient outcomes. TRG 1 represents absence of residual cancer, TRG 2 is characterized by predominant fibrosis containing scattered residual cancer cells, and TRG 3 shows residual cancer with minor component of fibrosis or absence of regressive changes. Major response to NAC was defined as absence of muscle invasive disease and lymph node involvement ( Results The 22/55 (40%) patients with major response to NAC had a significantly longer OS compared to the remaining patients (90% vs. 50% 5yr OS, p=0.005). TRG was successfully determined in all cases and concordance between both observers was high (91%). Of the 33/55 (60%) patients without major response, 13/55 (24%) and 20/55 (36%) were partial- and non-responders after combining TRG with the TNM stages. Kaplan-Meier estimates yielded an additional stratification of the cohort in 3 separated prognostic categories. Five-year OS of major-, partial- and non-responders was 90%, 65% and 40%, respectively. Multivariate survival analysis showed that the prognostic stratification of the cohort could be improved by integrating the TRG with the TNM stages (p<0.001). Conclusions Measurement of TRG after NAC is simple and reproducible. We successfully validated our prior discovery in an independent cohort. Moreover, integrating TRG with the current TNM classification significantly improved prognostic stratification. Funding none |
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MP34-06 |
Development and external validation of a novel 12-gene signature on muscle-invasive bladder cancer for prediction of overall survival: linkage to data from The Cancer Genome Atlas |
Bladder Cancer: Invasive II | 17BOS |
Abstract: MP34-06 Sources of Funding: This work was supported by grants from National Natural Science Foundation of China (81502192,81572531,81472377). Introduction We aimed to develop and validate a novel gene signature from published data and improve the prediction of survival in muscle-invasive bladder cancer (MIBC). Methods We search the published gene signatures of MIBC on overall survival (OS) and complied all the 237 genes to develop a novel gene signature. Statistics were conducted with R (version 3.2.1, The R Foundation for statistical computing). RNAseq data of TCGA bladder cohort was downloaded from website "https://genome-cancer.ucsc.edu/proj/site/hgHeatmap/", "TCGA_BLCA_exp_HiSeqV2-2015-02-24". All genes were enrolled in the univariate Cox hazard ratio model. We used a reduced multivariate Cox regression model, only genes fulfilled P<0.10 in univariate model were enlisted. A consecutive cohort with 172 patients in Fudan University Shanghai Cancer Center was treated as external validation set. Results Only with intact clinical and follow up data were enrolled and finally a total of 327 patients in TCGA cohort were enrolled. We identified 236 genes, from 9 published paper on OS of MIBC. Using the TCGA Database we identified a total of 12 genes that correlated with OS (P<0.05 in univariate and multivariate analysis both). By integrating these genes with the RT-qPCR data in our validation data set, we confirmed that the 12-gene panel prediction power of OS (the AUC were 0.741 and 0.727, respectively) was higher than just clinical data (including sex, age, T stage, grade and N stage) only (the AUC were 0.667 and 0.631, respectively). And combining the clinical and 12-gene data together, the AUC can increase to 0.768 and 0.757 respectively. Conclusions Applying published gene signatures and TCGA data, we successfully build and externally validate a novel 12-gene signature for OS of MIBC. The improved prediction for these high risk of disease progression or survival will be helpful to doctor-patient’s consultation and finally benefit our patients. Funding This work was supported by grants from National Natural Science Foundation of China (81502192,81572531,81472377).
Authors
Huyang Xie
Fangning Wan Beihe Wang Yiping Zhu Yijun Shen Dingwei Ye |
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MP34-07 |
Multiplex ligation-dependent probe amplification of genomic aberrations of circulating, cell-free DNA in bladder cancer patients treated with radical cystectomy: a prospective study |
Bladder Cancer: Invasive II | 17BOS |
Abstract: MP34-07 Sources of Funding: None Introduction To characterize genomic aberrations of circulating, cell-free DNA (cfDNA) in bladder cancer patients treated with radical cystectomy (RC), we established a new and rapid profiling method using multiplex ligation-dependent probe amplification (MLPA). In a single reaction, MLPA allows analyzing genomic variations in 43 chromosomal regions containing 37 genes. Methods We prospectively enrolled 85 bladder cancer patients treated with RC without neoadjuvant chemotherapy at our institution between 2011 and 2014. Blood samples were obtained from all patients preoperatively. Serum and plasma were prepared from 6ml whole blood in all patients. We extracted cfDNA from serum and plasma using various DNA extraction kits (QiAmp DNA Blood Mini kit, Qiagen, Hilden, Germany; QiAmp Circulating Nucleic Acid kit, Qiagen; NucleoSpin Plasma XS kit, Macherey Nagel, Dueren, Germany; PME free-circulating DNA Extraction kit, Analytik Jena, Germany). Following extraction of DNA with the applied commercial kits, we tested MLPA in serum and plasma, respectively. Eighteen probes served as references to control denaturation, ligation and amplification efficiency. Results To identify genomic aberrations, MLPA was suitable in cfDNA extracted from serum, but not in cfDNA extracted from plasma. Serum from 72 patients (84.7%) could be analyzed. In 35 patients (48.6%), one to 6 deleted and/or amplified chromosomal regions were detected. Most changes were located in the genes E-cadherin, ZFHX3 (both amplifications in chromosome 16), RIPK2 (deletion in chromosome 8) and PTEN (deletion in chromosome 10) in 15 patients (20.8%), 12 patients (16.7%), 9 patients (12.5%) and 7 patients (9.7%), respectively. Copy number variations of various genes were associated with presence of variant histology (TSG1, RAD21, KIAA0196, ANXA7; all p-values<0.029), pathologic tumor grade (TSG1, KIAA0196, RAD21, ANXA7, TMPRSS2; all p-values<0.029), presence of incidental prostate cancer (EZH2, miR-15a, CDH1, ZFHX3; all p-values<0.024), as well as increased risk of disease recurrence (RIPK2; p=0.038), overall (KLF5; p=0.033) and cancer-specific mortality (KLF5, ZFHX3; all p-values<0.022). Conclusions In serum cfDNA, MLPA represents an efficient method for the detection of genomic aberrations among numerous chromosomal regions and genes. Copy number variations of various genes are associated with aggressive pathologic bladder cancer features and seem to have a negative impact on disease recurrence and survival. Funding None
Authors
Armin Soave
Felix Chun Michael Rink Lars Weisbach Valentin Maurer Philipp Gild Bettina Steinbach Margit Fisch Klaus Pantel Heidi Schwarzenbach |
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MP34-08 |
HIPEC with Cytoreductive Surgery can cure Patients with Limited Peritoneal Carcinomatosis from Adenocarcinoma of the Urachus |
Bladder Cancer: Invasive II | 17BOS |
Abstract: MP34-08 Sources of Funding: none Introduction Urachal cancer (UraC) is a rare malignant disease. Patients usually present with advanced mucinous adenocarcinoma, which may disseminate to the peritoneal cavity, causing peritoneal carcinomatosis (PC). Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been shown to improve clinical outcomes for adenocarcinomas arising from the colon and the ovary. We report our experience of structured stepwise staging and HIPEC for UraC. Methods Between 01/1994 and 04/2016, 56 patients with UraC were treated and followed at our institute. For this study, we excluded 8 patients (urothelial carcinoma). Structured work-up included at least a chest X-ray and an abdominal/pelvic CT-scan. Starting in 2001 diagnostic supra-umbilical laparoscopy (dLap) was introduced in patients with initial negative CT and revealed limited PC in 6/26 (23%) patients. Overall, staging (imaging and/or dLap) revealed 11 metastatic patients and another 9 patients, who had limited PC and were eligible for local excision of the urachus, CRS and HIPEC with open bladder. Diagnostic laparoscopy was not performed in 22/48 (46%) patients (palliative 5x; primary resection elsewhere 4x; large tumor with mucinous fluid (? 8cm) 3x; small, presumed benign tumor (? 2cm) 3x; before 2001 7x). Results In total, 37 patients who had UraC received treatment with curative intent (28 local excision only and 9 CRS with HIPEC). Median follow-up for the 9 HIPEC patients was 33 months (IQR 59 months) and 6/9 (67%) HIPEC patients still have no signs of recurrence after median follow-up of 53 months (IQR 75 months) (see Table). After HIPEC, two patients had postoperative adverse events requiring intervention (grade3). Disease specific survival for the patients treated with HIPEC for limited PC was comparable to the patients who had local excision only and was superior to the metastatic UraC patients (Plog-rank = 0.034). Conclusions Laparoscopy can reliably detect limited PC in patients with UraC without radiological signs of metastasis. If limited PC is present, HIPEC represents a curative treatment with favorable oncological outcome and acceptable toxicity. Funding none
Authors
Mark Behrendt
Akash Mehta Elisabeth Fransen van de Putte Michiel Van der Heijden Simon Horenblas Luc Moonen Vic Verwaal Wim Meinhardt Bas Van Rhijn |
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MP34-09 |
Is a delay in the timing of radical cystectomy really detrimental? A retrospective study on a single centre cohort |
Bladder Cancer: Invasive II | 17BOS |
Abstract: MP34-09 Sources of Funding: None Introduction EAU guidelines recommends radical cystectomy (RC) within a time span of 90 days from the diagnosis, to avoid an impairment in the prognosis, but the literature on this issue is not univocal. This study aims to evaluate if the latency between the diagnosis and cystectomy (LDC) could affect oncological outcomes. Methods Retrospective analysis of a perspectively-maintained database that stores data of all the patients submitted to RC since 2009 at a tertiary academic institution._x000D_ LDC was defined as the days between RC and the last TURBT. The primary outcome was overall survival (OS), the secondary were: relationship between clinical and pathological features and a LDC >90 days and relationship between LDC and pathological upstaging (pUS) (shift from cT1-2 to pT3-4). Statistical correlations were evaluated by univariate and multivariate Cox regression and binary logistic models, considering as significant p values <0.05. Results Overall, 226 patients were included from January 2009 to June 2016 (mean/median LDC 89/79 days). A LDC>90 days was observed for 84 patients (37.2%), while pUS in 48 patients (25.7%). After a median follow up time of 17 months, the overall mortality rate was 47.3% (98/226). Table 1 summarizes results. Factors independently related to LDC >90 days were: age (OR=1.047), Charlson Comorbidity Index (CCI)=0 (OR= 0.428), diagnosis of recurrent BC (OR= 3.390) and lack of detrusor infiltration at TURBT (OR= 0.490). Factors related to pUS were: age (RR=1.045) and detrusor infiltration at TURBT (OR=0.307), whereas no relationship was found with LDC (upstaging rate LDC<90 vs >90 days 25.5% vs 26%). OS was independently related to female gender (RR=0.597), CCI>0 (OR=1.377), advanced clinical and pathological staging, and lymph node invasion (OR=2.096), but not to LDC (estimated 2 years OS rate LDC<90 vs >90 days 55% vs 59%). Conclusions Elderly and healthier patients with recurrent or clinically NMIBC are more frequently submitted to RC after a longer interval. In daily practice at referral institutions a comprehensive evaluation of the patient could balance known and unknown prognostic factors making negligible the impact of a delay in RC. A threshold of LDC of 90 days seems to affect neither the risk of pUS nor OS and should be discussed in further editions of Guidelines. Funding None
Authors
Alessandro Antonelli
Stefania Zamboni Maria Cristina Marconi Carlotta Palumbo Sandra Belotti Luca Cristinelli Vincenzo De Luca Claudio Simeone |
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MP34-10 |
Development and Validation of Cystectomy Assessment and Surgical Evaluation (CASE) Scoring for Male Radical Cystectomy |
Bladder Cancer: Invasive II | 17BOS |
Abstract: MP34-10 Sources of Funding: Roswell Park Alliance Foundation Introduction It is vital to ensure standardization and objective feedback during training and skill acquisition for optimal surgical outcomes and patient safety. We aimed to develop a structured scoring tool: CASE (Cystectomy Assessment & Surgical Evaluation) that objectively measures and quantifies performance during radical cystectomy (RC) for men. Methods A multinational expert panel (11 Surgeons who perform open and/or robot-assisted radical cystectomy) collaborated towards development and content validation of the male RC scoring. The critical steps were deconstructed into 9 key domains, where each domain was assessed by 5 anchors evaluating surgical principles, technical proficiency and safety. Content validation was done utilizing the Delphi methodology. Each anchor statement was assessed in terms of 3 aspects: contextual relevance, concordance between language and anchor score, and clarity of wording. An independent coordinator collated the comments and computed Content Validity Index (CVI) for each aspect of each anchor. If CVI was >=0.75, consensus was reached and the statement was removed. If consensus was not achieved, the coordinator incorporated comments from the panel and the updated scoring system was redistributed. This process was repeated until consensus was achieved for all statements. Experts were blinded to each other's assessment. Results The expert panel reached consensus after 4 rounds on all aspects. A ninth domain assessing Disposition of Tissue was removed from the system after the second round. CVI >= 0.75 was achieved in 8 (11%) statements in the first round, 44 (61%) statements in the second, 17 (24%) statements in the third and 3 (4%) statements in the 4th round. The final 8 domains included: Pelvic Lymph Node Dissection, Development of the Peri-ureteral Space, Lateral Pelvic Space, Anterior Rectal Space, Control of the Vascular Pedicle, Anterior Vesical Space, Control of the Dorsal Venous Complex, and Apical Dissection (Fig 1). Conclusions We developed and validated a scoring system for RC that can provide structured feedback for surgical quality assessment, training and feedback. Validation of the scoring system is in process. Funding Roswell Park Alliance Foundation
Authors
Kevin Sexton
Ahmed Hussein Meng Maxwell Abolfazl Hosseini Peter Wiklund Daniel Eun Siamak Daneshmand Bernard Bochner James Peabody Ronney Abaza Eila Skinner Richard Hautmann Khurshid Guru |
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MP34-11 |
Neoadjuvant Chemotherapy Prior to Radical Cystectomy for Muscle-Invasive Bladder Cancer with Variant Histology |
Bladder Cancer: Invasive II | 17BOS |
Abstract: MP34-11 Sources of Funding: None Introduction Neoadjuvant chemotherapy in pure urothelial bladder cancer provides a significant survival benefit. However, it is unknown if this benefit persists in histological variants of bladder cancer. We aimed to assess the effect of neoadjuvant chemotherapy on overall survival (OS) and upstaging at radical cystectomy in the five most common histological variants. Methods Querying the National Cancer Data Base, we identified 1,555 patients with histological variants undergoing radical cystectomy for muscle-invasive bladder cancer between 2003-2011. Neoadjuvant chemotherapy was defined as multiagent systemic therapy administered within 180 days prior to surgery. Histological variants were categorized as pure neuroendocrine tumors, squamous cell carcinoma, and adenocarcinoma, or micropapillary and sarcomatoid differentiation. Cox regression models were used to examine the effect of neoadjuvant chemotherapy on overall mortality in each variant subgroup. Logistic regression models estimated the odds of pathological upstaging at radical cystectomy for each histological variant, stratified by the receipt of neoadjuvant chemotherapy. Results In multivariate analyses, an OS benefit for neoadjuvant chemotherapy was only found in neuroendocrine tumors (hazard ratio [HR]=0.64; 95% confidence interval [CI]=0.45-0.90; P=0.012). Neuroendocrine tumors (odds ratio [OR]=0.38; 95% CI=0.22-0.67; P=0.001), along with micropapillary (OR=0.16; 95% CI=0.05-0.47; P=0.001) and sarcomatoid differentiated tumors (OR=0.34; 95% CI=0.14-0.87; P=0.025), were less likely to be upstaged at radical cystectomy when treated with neoadjuvant chemotherapy. In squamous cell and adenocarcinoma, no favorable pathological outcomes were seen in patients receiving neoadjuvant chemotherapy vs. radical cystectomy alone (all P>0.08). Specifically, patients with squamous cell carcinoma even trended towards worse pathology (i.e. upstaging) at RC if they received neoadjuvant chemotherapy (OR=1.81; 95% CI=[0.93-3.52]; P=0.081) compared to patients undergoing RC alone. Conclusions Patients with neuroendocrine tumors benefit from neoadjuvant chemotherapy, as evidenced by better OS and lower rates of pathological upstaging at radical cystectomy. In micropapillary and sarcomatoid differentiated tumors, neoadjuvant chemotherapy decreased pathological upstaging at cystectomy. However, this favorable effect did not translate into a statistically significant OS benefit for these patients, potentially due to the aggressive tumor biology. Funding None
Authors
Malte W. Vetterlein
Stephanie Mullane Thomas Seisen Richard Lander Björn Löppenberg Toni K. Choueiri Joaquim Bellmunt Mani Menon Adam S. Kibel Quoc-Dien Trinh Mark A. Preston |
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MP34-12 |
Overexpression of autophagy-related gene ATG7 promotes bladder cancer invasion via autophagic removal of pre-mRNA processing protein AUF1 and increased stability of RhoGDI? mRNA in vitro and in vivo |
Bladder Cancer: Invasive II | 17BOS |
Abstract: MP34-12 Sources of Funding: NIH/NCI CA165980, CA177665, CA112557, and NIH/NIEHS ES000260; the Natural Science Foundation of China (NSFC81229002, NSFC81372946) and Key Project of Science and Technology Innovation Team of Zhejiang Province (2013TD10) and the Xinmiao Talent Program of Zhejiang Province (2016R413068) Introduction Autophagy is an evolutionarily conserved mechanism that is critical for cellular homeostasis but its involvement in cancer in general has been controversial. Even less is known about the relationship between autophagy and bladder cancer development and progression. Here we explore the role of ATG7, a key autophagy-related regulator, in bladder cancer cell invasion. Methods Expression of ATG7 protein in human bladder cancer specimens, cell lines and N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)-induced mouse invasive bladder cancer specimens were assessed using immunohistochemistry and immunoblotting. After ruling out transcriptional regulation, the possibility of microRNA in ATG7 expression was tested by bioinformatics search for putative miRNAs that could target 3’-UTR of ATG7 mRNA, by assessing the expression of candidate miRNAs in bladder cancer tissues and cell lines and by studying the effects of miRNAs on ATG7 expression with stable transfection. The effects of ATG7 expression on invasion was evaluated after shRNA knockdown. The levels of cell invasion effectors (RhoGDI?, RhoGDI?, Rac1, 2, 3, and RhoA) were also determined. The upstream regulators of RhoGDI? were determined using RNA-IP and verified in xenografted tumors. Results ATG7 was markedly and reproducibly upregulated in human muscle-invasive bladder cancers, their cell-line derivatives and mouse invasive bladder cancer induced by BBN. Knockdown of ATG7 in human bladder cancer cell lines UMUC3 and T24 dramatically reduced their invasion. Mechanistic analyses showed that ATG7 overexpression was mediated by miR-190, which was also highly upregulated in bladder cancer tissues and cell lines. miR-190 bound to the 3’-UTR of ATG7 mRNA increasing its stability. A separate mechanism was that ATG7-mediated autophagic response could remove AUF1 protein and reduce AUF1 interaction with RhoGDI? mRNA, leading to increased RhoGDI? mRNA stability which then promotes invasion. Indeed, inhibition of ATG7-mediated autophagy led to AUF1 protein accumulation, RhoGDI? downregulation and decreased cell invasion. Conclusions Our results provide the first mechanistic link between autophagy and bladder cancer cell invasion. The signaling axis along ATG7-AUF1- RhoGDI? that is highly operative in bladder cancer cells might be explored further for developing novel diagnostic and therapeutic approaches to manage advanced bladder cancers. Funding NIH/NCI CA165980, CA177665, CA112557, and NIH/NIEHS ES000260; the Natural Science Foundation of China (NSFC81229002, NSFC81372946) and Key Project of Science and Technology Innovation Team of Zhejiang Province (2013TD10) and the Xinmiao Talent Program of Zhejiang Province (2016R413068)
Authors
Junlan Zhu
Yang Li Chuanshu Huang Xue-Ru Wu |
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MP34-13 |
Neoadjuvant sorafenib, gemcitabine, and cisplatin (SGC) for muscle-invasive urothelial bladder cancer (MIUBC): final results and translational findings of an open-label, single-arm, phase 2 study. |
Bladder Cancer: Invasive II | 17BOS |
Abstract: MP34-13 Sources of Funding: Research grant from the Fondazione IRCCS Istituto Nazionale dei Tumori Introduction Despite cisplatin-based chemotherapy (CT) is recommended in MIUBC, an unmet need is to identify new drugs or combinations to improve the outcomes. SGC combination was evaluated in an open-label, single-arm, phase 2 trial (NCT01222676). Methods After TURB, pts with T2-T4a N0 MIUBC received 4 cycles of cisplatin 70 mg/m2 d1, gemcitabine 1000 mg/m2 d1 and 8, q3 wks. Sorafenib 400 mg q12h was administered daily from day 1 until radical cystectomy. In a Simon&[prime]s 2-stage design, the primary endpoint was pathologic complete responses (pT0). Residual carcinoma in situ was considered pT0. ITT analysis was applied. Statistical hypothesis assumed H0: ≤0.20 and H1: ≥0.40 (α and β of 5% and 10%). ERCC1 immunohistochemistry (IHC) and next-generation sequencing (NGS) of TURB tissue, and measurement of baseline circulating VEGF levels, were planned. Results From 04/2011-06/2016, 45 pts were enrolled. 28 pts (62.2%) had macroscopical residual disease after TURB, 17 (37.8%) presented with clinical stage T3-4. pT0 was obtained in 19 pts (42.2%, 95%CI: 27.6-57.9); pT≤1 in 24 (53.3%, 95%CI: 37.9-68.3). After median follow-up of 35 months, median PFS was not reached (IQR: 29.4-NE), like median OS (IQR: 30.3-NE). Pathological response (pT0 vs pT≤1 vs other) predicted for both PFS (p=0.015) and OS (p=0.046). Hematologic (hem) G3-4 adverse events (AE): platelet 28.9%, neutrophils 15.6%, Hb (4.4%). Extra-hem AEs were seen in 9 pts (20%). 24 (53.3%) pts needed S temporary interruption (5 cases discontinuation)._x000D_ Tumor samples were available from 23 pts for ERCC1-IHC, 24 for NGS: ERCC1 IHC expression was associated with non response (pT≥2, p=0.033). ERBB2/ERBB3 mutations were found only in responders (pT≤1, 20%). PIK3CA/AKT mutations (missense, and newly-identified mutations) were more frequent in pT≥2 pts (35.7% vs 20%). Baseline VEGF levels did not predict for PFS/OS. NGS of the remaining pts of the trial is ongoing. _x000D_ Conclusions SGC combination was active and effective in MIUBC. Translational analyses are providing information to develop combination of CT with new more potent and selective TKIs, possibly in more selected pts. Funding Research grant from the Fondazione IRCCS Istituto Nazionale dei Tumori
Authors
Andrea Necchi
Salvatore Lo Vullo Daniele Raggi Patrizia Giannatempo Nicola Nicolai Davide Biasoni Mario Catanzaro Tullio Torelli Silvia Stagni Giuseppina Calareso Elena Togliardi Maurizio Colecchia Adele Busico Federica Perrone Luigi Mariani Roberto Salvioni |
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MP34-14 |
The Effect of Adjuvant Chemotherapy for Patients with Adverse Pathology after Neoadjuvant Chemotherapy for Muscle-Invasive Bladder Cancer |
Bladder Cancer: Invasive II | 17BOS |
Abstract: MP34-14 Sources of Funding: None Introduction While neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC) is recognized as the standard of care, the management of patients with locally advanced and/or nodal disease after NAC and radical cystectomy (RC) is not well defined. We sought to evaluate the association of adjuvant chemotherapy (AC) and overall survival (OS) among patients with adverse pathology after NAC and RC. _x000D_ Methods The National Cancer Database was reviewed to identify patients with adverse pathology (pT3N0, pT4N0, or pTanyN1-3) at RC following NAC from 2006-2012. Patients were stratified by receipt of AC. Clinical and pathologic variables were abstracted. OS was the primary end-point and differences on the basis of AC receipt among all patients and as stratified by pathologic stage were assessed by the Kaplan-Meier method and log-rank test. Multivariable Cox proportional hazards regression was used to assess the association of AC with OS controlling for age, sex, race, Charlson score, year of diagnosis, pathologic stage, and receipt of adjuvant radiotherapy. _x000D_ _x000D_ Results Adverse pathology following NAC and RC was identified in 1,361 patients from 2006-2012, of whom 328 (24.1%) received AC. Staging was pT3N0 in 444 (32.6%), pT4N0 in 162 (11.9%), and pTanyN1-3 in 755 (55.5%). Median OS for the entire cohort was 22.9 months, which differed by pathologic stage: 34.6 months (pT3N0), 21.4 months (pT4N0), and 19.3 months (pTanyN1-3)(p<0.01). No difference in OS was noted by receipt of AC in the overall cohort (median OS 24.6 months with AC vs 22.0 months without AC; p=0.18), or when stratified by pathologic stage. On multivariable analysis, receipt of AC was not significantly associated with overall mortality (HR 0.86; 95%CI 0.74-1.01; p=0.06) for all patients. When stratified by stage, AC was associated with a significantly decreased risk of mortality among patients with pT4N0 disease (HR 0.56; 95%CI 0.33-0.97; p=0.04), but not pT3N0 or pTanyN1-3 (p>0.05). _x000D_ Conclusions Patients with adverse pathology at RC after NAC have a median OS of approximately 2 years. AC was not associated with improved survival, except in the subgroup with pT4N0 disease. Clinical trials with newer systemic therapies are warranted for patients in this setting. Funding None
Authors
William Parker
Elizabeth Habermann Courtney Day Harras Zaid Igor Frank R. Houston Thompson Matthew Tollefson Stephen Boorjian Lance Pagliaro R. Jeffrey Karnes |
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MP34-15 |
A European multi-centre report on current Neoadjuvant chemotherapy administration rates in Robot-assisted Radical Cystectomy patients and the impact on pathological staging |
Bladder Cancer: Invasive II | 17BOS |
Abstract: MP34-15 Sources of Funding: None Introduction Neoadjuvant chemotherapy is considered the standard of care in patients with muscle-invasive bladder cancer (MIBC) and has been shown to confer overall survival advantages of 5% in RCTs. Data on neoadjuvant chemotherapy (NAC) administration rates in patients undergoing robot-assisted radical cystectomy (RARC) is limited, ranging from 0 to 31% in the published literature. We report administration rates of NAC from a multi-institutional European database focusing on the centres performing totally intracorporeal RARC. Reporting the effect of NAC on down-staging and up-staging rates from clinical staging (cT) to the pathological specimen (pT). Methods Retrospective review of the prospectively populated multi-institutional database identified 717 patients at 9 different Institutions (6 countries), with a minimum of 12 months follow-up, who underwent RARC for non-metastatic bladder cancer with curative intent between Dec 2003 and March 2015. Clinical stage was assigned based on a combination of specimen pathology from TURBT, EUA and imaging studies. Cisplatin based NAC was offered to patients with cT2-cT4, taking into account patient performance status. Clinical staging, pathologic staging and survival data at the latest follow-up were collected. Results Median age was 68 years, 78% were men. 95.2% of patients had TCC. 532 (74.2%) patients were alive at the time of the analysis. The median follow-up time for patients was 31 months (IQR 20-46). 465 patients (65%) had cT2-T4 TCC. In this series 25.3% of patients received NAC. See table 1 for upstaging and down-staging related to NAC. PSM rates were associated with upstaging (p<0.001). On multivariable analysis NAC was associated with down-staging in all patients OR 3.46 95% CI 2.34-5.13 p <0.001 and this effect increased in patients with non-organ confined disease OR 5.45 95%CI 2.15-13.8 p<0.001. The 5-year CSS, OS and RFS were 69.9%, 66.1% and 66.3% respectively. On multivariable analysis, pathological non-organ confined versus organ confined disease was found to impact CSS, OS and RFS (HR 4.4, 3.8 and 3.8 respectively). Conclusions NAC was associated with downstaging of MIBC. Increasing NAC administration rates would likely further improve oncological outcomes. Funding None
Authors
Justin Collins
Abolfazl Hosseini Christofer Adding Anthony Koupparis Edward Rowe Matthew Perry Rami Issa Tommy Nyberg Martin Schumacher Carl Wijburg A. Erdem Canda Mevlana Balbay Karel Decaestecker Christian Schwentner Arnulf Stenzl Sebastian Edeling Sasa Pokupik Ferderiek D'Hondt Alexandre Mottrie Peter Wiklund |
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MP34-16 |
Could adjuvant chemotherapy have therapeutic benefit after neoadjuvant chemotherapy in patients with equal to or greater than pT3 muscle invasive bladder cancer? |
Bladder Cancer: Invasive II | 17BOS |
Abstract: MP34-16 Sources of Funding: none Introduction Neoadjuvant chemotherapy (NAC) has been associated with improved prognosis in muscle invasive bladder carcinoma (MIBC) patients. However, the therapeutic effect of adjuvant chemotherapy (AC) following NAC remains unknown. Methods We retrospectively identified 576 patients who were treated by radical cystectomy for MIBC at our 7 institutions between 2007 and 2014. Among them, 196 patients with MIBC that was equal to or greater than pT3 were included in the present analysis. We compared the clinical characteristics and outcomes between MIBC patients with and without AC. Results Overall, 65 patients (33.2%) were treated by AC. The mean age of the patients with AC (AC group) was 65.9 years, which was significantly lower than that in their counterparts (73.7 years, p<0.001). The AC group had a higher incidence of pathological lymph node positive and concomitant CIS than their counterparts (p=0.002, p=0.018, respectively). The 5-year overall survival rate for the AC group was 46.0%, which was significantly higher than their counterparts (31.2%, p=0.03). Multivariate analysis revealed that the absence of AC (hazard ratio: HR, 1.93, p=0.015) was an independent indicator for death in addition to lymphovascular invasion (HR, 2.06, p=0.002) and pathological lymph node positive (HR, 1.9, p=0.011). In the subgroup of patients without NAC (N=139), 43 patients (30.9%) were treated by AC. The mean age of patients in the AC group was 65.3 years, which was significantly lower than that in their counterparts (74.9 years, p<0.001). The AC group had a higher incidence of pathological lymph node positive than their counterparts (p=0.006). The 5-year overall survival rate for the AC group was 47.5%, which was significantly higher than that in their counterparts (29.4%, p=0.015). Multivariate analysis revealed that the absence of AC (hazard ratio: HR, 2.16, p=0.028) was an independent indicator for death in addition to pathological lymph node positive (HR, 1.98, p=0.025). In the subgroup of patients with NAC (N=57), 22 patients (38.6%) were treated by AC. The 5-year overall survival rate for the AC group (40.2%) was not significantly higher than that in their counterparts (36.0%, p=0.932). Conclusions In MIBC patients with a pathological stage equal to or greater than pT3, AC seems to be associated with a better prognosis. However, our data does not support the addition of AC to patients previously treated with NAC. Funding none
Authors
Minami Omura
Eiji Kikuchi Koichiro Ogihara Kyohei Hakozaki Keishiro Fukumoto Go Kaneko Yasumasa Miyazaki Nobuyuki Tanaka Suguru Shirotake Kunimitsu Kanai Kazuhiro Matsumoto Hirohiko Nagata Akira Miyajima Mototsugu Oya |
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MP34-17 |
Prognostic significance of serum γ-glutamyltransferase in advanced urothelial carcinoma patients |
Bladder Cancer: Invasive II | 17BOS |
Abstract: MP34-17 Sources of Funding: None Introduction γ-glutamyltransferase (GGT), which is expressed in various human cancer cells, is known as a membrane-bound enzyme playing a protective role from oxidative stress. Recent studies indicated that GGT can also exert pro-oxidant effects at the membrane surface and the extracellular microenvironment, contributing to the regulation of proliferative/apoptotic balance, the acquisition of chemo-resistance, and cancer progression. Here, we explored the prognostic role of serum GGT in advanced urothelial carcinoma (aUC) patients. Methods This retrospective study included 126 consecutive aUC patients (inoperable cT4 and/or metastases to lymph nodes/distant organs) treated at a single cancer center from 2004 to 2016. Of the 126 patients, 93 (74%) received systemic chemotherapy. Variables collected included age, gender, performance status (PS), body mass index (BMI), hydronephrosis, primary site, lymph node/visceral metastasis, prior curative surgery, therapies for aUC, hemoglobin, white blood cell count, creatinine, albumin, alkaline phosphatase, lactate dehydrogenase (LDH), corrected calcium, C-reactive protein (CRP), aspartate/alanine aminotransferase, and GGT. We assessed variables associated with overall survival (OS) using the Cox proportional hazards model. Results The median (range) serum GGT was 26 (7-252) U/L. During follow-up (median 12M), 92 patients died (2Y OS rate 24%). On multivariate analysis, GGT was an independent predictor for OS (HR 1.01 as a continuous variable, p = 0.007) along with age (HR 1.04, p = 0.003), BMI (HR 0.92, p = 0.005), visceral metastasis (HR 1.92, p = 0.006), albumin (HR 0.49, p = 0.032), log LDH (HR 2.63, p < 0.001), and log CRP (HR 1.41, p < 0.001). Next, the optimal cut-off of GGT was determined. When patients with GGT ≥43 U/L were defined as elevated, HR was highest on univariate Cox proportional hazards analysis (2.16). The 2Y OS rates for patients with elevated and non-elevated GGT were 5% and 30%, respectively (p < 0.001). The prognostic significance of elevated GGT was confirmed in multivariate analysis (HR 2.29, p = 0.001). Incorporation of GGT into the Bajorin&[prime]s model (PS and visceral metastasis) improved the c-index from 0.654 to 0.685. Conclusions This study is the first to demonstrate the prognostic significance of serum GGT in aUC patients. Funding None
Authors
Hiroshi Fukushima
Yasukazu Nakanishi Madoka Kataoka Ken-ichi Tobisu Fumitaka Koga |
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MP34-18 |
Early detection of asymptomatic visceral recurrence by routine CT scan after radical cystectomy contributes better prognosis in patients with muscle invasive bladder cancer |
Bladder Cancer: Invasive II | 17BOS |
Abstract: MP34-18 Sources of Funding: none Introduction To assess whether routine followup with computed tomography (CT) to detect asymptomatic visceral recurrence after radical cystectomy improves patient survival, we investigated the impact of symptoms at recurrence on patient survival._x000D_ Methods A total 348 radical cystectomy for muscle invasive bladder cancer (MIBC) were performed at our institution between January 1996 and December 2013. All patients had regular followup examinations with urine cytology every 3 months, blood biochemical test, and CT of the chest and abdomen every 6 months. We investigated the first site and date of tumor recurrence. Overall survival in patients with recurrence stratified by the mode of diagnosis (asymptomatic vs. symptomatic) was estimated using the Kaplan-Meier methods and compared with the log rank test. Cox proportional hazard regression models were used to evaluate the impact of the mode of diagnosing recurrence on survival._x000D_ Results A total 91 patients (20%) experienced recurrence after surgery. Seven patients (8%) were excluded due to missing data. Finally, 84 patients were enrolled in this retrospective study. Of those, 46 (55%) were asymptomatic and 38 (45%) were symptomatic. The most common recurrence site and symptom were lymph nodes (55%) and pain (53%). Overall survivals after surgery and recurrence to death were significantly longer in patients with asymptomatic recurrence compared with symptomatic recurrence. Multivariate analysis showed that a symptomatic recurrence is one of the independent risk factors for overall survival after surgery and recurrence._x000D_ Conclusions Routine oncological followup for detection of asymptomatic recurrence may contribute better prognosis after radical cystectomy._x000D_ Funding none
Authors
Ayumu kusaka
Shingo Hatakeyama Hayato Yamamoto Atsushi Imai Takahiro Yoneyama Yasuhiro Hashimoto Takuya Koie Chikara Ohyama |
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MP34-19 |
Effect of Histological Variants on the Outcomes of Radical Cystectomy for Non-Metastatic Muscle-Invasive Urinary Bladder Cancer |
Bladder Cancer: Invasive II | 17BOS |
Abstract: MP34-19 Sources of Funding: None Introduction Knowledge of comparative oncological outcomes of histological variants after radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC) relies on small case series. Our aim was to compare the effect of squamous cell, adenocarcinoma, and neuroendocrine carcinoma vs. pure urothelial carcinoma of the bladder (UCB) on overall survival (OS) and pathological tumor, lymph node, and surgical margin status after RC. Methods Using the National Cancer Data Base, we retrospectively examined patients undergoing RC for MIBC between 2003-2011. Our cohort was stratified according to pure histology: squamous cell, adenocarcinoma, neuroendocrine, and UCB. Inverse probability weighting (IPW)-adjusted and facility-clustered Cox and logistic regressions were used to assess the impact of histological variants vs. UCB on OS and histopathological outcomes. Results Overall, 475 (4.4%), 224 (2.1%), 155 (1.4%), and 10,033 (92.2%) patients underwent RC for MIBC with pure squamous cell, adenocarcinoma, neuroendocrine carcinoma, and UCB, respectively. In IPW-adjusted analyses, squamous cell (HR=1.26; 95%CI=[1.07-1.49]; P=0.006) and neuroendocrine (HR=1.53; 95%CI=[1.21-1.95]; P<0.001) were associated with worse OS relative to UCB (Figure 1). Squamous cell (OR=1.58; 95%CI=[1.23-2.04]; P<0.001), adenocarcinoma (OR=1.49; 95%CI=[1.04-2.14]; P=0.030), and neuroendocrine carcinoma (OR=2.37; 95%CI=[1.58-3.55]; P<0.001) at diagnosis were associated with greater odds of ≥pT3 disease. Squamous and neuroendocrine variants were associated with decreased (OR=0.66; 95%CI=[0.48-0.91]; P=0.012) and increased (OR=1.58; 95%CI=[1.06-2.37]; P=0.026) odds of pN+ disease, respectively, while adenocarcinoma was associated with greater odds of positive margins (OR=2.14; 95%CI=[1.39-3.30]; P=0.001). Conclusions Pure squamous cell and neuroendocrine carcinoma is associated with worse OS relative to UCB, whereas no difference was found between adenocarcinoma and UCB. All histological variants were associated with higher pT stage at surgery compared to UCB. Funding None
Authors
Malte W. Vetterlein
Thomas Seisen Jeffrey J. Leow Mark A. Preston Maxine Sun David F. Friedlander Christian P. Meyer Felix K.-H. Chun Stuart R. Lipsitz Mani Menon Adam S. Kibel Joaquim Bellmunt Toni K. Choueiri Quoc-Dien Trinh |
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MP34-20 |
Can radical cystectomy be performed safely in the metastatic setting? Location of metastatic bladder cancer as a determinant of in-hospital mortality |
Bladder Cancer: Invasive II | 17BOS |
Abstract: MP34-20 Sources of Funding: none Introduction A recent study within a highly-select patient cohort suggested a survival benefit when local treatment is delivered in patients with metastatic bladder cancer (BCa). We relied on a similar patient cohort to examine in-hospital mortality (IHM) rates according to presence, absence and location of metastatic disease in BCa patients treated with radical cystectomy (RC). Methods We identified 25,004 BCa patients treated with RC between 2004 and 2013 from the hospital claims data in the National Inpatients Sample database. Using International Classification of Diseases, 9th edition (ICD-9-CM) diagnostic codes, we identified 5,049 patients with metastatic disease. Metastatic BCa patients were stratified according to the presence of non-regional lymph node metastases (NRNM) in absence of distant organ involvement vs. presence of distant organ metastases (DM), regardless of nodal status._x000D_ We tested postoperative IHM rates according to presence of metastases, as well as location of metastatic disease (NRNM vs. DM). Logistic regression analyses were adjusted for age, gender, race, comorbidities, length of hospitalization, hospital location, teaching status, hospital surgical volume and bed size. Results Overall, 3,323 patients (13.3%) had NRNM, 1,726 (6.9%) had DM, and 19,965 (79.8%) had non-metastatic disease. Virtually all metastatic patients had a single metastatic site involvement (n=4,458; 88.5%), while only a small proportion of individuals had metastatic involvement in 3 or more sites (n=57; 1.1%). The most common metastatic sites were lymph nodes (76.0%; n=3,830), other urinary organs (23.2%; n=1,168), intestine (4.7%; n=235) and retroperitoneum (4.1%; n=209). Interestingly, bone and liver metastases represented only 1.6% (n=81) and 1.1% (n=55) of cases, respectively._x000D_ IHM rates were 1.5% (n=51), 3.5% (n=60) and 2.0% (n=404) for NRNM, DM and non-metastatic patients, respectively. The difference in IHM rates between DM and non-metastatic BCa patients was statistically significant (p<0.001). Conversely, NRNM patients did not exhibit different mortality rates than their counterparts without metastatic disease (p=0.07). In multivariable logistic regression analyses, DM patients (OR: 1.68; 95% CI: 1.26-2.20; p<0.001), but not NRNM patients (OR: 0.84; 95% CI: 0.62-1.11; p=0.2), were at increased risk of IHM. Conclusions DM patients are at an increased risk of IHM, compared to NRNM or non-metastatic patients. If at all indicated, RC in metastatic setting should be limited to patients with NRNM. Funding none
Authors
Emanuele Zaffuto
Marco Moschini Sami-Ramzi Leyh-Bannurah Stephanie Gazdovich Paolo Dell'Oglio Raisa S. Pompe Shahrokh F. Shariat Francesco Montorsi Alberto Briganti Fred Saad Pierre I. Karakiewicz |
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MP35-01 |
Attitudes towards Fertility and Reproductive Health among Transgender Adolescents |
Infertility: Epidemiology & Evaluation II | 17BOS |
Abstract: MP35-01 Sources of Funding: none Introduction Transgender/gender non-conforming adolescents (TGNC-A) often pursue hormonal therapies (puberty blockers; cross-sex hormones) to alleviate gender dysphoria. These therapies may cause impairments in gonadal histology that lead to infertility, such that fertility preservation in adolescence may be pursued. Despite this, little is known about the reproductive desires of TGNC-A. We aimed to address this gap by assessing attitudes towards fertility among TGNC-A. Methods An online survey about sexual health in lesbian, gay, bisexual, transgender and queer (LGBTQ) adolescents ages 14-17 was conducted via Facebook from 9/16-10/16. We analyzed responses related to fertility and reproductive health among self-identified TGNC-A. Results 172 TGNC-A (median age 16 years; 35% transgender men [female-to-male], 5% transgender women [male-to-female], 49% genderqueer/gender non-conforming; 52% white, 27% Hispanic, 23% multiracial, 7% African-American, 6% Asian) responded. Overall, 38% were interested in biological parenthood and 71% in adoption. Discussions about hormonal therapies with healthcare providers were relatively uncommon (11% discussed puberty blockers; 21% cross-sex hormones). Accordingly, only 20% have discussed fertility with a provider, and 18% have specifically discussed effects of hormones on fertility. However, 59% of TGNC-A surveyed were interested in learning more about fertility and family building options. Figure 1 illustrates preferred sources for this information; websites and healthcare providers were most common. Key themes/issues derived from qualitative comments included: stigma of LGBTQ parenthood, concerns about body dysphoria, cost of assisted reproductive technologies, and technical questions related to biological parenthood. Only 17% of respondents indicated they were uncomfortable answering questions about fertility. Conclusions TGNC-A expressed interest in multiple family building options, including adoption and biological parenthood. Both survey responses and qualitative comments identified the need for more education about these options. Fertility medicine specialists should be aware of the unique needs facing this emerging and increasingly visible population. _x000D_ ?_x000D_ Funding none
Authors
Diane Chen
Ilina Rosoklija Courtney FInlayson Kathryn Macapagal Brian Mustanski Emilie Johnson |
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MP35-02 |
Variable Adoption of World Health Organization 2010 Semen Analysis Reference Ranges: The Difference Between "Normal" and "Abnormal" May Depend on Where You Go |
Infertility: Epidemiology & Evaluation II | 17BOS |
Abstract: MP35-02 Sources of Funding: None Introduction There is no universal agreement on normal reference ranges for semen analysis (SA). Many laboratories use the World Health Organization (WHO) reference ranges, however the newest 2010 edition (WHO 5) is not without controversy. It is unknown how many laboratories utilize WHO 5 values now six years after their release. Our objective was to determine rates of adoption of WHO 5 criteria among US andrology labs. Variable reference range adoption leads to different categorization of results as "normal" or "abnormal" depending on where men obtain their SA._x000D_ Methods Clinical Laboratory Improvement Amendments (CLIA) laboratories certified to perform SA were extracted from CLIA (http://www.cdc.gov/clia/Resources/Laboratoriesearch.aspx) using a keyword search with: "andrology," "infertility," and "semen analysis." De-identified SA reports and reference ranges used were obtained by phone or email. Rates of adoption were computed by comparing reported values to WHO criteria. A chi-square test was used to compare the rate of WHO 5 criteria adoption between academic and non-academic centers._x000D_ Results We contacted 280 laboratories in 46 states. A total of 132 laboratories responded, with 104 (79%) laboratories performing SA in 32 states. Among labs performing SA, WHO 5 criteria was utilized by 63 (61%), while 29 (28%) used WHO 4 criteria. 12 (12%) laboratories used modified WHO criteria. WHO 5 criteria adoption was higher among academic centers (n=14, 86%) compared to non-academic centers (n=90, 57%) (P=0.04). Adoption rates varied by geographic region, ranging from 94% (16/17) in the Midwest to just 42% (11/26) in the West. Conclusions While the majority of laboratories have adopted WHO 5 criteria, a large percentage (39%) still use other criteria six years after the WHO 5 criteria were released. This variability could result in a male patient being characterized as "fertile" in one center and "subfertile" in another. The lack of consensus amongst laboratories in SA reference ranges could thus substantially impact management of the patient and his partner depending on where they seek treatment. _x000D_ Funding None
Authors
Anuj S. Desai
Kevin Lewis Daniel J. Mazur Barbara E. Kahn Mary Kate Keeter Emmanuel Ogele Alexander J. Tatem Marah Hehemann Nelson E. Bennett Robert E. Brannigan |
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MP35-03 |
Sex Hormone Binding Globulin Independently Predicts Oligospermia in Male Fertility Patients |
Infertility: Epidemiology & Evaluation II | 17BOS |
Abstract: MP35-03 Sources of Funding: None Introduction We previously reported that due to the inherent variability of SHBG, clinical hypogonadism is over/under-diagnosed in 20% of patients. We further analyzed the data between classically hypogonadal men (G1 - total testosterone (TT) < 300) and those men who were “missed� but were hypogonadal using calculated bioavailable testosterone (cBT < 210) with the use of SHBG (G2). We analyzed the role of SHBG in the routine testing of male factor infertility by analyzing the relationship of TT and BT to common infertility parameters. Methods Retrospective review of 168 males seen in a fertility clinic from 2012-2014, to investigate the accuracy of TT in the biochemical diagnosis of hypogonadism using cBT as the reference value. The relationship between TT and other infertility parameters were calculated using nonparametric Spearman correlations. We compared semen parameters between G1 and G2 in men with and without azoospermia. We utilized a multivariable sub-analysis with linear regression with backward elimination of non-significant variables. The possible predictors in the model included age, TT, varicocele, FSH, and SHBG. Results Using Spearman correlations, SHBG independently predicted lower semen parameters by a similar magnitude as FSH for sperm concentration (r= -0.24, p = 0.0027) and motility (r= -.16, p=.0447). Semen parameters were available for 76 men who met criteria for G1 and 46 for G2. Only SHBG levels differed significantly upon initial group comparision (p=.0001). After excluding men with azoospermia, G1 had 62 and G2 had 45 men respectively. SHBG remained significant (P=.0001) and sperm motility (p = .057) and sperm concentration (p=.09) approached significance. Using a more stringent cutoff for G2 (T<156) sperm motility was significantly different in G1 and G2 (p=.014). Linear regression to predict sperm motility and concentration eliminated age, TT, and varicocele from the model – leaving just FSH and SHBG. When predicting sperm motility, SHBG was no longer statistically significant (p=.0973) when FSH (p=0.0231) was in the model. For sperm concentration, SHBG was significant (p=0.0186) when FSH (p=0.0079) was in the model. Conclusions Our data demonstrates the utility of SHBG in the initial hormonal evaluation of males seen in a fertility clinic. The addition of SHBG to TT serum testing facilitates more accurate diagnosis with FT and cBT, as SHBG was the only significant parameter able to distinguish between true hypogonadal and eugonadal patients. In addition, elevated SHBG levels independently predicted decreased sperm motility and sperm concentration. Funding None
Authors
Joshua Ring
Charles Welliver Mike Parenteau Stephen Markwell Nikhil Gupta Robert Brannigan Tobias Kohler |
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MP35-04 |
Effect of medical comorbidities and their treatment on spermatogenesis in male infertility patients |
Infertility: Epidemiology & Evaluation II | 17BOS |
Abstract: MP35-04 Sources of Funding: none Introduction A close relationship has been shown between male infertility and general health status. The aims of this study were to investigate the prevalence and effect of medical comorbidities on spermatogenesis in Japanese men and to determine whether the treatment of medical comorbidities is effective for improving semen parameters. Methods Under the approval of the institutional ethics committee, a retrospective chart review was performed for 5,337 men with a mean age of 35 years who were consecutively examined due to male infertility between April 2007 and September 2016. The initial evaluations were comprised of a history, a physical examination, at least two semen analyses, and endocrinology examinations in the morning. Further blood tests were ordered when surgery was indicated. Hormonal and spermatogenic parameters were compared between men with and without medical comorbidities. For men who were diagnosed with medical comorbidities during the infertility evaluation, the semen parameters were compared between those who did and did not undergo treatment of the comorbidities. Results Significant medical comorbidities were found in 525 of 5,337 (9.8%) men, including 1.9% with mental (e.g., depression), 1.8% with circulatory (e.g., hypertension), 1.7% with skin (e.g., atopic dermatitis), 1.3% with kidney, 1.2% with respiratory diseases, 1.2% with diabetes, 1.0% with hyperuric acid and 0.9% with dyslipidemia. Fifty-three men (1%) exhibited a Charlson comorbidity index of more than 1 point. Testicular size (p<0.05), semen volume (p<0.01), sperm concentration and motility (p<0.001) and serum testosterone were significantly lower, and FSH was significantly higher (p<0.01) in men with comorbidities than in men without comorbidities. Of the 115 (2.2%) men who were diagnosed with comorbidities during the infertility evaluation (mainly hypertension, diabetes, hyperuric acid, and dyslipidemia) and underwent no specific infertility treatment (e.g., varicocelectomy, hormonal therapy), significant improvements in sperm concentration and motility were observed after six months of follow-up in men who underwent immediate treatment for the medical comorbidities (n=73) compared to men who did not receive treatment (n=42) (p<0.05). Conclusions Medical comorbidities are associated with the impairment of sperm production. Male infertility evaluation offers not only specific corrective therapy to improve semen parameters but also therapy for non-specific medical comorbidities, which may be beneficial for restoring general health status and spermatogenesis. Funding none
Authors
Koji Shiraishi
Shintaro Oka Hideyasu Matsuyama |
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MP35-05 |
HIGH BLOOD PRESSURE IS MORE FREQUENT IN INFERTILE THAN IN AGE-COMPARABLE FERTILE MEN - FINDINGS OF A CASE-CONTROL AND CROSS-SECTIONAL REAL-LIFE STUDY |
Infertility: Epidemiology & Evaluation II | 17BOS |
Abstract: MP35-05 Sources of Funding: none Introduction The impact of high blood pressure (HBP) on seminal parameters in infertile men has been partly analysed. We assessed the prevalence of HBP, along with clinical and seminal impact of HBP in white-European men presenting for couple’s infertility. Methods Complete data from 2196 consecutive infertile men were analyzed. HBP was defined as blood pressure >140/90 mmHg. Comorbidities were scored with the Charlson Comorbidity Index (CCI; categorized 0 vs. ≥1). Semen analysis followed 2010 WHO reference criteria. Descriptive statistics tested the association between semen parameters, clinical characteristics and HBP. Clinical data of infertile men were compared with those of a homogeneous cohort of 394 age-comparable fertile men (as for WHO definition). Results Of all, HBP was found in 162 (7.4%) infertile men. HBP was more frequent in infertile than fertile individuals [162 (7.4%) vs. 17 (4.3)%; p=0.003]. Among infertile patients, hypertensive men were older (p<0.001), had a greater BMI (p<0.001) and a higher rate of CCI≥1 (p<0.001) than non-hypertensive. Mean value of testicular volume (F=4.7; p=0.03) and total testosterone (F=6.4; p=0.01) were lower for hypertensive men. Conversely, patients with HBP had higher LH (F=9.7; p=0.002) and tPSA (F=6.5; p=0.01) levels. Overall, oligozoospermia, asthenozoospermia and theratozoospermia were found in 694 (31.6%), 789 (35.9%) and 679 (30.9%) patients, respectively, with no differences between hypertensive and non-hypertensive men. Similarly, mean ejaculated volume, total progressive motility and sperm morphology did not differ between groups. At MVA, testicular volume (OR 0.8, p<0.001) and FSH (OR 1.2, p<0.001) were independent predictor of lower sperm concentration, after accounting for age, CCI, presence of varicocele and HBP. Likewise, only testicular volume was associated with lower motility (OR 0.9; p=0.03) and lower sperm morphology (OR 0.96; p=0.01) after adjusting for the same variables Conclusions HBP was more frequent in infertile than fertile men. Cross-sectionally, infertile men with HPB had worse clinical and hormonal parameters than men non-hypertensive men. Conversely, HBP did not seem to negatively impact on seminal parameters._x000D_ Funding none
Authors
Walter Cazzaniga
Luca Boeri Eugenio Ventimiglia Paolo Capogrosso Filippo Pederzoli Roberta Scano Rayan Matloob Federico Dehò Emanuele Montanari Franco Gaboardi Francesco Montorsi Andrea Salonia |
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MP35-06 |
Statin use is not detrimental to semen parameters in subfertile men |
Infertility: Epidemiology & Evaluation II | 17BOS |
Abstract: MP35-06 Sources of Funding: This investigation was supported by the University of Utah Study Design and Biostatistics Center, with funding in part from the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant 8UL1TR000105 (formerly UL1RR025764). _x000D_ Introduction Data from animal studies and small trials show conflicting results regarding the effects of statins on semen quality. Evidence is even more limited in subfertile patients. We aimed to assess the effects of statin use on semen parameters. To investigate this, we retrospectively compared semen parameters in statin users vs. non-users in subfertile men. _x000D_ Methods From 2002-2013, we reviewed data from 12257 subfertile men visited at our fertility clinic. Patients who reported using any statin drugs for >3 months before semen sample collection were identified. Data on patient age, medication use, and conventional semen parameters were extracted. 7698 subfertile men taking no medications served as controls. Patients who were using any known spermatotoxic medications were excluded from the study. Variables with non-normal distributions (concentration, total count, and total motile sperm count) were log-transformed for analyses and the corresponding coefficients were presented as ratios. Linear mixed effect regression models were used to test the effects of statin use on semen parameters adjusting for age. The model coefficients, 95% confidence intervals (CIs) and p-values were reported, and statistical significance was assessed at the 0.05 level._x000D_ _x000D_ Results A total of 109 patients were identified taking statins. Mean age was 38.3 (standard deviation: 7.3). Estimates from the age-adjusted regression model are presented in Table-1. Ejaculate volume was 0.3 ml lower (95% CI: -0.58, -0.02 ml, p-value=0.04) and sperm viability was 4.52% higher (CI: 1.65%, 7.39 %, p-value=0.002) in statin users compared to controls._x000D_ Conclusions Statin use was not adversely associated with semen parameters other than semen volume in subfertile patients. However, this should be interpreted cautiously given the limited sample size and retrospective nature of this study. Additional studies are needed to confirm these findings. Funding This investigation was supported by the University of Utah Study Design and Biostatistics Center, with funding in part from the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant 8UL1TR000105 (formerly UL1RR025764). _x000D_
Authors
James M. Hotaling
Sorena Keihani James R. Craig Chong Zhang Angela P. Presson Jeremy B. Myers William O. Brant Kenneth I. Aston Benjamin R. Emery Douglas T. Carrell |
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MP35-07 |
Proton-pump inhibitor use and semen quality in subfertile men: is there a harmful effect? |
Infertility: Epidemiology & Evaluation II | 17BOS |
Abstract: MP35-07 Sources of Funding: This investigation was supported by the University of Utah Study Design and Biostatistics Center, with funding in part from the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant 8UL1TR000105 (formerly UL1RR025764). _x000D_ Introduction Proton pump inhibitors (PPI) are among the most widely used drugs worldwide. PPI use is recently linked to adverse changes in semen quality in healthy men, however, the effects of PPI use on semen parameters remain largely unknown specifically in cases with male factor infertility. We examined whether PPI use was associated with semen parameters in a large population of subfertile men. _x000D_ Methods We retrospectively reviewed data from 12,257 subfertile men who visited our fertility clinic between 2003 and 2013. Patients who reported using any PPIs for >3 months before semen sample collection were identified. Data were gathered on patient age, medication use, and conventional semen parameters. 7698 subfertile men taking no medications served as controls. We excluded patients who were taking any known spermatotoxic medication. Values for sperm concentration, total count, and total motile sperm count were log-transformed for analysis and corresponding coefficients were reported as ratios. Linear mixed effect regression models were used to test the effect of PPI use on semen parameters adjusting for age. The model coefficients, 95% confidence intervals (CIs) and p-values were reported, and statistical significance was assessed at the 0.05 level._x000D_ Results A total of 247 patients were identified taking PPIs, providing 258 semen samples (158 PPI only and 100 PPI plus ≥1 non-spermatotoxic medication). Mean age was 33.3 years (standard deviation: 6.7). Age-adjusted results from the regression model are presented in Table-1. Overall there were no statistically significant differences in semen parameters between patients taking PPIs (+/- other medications) and controls. Similarly, there were no differences between patients taking PPIs only versus controls. Conclusions To our knowledge, this was the first study to compare PPI use with semen parameters in subfertile men. Using PPIs was not associated with detrimental effects on semen quality in this retrospective study. However, further studies are needed to confirm these findings. Funding This investigation was supported by the University of Utah Study Design and Biostatistics Center, with funding in part from the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant 8UL1TR000105 (formerly UL1RR025764). _x000D_
Authors
Sorena Keihani
James R. Craig Chong Zhang Angela P. Presson Jeremy B. Myers William O. Brant Kenneth I. Aston Benjamin R. Emery Douglas T. Carrell James M. Hotaling |
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MP35-08 |
IMPACT OF SEMINAL QUALITY ON THE ANEUPLOIDY EMBRYONIC RATE |
Infertility: Epidemiology & Evaluation II | 17BOS |
Abstract: MP35-08 Sources of Funding: None Introduction The male factor is implicated in approximately 50% of couples undergoing Assisted Reproductive Technology. It has been known semen alterations could be responsible for chromosomal abnormalities, poor embryonic development and repeated miscarriage._x000D_ The main objective of this study was to evaluate the possible impact of oligospermia on the aneuploidy embryonic rate, comparing oligo and normospermics patients._x000D_ Methods This study compared 203 oligo and normospermics couples who underwent in vitro fertilization with subsequent embryo biopsy for preimplantation genetic screening (PGS) during the period from July 2014 to October 2016. The female mean age was 38.9. The seminal parameters were evaluated according to WHO 2010. Were biopsied 741 embryos. The biopsies were performed on either day 3 or day 5. The techniques used for the analysis were Array Comparative Genomic Hybridization (aCGH) or Next-Generation Sequencing (NGS). The results were analyzed by the T test (p <0.05). Results Of the 203 patients, 40 patients (19.7%) were considered oligospermic and obtained 160 biopsied embryos. Of these, 42 (26.2%) were considered euploid embryos. Normospermics patients obtained 581 biopsied embryos, and 151 (25.9%) were considered euploid. Therefore, when considering only the seminal concentration, there is no difference between the aneuploidy embryonic rate. Conclusions This study showed no correlation between low seminal concentration and aneuploidy embryonic rate. Although low sperm quality is an indication for PGS, it has not yet been elucidated that there is a decrease in the rate of euploidy during in vitro fertilization as it is expected to occur with the natural conception. Therefore, it is advisable that further studies on the subject be carried out in order to corroborate these primary results._x000D_ Funding None
Authors
Caudio Teloken
David Kvitko, Ricardo Azambuja Virginia Reig Alice Tagliani-Ribeiro Alvaro Petracco Lilian Okada Mariangela Badalotti |
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MP35-09 |
Sperm Aneuploidy is Associated with Worse General Health in Infertile Men |
Infertility: Epidemiology & Evaluation II | 17BOS |
Abstract: MP35-09 Sources of Funding: AWP is a K12 scholar supported by a Male Reproductive Health Research (MRHR) Career Development Physician-Scientist Award (Grant # HD073917-01 to DJL) from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Program. This work is also supported in part by the Burnett Research Fund. Introduction Numerous studies have examined the relationship between male infertility and men&[prime]s health but most have not investigated specific causes of infertility and their health impact. Here we examine the relationship between general male health and sperm aneuploidy._x000D_ _x000D_ Methods We used the Charlson Co-Morbidity Index (CCI) to assess and compare the health status of men with abnormal sperm aneuploidy to five groups of men who received care at an academic infertility clinic: men with normal sperm ploidy (normal FISH), men with genetic abnormalities that may cause infertility (genetic infertile), men presenting for infertility with varicocele (varicocele), men with idiopathic infertility (idiopathic) and proven-fertile men. Sperm ploidy was assessed using fluorescence in situ hybridization (FISH). Genetic infertile men had proven Y chromosome microdeletions or abnormal karyotype. CCI for men with sperm FISH results was completed via telephone survey and CCI for genetic infertile men was extracted from intake forms. Men who were diagnosed with a varicocele or idiopathic infertility had not conceived after 12 months. Men with varicoceles, men with idiopathic infertility, and fertile controls completed the CCI in clinic. Fertile controls included men who presented for vasectomy and had fathered a child in the past 5 years. _x000D_ Results 402 men were included in this analysis: 92 with an abnormal sperm FISH results, 7 with a normal sperm FISH test, 49 genetic infertile men, 85 men with idiopathic infertility, 86 infertile men with varicocele, and 83 fertile controls. Mean age, semen density, and CCI of all groups are described in Table 1. Of note, malignancy was common in our cohort, exceeding rates in the SEER database for comparable age (Table 1). Controlling for age, we explored infertility groups as a predictor of elevated CCI score, and found that only men with abnormal sperm FISH (p=0.002) had increased risk of a higher CCI score. Age also increased the risk for a higher CCI score, with each additional year raising the CCI by 0.0117 points (p=0.009). _x000D_ _x000D_ Conclusions Men with elevated sperm aneuploidy have nearly double the prevalence of general health issues, particularly malignancy, when compared with men with infertility of other etiologies. These findings further support the relationship between genetic causes of male infertility and general health. _x000D_ _x000D_ Funding AWP is a K12 scholar supported by a Male Reproductive Health Research (MRHR) Career Development Physician-Scientist Award (Grant # HD073917-01 to DJL) from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Program. This work is also supported in part by the Burnett Research Fund.
Authors
Taylor P. Kohn
Alexander W. Pastuszak Katherine M. Rodriguez Zachary J. Solomon Matthew F. Cherches Dolores J. Lamb Larry I. Lipshultz |
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MP35-10 |
RELATIONSHIP BETWEEN SEMINAL PARAMETERS AND SPERMAL DNA FRAGMENTATION |
Infertility: Epidemiology & Evaluation II | 17BOS |
Abstract: MP35-10 Sources of Funding: none Introduction Over the years, a large number of tests have been proposed for clinical evaluation of semen quality, some are used in clinical practice, but few are routinely used. Given the complexity of the sperm cell, there is no single assay capable of providing complete information for diagnosis and prognosis of fertility._x000D_ Objective: To evaluate the correlation between DNA fragmentation and seminal parameters in patients who consulted for fertility._x000D_ Design: Observational cross-sectional retrospective_x000D_ Methods Materials and Methods: 1,562 samples man who consulted for fertility were studied. DNA fragmentation was performed by the TUNEL technique. (In Situ Cell Death Detection Kit Roche). A percentage of fragmentation <20% was used as the normal reference value. Seminal parameters were analyzed according to WHO Standards 2010._x000D_ Statistic: T-test was used for independent samples. The Chi2 ratios and the correlation of TUNEL with respect to seminal parameters were analyzed with Spearman's test. A p <0.05 was considered statistically significant._x000D_ Results Results: In the total group, 31.6% (494/1562) presented increased fragmentation. The proportion of men with increased TUNEL, according to the different seminal parameters was: Normal concentration (29%, 381/1319) vs Oligozoospermia (47%, 113/243); P <0.0001. Normal Mobility (25%; 291/1157) vs. Astenozoospermia (60%); P <0.0001. Normal morphology (24%) vs Teratozoospermia (50%, 203/405); P <0.0001. Patients with oligoastenoteretozoospermy (OAT) had a higher proportion of TUNEL increased, 53.7% [58/108], compared to the Normospermic group 22.4% (173/772), P <0.0001. We found no difference in the fragmentation between groups of patients with Toxic habits (Alcohol and Tobacco) and without them. Of patients exposed to agrochemicals, 45.3% showed increased DNA fragmentation._x000D_ A significant and negative correlation was found between TUNEL and concentration / ml, total concentration of the ejaculate; total motility; rapid progressive motility; morphology and nuclear maturity. (P <0.0001) _x000D_ Conclusions Conclusion: According to our results, we observed a significant negative correlation between TUNEL and seminal parameters. In agreement with other works we find that the exposure to environmental agrochemicals would produce a deleterious effect on the fragmentation of the DNA. Taking into account that an increased TUNEL was found in 22.4% of Normospermic patients, we emphasized the usefulness of this test to more fully study the fertility of the patients and thus to be able to take therapeutic measures that favor reproductive success.- Funding none
Authors
Jose Olmedo
Rosa Molina Andrea Tissera Enzo Malizia Tristan Dellavedova |
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MP35-11 |
HEAVY CIGARETTE SMOKING IS THE MOST DETRIMENTAL FACTOR FOR SPERM DNA FRAGMENTATION – RESULTS OF A CROSS-SECTIONAL STUDY IN PRIMARY INFERTILE MEN |
Infertility: Epidemiology & Evaluation II | 17BOS |
Abstract: MP35-11 Sources of Funding: none Introduction To cross-sectionally assess the impact of cigarette smoking on various sperm parameters in a homogeneous cohort of white-European men presenting for primary couple infertility. Methods Demographic, clinical and laboratory data a cohort of primary infertile men were analyzed. Comorbidities were scored with the Charlson Comorbidity Index (CCI; categorized 0 vs. >=1). Semen analysis was based on 2010 WHO reference criteria. Serum hormones and sperm DFI [sperm chromatin structure assay (SCSA); DFI <30% was defined as non-pathologic] were measured in every patient. Smoking status was categorized as: no current smokers (Group 1); moderate smokers (<10 cigarettes/day; Group 2); and, heavy smokers (>10 cigarettes/day; Group 3). Descriptive statistics and logistic regression models tested the association between smoking status and clinical, seminal and hormonal characteristics in our cohort. Results Overall, 132 (69.8%), 30 (15.9%), and 27 (14.3%) patients belonged to Group 1, 2 and 3, respectively. Groups did not differ in terms of hormonal milieu. Of all, a pathologic DFI was found in 104 (55%) patients. Smokers (Groups 2+3) more frequently reported a CCI>=1 (p=0.02), oligozoospermia (p=0.04), asthenozoospermia (p=0.003), and a pathologic DFI (p=0.04) compared to non-smokers. At multiple comparison analysis, sperm concentration (p=0.042) and progressive motility (p=0.03) were significantly lower in heavy smokers; similarly, DFI values were significantly higher in Group 3 patients than in no smokers (p=0.025). At multivariable analyses, FSH (OR 1.1, p=0.02) and being heavy smokers (OR 4.1, p=0.006) were independent predictors for pathologic DFI score after accounting for age, BMI and CCI. Similarly, being heavy smokers achieved independent predictor status for pathologic sperm count (OR 2.7, p=0.047) and pathologic total progressive motility (OR 6.3, p=0.002), after accounting for the same variables. Conclusions The routine assessment of DFI is getting increasing clinical relevance. Heavy cigarette smoking emerged as the most detrimental factor impacting on the DFI rate, along with an impaired sperm concentration and progressive motility. Funding none
Authors
Luca Boeri
Filippo Pederzoli Eugenio Ventimiglia Paolo Capogrosso Walter Cazzaniga Davide Oreggia Nicola Frego Rayan Matloob Franco Gaboardi Emanuele Montanari Francesco Montorsi Andrea Salonia |
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MP35-12 |
Surgical treatment of male factor infertility: Does insurance coverage matter? |
Infertility: Epidemiology & Evaluation II | 17BOS |
Abstract: MP35-12 Sources of Funding: None Introduction Disparities in access to fertility treatment are well established in the female population, with cost often cited as a limitation to treatment. Fifteen states mandate insurance coverage for female infertility; of those, only eight require coverage for male infertility. Studies have demonstrated higher utilization of in vitro fertilization, intrauterine insemination, and ovulation-inducing medications in states with mandated coverage for female fertility. There is no analogous data in the male population. Our objective is to compare the utilization of male surgical infertility treatment in states that mandate coverage with states that do not. Methods Case log data provided by certifying and recertifying urologists between 2001 and 2014 to the American Board of Urology was reviewed. Male fertility procedures were identified by CPT code: 10021, 10022, 54500, 54505, 54900, 54901, 55200, 55300, 55400, 74440. Men ages 18-64, who had procedures performed in the United States (US) were included. US Census Bureau data from 2007 was used to determine median household income and population of men ages 18-64 per state. Results Of the 1244 urologists who logged at least one male fertility case between 2001 and 2014, 94 (7.6%) report specializing in andrology or infertility. These specialists performed 1052 of 4669 fertility cases (23%). The total number of male infertility cases per million men of reproductive age in the US was 49 (range: 6 in WY to 145 in DC (Figure 1)). Twenty-three states exceeded the national rate. Three locations had more than double the national rate (DC, TX and UT), none of which have mandated insurance coverage. In states with mandated male coverage, the number of male infertility cases per million men of reproductive age averaged 49 (range: 12 in WV to 58 in MA), which was the same as the national rate. State-based median household income did not correlate with cases performed per million men. Conclusions The number of fertility cases per million men of reproductive age varies widely by state, but does not appear to be related to male infertility insurance coverage status or median household income. The lack of disparity in utilization of male surgical infertility treatment suggests that patients will pursue these treatments regardless of insurance coverage status and income. Funding None
Authors
Barbara E Kahn
Daniel J Mazur Mary Kate Keeter Marah Hehemann Alexander J Tatem Anuj S Desai Kevin Lewis Daniel Oberlin Sarah Flury Nelson E Bennett Robert E Brannigan |
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MP35-13 |
Vasectomy and the Gender Gap: Shifting Demographics of the Urologic Workforce |
Infertility: Epidemiology & Evaluation II | 17BOS |
Abstract: MP35-13 Sources of Funding: none Introduction Women comprise over 7% of the current urologic workforce and 23% of current urology trainees. Despite this, women urologists may encounter gender-based practice patterns that can potentially limit their scope of practice. Vasectomy is one of the most common procedures performed by urologists, with many authors estimating over 500,000 such cases performed in the United States each year. Given the changing demography of the urology workforce, we sought to elucidate the changing practice patterns of women urologists performing vasectomies over time. Methods Annualized case log data for vasectomy was obtained from the American Board of Urology (ABU) for all urologists certifying or recertifying from 2002 to 2013. We evaluated trends in vasectomy in regards to the gender of the performing surgeon and geographic location subdivided by AUA section. Linear regression was used to evaluate the percentage of vasectomies performed by women over time and establish both regional and national trends. Results From the 7,819 case logs submitted by urologists in the United States we analyzed 123,443 vasectomies. The percentage of vasectomies performed by women urologists nationally increased by approximately 0.33 percentage points per year from 0.92% in 2002 to 4.4% in 2013 (R2=0.75). Regional sub-analysis revealed that this trend was preserved across the country with faster rates of increase noted in the Western and New England AUA sections. Conclusions Women now account for 50% of medical school graduates and an increasing percentage of urologists. Our analysis indicates that this movement towards gender parity is reflected in the relative rise of vasectomies performed by women urologists with faster rates of rise in the Western and New England AUA sections. However, it is worth noting that women still perform disproportionately fewer vasectomies than would be predicted by current workforce composition. Further studies are warranted to determine the effects of gender on urologists' practice patterns and patients' selection of their surgeons. Funding none
Authors
Alexander J Tatem
Barbara E Kahn Marah Hehemann Daniel J Mazur Anuj S Desai Daniel Oberlin Mary Kate Keeter Kevin Lewis Sarah Flury Nelson E Bennett Robert E Brannigan |
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MP35-14 |
Does the stump size in vasovasostomy can be a predictive factor to improve the outcomes of semen analysis associated with vasal patency? |
Infertility: Epidemiology & Evaluation II | 17BOS |
Abstract: MP35-14 Sources of Funding: none Introduction Vasal patency, defined as the return of sperm in the ejaculation after the vasectomy reversal, is considered the best parameter for comparing the outcome of vasovasostomy. Post-vasectomy stump can be thought that it is also a factor to influence vasal patency. Thus, we evaluated the preoperative and intraoperative factors including post-vasectomy stump associated with vasal patency after vasovasostomy. Methods From February 2000 to 2016, we retrospectively reviewed 139 consecutive vasovasostomy procedures performed by a single surgeon. Excluding 55 patients (39 has lost follow up visiting and 16 refused semen analysis or failed to collect semen), 84 patients who performed semen analysis at 1 month after surgery were enrolled in this study. Vasal patency was represented by variables of semen analysis such as motility, morphology and the number of spermatozoa. The size of stump was measured by its length and diameter. The correlations between semen analysis and clinical variables including vasal obstruction interval, leukocyte differential count, and median size of bilateral stump were analyzed in univariable and multivariable method. Results The mean age (±SD) was 32.1±0.8 years and mean obstructive interval was 7.8±0.6 years. Clinical variables including vasal obstruction interval, leukocyte differential count and length of stump were no statistically significant association with semen analysis parameters. However, the diameter of stump was positively correlated with motility and morphology of semen analysis (rho=0.474, p<0.0001 vs rho=0.349, p=0.001). In linear regression model, diameter of stump was sole independent factor associated with motility of semen (B=27.843, p=0.003). Conclusions Our findings demonstrated that increased stump diameter was improved the outcomes of semen analysis after vasovasostomy. However, additional prospective studies with larger numbers of patients should be done to further define its clinical significance. Funding none
Authors
Phil Hyun Song
Jae Young Choi Young Hwii Ko Ki Hak Moon Hee Chang Jung |
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MP35-15 |
Trends in Diagnosis and Management of Varicoceles Among U.S. Men |
Infertility: Epidemiology & Evaluation II | 17BOS |
Abstract: MP35-15 Sources of Funding: Urology Care Foundation Research Scholars Award (AM) Introduction There is considerable variation in clinical practice patterns with respect to assessment of testicular function in the setting of varicoceles, as well as techniques for varicocele repair. This study investigated trends in the management of varicoceles using a population-based dataset. Methods We interrogated the inpatient and outpatient MarketScan Commercial Claims databases to identify all U.S. men diagnosed with varicoceles between 2009 and 2013, using CPT, ICD9, and HCPCS codes. Demographic and clinical characteristics of the men were analyzed, along with the types of procedures utilized for varicocele repair. Geographic variability in practice patterns for varicocele management was also reviewed. Unpaired t-tests and Chi-squared tests were used to evaluate differences in continuous variables, such as age, and categorical variables, such as geographic distribution, between men who did and did not undergo varicocele repair. SAS v.9.4 was used for all statistical analyses. Significance was set at p<0.05. Results 25,792 men were diagnosed with a varicocele between 2009 and 2013. Average age at diagnosis was 32.5 years (SD 13.6). 20% of men were younger than 18 years of age at the time of diagnosis, and 53% were aged 18-39. 9,307 men (36%) underwent varicocele treatment, with either open (N=7,106), laparoscopic (N=1,072), or microsurgical (N=889) repair. Semen analyses were performed in 1,376 men (14.8%) before, and 2,484 men (26.7%) after varicocelectomy. Serum testosterone was evaluated in 3,361 men (13%) before, and 2,425 men (9.4%) after varicocelectomy. 18,285 men (70.9%) underwent a scrotal ultrasound within 6 months of their varicocele diagnosis, but 13,072 of them did not undergo varicocelectomy. Of the four U.S. Census Bureau regions, the varicoceles were most commonly diagnosed in the South (34% vs. 26% or less, p<0.001), whereas varicocelectomy was more likely to be performed in the Northeast (42% vs. 36% or less, p<0.001). There were no significant regional differences with respect to patient age or type of treatment utilized. Conclusions We found regional differences in the frequency of varicocele diagnosis and treatment. Overall, approximately one-third of men diagnosed with varicoceles underwent repair, but a microsurgical approach was utilized in only 9% of cases. The use of scrotal ultrasound around the time of varicocele diagnosis and treatment was common._x000D_ _x000D_ Funding Urology Care Foundation Research Scholars Award (AM)
Authors
Akanksha Mehta
Dattatraya Patil |
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MP35-16 |
Isolated right varicocele and incidence of associated cancer |
Infertility: Epidemiology & Evaluation II | 17BOS |
Abstract: MP35-16 Sources of Funding: None Introduction Varicocele is a common clinical entity, of which the majority occur on the left side due to normal venous drainage of the testis. Given the low incidence of isolated right varicocele (IRV), it has been suggested that men who present with an isolated right varicocele undergo retroperitoneal (RP) evaluation to exclude other pathology. Although there are numerous case reports of IRV preceding an associated RP pathology, the actual incidence remains unknown. Methods A retrospective chart review was performed of all men diagnosed with varicocele within a large, tertiary, academic system from 2000 to 2015. Medical records were queried for demographics, side of varicocele, imaging, and subsequent diagnosis of cancer or vascular anomaly. Cancers were considered relevant if within the retroperitoneum or peritoneum, and included renal, colon, prostate, bladder, adrenal, testis, and small bowel. Descriptive statistics are presented as mean(standard deviation) throughout. Comparative statistics include analyses of variance followed by Tukey-Kramer pair-wise comparisons, or chi squared tests for categorical data. All p < 0.05 are considered significant. Missing data points were excluded from analysis. Results A total of 4,060 patients with a diagnosis of varicocele (3258 left, 337 right, 465 bilateral). 81.9% self-identified as Caucasian, 7.8% African American, and the remaining proportion another race or declined to respond. Right varicoceles were diagnosed at significantly older age (43.6±17.1) than left (33.4±14.9, p<0.0001 ) or bilateral (34.9±15.3, p<0.0001) varicoceles. Right varicoceles were diagnosed in men with significantly higher body mass index (28.9±5.7) than left (26.4±5.5, p<0.0001) or bilateral (26.5±5.5, p<0.0001) varicoceles. Laterality of varicocele was not significantly associated with a relevant cancer diagnosis (p=0.313) with cancer in 2.67% of right, 1.63% of left, and 2.15% of bilateral varicoceles. Rates of abdominal CT imaging significantly (p<0.0001) differed by varicocele laterality, with 30.3% of right, 8.7% of left, and 11.2% of bilateral varicoceles having abdominal imaging. Diagnoses of venous thombi did not significantly differ by varicocele laterality. Conclusions Right varicocele presents at an older age than left or bilateral varicocele and is associated with an increased body mass index and greater likelihood of undergoing abdominal imaging. Rates of relevant cancer diagnoses did not differ with varicocele laterality, questioning the historical mandate to perform retroperitoneal imaging in all isolated right varicoceles. Funding None
Authors
Daniel Greene
Bradley Gill Yaw Nyame Molly Elmer-Dewitt Samuel Haywood Edmund Sabanegh |
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MP35-17 |
Sperm ultrastructural defects in men with severe asthenospermia is not a poor prognosticator for varicocelectomy outcomes |
Infertility: Epidemiology & Evaluation II | 17BOS |
Abstract: MP35-17 Sources of Funding: None. Introduction Varicocele repair has been shown to improve semen parameters in men struggling with infertility, although the impact may be less clear in some subgroups, such as those with severe asthenospermia. Electron microscopy (EM) of sperm in men with severe asthenospermia and preserved viability has identified a higher frequency of subcellular ultrastructural defects (USDs) not identifiable with traditional microscopy. The impact of USDs on varicocelectomy results has not been explored, thus this study was designed to determine if the presence of EM-identified sperm defects predicts post-varicocele repair outcomes. Methods Data from our tertiary male infertility referral center is prospectively collected in a review board-approved database. Semen specimens with severe asthenospermia (<10%) and preserved sperm viability (>50%) at our center are referred for EM testing. We retrospectively reviewed all men with sperm EM testing between 2003-2013 who underwent either surgical varicocelectomy or embolization. Pre- and post-repair semen analyses within one year of repair were collected and analyzed. Statistical analyses were performed using Student's t test for continuous data with p<0.05 reported as significant. Results During our study time period, 54 men had sperm EM testing and underwent varicocele repair. Four patients had inadequate specimens for EM and were excluded. The mean age of the remaining 50 men was 36.1 years. Fold changes in pre- and post-repair sperm concentration, motility, and total motile count (TMC) were 1.50, 2.46, and 3.67, respectively. EM abnormalities were identified in 15/50 (30%) while no abnormalities were noted in 35 (70%). There were no significant differences between sperm concentration, motility, TMC, or morphology when comparing those with normal vs abnormal EM, 1 vs 2+ EM abnormality subtypes, or <50% vs 50+% sperm affected by USDs. Among men with <50% sperm affected by a USD, there was a 1.16 fold change in ejaculate volume as opposed to 0.64 change seen in men with 50+% sperm affected (p=0.03). Conclusions Post-varicocele repair outcomes in men with sperm EM abnormalities appear to be non-inferior to those without identified abnormalities. Certainly, it will be more challenging for these men with severe asthenospermia to approach normal parameters, but this small series demonstrates that the presence of EM abnormalities should not preclude a discussion about varicocelectomy. Funding None.
Authors
Sarah Ferrara
Keith Jarvi Jared Bieniek |
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MP35-18 |
Ultimate time to improvement in semen quality after subinguinal varicocelectomy |
Infertility: Epidemiology & Evaluation II | 17BOS |
Abstract: MP35-18 Sources of Funding: none Introduction The time needed for optimal improvement of semen parameters after varicocelectomy remains controversial. Our goal was to determine the ultimate follow up period required post ligation as a cutoff after which urologists could decide to advance in their management plan of a male infertility case. Methods 30 patients underwent subinguinal varicocelectomy for male factor infertility and were followed for 9 months. All patients were subjected to a full clinical evaluation including semen analyses, hormonal profile for those with oligozoospermia, and scrotal doppler ultrasonography. Postoperative follow up was at 3 month intervals. Semen parameters and pregnancy rates at each visit (pretreatment, 3 months, 6 months and finally 9 months post treatment) were compared. Results After 3 months patients showed significant improvements in sperm motility (mean [m]=13.3% +/-9.3 vs. m=23.83 +/-14.95) [p =0.0001]. A significant reduction in the percentage of abnormal forms from 20-90% (m=53.5 +/-17.5) to 10-70% (m=38.5 +/-16.56) was also detected [p=0.0001]. However, counts failed to show similar significant improvements. Forty percent of the subjects (12/30) were able to impregnate their wives during the 1st 3 months post ligation. After 6 months, further significant increases continued to show in sperm motility reaching 0-70% (m=27.58% +/-14.9) [p=0.0199]. However abnormal forms (42.2% +/-14.5) and sperm concentrations (16.9 million +/-10.7) did not show similar significant improvement [p=0.221 and 0.9395 respectively]. By the 6th month of follow up 18/30 couples had achieved natural conception (60%). Among the nonpregnant couples who remained for follow up at 9 months posttreatment, no significant changes were identified in all semen parameters. Conclusions The optimal effect of varicocelectomy may take more than 3 months to be reached with a maximum of 6 months after which no further improvement may be expected. In other words, a 3-month follow up period may be insufficient before alternative therapies for male infertility cases treated by varicocele ligation could be decided. Hence, a wait time of at least 2 spermatogenic cycles (6 months) may be suggested before shifting to further management. Funding none
Authors
Ahmed M. Ragheb
Ayman S. Moussa Taha A. Ahmed Amr M. Massoud |
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MP35-19 |
PRIMARY, SECONDARY, AND COMPENSATED HYPOGONADISM: A NOVEL RISK STRATIFICATION FOR INFERTILE MEN |
Infertility: Epidemiology & Evaluation II | 17BOS |
Abstract: MP35-19 Sources of Funding: none Introduction Recently, the cohort of men from the European Male Ageing Study (EMAS) has been stratified into different categories distinguishing primary, secondary and compensated hypogonadism. A similar classification has not yet been applied to infertile men, traditionally younger than those usually considered for population studies. We aimed to investigate the prevalence of different forms of hypogonadism and the eventual association of clinical, semen and hormonal parameters in a homogeneous cohort of white-European men presenting for primary couple’s infertility. Methods We performed a cross-sectional study enrolling 786 consecutive Caucasian-European primary infertile men segregated into: eugonadal [normal serum total testosterone (tT >= 3.03 ng/mL) and normal LH (=<9.4 mU/mL)]; secondary (low tT; low/normal LH); primary (low tT; elevated LH); and, compensated hypogonadism (normal tT; elevated LH). Logistic regression models tested the association between semen parameters, clinical characteristics and the defined gonadal status. Results Eugonadism, secondary, primary, and compensated hypogonadism were found in 80%, 15%, 2%, and 3% of men, respectively. Secondary hypogonadal men were at highest risk for obesity (OR [95% CI] 3.56 [2.03-6.13]). Primary hypogonadal men were those at highest risk for non-obstructive azoospermia (NOA) (23.5 [6.25-152.96]) and testicular volume <15ml (12.78 [3.42-82.91]). Compensated had a similar profile to primary hypogonadal men, though their risk of NOA (6.27 [2.79-14.81]) and small testicular volume (8.94 [3.57-27.19]) was lower. The risk of small testicular volume (1.6 [1.05-2.44]) and NOA (1.83 [1.15-2.89]) was increased, though in a milder fashion, in secondary hypogonadal men as well. Conclusions Overall, primary and compensated hypogonadism depicted the worst clinical picture in terms of impaired fertility. Though not specifically designed for infertile men, EMAS’ categories might serve as a clinical stratification tool even in this setting. Funding none
Authors
Eugenio Ventimiglia
Paolo Capogrosso Luca Boeri Walter Cazzaniga Filippo Pederzoli Nicola Frego Davide Oreggia Federico Dehò Franco Gaboardi Vincenzo Mirone Francesco Montorsi Andrea Salonia |
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MP35-20 |
The utility of alkaline phosphatase as a marker for response to testosterone replacement therapy in hypogonadal men |
Infertility: Epidemiology & Evaluation II | 17BOS |
Abstract: MP35-20 Sources of Funding: None Introduction Osteopenia and osteoporosis may be adverse sequelae of hypogonadism. In a recent publication, Dabaja, et al (2015) found elevated alkaline phosphatase (AP) in men with total testosterone (T) <250ng/dl, suggesting increased bone turnover. Following T therapy, decreased AP was associated with increased bone mineral density, suggesting that AP levels may be used as a marker of response to T therapy. We evaluated the association between T and AP levels in an outpatient setting in an effort to replicate these findings. Methods A retrospective chart review of 88 men who presented to our reproductive medicine clinic with symptomatic or clinical features of hypogonadism was performed. Men with total testosterone levels <350ng/dL were followed for 2 years with AP levels measured at baseline, 6, 12, and 24 months. 15 of the 88 men had both T and AP measured before treatment, and at 6, 12, and 24 months. Men were either treated with transdermal testosterone, intramuscular testosterone, or testosterone long-acting pellets._x000D_ Results Mean age (SD) of the patients was 61 (18) years, with an age range of 27 to 84. The mean (SD) testosterone level was 217 (75) ng/dL at baseline and 675 (538), 652 (373), 716 (516) ng/dL at 6, 12, and 24 months, respectively. AP levels decreased from a mean (SD) of 67 (14) U/L to 65 (14) U/L (P=0.353), 65 (12) U/L (P=.421), and 61 (14) U/L (P=.111), at 6, 12, and 24 months respectively._x000D_ Conclusions We found no correlation between testosterone replacement therapy and AP levels. Specifically, the significant decrease in AP levels following T therapy noted in the Dabaja study were not observed in this small cohort. There were significant differences between the two studies, including mean age (41 vs 61 years), mean initial level of AP (87 u/L vs 67 u/L), mean decrease in AP after two years of treatment (32 u/L vs 6 u/L), and mean testosterone level prior to treatment (264 ng/dL vs 217 ng/dL). The significant age difference between the two studies is noteworthy, suggesting that younger patients may be more susceptible to increased bone turnover as a result of T deficiency. Further investigation may be needed to determine whether AP can be used as a marker of response to T replacement therapy in a select group of patients._x000D_ Funding None
Authors
John Sheng
Ari Sapin Michael Benson Hossein Sadeghi-Nejad |
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MP36-01 |
Collagen cell carrier for urethral reconstructive surgery: first results of a long-term minipig model |
Trauma/Reconstruction/Diversion: Urethral Reconstruction (including Stricture, Diverticulum) I | 17BOS |
Abstract: MP36-01 Sources of Funding: Viscofan, BioEngineering, Weinheim, Germany Introduction Regarding urethral reconstruction of urethral stricures we demonstrated in a previous short-term pilot study that human urothelial cells (HUC) seeded on a bovine collagen cell carrier (CCC), used as a xenograft in minipigs is technically feasible for urethral reconstruction. The aim of this following study was to evaluate the use of CCC in a long-term animal model and to compare it with primary surgical reconstruction without CCC of the porcine urethra. Methods Twelve male Göttingen minipigs with immunosuppression (cyclosporine A) were used for this study. Eight weeks after urethral stricture induction and protective vesicostomy animals were subdivided in a short-term group (4 pigs with HUC seeded CCC) and a long-term group (2 pigs with static HUC seeded CCC, 2 pigs with CCC-only, 2 pigs with bioreactor cultivated dynamic HUC seeded CCC). As a control-group SHAM operated animals were selected (2 pigs without CCC and primary urethral reconstruction). HUC obtained from human benign ureteral tissue were stained by PKH26 before seeding on CCC. Follow-up timeframe was 2 and 4 weeks in the short-term group, 2 weeks in the sham operated group and 3 months in the long-term group. Hereafter animals were euthanized. Urethrography, histological assessment and immunofluorescence were performed. Results Surgery was well tolerated and technically feasible in all 12 mini-pigs. In the final urethrography no remaining significant stricture could be detected in the long-term group. In contrast both SHAM operated pigs showed a persistent urographic urethral stricture in the final examination. A radiological extravasation was only found in short-term (3/4) and SHAM (1/2) animals but not in the long-term group. The final histological examination showed the CCC close to the previously suture-tagged operating area (range 0.5-1.2 mm). In case of HUC seeded CCC near porcine urothelium PKH26 positive areas were found even if partially detached from CCC. However, porcine urethra revealed intact urothelium in the long-term group expressing CK20, E-Cadherin and ZO-1 whereas 1 of 2 SHAM animals had a histologically discontinuous urethra. Conclusions Compared to the control-group with primary urethral reconstruction CCC with or without HUC seems to increase the stability of the reconstructed urethra and supports survival and growth of seeded urothelial cells leading to an intact regeneration of the urothelial tissue. Finally, this study demonstrates that CCC in minipigs is technically feasible showing promising results for further studies. Funding Viscofan, BioEngineering, Weinheim, Germany
Authors
Stefan Aufderklamm
Alexandra Kelp Sabine Maurer Silke Busch Martin Vaegler Arnulf Stenzl Karl-Dietrich Sievert Bastian Amend |
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MP36-02 |
Cell-seeded Acellular Dermal Matrix Graft for Reconstruction of Long Urethral Defects in a Canine Model |
Trauma/Reconstruction/Diversion: Urethral Reconstruction (including Stricture, Diverticulum) I | 17BOS |
Abstract: MP36-02 Sources of Funding: none Introduction To investigate the feasibility of urethral reconstruction using xenogeneic acellular dermal matrix graft (ADMG) seeded with autologous urothelial cells in a canine preclinical model. Methods Autologous bladder epithelia obtained from 4 male dogs were cultured, expanded and seeded onto preconfigured acellular dermal matrix graft (ADMG) to construct tis-sue-engineered urethras. A 3-cm segment of anterior urethra was removed in 8 adult male canines. Urethroplasties were performed using ADMG seeded with urothelial cells in 4 animals in experimental group and with ADMG without cells in other 4 animals in the comparison group. Retrograde urethrography was performed at 6 months after surgery. Two animals were scarified from each group at 3, 6 months and grafts were harvested. We assessed the repairing effects by Hematoxylin and eosin (H&E), Masson's trichrome and immunohistochemistry staining. Results The expanded urothelial cells showed good attachment to the ADMG. Canines in the experimental group survived until sacrifice. Urethrography after 6 months of gafting showed wide-caliber urethras without any sign of strictures. In contrast, urinary fistula occurred in 1 dog in the control group after 8 days of surgery, and other canines in this group also suffered from varying degrees of dysuria. Histologically, an epithelial cell layer surrounded by muscle fiber bundles was observed on the cell-seeded constructs at both 3 and 6 months postoperatively. In the control group, no urothelium or muscle could be detected at 3 months postoperatively. 6 months after surgery, formation of an epithelial cell layer occurred in the unseeded constructs, but with disorder structure in some regions and fewer muscle fibers. Furthermore, obvious scaring appears in two canines in this group, which might be attributed to severe inflammation and hyper-fibrosis. The epithelial and smooth muscle phenotypes were confirmed with antibodies to pancytokeratins AE1/AE3 and smooth muscle–specific desmin. Conclusions ADMG seeded with autologous urothelial cells could be an alternative tissue-engineering material for urethra reconstruction. Funding none
Authors
Li Cheng
Jian Lin Zicheng Wang |
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MP36-03 |
LOW TESTOSTERONE LEVELS PREDISPOSE TO URETHRAL ATROPHY DUE TO DECREASED URETHRAL VASCULARITY VIA AN ANDROGEN RECEPTOR-MEDIATED PROCESS |
Trauma/Reconstruction/Diversion: Urethral Reconstruction (including Stricture, Diverticulum) I | 17BOS |
Abstract: MP36-03 Sources of Funding: None Introduction We recently identified that hypogonadism predisposes to artificial urinary sphincter (AUS) erosion. The aim of this study was to compare histologic features of human periurethral tissue among eugonadal and hypogonadal patients in order to identify pathologic mechanisms for this predisposition. Methods Among a cohort of over 1200 men having urethroplasty at our institution, we retrospectively identified 11 patients who had serum testosterone levels drawn within 2 years of surgery and who had tissue samples available. Low serum testosterone was defined as <280 ng/dl. Tissue samples were analyzed by immunohistochemistry to determine expression of androgen receptor (AR), TIE-2 (a downstream target of activated AR linking it to angiogenesis), and CD31 (to highlight vessels). Microscopic images were objectively evaluated for protein expression and vessel counts using Image J software. Results We found a significant decrease of AR expression (1.11%HPF vs. 1.62, p=0.016), TIE-2 expression (1.84%HPF vs. 3.08, p=0.006), and vessel counts (44.47 vessels/HPF vs. 98.33, p=0.004) in men with low serum testosterone. Expression levels of AR and TIE-2 were directly correlated to serum testosterone levels (rho 0.685, p=0.029, and rho 0.773, p=0.005, respectively). We did not find a difference in age, prior radiation, co-morbidities such as coronary artery disease or hypertension among patients with normal or low testosterone levels with the exception of higher body mass index in patients with low testosterone levels. Conclusions Men with low serum testosterone levels demonstrate decreased expression of AR and TIE-2 and lower vessel count in periurethral tissues. Our results provide a rationale for a mechanistic relationship between low testosterone levels and subsequent decreased periurethral vascularity. We believe that this results in urethral atrophy conferring a higher risk of AUS erosion. Funding None
Authors
Matthias D Hofer
Payal Kapur Billy H Cordon Farrah Hamoun David Russell Jeremy M Scott Claus G Roehrborn Allen F Morey |
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MP36-04 |
Low testosterone is common in patients with anterior urethral stricture: risk-factor or coincidence? |
Trauma/Reconstruction/Diversion: Urethral Reconstruction (including Stricture, Diverticulum) I | 17BOS |
Abstract: MP36-04 Sources of Funding: none Introduction Testosterone is known to have key involvement in urethral development with devastating consequences in its absence. It has also been shown to have an important role in mucosal healing. We hypothesized that urethral stricture formation may form in the background of low testosterone. We aimed to evaluate a hypothesis by McCullough and colleagues regarding an increased prevalence of low testosterone found in men with anterior urethral strictures. Methods Using a prospectively maintained male urethral stricture database from February 2014 to September 2016, we identified all men treated for anterior urethral stricture with a serum total testosterone level and stratified them by age. Prior to reconstruction, men with anterior urethral strictures had been advised to have testosterone levels drawn. Patients with radiation-induced stricture or pelvic fracture urethral distraction injuries were excluded. Prevalence of low-testosterone, defined as serum testosterone less than 300ng/dL, was calculated. Age-matched data from a national database (NHANES), were used as a reference. Results We identified 68/103 (66%) men with anterior urethral strictures who had pre-operative testosterone levels measured. Of these, an additional 5 were excluded for a study group of 63 patients._x000D_ _x000D_ Figure 1 describes the prevalence of low testosterone in our cohort and the NHANES database stratified by age group. Overall, low testosterone was found in 47.6% of men in the anterior urethral strictures group and 27.5% of patients in the national database. _x000D_ Conclusions Low testosterone is more common in this group of patients with urethral strictures than can be expected in the general population based on a national database. Further investigation is warranted into the relationship between serum testosterone and idiopathic anterior stricture formation. Funding none
Authors
Jeffrey Spencer
Michael Daughtery Stephen Blakely Dmitriy Nikolavsky Timothy Byler |
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MP36-05 |
Facilitating Faster Wound Remodeling and Maturation in a Rat Model of Substitution Urethroplasty Utilizing Anti-Inflammatory Nanofibers |
Trauma/Reconstruction/Diversion: Urethral Reconstruction (including Stricture, Diverticulum) I | 17BOS |
Abstract: MP36-05 Sources of Funding: None Introduction Tempering the postoperative inflammatory response following graft urethroplasty may accelerate urethral wound healing and minimize fibrosis and stricture recurrence. We investigate the use of anti-inflammatory peptides displayed on self-assembling nanofibers to modulate inflammation and accelerate scar maturation in a rat model of substitution urethroplasty. Methods Poly(diol-citrate) [POC] scaffolds were either coated with anti-inflammatory peptide amphiphile (AIF-PA1), control amphiphile (AIF-PA6) or left uncoated, and used in substitution urethroplasty (n=36 Sprague Dawley male rats). Urethral tissue analysis was performed at 2, 12 and 25 days post-operatively using H&E, Trichrome, picrosirius, myeloperoxidase (MPO), TNFα, CD68, IL-10 and IL-1β. Urethral patency was assessed at euthanization. Results 35/36 rats demonstrated urethral patency at euthanization by functional and anatomic assessment. AIF-PA1 coated POC scaffolds resulted in a 50% reduction of neutrophil (MPO) and inflammatory cytokine IL-1β levels, with simultaneous upregulation in anti-inflammatory cytokine IL-10 relative to controls at 2D and 12D postoperatively. Macrophage (CD68) levels were elevated 1.5-fold in the AIF-PA1 group during the immediate post-surgical period (2D), but demonstrated a rapid decrease to levels half that of control subjects by 12D. Treatment of graft with AIF-PA1 triggered an initial 2.5-fold spike in collagen III periurethral content (2D), consistent with initial, robust collagen deposition, followed by a dramatic shift in collagen type III to I (III:I ratio 15.7:1 [AIF-PA1] vs. 43.4:1 [control] vs. 38.0:1 [AIF-PA6]), consistent with an early transition to tissue remodeling and maturation. By 25D, inflammatory marker and collagen levels tended towards normalization in all groups. Conclusions AIF-PA1 nanofiber application onto POC promotes an accelerated wound healing program, characterized by an initial spike in macrophage wound infiltration, followed by a faster reduction of inflammatory markers. The end result is an accelerated wound healing course, with an expedited transition to wound remodeling and maturation with application of AIF-PAs at the time of surgery. Funding None
Authors
Joceline Fuchs
Matthew Bury Natalie Fuller Nida Ahmad Arun Sharma |
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MP36-06 |
Inflammation in Urethral Stricture Specimens is Underappreciated, Underanalyzed and in Need of a Standardized Pathologic Protocol |
Trauma/Reconstruction/Diversion: Urethral Reconstruction (including Stricture, Diverticulum) I | 17BOS |
Abstract: MP36-06 Sources of Funding: none Introduction Choice of urethroplasty technique is usually dictated by patient and surgeon preference, as well as the stricture length and location, as determined by retrograde urethrogram. Unlike oncologic surgeries, stricture pathology rarely dictates treatment choice. Furthermore, at our institution, urethral tissue sent during urethroplasty is not routinely analyzed for anything more than malignant change, nor is it routinely used to determine the chance of stricture recurrence. The purpose of this study was to retrospectively review urethral stricture pathology specimens for the presence of inflammation. We hypothesized that re-review of the slides would reveal significant specimen heterogeneity and that the degree and type of inflammation would predict for stricture recurrence. Methods Pathology from bulbar urethroplasties performed from 2010 to 2016 by one of two surgeons at a single institution were retrospectively reviewed. Original pathology reports were compared to reports provided on re-review by a single GU pathologist for the presence, type and degree of inflammation within the specimen as well as the presence of lichen sclerosus. Surgical outcomes were then compared to the updated pathologic findings. Results Of 181 bulbar urethroplasties performed in the study period, only 95 (52.4%) had tissue collected for pathologic analysis. Comparisons of original and re-review of pathology slides revealed increases in reported lymphocytic inflammation (25.3% vs 42.1%; p=0.02), squamous metaplasia with hyperkeratosis (12.6% vs 33.7%; p = 0.0009), nephrogenic adenoma (3.2% vs. 6.3%; p = 0.5) and lichen sclerosus (2.1% vs 5.3%; p = 0.44). The predominant inflammatory cell type was lymphocytic in 41 cases (B/T cell;43.2%), plasma cell in 5 (5.2%), eosinophilic in 8 (8.4%) and neutrophilic in only 1 (1.1%). Of the 15 (16%) patients noted to have urethroplasty failure, presence and type of inflammation was not significantly greater versus those with successful repairs (p=0.57). Conclusions Re-review of stricture pathology revealed more inflammation and greater inflammatory heterogeneity than was previously appreciated. While inflammation did not predict for recurrence, our specimen retrieval rates were unacceptably low, especially for substitution urethroplasties, which may have impacted the lack of association. We have since standardized tissue retrieval and analysis protocol which we believe may ultimately be used to elucidate stricture pathophysiology and predict surgical success. Funding none
Authors
Brennan Tesdahl
Laila Dahmoush James Mason Karl Kreder Bradley Erickson |
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MP36-07 |
Comparison of ultrasonography imagings and pathological findings in bulbar urethral strictures: a preliminary report. |
Trauma/Reconstruction/Diversion: Urethral Reconstruction (including Stricture, Diverticulum) I | 17BOS |
Abstract: MP36-07 Sources of Funding: None Introduction We investigated the role of ultrasonography imaging and whether or not it correlates with the pathological findings in bulbar urethral strictures. We tested the hypothesis that urethral ultrasonography is a reliable non-invasive tool for spongiofibrosis staging in bulbar urethral stricture diseases. Methods This is a prospective study of 35 patients, mean age of 43 years (range 18-79), with bulbar urethral strictures who underwent urethroplasty from January 2016 to June 2016. All the patients were preoperatively evaluated by urethral ultrasonography. The operator was requested to mark the following 3 points: a) the normal urethra; b) the most fibrotic site of spongiofibrosis; c) 1 cm distally and proximally to the spogiofibrotic site. The urethral ultrasonography was repeated intra-operatively and these 3 points were clearly identified by inserting a small needle before to open the bulbar urethra. The urethra was ventrally opened and biopsies were taken according to the needles positions: 2 in the normal urethra distally and proximally to the fibrotic site, 2 biopsies were taken at 1 cm distally and proximally to the most fibrotic site and 1 biopsy was take from the fibrosis area. Controls were represented by samples of normal urethra and periurethral tissue collected from male-to-female trans-sexual surgery. A single expert pathologist evaluated all the biopsies. The primary end point of the study was to correlate the imaging with the pathological examination. Results In the stenotic area, which was marked as “fibrosis� at the ultrasonography, the pathological examination of the area showed squamous metaplasia of the epithelium characterized by hyperkeratosis and acanthosis. In the lamina propria, marked fibrosis without inflammation was also evident in all patients. In the segment 1 cm proximal to the stenotic area pathological examination showed squamous metaplasia of the epithelium characterized by hyperkeratosis and acanthosis. In the lamina propria, mild fibrosis without inflammation was observed. In the segment 1 cm distal to the stenotic area the pathological examination showed squamous metaplasia of the epithelium characterized by hyperkeratosis and acanthosis. In the lamina propria, mild fibrosis and mild inflammation were observed. Two cm distal to the stenotic area we found a normal columnar and stratified epithelium and no inflammation or fibrosis were observed in the lamina propria. A normal epithelium was found in all the controls. Conclusions Our findings revealed chronic abnormalities in the urethral ends of all patients far from the stenotic area. An interesting observation was the normal urethra at imaging showed morphological alterations at the pathological examination, revealing that ultrasonography may fail to identify the true extension of stricture disease. However, further studies are mandatory before we can accept the clinical introduction of ultrasonography in staging pathological extension of fibrosis in patients with bulbar urethral stricture. Funding None
Authors
Guido Barbagli
Rosario Caltabiano Sofia Balò Salvatore Sansalone Carla Loreto Massimo Lazzeri |
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MP36-08 |
Underestimation of urethral stricture length in men with high-grade anterior urethral stricture |
Trauma/Reconstruction/Diversion: Urethral Reconstruction (including Stricture, Diverticulum) I | 17BOS |
Abstract: MP36-08 Sources of Funding: none Introduction Accurate radiographic assessment of urethral stricture length relies on both a retrograde urethrogram (RUG) and voiding cystourethrogram (VCUG). In men with high-grade strictures (very tight, very long or inflammatory strictures), it may be necessary to place a suprapubic cystostomy catheter (SPC) prior to urethroplasty in order to obtain accurate imaging. Using a panel of reconstructive surgeons to read the RUG/VCUGs, we sought to compare radiographic assessment of stricture length to intra-operative measurement in a cohort of men with SPC for high-grade stricture. Methods We queried our prospectively maintained urethroplasty database at the University of Minnesota for men with anterior urethral stricture and an SPC at the time of RUG/VCUG (n=49). To minimize responder fatigue, 20 pairs of radiographs were selected at random. All images were interpreted by eleven fellowship-trained reconstructive urologists. A single surgeon performed all reconstructions, during which, stricture length was noted. A two-tailed t-test was used to compare means between interpreted and observed lengths. Interclass correlation evaluated homogeneity amongst urologists. Linear regression analysis was performed to determine the association between observed stricture length and radiographic interpretation. Results Agreement among interpreting urologists was satisfactory with interclass correlation of 0.72. Of 20 identified patients, mean interpreted and observed stricture lengths were 3.8 cm (range 1-11) and 4.65 cm (range 1-14), respectively (p<0.0001). Deviation between interpreted and observed lengths increased with stricture length with a slope of 0.26cm (for every 1 cm increase in stricture length, deviation between interpreted and observed lengths increased by 0.26 cm) (p=0.0023, Fig. 1). Conclusions Despite optimal urethral imaging with an SPC in men with high-grade stricture, reconstructive urologists significantly underestimate the length by almost 1 cm; this underestimation increases with stricture length. This information may be useful for operative planning as decision making hinges upon accurate assessment of stricture length. Additionally, this information may impact consideration of endoscopic management of strictures that appear short on imaging. Funding none
Authors
Travis Moncrief
Ronak Gor Stephanie Jarosek Lei Zhang Nejd Alsikafi Alex Vanni Benjamin Breyer Bradley Erickson Joshua Broghammer Christopher McClung Jill Buckley Jeremy Myers Zhao Lee Bryan Voelzke Sean Elliott |
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MP36-09 |
Buccal Mucosa Graft (BMG) for Female Urethral Reconstruction is not Associated with Post-operative Voiding Dysfunction |
Trauma/Reconstruction/Diversion: Urethral Reconstruction (including Stricture, Diverticulum) I | 17BOS |
Abstract: MP36-09 Sources of Funding: None Introduction Female urethral stricture is an uncommon yet debilitating condition. While many techniques have been described to treat this condition, buccal mucosal graft (BMG) has emerged as one of the most novel and effective techniques to treat female urethral stricture. While few small series have reported on the efficacy and patency rate of female BMG urethroplasty (BMG-U), no recent series have focused on voiding dysfunction after female BMG-U. We performed a retrospective analysis of post operative voiding dysfunction in 20 patients who underwent BMG-U at our institution. Methods From July 2011 to Nov 2016, we identified 20 female patients (mean age,56; range,24-79) who underwent BMG-U to manage female urethral stricture. Inclusion criteria for repair included significant obstructive urinary symptoms, postvoid residual >100 ml, and stricture [le]8 French. 20 patients underwent outpatient female BMG-U using dorsal onlay (80%), ventral (10%) or a combination (ventral and dorsal onlay (10%). Mean stricture length was 1.5 cm (range, 0.5-2.5 cm). All strictures were at the mid or proximal 1/3 of the urethra. Distal 1/3 urethral strictures were treated using meatoplasty without BMG._x000D_ BMG was harvested from the cheek in all cases and prepared in the usual fashion for onlay using 4.0 absorbale suture material (Figure). Urethral catheterization was performed for 3 weeks. No post op urethrogram was performed during the voiding trial. Patients were administered UDI-6 pre and post procedure & specifically asked about the impact of urinary incontinence on their quality of life. _x000D_ Results Outcomes following female BMG-U are shown in the Table. Of the two patients with persistent obstructive symptoms, one remained patent after a second BMG-U was performed 6 months after a failed first BMG-U. Another patient required one session of urethral dilation in the OR & is doing well. Conclusions Early results indicate that BMG for female urethral stricture is an effective surgical procedure. Urinary incontinence is not noted and post op voiding dysfunction is rare. Long term data and larger series is warranted to support is observation. Funding None
Authors
Angelo Gousse
Lee J. Milas Hari Tunuguntla |
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MP36-10 |
Urethrovaginal fistula repair: Long?term outcomes |
Trauma/Reconstruction/Diversion: Urethral Reconstruction (including Stricture, Diverticulum) I | 17BOS |
Abstract: MP36-10 Sources of Funding: none Introduction Urethrovaginal fistula (UVF) is not highly prevalent in urologic practice but merits attention. There are few large published series. This is a review of management of all patients that have been treated over a 30?year period at our institution to assess etiology, operative management, and outcomes. Methods Between 1986 and 2016, a total of 36 UVFs were repaired. Retrospective review recorded presentation, history, etiology, surgical approach, and results. Long?term lower urinary tract symptoms (LUTS) were noted. All UVFs were closed in 3 or more layers. A variety of flaps were used as needed. A suprapubic or foley catheter was left indwelling for 3?4 weeks and healing was assessed by cystourethrogram. Results Mean patient age was 49.2 (range 21?81). 13 (36%) were long?time smokers. 8 patients had a history of urethral diverticulum and 3 had previously treated pelvic malignancies. All patients had prior pelvic surgery. The most common etiology was an incontinence procedure in 13 patients (36%) with mesh erosion in 6 of these. Other causes were urethral diverticulum repair in 7 (19.4%), forceps delivery in 5 (14%), self?intermittent catheterization in 3 (8%), cystectomy and neobladder in 2 (6%), and other vaginal procedures in 6 (17%). Incontinence was the primary complaint in 33 women and the diagnosis was made on cystoscopy in 34. Thirty?four (94%) were closed via transvaginal approach including 15 with simultaneous rectus fascia pubovaginal slings harvested through an abdominal incision. Two were approached transabdominally, and 1 was closed with a combined abdominal and vaginal approach. Thirteen repairs were done with flaps including Martius in 11 and omentum in 2. Mean hospital stay was 3.9 days (range 0.5?10). The overall repair success rate was 34/36 (94%). Mean follow?up time was 41.2 months (range 0.8?207.33). Long?term LUTS included frequency in 11 patients (31%), urgency in 10 (28%), urgency incontinence in 9 (25%), and stress incontinence in 6 (17%). Foley catheter drainage replaced suprapubic drainage in the past 10 years but did not change outcomes. Two recurrences (1 neobladder and 1 post?ileocystoplasty) occurred immediately and underwent continent diversion. Conclusions UVFs usually result from a surgical complication. Smoking may be a risk factor. Management techniques that optimized outcomes included multi?layer closure usually with flaps and/or rectus fascial sling, extended catheter drainage, and tailoring the repair to the problem. _x000D_ Funding none
Authors
Sender Herschorn
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MP36-11 |
Quality of Life Among Men After Rectourethral Fistula Repair |
Trauma/Reconstruction/Diversion: Urethral Reconstruction (including Stricture, Diverticulum) I | 17BOS |
Abstract: MP36-11 Sources of Funding: none Introduction Rectourethral fistulae (RUF) is a debilitating diagnosis and complex surgical dilemma. There are few data about quality of life (QOL) of men after RUF repair. QOL after RUF repair was analyzed. Methods Patients who underwent rectal sphincter-sparing transperineal RUF repair between 1/2009 and 5/2016 were assessed. An interposition muscle flap was utilized for all radiated/ablative RUFs and select non-radiated repairs. Patient data were abstracted via retrospective chart review. Patients were contacted by telephone to inquire about QOL following repair. Results 21 men underwent RUF repair (table). Six patients had a complication within 30 days (wound infection (3), GI bleed (1), pelvic abscess (1), renal insufficiency (1)). A successful surgical outcome was obtained in 20/21 patients. Ten patients subsequently underwent placement of an artificial urinary sphincter, of which 2 required explantation/revision. _x000D_ _x000D_ At the time of updated followup (mean 45.6 ± 27.1 months), 15 patients were contacted. Two had died of unrelated causes. 53% of patients reported perineal pain (mean 2.1 ± 1.3; 10-point scale). 43% reported residual problems related to the gracilis flap (one each with numbness, weakness, limited groin mobility, difficulty walking/climbing stairs, occasional leg cramping, and leg swelling). 80% of patients reported urinary incontinence, the majority with occasional mild leakage. Two patients reported fecal incontinence._x000D_ _x000D_ 21% of patients were unable to do the things they wanted in their daily lives due to the surgery. 80% reported the surgery led to a positive change in their lives (mean satisfaction 3.5 ± 0.7, 4-point scale). 87% of patients would undergo surgery again, and 80% would recommend it to others. Nine patients reported they would have done things differently: 4 - sought different treatment/provider for RUF-inciting medical condition, 3 - RUF repair sooner, 2 - see a reconstructive specialist in lieu of local repair, 1 - request bilateral over unilateral gracilis flap. None would have opted for complete urinary diversion. Conclusions RUF repair leads to patient satisfaction and improvement in QOL, despite possible residual issues such as perineal pain and urinary incontinence. Definitive RUF repair should be offered to radiated and non-radiated patients who are suitable operative candidates. Funding none
Authors
Lindsay Hampson
Wade Muncey Mika Sinanan Bryan Voelzke |
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MP36-12 |
Permanent perineal urethrostomy for complex anterior urethral strictures – a critical appraisal of long term outcomes, quality of life and Sexual health. |
Trauma/Reconstruction/Diversion: Urethral Reconstruction (including Stricture, Diverticulum) I | 17BOS |
Abstract: MP36-12 Sources of Funding: None Introduction Many of the patients at the present time undergo a one-stage repair for urethral strictures. The indications for a staged repair remain few, such as complex long segment penobulbar urethral strictures, strictures after multiple failed hypospadias repair, those associated with malignancy or radiotherapy and extensive lichen sclerosis related strictures. In the present study, we evaluate the long term voiding and sexual outcomes of permanent perineal urethrostomy and compare with the existing literature. Methods This study is a prospective evaluation of 116 patients who had permanent perineal urethrostomy at our institution from January 2000 to October 2015. All patients had complex or long segment anterior urethral strictures. The patients were evaluated with clinical history and examination, retrograde urethrography (RGU) and voiding cystourethrogram (VCUG). The patients were also evaluated with a self-completed nonvalidated questionnaire for their voiding and sexual function which was filled at their last visit. Results From January 2000 to October 2015, 212 patients underwent perineal urethrostomy either as a primary (permanent) or staged procedure. 96 patients opted for a secondary procedure for reconstruction of the urethra and were excluded. The remaining 116 patients with mean age of 58±7.3 years were analysed. Mean anterior urethral stricture length was 6.5±2.1 cm (4.0 to 12.0 cm). The etiology of the urethral stricture was unknown or multifactorial in 67/116 (57.7%) patients and Lichen sclerosus in 31/116 (26.7%) patients. The most common late postoperative complication was meatal stenosis of the urethrostomy (10.3%). The median peak flow rate on uroflowmetry after surgery was 18.5 mL/s which was significantly better than the median preoperative value (5.6mL/s) (p=0.001). 75.0% of the patients were satisfied with the overall results. Of those who were sexually active after surgery, 64.5% patients were able to have a satisfactory sexual intercourse. Conclusions Permanent perineal urethrostomy is an acceptable option for complex long segment anterior urethral strictures especially in elderly sexually inactive patients with excellent long term outcome. More than half of the sexually active patients also maintained satisfactory sexual health. Funding None
Authors
Sanjoy Sureka
Priyank Yadav Rahul Soni Aneesh Srivastava Uday Singh Rakesh Kapoor |
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MP36-13 |
Changes in Nocturnal Bladder Diary Parameters in Men After Urethroplasty for Anterior Urethral Strictures |
Trauma/Reconstruction/Diversion: Urethral Reconstruction (including Stricture, Diverticulum) I | 17BOS |
Abstract: MP36-13 Sources of Funding: None Introduction We evaluated changes in nocturnal voiding patterns of men before and after anterior urethroplasty for urethral stricture disease using a pre-operative and post-operative 24 hour bladder diary. Methods This was a retrospective study of men undergoing anterior urethroplasty for urethral stricture who completed a pre-operative and post-operative 24 hour bladder diary. Diaries done anytime prior to surgery and at least 1 month after surgery were included. Patients recorded the volume, time of void and degree of urgency of voids. Paired t-tests were performed on nocturnal voiding variables. Results 18 men had preoperative and post-operative 24 hour bladder diaries. The mean age was 45.4 years (median 46.5,range, 26-70). 13 strictures were bulbar (72.2%), 4 pendulous-bulbar (22.2%), and 1 in the penile urethra (5.6%). Type of surgery included 6 (33%) buccal mucosa onlay grafts (5 dorsal, 1 ventral), augmented anastomotic repair, (n=2, 11.1%), and excision and primary anastomosis (n=10, 55.6%). Mean days from surgery to first post-operative 24 hour bladder diary was 287.5 days (median 109, range, 32-1116). _x000D_ Maximum voided volume increased after surgery (p = 0.02). _x000D_ Overall, nocturnal voiding parameters improved after urethroplasty and trended towards significance primarily by increases in functional bladder capacity measured by the maximum voided volume (mean preop 333ml, post-op 406.6, p=0.02), number of nightly voids (mean 1.8 to 1.2, p=0.07), and the nocturnal bladder capacity index (mean 1.2 to 0.8, p=0.13) and the correlation of the degree of urgency with the voided volume (Spearman's rho mean 0.5 to 0.6, p=0.09). Urethroplasty did not improve nocturnal voiding parameters by changes in urine production as measured by changes in the 24 hour voided volume, nocturnal urine volume, the nocturnal urine production rate or the nocturnal polyuria index. _x000D_ _x000D_ Conclusions Anterior urethral reconstruction improves nocturnal voiding parameters by improving functional bladder capacity. The maximum voided volume, actual night time voids, nocturnal bladder capacity index and Spearman's rho most significantly improved. This is the first study evaluating changes in nocturnal voiding function after urethroplasty. Funding None
Authors
Rajveer Purohit
Jyoti D. Chouhan frank copeli Dennis Robins Andrew Tam Jeffrey P Weiss |
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MP36-14 |
Evaluation of Generic Versus Condition-Specific Quality of Life Indicators for Successful Urethral Stricture Surgery |
Trauma/Reconstruction/Diversion: Urethral Reconstruction (including Stricture, Diverticulum) I | 17BOS |
Abstract: MP36-14 Sources of Funding: None Introduction Overall health quality of life (QOL) indicators may capture non-urological issues such as back pain or arthritis when used as patient reported outcomes measures (PROM) for urethral stricture surgery. We hypothesize that generic health QOL indicators are not meaningful in the assessment of urethral stricture surgery and should be replaced with stricture-specific measures. Methods Patient data was obtained from the Trauma and Urologic Reconstructive Network of Surgeons (TURNS) collaborative database. Patients who underwent a successful urethroplasty, defined by passage of a cystoscope through the repair and no secondary procedure on post-operative evaluation, were included in this study. All patients completed pre- and post-operative questionnaires based on a recently published urethral stricture surgery questionnaire validated in 2013. Results Inclusion criteria were met by 201 patients who underwent successful urethroplasty at a mean age of 47 years. Post-operative questionnaires were completed at a mean time of 7.3 months after surgery. Urethral-stricture specific measures improved after surgery: mean LUTS score (13.1 to 4.0, p<0.05), Peelings voiding picture (3.1 to 1.7, p<0.05), and overall interference of urinary symptoms on life (3.0 to 1.6, p<0.05). Mean overall health status visual analog scale (74.2 to 80.0, p<0.05) and EQ-5D index scores (0.90 to 0.95, p<0.05) also improved; however, individual EQ-5D measures assessing mobility, self-care, and activity level did not change. Although individual EQ-5D measures for pain/discomfort (1.48 to 1.23, p<0.05) and anxiety/depression (1.33 to 1.21, p<0.05) improved, these measures did not correlate with a successful urethroplasty to the same extent as stricture-specific measures (Figure). Only 2 of the 11 patients who reported worse overall pain/discomfort also reported worse bladder or urethral/penile pain when asked about urological-specific pain. Conclusions Generic health QOL indicators may capture medical issues not related to stricture disease and should be replaced with urethral stricture-specific outcomes measures. As PROMs become more prevalent and utilized to evaluate surgeon outcomes and determine reimbursements, it is important to ensure that appropriate condition-specific measures are assessed. Funding None
Authors
Paul H Chung
Alex J Vanni Benjamin N Breyer Bradley A Erickson Jeremy B Myers Bryan B Voelzke |
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MP36-15 |
Live surgery in urology - evaluation of the educational benefit of the International Meeting On Reconstructive Urology (IMORU) |
Trauma/Reconstruction/Diversion: Urethral Reconstruction (including Stricture, Diverticulum) I | 17BOS |
Abstract: MP36-15 Sources of Funding: none Introduction There is an ongoing debate about the benefits and safety of live surgery; however, only few data is available. The International Meeting on Reconstructive Urology (IMORU) is a meeting of live and semi live reconstructive surgeries (e.g., urethroplasty, fistula repair, and implantation of artificial urinary sphincter and penile prostheses), performed by high-volume surgeons only. The aim of this study was to evaluate the participants&[prime] educational benefit including assessment of the quality of surgeries at the 2016 IMORU (VII). Methods At the IMORU VII, all visitors were invited to complete a standardized non-validated survey at each day of surgery. Visitors were able to evaluate the educational benefit and the quality of the surgeries using a Likert rating scale from excellent to bad (1-5). Results Participants&[prime] survey showed that overall the surgeons (1.34, n=22.9), the surgical technique (1.48 n=17.6) and the surgical presentation (1.55, n=19.8) were perceived as excellent. The structural quality of the meeting was found to be very high (faculty: 1.35, n=24; program: 1.38, n=24; presentation: 1.55, n=23.6; poster sessions: 1.82, n=21.67; technique: 1.4, n=23,34). Improvement of knowledge (1.8, n=24.3) and surgical armamentarium (2.06, n=23.7) were both rated good, suggesting that most participants value the educational benefit. Eighty seven percent of participants would attend the meeting again. Conclusions We demonstrated a high educational/learning benefit for visitors participating at a live and semi-live surgery meeting. Standardized participant surveys may be helpful to compare surgical outcomes and educational benefits of live and semi-live surgery meetings. Funding none
Authors
Victor Schuettfort
Jesssica Langetepe Roland Dahlem Christoph-Philip Reiss Clemens Rosenbaum Tim Ludwig Felix Chun Margit Fisch Luis Kluth |
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MP36-16 |
Salvage internal urethrotomy for management of urethral stricture following urethroplasty |
Trauma/Reconstruction/Diversion: Urethral Reconstruction (including Stricture, Diverticulum) I | 17BOS |
Abstract: MP36-16 Sources of Funding: None Introduction Recurrent urethral strictures following open urethral reconstruction can be challenging. We sought to determine the efficacy of salvage direct visualization internal urethrotomy (DVIU), and/or steroid injection in the post-urethroplasty setting, and to identify risk factors for subsequent failure. Methods We identified all patients (n=101) from two institutions who failed urethroplasty and underwent salvage DVIU. Triamcinolone (400mg) was injected intra-spongiosal in 86 patients at the time of the DVIU. The primary outcome of stricture recurrence was defined as need for an additional urethral procedure and inability to pass a 16 French flexible cystoscope. Baseline demographic and stricture characteristics for those with and without recurrence were compared using t-test, Chi square, and Mann-Whitney test where applicable. Univariable and multivariable logistic regression was performed to identify factors associated with salvage DVIU failure. Results Median age at DVIU among all patients (n=101) was 45.0 years (interquartile range [IQR] 35-57). Pre-urethroplasty stricture location was bulbar (n=82, 81.1%), bulbo-membranous (n=11, 10.9%), penile (n=5, 5.0%), and panurethral (n=3, 3.0%). Recurrent stricture length was 1.1 cm (mean). DVIU success rate was 68.3% with median follow-up of 44.5 months (IQR 21-75). Median maximum flow rate and International Prostate Symptom Score (IPSS) before and 6 months after DVIU was 7 vs 12 cc/s and 10 vs 6, respectively. Diabetes, smoking, age or initial stricture location had no association with salvage DVIU success. Patients with DVIU failure were less likely to have received triamcinolone vs. those without recurrence (75.0% vs 89.9%, p=0.05). On multivariable analysis, triamcinolone trended towards protection against recurrence, with an odds ratio [OR] 0.34, p=0.08. Patients without recurrence showed a trend towards greater improvement in IPSS at 6 months (-5 versus -1, p=0.88). Conclusions Conclusions: Salvage DVIU of short recurrent strictures after urethroplasty is moderately effective. Baseline demographic and stricture characteristics are poor predictors of success, while triamcinolone injection may add efficacy to DVIU. Funding None
Authors
Joshua Halpern
Billy Cordon Noel Armenakas Steven Brandes |
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MP36-17 |
The T-plasty as a modified YV-plasty for the treatment of highly recurrent bladder neck stenosis: High success and patient’s satisfaction rates |
Trauma/Reconstruction/Diversion: Urethral Reconstruction (including Stricture, Diverticulum) I | 17BOS |
Abstract: MP36-17 Sources of Funding: None Introduction Highly recurrent bladder neck stenosis (BNS) after surgery for benign prostatic hyperplasia (BPH) is a rare but troublesome problem. After multiple endoscopic treatment attempts, open surgery can be the last therapeutic option before urinary diversion. We present the extended follow-up of outcome and patient`s satisfaction of the previously described T-plasty: A modified YV-plasty of the bladder neck in patients with highly recurrent BNS. Methods In all, 30 patients who underwent T-plasty between December 2008 and July 2016 were retrospectively identified from our prospective urethroplasty data base. Patients were interviewed by telephone. Primary end point of was the treatment specific success rate defined as bladder neck patency without any history of recurrent stenosis or need of further intervention. Secondary endpoint was patient related outcome measurement. Results Mean age was 68.3 yrs. (range 47-86), mean follow up was 44.9 months (range 2-92). As initial surgery for BPH, 83.3% of patients (n=25) had a TURP, 10% had a HoLEP (n=3) and 6.7% had a Greenlight-Laser (n=2). Mean number of prior transurethral procedures to treat the BNS was 4.6 (range 1-19). Preoperatively mean Qmax was 6.8 ml/sec, mean post void residual volume was 141ml. _x000D_ Mean time of surgery was 111 min. (range 74-175). There was no relevant blood loss. No postoperative complications higher grad II according to Clavien-Dindo occurred. Mean time of hospital stay was 13.2 days (range 8-21). _x000D_ Success rate was 100%, one patient needed a permanent catheter due to acontractile detrusor. In one patient, preexisting stress incontinence increased. No de-novo stress incontinence occurred. In no patient further endoscopic or surgical treatment was needed. Postoperatively mean Qmax was 19.8 ml/sec, mean post void residual volume was 37ml. Both values were significantly improved compared to preoperative measurements (p=0.019 and p=0.01). _x000D_ In all 87.5% of patients were (very) satisfied. Only one patient was dissatisfied. In this patient preexisting stress incontinence increased postoperatively. Number of prior therapies did not correlate with patient`s satisfaction. _x000D_ Conclusions The T-plasty represents a successful and safe procedure to treat highly recurrent BNS after surgery for BPH. Success rate is 100%, no major complications were seen. The T-plasty improves quality of life with good satisfaction rates. Funding None
Authors
Clemens Rosenbaum
Philipp Reiss Oliver Engel Luis Kluth Margit Fisch Roland Dahlem |
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MP36-18 |
Patterns and Timing of Artificial Urinary Sphincter Failure |
Trauma/Reconstruction/Diversion: Urethral Reconstruction (including Stricture, Diverticulum) I | 17BOS |
Abstract: MP36-18 Sources of Funding: None Introduction The gold standard treatment for severe post-prostatectomy incontinence is implantation of an artificial urinary sphincter (AUS). There is a paucity of data regarding the timing of AUS placement after prostatectomy and other factors which predict device failure. Methods We identified all patients who underwent prostatectomy and subsequent AUS placement in SEER-Medicare from 2002-2011. These patients' demographic, clinical and pathologic characteristics were included in multivariable cox proportional hazard models, to identify predictors for device survival. We also analyzed factors impacting the time to revision or explantation from initial AUS implantation and prostatectomy. Results 841 men underwent AUS placement at a median 23 months (IQR:15-40.6) after prostatectomy. 236 (28%) men ultimately required revision or explantation. There were no differences in age, race or hospital setting for those undergoing reoperation vs. not (p>0.2). Patients who underwent reoperation were more likely to have had higher clinical stage cancer, undergone open prostatectomy, or had prior sling placement (p<0.01). There were no differences in rates of diabetes, smoking status, prior radiation therapy, or Charlson Comorbidity Index scores between those requiring reoperation vs. not (all p >0.15). Patients with delayed AUS placement (29%), defined as >3 years after prostatectomy, experienced prolonged device survival (Figure). Delayed patients were significantly more likely to have received radiation therapy [36.5% vs. 10.5% (p<0.001)]. Nonetheless, delayed repair was confirmed to be protective on multivariate analysis, after controlling for patient and disease characteristics including radiation history [HR:0.44 (95% CI: 0.32-0.62);p<0.01]. Factors independently associated with a shorter interval time until reoperation included history of radiation [HR: 1.69 (95% CI: 1.16-2.44);p<0.01] and history of prior sling [HR:1.88 (95% CI: 1.19-2.97);p<0.01]. Conclusions Delayed AUS implantation in the Medicare population is associated with prolonged device survival, while radiation exposure and prior urethral sling surgery predict for early reoperation. Further work is required to identify patient specific factors which may explain variability in timing for AUS after prostatectomy and how such factors contribute to device longevity. Funding None
Authors
Andrew Cohen
Kristine Kuchta Sangtae Park Jaclyn Corrine Milose |
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MP36-19 |
De novo penile deviation after urethroplasty wirh oral mucosa: a relevant problem? |
Trauma/Reconstruction/Diversion: Urethral Reconstruction (including Stricture, Diverticulum) I | 17BOS |
Abstract: MP36-19 Sources of Funding: None Introduction There are no reliable data about the incidence of de novo Penisschaftdeviation (PD) after urethral reconstruction using oral mucosa graft(OMG). We evaluated 700 patients who underwent a urethroplasty using OMG. _x000D_ Methods Of 800 operated patients between 04/1994 and 08/2013 700 were evaluated with a minimum follow up of 12 (12-205) months using a standardized questionnaire. All patients received a ventral onlay. We investigated the occurrence of de novo Deviation. In case of a de novo PD we asked about the impairment in sexual intercourse and whether the patient wants counselling and treatment. _x000D_ _x000D_ All patients who answered any of these questions with yes, were contacted once again telephonically. _x000D_ Results 442 (63.1%). 8.5% (38) answered with yes to at least one of the questions. The mean stricture length was 10.2 cm (2-25); 94.5% (36/38) could be contacted by phone again. _x000D_ 47.3% (18/38) had misinterpreted the question or had a PD preoperatively. 13.1% (5/38) had a preoperative Erectile dysfunction with a median IIEF-5 score of 5. Thus remaining 39.4% (15/38) with a de novo PD, i.e. 3.3% of the total population. Consultation request was 1.1% (5/442). _x000D_ _x000D_ 8/15 (53.3%) with de novo PD (stricture length 13-21) had a slight deviation laterally, 3/15 (20%) dorsally and 2/15 (13.3%) a deviation anteriorly. 2 patients could not be contacted. None of these patients wanted treatment or had problems with sexual intercourse._x000D_ Conclusions A de novo PD after urethroplasty with OMG occurs in 3.3%. The deviation is minimal and does not imply a desire for treatment, respectively impairment in sexual intercourse. These are the first data collected in a large population about the occurrence of PD after urethral reconstruction with OMG._x000D_ Funding None
Authors
Abhishek Pandey
Cristina Raita Joern Beier Hansjörg Keller |
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MP36-20 |
Outcomes of Staged Urethroplasty in the Management of Urethral Strictures Related to Hypospadias |
Trauma/Reconstruction/Diversion: Urethral Reconstruction (including Stricture, Diverticulum) I | 17BOS |
Abstract: MP36-20 Sources of Funding: none Introduction Urethral stricture disease related to hypospadias in adults can be challenging surgical problem due to poor quality and paucity of local tissue for repair. We report our experience with staged urethroplasty using buccal mucosal graft in this population. Methods Patients who underwent the first of staged urethroplasty using oral mucosa for hypospadias related strictures between 2002 and 2014 at our tertiary referral center were retrospectively reviewed. Patient characteristics, past surgical history, and surgical details were assessed with outcomes, which included complications, revisions, and voiding without obstructive symptoms. Statistical analysis was completed using univariable and multivariable logistic regression models and the Kaplan-Meier method. Results Fifty-one patients were identified, with a median follow-up of 17 months (IQR 7-59); 50 patients completed all stages of repair. Median age at the time of first stage urethroplasty was 36 years (IQR 26-49). A majority of patients had penile (38, 75%) or panurethral (12, 24%) strictures. Twenty-four (47%) of patients had subcoronal location of meatus prior to surgery. Following staged repair, 19 (37%) patients and 18 (35%) had subcoronal or orthotopic location of the meatus. Less than half patients (23, 45%) received previous endoscopic procedures. A total of 44 (87%) patients had undergone previous open repair, among these patients, 21 had ?2 prior repairs. Median length of buccal mucosal graft, used in all first stage repairs was 7 cm (IQR: 6-10). At 6 months, the complication rate was 12.5%; all complications in 13 (26%) patients presented by 12 months. 8 (16%) required a revision procedure. A majority of patients (49, 98%) were able to void without obstructive symptoms at median follow-up of 17 months. On multivariable analysis, stricture length, location, number of prior open repairs did not correlate with complications, ability to void without obstructive symptoms, or revisions. Conclusions Staged buccal graft urethroplasty demonstrated a high success rate in terms of the ability to void without obstructive symptoms or the need for instrumentation at intermediate follow-up in this challenging cohort of patients. Outcome was not related to stricture length, location, and prior surgical history. Funding none
Authors
Shree Agrawal
Amanda Chi Kenneth Angermeier Hadley Wood |
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MP37-01 |
Programmed death-ligand 1 (PD-L1) expression in Pheochromocytoma |
Adrenal | 17BOS |
Abstract: MP37-01 Sources of Funding: none Introduction Programmed death ligand-1 (PD-L1), a key target molecule for immunotherapy, is frequently overexpressed in several neoplasms. In the present study, we examined PD-L1 expression in pheochromocytoma because very few reports on this subject are available. Methods PD-L1 mRNA expression was compared across 184 pheochromocytoma, 492 prostate cancer, and 404 bladder cancer cases based on The Cancer Genome Atlas (TCGA). Furthermore, we enrolled 32 pheochromocytoma patients who were surgically treated at our hospital between June 2005 and February 2016. We conducted PD-L1 immunohistochemistry (IHC) using the SP142 assay. PD-L1 expression was scored at three diagnostic levels (0, 1, and 2). Results A comparison of PD-L1 mRNA expression based on the TCGA revealed that PD-L1 expression was significantly higher in pheochromocytoma than in bladder cancer and prostate cancer (p < 0.001). _x000D_ The SP142 assay of our 32 surgical pheochromocytoma cases revealed that the prevalence of a PD-L1(+) expression (IHC score 1 or 2) in tumor-infiltrating immune cells (TICs) was 25% (eight patients) and that in tumor cells (TCs) was 28.1% (nine patients). The tumor diameter was significantly different between PD-L1(+) TIC patients (3.36 ± 0.35 cm) and PD-L1(-) TC patients (5.37 ± 0.50 cm, non-paired t-test: p = 0.044). In our cohort, there were two cases of malignant pheochromocytomas but none of them were PD-L1(+). _x000D_ _x000D_ Conclusions PD-L1 expression is relatively higher in pheochromocytoma than that in bladder cancer and prostate cancer based on TCGA. The SP142 assay of our 32 surgical pheochromocytoma cases revealed that the tumor diameter in PD-L1(-) TIC cases was larger than that in PD-L1(+) cases. Further, there were no PD-L1(+) cases of malignant pheochromocytoma._x000D_ These findings suggest that PD-L1 expression in pheochromocytoma is relatively common and that PD-L1(+) expression in pheochromocytoma may not be associated with tumor aggressiveness._x000D_ Funding none
Authors
Yasuhiro Hashimoto
Atsushi Imai Shingo Hatakeyama Takahiro Yoneyama Takuya Koie Chikara Ohyama |
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MP37-02 |
Nutlin-3a as a Novel Anticancer Agent for Adrenocortical Carcinoma with CTNNB1 Mutation |
Adrenal | 17BOS |
Abstract: MP37-02 Sources of Funding: NONE Introduction Adrenocortical carcinoma (ACC) is a rare malignancy characterized with poor survival at advanced and metastatic stage, with no curative treatment available. CTNNB1 is frequently mutated in ACC and is identified as one of the driver mutations. Current targeted therapy for CTNNB1 in ACC is lacking and our study aims to screening for effective agents with antineoplastic activity against ACC with CTNNB1 mutation._x000D_ Methods In silico screening of the Genomics of Drug Sensitivity in Cancer (GDSC) database that included drug sensitivity data of 265 compounds in 1,074 cancer cells were conducted. Drug sensitivity in cells with CTNNB1 mutation was analyzed, and further in vitro and in vivo studies were performed using the compound. Results Only one compound, Nutlin-3a, an MDM2 inhibitor was significantly sensitive in 18 cancer cells with CTNNB1 mutation. However, mutation of TP53, which was also common in ACC conferred significant resistance to Nutlin-3a. Further analysis of the 18 cells revealed no significant efficacy between cells with both CTNNB1 and TP53 mutation indicating concomitant TP53 mutation did not impact on drug efficacy. We verified Nutilin-3a-inhibited cellular proliferation in ACC cell line NCI- H295R which harbored CTNNB1 mutation but not in SW13 cells which did not. Nutlin-3a induced cell apoptosis and G1 cell- cycle arrest in NCI-H295R cells. Nutlin-3a also decreased cellular migration and inhibited epithelial-to-mesenchymal transition (EMT) process in terms of EMT index. Moreover, Nutlin-3a resulted in decreased beta-Catenin level independent of p53 level in NCI-H295R but not SW13 cells. We also evaluated the effect of Nutlin-3a on hormonal secretion of NCI-H295R cells and found it resulted in decreased levels of cortisol, androgen, and progesterone. Nutlin-3a treatment inhibited ACC tumor growth and hormonal secretion with no observed toxicity in mice in vivo._x000D_ Conclusions Our study revealed Nutlin-3a, the first-generation MDM2 inhibitor potently inhibited ACC with CTNNB1 mutation. Several new derivatives of Nutlin-3a has now entered clinical trials, holding promise for targeted MDM2 inhibition in CTNNB1-mutant ACC. However, how p53/MDM2 axis coordinate with Wnt/beta-Catenin signaling in ACC warrants further study._x000D_ Funding NONE
Authors
Chenchen Feng
Shanwen Chen |
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MP37-03 |
Level of prenatal adrenal steroids hormones affects body weight at birth |
Adrenal | 17BOS |
Abstract: MP37-03 Sources of Funding: The Ministry of Health, Labour and Welfare, Health and Labour Sciences Research Grants, Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science, and the Environment Research and Technology Development Fund (5C-1252) from the Ministry of the Environment, Japan Introduction It is well known that prenatal environment affects infant development and prenatal stress has a negative impact on their child outcomes. The hypothalamic-pituitary-adrenal (HPA) axis is one of the major systems involved in stress response and its regulation. In fact, maternal cortisol also can pass through the placenta and affect fetal cortisol level and HPA development. In the present study, we investigated relationship between steroids levels in cord blood and body weight at birth. Methods Of 514 who participated in a prospective cohort study of birth in Sapporo, the following steroid hormone levels in 294 stored cord blood (135 boys and 159 girls) were measured; estradiol (E), testosterone (T), progesterone (P), androstenedione (4-dione), dehydroepiandrosterone (DHEA), cortisol and cortisone. Information of birth weight obtained from medical records at birth. The relationship between birth weight and steroid hormone levels in cord blood samples was calculated using a multiple linear regression analysis. The inclusion of covariates was based on biological considerations and adjustments were made for gestational age, maternal smoking and alcohol consumption during pregnancy, and body weight of parents. Significance levels were set to 0.05 for all comparisons. Results The median concentrations of T and T/E were significantly higher in males than in females, while the median concentration of DHEA was significantly higher in females. There was a trend that birth weight was heavier in boys than in girls. Mother’s weight before pregnancy, not father’s weight, significantly affected birth weight of their children. Regarding the hormone levels of P, Cortisone, 4-Dion/DHEA and Cortisone/Cortisol in cord blood, there was significant relationship with birth weight in boys, not in girls (Table). Conclusions The present study indicated that prenatal adrenal steroids affected body weight at birth. Further, 4-Dion/DHEA and Cortisol/Cortisone indicate activity of 3β-hydrosteroid dehydrogenase 11β-hydrosteroid dehydrogenase type 2, respectively. Thus, in addition to adrenal steroid hormones, converting enzymes such as 11β-hydrosteroid dehydrogenase type 2 and 3β-hydrosteroid dehydrogenase in the placenta and fetal adrenal gland may also have impact on birth weight in boys. Funding The Ministry of Health, Labour and Welfare, Health and Labour Sciences Research Grants, Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science, and the Environment Research and Technology Development Fund (5C-1252) from the Ministry of the Environment, Japan
Authors
Takahiko Mitsui
Atsuko Araki Sachiko Ito Chihiro Miyashita Kimihiko Moriya Takeya Kitta Kazutoshi Cho Keita Morioka Nobuo Shinohara Masayuki Takeda Reiko Kishi Katsuya Nonomura |
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MP37-04 |
The limited value of repeated hormonal examination in nonfunctioning adrenal incidentalomas. |
Adrenal | 17BOS |
Abstract: MP37-04 Sources of Funding: none Introduction Most adrenal incidentalomas are nonfunctioning cortical adenomas which do not cause classical clinical signs and symptoms of hormone excess syndromes. The optimal frequency and duration of follow-up for patients who have nonfunctioning adrenal incidentalomas are uncertain. The aim of this study was to investigate the value of long-term radiological and hormonal follow-up in the patients with nonfunctioning adrenal incidentalomas. Methods The present study is a retrospective register based cohort study of 315 patients who were diagnosed with adrenal tumors at Niigata University Hospital between the years 2000 and 2016. According to the initial radiological and hormonal examination, 106 patients were considered as having benign and nonfunctioning adrenal tumors. Twenty-three patients received adrenalectomy because of the initial tumor size or mass enlargement during the follow-up. The other 83 patients were followed with periodic computed tomography (CT). Regular hormonal examinations were performed in 41 patients (Group 1), but not in 42 patients (Group 2). Results The tumor size at diagnosis in patients who underwent adrenalectomy was 4.9±3.7 cm (mean±SD) and pathology showed no malignancy in all patients. As for the followed-up 83 patients, age (mean±SD: 59.1±10.7 and 62.7±12.7 years old), gender (48.8 and 59.5% were males), follow up periods (median: 65.0 and 62.0 months), tumor size at diagnosis (2.6±1.3 cm and 2.2±0.9 cm) were not significantly different between group 1 and 2, respectively. Majority of the patients (97.6% in each group) had no tumor growth on CT during prolonged follow-up. Only 1 patient in each group had adrenal mass enlargement ≥ 1.0cm during follow-up period, however, both tumors were likely benign because of their CT findings (tumor size ≤ 4.0cm, homogenous, and ≤ 10 Hounsfield Unit on unenhanced CT). No one showed hormone overproduction during follow-up period in group 1. No patients has clinical signs and symptoms of hormone excess syndromes in both group. Conclusions Patients with an initially normal hormonal screening may not need further hormonal examination during follow-up Funding none
Authors
Masayuki Tasaki
Takashi Kasahara Itsuhiro Takizawa Vladimir Bilim Kazuhide Saito Tsutomu Nishiyama Yoshihiko Tomita |
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MP37-05 |
Preoperative plasma aldosterone-to-renin ratio is a predictor of decrement in glomerular filtration rate after adrenalectomy for primary aldosteronism |
Adrenal | 17BOS |
Abstract: MP37-05 Sources of Funding: none Introduction In patients with primary aldosteronism (PA), excessive aldosterone causes glomerular hyperfiltration, which can be associated with increase in glomerular filtration ratio (GFR). After treatment of PA, correction of hyperfiltration may decrease GFR. Therefore, decrement in GFR can be a clinically significant problem after treatment of PA. The aim of this study was to determine the prevalence of renal deterioration and new onset chronic kidney disease (CKD), and identify the predictors of decreasing estimated GFR (eGFR) after laparoscopic adrenalectomy for aldosterone-producing adenoma. Methods In our institution, 64 patients underwent laparoscopic adrenalectomy for PA between 2001 and 2015. Of them, 41 patients who received postoperative surveillance for more than 12 months were included in this retrospective study. Preoperative parameters including age, sex, duration of hypertension, eGFR, the ratio of plasma aldosterone (pg/mL) to plasma renin activity (ng/mL/hr) ratio (ARR), tumor size and operation time were evaluated to determine risk factors for postoperative deterioration of eGFR (>25% decrement from preoperative level) and new onset CKD (eGFR <60 ml/min/1.73m2). Results Median followup was 58 months (range 12-187). Mean preoperative eGFR was significantly decreased from 73.6 ± 19.7 ml/min/1.73m2 at baseline to 61.0 ± 18.9 ml/min/1.73m2 at the latest followup (p<0.01). Fifteen patients (36.6%) showed postoperative deterioration of eGFR. ARR was the only significant predictive factor for postoperative deterioration of eGFR. Using a cutoff point of 2000, sensitivity and specificity were 62.5% and 77.2%, respectively. Excluding 11 patients who had CKD before operation, 13 (43.3%) of 30 patients developed new onset CKD after operation. We could not determine a significant predictor for postoperative new onset CKD. Conclusions Postoperative renal deterioration is prevalent in patients with PA. High ARR may be associated with the degree of glomerular hyperfiltration and irreversible renal damage and is a predictive factor of eGFR decrement after removal of adenoma. Postoperative surveillance of renal function and management of CKD are essential in patients who underwent adrenalectomy for PA. Funding none
Authors
Keiko Fujino
Toshiaki Tanaka Toshihiro Maeda Naoya Masumori |
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MP37-06 |
Super-selective adrenal venous sampling is useful for evaluating cortisol-producing adenoma |
Adrenal | 17BOS |
Abstract: MP37-06 Sources of Funding: The Japan Society for the Promotion of Science (KAKENHI-Grants to K.N [26893261]), Okinaka Memorial Institute for Medical Research (to KN), and Japanese Ministry of Health, Labour and Welfare (to TN). Introduction Conventional adrenal venous sampling (cAVS) is useful for identifying laterality of primary aldosteronism (PA). In cAVS, plasma cortisol concentration (PCC) is used for normalization of plasma aldosterone concentration (PAC). We have developed a novel super-selective adrenal venous sampling (ssAVS) method using a specialized microcatheter, which collect blood samples from adrenal tributary veins (TVs). PAC in ssAVS samples do not require PCC-normalization since the samples contain a limited amount of systemic venous blood, if any. The ssAVS method enabled us to identify and surgically treat adrenal segments responsible for excess aldosterone production in bilateral PA cases. In this study, we aimed to determine if ssAVS is useful for evaluating cortisol production in a PA case with subclinical Cushing's syndrome (SCS). Methods In the case, ssAVS data was evaluated with clinical and histological data. Results A computed tomography identified bilateral adrenal tumors (Fig. 1A). Right adrenal venography identified superior TV (blue arrow in Fig. 1B), lateral TV (red) that was downstream of the tumor, and inferior TV (green). Left adrenal venography identified superior-median TV (red arrow in Fig. 1C) with a filling defect presumably due to the left adenoma (green), superior-lateral TV (blue), and lateral TV (yellow). Blood samples were individually collected from these bilateral TVs by ssAVS. The PCC in right lateral TV (1,150 µg/dL) and PAC in left superior-median TV (30,400 pg/mL) were much higher than the others (indicated in Fig. 1B and 1C), suggesting that the right and left tumors were a cortisol-producing adenoma (CPA) and aldosterone-producing adenoma, respectively. Left partial adrenalectomy was performed and PA was cured. SCS is currently followed up without treatment, because his SCS has not caused hypertension or impaired glucose tolerance. Pathological diagnosis of left tumor was adrenal adenoma in hematoxylin and eosin staining (T in Fig. 1D), which was positive for aldosterone synthase (AS, Fig. 1E) but not for 11β-hydroxylase (11β, cortisol producing enzyme, Fig. 1F). 11β was negative in adjacent normal adrenal (N in Fig. 1F), suggesting that cortisol production was suppressed by the possible right CPA. These enzyme expression was consistent with ssAVS data. Conclusions This study suggested that ssAVS is useful for evaluating cortisol production in adrenal adenomas. Funding The Japan Society for the Promotion of Science (KAKENHI-Grants to K.N [26893261]), Okinaka Memorial Institute for Medical Research (to KN), and Japanese Ministry of Health, Labour and Welfare (to TN).
Authors
Koshiro Nishimoto
Kohzoh Makita Kanako Kitamoto-Kiriyama Tsugio Seki Masanori Yasuda Masafumi Oyama Mototsugu Oya Masao Omura Tetsuo Nishikawa |
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MP37-07 |
The ADRENAL Score: a Comprehensive Scoring System for Standardized Evaluation of Adrenal Mass |
Adrenal | 17BOS |
Abstract: MP37-07 Sources of Funding: NSFC, 81460389, to Gongxian Wang;_x000D_ Robotic Research Grant (Intuitive Surgical Operations, Inc), Robotic Adrenalectomy: Preoperative Evaluation of Surgical Risk, Standardization of Retroperitoneal_x000D_ Approach and Outcome Comparison with Transperitoneal Approach, to Gongxian Wang_x000D_ Introduction Treatment planning for adrenal tumors depends on a variety of qualitative and quantitative data, including tumor nature and anatomy, as well as the experience of the operating surgeon. Here, we have developed and propose a scoring system for adrenal masses designated as the A.D.R.E.N.A.L Score, to quantify the nature and anatomical characteristics of adrenal masses based on endocrinological assessment, computerized tomography and patient habitus. Methods The A.D.R.E.N.A.L score consists of 7 components including (A)ldosterone/cortisol/catecholamine secretion or suspicion of malignancy based on endocrinological and radiological study, (D)imension (tumor size as the maximal diameter), (R)elationship to adjacent organs, (E)nhancement on computerized tomography, (N)earness of the tumor to major vessels, (A)dipose (patient habitus as body mass index), and a combination of two (L)ocation descriptors [anterior (a) or posterior (p), left (L) or right (R)]. The A.D.R.E.N.A.L score was applied to 345 cases, including 212 laparoscopic retroperitoneal adrenalectomy cases and 105 robotic retroperitoneal adrenalectomy cases and 28 robotic transperitoneal adrenalectomy cases. Results For all three series, the A.D.R.E.N.A.L score accurately classified the complexity of cases in the above three series as evidenced by the positive correlation between the A.D.R.E.N.A.L score and surgical outcomes including the operative time and estimated blood loss, while BMI or tumor size did not as independent risk factor. Conclusions Standardized evaluation of an adrenal tumor is essential for individualized patient preparation, surgical planning and postoperative care which translate to patient safety and cost-effectiveness. The A.D.R.E.N.A.L score is a reproducible classification system based on endocrinological, oncological and anatomical characteristics of adrenal masses. This novel scoring system of adrenal masses may provide a common reference for the decision making of both endocrinologist and urologist, assessment of the surgical risks, patient safety-guided designing of adrenalectomy training programs, and stratified analysis and comparisons of adrenal surgeries within a single or among multiple institutions. Funding NSFC, 81460389, to Gongxian Wang;_x000D_ Robotic Research Grant (Intuitive Surgical Operations, Inc), Robotic Adrenalectomy: Preoperative Evaluation of Surgical Risk, Standardization of Retroperitoneal_x000D_ Approach and Outcome Comparison with Transperitoneal Approach, to Gongxian Wang_x000D_
Authors
Xiaochen Zhou
Bin Fu Weipeng Liu Cheng Zhang Gongxian Wang |
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MP37-08 |
A new insight for the treatment of Primary Macronodular Adrenal Hyperplasia: adrenal sparing surgery early outcomes |
Adrenal | 17BOS |
Abstract: MP37-08 Sources of Funding: none Introduction Partial Adrenalectomy (PA) has dramatically changed the treatment of patients affected by pathologies that affect both adrenal glands. Currently, evidences regarding the use of PA to treat primary macronodular adrenal hyperplasia(PMAH) are limited, including a small number of cases described as part of cohorts related to a variety of adrenal gland tumors. To date, the outcomes of this surgical treatment on hypercortisolism control is not known. In order to overcome the hormonal replacement caveats while minimizing the risks of hypercortisolism relapse, we performed a series of simultaneous total adrenalectomy of largest adrenal gland and contra-lateral partial adrenalectomy(adrenal sparing surgery) in patients with PMAH. Methods Ten patients diagnosed with PMAH were treated surgically with adrenal sparing surgery. Primary endpoint was hypercortisolism remission, considered when patients had physiologic cortisol levels (5-25 ?g/L) without hormonal reposition. Adrenal insufficiency and latent adrenal insufficiency were defined when oral hydrocortisone reposition was needed, with the dose of > 0,2 mg/kg/day and ? 0,2 mg/kg/day, respectively.Secondary endpoints were clinical and metabolic parameters improvement. Body mass index (BMI), blood pressure, cholesterol, lipid and glucose levels, were measured before and 12 months after the procedure. Medications to control comorbidities were also assessed and compared. Results There were no intra-operative complications and average operation time was 189 ± 34 minutes. Median hospitalization period was 7,5 days and one patient needed surgical hematoma drainage. With a median follow-up of 24 months (range: 13 to 63 months), 40% of the cohort had complete hypercortisolism remission, 20% persisted with latent adrenal insufficiency and 40% with adrenal insufficiency. Hypercortisolism recurrence was not observed. Median systolic/diastolic blood pressures were 155/95 before and 123/80 after the procedure (p < 0,001). Median number of medications to control blood hypertension diminished from 3 to 1(p < 0,001). There was no significant change in cholesterol, lipid and glucose blood levels as well as the number of diabetes and lipid lowering medications. Median BMI decreased from 31,7 ± 7,8 to 28,4 ± 4,7(p = 0.05). Conclusions An early assessment revealed that adrenal sparing surgery is a feasible procedure to treat patients affected by PMAH, providing hypercortisolism remission and potentially avoiding the drawbacks of lifetime corticosteroids replacement. Funding none
Authors
Fabio Tanno
Victor Srougi Vania Brondani Madson Almeida Berenice Mendonca Miguel Srougi Jose Chambo Maria Fragoso |
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MP37-09 |
Clinical outcome of laparoscopic adrenalectomy in sub clinical Cushing syndrome; Is surgical removal better or not? |
Adrenal | 17BOS |
Abstract: MP37-09 Sources of Funding: None Introduction Although no definitive surgical guide line exist in Sub-clinical Cushing Syndrome: SCS, surgical resection is considered based on the presence of hyper tension(HT), diabetes mellitus(DM) and hyper lipidemia(HL). Cortisole(CS) level > 3μg/dL after use of 1mg dexamethasone(Dex) was the U.S. guideline of SCS, while >1.8µg/dL in Japanese guideline. In this analysis, we have studied the clinical benefit of surgically removal in SCS tumor, especially patients with gray zone(between US and Japanese guideline);1.8≤CS<3.0µg/dL after Dex 1mg treatment. Methods Total of 112 patients diagnosed as SCS between 1997 and 2015 were included in this study. 94 patients underwent surgical adrenalectomy and 18 patients were none surgically observed. Clinical outcome such as HT, DM, HL and body mass index(BMI) were retrospectively analyzed. All the surgical adrenalectomies were performed by retroperitoneal laparoscopic adrenalectomy. Results Median age was 65 years. Median tumor diameters were 30 mm. Significant improvement in HT (P<.0001), HbA1c (P=0.016) and BMI (P=0.0018) were observed in overall surgically removed SCS patients. Significant improvements in HT (P=0.034) and BMI (P=0.042) were also observed in 1.8≤CS<3.0µg/dL group after surgery. However, clinical improvement were more evident in ≥3.0µg/dL group, such as HT (P=0.0002), HbA1c (P=0.028) and HDL-C(P=0.046), while no clinical improvement were observed in ≤1.8µg/dL groups. Although not reached statistical significance, surgical removal groups tends to show the reduction in prescribed drugs compare to none surgical groups(drugs related to DM 23 vs 10% p=0.073, HT 37 vs 11% P=0.078 and HL 43% vs 11% P=0.282) Conclusions The current data showed that surgically removal of SCS tumor mediated significant improvements in the clinical symptoms. Based on expected clinical benefit,the gray zone SCS patients; 1.8≤CS<3.0µg/dL after Dex 1mg treatment may also be a optimal candidate for laparoscopic adrenalectomy. Funding None
Authors
Miki Fuse
Shinichi Sakamoto Kodai? Sato Takaaki Tamura Akinori Takei Satoshi Yamamoto Yusuke Imamura Koji Kawamura Takashi Imamoto Akira Komiya Tomohiko Ichikawa |
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MP37-10 |
Incidence and Risk Factors for Adrenal Insufficiency Following Unilateral Adrenalectomy |
Adrenal | 17BOS |
Abstract: MP37-10 Sources of Funding: none Introduction Acquired adrenal insufficiency is a risk of unilateral adrenalectomy, performed either to remove a functional tumor or a gland with suspicion of cancer. All patients with evidence of a cortisol-secreting tumor receive a steroid taper in the first weeks after surgery, but some patients require an extended course of cortisol supplementation. Our objective was to determine the incidence of adrenal insufficiency at 30 days and at 1 year, as identified by requiring exogenous hormones to treat symptoms or abnormal laboratory values. Methods A retrospective review was performed for all unilateral adrenalectomies at our institution from 2008-2016. Patient characteristics such as age and gender were recorded as risk factors, and surgical parameters such as laterality and pathology result, as well as tumor functionality were recorded. Logistic regression was used to determine which factors were associated with adrenal insufficiency as measured by cortisol supplementation at 30 days and at 1 year. Results There were 115 unilateral adrenalectomies performed; 102 were laparoscopic and 13 were open. 62% of these were left-sided. Mean patient age was 56 and 64% of patients were female. 57 patients (50%) had biochemical evidence of a functional tumor prior to surgery. 9 patients (7.8%) required cortisol supplementation 30 days after surgery, and only 1 of these patients still required steroids (0.9%) at 1 year. All of these patients had signs and symptoms of hypercortisolism prior to adrenalectomy. Patients with a functional tumor were significantly more like to develop adrenal insufficiency (16%) at 30 days than those with a nonfunctional tumor (0%, p<0.005). Of the 9 patients requiring supplementation, 7 had adrenal cortical adenomas and 2 had adrenal hyperplasia. Gender was the only significant patient risk factor that predicted adrenal insufficiency at 30 days; (12% of females, 0% of males, p<0.05). Conclusions The incidence of adrenal insufficiency following unilateral adrenalectomy is low. Most patients who require hormone supplementation 30 days following surgery are able to wean off this requirement by 1 year. These data may help provide reassurance to patients undergoing adrenalectomy concerned regarding losing a functioning adrenal gland. Tumor functional status and female gender were significant predictors of adrenal insufficiency at 30 days. A larger sample size would likely be necessary to identify other significant predictors given the low incidence of insufficiency. Funding none
Authors
Jeffrey B. Walker
Brian D. Saunders Kathleen Lehman Jay D. Raman |
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MP37-11 |
Laparoscopic vs. Open Adrenalectomy: Urologic Outcomes from a National Prospective Database |
Adrenal | 17BOS |
Abstract: MP37-11 Sources of Funding: none Introduction For elective adrenalectomy, the decision between laparoscopic versus open adrenalectomies is made largely based on surgeon preference, and these surgeries are performed by both general surgeons and urologists. Here, we sought to examine the perioperative outcomes of laparascopic versus open elective adrenalectomies when performed by a urologic surgeon. Methods The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) Participant User Files (2007-2012) was queried using Current Procedural Terminology adrenal gland explorations (60540), laparoscopic adrenalectomy (60650), and adrenal gland exploration with excision of adjacent/ retroperitoneal tumor (60545). Only surgeries performed by urologic surgeons were included. Prolonged length of stay (pLOS), prolonged operative time (pOT), 30-day complications (including infectious, thromboembolic, renal, cardiac, pulmonary, and neurologic events), and need for blood transfusion, re-intubation, or reoperation were analyzed. pOT and pLOS were defined as an operating time and a hospital length-of-stay greater than the 75th percentile, respectively (pOT=193 minutes and pLOS>4 days). Results Two hundred ninety-one patients who underwent adrenalectomy were identified. Of those, 73 underwent open and 218 underwent laparoscopic elective adrenalectomy. Laparoscopic approach was utilized more frequently in patients with a body mass index (BMI) of >25 (p=0.0155), yet approach was not associated with ASA score (p=0.3897). The overall complication rate was 6.2% (18/291): 9.6% for open approach and 4.6% for laparoscopic (p=0.1468). When compared to open, laparoscopic adrenalectomies were associated with shorter operative time (p<0.0001), and shorter length of stay (p<0.0001). Laparoscopic approach was also associated with lower rates of postoperative deep vein thrombosis (p=0.0142) and decreased need for blood transfusions (p<0.0001). However, there was no significant difference in need to return for reoperation (p=0.1277). Conclusions Despite its more common utilization in overweight individuals, laparoscopic adrenalectomy is faster and results in shorter length of stay, decreased need for blood transfusions, and fewer deep vein thromboses. Otherwise, the 30-day post-operative outcomes between the laparoscopic and open approaches are comparable. Therefore, laparoscopic adrenalectomy should be attempted when possible. Funding none
Authors
Pamela W. Lu
Valary Raup Malte Vetterlein Bjoern Loeppenberg Christian Meyer Quoc-Dien Trinh Jairam Eswara |
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MP37-12 |
Robotic Excision of Large Adrenal Tumors via Retroperitoneal Approach: Experience from 21 Cases |
Adrenal | 17BOS |
Abstract: MP37-12 Sources of Funding: NSFC, 81460389, to Gongxian Wang; _x000D_ Robotic Research Grant (Intuitive Surgical Operations, Inc), Robotic Adrenalectomy: Preoperative Evaluation of Surgical Risk, Standardization of Retroperitoneal Approach and Outcome Comparison with Transperitoneal Approach, to Gongxian Wang Introduction Robotic adrenalectomy can be performed via transperitoneal or retroperitoneal approach. Growing evidence suggests the safety and feasibility of the retroperitoneal approach for the resection of even large adrenal tumors. Methods 21 robotic adrenalectomies of tumors with diameter > 6 cm (6 to 14 cm) were chosen from 106 consecutive retroperitoneal robotic adrenalectomies performed by a single surgeon between December 2014 and August 2016. All surgeries were performed via retroperitoneal approach as previously described. Medical information and surgical outcome were prospectively collected. Results 10 female and 11 male patients were included in the 21 cases. Average patient age was 46.9 ± 14,5 yr. Average BMI was 24.2 ± 4.0. Average diameter of tumor was 8.8 ± 2.4 cm, ranging from 6 to 14 cm. 12 cases were left and 9 cases were right adrenal lesions. All 21 cases were successfully performed robotically without conversion or transfusion. Postoperative pathology revealed adrenal indications of medulla lipoma (n = 6), pheochromocytoma (n = 4), cortical adenoma (n = 5), cyst (n = 3), B-cell lymphoma (n = 2) and cystic angiomyolipoma (n = 1). Average operative time was 169.0 ± 42.7 min. Average estimated blood loss was 138.5 ± 69.2 ml. Peritoneum rupture happened in 3 cases, which did not result in conversion to other surgical approaches. Patients were discharged at 3 to 6 days postoperatively. No regional recurrence was appreciated during a mean follow-up of 12 months (2 – 22months). Conclusions Despite limited working space and indirect access to the adrenal vein, retroperitoneal approach avoids entering the abdomen and has been shown to be a safe and effective surgical approach for the excision of even very large adrenal tumors in experienced hands. Due to limited working space, successful retroperitoneal adrenal surgeries rely on several key steps including suitable trocar configuration/angulation and adequate mobilization of the ipsilateral kidney. Funding NSFC, 81460389, to Gongxian Wang; _x000D_ Robotic Research Grant (Intuitive Surgical Operations, Inc), Robotic Adrenalectomy: Preoperative Evaluation of Surgical Risk, Standardization of Retroperitoneal Approach and Outcome Comparison with Transperitoneal Approach, to Gongxian Wang
Authors
Xiaochen Zhou
Bin Fu Weipeng Liu Cheng Zhang Gongxian Wang |
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MP37-13 |
Outcomes of adrenalectomy for adrenal metastasis of renal cell carcinoma in the era of adrenal-sparing radical nephrectomy : a multicenter study |
Adrenal | 17BOS |
Abstract: MP37-13 Sources of Funding: none Introduction Until the early 2000s, ipsilateral adrenalectomy at the time of radical nephrectomy was genrally recommended except in small tumors of the lower pole. In the current era, as radical nephrectomy sparing the adrenal gland has become the gold standard, the incidence of metachronous adrenal metastases has increased. However, to date no study has aimed to assess the outcomes of adrenalectomy for metastasis of renal cell carcinoma (RCC). The aim of this study was to report the outcomes of adrenalectomy for metastasis of RCC. Methods All adrenalectomies for suspected adrenal metastases of RCC performed in seven centers between 2006 and 2016 were included in a retrospective study. The adrenalectomies performed at the time of ipsilateral nephrectomy were excluded. Recurrence-free survival (RFS) and specific survival (CSS) were estimated using the Kaplan-Meier method. Prognostic factors of CSS were sought by univariate and multivariate Cox regression analyzes. Results Forty-eight patients were included. Mean tumor size was 40.8 mm. Histology of the primary tumor was clear cell renal cancer in most cases (94.8%). Metastases were unique in 77% of patients. Metastases were metachronous in 77% of cases and occurred after a mean interval of 8.1 months. The average hospital stay was 5.4 days. The rate of positive margins was 9%. The complication rate was 23.9% but with only three major complications (Clavien> 2; 6.2%). After a median follow up of 23 months, Estimated RFS and CSS rates at 5 years were 18.3% and 97.5% respectively. The only prognostic factor associated with CSS was the absence of other metastases at the time of adrenalectomy (OR = 6.1; p = 0.03). Conclusions In this multicenter study, adrenalectomy for adrenal metastasis of RCC offered satisfactory perioperative outcomes. Recurrence of disease was relatively common (5 year-RFS: 18.3%; only prognostic factor = single metastasis) but CSS was similar to those observed after partial nephrectomy for small renal tumors (5 year-CSS: 97.5%). Funding none
Authors
benoit peyronnet
nadja schoentgen andrea manunta jean-baptiste beauval franck bruyere francois-xavier nouhaud philippe grise georges fournier reem betari nicolas brichart alexandre gryn tristan grevez benjamin pradère samy oumakhlouf mathieu thoulouzan adham rammal anna goujon michel soulié fabien saint vincent joulin eric huyghe karim bensalah |
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MP37-14 |
Oncological outcomes of radical nephroureterectomy with and without synchronous ipsilateral adrenalectomy |
Adrenal | 17BOS |
Abstract: MP37-14 Sources of Funding: none Introduction During the past decade, the role and indications of adrenalectomy as part of radical nephrectomy for renal cell carcinoma have been clearly defined. In contrast, the impact of synchronous adrenalectomy during radical nephroureterectomy for upper tract urothelial carcinoma (UTUC) has never been evaluated. The aim of this study was to assess the impact of adrenal resection during radicla nephroureterectomy for UTUC. Methods _x000D_ The charts of all patients who underwent nephroureterectomy for upper tract urothelial carcinoma in a single-center between 1994 and 2014 were retrospectively reviewed. Patients were divided into two groups: synchronous ipsilateral adrenalectomy (A) and no synchronous ipsilateral adrenalectomy (NA). Perioperative outcomes (operative time, complications, positive margins, ...) were compared between the 2 groups using ?2 and Mann-Whitney tests. Survival outcomes were estimated using the Kaplan-Meier method. The impact of synchronous adrenalectomy on cancer-specific-survival (CSS) and recurrence-free survival (RFS) was evaluated using the log-rank test._x000D_ Results _x000D_ One hundred and forty five patients were included in the study. Among them 21 had synchronous ispilateral adrenalectomy but only one adrenal specimen was invaded by the UTUC on final pathology (4.8%) and this invasion was diagnosed on preoperative imaging. Synchronous adrenalectomy had no impact in terms of operative time (265 vs. 241 min; p = 0.22), transfusion rate (20% vs. 18.4%; p = 0.87), complication rate (38.1% vs. 39.8%; p = 0.89) or positive margins (9.6% vs. 13.2%; p = 0.64). CSS (79.6% vs. 62.8%; p = 0.18) and RFS (70% vs. 56.6%; p =0.33) at 5 years were comparable between both groups_x000D_ Conclusions _x000D_ In this single-center series, adrenal resection during nephroureterectomy for UTUC did not increase perioperative morbidity but did not provide oncologic benefit. Adrenal invasion by UTUC was rare (4.8%) and diagnosable on preoperative imaging. Hence, routine ipsilateral adrenalectomy during radical nephroureterectomy may not be indicated._x000D_ Funding none
Authors
benoit peyronnet
quentin alimi gregory verhoest lauranne tondut vivien graffeille anna goujon romain mathieu andrea manunta solene-florence kammerer-jacquet nathalie rioux-leclercq karim bensalah |
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MP37-15 |
Contralateral adrenal thickness predicts the duration of prolonged post-surgical steroid replacement for subclinical Cushing syndrome |
Adrenal | 17BOS |
Abstract: MP37-15 Sources of Funding: none Introduction Adrenal insufficiency after adrenalectomy in patients with cortisol secreting adenomas is potentially critical if not treated. Therefore, patients who undergo adrenalectomy for subclinical Cushing syndrome (SCS) require post-surgical glucocorticoid replacement treatment. By contrast, the total duration of steroid replacement is still controversial and varies among patients. Here we analyzed pre-treatment various factors potentially affecting the duration of post-surgical steroid replacement in patients after laparoscopic adrenalectomy for SCS. Methods This retrospective analysis included 66 patients who underwent unilateral laparoscopic adrenalectomy for SCS between March 2005 and May 2016 at Chiba University Hospital. Adrenal tumor and contralateral adrenal sizes together with various clinical factors were studied in association with the duration of post-surgical steroid replacement. Adrenal tumor and contralateral adrenal sizes were measured at the level of maximum size of adrenal glands using CT scan. Cox’s proportional hazard model was used for the statistical analysis. Results All 66 patients treated post-surgical steroid replacement after adrenalectomy. Median duration of the steroid treatment was 6 months. Median age of the patients was 59 years. Among 66 patients, 37 cases had left adrenal tumor and 29 cases had right tumor. Median size of the tumor was 26.5mm. Median operation time was 175 minutes. Only 1 case converted to open surgery. When assessing the duration of post-surgical steroid replacement, maximum tumor diameter (MTD) > 26.5mm (HR 1.92, P = 0.0493) and contralateral adrenal thickness (CAT) < 6.3mm (HR 4.38, P < 0.0001) were significant predictors of prolonged post-surgical steroid treatment on univariate analysis. On multivariate analysis, CAT < 6.3mm (HR 4.04, P < 0.0001)was the only independent predictive factor for the prolonged post-surgical steroid replacement. Conclusions Contralateral adrenal thickness was the significant predictive factor for the duration of post-surgical steroid replacement in SCS patients. Pre-surgical assessment in the imaging may help clinicians determine the total duration of steroid therapy after adrenalectomy. Funding none
Authors
Yusuke Imamura
Masahiro Sugiura Satoshi Yamamoto Tomokazu Sazuka Miki Fuse Kazuyoshi Nakamura Shinichi Sakamoto Koji Kawamura Takashi Imamoto Akira Komiya Tomohiko Ichikawa |
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MP37-16 |
Prognosis of Patients with Malignant Adrenal Pheochromocytomas: A Conditional Probability Analysis |
Adrenal | 17BOS |
Abstract: MP37-16 Sources of Funding: none Introduction Malignant Pheochromocytoma (PHEO) may present with metastatic disease earlier or later. The metachronous and synchronous metastatic disease may have different behavior. Besides, disease prognosis is not constant over time; consequently, the conditional survival (CS) of patients with malignant PHEO needs to be evaluated. Methods The Surveillance, Epidemiology, and End Results (SEER) database was queried for patients aged >18 years diagnosed with malignant PHEO between 1988 and 2012. Demographic, clinical and pathologic informations were collected. Conditional survival, CS(y/x), is the probability of surviving an additional y years, given that the patient has already survived x years. The mathematical definition of CS can be expressed as: CS(y/x)=S(x+y)/S(x). Results A total of 277 patients were identified.In univariate analysis, factors associated with lower overall survival (OS) included older age, larger tumor size, diagnosed with distant metastases, failure to underg any surgery and necessitating radiotherapy. Cox proportional hazards regression analysis showed that factors independently associated with higher overall mortality were older age, diagnosed with distant metastases and failure to undergo any surgery. Patients diagnosed with metastatic disease had a poor prognosis with a median OS of 23 months, while patients diagnosed with nonmetastatic disease had a longer median OS of 116 months. Patients of younger age, with smaller size and who underwent surgery had significantly better OS, while the clinical stage at diagnosis did not affect survival in the metachronous metastatic subgroup. CS estimates were more encouraging than static survival probabilities. During the first 5 years after their initial diagnosis, the 1-year CS of patients who had survived >24 months increased to approximately 90%, while OS decreased progressively from about 80% to 60%. The gains in 1-year CS over time were more pronounced in patients with poor prognostic factors, including older age, diagnosed with distant metastases and failure to undergo any surgery. These differences in 1-year CS between the different prognostic factor groups decreased with time from diagnosis, or even disappeared. Conclusions These findings provided a new perspective for understanding the prognosis of malignant PHEO. Funding none
Authors
Wenjun Xiao
Yao Zhu Dingwei Ye |
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MP37-17 |
Evaluation of the Accuracy of the National Surgical Quality Improvement Program (NSQIP) Risk Calculator for Predicting Complications following Adrenalectomy |
Adrenal | 17BOS |
Abstract: MP37-17 Sources of Funding: none Introduction Adrenalectomy is performed to treat functional pathology and to remove tumors of malignant concern. The NSQIP Risk Calculator predicts both length of stay and 30 day complications following a given surgery by inputting a set of risk factors. Our objective is to assess whether this tool accurately predicts complications following adrenalectomy thereby allowing accurate counselling regarding surgical risk. Methods A retrospective review was performed for all adrenalectomies at our institution between 2008-2016. 126 patients underwent adrenalectomy without concurrent resections. Predicted risk for NSQIP complications was calculated for each patient. The mean predicted and observed risks (%) at 30 days across all patients within each category were determined, and these were compared with a two-sided one-sample t-test. Results Of 126 adrenalectomies, 111 were laparoscopic and 15 were open. Mean age was 55 and 66% of patients were female. For laparoscopic adrenalectomy, 5 (4%) complications were observed including 3 (2%) Clavien III or greater. All observed complication rates were significantly different than predicted, except for surgical site infection. (Table) Rates of severe, any, and cardiac complications, as well as venous thromboembolism, renal failure, and death were less than expected, while rates of pneumonia, urinary tract infection, readmission, return to operating room, and discharge to rehabilitation were greater than expected. Mean observed length of stay (LOS) was significantly less than predicted (1.44 vs. 2.11 days, p<0.001). In the open adrenalectomy subgroup, there were no observed complications with observed mean LOS greater than predicted (6.67 vs. 5.27, p<0.05) without a higher readmission rate (6.67 vs. 5.83%, p=0.064). Conclusions Laparoscopic adrenalectomy has a low complication rate, and most patients leave the hospital in 1 to 2 days. Most of the NSQIP calculator's predictions were significantly different than observed; some complications were overestimated and others underestimated. Overall, absolute complication rates seem comparable when considered for clinical significance with a larger sample size requisite to better delineate which complications are most accurately predicted by the calculator. Funding none
Authors
Jeffrey B. Walker
Brian D. Saunders Kathleen Lehman Jay D. Raman |
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MP37-18 |
Longitudinal Evaluation of Health Related Quality of Life Following Laparoscopic Adrenalectomy: Impact of Adrenalectomy on Cortisol Producing Adenoma. |
Adrenal | 17BOS |
Abstract: MP37-18 Sources of Funding: none Introduction Cushing&[prime]s syndrome is caused by prolonged and excessive exposure to cortisol. It is suggested that this chronic exposure is associated with comorbidities contribute to poor quality of life. The purpose of this study was to evaluate patient-reported health related quality of life (HRQOL) of Cortisol producing adrenocortical adenoma (CPA) in comparison with that following Non-CPA (NCPA). Methods A total of 24 and 62 patients who underwent laparoscopic adrenalectomy in CPA and NCPA between January 2012 and September 2015 were included in the study. We assessed general HRQOL with the Short Form 8 (SF-8) instrument. We administered the SF-8 questionnaires at pre-operative baseline, and at 3, 6, 9, 12, 18 and 24 months after surgery. The impact of changes in two measurements of the physical (PCS) and mental (MCS) components summary scores of the SF-8 was evaluated in the prospective and longitudinal study. Results There was no significant inter-group difference in patient characteristics between the CPA and NCPA groups. Baseline PCS was significantly lower in the CPA than the NCPA group (43.6 vs. 49.0, p=0.0075). Subsequently, the PCS score was significantly lower in the CPA group at postoperative 3, 6, 9, 12 month. The PCS score was increased in the CPA group and there was no significant difference between both groups at postoperative 18 (48.1 vs. 50.2, p=0.1202) and 24 (48.0 vs. 50.8, p=0.3625) month (Fig. 1A). However, in baseline MCS score, there was no significant difference between both the CPA and NCPA group (43.7 vs. 45.6, p=0.3957).The MCS score in both groups was gradually increased and there was no significant difference between both group in all postoperative points (Fig. 1B). Conclusions The patients with CPA were improved in not the mental but the physical component after postoperative 18 months. Our study suggests that laparoscopic adrenalectomy contribute to improvement of HRQOL in the physical function. Funding none
Authors
Shogo Inoue
Tetsutaro Hayashi Keisuke Hieda Shunsuke Shinmei Jun Teishima Akio Matsubara |
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MP37-19 |
Short-term impact on health-related quality of life of laparoscopic adrenalectomy for primary aldosteronism in Japanese patients |
Adrenal | 17BOS |
Abstract: MP37-19 Sources of Funding: none Introduction Primary aldosteronism (PA) is one of the typical forms of secondary hypertension (HTN). Our previous study showed that the antihypertensive effect of laparoscopic adrenalectomy (LA) was not a little for elderly PA patients suffering from HTN for many years. However, the impact of LA on health-related quality of life (QOL) in those patients has not been evaluated. Methods According to Japanese diagnostic criteria for PA, a total of 178 PA patients who underwent LA between July 2012 and December 2015 were eligible for this study. Demographic data, perioperative outcomes and QOL were examined. QOL was assessed using the Short Form 36-Item Health Survey questionnaire before and at 6, 12, 18 and 24months after LA. Results Responses were analyzed for 96 of 136 patients (70.6%) who responded to the questionnaire. Median age was 55 years (range, 25-77 years) and median duration of HTN was 9 years (range, 1-43 years). Median follow-up was 12 months (range, 6-24 months) after LA. To evaluate the influence of the duration of HTN on health-related QOL, we compared differences in Norm-based Scoring in Japanese between patients with HTN for <10 years (median age, 51 years) and patients with HTN >10 years (median age, 60 years). In the former group, scores improved in all 8 health-related QOL domains from the baseline at the 6-month survey after LA (Figure A). In the latter group, scores of 4 domains did not improve in terms of Physical functioning, Bodily pain, Social functioning or Mental health. However, scores for another 4 domains improved from the baseline (Figure B). Furthermore no significant differences between groups were evident 6 months after LA in any domains scores. Conclusions To the best of our knowledge, normalizing aldosterone levels by LA contributes not only to antihypertensive effect, but also to protective effects against cardiovascular diseases. In our study, LA for PA patients with short-term HTN leads to much greater improvements in prognosis and QOL. However, improvements of QOL by LA was found among PA patients despite long-term use of HTN. The negative impact of LA for PA patients with long-term HTN on Social functioning and Mental health remains to be elucidated. More time is needed to evaluate the influence of LA on long-term QOL among PA patients with long-term HTN to achieve better outcomes from LA. Funding none
Authors
Yoshihide Kawasaki
Yasuhiro Kaiho Hideaki Izumi Naoki Kawamorita Shinichi Yamashita Hisanobu Adachi Koji Mitsuzuka Akihiro Ito Shigeto Ishidoya Yoichi Arai |
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MP37-20 |
NEW SEVERITY CLASSIFICATION SCALE FOR PHEOCHROMOCYTOMAS |
Adrenal | 17BOS |
Abstract: MP37-20 Sources of Funding: none Introduction Pheochromocytoma (PC) may present in a wide variety of clinical scenarios, including asymptomatic patients found to have an adrenal incidentaloma, to the critically ill patient in hypertensive crisis. No clinical classification scheme exists for PC that stratifies patients into different risk groups. We proposed and evaluated a severity classification scale for PC. Methods We evaluated 25 patients from two institutions who underwent adrenalectomy for PC from 2000-2015. We classified patients as follows: Class I: asymptomatic and normotensive; Class II: asymptomatic + controlled hypertension; Class III: symptomatic + controlled hypertension; Class IV: uncontrolled hypertension or hemodynamic crisis. We obtained all available pre-operative, normalized metabolic, clinical data, imaging studies, pathology (including PASS), and discharge information. Non-parametric regression and analysis of variance (ANOVA) were used for statistical considerations._x000D_ _x000D_ Results A total of 25 patients with 26 PCs were included in our study including 3 children (11%). About half of patients were asymptomatic. Most (83%) tumors enhanced on T2 MRI. There was no difference in age, gender, or BMI between the 4 groups. About 2/3 of all patients in the study had right sided lesions. Sixty-four percent underwent laparoscopic excision. From Class I to IV, patients experienced longer ICU (R2=0.39) and overall hospital stays (R2= 0.32), and worsening pathologic features (i.e. PASS , R2=0.22). From Class I to III, urinary and plasma catecholamine levels, intraoperative blood loss and operative time, and average tumor size increased. We found that Class IV cases did not have, on average, the highest metabolic abnormalities, more complications, or larger tumor sizes in the study even compared to some Class I patients._x000D_ _x000D_ _x000D_ Conclusions We present to our knowledge the first clinical severity scale for patients who present with PC. The I-IV scale correlated well with length of ICU and hospital stay and with pathologic findings while increasing catecholamine levels were seen comparing Class I to III. Class IV patients may represent a unique subset. Although Class IV patients did experience longer hospital stays and had higher PASS scores, multiple variables may be contributory to their critical hemodynamic collapse other than catecholamine excess alone. More research is needed to validate this scale._x000D_ _x000D_ Funding none
Authors
Joel Hillelsohn
Michael Zhang Michael Stern John Phillips |
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MP38-01 |
A Prospective Randomized Controlled Trial to Compare the Outcomes of 12 versus 20 core Ultrasound Guided Transrectal Prostate Biopsy |
Prostate Cancer: Detection & Screening IV | 17BOS |
Abstract: MP38-01 Sources of Funding: None Introduction Despite the unequivocal contribution of targeted MRI fusion biopsy, it is known that ultrasound-guided biopsy with systematic sampling still is the main tool for prostate cancer (PC) diagnosis in developing countries. However, the number of sampled fragments remains a matter of controversy. Our objective was to compare the cancer detection rate (CDR) and the complications of 12 versus 20-core ultrasound guided transrectal prostate biopsy. Methods A prospective controlled study was conducted enrolling 758 consecutive patients who underwent biopsy with 1:1 randomization ratio for 12-core versus 20-core biopsy under periprostatic block local anesthesia. 76 patients were on active surveillance and 284 had at least one previous biopsy. The overall and the significant (Gleason ≥7) CDR were compared between the 2 techniques. We also evaluated the CDR according to PSA, free PSA, PSA density, prostate volume, previous biopsy and suspicious digital rectal examination. We assessed the occurrence of complications and the pain immediately after the procedure using the visual analogue pain intensity scale. Results The CDR was 47.7% and 37.7% in 20-core and 12-core groups, respectively (OR 1.510; 95% CI: 1.130 to 2.018, p=0.0052). An overall 18.5% significant increase in Gleason score ≥7 detection rate was found in the 20-core group (83.7 vs. 65.2% p=0.0463). The CDR was also in favor of the 20-core when the active surveillance patients were excluded 45.6% and 32.9% (OR 1.712; CI 95% 1.215 to 2.412 p=0.002). Considering only the surveillance patients the 20-core protocol also showed higher CDR 66.7 vs. 52.5% (p=0,209). The CDR between the two techniques were similar according to PSA levels (p=0.874), prostate volume p=0.619), previous biopsy (p=0.5973), age (p=0.070), suspicious DRE (p=0.146), free-to-total (p=0.542) and PSA density (p=0.585).The occurrence of any complication and acute prostatitis were similar between the 20- and 12- core groups: 10.7 vs. 10.4% (p=0.899) and 6.5 vs. 4.2% (p=0.2166), respectively. The mean visual analogue pain intensity scale were also similar in 20-core when compared to 12-core group 2.35 vs. 2.19 (p=0.7977). Conclusions Our randomized trial revealed that the overall cancer positivity and the diagnosis of aggressive tumors were significantly higher in the 20-core prostate biopsy when compared to the 12-core protocol. The complication rates and the pain experienced by the patients were similar in both groups. _x000D_ _x000D_ ClinicalTrials.gov NCT02825225 Funding None
Authors
Jose Pontes-Junior
Petronio A S Melo Regis N Rodrigues Vinicius Meneguetti Davi Constantin Francisco Dada Neto Sidney R Seabra Júnior Carlos H W Silva Douglas Fontes Tiago A C Ferreira Matheus RM Rosa Sabrina T Reis Anderson Q Rocha Gabriel Durigon Claudio B Murta Adalberto Andriolo Junior Joaquim A Claro |
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MP38-02 |
Biparametric MRI: Could It Reduce The Cost Of MRI While Maintaining Diagnostic Accuracy For Prostate Cancer? |
Prostate Cancer: Detection & Screening IV | 17BOS |
Abstract: MP38-02 Sources of Funding: Ipsen and Tolmar Introduction Use of multiparametric MRI (mpMRI) has increased massively in prostate cancer diagnosis, not only in active surveillance and post negative TRUS biopsy, but as part of the upfront diagnostic algorithm. The prostate imaging-reporting and data system version 2 (PIRADS v2) rates the likelihood of significant prostate cancer on a scale from 1 to 5, which encompasses T2W images, diffusion-weighted imaging (DWI) and dynamic contrast-enhanced (DCE) MRI. DCE only affects the overall PIRADS score when a lesion is deemed PIRADS 3 on diffusion weighted imaging (DWI) in the peripheral zone. The aim of this study is to assess the utility of DCE, which requires the administration of intravenous contrast, adding cost and risks to patients. Methods Data on all patients undergoing their first prostate mpMRI for initial diagnosis, active surveillance and previous negative biopsies were recorded into a custom-made prospective REDCap database between July 2013 and May 2016. All mpMRIs were reported by experienced radiologists. Results 1191 mpMRI were performed during this time period. Mean patient age was 65.1 years and mean PSA was 7.43. 658 patients were undergoing their initial mpMRI without previous biopsies. Only 85 (7.1%) mpMRI had lesions with DWI PIRADS score of 3 in the peripheral zone. Of the initial mpMRIs without previous biopsies, only 56 (8.4%) had lesions with DWI PIRADS score of 3 in the peripheral zone. _x000D_ _x000D_ Of the 85 patients with a lesion that was equal to 3 on DWI in the peripheral zone, 58 had an mpMRI that had an overall PIRADS score of 3 and had a subsequent biopsy. 35 had clinically insignificant cancer or benign biopsy, 17 had grade group 2 on histology and 6 had grade group 3. 4 patients had an overall PIRADS score of 4 and a subsequent biopsy. 3 were benign or clinically insignificant cancer and 1 had grade group 2 cancer. _x000D_ _x000D_ 14 of these patients had a subsequent radical prostatectomy, which showed 1 grade group 1 histology, 7 grade group 2 histology and 6 grade group 3 histology. Lesions with DWI score of 3 only make up a small proportion of mpMRIs, and fewer patients require radical treatment._x000D_ Conclusions DCE appears to have a minor role in determining the overall PIRADS score of a lesion and is relevant in less than 9% of cases. By omitting the DCE, and therefore contrast administration, patients would be spared risks of nephrotoxicity and anaphylaxis, and healthcare costs could be cut without reducing diagnostic accuracy in the vast majority of cases. Funding Ipsen and Tolmar
Authors
Lana Pepdjonovic
Sean Huang Anthony Dat Sarah Mann Mark Frydenberg Daniel Moon Ross Snow Uri Hanegbi Adam Landau Richard O'Sullivan Andrew Ryan Jeremy Grummet |
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MP38-03 |
Predictive Value of Multiparameteric MRI (mp-MRI) for the Detection of Prostate Cancer using 12-core TRUS-Guided Prostate Biopsy – A United Kingdom Multicenter Study |
Prostate Cancer: Detection & Screening IV | 17BOS |
Abstract: MP38-03 Sources of Funding: None Introduction Many urooncology centers currently precede prostate biopsy with a multiparametric MRI (mp-MRI) scan. However, there is a paucity of information on the exact predictive value of the mp-MRI in determining final histology based on the outcome of 12-core transrectal ultrasound (TRUS) guided prostate biopsy. Herein, we aim to decipher the predictive value of mp-MRI in detection and exclusion of prostate cancer using TRUS prostate biopsy. Methods UK multicentre study. Data from 592 patients scheduled to undergo mp-MRI and/or 12-core TRUS-guided prostate biopsy from January till September 2016 was reviewed retrospectively from a prospective database. Mp-MRIs were reported using the Prostate Imaging Reporting and Data System (PI-RADS). Only patients who had pre biopsy mp-MRIs followed by prostate biopsy were included in the study. 108 patient were excluded as they did not have mp-MRI or biopsy due to contraindications. Results Prebiopsy mp-MRIs followed by a 12-core TRUS-guided prostate biopsy were completed in 484 patients. The sensitivity and specificity of mp-MRI for prostate cancer detected on prostate biopsy were 92.6% and 74.4%, respectively. The negative predictive and positive predictive values of mp-MRI for prostate cancer detected on biopsy were 89.7% and 80.8%, respectively. 129 patients had a PI-RADS score of 5 on mp-MRI, with prostate cancer detected in 92%(n=119) of patients on biopsy. The incidence of Gleason scores 6,7,8 and 9 in patients with PI-RADS 5 were 15.9%(n=19), 51.2%(n=61), 6.7%(n=8) and 26%(n=31), respectively. 117 patients had a PI-RADS score of 4 on mp-MRI, with prostate cancer detected in 53.8%(n=63) of patients on biopsy. The incidence of Gleason scores 6,7,8 and 9 in patients with PI-RADS 4 were 60%(n=36), 33.3% (n=21), 4.7% (n=3) and 1.5% (n=1), respectively. 153 patients had a PI-RADS score of 3 on mp-MRI, with prostate cancer detected in 29% (n=45) of patients on biopsy. The incidence of Gleason scores 6,7 and 9 cancers in patients with PI-RADS score of 3 were 68% (n=31), 26.6% (n=12) and 4.4% (n=2), respectively. Overall there was a statistically significant association between patients with PIRADS scores ≥3 and cancer positive biopsies (p=0.001) Conclusions Mp-MRI has a high predictive value for both diagnosing and excluding prostate cancer. Patients with PI-RADS scores ≥3 had a significant association with detection of prostate cancer on biopsy. These findings could aid in guiding follow-up protocols in men suspected of prostate cancer. Funding None
Authors
Iqbal Miakhil
Peter Macneal Iannish Sadien Tian Tian Yeong Tim Larner Sashi Kommu Chris Lockett Steve Garnett Peter Rimington |
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MP38-04 |
IS AN UPGRADED PIRADS 4 EQUIVALENT TO A TRUE PIRADS 4? A VALIDATION OF PIRADS VERSION 2 IN A PROSPECTIVE COHORT OF MEN UNDERGOING MRI-US FUSION BIOPSY OF THE PROSTATE |
Prostate Cancer: Detection & Screening IV | 17BOS |
Abstract: MP38-04 Sources of Funding: none Introduction An updated version of PIRADS (PIRADS v2) was introduced in August 2015 for MRI interpretation. While a similar scoring pattern ranging from 1-5 is used, PIRADS v2 employs a dominant sequence rule, where depending on the location of the target the overall score is the score from that particular sequence (DWI for PZ lesions, and T2 for TZ lesions). However, for lesions with an indeterminate score of 3, a secondary sequence is used (DCE for PZ targets, and DWI for TZ targets) to determine if the score should be upgraded to a 4 or left as a 3. Our objective was to validate whether the rate of detecting Gleason 7 or higher cancer was different between an upgraded PIRADS 4 lesion versus a true PIRADS 4. Methods A prospective cohort of 336 men underwent mp-MRI US fusion biopsy between August 2015 to August 2016 for evaluation of prostate cancer or active surveillance. Among these men, there were 462 targets that were biopsied. For this analysis we selected all targets that were scored as PIRADS 3 or 4, and differentiated between an upgraded PIRADS 4 and a &[Prime]true&[Prime] PIRADS 4 target. We report the detection rate of Gleason 7+ cancer between PIRADS 3 and 4 targets and use logistic regression to assess the association between PIRADS score and cancer detection. Results Among the 462 targets in our dataset, we had 333 targets that were either PIRADS 3 or 4. Among these targets, 166 were PIRADS 3, 49 were an upgraded PIRADS 4, and 118 were a true PIRADS 4. We had 190 targets that were located in the PZ, and 143 targets located in the TZ. For targets in the PZ, the detection of Gleason 7+ cancer was 8%, 27%, and 33% for PIRADS 3, upgraded PIRADS 4, and true PIRADS 4 targets, respectively (p <0.01). Compared to a PIRADS 3 in the PZ, the odds of Gleason 7+ cancer was 3.98(CI 1.41-11.23) for an upgraded PIRADS 4 and 5.42(CI 2.14-13.73) for a true PIRADS 4 target. We performed a similar logistic regression with upgraded PIRADS 4 as the reference group and saw no difference between a upgraded PIRADS 4 and true PIRADS 4 for the detection of Gleason 7+ cancer. We did not have enough significant cancer detected in the TZ to make any reliable comparisons in this zone. Conclusions Upgraded PIRADS 4 targets in the PZ have a higher rate of Gleason 7+ cancer compared to PIRADS 3 targets. We found no difference between an upgraded PIRADS 4 and a true PIRADS 4. Our findings validate the revised scoring system for PIRADS. Funding none
Authors
Nachiketh Soodana Prakash
Pratik Kanabur Leonardo Kayat Bittencourt Vivek Venkatramani Bruno Nahar Sanjaya Swain Chad Ritch Mark Gonzalgo Dipen Parekh Sanoj Punnen |
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MP38-05 |
Defining a cohort of men who may not require repeat prostate biopsy based on PCA3 and MRI: The double negative effect. |
Prostate Cancer: Detection & Screening IV | 17BOS |
Abstract: MP38-05 Sources of Funding: none Introduction Prostate Cancer (PC) overdiagnosis and overtreatment is a major concern for clinicians and policy makers. Multiparametric MRI (mpMRI) and the PCA3 urine test aim to limit this by identifying fewer cases of indolent cancer and more clinically significant cases. We explore whether the utility of the tests can be maximized by combining them for a group of patients with previous prostate biopsies. Methods We collected clinicopathologic data from all patients that underwent a urine PCA3 test from 2011 to June 2016 at the University Health Network at The University of Toronto in accordance with ethics committee approval. This included patients on active surveillance (AS) for low-risk PC and those without PC with previous negative biopsies and suspicion of occult, significant disease primarily based on rising PSA. We explored whether age, PSA, PCA3, mpMRI, DRE, family history and prostate size predicted for clinically significant prostate cancer on repeat biopsy as defined by Epstein criteria. We then stratified patients by mpMRI and PCA3 result to detect whether any particular combination of these test has exemplary negative predictive value (NPV) and considered the optimal sequence of tests. Results 470 patients met inclusion criteria with median (IQR) age and PSA of 62.5 ng/mL (58-68) and 6.3 (4.6-8.8), respectively. PCA3 was abnormal (≥35) in 32.5% of cases. 18.8% of men had a positive family history and 5.6% had suspicious DRE. Epstein criteria or worse PC was identified in 26.3% of cases. In the multivariate model, only age (OR 1.08, 95%CI 1.01-1.16), mpMRI score 4 (OR 16.6, 95%CI 3.9-70.0) or 5 (OR 28.3, 95%CI 5.7-138), and PCA3 (OR 2.9, 95%CI 1.0-8.8) predicted for clinically significant PC on biopsy. No patients with a negative mpMRI and normal PCA3 test were found to have clinically significant PC on biopsy (0 of 26, 100% NPV for double negative test, p<0.0001). Using mpMRI as the initial test diminishes the number of overall tests (11 fewer tests per 100 patients), adds spatial information for targeted biopsy when available, but is more expensive than starting with PCA3 test for all patients. Conclusions Both PCA3 and mpMRI are useful tests for predicting clinically significant PC on repeat prostate biopsy. In the 1 of 6 patients in our cohort with double negative tests no clinically significant PC was found on biopsy, which raises the question whether biopsy can be avoided in this group altogether. This study is limited by its retrospective design and selection bias. A prospective trial at our centre is currently ongoing examining this question for patients on AS. Funding none
Authors
Nathan Perlis
Thamir Al-Kasab Ardalan Ahmad Estee Goldberg Kamel Fadaak Rashid Sayyid Antonio Finelli Girish Kulkarni Alexandre Zlotta Rob Hamilton Neil Fleshner |
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MP38-06 |
Zero hospital admissions for infection after 1359 transperineal prostate biopsies |
Prostate Cancer: Detection & Screening IV | 17BOS |
Abstract: MP38-06 Sources of Funding: Ipsen and Tolmar Introduction Transrectal biopsy is plagued by an increasing rate of serious infection, despite use of recommended fluoroquinolone antibiotics. Transperineal biopsy (TPB), on the other hand, has been associated with an exceedingly low rate of serious infection. The aim of this study was to determine the rate of hospital admissions for infection after transperineal biopsy of prostate. Methods Patients underwent transperineal biopsy of the prostate (TPB) between May 2012 and October 2016 by a private group urology practice, at multiple hospitals across Melbourne. A standard brachytherapy template grid was used, taking a number of samples from left and right prostate posterior, mid and anterior regions. Some patients had extra core biopsies taken from target areas suspicious of cancer identified on prior MRI. Data collected from these patients were entered into an ethics approved prospective database including prophylactic antibiotics used and post operative complications. Results 1359 consecutive patients underwent TPB. Initially patients were treated with quinolone prophylaxis and then later patients received cephazolin only. 1030 (75.8%) had single dose IV cephazolin, 388 (28.6%) had an oral quinolone with IV cephazolin, 107 (7.9%) had IV ceftriaxone and 2 (0.1%) had IV clindamycin, 2 (0.1%) had IV meropenem and 1 (0.1%) had IV vancomycin prophylaxis. Routine practice shifted from use of quinolones to cephazolin during the study period. 25 (1.8%) patients developed acute urinary retention and 1 patient was treated in the community with oral antibiotics for prostatitis. No patients were readmitted to hospital with infection. Conclusions Sepsis post TPB is an exceedingly rare complication, with a 0% rate in this large prospective multicentre cohort. It is safe to use single dose cephazolin only as antibiotic prophylaxis prior to TPB, negating the need for quinolones. This study supports the current Australian Therapeutic Guidelines recommendation for TPB prophylaxis. Whether any antibiotic prophylaxis is needed at all for TPB is the subject of a future study. Funding Ipsen and Tolmar
Authors
Lana Pepdjonovic
Sean Huang Anthony Dat Sarah Mann Mark Frydenberg Daniel Moon Ross Snow Uri Hanegbi Adam Landau Jeremy Grummet |
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MP38-07 |
Should we aim for the centre of an MRI prostate lesion? Correlation between mpMRI and 3-Dimensional 5mm Transperineal Prostate Mapping biopsies from the PROMIS trial. |
Prostate Cancer: Detection & Screening IV | 17BOS |
Abstract: MP38-07 Sources of Funding: Medical Research Council UK Introduction mpMRI enables a new way to stratify prostate cancer patients through visualisation of a target to biopsy. However, prostate cancer is heterogeneous, even within the same focus. We aimed to determine deploying the needle to the centre of a mpMRI lesion would reflect the true risk of that lesion. Our study involved a unique cohort of men in whom a pre-biopsy mpMRI was carried out prior to Transperineal Prostate Mapping biopsies taken every 5mm within the PROMIS trial. _x000D_ Methods 94 patients included in this analysis comprised the pilot phase of the Prostate MRI Imaging Study (NCT01292291) investigating accuracy of mpMRI against standard of care with 3D 5mm TPM-biopsies as the reference test. All patients were biopsy-naive with a PSA below 15ng/ml, referred for suspicion of prostate cancer. Prior to biopsy, all patient underwent 1.5T mpMRI with standardized protocol (T2W, DWI , DCE) which were reported on a Likert scale, blinded to subsequent histology results. Patients then underwent TPM-biopsies blinded to the mpMRI findings so that the whole prostate was sampled every 5mm. Cores were separately labelled and oriented in space. A 3D digital map of the gland was reconstructed from the TPM-biopsies using in-house software. Prostates and mpMRI lesions were contoured (blind to pathology results), registered to the digital map by aligning gland boundaries._x000D_ We identified the MRI lesion centroid and the locations of biopsy cores containing the maximum Gleason score of the lesion. We considered two cores in particular. First, the one closest to the centroid and second, the one with the longest maximum cancer core length. We computed the distance from these two cores to the centroid of the MRI lesion_x000D_ Results 41 patients (median PSA 6.5ng/ml, median age 62) were found to harbour cancer at TPM-biopsies in this cohort, leading to 75 MRI lesions correlated with cancer. From the centroid, the mean distance to closest maximum Gleason core was 7.8mm (+/-6.6), and to core with the maximum cancer length was 13.8mm (+/-8.3). Conclusions The histological tissue that harbours the highest Gleason score within a prostate cancer lesion seen on mpMRI is not consistently located near the centre. MRI-lesion-based targeting should include sampling the entire lesion with a number of cores. _x000D_ Funding Medical Research Council UK
Authors
Clement Orczyk
Yi Peng Hu Eli Gibson Ahmed El-Shater Bosaily Alex Kirkham Shonit Punwani Louise Brown Esther Bonmati Yolana Coraco-Moraes Katie Ward Rick Kaplan Dean Barratt Mark Emberton Hashim U Ahmed |
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MP38-08 |
Evidence of grade progression from long-term follow-up of cohorts not subject to prostate-specific antigen screening |
Prostate Cancer: Detection & Screening IV | 17BOS |
Abstract: MP38-08 Sources of Funding: This work was supported by David H. Koch provided through the Prostate Cancer Foundation; the Sidney Kimmel Center for Prostate and Urologic Cancers; SPORE grant from the National Cancer Institute to Dr. H. Scher (grant number P50-CA92629); and a National Institutes of Health/National Cancer Institute Cancer Center Support Grant to MSKCC (grant number P30-CA008748). This work also received funding support in part from the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre Program in UK, the Swedish Cancer Society (project nr 14-0722), the Swedish Research Council (VR-MH project nr 2016-02974), and the Prostate Cancer Foundation Young Investigator Award 2012. Introduction Lead-time is of key importance in cancer early detection, but cannot be directly measured. We previously provided estimates of lead-time for prostate cancer using archived blood samples from cohorts followed for many years without screening. We determined the association between lead-time and grade at diagnosis to provide insight into whether grade progresses or is stable over time. Methods Participants were selected from three population-based Swedish cohorts followed without screening: 871 men aged 37 - 70 with PSA 3 - 10 ng / mL at blood draw and subsequently diagnosed with prostate cancer of whom 326 were diagnosed with high-grade disease (Gleason grade ≥7; Gleason grade group (GGG) ≥2). Multivariable logistic regression was used to predict high versus low-grade prostate cancer at diagnosis in terms of lead-time: time between elevated PSA and clinical diagnosis. Multivariable linear regression was used to test the association between lead time and PSA. Results After adjustment for cohort and age, the odds of high-grade disease increased 1.11 (95% C.I. 1.08, 1.14) per year increase in lead time (p<0.0001), with no evidence of differences by age group or cohort. Higher PSA predicted a shorter lead time of 0.44 (95% C.I. 0.25, 0.63; p<0.0001) years per 1 ng / mL higher PSA after adjustment for cohort and age. There was no interaction between PSA and grade, suggesting that the longer lead time of high-grade tumors is not simply related to age. PSA was significantly associated with grade after adjusting for lead time, cohort, and age (OR=1.09; 95% CI 1.00, 1.19; p=0.048) suggesting that both grade and PSA increase over time. A limitation is our assumption that men with an elevated PSA subsequently diagnosed with cancer would have biopsy-detectable cancer at the time of PSA elevation. Conclusions Our data support grade-progression, that were we to follow a prostate over time we would see a transition from benign to GGG 1, then to GGG 2 or higher disease. We cannot know whether this effect is because a GGG 1 becomes GGG 2, or a new focus of GGG 2 arises in a prostate already containing a GGG 1 tumor. Funding This work was supported by David H. Koch provided through the Prostate Cancer Foundation; the Sidney Kimmel Center for Prostate and Urologic Cancers; SPORE grant from the National Cancer Institute to Dr. H. Scher (grant number P50-CA92629); and a National Institutes of Health/National Cancer Institute Cancer Center Support Grant to MSKCC (grant number P30-CA008748). This work also received funding support in part from the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre Program in UK, the Swedish Cancer Society (project nr 14-0722), the Swedish Research Council (VR-MH project nr 2016-02974), and the Prostate Cancer Foundation Young Investigator Award 2012.
Authors
Melissa Assel
Anders Dahlin David Ulmert Anders Bergh Pär Stattin Hans Lilja Andrew Vickers |
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MP38-09 |
Prostate-specific antigen (PSA) levels in men aged 60 to 70 and development of lethal prostate cancer over 30 years: Implications for Risk-Stratified Screening |
Prostate Cancer: Detection & Screening IV | 17BOS |
Abstract: MP38-09 Sources of Funding: The Physicians Health Study was supported by the National Institutes of Health Grants No. CA-097193, CA-34944, CA-40360, HL-26490, and HL-34595. This work was also supported by the Dana-Farber Cancer Institute Mazzone Awards Program (M.A.P.), and the Prostate Cancer Foundation Young Investigator Award (L.A.M.); M.A.P. is an American Urological Association Urology Care Foundation Scholar._x000D_ Additional funding support provided from the National Cancer Institute Grants No. R33 CA127768-02, P50-CA92629, and P50-_x000D_ CA090381; Swedish Cancer Society Grant No. 3455; Fundaçion Federico; the Sidney Kimmel Center for Prostate and Urologic Cancers; David H. Koch through the Prostate Cancer Foundation; and a Cancer Center Support Grant from the National Cancer Institute made to Memorial Sloan Kettering Cancer Center Grant No. P30-CA008748 (S.C., and A.V.; PI: Craig B. Thompson). Introduction We sought to determine if a pre-diagnostic PSA level in men aged 60 to 70 predicts future risk of lethal prostate cancer and could be used to risk-stratify screening, potentially allowing men at low risk to be exempt from further screening. Methods We conducted a nested case-control study among men aged 60 (57.5-62.5), 65 (62.5-67.5) and 70 (67.5-72.5) years who gave blood before enrollment in the Physicians Health Study of primarily white, U.S. male physicians initiated in 1982. Baseline PSA levels were available for 109 lethal prostate cancer cases that were matched to 327 age-matched controls or non-lethal prostate cancer cases. Lethal was defined as metastatic (to bones or distant organs) or fatal prostate cancer. Conditional logistic regression was used to estimate odds ratios (ORs) with 95% confidence intervals (CIs), of the association between PSA and risk of lethal disease. Results Median PSA (ng/mL) among controls was 1.10 for men aged 60, 1.51 for men aged 65, and 1.52 for men aged 70. The 90th percentile of PSA levels among controls was 3.97 for men aged 60, 5.38 for men aged 65, and 5.17 for men aged 70. Median time from blood draw to lethal event among lethal cases was 15.3 years. Risk of lethal prostate cancer was strongly associated with baseline PSA levels: ORs (95% CIs) comparing PSA in the >90th percentile vs. ≤median were 7.5 (2.9, 19.1) for men aged 60, 19.3 (4.5, 82.0) for men aged 65, and 11.4 (3.0, 44.2) for men aged 70. 87% of lethal cases were in men with baseline PSA above the median. Conclusions Pre-diagnostic PSA level at age 60 to 70 strongly predicts future risk of lethal prostate cancer in a US cohort subject to opportunistic screening. This supports risk-stratified screening with consideration of exempting men with PSA below the median at age 60 onwards from further screening. Funding The Physicians Health Study was supported by the National Institutes of Health Grants No. CA-097193, CA-34944, CA-40360, HL-26490, and HL-34595. This work was also supported by the Dana-Farber Cancer Institute Mazzone Awards Program (M.A.P.), and the Prostate Cancer Foundation Young Investigator Award (L.A.M.); M.A.P. is an American Urological Association Urology Care Foundation Scholar._x000D_ Additional funding support provided from the National Cancer Institute Grants No. R33 CA127768-02, P50-CA92629, and P50-_x000D_ CA090381; Swedish Cancer Society Grant No. 3455; Fundaçion Federico; the Sidney Kimmel Center for Prostate and Urologic Cancers; David H. Koch through the Prostate Cancer Foundation; and a Cancer Center Support Grant from the National Cancer Institute made to Memorial Sloan Kettering Cancer Center Grant No. P30-CA008748 (S.C., and A.V.; PI: Craig B. Thompson).
Authors
Mark Preston
Mary Kathryn Downer Travis Gerke Sigrid Carlsson Howard Sesso Adam Kibel Quoc-Dien Trinh Hans Lilja Andrew Vickers Kathryn Wilson Lorelei Mucci |
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MP38-10 |
Complications following extended transperineal template mapping MRI/TRUS fusion biopsy of the prostate – initial experience from 421 procedures |
Prostate Cancer: Detection & Screening IV | 17BOS |
Abstract: MP38-10 Sources of Funding: none Introduction Transperineal template mapping MRI/TRUS fusion biopsy (TMBx) offers superior accuracy and allows optimal risk stratification for patients detected with prostate cancer. However, limited data is available regarding complications and morbidity following TMBx. The goal of this retrospective analysis was to obtain the complication rate follwing TMBx in a large series. Methods The records of 402 consecutive patients undergoing TMBx between June 2013 and August 2016 were reviewed. All patients received a single shot antibiotic prophylaxis with 80 mg gentamicin. All underwent transperineal fusion targeted biopsy of MRI-suspicious lesions (median 3 cores per lesion) and transperineal extended template biopsy (median 41 cores). The complications were reported according to the modified Clavien-Dindo classification system. Results Of the 421 biopsies, 371 (88.1%) had an uneventful biopsy without complications. Twenty patients (4.8%) showed post-biopsy complications requiring an outpatient consultation or hospital admission within 30 days of the procedure. According to the Clavien-Dindo classification there were 25 patients (5.9%) with grade I complications, 24 (5.7%) with grade II and one patient (0.2%) with a grade IIIb complication (TUR-P within 30 days as a patients desire). Eleven patients (2.6%) developed an urosepsis (fever >38.5°C), 38 (9%) had an urinary retention requiring urethral catheterization and two (0.5%) had an acute bacterial prostatitis. Of the eleven patients with urosepsis, seven carried Escherichia coli, the other four cases were ESBL, Enterococcus faecalis, Serratia marcenscens and Enterobacter cloacae complex with Staphyloccocus aureus. Those patients had to be hospitalised for 2.5 days on average (range 1-7 days). 37 patients (8.8%) mentioned haematospermia while 93 (22.1%) noticed haematuria within 30 days of the procedure. A binomial logistic regression showed that an increased prostate volume was associated with an increased likelihood of exhibiting urinary retention (p = 0.006). Conclusions In this analysis we demonstrated a low morbidity following TMBx. The procedure is very well tolerated and safe for patients. Especially the rate of major infections and urosepsis are low. Haematuria and haematospermia were very common but self-limiting in most of the cases. However, urinary retention is a major complication with 9% of all cases and is associated with increased prostate volume. Therefore we now leave the catheter for two days in patients with larger prostate glands. Funding none
Authors
Oliver Gross
Basil Kaufmann Ashkan Mortezavi Olivia Maerzendorfer Marian Wettstein Tullio Sulser Daniel Eberli |
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MP38-11 |
Prostate Cancer Volume on 3-Tesla Multiparametric Different Sequences: Correlated and Verified on Whole Mount Histopathology Sectioned with 3D-Printed Custom-Designed Molds |
Prostate Cancer: Detection & Screening IV | 17BOS |
Abstract: MP38-11 Sources of Funding: This work was supported by funds from the Integrated Diagnostics Program, Department of Radiological Sciences & Pathology, David Geffen School of Medicine at UCLA Introduction To evaluate Prostate Cancer (CaP) tumor volume (TV) of regions of interest (ROI) on prostate multiparametric magnetic resonance imaging (MP-MRI) (TVm) with concordant foci TV on whole mount histopathology (WMHP) (TVh), stratified by Gleason score (GS) and MP-MRI Prostate Imaging Reporting and Data system version 2 (PI-RADSv2) assessment. Methods A HIPAA-compliant, IRB-approved study of 105 men who underwent 3Tesla (3T) prostate MP-MRI before robotic radical prostatectomy was performed. Suspicious regions of interest (ROIs) were contoured on MRI and PI-RADSv2 was assigned per suspicious ROI. TVT2, TVDCE and TVDWI was calculated by delineation of suspicious tumor on T2-weighted, Dynamic Contrast Enhancement and Diffusion Weighted Imaging pulse sequences. A 3D patient-specific mold was printed to precisely fit the excised prostate based on MRI prostate segmentation. A pathologist contoured each tumor on all WMHP slides and graded the tumor by GS system. Custom software automatically imported the annotated contoured WMHP slides, reconstructed the tumors in 3D, and calculated the TVh. Spearman correlation coefficient(r) was calculated to determine strength of association between volumes of concordant lesion foci on each MRI and WMHP. Spearman correlation and Wilcoxon rank sum test were used. P-values<0.05 were considered significant. Results In 105 patients, 132 CaP foci (including 103 index tumors) on WMHP matched with MRI ROIs concordantly. Of 132 CaP foci GS was ≤6(3+3) in 24 (18.2%) and ≥7(3+4) in 108 (82.8%). PI-RADS was normal or mild suspicious(1-2) in 11(8.3%), 3 in 37 (28%), 4 in 48 (34.4%), and 5 in 36(27.3%). The median (IQR) of TVh, TVT2, TVDCE and TVDWI were 1.1cc (0.5-3.1), 1.3cc (0.8-2.7), 1.6cc (1-2.8) and 1.4cc (0.6-2.7) respectively. The r between TVh and TVT2, TVDCE and TVDWI was 0.53, 0.42 and 0.42 in all tumors,and 0.52, 0.47 and 0.53 in GS≥7(3+4) tumors respectively . The r between TVh and TVT2 was 0.33, 0.55 and 0.61 in PI-RADS 3, 4 and 5 lesions retrospectively. The r between TVh and TVDCE was 0.38,0.28 and 0.67 in PI-RADS 3,4 and 5 retrospectively. The r between TVh and TVDWI was 0.26, 0.40 and 0.61 in PI-RADS 3, 4 and 5 retrospectively (p<0.001). Conclusions Tumor volume on pathology (TVh) correlates with corresponding tumor volumes on 3T MP-MRI pulse sequences (TVT2, TVDWI and TVDCE) and it is stronger in high grade tumors and in tumors with higher PI-RADSv2. However, tumor volume on T2 (TVT2) consistently demonstrates the strongest correlation with pathology tumor volume (TVh). Funding This work was supported by funds from the Integrated Diagnostics Program, Department of Radiological Sciences & Pathology, David Geffen School of Medicine at UCLA
Authors
Pooria Khoshnoodi
Sepideh Shakeri Alan Priester Nazanin Asvadi Ashkan Shademan Leila Mostafavi Ely Felker Daniel Margolis Anthony Sisk Robert Reiter Steven Raman |
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MP38-12 |
Propensity Score Analysis of Pathological Outcome at Radical Prostatectomy for Magnetic Resonance Imaging-Transrectal Ultrasound Fusion Prostate Biopsy versus Untargeted Extended Transrectal Ultrasound Guided Prostate Biopsy |
Prostate Cancer: Detection & Screening IV | 17BOS |
Abstract: MP38-12 Sources of Funding: none Introduction Magnetic resonance imaging-transrectal ultrasound (MRI-TRUS) fusion-guided prostate biopsy has been shown to increase the detection of clinically significant prostate cancer (PCa) by targeting specific lesions at biopsy. Our objective was to evaluate the accuracy of MRI-TRUS fusion biopsy to determine final pathology at radical prostatectomy (RP) as compared to untargeted extended template TRUS-guided prostate biopsy. Methods From a single institution database, 2,201 patients were identified who underwent both prostate biopsy and RP between 2006 and 2016. Propensity score matching was performed with the nearest neighbor method using R-programming version 3.3.1 and a 4:1 match ratio. A total of 101 men were identified who underwent MRI-TRUS plus standard template biopsies were subsequently matched to 404 men who underwent untargeted extended template TRUS biopsy. Matched covariates included age at diagnosis, initial prostate specific antigen (PSA), race, clinical stage, total number of cores retrieved at time of biopsy, and history of prior TRUS biopsy. Continuous variables were compared using Wilcoxon rank-sum tests and categorical variables were assessed with χ2 test. The concordance of Gleason score from biopsy to RP was assessed. Results After propensity score matching, median age was 64 years (IQR 59.5-68.5), median PSA was 5.4 ng/mL (IQR 4.0-8.1), median prostate size was 48 grams (IQR 38.5-60), and median number of cores retrieved at time of biopsy was 15 (IQR 12-20). Of patients who received MRI-TRUS plus standard template biopsy, 67 of 99 (67.7%) showed concordant Gleason grading between biopsy and RP pathology, whereas 204 of 397 (51.4%) of extended template TRUS biopsy patients were concordant (p<0.01). Fewer MRI-TRUS plus standard template biopsy patients were either upgraded (26.3% versus 32.2%) or downgraded (6.1% versus 15.4%) from biopsy to RP (p<0.01). Conclusions Of men undergoing TRUS biopsy for the diagnosis of PCa, MRI-TRUS fusion plus standard template techniques have a higher concordance with final pathology at RP. Additionally, MRI-TRUS techniques demonstrated better accuracy with lower rates of upgrading and downgrading prostatectomy when compared to untargeted extended template TRUS biopsy independent of total number of cores taken. Funding none
Authors
Hans Arora
Ahmed Elshafei Yaw Nyame Daniel Sun Helen Liang Nitin Yerram Daniel Greene Dominic Grimberg Karishma Gupta Shree Agrawal Sudhir Isharwal Paurush Babbar Andrew Sun Khaled Fareed Michael Gong Ryan Berglund Eric Klein Andrew Stephenson Andrei Purysko J. Stephen Jones |
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MP38-13 |
Outcomes of MRI-US Fusion-Targeted Biopsy in Men with No Previous Biopsy: Opportunity to Reduce Biopsy Utilization and Secondary Over-Detection |
Prostate Cancer: Detection & Screening IV | 17BOS |
Abstract: MP38-13 Sources of Funding: Joseph and Diane Steinberg Charitable Trust Introduction The use of pre-biopsy MRI for risk stratification of men with no previous history of prostate biopsy remains controversial due to concerns of missed high grade cancers among men with low suspicion MRI. We evaluated the relationship of pre-biopsy MRI and MRI-ultrasound fusion-targeted prostate biopsy (MRF-TB) outcomes among men with no previous history of prostate biopsy. Methods Between 6/2012 and 9/2016, 1584 consecutive men presenting to our institution for prostate biopsy underwent pre-biopsy MRI followed by MRF-TB and systematic biopsy (SB), and were prospectively enrolled in an IRB-approved database. We evaluated the outcomes of 800/1584 men who had no previous biopsy. 109 men were excluded due to outside MRI, 1.5T MRI, or hip implants. 35 men were excluded as they did not undergo concomitant SB with MRF-TB. Men with no MRI lesion (MRI score of 1) underwent only SB. Results Among 656/800 men who met inclusion criteria (mean age 63±11 years; mean PSA 6.1±3.4 ng/mL), prostate cancer (PCa) was detected in 380 (58%) cases. Cancer detection rates (CDR) for SB and MRF-TB were 54% and 43%, respectively (p < 0.01). MRF-TB detected significantly less Gleason (GS) 6 PCa compared to SB [86/203 (42%) vs 176/203 (87%), p < 0.01] and more GS 3+4 cancers than SB [109/140 (78%) vs 87/140 (62%), p = 0.02]. There was no significant difference in detection of dominant GS pattern 4 PCa (Table 1)._x000D_ _x000D_ When CDR is stratified by MRI score (Table 2), detection of GS 3+4 and GS ≥4+3 in men with an MRI score of 1 or 2 is less than 5%. Deferral of prostate biopsy in 229 men with an MRI score of 1 or 2 would have missed 3% (7) of GS ≥4+3, 5% (11) of GS 3+4, and 28% (63) of GS 6 PCa, of which 75% (47/63) would have been clinically insignificant by Epstein criteria. _x000D_ Conclusions In men presenting for primary prostate biopsy, MRF-TB detects more GS 3+4 PCa than SB and reduces over-detection of GS 6 by 49%. Deferral of primary prostate biopsy in men with MRI scores of 1 or 2 would miss very few clinically significant PCa while avoiding over-detection of clinically insignificant disease in 21% of these men. Funding Joseph and Diane Steinberg Charitable Trust
Authors
Xiaosong Meng
Andrew Rosenkrantz Fang-Ming Deng Richard Huang James Wysock Marc Bjurlin William C. Huang Herbert Lepor Samir S. Taneja |
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MP38-14 |
Using multiparametric magnetic resonance imaging to predict the correct location of prostate cancer before biopsy – An Australian multicentre study |
Prostate Cancer: Detection & Screening IV | 17BOS |
Abstract: MP38-14 Sources of Funding: This work was carried out with support from the St Vincent&[prime]s Hospital (Melbourne) Research Endowment Fund. Introduction Multiparametric MRI (mpMRI), with enhanced visualization of tissue within the prostate, has been shown to improve the detection of prostate cancer with biopsy. Our study aims to determine the accuracy of mpMRI by precisely mapping the location and description of mpMRI lesions with the grade and location of positive biopsy cores. Methods Retrospective analysis across two Australian tertiary referral centres between 2012 and 2016 was performed. Patients underwent 3-Tesla mpMRI followed by prostate biopsy ≤3 months later, by cognitive or software fusion, with either transrectal or transperineal ultrasound guided techniques. _x000D_ Lesions on mpMRI were correlated to the location of positive biopsy cores after targeted biopsy, with a positive match being defined as both in the same or neighbouring location as per standard extended biopsy protocol. A suspicious mpMRI lesion was defined as having a Prostate Imaging Reporting and Data System (PI-RADS) score ≥4, whereas clinically significant cancer was defined as cancer with Gleason grade ≥3+4. Descriptive statistics and two-way t-tests were performed with STATA® 14. _x000D_ Results Of 355 patients, 49.3% (175/355) had a suspicious mpMRI lesion and 47.9% (170/355) of the cohort had significant cancer on biopsy overall. There was moderate sensitivity (67.1%), negative predictive value (71.3%), specificity (69.7%) and positive predictive value (60.9%) for the mpMRI detection of significant cancer in the same or neighbouring location at biopsy. Of the 56 patients with significant cancer but non-suspicious mpMRI (PI-RADS <4), 66.1% (37/56) were Gleason 3+4 and 32.1% (18/56) were matched to a PI-RADS 3 lesion._x000D_ For Gleason grade ≥4+4 cancers, 90.4% (47/52) had a corresponding mpMRI lesion with PI-RADS score ≥4. Examining all patients with significant cancer at biopsy matching to a suspicious mpMRI lesion, 84.2% (96/114) were the highest Gleason grade found on biopsy._x000D_ _x000D_ The mean size of suspicious mpMRI lesions with significant cancer on biopsy was significantly larger than those with Gleason 3+3 cancer or no cancer at biopsy (16.7 mm vs.13.9 mm respectively; p=0.03). _x000D_ Conclusions When precisely mapping the location of mpMRI lesions to positive prostate biopsy cores for significant cancer, a moderate sensitivity and positive predictive value was found suggesting that concomitant systematic biopsy cannot be abandoned. PI-RADS ≥4 lesions had excellent prediction of high-grade cancers at biopsy. Larger mpMRI lesions may yield more clinically significant cancers on biopsy. Funding This work was carried out with support from the St Vincent&[prime]s Hospital (Melbourne) Research Endowment Fund.
Authors
Dominic Gavin
Matthew Krelle Tom Sutherland Daphne Loh Jonathan Kam Yuigi Yuminaga Raymond Kim Kushlan Aluwihare Sean Khoury Finlay Macneil Rupert Ouyang Stephen Ruthven Mark Louie-Johnsun Lih-Ming Wong |
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MP38-15 |
Detection and Characterization of Disseminated Tumor Cells from the Bone Marrow in Localized Prostate Cancer Patients undergoing Radical Prostatectomy |
Prostate Cancer: Detection & Screening IV | 17BOS |
Abstract: MP38-15 Sources of Funding: This work is supported by NCI grant nos. U54CA143803, CA163124, CA093900, CA143055 to K.J.P as well as the Prostate Cancer Foundation, the Patrick C. Walsh Fund, and a gift from the Stutt family. E.E.vdT is supported by the Cure for Cancer Foundation. H.J.C. is supported by the Urology Care Foundation's Resident Research Award. Introduction Disseminated tumor cells (DTC) are prostate cancer cells that escape the primary lesion and enter the bone marrow (BM) niche, representing a first step towards conventionally detectable metastasis. It is unknown how frequently this occurs in clinically localized prostate cancer. We detected and characterized these cells by measuring gene expression of prostate-specific markers from BM samples taken at the time of radical prostatectomy (RP)._x000D_ Methods 5 mL of BM were harvested at RP for 36 clinically localized patients. A whole cell extract was assayed with the AdnaTest ProstateCancer Select kit (Qiagen). Reverse transcription (SensiScript RT kit, Qiagen) and real-time qPCR quantified expression of RPL13A (control, ribosomal protein), EPCAM (epithelial), NKX3.1 and HOXB13 (prostate-specific), and AR-FL (androgen receptor full length). Prostate markers known to be less sensitive or specific were also assayed in a subset of patients (TMPRSS2-ERG, AR-V7, PSA, and PSMA). DTC detection was defined as prostate-specific marker expression in the BM. Quality control was performed with Sanger sequencing. The associations of PSA and Gleason score (GS) with DTC detection were evaluated with the Mann-Whitney U Test and Fisher&[prime]s exact test respectively._x000D_ Results DTCs were detected via NKX3.1 expression in 30/36 patients (83%). HOXB13, AR-V7, and TMPRSS2-ERG were not detected in any sample. 100% of patients were EPCAM+, consistent with the known non-specific expression of EPCAM in the BM. AR-FL was also non-specifically expressed in 67% of NKX3.1+ and 83% of NKX3.1- patients. There was a trend toward DTC detection associating with higher PSA and GS, with 100% of NKX3.1- patients having low-risk PSA<10, and only one with primary GS >3 (17%, 1/6). Conversely 47% (14/30) of NKX3.1+ patients had primary GS≥4, and 27% (8/30) had PSA>10. Yet, this was not statistically significant (GS p=0.367, PSA p=0.302), and DTCs were detected across all Gleason scores._x000D_ Conclusions DTCs were detected based on NKX3.1 positivity in a large portion of clinically localized prostate cancer patients at all Gleason scores. Ongoing investigation with healthy patient BM will clarify whether NKX3.1 is truly prostate-specific, and if its expression associates with clinico-pathologic outcomes._x000D_ Funding This work is supported by NCI grant nos. U54CA143803, CA163124, CA093900, CA143055 to K.J.P as well as the Prostate Cancer Foundation, the Patrick C. Walsh Fund, and a gift from the Stutt family. E.E.vdT is supported by the Cure for Cancer Foundation. H.J.C. is supported by the Urology Care Foundation's Resident Research Award.
Authors
Stephanie Glavaris
Emma van der Toom Michael Gorin James Verdone Changxue Lu Jun Luo Kenneth Pienta Heather Chalfin |
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MP38-16 |
Combining 68Ga-PSMA-PET and multiparametric MRI: Enhancing the ability to detect intraprostatic tumour lesions and patients eligible for focal treatment ? |
Prostate Cancer: Detection & Screening IV | 17BOS |
Abstract: MP38-16 Sources of Funding: none Introduction Functional 68Ga-labelled PSMA or morphologic mpMRI-imaging detects intraprostatic prostate cancer (PCa) foci. To assess the diagnostic performance of 68Ga-PSMA-PET-CT or mpMRI alone and their combination for characterising side specific intraprostatic PCa cancer lesions, when performed in a sequential setting. Methods Overall, 30 patients with biopsy proven prostate cancer received a 68Ga-PSMA-PET-CT and mpMRI imaging prior radical prostatectomy (RP). Preoperative intraprostatic findings of both different modalities and their combination were compared with histological work up after RP. Lesions were classified positive with mpMRI (Likert scale >3) and PET/CT foci with elevated SUVmax (focus vs. background). Results Median PSA was 9.0 ng/ml (IQR 4.2-35.7). MpMRI and PET/CT identified (IQR) 2 (1-2) tumorfoci. Sidespecific sensitivity of mpMRI, PET/CT and the combined imaging approach was 83.3% (95%CI 70.7-92.1%), 79.6% (95%CI 66.5-89.4%) and 94.4% (95%CI 54.5-98.8%). Overall sidespecific specifity was 66.7% (95%CI 22.3-95.7%). Sensitivity per patient was 63.3% (95%CI 46.7-80% mpMRI), 56.7% (95%CI 40.0-73.3% PET/CT) and 83.3% (95%CI 70.0-96.7%) for the combined approach. Conclusions Combining functional 68Ga-PSMA-PET and morphologic mpMRI imaging increases the ability to detect intraprostatic tumour lesions without affecting the specifity. Our data demonstrate, that the sequential approach provides a tailored use of both imaging modalities, which reaches similar diagnostic performances as reported in series using whole-in-one MRI-PSMA/PET scanners. Further studies are necessary to validate these findings in patients harbouring low risk disease only. Funding none
Authors
Sami-Ramzi Leyh-Bannurah
Antonia Steves Dirk Beyersdorff Clemens Rosenbaum Klutmann Susanne Janos Mester Georg Salomon Markus Graefen Lars Budäus |
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MP38-17 |
Clinicopathologic Characteristics of Patients with Very Low-Risk (PI-RADS 1 or 2) Lesions by Multiparametric Prostate Magnetic Resonance Imaging |
Prostate Cancer: Detection & Screening IV | 17BOS |
Abstract: MP38-17 Sources of Funding: None Introduction Multiparametric prostate magnetic resonance imaging (mpMRI) utilizing the PI-RADS classification system attempts to identify clinically-significant [Gleason score (GS) 7 or higher] prostate cancer (PCa), with PI-RADS 1 or 2 typically corresponding to very low risk of clinically-significant PCa. In this study, we analyzed the clinicopathologic characteristics of patients undergoing prostate core biopsy (PBx) with PI-RADS 1 or 2 lesions. Methods All patients at a single large academic institution who had at most PI-RAD 1 or 2 lesions on mpMRI between 1/1/15 and 6/30/16 and underwent pre- or post-MRI PBx were retrospectively identified. All cases of clinically-significant PCa were re-reviewed by study pathologists to confirm pathologic findings; clinicopathologic data from all other cases was obtained from pathology reports and electronic medical records. Results 276 patients with PI-RADS 1 or 2 lesions were identified, of which 98 (35.5%) had either pre- (60) or post-MRI (38) in-house PBx. Six (6.1%) patients showed GS7 PCa (3 pre- and 3 post-MRI), including 2 with GS4+3=7 tumors. For the remaining patients, the most recent PBx findings included: GS6 PCa (22 pre- and 13 post-MRI); atypical glands (3 pre- and 2 post-MRI); high-grade prostatic intraepithelial neoplasia (5 pre- and 4 post-MRI); or, benign (27 pre- and 16 post-MRI). For patients with GS7 PCa, the median number of involved cores was 1 (range = 1-3), the median number of total cores was 20 (range = 12-30), the median % involvement of a single core was 12.5 (range = 5-25), and the median % Gleason pattern 4 was 30 (range = 5-90); types of Gleason pattern 4 included: poorly-formed glands only (4), cribriform glands only (1), or poorly-formed and cribriform glands (1). One GS7 tumor occurred in the post-radiation (XRT) setting, and one showed aberrant p63 expression; follow-up for patients with GS7 PCa included primary XRT (1), salvage XRT (1), and active surveillance (AS; 4). Nearly all patients (>90%) with GS6 PCa opted for AS; one patient underwent radical prostatectomy (pT2a GS6 PCa), and one patient was lost to follow-up. Conclusions The majority (58.2%) of patients with PI-RADS 1 or 2 lesions by mpMRI do not have detectable PCa on core biopsy, however, a small subset (6.1%) harbor GS7 PCa. Although long-term follow-up data are needed, PCa patients with PI-RADS 1 or 2 lesions by mpMRI appear to represent a very low-risk cohort that may be amenable to AS in the majority of cases. Funding None
Authors
Aaron Udager
Joel Friedman Nicole Curci John Wei Chandy Ellimoottil Rohit Mehra Scott Tomlins Jeffrey Montgomery Matthew Davenport Angela Wu Lakshmi Kunju |
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MP38-18 |
Clinicopathologic Characteristics of Patients Undergoing Prostate Core Biopsy with High-Risk (PI-RADS 5) Lesions by Multiparametric Prostate Magnetic Resonance Imaging. |
Prostate Cancer: Detection & Screening IV | 17BOS |
Abstract: MP38-18 Sources of Funding: None Introduction Multiparametric Prostate Magnetic Resonance Imaging (mpMRI) utilizes a PI-RADS classification system to identify clinically significant (Gleason score (GS) 7 or higher) prostate adenocarcinoma (PCa) with PI-RADS 5 lesions typically corresponding to a high-risk of clinically significant PCa. Methods All patients who underwent mpMRI between 1/1/2015 and 6/30/2016 at a large academic institution were identified. Patients with one or more PI-RADS 5 lesions who underwent an ultrasound-MRI fusion PBx were retrospectively reviewed to assess for presence or absence of PCa, location (targeted vs. 12-core/non-targeted cores), GS, and percentage pattern 4 in GS 7 tumors. Results 138 patients with PI-RADS 5 lesions {1 lesion (107), 2 lesions (27), 3 lesions (4)} were identified, of which 76 (55%) underwent an in-house MRI fusion PBx. In the targeted cores, 7 (9%) patients had no PCa and 69 (91%) patients showed PCa. In 7 patients without PCa (total 12 PI-RADS 5 lesions), the targeted cores showed extensive simple atrophy (2), florid adenosis (1), central zone histology (2), atypical small acinar proliferation (1), focal high-grade prostatic intraepithelial neoplasia (1), granulomatous inflammation (1), carcinoid (1), focal simple atrophy (2) and focal adenosis (1). Clinically significant PCa was noted in 79% (60/76) cases, {GS 3+4 (35), GS 4+3 (16) and GS 8-10 (9)}. In 7 (9%) patients with GS 7 or higher PCa, the highest GS was found in the non-targeted cores. The median % Gleason pattern 4 in GS 7 tumors was 30 (inter-quartile range = 10-60). Of the remaining 62 (45%) patients who did not receive an MRI fusion PBx, 3 had saturation PBx and 27 had a radical prostatectomy (all show GS 7 or higher PCa); 9 received radiation and/or hormone therapy. Conclusions The vast majority of patients (79%) with PI-RADS 5 lesions showed GS 7 or higher PCa on targeted cores; however, a small subset (9%) showed no evidence of malignancy. The benign mimickers of PI-RADS 5 lesions include florid adenosis (1), granulomatous inflammation (1), carcinoid (1), central zone acini (2) and simple atrophy (2). PI-RADS 5 lesions can be biopsied for confirmation of clinically significant disease in the vast majority of cases or used to guide the patient's treatment towards more definitive therapies. Funding None
Authors
Joel Friedman
Aaron Udager Nicole Curci Chandy Ellimoottil Rohit Mehra Scott Tomlins Jeffrey Montgomery John Wei Matthew Davenport Angela Wu Lakshmi Kunju |
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MP38-19 |
Multiparametric MRI/Ultrasound fusion biopsy improves but does not replace standard template biopsy for the detection of prostate cancer |
Prostate Cancer: Detection & Screening IV | 17BOS |
Abstract: MP38-19 Sources of Funding: None Introduction There exists a growing debate as to whether mp-MRI targeted biopsy alone without standard template is sufficient for evaluation of patients with suspicion of prostate cancer. We investigate and describe our experience with fusion biopsy. Methods We retrospectively reviewed medical charts of patients undergoing fusion transrectal US-guided biopsy from July 2014 through February 2016. Patients eligible for fusion biopsy had identifiable lesions on mp-MRI compatible to the fusion biopsy system. Each lesion was graded according to the Prostate Imaging Reporting and Data System version 2 (PIRADSv2) by a radiologist. The fusion biopsy procedure included a minimum of 2 core biopsies for each target lesion and a standard 12 core template biopsy. Clinically significant disease was defined as Gleason Score 7 or higher adenocarcinoma of the prostate. Results A total of 255 patients with a mp-MRI-identified lesion underwent fusion and standard template biopsy. Indications included elevated PSA without a prior biopsy (11.4%), rising PSA with a prior negative biopsy (52.4%), active surveillance for prostate cancer (33.3%) and isolated abnormal digital rectal exam (2.7%). Pathologic results from the fusion-targeted biopsy were compared to those from the concomitantly performed standard template biopsies (Table 1). Of patients with PIRADSv2 4 or 5 lesions (n=145), 40.0% had no cancer, 25.5% had Gleason 6, 25.5% had Gleason 7, and 9.0%, had Gleason 8-10 on final histopathology. Fusion Biopsy of PIRADSv2 3 lesions (n=66) revealed no cancer in 65.2%, Gleason 6 in 15.2%, Gleason 7 in 19.7% and Gleason 8-10,in 0% of patients. Of 83 patients with clinically significant cancer, 26 (31.3%) would have been missed on standard biopsy and 12 (14.5%) would have been missed using fusion biopsy alone. Concordance between both biopsy modalities was 63.1%. Conclusions mp-MRI targeted fusion biopsy improves the detection of clinically significant prostate cancer in select patients. However, our results demonstrate that a significant proportion of these cancers will not be detected by a targeted biopsy alone. Therefore, standard template biopsies should remain an integral component of any fusion biopsy program. Funding None
Authors
Nawar Hanna
Matthew F. Wszolek Francisco J. Gelpi-Hammerschmidt Keyan Salari Mukesh Harisinghani Douglas M. Dahl Micheal L. Blute Adam S. Feldman |
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MP38-20 |
Metabolic difference identified by proton MR-spectroscopy is associated with intra-tumor heterogeneity in prostate cancer |
Prostate Cancer: Detection & Screening IV | 17BOS |
Abstract: MP38-20 Sources of Funding: none Introduction One of the most important features of prostate cancer (PC) is the diverse biological activity attributed to heterogeneity within individual cancers. We hypothesize that metabolic difference identified by proton MR-spectroscopy (MRS) might be related to diverse biological potential resulting from heterogeneous cancer cell populations and well reflect the biological aggressiveness of PC. Methods In this study, 113 cases that underwent RALP were included. All patients performed 1.5T MRS examination prior to RALP. On MRS, each peak of the chemical shift between 0.5 and 4.2 ppm was determined by the computer-assisted objective measurement of MRS, and evaluated by cluster analysis or principal component analysis for measuring heterogeneity within individual cancers. The 1st principal component was considered as an index related to heterogeneity within individual cancers. The mean value, standard deviation (SD), coefficient of variation (CV) of the target shifts such as choline (3.2 ppm), citrate (2.6 ppm), N-acetyl-L-aspartate (NAA) (2.0 ppm) and alanine (1.48 ppm) were also calculated and compared with pathological findings as well as biochemical recurrence (BCR). Results Representative heatmaps of 2 different PC cases were shown in Figure. In this study, a correlation between the mean value and SD was positive in choline and NAA, (p<0.0001, both), while it was weak in alanine (p=0.0479). Based on this, the SD was used as an index of variation for choline and NAA, while the CV was used for alanine. The measured mean heterogeneity of our series predicted by the 1st principal component was 21.4%, which showed a significant correlation with SD for choline and NAA (p=0.0011and p<0.0001, respectively). On the other hand, the 1st principal component did not correlate with the CV for alanine, PSA or Gleason score. Although 8 out of 113 patients progressed into BCR, multivariate analysis showed that the SD for choline, followed by PSA and the SD for NAA, was an independent predictor of BCR (p=0.0354, p=0.0624 and p=0.0952, respectively). Conclusions To our knowledge, this is the first report of comprehensive analysis of MRS pattern to validate _x000D_ intra-tumor heterogeneity in PC, which can surely develop diagnostic and therapeutic strategy of PC._x000D_ Funding none
Authors
Hiroaki Shiina
Yusuke Nakanishi Naoko Arichi Masahiro Sumura Hirofumi Kishi Keiichi Onoda Hiroaki Yasumoto |
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MP39-01 |
Characterizing Recurrent and Lethal Small Renal Masses in Clear Cell Renal Cell Carcinoma Using Somatic Mutations |
Kidney Cancer: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP39-01 Sources of Funding: Funded in part by the Sidney Kimmel Center for Prostate and Urologic Cancers and the National Cancer Institute Training Grant T32 CA082088 (BM MG)._x000D_ Clinical and Translational Science Center at Weill Cornell Medical Center UL1TR00457 (BM) Introduction Management of small renal masses (SRMs) may include active surveillance (AS) in selected patients. Clear cell renal cell carcinoma (ccRCC) is the most common histology among these SRMs. Current AS algorithms largely rely on growth parameters of the masses measured over time. We sought to identify genomic biomarkers that could potentially refine the management of SRMs, especially in patients being evaluated for AS. Methods From four databases, we identified 205 patients who had SRMs (<4 cm) at time of surgery and had sequencing performed on their primary tumors. We included patients from our institutional prospective database (n=25), and from three publicly available cohorts, The Cancer Genome Atlas (n=110), University of Tokyo (n=38), and The International Cancer Genome Consortium (n=32). We analyzed the frequency of recurrent somatic mutations among the entire cohort. Using Chi-Square analysis, the frequency of mutations that occurred in at least 5% of patients were compared in patients who had recurrence or died from their disease during follow-up with those who did not. Kaplan?Meier survival plots were generated for these frequently mutated genes. Analysis was adjusted for multiple testing using the false discovery rate. Results Median follow-up was 43.1 months among survivors. Mutations in VHL, PBRM1, SETD2, BAP1, KDM5C, and MTOR were present in more than 5% of tumors. Of the 205 patients, 25 (12.2%) had recurrence or died of their disease. Mutations in KDM5C were found to be significantly more common in those who had recurrence or died of their disease (24% vs. 4%; adjusted p=0.02). Survival analysis showed patients with KDM5C having statistically significant inferior cancer-specific survival (adjusted p=<0.01) and a trend for inferior survival in those with SETD2 mutations (adjusted p=0.11) (Figure 1). Conclusions We identified mutations in SRMs that are associated with recurrence and lethality. The strongest association was seen with KDM5C mutations. Use of these potential genomic biomarkers may improve risk stratification of patients with SRMs and for those who may be appropriate for AS. Prospective evaluation of these markers is needed. Funding Funded in part by the Sidney Kimmel Center for Prostate and Urologic Cancers and the National Cancer Institute Training Grant T32 CA082088 (BM MG)._x000D_ Clinical and Translational Science Center at Weill Cornell Medical Center UL1TR00457 (BM)
Authors
Brandon Manley
Ed Reznik Maria Becerra Jozefina Casuscelli Daniel Tennenbaum Mazyar Ghanaat Mahyar Kashan Almedina Redzematovic Yusuke Sato Maria Arcila Martin Voss Darren Feldman Paul Russo Jonathan Coleman James Hsieh Ari Hakimi |
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MP39-02 |
Comparative Genomic Profiling of Matched Primary and Metastatic Tumors in Renal Cell Carcinoma |
Kidney Cancer: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP39-02 Sources of Funding: This study was supported in part by the Sidney Kimmel Center for Prostate and Urologic Cancers and by the National Cancer Institute T32 CA082088 (MG, BM)._x000D_ NIH Ruth L. Kirschstein National Research Service Award T32CA082088 _x000D_ German Research Foundation (DFG) Grant CA1403/1-1 Introduction Evaluation of genetic divergence among primary (P) and metastatic (M) tumors in renal cell carcinoma (RCC) is limited to small or unmatched P-M cohorts. We aim to better characterize somatic mutation (SM) disparities in a cohort of matched P-M tumors. Methods We prospectively sequenced 47 clear cell RCC (ccRCC) and 12 non-clear cell RCC (nccRCC) P-M matched pairs using Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT), a custom 410-gene (previously 341) next-generation sequencing assay. Results We detected 527 SM, with a mean (SD) of 4.5 (3.13) per sample. Overall concordance rate (shared mutations/total mutations) was 49% (46% for ccRCC vs 78% for nccRCC). Private mutations in the P tumors were present in 32 (68%) and 3 (25%) of the ccRCC and nccRCC cohorts, respectively. Private mutations in the M tumors were present in 32 (68%) of the ccRCC and in 3 (25%) of nccRCC patients (Figure 1a). Strikingly, SETD2 mutations were private to the M or the P in 70% (16/23), and PTEN alterations were private to the M in 66% (4/6). There were no shared ROS1 mutations, and 83% (5/6) of these were private to the M._x000D_ In a patient-by-patient analysis, 17% (10) of the pairs shared all SM; 15% (9) shared all of the SM in the M, with only private SM in the P; 25% (15) shared all SM in the P, with private SM only in the M; 42% (25) shared SM in the P-M; and some SM were private to either the P or the M. Only 14 pairs showed two SM in the same gene (Figure 1b); in 57% (8) the M presented a mutation in the same gene as the P but on a different location (convergent evolution), in 28% (4) the M presented both the mutation observed in the P and an additional mutation in the same gene (evolution of metastasis), and in 14% (2) the M showed a subclone of the SM observed in the P (sub-clonal seeding). _x000D_ Conclusions Our data suggest that both linear and parallel progression of metastases is observed in RCC. Although the absence of shared SM in matched pairs may be explained by tumor heterogeneity, metastasis-specific SM may represent cells of the P tumor with advantages to develop metastatic disease giving growth advantages in the studied samples. The extent to which the identified mutations contribute to the development of characteristics of metastatic spread needs to be analyzed further. Funding This study was supported in part by the Sidney Kimmel Center for Prostate and Urologic Cancers and by the National Cancer Institute T32 CA082088 (MG, BM)._x000D_ NIH Ruth L. Kirschstein National Research Service Award T32CA082088 _x000D_ German Research Foundation (DFG) Grant CA1403/1-1
Authors
Maria Becerra
Ed Reznik Daniel Tennenbaum Mahyar Kashan Mazyar Ghanaat Jozefina Casuscelli Brandon Manley Almedina Redzematovic Shawn Mendonca Maria Arcila Jonathan Coleman Paul Russo James Hsieh A. Ari Hakimi |
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MP39-03 |
Impact of Somatic Mutations on Patterns of Metastasis in Clear Cell Renal Cell Carcinoma |
Kidney Cancer: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP39-03 Sources of Funding: This study was supported in part by the Sidney Kimmel Center for Prostate and Urologic Cancers and by the National Cancer Institute T32 CA082088 (MG, BM)._x000D_ NIH Ruth L. Kirschstein National Research Service Award T32CA082088 _x000D_ German Research Foundation (DFG) Grant CA1403/1-1 Introduction Discovery and understanding of the molecular drivers of clear cell renal cell carcinoma (ccRCC) has led to the development of targeted therapies. Despite advances in these agents, metastatic disease remains largely incurable. Exploration of the biology of metastatic tumors may provide insights into patterns and routes of metastases that could lead to the identification of differences in therapeutic vulnerabilities. We aim to evaluate somatic mutations (SM) associated with organ tropism in a cohort of metastatic ccRCC patients. Methods We identified all patients with ccRCC who had a metastatic tumor sequenced at our institution from 2001 to 2016 using Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT), a next-generation sequencing assay studying a custom panel of 410 (previously 341) targetable genes commonly mutated in cancer. Fishers exact test was used to evaluate associations between recurrent SM and sites of metastasis. Results A total of 94 samples from 93 patients were analyzed. Metastatic tissue was obtained from the following sites: 26 (28%) lung, 20 (21%) bone, 13 (14%) lymph node, 7 (7%) adrenal gland, 7 brain (7%), and 21 other sites (22%). The most common alterations were VHL (85%), PBRM1 (45%), SETD2 (37%), BAP1 (20%). When analyzing samples by site, metastases to pleura presented with enrichment in BAP1 mutations (P=0.008), adrenal gland metastases had an enrichment in MED12 mutations (P=0.005), and NF2 alterations were found to be associated with bone metastases (P=0.08). _x000D_ _x000D_ Conclusions Our data suggest SM may be correlated with a site-specific pattern of metastatic spread. In our cohort, the presence of BAP1, MED12 and NF2 mutations was associated with increased pleural, adrenal gland, and bone metastasis, respectively. The extent to which the identified molecular factors contribute to the development of these characteristics needs to be analyzed in further studies. Patterns of SM in ccRCC metastasis could result in the creation of gene signatures predicting metastasis. Funding This study was supported in part by the Sidney Kimmel Center for Prostate and Urologic Cancers and by the National Cancer Institute T32 CA082088 (MG, BM)._x000D_ NIH Ruth L. Kirschstein National Research Service Award T32CA082088 _x000D_ German Research Foundation (DFG) Grant CA1403/1-1
Authors
Maria Becerra
Francisco Sanchez?Vega Ed Reznik Brandon Manley Mahyar Kashan Mazyar Ghanaat Jozefina Casuscelli Almedina Redzematovic Shawn Mendonca Maria Arcila Jonathan Coleman Paul Russo James Hsieh A. Ari Hakimi |
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MP39-04 |
Molecular and Clinical Characterization of Renal Cell Carcinoma with Unclassified Histology: NF2 Loss Predicts Worst Outcomes |
Kidney Cancer: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP39-04 Sources of Funding: Funded in part by the Sidney Kimmel Center for Prostate and Urologic Cancers and the National Cancer Institute Training Grant T32 CA082088 (BM, GM) Introduction Unclassified renal cell carcinoma (uRCC) is a rare, aggressive non-clear cell variant recognized by the World Health Organization (WHO) and which has no standard therapy. Currently, there is no consensus on further stratifying uRCC subtypes based on histological findings. We recently reported the findings of a molecular analysis of 62 high-grade primary uRCC from our institution ("discovery cohort") in which we identified recurrent somatic mutations in 29 genes (Chen et al, Nat Comm 2016). In this study we aim to report the clinical characteristics of the largest series of patients with uRCC and to validate the molecular features using an independent clinical cohort. Methods Tumor samples from primary renal (n=39) and metastatic sites (n=20) from 59 patients ("validation cohort") diagnosed with advanced uRCC by expert pathologists were analyzed using targeted next-generation sequencing for somatic alterations. Molecular and clinical characteristics of these samples were compared to the previously reported discovery cohort. Results Clinical patient and tumor characteristics of the discovery cohort (n=62) and the validation cohort (n=59) are depicted in table 1. The frequently mutated genes in the validation cohort were NF2 (27%), SETD2 (12%), FH (12%), TP53 (10%), TERT (8%), and PIK3CA (8%). NF2 and SETD2 were the two most frequently mutated genes, consistent with the discovery cohort. Systemic therapy was given to 42 patients. The median follow-up was 19.9 months. Seventeen patients died secondary to disease and one from other causes. Inactivating mutations of NF2 or other member of Hippo pathway (27%) accounted for 41% of cancer-specific death, with median survival of 21 months, representing the largest molecular subset of uRCC demonstrating poor outcomes. Conclusions URCC is an aggressive subtype of RCC, with data suggesting loss of NF2 to have the worst outcomes. Molecular analysis of our current uRCC validation cohort with more advanced disease reveals similar molecular subsets as in the discovery cohort of primary RCC. These findings open a new opportunity for precision medicine. Funding Funded in part by the Sidney Kimmel Center for Prostate and Urologic Cancers and the National Cancer Institute Training Grant T32 CA082088 (BM, GM)
Authors
Mazyar Ghanaat
Mahyar Kashan Maria Becerra Brandon Manley Jozefina Casuscelli Shawn Mendonca Almedina Redzematovic Maria Arcila Paul Russo Jonathan Coleman James Hsieh Yingbei Chen A. Ari Hakimi |
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MP39-05 |
Transposon mutagenesis drives renal cyst formation in vivo when combined with c-met hyperactivation: implications for acquired renal cystic disease |
Kidney Cancer: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP39-05 Sources of Funding: Research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number T32GM088129. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. No conflict of Interests exist for the authors. Introduction Acquired renal cystic disease (ARCD) imparts a high risk for renal cell carcinoma (8%) in patients with end-stage renal disease. The molecular mechanism of cyst formation in ARCD remains unknown, although increased hepatocyte growth factor / C-MET signaling have been implicated in cyst formation. To explore molecular mechanisms of renal cyst development relevant to ARCD, we developed a murine model system based on tissue-selectable C-Met activation and transposon-mediated mutagenesis. Methods To allow conditional activation of C-Met signaling, we engineered a tandem duplicated and mutated human C-MET coding sequence. Cre recombinase catalyzes exchange of the wild type C-Met locus with a constitutively active variant (M1248T). C-met+/M1248T mice were crossed with mice carrying the mutagenic Sleeping Beauty (Onc2) transposable element activated by a cre-dependent transposase (trpase). Localization to the renal epithelium was achieved by ggt-cre. Mice with activated C-Met and transposon mutagenesis (1: c-met+/M1248T; Onc2+/-, trpase+/-; ggt-cre+/-) were compared to mice with activated C-Met (2: c-met+/M1248T; ggt-cre+/-) or activated transposon mutagenesis (3: Onc2+/-, trpase+/-; ggt-cre+/-) alone. Mice were serial imaged by ultrasound and MRI. All kidneys were then examined grossly and histologically at necropsy after aging. Results All mice (N=5) with both C-Met hyperactivation and transposon activity (1) developed large renal cysts by 6 months. No mice with only C-Met hyper-activation (2; N=10) or transposon activity (3; N=10) developed cysts by 6 months. Histological analysis demonstrated fluid filled and hemorrhagic renal cysts without evidence for malignancy. Conclusions C-Met hyperactivation is insufficient to drive renal cyst formation in isolation. Combining M1248T with transposon mutagenesis drove renal cyst formation with 100% penetrance. By mapping transposon insertion sites in cyst-lining epithelial cells in this model, we can now begin to isolate these interacting genes, which may improve our understanding of the molecular mechanisms underlying ARCD. Funding Research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number T32GM088129. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. No conflict of Interests exist for the authors.
Authors
Jason Scovell
Juan Hernandez Adam Hollander Richard Link |
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MP39-06 |
Whole Genome Transcriptional Analysis Of Clear Cell Renal Cell Carcinoma With Venous Tumor Thrombus Reveals Intratumoral Heterogeneity And Genes Associated with Poor Outcome |
Kidney Cancer: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP39-06 Sources of Funding: None Introduction Overall, 4 to 10% of newly diagnosed renal cell carcinoma (RCC) patients have been found to have a venous tumor thrombus (VTT). Intratumoral heterogeneity may contribute to progression of the disease and metastases. Previous studies have focused on studying the heterogeneity of metastases, recurrence and tumor. There has been no study to date evaluating VTT and characterizing its transcriptional profile. We report results of the transcriptional analysis of primary tumor (PT), VTT and adjacent normal parenchyma (NP). Methods We performed Whole Transcriptome Sequencing on fresh tissue specimens from 6 patients with clear cell RCC and VTT collected at the time of radical nephrectomy with tumor thrombectomy. We evaluated transcriptional alterations between PT/NP, VTT/NP and VTT/PT. We compared our data set with The Cancer Genome Atlas (TCGA) data. For multiple testing corrections, we utilized false discovery estimation and differential expression criterion. Results 1. We surveyed 23,228 genes and identified differential expression in 1455, 1344 and 26 genes between tumor and normal parenchyma (PT/NP), tumor thrombus and normal parenchyma (VTT/NP) and tumor thrombus and primary tumor (VTT/PT) respectively. We identified altered key pathways (cytokine activity, regulation of apoptosis, cytoskeleton organization, immune response)._x000D_ 2. We compared these genes with TCGA data and identified 35 genes, which predicted poor outcome. _x000D_ 3. VTT demonstrated statistically significant differential expression of OSM (2.37 fold), INHBA (1.9 fold), CCL2 (2.3 fold), CCL20 (2.9 fold) and IL1B genes (4.5 fold) compared to primary tumor (TT/T), (Figure1). _x000D_ 4. We identified statistically significant higher expression of OSM, INHBA, CCL20, and IL1B genes in higher tumor thrombus level compared to lower tumor thrombus level._x000D_ Conclusions RNA sequencing of RCC with VTT reveals significant genomic intratumoral heterogeneity. We identified key molecular pathways and differential expression of genes in VTT compared to primary tumor (VTT/PT). Furthermore, these genes were found to be upregulated in higher VTT level compared to lower VTT level. These results will require validation in a larger cohort. Funding None
Authors
Dharam Kaushik
Wasim Chowdhury Ping Wu Teresa Johnson-Pais Yidong Chen Michael A. Liss Ronald Rodriguez |
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MP39-07 |
INTEGRATED ANALYSIS OF MICRORNA AND MRNA EXPRESSION PROFILES IN TUBEROUS SCLEROSIS COMPLEX ANGIOMYOLIPOMA |
Kidney Cancer: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP39-07 Sources of Funding: National Natural Science Foundation of China (81670611). Introduction Tuberous sclerosis complex (TSC) is a multisystem genetic disorder caused by mutations in the TSC1 and TSC2 genes. Over 80% of TSC patients developed angiomyolipomas (TSC-AML), but the molecular events contributing to TSC-AML in TSC are not well understood. However, little is known about the role of microRNAs in TSC-AML. Methods Total RNA was used to analyze miRNA and mRNA expression via miRCURY-TM Hy3-TM/Hy5-TM Power labeling kit and Human 12 x 135K Gene Expression Array, respectively. Both miRNA and gene expression profiles were integrated by correlation analysis to identify dysregulated miRNAs with their corresponding predicted target mRNA. Microarray data were validated with qRT-PCR. Regulation of BCL2 like 11 (BCL2L11) expression by miR-9-5p, miR-124-3p and miR-132-3 was determined by luciferase reporter assays. All analyses used a significance level of 0.05 and were generated in SPSS19.0 software. Results Using microarray profiling of 3100 miRNAs and 45033 mRNA transcripts, the analysis indicated that 350 of these miRNAs and 37284 mRNAs were expressed in TSC-AML, of which the relative expression of 16 miRNAs and 2881 mRNAs (fold change ≥ 1.5 or ≤ 0.67) was differentially expressed in TSC-AML as compared to non-TSC-AML. The validated results revealed that miR-9-5p, miR-124-3p and miR-132-3p were upregulated whereas BCL2L11 was downregulated in patients with TSC-AML. Further studies revealed that downregulation of miR-9-5p, miR-124-3p or miR-132-3p promoted TSC2-deficient angiomyolipoma-derived cell apoptosis. Moreover, luciferase results and western blot analysis confirmed that BCL2L11 was a target of miR-9-5p, miR-124-3p and miR-132-3p. Conclusions In conclusion, we identified a number of miRNAs that are differentially expressed between TSC-AML and non-TSC-AML and constructed posttranscriptional regulatory network miRNA-target gene pairs: BCL2L11 is an endogenous target of miR-9-5p, miR-124-3p and mir-132-3p in the TSC-AML of patients. Downregulation the expression of miR-9-5p, miR-124-3p and miR-132-3 could inhibit proliferation and promote apoptosis in comparison to negative controls TSC2-deficient AML-derived cell. Funding National Natural Science Foundation of China (81670611).
Authors
Yi Cai
Hanzhong Li Yushi Zhang |
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MP39-08 |
The microRNA expression signature of patients with renal cell carcinoma: tumor-suppressive miR-149-5p targeting FOXM1 |
Kidney Cancer: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP39-08 Sources of Funding: none Introduction Recently, tyrosine kinase inhibitors (TKIs) treatment is a standard treatment for patients with advanced renal cell carcinoma (RCC). During sequencing TKI-based therapies, RCC cells acquire the resistance to TKI-treatment. To date, no effective therapeutic resumes for patients with TKI-treatment failure, and overall survival of these patients is extremely poor. _x000D_ A unique characteristic of microRNA (miRNA) is that a single miRNA regulates a large number of RNA transcripts in human cells. Thus, dysregulated miRNA expression disrupts tightly regulated RNA networks in cancer cells. Currently, numerous studies have indicated that dysregulated miRNAs involved in cancer cell development, metastasis and drug resistance. Identification of aberrantly expressed miRNAs is the first step to defining the oncogenic and drug resistance RNA networks in RCC cells._x000D_ Our miRNA signature of RCC revealed that miR-149-5p was significantly reduced in RCC specimens. In this study, we focused on the functional significance of miR-149-5p in RCC cells by identifying the pathologic targets of miR-149-5p and the RNA networks that contribute to RCC aggressiveness and drug resistance._x000D_ Methods TCGA database was applied to investigate the clinical outcome of the patients. Gain-of-function studies were performed using transfection of mature miR-149-5p into RCC cell lines. Genome-wide gene expression analysis and in silico analysis were applied to investigate molecular targets regulated by miR-149-5p in RCC cells. Results The expression levels of miR-149-5p were significantly reduced in RCC clinical specimens (P < 0.001). Ectopic expression of miR-149-5p were significantly suppressed cancer cell proliferation. Gene expression and in silico analysis identified that Forkhead box protein M1 (FOXM1) was a target of miR-149-5p regulation. Knockdown study using si-FOXM1 showed that expression of FOXM1 enhanced RCC cell aggressiveness. A large number of cohort analysis based on TCGA data (n = 261) indicated that the overall survival of high FOXM1 expression group was significantly shorter than that of low expression of FOXM1 group (p < 3.35E-06). Conclusions Our present data indicated that miR-149-5p act as a tumor-suppressor targeting FOXM1 in RCC cells and this axis deeply involved RCC pathogenesis. Elucidation of tumor-suppressive miRNA-regulated molecular pathways and targets could provide new information on potential therapeutic strategies in the disease. Funding none
Authors
Atsushi Okato
Takayuki Arai Akira Kurozumi Mayuko Kato Yusuke Goto Satoko Kojima Yukio Naya Tomohiko Ichikawa Naohiko Seki |
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MP39-09 |
Impact of microRNA expression signature of patients with TKI failure: regulation of miR-10a-5p pathways in renal cell carcinoma |
Kidney Cancer: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP39-09 Sources of Funding: none Introduction Currently developed tyrosine kinase inhibitors (TKIs) based molecular targeted therapies have improved the prognosis of patients with advanced renal cell carcinoma (RCC). However, RCC cells acquire the resistance to TKI drugs during the course of sequencing treatment of TKIs. The overall survival of the patients with TKI-treatment failure is extremely poor and no effective treatment resumes for this disease. To identify key molecules and novel pathways involved in the resistance of TKI therapies for RCC is needed. In this study, we constructed a miRNA expression signature to identify pathways activated by TKI-treatment using autopsy specimens from patients with TKI-treatment failure. We have sequentially identified tumor-suppressive miRNAs and these miRNAs regulated RCC pathways based on the signature. The aim of this study was to investigate the functional significance of miR-10a-5p and to identify the molecular targets and pathways mediated by miR-10a-5p in RCC cells. Methods TCGA database was applied to investigate the clinical outcome of the patients. Gain-of-function studies were performed using transfection of mature miR-10a-5p into RCC cell lines. Genome-wide gene expression analysis and in silico analysis were applied to investigate molecular targets regulated by miR-10a-5p in RCC cells. Results The expression levels of miR-10a-5p were significantly reduced in RCC clinical specimens and RCC cell lines compared with non-cancerous kidney tissues (P < 0.001). TCGA data showed that the overall survival of low miR-10a-5p expression group was significantly shorter than that of high expression group (P = 0.00408). Restoration of miR-10a-5p significantly inhibited cancer cell migration and invasion in RCC cell lines (P < 0.0001). Spindle and kinetochore associated complex subunit 1 (SKA1) was identified as a direct target gene of miR-10a-5p by genome-wide gene expression analysis and in silico analysis. Overexpression of SKA1 was observed in RCC clinical specimens. Moreover, the overall survival of high SKA1 expression group was significantly shorter than that of low expression group by TCGA analysis (P = 1.44E-07). Conclusions Tumor-suppressive miR-10a-5p was identified based on the miRNA signature. Overexpression of SKA1 might be involved in RCC aggressiveness metastasis and drug resistance. Elucidation of tumor-suppressive miRNAs regulated molecular pathways and targets could provide new information on potential therapeutic strategies in the disease. Funding none
Authors
Takayuki Arai
Atsushi Okato Akira Kurozumi Mayuko Kato Yusuke Goto Satoko Kojima Yukio Naya Tomohiko Ichikawa Naohiko Seki |
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MP39-10 |
Intra-Tumor Heterogeneity in Renal Cell Carcinoma: Implications for Proteomic Analysis of Renal Mass Biopsies |
Kidney Cancer: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP39-10 Sources of Funding: NIH R21-CA169964 Introduction Intra-tumor heterogeneity (ITH) is the presence of cell clones with different genetic or histologic phenotypes that occupy distinct spaces within a tumor. Whether genomic ITH translates into functional ITH on the level of protein expression and activity is less well characterized. We hypothesized that variation in expression and activation of critical RCC signaling proteins is less than genomic ITH, resulting in a limited number of functional phenotypes in a tumor. This framework would allow for representative sampling of RCC using renal mass biopsy and advanced proteomic techniques. Methods We profiled the expression and activation state of extracellular signal-regulated kinase (ERK), a critical effector of the MAPK signaling pathway, in 131 ex vivo biopsies from 39 clear cell RCC tumors and adjacent normal parenchyma after nephrectomy. We performed fine-needle aspirate (FNA) biopsies of grossly representative sections after bivalving the kidney. We performed nano-scale immunoassays (NIA) to quantify the absolute and relative abundances of the phospho-isoforms of ERK1/2 using the Peggy Sue instrument (Protein Simple). ERK1/2 was interrogated with a pan-ERK antibody. Expression levels of ERK levels were compared across samples by normalization to the levels of the ubiquitously expressed protein HSP70._x000D_ Results ERK1 was infrequently activated, with most samples (69%) demonstrating no phosphorylation of ERK1. In contrast, ERK2 demonstrated phosphorylation in the majority of the samples. Two distinct mono-phosphorylated ERK2 isoforms were detected (pERK2a and pERK2b), with relative abundances ranging from 0-58% and 1-57%, respectively. The relative abundance of dual-phosphorylated ERK2 (ppERK2) ranged from 0-26%. The overall ITH of ERK2 activation was low (average standard deviation [SD] 6%) compared with the difference in ERK2 activation among the 39 tumors (SD 5% - 22%). Conclusions The abundance and activation of ERK1/2 can be measured from scant FNAs of RCC using novel proteomic methods. We found little ITH of ERK, which suggests that protein ITH is generally less than functional heterogeneity among tumors. These data suggest that a single renal mass biopsy may accurately measure the activity of relevant signaling pathways within a tumor, which may facilitate future precision medicine approaches. Funding NIH R21-CA169964
Authors
Rustin Massoudi
Christian Hoerner Thomas Metzner Jennifer O'Rourke Rachael Curtis Laurel Stell Chiara Sabatti James Brooks Alice Fan John Leppert |
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MP39-11 |
The newly found biomarkers of renal cell carcinoma by Proteinomics |
Kidney Cancer: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP39-11 Sources of Funding: None Introduction Renal cell carcinoma (RCC) is originated from the uriniferous tubule's epithelial system in renal parenchyma. RCC is the most fatal urinary tract tumor and also is not sensitive to radiotherapy and chemotherapy. So nowadays, surgery is the main treatment in clinic. But to the metastatic patients or post-operation transfer cases, surgeries have been unable to achieve a radical cure goal, which means targeted drug therapies are currently more reliable adjuvant ways. The development of targeted drugs treatment depended on the research of RCC biomarkers. The current targeted drugs remain low response rate. On the other hand, the imaging examination is not effective enough for the judgment of the prognosis and invasion of RCC. Therefore, in this study we urgently need to find unique biomarkers for early diagnosis and prognosis. It will be of great help for clinical guide to individualized treatment. Methods We collected 21 pathological diagnosis of renal clear cell carcinoma (the main subtype in RCC classification) patients’ peripheral blood, tumor tissues and para-carcinoma normal kidney tissues. All the specimens will be used in the proteinomics detection. LC/MS/MS, protein identification and quantitation are the most important procedures in proteinomics. Cytoscape3.1.1 and two plugins were used to analyze the protein interaction network. Results From all the samples, we have found more than 6000 proteins expressed and more than 400 proteins have different expression profile compared between groups. Only 10 proteins highly expressed in the tumor tissues compared with their normal tissues. Some tumor growth markers highly expressed in the peripheral blood of the patients and in their tumor tissues. Perilipin 2 (PLIN2), Lactate dehydrogenase A (LDHA) and Prostaglandin E2 ?PGE2?were highly expressed in tumor tissues. These markers are all correlated with tumor growth and angiogenesis, which indicated these proteins might be the novel predictive and prognostic markers in RCC. Conclusions In this study, we found tumor related proteins PLIN2, LDHA and PGE2 highly expressed in RCC by proteomics analysis. More research to find the tumor-regulation mechanism of these markers is ongoing. It will be of great help to the future prospects for novel medical treatments for RCC._x000D_ Funding None
Authors
Yimeng Song
Lijun Zhong Lulin Ma |
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MP39-12 |
Higher serum C-reactive protein level represents the immunosuppressive tumor microenvironment in patients with clear cell renal cell carcinoma |
Kidney Cancer: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP39-12 Sources of Funding: none Introduction C-reactive protein (CRP), a representative inflammatory marker, has been shown to be a prognostic biomarker for renal cell carcinoma (RCC) (Saito K et al. Nat Rev Urol. 2011). Recently, several studies have reported that the invasion of immunosuppressive regulatory T cells (Treg) and M2 macrophages correlates with poor clinical prognosis in various cancers. In this study, we investigated the association between tumor immune microenvironment including invasions of Treg and M2 macrophages and CRP in RCC patients to explore the mechanisms underlying the association between CRP level and prognosis. Methods Immunohistochemical (IHC) measurement of CD4, CD8, CD163 (M2 macrophages), and FOXP3 (Treg) was performed in clear-cell RCC (ccRCC) patients (n =111) treated with radical or partial nephrectomy. CD4+, CD8+, and CD163+ cells were counted and the optimal cut-off scores for CD4, CD8 and CD163 were determined through receiver-operating characteristic (ROC) analysis. Patients were classified into groups according to FOXP3 positive or negative status. The association between IHC status and preoperative serum CRP level and cancer-specific survival (CSS) was analyzed. Results Median follow-up period was 8.5 years. pT stage was pT1 in 58%, pT2 in 5%, pT3 in 35% and pT4 in 2% of patients. Lymph node involvement and distant metastasis were seen in 4% and 20% of patients, respectively. Thirty-three patients (30%) had a high CRP level (≥5.0 mg/L), and the CSS rate was significantly worse among these patients than among the remaining patients (p <0.0001). In patients with strong invasion of CD8+, CD163+ or FOXP3+ cells, CRP levels were significantly higher (Figure 1) and CSS was significantly worse (Figure 2) compared to patients with weak invasion. Conclusions Invasion of the immunosuppressive cells known as Tregs and M2 macrophages in the tumor microenvironment is associated with higher CRP and poor prognosis in ccRCC patients. CRP indicates an immunosuppressive microenvironment. Funding none
Authors
Takayuki Nakayama
Kazutaka Saito Yuma Waseda Hajime Tanaka Masaharu Inoue Masaya Ito Naoko Kawamura Minato Yokoyama Junichiro Ishioka Yoh Matsuoka Kazunori Kihara Yasuhisa Fujii |
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MP39-13 |
Identification of ISYNA1 as a potential prognostic biomarker for renal cancer |
Kidney Cancer: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP39-13 Sources of Funding: none Introduction In response to cellular stress, p53 exerts tumor-suppressive effects, such as apoptosis, cell cycle arrest, and senescence, through the induction of its target genes. Recently, p53 has been shown to control cellular homeostasis by regulating energy metabolism, glycolysis, antioxidant effects, and autophagy. A previous study has reported an association between the p53 expression pattern in immunohistochemical analyses of tumor and the prognosis of renal cell carcinoma (RCC). Although various tumors have p53 mutations, RCC has few p53 mutations. As such, we examined whether a p53 target gene might affect the prognosis of RCC patients. We identified a novel p53 target and examined whether it was useful as a prognostic factor for renal cancer. Methods To screen for novel p53 target genes, we conducted a cDNA microarray analysis using mRNAs isolated from HCT116 p53+/+ and HCT116 p53-/- cells that were treated with 2 µg/ml of Adriamycin. To investigate whether mRNA transcription is regulated by p53, we performed a reporter assay and a chromatin immunoprecipitation (ChIP) assay using U373MG cells. To evaluate the effect of the novel p53 target on the biosynthesis of myo-inositol (MI), we performed a MI assay using HEK293T cells that were transfected with a plasmid expressing the novel p53 target, or HCT116 p53+/+ and HCT116 p53-/- cells that were treated with Adriamycin. To examine whether the novel p53 target would be useful as a prognosis factor for renal cancer, we performed a prognostic analysis using the mRNA expression ratio (tumor / normal kidney tissues) of the novel p53 target in RCC. Results The results of the cDNA microarray analysis revealed inositol 3-phosphate synthase 1 ( ISYNA1 ) as a novel candidate gene. From the results of the reporter assay and the ChIP assay, we found p53 response elements in the promoter region and the seventh exon. As such, ISYNA1 was identified as a novel p53 target. The results of MI assay showed that ISYNA1 expression increased myo-inositol levels in the cells. In addition, DNA damage significantly increased the intracellular MI content in HCT116 p53+/+ cells, but did not affect the MI content in HCT116 p53-/- cells. The ISYNA1 mRNA expression ratios in renal cancer and renal clear cell carcinoma were significantly correlated with overall survival (p < 0.01). Conclusions We identified ISYNA1 as a novel p53 target gene and found that it regulated the intracellular MI content via a p53-ISYNA1 pathway. Our findings show that the ISYNA1 mRNA expression ratio is correlated to overall survival in RCC. Therefore, ISYNA1 might be useful as a novel prognostic factor for renal cancer. Funding none
Authors
Tomoyuki Koguchi
Kanako Matsuoka Junya Hata Yuichi Sato Hidenori Akaihata Masao Kataoka Soichiro Ogawa Nobuhiro Haga Nobuhiro Kushida Kei Ishibashi Ken Ikawa Yoshiyuki Kojima |
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MP39-14 |
Iron accumulation during renal cell carcinogenesis and reversal with tumor progression |
Kidney Cancer: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP39-14 Sources of Funding: This work was supported by the Roswell Park Cancer Institute Alliance Foundation and National Cancer Institute grant P30CA016056 Introduction The von Hippel Lindau-hypoxia inducible factor axis underlying clear cell renal cell carcinoma (RCC) is centrally involved in iron and oxygen metabolism. Iron is a key catalyst for DNA synthesis, an abundant ingredient of tobacco, and a potent cause of oxidative stress-induced RCC in rodents. Yet the role of iron in human RCC carcinogenesis is largely unknown. We investigated whether levels of iron and the main iron uptake protein, transferrin receptor 1 (TfR1/CD71), are altered during human RCC tumorigenesis and progression. Methods Over 1500 core sections from 587 tissues (272 primary tumors, 240 benign kidney, 75 metastases) of 288 RCC patients were stained for iron and TfR1 protein using Prussian Blue and immunohistochemistry, respectively. 178 tissue cores from 14 different body sites of non-cancer patients were included as controls. Staining was scored by a clinically blinded genitourinary pathologist based on the product of intensity and tissue percentage (Z-score), and tested for association with clinicopathologic features and survival using a Mann-Whitney U test, Kruskal Wallis test and Cox regression model. Results Renal epithelium from non-cancer patients had low iron content (mean Z-score, MZS= 0.1), but by far the highest TfR1 levels of any tissue site in the body (MZS= 153). Compared to non-cancer patients, iron content in RCC patients increased mildly (4-fold) in benign renal epithelium (MZS= 0.6) and dramatically (>100 fold) in primary tumors (MZS= 21, p< 0.001). Higher tumor iron content was accompanied by moderate TfR1 downregulation (MZS= 21, p< 0.001) and associated with clear cell and papillary histologies, male gender and tobacco usage (p< 0.05 each). Opposite to changes observed with tumorigenesis, iron and TfR1 levels decreased and increased, respectively, with progression in tumor size, grade, pT stage and metastatic stage (all p< 0.05). Iron loss and TfR1 upregulation were most apparent in metastatic lesions (MZS= 5 and 111, respectively) and each associated with patient anemia and worse RCC-specific survival (all p< 0.05). Conclusions Benign renal epithelium has uniquely high levels of the iron import protein, TfR1, potentially priming these cells for dysregulated iron uptake and large intracellular iron increases (>100 fold) during tumorigenesis. Reduction in iron content during RCC progression to metastasis, despite TfR1 increases, may reflect lower systemically available iron in advanced RCC patients and raises the possibility that these cancers might have increased susceptibility to iron deprivation as a novel therapeutic strategy. Funding This work was supported by the Roswell Park Cancer Institute Alliance Foundation and National Cancer Institute grant P30CA016056
Authors
Christopher Greene
Ramkishen Narayanan Cornelia Willis Nitika Sharma Gary Smith Kenneth Gross Bo Xu Eric Kauffman |
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MP39-15 |
SDCT2 as a Functional Biomarker of Renal Cell Carcinoma |
Kidney Cancer: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP39-15 Sources of Funding: Grant NCI/NIH 5R01CA72821; 5R01CA176691 Introduction Five-year survival of metastatic renal cell carcinoma (mRCC) patients is < 10% and African American (AA) males have the highest incidence. Identification of the molecular determinants of mRCC and racial disparity in RCC is critical for biomarker development and targeted therapy. SDCT2 expressed in kidney epithelial cells is a succinate/citrate transporter, however its role has not been examined in any disease. We examined SDCT2 expression in normal and RCC tissues and correlated it with clinical outcome and racial disparity. We also evaluated biological functions and molecular signaling regulated by SDCT2 in RCC cells. Methods Differential gene expression in the matched normal and RCC tissues (n=6/category) was evaluated by microarray analysis; results were validated by QPCR and immunoblotting in tissues from 53 patients (White=21; Hispanic=19; AA=13). VHL+ and VHL- RCC cells were stablely transfected with a SDCT2 construct. Transfectants were characterized for cell proliferation, cell cycle, motility, succinate/citrate transport and reactive oxygen species (ROS) measurement assays under normoxia and hypoxia. SDCT2 induction was evaluated following 5-azacytidine plus Trichostatin A (5-AZA/TSA) treatment. Results SDCT2 was 63- and 100-fold downregulated in low- and high-stage RCC tissues. Q-PCR validation showed 40-fold downregulation of SDCT2 in RCC tissues when compared to normal kidney (P< 0.0001). Downregulation was 40-fold in White and Hispanic patients, but 198-fold in AA patients (P=0.0049) and correlated with tumor stage and metastasis (P=0.009). Under hypoxia, SDCT2 expression caused 3-4-fold inhibition of proliferation, cell-cycle, motility in both VHL+ and VHL- cells (P<0.01); only VHL+ cells were inhibited under normoxia. SDCT2 expression induced ROS levels and succinate transport by >3-fold (P<0.01) and activated p16INK4a-RB pathway and apoptosis (caspase-3 and PARP activation). 5-AZA+TSA treatment induced SDCT2 expression by 50-fold (P<0.001). Conclusions This is the first study on a functional biomarker in RCC, SDCT2, that is possibly a novel tumor suppressor gene. SDCT2 loss promotes RCC growth, survival and inhibits cellular senescence and its downregulation correlates with metastasis and racial disparity. Funding Grant NCI/NIH 5R01CA72821; 5R01CA176691
Authors
Andre Jordan
Martin Hennig Axel Merseburger Marie Hupe Mario Kramer Mark Soloway Vinata Lokeshwar |
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MP39-16 |
Serum Tissue Factor as a biomarker for Renal Clear Cell Carcinoma |
Kidney Cancer: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP39-16 Sources of Funding: None. Introduction We have previously demonstrated that increased expression of Tissue Factor (TF) in tissue samples RCCC is an independent prognostic factor of aggressive behavior and of cancer specific mortality. We aimed to compare preoperative serum TF levels in RCCC patients with those of patients submitted to surgical interventions in patients without RCCC. Additionally, to verify the difference in preoperative and postoperative serum TF levels in RCCC patients in blood samples collected before surgery and after at least four weeks of the surgical procedure. Methods We conducted a prospective study of 30 patients with RCCC submitted to either partial or radical nephrectomy and 16 controls without RCCC treated surgically for other conditions. Serum TF was collected before surgery at the operating room and in the postoperative setting after at least four weeks. Serum samples were analyzed with a commercial ELISA kit for human TF (R&D Systems®). Results Mean preoperative serum TF levels in RCCC patients and in controls were 66.8 pg/dl and 28.4 pg/dl, respectively (p<0.001). Mean postoperative serum TF levels in RCCC patients were 26.3 pg/dl. In all patients with RCCC postoperative serum levels of TF were lower, with a mean reduction of 41.6 pg/dl in the postoperative setting (p<0.001). Linear regression revealed that tumor size was correlated with the postoperative reduction of serum TF levels (Pearson coefficient = -0.38 ;p=0.037). Conclusions We have shown a 3-fold reduction in the median preoperative serum levels of TF in patients with RCCC after surgery. We have also shown a difference of the same magnitude in the serum levels of TF compared with those of a control group of patients with benign diseases. TF appears to be a useful serum marker for the presence of RCCC. Further studies are needed to validate these findings. Funding None.
Authors
Daniel Silva
Bartira Pinheiro da Costa Jorge Antonio Pastro Noronha Gustavo Carvalhal |
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MP39-17 |
Mitochondrial DNA copy number variation as a potential predictor of renal cell carcinoma. |
Kidney Cancer: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP39-17 Sources of Funding: none Introduction Peripheral blood mitochondrial DNA (mtDNA) is suggested as a risk factor for several types of cancer. Previous studies have assessed the association between mtDNA and renal cell carcinoma (RCC), however, contradictory results were obtained. The aim of the present study was to assess the role of peripheral blood mtDNA in prediction and early detection of renal cell carcinoma in a cohort of Egyptian patients. Methods The study enrolled 57 patients with early localized RCC (TNM stage I and II), confirmed by histopathological examination. They were consecutively recruited between August 2012 and March 2015 after excluding patients with advanced RCC (TNM stage III and IV) (to omit the effect of disease progression on mtDNA content), patients with other malignancies, family history of kidney cancer, recurrent RCC, and patients who received neoadjuvant therapy. Sixty healthy individuals with matching age and sex were included as control. The Ethics Committee approved this study and all subjects gave informed consent._x000D_ Relative mtDNA copy number was measured using quantitative real-time PCR assay. Mitochondrial DNA (mtDNA) copy number was determined relative to the nuclear gene (HBB gene) using the formula-2δδCt._x000D_ Results Fifty seven patients (36 males, 21 females) diagnosed with early localized RCC were included: 50 clear RCC,5 papillary RCC and 2 chromophobe RCC cases. The mean age was 60.14 ± 6.83 years. Median mtDNA copy number was significantly higher in RCC cases than controls (166 vs 91, P<0.001). The role of mtDNA copy number as a risk factor for RCC was evaluated using unconditional logistic regression analysis. The median mtDNA content of the control group (91) was used as a cutoff value to analyze mtDNA copy number. It was found that patients with mtDNA content higher than 91 had a significant increase in RCC risk of 18 fold than those with lower levels with OR (odds ratio) of 18.0 (95% CI = 5.065-63.9) in univariate analysis and an adjusted OR of 18.9 (95% CI = 5.11-70.11) in multivariate analysis (after adjusting for age, gender, smoking status, hypertension and body mass index)._x000D_ The diagnostic value of mtDNA content in early detection of RCC was further assessed. Using receiver operating curve (ROC curve) analysis, it was found that mtDNA can detect RCC at a cutoff value of 108.5 with 86% sensitivity, 80% specificity, 80.3 % positive predictive value and 85.7% negative predictive value._x000D_ Conclusions Increased mtDNA copy number could be used as a potential independent predictor of RCC risk. In addition, it may serve as a promising non-invasive biomarker for early detection of RCC. Funding none
Authors
Eman Elsayed
Mohamed Mohieeldin Hashad Eman Elgohary |
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MP39-18 |
Mitochondria function change and activation of AMPK-PGC1? pathway through induction of clear cytoplasm in renal cell carcinoma |
Kidney Cancer: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP39-18 Sources of Funding: none Introduction Our studies aim to recover clear cytoplasm in renal cell carcinoma cell lines by inducing adipogenic transdifferentiation, and to determine the effect of such a change in cell activity. Methods An increase in the clear cytoplasm caused using adipogenic induction media (Lonza) in Caki-1 and Caki-2 cells. Human PCR array (Qiagen) was conducted for comparison of gene expressions which are related to adipogenesis and mitochondria. Western blotting and confocal microscopy were utilized to observe the protein expressions for mitochondria biogenesis. JC-1 dye staining (Cayman) to measure mitochondrial membrane potential was performed to observe mitochondrial function. Results Clear cytoplasm was found to increase more in Caki-1 cells than in Caki-2. The increases of clear cytoplasm in Caki-1 cells were induced up-regulation of adipogenesis-related genes. In particular, Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1?) which promotes mitochondrial biogenesis demonstrated an 11-fold increase (Fig. 1A). This up-regulation of PGC1? genes led increases in genes of voltage-dependent anion channels and cytochrome C oxidase subunit IV, ultimately promoting mitochondrial biogenesis (Fig. 1B, C). Also, in Caki-1 cells with increased clear cytoplasm, a mitochondrial healthy state was maintained with no impact on membrane potential, which is a significant role of mitochondria for cell’s homeostasis (Fig. 2A). Such activation of PGC1? was found to be caused by increased phosphorylation of AMP-activated protein kinase (AMPK) (Fig. 2B, C). Conclusions We demonstrated that morphologic characteristics of ccRCC could be recovered in the renal cell carcinoma cell line by increasing clear cytoplasm using adipogenic induction. This activates the AMPK-PGC1? pathway and promotes mitochondria biogenesis with no impact on membrane potential, resulting in mitochondria being observed in a healthy state. Progression of malignant differentiation in renal cell carcinoma resulted in a marked decrease in the number and function of mitochondria. This study is expected to provide valuable clues in characterizing and treating the progression of renal cell carcinoma. Funding none
Authors
Hyung Ho Lee
Sook Young Kim Young Eun Yoon Sung Ku Kang Jae Yong Jeong Kwang Hyun Kim Kyung Hwa Choi Joong Shik Lee Koon Ho Rha Young Deuk Choi Sung Joon Hong Woong Kyu Han |
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MP39-19 |
Sunitinib drives cell-to-cell mitochondrial trafficking in kidney cancer |
Kidney Cancer: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP39-19 Sources of Funding: Research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number T32GM088129. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Introduction When grown under stressed conditions, a subset of neoplastic cells can undergo cell-to-cell trafficking of mitochondria through dynamic structures termed tunneling nanotubes. This horizontal mitochondrial transfer (HMT) is a relatively newly described phenomenon that may contribute to chemotherapeutic resistance in several non-urologic cancers. Since HMT might represent a novel mechanism of acquired chemoresistance in renal cell carcinoma (RCC), we sought to determine if HMT occurs in response to treatment with Sunitinib, a first line chemotherapeutic agent. Methods RCC cell lines (A498 and 786-O) were differentially labeled by lentiviral transduction of cytoplasm-localizing enhanced green fluorescent protein (EGFP) or mitochondria-localizing mCherry. Mitochondrial localization of mCherry (mito-mCherry) was achieved by tagging the fluorescent protein with the cyclooxygenase-8 mitochondria targeting sequence. Differentially labeled RCC cells were cultured at a 1:1 ratio and were treated with sunitinib (0uM, 1.25uM, 2.5um, 5uM, 10uM, and 20uM) for 24 hours. HMT was quantified by flow cytometry and visualized by deconvolution microscopy. Results HMT occurred between differentially labeled RCC cells. Co-culture of mito-mCherry A498 cells with EGFP+ A498, 786-O, and ACHN cells demonstrated mitochondrial transfer at all concentrations of sunitinib tested. 2.4% of EGFP+ A498 cells received mCherry+ mitochondria in co-culture at 0uM of sunitinib. Mitochondrial transfer was enhanced by sunitinib treatment at all doses tested (e.g. 4.26% at 10uM sunitinib). This phenomenon was not cell line specific as EGFP labeled 786-O cells also acquired mCherry+ mitochondria (8.3%). Deconvolution microscopy of fixed co-cultured cells demonstrated mCherry+ mitochondria within EGFP+ 786-O cells. Conclusions Here we demonstrate for the first time that sunitinib exposure potentiates cell-to-cell transfer of mitochondria in kidney cancer cell lines. The biologic significance of this process in vivo remains to be determined. Our hypothesis is that HMT may contribute to clinically relevant acquired chemoresistance in RCC and experiments are under way to explore this possibility further. Funding Research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number T32GM088129. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Authors
Jason Scovell
Juan Hernandez Richard Link |
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MP39-20 |
Advances in the Diagnosis of Hereditary Kidney Cancer: Initial Results of a Multigene Panel Test |
Kidney Cancer: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP39-20 Sources of Funding: None Introduction Multigene panel testing has been recently introduced to evaluate hereditary cancer, however, limited information is available regarding its use in kidney cancer. In this study, we describe the outcomes of the first kidney cancer focused panel test. Methods We retrospectively reviewed test results and clinical data of kidney cancer patients who underwent targeted multigene panel testing of 19 genes associated with hereditary kidney cancer from 2013 to 2016. Age of onset, gender, race/ethnicity, and patient/family cancer history were noted. The frequency of positive, inconclusive, and negative results was evaluated. A logistic regression analysis evaluated predictive factors for a positive test. Results Patients undergoing testing (n=1,239) had a median age of diagnosis of 46 years, which is significantly younger than the U.S. population of kidney cancer (p<0.0001). Overall, 6.1%, 75.3%, and 18.6% of individuals had positive, negative, and inconclusive results, respectively. The most commonly altered genes included FLCN and FH, which were 1.8% and 1.3% of cases respectively. TSC2, MET, and PMS2 had the highest rates of variants of unknown significance (VUS) with 2.7%, 2.2%, and 1.7% of cases respectively. Early age of onset was the only factor found to be predictive of a positive test on multivariate analysis (OR 0.975, 95% p=0.0052). Furthermore, early age of onset may be the only identifying characteristic of low penetrant syndromes, such as those associated with MITF mutations, which did not have a single definitive histology nor a family history of kidney cancer, but had an early median age of onset of 39. Conclusions Multigene panel tests facilitate the identification of hereditary kidney cancer. This testing modality may be particularly useful when a specific syndrome is not suspected based on clinical/family characteristics. Our results support the use of early age of onset for genetic counseling and/or testing. Funding None
Authors
Kevin Nguyen
Jamil Syed Carin Espenschied Holly Laduca Ansh Bhagat Timothy O’Rourke Brian Shuch |
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MP40-01 |
Use of modified fascial pubovaginal sling for the treatment of stress urinary incontinence: up to 20 years follow up. |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Female Incontinence: Therapy I | 17BOS |
Abstract: MP40-01 Sources of Funding: none Introduction Multiple surgical procedures have been introduced for the treatment of (SUI) with variable morbidities. In this study, the results and long term follow up of fascial modified pubovaginal sling (MPVS) were evaluated. Methods from March 1995 to January 2016, 220 female patients complaining of SUI underwent MPVS. Preoperative evaluation included history, physical examination, and uroflow. Full urodynamics were performed in cases of mixed incontinence or recurrent cases. The patients had an average age of 45.7 years and parity 4. The presentations were pure SUI in 84 (38.2%) and mixed incontinence in 136 cases (61.8 %). MPVS (Ghoniem's modification) was performed using a 7 x 2.5 cm patch harvested from the rectus sheath with polypropylene sutures on both sides. With Stamy's needle, the sutures of the patch were guided up to the suprapubic region, and then cystoscopy was performed. The patients were followed up 3, 6, and 12 months, then annually every year up to 20 years in old cases. The patients were subdivided, according to duration of follow up, into 4 groups (I-IV) from 15- 20, 10-14, 5-9 and < 5 years respectively Results MPVS was performed alone in 157 (71.4%) and accompanied with cystocele and / rectocele repair in 63 cases (28.6 %). Intraoperative and postoperative complications were managed properly. After one year, 205 patients (93.2 %) cured, while 15 patients (6.8 %) failed. Follow up was lost in 20 patients for different causes. For 57 patients in group I, the success rate was reported in 53 (92.9%), 52 (91.2 %), 49 (86%) and 49 cases (86 %) after 5, 10, 15 and 20 years follow up respectively. Conclusions MPVS is very simple procedure without major complications. It has a satisfactory long term results and stable with time up to 20 years. Funding none
Authors
Abdelnaser Elgamasy
Tarek Jameel Mohamed Redwan Ahmed Elabd Mohamed A Elbakry Elbakry Mohamed A Elbakry Elbakry Salah Nagla Aymen Hagras Ahmed Gheith |
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MP40-02 |
Comparison of Outcomes between Simple and Complex Patients Undergoing Autologous Pubovaginal Sling Placement |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Female Incontinence: Therapy I | 17BOS |
Abstract: MP40-02 Sources of Funding: none Introduction Our objective was to determine if there were differences in outcome and reoperation rates between simple and complex patients undergoing autologous pubovaginal sling placement, and whether outcomes differed when mesh removal was performed at the same time as PVS placement. Methods We reviewed the charts of 239 patients who underwent autologous rectus fascia PVS placement by a single surgeon (BJF) from 2004 through 2015. Complex cases were defined as patients with urge incontinence or neurogenic bladder, urethral or vesicovaginal fistula, urethral diverticulum, or IUGA category 4 mesh complication (lower urinary tract mesh perforation). Cases were considered simple if they did not meet criteria for complex. 62 patients met criteria for the complex group, and 177 patients met criteria for the simple group. Logistic regression analysis was used to determine if there was a correlation between simple and complex patients and rates of cure (defined as <1 pad per day post-operatively), improvement, retention, reoperation, and complications (Clavien grade >2). We also examined whether concomitant mesh removal was correlated with differences in these outcome measures. Results Overall SUI improvement rate was similar in both groups (96.4% for simple group and 93.2% for complex group, p = 0.31). There was a trend toward higher SUI cure rate in the simple group, but this did not meet statistical significance (p = 0.062). Mesh removal and complex case were both associated with increased risk of reoperation (OR = 3.3 and 2.8, respectively). There was no statistical difference in rate of Clavien grade >2 complications (p = 0.55) between simple and complex cases. Concomitant mesh removal was associated with an increased risk of post-operative retention (OR = 2.9), but case complexity had no independent effect on post-operative retention rate (p = 0.91). Conclusions Complex patients undergoing PVS placement are at increased risk of undergoing a subsequent continence procedure. In addition, performing mesh excision and PVS in the same setting increases the risk of both post-operative retention and reoperation when compared to PVS alone. Funding none
Authors
Michael Maccini
Tamara Lhungay Tyler Doumaney Lisa Parrillo Brian Flynn |
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MP40-03 |
What is the impact of coital incontinence on women sexuality and sexual function? |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Female Incontinence: Therapy I | 17BOS |
Abstract: MP40-03 Sources of Funding: none Introduction To determine the impact of coital incontinence on women sexual activity. Methods Between May 2013 and July 2014, we performed a cross-sectional study to evaluated sexual active women with and without coital incontinence. All patients were evaluated by means of anamnesis, physical examination, self-answered questionnaires, including World Health Organization for Quality of Life (WHOQOL-BREF), International Consultation on Incontinence Questionnaire-short form (ICIQ-SF; score ranges from 0 to 21; the greater the values the greater the incontinence severity), Overactive Bladder Questionnaire (OAB Short-Form; patients with overactive bladder are those with cumulative scores greater than 8) and 1-hour pad test. We evaluated the sexuality by means of Sexuality Quotient – Female Version (SQ-F). The SQ-F consists of 10 questions, the overall score ranges from 0 to 100. Women with scores under 62 were considered as sexual dysfunctional. Results It was evaluated 108 women (mean age: 52.6±9.35 and range: 30-70 years-old). Out of them, 52 women (48.1%) self-reported coital incontinence. Patients with and without coital incontinence had similar age (p=0.405), BMI (p=0.104), marital status (p=0.518), deliveries (p=0.805), educational level (p=0.392), 1 hour pad test weight (p=0.287), intercourse frequency (p=0.675) and similar scores in all WHOQoL-Brief domains. Women with coital UI had higher scores (more symptomatic) on ICIQ-SF and OAB-q (Table 1). There was not any difference in SQ-F questionnaire between the two groups. The prevalence of sexual dysfunction was similar in both groups. Questionnaire’s data are shown in Table 2. Conclusions Women with more severe urinary incontinence symptoms seems to be more predisposed to present coital incontinence. The presence of coital incontinence did not have significant impact on sexuality or sexual function. Funding none
Authors
Mariana Felippe
Marcia Eli Girotti Maira dos Santos Monique Rodrigues Tatiana Rodarte Fernando Almeida |
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MP40-04 |
The Relationship of Female Urethral length with Stress Urinary Incontinence |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Female Incontinence: Therapy I | 17BOS |
Abstract: MP40-04 Sources of Funding: none Introduction The lack of urethral support is one of the important pathogenesis to explain stress urinary incontinence (SUI). The actual nature of urethra, which is supported by a surrounding structure, may influence SUI. In men, many studies have evaluated the impact of urethral length before radical prostatectomy and found out that continence slowly recovered in men with shorter urethras before surgery. There are currently no studies that have investigated the relationship of female urethral length with SUI, which is the reason why we have performed this study.To evaluate the association between female urethral length and urodynamic study (UDS) parameters in stress urinary incontinence (SUI). Methods We reviewed the clinical records of 391 women who were diagnosed with SUI. The patients underwent a physical examination and UDS. Uroflowmetry data included the maximal flow rate (Qmax), time to Qmax, voided volume and post-void residual urine volume (PVR). Filling cystometry data included the first strong desire to void, valsalva leak point pressure (VLPP) and cough leak point pressure (CLPP). The Maximal urethral closure pressure (MUCP) and functional urethral length (FUL) was measured by urethral profile from UDS. And the anatomical urethral length (AUL) was measured using Foley catheter. In order to determine a "actual urethral length", we calculated FUL/AUL ratio for this study. Results A total of 299 patients were included in our study. The mean patient age was 57.73 ± 10.18 years. The mean AUL and FUL were 26.89 ± 4.50 cm and 32.20 ± 16.09 cm, respectively. In Pearson correlation coef?cients, FUL/AUL ratio correlated with PVR (-0.064, p= 0.270), VLPP (0.193, p=0.001), CLPP (0.119, p=0.040) and MUCP (0.249. p=<0.001). Multivariate analysis revealed that FUL/AUL ratio (HR 2.452, p=0.001) and MUCP (HR 1.131, p=0.012) were significantly associated with success of surgery. Conclusions Our results showed that female urethral length was associated with UDS parameter of SUI. Also it can be used as a significant predictive factor for a successful surgery. Funding none
Authors
Myung Ki Kim
Jae Hyung You Yu Seob Shin |
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MP40-05 |
Using Data from the California Office of Statewide Health Planning and Development (OSHPD) to determine the 30-day Complication Rate from Urethral-sling Placement. |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Female Incontinence: Therapy I | 17BOS |
Abstract: MP40-05 Sources of Funding: None Introduction Surgical intervention for stress urinary incontinence is common with 200,000 repairs annually. The most common repair is mid-urethral sling placement. Although the long-term complication rate after a sling procedure has been rigorously studied, the short -term (30 day) complication rate has been incompletely assessed. We sought to evaluate unplanned hospital visits within 30 days of sling placement in the form of emergency department visits, inpatient admissions, or repeat surgery. Methods With approval from the California Protection of Human Subjects committee, we accessed non-public data from the Office of Statewide Health Planning and Development (OSHPD) in the state of California for the years 2005-2011. All female patients who underwent an ambulatory urethral sling procedure (CPT 57288) were identified, excluding other procedures aside from cystoscopy. All emergency department visits, inpatient admissions, and sling revision operations within 30 days of the original surgery were identified. We also examined the most common primary diagnoses associated with emergency department visits. Results 28,635 women were identified who underwent outpatient urethral sling placement as a sole procedure (aside from cystoscopy). 1,630 patients had at least one unplanned hospital visit (5.7%) within 30 days. This included 1,327 emergency department visits (4.7%), 295 inpatient admissions (1.0%) and 79 sling revisions (0.28%). The hospital visit rate was significantly higher in patients undergoing a third or fourth sling placement (14.3%) as compared to a first or second sling placement (5.7%) (p=0.02) (table 1). Urinary retention and Foley catheter problem were the most common emergency department visit diagnoses (18.7% of ER visits), followed by urinary tract infection (9.3% of ER visits). Conclusions One in eighteen females will have an unplanned hospital visit within 30 days of urethral sling placement, the majority of which are emergency department visits. Our findings can be used to improve patient counseling and suggest target areas to decrease unnecessary emergency department visits in the early postoperative period. Funding None
Authors
Kai Dallas
Christopher Elliott |
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MP40-06 |
PREDICTORS OF A FAILED VOIDING TRIAL AFTER SLING AND CONCOMITANT PELVIC SURGERY |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Female Incontinence: Therapy I | 17BOS |
Abstract: MP40-06 Sources of Funding: None Introduction While the impact of patient specific factors, such as Charlson comorbidity index, body mass index (BMI), age, and maximum flow rate on successful postop voiding trial (VT), are well documented, little is known about the impact of concomitant surgery on the VT. Moreover, there is no standard timing or ideal method of conducting a VT. We aim to elucidate the effect of concomitant surgery on postop voiding after rectus fascia (ARF) and midurethral slings (transobturator (TO) and retropubic (RP)). Methods This is an IRB approved, retrospective analysis of women who underwent 3 sling types ± concomitant pelvic surgery at our institution from 2004 to 2015. Inclusion criteria were: preop post void residual < 50 mL, no indication for prolonged postop catheter drainage, and no postop retention requiring sling revision. All women had VT the morning after surgery per protocol. At time of VT, all women were using only oral analgesics for pain control. Demographic and perioperative factors were abstracted from the clinic and hospital charts. Results Of 1748 women, 1077 (62%) met inclusion criteria (751 RP, 194 TO, 132 ARF). Overall, 876 (81%) women passed the initial voiding trial (RP 81%, TO 86%, ARF 75%). Of 499 women having only sling, 84.6% passed their VT (RP 87.3%, TO 85.3%, 73.5% ARF). ARF was associated with VT failure, while higher BMI was associated with successful VT. Several additional trends emerged. Concomitant abdominal surgery was strongly associated with successful VT, regardless of sling type. The addition of vaginal prolapse repairs to vaginal hysterectomy lowers the chance of successful VT. Increasing the number of compartments repaired vaginally, especially when transvaginal vault suspension is performed, lowers the chance of successful VT. However, colpocleisis is strongly associated with a successful VT. The addition of transvaginal prolapse repairs to laparoscopy and laparoscopic hysterectomy lowers the chance of successful VT (although the number of concomitant prolapse repairs was small). The addition of transvaginal prolapse repairs to robot assisted hysterectomy does not significantly lower the chance of successful VT (although the number of concomitant prolapse repairs was small). Conclusions Lower BMI and ARF sling were associated with initial VT failure. The addition of vaginal prolapse repairs to vaginal or laparoscopic hysterectomy decreases the chance for successful VT, while concomitant abdominal or robotic surgery is not associated with VT failure. This information may be useful in constructing a nomogram to identify women who may benefit from additional preoperative counseling and, perhaps, instruction in intermittent catheterization. Funding None
Authors
J. Margaret Lovin
Clifton F. Frilot II Alexander Gomelsky |
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MP40-07 |
&[Prime]WET AND HAPPY&[Prime] VS. &[Prime]DRY AND UNHAPPY&[Prime]AFTER SLING SURGERY: AN ANALYSIS OF DIVERGENT POSTOPERATIVE OUTCOMES |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Female Incontinence: Therapy I | 17BOS |
Abstract: MP40-07 Sources of Funding: None Introduction The debate regarding the optimal definition of success after sling surgery hinges on the following: is resolution of stress incontinence (SUI) at the expense of urinary retention or worsened urgency incontinence (UUI) preferable to unresolved SUI? Other than postoperative UUI, there is paucity of information regarding reasons behind &[Prime]surgical failure.&[Prime] We aim to evaluate the &[Prime]happy/wet&[Prime] and the &[Prime]unhappy/dry&[Prime] groups of women treated with autologous rectus fascia (ARF), transobturator (TO) and retropubic (RP) midurethral slings. Methods This is an IRB approved, retrospective chart review of all women who underwent sling surgery at our institution from 2004 to 2015 with ≥ 12 month follow up (FU). All had SEAPI scoring (stress incontinence, emptying, anatomy, protection, inhibition) and 10 point visual analog score (VAS) of satisfaction. Demographics and perioperative details were abstracted from the office and hospital charts. Cure of SUI equaled: no subjective or objective SUI, and no additional anti incontinence surgery. &[Prime]Dry/unhappy&[Prime] were women with no SUI and VAS < 8. Those with SUI and VAS ≥ 8 were &[Prime]wet/happy&[Prime]. Results Mean FU was 30 months. Of 1,748 eligible women who underwent sling surgery, 115 (7%) were considered &[Prime]dry/unhappy&[Prime](41 RP; 40 TO; 34 ARF). Incidence of other postoperative symptoms was: 36 (31%) worse or de novo voiding problems, 21 (18%) worse or de novo UUI, 15 (13%) pain, 13 (11%) dyspareunia, and 12 (10%) recurrent prolapse. Additional surgeries during FU period were: 10% sling incision (11 women, 14 incisions), 6% prolapse repair, 5% repeat sling (all dry afterwards), and 4% sling revisions (for pain or extrusion). Several women without objective mesh problems also developed concerns regarding their slings. In the 24 who had sling only, 38% and 25% had worsened voiding and UUI, respectively. There were 201 (11.5%) in the &[Prime]wet/happy&[Prime] group (96 RP; 64 TO; 41 ARF). Postoperative SUI status was: 139 (69%) improved, 13 (6%) de novo, and 9 (4%) worse. Additional surgeries during the FU period were: 6% prolapse repair, 3% bulking, 2% repeat sling, 2% sling revision, and 1% sling incision. In 62 women having sling only, 89% had SUI improvement. Concomitant surgery inversely correlated with satisfaction. Conclusions Even if initial cure is not achieved, SUI improvement typically leads to satisfaction after sling surgery. Along with UUI, postoperative pain, prolapse, and voiding problems contribute to dissatisfaction with sling surgery; however, these events are strongly associated with concomitant pelvic surgical procedures. Proper counseling regarding expectations after sling, with or without concomitant surgery, is paramount in improving outcomes and satisfaction. Funding None
Authors
Umar R. Karaman
Clifton F. Frilot II Alexander Gomelsky |
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MP40-08 |
CCL7, a stem cell homing factor, has low responsive expression during sling procedure associated with postpartum urinary incontinence |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Female Incontinence: Therapy I | 17BOS |
Abstract: MP40-08 Sources of Funding: NSF China 81670695; China America Promotion Society for Medical Doctors (CAPs MD) Introduction Chemokine (C-C motif) ligand 7(CCL7) is one of key factors homing stem cell to rescue injured urethra and related pudendal nerve for maintaining urinary continence, which increases in significance immediately after simulated birth injury. To explore if serious stress urinary incontinence (SUI) after birth injury has low CCL7 responsive expression at the local injury of urethra. Methods 437 SUI patients preparing for sling procedure enrolled in the study for testing CCL7 expression via collection the blood sample from systematic vein (baseline expression) and local incision (responsive expression), and for inquiry a history if having SUI at last vaginal delivery. 411 individuals successively completed a simplified urinary incontinence inquiry to their last vaginal deliveries. 380 individual blood samples were effectively collected and tested. 352 SUI patients with both above data were analyzed and then assigned to 4 groups according to postpartum no SUI, mild SUI (<1/ week), severe SUI (every day), and moderate SUI (between mild and severe). Results There were no significant differences at baseline expression of CCL7 between 4 groups. Compared to postpartum no SUI, the responsive expression of CCL7 was significantly low in the group of postpartum severe SUI (p<0.05). When CCL7 responsive expression standardized to the baseline expression, both groups of severe SUI (p<0.05) and moderate SUI (p<0.05) have lower CCL7 expression than group of postpartum no SUI. Conclusions The study demonstrated low local CCL7 responsive expression during sling procedure associated with postpartum SUI. CCL7 could become a biomarker indicating the risk of postpartum SUI. Delivery CCL7 might be an effective way to improve urinary continence immediately after birth injury. Funding NSF China 81670695; China America Promotion Society for Medical Doctors (CAPs MD)
Authors
Qi-Xiang Song
Hai-Yan Li Ling Qing Xiang-xiang Ye Limin Liao Hai-Hong Jiang |
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MP40-09 |
Establishment of a new large animal model for stress urinary incontinence using German landrace pigs |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Female Incontinence: Therapy I | 17BOS |
Abstract: MP40-09 Sources of Funding: none Introduction Stress urinary incontinence (SUI) is a serious problem amongst many women especially after giving child birth. In order to find a better treatment we established a large animal model displaying features of this disease. After evaluation of these animals the long-term goal will be to include this model in different preclinical projects to explore improved or novel methods for SUI diagnosis and therapy. Methods In this study, 9 female German landrace pigs (approx. 20 kg) were included. To induce incontinence group 1 (3 pigs) underwent dilatation of the bladder sphincter for 5 minutes using an 18 Chr balloon catheter filled with 20 ml liquid. Group 2 was treaded with an electro cautery by applying four distinct spots 1 cm from the bladder neck (10 sec, 16 Watt). Group 3 received a combination of dilatation and distal cauterisation (approx. 5 cm from the bladder neck). After 3 weeks standard (s-UPP) and high-definition urethral pressure profilometry (HD-UPP) were performed, the animals were sacrificed and the bladder tissue was harvested for cryo sectioning. AZAN and antibody stainings with reagents to desmin and fast myosin were performed to compare urethra from treated animals with control tissue. Results Immediately after treatment animals of all three groups showed a lower s-UPP or HD-UPP compared to the profiles obtained bevor surgical intervention. Only the urethral wall pressure of animals that received dilatation and cauterisation remained reduced after 3 weeks of observation. Animals from group 1 and 2 regenerated just fine and the UPP was even higher than before surgical intervention. _x000D_ AZAN staining and antibody stainings with desmin and fast myosin showed some morphological differences of the muscle tissue in animals of group 3 compared to group 1, 2 and the control. Additionally, signs of electro cautery were clearly visible in group 3._x000D_ Conclusions The study demonstrated that only dilatation combined with distal cauterisation of the urethra led to incontinent animals, whereas dilatation or proximal cauterisation alone showed no differences in the UPP after 3 weeks of observation. This animal model may represent a good source for further experiments to investigate improved methods for diagnosis or novel therapies for a damaged sphincter muscle. Funding none
Authors
Anika Albrecht
Alexandra Kelp Bastian Amend Mario Kluender Arnulf Stenzl Wilhelm K. Aicher |
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MP40-10 |
CAN URETHRAL BULKING AGENTS SALVAGE FAILED SLINGS? |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Female Incontinence: Therapy I | 17BOS |
Abstract: MP40-10 Sources of Funding: None Introduction While pubovaginal and midurethral slings are highly effective interventions for stress urinary incontinence (SUI), persistent or recurrent incontinence is not uncommon and can significantly impact patients' quality of life. Multiple studies have shown the relative success of repeat sling procedures in this population, however, not all patients desire further operative interventions. The goal of this study is to evaluate the efficacy of urethral bulking agents for SUI in the setting of failed prior sling which has only been studied in very small populations in the past. Methods This is a retrospective review of patients who underwent urethral bulking agent injections for a primary complaint of stress urinary incontinence following failed sling. The outcomes assessed were patient reported improvement, need for further interventions for incontinence and the Michigan Incontinence Symptom Index (M-ISI), which is a validated questionnaire that has a range of 0-32 for symptom score and 0-8 for bother score with higher scores indicating worse incontinence. Values for questionnaires were obtained from the patient's pre-procedure visit and following their last injection. Demographic data, type of prior sling procedure, and type of bulking agent utilized were also reported. Results From May of 2009 to March of 2016, 73 patient underwent injection of urethral bulking agents following failed sling. Of these patients, 49 had prior mesh midurethral slings, 20 had prior fascial pubovaginal slings, and 4 had undergone both procedures. Average time from sling placement was 40.5 months. Following injection, 67.1% of patients reported at least moderate improvement in incontinence, while 24.7% reported total resolution of incontinence and 32.9% endorsed minimal or no improvement. The majority of patients (75.3%) required further injections to maintain or augment their results. Only 19.2% of patients went on to undergo more invasive operative interventions for incontinence. Pre-procedure average M-ISI symptom score was 23.1 with a bother score of 5.2. Post-procedure, these values were 18.9 and 4.2 respectively. No difference was found in symptom resolution based on prior sling type or bulking agent used. Conclusions Urethral bulking agents are a viable option for improving SUI following failed sling procedures. The majority of patients have at least moderate improvement in symptoms and do not opt for more invasive interventions. Funding None
Authors
Elizabeth Dray
Anne Cameron Marybeth Hall J. Quentin Clemens John Stoffel |
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MP40-11 |
IS INITIAL RETENTION AFTER MACROPLASTIQUE® INJECTION A PREDICTOR OF SUCCESS? |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Female Incontinence: Therapy I | 17BOS |
Abstract: MP40-11 Sources of Funding: None Introduction To examine if initial postoperative urinary retention after transurethral Macroplastique® (MPQ) bulking agent injection for female stress urinary incontinence (SUI) is a predictor of success. Methods Following IRB approval, a prospective database of non-neurogenic women who underwent MPQ injection for SUI due to intrinsic sphincter deficiency under light anesthesia, and were followed for > 6 months was reviewed. Postoperative retention was defined as inability to void after injection requiring a catheter for 24-48 hours, or difficulty voiding immediately postoperatively (post void residual > 200 ml by bladder scan) as charted in the recovery room electronic medical record. Women on self-catheterization, with a supra-pubic tube, those who had a concomitant procedure, or with follow up < 6 months were excluded. Success was defined as patient reporting sufficient continence for not desiring any additional therapy, ie dry or with rare leakage at last visit. Patients were divided into Group 1: Retention post-operatively and Group 2: no retention postoperatively. Results From August 2011 to December 2013, 68 of 92 women met all inclusion criteria. Overall 24/68 (35%) patients had retention after surgery. Similar baseline demographics for Group 1 (N=24) and Group 2 (N=44) are shown in Table 1. Success was 88% for group 1 (21/24) versus 23/44 (52%) in group 2 (p<0.008) at median follow-up of 25 (7-52) months in group 1 and 24 (7-53) months in group 2. Similarly there was significantly higher number of patients who were completely dry in Group 1 (19/24) than in Group 2 (8/24) (p< 0.0001). Patients in Group 2 needed significant higher number of repeat endoscopic injections compared to Group 1 (p<0.002) Conclusions Postoperative transient retention was seen in nearly one third of women immediately after MPQ injection. At a median follow-up of 2 years, these women remained dry or were markedly improved, and did not desire additional SUI therapy more so than those who voided well initially. Funding None
Authors
Himanshu Aggarwal
Feras Alhalabi Philippe Zimmern |
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MP40-12 |
Robot-assisted artificial urinary sphincter implantation in female patients : a multicenter study |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Female Incontinence: Therapy I | 17BOS |
Abstract: MP40-12 Sources of Funding: none Introduction The morbidity related to artificial urinary sphincter (AUS) implantation in women is usually considered as the drawback which has limited its widespread. In order to decrease this morbidity, several teams have recently reported the use of a robotic approach to implant the AUS in female patients. The aim of this study was to report the perioperative and functional outcomes of robotic AUS implantation in women. Methods All female patients who underwent robotic AUS implantation between 2013 and 2016 in five institutions were included in a retrospective study. The indication for AUS implantation was type III stressurinary incontinence and intrinsic sphincter deficiency defined as a combination of a low urethral closure pressure (< 30 cm H2O), loss of urethral mobility and a negative Marshall/Bonney test (urine leakage on straining or coughing not corrected by urethral support). The robot-assisted approach was the only approach used for AUS implantation in women during the study period in the five institutions involved. The primary enpoint was the functional outcome categorized as : cured (complete continence, i.e. no pads used), improved (decrease > 80% in number of pads per day or in urine leakage assessed through pad test) or failure decrease < 80% in number of pads per day or urine leakage assessed through pad test). Results Forty patients underwent robotic AUS implantation by ten surgeons during the study period (1 to 12 procedures/surgeon). There were 6 intraoperative complications: 4 bladder neck injuries and 2 vaginal injuries. Nine patients experienced postoperative complications (22.5%) but only two were Clavien ?3 (5%) : one AUS explantation due to vaginal erosion and one reoperation for device infection. After a median follow-up of 12 months, explantation of the AUS device was needed in one case (2.5%) due to vaginal erosion. Thirty-five patients were cured of their incontinence (87.5%), three were improved (7.5%) and the procedure failed in two patients (5%)._x000D_ Conclusions This study is the first multicenter series asessing the outcomes of robotic AUS implantation in women. Despite a limited number of cases performed per surgeon, perioperative and functional outcomes appeared at least similar to those reported in large series of open AUS implantation from tertiary referral centers. Further data are needed tho confirm the findings of the present report. Funding none
Authors
benoit peyronnet
olivier belas gregoire capon sébastien vincendeau clément allenet andrea manunta lauranne tondut michel belas pierre callerot gilles pasticier stephane colla antoine valeri aurélien descazeaud grégoire robert georges fournier |
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MP40-13 |
The Impact of Perceived Stress and Health on Insomnia in Women with Overactive Bladder Symptoms |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Female Incontinence: Therapy I | 17BOS |
Abstract: MP40-13 Sources of Funding: Grant from Versacare (#5435 to AS). Introduction Sleep plays a vital role in health and overall quality of life. Insomnia, the difficulty of falling/staying asleep or nonrestorative sleep, is linked to numerous impairments in every major facet of life: physical, mental, emotional, and social. Elderly women who suffer from a medical condition (e.g., overactive bladder; OAB) have been found to be at a highest risk for insomnia. Previous research has focused on the impact of OAB on insomnia, with limited research focusing on other possible contributing risk factors. We aim to study the impact of perceptions of stress and general health on insomnia, while controlling for OAB in the vulnerable population of postmenopausal women. Methods Fifty-seven postmenopausal female patients over the age of 57 years presenting with OAB symptoms were recruited to study lower urinary tract symptoms and overall health-related quality of life. The Perceived Stress Scale was used to measure perception of stress. Perception of general health was measured using a single-item, “In general, your health is� (1 = excellent to 5 =poor). The Insomnia Severity Index was used to measure insomnia. OAB symptoms were measured using the Overactive Bladder Questionnaire. A hierarchical regression analysis was conducted to determine the effects of perceptions of stress and general health on insomnia, while controlling for OAB symptoms. Results The results indicated that perceived stress and general health accounted for 45.6% of the variance in insomnia, while controlling for OAB [F (3,46) = 12.86, p < .001]. Insomnia was significantly predicted by perceptions of stress (Beta = .451, t = 2.47, p < .05) and general health status (Beta = -4.47, t = 3.84, p < .001). Conclusions Insomnia in OAB patients is often attributed and dismissed to symptoms, such as nocturia, that keep them awake at night; however, the results suggest that other factors, not OAB-related symptoms, can contribute to insomnia. Physicians and other healthcare professionals should screen for potential risk factors, such as perceived stress and health, in order to provide their patients the necessary resources and to increase their overall quality of life. Funding Grant from Versacare (#5435 to AS).
Authors
K'dee Elsen
Christina Moldovan Jim Shen Mohamed Keheila Salim Cheriyan Matthew Pierce Andrea Staack |
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MP40-14 |
Cognitive Effects of transdermal Oxybutynin in Elderly patients with overactive bladder syndrome |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Female Incontinence: Therapy I | 17BOS |
Abstract: MP40-14 Sources of Funding: None Introduction Oxybutynin is a drug that has proven effective in the treatment of overactive bladder. With the oral presentation, a deterioration in cognitive function is described. The transdermal formulation has shown a decrease of the active metabolite of oxybutynin (N-DEO) involved in the onset of side effects._x000D_ Cognitive impairment of anticholinergic drugs are related to passage through the blood brain barrier and antagonism of M1 receptors in the central nervous system being the elderly population more susceptible._x000D_ Objective: To determine if there is impairment of cognitive function in elderly patients, between 65 and 80 years of age, treated with transdermal oxybutynin. As secondary objectives assessed the efficacy of the drug and adherence._x000D_ Methods Observational, retrospective, multicenter study._x000D_ Patients diagnosed with overactive bladder who met the criteria for inclusion / exclusion were assessed at office and treatment was indicated with Oxybutynin transdermal according to routine clinical practice and recommendations for use according to data sheet. Specific questionnaires pathology (Bladder Self-Assestment questionnaire (BSAQ), Patient Perception Bladder Control (PPBC)), of Adherence (Morisky-Green Test) and Assessment of Cognitive function (Impaired Memory, Test, Clock Drawing test) at the start and in the follow-up visit at 4 weeks of treatment were administered._x000D_ Statistical analysis: Results were treated with relative frequency measurement. For continuous variables, central tendency measures were used for comparisons Student t test, Wilcoxon and Chi-square test was used. The level of statistical significance was set at <0.05_x000D_ Results A total of 70 patients were evaluable with an average age of 71.37 years, 71.4% were women, 51.4% with basic education and 70% come from the urban environment with an average BMI of 28.68. Impaired Memory, Test results before and after treatment showed no significant differences in any of the areas of assessment of cognitive function. Similarly, no differences were observed in the Drawing Clock Test. Regarding adherence to treatment was 84% with improvement in symptoms and the PPBC and BSAQ questionnaires._x000D_ Conclusions In our study not impaired cognitive function in elderly patients with overactive bladder syndrome treated with transdermal oxybutynin was observed Funding None
Authors
Carlos Muller-Arteaga
Jose Emilio Batista Miranda Carmen Zubiaur Ainara Rabade Ferreiro Rafael El Khoury Moreno Gonzalo Morales Solchaga Javier Casas Nebra Manuel Leva Vallejo Oscar Gonzalez Garcia Salvador Arlandis-Guzman Carlos Errando-Smet |
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MP40-15 |
Use of third line therapy for overactive bladder in a practice with multiple subspecialty providers: are we doing enough? |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Female Incontinence: Therapy I | 17BOS |
Abstract: MP40-15 Sources of Funding: None Introduction Overactive bladder (OAB) impacts over 15% of the population over the age of 40. A recent review by Veenboer showed the median persistence rates for anticholinergic medications was 12-39% at one year, due either to minimal success or intolerable side effects. The introduction of third line therapies for OAB, including sacral neuromodulation, posterior tibial nerve stimulation, and intradetrusor injection of onabotulinumtoxinA, has improved the success rates for treatment of OAB. Despite availability of effective therapy for OAB, many patients do not receive optimal treatment. Here we examine the practice patterns and utilization of third line treatment in a tertiary referral center with expertise in female pelvic medicine and reconstructive surgery (FPMRS). Methods The electronic medical record was queried for all patients seen for OAB, from October 1, 2015 to September 30, 2016. Patients with a diagnosis of neurogenic bladder or BPH with obstruction were excluded. The number of visits associated with an OAB prescription and the number of patients who received third line therapy were determined and subcategorized by department, with FPMRS providers considered separately. Results 4,435 patients were seen for a total of 7,015 visits for OAB. 37% were seen in the urology department and 27% were seen by FPMRS providers. 30% of patients seen by urologists had an OAB prescription associated with their visit, compared with 16.6% of those seen in the institution as a whole. Of all the patients seen for OAB, 4.5% received third line therapy, compared with 11.7% and 15.8% of those seen in urology and by FPMRS providers, respectively. Conclusions Use of third line therapy for OAB has been reported to be less than 5%. This rate is higher at our institution, likely due to access to multiple FPMRS providers. The authors also use a care pathway that emphasizes early patient education on available options should they fail first and second line treatments. Even in a tertiary referral center it is likely that third line therapy is not being offered to many patients who would benefit from it. Our data demonstrate an opportunity for urologists to improve the quality of care and treatment success rates for OAB patients. Funding None
Authors
Dena Moskowitz
Sarah Adelstein Alvaro Lucioni Una Lee Kathleen Kobashi |
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MP40-16 |
Outcomes of treatment of stress urinary incontinence associated with female urethral diverticula: a selective approach |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Female Incontinence: Therapy I | 17BOS |
Abstract: MP40-16 Sources of Funding: none Introduction Female urethral diverticula (UD) may present with a variety of different symptoms including stress urinary incontinence (SUI). Surgical repair of SUI may be done concomitantly with urethral diverticulectomy. However, some surgeons may be reluctant to repair SUI at the time of urethral diverticulectomy due to the additional surgical time and potential morbidity of anti-incontinence surgery. We assessed surgical outcomes of the concomitant treatment of SUI at the time of transvaginal urethral diverticulectomy (TVUD) based on a selective approach. Methods Following IRB approval, we identified patients with a UD and SUI who underwent TVUD between July 2004 and January 2016. SUI was documented before and after surgery using subjective and objective parameters. Autologous pubovaginal slings (APVS) were used selectively based on surgeon and patient preference. Postoperatively, the majority of patients were imaged prior to catheter removal with voiding-cystourethrogram. Results A total of 61 patients underwent surgical treatment of urethral diverticula. There were 39 patients with UD and concomitant SUI. Mean age was 53 years (range 34-77). There were 22 Caucasians, and 17 African American patients. Mean follow-up was 16.2 months (range 1-72 months). There were 24 patients (62%) with SUI that underwent concomitant APVS. Of these 24 patients, 10 (42%) had prior SUI surgery. There was resolution of SUI in 20 of 24 patients (83%) who underwent a simultaneous APVS compared to 8 of 15 patients (53%) who underwent TVUD without APVS (2 patients lost to follow-up). One patient out of 22 developed de-novo SUI following TVUD. Surgery resulted in the improvement or resolution of the majority of preoperative symptoms including recurrent urinary tract infection (UTI) (82% vs. 15%), dyspareunia (64% vs. 8%), and urgency (56% vs. 13%) (preoperative vs. postoperative). Complications included two patients with prolonged urinary retention following APVS requiring sling lysis. There were 2 patients with a recurrent UD, one of which required repair 18 months post-operatively. Conclusions Female UD is often associated with SUI. Surgical reconstruction of UD often results in satisfactory control of urinary symptoms including SUI when both are treated concomitantly in those with bothersome symptoms. Treatment of SUI with APVS when undergoing TVUD is feasible with satisfactory outcomes. The decision whether or not to perform concomitant APVS at time of TVUD should be made on an individual basis after appropriate counseling. Funding none
Authors
Alyssa Greiman
Lauren Rittenberg Drew Freilich Ross Rames Ahmed El-Zawahry Michelle Koski Eric Rovner |
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MP40-17 |
Prospective randomized comparison of repairing simple vesicovaginal fistula with or without interposition flap: A tertiary care hospital study from Nothern India |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Female Incontinence: Therapy I | 17BOS |
Abstract: MP40-17 Sources of Funding: none Introduction Outcome assessment of simple vesicovaginal fistula (VVF) repair with or without the use of interposition flaps. Methods This prospective randomised study was conducted between 2012 to 2015 in department of Urology King George’s Medical University, Lucknow. Obstetric and gynaecologic fistula less than 4 cm were included. Those with complex or complicated fistula and fistula due to malignancy were excluded from this study. Patients were divided into two groups (group 1 and group 2) depending upon route of repair i.e. transvaginal or transabdominal respectively as per characteristics and location of fistula. These two groups were randomised into two subgroups (1A, 1B and 2A, 2B) based on with use and without use of interposition flap during fistula repair. Perioperative and post-operative parameters (blood loss, mean operating time, hospital stay, requirement of analgesics) were compared. All complications occurred in postoperative period till last follow –up were recorded and Clavien Dindo Classification was used to stratify them. Results _x000D_ Fifty-four patients underwent transvaginal repair- group 1 (27 with Martius flap-group 1A and 27 with no Martius flap – group 1B). Sixty-six patients underwent transabdominal repair-group 2 (33 with interposition flap- group 2A and 33 with no flap – group 2B). Blood loss, mean operating time, hospital stay, requirement of analgesics were comparable between sub-group 1A versus 1B; and 2A versus 2B. Overall success rate of repair across all groups was 92.7% (115/124). Success rate was 88.9% in transvaginal repair with martius flap versus 92.6 % in transvaginal repair with no flap (P=1.0) and it was 93.9 % in both subgroups of transabdominal repair (P=1.0). Mean follow up period was 33.6 months (range 12-46). 9 out of 27 patients (33.3%) with Martius flap interposition had significantly reduced sensation on labia majora. Of these 9 patients, 5 cases reported numbness and 4 had pain compared to patients in group IB who did not report any altered sensation in labia. (P = 0.001). Conclusions The success rates are similar in simple VVF repair irrespective of the use of interposition flaps. However, overall morbidity following repair with interposition flap is more when compared with repair without interposition flap either by transvaginal or by transabdominal route. Funding none
Authors
Vishwajeet Singh
RahulJanak Sinha Ankur Bansal Seema Mehrotra Kawaljit Singh |
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MP40-18 |
Hiatal Smooth Muscles: a Novel Anatomical Landmark for Female Nerve-Sparing Radical Cystectomy |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Female Incontinence: Therapy I | 17BOS |
Abstract: MP40-18 Sources of Funding: nond Introduction To histologically investigate the female fibromuscular construction and nerve distribution around the posterior and lateral regions of the vesicourethral junction. These findings will help improve the functional results seen after nerve-sparing radical cystectomy and clarify differences in elderly female cadavers, especially with regard to pelvic organ prolapse (POP). Methods Histological examination of 22 female cadavers with subsequent evaluation of immunohistochemistry was performed. Macroslices of 1) urethra, 2) anterior wall of the vagina and 3) inferomedial edge of the levator ani muscle was performed. Elastica Masson staining and immunohistochemical staining [anti-S100 protein, anti-neuronal nitric oxide synthase (nNOS), anti-vasoactive polypeptide (VIP), anti-tyrosine hydroxylase (TH), and anti-alpha smooth muscle actin (SMA)] was performed. Results The bladder detrusor merged with the vaginal wall smooth muscles in the posterior side of the urethra. Anterior and lateral parts of bladder detrusor were clearly separated from the urethral wall smooth muscles in the medial side of the upper reflection of the endopelvic fascia from the levator ani muscle to the external surface of the bladder. In 8 of the 22 cadavers, smooth muscle mass occupied in a space between the urethra and the inferomedial edge of the levator ani muscle and covered the inferior margin of the detrusor muscle. The rhabdosphincter was seen far inferior to the inferomedial edge of the levator. The endopelvic fascia contained abundant nerves coming from the pelvic plexus. The detrusor nerves entered the bladder and candidates of the cavernous and sphincter nerves ran inferomedially from the endopelvic fascia. Conclusions Smooth muscles and collagen fibers were found at the posterolateral corner of the vesicourethral junction in one-third of the cadavers (HSM). Autonomic nerve fibers innervating cavernous tissue and sphincter muscles run between the HSM and the urethra. There were variations in the ventrodorsal relationship between CSNs and DNs between cadavers. We report the first histological demonstration of nerves that innervate urethral sphincter in adult women. Funding nond
Authors
Nobuyuki Hinata
Ahmed Aly Hussein Tomoaki Terakawa Yukari Bando Gen Murakami Khurshid Guru Masato Fujisawa |
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MP40-19 |
Mirabegron in women with OAB: a real setting study |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Female Incontinence: Therapy I | 17BOS |
Abstract: MP40-19 Sources of Funding: none_x000D_ Introduction The aims of this study were to evaluate the medication adherence, the patient’s satisfaction and the improvement of symptoms and _x000D_ of quality of life in women with OAB after treatment with Mirabegron._x000D_ Methods This is an multicenter prospective study.Consecutive female patients affected by OAB were enrolled. Inclusion criteria were: women with OAB naïve, women with refractory OAB to antimuscarinic drugs. Exclusion criteria were:hypertension, renal and hepatic impairment, QT prolongation. Pre-treatment evaluation: microbiological analysis, abdominal ultrasonography, uroflowmetry (UF) with post-void residual (PVR) measurement and voiding diary (VD). They completed OABq- sf questionnaire. They received once-daily Mirabegron 50 mg for 6 months.They were followed up at 1,3,6 months post treatment with UF and PVR measurement and 3-days VD, OABq-sf, MMAS-4 sf, sVAS and PGI-I questionnaries. Statistical analysis : McNemar and Friedman tests, p-value <0.05 Results Ninety-two women (mean age of 56.4±13.4 years) were included in the study. 23 and 33 patients interrupted the treatment at 1 and 3 months respectively. Graph I (A,B) showed the discontinuation reasons. 36 out of 92 women were evaluated at 6 months with a high drug adherence (median MMAS-4 score of 0 (range 0-2) ). At 6 months follow-up patient’s satisfaction was high, infact median PGI-I and S-VAS were 2 (range 1-4) and 8 (2-10) respectively. At 1,3,6 months OABq-sf score showed a statistically significant improvement with a baseline median score of 36 (range 19-99), of 9 (range 7-24) at 6 months (p=0.001). Graph 1C showed an improvement of all the OAB symptoms at 1 and 3 months, but they were stable at 6 months. Furthermore a statistically significant decrement of the mean number of pads/die was evident at 6 month (1.45±1.58 vs 0.57 ± 0.98 p<0.0001).UF results showed no statistical changes at 1 month and at 6 months.The results are not different in women with OAB naïve and women with OAB refractory to antimuscarinic drugs Conclusions Mirabegron 50mg showed significant subjective and objective efficacy with a high in women with OAB at 1 and 3 months of treatment. For the low side-effects and its impact on QoL, it can be considered the first line therapy in these patients. Long term results are mandatory for patients perspective and counselling for tailored therapy._x000D_ _x000D_ _x000D_ Funding none_x000D_
Authors
Ester Illiano
Raffaele Balsamo Martina Milanesi Vincenzo Li Marzi Enrico Finazzi Agrò Franca Natale Stefania Maddonni Elisabetta Costantini |
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MP40-20 |
DO SURGEONS WISH TO KNOW ABOUT THEIR LONG-TERM COMPLICATIONS? |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Female Incontinence: Therapy I | 17BOS |
Abstract: MP40-20 Sources of Funding: None Introduction Inspired by our experience with handling long-term vaginal mesh complications, we aimed to assess practitioner&[prime]s interest in being made aware of their long-term surgical complications. Methods Prior to a lecture on this topic, a 3 question survey (table 1) was administered to 16 faculty operative surgeons (FS) in the Department of Urology and to 59 future attendants who had enrolled to attend the lecture, including private practice urologists, nurse and midlevel providers. Long-term complications were defined as those involving re-admissions or reoperations beyond 30 days post-surgery as those are not captured by most quality improvement programs and not reported in Morbidity and Mortality conferences. Results Of the 16 FS, 100% answered that doctors should be alerted of their post-surgical complications (question 1). And, of the lecture attendants, 95.6% also stated they wished to be alerted (10 skipped). Based on the second question on reasons for why we do not contact each other when we are made aware of a long-term complication, 60% of the FS and 53% of the attendants believed that a surgeon might not want to offend or lose a referral base. 13% of FS and 21% of attendants believed that surgeons not knowing his/her own outcomes data was a possible reason. 13% of surgeons and 21% of the attendants believe that the unwillingness to want to increase the operative surgeon&[prime]s legal risk could be a reason. 20% of surgeons and 17% of attendants believed that a surgeon might not think feedback decreases complication risks. Lastly 73% of FS and 72% of attendants believed that a surgeon being too busy to track down whom to contact is a primary reason. As far as the best method of providing this long-term tracking data (question 3), 94% of the FS and 84% of the attendants answered that a phone call was the best means for this feedback. The practicality of providing this feedback is hampered by unintended consequences of legal mandates related to patient protected health information. Conclusions Despite legal barriers in place prohibiting this process, this data suggest that operative surgeons and most urology care providers are interested in receiving information on their long-term post-surgical complications. Funding None
Authors
Jennifer Wimberly
Shawn Okpara Philippe Zimmern |
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MP41-01 |
Extracellular Vesicles Regulate Glomerular VEGF Homeostasis in Chronic Kidney Disease |
Stem Cell Research | 17BOS |
Abstract: MP41-01 Sources of Funding: CIRM, Alport Syndrome Foundation Introduction Tight regulation of paracrine VEGF signaling between podocytes and glomerular endothelial cells (GEC) is required for maintenance of the glomerular filtration barrier (GFB) structure and function. Disruption of VEGF homeostasis has been implicated in various types of glomerular diseases. However, current therapies neither specifically target the glomerulus nor the VEGF pathway but in addition present multiple side effects. Therefore, identification of new approaches aimed at restoring local VEGF remains a potential therapeutic target to treat glomerular disease. _x000D_ _x000D_ We previously showed that amniotic fluid stem cells (AFSC) are renoprotective in Alport Syndrome (AS), a model of CKD. They home within the diseased glomeruli and secrete extracellular vesicles (EVs). EVs play key role in stem cell mediated paracrine function, including the kidney. Herein, we demonstrate that AFSC derived EVs regulate VEGF/VEGFRs signaling balance in AS GEC via modulation of sFlt1, the soluble isoform of VEGFR1. _x000D_ Methods We measured VEGF activity in AS glomeruli by WB. We assessed VEGF/VEGF-Rs activity in GEC, including the sFlt1. We characterized AFSC-EVs cargo by FACS and by miRs arrays and evaluated their potential to affect VEGF biology in GEC. Results Glomeruli from AS mice showed increased VEGF activity through increased phosphorylation of VEGFR-2 early on during progression accompanied by modulation of sFlt1. These observations were associated with GEC damage that showed altered VEGFR signaling. Importantly, EVs presented with VEGFRs and angiomodulatory microRNA. These EVs successfully integrated within GEC and modulated VEGF activity. EVs lacking both the full and soluble VEGFR-1 failed to rescue GEC from VEGF inflicted damage. Conclusions In conclusion, we demonstrated for the first time the aberration of VEGF signaling within AS glomeruli. We further showed that AFSC derived EVs play important role in maintaining glomerular homeostasis of VEGF signaling, presenting with a potential for new targeted therapies in CKD. Funding CIRM, Alport Syndrome Foundation
Authors
Sargis Sedrakyan
Valentina Villani Stefano Porta Stefano Da Sacco Nikita Tripuraneni Andrea Achena Maria Lavarreda-Pearce Hasmik Soloyan Roger De Filippo Benedetta Bussolati Laura Perin |
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MP41-02 |
Prophylaxis against renal ischemia reperfusion injury in canine model: stem cell approach. |
Stem Cell Research | 17BOS |
Abstract: MP41-02 Sources of Funding: This project was supported financially by the Science and Technology Development Fund (STDF), Egypt, Grant No 4713) Introduction To date, there is no evidence exploring the protective effects of stem cells on minimizing ischemia reperfusion injury in a higher animal model. Methods A group of 60 dogs were maintained to perform kidney injury model. Ischemia of 90 minutes were performed by open occlusion of left renal artery in 57dogs. Group I included 27 dogs that were treated with Bone marrow derived Mesenchymal Stem cells (BM-MSC) while group II (27 dogs) treated with adipose tissue derived Mesenchymal Stem cells (AT-MSC). Each group was divided into 3 subgroups (9 dogs each), according to the stem cell dose (5, 10, 15 X 10 Results In group I, there was mean reduction of clearance of the investigated kidney by a mean of 78%,64% and 74% of the three used doses respectively at 2 weeks. At 3 months, these kidneys regained a mean of 84%, 92% and 72% respectively of its basal function. In group II, the reduction of clearance was much more modest with mean of 14%, 6% and 24% respectively at 2 weeks with more intense recovery of renal function by mean of 90%,100% and 76% respectively. Positive control showed more intense reduction of clearance by 90% at 2 weeks that regained 70% of basal function at 3 months. On histopathologic examination in group I, there was more significant tubular necrosis and delayed regeneration compared with group II. The histopathological insult was more pronounced in the control group with more delayed recoverability. Expressions of Pro-inflammatory markers were up regulated in both groups with higher and more sustained expression observed in group I. Conclusions Stem cell might protect against the ischemia reperfusion injury in canine model. AT-MSC would provide the best protective potentiality compared with BM-MSC. Funding This project was supported financially by the Science and Technology Development Fund (STDF), Egypt, Grant No 4713)
Authors
Yasser Osman
Sahar M. Hamed Nashwa Barakat Sherry Khater Mahmoud Gabr Ahmed Mosbah Mohamed Gaballah Atallah Shaaban |
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MP41-03 |
Five-year clinical effects of donor bone marrow cells infusions in kidney allograft recipients |
Stem Cell Research | 17BOS |
Abstract: MP41-03 Sources of Funding: none Introduction Augmentation of microchimerism in solid organ transplant recipients by donor bone marrow cells (DBMC) infusion may promote immune hyporesponsiveness and consequently improve long-term allograft survival. Methods Between March 2005 and July 2007, outcomes for 20 living unrelated donor (LURD) primary kidney recipients with concurrent DBMC infusion (an average of 2.19 ± 1.13 x 109 donor cells consisting of 2.66 ± 1.70 x 107 CD34+ cells) were prospectively compared with 20 non-infused control allograft recipients given similar conventional immunosuppressive regimens. Results With five years of clinical follow up, a total of 11 cases experienced rejection episodes (3 DBMI patients vs. 8 controls, p = 0.15). One DBMCinfused iopsy-confirmed) in the control patients. Actuarial and death-censored 5-y graft survival was significantly higher in infused patients compared with controls (p = 0.01 and p = 0.03, respectively). Long-term graft survival was significantly associated with pre-transplant anti-HLA antibodies (p= 0.01), slightly with peripheral microchimerism (p = 0.09) and CD4+CD25+FoxP3+ T cells (p = 0.09). Immunosuppressant dosing was lower in infused patients than controls, particularly for mycophenolate mofetil (p = 0.001). Conclusions The current findings as well as our previous reports on these patients indicates clinical improvement in long-term graft survival of renal transplant patients resulting from low-dose DBMC infusion given without induction therapy. Funding none
Authors
Ghasem Solgi
Vijayakrishna Gadi Gholamreza Pourmand Abdolrasoul Mehrsai Moslem Ranjbar Mousa Mohammadnia Behrouz Nikbin Ali Akbar Amirzargar |
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MP41-04 |
The efficacy of CHA1 mesenchymal stem cell in a chronic interstitial cystitis rat model |
Stem Cell Research | 17BOS |
Abstract: MP41-04 Sources of Funding: Korea Healthcare Technology R&D project, Ministry for Health, Welfare & Family Affairs, Republic of Korea (HI13C1398) Introduction To examined the therapeutic effects of mesenchymal stem cell (CHA1) on damaged bladder tissue in a chemically induced chronic interstitial cystitis (IC) rat model. Methods Female 10-week-old Sprague-Dawley rats were used for induction of chronic IC model._x000D_ Chronic IC model was induced with single intravesical instillation of protamine sulfate (0.5ml of PS, 30mg/ml) and lipopolysaccharide (0.5ml of LPS, 2.25mg/ml) for 1 month. Rats were divided into three groups (N=5~7): non treated control group(Control), sham operation group(Sham), chronic IC receiving a single bladder submucosal injection of phosphate-buffered saline (20 mL, PBS) or chronic IC treated with CHA1 (5×105 cells/20 μL, IV or BL(submucosa injection)). Four weeks after treatment, voiding spot was obtained using 6hr metabolic cage and analyzed with Image J program. The bladder was harvested for histologic examinations and toluidine blue staining for mast cell. All animal experiments were approved by the Institutional Animal Care and Use Committee at our institution._x000D_ Results Rats in the IV and BL group showed increased voiding frequency and decreased the spot size compared with control sham group (p<0.05). Significant improvement of voiding spot pattern in size was observed in the CHA1 treated IV and BL groups compared with PBS group (Figure 1). Hematoxylin/eosin staining demonstrated that loss of urothelial integrity in PBS group was restored in IV and BL group. Neutrophil infiltration was also decreased in IV and BL group compared with PBS group. Histological examination revealed a significant decrease in the total number of infiltrated mast cells in IV and BL rats compared with the PBS rats (p<0.05), (Figure 2). Conclusions This is the first study to investigate the efficacy of CHA1 for chronic IC model. Submucosal injection of CHA1 in chronic IC showed improvement of voiding pattern and histological restoration and this suggest that CHA1 might have a therapeutic potential for IC. Further studies are required to evaluate the mechanism of CHA1 treatment. Funding Korea Healthcare Technology R&D project, Ministry for Health, Welfare & Family Affairs, Republic of Korea (HI13C1398)
Authors
Kyung Hwa Choi
Young Eun Lee Seung Ryeol Lee Young Kwon Hong Dong Soo Park Jae Yup Hong |
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MP41-05 |
Biofabricated Bone Marrow-derived Cell Patches Restore Structure and Function of Radiation-Injured Urinary Bladders in Rat |
Stem Cell Research | 17BOS |
Abstract: MP41-05 Sources of Funding: None Introduction We showed that both injections and cell sheets of isolated single bone marrow-derived cells could restore structures and functions of radiation-injured urinary bladders. However, they had some limitations. Thus, we biofabricated bone marrow-derived cell patches with a bio 3-dimentional printer, Regenova (Cyfuse Biomedical K.K., Tokyo, Japan). We determined if the patches could restore structures and functions in the irradiated urinary bladders. Methods Twenty-four female 10-week-old Sprague-Dawley (SD) rats were irradiated with 2 gray once a week for 5 weeks. Bone marrow cells harvested from six male 17-week-old green fluorescence protein-transfected SD rats were cultured on collagen-coated dishes and flasks. The cultured bone marrow-derived cells were placed into U-type 96-well plates (3.0-5.0x10^4cells/100?l/well) to form spheroids. The spheroids were located on 9x9 arrayed needles of 4 mm square, and then it was accumulated with 3 layers. The accumulated spheroids were cultured in the perfusion chamber. After 7 days, the fused structures (patches) were pulled out from the needles. Each patch was transplanted into the irradiated anterior bladder wall (n=10). As controls, sham operations were performed (n=14). After 4 weeks, the urinary bladders were analyzed. Results In cystometric investigations, voiding interval and micturition volume in the patch-transplantation group were higher than those in the control group. Residual volume of the patch-transplantation group was lower compared to the control. At 4 weeks after, the transplanted patches detected on the bladder walls were organized into the recipient bladders (Fig.1A), and had blood vessels derived from the recipient tissues. In addition, there were many differentiated smooth muscle cells within the patches (Fig.1B-D). The chub-transplanted bladders reconstructed smooth muscle layers and nerve fibers. Conclusions The biofabricated bone marrow-derived cell patches could reconstruct structures and improve bladder functions in the irradiated urinary bladders. Funding None
Authors
Tetsuya Imamura
Teruyuki Ogawa Tomonori Minagawa Takashi Nagai Gautam Sudha Tetsuichi Saito Mitsuru Shimamura Nanami Hatakeyama Masaki Nakazawa Osamu Ishizuka |
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MP41-06 |
Multipotent adult progenitor cell treatment promotes bladder function recovery and decreases morbidity and duration of urinary tract infection in spinal cord injured rats |
Stem Cell Research | 17BOS |
Abstract: MP41-06 Sources of Funding: DARPA: W911NF-15-1-0074 Introduction Severe urinary tract infections (UTIs) in association with neurogenic bladder are common complications of spinal cord injury (SCI). In previous studies multipotent adult progenitor cell (MAPC®) treatment of SCI in rats improved locomotor and bladder (i.e., voiding volume and frequency) function recovery. This study investigated morbidity of UTIs following MAPC cell treatment of SCI in rats. Methods This study was a randomized, blinded, sham-controlled study in female Sprague-Dawley rats comparing intravenous treatment with 4 x 106 human MAPCs (n = 11) vs. saline (n = 11) at 24-hours post-SCI. Contusion SCI was induced at T8 using an Infinite Horizon Impactor (250 kilodyne impact). Bladders were manually expressed twice daily for 4 weeks post-SCI, and prophylactic antibiotic was administered for the first 5 days post-SCI. Rats with prolonged UTI symptoms or recurrent UTI episode received additional antibiotic treatment until the UTI resolved. The time and duration of the UTIs in the first 28 days post-SCI were recorded. Voiding frequency and volume were measured using metabolic cages at weeks 4, 6, 8 and 10 post-SCI. Results During the first 4 weeks post-SCI, only 3 of 11 (27%) MAPC cell -treated SCI rats compared to 8 of 11 (73%) saline-treated SCI rats had prolonged UTIs or recurrent episodes that needed additional antibiotic treatment (p = 0.03, Chi-sq). The duration of UTI was significantly shortened with the MAPC cell treatment compared to the saline treatment (2.4 vs. 5.4 days, p = 0.03, t-test). The MAPC cell-treated rats showed significant improvement in bladder function, evidenced by decreased voiding volume (p < 0.05, Fisher LSD, at week 8) and increased voiding frequency (p = 0.05, t-test, at week 4) compared to the saline-treated controls. Conclusions To our knowledge, this is the first report of MAPC cell treatment decreasing the morbidity and duration of UTIs in rats with SCI. MAPC cell treatment may decrease UTIs as a result of the positive effect of treatment on voiding volume and frequency, though the decrease in UTIs occurred prior to the measurement of improvement in voiding volume and frequency makes it possible that MAPC cell treatment may decrease UTIs through a mechanism distinct from or in addition to their positive impact on bladder function (e.g., MAPC cells may enhance anti-bacterial immunity, thereby reducing UTIs). These results suggest that MAPC cell treatment of SCI patients may decrease their UTIs, improving quality of life. Funding DARPA: W911NF-15-1-0074
Authors
James Jones
Marc DePaul MaiHua Zhu Bradley Lang Sarah Busch Cynthia Gregory Michael Rutten Lisa Buckley Kenton Gregory Hua Xie |
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MP41-07 |
Preclinical study and long-term in vivo confocal imaging of human embryonic stem cell derived multipotent stem cells targeted to interstitial cystitis/bladder pain syndrome |
Stem Cell Research | 17BOS |
Abstract: MP41-07 Sources of Funding: none Introduction Interstitial cystitis/bladder pain syndrome (IC/BPS) and ketamine induced cystitis (KC) are uncontrolled diseases which are characterized by severe pelvic pain and urinary frequency. Here, we show superior therapeutic efficacy of multipotent stem-cells (M-MSC) derived from human embryonic stem-cells (hESC) and long-term in vivo tracing of them. Methods We used three kinds of IC/BPS and KC rat model in order to show all major pathophysiology of IC/BPS and KC._x000D_ The therapeutic effect of M-MSCs was examined by awake cystometry, immunohistochemistry staining (H&E, Toluidine blue, Masson’s trichrome, TUNEL) after 1 week of MSCs injection. Additionally, we examined the expression of genes related to inflammation, mast cell infiltration and apoptosis by performing RQ-PCR analysis to show therapeutic effect underlying the benefits of M-MSC therapy after 1 week of transplantation.To confirm tumorigenesis or immune mediated transplant rejection of MSC, we performed micro-PET and autopsy after 1 year of transplantation of M-MSC. Furthermore we investigated mechanism of MSC therapy using longitudinal monitoring of infused M-MSCs using confocal micro-endoscopy and microscopy in living rat model after 6 months of transplantation of M-MSCs._x000D_ Results A single local transplantation of M-MSCs was effective to treat the IC and KC bladders as evidenced by ameliorated bladder voiding function and characteristic pathological features. In particularly, the therapeutic potency of M-MSCs was superior to that based on human umbilical cord blood-MSCs, reducing a required cell number up to 10 folds. Any adverse outcome regarding abnormal growth was not observed in either animal during 1 year investigation by micro-PET and autopsy. Longitudinal monitoring of infused M-MSCs using confocal micro-endoscopy and microscopy in living rat model demonstrated that living green florescent protein tagged cells keep alive and integrated as urothelium layer as well as vascular structure after 6 months of transplantation of M-MSCs. Conclusions This study provides the first evidence of the superior therapeutic efficacy, long-term safety, in vivo graft survival, and possible therapeutic mechanism of hESC-derived M-MSCs in preclinical studies. Funding none
Authors
Aram Kim
Hwan Yeul Yu Jisun Lim Ju Young Han Chae-Min Ryu Jun Ki Kim Hyung-Min Chung Dong-Myung Shin Myung-Soo Choo |
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MP41-08 |
CCR1 and CCL7 enhances mesenchymal stem cells engraftment after simulated birth injury |
Stem Cell Research | 17BOS |
Abstract: MP41-08 Sources of Funding: The First Affiliated Hospital of Wenzhou Medical University, NSF China 81670695, and China America Promotion Society for Medical Doctors (CAPs MD) Introduction Birth trauma is a widely recognized risk factor in the genesis of stress urinary incontinence (SUI) in women. Cell-based therapies for SUI have shown promising results. However, the treatment effects of mesenchymal stem cells (MSCs) transplantation are limited due to poor survival and engraftment in the injured tissues. Previous studies have shown that chemokine (C-C motif) ligand 7 (CCL7) production is increased significantly at the injured tissues around pelvic outlet after simulated birth injury. CCL7 enhances MSCs homing through interactions with its receptor, particularly C-C motif receptor 1(CCR1), on MSCs. We aim to determine if overexpression of CCR1 in MSCs and treatment with CCL7 can improve MSCs survival, migration, and engraftment after simulated birth injury. Methods Sprague Dawley rat MSCs were retrovirally transfected with enhanced green fluorescent protein (eGFP) or CCR1-eGFP. GFP expression in MSCs was evaluated and GFP-positive MSCs were sorted using flow cytometry. Migration and survival of CCR1-overexpressing MSCs stimulated by CCL7 were tested in vitro. In vivo, MSCs were intravenously administrated, and CCL7 or saline was injected suburethrally after simulated birth injury, vaginal distension. The injured tissues around pelvic outlet, including urethra and vagina, were harvested for analysis of MSCs homing 1 days or 1 week after simulated birth injury. Results In vitro, CCL7 stimulation increased migration of CCR1-overexpressing MSCs significantly (p<0.01), and protected CCR1-MSCs from apoptosis 12 hours after serum withdrawal (p<0.05). Quantitative analysis of MSCs in injured tissues around pelvic outlet demonstrated intravenous administration of CCR1-overexpressing MSCs and suburethral injection of CCL7 increased MSCs homing significantly both 1 day and 1 week after simulated birth injury (p<0.05). Conclusions Treatment of CCR1-overexpressing MSCs with CCL7 enhances their migration and survival in vitro. Intravenous administration of CCR1-overexpressing MSCs combined with suburethral injection of CCL7 increased MSCs engraftment, and may be a new therapeutic strategy for birth trauma-related SUI. _x000D_ Funding The First Affiliated Hospital of Wenzhou Medical University, NSF China 81670695, and China America Promotion Society for Medical Doctors (CAPs MD)
Authors
Hai-Hong Jiang
Jian-Li Feng Qi-Xiang Song Qi Ling Guiming Liu |
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MP41-09 |
Adipose-derived stromal vascular factor (SVF) injection in short recurrent bulbar stricture post DVIU – An initial experience |
Stem Cell Research | 17BOS |
Abstract: MP41-09 Sources of Funding: None Introduction _x000D_ A recent study showed that adipose-derived stem cells are able to counteract urethral stricture formation in rats. The aim of this study was to evaluate the feasibility of autologous adipose derived stromal vascular fraction (SVF) transplantation into male urethra stricture walls after direct vision incision of urethra (DVIU). _x000D_ Methods A prospective clinical study was undertaken after ethics approval and appropriate patient consent. The inclusion criteria were: male patients older than 18 years, with single short recurrent not-obliterating urethral stricture (<2 cm). The exclusion criteria were: patients not willing to consent, multiple strictures and those not deemed suitable for endoscopic management. Failure was defined as need for further interventions._x000D_ Preoperative workup included history, examination, retrograde urethrogram (RGU), voiding cystourethrogram (VCUG), urine culture, renal function tests, AUA score, IIEF, PROM. Plastic surgery team performs liposuction to extract 50 mls of fat from the patient’s abdominal wall. 50ml fat-SVF was obtained using a Goog Manufacturing Practice collagenase (Celase®, Cytori Therapeutics, San Diego, USA) according to a standard protocol. SVF was diluted in 5 ml saline solution for the injection. _x000D_ A cystoscopy was performed and the stricture evaluated, a glide wire was placed and an urethrotomy performed at 6 o’clock position in bulbar urethra. Gide wire was left in situ. The SVF solution was injected at the site of the stricture and on either side of the stricture. A 12 Fr urinary catheter was placed. The urinary catheter was removed after 24 hrs. Follow up was of 3.5 months._x000D_ Results Two patients were included in the study. The main characteristics are reported in table 1. No local or systemic side effects or complications were recorded. No recurrence of urethral stricture was detected in both patients after 3.5 months. _x000D_ Table 1 Conclusions This is the first study to demonstrate a successful autologous SVF transplantation in male urethral stricture after DVIU. Further studies are necessary to confirm the efficacy of SVF in preventing urethral stricture recurrence. Funding None
Authors
Pankaj Joshi
Fabio Castiglione Devang Desai Sandesh Surana Hazem Orabi Sanjay Kulkarni |
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MP41-10 |
Modelling prostate cancer using primary and metastatic canceroids |
Stem Cell Research | 17BOS |
Abstract: MP41-10 Sources of Funding: Swiss National Funds Introduction Prostate cancer (PCa)-associated mortality results from metastasis to bone and resistance to androgen deprivation or cytotoxic therapy. Despite early detection of primary PCa, advanced castration resistant prostate cancer (CRPC) and bone metastases (BM) are detected in 10% of patients already at the time of initial diagnosis. The majority of recurrences might be due to therapy resistant cancer cells with stem cell-like properties (cancer stem cell-like, CSC-like). CSC-like cells are highly tumorigenic and metastatic, however, current treatments target the differentiated tumor bulk cells. Our aim is to determine whether CSC-like cells from metastases tissues are responsive to the standard compounds used for the treatment of the primary tumor type. Methods To model metastatic CSC-like cells we have generated organoids (here termed as &[raquo]canceroids&[laquo]) from patient-derived biopsies and established patient-derived xenografts (PDXs). Cytotoxic compounds and androgen inhibitors are being tested on the canceroids from different BM or LN tissues in order to determine whether agents targeting the primary tumor are effective in the metastases. Viability assays and light sheet microscopy imaging are used. Results We have successfully derived canceroids from bulk tumor tissues, in particular; primary PCa, bone metastasis from PCa tissue (BM-PCa), established metastatic PDX models LAPC9 and BM18 and lymph node (LN) metastasis from PCa (LAPC4) PDX models. Canceroids maintain key features of the original tumor; the known luminal phenotype of BM18 is evidently maintained in the BM18 canceroids, based on positive cytokeratin (CK)18 and absent CK5 expression. LAPC4 organoids contain CK5 and CK18 cells, in line with the mixed basal and luminal phenotype. BM18 and LAPC9 canceroids are maintained in presence and absence of dihydrotestosterone in order to determine whether they adjust to androgen (in)dependent status of growth. Ongoing studies involve growth response of BM-PCa, BM18, LAPC4 and LAPC9 canceroids to chemotherapeutics (cabacitaxel, docetaxel) and hormone inhibitors (abiraterone, enzalutamide). Conclusions Identification of the oncogenic properties of metastatic CSC-like (sub)populations has both prognostic and therapeutic applications. Establishment of CSC-derived organoids from BM tissue is the first step towards routine derivation from metastasis or primary PCa tissues as a potential platform for personalized drug compound evaluation. Funding Swiss National Funds
Authors
Sofia Karkampouna
Federico la Manna Eugenio Zoni Lijkele Beimers Peter Kloen Antoinette Wetterwald Joel Grosjean Irena Klima Marco G. Cecchini Martin Spahn George N. Thalmann Marianna Kruithof-de Julio |
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MP41-11 |
A pilot clinical study to evaluate the efficacy and safety of docetaxel with ribavirin in patients with progressive castration-resistant prostate cancer targeting stem-cell related gene network. |
Stem Cell Research | 17BOS |
Abstract: MP41-11 Sources of Funding: none Introduction We previously reported a novel cell reprogramming approach, termed drug efficacy reprogramming, as a new model for identifying candidate antitumor drugs targeting the cancer stemness-related gene network, and identified ribavirin as a candidate drug for overcoming docetaxel-resistant castration-resistant prostate cancer (CRPC). This nonrandomized, open-labeled pilot clinical study explored the safety and efficacy of ribavirin, an antiviral drug, in combination with docetaxel in patients with progressive CRPC. Methods In this clinical study, patients received intravenous docetaxel 60–70 mg/mm2 on day 1 of 3–6-week cycles plus ribavirin 600 mg twice daily. The primary endpoint was safety, prostate-specific antigen (PSA) response and objective response rate. Secondary endpoints included health-related quality of life and overall survival. Patients with progressive CRPC based on PSA and/or radiographic criteria, performance status (PS) 0–1, and normal renal and hepatic function were eligible. Results Five patients were enrolled in this study; medium age was 73. Median serum PSA concentration was 53.1 ng/ml (range: 5.1–370.5). The median cycle and total dose of docetaxel received before the study was 31 cycles and 3625 mg, respectively. Overall, 80% of patients had disease progression during docetaxel treatment. The median time from last docetaxel dose to disease progression before participation was 1.5 months. Safety: median number of treatment cycles were 7 (range: 3–8) cycles. Grade 3/4 adverse events requiring dose modification were not observed. Grade 3 anemia and neutropenia were seen in two patients. Common adverse events were less than Grade 2. Efficacy: 3 (60%) patients had some degree of PSA decline and 2 (40%) had a decline of ?30%. Median follow-up was 10.0 months. Median progression-free survival was 6 months. Conclusions This combination of ribavirin with docetaxel was well tolerated with a promising response rate that justifies further investigations in docetaxel-resistant CRPC. This clinical study provides a useful drug re-positioning model in the area of translational medicine. Funding none
Authors
Takeo Kosaka
Takahiro Maeda Hirohiko Nagata Shunsuke Yoshimine Hiroshi Hongo Toshiaki Shinojima Mototsugu Oya |
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MP41-12 |
INDUCTION OF PROSTATE CANCER STEM CELL PROPERTIES IN MOUSE INDUCED PLURIPOTENT STEM CELLS VIA DEFINED CARCINOMA NICHE AND TRACKING DRUG RESPONSE IN PRECLINICAL RESEARCH |
Stem Cell Research | 17BOS |
Abstract: MP41-12 Sources of Funding: An efficient approach to enrich CSCs is extremely important for advancing cancer research. In current study, we converted mouse iPS cells into prostate CSCs with defined carcinoma niche. It is noteworthy that these induction CSCs model displayed stemness accompanied by high tumorigenicity, which could help design better agent for cancer therapeutic and suppress cancer relapse. Introduction Cancer stem cells (CSCs), that closely correlated with tumor growth, metastasis and provide a plausible explanation for chemoresistance and cancer relapse. CSCs were isolated and enriched from carcinoma cells usually, which were inconvenient, low-efficient, and even unreliable. The purpose of this study was to establish prostate CSCs converted from mouse induced pluripotent stem (iPS) cells, that would allow us to monitoring tumor progression and tracking novel drug response. Methods We converted mouse iPS cells into prostate CSCs with defined carcinoma microenvironment following exposure to conditioned medium (CM) derived from RM9-KLK3, a mouse prostate cancer cell line encoded by human KLK3/PSA gene. We also evaluated the expression of various stemness genes and cancer stem cell surface markers, including Oct3/4, Sox2, Nanog, Klf-4, c-Myc, CD44 and CD133, accompanied with the prostate special antigen (PSA) in these cells. In addition, in vivo transplantation experiment was performed to confirmed the tumorigenicity. Furthermore, we used these model on assess new drug response. Results These induction CSCs expressed embryonic stem cell markers, accompanied by significantly elevated expression of CSCs surface markers and PSA. Moreover, after subcutaneous injection into C57BL/6 mice, these cells displayed high tumorigenicity. The tumor derived from CSCs exhibited malignant phenotype and showed high expression of Ki-67 and CD31. We also confirmed that novel drug, such as cancer stemness inhibitor suppressed these induction cells significantly compared to the chemotherapy (in vitro and in vivo assay). RT-PCR and Western blot analysis suggested the possible mechanism underlying this effect was dependent on suppressing cancer stemness. Conclusions An efficient approach to enrich CSCs is extremely important for advancing cancer research. In current study, we converted mouse iPS cells into prostate CSCs with defined carcinoma niche. It is noteworthy that these induction CSCs model displayed stemness accompanied by high tumorigenicity, which could help design better agent for cancer therapeutic and suppress cancer relapse. Funding An efficient approach to enrich CSCs is extremely important for advancing cancer research. In current study, we converted mouse iPS cells into prostate CSCs with defined carcinoma niche. It is noteworthy that these induction CSCs model displayed stemness accompanied by high tumorigenicity, which could help design better agent for cancer therapeutic and suppress cancer relapse.
Authors
Naijin Xu
Xiezhao Li Aibai Xu Masami Watanabe Peng Huang Yasutomo Nasu Chunxiao Liu |
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MP41-13 |
Amniotic Fluid for the Treatment of Erectile Dysfunction |
Stem Cell Research | 17BOS |
Abstract: MP41-13 Sources of Funding: None Introduction There is demand for a non-pharmaceutical approach to treating Erectile Dysfunction (ED). Proflo is Amniotic Fluid (AF) which contains various cytokines and growth factors and is believed to facilitate angiogenesis and decrease inflammation. Therefore, it may prove to be a non-pharmacologic, long-term, cost effective alternative to treat ED. _x000D_ To determining the effectiveness of AF as a sustainable treatment for ED_x000D_ Methods A retrospective chart review of patients injected with ProFlo AF was performed. Proflo is amniotic fluid from a FDA cleared tissue bank, Vivex. It meets all the criteria to be regulated under the Public Health Service Act section 361. It is minimally manipulated, not combined with anything, not dependent on the metabolic activity of living cells, and being used homologously, since it is from the Genitourinary System and being used on the Genitourinary system. According to FDA draft guidance, Amniotic Fluid is a nonstructural biologic product that serves a biochemical role. A Penile Doppler measuring peak systolic velocity (PSV) and the International Index of Erectile Function Questionnaire (IIEF-5) were used to assess changes in erectile function. Patients were injected with 1cc - 2cc's of AF, and followed up to 6 months. Results 35 patients were injected with ProFlo AF. 15 patients injected with AF had pre and post PSV values, 12 patients had pre and post IIEF-5 scores. The average PSV after Trimix injection before administering AF was 26.65 cm/s. After AF injection in follow up, the average PSV was 37.83 cm/s (two-tailed t-test p-value < 0.005). Similarly, an increase was observed in the IIEF score for the group. IIEF score ranged from 5 to 21.5 before the initial AF injection and were between 8 to 24 after AF injection (two-tailed t-test p-value < 0.05). Patients only complaints were of minimal bruising and pain at the injection site for 2-7 days after injections. Conclusions Our results are very promising and statistically significant. We found improved erections on ultrasound and by patient reporting. The majority of patients expressed satisfaction with overall results following injections. Previously, safety data from multiple institutions has been reported on ProFlo Amniotic Fluid. This is the first study to evaluate the effectiveness of ProFlo AF injections. ProFlo AF needs larger studies but may prove to be a safe, effective and non-invasive treatment in men with ED. Funding None
Authors
Michael Zahalsky
Gina Dessources Melissa Marchand Jason Levy |
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MP41-14 |
Human Urine-Derived Stem Cells Genetically-Modified with PEDF Improve Cavernous Nerve Injury-Induced Erectile Dysfunction in a Rat Model |
Stem Cell Research | 17BOS |
Abstract: MP41-14 Sources of Funding: the National Natural Science Foundation of China (Nos. 81471449, and 81401197) Introduction The aim of this study was to investigate whether intracavernous injection of urine-derived stem cells (USCs) or USCs overexpressing pigment epithelium-derived factor (PEDF) could protect the erectile function and cavernous structure in a bilateral cavernous nerve injury-induced erectile dysfunction (CNIED) rat model._x000D_ Methods USCs were cultured from the urine of eight healthy male donors. Seventy-five rats were randomly divided into five groups (n = 15 per group): sham, bilateral cavernous nerve (CN) crush injury (BCNI), USC, GFP-USC , and PEDF-USC groups. The sham group received only laparotomy without CN crush injury and intracavernous injection with phosphate-buffered saline (PBS). All of the other groups were subjected to BCNI and intracav- ernous injection with PBS, USCs, GFP-USCs , or GFP/PEDF-USCs , respectively. The total intracavernous pressure (ICP) and the ratio of ICP to mean arterial pressure (ICP/MAP) were recorded. The penile dorsal nerves, the endothelium, and the smooth muscle were assessed within the penile tissue. Results The penile dorsal nerves, the endothelium, and the smooth muscle were assessed within the penile tissue. The USC and PEDF-USC groups displayed more significantly enhanced ICP and ICP/MAP ratio (p < 0.05) 28 days after cell transplantation. Immunohistochemistry (IHC) and Western blot analysis demonstrated that the protection of erectile function and the cavernous structure by PEDF-USC was associated with an increased number of nNOS-positive fibers within the penile dorsal nerves, improved expression of endothelial markers (CD31 and eNOS) and smoothelin, an enhanced smooth muscle to collagen ratio, decreased expression of TGF-b1, and decreased cell apoptosis in the cavernous tissue. Conclusions The paracrine effect of USCs and PEDF-USCs prevented the destruction of erectile function and the cavernous structure in the CNIED rat model by nerve protection, thereby improving endothelial cell function, increasing the smooth muscle content, and decreasing fibrosis and cell apoptosis in the cavernous tissue. Funding the National Natural Science Foundation of China (Nos. 81471449, and 81401197)
Authors
Qiyun Yang
Xin Chen Tao Zheng Kai Xia Xiangzou Sun Guihua Liu Yuanyuan Zhang Chunhua Deng |
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MP41-15 |
Stem Cell Activation in the Major Pelvic Ganglion is enhanced by Stromal Derived Factor-1 Penile Injections following Nerve Injury |
Stem Cell Research | 17BOS |
Abstract: MP41-15 Sources of Funding: None Introduction Stem cells are believed to play a role in nerve regeneration following nerve injury. Stromal Derived Factor-1 (SDF1) is potent stem cell chemokine. We investigated whether penile injections with SDF1 following bilateral nerve crush injury (BCNI) can enhance stem cell recruitment and activation in the major pelvic ganglion (MPG). Methods Sprague Dawley (350g) male rats underwent sham procedure or BCNI (n=10/group). Starting on the day of surgery, BCNI animals received penile injections with 1ug of SDF1 or saline QOD for 5 injections. Sham animals received saline penile injections only. 2 weeks after BCNI, intracorporeal pressure (ICP) response to cavernous nerve stimulation was assessed (n=5/group) and MPGs were collected and RNA was isolated (n=5/group). Stem cell activity in the MPG was assessed using a stem cell expression array expressed as mean fold-change ± SE normalized to sham. Results SDF1 penile injections resulted in improved ICP preservation following BCNI compared to animals receiving saline injections. Sham animals had significantly greater (P<0.05, 1-way ANOVA with Tukey’s post-hoc testing) than BCNI+saline at all voltages (2, 4, 6, 8v), whereas there was no significant difference between Sham and BCNI+SDF1 at any voltages. Additionally, BCNI+SDF1 had greater ICP at 2v and 4v compared to BCNI+saline (0.40±0.09 vs. 0.11±0.08, p<0.05 and 0.47±0.11 vs. 0.12±0.08, p<0.05, respectively). Stem cell-associated gene expression normalized to Shams was globally increased following BCNI and BCNI+SDF1 had a greater increase in expression compared to BCNI+saline (7.89±0.67 fold vs. 1.87±0.15 fold, p<0.0001). On subset analysis, stem cell pathways had significantly greater expression in BCNI+SDF1 compared to BCNI+saline including cytokines and growth factors (6.45±0.63 vs. 1.86±0.13, p<0.0001), Notch pathway (7.72±0.96 vs. 1.95±0.17, p<0.0001), Wnt pathway (7.01±0.68 vs. 1.87±0.12, p<0.0001), mesenchymal stem cell markers (6.33±1.16 vs. 1.82±0.40, p=0.0015), and neural cell lineage markers (6.63±0.51 vs. 1.85±0.14, p=0.0003). Conclusions SDF1 penile injections improve preservation of erectile function following BCNI and are associated with increased stem cell pathway activation in MPG. Funding None
Authors
Nikolai Sopko
Hotaka Matsui Takahiro Yoshida Xiaopu Liu Max Kates Trinity Bivalacqua |
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MP41-16 |
The efficacy of human testicular stromal cell and neuronal precursor cell in a mouse model of cavernous nerve injury |
Stem Cell Research | 17BOS |
Abstract: MP41-16 Sources of Funding: Basic Science Research Program (Young Researcher Program) through the National Research Foundation of Korea(NRF) funded by the Ministry of Science, ICT & Future Planning((NRF-2015R1C1A1A02037466) Introduction To investigated the efficacy of newly developed human testicular stromal cell (TSC) and neuronal precursor cell (NPC) for erectile function in a mouse model of cavernous nerve crushed injury (CNI) Methods Twelve-week-old NOD-SCID mice were divided into eight groups: sham operation group, bilateral CNI group receiving a single intracavernous injection of phosphate-buffered saline (20 μL), TSC1 (3 × 105 cells/20 μL) or TSC2 (6 × 105 cells/20 μL), NPC1 (3 × 105 cells/20 μL) or NPC2 (6 × 105 cells/20 μL), TSC+NPC combination(3 × 105 cells, each, in total 20 μL), ADMSC2 (6 × 105 cells/20 μL) or oral sildenafil group (5mg/kg). Two weeks after CNI and treatment, erectile function was measured by electrically stimulating the cavernous nerve. The penis was harvested for histologic examinations and Western blot analysis. All animal experiments were approved by the Institutional Animal Care and Use Committee (IACUC) at our institution. Results Significant improvement in erectile function was observed in the TSC2 and TSC+ NPC group which reached 29.8% and 38.1% of the sham control value, respectively (p<0.05). Both in immunohistochemistry and Western blot analysis, TSC2 and TSC+NPC group showed significantly increased expression of cavernous endothelial (PECAM-1, eNOS) and smooth muscle content (α-SMA). NPC2 and TSC+NPC group showed significantly increased expression of neurofilament content in the cavernosum tissue or dorsal nerve bundle (Neurofilament). TSC+NPC combination group showed significant recovery in both functional and molecular levels compared with the single cell treated group. Also the TSC+ NPC combination showed superior results than ADMSC2 or Sildenafil groups. Conclusions This is the first study to investigate the efficacy of newly developed TSC and NPC for erectile dysfunction in CNI mouse model. The combination of TSC and NPC successfully restored erectile function in CNI mice by restoring endothelial, smooth muscle, and neuronal content. Funding Basic Science Research Program (Young Researcher Program) through the National Research Foundation of Korea(NRF) funded by the Ministry of Science, ICT & Future Planning((NRF-2015R1C1A1A02037466)
Authors
Kyung Hwa Choi
Byeong Seong Ki Seung Ryeol Lee Young Kwon Hong Dong Soo Park Dong Ryul Lee |
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MP41-17 |
Safety and Potential Effect of a Single Intracavernous Injection of Autologous Adipose-Derived Regenerative Cells in Patients with Erectile Dysfunction Following Radical Prostatectomy: A 12-month follow-up |
Stem Cell Research | 17BOS |
Abstract: MP41-17 Sources of Funding: None Introduction Cell- and tissue-based therapeutic approaches are progressively gaining ground in the clinics. Evidence from animal models replicating post radical prostatectomy (RP) erectile dysfunction (ED) suggests intracavernous injection of stem cells as a promising treatment approach for ED. We report result from a phase 1 trial with autologous adipose derived regenerative stem cells (ADRCs) used freshly isolated after liposuction. Methods 21 men with ED after RP, performed 6-17 months prior were enrolled in this prospective phase 1 open label and single-arm study. All men tried full pharmacological intervention (PDE-5 or PGE1 analog) with insufficient effect prior to inclusion. The primary objective was to assess the safety of ADRC and secondary recovery of erectile function. Each patient received one treatment and was seen 1,3,6 and 12 months after the intracavernosal ADRCs transplantation. Erectile function was assessed by IIEF and EHS scores. Adipose tissue collection was performed with water-jet-assisted liposuction during general anesthesia. Following immediate isolation of ADRCs, using an automated processing Celution 800/CRS system, these were injected into corpus cavernosum. The Danish Health and Medicines Authority and Ethical Committee approval has been obtained. Results Overall, 8 of 14 (57%) continent men recovered their erectile function, and could implement sexual intercourse after 6 months and the effect sustained 12 months after stem cell treatment. Post-hoc stratification according to content/incontinent status was performed. Efficacy was solely demonstrated in the patients that were continent at inclusion. Accordingly, in continent men IIEF-5 score was unchanged one month after the treatment 6 (4) (median (IQR) (mean 8.5 (95% CI 5.26-11.3)) RM one-way ANOVA with Sidaks' multiple comparisons test), but significantly increased after 6 months to 11 (17) (14.27 (9.834 to 18.70), p< 0.001) and at 12 months (9 (20) (13.2 (8.833-17.57), p< 0.05). In contrast, incontinent men did not regain erectile function (median IIEF-5 6 months= 5 (1) 5.33 (95% CI 4.791-5.875)). No serious adverse events but 8 minor events related to the liposuction were reported._x000D_ Conclusions Freshly isolated autologous ADRCs statistically significantly improved erectile function in continent men. No serious adverse events were recorded after injection or during follow-up. We suggest that ADRCs represent a promising novel interventional therapy of ED following RP. Funding None
Authors
Martha Haahr
Charlotte Harken Jensen Jens Ahm Sørensen Søren Paludan Sheikh Lars Lund |
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MP41-18 |
Kdm5a inhibits gonocyte differentiation to spermatogonial stem cells by suppressing Ret gene function via epigenetic regulation |
Stem Cell Research | 17BOS |
Abstract: MP41-18 Sources of Funding: none Introduction Gonocytes differentiate to spermatogonial stem cells (SSCs), which helps maintain spermatogenesis throughout life. We previously showed that lysine (K)-specific demethylase 5A (Kdm5a) expression is higher in undescended testes than in normal testes of juvenile rats, indicating that Kdm5a regulates early spermatogenesis via histone H3K4 modification (J Urol., 2014). Here, we aimed to elucidate the function of Kdm5a in gonocyte differentiation. Methods Mouse spermatogonial GC-1 cells were harvested 24 h after transfection with pEZ-M03 (control), Gfp expression vector, or Kdm5a-Gfp expression vector. Western blot was then performed to assess H3K4 methylation status, and quantitative reverse transcription polymerase chain reaction (RT-PCR) was performed for 13 genes related to SSC development (Esr1, Esr2, Gdnf, Gfra1, Kit, Klf4, Myc, Nanog, Neurog3, Pgr, Pou5f1, Ret, Thy1). Next, chromatin immunoprecipitation (ChIP) assay was performed to clarify the association between SSC-related genes and H3K4 methylation status. Further, we performed microarray analysis to clarify the underlying regulatory mechanisms of Kdm5a overexpression. Results Kdm5a expression was significantly higher and H3K4me3 expression significantly lower in GC-1 cells overexpressing Kdm5a. Quantitative RT-PCR revealed that of the 13 genes related to SSCs development, the expression of Esr2, Neurog3, Pou5f1, Ret, and Thy1 was significantly higher in GC-1 cells overexpressing Kdm5a. ChIP assay revealed that H3K4me3 was markedly enriched at the Ret promoter. Microarray analysis showed high expression of Tet1 (fold change = 19.4), Btc (19.4), and Scml (16.4), and low expression of Wnt1 (108.2), Sox6 (26.7), and Sox8 (26.4). These genes are reportedly associated with epigenome and gonadal development. Conclusions Since Kdm5a removes the methyl groups from methylated H3K4, which is associated with transcriptional repression, it was suggested that Kdm5a suppresses Ret expression via epigenetic regulation. It was previously reported that Ret colocalizes with Gfra1 in SSCs, and Gdnf signaling via the RET tyrosine kinase/Gfra1 receptor complex is required for SSC self-renewal. In this study, it is suggested that SCC differentiation from gonocytes is inhibited by the action of Kdm5a on germ cells via suppression of Ret expression. Funding none
Authors
Hidenori Nishio
Taiki Kato Kentaro Mizuno Yoshinobu Moritoki Hideyuki Kamisawa Satoshi Kurokawa Akihiro Nakane Tetsuji Maruyama Yutaro Hayashi Takahiro Yasui |
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MP41-19 |
In vitro differentiation of human spermatogonial stem cells in a three dimensional (3D) testicular organoid system |
Stem Cell Research | 17BOS |
Abstract: MP41-19 Sources of Funding: We acknowledge the use of tissues acquired from the National Disease Research Interchange and funding sources including AFIRM II, Award No. W81XWH-13-2-0052, NIH grant 5U42RR006042 and WFIRM internal funding. Introduction Young boys who have undergone chemotherapy treatment are often plagued with infertility later in life. One of the expected options to generate fertility in these cancer survivors is in vitro differentiation of the patient&[prime]s own stored testicular cells, which contain spermatogonial stem cells (SSCs). Human spermatogenesis, however, is an intricate process that has not yet been replicated in vitro. Our laboratory has recently developed novel in vitro 3D human testicular organoid systems from both mature and immature testicular cells. These systems have the potential for in vitro androgen production and spermatogenesis. Our objective was to optimize the 3D testicular organoid system created from immature human testicular cells for in vitro spermatogenesis. Methods Human testis tissue from a 10-year-old brain dead patient was received via the National Disease Research Interchange. Immaturity of the testicular tissue was confirmed by performing Hematoxylin and Eosin (H&E) staining, Reverse Transcriptase-PCR (RT-PCR) and immunohistochemistry for undifferentiated and differentiated germ cell markers. Mechanical and enzymatic digestion was performed on tissue in order to isolate the four major testicular cell types, spermatogonia, sertoli, leydig, and peritubular cells. The cells were seeded in 2D culture in enriched StemPro medium. Cells propagated in 2D culture were then integrated into 3D organoids. Organoids were maintained initially in a medium containing bone morphogenetic proteins and retinoic acid for the first six days and then switched to a medium containing testosterone and follicle stimulating hormone for the rest of the culture period. The morphology of the organoids was examined by H&E staining. Live/dead staining and ATP assay evaluated their viability and metabolic activity. Spermatogenic differentiation within the organoids was tested by quantitative RT-PCR for protamine 1(PRM1) as a post meiotic marker. Results 2D testicular cell culture was established successfully and after 4 passages the cells were integrated into a 3D system. Cell viability and ATP levels in the organoids initially dropped, then both increased over the two weeks of culture. PRM1 expression increased 30 and 53-fold in the first and second weeks of 3D culture, respectively. Conclusions This novel 3D testicular organoid system from human immature testicular cells has the ability to differentiate SSCs to cells expressing the post meiotic marker PRM1. The next step will be to optimize the system and focus on the analysis of these potential post meiotic germ cells. Funding We acknowledge the use of tissues acquired from the National Disease Research Interchange and funding sources including AFIRM II, Award No. W81XWH-13-2-0052, NIH grant 5U42RR006042 and WFIRM internal funding.
Authors
Kara E. McAbee
Nima Pourhabibi Zarandi Anthony Atala Hooman Sadri-Ardekani Colin Bishop |
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MP41-20 |
Developmental Potential of Vitrified Mouse Testicular Tissue after Ectopic Transplantation |
Stem Cell Research | 17BOS |
Abstract: MP41-20 Sources of Funding: none Introduction Cryopreservation of immature testicular tissue should be considered as an important factor for fertility preservation in young boys with cancer. The objective of this study is to investigate whether immature testicular tissue of mice can be successfully cryopreserved using a simple vitrification procedure to maintain testicular cell viability, proliferation, and differentiation capacity. Methods In this experimental study, immature mice testicular tissue fragments(0.5-1 mm²) were vitrified-warmed in order to assess the effect of vitrification on testicular tissue cell viability. Trypan blue staining was used to evaluate developmental capacity. Vitrified tissue (n=42) and fresh (control, n=42) were ectopically transplanted into the same strain of mature mice (n=14) with normal immunity. After 4 weeks, the graft recovery rate was determined. Hematoxylin and eosin (H&E) staining was used to evaluate germ cell differentiation, immunohistochemistry staining by proliferating cell nuclear antigen (PCNA) antibody, and terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay for proliferation and apoptosis frequency. Results Vitrification did not affect the percentage of cell viability. Vascular anastomoses was seen at the graft site. The recovery rate of the vitrified graft did not significantly differ with the fresh graft. In the vitrified graft, germ cell differentiation developed up to the secondary_x000D_ spermatocyte, which was similar to fresh tissue. Proliferation and apoptosis in the vitrified tissue was comparable to the fresh graft. Conclusions Vitrification resulted in a success rates similar to fresh tissue (control) in maintaining testicular cell viability and tissue function. These data provided further evidence that vitrification could be considered an alternative for cryopreservation of immature testicular tissue. Funding none
Authors
Nazila Yamini
Gholamreza Pourmand Fardin Amidi Mojdeh Salehnia Nahid Ataei Nejad Seyed Mohammad Hossein Noori Mougahi |
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MP42-01 |
Quantitative study of Inward Rectifying Ion Channel in Detrusor instability |
Bladder & Urethra: Anatomy, Physiology & Pharmacology I | 17BOS |
Abstract: MP42-01 Sources of Funding: none Introduction Detrusor instability is characterized by sudden involuntary contraction of the detrusor smooth muscle (DSM) cells. In various smooth muscle cells, inward rectifying channel Ih has been playing an important role in regulating resting membrane potential (RMP) and basal tone. Therefore, a detailed biophysical study of Ih channel is essential to investigate DSM cell&[prime]s excitability towards detrusor instability. This current study aims to model Ih channel in DSM cells to analyze its&[prime] modulating effects in internal spontaneous myogenic electrical activities. Methods The DSM cell membrane is represented as a parallel resistor-capacitor circuit consisting of a membrane capacitance Cm and a variable Ih ion channel conductance gh. The voltage-gated Ca2+ and K+ channels, Ca2+ activated K+ channels and leakage currents are incorporated from a published model to generate electrical activities. In this model, Hodgkin-Huxley formalism is adapted for Ih ionic currents with parameters from literature. Results The RMP is set at -50 mV to mimic the experimental value in mouse DSM cell. The maximum conductance of Ih channel is set at 0.0002 mho/cm2 to generate the action potential (AP) shown in figure (Blue line) by inducing synaptic input to mimic effects of purinergic neurotransmitter. By reducing the maximum conductance to 0.00016 mho/cm2, DSM cell couldn&[prime]t generate any AP (black line in figure) as the cell is unable to open transient Ca2+ channels. However, higher activation time constant causes the AP (red line) with the higher peak and slower after hyperpolarization compared to control AP (blue line). The AP (red line) is generated early due to faster activation and early crossing of the threshold value. Conclusions The reduction of Ih channel conductance and activation time constant result hyperpolarization, slower afterhyperpolarization and a consequent reduction in DSM cell&[prime]s excitability. Presently, researchers are focusing much effort on developing novel compounds acting through different ways to minimize the severe side effects of anticholinergic agents like trospium chloride and oxybutynin. As the Ih channel blockers hyperpolarize the DSM cell, the pharmacological targeting of these channels may play a dominant role for treatment of detrusor instability. Funding none
Authors
Chitaranjan Mahapatra
Rohit Manchanda |
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MP42-02 |
Morphological changes of different populations of bladder afferent neurons detected by herpes simplex virus (HSV) vectors with cell type-specific promoters in mice with spinal cord injury |
Bladder & Urethra: Anatomy, Physiology & Pharmacology I | 17BOS |
Abstract: MP42-02 Sources of Funding: NIH P01 DK093424 Introduction Functional and morphological changes in bladder afferent pathways are reportedly involved in neurogenic detrusor overactivity (DO) after spinal cord injury (SCI). The present study examined the morphological changes in different populations of bladder afferent neurons in mice after SCI using an HSV vectors encoding mCherry fluorescent protein that is driven by cell type-specific promoters using mice. Methods SCI was induced by Th8/9 spinal cord transection in female C57BL/6N mice. Mice were divided into 8 groups; 1. spinal intact (SI) with CMV promoter (CMVp)-mCherry, 2. SI with CGRPp-mCherry, 3. SI with NF200p-mCherry, 4. SI with TRPV1p-mCherry, 5. SCI with CMVp-mCherry, 6. SCI with CGRPp-mCherry, 7. SCI with NF200p-mCherry and 8. SCI with TRPV1p-mCherry. Two weeks after vector inoculation into the bladder wall, L1 and L6 dorsal root ganglia (DRGs) were removed bilaterally for immunofluorescent staining using anti-mCherry antibody. Results The number of CMVp vector-labeled neurons was not altered after SCI. The numbers of CGRPp and TRPV1p vector-labeled neurons significantly increased compared to those of SI mice (p<0.001). The number of NF200p vector-labeled neurons significantly decreased compared to SI mice (p<0.001). Cell size distributions of CGRPp vector-labeled C-fiber and NF200p vector-labeled A-fiber neurons showed an increase in the number of C-fiber neurons and a decrease in the number of A-fiber neurons in L6 DRGs after SCI. The median cell size of CGRPp vector-labeled neurons shifted to a larger size (p<0.05) from 247.0 (SI) to 271.3 µm2 (SCI), while the median cell size of TRPV1p vector-labeled neurons shifted to a smaller size (p<0.01) from 245.2 (SI) to 216.5 µm2 (SCI). Conclusions Using an HSV vector-mediated novel neuronal labelling technique, we found that SCI induces morphological changes in bladder afferent pathways, including expansion of the C-fiber cell population that expresses CGRP and TRPV1, which could contribute to C-fiber afferent hyperexcitability and DO, after SCI. _x000D_ _x000D_ Funding NIH P01 DK093424
Authors
Nobutaka Shimizu
William F. Goins Shun Takai Naoki Wada Takahiro Shimizu Takahisa Suzuki Ei-ichiro Takaoka Akihide Hirayama Hirotsugu Uemura Joseph C. Glorioso Naoki Yoshimura |
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MP42-03 |
Effects of nerve growth factor neutralization on hyperexcitability of capsaicin sensitive bladder afferent neurons in mice with spinal cord injury |
Bladder & Urethra: Anatomy, Physiology & Pharmacology I | 17BOS |
Abstract: MP42-03 Sources of Funding: NIH P01 DK093424 Introduction Nerve growth factor (NGF) has been implicated as an important mediator to induce C-fiber bladder afferent hyperexcitability, which contributes to the emergence of neurogenic detrusor overactivity (NDO) following spinal cord injury (SCI). In this study, we examined whether NGF neutralization using anti-NGF antibody normalizes the SCI-induced changes in electrophysiological properties of capsaicin-sensitive C-fiber bladder afferent neurons in the mouse model. Methods In female C57BL/6 mice, the spinal cord was transected at the Th8/9 level. Two weeks later, an osmotic pump was placed subcutaneously to administer anti-NGF antibody at 10 µg/kg/h for 2 weeks. Bladder afferent neurons were labeled with axonal transport of Fast Blue (FB), a fluorescent retrograde tracer, injected into the bladder wall 3 weeks after SCI. Four weeks after SCI, freshly dissociated L6-S1 dorsal root ganglion neurons were prepared. Whole cell patch clamp recordings were then performed in FB-labeled bladder afferent neurons, and the data were compared between SCI and spinal intact (SI) mice. After recording action potentials (AP) or voltage-gated K+ (Kv) currents, the sensitivity of each neuron to capsaicin was evaluated. Results In capsaicin-sensitive bladder afferent neurons, the resting membrane potentials and the peak and duration of AP did not changed by SCI. On the other hand, the threshold for eliciting AP was significantly reduced in SCI vs. SI mice. Also, SCI increased the number of AP during 800 ms membrane depolarization. These SCI induced changes were reversed by NGF neutralization. SCI induced significant increases in the diameter and cell input capacitance of capsaicin-sensitive bladder afferent neurons, which were not reversed by NGF neutralization. Densities of slow decaying KA and sustained KDR currents evoked by depolarization to 0 mV were significantly reduced by SCI. NGF neutralization reversed the SCI-induced reduction in the KA current density. Conclusions In SCI mice, NGF plays an important role in hyperexcitability of capsaicin sensitive C-fiber bladder afferent neurons due to KA current reduction. Thus, NGF-targeting therapies could be effective for treatment of afferent hyperexcitability and NDO in SCI. Funding NIH P01 DK093424
Authors
Takahiro Shimizu
Tsuyoshi Majima Takahisa Suzuki Nobutaka Shimizu Naoki Wada Shun Takai Eiichiro Takaoka Joonbeom Kwon Pradeep Tyagi Motoaki Saito Naoki Yoshimura |
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MP42-04 |
Characterizing development of the human lower urinary tract: anatomic features and molecular expression of the ureteric bud and cloaca |
Bladder & Urethra: Anatomy, Physiology & Pharmacology I | 17BOS |
Abstract: MP42-04 Sources of Funding: Research funded by NIDDK U01 (DK110803). Specimens provided by the Joint MRC-Wellcome Trust Human Developmental Biology Resource (099175/Z/12/Z). Introduction Embryonic development of the lower urinary tract (LUT) occurs in a rapid and complex sequence where the bladder, urethra and ureters must connect in a stereotypical manner to assure proper form and function. Congenital anomalies of the kidney and urinary tract (CAKUT) are the most common human birth defects. There are limited studies of human developmental anatomy, with great reliance on animal models to infer human translation. This study examined human embryos to establish detailed information on LUT development with special focus on the ureteric bud and cloaca._x000D_ Methods With institutional review board approval, 22 human embryos from Carnegie Stage (CS) 14 to 23 were serially sectioned at 5 μM. Representative sections were analyzed after staining with hematoxylin and eosin (H&E) for histology and immunohistochemistry (IHC) for genetic expression. ICH used antibodies to Caspase-3, p63, uroplakin, keratin 5, FoxA2, and E-cadherin. Because mouse developmental anatomy and genetic expression are well studied, we compared human embryos to equivalent stages in mouse development. Results We created a timeline of human LUT development (figure). Insertion of the nephric ducts (ND, also called wolffian ducts) into the cloaca occurs before CS 14 (approximately day 24), establishing a connection between the upper tract and LUT. Shortly after, the ureteric bud emerges from the posterior aspect of the ND and the ureter is joined indirectly to the urogenital sinus via the posterior-most ND segment, the common nephric duct (CND). Contrary to the "Ureteral Bud Theory" (Mackie and Stephens, 1975), the CND does not differentiate into the bladder trigone but instead undergoes apoptosis (expressing Caspase-3 on IHC) between CS 15 to 18 (days 36 to 44). Apoptosis separates the ND and ureter in close proximity to the sinus ridge, an epithelial structure located at the dorsal urogenital sinus. Simultaneously, cloacal septation completes by CS 19 (day 48). These findings are consistent with previous mouse studies._x000D_ Conclusions This study provides an important basis for characterizing anatomic and molecular development of the human LUT. Defects in apoptosis and CND remodeling may contribute to reflux or obstruction. Further studies of human samples will be crucial to understand the CAKUT spectrum of pathology. Funding Research funded by NIDDK U01 (DK110803). Specimens provided by the Joint MRC-Wellcome Trust Human Developmental Biology Resource (099175/Z/12/Z).
Authors
Alexander C Small
Julia B Finkelstein Alejandra Perez Alessia Casale Ekatherina Batourina Cathy L Mendelsohn |
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MP42-05 |
Chronic oral administration of the guanylate cyclase-C agonist linaclotide attenuates colitis induced bladder afferent and dorsal root ganglion hyperactivity |
Bladder & Urethra: Anatomy, Physiology & Pharmacology I | 17BOS |
Abstract: MP42-05 Sources of Funding: NHMRC Australia, Ironwood Pharmaceuticals Introduction Patients suffering from IBS frequently suffer from urological symptoms characteristic of overactive bladder and interstitial cystitis. Cross-organ sensitisation between the bowel and bladder has also been described in pre-clinical studies. Rodents with active colitis exhibit bladder afferent sensitisation and altered cystometry [1,2]. We have previously shown in a model of chronic colonic hypersensitivity (CCH) that bladder mechanical hypersensitivity persists following the resolution of colitis, and that linaclotide, an FDA approved guanylate cyclase-C (GC-C) agonist, is able to attenuate these changes [3]. We hypothesise that these CCH-induced changes are the result of altered sensitivity of afferents both within the colon and bladder wall and within the dorsal root ganglion (DRG), and that oral linaclotide administration may act to reduce this hypersensitivity. Methods We investigated healthy C57BL/6J mice and mice with CCH, 28 days after intra-colonic TNBS administration. CCH mice were randomly assigned to either chronic linaclotide (3μg/kg/day) or placebo (water) administration, consisting of a once daily oral gavage for 2 weeks prior to experimentation. Ex-vivo electrophysiological recordings determined bladder afferent and contractile sensitivity to αβMe-ATP (30μM), carbachol (1μM), and capsaicin (10μM) as well as whole cell patch clamp of retrogradely traced bladder DRG neurons in all four groups. Results Bladder DRG from mice with CCH display hyperexcitability, with a significant reduction in rheobase compared to controls (p≤0.01). CCH mice also display significantly enhanced afferent responses to αβMe-ATP (p≤0.001), carbachol (p≤0.001), and capsaicin (p≤0.001). CCH mice treated with linaclotide display attenuated DRG hyperexcitability and normalised afferent responses to agonists (p≤0.01) compared to placebo (p≤0.01). Conclusions Mice with CCH also display increased bladder afferent excitability within both the DRG and bladder wall, indicating cross-organ sensitisation. Chronic oral administration of linaclotide, a locally acting GC-C agonist that inhibits colonic nociceptors, reverses these colitis-induced changes in bladder afferent sensitivity. Common sensory pathways may allow agents that reduce abdominal pain to improve urological symptoms. 1. Lamb, K., et al. AJPGI, 2006. 2. Ustinova et al, Neurourology and Urodynamics, 2010. 3. Grundy, L., et al., MP28-06. The Journal of Urology, 2016._x000D_ _x000D_ Funding NHMRC Australia, Ironwood Pharmaceuticals
Authors
Luke Grundy
Sonia Garcia-Caraballo Jessica Maddern Grigori Rychkov Pei Ge Gerhard Hannig Caroline Kurtz Ada Silos-Santiago Stuart Brierley |
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MP42-06 |
Expression and function of serotonin paraneuronal cells in the urethral epithelium of human and rodents |
Bladder & Urethra: Anatomy, Physiology & Pharmacology I | 17BOS |
Abstract: MP42-06 Sources of Funding: Ana Coelho is supported by an individual post-doc fellowship from Fundacao para a Ciencia e Tecnologia (SFRH/BPD/108468/2015). This work was financed by FEDER funds through COMPETE 2020, Operacional Programme for Competitiveness and Internationalisation (POCI) and Portugal 2020 under the framework of the project "Institute for Research and Innovation in Health Sciences" (POCI-01-0145-FEDER-007274). Introduction The urethral epithelium is deeply involved in the control of lower urinary tract functioning. Key elements of this process may be paraneuronal cells located among urethral epithelium that act as local sensors and influence urethral function through a putative paracrine mechanism. This work aimed to explore the expression of serotonin (5-HT) paraneuronal cells in human and rodent urethra in normal and pathological conditions as well as the contribution of 5-HT to the urethral function. Methods Female urethras were collected from human organ donors and rats and processed for immunohistochemistry (IHC). Antibodies against 5-HT, the pan-neuronal marker Beta3-Tubulin, calcitonin gene-related peptide (CGRP), vesicular acetylcholine transporter (VAChT) and the synaptic vesicle 2 (SV2) were used. Female urethras from rats with lypopolyshaccaride (LPS, 5 mg/ml) -induced inflammation or chronic spinal cord transection (SCT) at T8/T9 were also collected and processed for IHC or 5-HT quantification by HPLC. Bladder reflex activity of normal rats was evaluated by cistometry during infusion of 5-HT (1 mM). Results In human and rat urethra, cells expressing 5-HT were detected along the entire length of the urethral epithelium. These cells had a long thin extension reaching the urethral surface and stained for Beta3-Tubulin and SV2 confirming the paraneuronal function. Underneath the epithelium, a dense neuronal network contained cholinergic (VAChT+) and sensory (CGRP+) fibers. Appositions between CGRP fibers and the basal aspect of 5-HT paraneurons were observed. In inflamed rats the number of 5-HT paraneurons was significantly decreased when compared to intact animals (181,3+/-7,80 to 117,1+/-10,35; p?0.01). Accordingly, 5-HT levels measured by HPLC analysis were decreased (15,36+/-2,81 to 7,45+/-0,42; p?0.01). In SCT rats the number of 5-HT paraneurons was markedly increased (152,3+/-14,82 to 208,8+/-18,8; p?0.01). During 5-HT infusion in intact rats the frequency of voiding contractions was unaltered, however, maximal detrusor pressure was increased over controls (50,79+/-7.906 over 33,52+/-0,830; p?0.01) suggesting an increase in urethral resistance to flow. Conclusions Paraneurons are strongly expressed in the human and rat urethral epithelium exhibiting close contacts with sensory neurons and in close proximity to cholinergic fibers. The expression of 5-HT paraneurons is influenced by inflammation and neurogenic bladder dysfunction. The release of 5-HT from these cells might increase urethral resistance and may contribute to continence regulation. Funding Ana Coelho is supported by an individual post-doc fellowship from Fundacao para a Ciencia e Tecnologia (SFRH/BPD/108468/2015). This work was financed by FEDER funds through COMPETE 2020, Operacional Programme for Competitiveness and Internationalisation (POCI) and Portugal 2020 under the framework of the project "Institute for Research and Innovation in Health Sciences" (POCI-01-0145-FEDER-007274).
Authors
Ana Coelho
Raquel Oliveira Helena Cavaleiro Celia Duarte Cruz Francisco Cruz |
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MP42-07 |
Sonic hedgehog regulation of rhabdosphincter muscle |
Bladder & Urethra: Anatomy, Physiology & Pharmacology I | 17BOS |
Abstract: MP42-07 Sources of Funding: NIH/NIDDK DK079184 Introduction Removal and injury of rhabdosphincter muscle during prostatectomy surgery is a leading cause of stress urinary incontinence (SUI, 44%), which critically impacts patient mental and physical health. With current treatments, including implantation of artificial urinary sphincter, continence pad use is needed and device failure, erosion of the urethra and infection are significant side effects. Thus a critical unmet need exists to develop novel methods to regenerate rhabdosphincter muscle. We have identified sonic hedgehog (SHH) as an important regulator of muscle in another urogenital organ, the penis, and have developed innovative peptide amphiphile nanofiber hydrogel delivery of SHH protein to regenerate penile smooth muscle, post prostatectomy. If similar SHH signaling mechanisms regulate rhabdosphincter function, then this technology may be applied to regenerate rhabdosphincter muscle post prostatectomy. We hypothesize that SHH protein is critical for human rhabdosphincter homeostasis and regeneration and have examined this hypothesis in human rhabdosphincter tissue. Methods Human rhabdosphincter (n=3) was obtained from patients (n=3) undergoing cystectomy. Trichrome stain and immunohistochemical analysis for SHH pathway was performed. Results Trichrome stain showed that human rhabdosphincter is a complex mixture of collagen, muscle and elastin fibers. SHH protein was abundantly expressed in rhabdosphincter muscle. The SHH receptor Patched (PTCH1) was also identified, and strongly stained rhabdosphincter muscle. Conclusions The SHH pathway is active in adult human rhabdosphincter muscle, suggesting that similar mechanisms of muscle homeostasis and regeneration are present as in human penis tissue, and thus the previously developed peptide amphiphile nanofiber hydrogel delivery of SHH, may be useful for rhabdosphincter muscle regeneration. Funding NIH/NIDDK DK079184
Authors
Marah Hehemann
Shawn Choe Danuta Dynda Shaheen Alanee Tobias Kohler Kevin McVary Carol Podlasek |
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MP42-08 |
Male Urethral Sphincter Complex Revisited Using Novel MR Imaging Techniques |
Bladder & Urethra: Anatomy, Physiology & Pharmacology I | 17BOS |
Abstract: MP42-08 Sources of Funding: None Introduction Anatomical description of the male urethral sphincter complex (internal lissospincter and external rhabdosphincter) has undergone several revisions as previous conclusions were mostly derived from gross cadaveric dissection of adult male pelvis. These findings have been plagued by distortions of the anatomical structures in cadavers. Our objective was to elucidate the anatomy of the urethral sphincter muscles by resorting to in vivo, non-invasive imaging, using proton-density (PD), diffusion tensor imaging (DTI) and fiber tracking and thereby improve our understanding by avoiding the errors in cadaveric studies. Methods Normal healthy five male young subjects, (mean age ~25 yrs) were scanned on a 3T GE MR scanner, using a multi-channel cardiac coil, lying supine, feet-first. After acquisition of a high resolution sagittal scout scan (Fig. A), axial morphological proton-density scans were prescribed and acquired extending from a few slices below the base of the bladder to beyond the entry of the urethra into the penis (~18-22 slices depending on the height of the subject). Three mm thick DTI scans were acquired and analyzed to obtain first the tensor axial images (Fig. B-C) to construct fibers within this urethral complex. Results A consistent finding was that of possibly two sphincter like muscles (Fig. D-E), with one proximal near the bladder neck (yellow arrow in Fig. A, B) and the other more distal (Fig. C). In the tensor images, blue color indicates fibers oriented superior- inferior, red left-right while green anterior-posterior directions. Fiber tracking of these tensor images yields fiber structures within the urethral sphincter complex. The proximal sphincter is shown in Fig. D, the distal sphincter in Fig. E. The connecting superior-inferior longitudinal fibers are shown in blue in Fig. F. A consistent finding was the distance between the two sphincters is between 21 and 24 mm (i.e., 7 to 8 slices). Conclusions This is perhaps the first DTI and fiber tracking of the male urethral sphincter complex. Our findings support the two sphincter concept to constrict/close the urethral opening. These observations will form the basis of normal urethral morphology that can be monitored in post-surgery patients and correlated with age /urinary incontinence symptoms. Funding None
Authors
Kyoko Sakamoto
Valmik Bhargava Vadim Malis M. Raj Rajasekaran Shantanu Sinha |
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MP42-09 |
Atrogin is a Novel Marker of Age-Related Urethral Sphincter Muscle Atrophy |
Bladder & Urethra: Anatomy, Physiology & Pharmacology I | 17BOS |
Abstract: MP42-09 Sources of Funding: VA Rehabilitation Research Merit Award Introduction Previous studies show an age-related increase in the prevalence of urinary incontinence (UI) (10-15% in adults and ~30% % in older population >70 years). Age-related atrophic changes in urethral sphincter muscles are recognized as the most common cause for UI in the geriatric population. Recently, atrogin (a muscle-specific E3 ubiquitin ligase) is recognized as an important molecular pathway involved in age-related muscle atrophy. We tested the hypothesis that increased urethral sphincter atrophy during advanced aging is mediated by this novel atrogin pathway._x000D_ _x000D_ Methods We used a rabbit model to establish time course of age-related urethral sphincter muscle complex dysfunction and for further evaluation of molecular mechanisms of muscle dysfunction /atrophy in rabbits. We employed young (6-9 months), middle age (>12 months) and old rabbits (>30 months) and measured urethral muscle thickness (using transurethral ultrasound (US) technique (Fig A-inset) as well as urethral closure pressure (Fig A) in response to pelvic floor muscle electrical stimulation. We harvested bladder neck (for lissosphincter) and mid-urethra (for rhabdosphincter) samples to evaluate protein and mRNA levels of atrogin (marker of atrophy) using Western blot (protein) /qPCR studies respectively. Results Our rabbit studies confirmed age-related changes in the urethral sphincter muscle thickness (Fig A) and alterations in closure pressure (Fig A) as well as in protein/mRNA levels of marker of atrophy (atrogin; Fig B-D) in both bladder neck and mid-urethra . These observations confirm our hypothesis that age-related increase in atrophy mediated via atrogin pathway may contribute to sphincter muscle dysfunction. Conclusions Our physiological, imaging and molecular studies are consistent with our hypothesis that age-related increase in atrogin protein contribute to sphincter muscle dysfunction. Targeting atrogin may be a novel approach to prevent age-related urethral sphincter muscle atrophy. Funding VA Rehabilitation Research Merit Award
Authors
M. Raj Rajasekaran
Johnny Fu My-Uyen (Lilly) Nguyen Valmik Bhargava |
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MP42-10 |
Augmented Bladder Smooth Muscle Responsiveness to Hyperglycemia Through a Caveolae-Dependent Activation of Rho kinase Pathway |
Bladder & Urethra: Anatomy, Physiology & Pharmacology I | 17BOS |
Abstract: MP42-10 Sources of Funding: Department of Veterans Affairs, Research Service BX001790; BX002806 Introduction Diabetic bladder is characterized by an early compensatory phase in which bladder smooth muscle (BSM) exhibits augmented contractility. While little is known about the causes of this response, an upregulation of Rho-dependent signaling in response to hyperglycemia has been suggested. In other smooth muscle systems, RhoA-ROCK signaling has been shown to be dependent on caveolae, membrane invaginations involved in the regulation of a myriad of signaling pathways. Since alterations in caveolar elements have been reported in animal models of diabetes, this study investigated the involvement of these membrane microdomains in the Rho-dependent changes in contractility induced by hyperglycemia. Methods Longitudinal mouse bladder strips without mucosa were mounted in organ baths for isometric tension studies. Changes in the amplitude of bladder contractions in response to exogenous carbachol (1μM) were evaluated under euglycemia (11.5mM) as well as after exposure of BSM tissue to high glucose Krebs (23mM) for up to 8 hours. Separate experiments were similarly performed in Krebs supplemented with mannitol (11.5mM) to control for increased osmotic conditions. The effect of high glucose on contractile responses to CCh was investigated in the presence of Rho kinase inhibitor Y27632 (1μM), as well as after the depletion of BSM caveolae, achieved by incubation with mβCD (10mM, 1 hour). Results The amplitude of contractile responses to CCh measured in BSM were significantly higher after 2 hours of hyperglycemia compared to those measured under euglycemic conditions and remained elevated for 8 hours. Contractile responses to CCh remained unchanged over the same time period in the presence of mannitol. The augmented CCh responses induced by high glucose were completely prevented in the presence of Rho kinase inhibitor used at a dose that did not affected CCh responses under euglycemia. Similarly, augmented CCh responses induced by hyperglycemia were prevented after BSM caveolae were depleted by exposure to mβCD. Conclusions The increased detrusor responses to CCh during exposure to hyperglycemia is consistent with BSM hypercontractility reported in the compensated phase of diabetes. The effects of Rho kinase inhibitor and mβCD in preventing the increase in BSM responsiveness under hyperglycemic conditions suggest the involvement of Rho-mediated pathway and the requirement of intact caveolae in this process. These findings might provide a potential link between the diabetes-induced BSM hyperreactivity and the caveolae-mediated regulation of Rho signaling. Funding Department of Veterans Affairs, Research Service BX001790; BX002806
Authors
Vivian Cristofaro
Josephine A. Carew Suhas P. Dasari Raj K. Goyal Maryrose P. Sullivan |
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MP42-11 |
Bladder nerve-smooth muscle function remains intact after long-term decentralization |
Bladder & Urethra: Anatomy, Physiology & Pharmacology I | 17BOS |
Abstract: MP42-11 Sources of Funding: NIH-NINDS NS070267 Introduction The impact of autonomic nerve injury on smooth muscle is not well understood. We explored the integrity of the nerve-smooth muscle functional unit following sacral root decentralization._x000D_ _x000D_ Methods Female canines were surgically decentralized by bilateral transection of all spinal roots caudal to L7, including the dorsal root of L7. Video surveillance of housing cages allowed measurement of the frequency and duration of urination postures at monthly intervals post operatively (PO) by observers blinded to the surgical interventions. Retrograde labeling of pelvic plexus neuronal cell bodies was quantitated from Fluorogold injected near the ureterovesical junction 3 weeks before euthanasia. Functional integrity of the pelvic plexus-bladder innervation was determined by electrical stimulation of the pelvic plexus immediately prior to euthanasia. Bladder caspase-3 immunostaining for cellular apoptosis was quantified to confirm integrity. Results Micturition postures were observed in only 2/6 animals by 2 months PO and 3/6 by 4 months PO while postures remained intact in sham animals. Nerve stimulation caused a robust increase in detrusor pressure in both control and decentralized groups. Likewise, abundant Fluorogold-labeled neuronal cell bodies were observed in ganglia in the pelvic plexus of both sham and decentralized animals. Immunohistochemical stain for caspase-3 showed no difference across groups. No co-localization of Fluorogold-positive neuronal tissue and caspase-3 was observed. Conclusions Behavioral changes observed PO confirms that decentralization reduces sensation of bladder fullness. The ability of 3/6 animals to sense bladder fullness at 4 months PO may be from sensory nerve sprouting or variations in the bladder sensory innervation. Fluorogold-positive pelvic plexus ganglia in decentralized animals demonstrates that the ganglia remained intact up to 6 months after decentralization despite sensory losses. Caspase-3 staining results showed no increase in apoptosis in the neuronal tissues or bladder smooth muscle in decentralized dogs, suggesting no increased apoptotic cell death. No significant difference between detrusor pressure responses across groups after nerve-evoked stimulation indicates that the nerve-smooth muscle functional unit of the bladder is intact up to 12 months after injury and therefore, nerve reinnervation strategies could be successful. Funding NIH-NINDS NS070267
Authors
Danielle M Salvadeo
Ekta Tiwari Nagat Frara Alan S. Braverman Mary F. Barbe Michael Ruggieri |
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MP42-12 |
Muscarinic receptor antagonist regulates the extracellular matrix of bladder in rat partial bladder outlet obstruction model |
Bladder & Urethra: Anatomy, Physiology & Pharmacology I | 17BOS |
Abstract: MP42-12 Sources of Funding: none Introduction Previous studies have confirmed hypertrophy of extracellular matrix (ECM) can be found in bladder wall upon BOO, and muscarinic receptor antagonist can suspend the progression of bladder dysfunction caused by bladder outlet obstruction. However, the relationship between metabolism of ECM and muscarinic receptor activity remains unclear. Thus, we set up an animal experimental model of partial bladder outlet obstruction (PBOO) in female rat to explore how the muscarinic receptor antagonist affect extracellular matrix proteins, receptors and metabolism regulators in the pathological state. Methods Female Sprague-Dawley rats were used for the study. The rat was anesthetized and its proximal urethra were tied with 4-0 silk to create partial BOO. Tolterodine was used as the muscarinic receptor antagonist in the dosage of 0.36mg/kg/day from Day One after operation. Rats were randomly sub-divided into 3 groups: the sham group, the PBOO group and PBOO with tolterodine group. They were raised for 3 weeks and their bladder were harvested for further tests. Total bladder RNA was extracted according to the protocol, whole rat genome microarray and RT-PCR testing were performed to survey the gene expression of extracellular matrix proteins, receptors and metabolism regulators in rat bladder. The bladder specimens were fixed and paraffin-embedded, the slides were stained with Picrosirius red to examine the Integral Optical Density (IOD) of muscle and collage fiber. Those positive proteins in gene testing above were further tested with immunohistochemical staining following the protocol. Results Picrosirius red stain shows that, compared with the sham group, the IOD of muscle fiber was significantly increased in PBOO group and remained in PBOO with tolterodine group (p<0.05); while the collage fiber was significantly increased in PBOO group but decreased in PBOO with tolterodine group (p<0.05). The gene microarray and qPCR testing eventually revealed 34 significant genes related to extracellular matrix. None of collage gene subtypes exhibited significant change between groups. Yet, the matrix metalloproteinase (MMPs) exhibited significant decrease in PBOO group and increase in PBOO with tolterodine group (p<0.05). In addition, PBOO inhibited the expression of non-collagen ECM protein in rat bladder wall, while muscarinic receptor antagonist could promote the expression of non-collagen ECM protein and ECM receptor. The immunohistochemical staining supported above gene analysis. Conclusions Muscarinic receptor antagonist can decrease the volume fraction of collage via MMPs in rat bladder wall upon PBOO condition. Simultaneously, it can regulate the expression of extracellular matrix proteins and receptors. Such relationship between muscarinic receptor and extracellular matrix may associate with the improving effect of muscarinic receptor antagonist in bladder dysfunction caused by bladder outlet obstruction. Funding none
Authors
Tong-Xin Yang
De-Yi Luo Yi-Fei Lin Qiang Liu Xiang Cai Hong Li Kun-Jie Wang |
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MP42-13 |
Modulation of nicotinic receptor function by bladder decentralization and reinnervation |
Bladder & Urethra: Anatomy, Physiology & Pharmacology I | 17BOS |
Abstract: MP42-13 Sources of Funding: NIH-NINDS NS070267 Introduction We previously found that the depolarizing neuromuscular nicotinic receptor blocker succinylcholine decreased bladder pressure when reinnervated nerves were stimulated. We aim to explore the function and location of nicotinic receptors with respect to loss and recovery of bladder function. Methods Three groups of female dogs were used: sham (N=4), 12-month decentralized (N=3) and 6-month reinnervated (N=3). Decentralization was by bilateral transection of spinal roots caudal to L7, including dorsal roots of L7 and hypogastric nerves. The obturator nerve was connected to a bladder branch of the pelvic plexus for reinnervation. At euthanasia, contractile responses of mucosa-free bladder smooth muscle strips were determined. Results In reinnervated dogs, IV atracurium, a competitive neuromuscular nicotinic antagonist, decreased bladder pressure induced by transferred obturator nerve stimulation but not sacral nerve root stimulation in shams. Nicotine induced contractions in sham tissue to about 16% of that induced by KCl. ATR blocked nicotine-induced contractions but α,β-ATP did not. 100 μM 1,1 dimethyl-4-phenyl-piperazinium iodide (DMPP), a ganglionic-subtype nicotinic receptor agonist, induced similar contractions in all groups. 10 µM epibatidine (EPB) induced similar contractions in sham and reinnervated animals, but less responses in decentralized animals (p<.05). The α4β2 nicotinic receptor agonist TC2559 had no effect. TTX blocked EFS-induced contractions but not DMPP-, EPB- or nicotine-induced contractions across all groups. ATR and α,β-mATP significantly reduced EFS-evoked contractions in all groups but the competitive neuromuscular nicotinic receptor antagonist d-tubocurarine did not. Conclusions While nicotinic receptors mediate contractions in sham, reinnervated and decentralized bladders, pelvic decentralization significantly reduced nicotine-induced effects, suggesting alteration in nicotinic receptor expression. The effects of TTX and atropine on nicotine-induced contractions suggest that nicotinic receptors do not require action potentials to function and are likely located on the presynaptic membrane of cholinergic but not purinergic nerves. The EFS-induced contractions in the presence of d-tubocurarine in the reinnervated bladders indicate that the neuromuscular nicotinic receptors involved in the new neuronal pathway cannot be located in the bladder muscle or intramural ganglia and therefore must be more proximal, perhaps in pelvic plexus ganglia or the spinal cord. Funding NIH-NINDS NS070267
Authors
Danielle M Salvadeo
Nagat Frara Alan S. Braverman Mary F. Barbe Michael Ruggieri |
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MP42-14 |
Purinergic P2X4 Receptor Expression and Function in Rodent Bladder Smooth Muscle |
Bladder & Urethra: Anatomy, Physiology & Pharmacology I | 17BOS |
Abstract: MP42-14 Sources of Funding: Department of Veterans Affairs, Research Service BX001790; BX002806. Introduction Bladder smooth muscle (BSM) contractions in response to ATP are generally attributed to P2X1 receptor (P2X1R) activation. In rodents however, P2X1R antagonists do not completely inhibit the purinergic component of neurogenic bladder contractions, suggesting that other functionally relevant P2XR subtypes contribute to the smooth muscle response. In addition to pronounced expression of the P2X1 receptor subtype, BSM may also express P2X4R. This study examined whether the activation of P2X4R exerts a functional role in mouse and rat bladders. Methods P2X4R expression was investigated in BSM tissue without mucosa and cultured BSM cells from mice and rats. Longitudinal BSM strips from each species were mounted in organ bath for isometric tension studies. Purinergic contractions were elicited by α-β-methylene-ATP (αβmATP), and the purinergic component of electrical field stimulation (EFS) was isolated by pre-treatment with the muscarinic receptor antagonist atropine. Inhibitory effects of P2X4R selective antagonists, 5-BDBD or BX430, on αβmATP- and EFS-induced contractions were investigated in the presence of P2X1R antagonist NF449. The effect of ivermectin (IVC), a P2X4R positive modulator, on contractile responses to αβmATP was determined in mouse bladders. Results P2X4R expression was detected in BSM tissue and cultured BSM cells from both species. Though P2X1R activation is predominantly responsible for purinergic contractions in rodent bladders, a significant portion of the contractile response to both αβmATP (22.3±7%) and EFS (27.5±4% of purinergic component of EFS) was resistant to P2X1R inhibition. This P2X1R-resistant component was abolished by administration of P2X4R antagonists 5-BDBD or BX430. In addition, in mouse bladders, responses to exogenous αβmATP increased significantly (33.0±11%) in the presence of IVC. Conclusions Our data indicates that in rodents, a P2X4R-sensitive component of BSM contraction contributes significantly to ATP-mediated responses. Since purinergic signaling is significantly increased in overactive bladders and interstitial cystitis in humans, P2X4R may represent a potential target for the treatment of bladder dysfunction. Funding Department of Veterans Affairs, Research Service BX001790; BX002806.
Authors
Vivian Cristofaro
Josephine A. Carew Sean D. Carey Raj K. Goyal Maryrose P. Sullivan |
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MP42-15 |
The urothelium is the most predominant tissue in the body for superoxide production: key role of NADPH oxidases |
Bladder & Urethra: Anatomy, Physiology & Pharmacology I | 17BOS |
Abstract: MP42-15 Sources of Funding: BBSRC BB/P004695/1; NIA 1R01AG049321-01A1 Introduction Recognition of the urothelium as a new sensory structure has significantly advanced our understanding of bladder function. Key to further progress is the identification of novel pathological regulators in this tissue. Oxidative stress is a fundamental pathological mediator; ROS generating enzyme NADPH oxidase (Nox enzyme) has attracted intense interest recently as it is the only enzyme that produces ROS as its sole function and can be targeted without compromising normal biochemical oxidation. Our recent pilot study provided initial evidence for the presence of such system in bladder urothelium and its potential functional significance. This study aimed firstly to define the importance of urothelial superoxide production in the body and secondly to dissect the enzymatic sources of superoxide production in the bladder. Methods C57BL/6J mice were euthanized. Bladder and other types of tissue were isolated. Lucigenin-enhanced chemiluminescence quantified superoxide production in live tissue. Western blot determined Nox subtype expressions. Results Superoxide production in bladder mucosa (RLU/mg tissue: 536.8±104.8, mean±SEM) was many folds as high as those in detrusor muscle (21.8±3.8, n=15, p<0.01), aorta (67.2±26.6, n=7, p<0.05), brain (9.4±1.7, n=6, p<0.01), kidney (84.3±23.0, n=6, p<0.05), ventricle (21.8±3.8, n=6, p<0.01) and liver (80.8±12.9, n=7, p<0.05). NADPH oxidase inhibitor diphenyleneiodonium (DPI, 20µM)reduced superoxide production to 10.8±3.4 % of control (n=6, p<0.01) in bladder mucosa and to 30.8±8.4% of control (n=6, p<0.01) in detrusor. Mitochondria de-coupler FCCP (10µM) suppressed superoxide production to 51.8±10.5 % of control (n=6; p<0.01) in bladder mucosa and to 59.8±10.4 % of control (n=6, p<0.05) in detrusor. Xanthine oxidase inhibitor oxypurinol (100µM) produced no significant effect in bladder mucosa (87.9±17.4 % of control, n=6, p>0.05) but a small inhibition in detrusor (78.0±6.6% of control). Western blot showed specific bands for Nox1, Nox2 and Nox4 but no Nox3 expression in bladder mucosa and detrusor with significantly higher expression in bladder mucosa (p<0.05, n=4-6)._x000D_ Conclusions These data demonstrate for the first time that the urothelium is the most active tissue for superoxide production in the body. Nox enzymes are the main enzymatic source for superoxide in bladder. The main Nox subtypes are Nox1, Nox2 and Nox4, mainly located in the urothelium. Exceptionally high levels of Nox-driven superoxide explain why bladder urothelium is prone to oxidative stress, inflammation and sensory dysfunction. Funding BBSRC BB/P004695/1; NIA 1R01AG049321-01A1
Authors
Max Roberts
Josephine Amosah Lisa Adjei Guiping Sui Rui Wu Simon Archer Jonathan Johnston Michael Ruggieri Changhao Wu |
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MP42-16 |
Innervation of genitourinary structures: a neuronal tracing study in female dogs |
Bladder & Urethra: Anatomy, Physiology & Pharmacology I | 17BOS |
Abstract: MP42-16 Sources of Funding: NIH-NINDS NS070267 Introduction Many studies focus on afferent or efferent inputs (but not both), or on one structure of the genitourinary system. Only a few studies include information on inputs from sympathetic chain ganglia (SCG), and even fewer have examined the possibility of direct motor (autonomic or somatic) inputs from spinal cord ventral horns to genitourinary end organs. We sought to clarify origins of afferent and efferent information conveyed between the spinal cord, peripheral nervous system ganglia and genitourinary structures using retrograde and anterograde neurotracing dyes. Methods Dyes were injected into the bladder wall, external urethral sphincter (EUS) and clitoris of 14 female mongrel dogs (Fluorogold, True blue, or Nuclear Yellow). Dorsal root ganglia (DRG), SCG, caudal mesenteric ganglion (CMG), pelvic plexus ganglia and spinal cord ventral horns were examined for dye-labeled neuronal cell bodies. Detrusor muscle intramural ganglia were examined by injecting DiI into the pelvic nerve’s anterior vesicle branch. Results Retrograde labeled cells were observed in several DRGs, representative of afferent input from the bladder, EUS and clitoris (Table). Anterograde labeling revealed intramural ganglia in the bladder wall. Sympathetic efferents included: 1) labeled cells in the CMG primarily from the bladder, yet small numbers from the EUS and clitoris; 2) labeled cells in SCG primarily from the bladder (widespread) and more localized input from EUS and clitoris (Table); and 3) labeled cells in the intermediolateral cell column of thoracolumbar cord segments directly to the bladder and clitoris, a locale typically considered as sympathetic. Parasympathetic efferents included: 1) labeled neurons in pelvic plexus ganglia in bladder mesenteries; and 2) cells in lamina VII of sacral cord segments directly to the bladder and clitoris, a locale typically considered as sympathetic. Lastly, somatic (skeletal muscle) efferents to the EUS were evident as retrogradely labeled cells in sacral lamina IX cells. Conclusions Afferent and efferent inputs to genitourinary structures are complex, yet a clear knowledge is needed to understand dysfunction after spinal cord injury and mechanisms underlying chronic pain syndromes in this region. Funding NIH-NINDS NS070267
Authors
Mary F. Barbe
Sandra M. Gomez-Amaya Neil S. Lamarre Danielle M Salvadeo Michael Mazzei Alan S. Braverman Michael Ruggieri |
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MP42-17 |
Age Related Urethral Sphincter Muscle Dysfunction and Fibrosis: Possible Role of Wnt Signaling Pathways |
Bladder & Urethra: Anatomy, Physiology & Pharmacology I | 17BOS |
Abstract: MP42-17 Sources of Funding: VA Rehabilitation Research Merit Award Introduction Previous studies show an age-related increase in the prevalence of urinary incontinence (UI) (10-15% in adults and ~30% % in older population >70 years). Age-related degenerative changes to urethral sphincter muscles are recognized as the most common cause for UI in the geriatric population. Recently, Wntβ catenin signaling pathway is recognized as the major molecular pathway involved in age-related skeletal muscle fibrosis. We tested the hypothesis that increased urethral sphincter fibrosis during advanced aging is mediated by a novel Wnt-β catenin signaling pathways. Methods We used a rabbit model to establish time course of age-related urethral sphincter muscle complex dysfunction and for further evaluation of molecular mechanisms of muscle dysfunction /fibrosis in rabbits. We employed (n=3) young (6-9 months), middle age (>12 months) and old rabbits (>30 months) and harvested mid-urethra (for rhabdosphincter) samples to evaluate protein and mRNA levels of markers of fibrosis using Western blot (protein) /qPCR (mRNA) studies respectively. _x000D_ _x000D_ Results Our rabbit studies confirmed age-related changes in alterations in closure pressure as well as in protein/mRNA levels of markers of fibrosis (β-catenin, collagen-I, and TGF-β etc; Fig A-C). These observations confirm our hypothesis that age-related increase in fibrogenic proteins mediated via Wntβ catenin signaling pathways may contribute to sphincter muscle dysfunction. _x000D_ _x000D_ Conclusions Our physiological and molecular studies are consistent with our hypothesis that age-related increase in fibrogenic proteins contribute to sphincter muscle function. Targeting Wnt signaling pathway may be beneficial in preventing sphincter muscle fibrosis. Funding VA Rehabilitation Research Merit Award
Authors
M. Raj Rajasekaran
Johnny Fu My-Uyen (Lilly) Nguyen Valmik Bhargava |
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MP42-18 |
Endocannabinoid 2-arachidonoyl glycerol decreases visceral pain associated with experimental cystitis |
Bladder & Urethra: Anatomy, Physiology & Pharmacology I | 17BOS |
Abstract: MP42-18 Sources of Funding: NIH R01 DK 066349 Introduction Endocannabinoids exert potent analgesic and anti-inflammatory effects and may suppress clinical symptoms of painful inflammatory bladder diseases. 2-arachidonoyl glycerol (2-AG) is the most abundant endocannabinoid and the activity of 2-AG in the bladder has not been previously described. We investigated whether 2-AG has the potential to prevent visceral pain associated with experimental cystitis in mice. Methods Expression of diacylglycerol lipase-α and -β (DAGL-α and -β, primary enzymes of 2-AG synthesis) and monoacylglycerol lipase (MAGL, primary enzyme of 2-AG degradation) in urothelium was examined by real-time RT-PCR and immunohistochemistry. Cystitis was induced by intraperitoneal injection of cyclophosphamide (CYP, 150 mg/kg), and mechanical sensitivity of hind paws was determined. Effects of 2-AG were also evaluated in cultured human urothelial cells. Results DAGL-α, -β and MAGL were present in the mouse urothelium. CYP (3 hours) induced cystitis in mice characterized by submucosal edema. Pretreatment with a specific MAGL inhibitor JZL 184 (8 mg/kg/day, sc, 6 days) prior to CYP treatment did not appear to affect bladder inflammation. Mechanical sensitivity threshold was significantly reduced after CYP treatment in mice that received vehicle (basal: 2.9 ± 0.1 g; vehicle: 0.6 ± 0.1 g; n =6; p<0.01 vs basal). However, the increase of mechanical sensitivity was attenuated in JZL184-treated mice (basal: 2.8±0.1 g; JZL 184: 1.4±0.6 g; n =6, p<0.05 vs basal and vehicle-treated animals). CYP augmented expression of IL-6 mRNA in urothelium (151.8±34.1 fold increase compared to control animals, n=6, p<0.01 vs control) and JZL 184 inhibited increased IL-6 expression (79.5±23.4, p<0.05 vs control and vehicle-treated animals). In cultured human urothelial cells, 2-AG attenuated LPS-induced increased TNF-α mRNA expression in a concentration-dependent manner. Conclusions We demonstrated the presence of the 2-AG pathway in the bladder, and this is the first available evidence that treatment with a MAGL inhibitor decreased visceral pain associated with cystitis. Urothelial cells play an important role in the activity of 2-AG in bladder. Manipulation of 2-AG may provide a novel therapeutic option for treatment of bladder pain. Funding NIH R01 DK 066349
Authors
Zunyi Wang
Peiqing Wang Dale Bjorling |
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MP42-19 |
Is transient receptor potential channel involved in warming induced contraction of human and pig urethral smooth muscle? |
Bladder & Urethra: Anatomy, Physiology & Pharmacology I | 17BOS |
Abstract: MP42-19 Sources of Funding: none Introduction We have reported the novel mechanism which is sensitive to extracellular calcium concentration ([Ca2+]out) co-related with the force development of contraction in human and pig urethral smooth muscle (USM). In addtion to this mechanism, the present study first revealed the distinctive temperature sensitivity of the tension force development of USM. Focusing on this temperature sensitivity of USM, the contribution of TRPV (Transient receptor potential vanilloid) channel was investigated. Methods The procedures described have been approved by ethical committee at Kyushu University hospital. Human USM was obtained from patients with bladder cancer undertaken radical cystectomy, while pig one from local abattoir. Isolated intact USM were dissected. Responses to warming-induced contraction (WIC) corresponding to [Ca2+]out were investigated using isometric force recording. Various TRPV channel agonists and antagonists were examined. Results The graded extracellular temperature change from 10°C to 37°C increased a sustained contraction (4.1 ± 0.7g, N=6) in a temperature dependent manner in human and pig USM (fig, A,B & C) but not observed in detrusor. Extracellular Ca2+ free solution did not induce WIC. Contractility upon [Ca2+]out was variable to each temperature (fig, D). Even in the presence of tetrodotoxin (1 μM) and prazosin (1 μM), these responses were also reproducible. TRPV1 agonists, capsaicin (up to 1 mM) or resiniferatoxin (10 μM) and accordingly, a TRPV4 agonist, GSK1016790A (1 μM) failed to induce pig USM contraction. A TRPV channel family antagonist, Ruthenium Red (100 μM) never inhibited WIC. Conclusions Extracellular Ca2+ is essential for the generation of WIC, suggesting that the mechanism underlying WIC requires transmembrane Ca2+ entry or intracellular Ca2+ metabolic process. Though TRPV channel-related agents did not modulate USM contraction, it is strongly suggested that WIC results from TRPV channel activation. Subtype, splice-variant, or gene polymorphism of TRPV channel but not a typical one may be involved in WIC. This novel mechanism in urethra but not in detrusor might be a candidate for a treatment of lower urinary tract dysfunctions. Funding none
Authors
Ken Lee
Tomoko Maki Ryosuke Takahashi Masatoshi Eto Shunichi Kajioka |
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MP42-20 |
Identification of novel irritant sensing mechanisms in the bladder |
Bladder & Urethra: Anatomy, Physiology & Pharmacology I | 17BOS |
Abstract: MP42-20 Sources of Funding: NHMRC Australia Introduction Studies suggest that the symptoms associated with overactive bladder syndrome (OAB) and interstitial cystitis (IC) may be due to a disrupted mucosal barrier. Access of the urine to underlying sensory structures is hypothesised to induce bladder irritation which, in the absence of an ability to ‘scratch’ is manifest in the symptoms of urinary urgency and frequency. The TGR5 and MRGPR receptors have been implicated in mediating non-histaminergic itch responses in the skin and are responsible for bile acid, protease, and chloroquine induced pruritis (itch). Bile acids are secreted in high concentrations in the urine and we hypothesise that these itch mediators may be a novel mechanism responsible for the sensory abnormalities seen in OAB and IC. Methods Ex-vivo bladder afferent recordings were used to identify the role of TGR5 in bladder mechanosensation. Retrogradely traced bladder DRG neurons from C57/BL6 mice were isolated, dissociated and used for single cell RT-PCR. The TGR5 receptor agonist CCDC (10μM), and the MRGPR C11 and A3 agonists chloroquine (1μM), NPFF (2μM), and BAM 8-22 (2μM) were used in calcium imaging and whole cell patch clamp recordings from bladder DRG neurons. Results Single cell PCR data identified TGR5, MRGPR-C11, and MRGPR-A3 receptor mRNA expression in bladder afferent neurons. CCDC, chloroquine, NPFF, and BAM 8-22 were able to induce large calcium transients in 60% of bladder neurons. Application of CCDC/MRGPR mixed agonists to bladder DRG neurons induced significant hyperexcitability, with a significant reduction in rheobase (p≤0.001), and a significant increase in the frequency of action potentials at 2X rheobase (p≤0.01) compared to control. Intravesical infusion of CCDC into the bladder induced significant mechanical hypersensitivity to bladder distension (p≤0.001) with no change in muscle compliance. Conclusions This data shows for the first time that TGR5 and MRGPR receptors are functionally present on bladder DRG neurons and their activation is able to induce calcium transients, neuronal hyperexcitability and mechanical hypersensitivity. This suggests that histamine-independent itch mechanisms are not exclusive to somatic pathways, but are present and functional in the viscera and may be important in bladder hypersensitivity pathologies. Funding NHMRC Australia
Authors
Luke Grundy
Ashlee Caldwell Sonia Garcia-Caraballo Grigori Rychkov Stuart Brierley |
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MP43-01 |
CAN FREQUENCY OF PROSTATE BIOPSY ON ACTIVE SURVEILLANCE BE REDUCED WITHOUT SIGNIFICANTLY INCREASING RISK? |
Prostate Cancer: Localized: Active Surveillance II | 17BOS |
Abstract: MP43-01 Sources of Funding: This work was supported by the National Science Foundation (CMMI 0844511 to BTD, DGE 1256260 to CLB); any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the National Science Foundation. _x000D_ Introduction Active surveillance (AS) for prostate cancer (CaP) involves close follow-up with serial prostate biopsies. The optimal biopsy frequency during follow-up has not been determined, resulting in variation in practice. The goal of this investigation was to use longitudinal AS biopsy data to assess if the frequency of biopsy could be reduced without substantially prolonging the time to detection of Gleason ≥ 7 disease. Methods Using data from 1,500 men with very-low or low-risk CaP enrolled in AS at Johns Hopkins, we developed a hidden Markov model to estimate the probability of under sampling, the annual probability of grade progression to Gleason ≥ 7 and the 10-year cumulative probability of reclassification or progression to Gleason ≥ 7. We then simulated 1024 potential AS biopsy strategies where it was assumed a biopsy would or would not be performed each year for the 10 years following diagnosis. For each of these strategies the model was used to predict the average delay in detection of Gleason ≥ 7 disease, which was compared across strategies to identify potential alternatives to annual biopsy. Results The model estimated 10-year cumulative probability of reclassification from Gleason 6 to Gleason ≥ 7 was 46.0%. The probability of under sampling at diagnosis was 9.8% and the annual progression probability for men with Gleason 6 was 4.0%. Based on these estimates, simulation of an annual biopsy strategy estimated the mean time to detection of Gleason ≥ 7 disease to be 14.1 months. Alternative strategies that reduced the number of biopsies increased the time to detecting grade progression by 1.2 to 38.0 months; however, several strategies eliminated biopsies with only small (< 5 months) delays in detecting grade progression (Figure - Simulated increase in time to detecting grade progression based on number of biopsies eliminated from annual biopsy routine. Each point represents a unique AS biopsy strategy. Biopsies during a 10 year period would occur as indicated in the legend.) Conclusions While annual biopsy for low-risk men on AS is associated with the shortest time to detection of Gleason ≥ 7 disease, several alternative strategies may allow for less frequent biopsy without sizable increases in time to detecting grade progression. Funding This work was supported by the National Science Foundation (CMMI 0844511 to BTD, DGE 1256260 to CLB); any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the National Science Foundation. _x000D_
Authors
Christine Barnett
Gregory Auffenberg Zian Cheng Fan Yang Jiachen Wang John Wei David Miller James Montie Mufaddal Mamawala Brian Denton |
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MP43-02 |
Variation in use of confirmatory testing among active surveillance candidates |
Prostate Cancer: Localized: Active Surveillance II | 17BOS |
Abstract: MP43-02 Sources of Funding: Blue Cross and Blue Shield of Michigan and grant 1T32-CA180984 from the National Cancer Institute. Introduction Recognizing the importance of fully characterizing cancer severity prior to Active Surveillance (AS), many advocate for confirmatory testing (e.g., repeat biopsy, MRI) shortly after prostate cancer (CaP) diagnosis. In this context, we examined utilization of such testing among AS eligible men across urology practices in Michigan. Methods The Michigan Urological Surgery Improvement Collaborative (MUSIC) is a consortium of 43 urology practices. We identified all men with newly-diagnosed CaP entered into the collaborative&[prime]s registry from January 2012 through April 2016 that met MUSIC&[prime]s published AS appropriateness criteria (i.e., age < 80, any Gleason Score ≤6 or Gleason Score 3+4 with ≤3 positive cores and no more than 50% of any core involved). Among men with sufficient follow-up, we first calculated the proportion that received a confirmatory test (defined as receipt of a repeat prostate biopsy or prostate MRI) within 6 months and 12 months after diagnosis, respectively. For practices with at least 10 AS eligible patients, we then assessed practice-level variation in the rates of confirmatory testing. Finally, we fit regression models to identify characteristics associated with receipt of a confirmatory test. Results During this time period, 434/5,292 (7.6 %) and 695/4,614 (15.1%) eligible men received confirmatory testing within 6 and 12 months of diagnosis, respectively. At a practice level, rates of confirmatory testing varied widely for both the 6- (0 % to 27.5%; p<0.001) and 12-month intervals (0 % to 60.0%; p<0.001) (Figure). Patients with GS 3+4 tumors and PSA levels > 4 were less likely to undergo confirmatory testing, while such tests were more frequent among patients diagnosed more recently and in larger practices (Table). Conclusions Although increasing over time, utilization of repeat biopsy or prostate MRI to confirm risk stratification among men who are candidates for AS has been uncommon and highly variable across urology practices. These data have prompted ongoing efforts in MUSIC to increase and standardize use of such tests among men considering AS. Funding Blue Cross and Blue Shield of Michigan and grant 1T32-CA180984 from the National Cancer Institute.
Authors
Gregory Auffenberg
Zaojun Ye Brian Lane Susan Linsell Nikola Rakic Andrew Brachulis Michael Cher David Miller for the Michigan Urological Surgery Improvement Collaborative |
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MP43-03 |
DO PROSTATE BIOPSY-ASSOCIATED COMPLICATIONS INFLUENCE TREATMENT SELECTION FOR PATIENTS WITH NEWLY DIAGNOSED, CLINICALLY LOCALIZED PROSTATE CANCER? |
Prostate Cancer: Localized: Active Surveillance II | 17BOS |
Abstract: MP43-03 Sources of Funding: none Introduction Despite efforts to mitigate risk, complications after transrectal prostate biopsy remain a dreaded outcome. We assessed whether experiencing a complication associated with diagnostic prostate biopsy influences the decision regarding treatment modality after diagnosis of clinically localized prostate cancer (CaP). Methods We identified patients who were diagnosed with low risk (Gleason 6, clinical stage I) or low volume, intermediate risk (Gleason 3+4=7, clinical stage I) CaP following transrectal prostate biopsy in the SEER-Medicare linked database between 2009-2011. Patients experiencing infectious and non-infectious complications within 30 days after biopsy were recorded by ICD-9 diagnosis codes using previously described methods (Loeb, et al. J Urol 2013). We used multivariable logistic regression to determine whether biopsy-associated complications in patients who are eligible for active surveillance (AS) were associated with pursuing AS less commonly than active treatment, including prostatectomy, radiation, cryotherapy, and androgen deprivation. Results 8932 patients with a diagnosis of low risk or low volume, intermediate risk prostate cancer were included in analysis. Mean age at diagnosis was 71.7 years (± 4.6). 1538 patients (17.2%) experienced complication after prostate biopsy (2.2% infectious complications and 15% non-infectious complications). 1034 patients (11.6%) patients elected to pursue active surveillance while 7898 (88.4%) chose active treatment. On multivariable logistic regression (Figure 1), controlling for demographic and comorbid factors, we determined that experiencing a prostate biopsy-associated complication is associated with a decreased likelihood of choosing active surveillance over active treatment (OR 0.83, 95% CI 0.83-1.00, p<0.05). Conclusions Among patients who would be eligible for AS, those who experience a prostate biopsy-associated complication are significantly more likely to seek active treatment. With evidence that men with biopsy-associated complications have neither worse oncologic outcomes nor an increased risk of complications on subsequent biopsies, clinicians should continue to support AS in these men._x000D_ _x000D_ Funding none
Authors
Melanie Adamsky
Jacob Tallman Kristine Kuchta Brian Helfand |
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MP43-04 |
Impact of USPSTF Recommendation on Rates of Non-Definitive Management in Low Risk Prostate Cancer Utilizing the National Cancer Database |
Prostate Cancer: Localized: Active Surveillance II | 17BOS |
Abstract: MP43-04 Sources of Funding: none Introduction Since the 2011 U.S. Preventative Services Task Force (USPSTF) recommendation against prostate cancer (PCa) screening, there have been various modifications observed in the practice of urology. We hypothesized that low risk PCa is managed more conservatively secondary to the USPSTF recommendation and sought to evaluate the rates of non-definitive management (NDM) during this era. Methods We performed a retrospective cohort study of 105,295 patients in the National Cancer Database diagnosed with NCCN low risk PCa from 2010-2013. Our primary endpoint was to identify rates of NDM {active surveillance (AS) + watchful waiting (WW)} before and after the USPSTF recommendation against PSA screening in 2011. We performed multivariate logistic regression analysis to evaluate patient specific factors contributing to this form of management. These included age, race, clinical stage, facility volume, facility type, insurance, Charlson comorbidity index, PSA, year of diagnosis, geographic location, and neighborhood income. Results Of the 105,295 patients with low risk disease, 15,423 (15%) elected NDM versus 89,872 (85%) who elected active treatment. Of the 15,423 patients who elected NDM, 75% were on AS and 25% on WW. Median age of patients electing NDM versus treatment was 65 and 62 years old, respectively. As shown in Figure 1, the rate of NDM in years prior to the USPSTF recommendation was 10.1% and 12.9% in 2010 and 2011, respectively (OR 1.36, p<0.001). NDM increased in the years following the USPSTF recommendation of 2011 with the rate of NDM of 17.04% in 2012 (OR 1.92, p<0.001), and increasing to 21.6% in 2013 (OR 2.56, p<0.001). At the current rate of change of 3.85% per year, NDM utilization would reach 50% by the year 2021. Conclusions Since the USPSTF recommendation, NDM utilization has significantly increased in patients with low risk PCa. However, this data highlights the continued underutilization of surveillance in this patient population. Funding none
Authors
John F. Burns
John P. Flores Mazen Alsinnawi Sydney Akapame John Massman III Christopher Porter |
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MP43-05 |
Comparing practice- versus provider-level variation in use of Active Surveillance for men with low-risk prostate cancer |
Prostate Cancer: Localized: Active Surveillance II | 17BOS |
Abstract: MP43-05 Sources of Funding: Blue Cross and Blue Shield of Michigan and grant 1T32-CA180984 from the National Cancer Institute. Introduction Variation in the utilization of Active Surveillance (AS) across urology practices has been described, but less is known about the degree of variation among urologists in the same practice. Furthermore, the relationship between the volume of low-risk patients a urologist manages (i.e., panel size) and his/her rate of AS utilization is not well described. In this context, we compared rates of AS utilization for men with low-risk prostate cancer (CaP) both within and across practices in Michigan to clarify whether efforts to decrease variation are best focused at practices or individual surgeons. Methods The Michigan Urological Surgery Improvement Collaborative (MUSIC) is a consortium of 43 diverse academic and community urology practices that maintains a prospective clinical registry for all patients diagnosed with CaP. From the registry, we identified all MUSIC practices with at least five urologists that each managed ≥5 men with newly-diagnosed low-risk CaP (i.e., clinical stage ≤ T2a, PSA <10 ng/mL, and biopsy Gleason score ≤6) from 1/2012 through 7/2016. We then examined the proportion of men undergoing initial AS across different practices and among surgeons within a given practice. Subsequently, a regression model was fit to determine whether a urologist&[prime]s rate of AS was correlated with individual panel size. Results We identified 124 urologists from 13 practices that managed 2,646 men with low-risk CaP. The median practice and provider panel size was 166 (range 70-524) and 16 (range 5-141) patients, respectively. The proportion of men entering initial AS varied broadly across practices (range 30.6-72.9%; median 57.7%; p <0.001) (Figure). In most practices, surgeon-specific use of initial AS also varied widely, with a maximum range of 0-100% in a practice with 38 urologists (Figure). There was no significant relationship between a urologist&[prime]s panel size and his/ her rate of AS utilization (R2= 0.01, p=0.17). Conclusions The proportion of patients entering initial AS varies widely across urology practices, among surgeons in the same practice, and is not correlated with a urologist&[prime]s panel size. These data suggest that interventions aimed at optimizing AS practice patterns must be tailored to individual surgeons rather than larger organizations regardless of patient volume. Funding Blue Cross and Blue Shield of Michigan and grant 1T32-CA180984 from the National Cancer Institute.
Authors
Gregory Auffenberg
Apoorv Dhir Susan Linsell Brian Lane David Miller Michael Cher for the Michigan Urological Surgery Improvement Collaborative |
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MP43-06 |
The Effect of Targeted Antibiotic Prophylaxis in Men Undergoing Transrectal Ultrasound Guided Prostate Biopsy |
Prostate Cancer: Localized: Active Surveillance II | 17BOS |
Abstract: MP43-06 Sources of Funding: none Introduction To investigate whether targeted antibiotic prophylaxis (TAP) using rectal swab cultures (RSC) prior to transrectal ultrasound guided prostate (TRUSP) biopsy has an effect on hospitalization for infectious complications related to TRUSP biopsies. Methods We evaluated a cohort of men between 1995 and 2016 with prostate cancer on active surveillance (AS) receiving annual surveillance TRUSP biopsies. Routine RSC have been used to identify men with fluoroquinolone resistant (FQ-R) organisms since October 2012. Patients with FQ-R bacteria received TAP while patients without FQ-R bacteria received standard oral ciprofloxacin prophylaxis. We identified men with infectious complications requiring hospitalization for suspected post-biopsy sepsis via mailed questionnaires. The key questions identified patients hospitalized after a TRUSP biopsy for infection, and the date of admission. The incidence of infections requiring hospitalization was compared for patients receiving TAP vs. standard prophylaxis prior to TRUSP biopsy. The impact of FQ-R on hospitalization was assessed. Results Of 1167 men currently on the AS program at our institution, 825 returned the questionnaire and were included in the analysis. For these men, there were a total of 3361 biopsy events. A total of 7 (0.79%) of 886 biopsies preceded by RSC resulted in infectious complications leading to hospitalization compared to 24 (0.97%) of 2475 biopsies without RSC (odds ratio (OR) 0.81 (0.35-1.89),p=0.63). Among the 886 RSCs performed, FQ-R organisms were identified in 194 (21.9%). Six out of 194 (3.1%) biopsies with swabs positive for FQ-R organisms resulted in hospital admission while 1 out of 692 (0.14%) biopsies with swabs negative for FQ-R resulted in admission (OR 22.1 (2.6-184.3),p<0.01, Figure). Age, race, and PSA at diagnosis did not significantly differ while smaller prostate volume at diagnosis was significantly associated with hospitalization (40.4 vs. 50.3 grams,p=0.03). Conclusions Compared to empirical ciprofloxacin prophylaxis, TAP using RSC before undergoing TRUSP biopsy was associated with a nonsignificant decrease in rate of hospitalization for suspected post-biopsy sepsis. A RSC positive for FQ-R organisms and smaller prostate volume at diagnosis were associated with a higher rate of hospitalization. Funding none
Authors
Carling Cheung
Hiten Patel Patricia Landis H. Ballentine Carter Misop Han |
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MP43-07 |
Clinical Utility of MRI/fusion Biopsy in Prostate Cancer Patients on Active Surveillance |
Prostate Cancer: Localized: Active Surveillance II | 17BOS |
Abstract: MP43-07 Sources of Funding: none Introduction The role of magnetic resonance imaging (MRI)/fusion biopsy for prostate cancer patients on active surveillance (AS) remains unclear. Methods We compared MRI/fusion guided targeted biopsy (TB) to standard ultrasound-guided systematic biopsy (SB) for detection of clinically significant cancer in AS patients undergoing confirmatory biopsy. The primary outcome was upgrading defined as detection of Gleason sum ≥ 3 + 4 =7 disease. Results Of 356 AS patients at our institution, 195 (58%) underwent prostate MRI after the initial diagnostic biopsy. Of these, 138 (71%) had MRI-detectable lesions. After implementation of TB in May 2014, 42 AS patients underwent confirmatory MRI/fusion TB: n=9 (21.4%), n=19 (45.2%), n=7 (16.7%), and n=7 (16.7%) with PI-RADS 2, 3, 4, and 5 lesions, respectively. Compared to SB patients undergoing confirmatory biopsy (n=106), TB patients had higher PSA (5.3 ng/mL versus 3.5 ng/mL, p<0.001) and modestly higher PSA density (0.14 versus 0.09, p=0.01). There were no significant differences in age (0.29), BMI (p=0.21), family history (p=0.1.0), comorbid diseases (p=0.26-1.0), number of prior biopsies (p=0.167), or time since cancer diagnosis (p=0.58). Gleason sum ≥ 3 + 4 = 7 was diagnosed in 30 (29%) SB patients and 16 (38%) TB patients (p=0.33). Stratification by PI-RADS revealed Gleason ≥ 3 + 4 = 7 diagnosis in 0 (0%), 4 (21%), 6 (86%) and 6 (86%) of PI-RADS 2, 3, 4, and 5 lesions, respectively (p<0.001). Compared to SB, TB of PI-RADS ≥ 4 lesions detected 58% more Gleason ≥ 3 + 4 = 7 cancers (86% versus 28%, p<0.0001) and was associated with increased odd of upgrading in multivariable regression (p=0.012). The positive predictive value (PPV) of PI-RADS ≥ 4 lesions for Gleason ≥ 3 + 4 = 7 disease was 86%. Sensitivity analyses of patients with only 1 biopsy prior to confirmatory biopsy produced similar results. Conclusions A majority of patients on AS have MRI-detectable lesions. Compared to SB, selective TB of PI-RADS 4 and 5 lesions improves the detection of clinically significant cancers in those undergoing confirmatory biopsy. Funding none
Authors
Zachary Hamilton
Unwanaobong Nseyo Brittney Cotta Natalie Schenker-Ahmed David Karow A Karim Kader Christopher Kane J Kellogg Parsons |
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MP43-08 |
Impact of High Volume Centers on Management of High and Low Risk Prostate Cancer |
Prostate Cancer: Localized: Active Surveillance II | 17BOS |
Abstract: MP43-08 Sources of Funding: none Introduction Management of localized prostate cancer (PCa) is not uniform. There continues to be underutilization of non-definitive management (NDM) in low risk PCa and often an absence of hormonal ablative therapy (HT) in addition to external beam radiotherapy (EBRT) given to high risk patients. We attempted to identify the impact of facility volume (FV) stratification on the management strategies of low and high risk PCa. Methods We utilized the National Cancer Database (NCDB) and 344,107 patients diagnosed with localized PCa from 2010-2013 had data available for review. We analyzed two groups of patients: Group (1) included 105,295 patients with NCCN low risk PCa and Group (2) included 60,255 patients with High Risk (Gleason > 8) PCa. Hospitals were classified by average annual FV to determine if higher volume centers influenced choice of management for high and low risk patients. We performed logistic regression analysis which controlled for age, race, clinical stage, facility volume, facility type, insurance, Charlson comorbidity index, PSA, year of diagnosis, geographic location, and neighborhood income. Results For Group (1), the utilization of NDM (active surveillance or watchful waiting) continues to be underutilized and did not directly correlate with FV as shown in Figure 1a. The rate of NDM at the Top 5% FV was 16.9% versus 17.4% at Lowest Frequency FV. Significant predictors of NDM in low risk PCa were uninsured status OR 2.62 and unknown insurance status OR 1.76, as well as year of diagnosis (2013 OR 2.57 versus 2010). For Group (2), radical prostatectomy (RP) utilization correlated with higher FV centers; rates of RP at Top 5% FV were (49.7%) versus (13.9%) at the Lowest Frequency FV. EBRT utilization was inversely correlated with higher FV centers as shown in Figure 1b. HT was given in addition to EBRT on average (83.8%) of the time and was similar across all facilities (range 82.2%-85.3%). Conclusions FV did not correlate with choice of NDM in low risk patients. In high risk patients however, higher volume centers were more likely to choose RP and lower volume centers were more likely to utilize EBRT + HT. Funding none
Authors
John F. Burns
John P. Flores Mazen Alsinnawi Sydney Akapame Elliot Blau John Massman III Christopher Porter |
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MP43-09 |
“Active Surveillance” in the everyday care: Results from HAROW-a prospective, non-interventional study with a mean follow-up of 66.7 months. |
Prostate Cancer: Localized: Active Surveillance II | 17BOS |
Abstract: MP43-09 Sources of Funding: The HAROW study was initiated and conducted by the Foundation of Men's Health and financially supported by Gazprom Germania. Introduction Active Surveillance (AS) is a treatment option for selected patients with localized prostate cancer (PCa) and low risk for progression. Most data on AS result from clinical trials, conducted at academic- or tertiary care centers. In contrast, in clinical practice AS is mostly applied by office based urologists. In this prospective, non-interventional, health services research study the use of five treatment options for localized PCa were compared under everyday conditions: Hormone therapy (HT), AS, Radiation therapy (RT), Operation (RP) and Watchful waiting (WW). Data of the AS-subgroup are presented in terms of inclusion criteria and changes in treatment strategy. Methods The study was conducted from July 2008 to July 2013 at 259 study centers in Germany, in 86% office based urologists. Clinical data (tumor category, digital rectal examination, PSA level, Gleason score, comorbidities) and information about therapy and disease progression were collected at the time of study inclusion and subsequently at six-month intervals. According to the non-interventional study design, only recommendations were made for enrollment, course and discontinuation of AS. The final therapeutic decision rested with treating physicians. Results Overall, 2957 patients were enrolled, of whom 468 (15.8%) received AS. The AS-group was characterized by the lowest mean baseline level of PSA (5.8 ng/mL), the highest proportion of patients with a Gleason score <7 (92.5%) and with low-risk tumors (82.5%). The mean follow up was 28.5 months. Up to this time 112 patients had changed treatment strategy (RP:65, RT:30, HT:10, WW:7). On the basis of a separate survey until July 2016, the mean follow up was extended to 66.7 months. By that time treatment strategy had changed in another 87 patients (RP:31, RT:18, HT:8, WW:30). In these two periods the rates of therapy switches per month were RP:2.3, RT:1.1, HT:0,4, WW:0,2 and RP:0.8, RT:0.5, HT:0.2, WW:0.8, respectively. Fifteen AS-patients died, but no tumor related deaths were seen. Conclusions The results of HAROW indicate that AS is highly applicable in everyday care since the inclusion criteria were largely respected. The percentage of therapy switches of this health services research study (42.5% in 66.7 months) is comparable to the results from clinical AS-trials. With an increase of the observation period, a higher proportion of patients changed to WW when AS was terminated, and remained on a non-invasive strategy. Funding The HAROW study was initiated and conducted by the Foundation of Men's Health and financially supported by Gazprom Germania.
Authors
Jan Herden
Dietrich Schnell Axel Heidenreich Lothar Weissbach |
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MP43-10 |
The Role of Surveillance Biopsy with No Cancer as a Prognostic Marker for Reclassification: Results from the Canary Prostate Active Surveillance Study (PASS) |
Prostate Cancer: Localized: Active Surveillance II | 17BOS |
Abstract: MP43-10 Sources of Funding: Canary Foundation, Department of Defense (PC130355), and Institute for Prostate Cancer Research Introduction Many patients who are on active surveillance (AS) for prostate cancer (PCa) will have surveillance prostate needle biopsies (PNB) without any cancer evident. The prognostic meaning of these biopsies without cancer is unknown. We sought to define the association between negative surveillance PNB and risk of reclassification on AS. Methods All men were enrolled in the Canary Prostate Active Surveillance Study (PASS). Men were included if they had Gleason ≤ 3+4 PCa and ? 34% core involvement ratio at diagnosis and an on-study first surveillance PNB within 2 year of diagnosis. Reclassification was defined as an increase in primary or secondary Gleason grade and/or an increase in the ratio of biopsy cores with cancer to ≥ 34%. PNB outcomes were defined as: a) no evidence of cancer on biopsy, b) evidence of cancer on biopsy without reclassification, or c) reclassification. Results 657 men met inclusion criteria. On first surveillance PNB, 214 (33%) had no cancer, 282 (43%) had cancer but no reclassification, and 161 (25%) reclassified. Of the 496 men who did not reclassify, 313 had a 2nd PNB. On 2nd PNB, 120 (38%) had no cancer, 139 (44%) had cancer but no reclassification, and 54 (17%) reclassified._x000D_ _x000D_ In a multivariate analysis, significant predictors of future reclassification after 1st PNB were no cancer on PNB (HR = 0.50, p = 0.008), serum PSA, prostate size, and BMI (Table). Diagnostic Gleason score, maximum percentage of involved cores, race, T stage, and study site were considered and found to be non-significant. A finding of no cancer on the 2nd PNB was also associated with significantly decreased future reclassification on multivariate analysis (HR = 0.15, p = 0.003), regardless of first PNB result. Conclusions Men who have a surveillance PNB with no evidence of cancer are significantly less likely to reclassify on AS in the PASS cohort. These finding have implications for tailoring AS protocols. Funding Canary Foundation, Department of Defense (PC130355), and Institute for Prostate Cancer Research
Authors
James Kearns
Anna Faino Lisa Newcomb James Brooks Peter Carroll Atreya Dash William Ellis Michael Fabrizio Martin Gleave Todd Morgan Peter Nelson Ian Thompson Andrew Wagner Yingye Zheng Daniel Lin |
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MP43-11 |
Refined analysis of prostate specific antigen (PSA) velocity to predict outcomes in active surveillance: Results from the Canary Prostate Active Surveillance Study (PASS) |
Prostate Cancer: Localized: Active Surveillance II | 17BOS |
Abstract: MP43-11 Sources of Funding: Canary Foundation, Department of Defense (PC130355), Institute for Prostate Cancer Research Introduction For men on active surveillance (AS) for prostate cancer, utility of PSA kinetics in predicting pathologic reclassification remains controversial. We aimed to develop prediction methods for utilizing serial PSA and evaluate frequency of collection during AS. Methods Data were collected from men enrolled in the multicenter Canary PASS with Gleason ≤ 3+4, < 34% of biopsy cores positive, and no 5ARI use. PSA was collected every 3 months, and biopsies were performed at 6-12 months, 24 months, and then every 2 years from diagnosis. PSA velocity (PSAV) was determined by calculating a best linear unbiased predictor at each time point based on a linear mixed effect model (LMEM) that accounted for past and present serial logged PSA levels. The association of diagnostic PSA and/or PSAV with time to reclassification (increase in Gleason grade and/or increase to ≥ 34% of cores positive) was evaluated using Cox proportional hazards models. Models were adjusted for age, prostate size, biopsy parameters, and used serial PSA collected every 3 or every 6 months, where applicable. Results 908 men met study criteria, of whom 288 (32%) had a reclassification event within 5 years. Median follow up was 2.9 years. After adjusting for age, prostate size, biopsy parameters, and diagnostic PSA, PSAV was a significant predictor of reclassification (HR for each 10% increase in PSAV = 1.7 (95% CI 1.3-2.1, p < .0001). The PSAV model had slightly improved accuracy over diagnostic PSA at 3 year prediction: AUC for diagnostic PSA model was 0.79 (95% CI 0.73-0.83) and for PSAV model was 0.80 (95% CI 0.75-0.84). Model performance was essentially identical using calculations based on q6 month rather than q3 month PSAs. Conclusions PSA velocity calculated using LMEM significantly predicts biopsy reclassification. Models that use repeat PSA measurements outperform a model with diagnostic PSA only. Model performance is similar using PSA assessed every 3 or 6 months. These results inform how PSA may be incorporated into active surveillance protocols and risk calculators. Funding Canary Foundation, Department of Defense (PC130355), Institute for Prostate Cancer Research
Authors
Matthew Cooperberg
James Brooks Anna Faino Yingye Zheng James Kearns Peter Carroll Atreya Dash Michael Fabrizio Martin Gleave Todd Morgan Peter Nelson Ian Thompson Andrew Wagner Lisa Newcomb Daniel Lin |
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MP43-12 |
Predicting progression in active surveillance; external validation of the Canary PASS risk calculator with the Spanish Urological Association Registry on AS |
Prostate Cancer: Localized: Active Surveillance II | 17BOS |
Abstract: MP43-12 Sources of Funding: NONE Introduction The Spanish Urological Association Registry on Active Surveillance (AS) [AEUPIEM/2014/0001, piem.aeu.es?_x000D_ NCT 02865330, clinicaltrials.gov] has comparable design and similar aims to the recently published Canary Prostate Active Surveillance Study (PASS, NCT00756665, clinicaltrials.gov). _x000D_ An easy to use on line predictive tool of progression in FU biopsy (Bx) has_x000D_ been proposed by the PASS group, the PASSRisk Calculator (PASSRC). We perform an external validation of the PASSRC in our series, specially focused on clinical utility of PASSRC by selecting cutoff points of probability for clinical decision counselling._x000D_ Methods After matching for validation purposes, we select 498 patients with a minimum of one follow-up Bx? no other exclusion criteria were considered nor bias has been detected. PASSRC external validation is done by means of calibration curve and area under de ROC curve (AUC), identifying cutoffs of clinical utility by probability density functions (PDF) and clinical utility curves (CUC). Results We find significant differences in age, PSA and clinical stage between our validation cohort and the PASSRC generation cohort (p<.0001), with a progression rate of 10-22% on the successive follow-up Bx. No cancer was found in 44% of the first followup Bx. The calibration curve shows underestimation of observed progression. The AUC is 0.65 (C.I.95%: 0.60-0.71). PDF and CUC do not suggest a specific cutoff point for clinical use, because of the overlap of the distributions of probabilities between progressing and non-progressing patients_x000D_ _x000D_ Conclusions In the first external validation of the PASSRC we have obtained a moderate discrimination ability. Unfortunately, we cannot recommend cutoff_x000D_ points of clinical use from our study. Specific risk calculators from different cohort features, different prognosis models or the inclusion of new biomarkers and/or morphofunctional parameters from mpMRI should be stressed as potential predictors for progression within AS strategies_x000D_ Funding NONE
Authors
Angel Borque-Fernando
Jose Rubio-Briones Luis M. Esteban-Escaño Argimiro Collado-Serra Ana Soto Pedro A. López González Jordi Huguet Pérez Jose I. Sanz Velez Jesús Gil Fabra Enrigue Gómez Gómez Cristina Quicios Dorado Lluís Fumadó Sara Martinez-Breijo Juan Soto Villalba In behalf of rest of AI of AEU/PIEM/2014/0001 |
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MP43-13 |
Comparison of biochemical recurrence free survival after radical prostatectomy among men in active surveillance following grade reclassification and men newly diagnosed with similar grade disease |
Prostate Cancer: Localized: Active Surveillance II | 17BOS |
Abstract: MP43-13 Sources of Funding: None Introduction Evaluate the biochemical recurrence free survival (bRFS) in men after radical prostatectomy (RP) triggered by Gleason score (GS) grade reclassification (GR) during active surveillance (AS) in order to inform patient decisions. Methods We conducted a retrospective analysis of men undergoing RP from 1995-2015 and identified 2 groups; 122 men in AS who underwent RP following GR (7(3+4) or greater, grade group 2 and above) and 4433 men who underwent immediate RP (IRP) following a diagnosis of grade group 2 and above. bRFS was assessed using Kaplan Meir and multivariate Cox regression analyses. Results Of 122 men in AS, 13 (10.7%) had biochemical recurrence (BCR) as compared to 777 of 4,433 (17.5%) men that underwent IRP (p =0.007). As compared to the IRP group, men on AS were significantly older (p <0.001), had a higher proportion of low volume cancers (p <0.001), a lower PSA density (p =0.001), and a lower rate of GS upgrade at surgery (p <0.001). bRFS was higher for men in the AS cohort compared to IRP group (p = 0.046, Fig 1). After adjustment for confounders, the difference in bRFS between groups was no longer significant (HR = 0.77; 95% CI, 0.41 to 1.46). Conclusions AS patients that are reclassified to grade group 2 and above have a higher bRFS after surgery as compared to those undergoing IRP with similar grade disease. These differences are likely due to selection criteria for AS. Our findings help inform patient decisions regarding the risk of entering an AS program. Funding None
Authors
Clarissa Diniz
Ballentine Carter Jonathan Epstein Mufaddal Mamawala |
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MP43-14 |
Utility of a novel biopsy instrument with long side-notch needle in the selection of patients for active surveillance |
Prostate Cancer: Localized: Active Surveillance II | 17BOS |
Abstract: MP43-14 Sources of Funding: none Introduction Active surveillance (AS) is now an accepted strategy for men with low-risk prostate cancer (PCa). A critical factor for successful AS is the best possible patient selection. However, a recent large retrospective study indicates that currently available AS criteria are limited by a high rate of misclassification. We recently collaborated with a biopsy needle manufacturer, TSK Laboratory, to develop a novel 18-G biopsy instrument based on an existing instrument (PRIMECUT® II), by extending the side-notch length from 19 to 25 mm and the stroke length from 22 to 28 mm, to take a longer tissue core and to reach the anterior portion of the prostate. In this study, we evaluated utility of the novel biopsy instrument in the selection of patients for AS._x000D_ Methods A total of 167 PCa patients diagnosed with the long-notch needle (n=62; long-notch group) or normal-notch needle (n=105; normal-notch group), who subsequently underwent prostatectomy, were retrospectively analyzed. All patients were diagnosed with 12 transrectal ultrasound-guided standard cores. The sampled core length, correlation between total tumor length in biopsy specimens, and total tumor volume in prostatectomy specimens were compared between the two groups. Gleason score (GS) upgrading was also compared. Prostatectomy specimens of patients who met the criteria of the PRIAS study were compared for the two groups._x000D_ Results The mean length of tissue taken with the long-notch needle was significantly longer than that taken with the normal-notch needle (16.3 vs. 22.4 mm, p<0.001). The correlation coefficient between total tumor length in biopsy specimens and total tumor volume in prostatectomy specimens of the long-notch group was higher (r=0.701) than that in the normal-notch group (r=0.611). GS upgrading in the long-notch group was significantly lower than that in the normal-notch group (25.8 vs. 41.0%, p=0.0479) Only 1 patient with tumor volume >0.5 cc and GS 4+3 or more was included among the 5 who met the criteria of the PRIAS study in the long-notch group, while 6 patients were included among the 10 who met the criteria in the normal-notch group._x000D_ Conclusions We developed a novel biopsy instrument with a 25 mm side-notch for longer tissue samples, increased correlation between tumor volume in biopsy and prostatectomy specimens, and decreased GS upgrading. These results suggested the utility of the long-notch needle in the selection of patients for AS. Funding none
Authors
Kent Kanao
Keishi Kajikawa Ikuo Kobayashi Hiroyuki Muramatsu Shingo Morinaga Hiroshi Saiki Genya Nishikawa Yoshiharu Kato Masahito Watanabe Kogenta Nakamura Makoto Sumitomo |
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MP43-15 |
Clinical significance of detection of perineural invasion (PNI) on a surveillance biopsy in favorable risk men on active surveillance |
Prostate Cancer: Localized: Active Surveillance II | 17BOS |
Abstract: MP43-15 Sources of Funding: None Introduction 1) Evaluate the association between detection of perineural invasion (PNI) on a surveillance biopsy and grade reclassification (GR or Gleason score (GS) ≥ 7) during active surveillance (AS); 2) assess whether the presence of PNI alone should exclude men from AS. Methods The study cohort was 1559 men enrolled in an AS registry from 1995 to 2016, following diagnosis of favorable risk prostate cancer. The outcome of interest was GR on surveillance biopsy. A logistic model was used to evaluate the relationship between PNI and GR on next surveillance biopsy. The predictive accuracy of PNI for GR was compared with a recently published multivariable GR risk prediction tool that included period of diagnosis, age, cancer volume, risk status, PSA density, and number of previous biopsies without GR. Predictive performance was evaluated using concordance statistics (AUC), calibration and decision curve analysis Results Of 1559 men with a median follow-up of 4 years (IQR 2-7 years), 156 (10%) had PNI detected on at least one surveillance biopsy. Three hundred and nineteen men (20%) had GR. PNI was detected in a significantly higher proportion of men with GR than men without GR (19.7% vs. 7.5%, p = <0.0001). PNI was significantly associated with GR, OR = 2.91 (95% CI, 2.06 - 4.10, p = < 0.001; AUC = 0.58) in a univariable analysis. The multivariable prediction tool had an AUC of 0.75 (calibration slope = 0.84) for predicting GR with no significant gain in predictive accuracy by incorporating PNI (AUC of 0.77, calibration slope = 0.86). A decision curve analysis showed a positive net benefit of using multivariable risk prediction tools over PNI alone for future biopsy outcome predictions. Conclusions : Shared decisions on AS selection and monitoring should be based on individualized risk assessments from multivariable risk prediction tools rather than presence or absence of a single risk factor. Funding None
Authors
Mufaddal Mamawala
Patricia Landis Jonathan Epstein Bruce Trock H. Ballentine Carter |
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MP43-16 |
Variation in Active Surveillance Utilization for the Management of Prostate Cancer in a Regional Collaborative |
Prostate Cancer: Localized: Active Surveillance II | 17BOS |
Abstract: MP43-16 Sources of Funding: Data was provided with permission from the Pennsylvania Urologic Regional Collaborative (PURC), funded by participating urology practices and the Partnership for Patient Care, a quality improvement initiative supported by the Health Care Improvement Foundation, Independence Blue Cross, and southeastern Pennsylvania hospitals and health systems. Introduction Active surveillance (AS) is gaining increasing acceptance as an effective management strategy for men with low risk prostate cancer. We analyzed a regional prostate cancer collaborative in order to characterize variation in the utilization of AS among practitioners and identify factors influencing AS rates. Methods The Pennsylvania Urologic Regional Collaborative (PURC), established in 2014, is a voluntary collaborative of urology practices in Southeastern Pennsylvania focused on the evaluation and improvement of prostate cancer care. We prospectively identified men with newly diagnosed prostate cancer across 6 academic and private practice sites from PURC, and determined the percentage of men initially managed with AS. Variations in AS rates by individual practitioner were determined for men with NCCN very low or low risk disease. Demographic and clinicopathologic parameters were assessed to determine how these factors influenced AS rates. Results Between May 2015 and October 2016, 282 of 1154 (19.6%) men with newly diagnosed prostate cancer underwent AS as initial management strategy, including 82/104 (78.9%) men with NCCN very low and 133/322 (41.3%) with NCCN low risk disease. AS rates stratified by practitioner for men with very low or low risk disease ranged from 11.1% to 100% (Figure 1). Associations of demographic and clinicopathologic parameters with AS rates are shown in the Table. High PSA, Gleason score, clinical stage, and NCCN risk category were all strongly associated with decreased utilization of AS (all p-values < 0.01). Conclusions Recent data report AS rates as high as 91% and 74% for NCCN very low and low risk prostate cancer, respectively. In the PURC collaborative, we observed lower rates of AS utilization for men with low risk prostate cancer, and significant variation in AS utilization among practitioners. These findings demonstrate the potential importance of quality collaboratives such as PURC in helping to identify variations in care and targets for quality improvement within local markets. Funding Data was provided with permission from the Pennsylvania Urologic Regional Collaborative (PURC), funded by participating urology practices and the Partnership for Patient Care, a quality improvement initiative supported by the Health Care Improvement Foundation, Independence Blue Cross, and southeastern Pennsylvania hospitals and health systems.
Authors
Adam Reese
Claudette Fonshell Serge Ginzburg Thomas Guzzo Thomas Lanchoney Bret Marlowe Marc Smaldone Edouard Trabulsi Robert Uzzo on behalf of the Pennsylvania Urologic Regional Collaborative |
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MP43-17 |
MpMRI for Predicting Prostate Cancer Progression in Men on Active Surveillance: A Comparison to PSA Kinetics |
Prostate Cancer: Localized: Active Surveillance II | 17BOS |
Abstract: MP43-17 Sources of Funding: This research was supported by the Intramural Research Program of the National Cancer Institute, NIH Introduction Pathologic progression is identified in >25% of prostate cancer (CaP) patients on active surveillance (AS). Yet, the ability to identify which patients are at risk for progression is limited to PSA-based biomarkers with variable utility. Multiparametric MRI (mpMRI) with fusion-guided prostate biopsy (FBx) has demonstrated utility in risk stratification for patients considering AS. We compared mpMRI characteristics with PSA kinetics for the prediction of pathologic progression in patients on AS. Methods A review of men on AS with serial mpMRI and 2 or more FBx sessions was performed. FBx sessions consisted of targeted biopsies and a 12-core systematic biopsy. Men who met NIH Expanded AS criteria included those with low and intermediate risk CaP, Gleason score ? 3+4 with no restriction on percent core involvement. Progression was defined by patients with initial Gleason 3+3 to any Gleason 4, and Gleason 3+4 to a primary Gleason 4 or higher. MRI progression was defined as increase in lesion suspicion score, size, or new lesion on follow-up. PSA density (PSAD) > 0.15ng/ml2, velocity (PSAV) > 0.75ng/ml/year, doubling time (PSAdt) < 3 years, and imaging characteristics were examined for association with pathologic progression at surveillance biopsy. Results A total of 178 men were included for analysis. Median follow-up was 19 months [IQR 14-29]. Median age, PSA, and prostate volume of our cohort were 63 years [IQR 58-68], 5.0ng/ml [IQR 3.4-7.4] and 47.8ml [IQR 36.4-59.7] at enrollment. The sensitivity and specificity of predicting pathologic progression by mpMRI, PSAD, PSAV and PSAdt were 46% and 65%, 16% and 88%, 20% and 87%, and 30% and 75% respectively. A combination of MRI with PSAD, PSAV, or PSAdt yielded a sensitivity and specificity of 53% and 44%, 57% and 57%, or 63% and 49% respectively. Using a decision curve analysis, mpMRI offers a small additional benefit for predicting CaP progression. Conclusions MpMRI alone marginally outperforms PSA kinetics for predicting pathologic progression in men on AS for CaP. The combination of mpMRI with PSA parameters increases the sensitivity of identifying progression in AS patients, but still fails to capture a significant proportion of progression. Further research in prostate imaging and other biomarkers will be needed to more accurately risk stratify AS patients. Funding This research was supported by the Intramural Research Program of the National Cancer Institute, NIH
Authors
Mahir Maruf
Abhinav Sidana Amit L Jain Brian Calio Dordaneh Sugano Michael Kongnyuy Arvin K. George M Minhaj Siddiqui Akhil Muthigi Subin Valayil Thomas P. Frye Peter L. Choyke Baris Turkbey Bradford Wood Peter Pinto |
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MP43-18 |
FOR MEN ON ACTIVE SURVEILLANCE FOR PROSTATE CANCER, OLDER AGE AT DIAGNOSIS AND AT RADICAL PROSTATECTOMY PORTENDS POOR OUTCOMES |
Prostate Cancer: Localized: Active Surveillance II | 17BOS |
Abstract: MP43-18 Sources of Funding: None Introduction Compared to younger men with prostate cancer (PCa), older men with the disease are more likely to present at an advanced stage, and even when adjusting for stage and grade, to die of the disease. Despite this phenomenon, older men, often with competing comorbidities, are more likely to elect active surveillance (AS) rather than primary definitive treatment. We sought to investigate whether advanced age at PCa diagnosis is a risk factor for grade reclassification (GR) while on AS. Additionally, for men ultimately going on to have secondary radical prostatectomy (RP) after initial AS, we sought to investigate whether advanced age at RP is a risk factor for adverse post-operative outcomes, including pathologic Gleason score (GS) upgrading, adverse RP pathology, and biochemical recurrence (BCR)._x000D_ Methods Between 1995 and 2016, 1554 men aged 41-81 years (median 66 years) with NCCN very low (70%) and low (30%) risk PCa on AS were followed using an institutional database. We queried this database to determine rates of GR (biopsy GS≥3+4), as well as pathologic GS upgrading, adverse RP pathology (≥pT3a or pathologic GS≥4+3), and BCR in patients going on to RP. A competing risk analysis was used to evaluate the association between age and time to GR and BCR. Likewise, a multivariable logistic regression model was used to determine whether age at RP was a significant risk factor for pathologic GS upgrading and adverse RP pathology. Odds (OR) and hazard (HR) ratios were calculated for 10-year age increases. Results Of the 1554 men in our AS cohort, 331 (21%) had GR and 295 (19% of all men) went on to have RP. Of those who underwent RP, 155 (53%) had pathologic GS upgrading, 89 (30%) had adverse RP pathology, and 18 men (6%) developed BCR after a median of 3 years. Age at diagnosis of PCa was a significant risk factor for GR (HR 1.4; 95%CI 1.2-1.7; p=0.0003). Of those going on to RP, age at RP was a significant risk factor for pathologic GS upgrading (OR 2.2; 95%CI 1.3-3.7; p=0.005), adverse RP pathology (OR 2.6; 95%CI 1.4-4.9; p=0.004), and BCR (HR 3.6; 95%CI 1.1-11.2; p=0.03). Conclusions For men on AS, age at PCa diagnosis is a significant risk factor for GR, and age at RP after being on AS is a significant risk factor for pathologic GS upgrading, adverse RP pathology, and BCR. These observations have significant implications for monitoring older men on AS. Funding None
Authors
Sasha Druskin
Mufaddal Mamawala Jeffrey Tosoian H. Ballentine Carter Bruce Trock |
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MP43-19 |
Active Surveillance for Favorable-Risk Prostate Cancer in African Caribbean Men: Results of a Prospective Study |
Prostate Cancer: Localized: Active Surveillance II | 17BOS |
Abstract: MP43-19 Sources of Funding: none Introduction Active surveillance (AS) is a treatment option for favorable-risk prostate cancers (PCa). However, data concerning populations of African descent is missing. The objective of this study was to evaluate the safety and benefit of AS in an African Caribbean cohort with favorable-risk PCa. Methods Between 2005 and 2016, a monocentric prospective cohort study was conducted in Guadeloupe (French West Indies), including patients with low-risk PCa (prostate-specific antigen [PSA] ?10 ng/ml; Gleason ?6) or favorable intermediate-risk PCa (PSA, 10-20 ng/ml; Gleason ?7 (3+4); life expectancy <10 years) in AS. Treatment was recommended in case of histological progression, increase in tumor volume, PSA doubling time <36 months or patient’s wish. Outcomes were overall survival, disease-specific survival and duration of AS, calculated with the Kaplan-Meier method. Multivariate analysis was performed using the Cox proportional hazards model to identify predictors of AS termination. Results A total of 234 patients (median age 64 yr) were enrolled in the study. Median follow-up was 4 years (interquartile range: 2.3-5.5 yr). Overall survival at 30 months, 5 and 10 years was 99.5%, 98.5%, 90.7% respectively. Disease-specific survival at 30 months, 5 and 10 years was 100%. At 30 months, 5 and 10 years, 72.7%, 52.6%, 40.4% of patients respectively remained untreated and under AS. Age (hazard ratio [HR], 0.96 per additional year; 95% confidence interval [CI], 0.93-0.99) and PSA density (HR, 1.52 per additional 0.1; 95% CI, 1.20-1.89) were found to be independent predictors of AS termination. Conclusions AS seems to be safe and beneficial for African Caribbean men with favorable-risk PCa. The high rate of patients leaving AS may reflect a greater proportion of aggressive cancers in this population. PSA density could help to better select these patients. Longer follow-up is needed to confirm these results. Funding none
Authors
Matthias Meunier
Rémi Eyraud Cédric Sénéchal Gilles Gourtaud Virginie Roux Cécilia Lanchon Laurent Brureau Pascal Blanchet |
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MP43-20 |
Rates of Non-Definitive Management for Low and Intermediate Risk Prostate Cancer are Similar Between African Americans and Caucasians |
Prostate Cancer: Localized: Active Surveillance II | 17BOS |
Abstract: MP43-20 Sources of Funding: none Introduction Disparities exist with respect to race in the management of localized prostate cancer (PCa). We hypothesized that African American (AA) men with low and intermediate risk PCa (LIPCA) were more likely to choose non-definitive management (NDM) as well as less invasive treatment options versus Caucasian (CA) men. Methods We performed a retrospective cohort study of 219,862 patients diagnosed with LIPCa in the National Cancer Database from 2010-2013. Our primary endpoint was rates of NDM {active surveillance (AS) + watchful waiting (WW)} by AA men versus CA men. Our secondary endpoint was to identify the differences in treatment modalities between these two races. We performed multivariate logistic regression analysis that controlled for age, race, clinical stage, facility volume, facility location, facility type, insurance, Charlson comorbidity index, PSA, year of diagnosis, and geographic location. Results Of the 219,862 patients with LIPCa, 105,295 patients had NCCN low risk PCa and 114,567 patients had NCCN intermediate risk PCa. 179,372 (82%) were CA men, 31,358 (14%) AA men, and 9,132 (4%) Other Races. The median age for AA men, CA men, and Other Races was 61, 64, and 63 respectively. 21,544 (9.8%) of patients elected NDM and utilization was similar between CA men (9.6%) and AA men (9.9%) OR 1.098 p<0.001. As shown in Figure 1, Radical Prostatectomy (RP) was the most utilized treatment modality across all races but AA men were less likely than CA men to utilize this treatment (43.4% versus 53.5%), respectively p < 0.001. In addition, AA men were (8%) more likely to choose radiotherapy (RT) versus CA men, (38.1% versus 30%) p < 0.001. _x000D_ _x000D_ Conclusions AA men with LIPCa choose NDM at similar rates to CA men, however this rate is relatively low at 9.8%. Notably, AA were more likely to choose RT and less likely to choose RP compared to CA men. Funding none
Authors
John Burns
John P. Flores Mazen Alsinnawi Sydney Akapame John Massman III Christopher Porter |
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MP44-01 |
In vivo fluorescence imaging of an orthotopic rat bladder tumor model indicates differential uptake of intravesically instilled near-infrared labeled 2-deoxyglucose analog by neoplastic urinary bladder tissues |
Bladder Cancer: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP44-01 Sources of Funding: University of Oklahoma Introduction Bladder cancer is one of the most expensive cancers to manage due to frequent recurrences requiring life-long surveillance and treatment. Deoxyglucose radionucleotides have been shown to detect metastatic bladder cancer. This pilot study has explored differential uptake of intravesically administered IRDye800CW-DG, a near-infrared labeled 2-deoxy-d-glucose probe targeting glucose metabolism pathway, to detect surface cancer in an orthotopic rodent bladder tumor model. Methods Twenty-five female Fischer rats were randomly grouped to four conditions: control (n=3), control and intravesically instilled with IRDye800CW-DG (n=6), treated with GFP-labeled AY-27 rat bladder urothelial cell carcinoma cells and washed with saline (n=5), and treated with AY-27 and intravesically instilled with IRDye800CW-DG (n=11). Near-infrared fluorescence was measured from the opened bladder wall of anesthetized rat at an excitation wavelength of 750nm and an emission wavelength of 776nm, by using an in-house fluorescence imaging system. Results There is no statistically significant difference of the peak fluorescence intensity among the control bladders (n=3), the control bladders instilled with IRDye800CW-DG (n=6), and the GFP-labeled AY-27 treated bladders washed by saline (n=5). When compared to that of the control bladders instilled with IRDye800CW-DG (n=6), the fluorescence intensity of GFP-labeled AY-27 treated bladders instilled with IRDye800CW-DG and with histology confirmed neoplastic bladder tissue (n=11) was remarkably stronger (3.34 folds of the former) that was also statistically significant (p<0.0001). Conclusions The differential uptake of IRDye800CW-DG by the neoplastic urinary bladder tissues suggests the potential for cystoscopy-adaptation to enhance diagnosis and guiding surgical management of flat urinary bladder cancer. Funding University of Oklahoma
Authors
Joel Slaton
Carole Davis Robert Hurst Daqing Piao |
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MP44-02 |
Identification and validation of C1orf198 as an independent marker of bladder cancer metastasis in SEER and TCGA database |
Bladder Cancer: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP44-02 Sources of Funding: National Natural Science Foundation of China?8150100539? Introduction Determination of metastasis is urgent in the management of bladder cancer (BC). With the existing models predicting BC metastasis, we found two deviant groups that are unpredictable with clinical parameters. One is at high risk of pN+ but actually with pN0 (good prognosis group, G) and the other one is at low risk of pN+ but actually with pN+ (poor prognosis group, P). The present study aimed to determine the gene expression differences between these two groups with SEER database and TCGA database and validate the results in a cohort from Fudan University Shanghai Cancer Center (FUSCC). Methods 1603 patients with radical cystectomy (RC) from the SEER database were enrolled to build a multivariate model predicting BC metastasis. This model was applied in 248 patients from TCGA database to distinguish these two deviant groups (G and P). The different expressed genes of the two groups were compared by t-test. RT-qPCR was applied to validate the results in a consecutive cohort of 127 BC patients who underwent RC from FUSCC. Results The multivariate logistic regression model based on SEER population identified 256 patients as group G and 76 patients as group P. The similar phenomenon was observed in TCGA database with 37 patients of group G and 17 patients of group P respectively. 183 genes showed significant difference between these two groups. Finally, 18 genes achieved a significant statistical power (P<0.05) in predicting lymph node metastasis in the TCGA cohort excluding these two deviant groups. Furthermore, the RT-qPCR results of our own cohort identified C1orf198 (P=0.04) as the only gene that expressed differently in the two groups. Conclusions Our study suggested that C1orf198 might serve as an independent predictor of metastasis in patients with muscle-invasive bladder cancer. Funding National Natural Science Foundation of China?8150100539?
Authors
Beihe Wang
Fangning Wan Yijun Shen Yiping Zhu Yao Zhu Dingwei Ye |
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MP44-03 |
Low Grade Bladder Tumors Progress to High Grade via Two Distinct Mechanisms |
Bladder Cancer: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP44-03 Sources of Funding: None Introduction Low-grade (LG) urothelial carcinoma of the bladder (UCB) are common malignancies that are costly to surveil and infrequently progress to life threatening, high-grade (HG) malignancies. It is not clear whether the progression of LG to HG is a result of second primaries or transformation of LG tumors. We sought to examine tumor genetics in patients who progressed from LG to HG urothelial carcinoma and compared to patients with no progression. Methods An institutional cancer database at a tertiary referral center in the United States was queried for living patients who progressed from LG to HG UCB. Histologic re-review was performed by a genitourinary pathologist. Whole exome sequencing with correction for germline mutations by buffy coat subtraction was performed. Mutations were assessed for continuity or novelty between low grade tumors and subsequent same-patient HG tumors and for LG patients who did not progress. Individual genes were assessed for potential predictors of risk for progression. Results Five patients were identified with progression. Clinicopathologic variables were identified and median time to progression from initial low-grade diagnosis was 19 months. Both true tumor progression and de novo growth of high grade tumors were identified. Gene alterations associated with tumor grade progression in initial low grade tumors were FBN3, CIT and HECTD4. Conclusions Both true tumor progression and de novo high-grade tumors were observed in initial low grade urothelial carcinomas that progressed. Validation of the identified tumor genes that appeared associated with progression may provide a clinically valuable tool to providers managing patients with low grade urothelial carcinomas. Funding None
Authors
Ralf Kittler
Christine Shiang Ryan Hutchinson Rahul Kollipara Payal Kapur Franto Francis Yair Lotan |
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MP44-04 |
Significance of serum N-glycan profiling as a diagnostic biomarker in urothelial carcinoma |
Bladder Cancer: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP44-04 Sources of Funding: none Introduction The clinical diagnosis of urothelial carcinoma (UC) relies on invasive methods in patients with hematuria. Although more sensitive and noninvasive screening methods are required, a specific serum biomarker for UC is lacking._x000D_ To examine whether the serum glycan-based biomarkers can be applied to detecting UC. Methods Between April 1994 and June 2016, serum N-glycan concentrations were retrospectively measured in 212 patients with UC before treatment (UC group) and 212 pair-matched controls (VLT group) using glycoblotting and mass spectrometry._x000D_ N-glycan levels were compared between the groups using receiver operating characteristic (ROC) curves to select candidate N-glycans. We created an N-glycan score based on the combination of candidate N-glycans. The specificity and sensitivity of the candidate N-glycan score were evaluated using ROC curves._x000D_ Results The N-glycan score was calculated using six N-glycans (m/z 1566, 1687, 1769, 1871, 2011, 2337) that were significantly associated with UC. The median N-glycan score was significantly higher in the UC group than in the VLT group (5.0 vs. 1.0, P < 0.001). The predictive value of the N-glycan score for UC detection was significant, with a sensitivity, specificity, and area under the curve of 93%, 81%, and 0.95%, respectively. Conclusions Serum N-glycan content has the potential to be a specific and sensitive novel serum biomarker that may improve the accuracy of detection for UC and reduce unnecessary invasive screening. Validation of this test in a large-scale prospective study is needed. Funding none
Authors
Masaaki Oikawa
Shingo Hatakeyama Tohru Yoneyma Yuki Tobisawa Takuma Narita Hayato Yamamoto Yasuhiro Hashimoto Takuya Koie Shintaro Narita Atsushi Sasaki Norihiko Tsuchiya Tomonori Habuchi Ippei Takahashi Shigeyuki Nakaji Chikara Ohyama |
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MP44-05 |
Overexpression of immune co-stimulatory molecule B7-H4 is associated with poor survival in bladder urothelial carcinoma |
Bladder Cancer: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP44-05 Sources of Funding: This research was supported in part by the John P. Hanson Foundation for Cancer and Cellular Research. The results shown here are in part based upon data generated by the TCGA Research Network: http://cancergenome.nih.gov/ Introduction Currently, only 30% of patients respond to therapy with checkpoint inhibitors PD-1/PD-L1. Exploration of other members of the B7-CD28 family may provide additional targets for immunotherapy. B7-H4 (VTCN1) has previously been demonstrated to be associated with survival in renal cell carcinoma and breast cancer, but little is known regarding its expression in bladder cancer. Methods Mutational, RNAseq, and clinical data from The Cancer Genome Atlas (TCGA) provisional bladder urothelial carcinoma dataset (n=408) was downloaded from cBioPortal (http://www.cbioportal.org/). Normalized RNAseq data was correlated with the number of non-synonymous mutations using Spearman's correlation. Overall survival of patients with overexpression (z>2) of immune checkpoints was compared using Kaplan-Meyer analysis. TCGA samples were subtyped using the original TCGA molecular subtypes 1-4 (n=131). Expression of immune checkpoints was compared between subgroups using ANOVA. Statistical analysis was performed using R and GraphPad Prism. Results Overexpression (z>2) of B7-H4 is associated with poor survival (Figure 1). Expression of B7-H4 is not associated with expression of CD8A, or with the number of non-synonymous mutations, unlike PD-1, PD-L1, PD-L2, CTLA-4, TIM-3, and LAG-3. Expression of B7-H4 is highest in TCGA subtype II (luminal / p-53-like), unlike PD-1, PD-L1, CTLA-4, TIM-3, and LAG-3 (TCGA subtype IV, basal / claudin-low) (Figure 2)._x000D_ Conclusions Overexpression of B7-H4, a member of the B7-CD28 co-stimulatory family, is associated with poor survival in bladder urothelial carcinoma. B7-H4 is highly expressed in TCGA Subtype II (luminal), unlike PD-L1, which is highly expressed in Subtype IV (basal / claudin-low). Further study of B7-H4 and its function in bladder cancer is needed, but it may be a promising target for immunotherapy, especially for patients who do not respond to PD-L1 therapy. Funding This research was supported in part by the John P. Hanson Foundation for Cancer and Cellular Research. The results shown here are in part based upon data generated by the TCGA Research Network: http://cancergenome.nih.gov/
Authors
Alexander Glaser
Joseph Podojil Stephen Miller Joshua Meeks |
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MP44-06 |
Immunohistochemical Evaluation of Basal and Luminal Markers in Non-Muscle Invasive Urothelial Carcinoma of Bladder (NMIBC) |
Bladder Cancer: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP44-06 Sources of Funding: None Introduction The Cancer Genome Atlas (TCGA) collaboration has identified two intrinsic subtypes (basal and luminal) in urothelial bladder carcinoma. However, the study was limited to muscle invasive bladder cancer (MIBC). Subsequent studies suggested a limited panel of immunohistochemical markers could be used to assign basal vs luminal phenotype in MIBC with potential prognostic role. In this study we assess the applicability of the proposed phenotype classification in non-muscle invasive bladder cancer (NMIBC). Methods Three TMAs were constructed from 165 TURB specimens of 52 bladder cancer patients treated at one of author's institution (1998-2008). Follow up data on recurrence, grade or stage progression were obtained. Immunohistochemistry was performed using automated Ventana System for markers indicative of luminal (GATA3, CK20, ER, uroplakin, HER2/neu) and basal phenotype (CK5/6 and CD44). The extent, intensity and pattern of expression were evaluated for all markers by 3 urologic pathologists. HER2/neu was assessed using the breast and stomach scoring systems. Results By univariate analysis, using mean extent of expression as a cut off, higher proportion (83%; p=0.002) of tumors with stage progression demonstrated high CK5/6 expression. 15/143 (10.4%) of tumors with high CK5/6 expression demonstrated a higher stage on subsequent biopsy compared to 3/176 (1.7%) of those with low CK5/6. Higher proportion of tumors with stage progression had low levels of CK20 (75%;p=0.03) and CD44 (66%;p=0.009)._x000D_ Regarding recurrence, higher proportion of tumors with recurrence had low expression levels of CK5/6 (64%), CD44 (53%) and ER (91%) and high HER2/neu expression (53%) (p?0.002). There was no association between the rate of expression of any of the markers and grade progression upon recurrence. Conclusions Our findings suggest that both high CK5/6 and low CK20 expression are associated with higher likelihood of stage progression in NMIBC. Further analysis of potential role of basal and luminal markers, individually or in combination, in the prognostication of NMIBC in the context of known clinicopathologic parameters is needed. Funding None
Authors
Maria Del Carmen Rodriguez Pena
Aline C Tregnago Alcides Chaux Diana Taheri Walaa Borhan Katayoon Rezaei Marie-Lisa Eich Hirofumi Nonogaki Rajni Sharma George J Netto |
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MP44-07 |
A circular RNA (circLPAR1) as a novel biomarker of prognosis for bladder cancer |
Bladder Cancer: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP44-07 Sources of Funding: None Introduction Circular RNAs with a special form of non-coding RNAs play an important role in the development of human diseases, but few are known in various cancers. In the present study, we tried to explore the clinical application of circRNAs in bladder cancer. Methods Sanger sequencing, divergent primer amplification and RNAse R digestion were used to identify existence of a novel circRNA (circLPAR1,hsa_circ_0087960) from deep sequencing of RNA for bladder cancer. It was detected in 146 cancer tissues and 20 cases paracancer tissues to compare the different expression by qRT-PCR. A univariate and multivariate Cox regression was carried out to explore the correlation between circLPAR1 expression level and the overall survival(OS) of patients. We further investigated the possible network for circRNA-miRNA-mRNA by bioinformatics analysis. Results CircLPAR1 was composed of two exons with the size of 226bp. It was confirmed the objective existence and the circular structure, and first found to be significantly downregulated in bladder cancer tissues compared with paired paracancer tissues (P<0.001), which was verified by an external validation of other 60 pairs specimens(P=0.0001).On the univariate and multivariate analysis for 146 patients, a low circRNA expression level (2-?CT?0.0023) was significantly associated with poor OS compared to a high circRNA expression level (2-?CT?0.0023), and the mean OS was 64.9 months and 87.6 months, respectively (P<0.001). Four miRNA(hsa-miR-762, hsa-miR-323b-5p, hsa-miR-1183, hsa-miR-920) might be correlated with circLPAR1 and circRNA-miRNA-mRNA interaction network was drawn._x000D_ Conclusions Our findings suggested that circLPAR1(hsa_circ_0087960) might be a novel potential biomarker for the prognosis of bladder cancer and low expression of circLPAR1 indicated poor survival. Funding None
Authors
Guo-Wen Lin
Hao-Yue Sheng Hu-Yang Xie Yi-Jun Shen Guo-Hai Shi Ding-Wei Ye |
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MP44-08 |
The landscape of Her2 alterations in muscle-invasive bladder cancer: Impact on patient selection for targeted therapies? |
Bladder Cancer: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP44-08 Sources of Funding: none Introduction In contrast to cancers of the breast and stomach, targeting Her2 has not yet demonstrated anti-tumor activity in muscle-invasive bladder cancer (MIBC). We hypothesized that an integrated approach to Her2 characterization in MIBC may better guide patient prioritization for targeted therapy. Methods We investigated Her2 alterations on different biological levels (DNA, RNA and protein) in pre-chemotherapy MIBC of 127 patients who recieved at least 3 cycles of neoadjuvant chemotherapy prior to radical cystectomy (NAC cohort). The findings were underlined in the The Cancer Genome Atlas (TCGA) bladder dataset (n=407). Moreover, the signifcance of Her2 was analysed between the recently identified molecular subtypes (TCGA clusters). Results In the NAC cohort, FISH revealed that 16/83 tumors harbored ERBB2 amplification, while 24/127 had high Her2 protein expression by IHC (i.e. IHC score = 3). Samples with ERBB2 amplification had higher mRNA (p<0.001) and protein expression (p<0.001). However, 6/16 amplified samples had mRNA expression in the 1st tertile, and 10/16 had IHC scores of either 1 (n=5) or 2 (n=5). Interestingly, epigenetic regulation may downregulate Her2 expression. ERBB2 amplified tumors with low mRNA and protein expression showed a high ERBB2 methylation rate (R=-0.62, p<0.001). _x000D_ While the vast majority of ERBB2 amplified tumors (37/41), showed amplification of other known oncogenes (e.g. CCND1, CCDE1), 4 tumors showed ‘exclusively’ ERBB2 amplification._x000D_ In both datasets, Her2 alterations were most frequent in TCGA cluster I. None of the Her2 alterations harbored prognostic information in the TCGA dataset. In the NAC dataset, Her2 was a marker of unfavourable outcome in tumors assigned to TCGA cluster I. Conclusions Assessment of Her2 alterations on all biological levels provides a more comprehensive insight into Her2, than FISH or/and IHC alone. Failure of previous clinical trials may have confounded by this complex molecular landscape of Her2 alterations in MIBC. Our findings could help to improve patient selection for future clinical trials. Finally, Her2 activity is associated with molecular subtypes and therefore, future biomarker studies should take molecular subtypes into account. Funding none
Authors
Bernhard Kiss
Alexander Wyatt James Douglas Veronika Skuginna Fan Mo Shawn Anderson Diana Rotzer Achim Fleischmann Vera Genitsch Tetsutaro Hayashi Maja Neuenschwander Christine Buerki Elai Davicioni Colin Collins George Thalmann Peter Black Roland Seiler |
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MP44-09 |
Germline copy number polymorphism identified as potential prognostic marker for progression of non-muscle invasive bladder cancer |
Bladder Cancer: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP44-09 Sources of Funding: none Introduction Germline copy number polymorphisms (CNPs) are expected to affect various diseases including human malignancies, but the significance of CNPs in non-muscle invasive bladder cancer (NMIBC) remains unclear. PCSK6 is reported to regulate proliferation and tumor progression in breast and prostate cancer, and affect sodium homeostasis. The purpose of this study is to determine the prognostic value of CNPs for NMIBC. To our knowledge, this is the first report to confirm CNPs as a potential biomarker for assessing the prognosis of NMIBC. Methods Array comparative genomic hybridization (CGH) was performed to search for candidate CNPs related to NMIBC susceptibility. Next, quantitative real-time polymerase chain reaction was carried out to evaluate for CNPs related to patient's outcome in 190 NMIBC. Results Eleven CNPs were associated with NMIBC risk in array CGH. FAM81A and PCSK6 copy number according to those CNPs examined showed significant relationship with recurrence and disease progression in NMIBC. Patients with pT1 stage had significantly lower PCSK6 copy number than those with pTa (P = 0.0258). Interestingly, patients with lower PCSK6 copy number had significantly higher sodium levels in the blood than those with higher PCSK6 copy number (P = 0.0144). Univariate Cox proportional hazards regression analysis showed that tumor grade (P = 0.0073), pT stage (P = 0.0086), Cytology (P = 0.0045), FAM81A (P = 0.0173), and PCSK6 (P = 0.0011) copy number had a significant effect on progression-free survival. In multivariate analyses, PCSK6 copy number was an independent prognostic factor for progression-free survival (P = 0.0380, risk ratio 2.25, 95% confidence interval 1.05-5.03). Conclusions These data suggest that PCSK6 CNP is potentially a new tumor marker for estimating the prognosis of NMIBC. Funding none
Authors
Yoshiaki Yamamoto
Yutaka Suehiro Yoshihisa Kawai Ryo Inoue Hiroaki Matsumoto Hideyasu Matsuyama??? ? |
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MP44-10 |
Role of molecular Classification in High Grade (HG) non muscle invasive bladder cancer(NMIBC) |
Bladder Cancer: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP44-10 Sources of Funding: none Introduction There has been a growing interest in urothelial bladder cancer, probably due to new treatment modalities that will require molecular phenotyping. In order to tackle this issue, the aim of this study is to identify cases of HG-NMIBC at higher risk, by using the recently developed molecular classification of HG urotelian tumours: basal and luminal type. Methods We retrospectively analyzed data from 70 patients with primary or recurrent T1G3 NMIBC. All patients underwent complete transurethral resection of the bladder tumor including muscle in the sample. Every case received BCG induction. The study protocol (cod 2015/072) received approval from the ethics committee of clinical investigation of Galicia (Spain). Written informed consent was gained from all alive patients. Pathology specimens were reviewed by two independent investigators. Immunohistochemistry with prediluted antibodies against CD44 (Clone SP37), CK20 (Clone SP33), all of them from Ventana, and a concentrated antibody antiCK5 (Clone XM26, Novocasta) were used for categorized NMIBC as Luminal (CK5 and CD44 negative, CK20 positive) and Basal (CK5, CD44 positive and CK20 negative). Data were analyzed using SPSS version 19.0 for Windows IBM, Chicago, USA. A p value <0.05 was considered statistically significant. Results 76 % of cases (51/67) were categorized as Luminal and 3% (2/67) as Basal. Only 20.9% of cases (14/67) were not classifiable due to inconclusive test. Recurrence rate was lower in Luminal group (33%), compared with the basal group (50%). This differences do not reach statistical significance. Progression rate was lower in Luminal group (12%) compared with Basal group (50%), without statistical significance Conclusions Immunohistochemistry is useful for molecular classification of HR-NMIBC in luminal and basal types. In our study, most of HG-NMIBC belonged to the luminal type group. Given that cases in the basal group has presented a worse clinical outcome, and due to the availability of targeted treatment already used for other tumors, larger studies are needed to elucidate the role of this markers in the follow up and treatment for HG-NMIBC tumors. Funding none
Authors
Marina Gándara-Cortés
Manuel Carballo-Quinta María Elena López-Díez María Pilar San Miguel-Fraile José Antonio Ortiz-Rey Máximo Castro-Iglesias C Gómez de María Sheila Domínguez-Almúster Miguel Pérez-Schoch Joaquín González-Carreró |
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MP44-11 |
Biomarker-driven targeted oral treatment strategy for bladder cancer |
Bladder Cancer: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP44-11 Sources of Funding: 7R01 CA072821-16; 7R01CA176691-03 Introduction Hyaluronic acid (HA) family of molecules, HA-synthases (HAS-1,2,3), HA-receptors (CD44, RHAMM) and hyaluronidase (HYAL-1) are markers for bladder cancer (BCa) diagnosis and predicting prognosis. HA-family promotes tumor growth and metastasis by inducing epithelial mesenchymal transition (EMT). 4-Methylumbelliferone (4-MU) is an orally bioavailable dietary supplement that inhibits HA synthesis. We evaluated the expression of HA family and EMT markers in bladder tissues and antitumor effects of 4-MU in preclinical models of BCa. Methods mRNA expression of HA-family and EMT genes (beta-catenin, Twist, and Snail) in 72 bladder tissue specimens (28 normal; 44 tumor); follow-up: 20.3+/-2.5 months, was measured by QPCR. The effect of 4-MU (0-0.6 mM) on cell growth, apoptosis, HA-signaling were examined in BCa cell lines by Q-PCR, immunoblotting, proximal ligation and PI-3K activity assays. Effect of oral administration of 4-MU (100, 200-mg/kg) on tumor growth was analyzed in preclinical models. Results HAS-1, -2 -3, HYAL-1 and Snail levels were 10-20-fold elevated in BCa tissues as compared to normal bladder (P<0.001). In univariate analysis, HAS-1, -2, HYAL-1 and Twist levels correlated with metastasis (P<0.001); HYAL-1 was an independent predictor of metastasis. 4-MU inhibited cell proliferation, chemotactic motility and invasion in a dose-dependent manner; 50-70% inhibition at IC50 (0.4 mM) for HA-synthesis inhibition. 4-MU induced apoptosis (>3-fold) via the death receptor pathway. 4-MU downregulated HA-signaling; mRNA and/or protein levels of CD44, RHAMM, p-Akt, beta-catenin, p-beta-catenin(S552), snail and twist were downregulated by 3-5-fold, but p?catenin((T41/S45), pGSK-3alpha/beta and E-cadherin levels were elevated. 4-MU also inhibited CD44/PI-3K complex formation and PI-3K activity. HA addition or mAkt expression attenuated 4-MU effects. In xenograft studies, 4-MU oral treatment abrogated growth of established HT1376 tumors (vehicle, day 35: 766+/-221 mm3; 4-MU: 128+/-61, day 50). No weight loss or serum or organ toxicity was observed in treated mice. Conclusions This study demonstrates that HA-family and signaling is upregulated in BCa and can be specifically targeted for treatment by a non-toxic dietary supplement. Funding 7R01 CA072821-16; 7R01CA176691-03
Authors
Daley Schimmelpfennig
Michael W. Kemper Soum D. Lokeshwar Andre Jordan Vinata B. Lokeshwar |
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MP44-12 |
APOBEC-mediated mutagenesis is associated with expression of immune-related genes and overall survival in bladder cancer |
Bladder Cancer: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP44-12 Sources of Funding: This research was supported in part by the John P. Hanson Foundation for Cancer and Cellular Research. The results shown here are in part based upon data generated by the TCGA Research Network: http://cancergenome.nih.gov/ Introduction The APOBEC family of enzymes is responsible for a mutation signature characterized by a TcW->T/G mutation. APOBEC-mediated mutagenesis is implicated in a wide variety of tumors, including bladder cancer. However, less is known about regulation and function of the APOBEC genes and their subsequent mutation signature. In this study, we explore the APOBEC mutational signature in bladder cancer and the relationship with mutation burden, molecular classification, gene expression, and survival. Methods The Cancer Genome Atlas (TCGA) bladder urothelial carcinoma data was downloaded from cBioPortal (http://cbioportal.org) and the Broad Institute (http://gdac.broadinstitute.org). APOBEC enrichment score was calculated as previously described (Nat Genet 2013;45:970). Tumors with >2-fold enrichment with a Benjamini-Hochberg corrected p-value <0.05 were considered high in APOBEC enrichment. Statistical analysis was performed with R. Functional annotations were performed with DAVID (http://david.ncifcrf.gov). Results Expression of APOBEC3A and APOBEC3B are associated with the mutational burden in bladder cancer (r=0.18, p<0.001; r=0.334, p<0.001). High APOBEC enrichment score is associated with improved overall survival (Figure 1A). APOBEC enrichment does not vary between TCGA molecular subtypes 1-4 (Figure 1B). Of the top mutated genes in bladder cancer, patients with high APOBEC enrichment are more likely to have mutations in TP53, ERBB2, KMT2C and PIK3CA, but not ARID1A, CSMD3, RB1, KMT2D, KDM6A, or STAG2. Genes with expression positively associated with APOBEC enrichment (including PD-1, CTLA-4, TIM-3, and TIGIT) are involved in IFN-gamma signaling, antigen processing and presentation, and regulation of the immune response, while genes negatively associated with APOBEC enrichment are involved in translational initiation and ribosome assembly. Conclusions APOBEC enzymes are a major source of mutation in bladder cancer. Both luminal and basal subtypes of bladder cancer have similar APOBEC mutational signatures. This signature is associated with overall survival as well as expression of immune-related genes. Further study of regulation of APOBEC enzymes may provide further insight into the mutational landscape and potential therapeutics for bladder cancer. Funding This research was supported in part by the John P. Hanson Foundation for Cancer and Cellular Research. The results shown here are in part based upon data generated by the TCGA Research Network: http://cancergenome.nih.gov/
Authors
Alexander Glaser
Damiano Fantini Kalen Rimar Joshua Meeks |
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MP44-13 |
Molecular tracking of bladder cancerusing mutations detected in plasma cell-free DNA through radical cystectomy and chemotherapy. |
Bladder Cancer: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP44-13 Sources of Funding: none Introduction Genomic tracking from liquid biopsy such as urine and blood is a novel technique with the potential to monitor presence of tumour material non-invasively. To identify truncal mutations within heterogeneous tumours, an individualised or large panel multi-target approach must be used to monitor response. The complete response rate to chemotherapy for metastatic bladder cancer (BC) is limited, but the ability to identify response could be of significance in the neo-adjuvant setting. The aim of this study is to test the feasibility of detecting and monitoring somatic mutations in cell-free DNA (cfDNA) found in plasma of patients with BC pre and post-treatment. Methods 25 patients with muscle-invasive BC and 10 patients with metastatic BC were selected for this study. Patients with metastatic BC received at least 2 cycles of gemcitabine and cisplatin chemotherapy. 10 ml of blood was collected in EDTA tubes at each timepoint. Samples were taken at baseline for all patients, twelve weeks after surgery for the cystectomy cohort, and before each cycle of chemotherapy for the metastatic cohort. Plasma was separated by centrifugation, and cfDNA extracted with the QIAamp Circulating Nucleic Acid Kit. Targeted amplification was performed using duel indexed primers, followed by next generation sequencing (NGS) using a panel of known (TERT PIKC3, FGFR3, HRSA) and novel BC mutations. Changes in cfDNA mutation burden were compared with cross sectional imaging, and response was assessed using the RECIST criteria. Results cfDNA was isolated from all samples at baseline and subsequent treatment. Baseline DNA quantification was performed, and a mean of 77.5 and IQR 10.9-72.7 ng/ml (Qubit) collected. This did not correlate with baseline disease burden or subsequent response to chemotherapy. Mutation profiles varied between patients, but at least one mutation was identified the plasma cfDNA of all patients. Dynamic changes in the mutational burden were detected in several patients. In a few patients with nodal disease, mutational changes were still detectable post-cystectomy. Conclusions Plasma cfDNA is detectable in patients with BC but its quantity is not a reliable indicator of disease burden. Mutational analysis of plasma cfDNA is feasible for use as a non-invasive biomarker of therapeutic response to chemotherapy, and the presence of residual disease post-cystectomy. Dynamic changes in mutational burden for each patient are likely to be related to their individual tumour’s heterogeneity, and the expansion of sub-clonal populations in both primary and metastatic lesions. Funding none
Authors
Pramit Khetrapal
Liqin Dong Yien Ning Sophia Wong Wei Shen Tan Simon Rodney Benjamin Lamb Ashwin Sridhar Tim Briggs John Kelly Andrew Feber |
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MP44-14 |
Downregulation of miR-200b is associated with cisplatin-resistance in bladder cancer cells |
Bladder Cancer: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP44-14 Sources of Funding: none Introduction Chemoresistance to cisplatin (CDDP) is one of the major clinical issues in bladder cancer (BCa) treatment. MicroRNAs (miRNA) are noncoding RNAs that are potentially involved in chemoresistance in various cancers. We therefore aimed to determine the roles of miRNAs in the CDDP-resistance in BCa. Methods We established 2 CDDP-resistant BCa cell lines (T24RC and EJ138RC) by continuously treating parental T24 and EJ138 cells. Profiles of miRNA expression in BCa cells were assessed by TaqMan arrays (Applied Biosystems). BCa cells were transfected with a mimic or an inhibitor of miR-200b (Ambion), after which the sensitivities to CDDP were evaluated via cell viability assays. Methylation of a CpG island of the miR200b gene was assessed by bisulfite-pyrosequencing. BCa cells were treated with the DNA demethylating agent 5-aza-2’-deoxycytidine (5-aza-dC) to restore the expression of miR-200b. Results Of the 754 miRNAs analyzed, miR-200b was downregulated in CDDP-resistant BCa cells (Figure 1). Induction of miR-200b in T24RC cells restored the CDDP sensitivity (Figure 2a). In contrast, inhibition of miR-200b increased CDDP resistance in T24 and EJ138 cells (Figure 2b and 2c). The levels of methylation in the CpG islands of miR-200b were significantly increased in T24RC and EJ138RC as compared to their parental cells (T24RC, 83.3%; T24, 53.3%; EJ138RC, 77.0%; EJ138, 62.6%; P < 0.01, Student t test), and treatment with 5-aza-dC restored the miR-200b expression in resistant cells (Figure 3a and 3b). Moreover, treatment with CDDP and 5-aza-dC synergistically inhibited the growth of T24RC cells (Figure 3c). Conclusions Our results suggest that epigenetic downregulation of miR-200b may be causally related to the CDDP-resistance in BCa, and that it could be a potential therapeutic target. Funding none
Authors
Tetsuya Shindo
Naotaka Nishiyama Takeshi Niinuma Hiroshi Kitajima Masahiro Kai Takashi Tokino Nobuo Shinkai Hiromu Suzuki Naoya Masumori |
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MP44-15 |
ANXA10 and ATP7A are the mTOR pathway downstream to predict the recurrence and progression in non-muscle invasive high grade urothelial carcinoma of the bladder |
Bladder Cancer: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP44-15 Sources of Funding: This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology, Republic of Korea (2015R1A1A1A0500110). Introduction The cross-talk of mammalian target of rapamycin (mTOR) pathway is clinical limitation of mTOR inhibitor for the treatment of urothelial carcinoma (URCa) of the bladder. This study is to search mTOR pathway downstream genes to overcome cross-talk at non muscle invasive high grade (HG)-URCa of the bladder. Methods Gene expression patterns, gene ontology, and gene clustering by triple (p70S6K, S6K and eIF4E) siRNAs or rapamycin in 5637 and T24 cell lines were investigated by microarray analysis and we selected mTOR pathway downstream genes which were suppressed to siRNAs more than two fold, and rapamycin up-regulated or rapamycin down-regulated. And then we validated mTOR downstream genes with immunohistochemistry using tissue microarray of 125 non-muscle invasive HG-URCa patients whether genes can predict clinical aggressiveness and long-term outcomes, and knockout study to evaluate the synergistic effect with rapamycin. Results In the microarray analysis, we selected mTOR pathway downstream genes which consisted of 4 rapamycin up-regulated (FABP4, H19, ANXA10, and UPK3A), and 4 rapamycin down-regulated (FOXD3, ATP7A, plexin D1 and ADAMTS5). In tissue microarray, FABP4 and ATP7A were more expressed at T1, and FOXD3 was at Ta. ANXA10 and ADAMTS5 were more expressed at 3 cm or less than 3cm. In Kaplan-Meier curve, ANXA10 was a significant predictor of recurrence, and FABP4 and ATP7A were significant predictors of progression of HG-URCa of the bladder. In multivariate Cox regression model, ANXA10 was a significant predictor of recurrence and ATP7A was a significant predictors of progression in non-muscle invasive HG-URCa of the bladder. In ATP7A knock out model, rapamycin treatment showed synergistic effect to inhibit cell viability, wound healing, and invasion ability compared to rapamycin only. Conclusions ANXA10 and ATP7A might be mTOR pathway downstream genes to predict recurrence and progression in non-muscle invasive high-grade urothelial carcinoma of the bladder and ATP7A knockout overcome the rapamycin coss-talk. Funding This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology, Republic of Korea (2015R1A1A1A0500110).
Authors
Byung Hoon Chi
Subin Jin Young Mi Whang Seung Hyun Ahn Jae Duck Choi Shin Young Lee In Ho Chang Bongsuk Shim |
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MP44-16 |
NBR1 and KIF14 are the mTOR pathway downstream to predict the recurrence in non-muscle invasive low grade urothelial carcinoma of the bladder |
Bladder Cancer: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP44-16 Sources of Funding: This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology, Republic of Korea (2015R1A1A1A0500110), and (2015R1A2A1A15054364). Introduction The cross-talk of mammalian target of rapamycin (mTOR) pathway is clinical limitation of mTOR inhibitor for the treatment of urothelial carcinoma (URCa). This study is to search mTOR pathway downstream genes to overcome cross-talk at non muscle invasive low grade (LG)-URCa of the bladder. Methods Gene expression patterns, gene ontology, and gene clustering by dual (p70S6K and S6K) siRNAs or rapamycin in 253J and TR4 cell lines were investigated by microarray analysis and we selected mTOR/S6K pathway downstream genes which were suppressed to siRNAs, and rapamycin up-regulated or rapamycin down-regulated. We validated mTOR downstream genes with immunohistochemistry using tissue microarray of 90 non-muscle invasive LG-URCa patients whether genes can predict clinical outcomes, and knockout study to evaluate the synergistic effect with rapamycin. Results In the microarray analysis, we selected mTOR pathway downstream genes which consisted of 4 rapamycin down-regulated (FOXM1, KIF14, MYBL2, and UHRF1), and 4 rapamycin up-regulated (GPR87, NBR1, VASH1 and PRIMA1). In tissue microarray, FOXM1, KIF14, and NBR1 were more expressed at T1, and MYBL2 and PRIMA1 were more expressed at tumor size more than 3 cm. In multivariate Cox regression model, KIF14 and NBR1 were significant predictors of recurrence in non-muscle invasive LG-URCa of the bladder. In NBR1 knock out model, rapamycin treatment showed synergistic effect to inhibit cell viability and colony forming ability compared to rapamycin only. Conclusions KIF14 and NBR1 were mTOR/S6K pathway downstream genes to predict recurrence in non-muscle invasive LG-URCa of the bladder and NBR1 knockout overcome the rapamycin coss-talk. Funding This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology, Republic of Korea (2015R1A1A1A0500110), and (2015R1A2A1A15054364).
Authors
Byung Hoon Chi
Subin Jin Young Mi Whang Seung Hyun Ahn Jae Duck Choi Shin Young Lee In Ho Chang |
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MP44-17 |
Patient derived xenografts as preclinical models of urological malignancies |
Bladder Cancer: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP44-17 Sources of Funding: Swiss National Funds Introduction Prostate and bladder cancer (PCa, BLCa) are highly frequent and metastatic urological malignancies. Relevant models for the study of tumor heterogeneity and drug resistance mechanisms are required. Patient-derived xenografts (PDX) comprise excellent tools for the maintenance of the molecular and functional properties of the original tumor and allow the long-term study and in vivo drug response assays. The objective is to establish PDX models from primary and metastatic PCa and BLCa, which are currently of limited availability, and to develop a platform for standardized characterization and drug response tests of the PDX tumors in vivo and in ex vivo tissue slices system. Methods PDX are generated by needle biopsy implantation (PCa, BLCa) subcutaneously in immunocompromised NOD SCID gamma mice. Tumors are serially transplanted in vivo. Histopathological and RNA analysis of the different passages of PDX tumors is performed to identify morphological and molecular similarities with the original tumor. As preclinical model, PDX tumors are maintained ex vivo (ten days) and used for drug testing assays based on the standard treatment used for primary types of PCa and BLCa. Results PDX models from primary and metastatic PCa and BLCa (BMURO) maintain morphology similar to the original tumor. Tumors (clinical specimens, PDXs) are tested in ex vivo drug response assays using our developed methodology on whole tissue slice culture system. Histological morphology of Lymph node-PCa tumor slices is affected by exposure to cytostatic agents (cabazitaxel, docetaxel). Bone metastasis BLCa (BMURO) tumor slices treated ex vivo with drug compounds exhibit morphological changes at the lowest concentrations of cisplatin and gemcitabine. Ongoing studies aim to address whether the ex vivo and in vivo PDX drug response recapitulates the individual drug response observed during clinical treatment prior to surgery. Conclusions Xenograft models are promising tools for the study of personalized treatment and drug resistance mechanisms in PCa and BLCa. The ex vivo drug response assays on PDX tumor slices represent an experimental screening platform of patient-specific drug responses. Funding Swiss National Funds
Authors
Sofia Karkampouna
Eugenio Zoni Federico la Manna Letizia Astrologo Lijkele Beimers Peter Kloen Joel Grosjean Irena Klima Martin Spahn Marianna Kruithof-de Julio George N. Thalmann |
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MP44-18 |
Tumor escape in the microenvironment of penile carcinoma |
Bladder Cancer: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP44-18 Sources of Funding: none. Introduction In the complex interplay between cancer and the hosts immune system, the tumor is attacked by the natural anti-tumor response of cytotoxic T-cells (CTL). However, the tumor has several escape mechanisms: 1) regulatory T-cells (Tregs) inhibit CTLs, 2) aberrant HLA expression by the tumor cells misleads CTLs and 3) Programmed Death Ligand 1 (PD-L1) on tumor cells or on tumor infiltrating macrophages (TIM) deactivate CTLs. Clinically, HPV-positive penile cancers have a favorable outcome, presumably through micro-environmental factors. This study aims to gain insight in immunological factors, their biological interactions and their prognostic value for lymph node metastases and disease specific survival (DSS). Methods We revised histological sections of 213 penile cancer patients surgically treated between 2000 and 2009. HPV-status, different levels of HLA-expression and PD-L1-expression on tumor, stroma and TIM had previously been identified by our study group. Sections were stained for macrophage-marker CD163, CTL-marker CD8, and Treg-marker FoxP3. Macrophages were scored binary as high or low numbers present in the tumor cell fields. For T-cell balance, the CTL/Treg ratio was used for stroma and tumor. These parameters were included in multivariable regression models testing the prognostic value for lymph node involvement (LN+ or LN-) and DSS. To account for influences between the included parameters, interaction terms were also included. Results Scoring T-cell ratios (CTL/Treg), PD-L1 and CD163 was possible in 175, 200 and 208 samples respectively. HPV typing was known in all 213 tumors, HLA-expression was determined in 168 tumors. Multivariable analyses showed three independent prognostic factors for both lymph node status and DSS: 1) PD-L1+ TIM (unfavorable), PD-L1 margin expression (favorable), and a high intra-tumoral CTL/Treg ratio in the presence of PD-L1+ TIM (favorable). This indicates that PD-L1+ TIM and PD-L1 margin expression were independently predictive in absence of HPV, the interaction between CTL/Treg ratio and PD-L1+ TIM was predictive irrespectively of HPV-status. Conclusions A PD-L1 expression pattern predominantly at the tumor-stroma margin predicts good prognosis, while the negative predictive value of PD-L1+ TIM appear to be compensated by a high CTL/Treg ratio. All independent prognostic factors are PD-L1 related parameters. These results strengthen the rationale for anti-PD-1/PD-L1 immunotherapy in penile carcinoma. Funding none.
Authors
Sarah Ottenhof
Rosa Djajadiningrat Helene Thygesen Jeroen de Jong Simon Horenblas Ekaterina Jordanova |
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MP44-19 |
High-throughput chemical screening for sensitization of bladder cancer to gemcitabine and cisplatin chemotherapy |
Bladder Cancer: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP44-19 Sources of Funding: none Introduction Gemcitabine and cisplatin chemotherapy (GC) is the current standard regimen for locally advanced and metastatic bladder cancer (BC). Despite a relatively high initial response rate, some cases do not regress (intrinsic resistance) and the remaining cases often show regrowth after initial shrinkage (acquired resistance). To identify novel therapeutic agents for overcoming these resistances, we applied a high-throughput screening of chemicals administered in combination with GC. Methods As a high-throughput screening, 2100 compounds were administered alone or in combination with GC to human BC cell lines (J82, UMUC-3). Cell viability was determined after 3-day incubation and chemicals that enhanced inhibitory effect of GC were screened. The in vivo effect of disulfiram (DSF) was studied in UMUC-3 cell xenografts, and western blot, immunofluorescence, induced coupled plasma spectrometry and measurement of reactive oxygen species (ROS) were done in vitro for mechanistic exploration. Results The initial screening identified 26 compounds and further validation narrowed them into the most synergistic agent disulfiram, an FDA-approved drug for alcoholism. Combination index assay showed synergistic effects of DSF with cisplatin but not with gemcitabine in J82, UMUC-3, T24, HT1197 and HT1376 cells. Co-administration of DSF significantly increased DNA-platinum adducts by regulating cisplatin efflux transporter ATP7A and enhanced apoptosis by GC treatment in UMUC-3 cells, with significant increase of ROS production. Use of DSF in combination with GC (GCD) significantly inhibited tumor growth of UMUC-3 subcutaneous xenograft on athymic mice (by 39% compared with GC alone, p = 0.02). GCD regimen was as tolerable as GC and no significant differences were observed in body weight of treated mice between the two regimens. Conclusions Repositioning of DSF to a chemotherapy sensitizer is a promising treatment strategy, which can be translated rapidly in the future. Funding none
Authors
Yuki Kita
Takashi Kobayashi Atsuro Sawada Ryouichi Saito Toshinari Yamasaki Takahiro Inoue Osamu Ogawa |
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MP44-20 |
EGFR cell expression in bladder washings as a risk marker tool in non muscle-invasive bladder cancer. Preliminary experience |
Bladder Cancer: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP44-20 Sources of Funding: none Introduction Up to day, EGFR expression has been determined mainly in tissue specimens of muscle-invasive bladder cancer and its overexpression has been associated with worse prognosis and shorter survival. Urothelial EGFR status after NMIBC transurethral resection (TUR) could indicate the risk of recurrence and progression. We investigated the feasibility of EGFR measurement in bladder washings of patients undergoing intravesical adjuvant therapy for NMIBC and its usefulness in identifying risk subgroups. Methods Our prospective study included patients after TUR of NMIBC and healthy controls. A cellular pellet was obtained from bladder washing, and RNA extraction performed by miRNeasy Mini Kit (Qiagen®). Good quality of RNA was checked. The cDNA obtained from RNA was used to perform a gene expression analysis by a Real Time PCR, according to the method of the comparative quantification (δδCt) with an endogenous control (Cyclophilin). Every reaction was set in triplicate as a guarantee of quality. Patients were grouped for EAU risk class and maintained in follow-up. The EGFR expressions were statistically analyzed according to EAU risk groups and to patients&[prime] outcome. EGFR gene expression values were expressed in FOLDs of change compared to healthy controls (EGFR=1). Results Fifty-eight patients and 21 healthy age-matched controls were entered. An adequate cellular pellet was obtained in 50 patients (86.2%) showing a median EGFR expression of 2.0 folds (IQR 0.6-4.3, p=0.0004).After TUR and adjuvant intravesical therapy, 22 (55%) out of 40 high-risk patients, showed EGFR decrease to 1.3 folds (IQR 0.9-1.5), while 18 (45%) showed elevated EGFR, median 4.7 (IQR 4.1-11.6). At 25 months median follow-up (IQR 19.0-34.8), 20 (40%) patients recurred and 6 (12%) progressed. Among patients with or without EGFR gene increase,9 (22.5%) and 5 (12.5%) recurred and 5 (12.5%) and 1 (2.5%) progressed, respectively. Conclusions In our experience EGFR expression measurement was feasible in more than 85% of patients and resulted related to EAU risk classes for recurrence and progression, showing different behavior during intravesical therapy. It was possible to identify a subgroup of high risk patients overexpressing EGFR in spite of intravesical adjuvant therapy. EGFR evaluation in bladder washing could represent a repeatable and useful tool to identify a subgroup of patients at risk for progression unresponsive to intravesical adjuvant therapy and candidate to early radical cystectomy._x000D_ _x000D_ _x000D_ Funding none
Authors
Fabrizio Di Maida
Vincenzo Serretta Cristina Scalici Gesolfo Marco Vella Antonella Cangemi Antonio Russo Alchiede Simonato GSTU Foundation |
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MP45-01 |
Post-Translational Modification of Neuronal Nitric Oxide Synthase in the Human Erectile Tissue Following Radical Prostatectomy |
Sexual Function/Dysfunction: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP45-01 Sources of Funding: none Introduction Erectile dysfunction (ED) is a highly prevalent complication of radical prostatectomy (RP) with a reported incidence as high as 90%. Our previous studies in a rat model of bilateral cavernous nerve injury, which mimics nerve injury following RP, showed that neuronal nitric oxide synthase (nNOS) phosphorylation and uncoupling occurs in association with increased oxidative stress in the penis. However, the mechanisms of nNOS regulation in RP-associated ED in humans are poorly understood. We evaluated the effect of RP-associated cavernous nerve injury on nNOS post-translational modification in human erectile tissue. Methods Human erectile tissue was obtained from 6 patients with RP-associated ED (median age: 60 [50-71] years) (53.5 months [22-117] after RP) and from 4 patients with non-ED Peyronie&[prime]s disease (median age: 57.5 [53-59] years) as controls. RP group had severe ED (SHIM (The Sexual Health Inventory for Men) score=1 [1-2]) (preop RP SHIM score=22 [18-25]). Peyronie&[prime]s disease patients in control group did not have ED based on SHIM score (SHIM > 21) and penile doppler ultrasonography results. No patients in either group had comorbidities such as diabetes mellitus, hypertension, hypercholesterolemia or cardiovascular diseases. Samples were collected for molecular analyses of nNOS phosphorylation on activating (Ser-1412) and inhibitory (Ser-847) site, total nNOS expression, nNOS uncoupling (source of oxidative stress), caveolin-1 binding to nNOS (which decreases nNOS activity) and P-VASP Ser-239 (which indicates the integrity of nitric oxide signalling) by Western blot. Results nNOS protein expression was decreased (p<0.05) in RP group compared to Control group. nNOS phosphorylation on positive (Ser-1412) regulatory site was decreased (p<0.05) while phosphorylation on negative (Ser-847) regulatory site was increased (p<0.05) in RP group compared to Control group. Caveolin-1 binding to nNOS was increased (p<0.05), while P-VASP (Ser-239) expression was decreased (p<0.05) in RP group compared to Control group. nNOS uncoupling was not different between groups. Conclusions nNOS function in the penis is impaired by deranged phosphorylation and increased binding Caveolin-1 to nNOS, conceivably resulting in ED in the face of RP. Our description of molecular factors contributing to the pathogenesis of RP-associated ED at the human level is relevant for advancing clinically therapeutic approaches to restore erectile function in RP patients. Funding none
Authors
Serkan Karakus
Biljana Musicki Arthur L. Burnett |
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MP45-02 |
Alterations of microRNA Expression in a Cavernous Nerve Injury rat model |
Sexual Function/Dysfunction: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP45-02 Sources of Funding: None Introduction MicroRNAs (miRs) are noncoding, endogenous RNA molecules that regulate gene expression at the posttranscriptional level and play roles in various pathophysiological functions including erectile dysfunction (ED). The aim of this study was to identify miRs expressed in post-prostatectomy ED penis tissue and to analyze the target genes and signaling pathways regulated by the dysregulated miRs. Methods RNA was isolated from the penis tissues from shame group and rats with cavernous nerve injury induced erectile dysfunction. The P1 chip from Thermo Fisher was used to analyse the miRNA expression profiling. The miRNA profilings were further validated by real-time polymerase chain reaction. The TargetScan and DAVID were used for bioinformatic analysis. Results 124 miRNAs was found dysregulated in ED groups, in which 122 miRNAs were up-regulated. Of the 122 miRNAs, 21 miRNAs changed above twofold. miR-142, miR-101a and miR-200a were finally validated over-expressed in ED groups. TargetScan v7.1 was used to generate lists of target genes regulated by the two miRNAs. The lists were then sent to the bioinformatics database DAVID. GO and KEGG pathway analyses of the targets were performed. The results revealed that the three miRNAs could be involved in the processes of cell proliferation, differentiation, apoptosis, and so on. After bioinformatic analysis, Table 1 listed 4 pathways which correlated to the three miRNAs with statistical significance (P value < 0.05), and also might be involved in the pathogenesis of ED. Conclusions Three miRNAs were found up-regulated significantly in the corpus cavernosum of rats with cavernous nerve injury induced ED. The three miRNAs might play important roles in the development of ED by regulating several of pathways but future studies are needed to validate these regulation mechanisms directly. Funding None
Authors
Chunhui Liu
Yanna Cao Tien C Ko Run Wang |
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MP45-03 |
Age Related Penile hemodynamic Impairment and Fibrosis: Possible Role of GIV-Wnt Signaling Pathways |
Sexual Function/Dysfunction: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP45-03 Sources of Funding: UCSD Academic Senate Introduction Pathophysiology/ molecular mechanisms of age-related penile hemodynamic impairment are unclear. Previous studies suggest age-related increase in tissue fibrosis in several organs including male genital tissues leading to impaired hemodynamics and male erectile dysfunction (ED). We tested the hypothesis that increased penile/ perineal (ischiocavernosus; ICM) muscle fibrosis during advanced aging is mediated by a novel fibrogenic cascade involving GIV/girdin and Wnt signaling pathways. A clear understanding of these molecular mechanisms involved in penile fibrosis would enable development of optimal strategies to treat ED. Methods Young (n=3; 9 months) and old (n=6; 36 months) New Zealand White rabbits were anesthetized and penile tissue microcirculatory blood perfusion (perfusion units- PU) was measured using a novel PeriCam PSI system. Blood perfusion measurements were made before and after an intracavernosal injection of vasoactive agent- PGE1 (50 ng). Penile (corpus cavernosum) and ICM tissues were harvested and paraffin sections of these tissues were subjected to: (1) trichrome staining (marker of fibrosis) followed by image analysis for evaluation of fibrosis and (2) immunostaining for specific markers of fibrosis: 1. [beta]-catenin (central mediator of Wnt pathway) and 2. GIV/girdin. Results Representative tracings of time-course of penile blood perfusion measurements in response to intracavernosal PGE1 as well as age-related penile perfusion changes in young and old rabbits are shown in figure A. Photomicrographs of showing trichrome as well as immunostaining for fibrosis markers (GIV and [beta]-catenin) are depicted in Fig B. A significant impairment in penile perfusion (Fig A) and increased fibrosis of penile/ICM tissues was observed in old rabbits (Fig B) when compared to the young animals. Immunostaining studies revealed positive labelling for both GIV and and [beta]-catenin and increased immunoreactivity in the tissues from old rabbits (Fig B). Conclusions Our findings suggest age-related increase in penile/ perineal muscle (ICM) fibrosis may contribute to increased incidence of ED in older men. Targeting GIV-Wnt pathways may be beneficial in preventing age-related ED for the aging population Funding UCSD Academic Senate
Authors
Tung-Chin (Mike) Hsieh
Sadhna Kanoo Jay Parikh Valmik Bhargava M. Raj Rajasekaran |
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MP45-04 |
BENEFICIAL EFFECTS OF QUERCETIN ON RAT CORPUS CAVERNOSUM AFTER CISPLATIN TREATMENT |
Sexual Function/Dysfunction: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP45-04 Sources of Funding: none Introduction Cisplatin treatment leads to cytotoxic events and generates oxidative stress, which has deleterious effects on the function of several organ systems, including the corpus cavernosum. The present study was designed to investigate the putative beneficial effect of quercetin (QT) against cisplatin-induced corpus cavernosum damage. Methods Twenty-eight adult male Sprague Dawley rats were included in the study. Six-teen rats were administered intraperitoneally (i.p.) single dose cisplatin 7?mg / kg and divided in to 2 groups: The first group (n=8) received saline i.p., whereas the second group (n=8) fed orally with 20?mg / kg QT, respectively, for 21 days. The remaining 12 rats served as the control group after i.p. saline, where 6 treated with QT. _x000D_ After decapitation, corpus cavernosum strips were placed in organ bath and isometric contractions to phenylephrine and relaxations to carbachol (10-8 to 10-4 M) were recorded. In order to examine oxidative tissue injury, malondialdehyde (MDA), 8-hydroxydeoxyguanosin (8-OHdG) and glutathione (GSH) levels and superoxide dismutase (SOD) and caspase-3 activities and caspase-3 protein expression in corpus cavernosum tissues were measured along with histologic evaluations. _x000D_ Results In the cisplatin-treated corpus cavernosum, the contractile responses were lower than those of the control group and were reversed by treatment with QT (figure 1). On the other hand, increase in MDA and 8-OHdG levels, and caspase-3 protein expression and caspase 3 activities of tissues in the cisplatin group were significantly reversed by QT treatment (figure 2 and 3). Furthermore, treatment with QT also prevented the depletion of tissue GSH levels and SOD activity seen in the cisplatin group (figure 4). Histologic evaluations also supported the beneficial effects of QT treatment on corpus cavernosum. Conclusions According to the results, QT exerts beneficial effects against cisplatin-induced damage on corpus cavernosum through its anti-inflammatory and antioxidant effects. Funding none
Authors
Ilker Tinay
Selin Cadirci Ozge Cevik Feriha Ercan Kutay Koroglu Goksel Sener |
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MP45-05 |
Activation of Nrf2 improves endothelial function in corpus cavernosum from aged rats and in corpus cavernosum and penile arteries from ED patients |
Sexual Function/Dysfunction: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP45-05 Sources of Funding: None Introduction Adequate antioxidant response is essential for tissue homeostasis and function. However, systems responsible for antioxidant response are down-regulated in some pathological situations and aging. This is the case for Nrf2 that orchestrates cellular response to oxidative stress. The aim was to evaluate pharmacological activation of Nrf2 on the impairment of endothelial relaxation and reactive oxygen species-induced responses in corpus cavernosum (CC) from aged rats and in CC and penile arteries from patients with erectile dysfunction (ED). Methods Endothelium-dependent relaxations to carbachol and responses to H2O2 were evaluated in CC from 3-months (young) and 20-months (aged) old rats in the absence or the presence of the Nrf2-activators, sulforaphane (10 microM) and oltipraz (30 microM). Upregulation of Nrf2 was assessed by ELISA. The effects of these Nrf2-activators were also evaluated on endothelial relaxation and H2O2-induced responses in human corpus cavernosum (HCC) and penile resistance arteries (HPRA) obtained from patients undergoing penile prosthesis implantation. Results Aged rats CC displayed ED and impaired endothelium-dependent and H2O2-induced relaxation. Ex vivo exposure to either sulforaphane or oltipraz improved endothelial and H2O2-induced relaxation of CC from aged rats. HCC and HPRA were obtained from 19 patients (age: 60.7+/-2.0 years, hypertension: 8, dyslipidemia: 7, diabetes: 6, CVD: 4, obesity: 2). Treatment with sulforaphane improved endothelium-dependent (pD2 for acetylcholine: 5.18+/-0.28 vs 6.34+/-0.37*) as well as neurogenic relaxation (Emax: 45.7+/-6.4% vs 60.9+/-3.0%*) in HCC. Sulforaphane also improved endothelial (pD2 for acetylcholine: 5.82+/-0.38 vs 7.21+/-0.32*) and H2O2-induced vasodilation in HPRA (pD2 for H2O2: 4.13+/-0.13 vs 5.07+/-0.17*). Positive effects of Nrf2-activation were confirmed by the improvement of endothelial vasodilation driven by oltipraz in HPRA. Conclusions Pharmacological activation of Nrf2 improves cavernosal function in aged animals with ED. These effects were confirmed in human tissue, including penile arteries, from patients with ED, suggesting that Nrf2 activation could be a reasonable target for the management of ED. Funding None
Authors
Juan Ignacio Martínez-Salamanca
Mariam El Assar Argentina Fernández Alberto Sánchez-Ferrer Agustín Fraile Leocadio Rodríguez-Mañas Joaquín Carballido Javier Angulo |
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MP45-06 |
Optimization of Sonic hedgehog delivery from self-assembled nanofiber hydrogels to prevent ED and penile morphology changes in a rat prostatectomy model |
Sexual Function/Dysfunction: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP45-06 Sources of Funding: NIH/NIDDK DK079184 Introduction Sonic hedgehog (SHH) protein delivered by nanoparticle based peptide amphiphile (PA) hydrogels to the penis and cavernous nerve (CN), improve erectile function, promote CN regeneration, and suppress apoptosis in a rat CN injury model. We examine the hypothesis that suppression of apoptosis and penile morphology changes after CN crush will be maximized with optimization of SHH delivery to both the penis and CN via PA hydrogels. Optimization of delivery conditions is essential for clinical translation to prostatectomy patients. Methods The study was divided into 3 parts: 1.Optimization of SHH protein concentration delivered to the penis at the time of CN crush, 2. Maintain elevated SHH protein longer after CN crush with 2 SHH PA injections, 3. Examine additive effects with SHH delivery to both penis and CN at the time of CN crush. Bilateral CN crush was performed on Sprague Dawley rats (n=67) and SHH or mouse serum albumin (MSA, control) protein was delivered by PA injected into the corpora cavernosa. Rats were sacrificed after 4 and 9 days. 2X SHH protein was also assayed at 4 days. A second SHH PA injection at 5 days occurred prior to sacrifice at 9 days. Additional rats had SHH or MSA delivered to both the penis and CN by PA. TUNEL, trichrome stain and western analysis were performed. Results Apoptosis increased 54% 4 days after injury (p=0.0001). SHH PA suppressed apoptosis 27% at 4 days after CN injury (p=0.005). 2X SHH protein suppressed apoptosis 29% (p=0.003). Apoptosis increased 21% at 9 days after injury (p=0.014). Two SHH PA injections decreased apoptosis 22% at 9 days (p=0.021), while one SHH PA injection was indistinguishable from controls (p=0.830). SHH delivery to penis and CN decreased apoptosis 27% (p=0.0001). Conclusions Apoptosis suppression was similar in CN resection and crush models in response to SHH treatment. One SHH PA injection suppressed apoptosis until protein was depleted. Increasing the duration of SHH treatment, by a second SHH PA injection, suppressed apoptosis longer. Delivery of SHH to both penis and CN had beneficial effects on CN regeneration and apoptosis suppression. Optimization of SHH PA delivery is essential for translation to prostatectomy patients to prevent ED. Funding NIH/NIDDK DK079184
Authors
Shawn Choe
Daniel Harrignton Samuel Stupp Kevin McVary Carol Podlasek |
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MP45-07 |
Sonic hedgehog promotes cavernous nerve regeneration by inducing sprouting of neurons in the pelvic ganglia and cavernous nerve |
Sexual Function/Dysfunction: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP45-07 Sources of Funding: NIH/NIDDK DK079184. Introduction Sonic hedgehog (SHH) protein delivered by nanoparticle based peptide amphiphile (PA) nanofiber hydrogel to the cavernous nerve at the time of crush injury (prostatectomy model), is neuroprotective, promotes cavernous nerve (CN) regeneration, and return of erectile function, in a rat model. Little is known about the mechanism of how SHH promotes CN regeneration. We hypothesize that SHH promotes sprouting of pelvic ganglia and CN neurons that innervate the penis, in order to enhance regeneration. We examine this hypothesis in an in vitro organ culture model. Methods The caudal portion of the pelvic ganglia and CN were dissected from adult Sprague Dawley rats (n=47) and were grown on Matrigel in growth factor reduced medium for three to five days. Pelvic ganglia/CN were exposed to Affi-Gel beads containing: 1.) SHH protein, 2.) 5e1 and cyclopamine SHH inhibitors, and 3.) SHH protein delivered by PA. Additional pelvic ganglia/CN tissue underwent CN crush and were exposed to SHH protein or mouse serum albumin protein (control) by PA in vivo for 4 days with an additional 4 days in culture. Sprouting was evaluated for number of sprouts and their length, and by immunohistochemical analysis for sprouting markers (GAP43 and nNOS). Results Sprouting of neurons in the pelvic ganglia and CN were increased with SHH treatment. Sprouts were more abundant, longer in length, and had increased branching, in comparison to controls. Sprouting was even further enhanced in CN injured nerves with SHH treatment. Sprouting did not occur in the presence of either SHH inhibitor. The CN had similar sprouting potential at 4 and 9 days after crush injury. SHH induced sprouting even when not delivered to the CN until 4 days after injury. Sprouts continued to grow in organ culture once initiated with SHH PA in vivo. Localization of SHH delivery makes a difference in sprouting potential. Sprouts formed in response to SHH treatment stained strongly for nNOS protein. Conclusions SHH PA treatment promotes CN regeneration by enhancing sprouting of pelvic ganglia and CN neurons. Understanding the mechanism of SHH PA action on neuronal tissue is critical for translation to prostatectomy patients and to further enhance regeneration. Funding NIH/NIDDK DK079184.
Authors
Ryan Dobbs
Shawn Choe Gail Prins Daniel Harrington Samuel Stupp Kevin McVary Carol Podlasek |
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MP45-08 |
Cavernous nerve crush injury induces apoptosis in the pelvic plexus including pelvic and hypogastric nerves |
Sexual Function/Dysfunction: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP45-08 Sources of Funding: NIH/NIDDK: DK079184 Introduction Seventy-two percent of prostatectomy patients develop stress urinary incontinence (SUI) in the first week after surgery, and individuals who do not recover within 6 months, generally do no regain function without intervention (44%). Preoperative erectile function predicts post-prostatectomy continence and SUI recovery correlates with neurovascular bundle sparing, suggesting the importance of maintaining neural innervation. The hypogastric (HGN) and pelvic nerves (PN) control bladder neck and bladder contraction/relaxation. We hypothesize that the HPG and PN may be injured during prostatectomy, in a similar manner to cavernous nerve (CN) injury, and thus contribute to post-prostatectomy SUI development. We will examine HPG, PN and CN architecture and signaling in normal pelvic ganglia and in a rat prostatectomy model. Methods The pelvic plexus in normal (n=9), sham (n=6) and CN crushed (n=20) adult Sprague Dawley rats was examined for apoptotic index and sonic hedgehog (SHH) pathway signalling by immunohistochemical analysis for cleaved caspase-3 (apoptosis indicator), -8, -9, SHH and its receptors Patched and Smoothened. Results Cleaved caspase-3 was present in normal pelvic plexus and increased in the CN and PN with CN injury. Cleaved caspase-3 was identified primarily in glial cells surrounding PG neurons and in Schwann cells of the CN, at 4 days after CN injury, and in Schwann cells of the PN. Caspase-8 increased in PG/CN neurons and glia and in the PN. Caspase-9 was increased in CN Schwann cells but not in PN. SHH and its receptor patched were present in PN neurons, glia and Schwann cells, and HGN neurons and Schwann cells. Conclusions Interruption of CN innervation, as occurs in the majority of prostatectomy patients, results in induction of apoptosis in other regions of the pelvic plexus including the PN, thus affecting neural regulation of continence. Identification of HGN and PN contribution to SUI identifies novel treatment avenues for intervention. Involvement of the SHH pathway in maintaining HGN and PN morphology and function is significant, and there is potential for application of peptide amphiphile hydrogel SHH delivery to regenerate nerve function and prevent SUI. Funding NIH/NIDDK: DK079184
Authors
Marah Hehemann
Shawn Choe Kevin McVary Carol Podlasek |
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MP45-09 |
Radiation increased apoptosis of nitrergic neurons cultured from the major pelvic ganglia |
Sexual Function/Dysfunction: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP45-09 Sources of Funding: None Introduction A third of men diagnosed with prostate cancer will undergo radiation therapy (RT) which frequently results in erectile dysfunction (ED). Prostatic radiation is presumed to cause damage to the vasculature and the nerves supplying the penis. There are no effective treatment strategies to prevent or recover radiation-induced ED which significantly impacts the quality of life of prostate cancer survivors. This study examined the impact of low and high radiation on neurite growth, branching and survival of sympathetic and nitrergic neurons cultured from the major pelvic ganglia (MPG). Methods MPGs collected from male Sprague-Dawley rats (n=6) were dissociated and neurons plated on laminin coated glass cover slips. After 24 hours, neurons were irradiated at 2Gy or 8Gy, grown for an additional 48 hours and then compared to time-matched control neurons. Neurons were fixed and stained with immunofluorescence for neuron-specific class III beta-tubulin to measure axon length and branching, neuronal nitric oxide synthase (nNOS, nitrergic), tyrosine hydroxylase (TH; sympathetic) or TUNEL assay for apoptosis. Images were taken of all neurons on each cover slip at a magnification of 100x. Results Neurite length was unchanged with radiation, however, neurite branching significantly decreased with both doses of radiation (CON: 3.0±0.11, 2Gy: 2.6±0.16, 8Gy: 2.5±0.16; p<0.005). There was a 3 to 4-fold increase in the percentage of apoptotic TUNEL positive neurons in both groups following radiation (p<0.0001). There was no change in the relative number of sympathetic TH positive neurons with radiation. In contrast, a marked decrease in nNOS positive neurons increased with the dose of radiation (CON: 45±4.4%, 2Gy: 20±3.1%, 8Gy: 5±0.7%; p<0.0001). Conclusions These data demonstrate that RT stimulates an increase in neuronal cell death and a substantial decrease in the number of erectile promoting nitrergic neurons. Although there is no change in neurite length, neurite branching which is essential for the establishment of appropriate neuronal connections and regeneration was impaired. Future studies will examine the impact of prostatic RT in an animal model to determine if these neuronal impairments contribute to ED in order to elucidate the pathological mechanisms to lead to new therapeutic radioprotection strategies for prostate cancer survivors. Funding None
Authors
Elena Pak
Bridget Koontz Johanna Hannan |
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MP45-10 |
Histomorphometrical evaluation of the corpus cavernosum of hypertensive rats treated with 5-?-reductase inhibitors |
Sexual Function/Dysfunction: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP45-10 Sources of Funding: Faperj, CAPES, CNPq Introduction Benign prostatic hyperplasia (BPH) is a common disease in both normotensive and hypertensive man. Although 5-?-reductase inhibitors is the first line option for BPH treatment, some side effects are reported, including erectile dysfunction. Thus, the objective of the present study is to investigate the penile morphology in normotensive and hypertensive rats after 5-?-reductase inhibitors treatment. Methods Sixty male rats were assigned into 6 groups as following: WKY – group composed by untreated Wistar Kyoto rats (normotensive strain); WKY+D - Wistar Kyoto rats treated with dutasteride (0.5 mg/Kg/day); WKY+F - Wistar Kyoto rats treated with finasteride (5 mg/Kg/day); H - group composed by the strain of spontaneously hypertensive rats (SHR); H+D - SHR treated with dutasteride; H+F - SHR treated with finasteride. All treatments were given by gavage during 40 days after what the animals were killed and their penis were collected and processed for histomorphometrical analysis. Sections stained with hematoxylin and eosin were used to study the cross-sectional penile area, while Masson´s trichrome was used for study the surface density of smooth muscle fibers, connective tissue, and sinusoidal spaces of the corpus cavernosum. The surface density of elastic system fibers was studied in Weigert's resorcin fucsin stained section. The results were compared by one-way-ANOVA with Bonferroni´s post test, considering p>0.05 as significant. Results The cross-sectional penile area of normotensive animals that received dutasteride or finasteride was reduced by 39.9% and 40% in comparison to untreated normotensive animals. The connective tissue of H group was 13.7% higher than WKY, and H+D animals had an increase of 12.9% of connective tissue in comparison to untreated hypertensive animals. The sinusoidal space was reduced by 33.7% in H in comparison to WKY. In respect to the smooth muscle surface density, WKY+D showed a reduction of 26.1% in comparison to WKY, while both H+D and H+F showed reductions of 29.4 and 32.5% in comparison to untreated H. Despite no difference in the elastic system fibers surface density was observed between H and WKY, groups WKY+D, WKY+F, H+D, and H+F had an increase of 35,7%, 41,1% 82,6%, and 31,5% in comparison to WKY. Also, H+D showed a 45,8% increase in comparison to H. Conclusions Hypertension promoted important modifications on penile structure. Both 5-?-reductase inhibitors (dutasteride and finasteride) promoted modifications in penile morphology of normotensive and hypertensive rats, although these modifications were more prominent in hypertensive animals. Dutasteride was the drug that most affected the corpus cavernosum in this rodent model. Funding Faperj, CAPES, CNPq
Authors
Marcello Da Silva
Waldemar Costa Bianca Gregório Francisco Sampaio Diogo De Souza |
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MP45-11 |
DICKKOPF2 PROMOTES ANGIOGENESIS AND NEURAL REGENERATION THROUGH AN ANGIOPOIETIN-1-TIE2 PATHWAY AND RESCUES ERECTILE FUNCTION IN THE DIABETIC MOUSE |
Sexual Function/Dysfunction: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP45-11 Sources of Funding: This study was supported by MW (Ji-Kan Ryu, HI15C0508) and MRC (Jun-Kyu Suh, 2014R1A5A2009392) funded by MSIP, Republic of Korea. Introduction Introduction and Objective: Men with diabetic erectile dysfunction (ED) often have severe endothelial dysfunction and peripheral nerve damage, which result in poor response to oral phosphodiesterase-5 inhibitors. Dickkopf2 (DKK2), originally known as Wnt antagonists, is known to enhance neovascularization in animal models of both hind limb ischemia and myocardial infarction. The aim of this study was to investigate the mechanisms through which DKK2 restores diabetes-induced ED. Methods Methods: Four groups of mice were used: wild type (WT) mice, DKK2-Tg mice, WT mice receiving streptozotocin (STZ), and DKK2-Tg mice receiving STZ. Eight weeks after the induction of diabetes, we measured erectile function by electrical stimulation of the cavernous nerve. We also determined efficacy of DKK2 protein in STZ-injected WT diabetic mice 2 weeks after repeated intracavernous injections of DKK2 protein (days -3 and 0; 6 µg/20 µl). The penis was stained with antibodies to CD31, smooth muscle ?-actin, NG2, PDGFR-?, claudin-5, VE-cadherin, eNOS, phospho-eNOS, oxidized LDL, nNOS, ?III tubulin, and neurofilament. We also performed Western blot for DKK2, Ang1, Ang2, NGF, BDNF, NT-3, and TrkA in the corpus cavernosum tissue. Results Results: Overexpression of DKK2 by using DKK2-Tg mice or by administering DKK2 protein successfully restored erectile function through enhanced penile angiogenesis and neural regeneration. DKK2 decreased extravasation of oxidized-LDL by restoring pericyte content and endothelial cell-cell junction proteins. Ang1 expression was down-regulated and Ang2 expression was up-regulated in the diabetic penis compared with that in controls, and these changes were reversed by DKK2 treatment. DKK2-mediated penile angiogenesis and neural regeneration as well as erectile function recovery was abolished by inhibition of Ang1-Tie2 signaling with soluble Tie2 antibody or Ang1 siRNA. Conclusions Conclusions: The dual angiogenic and neurotrophic effects of DKK2, especially local therapy in the form of therapeutic protein, will open a new avenue to treat diabetic ED. Funding This study was supported by MW (Ji-Kan Ryu, HI15C0508) and MRC (Jun-Kyu Suh, 2014R1A5A2009392) funded by MSIP, Republic of Korea.
Authors
GUO NAN YIN
Hai-Rong Jin Jiyeon Ock Min Ji Choi Kang-Moon Song Anita Limanjaya Kalyan Ghatak Nguyen Nhat Minh Soo-Hwan Park Ji-Kan Ryu Jun-Kyu Suh |
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MP45-12 |
Chronic administration of a LIMK2 inhibitor improves cavernosal veno-occlusive dysfunction through suppression of cavernosal fibrosis in a rat model of erectile dysfunction after cavernosal nerve injury |
Sexual Function/Dysfunction: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP45-12 Sources of Funding: none Introduction Cavernosal fibrosis is a key pathophysiology of post-RP ED. Previously, we showed that ROCK1/LIMK2/Cofilin pathway could play a role in cavernosal fibrosis and ED in a rat model of cavernosal nerve (CN) injury. Also, our recent study noted that short-term administration of LIMK2 inhibitors (10.0 mg/kg) alleviated cavernosal fibrosis induced by CN injury. The aim of this study was to determine whether chronic adminstration of LIMK2 inhibitors could improve erectile function by alleviating cavernosal veno-occlusive dysfunction (CVOD) via suppressing cavernosal fibrosis in a rat model of CN injury. Methods Forty-two 11-week-old rats were equally randomized into three groups: sham surgery (S), CNCI (I), and CNCI treated with LIMK2 inhibitors (L). The L group was treated with daily intraperitoneal injection of LIMK2 inhibitors (10.0 mg/kg) for 4 weeks from the following day after surgery. The S and I groups were treated with daily intraperitoneal administration of saline vehicle only. At 4 weeks after surgery, erectile function was assessed using dynamic infusion cavernosometry (DIC). Penile tissue was processed for Masson’s trichrome staining, immunohistochemical staining to alpha-smooth muscle actin (?-SMA), Western blot, and double immunofluorescence with antibody to Vimentin and phosphorylated Cofilin. Results There was no signi?cant difference in body weight change and mean arterial pressue among the 3 groups. The I group showed significantly higher maintenance and drop rates as well as lower papaverine response, compared to the S group. Chronic inhibition of LIMK2 in the L group significantly improved the DIC parameters compared to the I group, although they were not completely restored to normal control values. Also, the I group showed a reduced smooth muscle-to-collagen ratio, decreased immunohistochemical staining of ?-SMA, increased fibroblasts positive for phosphorylated Cofilin and increased Cofilin phosphorylation, compared to the S group. Chronic inhibition of LIMK2 in the L group significantly alleviated the histological and molecular dysregulation compared to the I group. Conclusions Our data indicate that chronic inhibition of LIMK2 can improve CVOD and ED by alleviating cavernosal fibrosis via normalizing LIMK2/Cofilin pathway. Thus, a new therapeutic strategy targeting the LIMK2/Cofilin pathway may be helpful to alleviate CVOD and ED through prevention of cavernosal fibrosis after CN injury. Funding none
Authors
Juhyun Park
Chu Hong Park Inyoung Sun Sung Yong Cho Seung Baik Sang Jun Chun Kwang Ho You Kwanjin Park Hwancheol Son Hyeon Jeong Soo Woong Kim Jae-Seung Paick Min Chul Cho |
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MP45-13 |
INTRACAVERNOUS DELIVERY OF DICKKOPF3 GENE OR PEPETIDE RESCUES ERECTILE FUNCTION THROUGH ENHANCED CAVERNOUS ANGIOGENESIS IN THE DIABETIC MOUSE |
Sexual Function/Dysfunction: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP45-13 Sources of Funding: supported by MW (Ji-Kan Ryu, HI15C0508), Republic of Korea. Introduction Patients with diabetic erectile dysfunction (ED) often have severe endothelial dysfunction, which results in poor response to oral phosphodiesterase-5 inhibitors. Dickkopf-3 (DKK3), originally reported to interact Wnt signaling pathway during embryonic development, is known to involve in the endothelial cell proliferation. However, the role of DKK3 in ED is as yet not reported. The aim of this study was to investigate whether and how DKK3 gene or peptide restores erectile function in diabetic mice. Methods Eight-week-old C57BL/6 mice were used, and diabetes was induced by intraperitoneal injection of streptozotocin. At 8 weeks after the diabetes induction, the efficacy of DKK3 peptide or gene were determined by three independent experiments: Experiment 1 (DKK2 peptide; Control, DM + PBS, DM + DKK3 peptide [5 μg/20 μL]); Experiment 2 (DKK2 plasmid DNA with electroporation; Control, DM + empty vector (100 μg/20 μL), DM + DKK3 plasmid (10 μg, 40 μg, or 100 μg/20 μL, respectively); and Experiment 3 (DKK3 adenovirus; Control, DM + PBS, DM + Ad-GPF (1 x 109 vp/20 μL), DM + Ad-DKK3 (1 x 107, 1 x 108, 1 x 109 vp/20 μL, respectively). One (peptide) or two weeks (gene) after treatment, we measured erectile function by electrical stimulation of the cavernous nerve. The penis was then harvested for histologic examination. We also determined angiogenic activity of DKK3 in primary cultured mouse cavernous endothelial cells (MCECs). Results The protein expression of DKK3 was significantly lower in cavernous tissue of diabetic mice than in controls. Intracavernous injection of DKK3 peptide or gene partially restored erectile function in diabetic mice, which reached up to 70-80% of the control values. DKK3 significantly restored cavernous endothelial cell content and endothelial cell-cell junction proteins (ZO-1 and claudin-5) in diabetic mice. Treatment of MCECs with DKK3 peptide significantly increased the expression of basic fibroblast growth factor and angiopoietin-1, which accelerated tube formation and endothelial migration, and restored integrity of the endothelial cell-cell junction. Conclusions DKK3 restored erectile function in diabetic mouse through the restoration of cavernous endothelial cells and the integrity of endothelial cell-cell junction. Therapeutic cavernous endothelial regeneration by use of DKK3 may provide a good opportunity for treating ED from vascular causes. Funding supported by MW (Ji-Kan Ryu, HI15C0508), Republic of Korea.
Authors
Kang-Moon Song
Woo-Jean Kim Min Ji Choi Anita Limanjaya Kalyan Ghatak Nguyen Nhat Minh GUO NAN YIN Soo-Hwan Park Ji-Kan Ryu Jun-Kyu Suh |
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MP45-14 |
Evaluation of the Therapeutic Targeting Potential of microRNA-93 in the Treatment of Vasculogenic Erectile Dysfunction |
Sexual Function/Dysfunction: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP45-14 Sources of Funding: None Introduction Small non-coding RNAs, known as microRNAs (miR), have been shown to play a key role in the post-transcriptional regulation of gene expression. One of these, miR-93, has been shown to promote endothelial cell proliferation, survival, resistance to apoptosis, and enhanced vascular stability, especially with its ability to down-regulate VEGF. We sought to evaluate the presence and role of miR-93 in the mouse corpus cavernosum in mice with diet-induced hyperinsulinemia, a state known to predispose to erectile dysfunction (ED). Methods Studies from our group have shown that feeding C57BL/6 mice a high fat diet (HFD) where 45% of its daily calories come from fat caused obesity, hyperglycemia, and insulin-resistance. We first examined the corpus cavernosum in these mice to look for the effects of the hyperinsulinemic state. We then compared miR-93 expression in the corpora of mice with and without a HFD. Finally, intracorporal injections of pre-miR-93 were performed in some of the mice, and levels of three reported miR-93 targets were recorded. Results With regard to our first aim to characterize the corpus cavernosum of HFD rats, we found that a number of findings were consistent with ED including: a) abnormalities in corporal endothelium-dependent and endothelium-independent vasoreactivity; b) a decrease in the ratio of the smooth muscle to collagen content, c) a reduction in NADPH diaphorase staining (measure of bioavailable NO) and d) increases in apoptosis, as measured by TUNEL staining. Results for parts two and three are summarized in Figure 5. Conclusions These results demonstrate a few key factors. First, that the HFD mice tend to exhibit corporal changes consistent with vasculogenic ED. Second, that miR-93 expression is increased in these mice, likely as a response to elevated VEGF and other vasculopathic factors. And third, that injections of miR-93 precursors can alter gene expression of these known vasculopathic factors. This may provide a novel therapeutic target for vasculogenic ED with futher study. Funding None
Authors
Nathan Starke
Ryan Smith Jeffrey Lysiak |
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MP45-15 |
Effect of Icariin in combination with daily sildenafil on penile atrophy and erectile dysfunction in a rat model of bilateral cavernous nerves injury |
Sexual Function/Dysfunction: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP45-15 Sources of Funding: None Introduction The commonly utilized phosphodiesterase type 5 (PDE5) inhibitors does not lead to satisfactory penile erection after radical prostatectomy due to lack of nitric oxide (NO) released from the damaged cavernous nerves (CNs). The aim of this study was to assess the efficacy and mechanisms of Icariin (ICA) in combination with daily sildenafil on penile atrophy and neurogenic erectile dysfunction (ED) in a rat model of bilateral CNs injury (BCNI). Methods Sixty male Sprague-Dawley rats injected with 5-ethynyl-2-deoxyuridine (EdU; 50 mg/kg) at newborn. Fourty-eight rats of BCNI were randomized equally into gavage feeding of vehicle, sildenafil (10mg/kg), ICA (1.5mg/kg) and sildenafil+ICA, respectively. Twelve sham-operated rats served as control. Erectile function was assessed and histologic/molecular analyses were performed at 5 wk after surgery. The intracavernous pressure (ICP) and mean arterial pressure (MAP) was measured and midpenile cross-sections were histologically examined. Western blotting of cavernous tissue protein was performed. The data were analyzed using one-way analysis of variance followed by the Tukey-Kramer t test. Results Animals that received sildenafil+ICA had significantly higher mean ICP/MAP ratio relative to all other rats with BCNI (p<0.05). The circumference and mean cross-sectional area of the paired corpus cavernosum were effectively preserved in the sildenafil+ICA. In addition, the numbers of neuronal NO synthase (nNOS)-positive nerves and EdU-positive cells coexpressing S100 in the ICA-treated groups were greater compared with the control group (p<0.05). Conclusions The results indicate that ICA promotes endogenous SCs to differentiate into Schwann cells, which is essential for the regeneration of nNOS-positive nerves after BCNI; on this basis, sildenafil can then improve penile engorgement and prevent penile atrophy through the NO-derived smooth muscle relaxation. Therefore, the combinded use of ICA and daily sildenafil may be a candidate for the prevention and cure of neurogenic ED in the future. Funding None
Authors
Yongde Xu
Yuanyi Wu Yong Yang Zhongcheng Xin |
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MP45-16 |
Pioglitazone Mediates Improvement of Erectile Function After Cavernous Nerve Crush Injury via Insulin Growth Factor Type 1 |
Sexual Function/Dysfunction: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP45-16 Sources of Funding: None Introduction To investigate the mechanism of action of pioglitazone (Pio) on the major pelvic ganglion (MPG) and cavernous nerves in a rat model of bilateral cavernosal nerve crush injury (BCNI), to determine a clinically exploitable pathway to treat post-prostatectomy erectile dysfunction. Methods 26 Sprague-Dawley rats weighing 350-400 grams were divided into four groups: (a) sham, (b) BCNI, (c) BCNI + postsurgical Pio, (d) BCNI + Pio + JB-1, an insulin-growth factor-1 (IGF-1) antagonist (JB). Sham and BCNI-only rats were treated with phosphate-buffered saline (PBS), and both Pio and JB rats received 14 days treatment of 6.5 mg Pio per day. PBS and Pio were administered by oral gavage. Sham, BCNI and Pio rats had osmotic mini pumps placed subcutaneously, which delivered saline. JB rats received 100 mg/kg JB-1 trifluoroacetate salt dissolved in saline, delivered by subcutaneous osmotic mini pump. After treatment, animals underwent surgery for endpoint cavernosal response to define hemodynamic parameters of erectile function, reported as the ratio of intracavernosal pressure to mean arterial pressure (ICP/MAP). The MPG and cavernosal nerves were resected at 2 weeks in all rats and processed for Western blot and immunohistochemistry to assess neuronal nitric oxide synthase (nNOS), IGF-1, and ERK 1/2. Results Animals treated with Pio after BCNI exhibited improvements in the ICP/MAP ratio, with the Pio group achieving results similar to the sham group. Animals treated with JB-1 in addition to Pio after BCNI achieved results similar to BCNI. At 7.5 V, the ICP/MAP data revealed: sham, 0.627; BCNI, 0.294; Pio, 0.582; JB, 0.286 (P < .05). Both 5V and 2.5 V demonstrated similar results. Western blot and immunohistochemistry results support the surgical data and indicate that Pio&[prime]s positive effects are mediated by intercellular IGF-1 signaling activity. Conclusions JB-1 reverses the beneficial effects of Pio on erectile function in rats undergoing BCNI, suggesting that Pio acts through IGF-1 signaling pathway. Funding None
Authors
Daniel Heidenberg
Nora M Haney Bashir M Rezk Sudah Talwar Samuel C Okpechi Matthew Honda Bryant Song Kevin Swan Salah Awadallah Kenneth J DeLay Suresh C Sikka Asim B Abdel-Mageed Philip J Kadowitz Wayne JG Hellstrom |
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MP45-17 |
Maintenance of contractile phenotype in corpus cavernosum smooth muscle cells by overexpression of myocardin ameliorates erectile function in bilateral cavernous nerve injury rats |
Sexual Function/Dysfunction: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP45-17 Sources of Funding: The National Natural Science Foundation of China, 81571433, the Natural Science Foundation of Guangdong Province, China, 2014A030313302, and the Natural Science Foundation of Guangdong Province, China, 2015A030310075. Introduction The pathophysiology of erectile dysfunction (ED) following radical prostatectomy (RP) was not clearly clarified, and the low efficacy of the major PDE5i treatment remained a frequent complain clinically. This study aimed to demonstrate phenotypic modulation in bilateral cavernous nerve injury (BCNI) rats within 7 days, subsequently verify Myocardin gene therapy to maintain the contractile phenotype of corpus cavernosum smooth muscle cells (CCSMCs). Methods For the first part, 36 male rats were randomly assigned to BCNI and NC groups for histological and molecular measurements at 3, 5, 7 days. Afterwards, a single intracavernosal injection of 50uL PBS, Ad-Myocd (1x10^11 pfu/ml) or Ad-vector was given to three treatment groups with 10 animals each, defined as NC+PBS, BCNI+Ad-Myocd, BCNI+vector, at the day of molecular changing day found previously. Finally, the validity and mechanism of Myocardin transfection was explored in vivo and in vitro. Results Western blotting revealed canonical declined Myocd, a-SMA, Calponin and elevated OPN expression before corporeal SM-to-collagen ratio and morphological changes at 5th day after modeling. Overexpression of Myocardin maintained the contractile phenotype of CCSMCs, improved BCNI rat intracavernous pressures, as well as suppressed cell proliferative capacity and promoted contractility. In addition, confocal test showed up-regulation and co-localization of serum response factor (SRF) in gene-transfer cells. Conclusions In conclusion, our study was the first to investigate CCSM cell phenotypic switch in the early stage of BCNI rats, and Myocardin was capable of reversing phenotypic modulation by activating SRF. The experimental results validated the efficiency of gene therapy in erectile dysfunction. Funding The National Natural Science Foundation of China, 81571433, the Natural Science Foundation of Guangdong Province, China, 2014A030313302, and the Natural Science Foundation of Guangdong Province, China, 2015A030310075.
Authors
Anyang Wei
Haibo Zhang Shuhua He Zhiqiang Wang Fengzhi Chen Wei Ding Wenbin Liu Zerong Chen |
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MP45-18 |
CALORIE RESTRICTION REVERSES THE AGE-RELATED ALTERATION OF CAVERNOUS NEUROVASCULAR STRUCTURE IN THE RAT |
Sexual Function/Dysfunction: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP45-18 Sources of Funding: This study was supported by the NRF grant funded by the MSIP (Ji-Kan Ryu, 2016R1A2B2010087), Republic of Korea. Introduction Four groups of rats were used: young rats (7 months) + ad-libitum, old rats (22 months) + ad-libitum, young rats + CR diet, and old rats + CR diet. The ad-libitum group had free access to both food and water and CR groups were fed 60% of the food intake of their ad-libitum littermates, for 6 weeks before decapitation. The penis was harvested and stained with antibodies to vWF, smooth muscle α-actin, PDGFR-β, neurofillament, and S100. We also performed Masson trichrome staining and TUNNEL assay. The blood samples were collected for the measurement of plasma testosterone level. Methods Four groups of rats were used: young rats (7 months) + ad-libitum, old rats (22 months) + ad-libitum, young rats + CR diet, and old rats + CR diet. The ad-libitum group had free access to both food and water and animals in the CR groups were fed 60% of the food intake of their ad-libitum littermates, for 4 weeks. The penis was harvested and stained with antibodies to vWF, smooth muscle α-actin, PDGFR-β, neurofillament, and S100. We also performed Masson trichrome staining and TUNNEL assay. The blood samples were collected for the measurement of plasma testosterone level. Results The contents of endothelial cell, smooth muscle cells, pericytes, and neuronal cells as well as serum testosterone levels were significantly lower in old rats than in their young littermates. In old rats, but not in young rats, CR diet significantly restored cavernous endothelial cells, smooth muscle cells, pericytes, and neuronal cell contents; increased plasma testosterone level; and decreased endothelial cell apoptosis and cavernous fibrosis as determined by the ratio of collagen to smooth muscle contents. Conclusions CR diet successfully improved age-related derangements in penile neurovascular structures. Along with a variety of life style modifications, our study gave us a scientific rationale to use CR diet as a non-pharmaceutical strategy for treating or preventing erectile dysfunction in aged men. Funding This study was supported by the NRF grant funded by the MSIP (Ji-Kan Ryu, 2016R1A2B2010087), Republic of Korea.
Authors
Anita Limanjaya
Kang Moon Song Min Ji Choi Kalyan Ghatak Nhat Minh Nguyen Guo Nan Yin Ji Kan Ryu Jun Kyu Suh |
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MP45-19 |
Soluble Epoxide Hydrolase Inhibition Improves Erectile Function in Diabetic Mice through Attenuation of Fibrosis and Apoptosis |
Sexual Function/Dysfunction: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP45-19 Sources of Funding: This work was supported by grants from the National Natural Science Foundation of China (NSFC #81471451) Introduction Soluble epoxide hydrolase (sEH) can catalyze epoxyeicosatrienoic acids (EETs) to dihydroxyepoxytrienoic acids (DHETs), thereby reduces their biological activity, such as vasodilation and anti-apoptosis. We performed this study to investigate the effect of inhibition of sEH on the diabetic erectile dysfunction in mice. Methods Diabetes was induced in 8-week old male mice by introperitoneal injection of streptozotocin with the dose of 60mg/kg for 5 consecutive days. 16 weeks after the induction the mice were divided into 3 groups (8 mice in each group): (1) nondiabetic control group, (2) diabetic mice + vehicle group which were given tap water containing 0.01% DMSO for 4 weeks, and (3) diabetic mice + trans-4-[4- (3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid (t- AUCB) group, which received t- AUCB (an inhibitor of sEH, 2mg/L in drinking water containing 0.01% DMSO) for 4 weeks. Then erectile function of mice was measured by electrical stimulation of the cavernous nerve and ratio between intracavernosal pressure (ICP) and mean systemic arterial blood pressure (MAP) at the peak of erectile response was calculated. After that penis tissue was harvested. Expression of sEH, transforming growth factor beta 1 (TGF?-1) and collagen IV in corpus cavernosum were measured by western blot. The deposition of extracellular collagen was determined by Masson trichrome staining, while the content of ?-smooth muscle actin (?-SMA) was measured by immunofluorescence. Apoptosis was detected by terminal dexynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). Results The ICP/MAP was reduced in diabetic mice compared with control group, but was improved by t-AUCB treatment (p<0.05). The expression of sEH, TGF?-1 and collagen IV were all decreased by giving t-AUCB in diabetic mice (p<0.05). The ratio of smooth muscle to collagen and the content of ?-SMA were both increased in t-AUCB group compared with vehicle group (p<0.05). Besides, less apoptotic cells were found in t-AUCB group than in the vehicle group (p<0.05). Conclusions sEH might play a role in the development of diabetic erectile dysfunction. Inhibition of sEH could improve the erectile function in diabetic mice by reducing the fibrosis and apoptosis in corpus cavernosum. Funding This work was supported by grants from the National Natural Science Foundation of China (NSFC #81471451)
Authors
Hao Li
Liping Chen Tao Wang Shaogang Wang Jihong Liu |
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MP45-20 |
Improvement of Penile Histomorphological Structure and Function with Stem Cells in a Rat Model of Neurovascular Erectile Dysfunction |
Sexual Function/Dysfunction: Basic Research & Pathophysiology I | 17BOS |
Abstract: MP45-20 Sources of Funding: AFIRM Introduction Neurovascular injury induced erectile dysfunction is a common complication in complex pelvic trauma in men. This lesion remains difficult to treat despite advances in pharmacotherapeutic approaches. The goal of this study is to determine whether stem cells implanted into the corpora cavernosa could improve erectile function and restore histomorphological structure in a rat model of neurovascular erectile dysfunction (NVED). Methods NVED model was established in athymic rats by crushing bilateral cavernous nerves and ligations of bilateral internal pudendal bundles. Three different types of human stem cells were used: endothelial cells (ECs), adipose derived stem cells (ASCs) and amniotic fluid derived stem cells (AFSCs). Normal saline injection served as a control. Stem cells (2.5x106 cells/0.2 ml) were injected intracavernously into the penile tissue. Erectile function and histomorphological analyses of penile tissue were assessed 12 weeks after stem cell injection. Results The ratio of intracavernous pressure and mean artery pressure (functional indicator) was increased in the stem cell and endothelial cell therapy groups when compared to the NS injection group. Immunofluorescence staining showed that more cells expressing biomarkers of endothelial, smooth muscle, and nerve cells within the corpora cavernosa was seen in the cell therapy groups when compared to the NS injection group. Conclusions Stem cell therapy enhanced erectile function and ameliorated the histological structure in NVED rats, indicating that stem cell therapy may induce vascular, myogenic and neurogenic tissue regeneration in a rat model of NVED. Funding AFIRM
Authors
Ting Long
Liren Zhong Hua Shi Yuanyuan Zhang Wei Li Dong Chen HyunChul Chung Cara Clouse Sandy Sink sunil George Tom Lue James Yoo Anthony Atala John Jackson |
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MP46-01 |
Is the ICIQ-SF questionnaire reliable in a real-life setting? Results of a prospective single-center study |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Male Incontinence: Therapy | 17BOS |
Abstract: MP46-01 Sources of Funding: none Introduction The aim of the study is to assess functional outcomes, using validated questionnaires, in a large group of patients after robot-assisted radical prostatectomy (RARP) in a single center. We also assessed the correlation between ICIQ-SF and EORTC QLQ-C30 results in order to evaluate the association between objective measurements and &[Prime]return to normal activities&[Prime] which represents the &[Prime]real life&[Prime] functional goal of this technique. Methods 363 patients underwent RARP between September 2009 and August 31st 2016. All data were prospectively collected in a compulsory regional database (Flemish cancer registry). The database was accessed on August 2016. Pre- and post-operative ICIQ-SF and EORTC QLQ-C30 questionnaires were available for every patient. Minimal clinical important difference (MCID) values between pre and post-operative scores (defined as the smallest difference in score in the domain of interest which patients perceive as successful) were used to define a successful outcome after surgery. Paired T-test analyses were used to compare pre and post-operative results. Patients where then subdivided, according to the MSID, in two groups: patients with successful outcome and without successful outcome. Chi-squared test was used to investigate the relationship between ICIQ-SF and EORTC QLQ-C30 results. Results Mean follow up was 13.5 months (median 11, range 1-43). Before surgery, 81% of patients reported a ICIQ-SF score of 0. Using MCID= 4,11 points, this proportion decreased to 60% (N=227), p=0.26. At baseline 45% of patients had Global health scores of 100 (45%). After surgery this proportion was 52%. MCID was 6,67, (p=0.00). Before surgery 76% and 88% of patients resulted to have 100 points in Physical and Role functioning respectively. After surgery this proportion decreased to 71.6% and 67% (p=0.89, 0.043) respectively. MCID resulted to be 6.4 and 9.1 points respectively. The results obtained for each EORTC QLQ-C30 domain were compared to the objective results of the ICIQ-SF. Satisfactory EORTC outcomes were not associated to satisfactory ICIQ-SF scores (all p≤ 0.05). Conclusions According to our knowledge, this is the first prospective, single center study comparing ICIQ-SF results and the real-life outcomes addressed with EORTC QLQ-C30, of a big cohort of patients submitted to RARP. We showed that quality of life is not only determined by objective continence outcomes and should be associated with more true-life questionnaires, in order to improve the knowledge and the treatment of this group of patients._x000D_ _x000D_ Funding none
Authors
Manuela Tutolo
Youri Bekhuis Wouter Everaerts Alberto Briganti Steven Joniau Ben Van Cleynenbreugel Giulia Castagna Enrico Ammirati Emanuele Zaffuto Dirk De Ridder Frank Van Der Aa |
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MP46-02 |
Radical Prostatectomy and Recovery of Urinary Continence in Patients With Locally Advanced Prostate Cancer |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Male Incontinence: Therapy | 17BOS |
Abstract: MP46-02 Sources of Funding: None Introduction Few studies have been reported on the evaluation for recovery of urinary continence after radical prostatectomy in patients with locally advanced prostate cancer. We conducted a study of ≥pT3 patients to improve understanding of the natural history of continence state and to identify predictors useful in patient selection for incontinence management. Methods We reviewed the data ofpatientswith prostate cancer managed by open retropubicor robotic radical prostatectomyfrom January 2004 to May 2015.Excluding patients requesting short-term follow-up (< 12 months), 1,859 subjects were eligible for the study. Achievement of continence was defined as no pads or an occasional security pad. A total of 547 patients were diagnosed ≥pT3 disease. Multivariate logistic regression analyses were used to determine predictors for early continence (recovery within 3 months) or for persistent incontinence (no recovery after 12 months). Furthermore, ≤ pT2 patients were matched 1:1 to ≥pT3 patients based on the propensity score. Predictors of recovery of urinary continence were compared between ≥pT3 and ≤ pT2 patients. Results Of the 547 patients with ≥pT3, 63% underwent robotic surgery and 42%received bilateral nerve sparing procedure.Continence recovery at 1 month, 3 months, 6 months, 9 months, and 12 months was observed in 27%, 76%, 89%, 92%, and 95% of patients, respectively. Age (OR 0.967, p = 0.045), membranous urethra length (OR 1.120, p = 0.004), and bilateral nerve saving (OR 1.956, p = 0.006) had the significant predictive value for early continence. Additionally, open surgery (vs. robotic) was an independent risk factor for persistent incontinence (OR 3.146, p = 0.002). Of the ≤ pT2 patients, age, membranous urethra length, and bilateral nerve saving were also statistically associated with early continence recovery. However, open surgery did not show a significance to predict persistent incontinence (OR 0.656, p = 0.305)(table). Conclusions Urinary continence was achieved in most patients with ≥pT3 prostate cancer managed by radical prostatectomy. Our results highlight the advantage of robotic surgery for continence outcomes in patients with ≥pT3 prostate cancer compared with ≤ pT2. Funding None
Authors
Jung Keun Lee
In Jae Lee Tae Jin Kim Hakmin Lee Jong Jin Oh Sangchul Lee Jeong Hyun Kim Sung Kyu Hong Seok-Soo Byun Sang Eun Lee Seong Jin Jeong |
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MP46-03 |
Urinary function in 656 hypogonadal men improves over 8 years with testosterone undecanoate injections (TU) in comparison to an untreated control group independent of prostate volume |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Male Incontinence: Therapy | 17BOS |
Abstract: MP46-03 Sources of Funding: Bayer Pharma AG partially funded data entry and statistical analyses. Introduction Long-term data on effects of testosterone therapy (TTh) on urinary function in hypogonadal men published so far are from observational studies without a control group. We present registry data including an untreated hypogonadal control group. Methods Registry study in 656 men with testosterone ≤350 ng/dL and hypogonadal symptoms. 360 received TU 1000 mg/12 weeks following an initial 6-week interval (T-group). 296 men opted against TTh and served as controls (CTRL). 8-year data are presented. Changes over time between groups were compared by a mixed effects model for repeated measures with a random effect for intercept and fixed effects for time, group and their interaction. Changes were adjusted for age, weight, waist circumference, blood pressure, fasting glucose, lipids and quality of life to account for baseline differences between groups. In order to further validate results, propensity matching was performed for baseline age, BMI, and waist circumference. 82 men in each group fulfilled criteria. Results Total group: mean age was 57.4±7.3 years in the T-group and 64.8±4.3 in CTRL, median follow-up time 7 years for both._x000D_ In the T-group, IPSS decreased from 6.4±4.0 to 2.1±1.0 with a change from baseline of 5.0 points. In CTRL, IPSS increased from 4.5±2.0 to 6.5±2.6 after 8 years by 1.8 points (p<0.0001 for both). Residual urine volume decreased from 47.3±22.8 to 13.7±4.6 mL in the T-group and increased from 48.3±16.3 to 64.5±22.2 in CTRL. Prostate volume increased from 29.2±10.4 to 31.1±11.5 mL in the T-group (p<0.0001) and fell from 34.5±5.9 to 33.5±12.0 in CTRL (NS)._x000D_ _x000D_ Propensity-matched group: mean age was 61.7±5.1 years in the T-group and 61.6±2.9 in CTRL, median follow-up time 8 years in the T-group and 7 in CTRL._x000D_ In the T-group, IPSS decreased from 7.4±4.2 to 2.0±0.9 with a change from baseline of 5.4 points. In CTRL, IPSS increased from 4.3±2.3 to 7.0±2.6 after 8 years by 1.9 points (p<0.0001 for both). Residual urine volume decreased from 50.6±23.6 to 14.0±4.7 mL in the T-group and increased from 45.7±16.4 to 64.6±16.7 in CTRL. Prostate volume increased from 31.4±12.0 to 33.2±12.7 mL in the T-group (p<0.0001) and from 33.4±6.2 to 33.6±11.0 in CTRL (NS)._x000D_ Conclusions Urinary function is improved and preserved for a prolonged period of time by TTh in hypogonadal men and deteriorates in untreated hypogonadal men. The observed changes seem independent of prostate volume. Funding Bayer Pharma AG partially funded data entry and statistical analyses.
Authors
Ahmad Haider
Karim Sultan H Gheorghe Doros Abdulmaged Traish |
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MP46-04 |
HIGH PREVALENCE OF LOW SERUM TESTOSTERONE LEVELS AMONG ARTIFICIAL URINARY SPHINCTER PATIENTS |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Male Incontinence: Therapy | 17BOS |
Abstract: MP46-04 Sources of Funding: none Introduction Recent evidence suggests that low serum testosterone (LST) may be associated with artificial urinary sphincter (AUS) cuff erosion. While the role of androgen replacement therapy is currently poorly defined among men receiving AUS placement surgery, the prevalence of LST among AUS patients is also unknown. We report the prevalence of LST relative to other associated risk factors among a large group of men undergoing AUS placement at a single high-volume institution. Methods We retrospectively reviewed all men undergoing AUS procedures by a single surgeon from 2012-2016 to identify those men with pretreatment total serum testosterone levels. LST was defined as less than 280 ng/dL. All low serum testosterone levels underwent confirmatory testing. Clinical characteristics were compared between men with and without LST levels. Results Among 85 AUS patients having pretreatment serum testosterone levels available for review, nearly half (41/85, 48%) met criteria for LST. After excluding those patients on androgen deprivation therapy (N=13), 28 of 72 (29%) had primary LST levels. AUS cuff erosion was more common among men with LST levels (38% vs 9%, p=0.01). The median total serum testosterone level among men undergoing AUS placement was 331ng/dL (IQR 192-447). Testosterone levels were drawn at a median 1.5 months (IQR 0-5.8) before AUS surgery. Men with LST levels were more likely to have a history of coronary artery disease (88% vs 30%, p=0.002) and a trend in greater body mass index (mean 31 vs 28, p=0.09) relative to those with normal serum testosterone levels. There was no difference in patient age, history of radiation, time from cancer therapy, erectile dysfunction, or other comorbidities. Conclusions Approximately one-half of men with stress urinary incontinence undergoing AUS placement present with LST levels. Accordingly, given the association between LST and AUS cuff erosion, men with risk factors for LST should undergo further evaluation prior to SUI surgery. Funding none
Authors
Travis Pagliara
Jeremy Scott Boyd Viers Allen Morey |
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MP46-05 |
Predicting Urethral Atrophy in Patients Undergoing Primary Placement of Artificial Urinary Sphincter |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Male Incontinence: Therapy | 17BOS |
Abstract: MP46-05 Sources of Funding: None Introduction The artificial urinary sphincter (AUS) remains the gold standard for the surgical treatment of male stress urinary incontinence. Device failure or revision can be due to multiple etiologies including device erosion, infection, mechanical malfunction, and urethral atrophy. Despite the known risk, to date, few studies have evaluated factors that predispose patients to urethral atrophy. Here, we sought to identify preoperative and perioperative risk factors associated with urethral atrophy in men undergoing primary AUS placement. Methods From 1987 to 2013, a total of 1,068 men underwent primary AUS placement at our institution. Multiple clinical and surgical variables were evaluated for a potential association with revision for atrophy. Those found to be associated with atrophy were further evaluated on multivariable analysis including competing risks. Results With a median follow-up of 4.2 years (IQR 1.3-8.1), 89 men (8.3%) experienced urethral atrophy requiring reoperation for recurrent SUI. Median time to urethral atrophy was 4.5 years (IQR 1.9-7.6). On univariate analysis, only smaller cuff size (4.0-cm versus 4.5-cm; HR 3.1, p=0.04) was associated with an increased rate of urethral atrophy. Notably, patient age at the time of surgery (p=0.62), BMI (0.22), and smoking status (p=1.00) were not associated with a risk of atrophy. On multivariable analysis smaller urethral cuff size remained significant for increased risk of revision for urethral atrophy (HR 2.8, 95% CI 1.1-7.1; p=0.01). Conclusions Revision surgery for urethral atrophy occurs in approximately 8% of men undergoing primary AUS placement. Utilization of a smaller AUS cuff size appears to be an independent factor associated with increased rate of urethral atrophy. Funding None
Authors
Matthew Ziegelmann
Brian Linder Boyd Viers Laureano Rangel Marcelino Rivera Daniel Elliott |
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MP46-06 |
Comparison of Adjuvant Radiation Therapy Before or After Artificial Urinary Sphincter Placement: A Multi-Institutional Analysis |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Male Incontinence: Therapy | 17BOS |
Abstract: MP46-06 Sources of Funding: None Introduction Artificial Urinary Sphincter (AUS) remains the gold standard in the management of male stress urinary incontinence following radical prostatectomy. However, the impact of AUS placement before or after adjuvant radiation therapy has limited coverage in the literature. The objective of this study was to determine if the timing of radiation therapy has an impact on AUS outcomes, as well as identify predictors of AUS-related complications. Methods A retrospective review was conducted across five academic institutions of men who received AUS placement and adjuvant radiation therapy between 1993 and 2016. A total of 306 men were included in the study. Out of the 306 men, 292 (95.4%) received radiation before AUS placement (Group 1) and 14 (4.6%) men received radiation after AUS placement (Group 2). Collected variables included demographics, type of prostate cancer therapy, and AUS device specifications. Primary endpoints included complication rates, revision rates, and number of pads per day before and after AUS treatment. Bivariate analysis was used to examine the association between pretreatment comorbidities and the incidence of AUS-related complications postoperatively. Results Median duration of follow-up for the entire cohort was 30 months (range 4-148 months). Group 1 was followed for a median of 29 months (range 4-148 months), while Group 2 was followed for a median of 49 months (range 12-141 months). There was no difference between groups in the percentage of men who experienced postoperative complications (P = 0.832). In Group 1, 26.0% of patients experienced postoperative complications while 28.6% of patients in Group 2 experienced postoperative complications. While the number of pads per day decreased significantly from before AUS placement to after AUS placement, there was no significant difference in the average number of pads used per day between Group 1 and Group 2 (P = 0.907). The number of pads used per day in Group 1 before AUS placement was 5.24 ± 3.12 which decreased to 1.13 ± 1.31 (P < 0.001). In Group 2, the number of pads used per day before surgery was 6.09 ± 1.97 which decreased to 1.53±0.99 pads per day after AUS placement (P < 0.001). The percentage of men requiring revision in Group 1 was 31.2%, while the percentage of revisions in Group 2 was 14.3%(P = 0.028). The median time to revision was 14 months and 18.5 months for Group 1 and Group 2, respectively. The presence of peripheral vascular disease (PVD) and coronary artery disease (CAD) was associated with increased incidence of AUS-related complications (primarily refractory incontinence and cuff erosion) in both Groups (P = 0.032). The following factors were not significant: age, race, smoking, hypertension, diabetes mellitus, dyslipidemia, BMI, AUS device specifications, type of radiation therapy. _x000D_ _x000D_ Conclusions The timing of radiation therapy does not have a significant impact on complication rates or urinary continence as represented by number of pads used post-AUS placement. There is a non-statistical association between lower revision rates in patients who underwent radiation after AUS placement, as compared to before AUS placement. Patients with pre-existing PVD or CAD may experience more frequent postoperative complications, but this study is underpowered. Further research is needed to confirm these findings. Funding None
Authors
Kenneth DeLay
Nora Haney Andrew Gabrielson Jason Chiang Carrie Stewart Faysal Yafi Kenneth Angermeier John Lacy Hadley Wood Timothy Boone Alex Kavanagh Matthew Gretzer Stuart Boyd Jeff Loh-Doyle Wayne Hellstrom |
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MP46-07 |
Multicenter Analysis of Artificial Urinary Sphincter Outcomes In Patients After Both Radical Prostatectomy and Anastomotic Urethroplasty |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Male Incontinence: Therapy | 17BOS |
Abstract: MP46-07 Sources of Funding: None Introduction We sought to assess artificial urinary sphincter (AUS) outcomes in a subset of patients who have had a history of radical prostatectomy and anastomotic urethroplasty in order to describe outcomes after having two prior urethral transecting surgeries. Our null hypothesis is that multiple transections of the urethra do not increase the possibility of urethral erosion following artificial urinary sphincter placement. Methods We performed a retrospective review from five participating centers in the Trauma and Urologic Reconstruction Network of Surgeons. The study period included February 2010 - January 2016. Of the 445 incontinence procedures in our prospective database, there were 35 patients who underwent an AUS and had both a radical prostatectomy and anastomotic urethroplasty. Patients were excluded if they did not have a minimum of 6 months of follow up after AUS placement. Twenty-two patients met inclusion criteria. The surgeon independently determined choice of transcorporal or standard cuff technique. Results Median age was 67.5 years. Mean follow up time was 32.2 months (IQR 16.6 - 44.6 months). Twelve patients had a history of prior pelvic radiation for prostate cancer. Of the 22 patients, twenty patients had transcorporal cuff placement. There were 7 complications - 2 erosions, 3 hematomas, 1 infection, and 1 pump migration. Of these complications, four required additional surgery - the two erosions underwent AUS removal, one hematoma required exploration, and the patient with pump migration had his pump location adjusted. The overall AUS in situ rate in our cohort was 90.9% (20/22). History of prior radiation was not associated with AUS complications (p = 0.23). Conclusions AUS implantation can be performed in patients after two urethral transecting surgeries with an in situ rate of 90.9% at medium term follow up. Surgeons appear to prefer transcorporal placement in these scenarios. Funding None
Authors
Jonathan Wingate
Jeremy Myers Gregory Murphy Nejd Alsikafi Bradley Erickson Benjamin Breyer Bryan Voelzke |
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MP46-08 |
Urethral Strictures Are Not as Frequent as Thought After Artificial Urinary Sphincter Cuff Erosion |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Male Incontinence: Therapy | 17BOS |
Abstract: MP46-08 Sources of Funding: none Introduction Erosion of the artificial urinary sphincter (AUS) cuff is an uncommon problem after implantation of the AUS. The degree of injury secondary to the device erosion may lead to formation of scar around and within the urethra however the rate of secondary clinically significant strictures have not been well reported. We hypothesized that the stricture formation rate after an erosion was almost 100% in these patients and conducted a review of our single center experience to establish the natural incidence of stricture after erosion of the AUS cuff. Methods We conducted an internal review board approved review of males >18 years old with a history of AUS cuff erosion between January 1st, 2006 and January 31st 2013. Basic demographic, clinical and operative data were recorded. The degree of urethral erosion was stratified into 4 groups for comparison: 1) <25% circumference, 2) 25-50% circumference, 3) >50% and <100% circumference, 4) 100% circumference. A stricture was defined as clinically significant if it required intervention such as urethroplasty, direct visual internal urethrostomy, or dilation. Patients with less than 1 month follow up were excluded for stricture rate analysis. Results A total of 55 males with a history of AUS cuff erosion were identified. The mean patient age was 73.6 (±9.4). The mean device age was 50.5 months (range 1-160). Of the cohort, 47 were initially implanted at our institution and 8 elsewhere. An associated infection was noted in 20 patients. Of 55 patients, 13 (24%) had a prior history of AUS erosion. Of the 55 patients, 21 were in group 1, 13 in group 2, 7 in group 3, 5 in group 4, and the degree of erosion was not documented in 9. The median follow up after erosion in these patients was 9 months. Four patients did not have sufficient follow up to assess stricture rate (less than 1 month). The median length of catheterization was 30 days after removal of the AUS. The degree of erosion did not correlate with a longer period of catheterization (p=0.5). Of the patients with follow up, the overall rate of stricture in this cohort was 25%. The degree of erosion did not correlate with the risk of stricture occurrence (p=0.8). However, in the circumferential erosion group (n=5), 2 underwent a urethroplasty at the time of cuff removal. An infected and eroded cuff did not appear to correlate with a higher risk of stricture formation (p=0.7) Conclusions Erosion of the AUS cuff into the urethra leads to a urethral stricture in 25% of patients. However, the degree of erosion, prolonged urinary extravasation, or associated infection did not correlate with development of a urethral stricture. Funding none
Authors
Ramiro Madden-Fuentes
Stephanie Sexton Andrew Peterson |
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MP46-09 |
Previous incontinence surgery and surgical volume predict social continence and surgical revision: results of a large multi-institutional study. |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Male Incontinence: Therapy | 17BOS |
Abstract: MP46-09 Sources of Funding: none Introduction Artificial urinary sphincter (AUS) is considered the gold standard for moderate-to-severe male SUI. The aim of our study is to assess efficacy and safety in a large multi-institutional cohort of patients with long follow-up (FU) and to build a model to assess predictive factors of social continence (SC) and surgical revision (SR)._x000D_ Methods The study included 892 patients from 16 tertiary referral centres, submitted to primary AUS implant, between 1993 and 2012, with a minimum FU of 1-year. Patients were evaluated at 1, 6 and 12 months after surgery and yearly thereafter. SC was defined as 1 security pad or less and SR as any further surgery for failure or complications. To identify predictors of SC and SR we accounted for the following variables: age, diabetes mellitus (DM), anticoagulation therapy (AC), previous incontinence surgery (PIS), radiotherapy (RT), double cuff (DC), cuff size (CS) and surgical volume (SV). Patients were sub-divided into two groups according to the median number of implants per center/year (most informative cut-off), to define low and high SV centres. We also evaluated complication rate (CR): erosions and infections and failure rate (FR): urethral atrophy and mechanical failures. Results Overall 126/892 (14.1%) previously underwent TURP and 766 (85.9%) RP: the two groups differ only in terms of DM and AC (all p<0.05). Mean FU was 32 months (median 20, range 12-300); A total of 218/892 (24.4%) patients had PIS, namely: male sling surgery (n=75, 8.4%), peri-urethral injections (n=50; 5.6%) or peri-urethral balloons (n=92, 10.4%). Overall 257/892 (28.9%) patients had adjuvant RT. The median number of implants-per centre/year resulted to be 4: according to this cut-off value, 303 patients (34%) resulted to be treated in low-volume and 589 (66%) in high-volume centres. Erosion and infections were observed in 60/892 patients (6.7%) and 38/892 (4.2%) respectively. Urethral atrophy and mechanical failures were observed in 32/892 (3.5%) and 121/892 (13.5%), respectively. Overall SC and SR rates were 55% (n=489) and 30.6% (n=273) respectively. Multivariable analysis showed PIS to be the only predictor of lower SC rate (OR: 1.49, p=0.02) and SV the only variable associated with a higher risk of SR (OR: 1.53; p=0.016). Conclusions Our large-cohort long-FU study, confirms AUS as gold standard for post-op SUI. However it is still associated with high SR rates. PIS resulted to be negatively associated with SC. The results concerning SV confirm previous studies reporting no plateau for learning curve, with reduction of revisions only after 200 procedures. These results represent a further step in counselling and treatment of SUI after prostatic surgery. Funding none
Authors
Manuela Tutolo
Giulia Castagna Enrico Ammirati Marcus Drake Nikseh Tiruchelvam Kari Tikkinen Alexander Bachmann Ignacio Martinez-Salamanca Giorgio Bozzini Ricarda Bauer John Heesakkers Michele Favro Richard Lee Stéphane Larré Cosimo De Nunzio François Haab Sascha Ahyai Thomas Pichon Jean-Nicolas Cornu Frank Van Der Aa |
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MP46-10 |
Predicting Success After AUS: Which Preoperative Factors Drive Patient Satisfaction Postoperatively? |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Male Incontinence: Therapy | 17BOS |
Abstract: MP46-10 Sources of Funding: None Introduction To determine which preoperative factors impact patient quality of life after artificial urinary sphincter (AUS) implantation. Methods Men receiving AUS after prostate cancer treatment were identified from a prospectively collected dataset. Preoperative factors were collected at the time of initial incontinence consultation and most patients underwent urodynamic testing before surgery. Patients were surveyed by telephone at least 6 months after AUS, including the EPIC Urinary Domain (EPIC-UD) and Urinary Distress Inventory (UDI-6). Differences in postoperative maximum PPD (mPPD) and instrument scores were compared across preoperative factors using Wilcoxon-Rank sum test or Pearson correlation coefficient, with p≤0.05 indicating significance. Multiple regression analysis was performed with all factors having p≤0.1 on univariate comparisons. Results Phone survey was completed by 101 patients. Median age was 69 [63-75] years, BMI was 29 [26-32] kg/m2, and 41 (41%) patients had a history of radiation. Maximum PPD was 5 [3-9] preoperatively and 2 [1-3] postoperatively. Median EPIC-UD was 82 [67-89] and UDI-6 78 [64-89]. Postoperative outcomes did not significantly differ with or without a history of radiation. Postoperative mPPD was significantly lower in patients with the preoperative ability to store urine (2 [1-2] v 2 [1-4], p=0.046). Preoperative mPPD was positively correlated with postoperative mPPD (r=0.255, p=0.011). Regression for postoperative mPPD (R2=0.236, p=0.009) showed decreased use with bladder neck contracture (p=0.032) and lower preoperative mPPD (p=0.030). EPIC-UD was significantly lower with increased detrusor pressure at maximum flow (PdetQmax) (r=-0.346, p=0.013). No other variables were found to be significant. UDI-6 was significantly higher with increased PdetQmax (r=0.413, p=0.003). Regression for UDI-6 (R2=0.200, p=0.005) showed higher score with increased PdetQmax (p=0.005)._x000D_ Conclusions PdetQmax was most strongly associated with patient-reported outcomes. While postoperative pad use was associated with preoperative pad use, it was not associated with satisfaction as measured by UDI-6 and EPIC-UD. Funding None
Authors
Nathan Chertack
Bradley Gill Tianming Gao Kenneth Angermeier Drogo Montague Hadley Wood |
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MP46-11 |
Can Time To Failure Predict Artificial Urinary Sphincter Component Failure? |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Male Incontinence: Therapy | 17BOS |
Abstract: MP46-11 Sources of Funding: none Introduction Artificial urinary sphincter (AUS) malfunctions can occur in any of the individual components. Preoperative identification of the malfunctioned component may be valuable for preoperative counseling and determining surgical approach. As such, we sought to evaluate the relationship of time to failure with failed component. Methods A total of 1,082 male patients underwent primary AUS placement from 1983 to 2011 at our institution. Clinical variables were evaluated for association with component failure (urethral cuff, abdominal reservoir, scrotal pump, and tubing). Bootstrap was used to estimate the differences in the time to reach 1% failure for each pair of components. Results One hundred and fifteen patients experienced mechanical device malfunction at a median follow-up of 4.2 years (IQR, 0.8, 7.9). There were no differences in clinical variables between patients with and without device failure. Cuff, reservoir, pump and tubing malfunction occurred in 53 (4.9%), 26 (2.4%), 11 (1.0%), and 25 (2.3%) patients, respectively. Increasing age at time of primary surgery was associated with lower rates of cuff malfunction (HR 0.968, 95%CI 0.938-0.999, p=0.04). There was no evidence that clinical variables were associated with reservoir, pump or tubing failure. Likewise, there was no evidence proving a significant difference in time to 1% component failure between any pairwise comparisons of components. However, 3 years postoperatively, incidence of cuff failure appears to outpace other component failures (Figure 1) but further analyses would be required to confirm this trend. Conclusions Clinical predictors for AUS failure continue to be difficult to establish. There was no evidence proving differences in time to 1% component failure. Funding none
Authors
David Y Yang MD
Brian J Linder MD Laureano J Rangel MS Daniel S Elliott MD |
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MP46-12 |
Effects of perioperative complications on favorable outcomes after primary artificial urinary sphincter implantation for male non-neurogenic stress urinary incontinence |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Male Incontinence: Therapy | 17BOS |
Abstract: MP46-12 Sources of Funding: none Introduction The artificial urinary sphincter (AUS) is the gold standard approach for mild-to-moderate postoperative stress urinary incontinence (SUI) in male patients. However, peri- and postoperative complication rates are high. There is still limited data about how perioperative features can affect the outcome after AUS implantation. In the current study, we investigate the effect of surgical procedure variations and perioperative complications on patient-centered outcomes after AUS implantation in a contemporary European multicenter cohort. Methods Inclusion criteria were as follows: Non-neurogenic SUI, primary implantation of AUS between 2010 and 2012 in a high-volume center (>200 previous implantations), moderate-to-severe SUI (≥3 pads). Complications were graded using the Clavien-Dindo scale. Quality of life (QOL) was assessed with the validated IQOL score; continence was assessed by the validated ICIQ-SF score and pad use. Pain was assessed with visual analog scales. Subjective satisfaction rates were retrieved. Endpoints were QOL, patient satisfaction, pain, and continence (up to 1 safety pad). Statistical analysis included Mann-Whitney-U test, Chi2 test, and Spearman rank correlation (p<0.05). Results 105 patients [47.6% perineal approach; 52.4% penoscrotal] from 3 centers met the inclusion criteria. AUS had been explanted in 25 (23.8%), 4 (3.8) had been deceased. Questionnaires were sent to 76 patients, follow-up (FU) was available for 52 (68.4). Median FU was 38mo (25-58). Postoperative bleeding occurred in 5 (4.8), wound healing disorders (WHD) in 5 (4.8), urinary retention in 10 (9.5), and urinary tract infection (UTI) in 8 (7.6) patients. Postoperatively, median pad use was 1 (mean 1.2±1.1), median IQOL was 93 (84.8±22.5), and median ICIQ-SF was 8 (7.7±5.0). 23 (48.9) were continent. At FU, 17 (36.2) experienced pain. Satisfaction rate was 91.3%. Postoperative complications had no effect on continence success [p=0.489 (bleeding), p=0.596 (WHD), p=0.489 (urinary retention), p=0.543 (UTI)], patient satisfaction [p=0.913, 0.863, 0.913, 0.552], pain rates [p=0.389, 0.389, 0.637, 0.160], and IQOL scores [p=0.522]. Regarding the surgical procedure, duration of perioperative antibiotics prophylaxis significantly effected long-term pain rates (p=0.036), patient satisfaction rates (p=0.007), and correlated significantly with reduced IQOL scores (R=-0.531, p<0.001). Surgical approach, catheter size and indwelling time, and intraoperative complications had no significant effect on the analyzed endpoints. Conclusions This is the first study to analyze long-term effects of perioperative complications on favorable outcomes after AUS implantation. We show that perioperative morbidity does not lead to less favorable long-term results and therefore reassure both implanting surgeon and patient. Since duration of antibiotic prophylaxis had a negative effect on AUS outcomes, our results advocate a more restrictive use of perioperative antibiotics. Funding none
Authors
Alexander Kretschmer
Tanja Hüsch Frauke Thomsen Dominik Kronlachner Ralf Anding Tobias Pottek Alice Obaje Achim Rose Roberto Olianas Alexander Friedl Wilhelm Hübner Roland Homberg Jesco Pfitzenmaier Fabian Queissert Carsten M. Naumann Josef Schweiger Carola Wotzka Joanne N. Nyarangi-Dix Torben Hofmann Alexander Buchner Axel Haferkamp Ricarda M. Bauer |
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MP46-13 |
Evaluating the Role of Perioperative Antibiotics in Preventing Artificial Urinary Sphincter Explantation: Analysis of a Large National Prospective Database |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Male Incontinence: Therapy | 17BOS |
Abstract: MP46-13 Sources of Funding: University of Chicago Institute of Translational Medicine, Core subsidy grant Introduction Although frequently prescribed, the role of postoperative oral antibiotics in preventing artificial urinary sphincter (AUS) explant is unknown. We aimed to determine whether postoperative oral antibiotics are associated with decreased risk of explantation following AUS. Methods We queried the MarketScan database (a large national, prospectively-maintained database of private insurance claims) to identify male patients undergoing AUS placement between 2003 and 2014. The primary endpoint was AUS explantation, determined by CPT codes. Multivariate regression analysis assessed for independent predictors of explantation, including peri- and postoperative antibiotic administration. Results We identified 3594 patients who underwent AUS placement at mean age 68.1 years (±0.15). 141 of 3594 (3.9%) patients underwent AUS explant at a median 41.5 days (IQR 20-61) after index surgery. Rates of explant stratified by risk factors are detailed in Table 1. On multivariate regression analysis, controlling for age and multiple previously described comorbid risk factors, we identified age >75 years, diagnosis of diabetes, and Charlson comorbidity index >1 to be independently associated with AUS explant (Table 1). The 2300 patients (64%) who received postoperative oral antibiotics did not experience any reduction in explant rate relative to those not receiving postoperative oral antibiotics (3.91% vs 3.95%, adjusted OR 1.01, 95% CI 0.71-1.45). Explant rates were similar among the approximately one-quarter of patients for whom perioperative IV antibiotic data were available, with no difference in explant rates observed for the 64% of patients receiving an antibiotic regimen consistent with AUA guidelines (4.5% vs 4.3%, p=0.89). Conclusions Postoperative oral antibiotics are prescribed to nearly two-thirds of patients but are not associated with reduced risk of explant following AUS placement. Given the risks to individuals associated with use of antibiotics and increasing bacterial resistance, routine use of oral antibiotics after AUS should be reconsidered. Funding University of Chicago Institute of Translational Medicine, Core subsidy grant
Authors
Melanie Adamsky
William Boysen Andrew Cohen Sandra Ham Joseph Rodriguez Roger Dmochowski Sarah Faris Gregory Bales Joshua Cohn |
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MP46-14 |
Invalidation of the practice of adding fluid to the AMS 800 Artificial Urinary Sphincter pressure regulating balloon |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Male Incontinence: Therapy | 17BOS |
Abstract: MP46-14 Sources of Funding: None Introduction The artificial urinary sphincter (AUS) AMS 800 has proven to be very effective in treatment of stress urinary incontinence. However, surgeon practice patterns vary when the device does not provide the desired degree of dryness. A common approach utilized is to add additional fluid to the pressure regulating balloon (PRB). The goal of this study was to evaluate changes in pressure with the addition of fluid to the PRB. Methods Ex vivo pressure studies were conducted on Boston Scientific AMS 800 PRBs rated 51-60, 61-70 and 71-80 cmH2O in a controlled laboratory setting using the Laborie Aquarius TT urodynamics system. After calibration of the equipment and appropriate cycling of the balloons in a standardized technique similar to that performed in the operating room setting, PRBs were initially filled to 10mL using 0.9% normal saline and opening pressures were obtained. We reported mean and standard deviation. Balloons were inflated up to 35 mL and pressure-volume data sets were acquired for each device. Results The mean opening pressures at 10 mL fill volumes of the 51-60, 61-70, and 71-80 cmH2O PRBs were 51.0±4.8, 65.1±7.8, and 78.9±3.9 cmH2O, respectively. The pressure-volume curves appeared similar for all PRBs and rose to maximum pressures of 67.0±4.0, 87.3±5.1 and 105.7±2.4 cmH2O at fill volumes of 16, 17 and 16 mL, respectively for each type of PRB. The addition of any more volume to the balloons did not result in any additional increase in pressure up to a fill volume of 35 mL (see Figure 1). Following data collection, we continue filling the balloons to a volume of 500 mL. Even at these supra-physiologic volumes, pressures remained stable and only started slowly increasing to 100, 105 and 110 cmH2O respectively at 1 liter. Conclusions The AUS PRB is a very compliant device and adding more fluid to an in situ AUS PRB does not increase the pressure of the system. Although our study does not account for in vivo behavior within a possible capsule formation, we discourage this surgeon practice and recommend adopting a different corrective method for persistent urinary incontinence. Funding None
Authors
Zachary Koloff
Paholo Barboglio Romo Yooni Yi Bahaa Malaeb |
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MP46-15 |
REFINED SELECTIVITY USING STANDING COUGH TEST IMPROVES OUTCOMES OF MALE SLING SURGERY |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Male Incontinence: Therapy | 17BOS |
Abstract: MP46-15 Sources of Funding: none Introduction Although the AUS is still considered the gold standard for treatment of men with moderate or severe stress urinary incontinence (SUI), the transobturator male sling is a viable alternative for milder cases. We hypothesized that increasing selectivity of male sling patients improves clinical outcomes of the AdVance male sling procedure. We reviewed our 8 year experience with AdVance sling cases to determine the association of patient clinical characteristics and clinical outcomes over time at our institution. Methods We conducted a retrospective review of patients who underwent placement of the AdVance male sling for PPI between 2008 - 2015. Of those 231 patients identified, 166 had complete data for review including demographics and important pre-operative patient characteristics [pads per day (PPD), radiation history, time from cancer treatment, smoking, diabetes, hypertension, BMI, and physical demonstration of urine during Standing Cough Test (SCT) evaluation-determined as favorable (Grade 0-2) or unfavorable (Grade 3-4)]. We measured success post-operatively based on progression to further anti-incontinence surgery or lack of SUI improvement. Results Among 148 men who underwent AdVance sling placement with complete data available, 41(28%) failed during the mean follow up of 2 years. Median age and delay from prostate cancer treatment was similar between groups. Advance sling failure was associated with an increased PPD (median 2.5 [IQR 2-3.5] vs 1.5 [IQR 1-3]) (p=0.01). Those with unfavorable findings on SCT had a 50% failure rate, while those with favorable findings had a 25% failure rate (p=0.05). Patients with a history of XRT failed 63% of the time vs 23% who failed without radiation (p<0.0001). On multivariable analysis, each one pad increase in PPD (OR 1.46, 95%CI 1.10-1.94, p= 0.008), prior XRT (OR 6.59, 95%CI 2.36-19.56, p=0.0003), and unfavorable SCT (OR 4.04, 95%CI 1.11-15.59, p=0.03) were independently associated with sling failure. The addition of the SCT to the model significantly increased the ability to detect sling failure (AUC 0.77 vs 0.73). Conclusions Identifying patients with ideal characteristics preoperatively is associated with improved outcomes following AdVance male sling placement. Patients with a history of radiation and men found to have heavy leakage during standing cough test were at a significantly higher risk for failure of the sling. A model of prior XRT, PPD, and SCT evaluation had an improved selectivity for sling success. Funding none
Authors
Travis Pagliara
Maia VanDyke Boyd Viers Jeremy Scott Allen Morey |
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MP46-16 |
Post-operative transobturator male sling urinary retention resolves spontaneously with time and may be associated with higher long-term success |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Male Incontinence: Therapy | 17BOS |
Abstract: MP46-16 Sources of Funding: None Introduction Post-operative urinary retention (POUR) has been reported in 3-21% of patients undergoing a male transobturator sling (TOS) for post-prostatectomy urinary incontinence (PPUI). Our objective was to examine the natural history of POUR in men undergoing TOS, and review the treatment options and resolution rates to propose an algorithm for management. Methods We reviewed men undergoing a TOS at our institution from 2006 to 2012. Demographic data, post-operative complications and outcomes were extracted by chart review. Post-operative TOS success was defined as the use of 0 or 1 security pads/day, negative stress test on exam or pad weight less than 8 g/day. POUR was defined as patient reported inability to void requiring urological intervention. T-test, fisher&[prime]s exact test, cox regression model and Kaplan-Meier survival analysis were performed. Results 290 men with PPSUI that underwent a TOS were identified. POUR was reported in 11.7% (34/290). 33 of these 34 patients had a radical prostatectomy and 1 had a radical cystoprostatectomy with an orthotopic neobladder. POUR was associated with a lower average BMI (25± 2 versus 28± 3, p<0.01). Age, diabetes, pelvic radiation, a prior or concurrent bladder neck contracture had no correlation with POUR. We identified no urodynamic parameters that could distinguish patients that develop POUR during preoperative evaluation._x000D_ _x000D_ 67.6% (23/34) patients were taught and performed temporary clean intermittent catheterization (CIC), 29% (10/34) had a temporary indwelling foley placed. All patients resolved spontaneously with 85% (29/33) lasting 1-7 days and 12% (4/33) for 7-30 days. Figure 1 shows survival estimates of TOS failure in men who experienced short-term POUR versus those who did not (p=0.04). Those with POUR had better long term outcomes with a hazard ratio of 0.47 (95%CI 0.2- 1.0). None had permanent retention nor required surgical intervention such a sling release._x000D_ Conclusions We feel that this information is valuable in that all cases resolved spontaneously thus allowing us to avoid surgical intervention in these cases. We propose the following algorithm outlined in Figure 2 for the management of POUR. Funding None
Authors
Divya Ajay
Bryce Allio Ramiro Madden-Fuentes Andrew Peterson |
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MP46-17 |
Association between Early Postoperative Urinary Retention and Outcomes after Transobturator Sling Insertion for Treatment of Male Stress Urinary Incontinence |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Male Incontinence: Therapy | 17BOS |
Abstract: MP46-17 Sources of Funding: none Introduction Male stress urinary incontinence (SUI) is a common sequela of radical prostatectomy and occasionally benign prostatic hyperplasia surgery, causing significant impact on quality of life. The AdVance transobturator sling has been described as a safe and effective minimally invasive treatment for male SUI, but early postoperative urinary retention (EPUR) is not uncommon. This study evaluates the outcomes of patients who have EPUR after insertion of an AdVance transobturator male sling for treatment of SUI. Our hypothesis is that although EPUR can be concerning, it is usually transient and may be associated with favorable continence outcomes. Methods A review of all men with SUI treated with an AdVance transobturator sling by a single surgeon during the period of January 1, 2006 through August 1, 2016, was performed. Perioperative, continence and complication outcomes (including urinary retention, mesh erosion and reoperation) were assessed. Outcomes of men who experienced EPUR were compared with men who did not experience EPUR. Statistical analyses such as Chi Square test were performed in Microsoft Excel 2016. Results 257 men (mean age 68 years) underwent insertion of a transobturator sling for SUI during the study period. Mean follow up was 25 months; 5 men were lost to follow up. Overall, success rate was 84%, with 45% (114/252) of men reporting complete continence and 39% (98/252) reporting improvement only. Overall, the mean number of pads used per patient per day improved from 3.7 pre-sling to 1.3 post-sling insertion. 16% (41/252) of patients experienced EPUR which was treated with reinsertion of indwelling Foley urethral catheter and repeat void trial. Most cases of urinary retention resolved within weeks; one patient required explantation of the sling due to ongoing urinary retention beyond 3 months. In the group of patients who had EPUR, success rate was 98%, with 61% of men achieving complete continence and 37% reporting improvement only. By comparison, in the group of patients who did not have EPUR, success rate was 82%, with 42% of men reporting complete continence and 39% of men stating improvement only. The difference in continence success rate between the EPUR and no EPUR groups was statistically significant (p<0.05). Conclusions Insertion of an AdVance transobturator sling for treatment of male SUI was complicated by EPUR in 16% of men. Most cases of EPUR were transient. The continence success rate in the group of men who experienced EPUR was significantly better than in the group of men without EPUR. Funding none
Authors
Amanda Chung
Jack Zuckerman Oscar Suarez Ramon Virasoro Jeremy Tonkin Jessica DeLong Kurt McCammon |
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MP46-18 |
A LOGISTIC REGRESSION PREDICTION MODEL FOR THE SUCCESS OF THE MALE TRANSOBTURATOR SLING; VALSALVA LEAK-POINT PRESSURE (VLPP) GREATER THAN 70 CM H2O IS AN INDICATOR FOR SLING SUCCESS |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Male Incontinence: Therapy | 17BOS |
Abstract: MP46-18 Sources of Funding: None Introduction Urodynamic studies are often performed in the evaluation of post-prostatectomy stress urinary incontinence (PPSUI). The male transobturator sling (TOS) is a minimally invasive treatment for PPSUI. Many have reported their results with the specific Valsalva leak point pressure (VLPP) that predicts a good response to the TOS. Our objective was to determine the relationship of the pre-operative VLPP on the success rate of the male TOS in a high volume, single center. We hypothesized that the preoperative VLPP of 60cmH2O may better predict successful outcomes in these patients. Methods We reviewed patients undergoing a male TOS placement from 2006 to 2012 at our institution. Patients who underwent TOS placement were identified using our patient data portal (DEDUCE). Demographic, urodynamic, and follow-up data were extracted by chart review. Post-operative success was defined by the use of 0 or 1 security pad, a negative stress test on exam, or pad weight of less than 8 g per 24 hours. Cox regression model and Kaplan Meier Survival analysis were performed. Results 290 patients were included. All patients had undergone a radical prostatectomy for prostate cancer and presented with PPSUI. Average age at surgery was 66.3 (± 7.4) years and 84% were Caucasian. Median time to follow-up was 5 months (IQR 1-15). Figure 1 shows an inverse prediction curve for sling failure versus VLPP. The hazard ratio for failure with a VLPP of ≤70 cm H2O compared with a VLPP of >70 cmH2O, adjusted for pelvic radiation and 24 hour pad weight was 0.5 (95%CI 0.27-0.98). Conclusions There have been numerous papers written on the importance of patient selection for male TOS. We also know that men prefer a sling over an AUS. In our cohort of patients with PPSUI, those with a pre-procedural VLPP of > 70 cmH2O were 50% less likely to fail after TOS placement versus those with a VLPP ≤70 cmH2O. In our practice, we use this data to supports the use of VLPP cut off of 70 cm H2O as an indicator for success to help in the evaluation and counselling of patients. Funding None
Authors
Divya Ajay
Andrew Peterson |
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MP46-19 |
Mid-term follow up of the AdVance XP sling in the treatment of post-prostatectomy stress urinary incontinence – first 4-year results from a prospective multicenter trial |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Male Incontinence: Therapy | 17BOS |
Abstract: MP46-19 Sources of Funding: None. Introduction In recent years, several studies showed the effectiveness and safety of the AdVance sling for the treatment of male stress urinary incontinence (SUI). In 2010 the second generation of Advance, the AdVance XP was introduced. Aim of the study was to evaluate the efficacy and safety of the AdVance XP sling in male SUI after radical prostatectomy in a prospective multicenter study. Methods In total 115 patients were included. Patients with urine nocturnal incontinence, previous incontinence surgery, previous radiotherapy and coaptive zone <1cm in the preoperative repositioning test were excluded. Postoperatively, a standardized 24-hour-pad test, quality of life scores (IQOL and ICIQ-UI SF), VAS for pain, IIEF5, IPSS and PGI-score were performed. All patients with 0-5g in the pad test were defined as cured and improved with a reduction of urine loss >50%. All others were classified as failures. Significance analysis was performed with the help of Wilcoxon-test. Results Mean preoperative urine loss in the 24h pad-test was 272.0 g (median 272.0 g). _x000D_ After a follow-up of 3 months (n= 114) 64.9% of the patients were cured and 31.6% improved. Mean urine loss decreased significantly to 34.9 g (p<.001). After a follow-up of 24 months (n= 80) 68.8% of the patients were cured and 22.5% improved. Mean urine loss decreased significantly to 19.1 g (p<.001). After a follow-up of 36 months (n= 47) 66.0% of the patients were cured and 23.4% improved. Mean urine loss decreased significantly to 21.8 g (p<.001). After a follow-up of 48 months (n= 15) 60.0% of the patients were cured and 20% improved. Mean urine loss decreased significantly to 21.8 g (p<.001). There were no lost to follow-up._x000D_ Overall patients reported of no relevant pain (mean VAS: 0.5) and the patients´ satisfaction was high (mean PGI: 1.5). Mean I-QoL and ICIQ-UI SF improved significantly (p<.001, respectively) at maximum follow-up. There were no significant postoperative changes in IIEF5 and IPSS. No intraoperative and no long-term complications occurred. No erosion or explanations occurred._x000D_ Conclusions The AdVance XP shows good and stable effectiveness and low complication rates even in a mid-term follow-up of up to 4 years. Our results though highlight the importance of adequate preoperative patient selection. Funding None.
Authors
Markus Grabbert
Benedikt Klehr Alexander Kretschmer Christian Gozzi Peter Rehder Roland Homberg Florian May Peter Gebhartl Christian Stief Ricarda Bauer |
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MP46-20 |
Development of a Novel Artificial Urinary Sphincter (AUS): The Precision Medical Devices (PMD) Flow Control Device (FCD) for Management of Sphincteric Deficiency using Bluetooth Technology |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Male Incontinence: Therapy | 17BOS |
Abstract: MP46-20 Sources of Funding: Precision Medical Devices Introduction PMD has developed a new Bluetooth controlled AUS designed to improve patient satisfaction and allow for physician telemetry. The FCD fluid-free device is composed of 3 solid components: 1)Control Pack 2) Valve assembly 3)Activator. The control pack consists of a printed circuit board, stepper motor and a nickel-cadmium cell in a titanium casing. The valve assembly consists of a cable link, plunger and urethral cuff. The control pack opens and closes the plunger via a drive assembly which adjusts the closure pressure magnitude, allowing post-implant adjustments (via telemetry) without the need for re-operation. The handheld activator communicates with the implanted control pack via Bluetooth technology. The activator allows for either the physician or patient to communicate with the FCD for daily operation or diagnostics. Daily operations of the device are recorded and remote tele-monitoring is available. Methods The newest FCD prototype was implanted into 11 female mongrel dogs. The study length began at 12 weeks of observation after implantation for the initial animal and is extended to a 1 year follow-up for the most recent implants. There was no attempt to make the animals incontinent. Evaluations include renal ultrasound for each animal as well as weekly CBC, BMP and UA. Software and device performance was evaluated by telemetrically acquired data. Histology of explanted devices at the end of protocol is performed for each implant. Results The successful surgical implantation of 32 previous devices has allowed the development of the newest Bluetooth controlled AUS. We have currently implanted 11 animals with the newest prototype. Successful telemetry has been established for all implants. No device infections or urethral erosions were seen. There was one cutaneous erosion of the control pack. 3 animals developed urinary retention. Two cases were related to tissue overgrowth in the valve cap resulting in urethral kinking and the remaining case was due to a software malfunction causing elevated closure pressure on the urethra with associated loss of communication with the device. This observation was identified through post hoc analysis of the telemetry data. The implanted devices have undergone over 3,560 activation cycles to date. The device has also generated over 1,100 status reports, allowing the investigator to monitor device function. Conclusions The successful development of a fluid-free remotely controlled AUS that allows for post-implant adjustable settings and remote tele-monitoring capabilities is possible. Further modifications to the prototype to reduce battery size and the risk of urinary retention are needed prior to human trials. Funding Precision Medical Devices
Authors
Michael Ahdoot
Angelo Gousse Peter Sayet Christopher Gomez |
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MP47-01 |
Ultrasound-guided Transversus Abdominis Plane (TAP) block for Robot-Assisted Radical Prostatectomy |
Prostate Cancer: Localized: Surgical Therapy IV | 17BOS |
Abstract: MP47-01 Sources of Funding: none Introduction Several works underlines the importance of ultrasound-guided Transversus Abdominis Plane (TAP) block for postoperative analgesia and its versatility in every type of abdominal surgery, through laparotomic and laparoscopic via. The aim of this study was to evaluate the impact of TAP block on intra- and post-operative analgesia in the first 24 hours after Robot-Assisted Radical Prostatectomy (RARP). Methods TAP block is a new regional anaesthesia technique that provides analgesia after abdominal surgery. It involves injection of local anaesthetic into the plane between the transversus abdominis and the internal oblique muscles. The TAP block can be performed using a landmark technique through the lumbar triangle or with ultrasound guidance._x000D_ We evaluated the intra- and postoperative analgesic efficacy in 60 ASA I-III patients undergoing RARP under general anaesthesia without (A group, 30 patients) or with US-TAP block (B group, 30 patients), in the first 24 postoperative hours. After induction of general anesthesia, the US-TAP block was performed at 30 selected patients with Levobupivacaine at the dose of 150mg for each patient. All patients received postoperative analgesia with 1gr of Paracetamol three times a day, Tramadol and Ketoprofen were used as rescue drugs, whether NRS was >3. Results No complication was recorded during block performance._x000D_ We observed a significant reduction in intraoperative opioids administration, postoperative pain and postoperative drugs consumption in patients treated with US-TAP block (Tab 1)._x000D_ Seven patients, in A group, received Tramadol 100mg._x000D_ In B group only one patient received Tramadol 100mg, (first and second postoperative days) for surgical complication._x000D_ Conclusions The US-TAP block provided highly effective intra-operative and post-operative analgesia in the first 24 hours after RARP. A prospective further study is necessary to assess best protocol for all patients. Funding none
Authors
Fabrizio Dal Moro
Paola Pavarin Angelo Mangano Luca Aiello Claudio Valotto Filiberto Zattoni |
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MP47-02 |
Sentinel node technique in radical prostatectomy for prostate cancer patients: toward an individualized lymphadenectomy |
Prostate Cancer: Localized: Surgical Therapy IV | 17BOS |
Abstract: MP47-02 Sources of Funding: NONE Introduction To validate the technique of selective sentinel node biopsy for staging intermediate to high-risk prostate cancer by comparing the technique with conventional extended lymphadenectomy (eLFD) in a prospective, longitudinal comparative study. Methods This study included 58 patients. With a Briganti score > 5% the procedure was performed in 54 patients at the time of laparoscopic radical and in 4 patients with biochemical relapse after radiotherapy as primary treatment. Multidisciplinary team consists of urologists and physicians of the nuclear medicine department. The day before surgery, all patients underwent trans-rectal ultrasound guided intraprostatic injection with the radioactive 99mTc nanocolloid under tracking of a portable gammacamara (Sentinella®) to avoid extraprostatic injection. Single-photon emission computed tomography (SPECT/CT) was performed one hour later. The next day we removed laparoscopically the sentinel lymph nodes, guided by a portable Sentinella® gamma camera and a laparoscopic gamma-ray detection probe. The eLFD was completed to establish the negative predictive value of the technique. Results Patients. SPECT/CT showed radiotracer deposits outside the eLFD territory in 72%(42/58) of the patients and the laparoscopic gamma probe in 60% (35/58). The mean number of active foci per patient was 4.3 in the SPECT/CT and 3.2 in the laparoscopic gamma probe. The lymph nodes were metastatic in 15 patients (25%), 15% (11/54) when the prostatectomy was the primary treatment and in 100% (4/4) of the radiotherapy group. In all cases with metastatic lymph nodes, there was at least one positive sentinel node (NPV 100%). The sentinel nodes were the unique nodes affected in 53% (8/15) Metastatic sentinel lymph nodes were found outside the eLFD territory in 3/15 patients (20%). The sensitivity was 100%, the specificity was 94.73%, the positive predictive value was 81.81%, and the negative predictive value was 100%._x000D_ _x000D_ Nodes. Total number of removed nodes was1289, total of removed sentinel nodes 295 and total of positive nodes 51. The mean number of removed nodes was 22 (9-41) and the mean number of sentinel lymph nodes was 5 (0-14). _x000D_ Conclusions Sentinel node biopsy is superior to eLFD for diagnosing lymph node involvement during radical prostatectomy in intermediate and high risk prostate cancer patients. This technique can avoid eLFD when metastatic sentinel lymph nodes are not found (15 - 75% of patients), with the consequent functional advantages and cost saving properties. Funding NONE
Authors
Juan José Monserrat-Montfort
CESAR VERA-DONOSO Manuel Martinez-Sarmiento Jesús Betancourt-Hernández Ana Avargues Victor Vera-Pinto Pablo Sopena-Novales Francisco Boronat-Tormo Pilar Bello-Arques |
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MP47-03 |
Impact of additional radiation and/or ADT on functional outcomes after radical prostatectomy |
Prostate Cancer: Localized: Surgical Therapy IV | 17BOS |
Abstract: MP47-03 Sources of Funding: none Introduction While the optimal use and timing of secondary therapy after radical prostatectomy (RP) remain controversial, there are limited data on the patient-reported outcomes following multimodality therapy. Objective is to assess the impact of additional radiation (RT) and/or androgen deprivation therapy (ADT) on urinary continence, potency and quality of life (QoL) after RP. Methods Among 13150 men treated by RP from 1992-2013, 905 underwent RP+RT, 407 RP+ADT and 688 RP+RT+ADT. Urinary function, sexual function and overall QoL were evaluated annually using self-administrated validated questionnaires. Propensity score-matched and bootstrap analyses were performed, and the distribution of all functional outcomes were analyzed as a function of time after RP. Results Patients who received RP+RT had a 4% higher overall incontinence rate 3 years after surgery and 1% higher rate for severe incontinence (>3 pads/24h) compared to matched RP-only patients. ADT further increased the overall and severe incontinence rate by 4% and 3% compared to matched RP+RT patients. RP+RT was associated with a 18% lower rate of potency compared to RP alone, while RP+RT+ADT was associated with a further 17% reduction compared to RP+RT patients. Additional RT reduced QoL by 10% and additional ADT by a further 12% compared to RP only and RP+RT patients, respectively. The timing of RT after RP showed no influence on continence, but adjuvant compared to salvage RT was associated with significantly lower potency (37% vs 45%), but higher QoL (60% vs 56%). Conclusions Secondary RT and ADT after RP have an additive negative influence on urinary function, potency, and Qol. High-risk patients should be counseled on the potential net impairment in functional outcomes from multimodality treatment prior to RP. Funding none
Authors
Pierre Tennstedt
Meike Adam Derya Tilki Thomas Steuber Alexander Haese Georg Salomon Cordula Petersen Hartwig Huland Markus Graefen Wolfgang Huber Thorsten Schlomm |
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MP47-04 |
Obesity was associated with improved metastases-free survival after surgery in 13,667 prostate cancer patients |
Prostate Cancer: Localized: Surgical Therapy IV | 17BOS |
Abstract: MP47-04 Sources of Funding: None Introduction Obesity might negatively affect prostate cancer (PCa) outcomes. However, evidence according to the associations between obesity and metastases-free, as well as PCa-specific survival after radical prostatectomy (RP) is still inconsistent. Methods We relied on PCa patients treated with RP at the Martini-Klinik Prostate Cancer Center between 2004 and 2015. First, multivariable Cox-regression analyses examined the impact of obesity on metastases, PCa-specific death, and death of any cause after RP. Last, in a propensity score matched cohort, Kaplan-Meier analyses assessed metastases-free and overall survival according to body mass index (kg/m2) (BMI) strata (?30 vs. <25). Results Of 13,667 individuals, 1,990 (14.6%) men were obese (BMI ?30). Median follow-up was 36.4 month (IQR: 13.3-60.8). Obese patients were less likely to exhibit metastases after RP (HR: 0.7, 95% CI: 0.5-0.97, p=0.03, table 1). Similarly, after propensity score adjustment obesity was associated with increased metastases-free survival (log rank p=0.001). Obesity was not significantly associated with PCa-specific death (HR: 1.2; 95% CI: 0.5-2.7; p=0.8), but with higher risk of death of any cause after RP (HR: 1.7; 95% CI: 1.3-2.3; p=0.001). Similarly, after propensity score adjustment obesity was associated with decreased overall survival after RP (log rank p=0.001). Conclusions Obesity was associated with decreased risk of metastases after RP. Improved medical care of diabetes might have contributed to the latter observation. However, further research is needed to unravel the controversially debated association between obesity and PCa. Funding None
Authors
Pierre Tennstedt
Georg Salomon Derya Tilki Lars Budäus Raisa Pompe Sami-Ramzi Leyh-Bannurah Alexander Haese Hans Heinzer Hartwig Huland Markus Graefen Jonas Schiffmann |
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MP47-05 |
A systematic review of instrumental variable analyses using geographic region as an instrument in prostate cancer studies |
Prostate Cancer: Localized: Surgical Therapy IV | 17BOS |
Abstract: MP47-05 Sources of Funding: This work was supported by David H. Koch provided through the Prostate Cancer Foundation; the Sidney Kimmel Center for Prostate and Urologic Cancers; SPORE grant from the National Cancer Institute to Dr. H. Scher (grant number P50-CA92629); and a National Institutes of Health/National Cancer Institute Cancer Center Support Grant to MSKCC (grant number P30-CA008748). None of the funding sources had involvement in the conduct of the research or preparation of the manuscript. Introduction In many areas of prostate cancer research, such as comparing patient outcomes for radical prostatectomy versus radiotherapy for localized cancer, there are a limited number of randomized trials. Observational studies are used to address such comparisons. Instrumental variables analysis is a methodology to control for confounding in observational studies. Geographic area is being used increasingly as an instrument. We conducted a literature review to determine the properties of geographic area in studies of cancer treatments. Methods We reviewed the literature to identify cancer studies performed in the United States which incorporated instrumental variable analysis with area-wide treatment rate within a geographic region as the instrument. We assessed of the degree of treatment variability between geographic regions, assessed control of confounding afforded by geographic area and compared the results of instrumental variable analysis to those of multivariable methods. Results Geographic region as an instrument was relatively common, with 22 eligible studies identified, many of which were published in high-impact journals. Prostate cancer studies made up nearly half of the eligible studies found (10 of 22), including studies of surgery vs. conservative management, primary androgen deprivation vs. conservative management, surgery vs. radiotherapy and open vs. robotic surgery. Geographic region was only weakly associated with the intervention. Most studies reported an absolute difference in treatment rates between high and low use areas of 5% to 20%, with the largest difference being 31%. Absolute differences between high and low use areas reported in prostate studies ranged from 8% to 22%. Four out of seven of these studies reporting on covariate balance found at least one covariate to be associated with treatment prevalence. Eight out of eleven studies including five out of six prostate cancer studies found statistically significant effects of treatment on multivariable analysis but not for instrumental variables, with the central estimates of the instrumental variables analysis generally being closer to the null. Conclusions We recommend caution when using geographic region as an instrument in observational studies of treatments for prostate and other cancers. The value of geographic region as an instrument should be critically evaluated in other areas of medicine. Funding This work was supported by David H. Koch provided through the Prostate Cancer Foundation; the Sidney Kimmel Center for Prostate and Urologic Cancers; SPORE grant from the National Cancer Institute to Dr. H. Scher (grant number P50-CA92629); and a National Institutes of Health/National Cancer Institute Cancer Center Support Grant to MSKCC (grant number P30-CA008748). None of the funding sources had involvement in the conduct of the research or preparation of the manuscript.
Authors
Emily Vertosick
Melissa Assel Andrew Vickers |
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MP47-06 |
Oncological outcomes of pathologic node positive patients, following radical prostatectomy and extended pelvic lymph node dissection. |
Prostate Cancer: Localized: Surgical Therapy IV | 17BOS |
Abstract: MP47-06 Sources of Funding: none Introduction To evaluate oncological outcomes of patients affected by pathologic node positive (LN+) prostate cancer (PCa) following radical prostatectomy and extended pelvic lymph node dissection (ePLND)._x000D_ Methods We retrospectively evaluated 93 pts treated with open radical prostatectomy and ePLND between 2009 and 2014, with pathologic node positive disease (LN+). The ePLND consisted of the external iliac, obturator, internal iliac, presacral and common iliac nodal site up to the ureteric crossing. Specimens from each anatomic site were sent in separate packets. The estimated cancer-specific survival (CSS) and biochemical disease-free survival (bDFS) were calculate by Kaplan-Meier method. Multivariable Cox regression models assessed for prognostic factors of bDFS._x000D_ Results Median follow-up was 48 months (range 14-89); six pts (6%) died of disease at follow-up, while 39 (42%) experienced biochemical failure (PSA > 0.2 ng/ml). Out of 93 patients, 53 pts did not receive adjuvant hormone therapy (AdjHT), 46 pts harboring ≤2 LN+. The median number of nodes removed was 22 (range 9-61). The mean and median number of positive nodes was 2.7 and 1 (range: 1-18), respectively. The estimated 5-year CSS was 90%; 5-year bDFS was 45%. Pts with ≤2 LN+ had significant better 5-year bDFS than those with > 2 LN+ (59% vs 15%; p<0.001). Pts with Gleason score 7 had better 5-year bDFS than those with Gleason score 8-10 (58% vs 36%; p=0.039). At multivariable Cox regression analysis, presence of more than 2 LN+ was an independent predictor of worse bDFS (p=0.026; HR 2.2). Among pts who did not receive AdjHT, the estimated 5-year bDFS was 60%, and was significantly higher in pts with ≤ 2 LN+ than those with > 2 LN+ (64% vs 34%; p=0.032). Conclusions Among pts with pathologic node positive disease following radical prostatectomy and ePLND, those with ≤ 2 LN+ showed more than 50% bDFS at 5-year follow-up. Good cancer control seems to be achieved also without AdjHT, in pts with limited nodal burden._x000D_ _x000D_ Funding none
Authors
Marco Roscigno
Maria Nicolai Richard LJ Naspro Laura B Cornaghi Diego Angiolilli Antonino Saccà Michele Manica Luigi F Da Pozzo |
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MP47-07 |
Salvage Robotic-assisted Radical Prostatectomy: oncologic and functional outcomes from two high-volume institutions |
Prostate Cancer: Localized: Surgical Therapy IV | 17BOS |
Abstract: MP47-07 Sources of Funding: None Introduction Recurrent prostate cancer (PCa) will occur in approximately 25% of cases after primary radiotherapy (RT) and other ablative techniques. While no consensus on the optimal salvage treatment exists, only 3% of these patients will get salvage radical prostatectomy due to the assumed technical challenges of this procedure._x000D_ We aimed to analyze the perioperative, oncologic and functional outcomes of patients undergoing salvage robotic-assisted radical prostatectomy (sRARP) after primary treatment failure, at two high-volume institutions._x000D_ Methods Data was prospectively collected and retrospectively reviewed from a combined database of more than 14,800 patients who have undergone RARP. Between 2008-2016, we identified 96 patients who underwent sRARP after RT or ablative techniques. PCa recurrence was biopsy-proven in all cases. We analyzed primary cancer characteristics, surgical data, pathology results, perioperative complications, and oncologic and functional outcomes. Results Sixty-four patients (66.6%) were treated primarily with RT: 37 with External Beam RT (EBRT), 14 with Brachytherapy and 13 with EBRT + Brachytherapy. Eighteen patients (18.8%) received cryotherapy as their primary treatment, while 7 patients (7.3%) received HIFU. The remaining seven patients received treatment with either: Cyberknife, electroporation or microwaves._x000D_ The median surgical time was 128.47 min (98181). Sixteen patients (16.7%) had positive surgical margins, 46 (47.9%) show extraprostatic extension with 22 of them (23%), seminal vesicles invasion (pT3b). Complications were seen in 25 (26%) patients (21 minor and 4 major complications). Anastomotic leak was the most common complication, found in 14 (14.6%) of the cases. No rectal injuries ocurred. Fourteen (15%) patients had a biochemical failure after a median follow-up of 14(IQR 5-24) months. All 96 patients were continent prior to sRARP. Sixty-eight patients (71%) had social continence (0-1pad) and 55 (57%) of them self-reported to be pad free at 12 months, while 13 (13.5%) of them reported to be using 1pad/day. Seventeen(55%) of 31 preoperative potent patients (SHIM score >21), were potent with or without the use of PDE5i at 12 months._x000D_ Conclusions sRARP is a feasible alternative for PCa recurrence after ablative and radiation therapies. Rectal injuries are uncommon. Technically the procedure is challenging and should be performed by experienced prostate cancer surgeons. Continence and potency recovery is possible but at lower rates than for non-salvage patients. Patients should be counseled regarding the risks and benefits of salvage RARP. Funding None
Authors
Gabriel Ogaya-Pinies
Estefania Linares-Espinós Rafael Sánchez-Salas Eduardo Hernández-Cardona Xavier Cathelineau Vipul Patel |
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MP47-08 |
Comparison of oncological and functional outcomes following radical prostatectomy in clinical T2 and clinical T3 prostate cancers: findings from the SA-PCOCC database. |
Prostate Cancer: Localized: Surgical Therapy IV | 17BOS |
Abstract: MP47-08 Sources of Funding: None Introduction With improved surgical technique and understanding of the disease, radical prostatectomy (RP) is increasingly offered for locally advanced prostate cancer. RP in T3 prostate cancer may be associated with incomplete local tumour control, and functional outcomes may be worse because of the need for wider resection margins. We examined the oncological and functional outcomes in of patients undergoing RP in T2 and T3 prostate cancer. Methods A retrospective review was conducted including all patients listed in the SA-PCCOC database who underwent RP with stage pT2a-c or pT3a-b prostate cancer (any PSA, and any biopsy Gleason score). Demographics, PSA values, imaging characteristics, pathological details, intraoperative blood loss and length of stay were recorded. Oncological outcome was assessed by final histology report, margin status, and presence of and time to biochemical recurrence. Functional outcomes were assessed using the EPIC 26 questionnaire (urinary incontinence and erectile dysfunction domains). Results 1254 patients underwent RP for pT2, and 1297 patients for pT3 prostate cancer. In the patients with pT2 prostate cancer PSA values were <4 in 9.4%, 4-10 in 45.8%, 10-20 in 10.7% and > 20 in 1.4%. The patients with pT3 prostate cancer PSA values were <4 in 5.6%, 4-10 in 37.2%, 10-20 in 14.3% and > 20 in 3.6%. The Gleason scores in patients with pT2 were Gleason 3+3 in 51.9%, 3+4 in 30.3%, 4+3 in 9.4%, 4+4 in 5.2%, 5+4 in 3.2% patients. The Gleason scores in patients with pT3 were Gleason 3+3 in 25.8%, 3+4 in 35.1%, 4+3 in 21.7%, 4+4 in 16.1%, 5+4 in 1.3% patients. No significant difference was observed in blood loss and length of stay between the groups (p=0.85 and 0.83, respectively). Nerve sparing surgery was more frequently performed in patients with pT2 disease compared with pT3 (85.7% vs 75.8%, p<0.001). Despite this, the erectile dysfunction and urinary continence rates were comparable in the two groups. pT3 patients were at higher risk of biochemical recurrence (BCR) than pT2 patients (HR 1.96, 95% CI 1.6-2.5, p<0.001). Factors influencing biochemical recurrence were PSA >20 at presentation (HR 1.9, 95% CI 1.7-5.3, p<0.001), positive margin (HR 2.9, 95% CI 2.4-3.5, p<0.001), high Gleason scores- Gleason 4+3 (HR 4.2, 95% CI 3.0-5.9, p<0.001) and Gleason >7(HR 5.2, 95% CI 3.6-7.7, p<0.001). Conclusions Although T3 patients have an increased risk of BCR than T2 patients, the functional outcomes are comparable. This is despite a difference in the rate of nerve-sparing surgery in the groups. Funding None
Authors
Krishanu Das
Flavio V Ordones Andrew Fuller Michael O'Callaghan Nicholas R Brook |
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MP47-09 |
Timing of PSA Nadir after Radical Prostatectomy and Risk of Biochemical Recurrence: Does it Matter? Results from the SEARCH Database |
Prostate Cancer: Localized: Surgical Therapy IV | 17BOS |
Abstract: MP47-09 Sources of Funding: none Introduction Determining the risk of disease recurrence after radical prostatectomy (RP) is useful in early risk stratification. PSA nadir after RP is a strong predictor of biochemical recurrence (BCR). However, the time to nadir (TTN) has not been studied in the post-RP setting. We analyzed the association between PSA nadir level and TTN with BCR risk after RP among patients in the Shared Equal Access Research Cancer Hospital (SEARCH) Database. Methods Using SEARCH, we identified men who either had an undetectable PSA (0 ng/ml) within 1-3 months after RP, or a detectable PSA within 1-3 months after RP and a follow-up PSA within 3-6 months after RP (n=1882). Men with a BCR or secondary treatment within 6 months of RP were excluded. Nadir was the lowest PSA within 1-6 months. We divided patients into 4 nadir groups: undetectable nadir and TTN 3-6 months (n=139), undetectable nadir and TTN 1-2.9 months (n=1290), detectable nadir and TTN 3-6 months (n=146), and detectable nadir and TTN 1-2.9 months (n=307). A Cox model was used to test the association between nadir group and risk of BCR. Time zero for all groups was 6 months after RP. The model was adjusted for race, BMI, age, year, surgical center, pre-RP PSA, Gleason score, and pathological features. Results During a median follow-up of 65 months (IQR 29-111), 480/1882 (26%) men had a BCR. Among men with an undetectable PSA nadir and TTN 3-6 months, median time to first PSA was 1.6 months (IQR 1.3-2.1 months) after RP and median initial PSA was 0.02 (IQR 0.01-0.03). Among men with a detectable PSA at 1-3 months, 48% had a lower follow-up PSA 3-6 months after RP which was undetectable in 23% and lower but still detectable in 25%. Men with an undetectable PSA nadir and TTN 1-2.9 months had similar risk of BCR to men with an undetectable PSA nadir and TTN 3-6 months (HR 0.90, p=0.63). However, those with detectable nadir had increased risk of BCR (TTN 3-6 months: HR 2.01, p=0.009; TTN 1-2.99 months: HR 3.83, p<0.001), and those with shorter TTN (1-2.99 months) had higher risk of BCR than men with longer TTN (3-6 months) (p<0.001). Conclusions Among men undergoing RP with an undetectable PSA nadir, there was no association between TTN and risk of BCR. However, a shorter TTN was associated with an increased risk of BCR in men with detectable nadir. Intriguingly, nearly half of the men with a detectable PSA in first 3 months after RP had a lower follow-up PSA between 3 and 6 months after RP. This is contrary to common thinking that the first PSA after surgery is the nadir. Funding none
Authors
Stephanie L. Skove
Lauren E. Howard Jean-Alfred Thomas William J. Aronson Martha K. Terris Matthew R. Cooperberg Christopher J. Kane Christopher L. Amling Daniel M. Moreira Stephen J. Freedland |
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MP47-10 |
MRI use alters prostate cancer management patterns: Treatment trends in the image-guided biopsy era. |
Prostate Cancer: Localized: Surgical Therapy IV | 17BOS |
Abstract: MP47-10 Sources of Funding: This research was made possible through the National Institutes of Health (NIH) Medical Research Scholars Program, a public-private partnership supported jointly by the NIH and generous contributions to the Foundation for the NIH from the Doris Duke Charitable Foundation, The American Association for Dental Research, the Colgate-Palmolive Company, Genentech and alumni of student research programs and other individual supporters via contributions to the Foundation for the National Institutes of Health._x000D_ For a complete list, please visit the Foundation website at:_x000D_ http://fnih.org/work/education-training-0/medical-research-scholars-program Introduction As the use of MRI to diagnose prostate cancer (PCa) becomes established, knowledge of its effect on treatment patterns is needed to better counsel patients. We describe the distribution of PCa treatment modalities in the MRI/TRUS-fusion biopsy (FBx) era at our center to investigate the role of FBx in modulating PCa management patterns._x000D_ Methods A retrospective review was performed on a prospectively maintained database of all men who underwent MRI/TRUS FBx at the National Institutes of Health from 2007 to present. Patient demographics, clinical data, imaging, pathology, treatment and outcomes were recorded. Patients were stratified by treatment into active surveillance (AS), radical prostatectomy (RP), radiation therapy (RT) +/- androgen deprivation therapy, or other therapy (including experimental treatments, focal laser ablation (FLA) or medical therapy). Groups were compared using t-test, Fischer exact test, and ANOVA (Graphpad prism software). Progression free survival was estimated using Kaplan-Meier curves (SPSS software). Results 1260 men were reviewed (mean age 62.4 years; mean PSA 9.8 ng/dL). The overall PCa detection rate was 57.2% (n = 721). 517 men had available treatment data and either entered AS (38.9%, n=201), received RP (40.2%, n=208), RT +/- ADT (10.6, n=55), medical treatment (7.9%, n=41), or FLA (2.32%, n=12). The age, PSA, Gleason Scores (GI), and imaging characteristics are described for each of these groups in Table 1. Younger patients were more likely to choose RP over AS or RT (p<0.0001). The median PSA for those who received RT was higher than those on AS or who received RP (p<0.0001). The mean estimated progression free survival for AS was 105 months. The mean estimated BCR free survival was 71 months and 96 months for RP and RT, respectively (p=0.02). FBx upgrade (FBx GI > standard biopsy (SBx) GI) was significantly more common in patients who received either RP or RT when compared to SBx upgrade (p<0.0001). Conclusions MRI/TRUS-FBx use in the diagnosis of PCa results in more accurate assessment of disease burden and modulates treatment modality chosen by patients. FBx upgrade occurred in an increased proportion of patients choosing either RP or RT over AS. Further study is required to delineate the use and benefits of FBx when counseling patients on management options. Funding This research was made possible through the National Institutes of Health (NIH) Medical Research Scholars Program, a public-private partnership supported jointly by the NIH and generous contributions to the Foundation for the NIH from the Doris Duke Charitable Foundation, The American Association for Dental Research, the Colgate-Palmolive Company, Genentech and alumni of student research programs and other individual supporters via contributions to the Foundation for the National Institutes of Health._x000D_ For a complete list, please visit the Foundation website at:_x000D_ http://fnih.org/work/education-training-0/medical-research-scholars-program
Authors
Joseph A. Baiocco
Abhinav Sidana Raju Chelluri Kendrick Yim Arvin K. George Vladimir Valera Michael Kongnyuy Akhil Muthigi Matthew J. Watson Mahir Maruf Maria J. Merino Baris Turkbey Peter L. Choyke Bradford J. Wood Peter A. Pinto |
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MP47-11 |
Extended pelvic lymph node dissection for intermediate-high risk prostate cancer: frequency and distribution of nodal metastases. |
Prostate Cancer: Localized: Surgical Therapy IV | 17BOS |
Abstract: MP47-11 Sources of Funding: None Introduction Standard extended pelvic lymph node dissection (ePLND) included the removal of external iliac, obturator and internal iliac chains. However, mapping studies demostrated that extending template up to the ureteric crossing would remove approximately 75% of all primary landing sites, and suggested to add presacral node dissection to ePLND, in order to correctly remove nodal metastases in 97% of patients. _x000D_ The aim of this study is to describe the frequency and distribution of metastases to pelvic nodes, in patients (Pts) with clinically localised, intermediate-high risk prostate cancer (PCa) according to the EAU guidelines, treated with radical prostatectomy and ePLND. _x000D_ Methods We retrospectively evaluated 554 consecutive Pts with clinically localized, intermediate-high risk PCa, treated with open radical prostatectomy and ePLND between 2009 and 2015 at a single institution by multiple experienced surgeons. The ePLND always consisted of the external iliac, obturator, internal iliac, presacral and common iliac nodal site up to the ureteric crossing. Specimens from each anatomic site were sent in separate packets._x000D_ Results The median number of removed nodes was 22 (range 9-61). Positive nodes (LN+) were found in 119 patients (21.4%). The mean and median number of positive nodes were 2.9 and 1 (range: 1-18), respectively. The median number of removed nodes was 6, 8, 5, 2, and 1 for external iliac, obturator, internal iliac, common iliac, and presacral site, respectively. _x000D_ Out of the 119 Pts, nodal metastases were found in 54 (45.4%), 50 (42%), 56 (47.1%), 12 (10.1%) and 15 (12.6%) in the external iliac, obturator, internal iliac, common iliac, and presacral sites, respectively. However, when analyzing the presence of positive nodes only in a single anatomic area, nodal metastases were present in 19 (16%), 18 (15.1%), 25 (21%), 0, and 3 (2%) in the external iliac, obturator, internal iliac, common iliac, and presacral site, respectively. _x000D_ A limited LND would have correctly staged 92 (77%) Pts and would have removed all LN+ in 37 (31%) Pts. An extended LND would have correctly staged 116 (97%) Pts but removed all LN+ in only 93 (78%) Pts. _x000D_ Conclusions Internal iliac and presacral nodes harbored metastases in more than 60% of cases, and positive nodes were present only in these areas in 23% of cases. _x000D_ On the contrary, metastases at common iliac nodes were always associated with concomitant involvement of external iliac, obturator and/or internal iliac nodes._x000D_ An extended LND would have correctly staged 116 (97%) Pts but removed all LN+ in only 93 (78%) Pts. _x000D_ Funding None
Authors
Marco Roscigno
Maria Nicolai Richard LJ Naspro Federico Pellucchi Laura B Cornaghi Daniela Chinaglia Antonino Saccà Luigi F Da Pozzo |
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MP47-12 |
Impact of Proximity to NCI- and NCCN-Designated Cancer Centers on Outcomes for Patients with Prostate Cancer Undergoing Radical Prostatectomy |
Prostate Cancer: Localized: Surgical Therapy IV | 17BOS |
Abstract: MP47-12 Sources of Funding: none Introduction National Cancer Institute (NCI) and National Comprehensive Cancer Network (NCCN)-designated cancer centers (CCs) offer patients state-of-the-art treatment. We sought to identify whether proximity to NCI/NCCN CCs was associated with survival outcomes for prostate cancer patients who undergo radical prostatectomy (RP). Methods A total of 12,478 total patients diagnosed with clinical stage T1 or T2 prostate cancer between 2004–2011 using linked Surveillance, Epidemiology, and End Results (SEER)-Medicare data were included. Multivariable regression analyses were used to quantify overall survival and use of secondary therapies for RP patients according to proximity to NCI/NCCN CCs. Cox proportional hazards models were used to quantify the association between survival outcomes and access to NCI/NCCN CCs Results Patients with proximity to ?2 NCI centers and those diagnosed in 2011 enjoyed a statistically significant overall survival advantage when compared to no access to an NCI center (Hazard Ratio (HR) 0.72; 95% confidence interval (CI) 0.57–0.92, p<0.01). Proximity to an NCCN CC, when compared with men who did not have access, was associated with improved overall survival (HR 0.76; 95% CI 0.61–0.95, p=0.015). There was no significant difference in use of secondary therapies according to NCI or NCCN access. Conclusions Patients who undergo RP with access to an NCI/NCCN CCs experienced improved overall survival with no significant difference in utilization of secondary therapies. Given the need for improved health quality measures in cancer care, these findings may support health policy implementation and regionalization of care to these centers._x000D_ _x000D_ _x000D_ Funding none
Authors
Cameron Ghaffary
Zhigang Duan Brian Chapin Tamer Dafashy Christopher Kosareck Karim Chamie Simon Kim Thomas Ahlering John Davis Sharon Giordano Stephen Williams |
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MP47-13 |
Comparison between mid-term outcomes of high-dose-rate brachytherapy with external-beam radiotherapy combined with long-term androgen deprivation therapy and radical prostatectomy in patients with high-risk prostate cancer. |
Prostate Cancer: Localized: Surgical Therapy IV | 17BOS |
Abstract: MP47-13 Sources of Funding: none Introduction High-dose-rate brachytherapy (HDR) with external-beam radiotherapy (EBRT) combined with long-term androgen deprivation therapy (ADT) and radical prostatectomy (RP) are common treatment options for high-risk prostate cancer (PC). We retrospectively evaluated the mid-term outcomes of both treatment groups and compared the rates of biochemical recurrence (BCR) and clinical progression-free survival (CPFS). Methods Between 2004 and 2014, 589 patients with high-risk PC underwent RP (n = 302) or HDR (n = 287). RP included extended lymph node dissection. HDR was performed with EBRT and/or neoadjuvant and long-term adjuvant ADT. The definition of BCR for each treatment was different, namely prostate specific antigen (PSA) level 0.2 ng/mL for RP and PSA nadir plus 2 (Phoenix definition) for HDR. Kaplan-Meier analyses and multivariable Cox regression analyses were performed to predict BCR and CPFS. Results The median follow-up times of RP and HDR were 49 and 52 months, respectively. Patients who underwent HDR were significantly older (P < 0.001), had higher mean initial PSA levels (P < 0.001), higher clinical T stage (P = 0.093), and higher mean biopsy Gleason score (P < 0.001). Five-year BCR free survival was significantly better after HDR than RP (80.1% vs. 62.9%; P < 0.001). However, there was no significant difference in the 5-year CPFS between HDR and RP groups (88.9% vs. 91.8%; P = 0.68). After RP, 64.6% (195/302) of patients required no additional treatment. In multivariate analysis, clinical T stage (P < 0.01) and biopsy Gleason score (P < 0.01), but not modality (P=0.749), were significant predictive factors of CP. Conclusions In this 10-year investigation at our institute, patients who underwent HDR had worse pre-treatment characteristics; however, had better BCR-free survival than patients who underwent RP. However, CPFS was not significantly different between patients who underwent either of the treatments. Funding none
Authors
Hajime Onuma
Takahiro Kimura Kojiro Tashiro Yasutoshi Yoshiyama Masahito Kido Toshihiro Yamamoto Hiroshi Sasaki Jun Miki Yusuke Koike Tatsuya Shimomura Hiroki Yamada Kenta Miki Manabu Aoki Shin Egawa |
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MP47-14 |
Assessment of oncological outcomes after radical prostatectomy according to preoperative and postoperative CAPRA risk scores: Results of a large, two-center experience. |
Prostate Cancer: Localized: Surgical Therapy IV | 17BOS |
Abstract: MP47-14 Sources of Funding: none Introduction Preoperative, clinical risk profiles can influence biochemical recurrence-free (BSF) and metastatic disease-free (MSF) survival-rates in prostate cancer (PCa) patients that were primarily treated with radical prostatectomy (RP) and harboured aggressive disease (i.e. upgrading/upstaging). However, it remains unclear if the same phenomenon can be observed, when contemporary risk stratification tools, namely preoperative CAPRA relative to postoperative CAPRA-S risk-scores at RP, are used. Methods We evaluated 17,251 PCa patients treated with radical prostatectomy and pelvic lymph node dissection at two European tertiary care referral centres between 1991 and 2016. All patients were stratified into low(LR)-, intermediate(IR)- and high-risk(HR) according to pre- and postoperative CAPRA risk-scores (≤2, 3-5 and ≥6 points, respectively). Multivariable cox regression models were fitted to assess, whether preoperative CAPRA risk-score is an independent predictor of BSF and MSF. The model was quantified using the receiver operating characteristic-derived area under the curve Results Overall, 38.3 (n=6584), 45.3 (n=7806) and 16.4% (n=2825) were stratified as preoperative LR, IR and HR CAPRA, respectively. Within LR patients, 14.8% (n=976) upgraded to IR or HR CAPRA-S at RP, respectively. Similarly, within IR patients, 11.7% were upgraded to HR CAPRA-S at RP (n=912). The 5-yr BSF of CAPRA-S HR patients at RP that had preoperative LR profiles was 95.8% (95% CI 95.1-96.5%), relative to 90.6% (95% CI 89.2-92.0%) of those with preoperative IR/HR profiles (p <0.001). Similarly, 5-yr MSF of HR patients at RP with preoperative LR vs IR/HR profiles was 99.7% (95% CI 99.6-99.9) vs. 98.8 (95% CI 98.3-99.4%) (p=0.001). In MVAs assessing BSF and MSF, preoperative CAPRA risk-score was an independent predictor and increased the accuracy compared to CAPRA-S risk-score at RP alone. (AUC 76.8 vs. 78.8% and 82.6 vs. 84.4%). Conclusions In postoperative CAPRA-S risk-scores, the additional consideration of clinically derived, preoperative CAPRA risk scores show a significant influence on BSF and MSF. Specifically, BSF and MSF is lower in postoperative CAPRA-S HR patients, who had low preoperative CAPRA risk-scores. These results warrant attention when using existing nomograms and genetic markers developed for the prediction of adverse pathologic outcomes. Finally, our results strongly suggest that postoperative CAPRA-S should be combined with preoperative CAPRA risk-score whenever applicable. Funding none
Authors
Sami-Ramzi Leyh-Bannurah
Paolo Dell’Oglio Emanuele Zaffuto Raisa Pompe Hans Heinzer Hartwig Huland Markus Graefen Derya Tilki Francesco Montorsi Alberto Briganti Lars Budäus |
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MP47-15 |
Regional variation in the diagnosis and treatment of prostate cancer in a Medicare population |
Prostate Cancer: Localized: Surgical Therapy IV | 17BOS |
Abstract: MP47-15 Sources of Funding: The Hitchcock Foundation Introduction The Dartmouth Atlas has reported wide variation among geographic regions in the diagnosis and treatment of prostate cancer. The relationship between these events, however, is not well understood, and merits attention because of uncertainty regarding appropriate levels of diagnosis and treatment in older patients. We sought to delineate regional associations between diagnosis and treatment of prostate cancer in a Medicare population._x000D_ _x000D_ Methods We performed a cross-sectional analysis of a 100% Medicare fee-for-service sample from 2012, including men aged 68 years or older. The unit of analysis was hospital referral region (HRR) (n=306). Rates of prostate cancer diagnosis and definitive treatment (surgery or radiation therapy) were calculated, adjusting for age and race. Correlation coefficients were calculated between these events. Regions were stratified by quartile for each practice, and those with concordant or discordant practices were identified. Results There was wide regional variation in both the diagnosis and treatment of prostate cancer. Rates of diagnosis ranged from 0.4-2.2% (1.0%),and rates of treatment ranged from 0.0-0.3% (0.11%). There was moderate correlation between events (r=0.36; p<0.0001), which persisted within age-stratified samples. However, there was a wide range of both concordant and discordant practices in regional prostate cancer care, e.g. low diagnosis + high treatment, high diagnosis + low treatment, etc. Conclusions There is wide variation in regional rates of prostate cancer diagnosis and treatment among older Americans. Diagnosis and treatment correlated overall, highlighting risk of a “cascade” of events post-diagnosis and underscoring concerns for over-detection in the elderly. Interestingly, some regions evidenced “counterintuitive” practice patterns, e.g. low rates of diagnosis and high rates of treatment, and vice versa. Further study is needed to understand the impact of variation on prostate cancer care. Funding The Hitchcock Foundation
Authors
Rachel A. Moses
Andrea M. Austin Donald Carmichael Elias S. Hyams |
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MP47-16 |
Current delays from biopsy to radical prostatectomy do not appear to affect pathologic outcomes in low, intermediate, or high-risk disease |
Prostate Cancer: Localized: Surgical Therapy IV | 17BOS |
Abstract: MP47-16 Sources of Funding: None Introduction There is a small volume of varied literature reporting on the impact of time between prostate cancer diagnosis on biopsy and definitive intervention with radical prostatectomy with regards to adverse pathological outcomes. There are considerable, and in some cases increasing, delays in treatment for patients with prostate cancer in Canada's publicly funded healthcare system. We sought to evaluate our institutional outcomes using a large multi-surgeon database. Methods We retrospectively reviewed 2,728 patients who underwent radical prostatectomy between 2005 and 2014. Patients were stratified according to biopsy Grade Groups and pre-operative PSA levels. Pathologic outcomes were evaluated for patients with <2 months between biopsy and surgery and then at monthly intervals of up to 6 months. Adverse pathological outcomes were defined as Gleason upgrading from biopsy, the presence of extracapsular extension (pT3a) or seminal vesicle invasion (pT3b), positive surgical margins and positive lymph node involvement. The x2 test was used for statistical analysis. Results In total 2310 patients met our inclusion criteria. Median time from biopsy to surgery was 83 days (range: 61-109). Grade groups 1, 2, 3, 4, 5 comprised of 906 (39.2%), 1,048 (45.4%), 231 (10%), 69 (3%) and 56 (2.4%), respectively. In total 31.8% of patients were upgraded by Grade Group on final surgical pathology. The overall positive surgical margin rates were 25% for organ confined (pT2) disease and 49.8% patients with pT3 disease. Lymph node involvement was identified in 1.5% of patients. There was no observed difference in adverse pathologic outcomes for patients in any risk category with delays of up to 6 months between biopsy and radical prostatectomy. Conclusions Surgical delays of up to 6 months following prostate biopsy were not associated with an increased risk of Gleason score upgrading, extracapsular extension, seminal vesicle invasion, positive surgical margins, or lymph node involvement. Funding None
Authors
PREMAL PATEL
Leanne Ross Kiril Trpkov Geoffrey Gotto |
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MP47-17 |
Caprini Score Predicts Venous Thromboembolic Events in Patients Undergoing Robotic Assisted Prostatectomy |
Prostate Cancer: Localized: Surgical Therapy IV | 17BOS |
Abstract: MP47-17 Sources of Funding: None Introduction Postoperative venous thromboembolism (VTE) is associated with significant morbidity and mortality. VTE rates after radical prostatectomy range from 0.3% to 3.9% in the recent literature. Caprini and colleagues developed a model to identify surgical patients at greater risk for VTE. The Caprini score has been validated in high risk, reconstructive, and plastic surgery patients. We assessed the validity of this score as a predictor of VTE in patients undergoing robotic assisted laparoscopic prostatectomy. Methods We retrospectively reviewed our IRB-approved database and identified patients who developed VTE after robotic prostatectomy between December 2003 and February 2016. Non-VTE cases immediately preceding and immediately following each index VTE case were used as controls, accounting for surgeon and lymphadenectomy. The Caprini score and the Charlson Comorbidity Index (CCI) were calculated and basic clinical parameters were extracted. Analyses comparing the VTE and no VTE groups were performed using Wilcoxon Ranked Sum and Chi-Square tests of Proportion. Multivariate logistic regression and ROC curves were used to predict VTE. SPSSv21 and a significance level of .05 were used for all analyses. Results 3719 patients underwent robotic prostatectomy during the study period; 52 VTE (1.4%) cases were identified and 97 controls were selected. No significant differences in PSA, Gleason score, or stage were observed between the two groups; significant differences were observed in overall OR times but not in time on the robot (Table 1). The Caprini score was significantly higher for the VTE group. Caprini score (OR = 1.93; p=.002) and OR time (OR = 1.01; p=.007) were independently significant predictors of VTE on multivariate analysis. ROC analyses identified a Caprini score of 6 and an OR time of 3.4 hours as the predictive cut-points for VTE (AUC = .64, p = .004; AUC = .63, p=.01 respectively). Conclusions Tools are needed to identify patients at higher risk of VTE and protocols are needed to lower risk. Our data support the use of the Caprini score as a risk assessment tool in the prediction of postoperative VTE in patients undergoing robotic prostatectomy. Funding None
Authors
Jason K Frankel MD
Matthew Belanger Joseph Tortora BA Tara McLaughlin PhD Ilene Staff PhD Joseph Wagner MD |
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MP47-18 |
Contributors to the occurrence of inguinal hernia after robot-assisted radical prostatectomy. |
Prostate Cancer: Localized: Surgical Therapy IV | 17BOS |
Abstract: MP47-18 Sources of Funding: None Introduction Previous studies reported that about 10% of patients who underwent retropubic radical prostatectomy developed inguinal hernia (IH) after surgery. However, few studies have evaluated IH following robot-assisted radical prostatectomy (RARP). We retrospectively investigated the incidence and risk factors for IH after RARP. Methods Subjects included patients who underwent RARP for prostate cancer in our institution from February 2012 to January 2015. Those with previous/concomitant IH history, concurrent IH-prophylaxis surgery, and follow-up < 1 year were excluded. Demographic and clinical profiles were collected from medical records. Every RARP video record was reviewed by a blinded urologist to verify the existence of a patent processus vaginalis (PPV). Univariate and multivariate Cox proportional hazards models were used to determine relationships between post-RARP IH and age, body mass index (BMI), previous lower abdominal surgery, total International Prostate Symptom Score (IPSS), IPSS voiding score, IPSS storage score, IPSS question 5 (weak stream) and 6 (straining) score, maximum urethral closing pressure (MUCP) and functional profile length (FPL) on urethral pressure profile, prostate weight, and PPV. Pre- and postoperative IPSS, MUCP, and FPL were included. Results Of 284 patients in the study, 41 (14.4%) developed IH at a median 8 months after RARP. On univariate analysis, BMI ≥ 23, IPSS question 5 score ≥ 3, and PPV were significantly correlated with post-RARP IH (hazard ratio [HR] 0.46, 95% confidence interval [CI] 0.24 - 0.89, p = 0.02; HR 2.20, 95% CI 1.12 - 4.3, p = 0.02; HR 3.59, 95% CI 2.39 - 5.40, p < 0.001, respectively). On multivariate analysis, IPSS question 5 score ≥ 3, and PPV were significantly correlated with post-RARP IH (HR 2.77, 95% CI 1.40 - 5.51, p = 0.003; HR 3.87, 95% CI 2.46 - 6.07, p < 0.001). PPV was detected on the right (51 patients, 17.9%), left (23, 8.0%), and both (15, 5.2%) sides._x000D_ Twenty-three of 51 patients (45.0%) with right-side PPV, 5 of 23 (26.0%) with left-side PPV, and 5 of 15 (33.3%) with bilateral PPV developed IH after RARP._x000D_ Thirty-seven of 41 post-RARP IH cases (95.1%) were indirect, but only 4 cases (4.8%) were combined IH. _x000D_ Conclusions Weak stream and PPV were predictive of IH after RARP. Prophylactic surgery should be performed during RARP in patients at high risk for post-RARP IH._x000D_ _x000D_ Funding None
Authors
Tsuyoshi Majima
Yasushi Yoshino Yoshihisa Matsukawa Yasuhito Funahashi Naoto Sassa Masashi Kato Tokunori Yamamoto Momokazu Gotoh |
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MP47-19 |
Open vs Robotic Prostatectomy Between 2009-2014: A Contemporary Analysis of NSQIP outcomes |
Prostate Cancer: Localized: Surgical Therapy IV | 17BOS |
Abstract: MP47-19 Sources of Funding: NONE Introduction Prostate cancer is the most common non-skin cancer in men, with an estimated 220,800 new cases of prostate cancer diagnosed in the year 2015. The majority of men with intermediate or higher risk cancer will pursue primary treatment with approximately two-thirds undergoing primary surgical treatment. The purpose of this study is to compare 30-day peri-operative outcomes of open prostatectomy (OP) vs robotic prostatectomy (RP) using American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) data between the years 2009-2014. Methods ACS NSQIP participant use data files (PUF) were obtained between the years 2009-2014. Data was sorted by surgical specialty (Urology), then by principal procedure CPT code (OP-55840, 55842, 55845. RP-55866). Cases were excluded if other procedure CPTs coded for cystectomy, urinary diversion using intestinal segments, or kidney/liver/bone resection. Categorical variables were analyzed using chi square test and continuous variables were analyzed using T-test. Results 28858 cases were identified. 361 cases were excluded leaving 28497 cases for analysis. (OP n-5710, RP n-22787) Preoperative variables that reached significance included: use of hypertensive medications (OP-48%; RP-51%), age (OP-63; RP-62) and BMI (OP-28.46; RP-28.86). Perioperative variables that reached significance include: Operating time (OP-168; RP-209 minutes), length of stay (OP-2.8; RP-1.7 days), superficial wound infection (OP-1.4%; RP-0.3%), deep surgical site infection (OP-0.28%; RP-0.026%), wound disruption (OP-0.525%; RP-0.16%), pulmonary embolism (OP-0.66%; RP-0.42%), urinary tract infection (OP-2.52%; RP-1.55%), need for blood transfusions (OP-13.6%; RP-1.5%), sepsis (RP-0.77%; RP-0.5%) and return to operating room (OP-1.5%; RP-1.04%) . Conclusions In a large, centrally-maintained, standardized database, RP was shown to have a longer operative time to complete, but has significantly decreased post-operative complications and reduced length of stay when compared with OP._x000D_ _x000D_ _x000D_ The ACS NSQIP and the hospitals participating in the ACS NSQIP are the source of the data used herein; they have not verified and are not responsible for the statistical validity of the data analysis or the conclusions derived by the authors. Funding NONE
Authors
Erwin A. Tieva
George J.S. Kallingal |
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MP47-20 |
Predicting extracapsular extention to graduate nerve sparing during radical prostatectomy: a novel predicting tool developed on nearly 6360 patients |
Prostate Cancer: Localized: Surgical Therapy IV | 17BOS |
Abstract: MP47-20 Sources of Funding: none Introduction Nerve sparing (NS) procedures have demonstrated improved potency preservation in radical prostatectomy (RP). A better understanding of prostate neuroanatomy and advancement in surgical techniques has moved from the “all-or-noneâ€� concept to a graduated NS to get the best compromise between cancer control and functional outcome. However, the preoperative planning of a NS approach is mostly based on subjective pre or intraoperative variables. Our aim is to provide a user-friendly statistical tool, with a decision rule, to standardize decision making in grading the NS approach. Methods A total of 11794 prostatic lobes, from a cohort of 6360 patients who underwent robot-assisted RP between January 2008 and January 2016 in a high-volume centre have been evaluated. _x000D_ The amount of extracapsular extension (ECE) maximum width of every prostatic lobe was calculated. _x000D_ Clinicopathological features were included in a statistical algorithm. Five multivariable models were estimated for: presence of ECE and ECE width greater than 1, 2, 3, and 4 mm. A fiveÂzone decision rule is proposed. Using a graphical interface surgeons can view pre-treatment characteristics and a curve showing the estimated probabilities for ECE amount and the areas identified by the decision rule. Results Out of 6360 patients, 1803 (28.4%) were affected by non organ confined disease. Of 11794 prostatic lobes, ECE was present in 1351 lobes (11.4%) and was extended beyond the prostatic capsule for more than 1, 2, 3, 4 mm in 498 (4.2%), 261 (2.2%), 148 (1.3%), 99 (0.8%) cases, respectively. The width of ECE was up to 15 mm (IR 1.00 - 2.00)._x000D_ The 5 logistic models showed good predictive performance? the area under the ROC curve was: 0.81 for ECE, and 0.84, 0.85, 0.88, and 0.90 for ECE width greater than 1, 2, 3, and 4 mm, respectively._x000D_ The proposed graphical tool provides valuable support to the surgeon in the choice of the side-specific surgical strategy and in the counseling with the patient. Conclusions Our predictive tool based on 7 variables can accurately predict the presence and the amount of ECE in prostate cancer. Furthermore, a graphical interface supports surgeons in patient counselling and in the choice of the side-specific surgical strategy (Fig.1)._x000D_ Funding none
Authors
Bernardo Rocco
Marco Sandri ELISA DE LORENZIS Angelica Anna Chiara Grasso Franco Palmisano Giancarlo Albo Rafael Coelho Alexander Mottrie Tadzia Harvey Darian Kameh Peter Wiklund Silvano Bosari Paola Zuccolotto Giampaolo Bianchi Vipul Patel |
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MP48-01 |
Expression and function of a novel chondroitinase in bladder cancer |
Bladder Cancer: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP48-01 Sources of Funding: Grant NCI/NIH 5R01CA72821; 5R01CA176691 Introduction Hyaluronidase (HAase) family of enzymes degrades hyaluronic acid (HA). In the human genome there are 6 HAase gens clustered on chromosomes 3p21.3 (HYAL-1, -2, -3) and 7q31.3 (HYAL-4, PH20, HYALP1). HYAL-4 is suspected to be a chondroitinase (Chase), i.e. a chondroitin sulfate-degrading enzyme. To date no study has linked HYAL-4 to any disease or biological activity. Methods Q-PCR was performed for measuring the mRNA levels of 6 HAase genes in BCa cell lines, 59 bladder tissues (normal (NBL) = 22; tumor (TBL) = 37) and 160 urine specimens (BCa = 52; normal = 18; history of BCa = 30; benign conditions = 59). A subset of urine specimens was used to measure chase activity using a novel ELISA. By stable transfection of normal urothelial and BCa cells, HYAL-4 function was analyzed in vitro (proliferation, motility, invasion, immunoblotting, Q-PCR assays) and in vivo (s.c. and orthotopic xenograft models). Results HYAL1, HYAL4 and HYALP1 mRNA levels were significantly (6-13-fold) elevated in TBL tissues when compared to NBL tissues (P<0.001). In multivariate analysis, in addition to HYAL-1, HYAL-4 was an independent prognosticator of metastasis and death due to BCa (P<0.001). HYAL1, HYAL4 and HYALP1 mRNA levels were also significantly elevated in BCa patients&[prime] urine (P< 0.0001). Chase activity was significantly elevated in BCa patients, as compared to BGU or HXBCa patients (P<0.0001; 100% sensitivity and 84% specificity to detect BCa). Overexpression of HYAL-4 in normal urothelial and BCa cells significantly increased invasion and chemotactic motility (> 3-fold) and enriched a cancer stem cell phenotype-spheroid formation, increased ALDH1 expression and activity, and a cytokeratin 4, 14, 17 molecular signature. HYAL-4 expression up-regulated CD44, MMP-9 and Akt signaling. In s.c. and orthotopic BCa models, HYAL-4 expression increased both tumor growth and metastasis of BCa cells and tumor growth in normal urothelial cells. Conclusions This is the first study that links HYAL4 to cancer biology and demonstrates it to be a molecular determinant of BCa. Funding Grant NCI/NIH 5R01CA72821; 5R01CA176691
Authors
Marie Hupe
Soum Lokeshwar Martin Hennig Daley Schimmelpfennig Mario Kramer Axel Merseburger Mark Soloway Vinata Lokeshwar |
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MP48-02 |
Melanoma-Associated Antigen-A and Programmed Death-Ligand 1 Expression in Urothelial Carcinoma |
Bladder Cancer: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP48-02 Sources of Funding: Kite Pharma Inc. Introduction The melanoma-associated antigen-A (MAGE-A) family is a highly attractive target for cancer immunotherapy because of its broad representation in cancer tissues but restricted expression in normal tissues. Recent studies have shown significant expression of MAGE A antigen in urothelial carcinoma (UC). We aim to assess MAGE A and Programmed Death-Ligand 1 (PD-L1) expression in a large UC cohort spanning multiple grades, stages, and including metastatic disease to inform immunotherapeutic approaches to the treatment of UC. Methods Analysis of MAGE A and PD-L1 expression on neoplastic cells using immunohistochemical staining of tissue microarrays from patients with bladder cancer (T1-4, Nx, M0-1) was done using the H-score system (a measure that simultaneously accounts for frequency and intensity of expression). We compared differential expression as well as H-scores between superficial vs. invasive, low (LG) vs. high grade (HG) as well as localized (LO) (T1-2) vs. locally advanced (LA) (T3-4) and metastatic vs non-metastatic. Comparisons between groups were done using Student’s T-test for continuous variables and Chi-Square for categorical variables. Results There were a total of 443 cases, of which 40% stained positively for MAGE A. Furthermore, 26% of the cohort was > 50% positive for MAGE expression. Expression was positive in 36% of the LG vs. 64% of HG patients (p=<0.001). Expression of MAGE was 48% in LO vs. 52% in LA (p=0.02). Sub-stratifying by individual stage, pT2 had the highest expression (28%) and pT4 had the lowest (2%). Mean H-score for MAGE A between HG vs. LG was 59 vs. 30, respectively (p=<0.001), Tis (15) vs. T1-4 (45) was also significant (p=<0.001). LO vs. LA was not significant (p=0.8), similarly metastatic vs. non-metastatic (p=0.59). Mean H-score for PD-L1 was significantly higher in LA vs LO (26% vs. 10% p=0.02), and in HG vs. LG (21% vs. 2% p=<0.001). No significant difference was noted between metastatic vs. non-metastatic (p=0.71). There was no significant correlation between MAGE and PD-L1 expression for HG (p=0.08) or LA (p=0.12). Conclusions This is the largest report of the expression of MAGE A antigen in urothelial carcinoma showing a significant expression in higher grade and stage urothelial carcinoma as well as significant proportion of patients with >50% positive expression. In conjunction with high PD-L1 expression in HG and LA these data support MAGE targeted immune interventions, including adoptive therapy with TCR engineered T cells for UC with or without combination with checkpoint inhibitor. Funding Kite Pharma Inc.
Authors
Izak Faiena
Nils Kroeger Sebastian Fussek Stephanie Astrow Rajul Jain Adrian Bot Alexandra Drakaki |
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MP48-03 |
Intratumoral Heterogeneity of ERBB2 Amplification and HER2 Expression in Micropapillary Urothelial Carcinoma |
Bladder Cancer: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP48-03 Sources of Funding: Ruth L. Kirschstein National Research Service Award T32CA082088 Introduction Micropapillary urothelial carcinoma (MPUC) is a rare but an aggressive variant of urothelial carcinoma. Histologically, most of these tumors are associated with variable amounts of &[Prime]not otherwise specified (NOS)&[Prime] urothelial carcinoma. MPUC has been previously shown to be associated with ERBB2 amplification and HER2 protein overexpression. However, the status and distribution of these findings within MP and NOS components of MPUC have not been addressed. Therefore, we evaluated the ERBB2/HER2 expression in MP and NOS components by FISH and IHC. Methods We identified 44 cases of MPUC that had tissue available for FISH and IHC at our institute, of which an NOS component sufficient for both FISH and IHC was identified in 37 cases. We followed the updated ASCO/CAP Guidelines for breast cancer and as such amplification was defined by a HER2/CEP17 ratio of ≥2.0 or > 6 copies of the gene and HER2 overexpression was considered with IHC scores of 2+ and 3+. Results In urothelial tumors with both MP and NOS components (n = 37), ERBB2 amplification in MP and NOS components was present in 25 and 16 cases respectively. ERBB2 amplification was significantly higher in the MP component compared to NOS component within the same tumor (67.57% vs. 43.24%, p = 0.049). HER2 overexpression in MP and NOS components was present in 25 and 13 cases respectively. HER2 overexpression was significantly higher in the MP component compared to NOS component within the same tumor (67.56% vs. 35.13%, p = 0.012). In addition, ERBB2 amplification strongly correlated with HER2 overexpression in both MP (rho = 0.65, p<0.001) and NOS (rho = 0.74, p<0.001) components. _x000D_ _x000D_ In this cohort (n = 44), tumor stage and lymph node status were significant predictors for overall survival (p = 0.01, <0.001 respectively). However, ERBB2 amplification and HER2 overexpression in MP component were not associated with patients&[prime] survival outcome (p=1.00, 0.75 respectively)._x000D_ Conclusions The majority of MPUC is associated with ERBB2 amplification and HER2 overexpression. In MPUC, ERBB2 amplification and HER2 overexpression were preferentially but not exclusively identified in MP component compared to NOS component. Our findings provide evidence for intratumoral heterogeneity of ERBB2 amplification and HER2 expression in MPUC. Funding Ruth L. Kirschstein National Research Service Award T32CA082088
Authors
Sumit Isharwal
Hongying Huang Gouri Nanjangud François Audenet Ying-Bei Chen Anuradha Gopalan Samson Fine Satish Tickoo Gopakumar Iyer Jonathan Rosenberg Dean Bajorin Harry Herr Machele Donat Guido Dalbagni Bernard Bochner David Solit Victor Reuter Hikmat Al-Ahmadie |
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MP48-04 |
Expression and function of lysophosphatidic acid receptor 1 in bladder cancer |
Bladder Cancer: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP48-04 Sources of Funding: none Introduction Lysophosphatidic acid (LPA) is one of several physiologically active lipid mediators that promote cell proliferation, cell migration, and cell invasion and are present in serum, ascites, and urine. LPA receptor is considered a potential therapeutic target for treatment of some malignant cancers. Here, we evaluated the expression of LPA receptors, and effect of its receptor expression on recurrence, progression and survival rate in bladder cancer. Furthermore, we examined the bladder cancer invasion mechanism that LPA were associated. Methods Expression of LPA receptors in bladder cancer specimens from bladder cancer patients (Ta or T1; 49 patients and T2-T4; 17 patients) was examined using real-time PCR and immunohistochemical staining. Matrigel invasion assay, proliferation assay, cell morphological observations were conducted and Rho kinase (ROCK) expression, myosin light chain (MLC) phosphorylation were measured to assess the effects of LPA on T24 cells, which derive from bladder cancer. Results LPA receptor 1 (LPA1) mRNA expression was significantly higher in muscle-invasive bladder cancer (MIBC) specimens than in non-muscle-invasive bladder cancer (NMIBC) specimens. Strong LPA1 expression was evident on cell membranes of MIBC specimens. Cancer-specific survival rate was predominantly lower in LPA1 positive group. T24 cell invasion was increased by LPA treatment, and invasiveness was decreased by LPA1-siRNA or LPA1 inhibitor. LPA treatment increased Rho kinase1 (ROCK1) expression and phosphorylation of MLC, and induced morphological changes including lamellipodia formation and cell rounding. Conclusions Our results indicated that LPA1 expression was increased in bladder cancer with highly invasive potential. Furthermore, LPA signaling via LPA1 activation promoted bladder cancer invasion. Analyzing LPA1 expression might be useful for planning of bladder cancer treatment, and LPA1 can be a new therapeutic target for highly invasive bladder cancer. Funding none
Authors
masao kataoka
tomoyuki koguchi Michihiro Yabe Yuuichi Satoh Nobuhiro Haga Kei Ishibashi Ken Aikawa Yoshiyuki Kojima |
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MP48-05 |
Identification of CCDC34 as an oncogene in bladder cancer and its function during bladder carcinogenesis |
Bladder Cancer: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP48-05 Sources of Funding: National Natural Science Foundation of China (No.81172419) Introduction The coiled coil is a superhelical structural protein motif involved in a diverse array of biological functions, and the abnormal expression of the coiled-coil domain containing proteins has a direct link with the phenotype of tumor cell migration, invasion and metastasis. Here, we first reported the oncogenic roles of Coiled-coil domain-containing protein 34 (CCDC34), and investigated its biological functions in bladder carcinogenesis. Methods Immunohistochemical staining and western blot were used to detect CCDC34 expression in bladder cancers specimens and cell lines. Lentivirus-mediated RNA interference and overexpression strategies were used to assess the effects of CCDC34 expression on various malignant phenotypes. The biological functions of CCDC34 knockdown on cells (T24 and 5637) were investigated by examining cell proliferation using a high content screening assay (HCS), BrdU incorporation assay and colony formation assay, cell migration by in vitro wound healing assay, cell invasion by Transwell invasion assay, as well as cell cycle distribution and apoptosis by flow cytometry. The expressions of Bcl-2, c-Raf, c-Jun, N-cadherin and E-cadherin as well as the phosphorylation of MEK, ERK1/2 and AKT were also measured using Western blot. We further investigated the effect of therapeutic siRNA targeting CCDC34 on T24 xenograft tumor growth in nude mice. Results CCDC34 was up-regulated in human bladder cancer tissues and cell lines. CCDC34 was distributed mainly in the cytoplasm, and its expression was closely correlated with histological type, tumor grade and pathologic stage (n=87, P<0.05). Besides, Western blot confirmed that CCDC34 was expressed at higher level in human bladder cancer tissues compared with their paraneoplastic normal bladder tissues (n=18, P=0.012). Knockdown of CCDC34 significantly suppressed bladder cancer cells proliferation, migration and invasion (P<0.01), and induced cell cycle arrest at G2/M phase and increased apoptosis in vitro (P<0.01). Moreover, CCDC34 knockdown decreased phosphorylation of MEK, ERK1/2 and AKT, and the expressions of c-Raf, c-Jun and Bcl-2; while CCDC34 overexpression in T24 cells promoted cell migration and invasion with increased EMT, and treatment with MAPK/ERK1/2 and PI3K/AKT inhibitors blocked the phosphorylation of ERK1/2 and AKT, respectively. In addition, knockdown of CCDC34 suppressed bladder cancer cell growth in nude mice. Conclusions Our findings revealed for the first time a potential oncogenic role for CCDC34 in bladder carcinoma pathogenesis, and activation of MAPK/ERK1/2 and PI3K/AKT signaling pathways was required for CCDC34 modulation of bladder cancer cell proliferation, migration and invasion. CCDC34 may serve as a biomarker or even a therapeutic target for bladder carcinoma. Funding National Natural Science Foundation of China (No.81172419)
Authors
Yanqing Gong
Xianghui Ning Xinyu Yang Jian Lin Xuesong Li Yinglu Guo |
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MP48-06 |
3D TISSUE ENGINEERING BLADDER MODEL FOR CANCER INVASION STUDY |
Bladder Cancer: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP48-06 Sources of Funding: Bladder cancer Canada/CUOG Introduction Our understanding of the biological processes involved in bladder cancer (BCa) is greatly limited by the models currently available. In fact, the combination of in vitro and in vivo models of BCa has failed to elucidate all the fundamental aspects of the disease. The eighth most commonly diagnosed cancer in Western societies, BCa has become a growing public health concern, and more realistic models are needed to reveal the mechanisms involved in tumor initiation and progression. Methods Bladder substitutes have been constructed by tissue engineering with healthy human fibroblasts and urothelial cells, using the self-assembly method. Meanwhile, spheroids have been produced from non-invasive (RT4) and invasive (T24) BCa cell lines expressing DsRed fluorescent protein. The invasive potential of these spheroids was characterized in a type-I collagen gel (2.5mg/mL). Then, the spheroids were implanted on the surface of bladder substitutes, after which their development was followed by fluorescence microscopy. Results Both of the cancer cell lines used were able to form compact spheroids and grow on bladder equivalents. The invasive behaviour of spheroids varied depending on the nature of the cells used. The non-invasive RT4 cell line was unable to cross the basal lamina whereas the invasive T24 cell line was able to do so. Conclusions The establishment of such a model for studying cancer biology in a physiological environment will help bridge the gap between overly simple cell culture models and more complex transgenic mice models. This new model offers a unique opportunity to study separately the players involved in the development of BCa and thus represents a powerful tool for the mechanistic analysis of this complex pathology. Funding Bladder cancer Canada/CUOG
Authors
Cassandra R Goulet
Geneviève Bernard Stéphane Chabaud Frédéric Pouliot Stéphane Bolduc |
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MP48-07 |
Establishment and analysis of bladder mucosa reconstruction rabbit model with autologous peritoneal free graft |
Bladder Cancer: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP48-07 Sources of Funding: Independent research program of Tsinghua University Introduction To investigate the practicability of bladder mucosa reconstruction with autologous peritoneal free graft for treatment of nonmuscle invasive bladder cancer in animal models. Methods 24 New Zealand white rabbits (weighing 2.0-3.0 kg) were randomly divided into 2 groups. After avulsing all of the bladder mucosa, the autologous peritoneal free grafts from posterior abdominal wall were used to replace rabbit bladder mucosa in the experimental group (n=12), and the incision was directly sutured after incising the bladder in control group (n=12). The survival condition of animals was observed after operation. At 15 days, 1, 3, and 6 months after operation, the blood routine, urine routine,renal function, and electrolyte were tested by collecting the blood and urine samples. At 1, 3, and 6 months after operation, maximum bladder capacity, bladder leak point pressure, and bladder compliance were measured through urodynamic studies. Then gross observation was performed for the bladder, and the specimens of the bladder were harvested for HE staining ,masson staining and scanning electron microscope (SEM). For immunohistochemistry, tissue sections were stained with antibodies to pancytokerotins AE1/AE3, UPK3 and calretini. Results All the animals survived during the experiment. The tests of urine routine,renal function and electrolyte suggested no significant difference between 2 groups (P>0.05). The maximum bladder capacity and compliance in experimental group were significantly lower than those in control group at 3 and 6 months after operation (P<0.05), but no significant difference in bladder leak point pressure at each time point between 2 groups (P > 0.05). In experimental group at 1 months after operation, no peritoneum mesothelial cells were observed?and histological examination showed the constitutions of the reconstructed bladder mucosa were similar to the normal appearance?Neovascularization was evident beneath the mucosa and some chronic inflammatory cells and fibroblasts were present in the subepithelial layer.At 3 and 6 months after operation, the bladder mucosa was uniformly lined with 3-5 lays transitional epithelium?Immunohistological analysis of the epithelial cells demonstrated negative expression of calretini and positive expression of both CK AE1/AE3 and UPK3. Conclusions The autologous free peritoneal grafts could be successfully used as the bladder mucosa reconstruction. Funding Independent research program of Tsinghua University
Authors
Wenjia Wang
Shengwen Li |
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MP48-08 |
Heat shock protein 70 mediated silibinin-activated mitochondrial apoptotic signaling pathway in bladder cancer |
Bladder Cancer: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP48-08 Sources of Funding: Grants from the National Natural Science Foundation of China (NSFC 81101936 to JZ;NSFC 81172436 to YS; NSFC 81302227 to YC) Introduction We previously identified intravesical silibinin, a natural flavonoid, as a novel and effective chemopreventivetherapy against bladder cancer (BCa), which were accompanied with its proapoptotic effects. However, the exact mechanisms are not thoroughly understood.Heat shock proteins (Hsps) have been identified as key determinants of cancer cell survival, which can modulate apoptosis by directly interacting with components of the apoptotic machinery. Manipulation of Hsps by chemical agents represents a viable strategy against cancer. Therefore, the purpose of this study was to examine the role of Hsps in regulating silibinin-induced apoptosis in BCa. Methods Human BCa cell line RT4 and T24 served as the model system in vitro and in vivo. The expression of Hsps, heat shock factor-1(HSF1) and_x000D_ apoptosis related molecules after silibinin treatment were examined by western blot. Co-immunoprecipitation was used to determine the interaction between apoptotic protease activating factor-1 (Apaf-1) and Hsp70 or pro-caspase 9. Both nude mice xenografts and orthotopic rat bladder cancer tissues were analyzed for apoptosis molecular alterations after oral or intravesical silibinin treatment in vivo. Results Exposure of BCa cells to silibinin resulted in significant downregulation of Hsp70 both in mRNA and protein levels. No change of Hsp90,Hsp60, Hsp40 and Hsp27 were observed. Either heat shock pretreatment-induced expression of endogenous Hsp70 or overexpression of exogenous Hsp70 attenuated silibinin-induced cell apoptosis, while knocking down Hsp70 sensitized cells to apoptosis by silibinin. Silibinin-induced disruption of mitochondrial membrane potential and release of cytochrome c from mitochondria were inhibited by overexpression of Hsp70. Furthermore, silibinin inhibited the formation of complexes containing Apaf-1 and Hsp70 and increased the interaction between Apaf-1 and pro caspase-9. Additionally, the downregulation of Hsp70 by silibinin was correlated with a diminished presence of HSF1 in the nucleus, and the inhibition of transcriptional activity of HSF1. More importantly, silibinin competed with_x000D_ ATP for binding to the ATPase domain of Hsp70 as determined by silibinin-conjugated Sepharose pull-down assay. Consistently, either oral silibinin or intravesical instillation of silibinin suppressed the growth of xenografts in nude mice or orthotopic bladder cancer in rats respectively, which were accompanied with_x000D_ downregulation of Hsp70 and HSF1. Conclusions These findings firstly identify the role of Hsp70 in mediating mitochondrial apoptotic pathway induced by silibinin, and suggest selective targeting HSF1/Hsp70 signaling could produce synthetic lethality in the management of BCa. Funding Grants from the National Natural Science Foundation of China (NSFC 81101936 to JZ;NSFC 81172436 to YS; NSFC 81302227 to YC)
Authors
Jin Zeng
Yule Chen Kaijie Wu Yi Sun Lei Li Dalin He |
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MP48-09 |
Integrin signaling modulation demonstrates potential therapeutic strategy in bladder cancer using three-dimensional organoid culture |
Bladder Cancer: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP48-09 Sources of Funding: The Frederick J. and Theresa Dow Wallace Fund of the New York Community Trust, the Ferdinand C. Valentine Fellowship Award from the New York Academy of Medicine, and the National Institute of Health. Introduction Integrin signaling plays an important role in cellular proliferation and migration via interactions with extracellular matrix proteins. Prior studies indicate that integrin signaling facilitates tumor invasion and metastasis, and there are several ongoing clinical trials using agents that modulate this pathway. We recently identified clonal enrichment in mutations in the integrin cell surface interactions pathways in advanced urothelial carcinoma. An ideal strategy for investigating integrin signaling is via 3D organoid culture, maintaining intercellular interactions that replicate the epithelial microenvironment. We hypothesize that pharmacologic integrin signaling modulation will impair organoid growth in bladder cancer cells and demonstrate a therapeutic utility for this approach. Methods RT4 human bladder cancer cell line was used as well as a second cell line established from a patient-derived bladder cancer sample (PM748). Cells were grown in 3D organoid culture as previously described. For in vitro integrin modulation, defactinib, an orally-bioavailable selective inhibitor of focal adhesion kinase (FAK, a convergent and conserved enzyme activated by integrin ligand binding), was used. SDS-PAGE and immunoblotting were performed to show in vitro FAK inhibition. Single cell suspensions and organoids were plated in the presence of various concentrations of defactinib to determine the impact on organoid formation and regression. Results Defactinib caused a dose-dependent decrease in autophosphorylation of FAK for both cell lines, demonstrating effective FAK inhibition. 3D culture of single cells with defactinib produced a dose-dependent decrease in organoid size after 96 hours (mean size for DMSO only, 100nM, 1uM, and 10uM were 128um, 75um, 48um, and 26um, respectively; p<0.0001 versus DMSO for all dilutions). Established organoids showed a dose-dependent regression in size after 72 hours of defactinib exposure (mean size for DMSO, 100nM, 1uM, and 10uM were 225um, 96um, 70um, and 34um, respectively; p<0.0001 versus DMSO). Experiments utilizing Crispr-Cas9-mediated FAK knock-out as well as in vivo studies with FAK inhibitors in xenograft models are currently underway. Conclusions Integrin modulation via FAK inhibition with defactinib causes both inhibition of organoid formation as well as regression of formed organoids, and the effects are seen at concentrations well below the cytotoxic range for the drug. This study suggests a utility for these agents in bladder cancer treatment. Funding The Frederick J. and Theresa Dow Wallace Fund of the New York Community Trust, the Ferdinand C. Valentine Fellowship Award from the New York Academy of Medicine, and the National Institute of Health.
Authors
LaMont Barlow
Rebecca Meyer Ethan Shelkey David Golombos Tomasz Owczarek Lijie Rong Corinne Abate-Shen Michael Shen Bishoy Faltas Mark Rubin |
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MP48-10 |
Validation of Nrf2 Pathway Dysregulation in Urothelial Carcinoma |
Bladder Cancer: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP48-10 Sources of Funding: Not applicable. Introduction There is a well-established relationship between oxidative stress and the development and progression of bladder cancer. Prior clinical trials have shown a decrease in bladder cancer recurrence in patients on a high dose anti-oxidant vitamin regimen. In a previous integrative analysis of TCGA methylation data, we found genes in the Nrf2 pathway, an important regulatory pathway in response to oxidative stress, to be hyper-methylated and thus down regulated in bladder cancer. We sought to further characterize the activity of Nrf2 pathway gene expression in normal urothelium, and urothelium with non-muscle invasive and muscle invasive cancer. Methods We identified a publically available gene expression microarray dataset using the gene expression omnibus (GSE 3167) that included 10 patients with normal urothelium, 15 patients with stage Ta urothelial carcinoma, 8 patients with carcinoma in situ, and 13 patients with muscle invasive disease. We used the Nrf2 pathway signature discovered in our initial analysis. We evaluated the clustering of samples according to the Nrf2 pathway in an unsupervised pathway using the heatmap.2 function in R. Results Our clustering analysis on an independent dataset showed that the Nrf2 signature separates urothelial carcinoma from normal samples. The genes driving this clustering included KEAP1, GPX3, PGO, and TXN, all of which had higher levels of expression in normal tissue compared with tumor tissue, consistent with downregulation of Nrf2 dependent genes in tumor tissue. There did appear to be some independent clustering of low grade and muscle invasive disease, but this was less pronounced than the clustering of normal urothelium versus urothelial carcinoma. Conclusions This study corroborates prior findings and shows that genes in the Nrf2 pathway are inactivated in urothelial carcinoma. The expression of Nrf2 genes was decreased in patients with urothelial carcinoma. The lack of clear clustering among different stages of disease suggests that decreased expression of genes in the Nrf2 pathway is an early event in the pathogenesis of urothelial carcinoma. Our data demonstrate a biochemical description of the pathway by which antioxidant mechanisms may affect progression of urothelial carcinoma. Funding Not applicable.
Authors
Natalia Leva
Thomas Sanford Maxwell Meng Sima Porten |
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MP48-11 |
The Effect of Morphine and Its Inhibitors on RT112 Bladder Cancer Cell Growth |
Bladder Cancer: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP48-11 Sources of Funding: None Introduction Clinical studies suggest opioid use affects rates of metastasis in breast and prostate cancer. Results are variable and conflicting. _x000D_ _x000D_ This investigation tested the effects of morphine on bladder cancer cell growth in vitro and examined whether those effects can be reversed with receptor blockers. _x000D_ _x000D_ Methods Cell lines_x000D_ Adherent epithelial cell lines were used:_x000D_ RT-112 - Human urinary bladder transitional carcinoma cell lines, histological grade G2 (moderately differentiated). _x000D_ _x000D_ PNT2 - Normal (virally transformed) Human prostate epithelial cell line. _x000D_ _x000D_ These cells were grown using routine cell culture techniques supplemented with 10% foetal calf serum and antibiotics._x000D_ _x000D_ Proliferation assay_x000D_ The assay recorded residual viable biomass (RVB) 72 hours into exposure with the agent being studied_x000D_ Results Doubling dilution of morphine produced a bell-shaped curve, with high (non-clinical)concentrations inhibiting growth, followed by stimulation between 100 and 1 microgram per ml (clinically relevant concentrations shown in Figure 1 green circle), reverting to control levels thereafter._x000D_ _x000D_ The near-normal PNT-2 cell line showed minimal responsiveness to morphine_x000D_ _x000D_ Incubation with naloxone alone has little effect on residual biomass compared to controls_x000D_ _x000D_ Conversely, pre-incubating with a fixed concentration of Naloxone, then titrating morphine across the plate showed stimulation to decrease as the relative proportion of blocker rises (Figure 2)_x000D_ _x000D_ Conclusions Morphine in clinically relevant concentrations stimulated growth in the RT-112 transitional carcinoma cell line, as assessed by the MTT assay._x000D_ _x000D_ This effect was minimal under the same conditions using the virally transformed normal prostate cell line (PNT2)._x000D_ _x000D_ Treating cells with the antagonists Naloxone or Naltrexone inhibited the action of morphine. _x000D_ _x000D_ The tentative implication is that using opioids in cancer patients despite their important role in pain relief may also tend to promote tumour growth. _x000D_ Funding None
Authors
Brian Birch
Bashir Lwaleed Alan Cooper Phil Harper Iliana Giatsidou |
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MP48-12 |
Extraordinary elevation of SERPINB2 gene after anti-cancer drug treatment in bladder cancer |
Bladder Cancer: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP48-12 Sources of Funding: none Introduction The second line chemotherapy against advanced bladder cancer has not been established. We hypothesize that highly activated genes after anti-cancer drug treatment is related to the key for predicting the anti-tumor effect . For this purpose, a comprehensive analysis using cDNA microarray was performed to identify the common target genes after treatment of chemotherapeutic agent. Methods Bladder cancer cell lines of T24, RT4, UMUC3, and prostate cancer cell line of PC3 were used as control. Clinical samples from 26 cases with muscle invasive bladder cancer who underwent radical cystectomy were also used. Anti-cancer drugs used were docetaxel (DTX), gemcitabine (GEM) and Cis-platinum (CDDP). The cell viability was evaluated by an MTT assay. Gene expression profiles in T24 cells were identified using cDNA microarray, which showed significant difference before and after treamnent of 1.1mM docetaxel (DTX). Individual gene expression was validated by quantitative RT-PCR. Functional study of the candidate genes was performed using specific siRNA transfection. Results We identified SERPINB2 gene with the GO term of “negative regulation of apoptosis� as extraordinarily activated gene after DTX treatment (Z score=7.509) . In T24 and UMUC3 cells, SERPINB2 expression was significantly increased in a stepwise manner of DTX concentration, while no significant elevation of SERPINB2 was found in RT4 cells (Table). Likewise, CDDP extraordinarily enhanced the SERPINB2 expression in T24 and UMUC3 , but not in RT4. On other hand, GEM significantly accelerated the SERPINB2 expression in T24, while it did not in UMUC3 and RT4. UMUC3 cells, in which high SERPINB2 expression was found before treatment, showed significant reduction of cell viability after transfection of SERPINB2 siRNA, suggesting that SERPINB2 might function as oncogene. In addition, in PC3 where SERPINB2 was highly expressed before treatment, SERPINB2 knockdown by siRNA transfection showed significant reduction of cancer cell survival. In clinical samples, there was no significant difference in SERPINB2 expression between normal and cancer tissues. Interestingly, SERPINB2 expression was significantly higher in 4 cases who underwent both neoadjuvant chemotherapy (NAC) and cystectomy than in 22 cases who did cystectomy alone. Conclusions In certain bladder cancers, SERPINB2 might function as oncogene and is highly up-regulated. Activation of SERPINB2, which is frequently found after anti-cancer agent treatment, might provide the essential information regarding the chemotherapeutic strategy in bladder cancer. Funding none
Authors
Miho Hiraki
Naoko Arichi Hirofumi Kishi Haruki Anjiki Hiroaki Yasumoto Hiroaki Shiina |
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MP48-13 |
Loss of forkhead box protein O1 (FOXO1) in bladder cancer induces tumor progression as well as chemoresistance |
Bladder Cancer: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP48-13 Sources of Funding: None Introduction Recent preclinical evidence has indicated the involvement of androgen receptor (AR) signals in bladder cancer outgrowth as well as chemosensitivity. Meanwhile, we have demonstrated that AR signals modulate the expression and activity of FOXO1, a transcriptional factor known to induce apoptosis through the PI3K-Akt pathway, in bladder cancer cells. In this study, we investigated the role of FOXO1 in bladder cancer progression as well as resistance to cisplatin treatment. Methods We assessed the effects of FOXO1 inhibition via short hairpin RNA (shRNA) virus infection or inhibitor (AS1842856) treatment on bladder cancer cell proliferation (by MTT assay in the presence or absence of cisplatin), migration (by scratch wound healing assay), and invasion (by transwell invasion assay), apoptosis (by TUNEL assay), and the expression of their related molecules (by RT-PCR). We also immunohistochemically stained for phospho-FOXO1 (p-FOXO1), an inactive form of FOXO1, in tissue microarrays consisting of muscle-invasive bladder cancer specimens from patients who received at least 3 cycles of cisplatin + gemcitabine neoadjuvant chemotherapy prior to radical cystectomy. Results FOXO1 silencing via its shRNA in AR-positive bladder cancer lines, UMUC3 and 647V-AR, resulted in significant increases in cell viability, migration, and invasion, and the expression of MMP-2/VEGF, as well as significant decreases in apoptosis and the expression of cyclin-dependent kinase inhibitors p21/p27. In addition, FOXO1 knockdown cells were significantly more resistant to cisplatin treatment at its pharmacological concentrations, compared with control cells. In these control FOXO1-positive lines, AS1842856 treatment also significantly reduced cisplatin sensitivity. Immunohistochemistry in transurethral resection specimens further showed p-FOXO1 positivity in 25 (58%) of 43 cases, including 7 (41%) of 17 responders to chemotherapy versus 18 (69%) of 26 non-responders (P=0.068). Conclusions FOXO1, as a tumor suppressor, appears to play an important role in bladder cancer progression and correlates with cisplatin sensitivity. Accordingly, FOXO1 stimulation, with or without AR inactivation, has the potential of being a therapeutic approach for bladder cancer and may also be useful for overcoming chemoresistance. Funding None
Authors
Hiroki Ide
Satoshi Inoue Taichi Mizushima Eiji Kashiwagi Mototsugu Oya Alexander Baras Hiroshi Miyamoto |
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MP48-14 |
Long noncoding RNA lncRNA-BNCA promotes the progression of bladder cancer via regulating translation of P53 |
Bladder Cancer: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP48-14 Sources of Funding: None Introduction Long non-coding RNAs (lncRNAs) are important regulators in pathological processes, yet their potential roles in the progression of bladder cancer (BCa) are poorly understood. Understanding the molecule mechanisms is critical to effective treatment of BCa._x000D_ Methods In this study, we identified lncRNA-BNCA by Microarray results and evaluated the level of lncRNA-BNCA in BCa tissues and cell lines by ISH and qPCR. Both in vitro and in vivo models were used to demonstrate the role of lncRNA-BNCA on the progression of BCa. Moreover, the potential mechanism evaluated levels of of lncRNA-BNCA was explored by RNA pull down and RIP experiments. Results Here, we found that a novel lncRNA, lncRNA-BNCA, was upregulated in BCa and cell lines. Knockdown of lncRNA-BNCA impaired cell proliferation and invasion and induced cell apoptosis in vitro, whereas overexpression of lncRNA-BNCA had the opposite effect. Consistently, the growth and invasion effect of lncRNA-BNCA was also demonstrated in vivo. We further demonstrate a distinct mode of lncRNA-mediated gene regulation, wherein lncRNA-BNCA binds to the heterogeneous nuclear ribonucleoprotein (hnRNP) Q protein to restrain p53 protein induction via translation initiation regulation. These effects of lncRNA-BNCA were shown to be clinically relevant, as lncRNA-BNCA was found to be significantly correlated with malignant progression and poor survival. Conclusions Hence, lncRNA-BNCA provides an epigenetic mechanism that restrain the translation efficiency of p53 and may represent a new therapeutic target and prognostic marker. Funding None
Authors
Changhao Chen
Jian Huang Feng Sun Tianxin Lin |
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MP48-15 |
Circular RNA ITCH inhibits bladder cancer progression by sponging miR-17 and regulating p21 expression |
Bladder Cancer: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP48-15 Sources of Funding: none Introduction Recently?Circular RNAs (CircRNAs) have emerged as critical regulators in tumorigenesis and progression. However, the role and molecular mechanism of CircRNA ITCH in bladder cancer is still unclear. Methods Real-time PCR analysis was performed to measure the expression levels of circ-ITCH in bladder cancer tissues and cell lines. The biological function of circ-ITCH on bladder cancer cells were determined both in vitro and in vivo. Besides, bioinformatic databases including Starbase and CircInteractome were used to investigate the regulating relationship between circ-ITCH and miR-17 in bladder cancer cells. Western blotting was performed to detect the expression of p21 as a target of miR-17. Finally, the mechanism of competing endogenous RNA (ceRNA) between circ-ITCH and miR-17 was determined using bioinformatic analysis and luciferase assays. Results Circ-ITCH was significantly down-regulated in bladder cancer tissues and cell lines. Overexpression of circ-ITCH exerted tumor-suppressive effects by inhibiting cell proliferation, migration and invasion in vitro and tumor growth in vivo. Furthermore, an inverse relationship between circ-ITCH and miR-17 was found. Circ-ITCH could partly abolish the effect that miR-17 targets p21 and lowers its expression consequently. Conclusions circ-ITCH is down-regulated significantly in bladder cancer, and the newly identified circ-ITCH/miR-17/p21 axis could be a potential biomarkers or therapeutic targets for bladder cancer patients. Funding none
Authors
Pengchao Li
Jun Tao Xiao Yang Xiaheng Deng Qiang Lu |
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MP48-16 |
Targeting ERBB2 mutations in urothelial carcinoma |
Bladder Cancer: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP48-16 Sources of Funding: None Introduction ERBB2 encodes Human Epidermal growth factor Receptor 2 (HER2), a member of the EGFR family of receptor tyrosine kinases that signal through the pro-oncogenic MAP- and PI3K-kinase pathways. ERBB2 is altered by amplification and/or overexpression in various cancers, including urothelial carcinoma (UC). These alterations could confer sensitivity to ERBB2 kinase inhibitors in selected patients with UC._x000D_ Methods Patients diagnosed with UC were enrolled onto an institutional review board approved prospective sequencing protocol. Tumor and matched germline DNA were analyzed using the MSK-IMPACT assay that detects alterations in 410 oncogenes and tumor suppressor genes, including ERBB2._x000D_ Results Overall, 449 samples from 429 patients were sequenced from 2013 to August 2016. Genetic alterations in ERBB2 were found in 78 samples (17%). At the time of sample collection, 24 patients (31%) had non-muscle invasive bladder cancer (NMIBC), 30 patients (38%) had muscle-invasive bladder cancer (MIBC), 18 (23%) had metastatic disease and 7 (8%) had upper tract urothelial carcinoma (UTUC). Sixteen samples (21%) came from metastatic specimens. Of the observed 78 ERBB2 alterations, 20 samples had amplifications (26%) and 58 samples had mutations (74%). Seven samples (9%) had both. We identified 71 missense, 2 inframe and 1 fusion alteration, corresponding to a somatic mutation rate of 13.1%. Thirty-seven mutations (50%) were functionally characterized hot spots that are potentially actionable. Of note, the hot spot mutation S310F/Y was found in 29 samples (37%). Its mutation allele frequency varied significantly. There was a trend towards a higher mutant allele frequency of S310F/Y in higher stage disease without reaching statistical significance (Table). In our cohort, 3 patients were enrolled in clinical trials with ERBB2 kinase inhibitors based upon the presence of an ERBB2 alteration._x000D_ Conclusions ERBB2 is a frequent mutation at different stages of UC. In higher stage disease, clonal selection of the S310F/Y hot-spot mutation may occur and requires further study._x000D_ Funding None
Authors
François AUDENET
Sumit ISHARWAL Maria ARCILA Samuel FUNT Jonathan ROSENBERG Dean BAJORIN Eugene CHA Timothy DONAHUE Machele DONAT Harry HERR Guido DALBAGNI Bernard BOCHNER Michael BERGER Hikmat AL-AHMADIE David SOLIT Gopa IYER |
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MP48-17 |
Phenotypic-genotypic correlation of TP53 and RB1 in urothelial carcinoma |
Bladder Cancer: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP48-17 Sources of Funding: None Introduction In urothelial carcinoma, genetic alterations in multiple cell-cycle regulations genes are frequent, including key tumor suppressor genes like TP53 and RB1. Prior studies have shown that alterations of TP53 and RB1, analyzed through protein p53 and RB expression respectively have prognostic significance. The goal of this study was to evaluate the correlation between TP53 and RB1 genotypes and phenotypes._x000D_ Methods Tumor and matched germline DNA were analyzed using the MSK-IMPACT assay that detects alterations in 410 oncogenes and tumor suppressor genes, including TP53 and RB1. A correlation between TP53 and RB1 mutation status and protein expression was performed. Tissue microarrays (TMA) of urothelial carcinoma of the bladder were assessed for p53 and RB expression as a validation cohort. _x000D_ Results Overall, 171 patients with a median age of 69.4 years (IQR: 61.7-71.5) were included. Clinical stage was non muscle invasive bladder cancer in 14 (8.2%) patients, muscle invasive bladder cancer in 148 (86.5%) and metastatic in 9 (5.3%). Genetic alterations of TP53 and RB1 were found in 93 (53.8%) and 66 (38.2%) patients respectively. Protein expression was assessed from full section in 65 (38%) patients and from TMA in 106 (62%). Strong and diffuse p53 expression strongly correlated with missense TP53 mutations (n=43, 78.2%, p<0.0001). In addition, complete lack of p53 expression was seen in tumors harboring truncating TP53 mutations (n= 20, 58.8%, p<0.0001). Similarly, loss of RB expression strongly correlated with the presence of RB1 mutations (n=43, 86%, p<0.0001). Tumors with wildtype TP53 or RB exhibited variable p53 and RB expression. In cases with both invasive and non-invasive components (n=24), similar patterns of p53 and RB expression were observed._x000D_ Conclusions The most common pattern of p53 expression that correlated with the presence of TP53 mutations are strong and diffuse nuclear expression (missense mutation) and absence of nuclear expression (truncating mutation). RB1 mutations generally result in loss of RB expression. The concordant pattern of p53 and RB expression between invasive and non-invasive component within the same tumor indicate that alterations in these genes occur early in the development of urothelial carcinoma._x000D_ Funding None
Authors
François AUDENET
Sumit ISHARWAL Xiaoyong ZHENG Emmet JORDAN Gopa IYER Byron LEE Eugene CHA Timothy DONAHUE Machele DONAT Harry HERR Guido DALBAGNI Bernard BOCHNER Michael BERGER David SOLIT Hikmat AL-AHMADIE |
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MP48-18 |
Germline DNA repair single nucleotide polymorphisms in urothelial cancer patients. |
Bladder Cancer: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP48-18 Sources of Funding: Weill Cornell Medical College Introduction Single nucleotide polymorphisms (SNPs) in genes involved in carcinogenesis and cancer growth have been investigated for their prognostic value in several cancers, including urothelial (UC). Repair of DNA damage is a key process involved in development of chemotherapy-resistance. The role of germline DNA repair gene (DRG) SNPs in patients with UC has not been explored. We hypothesized that germline SNPs of DRGs could be enriched and potentially associated with outcomes in UC patients exposed to platinum agents. Methods We examined a cohort of 53 UC patients (median age 67, 42 males) enrolled in our IRB-approved Precision Medicine program. Patients had histologically confirmed UC (43 bladder, 10 upper tract UC) and received treatment with platinum-based chemotherapy. We isolated germline DNA from blood lymphocytes or buccal swabs, and used whole exome sequencing (WES) to examine germline SNPs. As a reference for SNP frequencies we used the Exome Aggregation Consortium (ExAC) database, the largest randomly selected germline WES database in general population, also including cancer patients. Results Twelve different DRG SNPs were identified in germline DNA samples from 53 patients, affecting genes involved in non-homologous end-joining (RECQL4, n=18, 54.50%; POLQ, n=2, 6%), nucleotide excision repair (ERCC6, n=2, 6%; XPA, n=1, 3%; CCNH, n=1, 3%; POLK, n=1, 3%), homologous recombination (RNF168, n=1, 3%; RAD17, n=1, 3%; POLE, n=1, 3%), Fanconi anemia pathway (POLN, n=1, 3%), mismatch repair (EXO1, n=1, 3%) and mitochondrial DNA repair (POLG, n=2, 6%). The frequency of rs11342077 of the DNA helicase RECQL4 was significantly higher in our cohort (18/53, 34%) compared to its frequency in the ExAC database (p<0.01). There was no significant difference in overall survival (OS) between patients with and without DRG SNPs (log-rank p=0.46). There was no significant association between the most commonly identified SNP rs11342077 and OS among UC patients with DRG SNPs (log-rank p=0.39). Overall, the presence of DRG SNPs in our cohort (33/53, 62.3%) occurred at a significantly higher frequency compared to the ExAC database (0.56%, Chi-square p<0.01). Conclusions Germline DRG SNPs are more common in UC compared to other cancers, and could play a role as potential biomarkers of response to UC treatment with DNA damaging agents. In addition, if confirmed in larger scale studies, heritable DRG SNPs could potentially be used for identifying patients who will achieve downstaging or complete pathologic response in the neoadjuvant setting. Funding Weill Cornell Medical College
Authors
Panagiotis Vlachostergios
Bishoy Faltas Tuo Zhang Linda Lam Olivier Elemento Mark Rubin |
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MP48-19 |
Molecular subtype classification of N-methyl-N-nitrosourea-induced urothelial cancers and ex-vivo cultured spheroids in rats. |
Bladder Cancer: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP48-19 Sources of Funding: Johns Hopkins Greenberg Bladder Cancer Institute Introduction Introduction and Objectives: Human urothelial cancers can be classified into luminal or basal subtypes based on RNA and protein expression that have distinct clinical behaviors and responsiveness to chemotherapy. Therefore, it is essential to classify experimental animal models of bladder cancer based on molecular subtypes. In this study, we characterized N-methyl-N-nitrosourea (MNU)-induced bladder tumors in rats and ex vivo-cultured spheroids derived from them to determine their similarities to the luminal and basal subtypes observed in human cancers. Methods Female Fisher 344 rats at age of 7 weeks received 4 intravesical doses of 1.5mg/kg MNU. By week 8, the MNU bladders displayed evidence of dysplasia and by week 16 small animal ultrasounds revealed papillary tumors with associated CIS, high grade non-invasive disease, or invasion into the lamina propria. In order to assess the subtype memberships of mature invasive tumors, rats were sacrificed at 30 weeks. Bladder tumors were evaluated by H&E staining and immunohistochemistry using antibodies against basal marker CK14 and luminal CK20. Ex-vivo culture of tumor cells was carried out using a spheroidal culture method. Partially digested tumor fragments were cultured in StemPro® medium. Viability of ex-vivo cultured cells was evaluated by Ki67 immunohistochemical staining and growth assay under microscope. Cultured cells were also tested by immnohistochestry using antibodies of CK14 and CK20. Results By about 30 weeks after exposure to MNU, rats developed 5-10-mm, protruding tumors in their bladders. Immunohistochemistry revealed enrichment of CK14-stained cells in CIS lesions and invasive tumors compared to normal urothelium, while the number of CK20-stained cells declined. Papillary tumors had a mixed staining pattern with both CK14 and CK20 positive staining. Partially digested fragments of tumors formed clear spheroids 24 hours after digestion. Immunohistochemistry revealed CK14-positive cells comprised 88% of spheroids and CK20-positive cells less than 5%. Conclusions The results of the present study demonstrate a pre-clinical model of urothelial cancer associated with progression of papillary non-muscle invasive bladder tumors with associated CIS to invasive cancers. CIS, invasive tumors, and ex-vivo cultured spheroids had the appearance of a basal subtype membership, while papillary tumors from the same model had staining patterns consistent with the urobasal/luminal tumor subtype. Funding Johns Hopkins Greenberg Bladder Cancer Institute
Authors
Takahiro Yoshida
Max Kates Niklai Sopko Alexander Baras George Netto Xiaopu Liu Charles Drake Noah Hahn David McConkey Trinity Bivalacqua |
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MP48-20 |
Expansion of Tumor Infiltrating Lymphocytes (TIL) from Primary Bladder Tumors |
Bladder Cancer: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP48-20 Sources of Funding: none Introduction Patients with advanced bladder cancer have limited therapeutic options resulting in a median overall survival (OS) between 12 and 15 months. At our institution, adoptive cell therapy (ACT) using tumor infiltrating lymphocytes (TIL) has resulted in a durable median OS of 52 months in patients with metastatic melanoma. Immune-mediated anti-tumor responses have been previously shown in bladder cancer, therefore we investigated the phenotype and function of TIL expanded from bladder tumors to establish feasibility of ACT for the treatment of bladder cancer. Methods Tumor specimens, including primary bladder tumors and lymph node metastases, were collected from 29 bladder cancer patients having standard of care tumor resection, who also had consented to an IRB-approved protocol for TIL generation. The tissue was minced into fragments, placed in individual wells of a 24-well plate, and propagated in high dose IL-2 for four weeks. TIL were considered expanded if they propagated to fill ?2 wells. The remaining tumor material was digested into a single cell suspension and frozen. TIL were phenotyped by flow cytometry and assessed for autologous tumor reactivity through co-culture with tumor digest and IFN-gamma ELISA. Results Twenty-seven of 29 tumors were harvested from radical cystectomy patients. Urothelial cell bladder tumors were cultured from 23 patients, of whom 19 (83%) demonstrated TIL expansion. Among these were 9/12 with preceding chemotherapy and 10/11 which had been chemotherapy naive. Expanded TIL were predominantly CD3+ (median 63%, range 10-87%) with a median of 30% CD8+ T cells (range 5-70%). Eight of 15 tested samples (53%) contained TIL that secreted IFN-gamma in response to autologous tumor. Microbial contamination was observed in six specimens. All lymphatic (5/5 samples) tissue collected demonstrated TIL expansion. Conclusions The study establishes the practical first step towards an autologous TIL therapy process for therapeutic testing in patients with bladder cancer. Human bladder cancer tissue can be used to expand tumor-specific TIL in vitro. TIL were also able to be expanded from patients that received chemotherapy prior to tumor resection. Future efforts will explore the ability to further expand bladder TIL cultures to clinically meaningful numbers to develop novel ACT strategies for patients with this diagnosis. Funding none
Authors
Michael Poch
Maclean Hall Krithika Kodumudi Kodumudi Cortlin Croft Mayer Fishman John Mullinax Amod Sarniak James Mule Shari Pilon-Thomas |
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MP49-01 |
PHASE 3 RANDOMISED TRIAL OF INTRAVENOUS MANNITOL VERSUS PLACEBO PRIOR TO RENAL ISCHEMIA DURING NEPHRON-SPARING SURGERY: IMPACT ON RENAL FUNCTIONAL OUTCOMES |
Kidney Cancer: Localized: Surgical Therapy II | 17BOS |
Abstract: MP49-01 Sources of Funding: Institutional Introduction To assess the significance of mannitol used as renal protective agent during nephron-sparing surgery (NSS) on renal functional outcomes after NSS._x000D_ Methods A prospective, randomized, placebo-controlled, double-blind, phase 3 trial (ClinicalTrials.gov identifier NCT01606787) designed to detect a 5% difference between treatment arms with a power of 90%. Patients were randomized 1:1 to receive mannitol (12.5 g) or normal saline solution placebo intravenously within 30 min prior to renal vascular clamping. Eligibility criteria included age >18 yr, renal artery clamping during NSS, and preoperative estimated glomerular filtration rate (eGFR) >45 mL/min/1.73m2. Intraoperatively, a standardized fluid management algorithm was used to maintain hemodynamic stability and urine output ≥0.5 mL/kg/h. Postoperatively, eGFR was obtained at 6 wk and 6 mo. A renal scan was obtained pre operatively and at the 6-mo endpoint._x000D_ An ANCOVA model was used to assess the differences in eGFR at 6 wk and 6 mo, and in renal scan at 6 mo after NSS. Differences in grade 3-5 complications were assessed using Fisher&[prime]s exact test. At the interim analysis on the first 88 patients, the O&[prime]Brien-Fleming stopping boundaries requiring a significance level of 0.0031 were not met (p = 0.6)._x000D_ Results A total of 105 patients per treatment arm were enrolled. After excluding 11 patients (7 in the placebo and 4 in the mannitol arm) who did not undergo NSS; 2 patients (1 in each arm) converted to radical nephrectomy, and 1 patient from the mannitol arm who never received the study drug, 98 and 101 patients in the placebo and mannitol arms, respectively, were evaluated. Median age was 56 yr (interquartile range [IQR] 48, 63) and 60 yr (IQR 50, 66) in the placebo and mannitol arm, respectively. Comparing placebo to the mannitol arm, the adjusted difference of 0.2 eGFR units at 6 mo after NSS was not significant (95% confidence interval [CI] -3.1, 3.5; p = 0.9). The adjusted difference of -2.6 eGFR units at 6 wk after NSS was not significant (95% CI -5.8, 0.7; p = 0.12). No significant differences were detected between treatment arms in median split function on 6-mo renal scan (difference -1.7; 95% CI -3.8, 0.4; p = 0.11), or in grade 3-5 complication rates within 90 days of NSS (difference 3.2%; 95% CI -4.1%, 11%; p = 0.4)._x000D_ Conclusions This randomized prospective trial provides evidence against the use of mannitol as renal protective agent during NSS since no clinical or statistically significant advantage to the use of intravenous mannitol in patients undergoing NSS was found._x000D_ Funding Institutional
Authors
Massimiliano Spaliviero
Nicholas E. Power Katie S. Murray Daniel D. Sjoberg Nicole E. Benfante Melanie L. Bernstein James D. Wren Paul Russo Jonathan A. Coleman |
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MP49-02 |
Perioperative morbidity of clamp vs off-clamp robotic partial nephrectomy: preliminary results from a multicentre randomized clinical trial (the CLOCK study) |
Kidney Cancer: Localized: Surgical Therapy II | 17BOS |
Abstract: MP49-02 Sources of Funding: None Introduction The impact of ischemic damage on kidney function residual to partial nephrectomy (PN) remains a controversial issue. The clamping of the artery is more frequent during minimally invasive PN compared with the open counterpart._x000D_ The CLOCK study (CLamp vs Off Clamp the Kidney during partial nephrectomy, clinicaltrial.gov registration n° NCT02287987) is a perspective, randomized, multicentre trial, started in September 2014, still recruiting, with the goal of 200 patients, to compare renal function preservation after robotic partial nephrectomy (RAPN). Local ethical committee approval was obtained by every center. Here an &[Prime]ad interim&[Prime] intention-to-treat analysis of the perioperative morbidity of the two procedures is reported. Methods Up to September 2016, 137 patients were centrally randomized to be submitted to clamp vs off-clamp RAPN at 6 institutions. Inclusion criteria were normal coagulative function, healthy contralateral kidney, estimated GFR ≥ 60 ml/min, R.E.N.A.L score ≤10 and previous surgeon experience >50 RAPN and center surgical volume >100 renal tumors/year. Split renal function was evaluated preoperatively and after 6 months by DTPA renal scan. Data were collected in an e-crf, centrally managed. Results No significant differences were observed for baseline features, duration of surgery, oncological outcomes and complications, whereas there was a difference in the severity of bleeding as perceived by the surgeon and in estimated blood loss (table no.1). A shift from an off-clamp to clamp technique was observed in 29/67 patients (43.3%), established preoperatively (3 cases, 10.3%), intraoperatively before starting the resection (10, 34.5%) or during the resection because of bleeding (16, 55.2%). A shift from clamp to off-clamp procedure was observed in 10/70 cases (14.3%), always pre-operatively. Conclusions Off-clamp and clamped RAPN are equally safe in terms of oncological outcomes and complications. However, even for tumors with a low/intermediate complexity, at high-volume centers and for skilled surgeons, despite the setting of a RCT, in a relevant rate of cases off-clamp PN is not feasible due to bleeding while only in a few cases clamping the artery is deemed as redundant. Funding None
Authors
Alessandro Antonelli
Luca Cindolo Marco Sandri Maria Furlan Alessandro Veccia Carlotta Palumbo Claudio Simeone Francesco Sessa Davide Facchiano Sergio Serni Marco Carini Bernardino De Concilio Guglielmo Zeccolini Antonio Celia Manuela Ingrosso Valentina Giommoni Filippo Annino Valerio Pizzuti Roberto Nucciotti Matteo Dandrea Angelo Porreca Andrea Minervini |
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MP49-03 |
The Superior Preservation of Postoperative Renal Function in Robotic Partial Nephrectomy, Compared with the Laparoscopic Procedure, is Associated with Less Parenchymal Volume Loss, Not Shorter Renal Ischemia Time: A Propensity Score-Matched Analysis |
Kidney Cancer: Localized: Surgical Therapy II | 17BOS |
Abstract: MP49-03 Sources of Funding: none Introduction Robot-assisted partial nephrectomy (RAPN) is reportedly superior to laparoscopic partial nephrectomy (LPN) in renal function preservation. This is partly due to the shortened warm ischemia time (WIT), but related evidence remains unclear. This study aimed to examine the cause of renal functional loss after minimally invasive partial nephrectomy. Methods A total of 273 patients underwent LPN (n = 141) or RAPN (n = 132) at a single institution between 2010 and 2015. The factors influencing the >10% decrease in the estimated glomerular filtration rate (eGFR) 6 months postoperatively were evaluated, and the percentage of decrease in eGFR and parenchymal volume were compared in LPN and RAPN matched cohorts. Results The mean WIT was significantly longer (24 vs. 18 minutes, p < 0.001) and the postoperative decrease in eGFR 6 months after surgery was significantly higher (-9.9% and -3.4%, p < 0.001) in LPN than in RAPN. Multivariate analysis showed that the >10% postoperative decrease in eGFR was significantly influenced by the surgical procedure (p = 0.0004), but not by WIT (p = 0.07). Patient variables, including age, sex, body mass index, tumor size, RENAL nephrometry score (RENAL-NS), preoperative eGFR, and WIT, were adjusted, and each group included 42 patients (mean tumor size 23 mm, RENAL-NS 6.4, preoperative eGFR 69 mL/min/1.73 m2, WIT 21 minutes). Six months after surgery, the percentage of decrease in eGFR (-9.4% vs. -1.9%, p = 0.0008) and parenchymal volume (-23% vs. -9%, p < 0.0001) was significantly higher in LPN than in RAPN. Conclusions The better preservation of renal function in RAPN, compared with LPN, is not caused by shortened WIT but by better preservation of parenchymal volume. Funding none
Authors
Hidekazu Tachibana
Toshio Takagi Tsunenori Kondo Kazunari Tanabe |
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MP49-04 |
Excised Parenchymal Mass and Devascularized Parenchymal Mass Associated with Partial Nephrectomy: Impact on Functional Recovery |
Kidney Cancer: Localized: Surgical Therapy II | 17BOS |
Abstract: MP49-04 Sources of Funding: none Introduction Loss of nephron mass is the predominant factor associated with functional outcomes after partial nephrectomy (PN), and can be due to excised parenchymal mass (EPM) and/or devascularized parenchymal mass (DPM). In this study, we are going to evaluate the importance of EPM and DPM relative to functional recovery after PN. Methods A total of 168 patients managed with PN had necessary studies to determine EPM and DPM and evaluate parenchymal mass changes and functional loss within the operated kidney. Parenchymal mass loss in the ipsilateral kidney was measured from CT scans <2 months prior and 3-12 months after PN. EPM was estimated from pathologic specimen by subtracting tumor volume from specimen volume. Tumor volume was measured from preoperative CT, and specimen volume estimated from defatted specimen weight after adjusting for tissue density and proportionate changes related to lack of blood flow ex vivo. DPM was defined as total parenchymal mass loss minus EPM. Patients with a contralateral kidney were required to have nuclear renal scans within the same timeframes. Pearson correlation evaluated the relationship between GFR preservation and parenchymal mass loss, and multivariable analysis assessed predictors for DPM. Results Median tumor size was 3.4 cm, median R.E.N.A.L score was 7, and 32 patients (19%) had a solitary kidney. Warm/cold ischemia were utilized in 100/68 patients, respectively. Median EPM and DPM were 9cm3 and 16cm3, respectively. Median GFR preserved was 89% globally and it was 79% in the operated kidney. While total parenchymal mass loss and DPM correlated strongly with GFR preservation in the operated kidney (both p<0.001), EPM failed to correlate with functional outcomes (r<0.2). Preoperative GFR and endophytic status associated with DPM on multivariable analysis. Conclusions Devascularization during reconstruction associates strongly with functional outcomes after PN, which has important implications regarding surgical technique. Prospective study will be required to further evaluate the relative values of EPM and DPM. Funding none
Authors
Wen Dong
Jitao Wu Chalairat Suk-Ouichai Elvis Carabello Diego Aguilar Palacios Erick Remer Jianbo Li Joseph Zabell Sudhir Isharwal Steven Campbell |
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MP49-05 |
Impact of Prolonged Ischemic Time on Chronic Kidney Disease Following Partial Nephrectomy: a Matched-Pair Comparison |
Kidney Cancer: Localized: Surgical Therapy II | 17BOS |
Abstract: MP49-05 Sources of Funding: None Introduction To preserve renal function, partial nephrectomy is recommended to patients with small renal masses. However, controversy still exists as to whether prolonged ischemic time adversely affects the incidence of chronic kidney disease. We assessed the effect of prolonged ischemic time to global renal function following partial nephrectomy. Methods We reviewed data from 1,588 patients who underwent open or robotic partial nephrectomy for clinical T1 renal tumor with normal renal function (estimated glomerular filtration rate [eGFR] ≥ 60 mL/min/1.732). Patients were subjected to group A (ischemic time ≤ 30 minutes) or group B (ischemic time > 30 minutes). Propensity score matching was used to adjust for potential confounders, which resulted in 320 patients in each group. Postoperative renal function was evaluated at the last follow-up visit. Multivariate analysis was used to determine predictors for the newly acquired CKD (eGFR < 60 mL/min/1.732). Results In the groups A and B, mean ischemic time was 19.8 and 40.2 minutes respectively. There were no statistically significant differences in other baseline variables between the groups. After a median follow-up of 37 months, mean postoperative eGFR was similar (84.5 vs. 83.2 mL/min/1.732, p = 0.424) and the rate of CKD did not differ in the two groups (6.3% vs. 7.2%, p = 0.636). Prolonged ischemic time did not affect the newly acquired CKD among the open partial nephrectomy subgroup (p = 0.847) and those with robotic partial nephrectomy (p = 0.160). Moreover, dividing ischemic time into five groups (≤ 20, 21-30, 31-40, 41-50, and ≥ 50 minutes) provided no further information on new onset CKD (7.5%, 4.8%, 7.0%, 7.9%, and 6.5%, p = 0.865) compared with the two groups with a cut-off at 30 minutes. Conclusions In patients with a normal baseline renal function, prolonged ischemic time is not an independent predictor of CKD following partial nephrectomy. Funding None
Authors
Jung Keun Lee
In Jae Lee Tae Jin Kim Hakmin Lee Jong Jin Oh Sangchul Lee Seong Jin Jeong Seok-Soo Byun Sang Eun Lee Sung Kyu Hong |
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MP49-06 |
When Partial Nephrectomy Is Unsuccessful: Understanding The Reasons For Conversion from Robotic Partial to Radical Nephrectomy At a Tertiary Referral Center |
Kidney Cancer: Localized: Surgical Therapy II | 17BOS |
Abstract: MP49-06 Sources of Funding: None Introduction Given the technical advantages offered by the robotic platform, there has been an upward trend in the utilization of robotic partial nephrectomy however little information exist on conversion from robotic partial nephrectomy (RPN) to radical nephrectomy (RN)._x000D_ Our aim was to identify the preoperative factors associated with conversion from RPN to RN, and to report the incidence of this event._x000D_ Methods Using our institutional review board-approved database, we abstracted data on 1023 RPN cases performed at our center between 2010 and 2015. Standard and converted cases were compared in terms of patients and tumor characteristics and perioperative, functional, and oncological outcomes. Logistic regression analysis was used to identify predictors of radical conversion. Results The overall conversion rate was 3.1% (32/1023). The most common reasons for conversion were tumor involvement of hilar structures (n=8, 25%), Failure to achieve negative margin on frozen section (n=7, 21.8%), suspicion for advanced disease (n=5, 15.6%), and failure to progress (n=5, 15.6%). Patients requiring conversion were older (p<0.01) and had higher Charlson scores (p<0.01), including increased prevalence of CKD (p=0.02). Increasing tumor size (5 vs. 3.1 cm, p<0.01) and R.E.N.A.L score (9 vs. 8, p<0.01) also were associated with increased risk of conversion. Worse baseline renal function (OR 0.98 95% CI 0.96-0.99 p=0.04), high tumor size (OR 1.44, 95% CI 1.22-1.7, p<0.01), and increasing R.E.N.A.L score (p=0.02) were independent predictors of conversion. Compared to converted cases, standard RPN cases had similar short-term oncological outcomes but better renal functional preservation (p<0.01) at latest follow-up. Conclusions At a high-volume center, the rate of RPN conversion to RN is 3.1% including 2.2% of preoperatively anticipated nephrectomy cases. Increasing tumor size and complexity and poor preoperative renal function are the main predictors of conversion. Funding None
Authors
Önder Kara
Matthew J. Maurice Pascal Mouracade Ercan Malkoç Julien Dagenais Ryan J. Nelson Jaya Sai Chavali Robert J. Stein Amr Fergany Jihad H. Kaouk |
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MP49-07 |
Incidence and risk factors of postoperative hypertension after partial nephrectomy for renal tumors |
Kidney Cancer: Localized: Surgical Therapy II | 17BOS |
Abstract: MP49-07 Sources of Funding: none Introduction Partial nephrectomy (PN) is now a preferred surgical option for small renal masses. However, renal parenchymal damage caused by PN has theoretic potential to induce hypertension (HT). We previously reported our preliminary findings indicating that PN could be related to the progression of HT in a small cohort (Inoue M, et al. Int J Urol. 2015). In this study, we aimed to clarify the effects of PN on the progression of HT, and investigate its risk factors in a larger cohort of patients with renal tumors. Methods Two hundred and ninety-five patients with renal tumors who underwent PN (N = 188) or radical nephrectomy (RN) (N = 107) between January 2012 and March 2016, and agreed to participate in this study, were enrolled. PN was carried out without vascular clamping in all but five patients (3%). We asked the participants to measure their home blood pressure (BP) in the morning and at bedtime for seven days, and to report these measurements and any use of antihypertensive medications at the time of the follow-up survey. Pre- and postoperative BP was calculated as the mean of the morning and bedtime BP measured on the day before the surgery, and the mean of all home BP measurements taken for postoperative seven days, respectively. The endpoint of this study was nephrectomy-related HT (NR-HT), defined as postoperative BP ≥ 140/90 mmHg with an increase of ≥ 20 mmHg from preoperative BP. Results In the PN and RN patients, the median age was 58 years and 62 years (p = 0.042), and tumor size was 2.5 cm and 5.0 cm (p < 0.001), respectively. Before the surgery, 72 (38%) of the PN patients and 42 (39%) of the RN patients were taking antihypertensive medications (p = 0.872). The median interval between the surgery and the follow-up survey was seven months. In the PN patients, mean pre- and postoperative BP was 125/74 mmHg and 129/79 mmHg, respectively, showing both systolic (p < 0.001) and diastolic BP (p < 0.001) increased significantly after the surgery. In the RN patients, there were no significant changes in BP after the surgery. Twenty (11%) of the PN patients and three (3%) of the RN patients developed NR-HT (p = 0.009). Antihypertensive medications were added postoperatively in 23 (12%) of the PN patients and six (6%) of the RN patients (p = 0.056). Multivariate analysis in the PN patients identified acute kidney injury (odds ratio (OR) 3.30, p = 0.034) and higher postoperative peak serum C-reactive protein level (OR 3.01, p = 0.026) as independent risk factors for NR-HT. Conclusions Postoperative HT was more common in PN patients than in RN patients. Renal parenchymal damage during PN may contribute to the progression of HT. Funding none
Authors
Masaharu Inoue
Yasuhisa Fijii Masaya Ito Toshiki Kijima Soichiro Yoshida Minato Yokoyama Junichiro Ishioka Yoh Matsuoka Kazutaka Saito Kazunori Kihara |
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MP49-08 |
On-clamp versus Off-clamp Partial Nephectomy: Propensity Score Matched Comparison of Long Term Functional Outcomes |
Kidney Cancer: Localized: Surgical Therapy II | 17BOS |
Abstract: MP49-08 Sources of Funding: none Introduction The elective indication for off-clamp (Off-C) partial nephrectomy (PN) in patients with good baseline renal function remains controversial. The aim of this study is to compare the risks of developing a severe (stage ≥3b) chronic kidney disease (CKD) in patients with cT1-2/N0/M0 renal tumors and baseline estimated glomerular filtration rate (eGFR) >60 ml/min after either Off-C or on-clamp (On-C) PN. Methods A prospective &[Prime]renal cancer&[Prime] database of two high volume centers was queried for &[Prime]cT1-2/N0/M0&[Prime] tumors, &[Prime]PN&[Prime] and &[Prime]baseline eGFR>60 mL/min&[Prime]. Overall 1073 patients met the inclusion criteria (483 Off-C and 588 On-C). A 1:2 propensity score-matched (PSM) analysis was employed to minimize the selection bias of non-random treatment assignment of patients. _x000D_ Kaplan-Meier method was used to compare the PSM cohorts specific risks of developing a CKD stage ≥ 3b during follow-up in the PSM cohorts, and the log-rank test was applied to assess statistical significance between groups. Univariable and multivariable Cox regression analyses were performed to identify independent predictors of developing a CKD stage ≥3b._x000D_ Results On-C patients were significantly younger (p=.001), less frequently smokers (.01), with a lower incidence of diabetes (.001) and hypertension (.001), lower ASA scores (<.001), higher baseline eGFR values (.003), smaller tumor sizes (<.001), and higher incidence of positive surgical margins (.021)._x000D_ After applying the PSM analysis, the two cohorts of 221 On-C and 485 Off-C PN cases did not differ for all clinical and pathologic covariates (Table 1; all p ≥ .06)._x000D_ The probability of developing a CKD stage ≥3b was significantly higher (log rank p=.006, Figure 1) in the On-C cohort (2, 5 and 8yr risk 0.9, 5.1 and 12.8% vs 0.6, 1.2 and 1.2% in the Off-C cohort, respectively). On-C technique was associated with a 5.2 fold increased risk of developing CKD stages ≥3b compared with the Off-C approach (HR 5.2 [95% CIs 1.4-18.9]; p=.012)._x000D_ At multivariable regression analysis, eGFR at discharge and Off-C PN were independent predictors of outcomes. For each increasing mL/min of eGFR at the discharge the risk of developing a CKD stage ≥3b was reduced by 5% (HR 0.95 [95&[permil] CIs 0.93-0.97]), while On-C approach was associated with a 5.8 fold increased risk of developing a CKD stage ≥3b (HR 5.8 [95% CIs 1.6-20.8]). Conclusions Conclusions: This study highlights the beneficial role of an Off-C approach in patients with cT1-2/N0/MO renal tumors and good baseline renal function candidate to elective PN. Funding none
Authors
Giuseppe Simone
Umberto Capitanio Alessandro Larcher Mariaconsiglia Ferriero Leonardo Misuraca Gabriele Tuderti Giuseppe Romeo Francesco Minisola Salvatore Guaglianone Fabio Muttin Alessandro Nini Francesco Trevisani Francesco Montorsi Roberto Bertini Michele Gallucci |
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MP49-09 |
Comparisons of Surgical Outcomes between the Resection and the Enucleation in Robot Assisted Laparoscopic Partial Nephrectomy for Renal Tumors According to the Surface-Intermediate-Base Margin Score |
Kidney Cancer: Localized: Surgical Therapy II | 17BOS |
Abstract: MP49-09 Sources of Funding: None Introduction Enucleation may be realistic method for preserving the normal renal parenchyma in partial nephrectomy (PN) if oncological or surgical outcomes are feasible. The surface-intermediate-base (SIB) score is proposed for the standardized reporting of resection techniques in PN. We compared surgical outcomes, defined according to SIB score, of robot-assisted laparoscopic partial nephrectomy (RAPN) between the resection and the enucleation._x000D_ Methods Patients who underwent RAPN between 2013 and 2016 participated in our study. SIB score was macroscopically evaluated immediately after the surgery. We divided patients into the following two groups: enucleation (SIB score of 1 or 2) and resection (SIB score of 3-5). The following outcomes were compared between the two groups: decrease in estimated glomerular filtration rate (eGFR), ischemia time, console time, estimated blood loss, surgical margin status, incidence of urological complications. Multivariate linear regression analysis was performed to demonstrate the predictive factors of decrease in eGFR. Postoperative eGFR was evaluated between 1 and 3 months after surgery._x000D_ Results This study included 283 patients, 48 patients in the enucleation and 235 patients in the resection. The patients&[prime] background (age, sex, and body mass index, preoperative eGFR) were not significantly different between the two groups. The patients in the enucleation had more complex (RENAL NS, 10-12; enucleation, 29% vs. resection, 8%) and larger tumors (enucleation, 34 mm vs. resection, 28 mm) than patients in the resection. The incidence rates of urological complication and negative surgical margin were not significantly different. Multivariate linear regression analysis revealed that higher age, higher-complexity tumor, longer warm ischemia time, better preoperative eGFR, and resection technique (vs. enucleation) were predictive factors of a higher decrease in eGFR (Table)._x000D_ Conclusions The enucleation was applied to high- complexity tumors. The multivariate analysis revealed that the enucleation might be better than the resection technique in terms of preservation of renal function with similar oncological outcomes._x000D_ Funding None
Authors
Toshio Takagi
Tsunenori Kondo Junpei Iizuka Hirohito Kobayashi Hidekazu Tachibana Kazuhiko Yoshida Hideki Ishida Kazunari Tanabe |
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MP49-10 |
Ischemia and Functional Recovery from Partial Nephrectomy: Refined Perspectives |
Kidney Cancer: Localized: Surgical Therapy II | 17BOS |
Abstract: MP49-10 Sources of Funding: none Introduction Partial nephrectomy (PN) is the standard treatment for localized renal cancer due to better preservation of renal function. Previous studies suggested that parenchymal mass preservation is a key determinant of functional outcomes, while ischemia plays a secondary role. Analyses that focus specifically on recovery of the kidney exposed to ischemia appear to be most informative, yet have only included limited numbers of patients. Our objective is to provide a more refined evaluation of the impact of ischemia type and duration using more robust numbers of patients analyzed in this manner. Methods A total of 401 patients with PN at our center (2007-2015) had necessary data for analysis, including serum creatinine-based estimated glomerular filtration rate (GFR) and contrast-enhanced cross-sectional imaging studies <2 months prior and 3-12 months after PN. Patients with 2 kidneys were also required to have split renal function from nuclear renal scans within the same timeframes. Recovery from ischemia was defined as percent function preserved in the ipsilateral kidney normalized by percent parenchymal mass preserved. Pearson correlation evaluated the relationships between functional recovery and parenchymal mass preserved or ischemia time. Multivariable linear regression assessed predictors for recovery. Results Median tumor size was 3.5 cm and median R.E.N.A.L. was 8. Cold/warm ischemia were utilized in 151/250 patients, and median ischemia times were 27/21 minutes, respectively. Parenchymal mass preserved correlated strongly with function preserved (r=0.63, p<0.001). Median recovery from ischemia, which normalizes for parenchymal mass preservation, was significantly higher for hypothermia than warm ischemia (99% vs. 92%, p<0.001) and remained consistently strong even with longer duration of cold ischemia. Multivariable analysis demonstrated that ischemia type and duration associated significantly with recovery from ischemia (p<0.05). However, each additional 10 minutes of warm ischemia associated with only 2.5% decline in recovery from ischemia. Conclusions Parenchymal mass preservation is the primary factor affecting functional outcomes after clamped PN. Beyond this, functional recovery is most reliable with hypothermia. Longer intervals of warm ischemia associate with reduced recovery; however, incremental changes are modest and of debatable clinical significance, particularly in patients with a normal contralateral kidney. Funding none
Authors
Chalairat Suk-Ouichai
Wen Dong Jitao Wu Elvis R Caraballo Erick Remer Jianbo Li Joseph Zabell Sudhir Isharwal Steven C Campbell |
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MP49-11 |
Renal Ischemia and Volume Loss Have a Compounding Effect on Acute Renal Dysfunction after Partial Nephrectomy |
Kidney Cancer: Localized: Surgical Therapy II | 17BOS |
Abstract: MP49-11 Sources of Funding: none Introduction Renal function immediately following partial nephrectomy (PN) may depend on the modifiable factors of warm ischemia time (WIT) and excisional volume loss (EVL). Our aim was to examine how their dynamic interaction influenced predicted rates of post-PN acute kidney injury (AKI) across a range of tumor complexities. Methods We retrospectively reviewed 1,162 patients in our single-institution robotic PN database and captured sociodemographic, clinical, and radiologic characteristics. EVL was calculated as the difference between specimen and tumor volume based on pathological assessment. AKI was defined as a change in preoperative GFR >25% within 72 hours of surgery, or stage 1 of the RIFLE criteria. Multivariate logistic regressions, followed by marginal effects, were run to examine the interaction effect of ischemia type, volume loss, and R.E.N.A.L. score on rates of AKI. Results There was a significant interaction effect of WIT and log EVL on predicted rates of AKI (p<0.001). Each doubling of EVL caused a 4.03% and 8.46% increased probability of AKI, respectively, for WIT of <25 minutes and >25 minutes. At excisional volume losses >5.5cm3, prolonged WIT had statistically greater odds of causing AKI (Figure 1). These predicted effects on AKI were amplified for increasing R.E.N.A.L. scores (p<0.001). Conclusions Rates of AKI after PN are highly correlated to the dynamic compounding influence of WIT and EVL. As excisional imprecision increases, the added insult from prolonged warm ischemia time become more profound, a &[Prime]two hit&[Prime] model for parenchymal insult. This effect was further modulated by tumor complexity, with increasing scores predicting an increased effect. Together, this suggests that limiting WIT and minimizing volume loss, especially in complex tumors, can mitigate rates of postoperative AKI. Given the associated morbidity and mortality of AKI, further efforts to carefully control these modifiable factors are of particular interest. Funding none
Authors
Julien Dagenais
Matthew Maurice Pascal Mouracade Onder Kara Ryan Nelson Ercan Malkoc Jihad Kaouk |
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MP49-12 |
Retroperitoneal versus transperitoneal robotic partial nephrectomy for posterior tumors: a multicenter match-paired case-control study |
Kidney Cancer: Localized: Surgical Therapy II | 17BOS |
Abstract: MP49-12 Sources of Funding: none Introduction Several authors have recently reported the feasibility of retroperitoneal robotic partial nephrectomy (RRPN) for excision of renal masses. However, very few study comprised an appropriate control group of transperitoneal robotic partial nephrectomy (TRPN). In this study, our main objective was to compare perioperative outcomes of TRPN and RRPN. Methods All patients who underwent RRPN in 4 departments of urology between 2010 and 2014 were included in the study. In 3 of these institutions, the retroperitoneal route was chosen mainly for posterior tumors and when it seemed technically feasible (large and complex posterior tumors were resected via a transperitoneal robotic approach). In the last institution, all renal tumors (either anterior or posterior) were resected through a transperitoneal robotic approach. RRPN were matched to TRPN in a 1 to 1 fashion according to the following variables : RENAL NEPHROMETRY Score ; anterior or posterior location of the tumor ; tumors size and surgeon’s experience (categorized a ? 50 procedures, 20-50 procedures or < 20 procedures). Perioperative data were compared between the TRPN and RRPN groups. Results Eighty-six RRPN were included for analysis and matched to 86 TRPN. Eighty-five tumors were posterior in each group (98.8%). Mean RENAL NEPHROMETRY Score was 6.7 and mean tumor size was 2.5 cm in both groups. Operative time (111 vs. 156 min ; p<0.0001) and warm ischemia time (11 vs. 14 min ; p=0.02) were shorter in the RRPN group. Patients in the RRPN group had lower estimated blood loss (116 vs. 386 mL ; p<0.0001) but with no impact on transfusion rates (4% vs. 7% ; p=0.37). Positive surgical margin rates (8% vs. 3.5% ; p=0.2) and major complication (i.e. ? Clavien grade 3) rates (6% vs. 6% ; p=0.89) were similar between both groups. There was a trand toward higher complication rate in the TRPN group (21% vs. 10% ; p=0.06). Length of stay was shorter in the RRPN group (3.5 vs. 5.4 days ; p=0.01). Conclusions RRPN, mostly performed for small posterior tumors, is associated with decreased operative time, warm ischemia time, blood loss and length of stay. Further data are needed to confirm its impact on complication rates. Funding none
Authors
benoit peyronnet
nicolas doumerc christophe vaessen thomas seisen mathieu roumiguie benjamin pradere charles chahwan jean-baptiste beauval francois-xavier nouhaud gregory verhoest laurent salomon morgan roupret karim bensalah alexandre de la taille |
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MP49-13 |
COMPARATIVE ANALYSIS OF THE OUTCOMES OF TRANSPERITONEAL AND RETROPERITONEAL ROBOT-ASSISTED PARTIAL NEPHRECTOMY: RESULTS FROM A MULTI-INSTITUTIONAL HIGH-VOLUME CENTERS EXPERIENCE |
Kidney Cancer: Localized: Surgical Therapy II | 17BOS |
Abstract: MP49-13 Sources of Funding: None Introduction We compared the outcomes of transperitoneal and retroperitoneal robot-assisted partial nephrectomy (RAPN) within a large multi-institutional series of patients with kidney tumors. Methods We reviewed data from a prospectively mantained multi-institutional database on patients subjected to either transperitoneal or retroperitoneal RAPN between 2010 and 2016 at three tertiary care centers . Tumor complexity was preoperatively assessed according to the PADUA score. The Margin Ischemia and Complications (MIC) score was used to define optimal surgical outcomes (absence of Clavien-Dindo >2 complications, warm ischemia time [WIT] <20 minutes and absence of positive surgical margins). Finally, logistic regression model were fitted to test whether the surgical approach affected perioperative outcomes after adjustment for patient age, gender, body mass index (BMI), Charlson comorbidity index (CCI), tumor size and tumor complexity Results Overall, 343 (64.6%) and 188 (35.4%) were respectively subjected to transperitoneal and retroperitoneal RAPN. No significant differences were observed in terms of age, gender and BMI (all p>0.05), while a higher CCI was observed in the retroperitoneal group (p<0.001). Tumor size and tumor complexity did not differ significantly between the two groups (p>0.05). Operative time did not differ between the two groups (p=0.824), while estimated blood loss and length of stay were lower in patients subjected to retroperitoneal RAPN (p?0.013). Conversely, WIT was significanty lower in the transperitoneal group (mean WIT 15.2 vs. 17.1 mins; p=0.002). The proportion of patients with CD>2 complications was higher for the retroperitoneal approach (5.3 vs. 2.6%), but this difference did not achieve a statistical significance (p=0.051). Finally, no difference in the rate of positive surgical margins was observed (3.8 vs. 2.7%; p=0.491). The optimal surgical outcomes rate was 77.0% vs. 69.1% in the transperitoneal vs. retroperitoneal group, respectively (p=0.049). However, after adjustment for multiple confounders, no statistically significant difference between the two approaches was observed (OR: 1.14; 95%CI: 0.712-1.826; p=0.585). Conversely, both increasing PADUA score and male gender were associated with worse surgical outcomes (p<0.001). Conclusions In expert hands, both the transperitoneal and the retroperitoneal approach can be safely adopted to perform a RAPN, with the latter being associated with lower EBL and length of stay. Funding None
Authors
Giovanni Lughezzani
Nicolo' Buffi Giuliana Lista Davide Maffei Giovanni Forni Nicola Fossati Alessandro Larcher Massimo Lazzeri Alberto Saita Paolo Casale Rodolfo Hurle Giorgio Guazzoni Alex Mottrie Jim Porter |
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MP49-14 |
Laparoscopic nephron-sparing surgery after superselective tumoral embolization in a hybrid operating room: feasibility and immediate oncological and functionnal results of the first 30 patients. |
Kidney Cancer: Localized: Surgical Therapy II | 17BOS |
Abstract: MP49-14 Sources of Funding: none Introduction Arterial clamping is often needed for laparoscopic partial nephrectomy (LPN) to control the hemorragic risk. It induces a transitory renal ischemia, the long-term consequences of which are controversial. In order to limit ischemia and operative bleeding we developed a LPN technique without arterial clamping, in a hybrid operating room, after hyperselective tumoral embolization (HSE). We evaluated the feasibility after 36 successive cases. Methods Between May 2015 and October 2016, 16 female and 20 male presenting a localized renal tumor were included. Median age and BMI were 59 y (32-82) and 25,9 kg/m2 (20,1-37,4). 11 patients had a biopsy prior to surgery. Three indications of partial surgery were imperative, one was preventive and all other were elective. Respectively 24 and 4 tumors were of moderate and high complexity according to the RENAL Score._x000D_ One singel interventional radiologist performed the HSE of tumoral vessels and controled the vascular exclusion of the tumor. Afterwards one single urologist performed a clampless LPN without dissection of the renal pedicle. If necessary, a suture of the parenchyma was made to control venous bleeding._x000D_ Results Median endovascular and surgical procedures durations were 45 min (21-120) and 77,5 min (32-150). Median blood loss was 50 mL (10-650). No peroperative transfusion was needed. One surgery was converted to a mini-laparotomy because of toxic fat, in order to control carcinological margins. Two Clavien II complications were a postoperative transfusion on a fragile patient and an unexplained sepsis. Median length of stay was 3,5 days (2-7). The procedure had no impact on renal function after one month of follow-up (p=0,09). Median tumoral size was 3 cm (1,5-8). Twenty-eight tumors (77.8%) were malignant. Surgical margins were postive for one patient (2,8%). Conclusions Clampless LPN in a hybrid operating room without pedicular dissection after previous tumoral embolization is a technically safe and carcinologically efficient mini-invasive alternative for the management of localized renal tumors. Funding none
Authors
Paul Panayotopoulos
Louis Besnier Antoine Bouvier Pierre Bigot |
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MP49-15 |
Safety and early effectiveness of robotic partial nephrectomy for large angiomyolipomas |
Kidney Cancer: Localized: Surgical Therapy II | 17BOS |
Abstract: MP49-15 Sources of Funding: none Introduction To evaluate a multicenter series of robotic assisted partial nephrectomy (RAPN) performed for the treatment of large angiomyolipomas (AMLs). Methods Between 2005-2016, 40 patients with large or symptomatic AMLs underwent RAPN at 5 academic centers in the United States. Patient demographics, AML characteristics, operative and postoperative clinical outcomes were recorded and analyzed. Surgical outcomes were compared between patients who underwent selective arterial embolization (SAE) before RAPN and patients who did not undergo pre-RAPN SAE. Results Median tumor diameter was 7.2 cm (interquartile range [IQR]: 5–8.5 cm), and the median nephrometry score was 9 (IQR: 7-10). Six patients (15%) had a history of tuberous sclerosis, and 11 (28%) had previously undergone SAE. Median operative time and median warm ischemia time were 207 minutes (IQR: 180-231) and 22.5 minutes (IQR: 16-28), respectively. Non-clamping technique was applied in 8 (20%) patients. Median blood loss was 200 ml (IQR: 100-245), and 4 patients (10%) received blood transfusion postoperatively. One intraoperative complication occurred (2.5%), and 7 postoperative complications occurred in 6 patients (15%). During a median follow-up time of 8 months (IQR: 1-15), none of the patients developed AML-related symptoms. The median eGFR preservation rate was 95%. There were no differences in operative or perioperative outcomes between patients who underwent SAE before surgery and those who did not. Conclusions RAPN appears to be a safe primary or secondary (post-SAE) treatment for large AMLs, with favorable perioperative morbidity profile and excellent functional preservation. Longer follow-up is required to fully evaluate therapeutic efficacy. Funding none
Authors
Shay Golan
Scott Johnson Matthew Maurice Jihad Kaouk Weil Lai Benjamin Lee Steve Kheyfets Chandru Sundaram David Cahn Robert Uzzo Arieh Shalhav |
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MP49-16 |
Modified Laparoscopic Simple Enucleation with Single Layer Suture Technique versus Standard Laparoscopic Partial Nephrectomy for Treating Localized Renal Cell Carcinoma |
Kidney Cancer: Localized: Surgical Therapy II | 17BOS |
Abstract: MP49-16 Sources of Funding: none Introduction Laparoscopic simple enucleation, which appears to reserve more renal parenchyma without compromising oncologic safety, may be an alternative to standard laparoscopic partial nephrectomy (SLPN). The aim of the present study is to examine the impact of modified laparoscopic simple enucleation (MLSE) with single layer suture technique versus SLPN on our large institutional experience in terms of intraoperative, early postoperative and pathologic outcomes. Methods We evaluated 385 consecutive patients who underwent MLSE or SLPN for renal tumors in our institution from January 2013 to December 2015 in terms of perioperative pathologic and oncologic outcome variables. In MLSE, the pseudocapsule of the tumor is bluntly dissected along a natural tissue plane without a visible rim of normal parenchyma.The single layer suture technique was performed for renal reconstruction. Results In total, 280 patients underwent MLSE and 105 underwent SLPN. The PADUA score was ? 10 for 62 (22.2%) MLSE patients and 12 (11.4%) SLPN patients (p=0.017). Highly-complex renal tumors (PADUA score ? 10) were mostly enucleated. Mean operative time was 182.1 and 192.8 min, respectively (p=0.078). Warm ischemic time was significantly lower in the MLSE than SLPN group (23.2 vs 25.4 min; p=0.004). The estimated blood loss was similar (p=0.537). Tumor bed suturing was performed in 9.3% and 82.9% of MLSE and SLPN cases (P=0.000). No hilar clamping was needed for 29 MLSE patients (10.4%) and 4 SLPN patients (3.8%) (p=0.041). Grade III complications were reported in 5 (1.8%) MLSE patients and 7 (6.6%) SLPN patients (p=0.034). The incidence of positive surgical margins was comparable between the MLSE and SLPN groups (1.8% and 5.7%, p= 0.086). After a median follow-up of 18 months, recurrence did not differ between the 2 groups: 9 (3.2%) MLSE patients and 4 (3.8%) SLPN patients (p=1.000). Conclusions MLSE may confer shorter warm ischemic time, almost no need for tumor bed suturing and less Grade III complications than SLPN, with similar oncologic outcomes. MLSE may be safe and acceptable for patients undergoing Nephron-sparing surgery. Funding none
Authors
Qun Lu
Xiaozhi Zhao Changwei Ji Guangxiang Liu Hongqian Guo |
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MP49-17 |
Robot-assisted partial nephrectomy for selected renal mass using off-clamp approach offered renal functional advantage over on-clamp |
Kidney Cancer: Localized: Surgical Therapy II | 17BOS |
Abstract: MP49-17 Sources of Funding: None Introduction Minimization or reducing on-clamp time during PN has led to alternative technical modifications. The concept of off-clamp PN aims to avoid the ischemic injury on the healthy parenchyma. The purpose of this study was to compare the outcomes of off-clamp to on-clamp approach during robot-assisted partial nephrectomy (RAPN)._x000D_ Methods Retrospective study of 940 patients who underwent RAPN between 2007 and 2016 for cT1a tumors using on-clamp or off-clamp approaches. We matched the patients in terms of confounding variables. Overall, 309 patients with on-clamp technique were matched to 103 patients with off-clamp technique. We compared the clinico-pathological characteristics, perioperative morbidity and late functional outcomes between the propensity score matched groups. The excisional volume loss was calculated on pathology specimen. Postoperative e-GFR was calculated between 3 to 12 months after PN. Results There were no difference in clinico-pathological characteristics between the 2 matched groups. While operative time (p=0.4), estimated blood loss (p=0.28), Clavien grade III-V complications (p=0.8), surgical reoperation (p=1), 30-day readmission (p=1) positive surgical margin (5.5% vs. 5.8%, p =0.9) were comparable between the 2 groups, there were significant difference in excisional volume loss (median, 7.08 vs. 3.51 cm3, p<0.01), e-GFR decline (median, -9.7 vs. -2.2 ml/min/1.73m2, p<0.01), percent of e-GFR preservation (median, 87% vs. 97%, p<0.01), and CKD upstaging (36.5% vs. 23.3%, p=0.01) in favor of off-clamp group. Excisional volume loss (p=0.01), off-clamp approach (p=0.01), and age (p=0.02) were predictors of renal function preservation, whereas excisional volume loss (OR=1.035, CI 95% [1.015-1.06], p<0.01) predicted CKD upstaging. Conclusions RAPN for selected renal mass using off-clamp approach offered renal functional advantage over on-clamp, without adding morbidities. Excisional volume loss, off-clamp approach, and age were independent predictors of renal function preservation. Funding None
Authors
Pascal Mouracade
Julien Dagenais Onder Kara Matthew Maurice Ryan Nelson Khaled Fareed Robert Stein Amr Fergany Jihad Kaouk |
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MP49-18 |
Off-clamp Robot-assisted Partial Nephrectomy: How Far Shall We Proceed? |
Kidney Cancer: Localized: Surgical Therapy II | 17BOS |
Abstract: MP49-18 Sources of Funding: none Introduction To describe our off-clamp robot-assisted partial nephrectomy (RAPN) and to evaluate perioperative and functional outcomes stratified by tumor size and PADUA classification. Methods Retrospective analysis of 62 patients who underwent off-clamp RAPN from September 2006 to January 2016 was performed. Increased estimated blood loss (EBL) was defined as intraoperative bleeding more than the 75th percentile. ROC analysis was used to determine the optimal threshold of tumor size for both increased EBL and chronic kidney disease (CKD) upstaging. Multivariable analysis was used to assess risk factors for increased EBL. Results Mean patients age was 53.5 years and mean tumor size was 2.6 cm. ROC analysis showed that tumor size of 3.2cm and 4cm were cut-off values for increased EBL (AUC=0.82, p<0.001) and CKD upstaging (AUC=0.87, p=0.004), respectively. On multivariable analysis, involvement of the urinary collecting system and tumor size were predictors of increased EBL (p=0.006 and 0.003, respectively). The 3-ys CKD upstaging free progression rate when stratified by tumor size (?4 cm and >4cm) was (97.1% and 51.4%, retrospectively, p<0.001). Conclusions Off-clamp RAPN can be safely performed in the hands of expert robotic surgeons; however, risk of intraoperative bleeding in order to achieve good functional outcomes must be adequately balanced before surgery for maximal patient’s safety. Our findings showed that tumors >3.2cm and those involving the urinary collecting system are associated with risk of increased intraoperative bleeding, while tumors >4cm have increased risk of CKD upstaging despite zero ischemia. Funding none
Authors
Ali Abdel Raheem
Glen Denmer Santok Lawrence HC Kim Kidon Chang Trenton GH Lum Young Eun Yoon Woong Kyu Han Young Deuk Choi Koon Ho Rha |
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MP49-19 |
Off-clamp vs. on-clamp robotic partial nephrectomy: a multicenter match-paired analysis |
Kidney Cancer: Localized: Surgical Therapy II | 17BOS |
Abstract: MP49-19 Sources of Funding: none Introduction The aim of this study was to compare the outcomes of on-clamp and off-clamp robotic partial nephrectomy (RPN). Methods The charts of all patients who underwent a RPN at 8 french departments between 2010 and 2014 were retrospectively reviewed. The patients who underwent an off-clamp RPN were matched to on-clamp RPN in a 1 to 4 fashion according to the following variables: RENAL SCORE, tumor size and surgeon’s experience. Pre, intra and postoperative datas were compared between the off-clamp and on-clamp groups. Results Among 525 RPN, 26 were performed off-clamp (5%). They were matched to 104 on-clamp RPN. In the off-clamp groups there were two types of tumors: small exophytic renal masses of low complexity (n=20; mean size=20 mm ; mean RENAL SCORE=4.7) and complex hilar tumors (n=6; mean size=50 mm ; mean RENAL SCORE=9.2). The complications rate (15.5% vs 7.7%, p=0.53), major complications rate (4.9% vs. 3.9%; p=0.82) and transfusions rate (0% vs. 4.9% ; p=0.58) did not differ significantly between the clamped and unclamped groups. Conversely, estimated blood loss was higher in the off-clamp group (266.4 vs 284.6 mL, p=0.048) and so was the rate of conversion to radical nephrectomy (0% vs 7.7%, p=0.04). There were no statistically significant differences between the on-clamp and off-clamp group in terms of preserving renal function in the early postoperative period (-6.9% vs. -0.2%; p=0.22) or at 6 months postoperatively (-5.7% vs. 0%; p=0.10). Conclusions Off-clamp RPN is feasible for a small subgroup of renal tumors without increased risk of post-operative complications but at the cost of higher estimated blood loss and increased risk of conversion to radical nephrectomy. This study did not show any significant differences between on-clamp and off-clamp RPN in terms of preserving postoperative renal function. Funding none
Authors
benoit peyronnet
khene zineddine benjamin pradere thomas seisen gregory verhoest alexandra masson-lecomte yohann grassano mathieu roumiguie jean-baptiste beauval stephane droupy alexandre de la taille hervé baumert nicolas doumerc jean-christophe bernhard christophe vaessen franck bruyere morgan roupret arnaud mejean karim bensalah |
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MP49-20 |
Multivariate assessment of robotic partial nephrectomy learning curve |
Kidney Cancer: Localized: Surgical Therapy II | 17BOS |
Abstract: MP49-20 Sources of Funding: none Introduction One of the presumed benefits of robot-assisted partial nephrectomy (RPN) would be a shorter learning curve compared to laparoscopic partial nephrectomy (LPN). To date, no study has aimed to assess the learning curve of RPN through a multivariate model, which has become the most accepted approach to analyze learning curve of surgical procedures The objective of this study was to evaluate the learning curve of the RPN through a multivariate model Methods The data of all patients who underwent an RPN in a single-center between 2010 and 2016 were collected prospectively. All RPN carried out by one of the surgeons were included in this study. The primary endpoint was the TRIFECTA defined as follows: no complications and warm ischemia time<25 minutes and negative surgical margins. According to the literature, the TRIFECTA achievement rate of an expert surgeon is 65% (Kalifeh et al, J Urol 2013). The achievement of TRIFECTA was analysed using a multivariate logistic regression model adjusting for surgeon experience, patients and tumors characteristics._x000D_ Results Two-hundred and one consecutive RPN performed by a single-surgeon were included in the study. Positive surgical margins rate was 3.4%, complications rate was 25.9% and mean warm ischemia time was 15.4 minutes. The TRIFECTA achievment rate was 67.2% when considering the whole cohort. According to the multivariate model, the « expert » level was reached after 60 procedures (figure 1). However, when performing a bootstraping projection, the TRIFECTA achievement rate would have continued to improve beyond the 200th procedure and would stabilize only after 500 procedures Conclusions In this study, the first to appropriately analyze the RPN learning curve through multivariate regression model, 60 procedures were necessary to obtain the outcomes of an expert surgeon. The boostraping allowed to estimate that perioperative outcomes could keep improving until the 500th procedure suggesting a longer learning curve than presumed. Funding none
Authors
benoit peyronnet
clara locher khene zineddine benjamin pradere romain mathieu gregory verhoest eric bellissant karim bensalah |
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MP50-01 |
Effect of Different Postoperative Pain Medications on Return for Unplanned Care after Ureteroscopy |
Stone Disease: Surgical Therapy V | 17BOS |
Abstract: MP50-01 Sources of Funding: none Introduction Ureteroscopy causes discomfort for patients postoperatively. This manifests as flank or bladder pain, and most postoperative medication regiments include a centrally acting opioid medication. Data on the most appropriate pain medication after ureteroscopy is limited. There is increasing scrutiny on narcotic prescriptions in America to reduce abuse, and narcotic use is associated with many undesirable and dangerous side effects. For this reason, we sought to evaluate whether different strengths of postoperative opioid medications impacted the rate of patient return to the emergency room (ER), unplanned clinic visits for pain, or overall 3 month readmission rate. Methods After IRB approval, retrospective chart review was performed for patients who underwent outpatient ureteroscopy for purposes of renal or ureteral stone removal from February 1, 2014 through March 31, 2016. The pain medication that was prescribed, and the patient’s postoperative course was evaluated for the first 3 months after surgery. Both ER visits, and clinic calls/visits were analyzed. Clinic and ER contacts were excluded if they did not pertain to urinary or flank pain. Pain medications were classified into 4 categories based on their DEA drug schedule: Schedule II, III, IV, and over the counter (OTC) medications. A Chi-square test was used for analysis. Results 475 patients were identified with complete charts and follow up. The results of our data are summarized in the table below. 199 patients received schedule II medicines, 165 received schedule III medications, 72 received schedule IV medications, and 39 received OTC medications. The rates of return to ER, clinic, or re-admission within 3 months were not significantly different from each other. Conclusions The strength of pain medication prescribed after ureteroscopy appears to have no bearing on whether a patient will contact the urologist due to pain. Specifically, medications such as hydrocodone and oxycodone, which have a higher abuse potential, do not prevent out of control pain in the postoperative period better than safer alternatives. Re-admission rate within 3 months was not impacted by postoperative pain medication either. This information should be considered to improve prescription narcotic stewardship in the world of increasing oversight, overdose, and abuse. Funding none
Authors
Preston Milburn
Graham Machen Amr Elmekresh Kristofer Wagner Erin Bird Marawan El Tayeb |
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MP50-02 |
The Impacted Ureteral Stone: Factors Predicting for Successful Outcome with Endoscopic Management |
Stone Disease: Surgical Therapy V | 17BOS |
Abstract: MP50-02 Sources of Funding: None Introduction Impacted ureteral stones have been variably defined as stones that have not moved for 2 months or that are not bypassable with a guidewire or with contrast. Impaction has been reported to lead to stricture rates as high as 24%, but the factors that predict for stricture formation, persistent hydronephrosis, or renal dysfunction have not been described in the literature. Methods A prospective series of 54 newly diagnosed consecutive patients with impacted ureteral calculi who were treated by a single surgeon between August 2014 and July 2016 with retrograde ureteroscopy and laser lithotripsy (URSLL) were assessed for preoperative (imaging and labs) and intraoperative (OR time, difficulty of case, need for stent, complications) factors. These factors were then correlated with outcome parameters including stone-free rates, complications such as stricture development, resolution of hydronephrosis, and change in serum creatinine. Results The average age of patients was 54 +/- 13 including 21 females and 33 males. Preoperative hydronephrosis was noted in 39 of the 49 patients (mild 19, moderate 14, severe 6). Serum creatinine was normal in 43 patients and elevated in 11. Site of impaction was proximal ureter in 18, mid ureter in 22, and distal ureter in 14. Mean stone size was 7.7 +/- 3.3 mm. Measured mean serum creatinine improved from 1.11 +/- 0.29 preoperatively to 0.97 +/- 0.18 post-operatively. Three patients had postoperative hydronephrosis, with a stricture diagnosed in the mid ureter in two patients. Both patients with strictures had failed initial URSLL at an outside institution which resulted in a severe inflammatory response with residual fragments likely embedded in the ureteral wall. Strictures were amenable to laser incision. Conclusions Impacted ureteral stones are successfully managed in 94% of patients with resolution of hydronephrosis and normal serum creatinine post treatment with URSLL. Preoperative factors such as hydronephrosis, elevated serum creatinine, stone size, and stone location do not reliably predict outcomes of URSLL for impacted stones. Intraoperative factors and technique are the most important factors affecting outcome. Silent obstruction can occur and all patients with impacted stones should have routine postoperative imaging to rule out hydronephrosis regardless of symptoms. Funding None
Authors
Sumit De
Sarina Gupta Megan Singh Rohit Chugh Harrison Bell Mantu Gupta |
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MP50-03 |
The Ureteric "Rendezvous procedure" to treat complex discontinuities |
Stone Disease: Surgical Therapy V | 17BOS |
Abstract: MP50-03 Sources of Funding: None Introduction The endoluminal approach is usually the first line to ureteric injury presenting early or late. In the cases of a failed antegrade or retrograde approaches to inserting a ureteric stent, the rendezvous procedure (RP), might be used to increase the success rate. The RP involves the antegrade insertion - with the assistance of uro-radiology, of a ureteric guidewire to the point of obstruction. The distal ureter is subsequently approached in a retrograde fashion via ureteroscopy - to the point of obstruction. A combination of methods can then be employed to traverse the discontinuity which is subsequently stented. Methods We retrospectively reviewed patients undergoing RP for ureteric discontinuities, treated between 2005 and 2016 at our Institution and completing at least a 12 month-follow up. We divided patients into two groups: late oncological/post-surgical stricture (group A), or early post-surgical obstruction, leakage or detachment (group B). If appropriate, we performed a retrograde study +/- rigid ureteroscopy to assess the stricture after 3 month from the procedure, followed by a MAG3 renogram at 6 and 12 months. Results 35 patients underwent a Rendezvous procedure, 25 in group A (Mean age 59.35, range: 49-74), 10 in group B (Mean age 52.44, range: 36-63). Strictures were successfully stented in 21 out of 25 patient (84%) in the group A, 7 out of 10 in group B (70%). After successful stenting, at 12 month 12/21 of group A required no further interventions and were stent free (56%), 7 (32%) were maintained with long term stenting. Only 2 (11%) required major reconstruction, 2 patients (11%) died during follow up from malignancy. In group B, 4/8 (50%) were stent free with no further interventions, 3/8 (38%) were maintained on long term stenting, only 1 required reconstruction. Conclusions With a combined antegrade and retrograde approach, the majority of complex ureteric stricture can be bridged and stented, avoiding major surgery in unfavourable circumstances and allows time for stabilisation and recovery of the patient. Interestingly, if successful, further interventions later may be unnecessary in up to 50-57% of patients. This is particularly useful in elderly patients with a malignant stricture, but also perhaps in young patients with benign discontinuities and a good blood supply to the ureter. Funding None
Authors
Giorgio Mazzon
Vimoshan Arumuham Rebecca Dale Marco Bolgeri Sian Allen Daron Smith Simon Choong |
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MP50-04 |
Preoperative DJ stent placement vs. direct ureteroscopy: a retrospective comparative study |
Stone Disease: Surgical Therapy V | 17BOS |
Abstract: MP50-04 Sources of Funding: None Introduction Ureteral stenting prior to ureteroscopy (URS) has been credited with improved stone-free rates and reduced operative times; however, the AUA guidelines on the surgical management of urolithiasis advocate against routine prestenting. We chose to compare the perioperative outcomes of patients with and without a ureteral stent at the time of URS at our institution. Methods After IRB Approval, a retrospective review of patients undergoing semi-rigid and/or flexible URS between February 2014 and April 2016 was conducted. Patient demographics and perioperative outcomes were compared based on the presence or absence of a double-J ureteral stent prior to URS. Nurse calls, return to the emergency department and readmission within 90 days were also compared. Chi-square analysis was used for categorical data while Student's t-test was used for interval data. Results 458 patients underwent URS during the study period. 295 patients were prestented (psURS) while 163 went directly for ureteroscopy (dURS). There was no difference in age, mean ASA score, indication for surgery or mean stone size (Table 1). PsURS had more proximal ureteral stones while dURS had more distal stones. PsURS was also more likely to have UTI prior to surgery. Prestenting did not influence operative time and psURS patients were more likely to undergo flexible URS (Table 2). The psURS cohort utilized an access sheath more often (p <0.001) and had less ureteral dilation (p<0.001). There was failure to reach the stone in 3 patients undergoing dURS vs. 0 patients with psURS (p=0.02); however, there was no difference in stone-free rates (p = 0.37). There was no increased risk of ureteral injury in the dURS cohort (p = 0.24). PsURS and dURS yielded no difference in calls to the nurse (p =0.20) and return to the ED within 90 days (p= 0.80). Readmission within 90 days was more likely after psURS (32 vs. 7 readmissions, p = 0.02). Conclusions Presence of a ureteral stent at the time of URS offers no advantage vs. dURS, but is associated with an increased risk of readmission within 90 days. Funding None
Authors
Andrew Navetta
Trey Durdin Amr Elmekresh Adam Cohen Marawan El Tayeb |
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MP50-05 |
Impact of laser fiber tip cleavage on power output for ureteroscopy and stone treatment |
Stone Disease: Surgical Therapy V | 17BOS |
Abstract: MP50-05 Sources of Funding: None Introduction Holmium:YAG laser is the most used laser for urolithiasis treatment. As recommended in the literature, we use metallic scissors to cut the fiber tip in order to restore its effectiveness._x000D_ Many cleaving methods have been described to avoid the fiber damage and to restore its greatest power such as metallic surgical scissors, scalpel, ceramic scissors or strippers. The aim of this study was to compare different methods of cleavage in order to improve the use of the laser in endo-urology. Methods New single use 272µm fibers (Rocamed®) were used with the MH01-ROCA FTS30W (Rocamed®) lithotripter. Five different kinds of fiber tip were compared: a new intact fiber, cleaved with ceramic scissors, cleaved with metallic scissors, first cleaved with ceramic scissors then stripped and first stripped then cut with ceramic scissors (Figure 1A-1B). The fibers were used against synthetic stones, with fragmentation and dusting settings. We measured power output at 0, 1, 5, 10 and 15 minutes and evaluated the laser beam after 1 minute (Figure 1C). Results At t0, all the fibers had less than 7.5W. For fragmentation parameters (Figure 2A), there was a statistical difference between the 5 groups at 0 minutes (p=0.042) and 1 minute of laser use (p=0.042). After 1 minute of laser use, there was no statistical differences between the 5 groups. For dusting parameters (Figure 2B), there was a statistical difference at 0 minutes (p=0.022). At the 1-minute analysis and after, all the results were not statistically different. _x000D_ Laser fibers are made with two layers of silica with different refractive indices, which allow the light to travel along the fiber until the fiber tip. When the interaction of the two layers of silica is damaged, as in lithotripsy, or after cleaving the fiber, the energy leaks through the fissures and the power output is decreased. Conclusions Cleaving the fiber tip may restore its effectiveness to the fiber but, as we demonstrated, only for a limited time. Though, cleaving the fiber tip may preserve the scopes from damages._x000D_ Funding None
Authors
Mattieu Haddad
Esteban Emiliani Steeve Doizi Yann Rouchausse Frederic Coste Laurent Berthe Olivier Traxer |
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MP50-06 |
Hydronephrosis After Ureteral Access Sheath Use |
Stone Disease: Surgical Therapy V | 17BOS |
Abstract: MP50-06 Sources of Funding: None Introduction Ureteral access sheaths (UAS) are commonly used at the time of ureteroscopic lithotripsy (URSL) for the treatment of nephrolithiasis to facilitate multiple scope passages, stone extraction, and improve irrigation flow. There is a potential risk of ureteral injury and stricture formation with UAS use. We sought to review our UAS experience to better define both the risk of and predictors of post-operative hydronephrosis and ureteral strictures. _x000D_ _x000D_ Methods 531 consecutive URSL with UAS (12/14 Fr) at a tertiary care center by a single surgeon were retrospectively reviewed between September 2010 to March 2016. We evaluated patient factors, operative details, and post-operative imaging in patients undergoing URSL with UAS. Results Ureteral access sheaths were successfully placed in 506 (95.3%) of patients. Table 1 lists the demographics and stone characteristics of the cohort. The mean aggregate stone size was 15.4 mm. 272 (51.4%) patients had a pre-operative stent. 74 (14%) patients needed additional procedures to clear residual stone burden. 53 (10%) patients had hydronephrosis on post-operative imaging. The hydronephrosis was mild in 39 (73.6%), moderate in 12 (22.6%), and severe in 2 (3.8%) patients. Follow-up demonstrated that hydronephrosis resolved without intervention in 39 (73.6%) of patients. The mean time to resolution of hydronephrosis on imaging was 222 days. An additional 10 (18.9%) of patients had persistent hydronephrosis without evidence of obstruction on functional imaging. Four patients (7.5%) had persistent hydronephrosis and some degree of obstruction on functional imaging. Univariate analysis found that an unsuccessful UAS placement was the only predictor for the development of post-operative hydronephrosis (28% vs 9.1%, p=0.002) Conclusions UAS use at the time of URSL was successful in most patients and the risk of long-term obstruction is low. Post-operative hydronephrosis was observed in 10% of patients, however the majority of this hydronephrosis was mild and resolved without intervention. Funding None
Authors
Brandon Otto
Stephanie Stillings VINCENT BIRD |
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MP50-07 |
Comparison of Parameters of standard reusable flexible uretero-renoscopes with a single use uretero-renoscope (Lithovue) |
Stone Disease: Surgical Therapy V | 17BOS |
Abstract: MP50-07 Sources of Funding: None Introduction The new single use digital flexible ureteroscope (fURS), LithoVue is an evolution in digital ureteroscope design. We aimed to assess the capability of this instrument in-vivo and in-vitro, and to compare it to commonly used flexible ureteroscopes in regard to these metrics and also its cost effectiveness Methods An analysis of standard flexible ureteroscope (Olympus URF-V) usage at our institution over 30 months was performed for a cost analysis of fURS practice. The LithoVue was then examined in-vitro for manoeuvrability and flow and compared to Olympus URF-V and Stortz Flex Xc. Finally, LithoVue was used in 3 patients for the treatment of renal calculi. The single-use ureteroscope (Lithovue®, Boston Scientific) and two reusable scopes (URV-F®, Olympus and Flex-Xc®, Karl Storz) were assessed. Angulation and irrigation fluid flow were examined first with an empty working channel and than with various instruments engaged: _x000D_ - hydrophilic guide wire _x000D_ - hydrophilic tip wire _x000D_ - laser fiber (200µm)_x000D_ - basket (1.9Fr) _x000D_ - biopsy forceps (3Fr)_x000D_ Results With regard to cost analysis 265 fURS procedures were performed over the study period. 20 instances of ureteroscope damage occurred – classed as 15 major and 5 minor. Total cost of repairs was $162,587 AUD. Including purchase price and repair costs, mean cost per fURS case was $1883 AUD. In regard to performance metrics, with an empty working channel the Lithuvue was superior to both the URF-V and Flex Xc in terms of movement. Flexion of the Lithovue is 285°, while the URF-V is 180° and the Flex Xc is 283°. Deflection for the Lithovue is 286°, the URF-V is 270° and the Flex Xc 219°. Superiority of the Lithovue over the two other ureteroscopes was maintained for movement in both directions with a variety of instruments placed within the working channel. Finally, the LithoVue was demonstrated to display satisfactory ergonomics, manoeuvrability and image quality in the treatment of renal stones in 3 patientsInstruments decreased the angulation range and fluid flow. However it was still possible to bend tested devices to almost 180 degrees in every case, which should be enough to reach all kidney calyxes. Furthermore there were only slight differences in fluid flow in used scopes Conclusions This version of a single use disposable flexible ureteroscope offers similar technical specifics to multiple use flexible ureteroscopes in regard to range of flexion and extension, and also in regard to fluid flow rates. It is likely to find utility in aspects of endourologic practice depending upon pricing issues. Based on purchase costs and rate of repair it may also represent a cost saving for hospitals in regard to an amortised cost per case for this procedure. Funding None
Authors
Grzegorz Fojecki
Derek Hennessy Nathan Lawrentschuk Damien Bolton |
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MP50-08 |
Limitations of the Lithovue single use digital flexible ureteroscope |
Stone Disease: Surgical Therapy V | 17BOS |
Abstract: MP50-08 Sources of Funding: None Introduction A new disposable flexible digital ureteroscope (Lithovue, Boston Scientific, Marlborough, Mass) was recently released as an alternative to nondisposable digital scopes. This series reviews our initial experience with this new device with a focus on identifying its limitations. Methods We retrospectively reviewed our first 75 cases with the 7.7Fr disposable flexible digital ureteroscope and identified any problems, difficulties, or complications related to the scope itself. Results Of the 75 patients, 47 were female 28 were male; 39 cases were left sided, 30 were right sided, and 6 were bilateral. The reasons for ureteroscopy include stone disease in 60 pts, ureteral stricture disease in 5 patients, and upper tract transitional cell carcinoma (TCC) in 10 patients. There was difficulty in getting up the ureter (ureterovesical junction) in 3 patients; one due to distal ureteral narrowing requiring balloon dilation, the other 2 due to proximal ureter narrowing requiring stenting. Passage of the scope was relatively effortless in the remaining retrograde URS patients. Two patients underwent antegrade ureteroscopy through an established nephrostomy tract to treat ureteroenteric anastomotic strictures. _x000D_ There was mild interference in the video system during laser lithotripsy of hard stones (calcium oxalate monohydrate but did not prevent treatment. But the system was incompatible with the use of electrocautery. During fulguration of upper tract TCC, the system continually shut down during the use of a 3Fr electrode. Another difficulty with visualization occurred during antegrade ureteroscopy for 2 ureteroileal anastomotic strictures. Due to problems with distant focusing, there was difficulty identifying the true lumen past the stricture, which lead to inaccurate incision of the soft tissue resulting in extravasation in both cases. _x000D_ Conclusions This new disposable ureteroscope works well for routine ureteroscopy with laserlithotripsy but should not be used with electrocautery and avoided for antegrade incision of ureteroenteric anastomotic strictures. Its strength is in near focusing rather than distant focusing which is fine for stones but not for the latter situation. Funding None
Authors
Saum Ghodoussipour
Eli Thompson Adit Shah Anirban Mitra Sameer Deshmukh Matthew Dunn |
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MP50-09 |
Robotic Flexible Ureteroscopic Treatment of Renal and Ureteral Calculi: First-In-Man Experience with a Novel Robotic System |
Stone Disease: Surgical Therapy V | 17BOS |
Abstract: MP50-09 Sources of Funding: The study was funded by Auris Surgical Robotics. Introduction To present the first in man experience with the Robotic Endoscopy System (RES) for the treatment of renal and ureteral calculi. Methods The RES is a novel system comprised of a remote-driven robotic flexible ureteroscope and robotic access sheath. The robotic ureteroscope incorporates digital optics and the system has the ability to control the laser fiber and irrigation inflow-outflow remotely. The system has a stroke length to navigate the collecting system from the urethra to the kidney. The primary performance endpoint was completion of the intended procedure; the primary safety endpoint was incidence of perioperative complication. The RES performance was graded on a visual analog scale of 1 (worst) to 10 (best) for stability, ease of locating stones, ability to fragment, control and visualization. P values were calculated using the Mann-Whitney U test or Fisher's exact test. Results Of 18 screened adult patients, 16 underwent flexible robotic ureteroscopy (11 with 1; 4 with 2 and 1 with 3 stones). Two patients were excluded intraoperatively due to ureteral strictures. The twenty-two treated stones were distributed throughout the collecting system (n = 7 lower pole, n = 5 renal pelvis, n = 5 interpolar, n = 3 upper ureter, n = 1 upper pole and n = 1 distal ureter). Median stone size was 10 (6 to 20) mm. All procedures were completed successfully using robotic control. One patient experienced fever (101 °F) that resolved without intervention. Overall, median total procedure time (TPT) was 73.5 (range = 21 to 131) minutes; median total robot time (TRT) was 42 (6 to 99) minutes. In patients with a single stone only, median TPT decreased from 98 (50 to 131) minutes (first 5 cases) to 40 (21 to 77) minutes (last 6 cases), P = 0.036; median TRT also decreased from 44 (20 to 89) minutes (first 5 cases) to 19.5 (6 to 43) minutes (last 6 cases), P = 0.055. In 5 patients with lower pole stones, median TPT was 50 (21 to 131) minutes; median TRT was 20 (16 to 76) minutes. Stability, ease of locating stone and control, as evaluated by number of scores greater than 9, improved significantly in the last 6 cases(P = 0.035). Conclusions The robotic ureteroscopy with calculi lithotripsy is safe and feasible using the RES. Future comparative studies to manual ureteroscopy are warranted. Funding The study was funded by Auris Surgical Robotics.
Authors
Mihir Desai
Shashikant Mishra Abhishek Singh Ravindra Sabnis Arvind Ganpule Mahesh Desai |
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MP50-10 |
Predicting Postoperative Fever and Systemic Inflammatory Response Syndrome After Ureteroscopy |
Stone Disease: Surgical Therapy V | 17BOS |
Abstract: MP50-10 Sources of Funding: None. Introduction Ureteroscopy (URS) is the standard of care for surgical management of small upper urinary tract stones. A common and life-treating complication of URS is post-operative infection. The objective was to identify risk factors for post-operative fever (POF) and systemic inflammatory response syndrome (SIRS) after URS. Methods We identified 2375 URS performed for stone disease in an integrated healthcare delivery system from 2008-2014. The primary outcome was POF (temperature greater than 100.4F) or SIRS (yes/no). The study team selected preoperative and intraoperative risk factors for data collection a priori. Univariate comparisons were performed between those who had POF/SIRS and those who did not. Variables with a p value <0.1 were entered into a stepwise logistic regression model. Results A total of 179 out of 2375 patients had POF/SIRS (7.5%). Subjects with POF/SIRS were older, female, had higher body mass index (BMI) and Charlson comorbidity index (CCI), bilateral stones, stone size >= 1cm, renal location, pre-stenting, positive preoperative urine culture, and post-operative antibiotics. Table 1 demonstrates the univariate analysis of candidate predictors and POF/SIRS. Sex, CCI, laterality (unilateral or bilateral), stone location (renal, ureteral, or both), and type of ureteroscope comprised the final model (Table 2). Conclusions Female sex, higher CCI, using both flexible and semi-rigid ureteroscopes, renal stones, and bilateral stones are associated with POF/SIRS after URS. This data may be used to identify and counsel high-risk individuals for surgical planning. Funding None.
Authors
Andrew Higgins
Amanda Young Korey Kost Brielle Schreiter Marisa Clifton Brant Fulmer Tullika Garg |
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MP50-11 |
The surgical experience influences the safety but not efficacy of RIRS for kidney stones: a propensity score analysis |
Stone Disease: Surgical Therapy V | 17BOS |
Abstract: MP50-11 Sources of Funding: none Introduction The safety and the efficacy of Retrograde IntraRenal Surgery (RIRS) is influenced by many factors such as stone burden and location but also by technical skills of the operating surgeon . The aim of this study is to evaluate if the surgeon experience could influence the outcomes of RIRS in terms of stone clearance and complication rate. Methods Data of patients who underwent RIRS for kidney stones were prospectively collected. Cases were divided in 2 groups. Group 1: cases operated by 3 surgeons in the early phase of learning curve (surgical experience less than 100 RIRS); Group 2: cases operated by two surgeons with a great experience in endourology (>400 RIRS). Patients and stone data, results and safety outcomes were analyzed. Multivariable regression model was used. Differences between groups was estimated using propensity scores to adjust for the bias inherent to the different patient characteristics Results 381 RIRS were analyzed (Group 1: 150 RIRS; Group 2: 231 RIRS). The clinical data and stone parameters were comparable between 2 groups (Table1). _x000D_ The SFR was 70% in Group 1 and 77.9% in Group 2 (p=0.082). Operative time was significantly shorter in the Group 2 (76.3 vs. 53.1min, p=0.001). _x000D_ The overall complication rate was significantly lower in Group 2 (20.7 vs. 8.7 p=0.001) (Table 2). _x000D_ At unadjusted analysis, a non significant difference was found between centers on SFR (OR 1.51 95%CI 0.95 to 2.41). Conversely, a significant difference was found on overall complications at unadjusted analysis (OR 0.36 95%CI 0.20 to 0.67) with lower overall complication in Group 2. Both results were confirmed by propensity score analysis (Fig.1 and Fig.2)._x000D_ Conclusions This study shows that surgeon experience influences the outcomes of RIRS mainly in terms of safety. Further studies will be needed to assess the exact number of procedures necessary to obtain a plateau in the rate of complications and success Funding none
Authors
Francesco Berardinelli
Piergustavo De Francesco Luca Cindolo Silvia Proietti Orietta Dalpiaz Derek Hennessey Cecilia Cracco Cesare Scoffone Luigi Schips Guido Giusti |
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MP50-12 |
Percutaneous nephrolithotomy in low body mass index patients: Can thinness influence perioperative outcomes and complications? |
Stone Disease: Surgical Therapy V | 17BOS |
Abstract: MP50-12 Sources of Funding: NONE Introduction Despite a considerable increase in obese and overweight population, there is also a significant portion of underweight people worldwide. There are plenty of papers about the relationship of the different BMI indexes on PCNL outcomes and morbidities. However, there is no literature about the correlation between underweight and PCNL results. The aim of the study was to compare perioperative variables of PCNL in patients with BMI scores, and to explore whether they have an effect on the outcomes of this surgery._x000D_ Methods We conducted a single-center retrospective evaluation of perioperative outcomes and complications in 182 patients who underwent PCNL surgery between 2010 and 2012. Patients were stratified as underweight BMI less than 18.5 kg/m2, normal weight BMI 18.5 to 24.99 kg/m2, overweight 25 to 29.99 kg/m2, and obese more than 30 kg/m2.The groups were assessed in terms of baseline characteristics, intraoperative and postoperative variables, including minor and majors complications. One-way ANOVA and univariate logistic regression analysis were used to assess the association between BMI (classified into 4 levels) and variables mentioned._x000D_ Results The distributions of the 182 patients in each BMI category were underweight 21 (12%), normal body weight 38 (21%), overweight 72 (39%), and obese 51 (28%). Most of the patients (91.2%) underwent previous unenhanced computed tomography scan in which 38% showed large pelvic stones, 41% staghorn and 2% of anomalous kidneys. There was no difference in the baseline characteristics of groups with respect to age, sex, or stone size. Stone free rates showed no significant differences between groups (p=0.76). Operative time was significantly longer in obese patients (p=0.001). On the other hand, postoperative leakage in days, and the presence of postoperative fever, was significantly higher in the underweight group (p=0.001). There was also one colonic perforation reported in the low BMI group._x000D_ Conclusions PCNL has demonstrated to be an efficacious and safe procedure in patients with different BMI scores. Our findings suggest that low BMI patients could be at higher risk of perioperative morbidities. Further investigation with a larger series of patients is needed to confirm this observation. Funding NONE
Authors
Jose Agudelo
Euro Arias Jhonan Chirinos Nasser Ktech Luis Urdaneta Juan Bustamante Manuel Riveros |
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MP50-13 |
Initial Lower Pole Access for Complete Staghorn Calculi: Is it Feasible without Compromising Success? |
Stone Disease: Surgical Therapy V | 17BOS |
Abstract: MP50-13 Sources of Funding: None Introduction Percutaneous nephrolithotomy (PCNL) is the treatment of choice for patients with staghorn calculi. Opinions tend to vary whether an upper pole (UP) versus lower pole (LP) approach offers the best access. The literature suggests an UP approach is more favorable due to higher stone-free rates (SFR), however this access carries a higher risk of bleeding and pleural injury. We developed a modified LP (more medial and inferior puncture angle) to allow single tract staghorn removal with better stone free rates while minimizing thoracic complications and compared this technique to primary UP access PCNL outcomes for staghorn stones._x000D_ Methods In this IRB approved retrospective analysis, 79 out of 473 patients had PCNL for staghorn calculi. 58/79 underwent our modified LP access technique and 21 patients had primary UP (17) or interopolar (4) access. Outcomes assessed included stone free rate (SFR), and number of punctures, EBL, OR time, and intra- and post-op complications._x000D_ Results A total of 58/79 (73%) patients received initial LP access using our modified technique. Of these 58 patients, 45 (78%) needed only a single tract, while 13 needed multiple accesses. In patients having primary UP access, 13/17 (76%) required only a single tract (no statistical difference). SFR’s are in Table 1. Complication rates were 6.7% for primary single site LP access (3.5% for all LP initial punctures) vs. 23.1% for primary single site UP access (29.4 for all UP initial punctures) (p < .05). There was no statistical difference in EBL, fluoro time, LOS, stone volume, or stone density among the groups. OR time was less in the single tract LP group (113 min vs. 148 min, p=0.006). There were 2 pulmonary complications in the UP group, with none in LP group; Table 1._x000D_ Conclusions Our modified LP access technique was feasible in 73% (58/79) of staghorn patients without increasing the need for multiple tracts compared to primary UP access. Complication rates were lower and SFR rates higher for our modified technique, which will be described in detail. _x000D_ Funding None
Authors
Kyle A. Blum
Egor Parkhomenko Julie Thai Timothy Y. Tran Mantu Gupta |
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MP50-14 |
Percutaneous Nephrolithotomy in a Free-Standing Ambulatory Surgery Center: First 100 Cases Reported |
Stone Disease: Surgical Therapy V | 17BOS |
Abstract: MP50-14 Sources of Funding: None Introduction Percutaneous Nephrolithotomy (PNL) is a procedure that has traditionally been performed in an inpatient setting with at least an overnight stay. Many surgical procedures have evolved over time from an inpatient setting to an ambulatory surgery center (ASC) setting. Feasibility of Ambulatory PNL (aPNL) was shown in our initial pilot series of 25 cases.1 This 100 case series is reviewed to further evaluate outcomes with a more robust data set. Methods We present a series of our initial 100 patients who underwent PNL in an ASC from April 2015 to October 2016. Each aPNL was performed by a single surgeon with the same operative team. The surgeon and operative team had extensive experience with PNLs performed in a hospital setting. All procedures were performed with the operative surgeon obtaining renal access and all procedures were performed tubeless (ureteral stent without a nephrostomy tube). All patients also had hemostatic plugs placed into the access tract with a local intercostal block performed to aid with pain control.2 All cases were reviewed and demographic date and case details were analyzed. Results Of the 100 aPNL reviewed (Table 1), there were 50 women, 52 left side, mean age 57 (21-83), mean BMI 30 (19-45), and mean stone burden 27mm (10-110). Stone free rate was 96%. Four patients had complications. One Clavien 4a pulmonary embolism (PE) required a 7 day hospital admission. There were three Clavien 1 presentations (two for pain and the other for nausea) of which two required hospital admission. Conclusions This consecutive 100 case series further demonstrates the safety of aPNL. While four patients experienced complications; none of the outcomes of the adverse events were affected by the site of service. The patients experienced complications not uncommon to many types of procedures (post-operative pain and nausea) that were managed with an ER visit or short hospital stay. The PE was managed in a routine manner. With an experienced surgeon, well trained operative team and with modifications to the procedure focusing on post-operative pain control, PNL can be safely and effectively performed in an ASC. Ongoing collaborative data collection is needed to continue to evaluate the safety of aPNL._x000D_ _x000D_ 1 Davalos JG J Urol April 2016 S1: MP57-11_x000D_ 2 Abbott JE J Endourol March 2015_x000D_ Funding None
Authors
Julio Davalos
Joel Abbott |
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MP50-15 |
Assessing the Volume-Outcome Relationship for PCNL in 2014 and 2015 - Analysis using National Registry Data of over 4000 Cases |
Stone Disease: Surgical Therapy V | 17BOS |
Abstract: MP50-15 Sources of Funding: none Introduction This study aims to investigate the relationship between surgeon case volume and outcomes after percutaneous nephrolithotomy (PCNL) within the UK._x000D_ Methods The study used data from the BAUS registry, a mandatory databse which records information on all PCNLs performed, for 2014 and 2015. Details were retrieved from the highest quartile volume surgeons and compared to the lowest quartiule volume surgeons._x000D_ _x000D_ A series of comparisons of outcomes was then made between the high volume and the low volume groups. These outcomes included clearance on imaging at day one, blood transfusion, sepsis, complcations and post-operative length of stay. These comparisons were made for all stones accoridng to their Guys Stone Score (GSS) complexity, graded from 1-4. Comparisons were carried out using Fishers exact test._x000D_ Results 4035 PCNL were recorded. Those surgeons in the lower quartile performed 5 and 4 PCNLs or less in 2014 and 2015 respectively, and those in the upper quartile over 18 and 17 in the same time frames._x000D_ _x000D_ Overall stone clearance, by imaging at day one, was higher in the higher volume surgeons for GSS1 (93% v 80%, p=0.01), GSS2 (74% v 63%, p=0.01), GSS3 (66% v 50%) and GSS 4 stones (37% v 35%, p=0.41), although not significantly for the latter. There was no difference in post op transfusion rates or sepsis. Conplication rates were higher for lower volume surgeons (9.6% v 4.7%, p=0.009)._x000D_ Conclusions Lower volume surgeons have higher complcations rates and lower stone free rates after PCNL. _x000D_ Funding none
Authors
John Withington
Sarah Fowler James Armitage Jonathan Glass William Finch Stuart Irving Neil Burgess Oliver Wiseman |
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MP50-16 |
Initial clinical experience with a single-use digital flexible ureteroscope |
Stone Disease: Surgical Therapy V | 17BOS |
Abstract: MP50-16 Sources of Funding: none Introduction The purpose of this study was to evaluate the initial clinical experience with a single-use digital flexible ureteroscope (LithoVueâ„¢ Single-use Digital Flexible Ureteroscope, Boston Scientific Corporation, Marlborough, MA) Methods A retrospective review was performed of all cases utilizing LithoVueâ„¢ Single-use Digital Flexible Ureteroscope at 11 institutions. Results A total of 159 ureteroscopy procedures were performed, which included 184 renal units. Mean operative time was 61 minutes (standard deviation 34.8 minutes). Ureteroscopy was performed for treatment of 40 ureteral stones (mean diameter 7.6 mm), 119 renal stones (mean diameter 12.2 mm), 6 ureteral tumors, and 5 renal pelvis tumors. Ureteral access sheath was used for 53.8% of renal units, and ureteral stent was left in 77% of renal units. There were no major surgical complications. There was 1 case of technical equipment failure (image disappeared, surgeon changed to reusable ureteroscope), 3 cases of failure to reach a stone (2 lower pole, 1 calyceal diverticulum). Electrocautery artifact of the digital image limiting use of electrocautery was noted during 2 procedures for urothelial carcinoma._x000D_ _x000D_ Conclusions LithoVueâ„¢ Single-use Digital Flexible Ureteroscope was used successfully in this initial clinical series of over 150 cases. In this pilot study, procedure failure rate was not inferior to reported rates of failure for reusable ureteroscopes. Funding none
Authors
Thomas Chi
Marshall Stoller Harrison Abrahams Vincent Bird Matthew Dunn Guido Giusti Silvia Proietti Kelly Healy Scott Hubosky Dylan Isaacson Francis Keeley Ravi Munver Olivier Traxer Michele Taslo Oliver Wiseman Manint Usawachintacit Brian Eisner |
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MP50-17 |
A review of percutaneous nephrolithotomy for small (less than 1cm) and staghorn renal stones: outcomes from the UK national data registry |
Stone Disease: Surgical Therapy V | 17BOS |
Abstract: MP50-17 Sources of Funding: None Introduction PCNL is an effective method of treating renal stones. Surgeons in the UK performing PCNL are mandated to submit data to the PCNL national registry. This study looks at differences in management and outcomes of patients with two subsets of stones: those under 1cm compared to all other stones and staghorn stones compared to all others treated by PCNL._x000D_ Methods The registry was analysed for stone characteristics (stones up to 1cm, staghorn stones and all others), procedure details and outcomes (complications and stone free rates) for the two year period period January 2014 - December 2015. The fisher test was used for statistical analysis except for length of stay (LOS) which used confidence interval analysis._x000D_ Results A total of 4166 procedures were performed by 183 UK surgeons (median number 17) over this time period. Of these 404 (9%) were for stones <1cm and 600 (14%) for staghorn stones. All other stones accounted for the remaining 3162. Females were more likely to have a staghorn stone (p < 0.01). Larger amplatz sheath sizes (27ch+) were used for staghorn stones (78% vs 29 % for smaller stones p<0.01). Staghorn stones were more likely to have a post-procedure nephrostomy tube (78% vs 69% for smaller stones, p<0.05) whereas stones <1cm were less likely to have a post-operative nephrostomy tube (p < 0.01).Overall intra-operative and post operative complications lower in the stones <1cm group (<0.05) where as these were higher in the staghorn group (sepsis p < 0.01 and transfusion rates p = 0.04) compared to all other stones. There was no difference in more severe (Clavien III+) complications in any of the stone size groups. LOS was significantly shorter for stones <1cm (mean LOS 3.09 days) and longer for staghorn stones (mean LOS 4.71 days). Stone free rates were as stones <1cm were as follows: 72.5% on fluoroscopic imaging and 77% on imaging at follow up. Stone free rates for staghorn stones were 44.8% on fluoroscopic imaging and 46.9% on imaging at follow up._x000D_ Conclusions Around 10% of PCNLs in the UK between Jan 2014 and Dec 2015 were done for small stones <1cm. Excellent stone free rates are achieved with few complications. It is expected that with miniturisation techniques, PCNL for small stones will continue to be utilised as an effective treatment option. 14% of all PCNLs performed in the UK were for staghorn stones. PCNL for staghorn stones was less likely to achieve complete stone clearance compared to other stone sizes (p < 0.01). Complications were higher in the staghorn stone group compared to PCNLs for smaller stone sizes and overall length of stay was longer._x000D_ Funding None
Authors
Ben Pullar
John Withington James Armitage Sarah Fowler William Finch Stuart Irving Jonathon Glass Neil Burgess Oliver Wiseman |
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MP50-18 |
Single Session Bilateral Versus Staged Bilateral Ureteroscopy for Nephrolithiasis: An Assessment of Safety and Efficacy |
Stone Disease: Surgical Therapy V | 17BOS |
Abstract: MP50-18 Sources of Funding: None Introduction While single session bilateral ureteroscopy (URS) (SSBU) has the advantage of one anesthetic procedure, some may pursue a staged approach due to the potential higher risk of complications and patient discomfort with two ureteral stents. The aim of this series is to compare outcomes of patients undergoing SSBU to those undergoing staged URS for bilateral nephrolithiasis. Methods We retrospectively identified patients undergoing SSBU and staged URS for nephrolithiasis between September 2007 and January 2014. Preoperative characteristics, intraoperative techniques, and postoperative outcomes were compared. Stone burden was calculated as cumulative stone diameter. Residual stone fragments were defined as any stone visible on postoperative imaging. Results Sixty-three nonconsecutive patients underwent SSBU and 37 underwent staged URS. Patients undergoing SSBU had significantly more stones in mid pole calyces (28% versus 16%, P = 0.0008) and the renal pelvis (5% versus 2%, P = 0.048), though both groups had similar stone burden based on cumulative maximal diameter (Table 1). Patients undergoing SSBU had longer operative time when compared to any single stage URS, however, total operative time was significantly longer for staged URS (139 versus 86 minutes, P < 0.0001) (Table 1). Patients undergoing staged URS were more likely to require laser lithotripsy per renal unit (RU) (99% versus 71%, P = 0.0001) and have a ureteral stent placed at the end of the procedure (96% versus 81% RUs, P = 0.003). There were no significant differences in complications, emergency room (ER) visits, need for additional procedures, or stone free rates (SFR). Conclusions SSBU is safe and effective with overall shorter operative times and similar SFR compared to staged URS. For patients with bilateral nephrolithiasis, urologists should strongly consider SSBU to limit anesthetic exposure, overall operative time, and health care costs. Funding None
Authors
Gabriel Fiscus
Tracy Marien Teerayut Tangpaitoon Joseph Kuebker Duke Herrell Nicole Miller |
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MP50-19 |
Intra-renal pressures during RA-RIRS (Robotic Assisted Retrograde Intra-renal Surgery): A critical evaluation based on ureteral access sheath (UAS) size and irrigation flow rate |
Stone Disease: Surgical Therapy V | 17BOS |
Abstract: MP50-19 Sources of Funding: None Introduction To evaluate effects of varying UAS sizes (10/12F - 12/14F) and changing irrigation flow rates modulated by custom designed pump system, on RA-RIRS intra-renal pressure levels. Methods To evaluate changing irrigation flow rate effects on intra-renal pressure values during RA-RIRS, a customized pump system adjusted for stepwise flow rate increases between 5-60 ml/min, was connected to two different flexible uretero-renoscopes (FlexX2 and FlexXC, Karl Storz GmbH, Germany) coupled to the Avicenna Roboflex. Free channel flow rates through each instrument working channel were measured several times for a set irrigant height. After assessing baseline flow rates with constant flow, the study was repeated using a custom designed pump system (ELMED, Turkey). RA-RIRS intrarenal pressures were measured percutaneously using 4 different manufacturer’s access sheaths positioned in the proximal ureter (9.5/11.5F Cook, 10/12F Rocamed, 10.7/12.7F Cook and 12/14F Boston Scientific). Studies were repeated subsequently in the Minnesota University kidney model with calyceal puncture, as with patients. Results Smaller sized UAS ( 9.5/11.5F) limited irrigant efflux along the outer side and resulted in increased intrarenal pressures in a short time even without a pump system. For larger UAS sizes, intrarenal pressures continued to remain <30cmH2O even with irrigation rates of up to 20ml/min. Lastly, when 12/14F UAS was used, intrarenal pressures were < 30cmH2O despite irrigation flow rates up to 60ml/min. Conclusions Using an appropriate sized UAS during RA-RIRS is of paramount importance. Careful irrigant flow rate adjustment with precisely controlled intrarenal pressure values, preferably using a specially designed pump system, can enable surgeons to perform RA-RIRS safely with clear vision with larger UAS sizes. This approach may increase stone free rates, and reduce pressure build-up plus infection-related complication risk, particularly in cases with large and complex stones needing longer operating times. Funding None
Authors
Nida Zafer Tokatli
Kemal Sarica Ahmet Sinan Kabakci Remzi Saglam Anup Patel |
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MP50-20 |
Does preoperative alpha blockers facilitates ureteroscope insertion at vesico ureteric junction? An answer from a prospective randomized study. |
Stone Disease: Surgical Therapy V | 17BOS |
Abstract: MP50-20 Sources of Funding: none Introduction To evaluate whether alpha blockers facilitate the negotiation of the ureteroscope through the ureteric orifice, if administered preoperatively, based on the role of alpha blockers mainly tamsulosin in MET of ureteric calculus. Methods A prospective, randomized study of 174 patients who underwent ureteroscopic stone removal for lower or mid ureteric calculi between November 2014 and March 2016. We included patients above the age of 14 years who were planned for ureteroscopic stone removal. We divided the patients into two groups, as those who were not prescribed alpha blockers prior to surgery (Group A – No alpha blocker; NAB) and group B including those patients who were started on alpha blockers tamsulosin 0.4 mg 3 days prior to surgery (Group-B - Alpha blocker; AB). We excluded patients with stone size > 1 cm, spontaneous stone passage prior to surgery, unable to perform URS and previous history of ureteroscopic intervention. Results Our study included 124 patients, among them 60 patients were prescribed alpha blockers preoperatively (group B). Mean age of the study population was 37.62 + 9.74 (15-64 years). Mean stone burden was 38.92 + 8.21 (15.94 - 58.12 mm2). The difference in rate of ureteroscope negotiation through ureteric orifice between NAB and AB group was not statistically significant (p=0.57). Conclusions In URS, preoperative administration of alpha blockers failed to demonstrate the benefits of technical ease and lower complication rate. Further large group, multi-centric studies required to reach up a definitive role of alpha blockers prior to URS. Funding none
Authors
Ashok Sokhal
Satyanarayan Sankhwar Apul Goel kawaljit Singh |
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MP51-01 |
Concurrent validation of automated evaluation of robotic surgery performance: correlation of performance metrics to Global Evaluative Assessment of Robotic Surgery (GEARS) |
Surgical Technology & Simulation: Training & Skills Assessment I | 17BOS |
Abstract: MP51-01 Sources of Funding: None Introduction Global Evaluative Assessment of Robotic Skills (GEARS) is a validated but subjective and time consuming tool. With a novel recording solution (&[Prime]dVLogger&[Prime]), we correlated objective surgeon performance metrics to GEARS during steps of robotic radical prostatectomy (RRP), attempting to automate performance evaluation._x000D_ Methods We collected surgeon movement data and recorded synchronized video from surgeons performing two distinct RRP steps: seminal vesicles dissection (SVD) and anterior vesicourethral anastomosis (AA), using the dVLogger provided by Intuitive Surgical&[prime]s research team. Two expert robotic surgeons blindly evaluated the video using GEARS. Performance metrics recorded by the dVLogger were correlated to GEARS scores using Spearman&[prime]s correlation test._x000D_ Results We evaluated 40 cases of RRP. Sixteen surgeons (median 175 (range 30-2000) console cases experience) participated. Total moving time of all robotic instruments and distance traveled by all robotic instruments inversely correlated with most GEARS scores for both SVD and AA steps (r=-0.3 to -0.6, p<0.05) (Table). Dominant and non-dominant hand instrument velocity strongly correlated to GEARS scores during AA (r=0.5 to 0.7, p<0.001) while only the dominant hand instrument velocity correlated with GEARS scores during SVD (r=0.4 to 0.5, p<0.03). Distance traveled by the camera inversely correlated with most GEARS scores only during SVD (r=-0.4 to -0.5, p<0.007). Inversely, frequency of camera position adjustment correlated with most GEARS scores only during AA (r=0.3 to 0.4, p<0.05). Frequency of energy pedal use was correlated with some GEARS scores during SVD (r=0.4, p<0.03). Conclusions We found significant correlation between key automated metrics and subjective GEARS scores during a dissection and suturing step of RRP. While strong correlation between automated and GEARS scores may suggest agreement in evaluation of a surgeon&[prime]s performance, disagreement or lack of statistical correlation does not infer that automated assessment or GEARS is superior. Further refinement of this analysis with more tailored performance metrics as well as correlation to clinical outcomes may better delineate the relative value of automated assessment to GEARS._x000D_ Funding None
Authors
Andrew Hung
Jian Chen Anthony Jarc Hooman Djaladat Inderbir Gill |
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MP51-02 |
CONSTRUCTION AND ASSESSMENT OF AN INNOVATIVE INDIGENIOUS ULTRASOUND GUIDED PERC SIMULATOR |
Surgical Technology & Simulation: Training & Skills Assessment I | 17BOS |
Abstract: MP51-02 Sources of Funding: NONE Introduction PCNL has a significant learning curve. Ultrasound guided puncture has its definite indications and ultrasound guided PERC simulators are still not available. We describe and validated our own, portable, active mannequin type of ultrasound guided perc simulator Methods A short anatomical study of the coronal sections traversing through the kidney and literature of anatomy was conducted. _x000D_ The ultrasound guided perc simulator was then designed, patented and constructed using a designed mix of ultrasound compatible medium, aluminium components, ultrasound compatible organ dummies and a mannequin. The simulator allowed ultrasound guided puncture, saline aspiration for confirmation and wire parking into the kidney/ureter. Evaluation using a 3 step test, GRS score and trainee feedback was analysed using Spearman rank order correlations and paired t test_x000D_ Results A total of 16 urology trainees and 2 experts participated in this single center study. Face and content validity as evaluated by the experts demonstrated a satisfactory replication of the retroperitoneal anatomy. The simulator could differenciate novices from the experts. All the subjects demonstrated statistically significant betterment (Spearman rank order correlations) in their GRS scores (p 0.001), total time (p 0.001), fluoroscopic time (p 0.001) and attempted needle punctures (p 0.001). Measured parameters of most trainees showed a shift, towards the control though they were significantly slower than the controls. This indirectly demonstrated the training capabilities of the simulator. Subjective simulator assessment of the trainees indicated a high degree of satisfaction on effectiveness of the simulator Conclusions Our portable ultrasound guided PCNL simulator is the first of its kind. It is portable, uses the usual initial puncture needle, any access technique. The end of task confirmatory saline aspiration and inspectory confirmation of the puncture facilitates faster learning. It allows evaluation and supervised, repetitive tailored learning in a controlled, low stress environment. It has low initial and maintenance cost with recyclable inserts. Further studies would be aimed at further assessment of training and proficiency abilities. The concept may open up newer avenues in PCNL simulation Funding NONE
Authors
Ashish Rawandale
Lokesh Patni |
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MP51-03 |
Older and Wiser? Changes in Unprofessional Content on Urologists' Social Media from Residency to Practice |
Surgical Technology & Simulation: Training & Skills Assessment I | 17BOS |
Abstract: MP51-03 Sources of Funding: None Introduction The AUA has encouraged social media use and published online professionalism guidelines. We previously found that at the completion of residency, 40% of recent urology graduates' public social media contained unprofessional (UP) or potentially objectionable (PO) content. This study examines changes in urologists' unprofessional social media content as they transition from residency to practice. Methods Facebook was queried with the names of all 2015 U.S. urology graduates 1 year after completion of residency. We determined UP/PO content using a rubric based on professionalism guidelines by the ACGME, AMA, and AUA. We noted users who publicly identified as a urologist or affiliated with the AUA. 3 reviewers conducted assessments with strong concordance (&[kappa]>0.90). Comparisons were made with data from this cohort collected at the completion of training. Results Of 281 urologists, 198 (70%) had publicly-identifiable Facebook profiles. Of these, 85 (43%) contained any UP or PO content, including 35 (18%) with UP content. Common examples included images of and references to intoxication, explicit profanity, unprofessional behavior at work, and offensive comments about patients. Of the 201 public profiles in this cohort at completion of residency 1 year prior, most profiles (183, 91%) have remained public; of the 18 that were no longer publicly accessible, 9 (50%) had previously had UP/PO content, indicating greater adherence by some urologists to the guidelines. Similarly, of the 80 urologists without public profiles 1 year prior, most (64, 80%) have remained unidentifiable; but of the 16 that have become publicly accessible since then, half had UP/PO content, suggesting parallel changes by other urologists against the guidelines. Of note, among the public profiles in the present analysis, 11 (6%) had posted new UP/PO content since entering practice. Comparing this cohort at present vs at completion of residency, there was minimal difference overall in how many had public profiles (70% vs 71%) or public UP/PO content (43% vs 40%). While more users now self-identified on Facebook as being a urologist (109 vs 85 one year prior), the proportion of them posting public UP/PO content increased (53% vs 47% one year prior). Conclusions Most urologists who recently entered practice continue to have public Facebook profiles, and about half of these contain unprofessional content. Amidst a steady rise in users identifying as urologists online, the majority now have public UP/PO content, raising concern about their professional identities and public perceptions of the specialty. Funding None
Authors
Max Schmidt-Bowman
Kevin Koo Zita Ficko E. Ann Gormley |
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MP51-04 |
A Decade of Robot-Assisted Radical Prostatectomy Training: Time-Based Metrics from Fellows and Residents |
Surgical Technology & Simulation: Training & Skills Assessment I | 17BOS |
Abstract: MP51-04 Sources of Funding: None Introduction Modern training in robot-assisted surgery is evolving towards curriculum-based training that includes didactics, dry-lab exercises, wet-lab operations, surgical assistance, and ultimately console performance under careful supervision. After a decade of training 4 clinical fellows and up to 12 residents per year, we have transformed their step-wise time metrics into a simple table to use to benchmark performance. A non-validated qualitative feedback was also recorded. Methods From July 2006 to January 2016, data of 2215 patients who underwent RARP were analyzed from a prospective cohort. RARPs were performed by 6 faculty surgeons. As trainee, a total of 94 uro-oncology fellows and residents were involved in the study. RARP was divided into 11 steps, staff times, trainee times and quality scores were recorded for each steps. The trainees were evaluated independently for time to complete a procedure step (objective evaluation) and quality of results (objective and subjective evaluations). Results Trainee was involved at least one in step in 1622 (73%) cases. In 593 (27%) cases, there was no console time due to circumstances including case complexity, late hours, or limited trainee experience. The median console times of staff and trainees, involvement rate of trainee for each step of the RARP procedure are shown in Table 1. In every steps the staffs’ time is significantly lower than the trainees. The rate of increase time of trainees differ from 15% to 120% (p < 0.001). The quality grading system results were shown in Table 2. Grade 4-5 success rate was over 95% in each steps. There is no grade 0 and a rare rate of grade 1 and 2 (under 1%). Conclusions Qualitative feedback under careful supervision indicate a high incidence of satisfactory performance or with minor corrections. The quantitative data can provide current trainees with an easy way to benchmark their time-based performance as a simple 25%-50%-75% ranking, compared to other trainees and experienced staff. Funding None
Authors
Muammer Altok
Mary Achim Surena Matin Curtis Pettaway John Davis |
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MP51-05 |
Does Trainee Performance Impact Surgeon's Stress during Robot-Assisted Surgery? |
Surgical Technology & Simulation: Training & Skills Assessment I | 17BOS |
Abstract: MP51-05 Sources of Funding: Roswell Park Alliance Foundation. Introduction Stress increases mental workload leading to reduction in surgical performance and subsequently risking patient safety. Console surgeon and their teams often experience mental stress, yet there is little research about objective measurement of stress levels in the operating room during Robot-assisted Surgery (RAS). In the study, brain activity data are used to differentiate between causes of mental stress of mentor surgeon and the impact of trainee performance during RAS. Methods EEG data from surgical mentor while observing 87 Urethro-Vesical Anastomoses (UVA) and 74 Pelvic Lymph Node Dissections (PLND) performed by 3 trainees, as well as performing 26 UVA and 26 PLND is recorded. Level and type of mental stress were determined using the power spectral density, during different frequencies, of signals from 20 channel EEG. Performance scores were used to identify the relationship between performance and stress. Stress caused by worry about ability of safe completion were estimated by using the brain activity during upper alpha (11-12 Hz), sensorimotor rhythm (SMR, 12-15 Hz), and low beta (19-22 Hz) bands in the "Cz" channel (area in motor cortex). The activity at the upper beta and gamma was used to estimate stress level and anxiety and fear caused by risk prediction. Results Mentor's brain faces two main types of stresses during RAS. While observing low quality performance by trainee surgeons, the cause of mentor's mental stress is mostly worries about lack of proficiency of trainee surgeon (Type 1). However, stress of mentor while performing surgery or observing a high quality performance by trainee surgeon, is mostly the result of situation awareness and risk prediction on the operative field (Type 2). These two types of stress activate different areas of the brain in specific frequencies. Conclusions EEG can be used to separate different types of stress experienced during performing and mentoring robot-assisted surgery. A deeper understanding of the difference and effect of these stresses and their outcomes can lead to targeted intervention and quality improvement. Funding Roswell Park Alliance Foundation.
Authors
Somayeh Shafiei
Ahmed Hussein Youssef Ahmed Justen Kozlowski Khurshid Guru |
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MP51-06 |
Assessment of flexible ureteroscopic stone extraction skills of Urology Postgraduate Trainees during Objective Structured Clinical Examinations: Is there a place for virtual reality simulators? |
Surgical Technology & Simulation: Training & Skills Assessment I | 17BOS |
Abstract: MP51-06 Sources of Funding: This work was partially sponsored by Fonds de la Recherche en Sante du Quebec (FRSQ) grants to Dr Mehdi Aloosh and Dr Sero Andonian. Introduction The first objective of this study was to assess whether UroMentorTM simulator could be used during an Objective Structured Clinical Examination (OSCE) to assess flexible ureteroscopic stone-extraction skills of urology postgraduate trainees (PGTs). The second objective was to determine whether previous experience in performing this task in the operating theatre or on the simulator correlated with performance during the OSCE. Methods After obtaining ethics approval, PGTs from post-graduate years (PGY) 3 to 5 were recruited from all 4 Quebec urology training programs to participate in the study during an OSCE. After a short orientation to the UroMentorTM simulator (Simbionix, Cleveland, Ohio, USA), PGTs were asked to perform Task 10 for 15 minutes, where two small stones from the left proximal ureter and renal pelvis were extracted using a basket. Objective assessments from the simulator and subjective evaluations using the validated Ureteroscopy-Global Rating Scale (URS-GRS) tool were used to assess competency of PGTs in performing the task. Performance reports generated by the simulator and the URS-GRS scores were analyzed using paired t-test and Pearson correlation. Results Out of thirty PGTs who participated in this study, 29 were right-handed. PGTs had performed a mean of 277.9 cystoscopies, 55.9 semirigid ureteroscopies, and 45.7 flexible ureteroscopies prior to the study. During the OSCE, mean URS-GRS score was 20.0 ± 4.4, mean operative time was 10.9 ± 2.1 minutes, mean fluoroscopy time was 7.0 ± 4.9 seconds, and mean number of traumas was 10.8 ± 3.8. Eight PGTs had practiced on the UroMentor simulator prior to the study with a mean URS-GRS score of 26.0 ± 7.2 on their last practice trial. At the OSCE, mean URS-GRS score of those who practiced on the simulator was significantly higher than the mean score of those who did not practice on the simulator (24.6 ± 3.0 vs. 18.3 ± 3.6, p<0.001). However, previous experience in the operating theatre and PGY level did not correlate with performance during the OSCE. Conclusions This study confirmed the feasibility of incorporating the UroMentor at OSCEs to assess competency of urology PGTs in ureteroscopic stone extraction skills. Moreover, PGTs who practiced on the simulator scored significantly higher than those who did not practice. Funding This work was partially sponsored by Fonds de la Recherche en Sante du Quebec (FRSQ) grants to Dr Mehdi Aloosh and Dr Sero Andonian.
Authors
Mehdi Aloosh
Félix Couture Sero Andonian |
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MP51-07 |
TEACHING COMMUNICATION SKILLS IN UROLOGY RESIDENCY PROGRAMS: A MISSED OPPORTUNITY FOR IMPROVEMENT? |
Surgical Technology & Simulation: Training & Skills Assessment I | 17BOS |
Abstract: MP51-07 Sources of Funding: None. Introduction Postgraduate medical education has historically focused on the acquisition of didactic knowledge and technical skills, with less overt emphasis on the development of interpersonal and communication skills. Recent emphasis on patient satisfaction and performance-based initiatives has made this third dimension of medical training increasingly relevant. To date, there have been no studies on how communication skills are taught or evaluated in surgical specialties, including urology. We undertook this study to describe the current state of communication skill teaching in ACGME-accredited urology training programs in the United States. _x000D_ Methods We surveyed 126 urology training programs via email and follow up phone calls, asking for an assessment of attending and resident communication skills as well as a description of how communication skills were taught in each program, and whether communication skills were evaluated (formally or informally) during interviews of prospective residents. Results 48 programs (38.1%) completed the survey. All program leaders characterized attending communication skills as at least "adequate," with most characterizing attendings as having "excellent" (52.2%) or "outstanding" (13.0%) communication skills. Most program leaders characterized residents as having "excellent" (50%) or "outstanding" (6.5%) communication skills, although 2.2% characterized residents as having "poor" communication skills. Only 10 (20.8%) programs had formal curricula to teach communication skills to residents. Resident observation of attendings (43/48=89.6%), faculty observation of residents (34/48=70.8%), and resident observation of other residents (29/48=60.4%) were cited as the most common ways for residents to learn communication skills. A minority of programs used dedicated didactic time (22/48=45.8%) or simulation (17/48=35.4%); formal feedback was provided to learners in only 5 (10.4%) programs. Prospective residents were evaluated on communication skills during the interview day either formally (6.4%) or informally (76.6%) by most programs._x000D_ Conclusions The importance of good communication skills in urology residents is acknowledged by the high proportion of programs that assess interpersonal skills during the resident selection process. However, comprehensive formal communication skills training during urology residency is lacking. These findings may be helpful to urology program directors wishing to augment their contemporary approach to communication skills teaching for their residents. _x000D_ Funding None.
Authors
Jorge Whitley
Geolani Dy Marcy Rosenbaum Byron Joyner Kathleen Kieran |
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MP51-08 |
Gender-Based Differences Asked of Urology Applicants During Residency Interviews |
Surgical Technology & Simulation: Training & Skills Assessment I | 17BOS |
Abstract: MP51-08 Sources of Funding: none Introduction Interviews are essential to the residency application process. Questions regarding marital status, child bearing, ethnicity, and religion violate employment law if asked by the interviewer. The purpose of this study was to determine the rates of discriminatory questions asked during urology residency interviews and to assess for differences by applicant gender. Methods A 22-question online anonymous survey was distributed following the Urology Match to 340 PGY1 urology applicants at Northwestern University. Questions were asked in a two-part, stepwise fashion. If a candidate replied "no" to whether they introduced a restricted topic in an interview, they were subsequently asked how often interviewers introduced a topic. An open-ended question asked applicants to comment on other potentially inappropriate questions._x000D_ _x000D_ Results The overall response rate was 50%, with 170 applicants (41 female, 129 male) completing the survey. Respondent characteristics are outlined in Table 1. _x000D_ _x000D_ Overall, 35% of respondents believed they were asked an inappropriate question. Females (39%) were more likely to report being asked discriminatory questions than males (23%). Men were most commonly asked about rank list. Females were most often asked about relationship status._x000D_ _x000D_ Statistical significance was found between males and females in inquiries related to current parental status (59% vs. 5%) (p=0.030) and intent for future children (42% vs. 13%) (p=0.001). There was a marked difference in questions about marital status (female 67% vs. male 42%), but this did not reach statistical significance (p=0.300). _x000D_ _x000D_ Regarding other restricted topics, 17% of respondents were asked about age, 13% national origin, and 4% religion, with no differences between genders. In the open-ended response, other topics considered inappropriate by respondents included weaknesses of other applicants, sexual orientation and home ownership._x000D_ Conclusions An alarming percentage of urology applicants are asked interview questions that violate employment law. Females are disproportionately questioned about relationships, parental status and plans for children. Education of applicant interviewers regarding legally restricted questions is warranted. _x000D_ _x000D_ Funding none
Authors
Mary Kate Keeter
Ashima Singal Nirali Shah Stephanie Kielb |
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MP51-09 |
The “Penana”: A Novel, Cost Effective, and Highly Efficacious Model for Teaching Male Urethral Anatomy and Safe Foley Catheter Technique |
Surgical Technology & Simulation: Training & Skills Assessment I | 17BOS |
Abstract: MP51-09 Sources of Funding: none Introduction Iatrogenic urethral catheter related injuries are common and have been shown to correlate with inadequate training among medical professionals. Urethral catheterization (UC) is a common procedure and often one of the first attempted by medical trainees. Simulation training enhances medical procedure teaching by decreasing trainee anxiety, improving patient safety and efficiently tailoring the experience for the learners, thus optimizing education. We sought to create an efficacious simulation model to teach medical students and residents male UC. Methods We developed a 50-minute educational curriculum utilizing didactic presentation and a banana with ends removed and longitudinal core created as a simulation model for the male urethra (&[Prime]Penana&[Prime]). The presentation focused on UC indications, male urethral anatomy, structure of standard and Coude catheters, and safe technique for UC. Procedural teaching utilized modified Payton technique; 1) Expert demonstration, 2) Explanation of steps, 3) Expert-guided Learner performance, 4) Learner-guided learner performance, 5) Independent Learner performance. Subjects completed pre and post intervention survey assessments to determine efficacy. Surveys measured learner knowledge and self-reported confidence at performing male UC. Results 126 learners participated in the workshop and (29 MS1, 40 MS2, and 60 PGY1) completed pre and post assessments. Prior to intervention, among medical students 36% and 1% had observed UC and 6% and 0% had performed UC using standard Foley and Coude, respectively. Following intervention, combined knowledge scores increased from 13±16% to 85±20% correct. On a 10 point scale, learners self reported confidence increased from 3.3±2.1 to 8.2±1.5 for male urethral anatomy, 1.7±1.4 to 7.9±1.6 for standard Foley UC, and 1.2±0.6 to 7.8±1.9 for Coude UC. On a 10 point scale with 10 representing very helpful, learners described the Penana model with a mean value of 8.6±1.9. Finally, 78% and 20% were extremely likely and likely, respectively, to recommend the course to a friend. Conclusions The Penana is a highly efficacious simulation model for teaching medical students and residents safe UC technique. The low cost and universal availability of the materials makes the model easily accessible for any resource-limited education setting. Funding none
Authors
Matthew Truesdale
Maya Overland Christy Boscardin Kirsten Greene |
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MP51-10 |
Assessing Surgical Skills Among Urology Resident Applicants: Can Crowd-Sourcing Identify the Next Generation of Surgeons? |
Surgical Technology & Simulation: Training & Skills Assessment I | 17BOS |
Abstract: MP51-10 Sources of Funding: none Introduction Surgical skills are key determinants of patient outcomes and as such there is an increasing interest in skills assessment. However using expert surgeon reviewers is both costly and time-consuming. Recently, crowdsourcing has been shown to provide an accurate assessment of surgical skills. We hypothesized that an assessment of surgical skills by experts and the “crowd� might be helpful in the selection of medical student applicants to our urology residency program. Methods After obtaining UC Irvine Institutional Board Review approval, our 2015, residency applicants performed four tasks: open square knot tying, laparoscopic peg transfer, and robotic suturing, and skill task 8 on the LAP Mentor™ (Simbionix Ltd., Lod, Israel). All interviewees were informed about the nature of the study and consented to such, two weeks prior to the interview date. Faculty experts and crowd workers (Crowd-Sourced Assessment of Technical Skills [C-SATS], Seattle, WA) assessed recorded performances using the Objective Structured Assessment of Technical Skills (OSATS), Global Evaluative Assessment of Robotic Skills (GEARS), and the Global Operative Assessment of Laparoscopic Skills (GOALS) validated assessment tools. Results A total of 25 resident interviewees were included and completed the study tasks. A total of 3938 crowd assessments and 150 expert assessments were obtained for the four tasks, requiring 3.5 hours and 22 days to gather all data, respectively. Inter-rater agreement between expert and crowd assessment scores for open knot tying, laparoscopic peg transfer, and robotic suturing was 0.62, 0.92 and 0.86 respectively. Agreement between applicant rank on skill task 8 on the LAP Mentor assessment and crowd assessment was poor, at only 0.32. The crowd match rank based solely on skills performance did not compare well with the final faculty match rank list (0.46); however, none of the bottom five crowd-rated applicants appeared in the top five expert-rated applicants and none of the top five crowd-rated applicants appeared in the bottom five expert-rated applicants. The crowd and experts agreed on 3 of the 5 lowest ranked applicants. Conclusions Crowd-source assessment of resident applicant surgical skills has good inter-rater agreement with expert physician raters but not with a computer-based objective motion metrics software assessment. The crowd was able to determine poor performers nearly as well as the experts. Funding none
Authors
Zhamshid Okhunov
Simone L. Vernez Victor Huynh Kathryn Osann Jaime Landman Ralph V. Clayman |
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MP51-11 |
Utilization of a Surgical Video Curriculum to Augment Resident Learning |
Surgical Technology & Simulation: Training & Skills Assessment I | 17BOS |
Abstract: MP51-11 Sources of Funding: none Introduction Teaching technical skill and transferring technical knowledge is difficult in any surgical residency. This difficulty is intensified for residents due to surgical complexity, clinical responsibilities, and duty hour restrictions. As a result, surgeries must be performed multiple times by residents in order to learn the nuances and pitfalls of the procedure. To gain the most from each surgical opportunity, efficient and thorough preparation is required by each resident. We theorize that a surgical video curriculum is an efficient way for residents to prepare for cases, augment intraoperative learning, and will be a resource as they expand beyond residency to independent operating._x000D_ Methods To evaluate resident acceptance and utilization of a surgical video curriculum, we selected a previously developed instructional video (https://youtu.be/6DcyLCE23AY) on vasectomy and compared this to a widely available book chapter on the same subject from Hinman's Atlas of Urologic Surgery, Third Edition by Joseph A. Smith. Twenty-one residents and visiting sub-interns from the University of Washington and Virginia Mason Hospital were randomized to receive either a video or chapter, 24 hours prior to a normally scheduled lecture on male fertility. Residents were given a survey and 5 point quiz based on AUA guidelines at the time of the lecture to assess resource utilization and knowledge. Responses were evaluated with the Student&[prime]s t-test. _x000D_ Results A total of 21 residents and sub-interns were randomized. The survey response rate was 85%. Significantly fewer residents utilized the Hinman's chapter compared to the Video for preparation. The amount of time to utilize the chapter versus the video and the average quiz scores were not significantly different between the two groups._x000D_ Conclusions Video resources are an efficient and effective way to disseminate information to residents. Such videos are well suited to surgical instruction, and may be similar in time requirement and teaching efficacy. Residents utilize video preferentially when compared to reading a chapter while balancing a heavy work schedule and operative/conference preparation. We plan to further validate and expand this video library to promote resident learning. Funding none
Authors
Wayne Brisbane
Marc Rogers Kevin Ostrowski Robert Sweet Hunter Wessells Thomas Walsh |
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MP51-12 |
A training course for the Urologist improves their ability to interpret clinically significant prostate cancer on multiparametric MRI |
Surgical Technology & Simulation: Training & Skills Assessment I | 17BOS |
Abstract: MP51-12 Sources of Funding: National Institute for Health and Research UK_x000D_ CIVCO_x000D_ SmartTarget_x000D_ IPSEN _x000D_ (No funding was related to production of the research, but funding was for running costs of delivering the course) Introduction MRI-targeted biopsy and MRI-targeted treatments for prostate cancer are often carried out by urologists specializing in this area, however we depend on expert Uroradiologists to interpret and convey MRI information. In an image-guided treatment driven era, MRI interpretation for use in interventional prostate cancer procedures is an important skill for Urologists to develop if they wish to perform accurate MRI-targeted prostate biopsy and treatment. We aimed to establish whether MRI interpretation skills could be gained by Urologists after a 2-day training course. Methods A 2-day training course in prostate MRI interpretation was delivered to 25 Urologists by a panel of expert Uro-radiologists._x000D_ _x000D_ Participants were assessed on their ability to interpret prostate MRI in a 2-hour test at baseline (test 1) and after teaching (test 2). Scans were chosen at random from a database of all men undergoing pre-biopsy multiparametric MRI followed by transperineal template biopsy at our institution. _x000D_ _x000D_ Prostates were scored by participants on a 1-5 Likert scale for suspicion of prostate cancer and compared to histological findings from transperineal template prostate biopsy. The average area under the curve (AUC) for the detection of clinically significant cancer (Gleason >= 3+4 and/or maximum cancer core length >= 4mm) was calculated for the group. The likelihood of extracapsular extension, involvement of urinary sphincter and participants’ confidence in their interpretation was also rated on a 1-5 Likert scale. Results The AUC for the detection of clinically significant cancer on a patient level from Test 1 was 0.59, 95% CI [0.55-0.65]. The AUC for the detection of clinically significant cancer from Test 2 was 0.74, 95% CI [0.70-0.79]. There was a significant improvement in participant’s average AUC after teaching, difference 0.15, 95% CI [0.09 - 0.2]. Mean confidence of participants in prostate MRI interpretation also improved significantly before and after teaching from 3.19 to 3.53 (p<0.0001). Conclusions Prostate MRI interpretation is an important skill that is transferrable to the Urologist. After a short teaching course, urologists improved significantly at detecting cancer. Whilst we will always require expert Uro-radiologists to report prostate MRI, courses in prostate MRI interpretation should be considered in the training of Urologists involved in MRI-targeted prostate biopsy and treatments. Funding National Institute for Health and Research UK_x000D_ CIVCO_x000D_ SmartTarget_x000D_ IPSEN _x000D_ (No funding was related to production of the research, but funding was for running costs of delivering the course)
Authors
Veeru Kasivisvanathan
Susan Charman Jan van der Meulen Lina Carmona Vasilis Stavrinides Clare Allen Alex Kirkham Shonit Punwani Mark Emberton Caroline Moore |
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MP51-13 |
Surgical skill quality improvement: Utilizing a peer video review workshop for surgeons performing robotic prostatectomy |
Surgical Technology & Simulation: Training & Skills Assessment I | 17BOS |
Abstract: MP51-13 Sources of Funding: Blue Cross and Blue Shield of Michigan _x000D_ Introduction Because surgical skill may be a determinant of patient outcomes, there is growing interest by practicing surgeons in improving their own technical skills. In the Michigan Urological Surgery Improvement Collaborative (MUSIC), we assessed the feasibility of a peer video review workshop for surgeons performing robot-assisted radical prostatectomy (RARP). _x000D_ Methods MUSIC urologists were invited to submit representative videos of a nerve-sparing RARP which were edited into videos of the anastomosis and nerve-sparing parts. All videos were reviewed by 56 peer surgeons for global, and procedure-specific, skill using validated instruments. Surgeons completed a Kolb Learning Style Inventory and were categorized into one of four learning styles: Converger, Diverger, Accomodator, or Assimilator. Surgeons were then paired based on peer ratings for skill and learning type. Optimal pairings are convergers/divergers and accommodators/assimilators (Kolb, 1984). At the workshop, paired surgeons reviewed each participant's videos for 60 minutes, using a structured template. At the end of the workshop, surgeons completed a survey evaluating the activity. _x000D_ Results The peer review workshop involved 24 surgeons. Videos were reviewed using a step-wise schema of (1) equipment, (2) set-up, (3) approach, (4) execution strategy, (5) evolution of technique, (6) lessons learned, and (7) difficult scenarios. Learning style for surgeons consisted of convergers (42%), assimilators (33%), accommodators (17%) and divergers (8%). The survey was completed by 96% of participants. Nearly all (96%) participants felt the workshop increased their self-awareness for improvement, helped identify changes to technique they could implement, and was an effective learning experience (Table). All but one surgeon expressed a desire to participate in another workshop; this surgeon was incorrectly paired for learning style (converger + accommodator). _x000D_ Conclusions Peer video review workshop for practicing surgeons performing RARP is feasible and appears to help surgeons identify technical skill improvement opportunities. Our work highlights the importance of matching surgeons with compatible learning styles. Future work will assess if video review improves technical skill and patient outcomes. _x000D_ Funding Blue Cross and Blue Shield of Michigan _x000D_
Authors
Richard Sarle
Nikola Rakic Tae Kim Andrew Brachulis Brian R. Lane Benjamin Stockton Susan Linsell David C. Miller James O. Peabody Khurshid R. Ghani for the Michigan Urological Surgery Improvement Collaborative |
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MP51-14 |
The Current State of Robotic Surgery Training Curricula in United States Urology Residency Programs |
Surgical Technology & Simulation: Training & Skills Assessment I | 17BOS |
Abstract: MP51-14 Sources of Funding: none Introduction Defining competence in procedural training may prove difficult. Historically, this has been via direct supervision by senior surgeons. There has been a push for the development and use of validated curricula. We assess robotics curricula (RC) and surgical simulation (SS) in U.S. urology residency programs (URPs). Methods Of all URPs, 129 were contacted. Program directors (PDs) were queried on use of a formal or validated RC, use of virtual reality (VR), graduation requirements, availability of a SS laboratory, and chief resident comfort level with robotic surgery. Results Response rate was 26.3 %. Of PDs, 17 (50%) reported a formalized RC but 82.3% did not utilize validated RC. Physical consoles exist in 73.5% and VR trainers exist in 50% of programs. Simulation laboratories were reported in 85.2% of programs. Completion of a RC was required for graduation in 38.2% while it was suggested in 50% of programs. Six programs (17.6%) are undergoing curriculum development/validation. Figure 3 outlines PD perceptions of chief resident operative comfort. Conclusions Our findings suggest that the majority (82.3%) of URPs do not employ validated RC. However, half of PDs report using VR modules, physical consoles, and online courses. By graduation, 91.1% of PDs reported that graduating chief residents are comfortable with robotic surgery. Funding none
Authors
Daniel Verges
Costas Lallas |
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MP51-15 |
Surgical Technical Performance Impacts Patient Outcomes in Robotic-Assisted Radical Prostatectomy |
Surgical Technology & Simulation: Training & Skills Assessment I | 17BOS |
Abstract: MP51-15 Sources of Funding: None Introduction The few studies that question the role of individual surgeon&[prime]s technical skill in influencing patient outcomes and safety have produced compelling results. To date, this linkage has not been published in urology. We designed a study to understand how surgeon skill and error rating contribute to functional outcomes in robotic-assisted radical prostatectomy (RARP). Methods We conducted a case-matched analysis of 28 prospectively collected RARP endoscopic videos performed by a single surgeon, between 2008 and 2015. Research Ethics Board approval was granted. Patient information was retrieved from an institutionally maintained database. The primary outcome parameter was continence status at 3 months post-operatively, defined as patient use of more than a single precautionary pad. A blinded observer with expertise in intraoperative video analysis evaluated clinically relevant steps of RARP using the Global Evaluative Assessment of Robotic Skill (GEARS), Robotic Anastomosis Competency Evaluation (RACE) and the Generic Error Rating Tool (GERT). Mann Whitney U tests explored differences in predictor variables between cases and controls (two-tailed, p≤0.05). Results 14 patients deemed to be incontinent at 3 months were matched for age, pre-operative International Prostate Symptoms Score (IPSS), use of posterior/anterior hitch, and prostate weight. Matching also accounted for position of the case on the surgeon&[prime]s learning curve. Statistically significant differences were detected on nonparametric testing in RACE (p=0.03) score and GEARS urethrovesical anastomosis score (p=0.02) between case and control groups. There were a greater number of errors committed during bladder neck dissection in the incontinent patient cohort (p=0.01). Conclusions Our study is the first that suggests a link between surgeon technical performance and continence outcomes in RARP. While this single surgeon, patient-matched case-control design limits confounding, multi-institutional prospective studies studying multiple surgeons of different abilities forms the basis of future research in this area. The implication of our findings are potentially far reaching, and moving forward, stakeholders in education and accreditation of RARP should incorporate both surgeon technical skill and error rating into judgments of surgical quality. Funding None
Authors
Mitchell G. Goldenberg
S. Larry Goldenberg Teodor P. Grantcharov |
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MP51-16 |
Development and Content validation of a training and assessment tool for RAPN |
Surgical Technology & Simulation: Training & Skills Assessment I | 17BOS |
Abstract: MP51-16 Sources of Funding: None Introduction Surgical trainees are under a multitude of pressures, thus there is requirement for efficient, safe training methods. There is a lack of procedure-specific guidance within minimally invasive surgery. This study sought to:_x000D_ 1. Develop a checklist-based training and assessment tool for RAPN_x000D_ 2. Content validate the assessment tool for use in surgical training. Methods This multi-institutional, prospective, longitudinal study occurred from September 2014-June 2015. Healthcare failure mode and effect analysis (HFMEA) was employed in development. The developed RAPN assessment tool was distributed internationally to 13 experts for content validation. Results The RAPN training tool contained six phases, 26 processes and 50 sub-processes (Figure 1)._x000D_ RAPN was divided into six phases constituting 28 processes, 64 sub-processes and 84 failure modes. "Preparation of operative field" constituted 9 phases, 15 sub-processes, 17 failure modes. "Exposure of surgical plane" had three processes, six sub-processes, 13 failure modes. "Dissection and control of hilum" included five processes, eight sub-processes, nine related failure modes. "Preparation for hilar clamping and tumour excision" was a five-process stage with seven sub-processes, 10 failure modes. "Hilar clamping, warm ischaemia time and tumour excision" encompassed three processes, 13 sub- processes, 19 failure modes. Lastly, "Finalising and closure" had four processes, 16 sub-processes, 19 failure modes. After excluding detectable failure modes and existing control measures, 45 failure modes had median hazard score 4 and were included in RAPN training tool._x000D_ Content validation occurred across eight institutions worldwide with 13 expert surgeons and their teams of anaesthetists, nurses and technicians. Additionally, the RAPN training tool was circulated among delegates at the European Association of Urology 2015 Annual Congress._x000D_ All participants agreed that the RAPN training tool incorporated crucial elements of the operation. Conclusions This study used HFMEA to develop and content validate a RAPN training tool. Hazard analysis and content validation developed a 26- step checklist. Future research will involve validation and application in clinical practice to evaluate the learning curves of RAPN. Funding None
Authors
Catherine Lovegrove
Eilidh Bruce Nicholas Raison Benjamin Challacombe Giacomo Novara Alex Mottrie Jaques Hubert Declan Murphy Prokar Dasgupta Kamran Ahmed |
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MP51-17 |
The RobotiX simulator: Face and Content validation using the Fundamentals of Robotic Surgery(FRS)curriculum |
Surgical Technology & Simulation: Training & Skills Assessment I | 17BOS |
Abstract: MP51-17 Sources of Funding: None Introduction Robotic surgical training is poorly delivered with limited skills-based training offered to trainees. To improve this, validated high quality robotic simulators need to be developed and made available. The RobotiX simulator is a new platform which this study sought to validate in the context of a recognised robotic surgery curriculum Methods Surgeons(n=29) with ranging robotic experience and experience with other simulators(da Vinci Backpack and Mimic) were invited to complete all 6 FRS curriculum exercises. Participant performance was scored using the Global Evaluation Assessment of Robotic skills(GEARS). Participants completed a Likert scale based face and content validity questionnaire graded as negative(1-2/5), neutral(3), or positive(4-5) Results Overall, analysis included 27 participants. There was good concurrent GEARS score reliability (Cronbach’s Alpha 0.801) between participants performing exercises on both the RobotiX and an alternative robotic simulator._x000D_ _x000D_ Conclusions The RobotiX simulator demonstrated excellent Face and Construct validity evidence both in terms of general usage and in the specific context of the FRS curriculum.(Table 2 Q1,2)The RobotiX performed at least as well as other simulators(da Vinci Backpack/Mimic) and was found to simulate a robotic platform such as the da Vinci Robot. (Table 2 Q4,5) Furthermore 81% of surgical trainees would recommend using the RobotiX(Table 2 Q3) Funding None
Authors
Ismail Omar
James Dilley Philip Pucher Philip Pratt Torath Ameen Justin Vale Ara Darzi Erik Mayer |
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MP51-18 |
Development and Validation of a Novel Cognitive Training Tool for Laparoscopic Suturing |
Surgical Technology & Simulation: Training & Skills Assessment I | 17BOS |
Abstract: MP51-18 Sources of Funding: Vattikuti Foundation Introduction The use of cognitive training in the form of mental imagery (MI) to develop surgical skill has been previously demonstrated. However inconsistent results and the limited practical application of current cognitive training methods has limited its uptake. We have developed the first generic cognitive training tool for surgical skills development and validated its use for laparoscopic suturing training. Methods The MI training tool was developed in conjunction with cognitive psychologists and expert laparoscopic surgeons. By providing a framework within which trainees develop a personalised MI script, the training tool enables participants to undertake independent cognitive training. Ongoing critical self-evaluation promotes further refinement and improvement in the quality of the MI._x000D_ _x000D_ The training tool was validated with a randomised controlled trial comparing MI to standard lecture based training for laparoscopic suturing. Participants randomised to cognitive training used the training tool to compose a personalised MI script. All participants then underwent 7 training sessions. Each session was video recorded and technical performance was blindly assessed post-hoc using a validated laparoscopic suturing score. Following training participants' opinions of the MI training tool were collected. Quality of the MI was measured using the validated MI questionnaire (MIQ). Results 27 novice participants completed the study. The MI training tool was found to be very effective, with mean ratings of 6.5/7 and 6.29/7 for content and effectiveness respectively compared to scores of 4.9/7 and 3.8/7 for standard training. The quality of MI was also rated highly with a mean MIQ score of 6/7. No significant differences in technical performance were found between the groups either at baseline assessment or during the 1st 4 training sessions. Cognitive training resulted in significantly better performance after the 5th training session with increasing divergence in scores between the two groups (Figure 1). Conclusions Our novel and highly adaptable cognitive training tool has been shown to effectively aid laparoscopic suturing training. Further validation of the cognitive training tool in more experienced robotic surgeons is now required to determine the optimal integration of cognitive training into surgical training. Funding Vattikuti Foundation
Authors
Nicholas Raison
Lauren Wallace Takashige Abe Fehmi Hafiz Matin Sheriff Christian Brown Prokar Dasgupta Kamran Ahmed |
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MP51-19 |
Multi-component video-based feedback using additional webcam inputs improves daVinci surgical skills simulator (DVSSS) performance |
Surgical Technology & Simulation: Training & Skills Assessment I | 17BOS |
Abstract: MP51-19 Sources of Funding: none Introduction Ergonomics is the study of the efficient movement in working environments. The da Vinci operating system is unique in that it consists of a separate human-machine interface at the operating console including master controls, camera pedal, and clutch. However, current robotic training approaches lack the ability to deliver specific feedback addressing each component. We demonstrate the use of additional web-camera inputs, offering multi-component summative feedback to improve virtual reality (VR) daVinci surgical skills simulator (DVSSS) training. Methods 18 medical students were enrolled in a study on a VR DaVinic surgical skills curriculum. They were randomized into three groups: Group A (n=6, control), no performance feedback; Group B (n=6, standard formative expert feedback), Group C (n=6, summative expert feedback using multicomponent video feedback of the VR task + webcam feedback of master controls and foot pedal). Each trainee completed each task six times. 4 tasks (Peg Board 2, Camera targeting 2, Ring walk 3 & Suture sponge 3) were chosen. Simulator-measured performance metrics included differences in total score, time and economy of motion over the five trials. Data were analyzed using SPSS version 15. Results A learning curve was observed across the five trials in all groups. A significant difference was seen between the three groups for change in overall score across the five trials. Ergonomic metric assessment showed that Groups B and C performed better than Group A (P .002 and P .000, respectively) and that the multicomponent feedback was more effective in tasks involving the use of multiple controls (Camera targeting & Ring walk). Conclusions Multi-component summative feedback (combination of task, master control, and camera pedal) is effective in significantly shortening the learning curve in the robotic training process, especially in complex tasks. _x000D_ Funding none
Authors
Scott Quarrier
Aisha Siebert Ahmed Ghazi |
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MP51-20 |
Prostate Specific Communications: What the next generation of Urology trainees are telling patients about prostate cancer screening, diagnosis, and treatment during a virtual objective structured clinical encounter. |
Surgical Technology & Simulation: Training & Skills Assessment I | 17BOS |
Abstract: MP51-20 Sources of Funding: Society of Urologic Chairpersons and Program Directors Introduction Prostate cancer screening, diagnosis, and treatment may have adverse physical, psychological, and social implications for a patient and his family. Studies suggest that urologists do not foster reasonable expectations when communicating with patients about these issues, often leading to decisional regret. We performed a qualitative analysis of communication skills exhibited by 12 Urology housestaff, as they perform objective structured clinical encounters (OSCEs) with a virtual-world prostate cancer patient. Methods Following informed consent, 12 Urology housestaff participated in several scripted, virtual- world OSCEs with a 52 year old avatar patient. The 'Wizard of Oz” technique was used in which an unseen associate portrayed a standardized patient. The encounters included shared decision making and PSA screening, delivering a prostate cancer diagnosis, and informed consent for a prostatectomy. De-identified audio recordings of the encounters were analyzed using open, axial, and selective coding. Results Ten residents successfully elicited the patient’s perspective of PSA screening and all shared their knowledge of the benefits of screening. All housestaff indicated that PSA screening was controversial, and may result in over-diagnosis of prostate cancer. Only one discussed overtreatment. All housestaff discussed prognosis and that surgery and radiation could be used. None of the housestaff mentioned cryo-therapy or focal therapy, and 11/12 discussed active surveillance. In delivering informed consent, the disclosed risks of ED post prostatectomy ranged from “ a small percentage” to “50-70%.” With regard to additional adverse sexual effects: climacturia was mentioned by one resident, and none mentioned painful orgasm or penile shortening. Disclosed estimates for urinary incontinence varied from “<10%” to “almost all men have some degree of incontinence.” Most housestaff directed the patient to on-line decision support materials. Conclusions Physician communications with patients regarding prostate cancer screening, diagnosis, and treatment directly impact patient expectations and may contribute to decisional regret. Despite our small cohort of providers, we have shown that the majority of housestaff were able to discuss the technical aspects of PSA screening, prognosis, and treatment options in a fairly consistent manner. However, there was tremendous variability in the estimated risks and the impact of ED and incontinence. Other complications, such as penile shortening, orgasmic dysfunction, and climacturia were rarely discussed. Funding Society of Urologic Chairpersons and Program Directors
Authors
Bruce Kava
Allen Andrade Robert Marcovich Jorge Ruiz |
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MP52-01 |
Development of new surgical device: A piezo-actuator pulsed water jet system reduces renal damages after off-clamp partial nephrectomy in a rat model |
Surgical Technology & Simulation: Instrumentation & Technology I | 17BOS |
Abstract: MP52-01 Sources of Funding: none Introduction A piezo actuator-driven pulsed water jet (ADPJ) system is novel surgical device that is not only able to preserve fine blood vessels without thermal coagulation, but also dissect at constant depth and decreases in water volume compared to conventional continuous water jet systems. The aim of this study was to clarify long term renal damages after off-clamp partial nephrectomy (PN) using the ADPJ system in animal experiments. Methods Sprague-Dawley rats were divided into 4 groups and subjected to sham operation, off-clamp PN by the ADPJ system, radio knife and soft coagulation. Urine and blood samples were collected, and residual kidney were harvested at 1, 7, 14, 30, and 90 days postoperatively. Renal function was evaluated by serum blood urea nitrogen (BUN). Morphological features and the extent of renal ischemia of resection surfaces were evaluated by Hematoxylin-eosin (HE) staining and by immunostaining using antibodies to 1-methyladenosine (m1A), respectively. Urinary and serum kidney injury molecule-1 (KIM-1) level, which might be elevated in the presence of renal injury, were measured by ELISA. In addition, the expression of KIM-1 RNA extracted from each resection surface were analyzed by quantitative real time reverse transcription polymerase chain reaction. Results Serum BUN level of the ADPJ group was significantly lower than soft coagulation group in 1 and 90 days (p<0.01). Although the HE staining of the ADPJ group revealed the crush injury and internal hemorrhage of the resection site in the early phase, the state was gradually recovered with the long-term course after surgery. On the other hands, broader necrosis due to coagulation was shown in radio knife and soft coagulation groups (thermal coagulation groups). The extent of m1A immunostaining were significantly smaller in the ADPJ group than thermal coagulation groups. Urinary KIM-1 level of the ADPJ group was significantly lower than those of soft coagulation group in all evaluation points. Furthermore, serum KIM-1 level of the ADPJ groups was significantly lower than those of soft coagulation groups after the 7 days (p<0.01). The expression of KIM-1 was also significantly lower in the ADPJ group than soft coagulation group in 7 and 90 days (p<0.05). Conclusions Renal damages after off-clamp PN using the ADPJ system were significantly less compared with commercialized thermal coagulation devices, contributing to improvement of outcomes after PN. Funding none
Authors
Yoshihiro Kamiyama
Shinichi Yamashita Atsuhiro Nakagawa Shinji Fujii Koji Mitsuzuka Yasuhiro Kaiho Akihiro Ito Takaaki Abe Teiji Tominaga Yoichi Arai |
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MP52-02 |
Does pneumoperitoneum cause transient renal injury in children? |
Surgical Technology & Simulation: Instrumentation & Technology I | 17BOS |
Abstract: MP52-02 Sources of Funding: None Introduction Laparoscopic and robotic surgeries are increasingly utilized in pediatric urology. The associated pneumoperitoneum increases intra-abdominal pressure (IAP), decreases systemic cardiac output and diminishes renal blood flow. This hypoperfusion may result in transient renal injury. The purpose of this study was to assess the short-term impact of pneumoperitoneum on renal function in children using sequential creatinine and cystatin C assays. Methods Prospective analysis of all children over 12 months old who underwent laparoscopic or robotic surgery at a single institution between 9/2014 and 7/2015. For each patient, blood samples were obtained in the OR immediately prior to surgery, upon transfer to the recovery room, and on the morning of POD 1 if the child stayed overnight. Intraoperative parameters, including anesthesia time (a subset of total surgical time), were recorded. The IAP was maintained at 8 mmHg for children <10 years old and at 10 mmHg for older patients. Paired t tests and linear regression were performed for statistical analysis. Results Over the 10-month study period, 20 children underwent laparoscopic (25%) or robotic (75%) surgery. 75% were boys. Patient and intraoperative characteristics are detailed in the table. The mean preoperative, immediate postoperative and POD 1 cystatin C values were 0.71 +/- 0.12, 0.65 +/- 0.10 and 0.60 +/- 0.12, respectively. Likewise, creatinine values were 0.35 +/-0.17, 0.41 +/- 0.18, and 0.36 +/- 0.17. There was no significant difference in cystatin C or creatinine values between the study time points. Linear regression analysis did not demonstrate an association between anesthesia time and postoperative creatinine or cystatin C values. Conclusions Pneumoperitoneum does not appear to affect renal function in children undergoing laparoscopic or robotic surgery. This study provides support for the use of low-pressure pneumoperitoneum and next generation valveless trocar systems. However, further investigation is warranted, given the limited sample size and relatively short duration of surgeries. Funding None
Authors
Julia Finkelstein
Solomon Woldu Alexander Small Nina Mikkilineni Sarah Lambert Pasquale Casale |
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MP52-03 |
Classification of Kidney tumors with 1064 nm dispersive Raman spectroscopy |
Surgical Technology & Simulation: Instrumentation & Technology I | 17BOS |
Abstract: MP52-03 Sources of Funding: none Introduction The number of small, incidentally detected renal masses increase steadily. About 6,000 benign cases are misclassified radiographically as malignant and removed surgically yearly. Raman spectroscopy (RS) has been widely demonstrated for tissue characterization, however current implementations with either 785 or 830 nm near-infrared excitation have been ineffectual in tissues with intense auto-fluorescence such as the kidney. Recently, a RS system using 1064 nm light source was described which may have greater sensitivity for malignant and benign tissue discrimination due to decreased bulk tissue auto-fluorescence. Our aim was to evaluate the ability of 1064nm RS to distinguish normal and malignant renal tissue. Methods Ex vivo specimens of Renal Cell Carcinoma and healthy human kidney were obtained from the Cooperative Human Tissue Network at Vanderbilt university. Measurements were made using of a benchtop dispersive 1064 nm Raman system. Multiple spectra were acquired from at least 5 physical locations across each specimen. A total of 93 measurements were used for the final analysis. _x000D_ The resulting spectra were put into a machine learning algorithm, sparse multinomial logistic regression (SMLR), to predict class membership of healthy and malignant tissues, and cross-validated using a leave-one-specimen out approach. Posterior probabilities of group classifications were extracted. Spectral bands that robustly differentiated between malignant and benign tissue were identified by the SMLR algorithm. A quantitative metric based on SMLR outputs called feature importance, defined as the product of the mean weight and frequency of usage of each feature, guided the association of spectral features with biological indicators of healthy and diseased Kidney tissue. _x000D_ Results The SMLR algorithm identified 152 significant Raman spectral bands. most important features are depicted in figure 1. Correct classification by the SMLR algorithm was obtained in 93.33% of the trials with sensitivity, specificity, negative and positive predictive value of 93.2%, 88.6, 92.9% and 89.2% respectively. Conclusions RS can accurately differentiate normal and malignant renal tissue. This suggests implications for utilizing RS for optical biopsy and surgical guidance in nephron sparing surgery. Funding none
Authors
Miki Haifler
Isaac Pence Benjamin Ristau Andres Correa shreyas Joshi Richard Greenberg David Chen Marc Smaldone Alexander Kutikov Rosalia Viterbo Robert Uzzo Amnon Zisman Anita Mahadevan-Jansen Chetan Patil |
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MP52-04 |
The decline of laparoendoscopic single-site surgery: a survey of the Endourological Society to identify shortcomings and guidance for future directions. |
Surgical Technology & Simulation: Instrumentation & Technology I | 17BOS |
Abstract: MP52-04 Sources of Funding: none Introduction Laparoendoscopic single-site (LESS) surgery for urologic procedures was initially embraced by many with great enthusiasm. However, it became clear that this was a technique with a steep learning curve biased towards skilled laparoscopic surgeons. The aim of this study was to analyze the most recent temporal trends in the adoption of urologic LESS, to identify the perceived limitations associated with its decline, and to determine factors that might revive the role of LESS. Methods A 15 question survey was created using Google Forms and sent to members of the endourological society in September 2016. Out of the 2800 email addresses listed in the database, we asked only members who performed LESS procedures in practice to respond to the survey. Results 106 urological surgeons responded to the survey. Most of the respondents were from the United States (35%) and worked in an academic hospital (84.9%). Standard LESS was the most popular approach (78.1%), while 14.3% used robotics and 7.6% used both. 2009 marked the most popular year to perform the initial and the majority of LESS procedures, 27.6% and 20%, respectively. The most common LESS procedure was a radical/simple nephrectomy at 51% followed by pyeloplasty at 17.3%. When asked approximately how many LESS procedures have you performed in the past 12 months, 63 (60%) urologists stated none. When asked to compare LESS to conventional laparoscopy, only cosmesis was deemed to be better. Over time, opinions changed about cosmesis such that an increase in 82% and a decrease in 26% of surgeons thinking LESS was no different and LESS was better than laparoscopy, respectively. Worsening shifts in enthusiasm for LESS also occurred with patient desire, marketability, cost, safety, and robotic adaptability (Figure 1). Factors rated the highest to help LESS gain popularity included a new robotic platform (4.25/5), instrument modifications (4.03/5), and improved suturing (3.97/5). Conclusions 2009 represented the peak year for implementation of LESS in urology. Several factors have contributed to the decline of the technique over the past 5 years. The availability of a purpose-built robotic platform and better instrumentation overcoming current ergonomic challenges might translate into a renewed future interest of LESS. Funding none
Authors
Igor Sorokin
Abhay Rane Brian Irwin Riccardo Autorino Evangelos Liatsikos Noah Canvasser Jeffrey Cadeddu |
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MP52-05 |
Differential Fluorescence for Intraoperative Margin Assessment with Near-Infrared Fluorescence Imaging during Robotic Partial Nephrectomy |
Surgical Technology & Simulation: Instrumentation & Technology I | 17BOS |
Abstract: MP52-05 Sources of Funding: none Introduction Near-infrared fluorescence (NIRF) technology in robotic surgery allows visualization of tissue fluorescence after giving intravenous indocyanine green (ICG). While this technology has been available for five years and has been adopted for perfusion assessment, it has not been widely adopted for achieving differential fluorescence (DF) of normal kidney versus tumors during robotic partial nephrectomy (RPN). Normal kidney fluoresces with NIRF due to bilitranslocase transport of ICG into proximal tubule cells while most renal tumors, including most renal cell carcinomas (RCC), should not fluoresce. This differential fluorescence of normal kidney and RCC allows better visualization of tumor edges and visual assessment of margins during and after tumor resection with fluorescence confirming a grossly negative margin. Most surgeons have abandoned using NIRF for DF citing inability to reliably achieve fluorescence of the kidney and not the tumor. While the dose of ICG is not critical when used to assess perfusion, improper ICG dosing will cause the tumor to fluoresce and make it indistinguishable from normal kidney. We developed an ICG dosing regimen providing reliable DF in most cases and report our success with NIRF. Methods RPN was performed with NIRF imaging in 253 tumors, the largest reported experience to date. Intraoperative assessment of tumor fluorescence was prospectively recorded at the time of surgery by the surgeon before pathologic assessment of tumors. The ICG dosing regimen included test doses beginning as low as 0.25cc to avoid overdosing and panfluorescence._x000D_ Results Mean age was 58yrs (26-89) with mean body mass index of 32kg/m2 (18-63). Mean tumor size on imaging was 3.4cm (0.7-9.7) with mean R.E.N.A.L. nephrometry score of 7.3 (4-11), including 32 hilar tumors and 164 tumors >50% endophytic. Mean operative time was 170min. Among all 253 tumors, DF was successfully achieved in 217 (86%). Among 36 tumors that undesirably fluoresced, 8 were oncocytomas and 4 were chromophobe RCC, which are both known to express bilitranslocase, with 4 angiomyolipomas. Among 25 oncocytomas, 8 fluoresced such that DF was only successful in 68% of oncocytomas. Among 209 RCCs, 186 did not fluoresce (89%). Only 1 positive margin occurred (0.4%). Conclusions Robotic NIRF imaging was highly reliable (89%) in visualizing DF of RCC versus normal parenchyma but less so in oncocytomas as expected. Further study is needed to determine whether this contributed to the <1% positive margin rate. Funding none
Authors
Ronney Abaza
Janice Rosenthal Jatin Gupta |
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MP52-06 |
Laparoendoscopic single site surgery (LESS) and minilaparoscopy (ML): an objective evaluation through a prospective randomized trail |
Surgical Technology & Simulation: Instrumentation & Technology I | 17BOS |
Abstract: MP52-06 Sources of Funding: none Introduction The key advantages of LESS are better cosmesis and less morbidity. Meanwhile, instrument clashing and loss of triangulation are the main limitations. ML overcomes such limitations but with multiple mini-incisions. The two approaches were compared. Methods A prospective randomized trial was conducted to compare the LESS versus ML nephrectomy. LESS nephrectomy was performed via a skin incision at the umbilicus. Three ports (5mm each) were placed through this incision. Meanwhile, ML nephrectomy was done through 3 ports (3-5 mm each) where the camera port was placed at the umbilicus.The cosmetic outcome (primary end point), operative time, blood loss, hospital stay and complications were recorded and compared. Patient scar assessment questionnaire (PSAQ) was used for evaluation of cosmetic outcome and patient satisfaction with the scars at 3 month postoperatively. The PSAQ consists of 5 sub-scales: appearance, symptoms, consciousness, satisfaction with appearance and satisfaction with symptoms. Each sub-scales consists of a set of items with 4 point categorical responses, scoring 1-4 points with 1 point assigned to the most favorable category and 4 assigned to the least favorable. Experienced laparoscopic surgeons performed all procedures. The estimate sample size was 62 patients. The cases were randomized using a computer generated numbers. Results Thirty-one patients were included in each arm. Preoperative data were comparable in both groups. The cosmetic outcome had no statistical difference in the two groups (Table:1). The operative time was significantly longer in LESS group (119 ± 23 versus 73 ± 14 min, p <0.001). The estimated blood loss was less in ML patients (55 ± 18 versus 102 ± 27 ml in LESS group, p <0.001). Extra port was needed in 3 and 4 patients in LESS and ML groups respectively (p>0.05). Conversion to conventional laparoscopy was recorded in one of LESS cases. Conversion to open surgery was reported in one patient in each group (p>0.05). The complication rates and grades were comparable in both groups. Hospital stay was 2.1 and 1.8 days for LESS and ML groups (p>0.05). Conclusions ML represents a real alternative to LESS with comparable cosmetic outcome, shorter operative time and less blood loss. Funding none
Authors
Ahmed Galal
Ahmed shoma Ahmed Mansour Nasr Eltabei |
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MP52-07 |
Does the use of 5 mm instruments affect the outcomes of robot-assisted laparoscopic pyeloplasty in smaller working spaces? A comparative analysis of infants and older children |
Surgical Technology & Simulation: Instrumentation & Technology I | 17BOS |
Abstract: MP52-07 Sources of Funding: none Introduction Pediatric robot-assisted laparoscopic (RAL) pyeloplasty has become a viable minimally invasive surgical option for ureteropelvic junction obstruction (UPJO) with several previous reports on its efficacy and safety. However, RAL pyeloplasty in infants can be a challenging procedure due to the smaller working spaces, and the use of the larger 8 mm instruments for these patients instead of the 5 mm instruments is common due to the shorter wrist lengths. We hypothesized that the use of 5 mm instruments for RAL pyeloplasty in infants with smaller working spaces will not affect the perioperative parameters and surgical outcomes in comparison to older children with larger working spaces. Methods We compared the perioperative parameters and surgical outcomes of RAL pyeloplasties performed by a single surgeon in infants and non-infant pediatric patients over a 2 year period using an 8.5 mm camera and 5 mm robotic instruments. Patient demographics, operative times, intra- and post- operative complications, hospital pain medication usage, hospital length of stay, and treatment success rates were compared between the two groups. Results A total of 65 pediatric RAL pyeloplasties were included in the study (16 infants and 49 non-infant pyeloplasties). There were no significant differences in gender, laterality, proportion of re-do pyeloplasty, or preoperative hydronephrosis grade between the two groups. All procedures were performed without conversion to open surgery or significant perioperative complications. There were no differences in segmental operative times (total operative time, console time, port placement time, time for dissection to UPJO, and anastomosis time), hospital pain medication usage, and hospital length of stay between the two groups (p > 0.05 for all comparisons). The treatment success rates were 93.8% (15/16) and 100% (49/49), respectively (p = 0.08). Conclusions RAL pyeloplasty is a safe and effective surgical modality even in infants with comparable perioperative parameters and outcomes as those in older children. The use of 5 mm instruments in infants with smaller working spaces does not affect these parameters as well, while offering the potential for improved cosmesis. Funding none
Authors
Minki Baek
M. Selcuk Silay Jason Au Gene Huang Abhishek Seth Nicolette Janzen David Roth Chester Koh |
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MP52-08 |
Technique and case series of MRI guided in-bore biopsy for patients without rectum |
Surgical Technology & Simulation: Instrumentation & Technology I | 17BOS |
Abstract: MP52-08 Sources of Funding: This research was supported by the Intramural Research Program of the National Cancer Institute, NIH Introduction MRI targeted biopsy has changed the evaluation paradigm of patients with elevated PSA. However, in patients without a rectum, the fusion platforms to target suspicious lesions on MRI cannot be utilized due to inability to use transrectal ultrasound. In-bore MRI guided biopsy is a potential alternative for targeting specific lesions in these patients. This report outlines the techniques used in a series of five patients undergoing in-bore MRI guided prostate biopsy using registration with the Visualase® (Medtronic) MRI guided laser ablation platform. Methods Patients without rectum with presence of suspicious lesions on prostate mpMRI were scheduled for biopsy in the MRI suite. Patients were placed under general anesthesia and prepped and draped on the MRI table in the frog-leg position. The biopsy grid was positioned to be flush with the perineum. T2W MR images of the prostate were obtained, transferred to the Visualase platform, and registered to the fiducials using the Visualase system. Serial T1W MR images were used to identify the location and depth of the lesion and then to confirm the location of the biopsy needles. A total of 2-8 cores were obtained from each patient. After completion of the procedure, patients were transferred to the recovery area in stable condition. Results Four patients with suspicion of prostate cancer on prostate mpMRI and surgical absence of rectum underwent prostate biopsy by above technique. The median age was 72 (58-77) years and median PSA was 4.28ng/ml (3.6-6.73). Patient 1 had ileoanal anastomosis and Patients 2-4 had APR, due to UC in Patients 1-3 and rectal cancer in Patient 4. Patient 1 was found to have Gleason 8 and patient 4 had Gleason 7(3+4). Patient 2 and 3 had negative targeted biopsy. No complications from in-bore biopsy were noted. Conclusions &[Prime]In bore&[Prime] MRI guidance as a technique during prostate biopsy has been in use since 2002. We report the technique of MRI targeted biopsy using the Visualase MRI guided laser ablation platform, which has traditionally been used for focal laser ablation. Use of this platform allows for accurate registration and targeting of the lesions in patients not eligible for MRI-TRUS fusion. Funding This research was supported by the Intramural Research Program of the National Cancer Institute, NIH
Authors
Dordaneh Sugano
Abhinav Sidana Collier Wright Brian Calio Mahir Maruf Amit Jain Maria Merino Peter Choyke Baris Turkbey Bradford Wood Peter Pinto |
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MP52-09 |
Intraoperative Identification of Nerves Using a Myelin-binding Fluorophore: Comparative Efficacy of Intravenous vs. Topical Administration |
Surgical Technology & Simulation: Instrumentation & Technology I | 17BOS |
Abstract: MP52-09 Sources of Funding: This study was supported the Sidney Kimmel Center for Prostate and Urologic Cancers, the NIH/NCI Cancer Center Support Grant P30_x000D_ CA008748, and by David H. Koch through the Prostate Cancer Foundation Introduction Intraoperative identification of nerves is essential in various surgical scenarios, where nerve injury can be inadvertent and cause loss of function. We compared the diagnostic efficacy of intravenous (IV) vs. topical administration of the fluorophore GE3126 to identify nerves in a surgical model. Methods Surgical models were created using Yorkshire pigs. Under general anesthesia, a laparotomy was performed and the retroperitoneum exposed. GE3126 was administered using an IV or topical route. Fluorescence was recorded using open and laparoscopic imaging systems. A retroperitoneal dissection was performed to harvest distinct fluorescent structures resembling nerves. Pigs were euthanized at the end of the procedure. Pathologic analysis of harvested tissues included microscopy and staining with hematoxylin and eosin (H&E) and Luxol fast blue. Fisher&[prime]s exact test was used to compare the positive predictive value of fluorescence after intravenous vs. topical administration of GE3126. Results Specimens were collected from 5 animals after IV administration of GE3126 (dose range, 0.7-10 mg/kg), and from 5 animals after topical administration of GE3126 (dose range, 100-900 mcg) A total of 15 distinct fluorescent structures were harvested after IV injection; 11 were harvested after topical application. The positive predictive value for nerve identification was 11/15 (73%) for the IV route vs. 8/11 (73%) for the topical route (p=1.0). The average diameter of nerves identified was 560 microns, ranging from 20 to 2,072 microns, with a similar diameter distribution between specimens collected after IV and topical administration. Conclusions Real-time anatomical enhancement of nerves was consistently achieved in a large animal model using the fluorophore GE3126, with similar diagnostic efficacy whether administered using an IV or topical route. Research in human subjects is warranted. Funding This study was supported the Sidney Kimmel Center for Prostate and Urologic Cancers, the NIH/NCI Cancer Center Support Grant P30_x000D_ CA008748, and by David H. Koch through the Prostate Cancer Foundation
Authors
Pedro Recabal
Takeshi Hashimoto Jozefina Casuscelli Aditya Bagrodia Katie S. Murray Jonathan Coleman Timothy Donahue Vincent P. Laudone |
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MP52-10 |
A prospective randomized controlled trial for assessment of perineal hydrodissection technique for nervesparing robot assisted radical prostatectomy |
Surgical Technology & Simulation: Instrumentation & Technology I | 17BOS |
Abstract: MP52-10 Sources of Funding: none Introduction To prospectively evaluate the safety and efficacy of perineal hydrodissection in robot assisted nervesparing prostatectomy in a randomized, controlled trial in patient scheduled for nerve sparing, robot assisted prostatectomy_x000D_ Methods Patients were randomized for perineal, ultrasound guided hydrodissection(HD) prior to radical prostatectomy and compared to standard treatment(ST). Perioperative parameters were assessed and included: erectile function (IIEF5-score), reported grade of erection, ability for sexual intercourse, continence, TNM stage and Gleason of prostatectomy specimen, blood loss and time for surgery, PSA. Follow-up was done every 3 months, including erectile function (IIEF5-score), reported grade of erection, ability for sexual intercourse, continence, PSA._x000D_ Results 21 patients were enrolled to this prospective study, 10 for ST and 11 for HD. Both groups showed comparable demographic and preoperative oncological data. Blood loss and time for surgery did not differ significantly. HD resulted in 66% (4/6) rate of positive surgical margins(PSM) in pT3 tumors vs. 50% in ST (1/2;p=0.67). Follow-up revealed higher IIEF scores, better ability for sexual intercourse and early continence in HD. _x000D_ Conclusions Perineal hydrodissection should not be performed in pT3 tumors. Although it can increase postoperative erectile function after radical prostatectomy, careful patient selection is needed to avoid PSM_x000D_ Funding none
Authors
Gencay Hatiboglu
Tobias Simpfendörfer Lorenz Uhlmann Stephan Macher-Göppinger Joanne Nyarangi-Dix Sascha Pahernik Boris Hadaschik Markus Hohenfellner Dogu Teber |
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MP52-11 |
Prospective randomized trial comparing Endosheath with Visera Elite System for clinical use & improved cost-effectiveness |
Surgical Technology & Simulation: Instrumentation & Technology I | 17BOS |
Abstract: MP52-11 Sources of Funding: Cogentix Medical Introduction Flexible cystoscopy is routinely performed by urologists as an outpatient procedure. The use of a disposable sheath can increase the cystoscope lifespan and reduce costs related to reprocessing. The aim of this study was to compare the Endosheath Technology with the Visera Elite System for the following parameters: urinart tract infection (UTI), patient satisfaction, physician assessment and cost-effectiveness. _x000D_ _x000D_ Methods This is a prospective, randomized, single center clinical trial (IRB#00036203) performed in patients referred for cystoscopy. Patients with UTI, chronic pelvic pain, urethral strictures were excluded. Urinalysis/culture were collected before and 14 days after cystoscopy using Visera Elite System (Olympus) or Endosheath System (Cogentix). After cystoscopy they filled a Visual Analog Scale (VAS) for pain/discomfort. Physicians filled 5-point Likert scales for the following elements: ease of insertion, manipulation, optical quality and overall use. The reprocessing time, cost analysis, which means staff-cost associated with reprocessing & retail-price per system, were compared._x000D_ Results Out of 74 patients enrolled, 40 completed the 2-weeks study; 20 underwent cystoscopy with Visera Elite System and 20 with Endosheath. There were 2 positive cultures at 14 days follow up in the Visera System. VAS, physicians assessment and reprocessing time data are shown in Table 1. The cost analysis are presented in Tables 2 and 3._x000D_ _x000D_ Conclusions There was no increase in the risk of infection using the Endosheath System. It has a lower cost and reprocessing time. Regarding patient VAS and physician subjective assessment there was no difference in a comparative analysis. _x000D_ _x000D_ Funding Cogentix Medical
Authors
Thomas Watkins
Joao Zambon Ashok Hemal Robert Evans Ryan Terlecki Jorge Gutierrez Majid Mirzazadeh Gopal Badlani |
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MP52-12 |
Accurate transurethral resection of bladder tumor located in lateral bladder wall: a novel technique obtaining En Bloc resection and obviating obturator nerve stimulation. |
Surgical Technology & Simulation: Instrumentation & Technology I | 17BOS |
Abstract: MP52-12 Sources of Funding: none Introduction The lateral bladder wall harbors 46.8% of all bladder tumors. Transurethral resection of bladder tumor (TURBT) in these cases remain as a challenge because adductor muscle spasm often occurred. Bladder perforation, bleeding, incomplete resection, and extravesical spread of tumor are major risks of this reflex. TURBT is performed conventionally with an electrocautery loop. The piecemeal resection specimens are inappropriate for pathological evaluation. Obturator nerve block (ONB) can prevent obturator jerks with various success rates. However,insufficient ONB often occurred.There is urgent need to investigate a reliable method to resect tumors nested in lateral bladder wall. In this study we achieved this goal by accurate transurethral resection of bladder tumor (ATURBT). Methods This study includes 42 males and 23 females. Mean patient age was 61.1±16.2 years. Only tumors nested in the lateral bladder wall were recorded and tumors > 2.5 cm in diameter were excluded. ATURBT was performed using a plasma kinetic needle electrode under subdural anesthesia without ONB. After electrocautery of the bladder mucosa by coagulation current, the needle was then inserted into the muscle layer and the muscle bundles were stretched away from the lateral bladder wall, followed by cutting with the electroresection current. The tumor as well as its base was dissected bluntly with the needle. The intact tumor specimen was retrieved through the resectoscope sheath and sent for pathological examination. Postoperative bladder irrigation was not performed unless hematuria occurred. Catheter was removed within 2 days after operation. Intravesical perfusion with epirubicin or BCG was applied once or weekly for 8 weeks after operation, followed by monthly maintenance to 12 months. Results 65 patients with tumors located in the lateral bladder wall received ATURBT under epidural anasthesia without any obturator nerve block. 76 tumors were resected with diameter of 0.5-2.5 cm (mean1.9±0.4 cm). The resection time of one tumor was 1-10 min (mean 4.3±2.4 min). No obturator nerve reflex occurred. No bladder wall perforation or severe bleeding occurred. Precise TNM stage were obtained, including 36% pTa, 54% pT1, and 10% pT2. 4 cases had tumor recurrence during a mean follow-up of 28.6 (9-38)months. No recurrence at the resection site occurred. Conclusions ATURBT can resect tumors located in the lateral bladder wall without obturator nerve reflex. The en bloc specimen helps to make accurate pathological diagnosis. Funding none
Authors
Shengkun Sun
Axiang Xu Guangfu Chen Xu Zhang |
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MP52-13 |
Transperineal MR-guided prostate needle interventions using a patient-specific template |
Surgical Technology & Simulation: Instrumentation & Technology I | 17BOS |
Abstract: MP52-13 Sources of Funding: This research was supported by the Intramural Research Program of the National Cancer Institute, NIH Introduction The aim of the study is to test the feasibility of a low cost, patient-specific template that allows for angulated insertion of needles during transperineal MR-guided biopsy and treatment for prostate cancer. Currently, transperineal MR-guided biopsy can be performed with a standard straight grid, or with a robotic device. The straight grid does not incorporate information on patient-specific anatomy or disease, and renders it difficult to avoid structures such as the pubic arch. Robotic devices are not currently in widespread use due to regulatory issues, and can be prohibitively expensive. We propose a two-plate template in which guide holes drilled mid-procedure, using an MR image registered with 3D imaging software, allow for accurate direction of biopsy needles to specific tumor locations. Methods The two-plate template was attached to a platform in a fixed position relative to a prostate phantom. A 3T MR image of the template (with gadolinium fiducials) and the phantom was obtained, and the template and phantom were registered to MRI coordinates. The MR images were uploaded onto a custom-made module in 3D slicer. Four fiducials were localized in the image and registered to their physical locations on the template, allowing the user to plan needle trajectories and calculate insertion depths to the targets. These trajectories can be manually translocated as necessary in order to minimize contact with other trajectories and nearby structures. The disposable plates were placed into a portable milling machine, which then drilled the corresponding guide holes according to the plan. The plates were replaced into the template frame, and biopsy needles were inserted into the phantom at the angle constrained by the guide holes. The phantom, template, and needles were imaged via CT scan for confirmation of placement accuracy. Results Three MRI-visible targets were identified in the image. Mean and standard deviation of error was 2.83mm ±1.42 for user 1 and 4.70mm ±3.66 for user 2. Conclusions It is feasible to use a patient-specific template for low-cost, angulated transperineal MR-guided prostate biopsy. The method has potential applications not only in prostate biopsy, but also in other forms of targeted therapy. Future studies will consider further tests of accuracy, efficiency, convenience, and applicability. Funding This research was supported by the Intramural Research Program of the National Cancer Institute, NIH
Authors
Dordaneh Sugano
Sheng Xu Reza Seifabadi Ivane Bakhutashvili Neil Glossop Peter Choyke Peter Pinto Reto Bale |
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MP52-14 |
TRUS Robot-Assisted Prostate Biopsy: A Feasibility Study |
Surgical Technology & Simulation: Instrumentation & Technology I | 17BOS |
Abstract: MP52-14 Sources of Funding: Study supported by the Patrick C. Walsh Prostate Cancer Research Fund. The ultrasound equipment used in this study was provided by Hitachi Aloka Medical America, Inc. Introduction A freehand TRUS-guided prostate biopsy has significant limitations with spatially clustered and poorly targeted biopsy cores (J Urol. 2012 Dec;188(6):2404-9.) We have developed a novel, 4 degree of freedom (DoF) robotic TRUS probe manipulator (TRUS Robot) (Urology 2011; 77:502-7). Here, we examined the feasibility of image-guided navigation during prostate biopsy using TRUS Robot by obtaining TRUS images of the prostate gland and guiding the biopsy using a geometrically distributed biopsy cores._x000D_ Methods TRUS Robot was updated to allow handling of an end-fire TRUS probe and an easy passage of the prostate biopsy needle. Three-dimensional (3-D) image reconstruction, navigation, and core placement software were also developed to allow the geometric core distribution and to align the probe on target for biopsy with minimal motion of the probe around the prostate and between the biopsy cores. _x000D_ Results After IRB approval and informed consent were obtained, 3 subjects underwent TRUS Robot-guided prostate biopsy without complications. The TRUS Robot allowed a steady handling and remote manipulation of the TRUS probe during biopsy. After a manual positioning of the TRUS probe, an automated spin motion of TRUS Robot allowed the acquisition of the entire gland and its 3-D reconstruction. Selection of the extended sextant biopsy core locations was done in the images. Then, the robot oriented the TRUS probe on each target and biopsy cores were obtained manually through the needle guide under direct ultrasound visualization. TRUS Robot and software allowed a smooth and minimal movement between biopsy cores. The accuracy and precision of core targeting according to the plan were 0.49 and 0.22mm, respectively._x000D_ Conclusions TRUS Robot-guided prostate biopsy is safe and feasible. It helps define a biopsy plan, provides a mechanism to accurately sample the gland accordingly, and gives a quantitative quality control on the actual distribution of the cores. A successful TRUS Robot-guided prostate procedure provides crucial spatial information of the biopsy cores for improved cancer detection, treatment, and monitoring._x000D_ Funding Study supported by the Patrick C. Walsh Prostate Cancer Research Fund. The ultrasound equipment used in this study was provided by Hitachi Aloka Medical America, Inc.
Authors
Misop Han
Sunghwan Lim Changhan Jun Doru Petrisor Dan Stoianovici |
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MP52-15 |
COMPARATIVE ASSESSMENT OF CORE BIOPSY NEEDLES |
Surgical Technology & Simulation: Instrumentation & Technology I | 17BOS |
Abstract: MP52-15 Sources of Funding: none Introduction A number of core biopsy needles are available on the market. We compared the performance of six 18-gauge forward throw, fully automated types. Methods Measured properties are sample quality, needle tip deflection, noise level, ultrasound visibility, and needle specifications and dimensions. Sample quality (core length, weight, and fragmentation) was assessed based on cores obtained from porcine tissues. Fragmentation is defined as 0=sample not fragmented, and 1= fragmented. Needle tip lateral deflection was measured at a 102 mm insertion depth in 4 media – gelatin, porcine loin, chicken breast, and bovine liver tissues. The noise level of each instrument was measured with a digital decibel meter (BAFX Product®) at a distance of 100 mm between the needle and the meter. Ultrasound visibility was assessed with an ultrasound probe (Hitachi Preirus, EUP-B512) in water tank. Results There were significant differences in performance between the needles (Table 1). Average core length was longest with the Cook needle (9.9mm, p=0.0002). Core fragmentation was highest with Cook (80%, p=0.003). Average weight per core was highest with Cook (4.15mg) and lowest with Bard Max-Core (2.60mg, p<0.0001). Needle tip deflection varied by needle and by medium (p<0.0001 for all media; Figure 1). Deflection in all 4 media was lowest with BioPince and highest with TSK. The noise level ranged from 100.62dB for Bard Max-Core to 107.24dB for TSK (p<0.0001)- a sound pressure difference of approximately 2.2 times. No difference in ultrasound visibility was detected. Of note, in the present study, the BioPince needle did not exhibit “zero biopsy”, as reported by patient studies. Conclusions Six core biopsy needles demonstrate significant differences in quantitative measures of overall sample quality, needle tip deflection, and noise level. These can be used for needle selection in the clinical setting. Funding none
Authors
Carling Cheung
Changhan Jun Doru Petrusor Bruce Trock Misop Han Dan Stoianovici |
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MP52-16 |
Intraparenchymal therapy delivery in the prostate: the role of imaging and device design |
Surgical Technology & Simulation: Instrumentation & Technology I | 17BOS |
Abstract: MP52-16 Sources of Funding: National Institutes of Health, the Institute of Diabetes and Digestive and Kidney Diseases_x000D_ (NIH/NIDDK)_x000D_ Introduction New protein toxin therapies directly injected into the prostate are in clinical trials for prostatic diseases. A major challenge is predictable control of distribution. Magnetic resonance imaging (MRI) can potentially provide useful insight into the movement of liquid agents within organs after injection. Our objectives are to evaluate the distribution of injected liquids as a function of prostate anatomy and physiology, and of device design Methods Injections of MRI contrast reagents were placed into 18 ex-vivo human prostates after surgical excision in standard of care therapy for invasive bladder cancer patients, with IRB approval. Contrast agents were infused into the specimens via standard hollow needles and needles with a porous customizable length, and their performances were compared. MRI images were acquired using sequences to quantify volume delivered, distribution, and backflow. Results MRI analysis revealed heterogeneous distribution of infusates in the specimens. Tracer distribution in the tissue was significantly higher in the porous needle [1480 ± 802 ul vs 624 ± 767 ul, p-value = 0.036]. The porous needle design demonstrated a 3-fold greater delivery of infusate into the ex vivo prostate, a 2-fold greater volume of distribution, and 2-fold greater fraction of infused distribution compared to standard needle. The volume of distribution divided by the amount infused (Vd/Vi) increased by 80% with the porous needle, though no statistically significant association due to small sample size. Conclusions This study demonstrated that prostatic tissue is anatomically heterogeneic, which presents considerable challenge to achieving a desired distribution, particularly from a standard needle. Use of a porous needle provides improved distribution over the standard needle. MRI demonstrated infusate distribution and obstacles, and may be of value in pre-injection therapy planning. Funding National Institutes of Health, the Institute of Diabetes and Digestive and Kidney Diseases_x000D_ (NIH/NIDDK)_x000D_
Authors
Hoang-Kim Le
Martin Brady King Scott Coffield Thomas Kuehl Raghu Raghavan V. O. Speights, Jr. Belur Patel Scott Wilson Mike Wilson Rick Odland |
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MP52-17 |
Evaluation and Comparison of Contemporary Energy-Based Surgical Vessel Sealing Devices |
Surgical Technology & Simulation: Instrumentation & Technology I | 17BOS |
Abstract: MP52-17 Sources of Funding: none Introduction We evaluated the performance of 5 currently available energy-based vessel-sealing devices (VSD). Methods We tested the Caiman 5(C5), Harmonic Scalpel Ace Plus (HA), Harmonic Ace +7 (HA7), LigaSure (LS) and Enseal G2 (ES) on small (2-5mm), medium (5.1-7mm) and large (7.1-9mm) vessels in 16 Yorkshire pigs. Vessels were randomized to one of the five devices and then were sealed and transected. Sealing and transection time, thermal spread and burst pressures (BP) were recorded for each trial. The surgeon subjectively rated charring/carbonization, tissue sticking, seal quality and transection quality on a 1-5 scale (1 best and 5 worst). Specimens were sent for histopathologic evaluation of seal quality and thermal spread. BP was measured by inserting an 18-gauge angiocatheter into the lumen of each vessel and pressurizing the irrigant until the vessel ruptured or the seal failed. The angiocatheter was then attached to a digital pressure manometer. BP failure was defined as rupture at pressures less than 300mHg for arteries and 30mmHg for veins. Results A total of 246 vessels were evaluated; 125 were arteries and 121 were veins. _x000D_ _x000D_ Arteries: There was no difference in BP for small size arteries. However the ES had a 10% BP failure rate. For medium arteries the C5 provided the highest BP (proximal and distal jaw), followed by HA7, ES, LS and HA. All mean pressures were more than two times super physiologic for all devices. However, for HA there was a 20% failure rate and for ES the failure rate was 40% at mean pressures of 320 and 480 respectively. For large arteries C5 and LS provided highest BP followed by HA7, ES and HA: 1,676, 530, 467, 467 and 254 mmHg, respectively. HA had BP failure of 40% while ES had a failure rate of 80%, respectively._x000D_ _x000D_ Veins: The C5 provided the highest BP (proximal and distal jaw) across all vein sizes followed by LS, HA7 and HA. Among the small, medium and large veins (up to 9mm), there were no BP failures for all the devices. _x000D_ _x000D_ With regard to thermal spread, all of the devices had similar outcomes with an average of 1 to 2 mm on either side of the jaws. _x000D_ Conclusions In this study, the C5 outperformed all other devices. Thermal spread is minimal with all devices. With all devices, the seal remained intact up to pressures of 250 mm Hg or twice physiologic; of note, the seals with the C5, HA7, and LS were stronger than the vessel wall itself. Funding none
Authors
Zhamshid Okhunov
Renai Yoon Kyle Spradling Achim Lusch Christina Hwang Kathryn Osann Jiaoti Huang Jaime Landman |
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MP52-18 |
Evaluation of a novel three-dimensional funnel mesh for parastomal hernia repair after ileal conduit diversion |
Surgical Technology & Simulation: Instrumentation & Technology I | 17BOS |
Abstract: MP52-18 Sources of Funding: none Introduction Using cross-sectional imaging parastomal hernia (PSH) is detected with a frequency of up to 65% in patients treated with cystectomy and ileal conduit (IC) diversion. While many patients initially remain asymptomatic, up to 30% need surgical repair due to clinical symptoms impacting quality of life. Common repair methods to treat this most frequent complication after IC diversion using native tissue show unacceptable high recurrence rates (>70%), which has led to mesh based repair techniques. Effective and safe surgical techniques and outcomes need to be reported in the urologic literature. _x000D_ We report our open surgical technique and results using an intraperitoneal onlay mesh with a central funnel for the conduit aiming to minimize mesh penetration and PSH recurrence._x000D_ Methods Between 1/2004 and 12/2015, 643 patients were treated with ileal conduit urinary diversion at our institution. Subsequently 40 Patients (6,2%) underwent open PSH repair between 2/2009 and 3/2016 using a novel intraperitoneal-onlay-mesh with a central hole (2cm diameter) and funnel for intestinal parts (DynaMesh IPST). As surgical access we used a 4 cm longitudinal incision below and above the stoma. The mesh was placed intraperitoneally as an onlay and fixed at four corner points with non-absorbent sutures. Patients received clinical and ultrasound follow-up to monitor treatment success and effectiveness. While perioperative data was available for 40 patients, 13 could not be followed at our institution, leading to 27 patients with follow-up data. Results Of the 40 patients perioperatively only one patient developed a wound infection, which was managed with multiple surgical debridements keeping the mesh in place._x000D_ 27 Patients (16 male, 11 female) with a median age of 74 years and a median BMI of 29.4 kg/m2 (IQR 25; 31) could be followed with a median follow up of 29 months (IQR 16; 63). Two patients developed a stoma stenosis (7%) with consecutive dilation of the renal pelvis which needed to be drained with a nephrostomy. Only two patients (7%) developed a PSH recurrence after mesh implant with one of them being in need of revision at last follow-up._x000D_ No patient showed a penetration of the mesh into the intestine, stoma necrosis or stoma prolapse._x000D_ Conclusions The described open surgical technique shows a low perioperative complication rate and a promising low PSH recurrence rate of only 7%. A specifically designed 2-component mesh with a central funnel implanted as an intraperitoneal onlay seems to provide an effective treatment option for PSH repair after ileal conduit diversion. Funding none
Authors
Karl Tully
Florian Roghmann Jobst Pastor Rein Jüri Palisaar Joachim Noldus Christian von Bodman |
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MP52-19 |
The experience of using a dual channelized flexible cystoscope with an Impact Shooter for resection of bladder tumors in human cadavers embalmed by Thiel’s model. |
Surgical Technology & Simulation: Instrumentation & Technology I | 17BOS |
Abstract: MP52-19 Sources of Funding: none Introduction Transurethral en bloc resection of bladder tumor with a dual channelized flexible cystoscope using an Impact Shooter in human cadavers embalmed by Thiel&[prime]s model. Methods This study was approved by the institutional review board of Sapporo Medical University. Four human male cadavers (73 to 86 years old) embalmed by Thiel&[prime]s method were used as a model for performing ESD. A flexible cystoscope (CYF-200; OLYMPUS) was used to perform ESD (Fig. 1a). We used a transparent attachment with a tube of diameter 2.8-mm (Impact Shooter N type 6.0-mm diameter; Top Co.). It is designed for devices such as ESD knives and enables the endoscope to work like a dual channel scope (Fig. 1b). We used an electrosurgical knife (Dual Knife, 2.7-mm diameter; OLYMPUS), commonly used for gastrointestinal tract&[prime]s ESD (Fig. 1c). A circular area of 1.0-2.0-cm diameter was defined in the bladder and identified as the target area for resection (Fig.2a-c). Results The ESD technique was applied into 5 places of bladder per cadaver. Although the target areas were successfully resected from the four cadavers (Fig.2d), one small bladder perforation occurred. In total 20 procedures, the median size of the resected pieces ex vivo was 1.4 cm (range 0.8-2.0 cm), and the median time taken to resect each target piece was 9.0 min (range 4.0–17.0 min). Endoscopic procedures of bladder using a flexible cystoscope with an Impact shooter was technically feasible in the human male cadavers. However, the handling of the tool was slightly difficult because of the poor flexibility of the additional attachment and the influence of the relative hardness of the urethra of cadavers as compared to healthy persons. Conclusions Transurethral ESD technique using a flexible cystoscope was considered technically feasible for the small bladder tumors. We hope that in the near future a new flexible cystoscope with dual and large caliber channels will be developed in order to facilitate ESD technique. Funding none
Authors
Shuichi Morizane
Toshihiro Maeda Ryoma Nishikawa Masashi Honda Yuichiro Ikebuchi Kazuya Matsumoto Masaru Ueki Naoya Masumori Mineko Fujimiya Atsushi Takenaka |
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MP52-20 |
Safety of spontaneous detachment of the no-flip ShangRing circumcision for adolescents & adults: A randomized clinical trial (RCT) in Kenya. |
Surgical Technology & Simulation: Instrumentation & Technology I | 17BOS |
Abstract: MP52-20 Sources of Funding: The Bill & Melinda Gates Foundation (Global Health Grant Number OPP1084493) to EngenderHealth and Weill Cornell Medicine. Introduction Male circumcision (MC) reduces the risk of HIV and other STIs. ShangRing (SR) obtained WHO-prequalification in 2015. Previous studies have indicated that SR MC provides a safe, simple, quick, and minimally invasive approach to MC. In this study, we evaluated an innovative no-flip SR technique which is purported to be faster, simpler, and equally safe in comparison with the standard SR technique. Methods The no-flip technique involves inserting the inner ring of the SR under the foreskin followed by securely clamping the outer ring, providing hemostatic occlusion. The foreskin distal to the device is then excised. In this two-center RCT, the SR device was either removed at a 7-day follow-up or allowed to spontaneously detach. Each group was further divided into two sub-groups; 10-15 years and >15 years of age. Data on pain scores, adverse events (AEs), time to complete wound healing, and overall participant experience were collected. Results Of the 230 participants circumcised at the two study sites, 114 were allocated to the 7-day removal group, and 116 to the spontaneous detachment group. All participants were eligible for SR MC without the limitation of phimosis and adhesions. Pain 20 minutes postoperatively was similar in both groups (median score of 3). 8.4% of participants from ring removal group required additional analgesia at the time of ring removal vs. 2.8% in spontaneous group during the postoperative period (p=0.08). 27.6% of participants in the spontaneous detachment group requested device removal due to pain or discomfort. No AEs were severe. Moderate AEs were noted in 5.3% in the ring removal group vs. 1.7% in the spontaneous detachment group (p=0.14). Wound healing on day-42 was comparable, 90% of participants in the spontaneous detachment group showed healing vs. 78% of ring removal participants (p=0.57) (Figure 1). 97.7% of all participants were satisfied with the healed cosmetic appearance, and 99.5% were willing to recommend SR MC to others. Conclusions The no-flip SR technique was safe and effective; spontaneous detachment was generally acceptable to participants, allowing for comparable pain scores, wound healing, AE rates as well as equivalent safety compared to planned ring removal. Funding The Bill & Melinda Gates Foundation (Global Health Grant Number OPP1084493) to EngenderHealth and Weill Cornell Medicine.
Authors
Omar Al Hussein Alawamlh
Quentin Awori Benjamin V Stone Phil V Bach Ryan Flannigan Marc Goldstein Mark Barone Philip S Li Richard K Lee |
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MP53-01 |
Does baseline serum testosterone influence androgen deprivation therapy outcomes for advanced prostate cancer patients |
Prostate Cancer: Advanced (including Drug Therapy) III | 17BOS |
Abstract: MP53-01 Sources of Funding: none Introduction The predictive value of baseline serum testosterone (s-T) level in advanced prostate cancer (PCa) patients receiving androgen deprivation therapy (ADT), was studied. Methods PCa patients with rising prostate specific antigen (PSA) who received 1 year continuous luteinizing hormone releasing hormone (LHRH) antagonist or agonist ADT, from two large, prospective, randomized, parallel arm, phase 3 trials (NCT00295750 and NCT00928434), with 1 year follow up, were pooled for analysis, comparing low (≤250ng/dL) vs. normal (≥250ng/dL) s-T level groups, and lowest vs. highest quartiles. Kaplan-Meier (K-M) survival estimates and Cox proportional hazards regression models were used to evaluate time to PSA rise, progression-free survival (PFS), and overall survival (OS). Results 838 men (median age 72 years) were eligible for inclusion on an intention to treat analysis basis. 138 (16.5%) had baseline s-T ≤250ng/dL, and lower s-T quartile (n=206) was [le]282ng/dL vs. ≥503ng/dL for highest quartile (n=210). s-T groups ≤250 vs. ≥250ng/dL respectively had comparable Gleason Grade 7-10 (55 vs. 58%), PSA ≥20ng/ml (38% each), locally advanced (15 vs. 24%) and metastatic stage (35 vs. 38%), with 30 vs. 32% unclassified stage at enrollment. Both analyses showed significantly worse survival end-points (p≤0.05) for low baseline s-T PCa patients, except time to PSA progression (K-M plots below), with PFS and OS hazard ratios 1.86 and 4.85 respectively. Conclusions According to this analysis, biochemically hypogonadal, advanced PCa patients were disadvantaged by significantly worse 1-year progression-free and overall survival after continuous LHRH based medical castration. This new evidence should prompt International guidelines to recommend incorporating baseline s-T measurement in all hormone-naïve advanced PCa patients, to identify and better inform those with low baseline s-T levels for potential inclusion into future new treatment strategy trials versus ADT. Funding none
Authors
Anup Patel
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MP53-02 |
Serum testosterone level is a useful biomarker to aid optimal treatment selection in men with castration-resistant prostate cancer |
Prostate Cancer: Advanced (including Drug Therapy) III | 17BOS |
Abstract: MP53-02 Sources of Funding: none Introduction Enzalutamide and abiraterone are frequently used for castration-resistant prostate cancer (CRPC), because of improved tolerability of them compared to taxanes. However, there are no predictive biomarkers to make a decision of how to best use abiraterone or enzalutamide. The aim of this study was to clarify the impact of serum testosterone in a decision-making of treatment selections (enzalutamide or abiraterone) for CRPC. Methods We retrospectively evaluated consecutive CRPC patients treated at our institution and other satellite hospitals between 2013 and May 2016. A total of 115 patients received enzalutamide or abiraterone for CRPC and had serum testosterone measure at the initiation of the treatment were included in this study. The patients were divided into two groups by serum testosterone before enzalutamide or abiraterone: 54 in the testosterone <5 ng/dl group and 61 in the testosterone ≥5 ng/dl group. Prostate-specific antigen (PSA) response rates (defined as ≥50% PSA declines), PSA progression-free survival (PSA-PFS), and overall survival (OS) were compared between groups. Results A total of 72 patients were treated with enzalutamide and 43 with abiraterone. In the testosterone <5 ng/dl group, the PSA response rates were significantly lower with enzalutamide than that with abiraterone (32% vs. 62%, p=0.033), whereas there was no difference in the testosterone ≥5 ng/dl group (81% vs. 93%, p=0.429). During the median follow-up period of 12 months, 68 men (59%) had PSA relapse. In the testosterone <5 ng/dl group, the median PSA-PFS was significantly lower with enzalutamide than that with abiraterone (2.8 months vs. 6.4 months, p=0.004) (Figure). Likewise, it was significantly lower with enzalutamide than that with abiraterone in the testosterone ≥5 ng/dl group (7.6 months vs. no available, p=0.004) (Figure). Multivariate analysis reveals that testosterone ≥5 ng/dl was an independent predictive factor for PSA-PFS (HR 3.1, p<0.001). However, there was no significant difference in the median OS according to the different testosterone groups. Conclusions This result suggests that serum testosterone level is a useful biomarker in a decision-making of treatment selections in the novel hormonal therapy for CRPC. Funding none
Authors
Kohei Hashimoto
Tetsuya Shindo Hidetoshi Tabata Toshiaki Tanaka Jiro Hashimoto Ryuta Inoue Takashi Shimizu Takashi Muranaka Hiroshi Hotta Atsushi Takahashi Masahiro Yanase Naoya Masumori |
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MP53-03 |
Impact of Lower Castrate-Level Testosterone on Progression to Castrate-Resistant Prostate Cancer for Patients Undergoing Continuous Androgen Deprivation Therapy: A Prospective Cohort Study |
Prostate Cancer: Advanced (including Drug Therapy) III | 17BOS |
Abstract: MP53-03 Sources of Funding: None Introduction We investigated whether lower testosterone threshold compared to traditionally accepted level of castrate-level testosterone (< 50 ng/dl) has an impact on time to progression to castrate-resistant prostate cancer (CRPC) in patients undergoing continuous androgen deprivation therapy (ADT). Methods A single-center, prospective review of 153 consecutive patients undergoing ADT from 2006 to 2016 was performed. Patients were excluded from the analysis if they received intermittent ADT, concurrent ADT with external beam radiation therapy, or if they did not achieve castrate-level testosterone (< 50 ng/dl). Serum testosterone was measured every three months after initiation of ADT. Patients were categorized based on their 1-year mean testosterone value (< 20 ng/dl, 20-32 ng/dl, 32-50 ng/dl, > 50 ng/dl) and outcome measures were compared. Progression to CRPC was assessed with the Kaplan-Meier method. Statistical analysis was performed using the log-rank, Breslow, and Tarone-Ware tests to compare the groups. Results A total of 112 patients were included in the analysis. Median age at diagnosis was 67.9 (range: 50.9-89.1). Median follow-up was 27.9 months (range: 3.3-114.6). Median PSA prior to initiation of ADT was 18 ng/mL (range: 0.61-2940). 72.3% of patients achieved a 1-year mean T < 20 ng/dl; 18.6% achieved 20-32 ng/dl; 5.4% achieved 32-50 ng/dl; and 3.6% achieved > 50 ng/dl. There was no statistically significant difference in progression-free survival between patients with different levels of 1-year mean testosterone values (log-rank p=0.813). Conclusions The results suggest that there may not be a significant impact of strict testosterone control beyond what is considered the traditional castrate-level testosterone. However, only a small proportion of patients had 1-year testosterone > 32 ng/dl (9.0%). A larger study may reveal a beneficial role of strict testosterone reduction in the management of advanced prostate cancer. Funding None
Authors
Taehyoung Lee
Stuti Tanya Bobby Shayegan |
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MP53-04 |
Comparison of the Length of Time from Initiation of Androgen Deprivation Therapy to Salvage Chemotherapy in African American Males and Caucasian Males with Castrate Resistant Prostate Cancer |
Prostate Cancer: Advanced (including Drug Therapy) III | 17BOS |
Abstract: MP53-04 Sources of Funding: Center for Healthy African American Men through Partnerships(CHAAMPS) Grant Number U54MD008620 Introduction Studies have shown that systemic chemotherapy can improve survival in patient who develop castration resistant prostate cancer. We evaluate the time to chemotherapy from initiation of ADT by racial subgroups in men with prostate cancer. Methods We identified 81,579 men diagnosed with prostate cancer between 2004-2009 from the Surveillance, Epidemiology and End Results database (SEER). We then risk stratified the men based on the DAmico criteria. Those with one or more unknown tumor variables (prostate specific antigen, T stage and/or Gleason Score) were labeled unknown. Of this group, we identified 2370 men who received chemotherapy after ADT, 2137 non-Hispanic Caucasian and non-Hispanic 233 African American. Overall and risk-stratified analyses were performed using T-test and multiple linear regression which compared the time interval from diagnosis to chemotherapy and from initiation of ADT to initiation of chemotherapy in African Americans vs. Caucasians. Results The median time from diagnosis to chemotherapy was 32 months and from initiation of ADT to chemotherapy was 25 months. The median time from ADT to chemotherapy for the low risk group was 16 months (n= 119), intermediate risk was 29 months (n = 313), high risk 29 months (n = 920) and unknown 21 months (n = 1018). African American males had a median length of 18 months compared to Caucasian males 25 months (p value from t-test = 0.006). After adjusting for age, year of diagnosis, income, education, Charlson comorbidity score, and risk of prostate cancer, the difference is still significant: the least squares mean time from ADT to chemo is 22.5 months in AA vs. 27.5 months in CA (p=0.006). Conclusions The length of time from ADT to salvage chemotherapy in African American males is shorter compared to Caucasian males. This may suggest that AA men have cancers that progress faster on ADT compared to prostate cancer in Caucasian men. Funding Center for Healthy African American Men through Partnerships(CHAAMPS) Grant Number U54MD008620
Authors
Maria Uloko
Yunhua Fan Stephanie Jarosek Barinath Konety |
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MP53-05 |
Testosterone recovery after long time deprivation therapy: predicitive factors and models (nomograms) |
Prostate Cancer: Advanced (including Drug Therapy) III | 17BOS |
Abstract: MP53-05 Sources of Funding: None Introduction Chemical castration (Total Testosterone, TT,<0,50 ng/mL) is common treatment in intermediate/high risk prostate cancer (PCa) adjuvant to radiotherapy, and in advanced/metastatic PCa._x000D_ After androgen deprivation therapy (ADT) we assume variability and delay until recovery over castration and/or eugonadic state (TT>3.5 ng/mL)._x000D_ We evaluate variability, associated factors, and the design of nomograms for TT recovery after ADT withdrawal._x000D_ Methods Ambispective study on 205 patients after ADT cessation._x000D_ Predictive variables: age at initiation/cessation of ADT, biopsy/surgical specimen (in case) Gleason score, duration of ADT, primary therapy of PCa, and LHRH agonist. Result variables: Recovery of TT over castrate level and eugonadic level. Univariate analysis: Kaplan-Meier curves (log rank test). Multivariate models are built by Cox proportional hazards model._x000D_ The calibration and the discrimination ability of the model, and probability density functions and clinical utility curves are evaluated._x000D_ Results The median biochemical and clinical follow-up are 27 (P25-75:15-39.5? Range: 1-98) and 39 months (P25-75:_x000D_ 28-51? Range: 1-107 months). We find high individualised variabilty in TT recovery._x000D_ - Recovery over castration levels: 25% of patients do not recover. Our intervals of recovery for 25, 50, 75 and 100% of recoverer patients are 4, 7, 10 and 42 months._x000D_ - Recovery over eugonadic levels: 84% of patients do not normalize TT. After 12 months of ADT withdrawal only 8% of patients recovered normal levels, the maximum rate of recovery is at 32 months, no one patient recovered later on._x000D_ In multivariate analysis "duration of ADT" and "age at ADT withdrawal" are significant predictors (H.R:0.69,p=0.0002 and HR:0.44,p<0.0001, for 0.5-Recovery? and HR:0.45,p=0.0006 and HR:0.39,p=0.0002, for 3.5-Recovery)._x000D_ We build two nomograms of recovery at 1, 2 and 3 years, with light overestimation for intermediate values in calibration analysis and a discrimination capacity ('c index') of 0.709 and 0.723,_x000D_ with AUC of 0.778, 0.813 and 0.805, and 0.707, 0.788 and 0.811 at 1, 2, and 3 years, respectively._x000D_ Conclusions We confirmed a high variability in TT recovery after ADT withdrawal._x000D_ We found as the most relevant predictors "duration of ADT" and "age at ADT withdrawal"._x000D_ We obtained accurate calibrated and discriminative predictive nomograms of castration and eugonadic recovery._x000D_ Those models would allow us to estimate and counsell functional recovery after adjuvant therapy, and to keep castration after ADT withdrawal or intermittency in a more cost-effectiveness practice._x000D_ Funding None
Authors
Fernando Estrada
Ángel García de Jalón Angel Borque Luis Esteban Mª Jesús Gil Gerardo Sanz |
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MP53-06 |
The?Effective Period of first Androgen Deprivation Therapy becomes an Prognostic The Effective Period of First Androgen-Deprivation Therapy Becomes an Prognostic Factor in Docetaxel Chemotherapy for Castration-Resistant Prostate Cancer Patients |
Prostate Cancer: Advanced (including Drug Therapy) III | 17BOS |
Abstract: MP53-06 Sources of Funding: none_x000D_ Introduction There is an ongoing debate whether the effective period of androgen-deprivation therapy (ADT) or nadir prostate-specific antigen (PSA) level during non-castration-resistant prostate cancer affects the further therapeutic effect of docetaxel when patients become castration resistant. Herein, our aim was to investigate the prognostic value of response duration of ADT in castration-resistant prostate cancer (CRPC) treated with docetaxel chemotherapy. Methods We retrospectively reviewed the medical records of 201 patients who received ADT therapy before docetaxel treatment. Docetaxel at a dose of 75 mg/m2 was administered every 3 or 4 weeks. We defined the effective period of first ADT based upon prostate cancer clinical trials working group 3 (PCWG-3) criteria. Patient clinico-pathological data were collected to assess the prognostic factors for cancer-specific survival (CSS). Results Among the 201 patients, median age was 73 years and the median follow-up period was 45.5 months. Bone metastases were found in 134 (66.7%) patients, and 85 (42.3%) patients had an EOD grade of 2 or higher. Visceral metastases were found in 47 patients (23.4%). Median CSS and progression-free survival were 21.5 months and 13.5 months, respectively. The median response duration of ADT was 29.2 months. Overall, 121 (60.2%) patients achieved PSA nadir <0.2 ng/ml during first ADT. According to the Kaplan–Meier method, the 2-year CSS rate for first ADT ≥16 months was 62.9%, whereas the counterpart was 32.1% (p<0.001). Furthermore, the 2-year survival rate for nadir PSA <0.2 ng/ml was 65.4%, whereas the counterpart was 40.2% (p=0.002). Multivariate analysis indicated that first ADT response <16 months, pretreatment PSA level ≥20 ng/ml, visceral metastasis, and ALP ≥284 were independent prognostic factors for CSS (HR=2.28, HR=1.69, HR=2.65, and HR=1.98, respectively). However, the degree of nadir PSA level during ADT did not have a significant association with CSS. Conclusions Our results clearly suggested that the effective duration of first ADT was a significant biomarker for predicting the treatment response for CRPC treated with first-line docetaxel. Funding none_x000D_
Authors
Keisuke Shigeta
Takeo Kosaka Ryuichi MIzuno Toshiaki Shinojima Eiji KIkuchi Akira MIyajima Hitoshi Tanoguchi Shintaro Hasegawa Mototsugu Oya |
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MP53-07 |
Impact of metformin on prostate cancer PC outcomes in the E3805 CHAARTED trial |
Prostate Cancer: Advanced (including Drug Therapy) III | 17BOS |
Abstract: MP53-07 Sources of Funding: Partial support and drug supply by Sanofi (NCT00309985) Introduction To evaluate whether metformin (Met) a widely-used, nontoxic oral antidiabetic drug with putative anticancer properties leads to improvements in prostate cancer (PC) outcomes in the CHAARTED trial. Methods In the CHAARTED database where metformin use at baseline was recorded prospectively, we identified patients with metastatic PC who underwent either ADT alone or ADT and docetaxel (D) chemotherapy. Cox proportional hazards models were used to determine the effect of Metformin on outcomes. Results A total of 788 patients (median age, 63 y) had complete data after randomization. Comparison of ADT+D+Met (n=39) to ADT+D (n=357) and ADT+Met (n=29) to ADT alone (n=363) revealed similar clinicopathologic characteristics. Cause of death was PC in 13(81%) of ADT+D+Met, 72(85%) ADT+D, 9(82%) ADT+Met and 105(84%) ADT alone groups. See table for PC outcomes and overall survival by metformin use. Cox regression analysis for overall survival stratified by stratification factors at randomization demonstrates Met use was associated with a trend for worse overall survival (HR 1.47 95%CI: [0.95,2.26], p=0.08) with adjustment for treatment arm and prior local therapy. In contrast, ADT+D use (HR 0.62; 95%CI: [0.47,0.81]) and prior local therapy with surgery or radiation (HR 0.56; 95% CI: [0.38, 0.82]) were associated with improved survival. Conclusions In this study, baseline metformin use for patients with advanced metastatic PC did not improve PC outcomes. However, early ADT and docetaxol improved survival as did a history of local treatment of the primary tumor. Funding Partial support and drug supply by Sanofi (NCT00309985)
Authors
David Jarrard
Yu-Hui Chen Glenn Liu Michael Carducci Mario Eisenberger Yu-Ning Wong Noah Hahn Manish Kohli Matthew Cooney Robert Dreicer Nicholas Vogelzang Joel Picus Daniel Shevrin Maha Hussain Jorge Garcia Robert DiPaola Christopher Sweeney |
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MP53-08 |
Metformin Use Is Associated with Improved Survival in Veterans with Advanced Prostate Cancer On Androgen Deprivation Therapy |
Prostate Cancer: Advanced (including Drug Therapy) III | 17BOS |
Abstract: MP53-08 Sources of Funding: Department of Defense Introduction Metformin is a commonly prescribed glucose-lowering therapy for patients with type 2 diabetes mellitus (T2DM). Basic research supports a synergistic anti-neoplastic effect of metformin for various cancers including prostate cancer (PC). We hypothesize that metformin plus androgen deprivation therapy (ADT) may be synergistic in men with advanced PC. Methods Using national Veterans Affairs databases, we identified all men diagnosed with PC between 2000-2008 that were treated with ADT and had follow-up through October of 2015. We excluded patients that were treated with ADT for ≤6 months or were receiving ADT concurrently with localized radiation therapy. Three cohorts were identified including non-diabetics, diabetics on metformin, and diabetics not on metformin. Our primary outcome was overall survival (OS) and secondary outcomes included skeletal related events (SRE) and PC-specific survival. Results The total cohort after exclusions consisted of 87,344 patients of which 53,893 (61%) were non-diabetics, 14,517 (17%) were diabetics on metformin and 18,934 (22%) were diabetics not on metformin. Mean age was 75 ±11y (non-diabetics), 71 ±12 (diabetics on metformin), and 75 ±10 (diabetics not on metformin), p<0.001. The median OS was 7.1, 9.1 and 7.4 y respectively (p<0.001). Multivariable Cox proportional hazards analysis assessing for predictors of OS showed improved survival in diabetics on metformin (HR 0.77, 95% CI 0.74-0.81; p<0.001) vs. diabetics not on metformin (HR 0.99, 95% CI 0.95-1.03; p=0.5) with non-diabetics as referent group while controlling for age, co-morbidity, and Gleason score. Assessing for predictors of SRE revealed no association between metformin use (HR 0.99, 95% CI 0.92-1.07; p=0.8) and SRE. Lastly, PC-specific survival was improved in diabetics on metformin (HR 0.72, 95% CI 0.67-0.78; p<0.001) and to a lesser extent diabetics not on metformin (HR 0.87, 95% CI 0.81- 0.93; p<0.001) with non-diabetics as referent group. Conclusions Metformin use in Veterans with advanced PC receiving ADT is associated with improved OS and cancer-specific survival. Improved outcomes for PC patients receiving metformin should be evaluated in a prospective clinical trial. Funding Department of Defense
Authors
Kyle Richards
Jinn-ing Liou Vincent Cryns Tracy Downs Jason Abel David Jarrard |
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MP53-09 |
The Number Of Lymph Nodes Sampled During Radical Prostatectomy Does Not Impact the Risk of Biochemical Recurrence in Patients With Seminal Vesicle Invasion |
Prostate Cancer: Advanced (including Drug Therapy) III | 17BOS |
Abstract: MP53-09 Sources of Funding: None Introduction Seminal vesicle invasion (SVI) is a risk factor for poor oncologic outcome in patients with prostate cancer (PC). The total number of lymph nodes removed (lymph node yield [LNY]) during radical prostatectomy (RP) has been reported to have a diagnostic and therapeutic benefit in patients with clinically localized disease regardless of node positivity. This benefit in patients with SVI has not been previously assessed. Methods We identified 221 patients retrospectively from two medical centers who underwent RP without adjuvant treatment between 1990-2015 and had PC with SVI (i.e. pT3b). BCR was defined as a postoperative PSA >0.2 ng/mL, or use of salvage androgen deprivation therapy (ADT) or radiation in response to a clinical suspicion of progression. Multivariable cox proportional hazards models were used to determine if LNY was predictive of BCR. The Kaplan-Meier method was used to determine the 3-yr freedom from BCR. Results Median LNY was 8 (IQR: 4-13). With a median follow-up of 56.9 months, the estimated 3-year freedom from BCR for overall, N0, and N1 patients was 55.7%, 59.0% and 28.3% respectively. Results from multivariable analysis demonstrated that LNY was not significantly associated with risk of BCR for overall (HR=1.01, p=.734), for pN0 (HR=1.00, p=.825) or pN1 patients (HR=1.02=.744). PSA (HR=1.02, p<.001), pathologic Gleason sum ? 9 (HR=1.90, p=.006), more recent RP (HR=1.07, p=.004), bladder neck invasion (HR=1.98, p=.056) and N1 disease (HR=2.19, p=.003) were associated with an increased risk of BCR. Increasing LNY increased the likelihood of detecting more positive lymph nodes (?=0.19, p=.003) in pN1 patients. Conclusions SVI after RP is associated with a high risk of BCR. While greater LNY facilitate increased accuracy in staging, our study demonstrates that in the setting of SVI, pathologic Gleason score and PSA at diagnosis are the primary drivers of BCR. Funding None
Authors
Ketan Badani
Balaji Reddy David Paulucci Michael Whalen Douglas Skarecky Thomas Ahlering |
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MP53-10 |
Robot-assisted Salvage Node Dissection For Oligometastatic Nodal Disease Detected By 68Gallium-PSMA PET/CT: A Multicentre Retrospective Series |
Prostate Cancer: Advanced (including Drug Therapy) III | 17BOS |
Abstract: MP53-10 Sources of Funding: This research is funded by the Australian Department of Health and Ageing by funding of the Australian Prostate Cancer Research Centre-NSW, and the St Vincent's Prostate Cancer Centre. Introduction 68Ga-PSMA PET/CT is an emerging imaging modality allowing early detection of metastases in patients with biochemical recurrence (BCR) after primary treatment for prostate cancer. In oligometastatic node-only disease, this raises the question of whether patients may benefit from early salvage treatment of lymph node metastases (LNM). Robot-assisted salvage node dissection (RASND) based on 68Ga-PSMA imaging may represent an option for selected patients with the aim of cure or at least postponing systemic therapies and their inherent quality of life burden. Methods Between February 2014 and April 2016, patients who underwent RASND for 68Ga-PSMA-detected oligometastatic node disease across two centres were analysed. Safety and oncological results were reviewed. Definitions of PSA Treatment Response (TR) to RASND were based on primary treatment; success was defined as 6-week PSA<0.2ng/ml (broad) or PSA<0.03ng/mL (strict) in those who had primary prostatectomy, and 6-week PSA < post-RT nadir in those who had primary radiotherapy. Results Overall, 35 patients were included in the analysis. A total of 58 lesions were detected on 68Ga-PSMA imaging. Median pre-RASND PSA was 2.2ng/ml (IQR 0.5-5.6) and median time from primary treatment was 61.3 months (IQR 20.5-90.9). 14 patients had targeted dissections, 19 patients unilateral or bilateral extended template dissections and 2 patients a combination of both. In total, 372 lymph nodes were excised. 32 patients (91%) had positive histopathology, with a total of 87 LNM and a median of 2 LNM per patient (IQR 1-3). 8 patients experienced complications, all Clavien Dindo grade ?2. Median follow-up was 12 months (IQR 7.3-18.2). TR was seen in 15 (42.9%) and 11 (31.4%) patients using broad and strict definitions respectively. BCR-free survival (BFS) at a median follow-up of 12 months was 22.9% (broad definition) vs 14.3% (strict definition) for the entire cohort. In those with initial TR, median time to BCR was 3.4 months (IQR 1.8-10.5) and 5.4 months (IQR 1.7-11.8), with broad and strict definitions of initial TR respectively. Clinical progression occurred in 12 patients (34.3%), 2 of which had an initial TR (strict definition). Conclusions RASND appears safe and feasible. In our cohort, less than half of patients had a TR to RASND. Given that 68Ga-PSMA imaging may underestimate micro-metastatic disease, long-term cure is unlikely with RASND. Long-term follow-up is required to assess potential QOL and mortality benefits in the subset that achieved BFS at a median follow-up of 8.5 months. Funding This research is funded by the Australian Department of Health and Ageing by funding of the Australian Prostate Cancer Research Centre-NSW, and the St Vincent's Prostate Cancer Centre.
Authors
Amila Siriwardana
James Thompson Shaela Doig Pim van Leeuwen Anton Kalsbeek Louise Emmett Warick Delprado Hemamali Samaratunga Anne-Maree Haynes Geoff Coughlin Phillip Stricker |
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MP53-11 |
Salvage extended pelvic lymph node dissection in patients with recurrent prostate cancer: 5-year follow-up |
Prostate Cancer: Advanced (including Drug Therapy) III | 17BOS |
Abstract: MP53-11 Sources of Funding: none Introduction The role of salvage extended pelvic lymph node dissection (ePLND) in patients with prostate cancer (PCa) recurrence remains unclear due to the lack of long-term follow-up and survival data. The combination of surgical treatment methods with consecutive androgen deprivation therapy (ADT) as well as with new drugs makes it difficult to evaluate the impact of salvage ePLND alone on cancer specific survival (CSS) and overall survival (OS). Methods We are presenting a retrospective single-center study based on a cohort of 61 patients with biochemical recurrence (BCR) of PCa. In all patients, salvage ePLND was performed between November 2003 and February 2016. The indication for salvage ePLND was based on BCR of PCa and/or suspicious findings in 11C-PET/CT or later in 68Ga-PSMA-PET/CT. None of the patients had proven visceral or bone metastases at the time of salvage ePLND. Surgery was performed according to our standardized Kiel salvage template. We analyzed the dynamics of the PSA level, biochemical recurrence-free (BCRF) survival, OS and CSS and also took into consideration ADT as well as incidence of metastastic development. Results The mean follow-up was 60± 38 months (max 152, min 9); median follow-up was 59 months. The mean number of removed lymph nodes was 22.6. 40 (65.6%) patients were hormone-resistant prior to salvage ePLND; another 21 (34.4%) patients did not receive ADT at all prior to salvage ePLND. 52 (85.2%) of all patients received ADT after salvage ePLND. Immediately after salvage ePLND the PSA level dropped in 40 (65.6%) patients and reached a level below BCR cut-off in 14 (23.0%) patients. 39 (64.0%) patients had a BCR-free period during follow-up and in 24 (39.3%) patients this has continued until the time of analysis. The mean BCR-free survival was 42±34 months. The median BCR-free survival was 33 months. 9 (14.8%) patients died during the follow-up, 8 of them died from PCa metastases. In 4 (6.6%) patients BCR-freedom after salvage ePLND was achieved without ADT and still continues. 2 of these 4 patients also did not undergo ADT before salvage ePLND. 3- and 5-year CSS and OS were equal 93.9%±3.4% (3-year CSS and OS) and 88.2%±5.1% (5-year CSS and OS). Conclusions Salvage ePLND for selected patients with BCR and clinically recurrent nodal disease can lead to BCR-free survival in nearly 65% of the patients. Due to the PSA response after salvage ePLND, ADT can be started later in many patients. Moreover, patients with preoperatively hormone-resistant PCa respond again to ADT after salvage ePLND. Multi-central prospective studies with control groups are needed. Funding none
Authors
Alexey V. Aksenov
Carsten M. Naumann Moritz F. Hamann Diethild A. Melchior Klaus-Peter Juenemann Daniar K. Osmonov |
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MP53-12 |
Standard of care versus metastasis-directed therapy for nodal oligorecurrent prostate cancer following multimodality treatment: a case-control study |
Prostate Cancer: Advanced (including Drug Therapy) III | 17BOS |
Abstract: MP53-12 Sources of Funding: None Introduction There are several retrospective series regarding metastasis-directed therapy (MDT), in the form of either salvage lymphadenectomy (sPLND) or stereotactic body radiotherapy (SBRT), to PET-positive lymph node recurrences after initial radical prostatectomy (RP) and postoperative radiotherapy (PORT). However, these studies are single arm studies without a control group of patients not receiving MDT, which is still considered standard of care (SOC). We pooled data from 5 institutions and performed a retrospective case-control study to assess the influence of MDT to pelvic lymph node metastasis on cancer-specific survival (CSS). Methods The SOC-cohort consisted of 2270 men who underwent RP+PORT (adjuvant or salvage) between 1996-2013 at a single institution (Hamburg) and experienced subsequent biochemical failure managed with systemic treatment administered at physicians&[prime] discretion. The MDT-cohort comprised 227 patients treated with RP+PORT between 1996-2013 who experienced a biochemical recurrence (BCR) followed by a Choline or PSMA PET-detected nodal recurrence. This recurrence was managed with either sPLND (n= 150) or SBRT (n= 77). In case of further systemic progression, systemic treatment was administered at physicians&[prime] discretion. Disease characteristics and the impact of MDT on cancer-specific survival (CSS) was assessed using Cox proportional hazard models. CSS was measured from time of BCR following RP+PORT. A propensity-score matched pair analysis between SOC and MDT patients was performed based on known prognostic factors at initial diagnosis (PSA prior to RP, year of RP, RP Gleason Grade, age, pN-status and pT stage). Results In total, 384 were matched (187:187) with a median follow-up of 64.2 months. Type of treatment (SOC vs. MDT), age at RP, RP Gleason Grade and margin status were significantly associated with cancer-specific survival in multivariate analysis (all p<0.05). After matched-pair analysis, 10 year CSS was 79.4% (95% CI 66.5-88.2)for SOC and 98.8% (95% CI 91.4-98.8) for MDT(p= 0.002). Conclusions MDT to pelvic nodal recurrences of PCa is associated with improved CSS compared to SOC. These data should be considered hypothesis-generating and inform future randomized trials in this setting. Funding None
Authors
Thomas Steuber
Vidit Sharma Piet Ost Karel Decaestecker Thomas Zilli Barbara A Jereczek-Fossa Cordula Jilg R. Jeffrey Karnes |
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MP53-13 |
Freedom from androgen deprivation and radiotherapy therapy after upfront minimally invasive surgery for high-risk prostate cancer |
Prostate Cancer: Advanced (including Drug Therapy) III | 17BOS |
Abstract: MP53-13 Sources of Funding: None Introduction Up front tailor-made wide excision surgery is sometimes offered to men as part of combined modality treatment with adjuvant radiotherapy +/- androgen deprivation therapy (ADT) for high risk and non-metastatic prostate cancer. Particularly young men want to avoid long periods of ADT which is required for primary radiotherapy treatment. Upfront surgery is therefore seen as a reasonable alternative to achieve cure without ADT. We prospectively assessed short term PSA recurrence rates, the need for adjuvant radiotherapy and ADT._x000D_ Methods 278 patients with high risk PCa (47.5% were locally advanced), underwent laparoscopic or robotic radical prostatectomy with pelvic lymphadenectomy from July 2007 to July 2016 at three inner London tertiary referral centres. D&[prime]Amico criteria (cT2c, PSA>20, Gleason grade 8-10) were used to define high risk._x000D_ Supersensitive PSA measurements were used. PSA recurrence was defined as two tests results above 0.02. Kaplan-Meier survival estimates were generated. A small number of patients were offered radiotherapy +/- ADT for undetectable PSA nadir based on the presence of pathological risk factors. Some patients were randomised to the RADICALS study(CRUK/07/008)._x000D_ Uni and multivariate analysis was performed on all available variables. Kaplan-Meier estimates were calculated. Cox multivariate regression analysis was computed to identify pre- and post-operative factors associated with PSA recurrence. Results Median follow up was 34 months (range 0.9-98 months). Of all patients 55.4% did not have PSA recurrence, 38.1% required radiotherapy and 25.2% ADT. Positive margins (p=0.014)and tumour volume (p=0.041) were independently predictive of PSA recurrence. _x000D_ Tumour volume >4cm3 may be predictive of almost certain biochemical recurrence with supersensitive PSA. 5 year free recurrence survival was 51% globally and 50.3% and 18.4% for tumour volume <4cm3 and >4cm3 respectively. Conclusions Young men may have a high chance to avoid ADT (75% in three years) if treated with surgery alone or in combination with radiotherapy. _x000D_ Tumour volume in addition to margin status is a strong predictor of biochemical recurrence in high risk prostate cancer. _x000D_ Since tumour volume can now be obtained pre-operatively with later generation CAD (computer-aided design) software it could be a meaningful pre-operative risk stratification tool for treatment selection and new study designs._x000D_ Funding None
Authors
Pol Servian Vives
Amit Patel David Eldred-Evans Declan Cahill Christian Brown Ben Challacombe Mathias Winkler |
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MP53-14 |
Multimodal treatment for high-risk prostate cancer with high-dose intensity-modulated radiation therapy, concurrent intensified-dose Docetaxel and long-term androgen deprivation therapy after radical prostatectomy and lymphadenectomy: results of a prospective phase II trial. |
Prostate Cancer: Advanced (including Drug Therapy) III | 17BOS |
Abstract: MP53-14 Sources of Funding: None Introduction To evaluate the safety and oncologic outcomes of adjuvant chemo (CHT), high-dose intensity-modulated radiation therapy (IMRT) and long-term androgen deprivation (ADT) therapy following radical prostatectomy (RP) and extended lymphadenectomy (PLND) in high risk prostate cancer patients. Methods Data of patients were collected in prospectively maintained database after IRB approval. Inclusion criteria of the study were: 1) high-risk localized (PSA level ≥20 ng/ml or clinical stage T2c or Gleason score ≥8) or locally advanced (clinical stage T3 or N+, any PSA level, any Gleason score) prostate cancer after RP and PLND 2) patients suitable to receive CHT and RT after surgery. Exclusion criteria were: 1) uncontrolled chronic disease; severe infection; peripheral neuropathy or prior malignancy within the last 5 years before study entry; 2) prior CHT, pelvic RT or local treatments for prostate cancer. Adjuvant IMRT with concurrent Docetaxel and long-term ADT were stared after 3-6 months form surgery. IMRT was performed in 4 to 6 field technique with 15-to 18-MV. Docetaxel was administered in a standard 1-hour intravenous weekly dose (30 mg if body surface area <1.8 m2 and 40 mg if body surface area ≥1.8 m2) for 6-7 weeks. ADT was maintained for 2 years. Acute and late toxicity were evaluated with the Common Terminology Criteria for Adverse Events version 3.0. Biochemical and clinical recurrence-free survival were explored with the Kaplan-Meier method. Results Overall 42 patients were included in the study. Acute Genito-Urinary (GU) toxicity was observed with grade I, II and III in 4 (9.5%), 2 (4.8%), and 1 (2.3%) patients, respectively. Acute Gastro-Intestinal (GI) toxicity was found found with grade I and II in 12 (29.3%) and 3 (7.2%), respectively. In those patients with acute toxicity, concomitant GU and GI toxicity occurred in 3 (7.2%) cases. No acute grade ≥IV toxicity was detected. A residual GU grade I toxicity was present only in 1 patient. Allergy due to CHT has been evaluated in 3/42 (7.1%) patients. Continence (defined as absence of any urinary leak) after RP and post IMRT was achieved in 29 (69%) and 27 (64.3%), respectively. After a median follow up of 3.4 years, a PSA recurrence and clinical recurrence were observed in 7 (16.7%) and 4 (9.5%) patients. A 5-year biochemical and clinical recurrence-free survival rate were 70.7% and 84.0%, respectively. 5-year overall free survival was 93.6%. None of patients died for prostate cancer during follow up. Conclusions This phase II trial test a novel multimodal treatment paradigm for high-risk prostate cancer. Toxicity was acceptably low and long term oncological outcomes were good. Further studies are needed to compare this novel treatment paradigm to the standard of care. Funding None
Authors
Fabio Zattoni
Roberto Bortolus Alessandro Morlacco Mauro Arcicasa Fabio Matrone Filiberto Zattoni |
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MP53-15 |
Local Therapy in Metastatic Prostate Cancer: Does the Burden of Disease Matter? Results from a National Population-Based Cancer Registry |
Prostate Cancer: Advanced (including Drug Therapy) III | 17BOS |
Abstract: MP53-15 Sources of Funding: None Introduction INTRODUCTION: Recent studies have shown a possible survival advantage for men with metastatic prostate cancer (MPCa) who undergo local treatment of the primary tumor in addition androgen deprivation therapy (ADT) when compared to ADT alone. We hypothesize that this benefit will depend on the degree of metastatic burden. We assess this by looking at men with varying levels of metastatic disease, and comparing the overall survival (OS) between those who did and did not undergo local therapy in addition to ADT. _x000D_ Methods METHODS: Patients with MPCa (cN+ or cM+) who received ADT were identified from the National Cancer Database (NCDB) (2004-2013). We categorized men based on the extent of metastatic disease (NIM0, M1a, m1b and M1c). Within each group we modeled the propensity to receive local therapy to the primary. We then compared those undergoing local therapy in addition to ADT to those undergoing ADT alone in a 1:1 propensity matched analysis. Kaplan-Meir curves and Cox proportional Hazards regression were used to compare overall survival (OS) in men receiving local therapy with ADT to ADT alone within each metastatic category. _x000D_ Results RESULTS: A total of 17,950 men with MPCa who received ADT were identified. Of these, 1,109 received local treatment and 16,841 did not. After propensity matching we had 1876 patients in the N1M0 group, 76 patients in the M1a group, 244 patients in the M1b group and 12 patients in the M1c group, with an even distribution of men between the two treatment groups in each metastatic category. Survival was not analyzed in the M1c group due to the low number. We found that there was a significant benefit in OS for men underging local therapy in all other sub-groups (Figure 1). Cox regression analysis revealed a benefit from local therapy in all analyzed groups: N1M0: HR=0.56, 95%CI 0.47-0.67, p<0.001, M1a: HR=0.3, 95%CI 0.12-0.73, p=0.008, M1b: HR=0.54, 95%CI 0.38-0.77, p<0.001._x000D_ Conclusions CONCLUSIONS: Our study shows a significant benefit in OS for men with MPCa undergoing local therapy in addition to ADT, versus ADT alone in men with N1M0-M1b prostate cancer. These results require further validation, ideally via prospective randomized trials. _x000D_ Funding None
Authors
Vivek Venkatramani
Tulay Koru-Sengul Feng Miao Bruno Nahar Nachiketh Soodana Prakash Mahmoud Alameddine Sanjaya Swain Chad Ritch Mark Gonzalgo Dipen Parekh Sanoj Punnen |
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MP53-16 |
LONG-TERM ONCOLOGIC OUTCOMES OF ADDING RADICAL PROSTATECTOMY TO CASTRATION FOR PATHOLOGICAL NODE-POSITIVE PROSTATE CANCER |
Prostate Cancer: Advanced (including Drug Therapy) III | 17BOS |
Abstract: MP53-16 Sources of Funding: None Introduction Long-term data on the outcomes of aggressive loco-regional surgical resection in prostate cancer (PCa) with nodal involvement are lacking. The present study reports on the impact of adding radical retropubic prostatectomy (RRP) to surgical castration on long-term cancer-specific (CSS) and overall survival (OS) outcomes in men with pathological node-positive (pN+) PCa. Methods Men with pN+ PCa who underwent pelvic lymphadenectomy and early bilateral orchiectomy (within 90 days of surgery), with (n=382) or without (n=79) RRP, were identified (1966-1995). Men who underwent RRP + orchiectomy and men who underwent orchiectomy alone were matched 1:1 on age, year of surgery, clinical grade, clinical stage, number of positive nodes, and pre-operative serum PSA level (after 1987). Kaplan-Meier and Cox regression analyses were used to compare CSS and OS between groups. Results The cohort included 158 men (79 in each group) with a mean age of 66 years (SD=6), of whom 146 (92%) were followed until death. Groups were balanced on all matched parameters. Among men undergoing orchiectomy alone, 76 died, with 60 dying from PCa. Among patients undergoing RRP + orchiectomy, 70 died, with 28 dying from PCa. On Kaplan-Meier analyses, RRP + orchiectomy versus orchiectomy alone was associated with significantly improved CSS at 10 years (79% vs. 35%) and 20 years (59% vs. 18%) (log-rank p<0.001). Likewise, RRP + orchiectomy versus orchiectomy alone was also associated with prolonged OS at 10 years (66% vs 27%) and 20 years (22% vs. 9%)(log-rank p<0.001). In Cox models, RRP + orchiectomy versus orchiectomy alone was associated with significantly improved CSS (HR=0.28, 95%CI=0.17-0.46, p<0.001) and OS (HR=0.48, 95%CI=0.34-0.66, p<0.001). Findings were similar in the subset with available pre-operative PSA (CSS: HR=0.31, 95%CI=0.16-0.61, p<0.001; OS: HR=0.45, 95%CI=0.26-0.77, p=0.004). Conclusions With nearly the entire cohort having lifelong follow up, this analysis demonstrates that the addition of RRP to surgical castration for pN+ PCa is associated with improved CSS and OS. When technically feasible in well-selected patients, aggressive loco-regional resection should be considered in node-positive PCa as a part of a multi-modal approach. Funding None
Authors
Bimal Bhindi
Laureano Rangel Ross Mason Matthey Gettman Igor Frank Eugene Kwon Matthew Tollefson R. Houston Thompson Stephen Boorjian R. Jeffrey Karnes |
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MP53-17 |
Current Management of Prostate Cancer with Node-Positive disease after Radical Prostatectomy and its Impact on Overall Survival |
Prostate Cancer: Advanced (including Drug Therapy) III | 17BOS |
Abstract: MP53-17 Sources of Funding: None Introduction The optimal treatment approach for lymph node positive prostate cancer (PC) disease (pN1) at the time of radical prostatectomy (RP) and pelvic lymph node dissection (PLND) is uncertain. The aim of our study is to examine current treatment of pN1 and evaluate patient and disease-specific predictors of overall survival (OS). Methods The National Cancer Database (NCDB) was used to identify pN1 patients between 2004-2013. We examined subsequent treatment; radiation (RT) and/or antiandrogen therapy (ADT). Logistic regression was used to identify clinical and oncologic characteristics associated with different treatments. Finally, survival analyses were performed to examine the effect of these treatments on overall survival (OS), adjusted for covariates. Results A total of 336,798 PC patients had undergone RP & PLND. pN1 was recorded in 11,742 (3.5%). Approximately half underwent observation (51%), RT alone was used in 7%, RT&ADT were used in 17% and ADT alone was used in 25%. Adjusted multivariate logistic regression indicated that RT+/-ADT was used for younger and healthier patients who had underwent limited PLND (≤5 nodes examined), with adverse pathological feature (i.e. intermediate or high grade Gleason score, with locally advanced disease (pT3 or T4) and positive margins. Median follow-up for the entire cohort was 48 months. Unadjusted Kaplan Meier analysis demonstrated significant differences in OS favoring RT+/-ADT over observation and ADT alone (p<0.0001). Five-year OS was 85.7% for observation, 88% for RT& ADT, 89.5% for RT alone and 83% for ADT alone (p<0.0001). Adjusted Cox proportional hazards regression demonstrated an improved OS for RT+ADT compared with other groups (Hazard ration 0.75, 95%CI( 0.64 to 0.89), P=0.001). OS was worse in older men, with worse comorbidity score, higher Gleason score and stage, positive margins and > 2 positive LNs. Conclusions Our study suggests that pN1 disease may be currently undertreated. The combination of RT&ADT appears to offer a survival advantage in select patients. These results highlight the importance of a multimodal approach in the treatment of node-positive prostate cancer._x000D_ Funding None
Authors
Alaa Hamada
Simon Kim Hui Zhu Robert Abouassaly |
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MP53-18 |
Efficacy of local treatment in prostate cancer patients with clinically pelvic lymph node-positive disease at initial diagnosis |
Prostate Cancer: Advanced (including Drug Therapy) III | 17BOS |
Abstract: MP53-18 Sources of Funding: None Introduction There is limited evidence supporting the use of local treatment (LT) for prostate cancer (PCa) patients with clinically pelvic lymph node-positive (cN1) disease. Against this backdrop, we sought to examine the efficacy of any form of LT+/-androgen deprivation therapy (ADT) in treating these individuals. Methods Within the National Cancer Data Base (2004-2012), we identified 2,967 individuals who received LT+/-ADT vs. ADT alone for cN1 PCa. Only radical prostatectomy (RP) and radiation therapy (RT) were considered as definitive LT. Instrumental variable analyses (IVA) were performed using a two-stage residual inclusion approach to compare overall mortality-free survival between patients who were treated with LT+/-ADT vs. ADT alone. The same methodology was used to further compare overall mortality-free survival between patients who were treated with RP+/-ADT vs. RT+/-ADT. Results Overall, 1,987 (67.0%) and 980 (33.0%) patients received LT+/-ADT and ADT alone, respectively. In the LT+/-ADT group, 751 (37.8%) and 1,236 (62.2%) patients received RP+/-ADT and RT+/-ADT, respectively. In IVA, LT+/-ADT was associated with a significant overall mortality-free survival benefit (HR=0.31; 95% CI=[0.13-0.74]; P=0.007), when compared to ADT alone (Figure 1). At 5-year, overall mortality-free survival was 78.8% (95% CI: 74.1%-83.9%) vs. 49.2% (95% CI: 33.9%-71.4%) in the LT+/-ADT vs. ADT alone groups. When comparing RP+/-ADT vs. RT+/-ADT, IVA showed no significant difference in survival between the two treatment modalities (HR=0.54; 95% CI=[0.19-1.52]; P=0.24; Figure 2). Conclusions Our study shows a significant overall mortality-free survival benefit for cN1 PCa patients who were treated with LT+/-ADT as compared to their counterparts treated with ADT alone. Conversely, no significant survival difference was observed between patients treated with RP+/-ADT vs. RT+/-ADT. Funding None
Authors
Thomas Seisen
Malte W Vetterlein Patrick Karabon Tarun Jindal Akshay Sood Luigi Nocera Paul L Nguyen Toni K Choueiri Quoc-Dien Trinh Mani Menon Firas Abdollah |
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MP53-19 |
Cytoreductive radical prostatectomy (cRP) is feasible in men with hormone-naive, metastatic prostate cancer (mPCA). |
Prostate Cancer: Advanced (including Drug Therapy) III | 17BOS |
Abstract: MP53-19 Sources of Funding: None Introduction Androgen deprivation represents the standard treatment for prostate cancer with osseous metastases. We explored the role of cRP in the largest cohort of contemporary patients with mPCA treated in 4 tertiary referral centres. Methods A total of 114 patients with mPCA, lymph node, osseous or visceral metastases underwent cRP. Surgery related complications (Clavien-Dindo classification) and functional outcome were analysed. Oncologic outcome parameters such as cancer specific & overall survival as well as biochemical and clinical-free survival were evaluated using descriptive statistical analysis._x000D_ Results Mean patient age was 61 (42-69) years. Mean and median follow-up was 39.7 months (7-75) and 47 months (28-96), resp. 93 (81.6%) and 21 (18.4%) patients had low volume and high volume mets, resp.,. 80(70.2%) pts underwent neoadjuvant ADT with LHRH analogues. Surgical approach was open retropubic RP in 104 (92%) pts and 2 (1.8%), 10 (8.8%) and 101 (89.4%) pts underwent no, limited or extended pelvic LAD, resp. Adjuvant therapy was delivered in 99 (86.8%) pts. Pathohistology revealed significant vital PCA in 100% of cases: n=16 (14.0%) exhibited pT4a, n=21 (18.4%) had pT2 and the remainder had pT3a/b PCA. Positive lymph nodes or positive surgical margins were identified in 61.6% and 36.8%, resp.. 110 (96.5%) are alive and 66.7% are relapse-free. Continence as defined by the use of 0-1 pad/day was achieved in 68.1% pts whereas 17.7% and 14.1% had mild and severe incontinence, resp. 74 (64.9%) pts did not experience any surgery related complications; 15 (13.1%) pts experienced Clavien Dindo grade IIIb/IV complications and underwent minimally invasive or surgical reintervention. _x000D_ The following parameters were associated with relapse: low versus high volume (32.2% vs 50%, p=0.03), PSA at cRP < 1ng/ml vs PSA > 4 ng/ml, (18.9% vs 45.6%, p= 0.02). The following parameters were associated with the Clavien-Dindo complications IIIb (p<0.05): low vs high volume disease (7.1% vs 32.1%), PSA < 4ng/ml vs PSA > 4 ng/ml (6.1% vs 47.8%) and neoadjuvant vs no neoadjuvant therapy (8.75% vs 24.2%). Conclusions cRP is feasible in men with mPCA independent on the extent of disease with a low rate of significant complications and good functional outcome. About two thirds of the patients remain relapse-free after a median follow-up of close to 4 years. cRP might be an individualized treatment option in the multimodality management of mPCA._x000D_ Funding None
Authors
Axel Heidenreich
Jeff. R. Karnes Alberto Briganti Shahrokh Shariat Daniel Porres Nicola Fossati Francesco Montorsi Nazareno Suardi David Pfister |
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MP53-20 |
Radium-223(RAD) in men with symptomatic castration-resistant prostate cancer: guideline versus clinical reality. |
Prostate Cancer: Advanced (including Drug Therapy) III | 17BOS |
Abstract: MP53-20 Sources of Funding: None Introduction RAD is one of the new life prolonging therapeutic aproaches in symptomatic mCRPC prior to or after docetaxel treatment. According to guidelines RAD should be initiated early in the progression of mCRPC and it is not to be used as palliative therapy. We analysed the data of RAD therapy in a large single centre cohort of mCRPC patients with the purpose to explore the guideline compliance._x000D_ Methods A total of 94 patients with symptomatic mCRPC were retrospectively analyzed. All patients had skeletal metastases and no evidence of visceral metastases. The following data were analyzed: proper pretherapeutic work-up including PSA, Hb, platelets, alk. Phos., VAS, creatinine, ECOG performance status, in-house versus external referals, number of cycles, type of pre-treatment. Oncologic outcome parameters such as cancer specific & overall survival as well as biochemical and clinical-free survival were evaluated using descriptive statistical analysis. _x000D_ Results Mean patient age was 72.9 (52-84) years. 46 (48.9%) pts received prior DOC; 34 (36.2%) were DOC-naive and in 14 (14.9%) pts the status was unknown. Mean PSA was 267,69 (2.5-4710) ng/ml, mean alk.Phosp. was 177,4 (54.5-594) U/l and mean HB was 12.01 (9.8-15.1) g/dl. Required lab values were missing in 22.3% of pts. ECOG performance status was 0,1 and 2 in 45 (47.9%), 14 (14.9%) and 8 (8.5%), resp.; in the remainder no ECOG was documented. Pts received a mean number of 4 (1-6) cycles; 43 (47.8%) pts received 6 cycles whereas 17 (18.9%), 5 (5.6%) and 25 (27.8%) pts received 4, 5, and 3 cycles, resp. Reason for early discontinuation was: disease progression in 12, poor performance status in 10 and bone marrow suppression in 4. All in-house referals but only 21.5% of outside referals received 6 cycles Rad223. After a mean follow-up of 23.2 (3-30) months, 25 (26.6%) are DOD, 63 (67%) pts are alive and in 6 (6.4%) pts the status is unknown. There was a significant difference in survival rates between 3 and 6 cycles with 62.5% vs 81.1% (p < 0.02) as well as between outside and in-house referals (p < 0.02)._x000D_ Conclusions Although RAD is guideline recommended therapy, clinical reality demonstrates that there the treatment is still inappropriately in 50% of the patients with a significant difference between tertiary referal centres and the community. Observed survival differences are most probably due to the low number of cycles which reflect the terminal stage of disease. More information has to be distributed in the community. _x000D_ Funding None
Authors
Isabel Heidegger
Saskia Kanzelmeyer David Pfister Daniel Porres Pia Paffenholz Axel Heidenreich |
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MP54-01 |
Evaluation of postoperative complications after radical cystectomy using the comprehensive complication index |
Bladder Cancer: Invasive IV | 17BOS |
Abstract: MP54-01 Sources of Funding: none Introduction To examine postoperative complications in a contemporary series of patients after radical cystectomy (RC) using the comprehensive complication index (CoCI), a new extension of the Clavien-Dindo-Classification (CDC), that integrates not only the most severe but all events with their respective severity. Methods Using the CoCI, we assessed the 90-day postoperative clinical course of 804 bladder cancer patients who underwent open RC and urinary diversion (ileal conduit n = 510, ileal neobladder n = 294) between June 2003 and December 2015 at a single institution. All Martin criteria for standardized reporting of complications were met. The CoCI is calculated as the sum of all CDC events that are weighted for their severity. The final formula yields a continuous scale to rank the severity of any combination of complications from 0 to 100 in a single patient. Cut-off of the CoCI was set at 26.2%, the equivalent of a single CDC IIIa complication, to assess major complications. Uni- and multivariable analyses for prediction of complications were carried out; covariables included body mass index, Charlson Comorbidity Index (CCI), age, sex, American Society of Anesthesiologists Score (ASA), neoadjuvant chemotherapy, prior abdominal or pelvic surgery, clinically localized tumor and urinary diversion type. Results The 90-day rates for overall (CDC I-V) and high-grade complications (CDC III-V), as well as mortality (CDC V), were 58.8, 21.8 and 3.7%, respectively. The median CoCI was 20.9 (IQR 0-29.6) with a CoCI≥26.2 in 29.2% of the study population. Patients that received an ileal neobladder had a significantly lower CoCI, 8.7% (IQR 0-22.6), compared to those that received ileal conduit, 20.9% (IQR 0-33.7, P=0.013). Independent risk factors for overall complications were BMI≥30 (OR 1.75), female gender (OR 1.66) and ASA≥3 (OR 1.47). Risk factors for a CoCI≥26.2 were BMI≥30 (OR 1.52), CCI≥3 (OR 1.63) and ASA≥3 (OR 1.72, all P<0.05). Conclusions RC is associated with significant morbidity; nevertheless, the majority of complications are minor. CCI, ASA and BMI might help to identify patients at risk for major complications after radical cystectomy. The comprehensive complication index gives detailed and acurate information on the individual burden of complications. Funding none
Authors
Florian Roghmann
Nicolas von Landenberg Jana Schmidt Julian Hanske Björn Löppenberg Christian von Bodman Peter Bach Marko Brock Jüri Palisaar Joachim Noldus |
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MP54-02 |
Post-Operative Outcomes After Radical Cystectomy in Radiated Patients |
Bladder Cancer: Invasive IV | 17BOS |
Abstract: MP54-02 Sources of Funding: None Introduction Radical cystectomy (RC) can be a morbid surgery with complication rates as high as 64%. Patients with a history of prior abdominal/pelvic radiation (RT) are thought to be at increased risk for post-operative complications and adverse pathology with RC. Hence, RC may be underutilized in this population. Our objective was to compare post-operative complication rates and pathologic outcomes after RC in patients with prior abdominal/pelvic RT versus those without a RT history. Methods An IRB approved retrospective cohort study for patients who underwent RC for urothelial carcinoma (UC) at our institution between 2008-2016 was performed. The cohorts included: any prior abdominal/pelvic RT and no prior RT. Outcomes assessed between cohorts included diversion type, final pathology, length of surgery (ORT) and hospital stay (LOS), blood loss (EBL) and post-operative recovery and complications. Results We identified 519 patients who underwent RC for UC during the time period studied. Of these, 56 (11%) patients had a history of abdominal/pelvic RT. All previously radiated patients had received RT for pelvic malignancy, most commonly for prostate cancer (60%). When stratified by prior RT, there were no significant differences in EBL, intra-operative transfusion, and time to bowel function. The overall complication rate in RT patients versus those without prior RT was 48% and 52% respectively (p = 0.74). While there was no statistical difference in fascial dehiscence rate (p = 0.075), there did appear to be a clinically significant difference in rate (25% in those with RT versus 9% in those without RT. Comparisons of pathologic features demonstrated no significant difference between the groups for histology, metastases, margin status, cancer specific and overall survival. However, a significant difference in T-classification was observed, with RT patients being more likely to have pT4 disease (p=0.04). Conclusions Although RC remains a surgical procedure with high complication rates, patients with a history of prior abdominal/pelvic RT do not appear to have a higher complication rate and should not be excluded from RC on the basis of prior RT alone. Despite the fact that radiated patients are at greater risk for higher pathologic stage, there were no detectable differences in cancer specific and overall survival. Additional prospective studies are needed to better evaluate this cohort of patients to inform treatment decisions. Funding None
Authors
Philip Fontenot
William Parker Hadley Wyre Eugene Lee Moben Mirza James Thrasher Jeffrey Holzbeierlein |
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MP54-03 |
Benefits and complications during inpatient follow-up treatment after radical cystectomy for bladder cancer |
Bladder Cancer: Invasive IV | 17BOS |
Abstract: MP54-03 Sources of Funding: none Introduction A three-week inpatient follow-up treatment (FT) in government-approved rehabilitation clinics is offered after radical cystectomy (RC) for bladder cancer (BC) for all patients in Germany. We investigated both the physical condition and expectations of the patients at the beginning of the FT as well as complications during the 3-week period and results thereafter. Methods 81 patients from different urological departments who underwent RC for BC and an orthotopic neobladder reconstruction were included. Time from hospital discharge until beginning of FT, BMI, initial blood count, Karnovsky scale, antibiotics, antithrombotics and use of incontinence pads were assessed. Furthermore patients were asked for main complaints as well as expectations towards the three-week FT. Complications like metabolic acidosis and urinary tract infections during FT as well as medication, incontinence pad use and patients` complaints after FT were monitored. Results Median time between RC and discharge from the primary hospital to FT was 35 days (interquartile range [IQR] 25-41 days) and 13 days ([IQR] 4-16 days) respectively. The medical condition at the beginning of FT was good: mean Karnovsky 72% ([IQR] 70-88%), mean BMI 23.1 ([IQR] 20.9- 27.7), mean hemoglobin, creatinine and leukocytes in the normal range. The five most common complaints mentioned are general weakness (79%), incontinence (77%), pain (31%), fatigue (30%), and mental distress (43%). The three most important expectations towards FT were improvement of the general physical capacity (86%), followed by improvement of incontinence (81%) and reduction of mental distress (31%). During FT 25.9% of patients had a urinary tract infection requiring antibiotics and 8.6% had a symptomatic metabolic acidosis. Only 18.1% were under antithrombotic medication at the beginning of FT. Antibiotic use decreased from 19.8% to 17.3%. Incontinence pad use increased from 2.14 to 2.55 pads per day on average. At the end of FT, patients indicated improvement of incontinence, physical capacity and mental distress in 60.5%, 74.1% and 30.86%. Conclusions Compared to the pre- and perioperative management of BC, there is a scarcity of studies investigating FT of BC. A multitude of significantly different FT models have been implemented in different countries. Both from the economic as well as medical point of view high-quality FT must be strived for. Our study gives insights into the current state of FT in Germany and shows both benefits as well as unsolved challenges. Funding none
Authors
Gerald Schulz
Tobias Grimm Alexander Buchner Friedrich Jokisch Markus Grabbert Birte-Swantje Schneevoigt Alexander Kretschmer Christian Stief Alexander Karl |
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MP54-04 |
Hospitalization and Readmission Costs after Radical Cystectomy in a Nationally Representative Sample: Neobladder vs. Ileal Conduit |
Bladder Cancer: Invasive IV | 17BOS |
Abstract: MP54-04 Sources of Funding: None Introduction Current studies have failed to show clear long-term differences in oncologic outcomes or quality of life between Ileal Conduit (IC) and neobladder after Radical Cystectomy (RC). However, few studies have assessed cost differences between diversion types. We analyzed the differences in hospital costs during initial hospitalization and readmissions between neobladder and IC in a nationally representative sample. Methods The 2013 Nationwide Readmissions Database (NRD) was queried for patients with bladder cancer undergoing RC. Sociodemographic characteristics, Length of Stay (LOS), hospital costs, and causes of readmission were compared between neobladder and IC. Univariable and multivariable logistic regression models were utilized to assess the impact of urinary diversion type on LOS, readmission rates, and hospitals costs. Costs were modeled using the gamma distribution to account for skewness of data. Results Among 4,283 patients included in the analysis, 325 (7.5%) underwent neobladder reconstruction with the remainder undergoing IC. Patient’s with a neobladder were younger (mean age 62 years vs. 69, p <0.001), had a lower Charlson Comorbidity Index (CCI) (CCI of 0 – 69%, vs. 47%, p<0.001), private insurance (44% vs. 24%, p <0.001), higher median household income (Top quartile – 35% vs. 24%, p= 0.02), and were more likely to be treated at high volume metropolitan teaching centers (High volume – 54% vs. 33%, p<0.001). Between the two groups, there was no difference in initial hospitalization LOS, readmission rate, readmission LOS, or 90-day mortality. Neobladders were more likely to be readmitted for hydronephrosis (2.7% vs. 0.3%, p < 0.001) and UTI/Pyelonephritis (18.9% vs. 11.4%, p = 0.066) though the latter did not reach statistical significance. Neobladder mean costs were higher for the initial hospitalization and at 30-day and 90 days. At 90-days, neobladders cost on average $14,000 more per patient than IC. On multivariable analysis, neobladder was an independent predictor of increased cost during readmission (OR 3.41, p < 0.001). Conclusions Neobladder diversion after RC is more costly compared to IC both during initial admission and at 90-days despite similar LOS and readmission rates. The increased cost of care may be secondary to increased treatment for obstructive and infectious complications. In an era of changing reimbursements, cost of diversion may also need to be considered when selecting diversion type. Funding None
Authors
Gregory Joice
Meera Chappidi Hiten Patel Max Kates Nikolai Sopko CJ Stimson Phillip Pierorazio Trinity Bivalacqua |
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MP54-05 |
Validation of National Surgery Quality Improvement Program (NSQIP) Risk Calculator of Post-Op Complications and Readmission after Radical Cystectomy |
Bladder Cancer: Invasive IV | 17BOS |
Abstract: MP54-05 Sources of Funding: None Introduction The American College of Surgeons National Surgical Quality Improvement Program Risk Calculator (NSQIPRC) is widely used to predict post-op morbidity and mortality in procedure specific models. No validation has been done of its accuracy for urologic surgeries. The goal of this study is to evaluate the ability of NSQIP surgical risk calculator to predict the 30-day complications, readmission, reoperation, and mortality after radical cystectomy for bladder cancer. Methods Medical records of all bladder cancer patients who underwent radical cystectomy between 2008 and 2015 were retrospectively reviewed. The data were collected according the NSQIP’s definitions. NSQIP calculator was used to predict the probability of complications for these patients. NSQIPRC predicted complication rates were compared to the observed complication rates in our institute using c-statistics, the area under the receiver operating characteristic (ROC) curve, and Brier’s score to measure the calibration and discrimination. Results We identified 439 who underwent radical cystectomy for bladder cancer. One main weakness of the NSQIPRC is its inability of predicting gastroenterological and urinary tract complications, these complications occurred in 136 (30%) and 49 (11%) patients respectively. Even after eliminating these complications from our analysis, the mean NSQIPRC predicted rates were lower than the observed rates of serious complications ( 25% vs 34%), any complications (28% vs 35%), readmission (19% vs 27%), and reoperation (4% vs 6.5%) respectively. The NSQIPRC did not perform well with area under the ROC curve was (0.563) for serious complication, (0.551) for any complication, (0.515) for readmission, and (0.587) for reoperation. However, the calculator had acceptable prediction of mortality (c-statistic 0.729, Brier’s score 0.02), and poor in predicting pneumonia (c-statistic 0.629, Brier’s score 0.022) and deep venous thrombosis (c-statistic 0.625, Brier’s score 0.032). Conclusions NSQIP risk factor calculator underestimates the probability of post-op morbidity. It underperforms in predicting the rates of serious complications, any complication, readmission, and reoperation. Nonetheless, it is reasonable in predicting mortality after surgery. Major improvements in data processing and calculator design are needed. Funding None
Authors
Saad Hatahet
Mohamed Hendawi Ahmad Shabsigh |
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MP54-06 |
Impact of surgical volume on survival following RARC in a large, national cohort |
Bladder Cancer: Invasive IV | 17BOS |
Abstract: MP54-06 Sources of Funding: None Introduction Robotic-assisted radical cystectomy (RARC) has become increasingly utilized in treatment of muscle-invasive bladder cancer, yet the limited data to support its oncologic efficacy comes largely from high volume centers. RARC represents a technically demanding procedure, and results may not be reproducible across multiple surgeons and institutions. We aim to assess the effect of center volume on survival outcomes in patients undergoing RARC. Methods Using the National Cancer Data Base (NCDB) we identified patients undergoing RARC from 2010-2012. Center volume was defined by the number of RARC performed over the study period. Low volume centers were defined by <10 RARC, representing the lowest tertile. Univariable and multivariable regression modeling was used to identify patient and disease variables, including RARC volume, associated with overall and additional treatment-free survival. Results Of the 2,773 patients that underwent RARC, 975 (35%) died during follow-up. 948 RARC were performed at &[Prime]low volume centers&[Prime] (table 1). On multivariable analysis (table 2), age >80 years (HR 1.91, 95% CI 1.06-3.43, p=0.03), stage (vs. Conclusions Accounting for disease and hospital related variables, patients undergoing RARC at low volume centers had worse overall and additional treatment free survival. This suggests that adequate center volume may be important for conferring surgical quality and ultimately survival outcomes. Funding None
Authors
Patrick Lewicki
David Golombos Padraic O'Malley Clara Oromendia Abimbola Ayangbesan LaMont Barlow Douglas Scherr |
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MP54-07 |
Pentafecta and Trifecta Criteria for reporting outcomes of Radical Cystectomy for Muscle Invasaive Urothelial Bladder Cancer (MIBC). |
Bladder Cancer: Invasive IV | 17BOS |
Abstract: MP54-07 Sources of Funding: non Introduction Pentafecta and trifecta provide a comprehensive approach for standardized outcome reporting of radical cystectomy.These criteria were proposed by an expert panel of fifty urologists including oncologic and functional outcomes. We aimed to assess the rate and predictors of achieving trifecta and pentafecta criteria in bladder cancer patients treated with radical cystectomy. Methods A retrospective analysis of a computerized database of patients treated with radical cystectomy and urinary diversion between January 2004 till January 2014 was performed. Inclusion criteria included: age ? 75, ASA score ?3, urothelial carcinoma and definitive pathology ?T3NoMo._x000D_ Trifecta criteria included: negative soft tissue surgical margin (STSM), retrieval of ? 16 lymph nodes and absence of high grade complication (GIII-V) within 90 days after surgery. Pentafecta included, in addition, time elapsed between TURBT and cystectomy < 3 months and absence of recurrence within 12 months after surgery. _x000D_ Multivariate binary logistic regression was used to evaluate the impact of age, gender, BMI, preoperative anaemia and hypoalbuminemia on achieving trifecta and pentafecta._x000D_ Results After exclusions, a total of 822 patients were included in the study. Mean age was 59±7.9 years. Organ confined disease was seen in 572 (69.6%) patients. Pentafecta and trifecta criteria were met in 293 (35.6%) and 316 (38.4%) respectively (Table1). On univariate analysis, patients who missed trifecta and pentafecta were more likely to be older and have higher ASA score (Table-2). On multivariate analysis, high ASA score was the only predictor of achieving both pentafecta and trifecta criteria. Conclusions After 30-years of experience in a tertiary referral center, only one third of patients met the pentafecta. This finding may motivate us to search for new modalities for management of MIBC. Higher ASA score was the only predictor of missing trifecta or pentafecta and this should be considered during patient counseling before surgery. Funding non
Authors
Mahmoud Laymon
Ahmed Mansour Mohamed M. Elsaadany Ahmed Mosbah Shaaban AA Hassan abol-enein |
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MP54-08 |
A total population analysis of in-hospital outcomes of radical cystectomy in Germany from 2006 to 2013: impact of surgical approach and annual caseload volume. |
Bladder Cancer: Invasive IV | 17BOS |
Abstract: MP54-08 Sources of Funding: MedDrive Grant of the Medical Faculty, TU Dresden Introduction Radical cystectomy (RCE) shows the highest mortality and morbidity among urologic routine surgery. We analysed in-hospital outcomes of all RCE in Germany from 2006 to 2013 with a focus on the institutions’ annual caseload and surgical approach. Methods By using remote data processing we analysed the nationwide German hospital billing data from 2006 to 2013. All cases with a bladder cancer diagnosis combined with RCE were eligible for evaluation. We calculated mortality and transfusion rates during the hospital stay and the length of stay. The results were stratified for hospital characteristics, caseload, and the surgical approach. Results Total annual RCE numbers increased from 5,627 in 2006 to 7,399 in 2013. The share of open surgery declined from 99.3% to 96.6%, conventional laparoscopy increased from 0.7% to 1.6%, and the robot-assisted approach from 0% to 1.8%. The patients’ mean age was 68.2 ± 9.9 years. The average in-hospital mortality rate was 4.5% for open RCE; in comparison it was lower with 3.8% for laparoscopic (p=0.35) and 2.5% for robotic RCE (p=0.002). Hospitals with high annual caseloads >50 RCE showed lower mortality rates with 3.3% vs. 4.1% (26-50 RCE), 5.0% (11-25 RCE), 5.2% (4-10 RCE), and 7.0% (<3 RCE) (p<0.001). The need for blood transfusion during the hospital stay was higher for open with 60.0% vs. laparoscopic 50.6% vs. robotic RCE with 35.9% (p<0.0001). The mean length of stay was longer for open with 25.3 days and laparoscopic RCE with 26.0 days vs. robotic RCE with 21.4 days (p<0.0001). Hospitals with high annual caseload >50 RCE showed a shorter hospital stay with 23.3 days vs. 24.7 days (26-50 RCE), 26.1 days (11-25 RCE), 26.3 days (4-10 RCE), and 24.5 days (<3 RCE) (p<0.0001). _x000D_ Multivariate models indicated that the patient’s age and the type of urinary diversion were the most important factors for mortality and the need for blood transfusion (p<0.0001). Also on multivariate analysis hospitals with very low annual caseload (<3 RCE) had higher mortality (p=0.02), blood transfusion (p=0.0004), and a longer hospital stay (p<0.0001)._x000D_ Conclusions Hospitals with high annual caseload volumes show an improved outcome with lower rates of in-hospital mortality, blood transfusion, and a shorter hospital stay. Compared to the open approach robotic RCE showed lower rates of in-hospital mortality, blood transfusion and a shorter hospital stay. Whether this result is due to selection bias warrants further examinations. Funding MedDrive Grant of the Medical Faculty, TU Dresden
Authors
Christer Groeben
Rainer Koch Martin Baunacke Manfred Wirth Johannes Huber |
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MP54-09 |
Trends in Surgical Approach and Outcomes for Radical Cystectomy: A Contemporary Population-Based Analysis |
Bladder Cancer: Invasive IV | 17BOS |
Abstract: MP54-09 Sources of Funding: None Introduction The adoption of the da Vinci Surgical System (Intuitive Surgical, Inc, Sunnyvale, CA) for robotic surgery requires a substantial financial investment by hospitals, acquisition of new surgical skills by surgeons, and demand from patients. The adoption rate and factors influencing the utilization of robotic surgery in the surgical management of patients with bladder cancer is currently unclear. Our aim was to evaluate trends in surgical approach and outcomes for radical cystectomy in the United States. Methods Using the Premier Healthcare Database, we captured all patients who underwent a RC (ICD-9 code 57.71) from 2003 to 2015. To identify robot-assisted (RARC) and laparoscopic RCs (LRC), we performed a detailed review of the hospital chargemaster. Multivariable regression analyses were performed after adjusting for survey weighting and clustering to evaluate factors associated with RARC use. Results Across the study period, there were a total of 71,844 RC (58,779 ORC, 3847 LRC, 9218 RARC). There is a gradual rise in the use of RARC from 0.1% in 2003 to 33.9% in 2015), overtaking the laparoscopic approach in 2009 (15.2% vs. LRC. Major (Clavien?3) and overall (Clavien?1) complication rates showed a rising trend up to 19.6% and 68.7% respectively in 2011 before plateauing (Figure 1). Factors significantly associated with RARC include older age (OR 1.01, p=0.03), male gender (OR 1.36, p=0.01), married (vs. non-married, OR 1.23, p=0.02), private insurance (vs. Medicare, OR 1.34, p<0.01), East North Central division (vs. South Atlantic, OR 2.13, p=0.03), Middle Atlantic (OR 2.99, p=0.01), hospital volume >90th percentile (>26/yr) (vs. ?90th percentile, OR 2.10, p=0.03) and later time period (vs. 2003-2006, OR for 2007-2010: 7.74, OR for 2011-2015: 18.99, both p<0.001). Patient with Charlson comorbidity index (CCI) ?2 (vs. CCI 0, OR 0.71, p<0.01) and at West South Central division (OR 0.36, p=0.04) were less likely to undergo RARC. Conclusions Currently, 1 in 3 RC cases are performed using robotic assistance. A variety of patient and hospital geographic characteristics appear to influence this increased utilization. This may be attributed to the acquisition of robotic surgical skills and familiarity with transperitoneal pelvic anatomy following the widespread use of robotic radical prostatectomy. Funding None
Authors
Jeffrey Leow
Benjamin Chung Steven Chang |
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MP54-10 |
ANALYSIS OF QUALITY INDICATORS FOR CYSTECTOMY USING DATA FROM THE NATIONAL CANCER DATABASE |
Bladder Cancer: Invasive IV | 17BOS |
Abstract: MP54-10 Sources of Funding: none Introduction OBJECTIVE: To examine the national patterns of quality indicators for cystectomy and identify facility characteristics predictive of high quality care. Methods METHODS: We performed a retrospective cohort study of patients who underwent cystectomy for cT2-cT4, N0 bladder cancer between 2008 and 2013 using the National Cancer Database. Quality indicators were defined as 1) surgical margin status, 2) lymph node yield, and 3) receipt of neoadjuvant chemotherapy. Univariate analysis and multivariate analysis was used to assess the relationship between academic facility type and annual cystectomy volume and quality indicators while controlling for demographic and pathologic characteristics. Results RESULTS: A total of 12,083 patients met our inclusion criteria. On multivariate analysis, while controlling for demographic and pathologic characteristics, treatment at academic facilities was associated with higher rates of negative margins (OR: 0.80; 95%CI: [0.67-0.95], p=0.01), greater lymph node yields (OR: 0.49; [0.44-0.55], p<0.001), and higher rates of neoadjuvant chemotherapy(OR: 0.73; [0.64-0.55], p<0.001). High volume facilities (>24 cystectomies/year) were associated with greater lymph node yields (OR: 2.69; [2.08-3.47], p<0.001), but not significantly associated with increased neoadjuvant chemotherapy use. Intermediate volume centers (12-24 cystectomies/year) were associated with increased neoadjuvant chemotherapy use (OR: 1.60; [1.36-1.88], p<0.001). Conclusions CONCLUSIONS: At a national level, high quality indicators of cystectomy (negative surgical margin, adequate lymph node yields, and receipt of neoadjuvant chemotherapy) were more likely to occur at academic facilities. High volume centers were associated with higher lymph node yields. Such data support the regionalization of cystectomy care to these centers. Funding none
Authors
Andrew Bachman
Alexander Parker Marshall Shaw Brian Cross Kelly Stratton Michael Cookson Sanjay Patel |
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MP54-11 |
Comparison of readmission and short-term mortality rates between different types of urinary diversion in patients undergoing radical cystectomy |
Bladder Cancer: Invasive IV | 17BOS |
Abstract: MP54-11 Sources of Funding: none Introduction Radical cystectomy (RC) is a complex and morbid procedure primarily because of the urinary diversion required after bladder removal. Choosing the optimal diversion type can be challenging and depends on clinical parameters, as well as the potential morbidity related to each approach. We analyzed a large national oncology outcomes database and compared 30 day readmission rates, as well as 30 and 90 day mortality rates between different types of urinary diversion among patients undergoing RC. Methods We identified patients who underwent RC for bladder cancer in the National Cancer Data Base (NCDB) from 2004 to 2013. Patients were grouped based on the type of urinary diversion performed: non-continent (ileal conduit [IC]) or two continent techniques (pouch [CP] or orthotopic neobladder [NB]). We used multivariable logistic regression models to compare 30 day unplanned readmission and 30 and 90 day mortality between the different types of urinary diversion. In order to control for residual confounding we performed a propensity score matching and repeated the analysis. Results Among 11,933 patients who underwent RC, we identified 10,197 (85.5%) IC, 1,044 (8.7%) CP, and 692 (5.8%) NB. Patients who received IC were significantly older and had more comorbidities (p<.0001). Continent diversions were more likely to be performed at an academic center (p<.0001). In multivariate analysis, patients undergoing NB had an increased likelihood of being readmitted (OR 1.41, p=.010), but decreased risk of dying within 90 days (OR 0.47, p=.007). However, after propensity score matching there was no significant difference in short-term mortality within groups. Surgery performed at a non-academic center was an independent predictor of readmission within 30 days of discharge (OR: 1.19, p=.010) and death within 30 days of surgery (OR 1.27, p=.043). Conclusions Patients undergoing NB had increased rates of readmission compared to IC. Similar short-term mortality rates were observed among the different types of urinary diversion. Surgery performed at a non-academic center was associated with a higher readmission and 30-day mortality rates. Funding none
Authors
Bruno Nahar
Tulay Koru-Sengul Nachiketh Soodana Prakash Vivek Venkatramani Feng Miao Aliyah Gauri David Alonzo Sanjaya Swain Alameddine Mahmoud Chad Ritch Sanoj Punnen Dipen Parekh Mark Gonzalgo |
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MP54-12 |
Sarcopenia as Measured by Iliopsoas and Erector Spinae Muscle Density is Associated with Higher Incidence of Postoperative Complications Following Radical Cystectomy for Bladder Cancer |
Bladder Cancer: Invasive IV | 17BOS |
Abstract: MP54-12 Sources of Funding: none Introduction Sarcopenia, an objective measurement of frailty, has been associated with poor outcomes in lung, gastrointestinal, and breast cancers. We examined the relationship between sarcopenia and postoperative complications in patients undergoing radical cystectomy for bladder cancer. Methods 151 patients who underwent radical cystectomy for high risk or muscle invasive bladder cancer were identified from a prospectively collected institutional database from November 2008 to April 2016. All patients had preoperative computed tomography imaging within 30 days of surgery for inclusion. Regions of interest (ROI) were drawn around the iliopsoas and erector spinae (ES) muscular compartments bilaterally, and the density was recorded as an average of measurements by a genitourinary radiologist blinded to postoperative outcome. Postoperative complications were identified as defined by the American College of Surgeons National Surgery Quality Improvement Program within a 90-day follow-up period. Results 276 complications were identified in 114 patients (75.5%). Iliopsoas muscle density correlated moderately with ES muscle density (r2 = 0.344, p <0.001) and both iliopsoas and ES density correlated with age (r2 = 0.082, p <0.001 and r2 = 0.165, p <0.001 respectively). While no overall association was found between iliopsoas muscle density and complications, lower ES density was associated with incidence of any complication (22.2 HU vs. 30.1 HU, p = 0.016) and an increased number of complications (r2 = 0.032, p = 0.014). Lower iliopsoas muscle density was associated with increased incidence of wound infection (36.5 HU vs. 42.7 HU, p = 0.019), whereas lower ES density was associated with the need for reoperation (12.3 HU vs. 25.2 HU, p = 0.041)._x000D_ Conclusions Sarcopenia is associated with a higher incidence of postoperative complications in patients undergoing radical cystectomy for bladder cancer. Preoperative iliopsoas density and a novel measure, ES density, may be helpful to identify those patients at greater risk of major post-operative complications. Funding none
Authors
William Rawls
Mark Currin Austin DeRosa James Rosoff John Roebel Matthew Jaenicke Thomas Beckham Andrew Hardie Sandip Prasad |
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MP54-13 |
MALNUTRITION STATUS AND AN INTERVENTION FOR MALNUTRITION IN PATIENTS UNDERGOING RADICAL CYSTECTOMY |
Bladder Cancer: Invasive IV | 17BOS |
Abstract: MP54-13 Sources of Funding: The trial was supported by grant IRG-09-062-05 from the American Cancer Society (Jill Hamilton-Reeves), a Nestle ? HealthCare Nutrition Research Grant (Jill Hamilton-Reeves), and the KL2 Scholars Award KL2 TR000119-04 (Jill Hamilton-Reeves). Support for B. Barnes was provided by the Roberts Foundation Introduction Underdiagnosing malnutrition in high-risk surgical patients is problematic. Rapid skeletal muscle wasting is a serious and common complication following radical cystectomy (RC) to treat muscle-invasive bladder cancer. Specialized immunonutrition (SIM) intake before and after RC may help counteract muscle wasting in the post-operative period. Methods Men with muscle-invasive cancer scheduled for radical cystectomy were randomly assigned to oral SIM providing supplemental L-arginine, fish oil, vitamin A, and nucleotides (n = 14) or a calorie- and nitrogen-matched oral nutrition supplement [ONS (n = 15)] for 5 days before and 5 days after RC. Malnutrition was assessed by a trained research team using the Patient-Generated Subjective Global Assessment (PG-SGA) tool. Dual Energy X-Ray Absorptiometry scans were obtained at baseline, 14 days, and 30 days after surgery to calculate relative skeletal muscle index (RSMI). Discrepancies between the malnutrition diagnoses using the PG-SGA tool and the UHC Billing database on the same patients were compared. Results Using the PG-SGA tool, 21% of patients were identified as well nourished, 66% were moderately malnourished, and 14% were severely malnourished prior to RC. Billed and coded data showed 86% of patients were well nourished, 7% were moderately malnourished, and 7% were severely malnourished prior to RC. Relative Skeletal Muscle Index (RSMI) was better preserved in the SIM group at 14 days (7% vs. 17% in the ONS group). Conclusions The large discrepancy between patients identified as malnourished using the PG-SGA as compared to the billing data suggests a problem of underdiagnosing malnutrition in this population. Improving nutrition status through specialized immunonutrition could be a low risk, high-impact means of counteracting muscle wasting after RC for bladder cancer Funding The trial was supported by grant IRG-09-062-05 from the American Cancer Society (Jill Hamilton-Reeves), a Nestle ? HealthCare Nutrition Research Grant (Jill Hamilton-Reeves), and the KL2 Scholars Award KL2 TR000119-04 (Jill Hamilton-Reeves). Support for B. Barnes was provided by the Roberts Foundation
Authors
Woodson Smelser
Misty Bechtel Jeffrey Holzbeierlein Brian Barnes Moben Mirza Eugene Lee Jill Hamilton-Reeves |
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MP54-14 |
Bladder Cancers are not all the same: de novo muscle invasive disease has improved survival compared to invasive disease progressing after intravesical therapy |
Bladder Cancer: Invasive IV | 17BOS |
Abstract: MP54-14 Sources of Funding: None Introduction Recent studies suggest that patients undergoing radical cystectomy (RC) for superficial bladder cancer that fails intravesical therapy (progressive muscle invasive disease, P-MIBC) do significantly worse than RC for de novo muscle invasive disease (DN-MIBC). We studied the impact of neoadjuvant (NAC) or adjuvant chemotherapy (AC) on survival in P-MIBC and DN-MIBC, using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Methods SEER-Medicare was used to identify patients from 2004- 2011 who underwent RC for pT2-pT4 MIBC, and their patterns of NAC and AC use. P-MIBC patients were defined as those who were pT2-pT4 on RC pathology, with a history of Bacillus Calmette-Guerin therapy (BCG) or ≥3 transurethral resection of bladder tumor (TURBT). DN-MIBC patients were those with pT2-pT4 disease on RC pathology who had no history of BCG exposure or ≤2 TURBTs prior to RC. Kaplan Meier (KM) survival analysis and multivariable Cox models were used to compare overall survival (OS), cancer specific survival (CSS), and recurrence free survival (RFS) between P-MIBC and DN-MIBC patients who underwent RC with or without chemotherapy. Results A total of 1,029 DN-MIBC and 97 P-MIBC patients undergoing RC were identified. Compared to DN-MIBC, P-MIBC patients had smaller primary tumors (p= 0.0009), lower cT stage (p= 0.0002), and AJCC stage (p= 0.0005). On KM analyses, P-MIBC patients had significantly worse OS (p = 0.0048), RFS (p = 0.0014), and nearly significantly worse CSS (p= 0.0724) compared to DN-MIBC (Fig. 1). On multivariable analysis, older patients (>75 vs. ≤70 years, HR=1.44, p<0.01), blacks (vs. white HR=1.54, p=0.036) and higher Charlson Deyo score (≥2 vs. 0, HR=1.59, p<0.001) were associated with shorter OS. While OS, RFS and CSS were no longer significantly different between P-MIBC and DN-MIBC on multivariate analysis, NAC before RC was associated with significantly longer OS (HR=0.71, p= 0.0150) compared to RC alone. Conclusions Progression to MIBC after intravesical therapy failure is associated with worse OS and RFS than DN-MIBC cases. Future studies may need to distinguish P-MIBC from DN-MIBC, as they appear to be biologically different, and NAC should be used more aggressively in the P-MIBC population before RC. Funding None
Authors
Raj Bhanvadia
Kristine Kuchta Sangtae Park |
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MP54-15 |
Pure but not mixed histological variants are associated with poor survival at radical cystectomy in bladder cancer patients |
Bladder Cancer: Invasive IV | 17BOS |
Abstract: MP54-15 Sources of Funding: none Introduction To evaluate the impact of pure and mixed histological variant versus pure urothelial carcinoma in nonmetastatic bladder cancer (BCa) patients treated with radical cystectomy (RC) in a single institution center. Methods We evaluated data from 1,067 patients treated at a single institution with RC and pelvic lymph node dissection between 1990 and 2013 at a single institution tertiary care referral center. All specimen were evaluated by dedicated uropathologists. Univariable and multivariable Cox regression analyses tested the impact of the presence of pure and mixed histologic variants vs. pure urothelial and recurrence, CSM (cancer specific mortality) and OM (overall mortality) after accounting for all available confounders. Results In total, 201 (19%) and 137 (13%) patients were found with mixed and pure variant at RC, respectively. Mixed variant were preponderant in sarcomatoid, lymphoepitelial, squamous and glandular variants, on the other hand, small cell and micropapillary variants were found mostly as pure variants. With a median follow up of 6.5 years, patients who harbored pure variant were found at multivariable_x000D_ analyses with lower survival outcomes when compared with pure urothelial carcinoma (all p<0.01). Conversely no differences were found between mixed variant vs. pure urothelial at multivariable Cox regression analyses predicting recurrence, CSM and OM (all p>0.1). Conclusions Presence of histologic variants at RC is a common finding accounting for approximately 30% of specimens. In this setting, the presence of a pure variant but not the presence of mixed variant with urothelial carcinoma is related to a detrimental effect on survival outcomes after RC. Funding none
Authors
Marco Moschini
Renzo Colombo Giorgio Gandaglia Ettore Di Trapani Giusy Burgio Rocco Damiano Agostino Mattei Shahrokh Shariat Andrea Salonia Alberto Briganti Francesco Montorsi Andrea Gallina |
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MP54-16 |
SURVIVAL ANALYSIS OF PATIENTS WITH MUSCLE INVASIVE BLADDER CANCER NOT SUITABLE FOR TREATMENT WITH A CURATIVE INTENT |
Bladder Cancer: Invasive IV | 17BOS |
Abstract: MP54-16 Sources of Funding: None. Introduction Bladder cancer is the ninth most commonly diagnosed cancer worldwide, with more than 300,000 new cases per year, and it causes around 150,000 deaths every year. Despite these figures, there is scarce data in the literature on the prognosis of patients with muscle invasive bladder cancer (MIBC) who are unfit for curative treatment. Our aim is to find out the survival of patients diagnosed with MIBC who were not suitable for treatment with curative intent in our center. We also analyze variables associated with survival, as well as the number of visits to the emergency room and palliative procedures needed. Methods Retrospective analysis of a cohort of patients with histopathologic diagnosis of MIBC dismissed for treatment with curative intent (cystectomy, radiotherapy and/or chemotherapy), between January 2007 and December 2012. We analyzed overall survival (OS) and cancer-specific survival (CSS), as well as their relationship with demographic (age, gender) and clinical/pathological variables (comorbidities, tumor stage, reason for dismissing curative treatment and urinary tract obstruction at diagnosis). We also evaluated the number of visits to the emergency room due to bladder cancer and palliative procedures needed: hemostatic transurethral resection (TUR), radiotherapy or nephrostomy catheter. Results We included 110 patients (96 males/14 females), with a mean age of 79. Regarding American Society of Anesthesiologists (ASA) risk, 67.3% of them were ASA III or higher; 63.6% presented with localized stage and 21.8% with metastases at diagnosis. Around half of our patients (50.9%) had urinary tract obstruction at diagnosis. The main causes to dismiss treatment with curative intent were comorbidities (39.1%) and advanced stage (36.4%). OS at 1 and 2 years was 30% and 14% respectively, with a median OS of 7.17 months. CSS at 1 and 2 years was 50% and 28% respectively, with a median CSS of 12.1 months. Variables associated with a worse survival were advanced clinical stage and urinary tract obstruction. Patients attended the emergency room a mean of 2.85 times due to their cancer. In our series, 18.2% of the patients underwent hemostatic TUR, whilst 10% needed hemostatic radiotherapy and nephrostomy catheters were placed in 24.5% of them. Conclusions In our series we find out an OS under 2 years in most of the patients, with a median OS under 1 year. Factors associated with worse prognosis were the presence of urinary tract obstruction at diagnosis and advanced clinical stage. Funding None.
Authors
Félix Guerrero Ramos
Santiago Pérez Cadavid Angel Tejido Sánchez Esther García Rojo Daniel Antonio González Padilla Raquel Sopeña Sutil Felipe Villacampa Aubá José Manuel Duarte Ojeda Federico de la Rosa Kehrmann Juan Passas Martínez |
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MP54-17 |
Do Patients with Muscle-invasive Bladder Cancer Undergoing Bladder-preserving Radiotherapy/Chemoradiotherapy at Academic Centers have Improved Survival Outcomes Compared to Those Treated at Non-academic Centers? |
Bladder Cancer: Invasive IV | 17BOS |
Abstract: MP54-17 Sources of Funding: none Introduction Bladder-preserving therapy with transurethral resection of bladder tumor followed by radiotherapy (RT), preferably with concurrent chemotherapy (CRT) is an alternative to Radical Cystectomy (RC) in select patients. Studies suggest improved outcomes with RC at academic centers (ACs) compared to non-academic centers (NACs). There are no data describing the impact of facility type on RT-based treatment. Yet, given the multidisciplinary care needed to execute high-quality multimodality bladder-preserving approaches, some argue that the excellent outcomes seen in bladder-preservation trials can only be reproduced at select centers of excellence, typically AC. We analyzed the National Cancer Database to determine if treatment at an AC is associated with improved overall survival (OS) for patients undergoing RT or CRT for muscle-invasive bladder cancer (MIBC)._x000D_ Methods Patients diagnosed with cT2-4 N0-3 M0 transitional cell MIBC from 2008 to 2012 and treated with RT or CRT were selected. Facility type was dichotomized into AC and NAC. The Kaplan-Meier method was used for OS. Univariate analysis (UVA) for OS was performed using the Log-Rank test for all clinical, demographic, and treatment-related covariates. Multivariable analysis (MVA) using the Cox proportional hazards model was used to assess the association of facility type with OS while controlling for facility case volume and all other covariates with p-value <0.1 on UVA. Results 872 patients at 452 unique facilities were selected. 502 (58%) patients received RT, and 370 (42%) patients received CRT. 237 (27%) were treated at an AC, and 635 (73%) were treated at a NAC. 2-year OS was 61% and 53%, for patients receiving 60 Gy or greater at ACs and NACs, respectively. On UVA, facility type was not associated with OS (p=.11). MVA, controlling for facility case volume, age, sex, education, T Stage, N Stage, RT dose, Charlson-Deyo comorbidity score, census region, and population density, demonstrated that although there was a trend, treatment at an AC was not associated with improved OS (Hazard Ratio .86, 95% Confidence Interval .71-1.04; p=.06)._x000D_ Conclusions Similar survival outcomes are seen in patients with MIBC treated with RT and CRT at ACs and NACs. Thus, these approaches can confidently be offered at all centers with multidisciplinary collaboration and clinician experience, and bladder-preserving therapy should be discussed with patients as a valid option when counseling them prior to treatment. Funding none
Authors
Amishi Bajaj
Robert Blackwell Brendan Martin Alec Block Mark Korpics Ellen Gaynor Elizabeth Henry Matthew Harkenrider Gopal Gupta Abhishek Solanki |
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MP54-18 |
The use of urethral frozen section during radical cystectomy may improve cancer-specific and recurrence-free survival |
Bladder Cancer: Invasive IV | 17BOS |
Abstract: MP54-18 Sources of Funding: none Introduction Routine use of urethral and uretreral frozen section (FS) during radical cystectomy for bladder cancer is a controversial issue with contradictory findings concerning ureteral FS and very few data concerning urethral FS. Moreover, previous reports aimed to assess the impact of positive FS on oncological outcomes but none have compared the impact of FS vs. no FS on oncological ouctomes. The objective of this study was to evaluate the impact of urethral and ureteral FS use on oncological outcomes after radical cystectomy for bladder cancer. Methods All patients who underwent a radical cystectomy for bladder cancer between 1995 and 2015 were included in a single-center retrospective study. The use of ureteral and urethral FS varied according to surgeons preference (routine for some, never for others) but not according to the tumors’ characteristics. Patients were divided into different groups according to the use of ureteral and/or urethral FS (FS vs. no FS). Preoperative data and the rate of positive margins were compared between groups. The prognostic factors for cancer-specific survival (CSS) and recurrence-free survival (RFS) were sought in univariate analysis using the log-rank test and in multivariate analysis using a cox regression model. Results Out of 329 patients included in this study, ureteral FS were performed in 132 (40%) and urethral FS in 183 (56%) respectivley respectively. Thirteen urethral FS were positive (7.1%) resulting in 10 additional urethrectomy. Fourteen ureteral FS (10.6%) were invaded resulting in 8 additional ureteral resections and 1 nephroureterectomy. The use of urethral FS was associated with a decrease in positive margins rate (6% vs. 23%; RR = 0.27; p <0.0001). Conversely, the use of ureteral FS had no impact on the rate of positive margins (12% vs.14%; RR = 0.85; p = 0.58). The use of ureteral FS had no impact on survival whereas the routine use of urethral FS was a prognostic factor for RFS and CSS in univariate (5-years RFS: 51.5% vs. 32%; p <0.0001 and 5-year CSS: 65.1% vs. 50.5%) and multivariate analysis (HR = 1.7; p= 0.003 and HR=1.4; p=0.04 respectively)._x000D_ Conclusions This study is the first to asses the impact of urethral and ureteral FS use on oncological outcomes after radical cystectomy. The routine use of urethral FS was associated with adecreased rate of positive surgical margins and improved recurrence-free survival and cancer-specific survival. Conversely, the use of ureteral frozen section had no impact on oncological outcomes. Funding none
Authors
benoit peyronnet
gregory verhoest quentin alimi lauranne tondut vivien graffeille romain mathieu andrea manunta karim bensalah francois guille solene-florence kammerer-jacquet nathalie rioux-leclercq |
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MP54-19 |
Impact of prostate involvement on outcomes in patients treated with radical cystoprostatectomy for bladder cancer |
Bladder Cancer: Invasive IV | 17BOS |
Abstract: MP54-19 Sources of Funding: none Introduction The impact of the different types of prostate involvement by urothelial carcinoma (PUC) or prostate adenocarcinoma (PCa) at the time of radical cystoprostatectomy (RCP) has not been fully investigated. Methods Data from 893 male patients treated with RCP and pelvic lymph node dissection at a tertiary referral center for nonmetastatic bladder cancer between 1992 and 2012 were assessed. Significant PCa was defined as extracapsular disease and/or Gleason Score ? 7. Prostatic urothelial carcinoma (PUC) was stratified as stromal versus urethral/duct involvements. Multivariable Cox regression analyses were built to test the impact of the presence of incidental PCa and PUC on outcomes. Results PCa was present in 319 (35.7%) patients, of which 45 (14.1%) had significant disease. While, the proportion of significant PCa did not change significantly (p=0.8), the rate of indolent PCa increased from 17.1%, to 29.4% to 37.9%, respectively (p<0.001). PUC was identify in 181 patients (20%): 75 (41.1%) with urethral/duct involvement and 106 (58.6%) with stromal. Within a median follow-up of 72 months, stromal PUC, but not the other forms of PUC or PCa, was associated with disease recurrence and cancer-specific mortality. In multivariable analyses adjusted for the effects of standard features, stromal PUC remained associated with recurrence (Hazard Ratio [HR]:2.01, p=0.03) cancer-specific mortality (HR: 1.65, p=0.01) and overall mortality (HR: 1.45, p=0.03). Conclusions PCa involvement does not affect outcomes in patients treated with RCP for bladder cancer. Conversely, prostatic stromal invasion with urothelial carcinoma confers a poor survival confirming its aggressiveness. Funding none
Authors
Marco Moschini
Andrea Gallina Giusy Burgio Paolo Dell´Oglio Emanuele Zaffuto Agostino Mattei Rocco Damiano Shahrokh Shariat Vincenzo Mirone Andrea Salonia Alberto Briganti Francesco Montorsi Renzo Colombo |
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MP54-20 |
Do men with a history of prostate cancer have worse bladder cancer outcomes? |
Bladder Cancer: Invasive IV | 17BOS |
Abstract: MP54-20 Sources of Funding: None Introduction To review the perioperative outcomes and histopathologic features of men undergoing radical cystectomy (RC) for invasive bladder cancer with a history of prostate cancer (PCa). Methods IRB approved, retrospective chart review was performed on 500 patients who underwent RC at a single tertiary center between 2001-2014. After excluding females, we identified a total of 90 patients with a history of PCa prior to RC. Of those, 57 patients underwent RC as definitive treatment for bladder cancer. Clinicopathologic data of both malignancies were collected as well as details regarding prostate cancer treatment. Peri-operative RC variables were recorded, including approach (open vs. robotic), type of diversion, estimated blood loss, lymph node yields, intra-operative and post-operative complications. Complications were defined using the standardized Clavien-Dindo classification. A genitourinary pathologist evaluated all pathologic specimens. Results 57 patients at a median age was 77 years old underwent RC who had a history of PCa. Thirty five (61%) were treated with radiation prior to RC as either single or multimodal therapy for PCa. Compared to the non-irradiated group, patients in the irradiated group had higher stage (pT3/4) bladder disease (48.6% vs. 9.1% p=0.021), higher rates of lymphovascular invasion (37.1% vs. 2% p=0.006), and higher rates of variant bladder histology (42.9% vs. 13.6% p=0.021). There was no significant difference is GFR, ASA classification, BMI, smoking history, or utilization of neoadjuvant chemotherapy between the two groups. The majority of cystectomies were approached robotically, regardless of prior radiation history (72% overall vs. 71% in irradiated group p=0.915). History of prior radiation did not significantly change type of diversion performed, length of surgery, estimated blood loss, length of stay, or lymph node yield. Interestingly, there was a trend towards a lower rate of major complications with a robotic approach (p=0.057). Conclusions In men with a history of PCa, those treated with radiation had significantly higher stage disease, rates of lymphovascular invasion, and variant bladder cancer histology. Robotic assisted RC performed similarly to an open approach with respect to objective indicators of surgical quality with no increased risk of perioperative or postoperative complication across all types of diversions. Funding None
Authors
David Golombos
Abimbola Ayangbesan Patrick Lewicki LaMont Barlow Padraic O'Malley Douglas Scherr |
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MP55-01 |
Mixed Epithelial and Stromal Tumor Family: A single institutional experience with this rare renal entity |
Kidney Cancer: Localized: Surgical Therapy III | 17BOS |
Abstract: MP55-01 Sources of Funding: Funded in part by the Sidney Kimmel Center for Prostate and Urologic Cancers and the National Cancer Institute Training Grant T32 CA082088 (BM, MG) Introduction In 2016 the World Health Organization coined the term mixed epithelial and stromal tumor family (MESTF) to encompass adult cystic nephroma (ACN) within the classification of mixed epithelial and stromal tumors (MESTs) on the basis of overlapping clinical and pathologic profiles. MESTs have traditionally been regarded as benign, with only a few reports of malignant transformation or recurrence in the literature. Diagnosis requires histopathological evaluation, as radiologic imaging cannot accurately determine whether such tumors are benign or malignant. We aim to characterize our institutional experience with this rare neoplasm. Methods We identified all patients with a pathological diagnosis of MEST or ACN from our prospectively collected institutional database between Jan 1995 - Dec 2015. Available imaging was re-reviewed by a single expert radiologist (AH). Demographic, radiologic, and clinical characteristics were recorded. Results Data was available for 40 patients. The median age at diagnosis was 48.8 years (31.5-73.4). Thirty-seven (92.5%) patients were female and three (7.5%) were male. Imaging was available for re-review for 29 (72.5%) patients. The mean diameter of the tumor on preoperative imaging was 5.8 cm (1.9-16.1). Patients presenting with symptoms at diagnosis had a mean diameter of 7.4 cm (4-16.1). On imaging, 25 (86.2%) tumors where characterized as Bosniak 3 lesions and four (13.8%) were described as Bosniak 4 lesions. All patients underwent surgical resection, with partial nephrectomy performed in 72.5% of cases. Mean pathological tumor size was 5.9 cm (1.5-15). Median follow-up was 71.6 months (1-217). Two (4.9%) patients died from non-tumor related causes. At last follow-up, all patients showed no evidence of disease. Conclusions MESTF are indolent tumors with a female predominance. They are usually detected incidentally as Bosniak 3 or 4 lesions. Partial nephrectomy should be performed whenever possible to resect the tumor and preserve renal function. Given the low likelihood of recurrence following excision, we believe that, once pathologically identified, patients have an excellent long-term prognosis and require minimal surveillance imaging on follow-up. Genomic characterization is currently underway. Funding Funded in part by the Sidney Kimmel Center for Prostate and Urologic Cancers and the National Cancer Institute Training Grant T32 CA082088 (BM, MG)
Authors
Mahyar Kashan
Mazyar Ghanaat Maria Becerra Andreas M. Hötker Brandon Manley Jozefina Casuscelli Nicole Benfante Shawn Mendonca Satish Tickoo Oguz Akin Paul Russo Jonathan Coleman A Ari Hakimi |
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MP55-02 |
Impact of Necrotic and Sarcomatoid Components on Oncological Outcomes in Patients with Non-Metastatic Renal Cell Carcinoma |
Kidney Cancer: Localized: Surgical Therapy III | 17BOS |
Abstract: MP55-02 Sources of Funding: None Introduction We investigated the impacts of pathologically identified necrotic and sarcomatoid components on oncological outcomes in patients non-metastatic renal cell carcinoma (RCC). Methods After excluding patients with metastatic and/or lymph node invasive RCC, 1161 patients with the pathologic reports regarding the necrotic and/or sarcomatoid components were finally included for the analysis. Initially, the components of sarcomatoid and necrotic were tri-chotomized (0%, ?20%, >20%), respectively, and the impacts of each components were assessed using multivariate analysis. Mean follow-up duration was 65 months. Results Mean tumor size was 4.2 cm and pathologic stage was as follows; T1a in 702 (60.5%), T1b in 228 (19.6%), T2 in 81 (7.0%) and T3a in 124 (10.7%) and T3b or greater in 26 patients (2.2%). Sarcomatoid and necrotic component were pathologically identified in 37 (3.2%) and 184 patients (15.8%), respectively. In Kaplan-Meier analysis, 5-year recurrence-free survival was 92.3% in patients without sarcomatoid component and 48.9% in patients with sarcomatoid component (p<0.001). In addition, 5-year recurrence-free survival was 95.8% and 64.6% in patients with necrosis and without necrosis, respectively (p<0.001). In multivariate analysis, age at surgery (HR; 1.029, p=0.002), tumor size (HR; 1.175, p<0.001), locally advanced RCC (HR; 5.220, p<0.001), presence of necrosis (HR; 2.891, p<0.001) and % sarcomatoid component > 20% (HR; 2.963, p=0.002) were significant factor for predicting recurrence after surgery. Conclusions RCC patients with sarcomatoid component >20% and/or any necrotic component on pathologic examination should be carefully followed-up after surgery because of increased risk for the recurrence. Funding None
Authors
Sangjun Yoo
Jeman Ryu Han-Kyu Chae Jae Hyeon Han Se Young Choi Dalsan You In Gab Jeong Cheryn Song Bumsik Hong Jun Hyuk Hong Hanjong Ahn Choung-Soo Kim |
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MP55-03 |
Does Histology Subtype need to be Considered after Partial Nephrectomy in Patients with Pathologic T1a Renal Cell Carcinoma?: Papillary vs. Clear Cell Renal Cell Carcinoma |
Kidney Cancer: Localized: Surgical Therapy III | 17BOS |
Abstract: MP55-03 Sources of Funding: None Introduction We assessed the impact of papillary renal cell carcinoma (RCC) on oncological outcomes after partial nephrectomy compared to clear cell RCC in patients with pathologic T1a RCC. Methods After excluding patients with synchronous multiple renal tumors, familial renal cell carcinoma, pathologic T1b or greater disease, and metastatic disease, 759 patients with clear cell and 84 patients with papillary RCC were included for the analysis. We compared the impacts of papillary RCC with clear cell RCC on oncologic outcomes. Median follow-up duration was 67 months. Results There was no differences in patient and tumor characteristics between the 2 groups except for Fuhrman grade (p=0.006). In Kaplan-Meier analysis, 5-year recurrence free survival was 98.7% in patients with clear cell RCC and 95.6% in patients with papillary RCC. However, 10-year recurrence free survival in patients with clear cell and papillary RCC was 96.1% and 73.0%, respectively (p<0.001). Median time to recurrence was 31 months in patients with clear cell RCC and 77 months in patients with papillary RCC although statistical significance was not achieved (p=0.190). In multivariate analysis, papillary RCC (HR; 5.309, p=0.001) was determined as a significant risk factor for recurrence after partial nephrectomy in pathologic T1a RCC patients in addition to tumor size (HR; 1.861, p=0.038) and Fuhrman grade (?3) (HR; 5.176, p=0.003). Conclusions Recurrence after partial nephrectomy was more commonly occurred in pathologic T1a papillary RCC compared to clear cell RCC. Because median time to recurrence in papillary RCC was greater than 5-year after surgery, longer follow-up is needed for patients with papillary RCC even though pathologic stage is T1a. Funding None
Authors
Sangjun Yoo
Jeman Ryu Han-Kyu Chae Jae Hyeon Han Se Young Choi In Gab Jeong Cheryn Song Bumsik Hong Jun Hyuk Hong Hanjong Ahn Choung-Soo Kim |
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MP55-04 |
Perinephric versus sinus fat invasion in pT3a tumors managed by partial nephrectomy |
Kidney Cancer: Localized: Surgical Therapy III | 17BOS |
Abstract: MP55-04 Sources of Funding: None Introduction With adoption of partial nephrectomy (PN), the last few years have been marked by a growth in the use of PN for complex renal masses. This has led to an overall increase in the number of tumors found to have adverse pathological features. There are two types of pathological findings in the current T3a fat invasion renal cell carcinoma (RCC): renal sinus fat invasion (SFI) and perinephric fat invasion (PFI). From an anatomical perspective, after PN, RCC with SFI could be considered more likely to develop recurrence and may be associated with worse prognosis. _x000D_ The aim of our study was to evaluate the influence of SFI and PFI on progression-free survival and overall survival after PN for stage pT3a RCC. Methods We retrospectively reviewed our institutional review board-approved PN database. Data consisted of consecutive records of patients who underwent PN for cT1-3a renal cell carcinoma (RCC) between 2007 and 2016. Overall 1306 patients were included in this study. Of this cohort, 143 patients were staged pT3a with SFI (85 patients) or PFI (58 patients) on final pathology. Demographic, perioperative and pathological variables were reviewed. We compared the clinico-pathological characteristics, perioperative morbidity and oncological outcomes between SFI and PFI groups. Progression-free survival (PFS) and overall survival (OS) analyses were performed. Survival curves were compared using Log-rank test. Results There were no differences between the 2 groups in terms of age, gender, race, Body mass index, Charlson comorbidity index, cTstage and surgical approach. SFI group had a higher clear cell subtype (p<0.01), Higher R.E.N.A.L score (median 9 vs. 7, p<0.01), Higher hilar (h) location (p<0.01). Positive surgical margin rate was higher in SFI group (21.1% vs. 10.3%) but the difference was not statistically significant(p=0.09). _x000D_ SFI group had higher warm ischemia time (median 28 vs. 21, p<0.01), while estimated blood loss (p=0.6), transfusion rate (p=0.2), Clavien complications (p=0.6) were not different between the 2 groups. After a median 28 months, there were 19 recurrences (13.3%) and 7 deaths (4.9%). _x000D_ When comparing the survival curves between the 2 groups, there were no differences in PFS (Log rank, p=0.5) and OS (Log rank, p=0.8). Tumors size (HR:1.5, 95% CI [1.1-1.9], p <0.01, and tumor grade (HR:3.6, 95% CI [1.1-4.6], p=0.04) were independent predictors of recurrence. Conclusions In our cohort of patients with pT3a renal cell carcinoma following partial nephrectomy, sinus fat invasion compared to perinephric fat invasion was not associated with an increased risk of progression or death. The independent predictors of recurrence in this population were tumor size and tumor grade. Funding None
Authors
Pascal Mouracade
Onder Kara Matthew Maurice Julien Dagenais Ercan Malkoc Ryan Nelson Jeremy Reese Jihad Kaouk |
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MP55-05 |
Partial nephrectomy in the treatment of renal tumors with concomitant venous tumor thrombosis (VTT) of renal vein branches: retrospective, multi-center analysis of perioperative, functional, and oncologic outcomes |
Kidney Cancer: Localized: Surgical Therapy III | 17BOS |
Abstract: MP55-05 Sources of Funding: None Introduction To evaluate the perioperative, functional, and oncologic outcomes of partial nephrectomy (PN) in renal tumors with concomitant venous tumor thrombosis (VTT) of renal vein branches. Methods Data of open, laparoscopic or robotic PN with concomitant VTT removal was collected retrospectively in a multi-center study and compared to radical nephrectomy (RN) performed in the same centers for tumors of comparable diameter and VTT. Demographics, perioperative complications, functional, and oncologic outcomes were compared between the two groups. Mean, median, standard deviation, and interquartile range (IQR) were used to report continuous variables, as appropriate. Survival analysis were used to assess recurrence free survival (RFS), cancer specific survival (CSS) and overall survival (OS). Univariable (UVA) and multivariable (MVA) analyses were used to evaluate variables predicting complications, OS, CSS and RFS, and end-stage renal disease (ESRD, eGFR<30). Results Overall, 63 cases and 176 control were enrolled in the study. VTT was unsuspected pre-operatively in 46 (73%) of PN cases. Any grade and high grade postoperative complications were recorded in 41.9% and 22.2% for PN patients, respectively, and in 21.7% and 7.9% for RN patients, respectively (p values <0.05). Once adjusted for covariates, PN was associated with a significantly higher risk of any grade postoperative complications (OR 0.4; p=0.026), whereas only a non-significant trend was identified for high grade complications (OR 0.3; p=0.05). Median follow-up duration of the patients alive and disease free was 26.6 mo (IQR 8.7-39 mo) and 30 mo (IQR 13 - 64 mo) in the PN and RN group, respectively (p=0.5). The two-year RFS, CSS and OS survival estimates were 91.8%, 94.0%, 88.1%, for PN, respectively, and 95.8%, 94.6%, 92.9% for RN, respectively. PN site of recurrence were: local in 3 (4,9%), nodal in 3 (4,9%) and distant in 11 (18%). No differences in RFS, CSS and OS survival estimates were found between PN and RN, both in UVA and MVA analyses, where only the classic pathological variables were independent predictors of RFS, CSS, and OS. Preoperative eGFR was similar in both groups, with roughly 3% of the patients presenting with ESRD at initial diagnosis. At follow-up, eGFR was similar in both groups, whereas the prevalence of ESRD was significantly higher in the PN group (32.7% vs 13.2%, p<0.01). However, in MVA analyses, baseline eGFR was the only independent predictor of ESRD (HR 1.0; p<0.01), whereas only a non-significant trend was identified for the type of surgery (HR 0.5; p=0.07). Conclusions PN in tumors with concomitant intraparenchymal vein branches thrombosis is feasible but it is associated with higher risk of complications. RFS, CSS and OS were similar in the two groups. Finally, we found a non-statistically significant trend in favor of PN for ESRD prevention. Funding None
Authors
Fabio Zattoni
Robert H. Thompson Umberto Capitanio Alessandro Crestani Vincenzo Ficarra Alexander Kutikov Alessandro Larcher Brian R. Lane Bradley C. Leibovich Andrew McIntosh Francesco Montorsi Daniel Moon Tim Muilwijk Katie Murray Sabrina Noyes Paul Russo Robert G Uzzo Hein Van Poppel David Yang Filiberto Zattoni Alexander Mottrie Giacomo Novara |
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MP55-06 |
PRE-OPERATIVE PREDICTORS OF INCIDENTAL pT3a UPSTAGING FOLLOWING PARTIAL NEPHRECTOMY FOR CLINICAL T1 RENAL CELL CARCINOMA |
Kidney Cancer: Localized: Surgical Therapy III | 17BOS |
Abstract: MP55-06 Sources of Funding: None Introduction Nearly half of all patients undergoing partial nephrectomy (PNx) for cT1 tumors will have adverse final pathologic features such as high Fuhrman grade or pT3a disease. While renal mass biopsy can aid in the identification of high grade disease, tools to predict tumor upstaging are limited. Given that preoperative risk factors associated with pT3a upstaging are not well defined we sought to identify predictors of pT3a disease in patients undergoing PNx for cT1 disease. Methods A retrospective chart review was completed to identify patients with cT1 renal masses who underwent open or minimally-invasive PNx between 2000-2014. All patients with imaging sufficient for R.E.N.A.L Nephrometry scoring were included. The primary outcome was upstaging to pT3a disease at final pathology. All patients with benign final pathology were excluded. Univariate and multivariate logistic regression analyses were performed to identify characteristics independently associated with pT3a upstaging. All variables with a p-value of ≤ 0.1 on univariate analysis were included in the multivariate analysis. Results A total of 508 patients were identified, of which 449 (88%) had final pT1 and 59 (12%) had final pT3a disease. The etiology of pT3a upstaging was perinephric adipose extension in 69% (41/59), renal sinus fat invasion in 28% (14/59), and microscopic segmental or renal vein invasion in 7% (4/59). Patient age (p=0.012), ASA classification (p=0.005), preoperative radiologic tumor size (p=0.079), and high R.E.N.A.L Nephrometry Score complexity (p=0.017) were all associated with pT3a upstaging on univariate analysis. Multivariate analysis demonstrated a significant and independent association of patient age (p=0.025), preoperative radiologic tumor size (p=0.014), and high R.E.N.A.L Nephrometry Score complexity (p=0.019) with pT3a upstaging. Conclusions In patients who undergo PNx for cT1 disease, patient age, preoperative radiologic tumor size, and high R.E.N.A.L Nephrometry Score complexity represent readily measurable preoperative characteristics that are associated with increased risk of pT3a upstaging. The presence of these features may be utilized for operative planning to ensure adequate resection and negative margins in patients at increased risk for pathologic upstaging. Funding None
Authors
Christopher M. Russell
Amir H. Lebastchi Adam Niemann Rohit Mehra Todd M. Morgan David C. Miller Ganesh S. Palapattu Khaled S. Hafez J. Stuart Wolf Alon Z. Weizer |
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MP55-07 |
Long Term Outcomes of Patients with Cystic Clear Cell Renal Cell Carcinoma |
Kidney Cancer: Localized: Surgical Therapy III | 17BOS |
Abstract: MP55-07 Sources of Funding: none Introduction Cystic clear cell renal cell carcinoma (ccRCC), defined as multilocular cystic renal neoplasms of low malignant potential or ccRCC with cystic change, comprises less than 5% of renal cortical neoplasms and has been associated with a favorable prognosis in small retrospective studies. Because studies are limited due to the rarity of this variant, we reviewed our experience with ccRCC and report on long term oncologic outcomes of cystic ccRCC. Methods We identified 3,865 patients treated with radical or partial nephrectomy for unilateral, sporadic ccRCC between 1970 and 2010. One urologic pathologist re-reviewed all pathologic slides, blinded to patient outcome. Cancer-specific survival (CSS) was estimated using the Kaplan-Meier method and compared between those with and without cystic ccRCC using log-rank tests. Results Overall, 158 of 3,865 (4%) patients had cystic ccRCC. Compared to patients with non-cystic ccRCC, patients with cystic ccRCC were younger (median 58 vs. 63 years, p<0.001), were more likely to have radiographic evidence of cystic structures (60% vs. 17%, p<0.001), were less likely to have distant metastases at surgery (0% vs. 14%, p<0.001), and had smaller tumors (median 3.0 vs. 6.0cm, p<0.001) that were less likely to contain coagulative tumor necrosis (1% vs. 29%, p<0.001) or sarcomatoid differentiation (0% vs. 5%, p=0.006).With a median follow-up for survivors of 10.5 years (IQR 7.3-14.9), 63 patients with cystic ccRCC died at a median of 7.7 years after surgery (IQR 3.8-11.9). However, only one patient died from RCC after developing metastases 22 years after the initial surgery. CSS rates at 25 years following surgery were significantly better for cystic ccRCC compared to non-cystic ccRCC (88% vs. 52%, p<0.001) (Figure 1), even among the subset of pT1, pNX/0, M0 patients (100% vs. 83%, p=0.001). Conclusions In a large cohort of ccRCC patients with pathologic re-review and long-term follow-up, our results suggest that cystic ccRCC is both uncommon and associated with a very favorable prognosis. Funding none
Authors
Mary E. Westerman
Vidit Sharma Christine M. Lohse Stephen A. Boorjian Bradley C. Leibovich John C. Cheville R. Houston Thompson |
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MP55-08 |
Diagnosis, Management, and Clinical Outcomes of Cystic Renal Cell Carcinoma |
Kidney Cancer: Localized: Surgical Therapy III | 17BOS |
Abstract: MP55-08 Sources of Funding: Funded in part by the Sidney Kimmel Center for Prostate and Urologic Cancers and the National Cancer Institute Training Grant T32 CA082088 (BM, GM) Introduction Complex cystic masses pose a clinical challenge given lack of certainty for malignant potential. Cystic changes are common in renal cell carcinoma (RCC); however, there is limited data on cystic RCC (cRCC) specifically. The Bosniak classification system is used to categorize these lesions and help predict risk of malignancy. Current literature suggests that cRCC has a more favorable and benign course, but with no consensus on proper diagnosis and intervention. We aim to better categorize cRCC and the natural history of this disease. Methods We identified all patients with pathologically confirmed cRCC, multilocular cRCC, or RCC with cystic features between Jan 2000 - Dec 2015 from our institutional database. Patients with follow-up of <1 year, previous history of RCC, familial syndromes, multifocal tumors, and lesions with >50% solid component on imaging were excluded from our analysis. Available imaging was re-reviewed by a single expert radiologist (AH). Radiological, clinical, and pathological characteristics were recorded. Results Of 128 patients identified for analysis, 76 (59.4%) were male and 52 (40.6%) were female. Median age at surgery was 54.4 years (17.3-78.4). Twenty (15.6%) patients had a family history of RCC. The majority of lesions were found incidentally on imaging (89.1%). Fourteen (10.9%) patients had local symptoms, with flank pain (8.6%) being the most common. Partial nephrectomy was performed on 116 (90.6%) patients and radical nephrectomy on 12 (9.4%); open technique was used in >80% of cases. Pathologic and imaging characteristics are shown in Table 1. On median follow-up of 66.1 months, there were no tumor recurrences or metastatic disease. A total of 5 (3.9%) patients died from other conditions. Conclusions Diagnosis of cRCC should include cystic lesions with <50% solid component on imaging. Our data shows that cRCC includes a wide variety of tumors, most commonly with clear cell features. Most of these lesions are discovered incidentally on imaging as Bosniak grades 3 or 4 and are surgically resected. These patients uniformly do well with minimal risk of recurrence or metastasis on follow-up, thus, nephron sparing surgery is recommended. Given the indolent nature cRCC, enrollment of these patients into active surveillance protocols should be considered. Funding Funded in part by the Sidney Kimmel Center for Prostate and Urologic Cancers and the National Cancer Institute Training Grant T32 CA082088 (BM, GM)
Authors
Mahyar Kashan
Mazyar Ghanaat Maria Becerra Andreas M. Hötker Michael Chiok Brandon Manley Nicole Benfante Jozefina Casuscelli Shawn Mendonca Satish Tickoo Oguz Akin Paul Russo Jonathan Coleman A Ari Hakimi |
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MP55-09 |
Open partial nephrectomy vs. robot-assisted partial nephrectomy for cystic renal masses: impact of peroperative cystic spillage and oncological results. |
Kidney Cancer: Localized: Surgical Therapy III | 17BOS |
Abstract: MP55-09 Sources of Funding: none Introduction It is recommended to remove suspect cystic renal tumours when they are classified as Bosniak ≥3. These masses are fragile and may rupture during dissection or tumour excision. The impact of this intraoperative spillage on oncological outcomes remains uncertain. The objective of this study was to assess incidence of intraoperative cystic rupture according to surgical approach and its impact on oncological outcomes._x000D_ Methods Between 2005 and 2015, patients who had a partial nephrectomy (PN) in height European centres have been retrospectively analysed. We specifically sought if there was a cystic spillage during the procedure. Oncological outcomes included overall survival (OS), disease specific survival (DSS) and recurrence-free survival (RFS). We performed a sub-group analysis on surgical approach (open partial nephrectomy (OPN) vs. robot-assisted partial nephrectomy (RAPN)) and on the existence of intraoperative cystic spillage (ICS) to determine their impact on oncological outcomes. Kaplan-Meier curves of RFS were produced. A multivariate analysis with logistic regression model was used to assess predictors of intraoperative cystic spillage._x000D_ Results Overall, 268 patients were included. Malignancy of cystic renal masses was found in 75% of cases. Among them, 84.5% were Bosniak IV, 68% were Bosniak III and 62.5% were Bosniak IIF on preoperative CT-scan. With a mean follow-up of 32 months, OS was 95.1%, only 2% had a local recurrence, metastatic progression was found in 2% of cases and there was no specific-disease death. We reported intraoperative cystic spillage (ICS) in 18.7% (n=50) of cases (20% during RAPN vs. 18% during OPN). Among them, 77.5% were confirmed to be malignant after pathological analysis. In the ICS subgroup, with a median follow-up of 38 months, no local recurrence or metastatic progression was reported. Analyses of RFS did not found any difference among subgroups: ICS vs. no ICS (P=0.23) (Figure 1), OPN vs. RAPN (P=0.91) (Figure 2). No predictive factor of ICS was found. Conclusions Intraoperative cystic spillage is rather common regardless the surgical approach, and it does not seem to impact mid-term oncological outcomes. Funding none
Authors
Benjamin PRADERE
Benoit PEYRONNET Quentin Manach Zineddine Khene Gauthier Delporte Jérome Rizk Jean Baptiste Beauval Thomas Seisen Morgan Moulin Nicolas Brichart Axel Bex Morgan Roupret Franck Bruyère Karim BENSALAH |
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MP55-10 |
Increased B4GALT7 expression is associated with adverse oncologic outcome in localized clear cell renal cell carcinoma |
Kidney Cancer: Localized: Surgical Therapy III | 17BOS |
Abstract: MP55-10 Sources of Funding: none Introduction B4GALT7 is one of seven beta-1,4-galactosyltransferase (beta4GalT) genes, which encode type II membrane-bound glycoproteins that appear to have exclusive specificity for the donor substrate UDP-galactose. According to previous studies aberrant B4GALT7 expression has distinct functions in different tumors. Here, we evaluate the association of B4GALT7 expression with oncologic outcomes in patients with localized clear cell renal cell carcinoma (ccRCC) managed by surgery. Methods A retrospective analysis of 207 and 231 patients with localized ccRCC undergoing RN or NSS at two academic medical centers respectively between 2005 and 2009 was performed. The first cohort with 207 patients was treated as training set and the other as validation set. Tissue microarrays (TMAs) were created in triplicate from formalin-fixed, paraffin embedded specimens. Immunohistochemistry with a commercially available monoclonal B4GALT7 antibody was performed with the intensity (0 to 3) and percentage (0 of 100) of staining recorded. The association of B4GALT7 expression with standard pathologic features and prognosis were evaluated. Results B4GALT7 expression was significantly associated with tumor T stage (P<0.001 and P<0.001, respectively), Fuhrman grade (P<0.001 and P<0.001, respectively) and necrosis (P=0.021 and P=0.002, respectively) in both training and validation sets. Moreover, high B4GALT7 expression indicated poor overall survival (OS) (P<0.001 and P<0.001, respectively) in the two sets. The incorporation of B4GALT7 into T stage and Fuhrman grade would help to refine individual risk stratification. Furthermore, B4GALT7 expression was identified as an independent adverse prognostic factor for survival. Conclusions Increased B4GALT7 expression is a potential independent adverse prognostic factor for overall survival in patients with localized ccRCC. Inhibiting B4GALT7 pathway might be a promising target of postoperative adjuvant therapy for these ccRCC patients. Funding none
Authors
Huyang Xie
Zewei Wang Qiang Fu Jiejie Xu Dingwei Ye |
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MP55-11 |
Prognostic value of vascular endothelial growth factor (VEGF), VEGF receptor 2, platelet-derived growth factor-? (PDGF-β), and PDGF-β receptor expression in papillary renal cell carcinoma |
Kidney Cancer: Localized: Surgical Therapy III | 17BOS |
Abstract: MP55-11 Sources of Funding: None Introduction We evaluated the prognostic value of the expression of vascular endothelial growth factor (VEGF), VEGF receptor 2 (VEGFR2), platelet-derived growth factor-β (PDGF-β), and its receptors (PDGFR-β) for papillary renal cell carcinoma (pRCC). Methods A total of 145 patients, who were confirmed to have pRCC, were analyzed. Expression levels of molecular markers were assessed by immunohistochemical staining. Results The median follow-up period for all subjects was 52.0 (interquartile range, 34.5-90.5) months. Among the cohort of 145 patients, high VEGF expression was observed in 100 (69.0%) patients, whereas high expression of VEGFR2, PDGF-β, and PDGFR-β was observed in 64 (44.1%), 42 (29.0%), and 30 (20.7%) patients, respectively. Only individuals with high VEGFR2 expression exhibited improved 10-year recurrence-free survival (85.3 vs. 58.1%; p=0.005) and cancer-specific survival (86.4 vs. 70.1%; p=0.014) rates compared to individuals who exhibited low expression. Multivariate analysis revealed that high VEGFR2 expression was an independent prognostic factor for recurrence (HR, 0.326; p=0.006) and cancer-specific mortality (HR, 0.334; p=0.046). During follow-up, 17 patients received targeted drug therapy. Patients with high VEGFR2 expression showed a better initial response (PR, 40%; SD, 20%; PD, 40%) than patients with low expression did (PR, 0%; SD, 58.3%; PD, 41.7%; p=0.052). Conclusions pRCC with high VEGFR2 expression correlates with a better initial response to targeted drug therapy and a better prognostic outcome. Funding None
Authors
Myong Kim
Jong Keun Kim Myungchan Park Sang Hyun Park In Gab Jeong Cheryn Song Jun Hyuk Hong Choung-Soo Kim Tai Young Ahn Hanjong Ahn |
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MP55-12 |
Long-term assessment of mortality patterns after surgical treatment for non-metastatic kidney cancer: a competing risk analysis |
Kidney Cancer: Localized: Surgical Therapy III | 17BOS |
Abstract: MP55-12 Sources of Funding: none Introduction Accurate estimation of long-term risk of cancer-specific [CSM] and other-cause mortality [OCM] is of utmost importance for clinical management of patients diagnosed with kidney cancer. The aim of the study is to assess long-term mortality rates of a contemporary cohort of patients surgically treated for non-metastatic kidney cancer. Methods 1,704 patients with non-metastatic kidney cancer treated with either radical or partial nephrectomy between 1987 and 2015 in a prospectively collected institutional database were assessed. Outcomes of the study were the 10-year rates of CSM and OCM. A multivariable competing risk regression model was fitted to predict CSM and OCM. Covariates consisted of age, gender, Charlson comorbidity index [CCI], pre-operative estimated glomerular filtration rate, haemoglobin and platelets, clinical tumour size, clinical tumour [cT] and nodal stage [cN], presence of local symptoms at diagnosis and year of surgery. Smoothed Poisson's incidence plots were used to estimate 10-year CSM and OCM rates in the overall population as well as in 4 sub-cohorts defined as: A.age ?60 and stage T1; B.age >60 and stage T1; C.age ?60 and stage >T1; D.age >60 with stage >T1 Results At a median follow-up of 72 months, 10-year rates of CSM and OCM were 11 and 14%, respectively. At competing risk regression analysis, age, platelets, cT and cN resulted associated with higher risk of CSM (all p<0.05). Conversely, female gender and year of diagnosis were associated with lower risk of CSM (all p<0.05). Moreover, age, CCI and tumour size resulted associated with higher risk of OCM (all p<0.05). Conversely, female gender and year of diagnosis were associated with lower risk of OCM (all p<0.05). After stratification according to age and cT (Figure 1), the 10-year CSM and OCM rates resulted 3.4 and 5% in group A; 8 and 24% in group B; 22 and 7.7% in group C and 31 and 24% in group D, respectively. Conclusions The relative impact on CSM and OCM in patients treated with surgery for kidney cancer is extremely heterogeneous according to host and cancer characteristics. The 10-years rates of CSM and OCM resulted 3.4 and 5% in younger patients with cT1 and 31 and 24% in older patients with cT2 or higher stage. These figures can aid clinical decision making providing a precise long-term mortality risk estimation. Funding none
Authors
Alessandro Larcher
Alessandro Nini Fabio Muttin Francesco Trevisani Francesco Ripa Zachary Hamilton Ithaar Derweesh Cristina Carenzi Domenico Fichera Patrizio Rigatti Federico Dehò Francesco Montorsi Umberto Capitanio Roberto Bertini |
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MP55-13 |
Comparing predictive accuracy for four prognostic models of recurrence following surgery in non-metastatic renal cell carcinoma with thrombus using contemporary data from six institutions |
Kidney Cancer: Localized: Surgical Therapy III | 17BOS |
Abstract: MP55-13 Sources of Funding: none Introduction Predictive models for recurrence in non-metastatic renal cell carcinoma (RCC) have been developed from general populations of RCC patients, including very few high risk patients. According, these models may not be ideal to stratify high risk patients for enrollment in adjuvant clinical trials such as patients with venous tumor thrombus. The purpose of this study was to compare predictive accuracy for a nomogram developed from non-metastatic RCC patients with venous tumor thrombus with 3 existing prognostic models for RCC recurrence following surgery. Methods A nomogram was developed from independent predictors after multivariable modeling of common clinical and pathologic variables. Receiver operator characteristic (ROC) curves were constructed to compare predictive accuracy of the nomogram with the University of California?Los Angeles Integrated Staging System(UISS), Stage Size Grade Necrosis (SSIGN) and Sorbellini models. Results A total of 669 consecutive non?metastatic RCC patients with tumor thrombus were treated surgically from 2000?2014 at 6 institutions. Variables independently associated with RCC recurrence were increased tumor diameter per centimeter, body mass index per point, preoperative hemoglobin < lower limit of normal, IVC thrombus level above hepatic vein, perinephric fat invasion, and non?clear cell histology. Estimated overall 5?year RFS was 49%. A nomogram was developed using weighted variables in a development cohort (n=465) and validated in a separate cohort (n=204). _x000D_ _x000D_ The AUC for the thrombus nomogram was 0.738, which was significantly higher than AUC for the Sorbellini model (0.623), UISS model (0.615) and SSIGN model (0.584)._x000D_ _x000D_ Conclusions A nomogram developed specifically for non?metastatic RCC patients with venous tumor thrombus has significantly greater predictive accuracy than general prognostic models in this high risk population. Funding none
Authors
Shivashankar Damodaran
Jose A. Karam Timothy A. Masterson Viraj A. Master Vitaly Margulis Datta Patil Tyler Bauman Michael Blute, Jr. Evan Bloom Haley Robyak Matthew Kaag Jay D. Raman Christopher G. Wood E. Jason Abel |
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MP55-14 |
The ability of three comorbity indeces to predict postosperative mortality in renal cell carcinoma patients: the impending need of a new disease-specific index |
Kidney Cancer: Localized: Surgical Therapy III | 17BOS |
Abstract: MP55-14 Sources of Funding: none Introduction To date no studies assessed whether Charlson Comorbidy Index (CCI), American Society of Anesthesiologists score (ASA) and Eastern Cooperative Oncology Group performance status (ECOG) have the same ability to predict postoperative mortality in renal cell carcinoma (RCC) patients who undergo radical (RN) or partial nephrectomy (PN). The aim of the study was to assess the predictive ability of these indeces on other cause mortality (OCM) in patients treated with surgery for kidney cancer. Methods We identified 2,648 T1-T4 patients treated with RN or PN for RCC between 1987 and 2014 at a single centre. Patients with distant metastases at diagnosis, with multiple lesions and with Von Hippel Lindau were excluded. Four multivariable Cox regression analyses (MVA) were performed to assess OCM predictors. Predictors included in Model 1 were age at surgery and gender (basic model). Predictors in Model 2, 3 and 4 were the same included into Model 1 plus CCI, ASA and ECOG, respectively. The discrimination of the accuracy of each model was quantified using the receiver operating characteristic-derived area under the curve with a time frame at 3-year. Decision curve analyses were performed to evaluate and compare the net-benefit associated with the use of the 3 indeces relative to the basic model. Results 249 patients (9.4%) died of other causes. Overall, 82 (3.1%) patients died within 3 years after surgery. The median follow-up in patients who survived was 63 months (IQR 30-118). At MVA of Model 1, age (HR 1.1) and gender (HR 1.5) were independent predictors of OCM (all p0.004). At MVA of Model 2, 3 and 4, age and gender remained independent predictors of OCM (all p0.04). Furthermore, at MVA of model 2, 3 and 4 CCI (HR 1.3), ASA (HR 1.09) and ECOG (HR 1.9) reached the independent predictor status (all p<0.001). The accuracy of Model 1, 2, 3 and 4 were 74.5 vs 77.6 vs 76.3 vs 76.3. After decision curve analyses, there was no superior net-benefit of one model relative to the others. Conclusions We provided evidence that the difference in accuracy between the CCI, ASA and ECOG is clinically negligible. Interestingly, the increase in accuracy relative to the basic model of all three index is limited and there is no superior net-benefit of any of the examined indeces relative to the basic model. These findings suggest that there is an impending need of a disease-specific index to predict OCM in RCC patients submitted to surgery. At the moment, clinicians may use any of these indeces for RCC patients counselling to predict postoperative mortality after surgery. Funding none
Authors
Paolo Dell’Oglio
Alessandro Larcher Fabio Muttin Francesco Cianflone Alessandro Nini Zachary Hamilton Ithaar Derweesh Francesco Trevisani Cristina Carenzi Andrea Salonia Alberto Briganti Francesco Montorsi Roberto Bertini Umberto Capitanio |
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MP55-15 |
Impact of intraoperative blood transfusions on survival after surgery for renal cell carcinoma |
Kidney Cancer: Localized: Surgical Therapy III | 17BOS |
Abstract: MP55-15 Sources of Funding: None Introduction Many previous reports have shown an increased risk of cancer recurrence in oncological patients receiving blood transfusions at surgery. In renal cell carcinoma (RCC), it has been postulated that blood transfusion might impact the immunosuppressive response with a subsequent decreased host-tumor surveillance. We aimed to evaluate if intraoperative blood transfusion (IBT) may be associated with cancer specific mortality (CSM) and overall mortality (OM) in RCC candidates to surgical treatment. Methods We evaluated 2,528 consecutive patients diagnosed with RCC and treated with partial or radical nephrectomy between 1987 and 2011. IBT was defined as transfusion of allogenic red blood cells during surgery. Univariable and multivariable Cox proportional hazards regression analyses were used to predict CSM and OM. Covariates included age at surgery, gender, pathological T stage, pathological N stage, pathological grade, lymph vascular invasion, tumor size, Charlson Comorbidity Index (CCI), year of surgery, symptoms at the presentation and tumor necrosis. Preoperative hemoglobin and bleeding were also included in a second model to test the independent effect of IBT on the outcomes of interest. Results Overall, 784 patients out of 2,528 (31%) received IBT. In those patients, the median number of units transfused was 3 (range 1-7). Patients receiving IBT were significantly older (median age 61 vs. 64, p<0.001), with higher CCI (median CCI 5% vs. 8%, p<0.001), more symptomatic (35% vs 50%, p<0.001) and with more advanced pathological characteristics, such as high grade (Fuhrman 3-4: 25% vs. 43%, p<0.001), tumor stage (pT3-4 17% vs. 45%, p<0.001) and lymph node invasion (pN1: 4 % vs. 14%, p<0.001). Median follow-up was 72 months (IQR 10-90). Receipt of IBT was associated with CSM (HR 3.15 95%CI: 2.54-3.92, p<0.001) and OM (HR 2.40 95%CI: 2.07-2.78, p<0.001). At multivariate analyses, IBT was associated with higher risk of OM (Hazard ratio [HR] 1.09; [CI] 1.006-1.192; p<0.05). Among patients who received IBT, an increasing number of units transfused was independently associated with increased OM (HR 1.14 [CI] 1.05-1.21; p< 0.05). Conclusions When observing long-term follow-up, IBT is associated with a significantly increased risk of both CSM and OM after nephrectomy. Further investigations are needed to fully understand the impact of blood transfusions on RCC and the pathological mechanisms which can be modified by adequate intraoperative and post-operative patient management. Funding None
Authors
Giovanni La Croce
Fabio Muttin Marco Moschini Alessandro Larcher Paolo Dell’Oglio Alessandro Nini Francesco Ripa Francesco Cianflone Ettore Di Trapani Cristina Carenzi Federico Dehò Francesco Montorsi Roberto Bertini Umberto Capitanio |
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MP55-16 |
Radical Nephrectomy With or Without Lymph Node Dissection for Non-Metastatic Renal Cell Carcinoma: A Multi-Institutional Analysis |
Kidney Cancer: Localized: Surgical Therapy III | 17BOS |
Abstract: MP55-16 Sources of Funding: None Introduction The role of lymph node dissection (LND) in the management of renal cell carcinoma (RCC) has been controversial, with conflicting data regarding its oncologic benefit. Proponents of LND have suggested that it may benefit patients at increased risk of lymph node (LN) metastases, which prior studies may have been underpowered to detect. We therefore utilized a large, multi-institutional cohort to evaluate the association of LND with survival among patients undergoing RN for RCC. Methods We identified 2,722 patients who underwent RN for M0 RCC between 1990 and 2010 at Mayo Clinic and San Raffaele Scientific Institute, including 1,215 (45%) with concomitant LND. A propensity score (PS) for receipt of LND was constructed using clinicopathologic features. The associations of LND with development of distant metastases, cancer-specific mortality (CSM), and all-cause mortality (ACM) were evaluated using Cox regression models adjusted for PS quintile or stabilized inverse probability weights (IPW). Internally predicted probabilities for pN1 disease were estimated using logistic regression. Results Overall, 171 (6.3%) patients were pN1. There were no statistically significant differences in clinicopathologic features stratified by LND after PS adjustment. Median follow-up among survivors was 9.6 years, during which time 787 patients developed distant metastases and 622 died from RCC. Overall, LND was not significantly associated with a reduced risk of distant metastases, CSM, or ACM using any of the PS techniques (Table). More importantly, we examined the association of LND with oncologic outcomes among patients at increased risk of pN1 disease. Here, LND was not associated with oncologic outcomes among patients with preoperative radiographic lymphadenopathy (cN1), and no consistent association with improved oncologic outcomes was noted across increasing probability thresholds for pN1 disease from 0.10 to 0.50. Conclusions The current analysis of a large, international cohort indicates that LND is not associated with improved oncologic outcomes among patients undergoing RN for M0 RCC, including patients at increased risk of LN metastases such as those with radiographic lymphadenopathy (cN1) or across increasing probability thresholds for pN1 disease. _x000D_ Funding None
Authors
Boris Gershman
R. Houston Thompson Stephen Boorjian Alessandro Larcher Umberto Capitanio Francesco Montorsi Cristina Carenzi Roberto Bertini Alberto Briganti Christine Lohse John Cheville Bradley Leibovich |
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MP55-17 |
Assessment of metastasectomy complications in renal cell carcinoma |
Kidney Cancer: Localized: Surgical Therapy III | 17BOS |
Abstract: MP55-17 Sources of Funding: none Introduction Metastasectomy (MSx) is a viable option in patients with metastatic renal cell carcinoma (mRCC). Available information on perioperative outcomes is scarce. We assess complications of MSx in a large population-based US cohort. Methods The Nationwide Inpatient Sample (2000-2011) was utilized to abstract all patients with a primary diagnosis of mRCC. MSx was defined as an organ-specific resection as a diagnosis of a metastasis to a corresponding site (liver; lung; brain; bones; lymph nodes; adrenal) during the same admission. All procedures concomitantly performed with radical or partial nephrectomies were excluded. Baseline characteristics and multivariable logistic regression analyzes described in-hospital complications, length of stay, and mortality following MSx. Results Overall, 26990 weighted patients had mRCC. Of those, 949 were treated with a MSx (3.5%). Common sites of MSx were liver (47.8%) and lung (33.2%). MSx patients were significantly younger than non-MSx patients (60 vs. 62 years, p=0.013). Overall in-hospital mortality rate was 2%. The most common in-hospital complications were prolonged length of stay, defined as ?7 days (38.5%), respiratory complications (17.1%), vascular complications (14.8%), and blood transfusions (16.3%). In multivariable analyses neither patient nor hospital characteristics were significant predictors of overall complication rates. Conclusions This study suggests that MSx is a sensible and safe approach for the treatment of mRCC. We did not find significant predictors of complications for MSx in mRCC patients. Nevertheless, postoperative care should be optimized to prevent unnecessary complications and prolonged length of stay. Funding none
Authors
Christian P. Meyer
Quoc-Dien Trinh Malte W. Vetterlein Philipp Gild Felix K. Chun Margit Fisch Nicolas von Landenberg Björn Löppenberg Julian Hanske Thomas Seisen Firas Abdollah Mani Menon Adam S. Kibel Steve Chang Maxine Sun |
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MP55-18 |
Comparative Efficacy of Extirpative Surgery, Thermal Ablation, and Active Surveillance for Patients with Small Renal Masses: Results from the DISSRM Registry |
Kidney Cancer: Localized: Surgical Therapy III | 17BOS |
Abstract: MP55-18 Sources of Funding: National Institutes of Health (NIH), Grant Number TL1 TR001078. Introduction Little prospective data exists evaluating comparative oncologic, renal function, and quality of life outcomes for patients with small renal masses (cT1a, ≤4.0 cm). We sought to elucidate these outcomes in the prospectively-maintained Delayed Intervention and Surveillance for Small Renal Masses (DISSRM) registry. Methods Patients were enrolled following a choice of primary intervention or active surveillance (AS). Patients who received intervention were further defined by the type of treatment: partial nephrectomy (PN), radical nephrectomy (RN), or ablation. Cancer-specific and overall survival rates were estimated with the Kaplan-Meier method and compared using the log-rank test. Glomerular filtration rate (GFR) was compared across groups at enrollment, 3, 6, and 12 months, and last available measurement. The Short Form 12 (SF-12) questionnaire was administered at enrollment, 6 and 12 months, and every year thereafter. The Physical Component Summary (PCS) and Mental Component Summary (MCS) of the SF-12 were evaluated among groups and over time using ANOVA and linear regression mixed modeling. Results Of the 615 enrolled patients, 317 originally chose AS. A total of 256 patients underwent PN, 47 RN, and 36 ablation. PN patients were younger (P < 0.001) and had fewer comorbidities (P < 0.001) than AS patients. Cancer-specific survival at 7 years did not differ among groups (P = 0.5), but overall survival was lower in the AS group (65.9%, P = 0.01) compared to PN (91.9%), RN (89.6%), and ablation (82.9%). From 193 patients, median GFR at enrollment was similar at 71.3, 68.1, 55.5, and 69.5 mL/min/1.73 m2 in the PN, RN, ablation, and AS groups, respectively (P = 0.7); at a median follow-up time of 1.5 years, the median GFR was 69.3, 43.7, 55.7, and 68.0 mL/min/1.73 m2 across the respective groups (P = 0.2). From a total of 1,932 SF-12 questionnaires, PN patients reported significantly higher PCS scores compared to AS patients at enrollment and annually thereafter until year 5. Patients in AS demonstrated lower PCS scores over time (P = 0.01), but MCS was not meaningfully different among groups or across time. Conclusions Superior overall survival and PCS outcomes in PN patients compared to AS patients are attributable to more favorable health characteristics at baseline. However, kidney function at enrollment was not a factor in determining management and does not vary appreciably after intervention type. Funding National Institutes of Health (NIH), Grant Number TL1 TR001078.
Authors
Ridwan Alam
Hiten D. Patel Alice Semerjian Mark F. Riffon Bruce J. Trock Peter Chang Andrew A. Wagner James M. McKiernan Mohamad E. Allaf Phillip M. Pierorazio |
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MP55-19 |
Minimally invasive conservative treatment of localized renal tumors: a single center experience on percutaneous ablations and robot-assisted partial nephrectomy |
Kidney Cancer: Localized: Surgical Therapy III | 17BOS |
Abstract: MP55-19 Sources of Funding: none Introduction Minimally-invasive treatments of clinically localized renal tumors such as robot-assisted partial nephrectomy (RAPN) and percutaneous Thermal Ablations (TA) are routinely performed in our institution. The objectives were to describe our indications and assess the morbidity and the efficacy of each one of the techniques Methods . From our prospectively maintained database UroCCR (French national Database on Kidney Cancer), we retrospectively reviewed RAPN and TA procedures performed between 2003 and 2016. Pre-operative, intra-operative, postoperative and follow up data were collected. Chi2 and Wilcoxon tests were used for comparisons. Kaplan Meier curves and Log rank test were used to determine survivals and predictive factors of local recurrence. Results We reviewed 397 procedures including, 232 RAPN and 165 TA. RAPN patients were younger (61 vs 73 yo, p<0.001), less often solitary kidney (4.9% vs 34.8%, p<0.001) or bilateral tumor (p<0.001) and had a lower ASA score. Post-operative complications occurred in 34 and 18 cases after RAPN and TA respectively (14.6% vs 10.8%, p=0.08). RAPN patients had more post-operative transfusion (7.7% vs 0.6%, p<0.001) and the Clavien grade of complications was higher (p=0,016). There was no difference on post-operative glomerular filtration rate (GFR) between the 2 groups (-5.3 vs -5.6 ml/min/1.73m2, p=0.32). Among the 342 patients with a proven malignant tumor, the rate of local recurrence, metastatic progression and death were lower with RAPN (3%, 2.4%, 1.9%, respectively) than TA (17.5%, 10.3%, 13.8%, p<0.001). In multivariate analysis, the only independent predictive factor of local recurrence was the endophytic character of the tumor OR 3.51 (1.01-12.20), p=0.04 Conclusions RAPN and TA allow offering a safe minimally invasive treatment whatever the patients profile is. Post-operative renal function and complication rates were not significantly different between the 2 groups. However, we experienced more major complications after RAPN and more local recurrence after TA Funding none
Authors
Yohann GRASSANO
Francois Cornelis Nicolas Grenier Clement MICHIELS Gregoire CAPON Henri BENSADOUN Gilles PASTICIER Gregoire ROBERT Jean-Marie FERRIERE Jean-Christophe BERNHARD |
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MP55-20 |
Adoption of Robotic Partial Nephrectomy: Its Effect on Renal Cancer Surgery and Kaiser Permanente Southern California Practice Patterns |
Kidney Cancer: Localized: Surgical Therapy III | 17BOS |
Abstract: MP55-20 Sources of Funding: none Introduction The rapid adoption of robotic surgery in the US has introduced a paradigm change, with over 80 percent of all prostatectomies for prostate cancer being performed robotically in 2015. For renal cancer, the trend has not been previously reported. We aim to evaluate the trend in surgical management of renal cancer in the last 8 years at Kaiser Permanente Southern California (KPSC). Methods From Jan 2008 to Dec 2015, all patients at KPSC who underwent surgical treatment for renal cancer were included retrospectively. Trends in surgical technique and approach, patients’ age, gender, clinicopathology, Charlson Comorbidity Index score, chronic kidney disease status were used to identify factors associated with the surgical technique using robust Poisson multivariate regression models. Results During this period 3163 patients were included. Robotic partial nephrectomy (PN) was approved by KPSC in March 2011, and its relative use amongst all renal cancer surgery increased by 125%, 45%, and 14% the following 3 years. Laparoscopic PN and laparoscopic radical nephrectomy (RN) were the most common surgeries, but decreased when robotic PN was introduced, and was surpassed by robotic PN in 2012 and 2014, respectively. In a multivariable model, use of partial nephrectomy was associated with lower pathologic T stage (p < 0.001) and lower Charlson Comorbidity Index score (p = .0037) compared with RN. Within subset analysis of partial nephrectomies performed from 2011-2015, minimally invasive approach was not associated with any of the considered covariates. Conclusions Since adoption in 2011, robotic PN has rapidly become the most common surgical modality to treat localized renal cancer. Further studies are necessary to understand the relationship between patient clinical data and surgical approach. Funding none
Authors
Ramzi Jabaji
Heidi Fischer Gary Chien |
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MP56-01 |
Racial Variations in Response to Intralesional Collagenase Clostridium Histolyticum in Men with Peyronie’s Disease |
Sexual Function/Dysfunction: Peyronie's Disease II | 17BOS |
Abstract: MP56-01 Sources of Funding: None Introduction It is generally accepted that Peyronie&[prime]s disease (PD) is more common in Caucasian (CA) males than it is in African-American (AA) males. Differences in wound healing have been noted between CA and AA men; however, the racial variation between CA and AA men with PD who undergo intralesional collagenase clostridium histolyticum (CCH) treatment remains unclear. The objective of this study was to determine if race has an impact on response to intralesional CCH. Methods We conducted a retrospective medical chart review at our institution of the records of all patients treated with CCH for PD between 04/2014 and 01/2016. Collected variables included demographics, including age and race, sexual function, penile curvature, and treatment outcomes. The primary outcome was a significant (≥20%) decrease in penile curvature over baseline at the conclusion of treatment. _x000D_ _x000D_ Results The retrospective chart review yielded 76 total patients who underwent CCH therapy for PD. Out of these patients, 66 designated themselves as CA and 5 designated themselves as AA. The remaining 4 patients designated themselves as &[Prime]other&[Prime] and were excluded from the analysis. A significant difference between racial groups was duration of PD, which was shorter for AA patients at an average of 5.4±4.45 months duration compared to an average of 30.5±63.1 months duration in CA patients (p=0.0025). AA men experienced an average curvature improvement of 9.0±6.52 versus 16.3±13.2(p=0.066). There were no significant differences between patients of different races in age, IIEF values both before and after treatment, penile length, or penile circumference. Conclusions While the PD patient population is predominantly CA, the difference in response between AA and CA trended towards statistical significance. Further studies with larger databases are needed to determine if there are differences in response to CCH between these two groups. Funding None
Authors
Kenneth DeLay
Nora Haney James Anaissie Faysal Yafi Wayne Hellstrom |
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MP56-02 |
Safety and Efficacy of Collagenase Clostridium Histolyticum in the Treatment of Active Phase Peyronie's Disease |
Sexual Function/Dysfunction: Peyronie's Disease II | 17BOS |
Abstract: MP56-02 Sources of Funding: None Introduction To examine the efficacy and safety of collagenase Clostridium histolyticum (CCH) in the treatment of acute phase Peyronie's Disease (PD). Methods We conducted a retrospective review of the records for all patients treated with CCH for PD between 04/2014 and 03/2016. Patients qualified as being in the acute phase of PD if they reported penile pain and duration of PD < 12 months at presentation. The primary outcomes of interest were final change in curvature after CCH treatment regardless of number of CCH cycles received, and frequency of treatment-related adverse events (TRAE). Paired t-Test and Chi-squared tests were performed to determine statistical significance (P<0.05). Results A total of 77 patients were included in the study, of which 21 (27%) qualified as acute phase PD and the remaining 56 (73%) as stable phase. Median duration of PD was 8 months for acute phase patients, and 21 months for stable phase (p=0.033). There was no significant difference in final change in curvature between the acute and stable phase of PD (16.2° vs. 14.9°, p=0.702). There was a significant difference in change in curvature reported after the first cycle of treatment between the acute and stable phase (21.7° vs. 12.5°, p=0.037). There was no statistically significant difference in frequency of TRAEs between the acute phase (3, 14%) and the stable phase (4, 7%) (p=0.332). Conclusions Although CCH is currently contraindicated during the acute phase of PD, preliminary results suggest that CCH use during this setting may be both effective and safe. There was no statistically significant difference in final change in curvature or TRAEs after CCH therapy between the acute and stable phase of PD. Funding None
Authors
James Anaissie
Kenneth DeLay Nora Haney Faysal Yafi Wayne Hellstrom |
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MP56-03 |
Intralesional Collagenase Clostridium Histolyticum Does Not Change Penile Vascular Parameters In Men With Peyronie's Disease |
Sexual Function/Dysfunction: Peyronie's Disease II | 17BOS |
Abstract: MP56-03 Sources of Funding: None Introduction To examine the change in penile vascular parameters after administration of collagenase Clostridium Histolyticum (CCH) in patients with Peyronie&[prime]s disease (PD). Methods We conducted a retrospective review of the records for a cohort of collagenase patients treated with CCH for PD between 04/2014 and 03/2016 who underwent penile duplex Doppler ultrasound (PDDU) after pharmacologically induced erection both before and after CCH treatment. The primary outcomes measured were changes in peak systolic velocity (PSV), end diastolic velocity (EDV), and resistive index (RI) after CCH treatment. Paired t-Tests were performed to determine statistical significance (P<0.05). Results A total of 24 patients were included in the study, of which 20 (83%) completed four cycles of treatment (consisting of eight total injections) and 4 completed three cycles. After 3-4 cycles of CCH therapy, there was no statistically significant change in EDV, RI, or International Index of Erectile Function (IIEF) score when compared to baseline. PSV, however, improved significantly from 48.4±11.9 cm/s at baseline to 52±10.9 cm/s (p<0.05) after CCH therapy. There was also a statistically significant change in penile curvature (56.5±18.7° to 34.7±18.1°, p<0.001) and erect penile circumference (11.5±1.2 cm to 11.9±1.3 cm, p<0.05) after treatment. Conclusions In spite of a significant change in penile curvature, this change did not correlate with changing penile vascular parameters. There was a significant increase in PSV after completion of CCH therapy, although this change did not translate into improved subjective erectile function. However, as suggested by the lack of change in EDV and RI before and after treatment, as well as the absence of any clinical correlation with PSV, EDV, or RI, CCH therapy likely has a negligible impact on penile vasculature, further supporting a favorable safety profile of CCH. Funding None
Authors
James Anaissie
Nora Haney Faysal Yafi Kenneth DeLay Wayne Hellstrom |
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MP56-04 |
Safety and Effectiveness of Collagenase Clostridium Histolyticum in the Treatment of Peyronie's Disease Using a New Shortened Protocol |
Sexual Function/Dysfunction: Peyronie's Disease II | 17BOS |
Abstract: MP56-04 Sources of Funding: Non Introduction Collagenase clostridium histolyticum (CCH)is the only licensed product for the treatment of Peyronie's disease (PD). The clinical safety and efficacy of CCH in PD was shown in two large clinical trials; IMPRESS I & II._x000D_ _x000D_ The aim of this study is to evaluate the efficacy and safety of CCH in the treatment of PD using a new modified treatment protocol which aims at reducing the number of injections needed and reducing patient visits, thus reducing the cost and duration of treatment._x000D_ Methods A prospective study of 50 patients with PD who are having treatment with CCH at a single centre using a new modified protocol. _x000D_ _x000D_ Patients with active disease, complete plaque calcification or ventral curvature were excluded._x000D_ _x000D_ The angle of curvature assessment after an intra-cavernosal injection of PGE1, IIEF and Peyronie's disease questionnaire (PDQ) were performed at baseline and at week 12. The global assessment of PD questionnaire was performed at week 12. _x000D_ _x000D_ Under a penile block of 10ml of lignocaine 1%, a total of 3 intra-lesional injections of CCH (0.9mg) were given at 4 weekly intervals using a new modified injection technique. CCH was injected in the plaque along 3 lines separated by 2mm at the apex of the curvature with the penis in the flaccid state. _x000D_ _x000D_ Six patients requested an additional 3 injections to have a total of 6 injections._x000D_ _x000D_ In between injections patients used a combination of home modelling, stretching and a vacuum device on a daily basis in order to mechanically stretch the plaque. _x000D_ _x000D_ Investigator modelling was not performed._x000D_ Results So far 46 patients have completed treatment; all had 3 injections._x000D_ _x000D_ At baseline, the mean penile curvature was 53.8°(30°-90°). Overall, 44 patients (95.6%) had an improvement in curvature with a mean value of 17.08° (0°-40°) or 30.8% from baseline (0-57%) after 3 injections. The end mean curvature for all patients after 3 injections was 37° (12°- 75°; p≤ 0.001). _x000D_ _x000D_ There was a statistically significant improvement in each of the IIEF questionnaire domains, all 3 PDQ domains and the global assessment of PD questionnaire._x000D_ _x000D_ The 6 patients who had 3 more injections continued to have additional curvature improvement, mean 19.8° (0°-40°). _x000D_ _x000D_ CCH was well tolerated by all patients with only mild and transient local side effects. _x000D_ _x000D_ The results of this study with only 3 CCH injections are comparable to those of the clinical trials using 8 CCH injections. With the new protocol, only 4 patient visits are needed including assessments versus 14 visits as per trial protocol._x000D_ Conclusions The new shortened protocol for CCH in PD is safe, effective and cost efficient. Funding Non
Authors
Amr Abdel Raheem
Marco Capece Ayo Kaljaiye Amr Mobasher Giulio Garaffa Nim Christopher David Ralph |
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MP56-05 |
Towards Standardization of Protocols for Intralesional Collagenase Clostridium Histolyticum (CCH): Survey Results of SMSMA Membership |
Sexual Function/Dysfunction: Peyronie's Disease II | 17BOS |
Abstract: MP56-05 Sources of Funding: None Introduction CCH is the only FDA approved medical treatment for peyronie's disease. Variable protocols exist regarding pretreatment evaluation, patient selection, procedural therapy and post treatment protocols. The objective of this study was to identify practice patterns of SMSNA members with respect to CCH treatment to better standardize protocols for safety and efficacy. Methods A 10 question survey was sent via survey monkey to SMSNA membership in November 2016. Questions solicited frequency of administration, use of formal peyronie's disease questionnaires (PDQ), use of other intralesional therapies, preprocedure objective measurements, remeasuring frequency, post procedure local wound care, use of post op modeling and stretch options. Off label use and in office and home modeling protocols were queried as well. Results 85% of respondents typically inject at least 10 CCH injections/per month._x000D_ _x000D_ Refer to table 1 for questions_x000D_ _x000D_ Off label use of CCH included ventral (17%), pain only (9.4%), curvature of less than 6 months duration (59%), unstable active disease (28%) and conformational architectural changes (78%). 45.8% will do only in office modeling once and all subsequent is done at home, while 30.5% do in office modeling and home modeling with each cycle._x000D_ Conclusions Most SMSNA members that took the survey used intralesional CCH frequently. Most do NOT use a Peyronie's PDQ prior to therapy and most measure curvature prior to therapy with intracavernosal injection, but not after each cycle. 62% offer other intralesional therapy in their practice. As November 2016, most did not use a stretching device or vacuum erection device in the modeling process. Most commonly, in office modeling is usually done just ONCE in the office. Many SMSNA members use CCH for off label indications such as active disease, prior to 6 month duration and ventral curvature. This data offers the information about the variety of protocols utilized by active CCH users. Funding None
Authors
Campbell Bryson
Stanton Honig |
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MP56-06 |
Clinical outcomes of the use of Collagenase Clostridium Histolyticum (CCH) for Peyronie's Disease (PD) |
Sexual Function/Dysfunction: Peyronie's Disease II | 17BOS |
Abstract: MP56-06 Sources of Funding: None Introduction To examine our early experience on the efficacy and safety of CCH for PD patients. Methods Between June 2014 and September 2016, we evaluated and treated 52 patients with stable PD Curvature (predominately dorsal with palpable plaque) Our protocol consists of 3 month cycles it begins with a one CCH injections for the first 2 weeks giving a total dose of 0,58 mg, following by modeling under local anesthesia during the initial month and two months of "Triple Therapy" - tadalafil 5mg daily, pentoxifiline 400mg twice a day and 6-8 hours of penile traction therapy. Results The cohort mean age was 56 (43-71) years with a mean curvature of 54º (30-90) degrees. During our mean follow up of 10 months, we noted significant clinical improvement in in PDQ bother scores from 7.5 to 4.2. Likewise there was PDQ symptoms improvement from 11.5 to 7.8. There was a median of 2 cycles (1-4) per patient and 75% had positive responses after 2 cycles. The mean curvature reduction or degree improvement per cycle was 14 grades (11-18). Five patients (9%) have required surgery for complete PD resolution. All side effects were mild, except two cases of plaque rupture, managed conservatively, with very good clinical outcome. Conclusions Using our modified-protocol combining CCH therapy, modeling and standard conservative therapy we achieved these promising preliminary results. Funding None
Authors
Juan Ignacio Martínez-Salamanca
Natalia Carballo Eugenio Cerezo Agustín Fraile Francois Peinado Esaú Fernández Pascual Joaquín Carballido |
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MP56-07 |
Outcomes of Intralesional Collagenase Clostridium Histolyticum (CCH) in Men With Peyronie's Disease |
Sexual Function/Dysfunction: Peyronie's Disease II | 17BOS |
Abstract: MP56-07 Sources of Funding: none Introduction Intralesional (IL) injection of CCH is the first FDA approved pharmacotherapy for the treatment of men with PD. This analysis was conducted to define the outcome of IL CCH in our program. Methods Study population included men with PD, had stable disease for >3 months, met the other label criteria and underwent IL CCH. Men received up to 8 injections of CCH divided into 4 treatment cycles. Curvature assessments were done at baseline, between cycles 2 and 3 and after cycle 4. Traction therapy was used as our modeling technique to standardize the mechanical therapy. Patient demographics, PD factors and IL CCH complications were recorded. Multivariable analysis (MVA) was used to explore predictors of improvement. Two definitions were used: >10° and >25% improvement. _x000D_ _x000D_ Results To date, 69 subjects have completed baseline and the mid-treatment assessments (mean age=55±10 years). 25 of these subjects also completed the end of treatment assessment. As baseline, the mean duration of PD was 20.5±20 months. 62% had dorsal curvature, 18% had an hourglass deformity, and 6% had tapering. Mean curvature was 44±20°, and decreased at mid-treatment to 40±20° (p=0.01). For the 25 men who completed the end of treatment assessment, their baseline curvature was 49±23°, and decreased at end of treatment to 44±23° (p=0.12). Three categories of curvature change were created: &[Prime]improvement&[Prime] (>10°); &[Prime]no change&[Prime] (±10° change), and &[Prime]worsened&[Prime] (>10°). After 4 IL CCH injections: 33% improved, 54% had no change, and 13% worsened. After 8 IL CCH injections: 36% improved, 48% no change, and 15% worsened. On univariable analysis, only degree of baseline curvature (r=0.4, p=0.01) was positively correlated to improvement. On multivariable analysis, predicting improvement, baseline curvature remained the only significant predictor of improvement (OR=1.04; 95% CI 1.01-1.07, p=0.04). For improvement defined as >25%, after 4 IL CCH injections, 32% improved and after 8 48% improved. While clinically significant, this difference (between 4 and 8 injections) did not reach statistical significance (p=0.21). There were no significant predictors of improvement of >25% at mid-treatment assessment in either univariable or multivariable analyses. Conclusions These data reflect our clinical experience, which is quite different to those presented in the IMPRESS trials. Approximately one third of men significantly improve their penile curvature and it appears that maximum response occurs after 4 injections of CCH. Funding none
Authors
Jean-Etienne Terrier
Christian J Nelson John P Mulhall |
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MP56-08 |
Candidates for Collagenase Clostridium Histolyticum Therapy: A Retrospective Review of the Structural and Hemodynamic Characteristics of Men with Peyronie’s Disease (PD) |
Sexual Function/Dysfunction: Peyronie's Disease II | 17BOS |
Abstract: MP56-08 Sources of Funding: none Introduction Peyronie&[prime]s Disease (PD) is a fibrotic disorder affecting the tunica albuginea of the corpora cavernosa. Stepwise intralesional injections of Collagenase Clostridium Histolyticum (CCH) was approved for use in 2013. This study sought to examine a large cohort of men presenting with PD prior to FDA approval of CCH therapy. All patients were carefully staged for reconstructive surgery or penile implant by Color Duplex Ultrasonography. Methods A retrospective review was completed of all patients complaining of PD who underwent in office testing with intracavernous pharmacologic erection augmented by visual sexual stimulation and CDDU from 2008 to 2013 by one Urologist. Patients were further characterized by age, BMI, cardiovascular risk factors, co-morbid diagnosis of Dupuytren’s contracture, hypogonadism, self reported ED by Sexual Health Inventory for Men score (SHIM), and prior history of prostate surgery. CDDU characteristics recorded were: peak systolic velocities (PSV) and resistive indices (RI), tunica albuginea plaque characteristics (calcifications), degree and type of penile curvature (dorsal, ventral, lateral, complex). Results A total of 451 patients were found to have PD, mean age of 63 years (26-95) and a mean BMI of 27.1 (range 18.1-46.1). 255/451 (56.5%) of patients had a moderate degree of curvature, >30 and <60°. Minor curvature (<30°) was noted in 22.5%. Severe curvature (>60°) was noted in 21%. Of the moderate curvature patients, 84/255 (33%) had normal penile hemodynamic parameters; 25/255 (10%) had arterial insufficiency, 82/255 (32%) had cavernous venous occlusive dysfunction, and 64/255 (25%) patients had mixed vascular disease. Conclusions In examining these pre-CCH era presentations, approximately 56% of PD patients presented with moderate penile curvature (>30 and <60°). Xiaflex is indicated for adult men with curvature > 30° and post-marketing studies confirm average curvature improvements of 30-35% or 20°. Using curvature as the only criteria for selection of Xiaflex, one-third of our patients could have been treated with CCH without need for any additional therapy to manage ED (normal Doppler exams). Additional counseling and treatment for men with some degree of erectile dysfunction (abnormal Doppler exams), would be needed to effectively manage the remaining 76% of men following CCH. There remains the need to effectively counsel PD patients with severe curvature and / or moderate curvate with concomitant ED about surgical options for PD. Funding none
Authors
Ram Pathak
Gregory Broderick |
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MP56-09 |
Intermediate Outcomes of Concurrent Tachosil Grafting with Inflatable Penile Prosthesis Placement |
Sexual Function/Dysfunction: Peyronie's Disease II | 17BOS |
Abstract: MP56-09 Sources of Funding: none Introduction Implant with grafting is the gold standard approach to men with severe curvature and concurrent severe erectile dysfunction. Hatzichristodoulou et al have shown excellent results with the use of Tachosil, an equine graft coated with fibrinogen and thrombin that is self-adherent and does not require suture fixation for Peyronie's repair without implant. We review our now intermediate series of patients who received a Tachosil graft in addition to an inflatable penile prosthesis (IPP), an expeditious approach that obviates possible device puncture. Methods Surgical technique involved a circumcision incision without or without separate peno-scrotal incision for implant placement. The IPP (Coloplast Titan) was placed first and inflated to reveal true degree of curve (often greater than pre-operative Doppler curve assessment). The dartos layer was dissected off and preserved providing coverage of the tachosil graft. The neurovascular bundle was next elevated if necessary which often resulted in significant dorsal curve improvement. Plaque incision(s)/partial excisions were performed at the point(s) of maximum deflection. Upon re-inflation the new enlarged defect was covered with a tachosil graft. The tachosil was then molded to the penis and covered with previously preserved dartos layer. A catheter and compressive dressing are left overnight. The device was left inflated for 4 weeks following the procedure. Results Twelve patients underwent IPP with tachosil graft. Average age of patients was 56. The average pre-operative curvature was 75 degrees (45-120) on doppler. Curvature was multiplanar dorsolaterally (left) in 11/13 patients. Average time was 145 minutes with < 100 ml of blood loss. Mean follow up time is 10 months. One patient developed an infection which necessitated device removal. There have been no signs of device aneurysm to date. Curvature correction was < 30 degrees in 12/13 patients with one patient having residual 40 degree lateral curvature with max inflation. Several patients have lateral deflection with the device uninflated. Two patients had Xiaflex injections prior to their procedure which did not appreciably influence the difficulty of the case. Conclusions Our intermediate results continue to reveal that Tachosil offers a feasible, fast and safe alternative to grafting with IPP that does not require the graft to be sewn in place. Funding none
Authors
Neil Patel
Kevin McVary Nikhil Gupta Michael Butcher Tobias Kohler |
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MP56-10 |
National Trends in Utilization of Penile Prosthesis Surgery in the Treatment of Peyronie&[prime]s Disease |
Sexual Function/Dysfunction: Peyronie's Disease II | 17BOS |
Abstract: MP56-10 Sources of Funding: Boston Scientific Introduction Surgical management for the treatment of Peyronie&[prime]s disease (PD) is indicated when men fail medical therapy such as intralesional collagenase clostridium histolyticum (CCH) injections. For men with severe curvature and concomitant erectile dysfunction (ED) not responsive to CCH and phosphodiesterase 5 inhibitor (PDEi) therapy, penile prosthesis (PP) surgery is a treatment option. We sought to evaluate trends in PP surgery for the treatment of PD and examine the effect of medical therapy on practice patterns. Methods Analysis of 21 years of a national prospectively maintained American Medical Systems database was performed (1995-2015). Utilization of PP was compared with ANOVA analysis between four distinct time periods: Pre-PDEi use for ED treatment (1995-1997); post-sildenafil (1998-2003); post-tadalafil and vardenafil (2004-2013); post-CCH approval (2014-2015). Comparison was made between patients who underwent PP surgery for PD as sole etiology versus all other patients (non-PD) using Chi-square or t-test. Results 6701 PP surgeries for the treatment of PD were included in the study period. Number of PP cases decreased annually from 494 (7.4%) in 1995 to 203 (3.0%) in 2015 (Figure 1). Significant decrease in PP surgery occurred for PD patients between each of the time intervals (&[prime]95-&[prime]97, &[prime]98-&[prime]03, &[prime]04-&[prime]13, &[prime]14-&[prime]15) [p<0.05] (Table 1). For non-PD patients, PP surgery decreased after the introduction of sildenafil only. PD patients were younger than those without PD (59.4 ±8.6 vs. 62.2 ±10.0 years, p<0.001). Proximal and distal measurements were lower in PD vs. non-PD group (Proximal 9.6 ±2.4 vs. 10.0 ±2.6 cm; Distal 9.0 ±2.4 vs. 9.5 ±2.7 cm, p<0.001). Penoscrotal is the most common surgical approach (p<0.05). Conclusions Decrease in PP surgery for the treatment of PD was observed between 1995-2015 notably due to the introduction of PDEi and CCH therapy. In contrast, PP surgery for men without PD has remained stable over the past decade. Further study is needed to determine if similar trends in utilization of PP surgery will continue for PD patients. Funding Boston Scientific
Authors
Michael Benson
David Shin Fatima Elgammal Dongfeng Qi Guanghui Liu |
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MP56-11 |
Outcome analysis of patients with Peyronie's disease who elect for non-invasive management |
Sexual Function/Dysfunction: Peyronie's Disease II | 17BOS |
Abstract: MP56-11 Sources of Funding: None Introduction Peyronie's disease (PD) affects approximately 5% of men and has numerous proposed treatments. Invasive management options include surgical or injectable therapy, while penile traction therapy with vacuum erection device (VED) represents a non-invasive approach. The objective of the present study is to assess outcomes for patients with PD who opt for non-invasive management. Methods Retrospective analysis of clinical data was performed for patients assessed for PD between July 2014 and August 2016 who were followed for at least 3 months and opted for non-invasive therapy. All patients were instructed to initiate traction therapy with VED for 10 minutes twice per day. Patients were assessed for degree of Peyronie's deformity and erectile function (SHIM score) at initial and subsequent encounters._x000D_ Results In all, 35 patients met the inclusion criteria. The mean [standard deviation (SD)] age was 58 (10.7) years, and the mean (SD) duration of PD prior to assessment was 24 (15.6) months. The mean (SD) duration of follow up was 11 (5.9) months. At follow-up, 24 men had not purchased a VED. Among patients who did not use a VED, 6 showed improvement, 16 remained stable and 2 had worsening curvature. Overall, the control group did not have a significant change in curvature, with a mean improvement (SD) of 2.5 (9.1)° (p=0.10). All 11 men who initiated VED traction therapy had an improvement in curvature with a significant mean (SD) improvement of 29.6 (17.1)° (p<0.001). Using linear regressions, we found a significantly greater percentage reduction in penile curvature with decreasing patient age for the VED group (r = 0.66, p = 0.03). No such correlation was identified in the control group (r = -0.13, p = 0.57). Changes in SHIM scores did not vary significantly between groups. No complications were noted. Conclusions In patients who opt for non-invasive management of PD, VED traction therapy provides improved curvature resolution compared to those who do not use such a device. Furthermore, VED therapy is potentially more effective in relatively younger patients._x000D_ Funding None
Authors
Landan MacDonald
Kyle Lehmann Luke Armstrong Gavin Langille |
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MP56-12 |
Concerns of Female Peyronie&[prime]s Disease Partners: A Narrative Analysis |
Sexual Function/Dysfunction: Peyronie's Disease II | 17BOS |
Abstract: MP56-12 Sources of Funding: None Introduction Peyronie&[prime]s Disease (PD) is known to have a significant negative impact on the psychosocial and relationship functioning of male patients, with studies finding increased depression, distress, and sexual dysfunction in men with PD. In just the past year, researchers have also begun to attend to the female partners of these men, studying their own sexual function, relationship satisfaction, and mood. However, these few studies are flawed: by using the male patient as a gateway to access his female partner, they limit their access to women whose partners are comfortable making such a referral; by using surveys that emphasize sexual function, they restrict the opportunity for the partners to define their own concerns. This study seeks to address these problems, using narrative content analysis of Internet posts made by female PD partners to describe and rank the concerns expressed by these women, independent of their interactions with researchers and male partners. Methods This is a qualitative study, analyzing the content of Internet posts made by female PD partners on two patient-centered and member-operated, English-language PD support forums. In deference to ethical concerns regarding consent to research, only those posts within the public domain and readily accessible to non-members via Google search were analyzed. A Grounded theory process was used, with open coding to identify themes of concern. Results From 2/2005-10/2016, a total of 793 posts were published online, by 48 female PD partners. The primary concern expressed by these women related to difficulty communicating with their partners about PD, with 24/48 (50%) posting about this issue. Secondary concerns were partners&[prime] emotional (18/48 (38%)) and physical (12/48 (25%)) pain. Only 10/48 (21%) expressed concern about their own diminished sexual pleasure, with 4/48 (8%) describing how their partners&[prime] curvature enhanced their sexual experience. Conclusions When evaluated through the nonintrusive method of Internet narrative analysis, female PD partners are most concerned with poor communication, followed by their partners&[prime] emotional and physical pain. While their sexual needs do merit attention, this study suggests that interventions targeting the psychosocial needs of patients and their partners would be most meaningful for this population. Funding None
Authors
Barbara Chubak
Lawrence Hakim |
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MP56-13 |
Clinical Factors Negatively Impacting Sexual Relationships in Men with Peyronie’s Disease |
Sexual Function/Dysfunction: Peyronie's Disease II | 17BOS |
Abstract: MP56-13 Sources of Funding: None Introduction Multiple studies have shown that Peyronie’s disease (PD) negatively impacts psychological factors including patient/partner satisfaction and overall sexual well-being. Given a relative paucity of data in this area, we sought to understand clinical factors in men who report that PD negatively impacts their sexual relationships. Methods We identified all men undergoing initial evaluation for PD between March 2014 and August 2016 at our institution. Patients without a current partner were excluded. During initial consultation, a detailed sexual questionnaire covering domains including erectile dysfunction, libido, ejaculatory dysfunction, and penile curvature was administered, which included a question on whether or not PD negatively impacted the current sexual relationship. Questionnaire results were subsequently compared between men based on their response to this question. Subset analysis of patients with objective curvature data was also performed. Statistical analyses including univariate and multivariate analysis was used to identify differences in those reporting negative relationship effects. Results 242 men with PD comprised our study cohort including 146 patients (60.3%) who reported that PD had a negative impact on their sexual relationships. Median (IQR) PD duration was 18 (9;36) months and patient-estimated penile curvature was 30 (20;45) degrees. On univariate analysis, patients reporting negative relationship effects had shorter relationship durations (23 versus 27 years, p=0.04), lower IIEF-ED domain scores (14 versus 19, p=0.01), and reported higher rates of buckling (OR 2.41, p=0.003), penile shortening (OR 2.17, p=0.006), penile trauma (OR 2.38, p=0.01), and partner pain with intercourse (OR 4.12, p=0.001). On multivariate analysis, penile shortening, partner pain with intercourse, and shorter relationship duration were associated with a negative relationship effect (p?0.04). A sub-analysis of 72 men with objective curve assessment did not reveal any significant difference in negative relationship effects based on penile curvature, calcification, hourglass deformity, or stretched penile length. Conclusions Several patient-reported variables including penile shortening and partner pain with intercourse are associated with a higher-reported rate of negative impact on sexual relationships in patients with PD, while longer relationship durations may be protective. Funding None
Authors
Matthew Ziegelmann
Mary Westerman Brett Watson Francisco Maldonado Landon Trost |
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MP56-14 |
Predictors of Penile Instability in Men with Peyronie’s Disease (PD) |
Sexual Function/Dysfunction: Peyronie's Disease II | 17BOS |
Abstract: MP56-14 Sources of Funding: None Introduction Penile instability (PI) defined as the tendency of the penis to buckle during axial loading is a significant problem for men with PD, as it contributes to difficulty with penetration and leads to increased patient bother and sexual dissatisfaction. Our objective was to investigate the prevalence of PI in men with PD and to evaluate predictors of PI. Methods The study population included men with PD, who had a curvature assessment during a rigid erection following an in-office intracavernosal injection. To define PI, axial loading was applied by hand to the glans penis during maximum rigidity. Buckling tendency was recorded as a dichotomous variable. Predictors of PI were determined using multivariable analysis. Parameters evaluated as potential predictors were: degree of curvature, complexity of deformity, direction of curvature, presence of tapering, stretched flaccid penile length. Results Mean age of 195 subjects was 55±11 years. 3 evaluators were involved in this analysis. 82% were in a stable relationship and 94% were heterosexual. Mean duration of PD was 16±21 months and mean magnitude of curvature was 39±21 degrees. 15% had hourglass deformity (HGD) and 66% had a unilateral indentation. 48% had instability. On univariate analysis, the following variables were related to PI: degree of curvature (<30°, 31%; 31-59°, 53%; >60°, 75%, p<0.001), presence of an indentation (29% vs. 14%, p=0.02), and presence of dorsal curvature (62% vs. 44%, p=0.01). On multivariable analysis, degree of curvature (OR=3.3, 95% CI 1.9-5.8, p<0.001), presence of an HGD (OR=2.9, 95% CI 1.0-7.9, p=0.04), and a presence of an indentation (OR=3.5, 95% CI 1.5-8.5, p=0.01) were predictors of PI. Conclusions PI is very common in men with PD. PI is most likely to occur in men with severe curvature and presence of HGD or indentation. Funding None
Authors
Eduardo P. Miranda
Jean E. Terrier Christian J. Nelson John P. Mulhall |
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MP56-15 |
Beyond Curvature: Prevalence and Characteristics of Penile Volume Loss Deformities in Men with Peyronie's Disease |
Sexual Function/Dysfunction: Peyronie's Disease II | 17BOS |
Abstract: MP56-15 Sources of Funding: none Introduction We sought to describe the prevalence and functional impact of non-curvature, penile volume loss deformities in our cohort of men with Peyronie’s disease (PD). Methods We retrospectively examined medical records of patients with PD who consecutively underwent penile duplex doppler ultrasound (PDDU) with physical examination of the erect penis after intracavernosal injection by a specialized urologist from December 2012- July 2015. Curvature was measured with goniometer. Volume loss deformities were characterized as hourglass deformities, unilateral indentations, and distal tapering based on physical examination. Axial instability was determined subjectively as present when application of axial force resulted in penile buckling. Each patient completed the Male Sexual Health Questionnaire (MSHQ) and was asked if they experienced anxiety about sexual performance. Clinical data of patients with and without volume-loss deformities were compared using chi-squared tests and two-sided t-tests. Results 54% of the cohort (62/114) had volume-loss deformities. Hourglass deformities, distal tapering and unilateral indentations were present in 27 (24%), 17 (15%), and 18 (16%) patients, respectively. Curvature was present in 109 patients (96%). The patients with volume-loss deformities had significantly higher rates of axial instability (40% vs. 22%, p=0.04) and anxiety about sexual function (18% vs. 6%, p=0.05) compared to patients without volume-loss deformities. We did not observe differences in PDDU parameters or any of the 5 MSHQ sexual function domain scores between patients with and without volume-loss deformities, although men with volume-loss deformities had more instances of perceived delayed ejaculation (4.1 vs. 3.5, p=0.04). Conclusions Volume-loss deformities are highly prevalent in men with PD. These non-curvature deformities are associated with axial instability and anxiety about sexual performance; and may be linked to delayed ejaculation. Funding none
Authors
Ezra J. Margolin
Matthew J. Pagano Carrie M. Mlynarczyk Ifeanyi C. Onyeji Peter J. Stahl |
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MP56-16 |
Patient’s choice of health information and treatment modality for Peyronie’s Disease |
Sexual Function/Dysfunction: Peyronie's Disease II | 17BOS |
Abstract: MP56-16 Sources of Funding: None Introduction Various treatment options exist for men diagnosed with Peyronie’s disease (PD), but the literature is relatively sparse regarding patient utilization of available therapies and their own perception of treatment success over time. Our data explore the resources used and treatment choices made by men following their diagnosis with PD. Methods A mailed survey was sent to 719 randomly selected PD men who were evaluated at our institution from 1990-2012. Specific question stems included evaluation of various treatments and their associated efficacies as well as preferred resources for further information on PD. Results were summarized as a descriptive report with statistical analyses performed as indicated. Results A total of 162 men (median age 55) responded to the survey with a median PD duration of 9.2 years. Respondents used a variety of sources for information about PD including medical websites (38.9% of respondents), physician (35.8%), and books / internet forums (<1%). Overall, patients felt that 59% (SD= 40) of the physicians they had consulted had a good understanding of PD while the remainder appeared to lack an adequate understanding of the disease. Less than 1% used books or internet forums for information. Regarding treatments, 53.1% of men had tried at least one of surgery, medication, topical therapy, injection, vacuum or traction devices with 37.2% trying two or more therapies. In comparing therapies, 82.8% of those undergoing surgery reported improvement, compared to 60% on oral medication, 57.1% of injection therapies (note: prior to collagenase era), and 30.2% of vacuum / traction devices. _x000D_ A subset analysis of 49 patients who tried vacuum (43/49) or traction (6/49) devices was performed and demonstrated that 46.9% reported improved curvature and 8.2% improved length._x000D_ No correlations were noted between subjective increase in penile length and the duration of vacuum or traction therapy. _x000D_ Conclusions Among a cohort of PD men responding to a mail-in survey, medical websites were the most widely used source of information on PD, with nearly 30% of physicians perceived to lack an understanding of the disease. Almost half of PD patients choose not to pursue any kind of treatment. These results suggest a need for additional patient and provider education on the diagnosis and available therapies for PD therapies. Funding None
Authors
Raevti Bole
Matthew Ziegelmann Ross Avant Jack Andrews Kevin Hebert Manaf Alom Landon Trost |
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MP56-17 |
The Histopathologic Effects of Intracavernosal MItomycin-c Injection In A Rat Peyronie's Disease Model |
Sexual Function/Dysfunction: Peyronie's Disease II | 17BOS |
Abstract: MP56-17 Sources of Funding: Scientific and Technical Research Council of Turkey (TUBITAK), Grant No: 114S738._x000D_ Introduction Peyronie's disease (PD) is characterized by the formation of fibrous plaques in the tunica albuginea (TA). It causes penile curvature, erectile dysfunction and pain during erection. Our aim is to evaluate whether or not Mitomycin-C (MMC) has an antifibrotic effect on (Transforming Growth Factor-beta (TGF-?) induced PD in a rat model. Methods Eighteen 12-week-old male Sprague-Dawley rats were divided into 3 groups: Group 1= TGF-?1 (n:7), Group 2= TGF-?1+MMC (n:7), and Group 3= Sham group (0.25 ml bovine serum albumin injected) (n:4). All groups were sacrificed on the 6th week of the procedure, and their penises were excised. All penis specimens were evaluated semiquantitatively and quantitatively with histochemical, immunohistochemistry and image analysis. Results Both group 1 and group 2 had significantly higher fibrosis scores and lower elastic fibers in both outer surface of TA and subsinusoidal area compared with sham group (Group 3). When compared group 1, the amount of collagen were significantly decreased in group 2. Intracavernosal MMC injection (group 2) ended up lower elastic fibers when compared with group 1(Table 1-Figure 1)._x000D_ According to the quantitative analyses, when compared with group 1 and group 3, lower dorsal, ventral and trabecular thickening values were seen in group 2. These parameters were only statistically significant when compared with group 1, suggesting the antifibrotic effect of TGF-?1 induced fibrosis (Table 2-Figure 1)._x000D_ Both group 1 and group 2 showed lower decorin staining levels in subsinusoidal areas of tunica albuginea (SATA) and subsinusoidal areas of trabecular wall (SATW) when compared with group 3. The statistically significant difference was only detected between group 1 and group 3. _x000D_ Conclusions The fact that amount of collagen bundles decreased and elastic fibers increased in MMC group (group 2) compared TGF-?1 group (group 1) was demonstrated by histopathological (semi-quantitative) and image analysis program (quantitative). These results were statistically significant. Our study demonstrates the antifibrotic effects of MMC on Peyronie Disease. Further clinical studies are assured to make some inferences regarding its clinical use. Funding Scientific and Technical Research Council of Turkey (TUBITAK), Grant No: 114S738._x000D_
Authors
Engin Kaya
Yusuf Kibar Sercan Y?lmaz Ayhan Ozcan Burak Kopru Hasan Cem Irk?lata Turgay Ebiloglu |
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MP56-18 |
The Mouse Corpus Cavernosum Glandus is Biomechanically Analogous to the Human Corpus Cavernosum |
Sexual Function/Dysfunction: Peyronie's Disease II | 17BOS |
Abstract: MP56-18 Sources of Funding: RO1 DK10509701 (TL); R21 DK109912 (SPH,MLS); R01 DE022032 (SPH) Introduction Calcified Peyronie's plaque (CPP) is postulated to be of bone phenotype within a human penis. Rodents are used as models to investigate spatiotemporal mechanistic processes leading to CPP in humans; however, there are specific biomechanical differences between species. The comparable regions to program insults within rodents to induce the pathologically mineralized tissue similar to CPP are not well correlated. The objective of this study is to illustrate that the mouse corpus cavernosum glandus (CCG), instead of the mouse corpus cavernosum penis (CPP), is more analogous to the human corpus cavernosum (HCC). Methods Penile tissues from 12 Scx-GFP mice with ages 4 week, 5 week, 6 week, and 1.2 years, were dissected and processed following routine histology protocols. 6μm thick sections were stained with H&E, Massons' trichrome (TRI), Verhoeff's elastin (ELA), and DAPI. All sections were imaged using bright field or fluorescence microscopy techniques. Cell orientations along collagen fibers with age were analyzed using Image J Fiji. Results Figure: With age, CCG illustrated well-oriented struts at an angle of 32° to the baculum. Additionally, scleraxis and elastin expressions, and smooth muscle content increased within the struts, specifically in the 6 week-old mice. The expression of scleraxis indicated that the CCG contains mechanoactive collagenous and elastin-ridden struts that support biomechanical function of the baculum. Within the CCG of the mouse, there was more sinusoidal space in the younger age groups (4-6 weeks), and this space decreased with age, and elastin expression increased significantly (see 1 year). Compared to the CCG (A,C,E,G), the CCP (B,D,F,H) illustrated significantly lower expressions of scleraxis, elastin, and smooth muscle. Conclusions The collagen-producing fibroblasts within the CCG and CCP express scleraxis, indicative of local mechanoactive areas. Based upon orientation of cells expressing scleraxis, the biomechanical function of the CCP is to push the glans of the penis like a piston, while the CCG stiffens the penis during erection and pulls the glans of the penis back into the prepuce post-erection. The CCG is similar to the HCC with regard to compositional ratio of collagen to muscle, elastin localization, and biomechanical function and as such is a good model to study human penile physiology. Funding RO1 DK10509701 (TL); R21 DK109912 (SPH,MLS); R01 DE022032 (SPH)
Authors
Matthew Hennefarth
Ling Chen Ryan Hsi Misun Kang Amanda Reed-Maldonado Guiting Lin Marshall Stoller Tom Lue Sunita Ho |
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MP56-19 |
Comparing Plaque Morphology Between Men Developing Peyronie’s Disease (PD) After Radical Prostatectomy (RP) To That of De Novo Peyronie’s Disease Patients |
Sexual Function/Dysfunction: Peyronie's Disease II | 17BOS |
Abstract: MP56-19 Sources of Funding: none Introduction Increasing awareness now exists of the association between RP and development of PD. Yet, little is known about how RP-associated PD (RPD) differs from de novo PD (DPD). This study was undertaken to compare patient and plaque characteristics between men with RPD and DPD. Methods Consecutive patients developing RPD within 2 years of their operation and patients with DPD had demographic, comorbidity, and PD characteristics recorded. All patients had an in-office curvature assessment and a penile duplex Doppler ultrasound (PDDU) following injection of an intracavernosal vasoactive agent to achieve penile rigidity. Particular attention was paid to plaque morphology as defined by an experienced sexual medicine physician. Plaque morphology was defined according to the following classification system: linear, full length, linear partial length, plate-like, septal. ‘Bilateral’ plaques (dorsal plus ventral) and calcification status (defined on ultrasound) were also recorded._x000D_ _x000D_ Results 377 men with RPD and 737 consecutive DPD patients enrolled over the same time period were studied. Mean age: RPD 64±12 vs DPD 54±16 years (p<0.01). Diabetes prevalence: 4% vs 7% (p<0.05). There were no differences in: race (87% overall Caucasian), mean early morning serum total T levels (overall 469 ng/dl), degree of curvature (38±10 degrees), direction of primary curvature (67% dorsal), presence of plate-like calcification (14%), presence of septal plaque (2%) and erectile hemodynamics (88% normal). Overt differences in plaque morphology are presented in the table. Conclusions Men developing PD after RP have an ethnic and comorbidity profiles similar to those of men developing PD de novo. RPD patients are more likely to have full-length linear plaques, to have concomitant dorsal and ventral plaques and less likely to have a plate-like plaque. Funding none
Authors
John Sullivan
Yanira Ortega Kelly Chiles Lawrence Jenkins John Mulhall |
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MP56-20 |
Comparison of Clinician and Patient Measurements Using a Mobile Phone Application to Assess Penile Angulation |
Sexual Function/Dysfunction: Peyronie's Disease II | 17BOS |
Abstract: MP56-20 Sources of Funding: none Introduction Peyronie's disease is an inflammatory condition involving the tunica albuginea causing penile deformity resulting and sexual dysfunction. Clinical assessment of Peyronie’s disease requires an erection. Generating a patient erection in clinic is time-consuming, costly and invasive. We previously demonstrated that a smartphone application, the University of Washington Peyronie's Examination Network (UWPEN) application was correlated with measurements obtained from a goniometer using penile models. In this study, we aimed to demonstrate that UWPEN measurements are equivalent when performed by a patient and clinician. Methods We underwent an IRB approved prospective evaluation comparing clinician and patient measurements utilizing the UWPEN application for measurement of penile angulation. Patients presenting to the University of Washington with Peyronie's disease and clinical indication for duplex ultrasound were consented and given an intracavernosal injection of Alprostadil. A clinician took measurements using a goniometer and tape measure as a gold standard. Follow-up measurements were obtained using the UWPEN application. The clinician left the room while the patient took UWPEN application measurements. We compared measurements between the goniometer, clinician, and patient using an ANOVA test in the statistics package R. As a secondary outcome, we also evaluated survey results from patients regarding their experience with using the application._x000D_ Results There was no significant difference in measurements between goniometer, clinician, and patient measurements of the penis while erect; for dorsal measurements (p = 0.78), lateral measurements (p = 0.20) and girth (p = 0.99). We observed some variability in lateral measurements early in our experience. Overall, patients felt positive about using the application and were interested in home use to evaluate their progress with treatment. Conclusions Artificial elections to assess the degree and direction of penile angulation in clinic is time-consuming, costly and invasive. The UWPEN application may help make standardized measurements at home. There is a large degree of consistency between clinician and patient measurements. The majority of patients felt comfortable using the application. Funding none
Authors
Wayne Brisbane
Ryan Hsi Marc Rogers Kevin Ostrowski Hunter Wessells Thomas Walsh |
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MP57-01 |
Germline Mutations in DNA Repair Genes Are Significantly Enriched in Lethal Prostate Cancer and Are Associated with Disease Survival |
Prostate Cancer: Advanced (including Drug Therapy) IV | 17BOS |
Abstract: MP57-01 Sources of Funding: The study is partially supported by the National Key Basic Research Program Grant 973 of China (2012CB518301), the Key Project of the National Natural Science Foundation of China (81130047), PCW Fund,and the Rob Brooks Fund for Personalized Cancer Care at NorthShore University HealthSystem. Introduction Germline mutations in several DNA repair genes were recently found to be associated with metastatic prostate cancer (PCa). The objective of this study was to systematically assess whether the spectrum of pathogenic germline mutations found in lethal PCa is enriched in DNA repair genes and whether these mutations distinguish lethal PCa from indolent PCa. Methods A retrospective case-case study of 313 patients who died of PCa and 486 patients with localized PCa of European, African, and Chinese descent. Germline DNA from each of the subjects was sequenced for DNA repair genes and cancer-related genes through whole exome sequencing (WES) or targeted sequencing. Pathogenicity of mutations was called according to the American College of Medical Genetics guidelines. Enrichment pathway analysis was performed using Chi-square test. Mutation carrier rates and their effects on PCa-specific survival were analyzed using log-rank test and Chi-square trend test. Results Based on WES results, pathogenic or likely pathogenic mutations in 178 DNA repair genes (Wood RD, et al., 2001) were significantly enriched in lethal PCa in both European Americans (P=1.58e-6) and African Americans (P=0.0028) (WES was not performed in Chinese samples). This suggests that men who will develop lethal PCa tend to have an increased burden of inherited DNA repair mutations when compared with genes in other cellular pathways. In the entire study population, the carrier rates differed significantly among lethal PCa patients as a function of age at death (P-trend=0.028) and time to death after diagnosis (P-trend=0.0007) (Table). In the survival analysis, DNA repair gene mutation carriers had a significantly shorter median survival time (14.0 years, 95%Confidence Interval: 11.5-16.5 years) than non-carriers (16.0 years, 95%Confidence Interval: 14.9-17.1 years, log-rank P=0.021). Conclusions Germline mutations in DNA repair genes are significantly enriched in patients with lethal PCa. DNA repair gene mutation status was associated with both earlier age at death and shorter survival time. Funding The study is partially supported by the National Key Basic Research Program Grant 973 of China (2012CB518301), the Key Project of the National Natural Science Foundation of China (81130047), PCW Fund,and the Rob Brooks Fund for Personalized Cancer Care at NorthShore University HealthSystem.
Authors
Rong Na
S. Lilly S. Lilly Misop Han Hongjie Yu Deke Jiang Sameep Shah Charles Ewing Liti Zhang Kristian Novakovic Jacqueline Petkewicz Kamalakar Gulukota Donald Helseth Jr Margo Quinn Elizabeth Humphries Kathleen Wiley Sarah Isaacs Yishuo Wu Xu Liu Ning Zhang Chi-Hsiung Wang Janardan Khandekar Peter Hulick Daniel Shevrin Kathleen Cooney Zhoujun Shen Alan Alan H. B. Carter Michael Carducci Mario Eisenberger Sam Denmeade Michael McGuire Patrick Walsh Brian Helfand Charles Brendler Qiang Ding Jianfeng Xu William Isaacs |
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MP57-02 |
TET, sensitizes CRPC cells to Enzalutamide by promoting cell death in part by decreasing levels of AR and ARv7. |
Prostate Cancer: Advanced (including Drug Therapy) IV | 17BOS |
Abstract: MP57-02 Sources of Funding: Studies supported in part by VA Merit Award-01BX001258 (HK), NIH/NCI R01CA161880 (HK), Carroll W. Feist endowed Chair Funds (Koul H), and FWCC (KK)._x000D_ Introduction Prostate cancer (PCa) is the second leading cause of cancer deaths in men. AR signaling is known to play a critical role in androgen responsive prostate cancer cells. Androgen deprivation therapy (ADT) is a standard of care for patients when prostate cancer has spread beyond the prostate. Almost all the prostate cancer (PCa) deaths result from castration resistant prostate cancer (CRPC). With the development of newer anti-androgen Enzalutamide (ENZ) there has been a marked improvement in CRPC. However, almost all patients develop resistance to ENZ in part due to expression of ARv7. Thus, to date, no acceptable treatment options are available for ENZ resistant CRPC. In the present study we evaluated the effects of TET, a derivative of bis-benzyly isoquinoline, Tetrandrine on two enzalutamide resistant prostate cancer cell lines on sensitizing these cells to Enzalutamide. We also evaluated the effects of TET on AR and ARv7 levels._x000D_ Methods Enz resistant Prostate cancer cell lines (22rv1 and LNCaP-abl) were used in the present study. Cells were grown in supplemented media and maintained at 370C in a 5%CO2 incubator (as described elsewhere). Where indicated cells were treated with Enzalutamide or TET alone or in combination. Cell viability was measured by crystal violet and MTT assays. Protein levels were measured by Western Blot assays. mRNA expression measured in RTPCR assays._x000D_ Results Treatment with Enz had only a marginal effect on growth and viability of 22rv1 cells. TET inhibited growth and proliferation of enzalutamide resistant prostate cancer cells in both dose and time dependent manner with an IC50 in the range of 5-10uM at 72 hr. However TET treatment did not result in death of RWPE cells, a line of normal prostate cells. Moreover, combination of TET and Enz was more effective than either treatment alone. Treatment with TET resulted in decreased levels of full length AR as well as ARv7 within 24-48h. We also observed that TET treatment was associated with decreased cyclin D1 and increased CDK inhibitors p21 and p27. Over all Tet alone and in combination with Enz promoted cell growth arrest and cell death in ENZ resistant CRPC cells and sensitized these cells to Enz._x000D_ Conclusions This study shows that TET sensitizes CRPC cells to Enz in part by decreasing protein levels of AR and ARv7. Funding Studies supported in part by VA Merit Award-01BX001258 (HK), NIH/NCI R01CA161880 (HK), Carroll W. Feist endowed Chair Funds (Koul H), and FWCC (KK)._x000D_
Authors
Kashyap Koul
Sweaty Koul Quin Dong Hari Koul |
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MP57-03 |
Identification and characterization of Selective Androgen Receptor Degraders (SARDs) for the treatment of enzalutamide unresponsive and/or resistant prostate cancer |
Prostate Cancer: Advanced (including Drug Therapy) IV | 17BOS |
Abstract: MP57-03 Sources of Funding: GTx Inc. Introduction The clinical success of new androgen receptor (AR)-targeted therapies in patients with castration-resistant prostate cancer (CRPC) emphasizes the continued importance of the AR signaling axis in the disease. Despite the use of this new generation of therapies, some men with CRPC do not respond and resistance to these therapies typically develops for those that do. Mechanisms attributed to the emergence of this non-responsive CRPC include the expression of splice variants of the AR (AR-SV), mutant forms of the AR, hyperactive AR, and others. The objective of this work is to develop selective androgen receptor degraders (SARDs) that degrade all forms of the AR and provide advanced treatment options to men with CRPC. Methods AR ligand binding, transactivation, fluorescence polarization, nuclear magnetic resonance (NMR), and Western blot assays were performed to screen novel SARDs. Prostate cancer cell line gene expression, proliferation, cell line and patient-derived xenografts (PDX) were performed to evaluate the efficacy of the SARDs. Molecular mechanistic studies were performed to understand the mechanism of action. Results This report details a novel series of highly potent SARDs that bind to the AR-LBD and inhibit transactivation at nM concentrations. One of the lead SARDs, UT-155 antagonizes AR with an IC50 of 78nM in comparison to enzalutamide with an IC50 of 465nM. In addition to their antagonistic activity, the SARDs degrade full-length, mutant and variant AR in the low μM range and inhibit the proliferation of AR-FL and AR-SV- dependent PCa cells with potencies better than that of the comparators. The SARDs robustly inhibit the growth of the LNCaP androgen-dependent prostate cancer (PCa) xenograft, the 22RV1 CRPC xenograft, and AR- and AR-SV- positive CRPC patient-derived xenografts (PDX). No significant toxicities have been observed in the animal studies that have been performed. NMR analysis as well fluorescence quenching support an interaction between the SARDs and the AR activation function domain (AF-1), making these molecules first-in-class dual-interacting AR antagonists and degraders. Conclusions Novel highly potent SARDs that interact with both AF-1 and LBD of the AR were discovered and characterized as a potential next-generation treatment option for advanced prostate cancer that is resistant to enzalutamide treatment. Clinical development of these compounds is ongoing. Funding GTx Inc.
Authors
Suriyan Ponnusamy
Robert Getzenberg Thirumagal Thiyagarajan Dong-Jin Hwang Yali He Iain McEwan Carolyn Watt Tudor Moldoveanu Duane Miller Ramesh Narayanan |
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MP57-04 |
Novel therapies targeting androgen receptor variants in an in vitro model of castrate resistant prostate cancer. |
Prostate Cancer: Advanced (including Drug Therapy) IV | 17BOS |
Abstract: MP57-04 Sources of Funding: This research was made possible through the National Institutes of Health (NIH) Medical Research Scholars Program, a public-private partnership supported jointly by the NIH and generous contributions to the Foundation for the NIH from the Doris Duke Charitable Foundation, The American Association for Dental Research, the Colgate-Palmolive Company, Genentech and alumni of student research programs and other individual supporters via contributions to the Foundation for the National Institutes of Health._x000D_ For a complete list, please visit the Foundation website at:_x000D_ http://fnih.org/work/education-training-0/medical-research-scholars-program Introduction VT464 is currently in clinical trials for the treatment of castration-resistant prostate cancer (CRPC). Interestingly, VT464 displays dual properties: it decreases androgen synthesis by inhibiting CYP17A1 and may also block AR function by binding to the ligand-binding domain (LBD) of full-length androgen receptor (ARFL). However, expression of AR variants (e.g. ARv7) lacking a LBD is a common occurrence in CRPC. Thus, ARv7 may be insensitive to direct inhibition by VT464 and other targeted agents may be necessary to blunt ARv7 expression and ARv7 regulated pathways for efficacy in CRPC._x000D_ ARv7 is stabilized by heat shock proteins (Hsp) 40 and Hsp70, which bind the AR and ARv7 N-terminal domain to prevent aggregation. Our novel compounds C86 and JG98 are inhibitors of Hsp40 and Hsp70, respectively. As such, we hypothesized that inhibition of the Hsp40/70 axis would lead to decreased CRPC cell viability and altered AR/ARv7 expression, which could be amplified in combination with VT464. Additionally, ARv7 leads to changes in cell metabolism such that cells are more dependent on glutaminolysis and fatty acid synthesis. Thus, we also hypothesized that the glutaminase inhibitor, CB839, and fatty acid synthase inhibitor, 3V-Biosciences 3166, would act in concert with VT464 for efficacy in CRPC. _x000D_ Methods Using the CRPC cell line 22Rv1, we analyzed the effects of VT464, C86, JG98, CB839, and 3V-3166 on cell viability (MTT, Cyquant) as single agents and in combination. Western blot analysis of treated 22Rv1 cells was used to correlate protein expression changes of ARFL and ARv7 to the respective cell viability data. Results VT464 caused a dose-dependent decrease in 22Rv1 viability, as did C86 and JG98. Combination of either C86 or JG98 with VT464 showed additive toxicity. Importantly, both C86 and JG98 decreased ARFL and ARv7 protein expression and their downstream transcriptional activity, which may explain these combinatorial effects. Similarly, treatment with of 22Rv1 cells with 3-V3166 and CB839 inhibited cell viability, which was further decreased when combined with VT464. Conclusions C86 and JG98 are novel agents that inhibit AR and ARv7 stability. When combined with VT464, both agents display combinatorial activity. Further, 3V-3166 and CB839, drugs that target enzymes crucial to cells expressing ARv7, also inhibit viability to a greater extent when combined with VT464. Collectively, C86, JG98, 3V-3166, and CB839 are all promising novel therapies for CRPC, particularly for tumors which express ARv7. Further mechanistic and in vivo assays are warranted. Funding This research was made possible through the National Institutes of Health (NIH) Medical Research Scholars Program, a public-private partnership supported jointly by the NIH and generous contributions to the Foundation for the NIH from the Doris Duke Charitable Foundation, The American Association for Dental Research, the Colgate-Palmolive Company, Genentech and alumni of student research programs and other individual supporters via contributions to the Foundation for the National Institutes of Health._x000D_ For a complete list, please visit the Foundation website at:_x000D_ http://fnih.org/work/education-training-0/medical-research-scholars-program
Authors
Joseph A. Baiocco
Michael Moses Matthew J. Watson Raju Chelluri Jason Gestwicki Jane Trepel Len Neckers |
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MP57-05 |
Longitudinal Pain Scores as a Prognostic Factor of Overall Survival in Men with Metastatic Castration-Resistant Prostate Cancer |
Prostate Cancer: Advanced (including Drug Therapy) IV | 17BOS |
Abstract: MP57-05 Sources of Funding: none Introduction Debilitating pain in men with castration-resistant prostate cancer (CRPC) is one of the most common, yet understudied morbidities. There is evidence that baseline pain is an important predictor of survival outcome in men with CRPC. Understanding the dynamic nature of pain, we seek to develop a prognostic model of overall survival (OS) based on the longitudinal pain score trajectories in men with CRPC. Methods 729 patients with metastatic CRPC from the control arms of three phase III, randomized, double-blind, placebo-controlled clinical trials (NCT00519285, NCT00988208, and NCT00638690) were accessed from the Prostate Data Sphere and were analyzed. Joint latent class modeling (JLCM) method was applied to stratify our study cohort into different subpopulations with three different pain score trajectories. Patient reported brief pain inventory (BPI) or the present pain intensity index (PPI) instruments were obtained to characterize longitudinal pain scores. The OS was measured as the time-to-event outcome from randomization to death or censoring. Results 536 (73.5%) patients were found to have a stable pattern of pain scores. 111 (15.2%) and 82 (11.3%) patients had rapidly increasing and decreasing trends, respectively. Patients with stable pain levels had the most favorable OS while rapidly increasing pain was associated with the worst OS (HR: 11.36, p-value<0.01 when compared to those with stable pain). Conclusions Patients having both increasing and decreasing patterns of pain had higher risk of death when compared to those with stable pain levels. Longitudinal pain scores can be used as a prognostic factor for overall survival in patients suffering from metastatic CRPC. Funding none
Authors
Wei Wang
Young Suk Kwon Lixiao Su Isaac Yi Kim Shou-En Lu |
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MP57-06 |
Management of enzalutamide-related adverse events for CRPC patients by using patient reported outcomes leads better prognosis. |
Prostate Cancer: Advanced (including Drug Therapy) IV | 17BOS |
Abstract: MP57-06 Sources of Funding: none Introduction The clinical benefit of enzalutamide for castration-resistant prostate cancer (CRPC) is its high efficacy and favorable safety profile. Subjective symptoms such as fatigue and appetite loss, which are common adverse effects (AEs) for enzalutamide, tend to be underestimated in clinical trials and may lead discontinuation of enzalutamide. Recently, attention has been directed at patient reported outcomes (PROs) as self-administrated assessment in the health-related quality of life (HRQoL) evaluation of cancer patients. The identification of PROs by questionnaires for subjective AEs are important in the clinical practice for their impact on HRQoL and may be different from doctor reported outcomes (DROs). Methods Fifty-eight CRPC patients (39 pre and 19 post docetaxel) treated with enzalutamide were assessed by PROs for subjective AEs at the time of the medical visit. Results Although 44 and 40 of 58 patients reported fatigue and appetite loss by PRO, only 32 and 24 patients had G1 or over fatigue and appetite loss by doctor reported outcomes (DROs) (Table. 1). Eighteen patients needed the dose reduction or interruption by fatigue or appetite loss and 14 of 18 patients, their subjective symptoms were improved quickly and they can continue to take without AEs (Fig. 1). Surprisingly, the patients who needed the dose reduction of enzalutamide had longer time to treatment failure (Fig.2). Conclusions The DROs assessment of subjective AEs of enzalutamide differed from the PRO assessment. The prompt dose reduction of enzalutamide in response to the PRO assessment improved the symptoms and prevented dropping out due to AEs. PRO assessment is a useful tool to rapidly identify AEs which can lead to prompt dose modification, decreased patient drop out and improved outcomes to Enzalutamide treatment. Funding none
Authors
Taro Iguchi
Sayaka Yasuda Minoru Kato Takeshi Yamasaki Yasuomi Shimizu Yuji Takeyama Satoshi Tamada Tatsuya Nakatani |
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MP57-07 |
Patient-Identified Factors Affecting Treatment Decisions for Advanced Prostate Cancer |
Prostate Cancer: Advanced (including Drug Therapy) IV | 17BOS |
Abstract: MP57-07 Sources of Funding: AHRQ 1K12HS022990-01 (DP) Introduction Recent therapeutic advances have resulted in a rapidly growing population of advanced prostate cancer survivors. Guidelines do not definitively direct treatment choice in the advanced prostate cancer setting, and communication and patient preferences are critical to therapeutic decision making. We sought to identify factors men consider when making treatment decisions for advanced prostate cancer and to determine any differences based on demographics. Methods We completed 3 focus groups of men with metastatic prostate cancer (mPC) to identify factors considered by patients facing treatment decisions. Between 6/1/15 and 9/29/16, 96 men with mPC completed surveys developed using the focus group data to define the importance of identified factors during their current mPC treatment decision. We used frequencies and relative frequencies to describe treatment decision factors, and proportional odds models with robust standard errors to assess the association between treatment decision factors, clinical characteristics, and sociodemographic factors. _x000D_ Results Overall, the three highest factors with which men had strong agreement on treatment choice were 1-feeling well enough to spend quality time with family (70.3%), 2-being able to die in a manner consistent with their wishes (69.4%), and 3-liking when the physician gives choices for treatment (67.6%). The three factors with the lowest percentage of strong agreement were 1-accepting severe side affects to avoid being debilitated (33.6%), 2-finding a treatment that minimizes pain (23.4%), and 3-avoiding financial trouble due to treatment (2%). Avoiding financial trouble due to treatment was the least important factor regardless of race, marital status, employment status, self-reported health status, or age. Conclusions Personal factors such as quality of life, time with family and being offered treatment choices appear to have the strongest impact on patient decision making for treatment of mPC. While financial concerns were the least important factor, this may be a reflection of an insured population. Efforts to understand patient considerations during treatment for advanced prostate cancer should be made in clinical settings and further investigated. Funding AHRQ 1K12HS022990-01 (DP)
Authors
Kelvin Moses
Liping Du Ivy Ahmed David Penson Alicia Morgans |
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MP57-08 |
Population-based analysis of treatment toxicity among men with castration-resistant prostate cancer |
Prostate Cancer: Advanced (including Drug Therapy) IV | 17BOS |
Abstract: MP57-08 Sources of Funding: Ajmera Family Chair in Urologic Oncology Introduction There is little phase 4 data regarding the toxicity and effectiveness of contemporary metastatic castrate-resistant prostate cancer (mCRPC) treatments. We examined hospital admissions and emergency room (ER) visits and survival among patients in the Province of Ontario treated with abiraterone, enzalutamide, docetaxel, or cabazitaxel for mCRPC. Methods We performed a population-based, retrospective cohort study of 2439 men over the age of 65 treated with abiraterone, enzalutamide, docetaxel, or cabazitaxel for mCRPC from 2003-2015 in Ontario, Canada. Outcomes were toxicity (hospitalizations and ER visits) and overall survival. We used multivariable Cox proportional hazards models with time-varying exposures to calculate hazard ratios (HR). Results Among 2439 patients, cumulative exposure was greatest for docetaxel (n=1886 (77.3%); 11,436 person-months), followed by abiraterone (n=893 (36.6%); 5143 person-months), enzalutamide (n=52 (2.1%); 351 person-months) and cabazitaxel (n=18 (0.7%); 61 person-months). Abiraterone exposure was not significantly associated with any-cause (HR 0.88, 95% CI 0.72-1.07) or treatment-related (HR 1.09, 95% CI 0.87-1.37) hospitalizations or ER visits. Enzalutamide was not significantly associated with any-cause (HR 1.20, 95% CI 0.69-2.07) or treatment-related (HR 0.85, 95% CI 0.43-1.68) toxicity. Docetaxel exposure was associated with a significantly increased risk of any-cause (HR 1.29, 95% CI 1.15-1.44) and treatment-related (HR 1.52, 95% CI 1.33-1.74) toxicity. Cabazitaxel exposure was also associated with treatment-related (HR 5.94, 95% CI 1.87-18.92) but not any-cause (HR 2.37, 95% CI 0.59-9.63) toxicity. Patients who began CRPC treatment after the introduction of oral therapies had improved overall survival compared with those treated prior to their introduction (aHR 0.70, 95% CI 0.64-0.77). Conclusions Among patients with metastatic CRPC, treatment with chemotherapy (docetaxel or cabazitaxel) is associated with an increased risk of hospitalizations and emergency room visits. We failed to show a significantly increased risk for patients treated with oral agents (abiraterone or enzalutamide). Funding Ajmera Family Chair in Urologic Oncology
Authors
Robert Nam
Christopher Wallis Refik Saskin Symron Bansal Urban Emmenegger Raj Satkunasivam |
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MP57-09 |
Chemical Castration Decreased the Risk of Dementia in Patient with Prostate Cancer - From 13368 patients, Taiwan National Health Insurance Research Database |
Prostate Cancer: Advanced (including Drug Therapy) IV | 17BOS |
Abstract: MP57-09 Sources of Funding: none Introduction To investigate the association between the use of androgen deprivation therapy (ADT) and the subsequent risk of dementia in Asian men with prostate cancer (PC) by employing a population-based dataset. Methods We retrieved the study sample from the Taiwan National Health Insurance (NHI) Database. The cohort included 6684 patients with PC who had received ADT as the study group, whereas 6684 patients with PC who had not received ADT served as the comparison group. The men were newly diagnosed between 2000 and 2008. Each ADT user was randomly frequency-matched for age and the year of index date with one non-ADT user. The Cox proportional hazards regression model was used to estimate the relative risks of dementia after adjusting for age, index year, cerebrovascular disease, parkinson's disease, head injury and other comorbidities. Results Among 13368 men with prostate cancer, there was a statistically significant negative association between use of ADT and risk of dementia (hazard ratio (HR), 0.79; 95% CI, 0.70-0.90; p < .001). Age-stratified analysis demonstrated that the adjusted hazard ratio of dementia was particularly lower in individuals aged above 75 years (p <0.05) and between 65-69 years (p <0.05). Chemical castration has a lower risk of subsequent dementia compared to those who had not received ADT (HR, 0.77; 95% CI, 0.69-0.89; p < .001). However, surgical castration showed no correlation with developing dementia. Those who have ADT duration more than 180 days is associated a lower risk of dementia than those have ADT duration less than 180 days. Conclusions We concluded that chemical castration is associated with a lower risk of dementia. Longer ADT duration and age above 75 years are associated with even lower risk of dementia. Funding none
Authors
Chieh-Chun Liao
Jian-Hua Hong Yu-Chuan Lu Chao-Yuan Huang |
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MP57-10 |
Relationship Between Quality of Life and Overall Survival in Metastatic Castration-Resistant Prostate Cancer Patients in ALSYMPCA: Analysis by Prior Docetaxel Subgroup |
Prostate Cancer: Advanced (including Drug Therapy) IV | 17BOS |
Abstract: MP57-10 Sources of Funding: Bayer HealthCare Introduction Radium-223 improved overall survival (OS) with meaningful improvements versus placebo in health-related quality of life (HRQoL) in phase 3 ALSYMPCA (Parker NEJM 2013; Nilsson Ann Oncol 2016). We examined the relationship of OS to baseline HRQoL scores or change from baseline by prior docetaxel subgroup. Methods HRQoL in ALSYMPCA was assessed by Functional Assessment of Cancer Therapy--Prostate (FACT-P) questionnaire at baseline, during treatment (wk 16, 24), and during follow-up. Cox proportional hazards model for OS was fitted using HRQoL baseline scores and included previously identified covariates: treatment (radium-223 vs placebo); log10 baseline lactate dehydrogenase, alkaline phosphatase, and prostate-specific antigen; age; baseline Eastern Cooperative Oncology Group performance status; and albumin. A time-dependent model also included change from baseline HRQoL scores. Results are presented by prior docetaxel subgroup. Results The analysis included patients with baseline HRQoL scores: 466-485 patients with prior docetaxel and 354-362 with no prior docetaxel for various FACT-P metrics. Significant associations were seen between OS and FACT-P total score at baseline or change from baseline regardless of prior docetaxel use. Every 10-point increase in FACT-P total score from baseline (ie, improvement) was associated with an 18-21% decreased risk of death. FACT-P subscale results were similar, except social well-being. (Table). Conclusions Improvement in HRQoL was associated with better OS in ALSYMPCA patients with metastatic castration-resistant prostate cancer regardless of prior docetaxel treatment. Funding Bayer HealthCare
Authors
Neal D. Shore
Sten Nilsson Oliver Sartor Nicholas J. Vogelzang Robert E. Coleman Joe M. O'Sullivan Daniel Heinrich David Bottomley Peter Hoskin Lars Franzen Arne Solberg Jonathan Reuning-Scherer Lin Zhan Christopher Parker |
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MP57-11 |
Androgen-Deprivation Therapy and Cardiovascular Risk (ADTCR): A nationwide population-based cohort study |
Prostate Cancer: Advanced (including Drug Therapy) IV | 17BOS |
Abstract: MP57-11 Sources of Funding: Programme Hospitalier de Recherche Clinique (PHRC) 2013. Number of project: 13-0257 Introduction Background. Observational studies suggested that androgen deprivation therapy (ADT) is associated with an increased cardiovascular (CV) risk. They all compared ADT-treated cancer patients to non-treated patients or non-cancer subjects and there has not been to date a single trial with CV harm as a primary end point._x000D_ Objective. To evaluate whether CV risk differs by type of ADT._x000D_ Methods Design. Through nationwide population-based claims reimbursement database linked to hospital discharge database, we identified adult men with prostate cancer who initiated ADT (GnRH agonist or antagonist, antiandrogen [AA], combined androgen blockade [CAB]) or had orchiectomy (OT) between 1st July 2010 and the 31st December 2011, and followed them up to 31st December 2013. _x000D_ _x000D_ Outcome measurements and statistical analysis. The main analysis followed an 'on-treatment' approach that censored all patients at the time of first therapeutic modification; it used Cox regression analysis to estimate hazard ratios (HR) for hospitalizations for ischemic events (myocardial infarction or ischemic stroke, whichever came first), adjusted on age, baseline co-morbidities and taking into account death as a competing risk._x000D_ Results Among the 35 118 new ADT users, 70.8% received GnRH agonist (reference group), 12.1 % CAB, 13.0 % AA, 3.6 % GnRH antagonist and 0.6 % had OT. During a median follow-up of 972 days, we observed 5 258 (15.0 %) overall death in a median time of 525 days. Through the 'on-treatment' approach, 472 ischemic events were eligible: 213 MI and 259 strokes. CAB was associated with an increased risk (adjusted HR [95%CI], 1.60 [1.27-2.03]) and AA with a decreased risk (adjusted HR [95%CI], 0.61 [0.43-0.88]) of ischemic events when compared to GnRH agonist. No significant association was found with GnRH antagonist (adjusted HR [95%], 1.20 (0.67-2.14)). Residual confounding might exist as CV risk factors have been under-estimated though non-differentially. Conclusions CV risk appeared different across ADT modalities and had to be taking into account as regard oncologic benefit of each modality. The probability of a clinically meaningful difference when comparing GnRH antagonists to agonists appears rather low. Funding Programme Hospitalier de Recherche Clinique (PHRC) 2013. Number of project: 13-0257
Authors
Lucie-Marie SCAILTEUX
Sébastien VINCENDEAU Frédéric BALUSSON Christophe LECLERCQ André HAPPE Béranger LE NAUTOUT Elisabeth POLARD Emmanuel NOWAK Emmanuel OGER |
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MP57-12 |
Short-term androgen deprivation therapy increases brain-type natriuretic peptide levels in patients with prostate cancer: Possible adverse impact on cardiac function |
Prostate Cancer: Advanced (including Drug Therapy) IV | 17BOS |
Abstract: MP57-12 Sources of Funding: none Introduction Androgen deprivation therapy (ADT) plays an important role in managing prostate cancer, both as a primary treatment for metastatic disease and as a useful adjunct to radiotherapy or surgery with curative intent. However, some reports showed that ADT significantly increased cardiovascular risk. It has also been proposed that gonadotrophin-releasing hormone (GnRH) agonist may have negative effects on cardiac function at the receptor level. At present, little is known as to whether or not short-term ADT affects cardiac function. Brain-type natriuretic peptide (BNP) is in widespread use as a cardiac marker that can identify the risk of cardiovascular events. In order to assess the adverse impact of short-term ADT on cardiac function, we evaluated the change in BNP levels in patients undergoing radical prostatectomy (RP) with or without preoperative ADT. Methods Between 2014 and 2016, 112 Japanese patients underwent RP in our hospital. Of them, 64 patients whose BNP levels were available and who had no prior cardiovascular disease were included in this retrospective study. BNP levels were evaluated before prostate biopsy and before RP. In this cohort, 31 patients received ADT preoperatively by combined androgen blockade using GnRH agonist and bicalutamide (ADT group), and the other 33 patients underwent RP without ADT (control group). The change in BNP levels was assessed in each group. Results The median age and initial PSA level were 68 years and 8.8 ng/ml, respectively. No patients newly developed cardiovascular events during the study period. There were no significant differences between the two groups in age, body mass index, serum testosterone level, and comorbidities such as hypertension, diabetes, and dyslipidemia. The median BNP level before prostate biopsy was 13.9 pg/ml in the ADT group and 12.1 pg/ml in the control group (p = 0.73). The median interval between evaluations of the BNP level was 12 (range 9-26) months in the ADT group and 6 (range 1-9) months in the control group. The median duration of ADT in the ADT group was 12 (range 8-25) months. In the ADT group, the median BNP level after ADT was 23.1 pg/ml, which was significantly higher than that before ADT (p < 0.01). In the control group, the median BNP level before RP was 12.8 pg/ml, showing no significant change from that before prostate biopsy (p = 0.54). Conclusions The current study demonstrated a significant increase in BNP levels after short-term ADT in patients with prostate cancer, which might reflect the adverse impact of ADT on cardiac function. Funding none
Authors
Masaya Ito
Masaharu Inoue Hajime Tanaka Toshiki Kijima Soichiro Yoshida Minato Yokoyama Junichiro Ishioka Noboru Numao Yoh Matsuoka Kazutaka Saito Kazunori Kihara Yasuhisa Fujii |
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MP57-13 |
Early Cardivascular Morbidity In A Pilot Prospective Randomized Trial Comparing LHRH Agonist And Antagonist Among Patients With Advanced Prostate Cancer |
Prostate Cancer: Advanced (including Drug Therapy) IV | 17BOS |
Abstract: MP57-13 Sources of Funding: Clinical trial was funded by Ferring Pharmaceuticals inc. Company does not have access to data. Introduction Androgen-deprivation therapy (ADT) used in prostate cancer patients may increase their risk of cardio-vascular events. Recent data suggests that LHRH-antagonist may be associated with lower risk of these events compared to LHRH-agonist. Our laboratory data suggest a role for FSH in mediating ADT induced atherosclerosis. We now report our early cardio-vascular outcome and change in FSH levels from a pilot randomized controlled study. Methods A bicenteral randomized open-label study of the use of Degarelix compared to LHRH agonists among prostate cancer patients with pre-existing cardiovascular disease with scheduled to start ADT for at least a year. _x000D_ A Cardiovascular event was considered one of the following: myocardial infarction, ischaemic or haemorrhagic cerebrovascular event, arterial embolic and thrombotic events, emergency room visit or hospitalization due to ischaemic heart disease conditions, coronary artery or iliofemoral artery revascularization (percutaneous or surgical procedures(, peripheral vascular disease event (vascular surgery/intervention). These events were prospectively collected. _x000D_ Serum levels for hormonal profile were taken at baseline and every three months. _x000D_ Results Forty six patients were enrolled (23 randomized to each arm), with a median follow up of 6.3 months. No difference in age, stage of prostate cancer and baseline cardiovascular were observed between the two arms._x000D_ During follow-up six patients developed a new cardio-vascular event. Four of the six patients were hospitalized due to ischemic heart disease, one patient suffered from a myocardial infarction and one from a new ischemic cerebrovascular event. All six patients were randomized to the LHRH-agonist arm of the trial (26%). None of the patients randomized to the Degarelix arm experienced any new cardio-vascular event during follow-up. _x000D_ All patients achieved castrate testosterone levels. FSH decreased from pre-ADT levels by a median of 93% among the Degarelix arm compared to 27% reduction in the agonist arm (p=0.00011). Within the agonist arm, patients with a lower than 30% FSH decrease had a 50% probability of a cardiovascular event, compared to only 12.5% of patients with a higher effect on FSH levels._x000D_ Conclusions Our pilot study suggests that cardio-vascular events may develop early in patients receiving LHRH-agonist compared to antagonist. These events may be linked to reduce suppression of FSH during ADT. Funding Clinical trial was funded by Ferring Pharmaceuticals inc. Company does not have access to data.
Authors
David Margel
Avivit Peer Yaara Ber Marina Shaparberg Sivan Sela Rachel Ozalvo Jack Baniel Wilhelmina Duivenvoorden Jehonathan Pinthus |
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MP57-14 |
The Association of BMI and DM with Survival Among Patients with Metastatic or Castration-Resistant Prostate Cancer. |
Prostate Cancer: Advanced (including Drug Therapy) IV | 17BOS |
Abstract: MP57-14 Sources of Funding: none Introduction The majority of deaths from prostate cancer are among men with metastatic (mPCa) and/or castration-resistant prostate cancer (CRPC). Long-term outcomes of these patients are generally not well characterized as data from most randomized trials were censored at interim analysis. The objective of our study is to investigate factors associated with survival in a dedicated outpatient clinic. Variables of interest included body mass index (BMI) and comorbidities such as diabetes (DM) at diagnosis._x000D_ Methods All patients with mPCa and/or CRPC seen in the Vanderbilt Comprehensive Prostate Cancer Clinic were eligible. Demographic and pathologic information were extracted from the electronic record under IRB-protocol. Overall survival (OS) was estimated using the Kaplan-Meier method. Multivariate analyses using Cox proportional hazard models were also performed. _x000D_ Results Complete clinicopathological data was available for 79 patients. Median follow-up was 7.1 years, 18/79 (22.7%) patients had pre-existing DM and median BMI was 28.5 kg/m2. Disease characteristics included 39 (49.3%) with Gleason 8 or greater on biopsy, median PSA of 14.91, and 20 (25.3%) presenting with M1 disease. Preexisting DM was associated with worse 5-year mortality (22.9% vs. 9.3%, p=0.042). There was a trend towards significant association of BMI >30 kg/m2 with lower 5-year mortality (6.1% vs. 13.9% BMI <30 kg/m2, p=0.052). Multivariate analysis showed BMI is independently associated with OS (HR 0.83 (95% CI 0.69-0.98), p=0.036) correcting for age, DM, stage, PSA and Gleason score at diagnosis. _x000D_ Conclusions We show BMI and DM are associated with survival for patients who develop advanced prostate cancer. Furthermore, BMI is significantly associated with survival in this cohort. Our findings should prompt further analysis of the impact of clincopathlogic factors and treatment response in a larger cohort. _x000D_ Funding none
Authors
Zachary A Glaser
Svetlana Avulova Blair Stocks David F Penson Kelvin A Moses |
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MP57-15 |
Predictive factors of dyslipidemia in patients with androgen deprivation therapy for prostate cancer: A prospective study |
Prostate Cancer: Advanced (including Drug Therapy) IV | 17BOS |
Abstract: MP57-15 Sources of Funding: none Introduction Although both therapeutic effects and adverse events of androgen deprivation therapy (ADT) are well known, serum lipid profile changes by ADT have quite recently been studied. ADT increases the risk for cardiovascular disease (CVD), which is affected by serum lipid profiles as the pathogenesis of atherosclerosis. Moreover, the low-density lipoprotein cholesterol (LDL-C) /high-density lipoprotein cholesterol (HDL-C) (L/H) ratio has been recognized as a strong risk predictor of CVD. The aim of this study was to investigate changes of serum lipid profiles and L/H ratio in prostate cancer (PC) patients who received ADT. Methods A prospective study assessed the changes of serum lipid profiles and L/H ratio using clinical laboratory variables among 68 PC patients treated with ADT for 6 months. The patients who did not take lipid-lowering drugs were divided into two groups based on L/H ratio less than 2.5 or not. Furthermore, patients who had a high risk of worsening L/H ratio after ADT were investigated. Results At 6 months after the start of ADT, serum levels of total cholesterol, HDL-C, and LDL-C increased significantly in both groups. On the other hand, L/H ratio increased significantly in the patients with pretreatment L/H ratio less than 2.5. On univariate analyses, systolic blood pressure (sBP, p =0.007), diastolic blood pressure (dBP, p =0.004), and HDL-C (p =0.012) were significantly associated with worsening L/H ratio. HDL-C was found to be an independent predictor of worsening L/H ratio on multivariate analysis (Odds ratio:1.11, p =0.03). Conclusions PC patients treated with ADT have a higher risk of worsening L/H ratio. These findings suggest that clinicians can identify and manage PC patients more effectively with a greater risk of worsening L/H ratio after ADT. Funding none
Authors
Oka Ryo
Takanobu Utumi Takumi Endo Masashi Yano Syuichi Kamijma Daisuke Nishimi Naoto Kamiya Hiroyoshi Suzuki |
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MP57-16 |
Metabolic syndrome in patients with prostate cancer undergoing intermittent androgen-deprivation therapy |
Prostate Cancer: Advanced (including Drug Therapy) IV | 17BOS |
Abstract: MP57-16 Sources of Funding: None Introduction The presence of metabolic syndrome in men with prostate cancer (PCa) undergoing androgen-deprivation therapy (ADT), especially intermittent type, has not been completely evaluated. The aim of this study is to evaluate metabolic syndrome in men with PCa undergoing intermittent ADT. Methods In this longitudinal study, we studied the prevalence of metabolic syndrome and its components in 190 patients who were undergoing intermittent ADT. The metabolic syndrome was defined according to the Adult Treatment Panel III criteria. All metabolic parameters, including lipid profile, blood glucose, blood pressures, and waist circumferences of the patients were measured six and 12 months after treatment. Results Mean age of the patients was 67.5 ± 6.74 years. The incidence of metabolic syndrome after six and 12 months was 6.8% and 14.7%, respectively. Analysis of various components of the metabolic syndrome revealed that patients had significantly higher overall prevalence of hyperglycemia, abdominal obesity, and hypertriglyceridemia in their six- and 12-month follow ups, but blood pressure has not been changed in the same period except for diastolic blood pressure after six months. Conclusions Although there was an increased risk of metabolic syndrome in patients receiving intermittent ADT, it was lower than other studies that treated the same patients with continuous ADT. Also it seems that intermittent ADT has less metabolic complications than continuous ADT and could be used as a safe alternative in patients with advanced and metastatic PCa. Funding None
Authors
Mohammadali Mohammadzadeh Rezaei
Alireza Ghoreifi Mohammadhadi Mohammadzadeh Rezaei Behzad Feyzzadeh Kerigh |
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MP57-17 |
Polymer delivered, subcutaneously administered leuprolide acetate provides stable and long-term drug delivery and testosterone suppression across 4 pivotal trials |
Prostate Cancer: Advanced (including Drug Therapy) IV | 17BOS |
Abstract: MP57-17 Sources of Funding: TOLMAR, Inc. Introduction Prostate cancer patients receive androgen deprivation therapy (ADT) to suppress testosterone (T) to prevent proliferation of cancer cells. T suppression levels achieved by bilateral orchiectomy remain the gold standard for the target of suppression by ADT. Although the historical threshold definition of castration is T ≤50 ng/dL, increasing evidence suggests a T lower than 20 ng/dL may improve clinical outcomes, e.g., increased cancer specific survival and delayed disease progression. However, it has not been established what level of serum LA is required to achieve T suppression below this more rigorous threshold. To determine the level of serum leuprolide required to maintain level T suppression ≤20 ng/dL in prostate cancer patients, data from 4 pivotal trials evaluating long-acting, subcutaneously (SC) administered leuprolide acetate (LA) formulated with a biodegradable polymer were pooled. Methods 438 eugonadal prostate cancer patients (age 40-86) were treated with SC-LA 7.5, 22.5, 30, or 45mg delivered with a single dose lasting over 1, 3, 4, or 6 months (n=120, 117, 90, 111), respectively in 4 open-label, fixed-dose, pivotal trials. Descriptive statistics were used to summarize the median concentration of leuprolide acetate at each time point as well as to determine level of T suppression. Results Over the dosing intervals of the 1, 3, 4 and 6-month SC-LA formulations, median serum leuprolide levels were consistent. In the pooled analysis (n=66 with PK assessments), 60(91%) patients with LA ≥0.1 ng/mL achieved T ≤20 ng/dL by week 5. Of all patients (n=438), 90-96% achieved T ≤20 ng/dL by week 6 and 90-97% maintained T ≤20 ng/dL from weeks 6-24. Conclusions These data suggest that SC-LA achieves consistent and prolonged drug delivery and that serum LA levels above 0.1 ng/mL provide favorable T suppression below 20 ng/dL. Consistent achievement of these levels may have implications for improved clinical outcomes, e.g., increased cancer specific and progression free survival. Funding TOLMAR, Inc.
Authors
Franklin Chu
John McLane Stuart Atkinson Debbie Boldt-Houle Christopher Pieczonka |
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MP57-18 |
Development and validation of novel genomic classifiers for prediction of adverse pathology after prostatectomy |
Prostate Cancer: Advanced (including Drug Therapy) IV | 17BOS |
Abstract: MP57-18 Sources of Funding: none Introduction To develop and validate novel genomic signatures to predict adverse pathology (AP) after radical prostatectomy (RP). Methods We developed three classifiers aimed at predicting 1) high-grade disease on final pathology (primary Gleason grade 4/5) and 2) AP (seminal vesicle or bladder neck invasion or lymph node positive disease). For the development of the Grade Group (GG) classifier, we performed genome-wide differential expression analysis between high- (primary pattern 4/5) and low- (primary pattern 3) Gleason grade disease on 967 high-risk prostate cancer (PCa) patients from the Decipher genomic resource information database (GRID®, NCT02609269). For the development of the high-grade disease 1 (HGD) classifier, we used differential expression analysis comparing high (≥7) and low (≤4) CAPRA-S scores in a retrospective cohort of 425 high-risk RP patients treated at Mayo Clinic and for HGD 2 classifier, we compared patients with a Decipher score ≥0.7 and Gleason score ≥8 to those with lower-risk scores in _x0007__x0008_a prospective cohort of 1817 high-risk RP patients available in GRID. The GG classifier was trained using a deep neural network model with 3 hidden layers consisting of 79 genes using the &[Prime]h2o&[Prime] package in R v3.1. The HGD 1 and HGD 2 classifiers were based on an elastic net algorithm consisting of _x0007_109 _x0008_and _x0007_60 _x0008_genes, respectively. Two validation cohorts were used: 1) 6,739 Decipher RP profiles (not used in training) in the GRID ordered by 285 centers over 2015-2016 and 2) a retrospective biopsy (Bx) cohort consisting of 107 Decipher biopsy profiles from 4 academic institutions. Discrimination performance of the classifiers was evaluated via the c-index and logistic regression. Results On the RP validation cohort, the GG, HGD 1 and HGD 2 classifiers had c-indices of 0.65 (95% confidence interval [CI] 0.64-0.67), 0.67 (95% CI 0.65-0.69) and 0.69 (95% CI 0.67-0.70) for prediction of the AP endpoint, respectively. On the Bx cohort, the GG, HGD 1 and HGD 2 classifiers had c-indices of 0.80 (95% CI 0.70-0.90), 0.82 (95% CI 0.71-0.93) and 0.84 (95% CI 0.74-0.93), respectively, for the prediction of AP after surgery. Conclusions GG and HGD classifiers were all predictive of adverse pathology on RP using two validation cohorts of RP and Bx specimens with high accuracy. This study shows how prospective data may be used to develop and validate novel genomic classifiers that provide an independent assessment of high-risk disease at the time of initial diagnosis that complements clinical risk factors and prognostic test to further help optimize treatment decision-making. Funding none
Authors
Firas Abdollah
Hussam Al-Deen Ashab R. Jeffrey Karnes John W. Davis Nicholas Erho Qiqi Wang Ewan A. Gibb Zaid Haddad Voleak Choeurng Kasra Yousefi Elai Davicioni Christopher J. Kane Robert Den Ashley E. Ross Eric A. Klein |
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MP57-19 |
Targeting AKR1C3 activation by indomethacin overcomes resistance to enzalutamide and abiraterone |
Prostate Cancer: Advanced (including Drug Therapy) IV | 17BOS |
Abstract: MP57-19 Sources of Funding: This work is supported in part by grants NIH/NCI This work was supported in part by grants NIH/NCI CA140468, CA168601, CA179970, and DOD PCRP PC150040. Introduction Resistance of prostate cancer (CaP) cells to enzalutamide and abiraterone, may be mediated by a multitude of survival signaling pathways. In this study we tested whether AKR1C3 activation and intracrine androgens induce CaP cell resistance to enzalutamide and abiraterone and whether targeting these resistance mechanisms overcomes resistance to enzalutamide and abiraterone and thus improve therapy. Methods Global gene expression analysis was analyzed by microarray and transcriptome was analyzed by RNA-seq. Steroid profile including androgens was analyzed by Liquid Chromatography-Mass Spectrometry (LC-MS). The effects of AKR1C3 expression and activation were examined by knock down of AKR1C3 expression by shRNA or inhibition of AKR1C3 enzymatic activity by indomethacin. The effects of AKR1C3 activation on enzalutamide and abiraterone sensitivity were examined in vitro and in vivo. A Phase I/II clinical trial with enzalutamide plus indomethacin has been designed. Results Global gene expression analysis showed that steroid biosynthesis pathway is activated in enzalutamide and abiraterone resistant prostate cancer cells. One of the crucial steroidogenic enzymes, AKR1C3, was significantly elevated in enzalutamide/abiraterone resistant cells. In addition, AKR1C3 is highly expressed in metastatic and recurrent prostate cancer and in enzalutamide resistant prostate xenograft tumors. Liquid Chromatography-Mass Spectrometry (LC-MS) analysis of the steroid metabolites revealed that androgen precursors such as cholesterol, DHEA and progesterone, as well as androgens are highly up regulated in enzalutamide/abiraterone resistant prostate cancer cells compared to the parental cells. Knock down of AKR1C3 expression by shRNA or inhibition of AKR1C3 enzymatic activity by indomethacin resensitized enzalutamide/abiraterone resistant prostate cancer cells to enzalutamide/abiraterone treatment both in vitro and in vivo. In contrast, overexpression of AKR1C3 confers resistance to enzalutamide and abiraterone. Furthermore, the combination of indomethacin and enzalutamide/abiraterone resulted in significant inhibition of enzalutamide and abiraterone-resistant tumor growth. These results suggest that AKR1C3 activation is a critical resistance mechanism associated with enzalutamide/abiraterone resistance. In a Phase I/II combination of indomethacin with enzalutamide trial funded by Department of Defense, patients with mCRPC, good performance status (ECOG 0-2) and vital organ function, and no history of enzalutamide or indomethacin treatment will be recruited. The co-primary objective is to assess the toxicity and prostate-specific antigen (PSA) response (?50% reduction). We will also assess the overall response as determined by the Prostate Cancer Working Group 2 criteria, progression-free survival and molecular correlative studies. Conclusions AKR1C3 activation and resulting in an increase in intracrine androgens are critical resistance mechanisms confer resistance to enzalutamide and abiraterone. Targeting AKR1C3 activation may provide a potential treatment strategy for metastatic prostate cancer patients who develop resistance to enzalutamide and abiraterone. Funding This work is supported in part by grants NIH/NCI This work was supported in part by grants NIH/NCI CA140468, CA168601, CA179970, and DOD PCRP PC150040.
Authors
Chengfei Liu
Wei Lou Joy Yang Chong-Xian Pan Marc Dall'Era Christopher Evans Allen Gao |
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MP57-20 |
Differentiating Clinically Significant from Insignificant Biochemical Recurrence after Radical Prostatectomy |
Prostate Cancer: Advanced (including Drug Therapy) IV | 17BOS |
Abstract: MP57-20 Sources of Funding: This work was supported by Roswell Park Cancer Institute and National Cancer Institute (NCI) grant P30CA016056. Introduction Our group reported on low detectable prostate-specific antigen (PSA) during the first 3 years after radical prostatectomy and proposed criteria to predict subsequent biochemical recurrence (BCR). The purpose of this study is to extend follow-up, add new patients, and compare specific predictors of low detectable PSA that progress to BCR. Methods An institutional database was queried to identify men with ultrasensitive PSA monitoring who underwent open or robot-assisted radical prostatectomy (RARP) between Jan 1993 to Dec 2011. Serum PSA and its pattern during the first 3 years of follow-up divided 663 men into 3 groups: 1)undetectable PSA (≤detectable PSA in lab where measured), 2) low detectable-stable PSA (≥detectable PSA in lab where measured and <0.2 ng/ml, no 2 subsequent increases and/or PSA velocity <0.05 ng/yr), 3)low detectable-unstable PSA (≥detectable PSA in lab where measured and <0.2 ng/ml, 2 subsequent increases and/or PSAV ≥0.05 ng/yr). The primary endpoint was BCR, defined as PSA of 0.2 ng/ml or greater, or receipt of radiation therapy beyond 3 years of follow-up. Time to BCR was summarized using standard Kaplan-Meier and log-rank tests. Results The five and ten-year BCR- free survival for all groups was 93% (95% CI: 0.9-0.95) and 73% (95% CI: 0.67-0.79), respectively. Five-year BCR-free survival differed among the 3 groups (p<0.001): 99% (95% CI 0.97-0.99) for undetectable; 89% (95% CI: 0.82-0.94) for low detectable-stable group; and 62% (95% CI: 0.48-0.74) low detectable-unstable group. Ten-year BCR-free survival was 80% (95% CI 0.72-0.86) for undetectable, 67% (95% CI: 0.53-0.78) for low detectable-stable group, and 46% (95% CI: 0.29-0.61) low detectable-unstable group (p<0.001). Low detectable-stable patients were more likely to have lower NCCN risk category (57.3% vs. 39.6%, p=0.04), low pre-operative PSA (91.2% vs. 88.7%, p=0.03), and an open procedure (30.1% vs. 15.1%, p=0.04) than low detectable-unstable patients. No difference in ≥pT2 stage (31.9% vs. 34%, p=0.79), pathologic Gleason score >7 (8% vs. 9.4%, p=0.38), positive margin status (22.1% vs. 24.5%,p=0.73), or extent of focal margin positivity (44% vs. 61.5%, p=0.38) was found. Conclusions Low detectable PSA patients have risk of BCR more similar to undetectable PSA patients and may warrant monitoring instead of salvage radiation. Funding This work was supported by Roswell Park Cancer Institute and National Cancer Institute (NCI) grant P30CA016056.
Authors
Alexandr Pinkhasov
Ruben Pinkhasov Ahmed Hussein Kristopher Attwood Elena Pop Gaybrielle James James Mohler |
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MP58-01 |
Incompleteness of the transurethral resection as a predictor of adverse pathological features at the time of radical cystectomy: implications for neoadjuvant chemotherapy selection |
Bladder Cancer: Invasive V | 17BOS |
Abstract: MP58-01 Sources of Funding: none Introduction Neoadjuvant chemotherapy (NAC) before radical cystectomy improves survival expectations in cT2-T4a bladder cancer (BCa) patients. However, this effect is more evident in patients with cT3 or higher disease. Several studies evaluated factors associated with might help in selecting patients who might benefit more from NAC before RC. However, none of them investigated the role of the completeness of transurethral resection (TUR) before RC which may represents a useful proxy of tumor extension in RC candidates. We therefore evaluated a cohort of patients treated with RC due to BCa stratifying according the completeness of TUR before RC. Methods We retrospectively analyzed data of 481 patients treated with RC and bilateral PLND without NAC due to nonmetastatic BCa between 1990 and 2013 and complete data regarding the completeness of pre-cystectomy TUR. TUR were completed when possible, when not feasible physicians reported this aspect in a prospective maintained database. Demographics and preoperative RC data were available for all patients. Univariable and multivariable logistic regression were built predicting the impact of completeness of TUR and adverse pathologic T stage (defined as T3-T4), lymph node invasion (LNI) and positive soft tissue surgical margin (STSM) status. Multivariable models were adjusted for clinical T stage, presence of CIS or lymphovascular invasion at TUR, histology at TUR, age and preoperative idronephrosis. Area under curve (AUC) was calculated predicting adverse pathologic features with and without the completeness of TUR. Results Overall, TUR has been completed in 326 (67.8%) patients submitted to RC. Patients where the TUR was not completed had higher cT3-4 disease, higher LVI, higher CIS and higher cN+ diseases. At univariable analyses, incompleteness of TUR was a predictor of_x000D_ LNI (odds ratio [OR]: 1.66, confidence interval [CI]: 1.08-2.55, p=0.02), adverse pathologic stage (OR: 1.78, CI: 1.21-2.62, p=0.003), positive STSM (OR: 2.15, CI: 1.13-4.10, p=0.02). At multivariable analyses, completeness of TUR was a predictor of positive STSM (OR: 2.18, CI: 1.12-4.25, p=0.02) and adverse pathologic T stage (OR: 1.57, CI: 1.03-2.40, p=0.03) but not in the prediction of LNI (p=0.06). The inclusion of completeness of TUR in our preoperative model increases of 3.5% its accuracy (AUC: 76.2 vs. 72.7 with or without completeness of TUR, respectively). Conclusions Incompleteness of the TUR before RC represents a predictor of adverse pathologic features at RC. Physicians should consider this aspect in predicting RC patients’ survival and eventually the necessity of neoadjuvant chemotherapy. Funding none
Authors
Marco Moschini
Marco Bandini Giusy Burgio Giovanni La Croce Emanuele Zaffuto Andrea Gallina Agostino Mattei Rocco Damiano Vincenzo Mirone Shahrokh Shariat Alberto Briganti Francesco Montorsi Renzo Colombo |
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MP58-02 |
Genomic Differences Between “Primary” and “Secondary” Muscle Invasive Bladder Cancer: Implications for Neoadjuvant Chemotherapy |
Bladder Cancer: Invasive V | 17BOS |
Abstract: MP58-02 Sources of Funding: Supported by the Sidney Kimmel Center for Prostate and Urologic Cancers at Memorial Sloan Kettering Cancer Center, Pin Down Bladder Cancer, and the Michael A. and Zena Wiener Research and Therapeutics Program in Bladder Cancer. Introduction We recently reported that patients with secondary muscle-invasive bladder cancer (MIBC) have substantially worse outcomes with neoadjuvant chemotherapy compared to primary MIBC (Pietzak, et al. AUA 2016). We subsequently used next-generation sequencing to investigate genetic differences between primary and secondary MIBC specimens. Methods We examined MIBC specimens from the Cancer Genome Atlas (TCGA) (n=131), our institutional genomic research database (n=569), and a prospective clinical sequencing protocol (n=214) to identify 342 chemotherapy-naive urothelial MIBC specimens (270 primary and 72 secondary) that underwent whole-exome or targeted exon-capture sequencing. Primary and secondary MIBC specimens were compared for genomic alterations in 341 known cancer genes. Primary MIBC was defined as clinical stage ≥T2 on either initial or re-staging TUR on first bladder tumor diagnosis. Patients with a history of NMIBC (Tis, Ta, or T1 with uninvolved detrusor muscle in specimen) confirmed by a second cystoscopy prior to the eventual diagnosis of clinical stage ≥T2 were considered to have secondary MIBC. Results We compared 270 primary and 72 secondary MIBC specimens for differences in genomic alterations in 341 cancer-associated genes. We identified significantly different rates of ERCC2, APC, and FGFR3 alterations. FGFR3-activating mutations (S249C, Y373C) occurred more frequently in secondary MIBC specimens (18% [13/72] vs. 9% [24/270], p=0.03). APC mutations were only seen in primary MIBC specimens (5% [14/270] vs. 0% [0/72], p=0.047). Surprisingly, ERCC2 missense mutations, which are associated with extreme sensitivity to cisplatin chemotherapy, only occurred in primary MIBC specimens (12% [32/270] vs. 0% [0/72], p<0.001). After adjusting for multiple comparisons using the Benjamini-Hochberg false discovery rate method, only ERCC2 mutations remained significant (adjusted p =0.016). Conclusions ERCC2 is involved in repair of cisplatin-induced DNA damage, and mutations in ERCC2 are associated with clinical responses to cisplatin. ERCC2 mutations occurred exclusively in primary MIBC patients and may account for their improved outcomes with neoadjuvant chemotherapy compared to secondary MIBC patients. Funding Supported by the Sidney Kimmel Center for Prostate and Urologic Cancers at Memorial Sloan Kettering Cancer Center, Pin Down Bladder Cancer, and the Michael A. and Zena Wiener Research and Therapeutics Program in Bladder Cancer.
Authors
Eugene Pietzak
Aditya Bagrodia Hikmat Al-Ahmadie Harry Herr Emily Zabor David Barron Qiang Li Francois Audenet Samuel Funt Ahmet Zehir Maria Arcila Priscilla Baez Michael Berger Nikolaus Schultz David Solit Dean Bajorin Jonathan Rosenberg Eugene Cha Bernard Bochner Gopa Iyer |
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MP58-03 |
Dose Dense MVAC Prior To Radical Cystectomy: A Retrospective Multi-Institutional Experience |
Bladder Cancer: Invasive V | 17BOS |
Abstract: MP58-03 Sources of Funding: None Introduction Level I evidence supports the utility of neoadjuvant chemotherapy (NAC) for muscle invasive bladder cancer (BCa). Although this evidence is derived primarily from phase III trials that used the combination of methotrexate/vinblastine/doxorubicin/cisplatin (MVAC) or cisplatin/methotrexate/vinblastine (CMV), the alternative and less toxic regimen gemcitabine/cisplatin (GC) is currently used more commonly for NAC. Since dose dense (dd)-MVAC has mostly replaced traditional MVACOur primary endpoint was to assess the rate of pT0N0 and ≤pT1N0 for patients with BCa treated with the accelerated or dose dense MVAC (ddMVAC) chemotherapy followed by radical cystectomy (RC) in this real-word multi-institutional cohort. _x000D_ Methods We retrospectively reviewed records of patients with urothelial cancer who underwent ddMVAC and RC at seven contributing institutions from 2000-2015. Patients with cT2–4a,M0 BCa were included. Presence of cT3-4 disease, hydronephrosis, lymphovascular invasion and/or existence of sarcomatoid, or micropapillary features on the initial transurethral resection of bladder tumor specimen was defined as high-risk disease. Logistic regression models for prediction of pT0N0 and ≤pT1N0 were generated for the entire cohort as well as for the cN0 subgroup. The multivariable Cox proportional hazards regression model for survival using post RC data was used to assess hazard ratios (HRs) for the variables of interest._x000D_ Results A total of 345 patients received ddMVAC chemotherapy during the study period. The observed rates of pT0N0 and ≤pT1N0 were 30.4% and 49.3%, respectively among cN0 patients. On the multivariable regression model, the presence of more than one clinical high-risk element was associated with 70% (OR 0.30 95%CI (0.10-0.86); p=0.02) reduction in the probability of achieving partial pathological response. Conclusions A complete response (pT0N0) was observed in one third of patients after neoadjuvant ddMVAC therapy, and a partial response (≤pT1N0) was observed in nearly half of the cases in this real-world experience with this regimen. To our knowledge, this represents the largest experience outside clinical trial settings. _x000D_ Funding None
Authors
Homayoun Zargar
Jay B Shah Elisabeth E Fransen van de Putte Kylea R. Potvin Kamran Zargar-Shoshtari Bas W van Rhijn Siamak Daneshmand Jeff M Holzbeierlein Philippe E Spiess Eric Winquist Simon Horenblas Colin Dinney Peter C Black Wassim Kassouf Homayoun Zargar |
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MP58-04 |
Dense dose MVAC versus GC in patients with cT3-4a bladder cancer treated with radical cystectomy: a real world experience |
Bladder Cancer: Invasive V | 17BOS |
Abstract: MP58-04 Sources of Funding: None Introduction Level I evidence supports the utility of neoadjuvant chemotherapy (NAC) for muscle invasive bladder cancer (BCa). Although this evidence is derived primarily from phase III trials that used the combination of methotrexate/vinblastine/doxorubicin/cisplatin (MVAC) or cisplatin/methotrexate/vinblastine (CMV), the alternative and less toxic regimen gemcitabine/cisplatin (GC) is currently used more commonly for NAC. Since dose dense (dd)-MVAC has mostly replaced traditional MVAC, we aimed to compare pathological response and survival rates in patients with locally advanced BCa receiving ddMVAC versus GC. _x000D_ Methods We retrospectively reviewed records of patients with urothelial cancer who received NAC and underwent cystectomy at 19 contributing institutions from 2000-2013. Patients with cT3-4aN0M0 were selected for this analysis. The rate of pT0N0 and pT≤1N0 was compared between GC and ddMVAC regimens. A Multivariable Cox proportional hazards regression model for overall mortality was generated to evaluate hazard ratios (HRs) for variables of interest (age, LVI, hydronephrosis, type of chemotherapy regimen, surgical margin). _x000D_ Results Of 1865 patients undergoing NAC and RC during the study period, 319 met our inclusion criteria (table 1). A significantly lower rate of pT0N0 was observed in the GC arm compared to ddMVAC (14.6% vs. 28.0%; p=0.005). The rate of pT≤1N0 was 30.1% for GC compared to 41.0% for ddMVAC (p=0.07). The Kaplan-Meier mean estimate of overall survival for GC and ddMVAC patients was 4.2 and 7.0 years, respectively (p=0.001). In multivariable cox regression analysis, GC patients were at higher risk of death compared to ddMVAC patients (HR 1.9, 95%CI (1.2-3.1); p=0.006). Presence of LVI (HR 2.1, 95%CI (1.2-3.6); p=0.007), hydronephrosis (HR 1.9, 95%CI (1.3-2.9); p=0.002) and positive surgical margin (HR 1.4, 95%CI (1.2-1.7); p<0.001) were also associated with higher risk of death._x000D_ Conclusions In our retrospective cohort of locally advanced BCa patients, ddMVAC was associated with a higher rate of pathologic down-staging response and improved longer survival when compared to GC. A clinical trial is warranted to validate these hypothesis-generating results superiority of neoadjuvant ddMVAC in patients with locally advanced BCa._x000D_ Funding None
Authors
Homayoun Zargar
Jay B Shah Elisabeth E Fransen van de Putte Kylea R. Potvin Kamran Zargar-Shoshtari Bas W van Rhijn Siamak Daneshmand Jeff M Holzbeierlein Philippe E Spiess Eric Winquist Simon Horenblas Colin Dinney Adrian S Fairey Evan Kovac Laura-Maria Krabbe Michael S Cookson Niels-Erik Jacobsen Nilay Gandhi Joshua Griffin Jeffrey S Montgomery Nikhil Vasdev Evan Y Yu Evanguelos Xylinas Nicholas J. Campain Jo-An Seah Cesar E Ercole Srikala S Sridhar John S McGrath Jonathan Aning Shahrokh F Shariat Jonathan L Wright Andrew C Thorpe Todd M Morgan Petros Grivas Andrew J Stephenson Trinity J Bivalacqua Scott North Daniel A Barocas Yair Lotan Peter C Black Wassim Kassouf |
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MP58-05 |
Basal and Luminal Immunohistochemical Phenotypes in Muscle Invasive Bladder Urothelial Carcinomas (MIBC) Treated with Neoadjuvant Chemotherapy (NAC) |
Bladder Cancer: Invasive V | 17BOS |
Abstract: MP58-05 Sources of Funding: None Introduction MIBC patients who respond to cisplatin based NAC, defined as stage Methods Pre-treatment tissues from a cohort of 71 NAC treated MIBC patients at our institution between 2000 and 2013 were incorporated in tissue microarray and stained for CK5/6 and GATA3 (Ventana Medical Systems, AZ). Cases were assigned as luminal or basal phenotype based on the extent (70% cut off) of tumor cells with ?2+ staining intensity, Figure 1A. We limited our analysis of CSS to the 40 patient who were able to tolerate ?2 doses of NAC to avoid the confounding effect of patients who were not adequately dosed. Results As expected, there was an inverse association for CK5/6 and GATA3: 77% (43/56) of strong GATA3 cases exhibited weak/negative CK5/6 staining, most consistent with the luminal phenotype, and 73% (11/15) of the GATA3 weak/negative cases exhibited strong CK5/6, most consistent with the basal phenotype (Fisher's exact p-value 0.0003). Interestingly there was a ? 2 fold enrichment of basal the phenotype in cases with residual MIBC following NAC, Figure 1B. Conclusions Our results suggest a differential responsiveness to NAC for MIBC based on assignment of basal and luminal phenotypes. The current findings should be further evaluated taking P53 gene expression status into account, given previous suggestion of chemotherapy resistance in P53 intact (p53-Like) MIBC. Furthermore, comparison to IHC luminal/basal MIBC phenotypes in our cohort of cystectomy only treated patients is ongoing to help discern the prognostic vs predictive role of this classification for NAC. Funding None |
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MP58-06 |
The benefits of adjuvant chemotherapy after radical cystectomy with pelvic lymph node dissection in patients with urothelial carcinoma of bladder according to the lymph node density on final pathology |
Bladder Cancer: Invasive V | 17BOS |
Abstract: MP58-06 Sources of Funding: None Introduction It has been reported that lymph node density is superior to TNM nodal status in predicting oncologic outcome after radical cystectomy (RC) for urothelial carcinoma of bladder (UCB). The survival benefits of adjuvant chemotherapy (AC) following RC according to LND were assessed in this study. Methods Of 888 consecutive UCB patients undergoing RC with pelvic lymph node dissection (PLND), 164 (18.5%) received the AC. After controlling preoperative and postoperative clinical and pathological variables, recurrence-free (RFS) and cancer-specific survival (RFS) after RC with PLND were compared between the AC and non AC groups. Results After the strict propensity scored matching (both discard, caliper=0.1), 130 patients with AC were not significantly different with 130 matched patients without AC, in age (62.5 vs. 61.8 years), pT stage (≥pT3, 78.5 vs. 77.7%), pN stage (pN1, 23.8 vs. 30.8% ;≥pN2, 32.3 vs. 32.3%), tumor grade (high, 95.4 vs. 87.7%), carcinoma in situ (23.1 vs. 28.5%), lymphovascular invasion (62.3 vs. 58.5%), positive surgical margin (10.0 vs. 10.0%), dissected LN number (19.8 vs. 22.4), and LN density (0.14 vs. 0.15; p range, 0.071-1.000). During median 43.0 months follow-up after the RC with PLND, median RFS of AC group was similar to that of non AC group (37.0 vs. 30.0 months, p=0.612). CSS were not also different between two groups (60.0 vs. 55.0 months, p=0.313). However, better RFS (20.0 vs. 9.0 months, p=0.008) and CSS (44.0 vs. 18.0 months, p=0.009) of AC group were observed in subgroup of patients with LND ≥0.05 (N=122). Conclusions After adjusting the possible confounders and selection biases, AC demonstrated better oncological outcomes in patients with LND ≥0.05. Patients with LND ≥0.05 on final pathology should be considered the AC for better survival outcomes. Funding None
Authors
Myong Kim
Jong Keun Kim Myungchan Park Sang Hyun Park In Gab Jeong Cheryn Song Jun Hyuk Hong Choung-Soo Kim Tai Young Ahn Hanjong Ahn |
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MP58-07 |
Use of adjuvant chemotherapy in patients with advanced bladder cancer after neoadjuvant chemotherapy |
Bladder Cancer: Invasive V | 17BOS |
Abstract: MP58-07 Sources of Funding: none Introduction Patients with non-organ confined disease at radical cystectomy (RC) have a poor prognosis, especially after neoadjuvant chemotherapy (NAC). We hypothesized that use of adjuvant chemotherapy (AC) is associated with improved survival compared to observation along among patients with advanced disease at RC after NAC. Methods Using the National Cancer Database, we identified patients who received NAC prior to RC and had advanced stage (pT3/4) or pathologically involved nodes (pN+) at the time of surgery from 2004-2013. We determined whether patients then received AC or were managed with observation only and used multivariable proportional hazards regression to estimate the impact of AC on overall survival. Results Overall 34% (N=723) of patients who received NAC and underwent RC were pT3/4 and/or pN+. Of these patients, 24% (N=170) received subsequent chemotherapy and the rest were observed. Median survival for the entire cohort was 21 months (IQR 12-45). Compared to the observation group, the AC group had longer median survival however this was not statistically significant (23 months [IQR 14-46] versus 20 months [IQR 12-46], log-rank p = 0.52). On multivariate analysis there was no survival advantage for the AC cohort. Subgroup analysis of pN+ patients who received AC showed also did not show a survival advantage. Conclusions Patients who are pT3/4 and/or pN+ after NAC and RC have a poor prognosis. The addition of AC does not seem to be beneficial. Further research should focus identifying patients who may benefit from additional chemotherapy. Funding none
Authors
Wilson Sui
Emerson Lim Guarionex DeCastro James McKiernan Christopher Anderson |
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MP58-08 |
The B4GALT1 expression is prognostic and predictive for postoperative adjuvant chemotherapy benefit in patients with muscle-invasive bladder cancer |
Bladder Cancer: Invasive V | 17BOS |
Abstract: MP58-08 Sources of Funding: This study was funded by grants from National Natural Science Foundation of China (81472377, 81572531) Introduction Beta-1, 4-Galactosyltransferase gene (B4GALT) family consists of seven members, which encode corresponding enzymes known as type II membrane-bound glycoproteins. These enzymes catalyze the biosynthesis of different glycoconjugates and saccharide structures, and have been recognized to be involved in various diseases. In this study, we sought to determine the bladder cancer cell's B4GALT1 expression and its association with the infiltrated CD8+ T cell number, together with the association with the patients’ outcome, as well as the benefit from adjuvant chemotherapy in patients with muscle-invasive bladder cancer (MIBC). Methods We recruited 201 and 172 patients consecutively with bladder cancer treated by radical cystectomy from 2008 to 2012 in Shanghai Zhongshan Hospital and Fudan University Shanghai Cancer Center (FUSCC), respectively. The first cohort with 201 patients was treated as training set and the other as validation set. TMAs were created in triplicated from formalin-fixed, paraffin embedded specimens. Immunohistochemistry was performed to assess the expression of B4GALT1 in tumor cores and CD8 in both tumor and peri-tumor cores, and its association between B4GALT1 and the infiltrated CD8+ T cell number, also with clinical outcomes. Results B4GALT1 expression was significantly associated with tumor size (P=0.005 and P=0.014, respectively), T stage (P=0.017 and P=0.004, respectively), OS (P<0.001 and P<0.001, respectively) and PFS (P=0.033 and P=0.034, respectively) in both cohorts. Furthermore, high expression of B4GALT1 was an independent indicator of poor OS (P=0.022 and P=0.017, respectively) in patients with MIBC. The prognostic model containing B4GALT1 showed a better predictive accuracy than the basic models. And the B4GALT1 expression was inverse correlated with the number of peri-tumor infiltrated CD8+ T cell, but not with the number of tumor infiltrated CD8+ T cell. Most importantly, the benefit of adjuvant chemotherapy observed in non-organ confined bladder cancer patients with low B4GALT1 expression was superior to patients with high expression. Conclusions Our study suggested that B4GALT1 is a potential prognostic biomarker of MIBC, and might be a predictive marker for the patients’ selection of adjuvant chemotherapy in high recurrence risk subgroup patients. Funding This study was funded by grants from National Natural Science Foundation of China (81472377, 81572531)
Authors
Huyang Xie
Yu Zhu Zewei Wang Qiang Fu Jiejie Xu Dingwei Ye |
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MP58-09 |
Predicting local failure after radical cystectomy in bladder cancer patients: implications for the selection of candidates at adjuvant radiation therapy |
Bladder Cancer: Invasive V | 17BOS |
Abstract: MP58-09 Sources of Funding: none Introduction Local failure (LF) after radical cystectomy (RC) due to bladder cancer (BCa) is a common and deadly event. Clinical trials are currently evaluating the impact of adjuvant radiotherapy on the reduction of LF, however scarce data exists about selection of candidates who might benefit from multimodal approach. Methods We focused on 1112 patients treated with RC and pelvic lymph node dissection, between 1990 and 2012, at a single tertiary referral center. LF was defined as imaging evidence of recurrence in the pelvic soft tissues or nodes below the aortic bifurcation before or within 3 months of detection of distant metastases. Kaplan-Meier log-rank, univariable and multivariable competing risk analyses tested the relationship between clinical and pathological factors and the risk to develop LF during follow up period. Regression tree analysis stratified patients into risk-groups based on their tumor characteristics and the corresponding LF rate. Results Of the 1,122 individuals included in the study, 50 (4.5%) developed LF during follow up period. Median (IQR) follow-up was 62 (35-92) months. At univariable competing risk regression, pathological T stage pT4 vs. pT3 (Hazard Ratio [HR]: 2.55, p=0.003), positive soft tissue surgical margin (STSM) vs. negative (HR: 2.95, p=0.005) and non-pure transitional vs. pure transitional histology (HR: 1.79, p=0.03) were associated with an increased risk of developing LF. On the basis of these variables, the cohort was stratified into four risk groups: very low risk (?pT3a disease, pure transitional histology and negative STSM), low risk (?pT3a disease, non-pure transitional histology and negative STSM), intermediate risk (pT4 disease, negative STSM and any histology), and high risk (all patients with positive STSM). Conclusions LF is a common event in RC patients. We developed a new risk model based on BCa characteristics. Our findings should be considered by threating physicians when deciding the necessity of adjuvant radiotherapy. Funding none
Authors
Marco Moschini
Andrea Gallina Nicola Fossati Stefano Luzzago Rocco Damiano Agostino Mattei Shahrokh Shariat Vincenzo Mirone Giusy Burgio Andrea Salonia Alberto Briganti Francesco Montorsi Renzo Colombo |
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MP58-10 |
Preoperative hemoglobin to platelet ratio as a predictor of survival after radical cystectomy. |
Bladder Cancer: Invasive V | 17BOS |
Abstract: MP58-10 Sources of Funding: none Introduction The role of cancer-related inflammation pathways as proxy of aggressiveness is well known in several cancers. Preoperative anemia and thrombocytosis are known to be associated with aggressive disease features in bladder cancer (BCa). Accordingly, we hypothesized that a single variable including hemoglobin (HB) and platelet count (PLT) (HB to PLT ratio [HPR]) could consider the synergic effect of both factors. We aim to evaluate if HPR can represent a predictor of cancer specific mortality (CSM) or overall mortality (OM) in patients treated with radical cystectomy (RC) for BCa Methods We evaluated 963 patients diagnosed with BCa and treated with RC between 1987 and 2015 at our institution. Routine laboratory measurements were performed preoperatively the day before surgery. Univariate and multivariable Cox proportional hazards regression analyses were used to predict CSM and OM. Covariates included age at surgery, gender, pathological T stage, pathological N stage, preoperative hydronephrosis, ASA score, surgical margins, lymph vascular invasion and neoadjuvant chemotherapy Results Median age was 69 years (IQR 62-75 years). HB was measured as g/L while PLT was measured as 10^9 L-1. Preoperative median HPR was 0.55 (IQR 0.41-0.70 ). Overall, 304, 129 and 540 patients were recorded with lymph node metastases, positive surgical margins and pT3-4 stage, respectively. CSM was observed in 385 (39%) patients, whereas OM was observed in 148 patients (48%). Median follow-up was 58 months (IQR 15-84 ). Patients with a HPR lower than 0.55 had adverse pathological characteristics, such as high grade (P < 0.001), advanced T stage (P < 0.001) and lymph node invasion (P < 0.001). At univariate analysis HPR higher than 0.55 was associated with lower risk of CSM and OM (respectively HR 0.224 and 0.291; CI 0.131-0.381 and 0.291-0.468; all p <0.001). At multivariate analysis preoperative HPR was associated with lower risk to incur CSM and OM (respectively HR 0.134 and 0.162; CI 0.05-0.37 and 0.07-0.41; all p <0.001). Other predictors of CSM were N stage and positive margins while neoadjuvant chemotherapy was inversely associated to CSM. Other predictors of OM were ASA score, age at surgery and N stage while neoadjuvant chemotherapy was inversely linked to OM Conclusions Despite the well known role of anemia and thrombocytosis as predictors of survival in BCa, HPR (that include both factors) should be considered as a powerful prognostic marker, expression of inflammation and of the disease aggressiveness. However further investigations are needed to fully understand the impact of inflammation in BCa Funding none
Authors
Giovanni La Croce
Marco Moschini Alessandro Nini Dell'Oglio Paolo Eugenio Ventimiglia Ettore Di Trapani Andrea Salonia Alberto Briganti Francesco Montorsi Andrea Gallina Renzo Colombo |
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MP58-11 |
Impact of intra- and post-operative blood transfusion on the incidence, timing and pattern of disease recurrence after radical cystectomy |
Bladder Cancer: Invasive V | 17BOS |
Abstract: MP58-11 Sources of Funding: none Introduction Administration of blood transfusion (BT) has been associated with a decrease in survival expectancies in patients treated with radical cystectomy (RC). However, mechanisms associated to this relation are unknown. To test the postulated immunosuppressive effect mediated by BT in RC patients. Specifically, we evaluated if the usage of BT may influence risk and pattern of distant recurrences development after RC. Methods we evaluated 1,081 contemporary patients with clinically non metastatic BCa with available follow-up and recurrence site information, treated with RC and pelvic lymph node dissection (PLND) at a single tertiary care referral center (testing cohort) between_x000D_ 1990 and 2013. Findings from the first dataset were subsequently evaluated in an independent cohort composed of 433 patients who were treated with RC and PLND for clinically non-metastatic BCa between 1988 and 2003. Distant recurrences were separetely evaluated for the two studied cohort. Cox regression analyses evaluating the risk of developing distant recurrence after RC were built. Results In the primary cohort composed by 1,081 patients 445 (41.2%) received a perioperative BT. The median follow up was 52 months_x000D_ (Interquartile range: 44-61 months). Overall, 277 (25.6%) patients incurred in distant recurrence during follow up period. In the second cohort composed by 433 patients treated at a single institution 183 (42.3%) patients received perioperative BT. The median follow up was 83 months (Interquartile range: 75-91 months). Distant recurrence during the follow up period were recorded in 127 (28.3%) patients. One, three and five-years distant recurrence rates were 81% vs. 85%, 65% vs. 70% and 60% vs. 68% for patients who received intraoperative vs. no BT transfusion (p=0.03). One, three and five-years distant recurrence rates were 81% vs. 85%, 64% vs. 70% and 53% vs. 68% for patients who received postoperative vs. no BT transfusion (p=0.4). Similar findings were observed in the validation studied cohort (all p ?0.05). At multivariable analyses predicting distant recurrences, BT were not related to an increased risk to incur in distant recurrence (all p?0.2) or different recurrence patterns in both studied cohorts. Conclusions BT administration in RC patients is not associated with different pattern or higher rates of distant recurrences when compared to patients who not received BT. New data are needed to investigate mechanisms behind the association between BT and survival in RC patients. Funding none
Authors
Marco Moschini
Andrea Gallina Marco Bandini Paolo Dell´Oglio Giovanni La Croce Giusy Burgio Agostino Mattei Rocco Damiano Vincenzo Mirone Alberto Briganti Francesco Montorsi Renzo Colombo Shahrokh Shariat |
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MP58-12 |
Clinical Destiny of Indeterminate Pulmonary Nodules in Patients Undergoing Radical Cystectomy for Urothelial Carcinoma of the Bladder |
Bladder Cancer: Invasive V | 17BOS |
Abstract: MP58-12 Sources of Funding: None Introduction Perioperative risks and significant quality of life concerns following radical cystectomy (RC) render accurate pre-operative staging paramount. Incidental indeterminate pulmonary nodules (IPNs) are a common pre-operative finding in clinical practice, thus representing a significant management challenge since metastatic patients are unlikely to benefit from extirpation. Thus, we sought to evaluate the natural history of IPNs in a large institutional cohort that underwent RC._x000D_ Methods We reviewed our institutional database for patients who underwent RC from 2000-2014 for urothelial carcinoma (UCC) of the bladder & had ≥1 identifiable pulmonary lesion on preoperative staging imaging measuring <2cm in any axis. Patients who were M1 at surgery or had non urothelial histology were excluded. Cumulative incidence of any lung metastasis was estimated, adjusting for competing risk of death; overall survival (OS) was estimating using Kaplan Meier methods. We sought to determine the natural history of these pulmonary lesions and evaluated predictors of metastatic etiology._x000D_ Results During the study period, 681 RC were performed at our institution. Of which, 73 patients with an identifiable preoperative IPN met inclusion criteria & underwent RC. In this subset, 23% were female, 22% were active smokers & 55% former smokers. The median age at surgery was 70 yrs (range 43-88). 51% received neoadjuvant chemotherapy & 62% of RC were performed using the traditional open approach (vs 38% robotically). Final pathologic staging included 16% pT0N0Mx, 19% pTa/Tis/T1N0Mx, 43% pT2-4N0Mx, & 22% pTanyN+Mx. Median IPN size was 0.7±0.3cm. At median follow up of 23.5 months, the IPNs in 92% (67/73) of patients were clinically benign, with metastatic urothelial cancer confirmed in only 5 patients, & a primary lung malignancy diagnosed in 1 patient. In the IPN cohort, lung metastasis at non-IPN sites were detected in 2 additional patients. Cumulative incidence of any lung metastasis at 12, 24 & 36 months was 5.9% (95%CI 1.9-13.3%), 7.6% (95%CI 2.8-15.7%), & 10.3% (95%CI 3.9-20.2%), respectively. OS at 12, 24 & 36 months was 75.3% (95%CI 62.3-83.9%), 65.8% (95%CI 53-1-75.9%), & 54.0% (95%CI 39.7-66.2%), respectively. _x000D_ Conclusions The majority of IPNs in patients who proceeded to RC for UCC of the bladder were stable upon follow-up & rarely represented malignancy. Patients with IPNs have OS consistent with previously published literature. As such, in appropriately screened UCC patients, IPNs should not be a barrier to proceeding with extirpative surgical therapy. Funding None
Authors
David Cahn
Brian McGreen Albert Lee Karen Ruth Elizabeth Plimack Daniel Geynisman Matthew Zibelman Benjamin Ristau Marc Smaldone Richard Greenberg Rosalia Viterbo David Chen Robert Uzzo Alexander Kutikov |
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MP58-13 |
Is transurethral resection alone enough for diagnosis histological variants? A single center study |
Bladder Cancer: Invasive V | 17BOS |
Abstract: MP58-13 Sources of Funding: none Introduction Urothelial carcinoma of the bladder presents often morphological features that differ from the urothelial common aspect. Specifically, this parameter may change the therapeutic approach at the time of transurethral resection (TUR). However, data are scarce regarding the concordance of histological variants at TUR using radical cystectomy (RC) features as a reference. The aim of our study was to report incidence of histological variants in TUR and RC and to evaluate the agreement between TUR and RC considering histological variants. Methods A total of 779 patients treated with TUR and subsequently with RC and pelvic lymph node dissection between 1990 and 2013 at a single tertiary referral center were included in the study. Patients treated with neoadjuvant chemotherapy were excluded from the study due to the aim of work. Dedicated uropathologists evaluated TUR and RC at the same tertiary referral center. Variant histology classification used in our analyses were: sarcomatoid, small cell, squamous or micropapillary. All the other variants were group together as found in less than 10 patients. Grade agreement was calculated using the Cohen kappa coefficient. Absolute value ranges between 0 and 1, where 0 represents pure chance agreement, and 0.1 to 0.4, 0.4 to 0.75, and 0.75 to 1.0, respectively, represent poor, intermediate, and good agreement. Univariable and multivariable logistic regression evaluated the association between the presence of histological variants at TUR and the risk of incur in adverse pathologic features at RC. Results Considering TUR, 213 (27.3%) patients were diagnosed with histological variants. Of these, 2.1% (n=16) were found with sarcomatoid variant, 1.7% (n=13) with small cell, 7.1% (n=55) with squamous, 12.5% (n=97) with micropapillary and 4.1% (n=32) defined as others. Considering RC, 212 (27.2%) patients were diagnosed with histological variants. Of these, 2.1% (n=16) were found with sarcomatoid variant, 1.7% (n=13) with small cell, 3.9% (n=30) with squamous, 10.2% (n=78) with micropapillary. Cohen kappa concordance was used to analyze agreement between TUR and RC considering histological variants. In general, poor agreement was found considering micropapillary variant and the presence of an histological variant in general (0.11 and 0.27, respectively). On the other hand, intermediate agreement was found analyzing the presence of sarcomatoid, small cell and squamous variants (0.43, 0.61 and 0.61, respectively). At multivariable analyses, none of the histological variants evaluated at TUR were found to be associated to adverse pathologic stage or node positive disease at RC (all p>0.06). Conversely diagnosis of small cell carcinoma at TUR was found associated with an increased risk of harboring positive STSM (Odds ratio:2.08, confidence interval:1.27-3.41, p=0.03). Conclusions The presence of histological variants is a common finding in BCa patients. However, considering this aspect we found poor concordance between TUR and RC. Our findings highlight the necessity of developing new biomarkers to increase the diagnostic value of TUR which may change the therapeutic indication for RC or the necessity of neoadjuvant treatment. Funding none
Authors
Marco Moschini
Renzo Colombo Shahrokh Shariat Giusy Burgio Rocco Damiano Agostino Mattei Marco Bandini Paolo Dell´Oglio Emanuele Zaffuto Andrea Salonia Francesco Montorsi Alberto Briganti Andrea Gallina |
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MP58-14 |
Limits of transurethral resection in detecting uncommon histological variants within bulky bladder tumors in real-life clinical practice |
Bladder Cancer: Invasive V | 17BOS |
Abstract: MP58-14 Sources of Funding: none Introduction Rare histotypes represent almost 10% of bladder tumors, more often represented within large and muscle invasive transitional cell carcinomas of the bladder (MIBC). Neoadjuvant chemotherapy is recommended (Grade A) by international guidelines. Rare histological variants, more aggressive and less responsive to systemic chemotherapy might remain unrecognized at initial transurethral resection (TURBT) in everyday clinical practice. We investigated the accuracy of TURBT in detecting rare histological variants in patients with large bladder tumors candidate to cystectomy. Methods The clinical and pathologic data of 540 patients submitted to TURBT and/or cystectomy for bladder cancer between Jan. 2010 and Oct. 2016, were reviewed. The presence of uncommon histotypes within urothelial bladder carcinoma has been assessed. Rare variants were diagnose according WHO criteria. Standard hematoxilyn-eosin stain was adopted and further immunohistochemistry was performed. Inferential statistical analysis was performed._x000D_ Results Out of 540 patients, 43 (7,9%) showed rare histotypes of bladder cancer. In 5 (11,6%) cases the uncommon histotypes was revealed by palliative TURBT . The remaining 38 patients were submitted to cystectomy for bladder tumors of considerable size (mean diameter 7,8 cm; range of 5-11 cm); 14 (36,8%) harbored a pT4 tumor._x000D_ The rare histotypes were: squamous carcinoma 6 (13,9%), sarcomatoid 2 (4,8%), undifferentiated 5 (11,6%), neuroendocrine 3 (6,9%), mixed 27 (62,8%). _x000D_ TUR revealed an uncommon histotypes in 26 (68,4%) cases only. _x000D_ Moreover, in 5 (23.8%) patients an additional uncommon histology not detected by previous TUR, was demonstrated in cystectomy specimens. _x000D_ Conclusions The prognostic role of uncommon histotypes in bladder cancer is well documented. Unrecognized rare histotypes might have important therapeutic implications since possibly less responsive to neoadjuvant chemotherapy. These patients could benefit from an immediate cystectomy avoiding neo-adjuvant chemotherapy. _x000D_ The inaccuracy of TUR in everyday clinical practice in detecting uncommon variants could be explained by an inadequate sampling of large tumors. The &[Prime]pre-cystectomy&[Prime] TUR is often performed only to confirm the infiltration. As a matter of fact, the pathologists might not receive an adequate amount of tissue. To standardize the TURBT strategy including sampling of different areas of bulky tumors could be of clinical value in patients undergoing neoadjuvant chemotherapy._x000D_ _x000D_ Funding none
Authors
Cristina Scalici Gesolfo
Alessio Guarneri Sandro Billone Marco Moschini Renzo Colombo Matteo Ferro Ottavio De Cobelli Alchiede Simonato Vincenzo Serretta |
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MP58-15 |
Impact of Tumor Histopathologic Types on Pattern of Tumor Recurrence after Radical Cystectomy for Muscle Invasive Bladder Cancer (MIBC). |
Bladder Cancer: Invasive V | 17BOS |
Abstract: MP58-15 Sources of Funding: non Introduction To compare patterns of tumor recurrence of common histological types of bladder cancer after radical cystectomy. Predictors of cancer specific survival (CSS) were also identified. Methods The records of 1737 consecutive patients treated with radical cystectomy between January 2004 till February 2014 were reviewed. _x000D_ A total of 937, 318, 223and 70 patients were diagnosed with urothelial carcinoma (UC), SCC,UC with squamous differentiation (SqD) and adenocarcinoma (AC) respectively. Clinical tumor recurrences were classified as local, when recurred in the soft tissue of pelvis and / or pelvic lymph nodes. Distant metastasis, on those recurred in remote sites including extrapelvic lymph nodes._x000D_ Cancer specific survival (CSS) was estimated using Kaplan-Meier survival method and compared with log rank test._x000D_ Results Mean patient age was 58.4±8.1 years. Median follow up period was 23 months (IQR 9-57 months). Patients’ characteristics are demonstrated in Table1._x000D_ Five year CSS was 77.9% , 77.8% , 67.3% and 59.8% for SCC, AC, UC and SqD respectively (p = 0.009). _x000D_ Patients with SqD had the highest incidence of local pelvic recurrence reaching 21% followed by SCC (15.4%). Distant metastasis was observed in 157 (16.8%) and 41(18.4%) patients with UC and SqD respectively in comparison to 7(10%) and 20 (6.3%) in adenocarcinoma and SCC cases respectively. Bone was the commonest site of distant metastasis._x000D_ The independent prognostic factors of CSS , of all treated patients, on multivariate analysis were T stage (pT3-4 vs pT0-2) (HR 3, 95% CI 2.3-3.9, P < 0.0001), lymph node metastasis (HR 1.7, 95% CI 1.29-2.2, P <0.0001), lymphovascular invasion (HR 1.5, 95% CI 1.1-2, P = 0.001) and obstructive uropathy at presentation (HR 2.2, 95% CI 1.4- 3.4, P < 0.0001)._x000D_ Conclusions After radical cystectomy, distant tumor metastasis was more frequently observed in UC and its variant while local recurrence was more common in patients with SCC and adenocarcinoma. Funding non
Authors
Ahmed Mansour
Mahmoud Laymon Mohamed M. Elsaadany Ahmed Mosbah Shaaban AA Hassan Abol-enein |
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MP58-16 |
Oncologic Outcomes of Squamous Cell Carcinoma versus Urothelial Carcinoma with Squamous Differentiation after Radical Cystectomy for Muscle Invasive Bladder Cancer (MIBC) |
Bladder Cancer: Invasive V | 17BOS |
Abstract: MP58-16 Sources of Funding: non Introduction To compare clinicopathological characteristics and oncologic outcomes between patients treated with radical cystectomy for pure squamous cell carcinoma (SCC) and urothelial carcinoma with squamous differentiation (SqD). We also, aimed to identify predictors of cancer specific survival (CSS) for each histologic variant. Methods We reviewed data of 1737 consecutive patients treated with radical cystectomy between January 2004 till February 2014. _x000D_ A total of 318 and 223 patients were diagnosed with SCC and SqD respectively. Squamous differentiation was defined as intercellular bridges or keratinization in the tumor._x000D_ Kaplan-Meier survival curves were used to estimate CSS._x000D_ Results Patients’ demographics are illustrated in Table1. Patients with SqD were significantly more likely to have extravesical (58.3% vs 46.2%.p = 0.006) and nodal positive disease (34.5% vs 14.5%. p<0.0001) than SCC patients. Bilharzial eggs were found in 61% of SCC vs 46% of SqD (p=0.001)._x000D_ Median follow up period for SCC was 3.9 ( 0-12.4) versus 2 years (0-12) for SqD. During this period, 49 (15.4%) patients with SCC recurred locally and 20 (6.3%) recurred distally. Meanwhile, among SqD group 41 patients (18.4%) developed distant metastasis and 47 (21. 2%) experienced local recurrence. The estimated 5-year CSS was 77% and 59.8 % for SCC and SqD respectively (Fig.1) (Log rank <0.0001)._x000D_ _x000D_ In patients with SCC, Cox regression models identified higher T-stage (HR 2.3, 95% CI 1.3-3.9, P= 0.002) and preoperative anaemia (HR 1.7, 95% CI 1.035-2.8, P= 0.036) to be significantly associated with worse CSS. In patients with SqD, higher T-stage (HR 1.7, 95% CI 1.06-3, P= 0.028) and nodal metastasis (HR 2.2, 95% CI 1.3-3.5, P = 0.002) were associated with reduced CSS._x000D_ Conclusions Patient with SCC had better 5-year CSS in comparison to SqD. The higher rate of extravesical disease and lymph node metastasis in SqD patients is indicative of aggressive behavior of this histologic type. Funding non
Authors
Mahmoud Laymon
Ahmed Mansour Mohamed M. Elsaadany Ahmed Mosbah Shaaban AA Hassan Abol-enein |
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MP58-17 |
Prevalence of advanced bladder cancer in squamous cell vs. urothelial cell carcinoma- implications for differences in oncologic outcome |
Bladder Cancer: Invasive V | 17BOS |
Abstract: MP58-17 Sources of Funding: none Introduction Squamous cell carcinoma of the bladder (SCC) is the second most common histological subtype of bladder cancer after urothelial carcinoma (UC). We sought to compare clinical outcome and differences in staging between both subtypes. Methods In our institution, follow-up data of 714 patients with pure UC and 39 patients with pure SCC undergoing radical cystectomy (RC) between 2004 and 2015 is available. First, cancer-specific survival (CSS) was analyzed among both subtypes. As a second step, staging, grading and histological subtypes were compared in a multivariate Cox-regression analysis. Lastly, distribution of advanced disease (pT3-4, pN+, M1, G3) between UC and SCC was assessed. Results CSS of patients with SCC is significant worse compared to UC in a univariate analysis (p=0.032). In a multivariate analysis only T score pT<3 vs. pT3-4 (hazard ratio [HR] = 3.2; 95% CI: 2.3-4.5, p<0.001), N score pN0 vs. pN+ (HR = 2.0; 95% CI: 1.5-2.6, p<0.001) and M score M0 vs. M1 (HR = 2.8; 95% CI: 2.0-4.0 p<0.001) were significantly associated with CSS. There was no significant impact of grading G1-2 vs. G3 (HR = 1.2; 95% CI: 0.7-1.9 p<0.517) and histological subtype UC vs. SCC (HR = 1.4; 95% CI: 0.8-2.5 p<0.176) on CSS. Compared to UC, SCC presents with pT3-4 nearly twice as often (44% vs. 85%, p<0.001). High grade (G3) is more common in UC compared to SCC (89% vs. 64%, p<0.001). There is no significant difference between N score (UC 28% vs. SCC 29%, p=0.808) and M score (UC 11% vs. SCC 5%, p=0.262) between both bladder cancer subtypes. Conclusions Compared to UC, patients with SCC have a decreased CSS. The reason for this phenomenon may not lie within the histological subtype itself, but rather in a more progressive disease at the point of RC. This is reflected by the prevalence of pT3-4 stage, which is nearly twice as often in SCC compared to UC. Future studies concentrating on early detection of SCC should be encouraged in order to improve CSS of the latter bladder cancer entity. Funding none
Authors
Gerald Schulz
Tobias Grimm Alexander Buchner Friedrich Jokisch Markus Grabbert Birte-Swantje Schneevoigt Alexander Kretschmer Christian Stief Alexander Karl |
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MP58-18 |
Unreliability of Comparing Lymph Node Yields between Institutions |
Bladder Cancer: Invasive V | 17BOS |
Abstract: MP58-18 Sources of Funding: None Introduction Lymph node yield after cystectomy has been proposed as a quality measure for surgeons, but multiple factors beyond surgeon ability are known to impact node count. We previously demonstrated no difference in nodal yield between open and robotic cystectomy (RC) at a single, high-volume academic institution. We now assessed whether institutional variations in specimen processing can impact nodal yield following RC, as has been shown with open surgery, since this could help explain wide variations in yields between institutions performing RC even with similar templates. Methods Consecutive robotic cystectomy procedures performed by a single surgeon with the same assistant were retrospectively reviewed. All procedures were performed with an identical technique and extended template but at two different hospitals including one high-volume academic center with a standardized protocol for node assessment (site A) and one low-volume community hospital (site B). Nodes were dissected en bloc and submitted as no more than one or two specimens. Results A total of 57 procedures were performed at site A and 44 at site B. Neoadjuvant chemotherapy was given in 40% of site A and 27% of site B patients (p=0.04). Mean body mass index was 29kg/m^2 at site A and 27kg/m^2 at site B (p=0.09). Despite an identical surgical team, technique, and template, a significant difference in mean node count was identified between the two hospitals with a mean of 34 nodes (range 10-67) at site A and 22 nodes (range 7-40) at site B (p<0.01). There was no difference in the proportion of patients found to have involved lymph nodes on pathologic examination at 32% and 32%, respectively (p=0.73). There was also no difference in the mean number of involved nodes identified per patient in those with metastasis (4 vs 6, p=0.47). Conclusions Variations in nodal yield with RC can be related to differences in institutional handling of nodal specimens. The wide differences in node counts between surgeons performing RC with similar templates may depend more on variations in their pathology departments rather than surgeon ability. This has implications for using nodal yield as a surrogate for the quality of surgery and for comparing node counts between surgeons or between open and robotic surgery at different institutions. Funding None
Authors
Ronney Abaza
Janice Rosenthal Jatin Gupta |
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MP58-19 |
Surgical treatment for clinical node positive bladder cancer patients treated with radical cystectomy |
Bladder Cancer: Invasive V | 17BOS |
Abstract: MP58-19 Sources of Funding: none Introduction Survival expectancies is poor for bladder cancer (BCa) patients with disseminated disease. On the other hand, several reports showed that patients with survival in node positive patients treated with radical cystectomy (RC) is not invariably poor. However, at the time only scarce data exists about the efficacy of surgery in clinical node positive BCa patients with a limited disseminated disease. Methods We evaluated a total of 192 patients with BCa and concurrent node positive disease in the pelvis. All patients were treated with RC and pelvic lymph node dissection (PLND) without neoadjuvant chemotherapy between 2001 and 2013. Adjuvant chemotherapy was offered to patients on the bases of their characteristics and physicians preferences. We analyzed concordance between clinical and pathological findings. Moreover, Kaplan Meier analyses and Cox regression analyses were used to assess the impact of this features on recurrence, cancer specific survival (CSS) and overall survival (OS) after surgery. Results With a median follow up of 48 months, we recorded 5 year recurrence, CSS and OS of 46%, 44% and 38%, respectively. Overall, 99 patients (51.6%) where found without node metastases at RC, while 18 (9.4%), 58 (30.2%) and 17 (8.9%) patients were found pN1, pN2 and pN3, respectively. 5 year CSS survival rates were 54%, 42%, 32% and 18% for pN0, pN1, pN2 and pN3, respectively. Overall, 36 (18.8%) patients were treated with adjuvant chemotherapy. At univariable Cox regression analyses, the use of adjuvant chemotherapy was not associated with improved recurrence, CSS and OS after RC (all p>0.2). On the other hand, when only pN+ patients were considered,_x000D_ adjuvant chemotherapy was associated with improved OS (Hazard ratio [HR]: 0.42, confidence interval [CI]: 0.20-0.86, p=0.02). Conclusions We report excellent survival outcomes in clinical node positive patients treated with RC. The use of adjuvant chemotherapy_x000D_ after surgery was not associated with improvement in survival expectancies in cN+ patients, on the other hand, when only pN+ patients were considered adjuvant chemotherapy showed increased overall survival expectations. Our data needs to be further evaluated in high quality prospective study. Funding none
Authors
Marco Moschini
Andrea Gallina Giovanni La Croce Ettore Di Trapani Giusy Burgio Agostino Mattei Shahrokh Shariat Rocco Damiano Vincenzo Mirone Andrea Salonia Alberto Briganti Francesco Montorsi Renzo Colombo |
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MP58-20 |
Pattern of positive node metastases in patients treated with extended and super extended pelvic lymph node dissection and radical cystecotmy due to bladder cancer |
Bladder Cancer: Invasive V | 17BOS |
Abstract: MP58-20 Sources of Funding: none Introduction Pelvic lymph node dissection (PLND) has a foundamental role during radical cystectomy (RC) in bladder cancer (Bca) patients. Some series reported the absence of sentinel lymph node in Bca patients, on the other hand, at the time no data supports the use of extended PLND since the data available from the randomized trial on this topic failed to assess significant survival benefit for patients treated with ePLND when compared patients trated with limited PLND. Therefore we sought to describe incidence and location of node metastases in patients treated with extended and super extended PLND highlighting its association with adverse pathologic features. Methods we evaluated 653 contemporary patients with clinically non metastatic BCa treated with RC and extended or super extended pelvic lymph node dissection (PLND) at a single tertiary care referral center between 1990 and 2013. Limited PLND is defined as the removal of obturator and internal illiac nodes. Standard included also the external illiac nodes. Extended includes also common and presacral nodes. Finally super extended PLND includes all the nodes removed within inferior mesenteric artery. We evaluated incidence of pathologycaly node metastases. Moreover we describe the location of the metastases and its association with other pathologic adverse_x000D_ features. Results Overall, 191 (29.3%) patients were found with pathologically node confirmed metastases. Of these, 57 (29.5%) patients were_x000D_ found with a single node metastases, while 136 (70.5%) had multiple node metastases. The vast majority of patients were found with node metastases in limited and standard templates only (n=150, 23.0%), on the other hand 43 (6.6%) patients had node metastases in the extended and super extended PLND template. Only 2 patients were found with node metastases in the extended or superextended PLND template without having concomitant node metastases in the standard template. The presence of node metastases in the extendeed or super extended PLND was found higher in pT3-pT4 patients (n=40, 93.0%) when compared to pT0-pT2 patients (n=3, 7.0%) patients (p value<0.001). On the other hand, no difference were found considering lymphovascular invasion (p=0.4), presence of carcinoma in situ (p=0.3), age (p=0.7) or gender (p=0.6). Conclusions We found that the majority of patients harbored node disease in the limited or standard node dissection pattern. On the other hand only a minority of patient were found with a disease in extended or super extended template without harboring a concomitant node disease in the limited pattern. Considering demographics and pathological features, only pT3-pT4 disease were associated with an increased risk of node metastases in the extended and superextended template. Funding none
Authors
Marco Moschini
Renzo Colombo Nazareno Suardi Giusy Burgio Marco Bandini Emanuele Zaffuto Rocco Damiano Agostino Mattei Vincenzo Mirone Shahrokh Shariat Alberto Briganti Francesco Montorsi Renzo Colombo |
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MP59-01 |
Is retro the way forward? Retroperitoneal robotic-assisted partial nephrectomy: Single institution experience. |
Kidney Cancer: Localized: Surgical Therapy IV | 17BOS |
Abstract: MP59-01 Sources of Funding: none Introduction The majority of robotic-assisted renal surgery is performed via the transperitoneal route (T). Retroperitoneal robotic-assisted partial nephrectomy (R-RAPN) allows direct access to hilar structures and the posterolateral surface of the kidney. In the few comparative studies published, it has shown potential advantages. We review our institution's experience with RAPN. Methods Data from all consecutive patients who underwent RAPN at our single institution between June 2010 and October 2016 were prospectively collected. Demographics, R.E.N.A.L. nephrometry score, and perioperative outcomes were evaluated and comparisons between R-RAPN and T-RAPN were made. Results 258 patients (119 male, 139 female) underwent RAPN (232 R-RAPN vs 26 T-RAPN). The mean age was 59.7 vs 55.9 (SD±11.9 vs 8.9), mean body mass index was 28.9kg/m2 vs 29.0 (SD±5.5 vs 5.3), and median ASA was 2 (range 1-4 vs 1-3). The mean nephrometry score was 6.1 vs 6.5 (SD±1.7 vs 1.5), tumour size 30.6mm vs 26.8 (SD±12.7 vs 9.8), estimated blood loss 78.9mL vs 116.6 (SD±244.7 vs 178.4), and warm ischaemia time 20.4 minutes vs 20.0 (SD±6.9 vs 6.4). The mean operative time was 130 minutes vs 168 (SD±35.6 vs 32.2) [p<0.05] with a median hospital stay of a single overnight stay vs two. 1.7% patients required blood transfusions in the R-RAPN vs 3.8%. 1.3% cases were converted to robotic-assisted radical nephrectomy in the R-RAPN group vs 3.8% in the T-RAPN group and two cases were converted to open partial nephrectomy in the R-RAPN group. The rate of Clavien III or higher was 1.7% vs 3.8%. There were no renal cancer-related mortalities in this series. Conclusions The current series represents the largest single-institution series on R-RAPN, which accounts for 90% of our robotic partial nephrectomy experience. The retroperitoneal route allows direct access to the renal hilum with no requirement for bowel mobilisation. This approach has been shown to decrease operative times, opiate requirement, and allows for quicker return of bowel function. Furthermore, there does not appear to be any increase in perioperative complications using this approach. R-RAPN is an effective alternative to T-RAPN and can be safely and successfully applied to the majority of patients with tumours amenable to nephron preservation. Funding none
Authors
Muddassar Hussain
Joanne Oakley Georg Muller Amr Emara Neil Barber |
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MP59-02 |
Analysis of the impact of assistant surgeon experience on peri?operative outcomes of robotic partial nephrectomy |
Kidney Cancer: Localized: Surgical Therapy IV | 17BOS |
Abstract: MP59-02 Sources of Funding: none Introduction The surgical robot offers three-dimensional vision, tremor filtering, improved dexterity, increased visualization and an ergonomic setting to enhance surgeon comfort and precision. However, the surgeon is physically separated from the patient. As a result, it necessarily mandated the presence of an assistant surgeon who ensures the smooth running of the intervention. This current study aimed to investigate the impact of the assistant surgeon’ s experience on peri-operative outcomes of robotic partial nephrectomy (RPN)._x000D_ Methods We performed a retrospective analysis of 221 patients who underwent RPN for a small renal tumour at a single institution. All RPN were performed by two experienced surgeons. Patients were divided into two groups according to the level of experience of the assistant surgeon. A junior level assistant was defined as a resident in his/her three first post-graduate years (PGY)(junior group). Senior-level assistant was defined as a resident in its fourth or fifth post-graduate year (senior group). Peri-operative parameters were compared between the two groups. Multivariate analyses were performed using linear and logistic regression models to seek for predictors of main perioperative outcomes._x000D_ Results There were 106 RPN involving a junior assistant and 115 RPN involving a senior assistant. The patients characteristics were comparable in both groups. Operative time (OT) and length of stay were longer in the junior group (165 vs. 146 min; p < 0.003, 5.3 vs. 4.2; p = 0.04 respectively). Junior group was associated with an increased risk of positive surgical margin (9% vs 2%; p=0.03). There were not statistically significant differences regarding blood loss (386 vs 417 ml;p=0.73), warm ischemia time (16.4 vs 15.8 min;p=0.29) and risk of conversion to an open approach (3.7 vs 6.7%;p=0.37) between junior and senior groups. The incidence of post-operative complications was comparable between the two groups (11.3 vs 6%; p=0.35). In multivariable analysis that adjusted for the effect of tumour complexity, tumour size, ASA classification and anticoagulant therapy, junior group was significantly associated with a longer OT ([beta]=0,23;p=0,001), positive surgical margin rates (OR=10.8;p=0.009) and length of stay ([beta]=0,13;p=0,05)_x000D_ Conclusions The results of the present study suggest that the experience of the assistant surgeon influences the peri-operative outcomes of robotic partial nephrectomy, notably operative time and positive surgical margins rate._x000D_ Funding none
Authors
Zine-Eddine KHENE
Benoit Peyronnet Elise Bosquet Benjamin Pradère Gregory Verhoest Romain Mathieu Solène-Florence Kammerer-Jacquet Nathalie Rioux-Leclercq Karim Bensalah |
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MP59-03 |
May robot-assisted partial nephrectomy be taught to fellows without affecting perioperative outcomes? |
Kidney Cancer: Localized: Surgical Therapy IV | 17BOS |
Abstract: MP59-03 Sources of Funding: none Introduction Surgical teaching may potentially influence patient care. A safe, high-quality surgery practice requires dedicated and specialized training commonly acquired during a fellowship. The purpose of this study was to determine whether robot-assisted partial nephrectomy (RAPN) may be taught to fellows without influencing operative outcomes. Methods We analyzed 276 patients who underwent RAPN for a small renal tumour. We stratified our cohort in two groups according to the involvement or not of a surgeon in training during the procedure: expert surgeon operating alone (expert group) or surgeon in training operating under the supervision of the expert surgeon (fellow group). Patients who underwent RAPN during the early learning curve of the expert surgeon (first 60 NPRA) were excluded. Peri-operative data were compared between the two groups. Linear and logistic regression analyses were performed to assess the impact of fellows involvement on perioperative and postoperative outcomes. _x000D_ Results Fellows were involved in a total of 89 procedures (41 %) and 127 (59 %) of cases were done by the expert surgeon alone. The patients characteristics were comparable in both groups. Operative time (OT) and warm ischemia time (WIT) were longer in the fellow group (188.2 vs. 129.9 min; p < 0.001, and 17.7 vs. 14.8 min; p<0.001, respectively) as was LOS (5 vs. 4.3; p = 0.05). Patients in the fellow group had a higher blood loss (491.8 vs.409.6 ml ; p = 0.01) but this had no impact on the transfusion rate (14 vs. 11%; p =0.43). Positive surgical margin rates were similar between expert and fellow groups (6.9 vs. 5.8%; p = 0.78). The major complications rate was higher in the fellow group (12%) but this difference did not reach statistical significance (p= 0.12). In multivariable analysis, fellow involvement was predictive of increased WIT ([beta]=0.21;p<0.004) and OT ([beta]=0.49;p<0.0001) but was not associated with LOS ([beta]=0.12, p=0.11). Conclusions Fellows involvement in RAPN is associated with increased OT and WIT. However, it does not adversely affect complication rates or surgical margins._x000D_ Funding none
Authors
Zine-Eddine KHENE
Benoit Peyronnet Elise Bosquet Benjamin Pradère Gregory Verhoest Romain Mathieu Solène-Florence Kammerer-Jacquet Nathalie Rioux-Leclercq Karim Bensalah |
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MP59-04 |
Conversion of Robotic Partial to Radical Nephrectomy; a Prospective Multi-Institutional Study |
Kidney Cancer: Localized: Surgical Therapy IV | 17BOS |
Abstract: MP59-04 Sources of Funding: None Introduction Robot-assisted partial nephrectomy (RAPN) has become a standard approach for small renal masses. Studies about RAPN are mostly retrospective and do not comprehensively capture factors and rates of scheduled RAPN that end with conversion to robotic radical nephrectomy (RRN). We describe the rate as well as patient and tumor characteristics for RAPN cases that convert to RRN using a multi-institutional prospective database. Methods We prospectively identified 430 patients who underwent attempted RAPN between 2014 and 2016 at multiple international centers as part of the Vattikuti Collaborative Quality Initiative (VCQI) database. These patients were permanently logged for RAPN prior to the date of surgery and remained in the prospective database regardless of whether intraoperative conversion to RRN was performed. Results 5.3% (23 of 430 patients) of scheduled RAPN cases ended with RRN. Patients converted to RRN were older (mean age 64.3 vs. 59.1, p=0.01) with more comorbidities (mean Charlson age-adjusted comorbidity score 5.57 vs. 4.23, p=0.003) but had a similar pre-operative eGFR (70.7 to 79.2; p=0.09). Patients converted to RRN were more likely to have a tumor size >4cm (47.8% to 32.3%, p=0.05), an upper pole location (52.2% vs. 31.7%, p=0.04), a RENAL nephrometry score between 10-12 (30.4% vs. 11.5%, p=0.03), a higher mean RENAL nephrometry score (8.17 vs. 7.16, p=0.01), and intraoperative complications (30.4% vs. 3.9%, p=<0.0001). On pathological examination, patients converted to RRN were more likely to have invasion of perirenal fat (21.7% vs. 3.5%, p<0.0001), sinus fat (8.7% vs. 0.7%, p=0.0006), Gerota's fascia (4.8% vs. 0.5%, p=0.03), and involvement of segmental renal vein branches (14.3% vs. 0.5%, p<0.0001). Conclusions Prospective data collection of intended RAPN increases the detection of conversions to RRN. Our data suggests that difficult cases are initially attempted as RAPN, and the decision to perform RRN may be in part determined by tumor characteristics and patient comorbidities. Patients converted to RRN were more likely to have comorbidities, complex tumors, intraoperative complications, and poor pathologic features. Funding None
Authors
Brian Chun
Deepansh Dalela Mouafak Tourojman Ronney Abaza Rajesh Ahlewat James Adshead Benjamin Challacombe Prokar Dasgupta Daniel Moon Giacomo Novara Francesco Porpiglia Mahendra Bhandari Alexander Mottrie Craig Rogers |
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MP59-05 |
Critical analysis and assessment of clinical utility of nephrometry scores for the prediction of complications after nephron sparing surgery |
Kidney Cancer: Localized: Surgical Therapy IV | 17BOS |
Abstract: MP59-05 Sources of Funding: none Introduction Despite the association between nephrometry scores and the risk of complications following nephron sparing surgery [NSS] is established, data regarding predictive accuracy [PA] and clinical net-benefit [NB] of nephrometry scores-based prognostication are scarce. The aim of the study was to perform a head-to-head comparison of PADUA score-, RENAL score- and clinical tumour size-based prognostication of complications following NSS. Methods 214 patients diagnosed with a cT1-2 cN0 cM0 renal mass elected for NSS and collected into a prospective database were assessed. The outcomes of the study were overall and Clavien-Dindo [CD] grade ≥2 complication rates. Logistic regression analyses predicting overall and CD grade ≥2 complications were fitted. PA was estimated with C index. NB was evaluated with decision curve analysis. Results The overall complications rate was 36%. The CD grade ≥2 complications rate was 20%. The most common specific complication was anemia/haematoma. At logistic regression analysis, PADUA score resulted associated with higher risk of overall complications rate (Odds ratio [OR] 1.24; 95% Confidence intervals [CI] 1.03-1.50; p=0.03). Conversely, RENAL score (OR 1.16; CI 0.95-1.41; p=0.1) and clinical tumour size were not associated with the risk of overall complications (OR 1.21; CI 0.99-1.47; p=0.058). Moreover, PADUA score, RENAL score and clinical tumour size were not associated with the risk of CD grade ≥2 complications (p>0.05). Harrel&[prime]s C index resulted 0.59 for PADUA score-, 0.57 for RENAL score- and 0.59 for clinical tumour size-based prediction. At decision curve analysis, the recorded NB was consistently low regardless of the prediction strategy (Figure 1). Conclusions PADUA and RENAL score were not associated with the risk of clinically relevant complications after NSS. Moreover, their ability to predict complications is diagnostically inadequate. Neither PADUA nor RENAL score were superior to the use of clinical tumour size only with respect to PA or NB. These findings suggest that, despite PADUA and RENAL scores represent accurate classification systems for the anatomic complexity of renal tumours, none of them is an optimal predictor of clinical outcomes. Funding none
Authors
Alessandro Larcher
Fabio Muttin Nicola Fossati Paolo Dell’Oglio Francesco Ripa Francesco Trevisani Alexandre Mottrie Zachary Hamilton Ithaar Derweesh Andrea Salonia Alberto Briganti Francesco Montorsi Roberto Bertini Umberto Capitanio |
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MP59-06 |
Analysis of predictive factors associated with prolonged operative time during robot-assisted partial nephrectomy |
Kidney Cancer: Localized: Surgical Therapy IV | 17BOS |
Abstract: MP59-06 Sources of Funding: none Introduction During robot-assisted partial nephrectomy (RAPN), surgeons often face difficulty exposing the renal hilum and tumor before tumor resection and renorrhaphy. Consequently, operative time may be prolonged. In the present study, we aimed to identify the predictive factors associated with prolonged operative time for RAPN. Methods Patients who underwent transperitoneal RAPN for renal tumor at our institution between 2012 and 2015 were retrospectively analyzed. Early cases managed after the adoption of the da Vinci surgical system were excluded. Multivariate regression analysis was used to test associations between prolonged operative time (>150 min) and perioperative factors. Results In total, 297 patients were included in this study; however, 95 early cases were excluded. RAPN was performed by 3 experienced surgeons using an early unclamping technique. The median operative time was 132 min (interquartile range, 109–155 min) and operative time was prolonged in 62 cases. The cohort of patients with prolonged operative time (prolonged group) was significantly older (P=0.0018), had a higher male–female ratio (P=0.02), and had higher BMI (P=0.0093) than the group with shorter operative times (standard group). In addition, the tumor was also more likely to be larger (P=0.025), on the left side (P=0.005), and posteriorly positioned (P=0.03). Furthermore, the RENAL nephrometry score was likely to be higher for the prolonged group compared with the standard group. Moreover, warm ischemia time was longer (21 vs. 16 min; P<0.0001) and postoperative decrease in renal function (3 months) was greater (–9.0 vs. –4.7%; P=0.038) for the prolonged group than for the standard group. Multivariate analysis indicated that age (odds ratio [OR], 1.04; P=0.0015), BMI (OR, 1.12; P=0.013), left-sidedness (OR, 3.21; P=0.0007), posterior position (OR, 2.47; P=0.016), and high RENAL score (OR, 3.39; P=0.012) were significantly associated with prolonged operative time. Conclusions In addition to tumor complexity, age, BMI, and left-sidedness are predictive of prolonged operative times for RAPN. These factors may contribute to the difficulty exposing the renal hilum and renal tumor. Further investigation of the time spent during each part of the procedure is indicated. Funding none
Authors
Hidekazu Tachibana
Toshio Takagi Tsunenori Kondo Kazunari Tanabe |
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MP59-07 |
Post-operative complications increase the risk of chronic kidney disease after elective nephron sparing surgery |
Kidney Cancer: Localized: Surgical Therapy IV | 17BOS |
Abstract: MP59-07 Sources of Funding: none Introduction Complications following nephron sparing surgery might stress renal function with multiple mechanisms. However, information regarding a detrimental effect of post-operative complications following nephron sparing surgery [NSS] on long term renal function is scarce. The aim of the study was to investigate the impact of post-operative complications on the long-term risk of chronic kidney disease [CKD] after NSS. Methods 595 patients with estimated glomerular filtration rates [eGFR] ≥60 ml/min/1.73m2 diagnosed with a cT1 cN0 cM0 renal mass and elected for NSS were assessed in a prospective institutional database. Cox regression models were fitted to estimate hazard ratios [HR] and 95% confidence intervals [CI] for CKD defined as estimated glomerular filtration rates <60 ml/min/1.73m2. The variable of interest was any postoperative complication, defined according to the Clavien-Dindo classification system. Covariates included age, Charlson comorbidity index [CCI], hypertension, diabetes, tumour size, ischemia time, and preoperative eGFR. Results Mean patient age was 59 years (Inter-quartile range [IQR] 50-67). Median clinical tumour size was 3 cm (IQR 2-4). Median ischemia time was 15 minutes (IQR 9-20). Forty-eight (8%) patients had diabetes, 236 (40%) had hypertension, 23 (4%) had uncontrolled hypertension. Median follow-up was 53 months (IQR 26-91). Overall, 118 (20%) developed grade 1-2 and 19 (3%) grade 3-4 complications. The most common complication was anaemia/haematoma (9%). No difference was recorded between patients with or without post-operative complications with respect to age, comorbidities, tumour size and ischemia time (all p >0.05). Overall, 142 patients (24%) developed any grade of CKD during the follow-up period. Patients experiencing either grade 1-2 (HR 1.74; CI 1.11-2.72; p=0.02) or grade 3-4 complications (HR 2.52; CI 1.20-5.30; p=0.01) were at increased risk of developing CKD during the follow up at multivariate analysis, after accounting for the aforementioned covariates. Conclusions Our findings outline how post-operative complications may have a detrimental impact on post-operative renal function in men submitted to NSS. Efforts aiming at limiting the occurrence of post-operative complications might be advantageous for reducing the rate of long-term CKD. Moreover, those patients who experienced a complication deserve a more stringent functional follow-up after NSS. Funding none
Authors
Eugenio Ventimiglia
Alessandro Larcher Fabio Muttin Paolo Dell'Oglio Nini Alessandro Francesco Ripa Francesco Trevisani Cristina Carenzi Ithaar Derweesh Zachary Hamilton Federico Dehò Andrea Salonia Francesco Montorsi Roberto Bertini Umberto Capitanio |
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MP59-08 |
External validation of renal tumour Contact Surface Area (CSA) in patients who underwent Partial Nephrectomy |
Kidney Cancer: Localized: Surgical Therapy IV | 17BOS |
Abstract: MP59-08 Sources of Funding: None Introduction The renal tumour Contact Surface Area has been recently proposed to predict perioperative outcomes in patients who underwent partial nephrectomy. However, until now no study performed an external validation of this system. The aim of this study was to test the role of CSA to predict intraoperative and postoperative parameters in a series of consecutive patients who underwent PN. Methods We prospectively evaluated the clinical and pathological records of 81 consecutive patients who underwent open PN at our Institution between July 2013 and July 2016. All the clinical and pathological records are collected in a dedicated database. The CSA was calculated using the preoperative abdominal CT scan images and applying the formula recently described by Leslie et al [Eur. Urol. 2014; 66: 884]. Then, this continuous variable was categorized in two groups according to the predefined 20 cm2 cut-off value. The following outcomes were considered: clamping of the renal artery, early unclamping technique, warm ischemia time (WIT), estimated blood loss (EBL), overall postoperative complications. ROC curve analyses were used to compare PADUA score and CSA. Results The median value of CSA was 13.6 (IQR 8-23.6) cm2. In 23 (28.3%) cases a no clamp technique was performed. In the remaining 58 (71.6%) cases the median warm ischemia time was 13 min. An early unclamping technique was performed in 41/81 (50.6%). The median EBL was 300 ml. Overall postoperative complications were detected in 27/81 (33.3%) cases. However, major complications (grade 3-4) were reported only in 6 (7.4%) cases. The CSA predicted the clamping of the main artery (p=0.001), the use of an early unclamping technique (p=0.005), the WIT (p<0.0001), the EBL (p<0.001), the overall postoperative complications (p=0.002). PADUA score and CSA resulted overlapping to predict clamp versus no clamp technique (AUC 0.84 Vs 0.84) and overall complications (AUC 0.68 Vs 0.68). Conversely, CSA resulted better than PADUA score to predict WIT > 20 min (AUC 0.77 Vs 0.63). Conclusions The renal tumour CSA seems to be a valid predictor of postoperative PN outcomes. Its role must be confirmed in larger series. Moreover, CSA seems to give information similar to PADUA score. Contact surface area seems to be a valid predictor of postoperative outcomes after partial nephrectomy. Funding None
Authors
Marta Rossanese
Valeria Lami Fabio Zattoni Alessandro Crestani Barbara Grossetti Gianluca Giannarini Vincenzo Ficarra |
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MP59-09 |
Functional change of contralateral kidney after partial nephrectomy using diethylene triamine penta?acetic acid (DTPA) renal scintigraphy: long term analysis |
Kidney Cancer: Localized: Surgical Therapy IV | 17BOS |
Abstract: MP59-09 Sources of Funding: none Introduction Partial nephrectomy aims to maintain renal function by nephron sparing. However, the functional change of contralateral kidney remains to be known. We evaluated the functional change in contralateral kidney using DTPA renal scan and determined the predicting factors of contralateral kidney function after partial nephrectomy. Methods From 2001 to 2012, 699 patients underwent partial nephrectomy and we performed DTPA renal scan before and after surgery in all patients to assess the exact renal function of each kidney. Patients were divided into 3 groups according to initial contralateral glomerular filtration rate (GFR) (group 1: <30ml/min/1.73m2, group 2: 30~45ml/min/1.73m2, and group 3: ≥45ml/min/1.73m2). We evaluated separate renal functions using DTPA up to 5 year after surgery. Logistic regression analysis was used to identify the factors associated with increased GFR of contralateral kidney. Kaplan-Meier method was used for overall survival. Median follow-up period was 45.1 month. Results Patients of group 1 were older age (64.2±9.8 vs 55.0±11.0 vs 48.0±9.5, p<0.001), more hypertension history (59.5% vs 39.3% vs 20.9%, p<0.001), worse American society of anesthesiologists (ASA) score (≥2; 94.0% vs 89.5% vs 80.2%, p<0.001), and shorter ischemic time (19.9±8.0 vs 22.3±8.7 vs 22.8±8.9, p=0.025) among three groups (respectively). Tumor size, resected weight, RENAL nephrometry score and ischemic type were not different among three groups (p=0.293, p=0.255, p=0.582 and p=0.967, respectively). The mean ipsilateral GFR changes were -7.5%, -1.6%, and -21.2% in group 1, 2, and 3, respectively and contralateral GFR changes were 33.9%, 19.9%, and 7.3% in group 1, 2, and 3, respectively at 5 year after partial nephrectomy. On multivariable analysis, ASA score (OR 0.54, 95% confidence interval [CI] 0.31-0.92 p=0.0277) and preoperative contralateral GFR (OR 0.97, 95% CI 0.95-0.99 p=0.0011) were the significant predictive factors for increased GFR of contralateral kidney within 5 years. 5 year overall survival rates were 86.1%, 93.1% and 97.4% in group 1, 2, 3, respectively. Conclusions Contralateral kidney compensated for the functional loss of ipsilateral kidney. The increase of GFR in contralateral kidney is more prominent in healthy patients with decreased contralateral renal function. Funding none
Authors
Se Young Choi
Jeman Ryu Jae Hyeon Han Wonchul Lee Han Kyu Chae Sangjun Yoo Dalsan You In Gab Jeong Cheryn Song Bumsik Hong Hanjong Ahn Choung-Soo Kim |
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MP59-10 |
Evaluating kidney volume loss after partial nephrectomy: comparing immediate postoperative to 6month volume loss using three-dimensional modeling |
Kidney Cancer: Localized: Surgical Therapy IV | 17BOS |
Abstract: MP59-10 Sources of Funding: none Introduction Renal volume losses near 20% are seen following partial nephrectomy for small renal masses despite minimizing resection margins to <1cm and ischemia time to <20minutes. The time course of volume loss is not well understood as immediate postoperative imaging is rarely obtained. This study compares volume loss immediately after surgery (day 3-4) to 4-6months after surgery._x000D_ Methods Patients undergoing robotic partial nephrectomy for small renal masses with available imaging were included. Those with tumors <2cm or requiring postoperative embolization were excluded. Computed tomography (CT) imaging was available at three time points: preoperatively, post-operative day 3 or 4, and 4-6months. The post-operative day 3 or 4 scan was obtained prospectively to assess for asymptomatic pseudoaneurysms. A running base-layer and sliding clip cortical renorrhaphy were used. Philips Intellispace Portal was used to construct three-dimensional models of the operated kidneys using slice-by-slice semi-automatic segmentation. Manual exclusion of tumor volume and hilar structures was performed. Stata 13.1 was used to perform descriptive statistics and the Mann-Whitney U-test to compare volume losses._x000D_ Results Twenty-three patients between January 2013 and March 2015 met criteria and were included. The median (IQR) age, BMI, and tumor diameter were 55years (41-62), 24.8kg/m2 (23-27), and 2.6cm (2.4-3.6), respectively. The nephrometry score median (IQR) was 6 (6-8). The percent male gender was 78%, and 61% were right sided. The operative time, warm ischemia time, and estimated blood loss were 178minutes (171-218), 20minutes (17-27), and 50mL (10-100). All tumors were renal cell carcinoma and had negative margins. There was one urine leak that did not require intervention. The preoperative, 3day, and 6month mean (SD) volumes for the operated kidney were 153.4cm3, (24), 149.6cm3 (24), and 127.4cm3 (25). The mean percent volume loss at 3days was 2.3% and at 6months was 14.6% (p-value < 0.0001). Conclusions The majority of volume loss after partial nephrectomy was not detected in the immediate postoperative period, but was seen by 4months. This supports the hypothesis of delayed atrophy from ischemia or reconstructive injury._x000D_ Funding none
Authors
Clinton Bahler
Chandru Sundaram Tsunenori Kondo |
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MP59-11 |
Clinical application of calculated split renal volume using computed tomography-based renal volumetry after partial nephrectomy: correlation with 99mTc-DMSA renal scan data |
Kidney Cancer: Localized: Surgical Therapy IV | 17BOS |
Abstract: MP59-11 Sources of Funding: None Introduction To evaluate the clinical application of computed tomography (CT)-based measurement of renal cortical volume (RCV) and split renal volume (SRV) as a single tool to assess the anatomy and renal function in patients with renal tumors before and after partial nephrectomy, and compare the findings with 99mTc-DMSA renal scan. Methods The data of 51 patients with a unilateral renal tumor managed by partial nephrectomy were retrospectively analyzed. The RCV of tumor-bearing and contralateral kidneys was measured using ImageJ software. Split estimated glomerular filtration rate (eGFR) and SRV calculated using this RCV were compared with the split renal function (SRF) measured with 99mTc-DMSA renal scan. Results A strong correlation between SRF and SRV of the tumor-bearing kidney was observed before and after surgery (r = 0.89, p < 0.001 and r = 0.94, p < 0.001). The preoperative and postoperative split eGRF of the operated kidney showed moderate correlation with SRF (r = 0.39, p = 0.004 and r = 0.49, p < 0.001). Correlation between reductions in SRF and SRV of the operated kidney (r = 0.87, p < 0.001) was stronger than that between SRF and percent reduction in split eGFR (r = 0.64, p < 0.001). Conclusions Compared with split eGFR, the SRV calculated using CT-based renal volumetry has a strong correlation with the SRF measured using 99mTc-DMSA renal scan. CT-based SRV measurement before and after partial nephrectomy can be used as a single modality for anatomical and functional assessment of the tumor-bearing kidney. Funding None
Authors
Chan Ho Lee
Ja Yoon Ku Hong Koo Ha |
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MP59-12 |
Validation of a mathematical model to predict renal function after nephron sparing surgery |
Kidney Cancer: Localized: Surgical Therapy IV | 17BOS |
Abstract: MP59-12 Sources of Funding: none Introduction Several nephrometry scores have been published in recent years for the purpose of standardizing the anatomy of renal tumors. The most common is the RENAL nephrometry score (NS) that has been associated with peri-operative outcomes. The association of NS with post-operative renal function is still unclear. Recently the concept of Contact Surface Area (CSA) has been introduced and shown to correlate with post-operative renal function. Our aim was to validate CSA as a predictive tool for renal function after nephron sparing surgery (NSS). Methods The study included all patients who were diagnosed with renal cell carcinoma and underwent NSS at our institute between 1998 and 2014. Patients without renal function, adequate cross sectional imaging or NS information were excluded. CSA was calculated based on abdominal computerized tomography or magnetic resonance imaging using the formula developed by Hsieh et al (The Journal of urology;196(1):33-40). eGFR was calculated using the most recent pre-operative and last follow-up creatinine. The correlation between CSA and NS, absolute and percent change in eGFR (ACE and PCE respectively) was examined by spearman correlation coefficient (SCC). Linear regression model was fitted to examine the association of NS and CSA with ACE and PCE. ROC curve analysis was performed to examine CSA and NS ability to predict more than 10% loss in renal function. Results 234 patients underwent NSS and had sufficient renal function, NS information and adequate imaging to assess CSA (all between 2005-2014). Mean (SD) CSA was 35.3 (52.1) cm2 and median (IQR) NS was 9 (7-10). Median follow-up was 55 months (IQR 37-78). CSA was significantly correlated with NS (SCC 0.727, p<0.001). Furthermore, CSA was significantly correlated with ACE and PCE (SCC -0.97 and -0.95 respectively, p<0.001). Both CSA and RS independently affected change in renal function on multivariable analysis (p<0.001). However, CSA better predicted 10% renal function decline compared with NS on ROC curve analysis (figure, AUC 0.93 vs 0.83). Conclusions CSA is significantly correlated with NS. Both CSA and NS are significantly correlated with renal function change after NSS. However, CSA is a better predictor of renal function decline compared to RS._x000D_ Funding none
Authors
Miki Haifler
Andrew Higgins Benjamin Ristau Andres Correa shreyas Joshi Richard Greenberg David Chen Alexander Kutikov Rosalia Viterbo Amnon Zisman Robert Uzzo |
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MP59-13 |
A useful method for assessing differences of compensatory hypertrophy in the contralateral kidney before and after radical nephrectomy in patients with renal cell carcinoma: Ellipsoid formula on computed tomography |
Kidney Cancer: Localized: Surgical Therapy IV | 17BOS |
Abstract: MP59-13 Sources of Funding: none Introduction To investigate the impact of tumor size and the usefulness of the ellipsoid formula for assessing compensatory hypertrophy of the contralateral kidney on preoperative and postoperative computed tomography in renal cell carcinoma(RCC) patients. Methods We retrospectively identified 389 patients who had radical nephrectomy for RCC between 2011 and 2015. Contrast-enhanced CT was performed within three months preoperative and at 1 year postoperative. The kidney volumes were calculated from CT images using the ellipsoid formula(volume = length x thickness x width x π/6). We subdivided patients into three groups based on tumor size(A: ?4cm, B: 4-7cm, C: >7cm). Volumetric renal parameters were compared and multivariate linear regression analyses were performed to determine predictors associated with preoperative and postoperative compensatory hypertrophy. Results Kidney volume measurements using the ellipsoid method took a median of 51 seconds. Group C had a significantly larger median preoperative contralateral renal volume than groups A and B(A: 140.4, B: 141.6, C: 166.7mL, p<0.05). However, the median ratio of postoperative contralateral renal volume change was significantly higher in groups A and B than in group C(A:0.36, B:0.23, C:0.12, p<0.001)(Table1). On multivariate analysis, tumor size revealed the strongest positive association with preoperative contralateral kidney volume (β=30.8, >7cm) and ratio of postoperative contralateral kidney volume change(β=0.214, A vs. C; β=0.168, B vs. C)(Table2). Conclusions Kidney volume measurements for assessing preoperative and postoperative compensatory hypertrophy of the contralateral kidney in RCC patients can be easily and rapidly performed from CT images using the ellipsoid formula. Additionally, tumor size is the strongest factor associated with compensatory hypertrophy in the contralateral kidney before (>7cm) and after (?4 or 4–7 cm) radical nephrectomy. Funding none
Authors
Bong Hee Park
Sung Hak Kang Joon Se Jung Sang Rak Bae Yong Seok Lee Chang Hee Han |
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MP59-14 |
RENAL FUNCTIONAL OUTCOMES IN PATIENTS UNDERGOING PARTIAL NEPHRECTOMY OR PERCUTANEOUS CRYOABLATION FOR A SOLITARY RENAL MASS |
Kidney Cancer: Localized: Surgical Therapy IV | 17BOS |
Abstract: MP59-14 Sources of Funding: None Introduction Renal functional outcomes are an important consideration when deciding among treatment options for a renal mass. However, there are conflicting data on renal functional outcomes when comparing partial nephrectomy (PN) and percutaneous cryoablation (CA). We therefore compared the changes in renal function between PN and CA patients with a solitary renal mass. Methods We retrospectively reviewed the Mayo Clinic nephrectomy and ablation registries to identify all patients who underwent PN or CA for a solitary renal mass between 2003-2013. Estimated glomerular filtration rates (eGFR) were calculated at baseline, prior to discharge, and at 3 months follow-up using the CKD-EPI equation and are reported as the percent change from baseline. Multivariable linear regression was used to compare the change in renal function between groups controlling for age, tumor size, and baseline eGFR. Subgroup analyses were performed in patients with baseline stage 3 or 4 chronic kidney disease (CKD) and those with a solitary kidney. Results There were 1650 PN and 481 CA identified, including 370 (22%) PN and 227 (47%) CA with stage 3 or 4 CKD at baseline and 91 (6%) PN and 69 (14%) CA with a solitary kidney. Overall, PN patients were younger (mean 59 vs 69 years, p<0.001), had a higher baseline eGFR (74.6 vs 62.7 ml/min/1.73m2, p<0.001), and had larger tumors (mean 3.5 vs 3.1 cm, p=0.001) compared to CA patients. On multivariable analyses, mean changes in eGFR from baseline at discharge and at 3 months follow-up for PN vs CA were -0.9% vs -5.9% (p<0.001) and -1.8 vs -7.0% (p<0.001), respectively. Similar results were found in the subgroup of patients with baseline stage 3 or 4 CKD at both discharge (4.2 vs -4.1%, p<0.001) and at 3 months follow-up (1.7 vs -5.2%, p<0.001), respectively. Among patients with a solitary kidney, no significant difference in the change in eGFR was found between PN and CA at either discharge (-13.2% vs -9.4%, p=0.27) or 3 months follow-up (-8.6 vs -12.6%, p=0.19). Conclusions Neither PN or CA cause clinically significant changes in renal function, including among patients with pre-existing renal dysfunction or a solitary kidney. While we observed a greater decline in renal function when CA was compared with PN, this difference was not significant in the subset of patients with a solitary kidney. Funding None
Authors
Ross Mason
Thomas Atwell Bimal Bhindi Grant Schmit Adam Weisbrod Christine Lohse Stephen A. Boorjian Bradley Leibovich R. Houston Thompson |
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MP59-15 |
LONG?TERM OUTCOMES AFTER RENAL CANCER SURGERY: PREDICTORS OF CHRONIC KIDNEY DISEASE AND NON?RENAL CANCER MORTALITY |
Kidney Cancer: Localized: Surgical Therapy IV | 17BOS |
Abstract: MP59-15 Sources of Funding: None Introduction Renal cancer surgery can adversely impact long-term renal function and survival. We evaluate predictors of 5-year risk of chronic kidney disease (CKD) and 10-year risk of non-renal cancer mortality (NRCM) after renal cancer surgery (RCS). Methods We analyzed 4,283 patients undergoing RCS at Cleveland Clinic between 1997 and 2008. Radical nephrectomy (RN) was performed in 1,982 patients (46%) and 2,301 (54%) underwent partial nephrectomy (PN). Cumulative probability ordinal modeling was used to predict varying levels of CKD (defined as glomerular filtration rate (GFR) <45, <30, or <15 ml/min/1.73m2) at 5 years after surgery. Multivariable logistic regression was used to develop a separate model predicting NRCM at 10 years postoperatively. Race, gender, preoperative GFR, new baseline GFR, and relevant clinical comorbidities were included in the models. Preoperative GFR, new baseline GFR, and GFR loss following surgery were included in the models, rather than type of surgery (PN vs RN), to reduce potential selection biases associated with choice of surgical procedure. Results Median age was 62 years (IQR=52-71). Significant predictors for 5-year CKD were preoperative GFR, GFR loss at 6 weeks post-op, male gender, age, and African-American race (all p<0.05). A predictive nomogram was created from the multivariable model (Spearman rho of 0.779) demonstrating preoperative GFR and GFR loss at 6 weeks post-op as the most important predictive factors. 10-year overall risk of NRCM was 29%. Significant predictors of NRCM were preoperative GFR, new baseline GFR, age, diabetes, and hypertension (all p<0.05). A predictive nomogram for 10-year NRCM was created with a c-index 0.71, demonstrating age and preoperative GFR as the most important predictive factors. GFR loss with surgery, as would be seen with typical PN vs. RN, only changed absolute mortality risk by 1-3% in nomogram-based examples (see Figure). Conclusions GFR loss with RCS, which is directly related to choice of PN vs RN, strongly influences risk of developing CKD, but has much less impact on long-term survival. In contrast, age and preoperative GFR are much more robust predictors of 10-year NRCM. Funding None
Authors
Joseph Zabell
Sevag Demirjian Steven C. Campbell |
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MP59-16 |
Vascularized Parenchymal Mass Preservation with Partial Nephrectomy: Functional Impact and Predictive Factors |
Kidney Cancer: Localized: Surgical Therapy IV | 17BOS |
Abstract: MP59-16 Sources of Funding: None Introduction Vascularized parenchymal mass preservation (VPMP) can be measured before and after partial nephrectomy (PN) and appears to be an important contributor to functional outcomes. In this study, we assess the functional impact of VPMP in a large cohort of patients and evaluate potential predictive factors. Methods A total of 401 patients managed with PN for a renal mass at our center with necessary studies to determine VPMP and function preserved within the operated kidney were analyzed. VPMP was measured from CT scans <2 months prior and 3-12 months after PN. Renal function was estimated by glomerular filtration rate (GFR), using the MDRD-2 formula. Patients with 2 kidneys were also required to have split renal function from nuclear renal scans within the same timeframes, and all analyses focused on the operated kidney. Recovery from ischemia was defined as percent GFR preserved in the operated kidney normalized by percent VPMP. Pearson correlation evaluated the relationship between renal function preservation and VPMP. Multivariable logistic regression assessed predictors for VPMP. Results Eighty-seven patients (22%) had a solitary kidney, while 314 patients (78%) had a contralateral kidney. Median tumor size was 3.5 cm and median R.E.N.A.L. score was 8. Cold and warm ischemia were utilized in 151/250 patients, and median ischemia times were 27/21 minutes, respectively. Median preoperative vascularized parenchymal mass in the operated kidney was 197 cm3 (IQR: 153-246) and median postoperative vascularized parenchymal mass was 157 cm3 (IQR: 122-202), resulting in median 84% VPMP. Pearson’s correlation analysis showed that GFR preservation correlated strongly with VPMP (r=0.63, p<0.001). Recovery from ischemia was suboptimal (<80%) in 61 patients (15%), while suboptimal VPMP (<80%) was a more common adverse event, occurring in 140 patients (35%)(p<0.05). Multivariable analysis demonstrated that increased tumor size and R.E.N.A.L. score correlated with reduced VPMP (p=0.043 and <0.001, respectively), and solitary kidney status correlated with increased VPMP (p=0.006). Increased ischemia time also correlated with reduced VPMP (p=0.027), reflecting the complexity of surgery. Conclusions Our data suggest that vascularized parenchymal mass preserved (VPMP) correlates strongly with functional outcomes after PN. Larger tumor size and increased tumor complexity correlate with reduced VPMP while VPMP tended to be greater for solitary kidneys. Funding None
Authors
Jitao Wu
Wen Dong Chalairat Suk-Ouichai Elvis Antonio Carabello Erick Remer Jianbo Li Joseph Zabell Sudhir Isharwal Steven Campbell |
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MP59-17 |
Subclinical Rhabdomyolysis: An Under-Recognized Contributor to Postoperative Acute Kidney Injury in Patients Undergoing Minimally Invasive Urologic Surgery |
Kidney Cancer: Localized: Surgical Therapy IV | 17BOS |
Abstract: MP59-17 Sources of Funding: None Introduction Rare cases of clinically apparent rhabdomyolysis have been reported in patients undergoing minimally invasive urologic surgery. This study aims to estimate the incidence of subclinical postoperative rhabdomyolysis and determine its effect on renal function._x000D_ Methods Daily postoperative serum creatinine kinase level was prospectively collected on 1034 patients who underwent urologic surgery. Rhabdomyolysis was defined as serum creatinine kinase (CK) ≥1000 U/L. Univariate and multivariate analysis was performed in order to identify factors associated with postoperative rhabdomyolysis. Patients were stratified by degree of CK elevation. Kruskal-Wallis tests were performed in order to determine the association between degree of CK elevation and peak postoperative serum creatinine level. p < 0.05 indicated statistical significance. Results Rhabdomyolysis occurred in 13.7% of patients (142/1034), with 97.2% (138/142) being subclinical. On multivariable analysis, sex, BMI, operative time, use of a hand-assisted surgical approach, and flank position were associated with development of rhabdomyolysis. Subclinical rhabdomyolysis was associated with postoperative acute kidney injury in surgeries involving complete loss of renal unit, with higher peak serum CK levels being associated with higher peak serum creatinine levels (Table 1). Conclusions Rhabdomyolysis is often clinically silent and may represent an under-recognized contributor to postoperative acute kidney injury in patients undergoing minimally invasive urologic surgery. Recognition of risk factors associated with rhabdomyolysis is important in order to maintain an appropriate index of suspicion during the postoperative period. Further study is required to determine if treating subclinical rhabdomyolysis improves outcomes. Funding None
Authors
Jim Shen
Mohamed Keheila Samuel Abourbih Patrick Yang Ingrid Wahjudi Liang Ji Salim Cheriyan Nazih Khater D. Duane Baldwin |
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MP59-18 |
Impact of Mayo Adhesive Probability Score on the Complexity of Robot-assisted Partial Nephrectomy. |
Kidney Cancer: Localized: Surgical Therapy IV | 17BOS |
Abstract: MP59-18 Sources of Funding: none Introduction Adhesive perinephric fat (APF) increases the complexity of robot-assisted partial nephrectomy (RAPN). The Mayo adhesive probability (MAP) score is an index for quantifying APF and predicting prolonged operation time or increased surgical complication rate. However, the part of the operation influenced by increased MAP score remains unclear. Methods The study subjects were 311 patients who underwent RAPN between January 2013 and June 2016 in our institute. MAP score was calculated to quantify APF. The perinephric fat thickness and stranding were used to calculate the MAP score. Operation time was divided into a dissection phase (from robotic manipulation to hilar clamping) and resection phase (from hilar clamping to robotic surgery completion). Results The patients’ mean age, body mass index (BMI), total operation time, console time, dissection phase time, and resection phase time were 60±13 years, 23.5±3.5 kg/m2, 180.8±40.7 minutes, 132.6±36.5 minutes, 84.9±27.6 minutes, and 47.6±18.3 minutes, respectively. The MAP score was 0 in 98 patients (32?), 1 in 86 (28?), 2 in 21 (7?), 3 in 48 (15?), 4 in 44 (14?), and 5 in 14 (4?). The dissection and resection phase times significantly increased as the MAP scores increased (Figure 1). The dissection phase times were 71.2, 79.1, 88.9, 97.0, 99.7, and 118.8 minutes as the MAP score increased by 1 point from 0 to 5 (p<0.001). The influence of MAP score was more remarkable to the prolongation of the dissection phase than to that of the resection phase. In the patients with MAP scores of ?3, the dissection phase time was not significantly influenced by the learning curve (100.8±25.2, 103.7±29.4, and 98.2±31.4 minutes in 1st–100th, 101st–200th, and 201st–311th, respectively). We further examined the factors that influenced the dissection phase time of 100 minutes by using the logistic regression model. In the multivariate analysis, left side, early surgical experience (first 100 cases), the number of the renal arteries to be clamped and MAP score (?3) were the independent factors of prolonged dissection phase. Conclusions MAP score is an independent predictive factor of prolonged RAPN dissection phase. The complexity of RAPN in the patients with high MAP scores was still high even for experienced surgeons. Funding none
Authors
Ryo Ishiyama
Tsunenori Kondo Toshio Takagi Junpei Iizuka Hirohito Kobayashi Kenji Omae Norihiro Fukuda Hiroki Ishihara Kazunari Tanabe |
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MP59-19 |
Outcome of kidney function after ischaemic and zero-ischaemic laparoscopic and open nephron-sparing surgery for RCC |
Kidney Cancer: Localized: Surgical Therapy IV | 17BOS |
Abstract: MP59-19 Sources of Funding: none Introduction Kidney failure is less frequently seen in nephron-sparing surgery (NSS) for renal tumours compared to radical nephrectomy. Thus, reduction of the renal function (RF) is seen in NSS patients mainly related to nephron tissue removal, renal ischaemia and a reduced baseline RF. Therefore, it remains controversial whether open NSS (ONSS) and laparoscopic NSS (LNSS) have different effects on the postoperative (p.o.) RF and whether zero-ischaemia (ZI) has a protective effect on the RF. Methods Between 1999 and 2010 a total of 444 cases (211 LNSS, 233 ONSS) including 57 ZI cases with RCC were retrospectively included into this study. The GFR (glomerular fitration rate) was estimated before surgery and for various p.o. measurements: (A) lowest value during the first 48h p.o. and (B) during the planned hospital stay prior to discharge (day 4 (2-6)), (C) an average 47 (30-105) days, (D) 13 (12-15) months, and (E) 44 (33-76) months (last follow-up) p.o. We used multiple regression models to predict the relative change of the eGFR from baseline at time B (model 1) and at time D (model 2), and to identify predictors of acute kidney injury (AKI) within 48h p.o. (model 3) and a decreased eGFR <60ml/min/1.73m2 at time D (model 4). A spline function was used to estimate the correlation between the ischaemia time (IT) and the relative change of the eGFR at time B in model 1 and at time D in model 2 and the correlation between the IT and the probability of AKI in model 3 and its interaction with the baseline RF, respectively. Continuous data are shown as median values with IQR. Results Postoperatively 38.5% of the patients developed AKI and 28.9% developed an eGFR <60ml/min/1.73m2 at time D. Fig. 1.1 and 1.2 show the plot of the spline function in model 1 and 2. Fig. 1.3 shows the probability of AKI in model 3. On regressional analysis in model 1 baseline eGFR (beta (b) -0.20), ONSS (b -13.49), BMI (b -0.88), IT (b -0.27), major complications (b -10.97), and the operation time (b -0.06), and in model 2 baseline eGFR (b -0.32), the Charlson score (b 1.80), and the tumour diameter (b -1.57) were all significant factors for changes in eGFR. Predictors for AKI (model 3) was ONSS (OR 4.1), male gender (OR 2.55), Charlson score (OR 1.22), BMI (OR 1.13), IT (OR 1.02), and the operation time (OR 1.008). The only significant predictor for model 4 was the baseline eGFR (OR 0.90). Conclusions IT influences the short-term change in RF. The development of AKI is not always linear and the impact of ischaemia is also dependent on the baseline RF. ZI surgery was not shown to influence the outcome variables significantly. ONSS was identified to be a risk factor for impairement of the RF and the developemnt of AKI compared to LNSS. Additional factors influencing the RF at 13 months p.o. was the baseline eGFR and the tumour diameter as a surrogate for volume of parenchyma removed during NSS. Funding none
Authors
Jan Ebbing
Kurt Miller Frank Friedersdorff Florian Fuller Jonas Busch Hans H. Seifert Peter Ardelt Christian Wetterauer Justin Collins Christofer Adding Paolo Frumento Carsten Kempkensteffen |
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MP59-20 |
Multicenter Analysis of Oncologic and Renal Functional Outcomes of Radical and Partial Nephrectomy in Stage II Renal Cell Carcinoma |
Kidney Cancer: Localized: Surgical Therapy IV | 17BOS |
Abstract: MP59-20 Sources of Funding: Stephen Weissman Kidney Cancer Research Fund. NIH grants UL1TR000100 and UL1TR001442. Introduction While partial nephrectomy (PN) is an accepted standard for small renal mass, utilization for large (>7cm) renal mass is controversial. We conducted a comparative analysis of survival and functional outcomes of PN and radical nephrectomy (RN) for clinical T2 Renal Mass (cT2RM). Methods Retrospective international multicenter analysis of PN and RN for cT2RM (T2N0M0) from 1987-2016. Primary outcome was change in glomerular filtration rate (delta eGFR). Secondary outcomes were de novo Stage 3 Chronic Kidney Disease (CKD, eGFR<60), eGFR<45 at last follow up, overall survival (OS), and complication rates. Multivariable (MV) logistic regression was used for outcomes, and Kaplan-Meier (KM) curves were created for OS. Results Study cohort with 1125 patients (239 PN, 886 RN), mean age 60.3 years, median follow up 38.9 months, mean clinical tumor size 9.9 cm, 70.5% cT2a / 29.5% cT2b. PN had higher BMI (29.6 vs. 27.3, p<0.001), as well as higher rate of hypertension (HTN, 59% vs. 47%, p=0.001) and diabetes (DM, 20.9% vs. 13.4%, p=0.005). RN cohort had larger tumor size (10.0 vs. 9.2 cm, p<0.001) and more cT2b disease (32.6% vs. 18.0%, p<0.001). Mean ischemia time for PN was 34.6 min. No significant differences were noted in hospital stay (p=0.697) or 30 day complications (36.0% vs. 36.9%, p=0.821). RN had higher all-cause mortality rate (32.6% vs. 13.4%, p<0.001). KM analysis revealed 5 year OS of 66.9% for RN and 82.2% for PN (p<0.001). KM stratified by cT stage PN vs. RN revealed 5 year OS for cT2a (83.2% vs. 70.1%, p=0.004) and for cT2b (84.6% vs. 60.2%, p=0.003) (figure). Preoperative eGFR was similar (79.4 vs. 77.3, p=0.23), and mean delta eGFR was higher for RN (-20.2 vs. -10.4, p<0.001). RN had worsened renal functional outcomes with respect to de novo GFR <60 (51.2% vs. 28.9%, p<0.001) and de novo GFR <45 (22.8% vs. 14.0%, p<0.001). MV Cox model for OS was significant for age (HR 1.02, p<0.001), DM (HR 1.54, p=0.021), tumor grade 3/4 (HR 2.22, p<0.001), lymphovascular invasion (LVI, HR 1.74, p=0.001), and RN (HR 3.24, p<0.001). Conclusions PN when performed in the setting of cT2RM provides renal functional benefit and may have survival benefit. Consideration may be given to PN when technically feasible for cT2RM in appropriately selected patients. Prospective data are requisite to confirm. Funding Stephen Weissman Kidney Cancer Research Fund. NIH grants UL1TR000100 and UL1TR001442.
Authors
Zachary Hamilton
Andres Correa Alessandro Larcher Zineddine Khene Katherine Fero Daniel Han Aaron Bloch Charles Field Benoit Peyronnet Umberto Capitanio Francesco Montorsi Karim Bensalah Robert Uzzo Ithaar Derweesh |
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MP60-01 |
DAB2IP stabilizes p27 via suppressing PI3K/AKT signaling in renal cell carcinoma |
Kidney Cancer: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP60-01 Sources of Funding: This work was supported by the Shaanxi Provincial Natural Science Foundation (2016JQ8011 to J. Zhou) and the National Natural Science Foundation of China (NSFC 81502205 to L. Liang, 81602237 to J. Zhou). Introduction Renal cell carcinoma (RCC) is the most lethal urologic malignancy, however, the molecular events involved in RCC pathogenesis and progression are still not well defined. DAB2IP, a novel member of Ras GTPase-activating protein gene family, is associated with cell proliferation, apoptosis, metastasis and chemo- or radio-resistance in several cancers. We have recently reported the tumor suppressive role of DAB2IP in RCC development, and identified one CpG methylation biomarker located at upstream of the transcription start site of DAB2IP that was associated with poor survival in three independent large-scale cohorts of RCC patients. In the present study, we determined molecular mechanisms of DAB2IP in suppressing the growth of RCC. Methods DAB2IP knockdown (KD) and overexpressing cells were generated by RNAi or cDNA transfection technologies. MTT, cell-cycle assays and xenograft models were performed to investigate the effect of DAB2IP on RCC cell growth. Mechanisms of DAB2IP in regulating cell growth were delineated by a variety of molecular biologic techniques such as real-time PCR, western blot, and immunoprecipitation. Relationships between DAB2IP, its downstream gene and tumor size were validated by clinical samples, and the associations of critical proteins and RCC patient survival were analyzed. Results DAB2IP KD cells exhibited promoted G1/S phase cell-cycle progression and enhanced cell proliferation, whereas, DAB2IP-overexpressing cells showed decreased growth ability. Mechanistically, DAB2IP promoted ubiquitination and degradation of a critical negative regulator of the cell-cycle, p27 (Kip1). Further signaling cascade profiling demonstrated that the Proline-rich domain in C terminal (CPR) of DAB2IP inhibited the activity of AKT phosphorylation (S473). Loss of DAB2IP, thus, promoted the phosphorylation of p27 on Serine 10 (S10) by AKT. Phosphorylated p27 was then sequestrated in cytosol, and subsequently ubiquitinated for degradation. Introduction of a constitutively activated AKT which was not affect by DAB2IP ablated the effect of DAB2IP on RCC growth, while introduction of a mutated p27 (p27 S10A) which escaped from the phosphorylation of AKT significantly restored the suppressive role of DAB2IP. In RCC patients, DAB2IP negatively correlated with tumor size and positively correlated with p27 expression. Survival analysis indicated that DAB2IP was associated with a better overall survival of RCC patient. Conclusions This study identifies DAB2IP as a tumor suppressor in RCC, and its mechanism of action is to stabilize p27 via suppressing PI3K/AKT signaling. Funding This work was supported by the Shaanxi Provincial Natural Science Foundation (2016JQ8011 to J. Zhou) and the National Natural Science Foundation of China (NSFC 81502205 to L. Liang, 81602237 to J. Zhou).
Authors
Jiancheng Zhou
Yongyi Cheng Kaijie Wu Dalin He Jer-Tsong Hsieh |
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MP60-02 |
Iron deprivation downregulates HIF2-α and induces cancer-specific apoptosis in clear cell renal cell carcinoma |
Kidney Cancer: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP60-02 Sources of Funding: This project was supported by the Roswell Park Cancer Institute Alliance Foundation. Introduction The von Hippel Lindau (VHL)/hypoxia inducible factor-alpha (HIF-α) pathway is commonly dysregulated in clear cell renal cell carcinoma (ccRCC) and potentially exacerbated by oxidative stress. Ferric iron is the most abundant heavy metal in the human body and is required for nephrogenesis in utero; it is also a major source of intracellular oxidative stress capable of inducing ccRCC tumorigenesis in rodent models. In addition to its known requirement for DNA synthesis, iron was recently shown to stabilize HIF2-α transcript by inhibiting iron regulatory protein 1. Still, a role for iron in human ccRCC tumorigenesis remains largely unexplored. Here we test the hypotheses that intracellular iron levels are increased in ccRCC cells and that iron reduction can effectively reduce HIF2-α expression and suppress ccRCC cell growth. Methods Iron levels were measured in 100 RCC patient tumors using Prussian Blue stain and compared to levels in benign renal tubule epithelium. Protein levels of the main iron uptake protein, transferrin receptor 1 (TfR1/CD71), were compared between 4 VHL-deficient ccRCC cell lines and 2 benign renal epithelial cell lines by flow cytometry and western blot. Micromolar concentrations of 3 clinically approved iron chelator drugs, deferoxamine (DFO), deferiprone (DFP), and deferisirox (DFX) were tested by MTT assay for effects on ccRCC versus benign renal cell proliferation. Cell viability and apoptosis induction with DFO treatment was measured in select ccRCC cell lines using flow cytometry analysis of annexin-V and 7-AAD stains, as were effects of DFO on ccRCC HIF2-α protein levels. Results Increased intracellular iron was detected in ccRCC tumors compared to benign renal tubule epithelium. All ccRCC cell lines had elevated TfR1 expression compared to benign renal cell lines. Iron chelation treatment using DFO, DFP, or DFX achieved 80-90% growth reduction in all ccRCC cell lines at clinically relevant concentrations, while benign renal cell lines were relatively resistant. The mechanism underlying ccRCC growth inhibition included cell death via apoptosis, whereas benign renal cells had no increased death even after prolonged iron chelation treatment. Intriguingly, iron chelation in ccRCC cell lines effectively downregulated HIF2-α in a time- and concentration-dependent manner. Conclusions These data indicate that intracellular increases in iron content occur during human ccRCC tumorigenesis and support iron chelation as a potential therapeutic strategy for targeting HIF2-α and inducing cancer cell death in ccRCC patients. Funding This project was supported by the Roswell Park Cancer Institute Alliance Foundation.
Authors
Christopher Greene
Nitika Sharma Gary Smith Kenneth Gross Eric Kauffman |
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MP60-03 |
NF2/MERLIN as a Modulator of Invasiveness and Metastasis in Renal Cell Carcinoma |
Kidney Cancer: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP60-03 Sources of Funding: Research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number T32GM088129. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. No conflict of Interests exist for the authors. Introduction Despite advancements in surgical technique and targeted therapy, metastatic renal cell carcinoma (RCC) remains deadly with a <15% five-year survival. Understanding the molecular machinery driving the transition from localized malignancy to invasion/metastasis is critical if we are to improve patient outcomes. We hypothesize that loss of function of the tumor suppressor MERLIN (encoded by the neurofibromatosis type 2 gene, NF2) may be a key player in this transition. We set out to determine (1) the association between patient outcomes and NF2 mutation status, (2) MERLIN function in established RCC cell lines derived from primary and metastatic sites, and (3) to correlate MERLIN activity to in vitro measures of invasiveness and metastatic potential. Methods Utilizing publicly available tumor sequencing datasets, we determined the clinical association between NF2 mutations and tumor stage and clinical outcome. We characterized mRNA expression of NF2 and protein levels of MERLIN by quantitative PCR and Western immunoblotting in metastatic-derived (Caki1, ACHN) and non-metastatic-derived (786-O, A498, Caki2) RCC cell lines. Potential for invasion and metastasis were assayed in vitro using transwell invasion and colony forming assays, and in vivo by mouse xenograft (NU/J). The relative expression of MERLIN was assessed in a tissue microarray containing 31 primary tumors, 8 paired metastatic tumors, and 8 paired normal kidney samples by immunohistochemistry. Results NF2 mutations are enriched in higher grade (>pT3, pT4) and metastatic tumors compared to low grade or non-metastatic tumors (20-30% vs. 1.5%), and are associated with a decreased disease-free survival. Cell lines derived from metastatic RCC have lower NF2 expression than cell lines derived from local tumors, more importantly, MERLIN protein levels are decreased or undetectable by Western blot or IHC in metastatic derived cell lines. The metastatic lines Caki1 and ACHN have increased metastatic potential as measured by increased colony formation. MERLIN was absent in a tumor with sarcomatoid differentiation but was present in all 8 metastatic samples. Conclusions These results support a potential intriguing role for MERLIN loss of function in the clinically-relevant phenotypic transition from localized to invasive RCC. The model system described here will provide a crucial framework for testing MERLIN&[prime]s influence on invasiveness through knockdown and rescue of MERLIN activity in appropriate RCC cell lines. Funding Research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number T32GM088129. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. No conflict of Interests exist for the authors.
Authors
Juan Hernandez
Jason Scovell Richard Link |
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MP60-04 |
ERK2 phosphorylate T-LAK cell-originated protein kinase at Ser32 promotes tumorigenesis of renal cancer |
Kidney Cancer: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP60-04 Sources of Funding: This project was supported by the national Natural Science Foundation of China (No.81572529). Introduction T-LAK cell-originated protein kinase (TOPK), a serine/threonine protein kinase, was reported highly expressed in a variety of human tumors, and associated with poor prognosis of many kinds of human malignancies, but its activation mechanism is still uncovered. It is well known there is a bidirectional signals transduced between TOPK and ERK2, and ERK2 could phosphorylate TOPK at Thr9. The objective of the present study is to explore whether there is other site on TOPK that can be phosphorylated by ERK2, the function of the phosphorylation site was also be investigated. Methods Potential phosphorylated serine/threonine sites of TOPK were predicted by NetPhos 2.0 software program. Peptide mapping assay was used to testify the phosphorylation site. Anti-phospho-TOPK at S32 was prepared, the endogenous phosphorylation of TOPK at S32 was detected in renal cancer cells and tissues of renal cancer patients. In order to investigate the function of S32 site, S32 mutated TOPK (S32A) was transient transfected into 293T cells and stably transfected into JB6 or Caki-1 cells, the in vitro kinase assay was performed, the anchorage-independent growth ability and tumorigenesis of TOPK-S32A cells were compared. The ERK2 was knocked down from the TOPK highly expressed renal cancer cells, the level of phosphorylation TOPK (S32) and other downstream genes were detected. Results We found that ERK2 directly bound with and phosphorylated TOPK at S32 in vitro. The phosphorylation was inhibited in cells expressing low levels of ERK2 or the cells that ERK2 was knocked down. When the S32 mutated TOPK was stably transfected into JB6, the anchorage-independent growth ability and tumorigenesis of the cells were suppressed compared with those of wild type TOPK (TOPK-WT) ex vivo and in vivo. The phosphorylation level of TOPK substrate, Histone H3 at Ser10 was also decreased dramatically ex vivo or in vivo. The phosphorylation level of TOPK was higher in high stage tissues of renal cancer than those in low stage ones. Conclusions Taken together, the phosphorylation of TOPK at S32 by ERK2 increases the activity of TOPK, and promotes the tumorigenesis of renal cancer. It may provide opportunities for TOPK based prognosis and targeted therapy for renal cancer patients. Funding This project was supported by the national Natural Science Foundation of China (No.81572529).
Authors
Huimin Sun
Juanjuan Xiao Lei Zhang Juntao Yue Shijie Liu Junshen Wu Rongliang Qin Lijun Yang Fuli Wang Bo Yang Feng Zhu Chen Shao |
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MP60-05 |
Erythropoietin receptor may become a target for renal cell carcinoma |
Kidney Cancer: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP60-05 Sources of Funding: This work was supported by the National Natural Science Foundation of China (Grant Number: 81172418 and 81572506) Introduction Drugs targeting the molecules downstairs VHL gene have improved progression-free survival and replaced non-specific immunotherapy with cytokines in metastatic renal cell carcinoma (RCC). While the fact remains that despite a decade of established targeted therapy for RCC, the median survival of patients with metastatic RCC is still unsatisfying. Novel targeted therapies will have decisively improved the outlook for patients with renal cell cancer. In this study we evaluate the function of erythropoietin (Epo) and its receptor (EpoR) in RCC and whether it can be a target for RCC. Methods RNA interference method was used to down regulate EpoR in RCC cell lines to investigate the function of Epo/EpoR pathway in human RCC cells. We also prepared polyclonal rabbit anti-EpoR antibody (EpoR Ab) by immunizing rabbits with the transmembrane domain polypeptide of EpoR, and tested the effect of the EpoR Ab for RCC cells in vitro and vivo. Results Epo and EpoR co-express in RCC cell lines. Down-regulation of EpoR expression in RCC cells by lentivirus-introduced siRNA resulted in inhibition of growth and invasiveness of RCC cells. The EpoR Ab could bound to RCC cells and inhibited the cancer cells proliferation in both vitro and vivo. Conclusions Our results suggested that Epo/EpoR pathway is involved in cell growth, invasion and survival in RCC cells. EpoR might be a new therapeutic target for renal cell carcinoma, and antibody against EpoR may become an effective agent for RCCs. Funding This work was supported by the National Natural Science Foundation of China (Grant Number: 81172418 and 81572506)
Authors
Teng Li
Kan Gong Pengjie Wu Shengjie Liu Xianghui Ning Shuanghe Peng Jiangyi Wang |
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MP60-06 |
HAI-2 regulates the invasive growth of RCC cells in bone metastasis through suppression of matriptase-induced HGF activation |
Kidney Cancer: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP60-06 Sources of Funding: None. Introduction We previously reported that high MET and matriptase expression in RCC cells in bone metastasis indicates their importance in bone metastasis (Mukai et al. Hum Cell, 2015). MET is a high-affinity receptor tyrosine kinase of hepatocyte growth factor (HGF). HGF is secreted as an inactive single-chain precursor, which requires proteolytic activation for conversion to an active form. Matriptase is the most efficient known cellular activator of pro-HGF. Furthermore, activation of matriptase is regulated by HGF activator inhibitor (HAI). In this study, we employed a previously reported mouse model of bone metastasis (Strube et al. Clin Exp Metastasis, 2010) to clarify the significance of the matriptase-induced HGF/MET signaling axis in RCC bone metastasis. Methods Luciferase-transfected 786-O cells were injected into the left cardiac ventricle of female nude mice (5 weeks old). After 6 weeks, we confirmed the formation of bone metastasis by whole-body bioluminescent imaging, and extracted specimens. Expression of matriptase, MET and HAI was analyzed by PCR, immunohistochemistry (IHC) and immunoblots. Phosphorylation of MET was also investigated. Based on the result, we produced HAI-2 (specific inhibitor of matriptase) stable knock down (KD) 786-O cells, and analyzed the difference of expression in each molecule, cell-migration assay and invasion assay. Results Expression of matriptase was increased significantly in bone metastasis compared with parent cell line, and we confirmed increased phosphorylation of MET in bone metastasis. On the other hand, decreased expression of HAI-2 was observed in bone metastasis. Interestingly, increased matriptase expression was observed by HAI-2 KD in 786-O cells. In addition, invasive activity was increased significantly by knock down of HAI-2. Conclusions These results have suggested that matriptase contributes to the HGF-dependent MET activation in the pericellular microenvironment of bone metastasis in RCC. In addition, upregulation of matriptase and downregulation of HAI-2 may have important roles in their progression. Funding None.
Authors
Koji Yamasaki
Toyoharu Kamibeppu Shoichiro Mukai Toshiyuki Kamoto |
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MP60-07 |
The Calcium-sensing receptor (CaSR) is responsible for the development of bone metastasis in renal cancer |
Kidney Cancer: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP60-07 Sources of Funding: Wilhelm Sander Foundation Introduction Bone metastasis has a great impact on the prognosis and clinical morbidity of patients with renal cell carcinoma (RCC). Overexpression of the Calcium-sensing receptor (CaSR) has been associated with the development of bone metastasis in several tumor entities. The goal of our study was to evaluate the impact of the CaSR in the development of bone metastasis in renal cancer. Methods The human clear cell RCC line 786-O was stably transfected with the CaSR gene. Cell adhesion to endothelial cells and the extracellular matrix compounds fibronectin, collagen I and IV and a BSA control was determined after calcium treatment of the cells.Chemotactical cell migration was assessed using a Boyden migration chamber with calcium as chemotaxin. Cell proliferation after calcium treatment was quantified via BrdU incorporation. Signalling pathway activation after calcium treatment of the CaSR overexpressing cells was determined by a human phospho-kinase array and Western blot. Development of bone metastasis was evaluated in vivo by an intracardiac injection mouse model. Results Calcium treated overexpressing CaSR 768-O cells show an increased adhesion to endothelial cells and the extracellular matrix components fibronectin and collagen I, but not to collagen IV. The chemotactical cell migration and proliferation was also induced by calcium treatment. The signalling mediators SHC, AKT, ERK, p38a JNK, p90RSK, CREB were enhanced, SRC reduced active after calcium treatment of CaSR overexpressing cells, but not of control cells. These effects were abolished by the CaSR inhibitor NPS2143. Intracardiac injection of CaSR overexpressing 768-O cells showed an increased rate of bone metastasis in vivo compared to control cells detected by MRI and bioluminescence. Conclusions CaSR is an important component in the mechanism of bone metastasis in RCC in vitro and in vivo. Therefore, targeting CaSR may be beneficial in patients with advanced RCC with high CaSR expression. Funding Wilhelm Sander Foundation
Authors
Sebastian Frees
Tobias Haber Igor Moskalev Ines Breuksch Werner Struss Joachim Thüroff Martin Gleave Dirk Prawitt Alan So Walburgis Brenner |
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MP60-08 |
Intracrine Androgen Biosynthesis in Renal Cell Carcinoma |
Kidney Cancer: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP60-08 Sources of Funding: Cancer Institute of New Jersey Introduction The presence of androgen receptor (AR) in renal cell carcinoma (RCC) has been shown to be associated with higher tumor stage irrespective of gender. Our previous data have also demonstrated that anti-androgen therapy results in tumor suppression in a xenograft model of AR-positive RCC. Therefore, we hypothesize that intratumoral steroidogenesis is a source of androgens in AR-positive RCC. Methods Using enzyme-linked immunosorbent assay (ELISA), testosterone (T) and dihydrotesterone (DHT) levels were measured in AR-positive human RCC cell lines and human female RCC tissues. Nude mice were also injected with an AR-positive RCC cell line, Caki2. When tumors became palpable, surgical castration was performed and anti-androgen therapies with enzalutamide and abiraterone acetate were initiated. ELISA was then used to measure serum and intratumoral androgen levels. Real-time polymerase chain reaction (RT-PCR) was used to measure the expression levels of key enzymes required for steroidogenesis in RCC cell lines, human RCC tissues, and xenografts. Results AR-positive human RCC cell lines and tissues were found to have elevated levels of androgens compared to AR-negative controls (p<0.05), and both expressed key enzymes required for intracellular steroidogenesis. Intratumoral androgen concentrations also remained high following castration even with significant reduction in the serum levels of androgen in a xenograft model. Significant reduction of intratumoral androgen levels was also seen with androgen synthesis inhibitor (p<0.05). Moreover, increased expressions of key enzymes were seen following castration in the xenografts. Conclusions Intracrine androgen biosynthesis is a potential source of androgen in AR-positive RCC, and the androgen signaling axis is a potential target of intervention in AR-positive RCC. Funding Cancer Institute of New Jersey
Authors
Geun Taek Lee
Christopher Han Young Suk Kwon Rutveej Patel Parth Modi Seok Joo Kwon Izak Faiena Neal Patel Han-Jong Ahn Wun-Jae Kim Eric Singer Isaac Kim |
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MP60-09 |
Lim1 oncogene as a new therapeutic target in advanced human renal cell carcinoma |
Kidney Cancer: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP60-09 Sources of Funding: INSERM, University of Strasbourg, Ligue Contre le Cancer Introduction Clear cell renal cell carcinoma (CCC) is resistant to therapies. We and others have shown the oncogenicity of various signaling pathways/markers including the PI3K/Akt, NF-kB, MAPK, sonic hedgehog (SHH)-Gli and Notch pathways and Pax2 transcription factor. These are also pathways/markers involved in nephrogenesis leading us to hypothesize that tumor cells hijack developmental signaling pathways/markers for their own growth. Among Gli targets, we have identified the developmental Lim1 transcription factor as a new oncogene in CCC, regulating tumor growth. Preliminary results also suggested a role in metastasis development. Here, we subsequently investigated whether Lim1 has a role in advanced CCC. Methods Human 786-0, A498 (VHL-) and Caki2, ACHN (VHL+) cells were used. No chemical inhibitor of Lim1 is available. We thus investigated its role in tumor invasion using siRNA and Lim1 expressing vector. In vitro, Lim1 effect on cell motility, migration and invasion was studied in cells transiently transfected with Lim1 siRNAs for 24-96h, by wound healing assay, and using uncoated and Matrigel-coated Boyden chamber respectively. We assessed the expression of various proteins involve in cell movements after Lim1 silencing by Western blot and PCR. We also analyzed Lim1 expression in 8 metastatic samples (lymph node and adrenal metastases). To study the impact of Lim1 in vivo, we developed a model that we calibrated for metastasis spread qualitatively and quantitatively through injection of 50 000 tumor cells into the tail vein of nude mice. Untransfected cells and cells transfected with a vector expressing Lim1 or Lim1 siRNA were used. 10 days after cell injection mice were euthanized and organs were harvested for metastases analysis and molecular studies using the HTG EdgeSeq Oncology Biomarker Panel Assay (2560 genes). Results Lim1 expression was downregulated by > 95% after siRNAs transfection. In all cell lines, the depletion of Lim1 inhibited not only cell movements by up to 50 % in a time-dependent manner, but also the expression of various proteins including Fibronectin, MMP8/9, Paxillin, and CXCR4. Lim1 was found in all metastatic samples and the corresponding primary tumor. As expected, in vivo, lung and liver metastasis developed within 10 days post-injection. We are currently analyzing organs in terms of size and number of metastases. First results suggest that Lim1 is involved in metastasis development. Upcoming experiments will define the molecular mechanisms of such effects. Conclusions These results show that targeting Lim1 has therapeutic potential in this refractory disease. Funding INSERM, University of Strasbourg, Ligue Contre le Cancer
Authors
Imène Hamaidi
Sabrina Danilin Valérian Dormoy Sylvie Rothhut Catherine Coquard Claire Béraud Mariette Barthelmebs Véronique Lindner Hervé Lang Thierry Massfelder |
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MP60-10 |
Loss of PBRM1 Increases Proliferation and Invasion in Renal Cell Carcinoma by Regulating Chemokine/Chemokine Receptor Interaction Pathway Short Title: PBRM1 and Chemokine Pathways in Kidney Cancer |
Kidney Cancer: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP60-10 Sources of Funding: none Introduction PBRM1 is a novel tumor suppressor gene that can inhibit cancer cell proliferation and predict outcome of renal cell carcinoma(RCC), but its biological role still needs further elucidation. Methods We examined the expression of the PBRM1 gene in RCC cell lines and the effect of PBRM1 on cell proliferation and invasion in RCC ACHN cells. Microarray processing and analysis was used to explore novel pathways involved in PBRM1 tumorigenesis. Results PBRM1 was expressed at high levels in ACHN cells, while lentivirus-mediated PBRM1 knockdown in RCC ACHN cells caused cell-cycle increase in the S phase and dramatically promoted proliferation and invasion in culture. In vivo experiments showed that down expression of PBRM1 could promote tumorigenesis in nude mice. Pathway gene chip analysis revealed that PBRM1 knockdown resulted in the chemokine/chemokine receptor interaction pathway with the most different gene expression. Increased protein levels of IL6ST and CCL2, whereas the protein levels of IL8, IL6 and CXCL2 were decreased. Conclusions These findings demonstrate that PBRM1 can alter cell cycle, inhibit proliferation and invasion of ACHN cells through the chemokine/chemokine receptor pathway. Funding none
Authors
Hongkai Wang
HaiLiang Zhang DingWei Ye |
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MP60-11 |
Epigenetic inactivation of HOXA11 as a novel functional tumor suppressor for renal cell carcinoma |
Kidney Cancer: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP60-11 Sources of Funding: none Introduction HOXA11 is a member of HOX transcription factors, the HOX genes encode transcription factors that play an essential role in regulating cell differentiation and proliferation. The hypermethylation of HOXA11 promoter region has been reported in various cancers. However, the epigenetic alteration and function of HOXA11 in human renal cell carcinoma (RCC) has not been explained. Therefore, to investigate the expression and function of HOXA11 is significant. Methods PCR and IHC were used to check the expression of HOXA11 in RCC cells and tissues. To detect the methylation status of HOXA11 promoter, MSP (methylation specific PCR) and BGS (bisulfite genomic sequencing) were used. We also used colony formation, CCK8, wound healing, Transwell, Annexin V apoptosis assay and Western-blot to assess the function and related mechanism of HOXA11 in renal cell carcinoma. Finally, we used Fisher’s exact test, Student’s t test and Chi-square test to analyze the correlation between clinical features and HOXA11 promoter methylation. Results HOXA11 was down-regulated by promoter aberrant methylation in both RCC cell lines and tissues compared with normal kidney cell line and tissues. HOXA11 methylation was found at higher prevalence (70.5%, 68/95) in human RCC tissues than in adjacent non-malignant renal tissues (13%, 3/23) and associated with higher TNM classification of RCC (p<0.05). In addition, restoration of HOXA11 expression reduced the proliferation, colony formation, migration and invasion abilities and induced RCC cells apoptosis. Moreover, HOXA11 was found to inhibit Wnt signaling. Conclusions Our study demonstrated that HOXA11 function as a tumor suppressor in RCC which is mainly regulated by epigenetics. Funding none
Authors
wang lu
cui yun jingdong sheng guanyu kuang yang yang fan yu jin jie zhang qian |
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MP60-12 |
FOLLICULIN TUMOR SUPPRESSOR BINDS TO TRANSLATION INITIATION FACTORS EIF2G & EIF5B AND SUPPRESSES PROTEIN SYNTHESIS |
Kidney Cancer: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP60-12 Sources of Funding: This work was supported by the Mildred Scheel Fellowship from the German Cancer Aid (MS) and NIH/NCI 1R01CA104574 (OI). Introduction Patients with Birt-Hogg-Dube (BHD) disease develop renal cancers of any known histology, skin fibrofolliculomas and spontaneous pneumothoraces. The disease is caused by a germline mutation in the tumor suppressor gene Folliculin (FLCN). Cancer associated mutations often result in a truncation of the C-terminus of the protein. The objective of our study was to discover novel insights into the molecular mechanism of tumor suppression by FLCN. Methods To gain further insight into the cellular function of FLCN, we isolated FLCN-containing protein complexes from the lysates of the FLCN-/- UOK257 human clear cell renal cell carcinoma cell line and its FLCN-replete isogenic derivative cells. Mass spectrometric analysis of affinity-purified complexes indicated that FLCN associates with several factors of the protein translation machinery, including the protein translation initiation factors. Results Here we report that FLCN localizes to the polysomes and associates with factors regulating the initiation of protein translation, including EIF2G and EIF5B. The FLCN C-terminal domain, which is deleted by tumor-associated FLCN mutations, is necessary for the interaction of FLCN with EIF2G and EIF5B. Reintroduction of wild type but not a C-terminus FLCN mutant into FLCN-/- cells results in suppression of serum or amino acid stimulated protein translation, independently of mTORC1/2 activity. Conclusions Our data provide insights into a novel mechanism of cell growth restriction by FLCN. Here we report that FLCN binds to protein translation initiation factors, resulting in repression of protein translation, downstream of mTORC1. This observation predicts that mTOR inhibitors may have limited efficacy in treating FLCN-related RCC and highlights protein translation as a therapeutic target for FLCN-related tumors. Funding This work was supported by the Mildred Scheel Fellowship from the German Cancer Aid (MS) and NIH/NCI 1R01CA104574 (OI).
Authors
Meike Schneider
Taha Hagar Katja Dinkelborg Syed I.A. Bukhari Axel Haferkamp Shobha Vasudevan Othon Iliopoulos |
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MP60-13 |
Loss of Fat Mass and Obesity Associated Gene (FTO) Decreases Proliferation and Invasion in Renal Cell Carcinoma Cell-line by Upregulation of NF-kappa B signaling pathway |
Kidney Cancer: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP60-13 Sources of Funding: none Introduction FTO was the first GWAS identified gene which was associated with obesity, considering the interaction between obesity and renal cell carcinoma(RCC), the biological role of FTO in RCC is of great interest. Methods We examined the expression of the FTO gene in RCC cell lines and the effect of FTO on cell proliferation and invasion in RCC A498 and 786-O cells. Microarray processing and analysis was used to explore novel pathways involved in FTO tumorigenesis. Results TO was expressed at high levels in A498 cells and low levels in 786-O cells. Lentivirus-mediated FTO knockdown in RCC A498 cells caused cell-cycle increase in the G1/S phase and dramatically inhibited proliferation and invasion in culture. By contrast, over-expression of FTO in 786-O cells increased proliferation and invasion. Pathway gene chip analysis revealed that FTO knockdown resulted in the NF-kappa B signaling pathway activation. IL-1R, TLR4, BIRC2, RIG-I were significantly upregulated after FTO knockdown. Conclusions These findings demonstrate that FTO may alter proliferation, invasion and cell cycle of renal cell carcinoma cell lines through the NF-kappa B signaling pathway. Funding none
Authors
Hongkai Wang
JunLong Wu HaiLiang Zhang GuoHai Shi Yao Zhu DingWei Ye |
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MP60-14 |
The von Hippel Lindau (VHL) Tumor Suppressor Inhibits p53 Target Gene Expression to Promote Apoptosis-Resistance in Cancer |
Kidney Cancer: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP60-14 Sources of Funding: CIHR, Vanier Canada Graduate Scholarships Introduction VHL is characterized as a tumour suppressor, being suppressed in up to 90% of clear cell Renal Cell Carcinomas (ccRCC). Canonically, VHL binds to and mediates degradation of hypoxia inducible factors (HIF). However, VHL has been discovered to bind other proteins, like p53, thereby altering the cell in more ways than just HIF degradation. Furthermore, there are conflicting reports on the impact of VHL on cancer proliferation and apoptosis, which can be regulated by p53 target genes, like p21 and PUMA. We hypothesize that VHL inhibits p53 activation paradoxically leading to increased proliferation and reduced apoptosis in cancer cells. Methods VHL-deficient cells were transiently (adenoviral) or stably (lentiviral) transduced with VHL. We generated VHL knockout cells using CRISPR/Cas9 genome editing technology. HIF overexpression was achieved using hypoxia or a non-degradable HIF-expressing adenovirus. Immunodeficient nude mice were injected with tumor cells bilaterally (left, -VHL; right, +VHL) and treated with weekly injections of doxorubicin (2mg/kg, IP). Co-immunoprecipitations, immunoblots, confocal imaging and siRNA transfections were performed using standard techniques. Results Transient and stable VHL overexpression robustly decreased, while knockout of VHL increased p21/PUMA mRNA and protein levels. VHL-deficient cells lacking HIF (via siRNA) had unaltered p21. Conversely, VHL and non-degradable HIF mutant co-expressing cells exhibited low p21 levels compared to VHL-deficient cells. Taken together, these data suggest that VHL-mediated p53 regulation is independent of HIF. VHL over-expression significantly attenuated induction of apoptosis in doxorubicin (p53 activator) treated cells. Prior to treatment, VHL-deficient tumors grew larger than VHL expressing tumors. However, doxorubicin resulted in a more significant reduction in tumor size in VHL-deficient tumors. Conclusions These results suggest an inhibitory interaction between VHL and p53, in which VHL mediates reduces p53 target gene expression. Furthermore, the attenuation of doxorubicin treatment in VHL-expressing cancer cells suggests that this chemotherapy may be more effective against VHL-deficient tumors or in combination with a VHL inhibitor. This work suggests that through a previously undescribed mechanism, a known tumor suppressor may paradoxically be capable of potentiating cancer growth and apoptosis resistance. Funding CIHR, Vanier Canada Graduate Scholarships
Authors
Adam Kinnaird
Peter Dromparis Aristeidis Boukouris Vikram Gurtu Bruno Saleme Sotirios Zervopoulos Gopinath Sutendra Evangelos Michelakis |
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MP60-15 |
MicroRNA-224 promotes tumor growth and progression in clear cell renal cell carcinoma by down-regulation of Eyes absent 4 as a new tumor suppressor gene. |
Kidney Cancer: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP60-15 Sources of Funding: none Introduction MicroRNA-224(miR-224) has been reported to promote tumor growth and invasion in several cancers and the expression of miR-224 was significantly higher in clear cell RCC (CCRCC) compared with normal kidney. However, the function of miR-224 in CCRCC remains unclear. In this study, we focused on the role of miR-224 in CCRCC as well as examination of miR-224 expression pattern in tissues and identified candidate tumor suppression gene, eyes absent 4(EYA4) as target gene of miR-224. Methods We investigated the expression level of miR-224 in 118 CCRCC patients who underwent surgical treatment at our institution and analyzed the relationship between the expression of miR-224 and clinic-pathological parameters. Then we did functional analysis of miR-224 using RCC cells and normal cell (RPTEC). EYA4 was identified as target gene of miRNA-224 using computer algorithm. The direct interaction analysis between miR-224 and EYA4 was also performed. We investigated functional analysis of EYA4. Results The expression level of miR-224 was higher in CCRCC tissues compared to matched normal kidney tissues. We divided 118 patients to two groups. A high miR-224 expression was associated with worse prognosis in CCRCC patients (Fig 1). Higher miR-224 expression was only risk factor related to progression, cancer-specific death, and overall survival. After knocking down of miR-224 in RCC cells, cell viability, invasion, migration ability were significantly decreased, whereas significantly increase of cell apoptosis in cell lines. There was an inverse correlation between miR-224 and EYA4 protein expression in CCRCC patients. After overexpression of EYA4, the cell viability and invasion were significantly inhibited in EYA4-transfected cells. Percentages of apoptotic cells were significantly increased in EYA4 transfected RCC cells compared with empty vector. Conclusions This is the first report to demonstrate that miR-224 expression is significantly increased in CCRCC as an oncogenic function by inhibiting EYA4 expression and may be potentially useful for a prognostic biomarker. These results also suggest that miR-224 may have therapeutic potential target for the treatment of CCRCC. Funding none
Authors
Nakanori Fujii
Hiroshi Hirata Koji Ueno Junichi Mori Kosuke Shimizu Yoshihisa Kawaii Ryo Inoue Yoshiaki Yamamoto Hiroaki Matsumoto Tomoyuki Shimabukuro Hideyasu Matsuyama |
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MP60-16 |
CRISPR/Cas9-mediated miR-210-3p depletion promoted tumorigenesis through revival of TWIST1 in renal cell carcinoma |
Kidney Cancer: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP60-16 Sources of Funding: none Introduction CRISPR/Cas9 technology was introduced as an efficient, powerful and broadly used genome editing tool. The aim of this study was to utilize the CRISPR/Cas9 system to control miRNA expression in cancer research. Methods In our miRNA expression signatures in clear cell renal cell carcinoma (ccRCC), we focused on miR-210-3p which was one of the most upregulated miRNAs. We used lenti-CRISPR vector to knock out miR-210-3p with two different single guide RNAs against miR-210-3p. We performed cell function studies and xenograft assay with miR-210-3p- depleted cells. Putative target genes of miR-210-3p was examined in miRNA binding assay. In addition, overall survival between high and low expression of miR-210-3p or the target gene were analyzed by the Kaplan-Meier method. Results In cells transfected with sgRNA targeting miR-210-3p itself, more than 98% miR-210-3p knock out efficiency was observed in all three cell lines (786-o, A498 and Caki2). miR-210-3p depletion significantly increased invasive capacity (P < 0.01) in vitro, and dramatically promoted tumorigenesis in xenograft experiments (P = 0.0039), which was unexpected due to the fact that these miRNAs were up-regulated in RCC. We also found that twist family bHLH transcription factor 1 (TWIST1) was identified as a direct target of miR-210-3p based on target analyses (P < 0.05). The Cancer Genome Atlas (TCGA) database of ccRCC showed that there was a negative correlation between miR-210-3p and TWIST1 expression (P < 0.0001). In accordance with the results in vivo and in vitro analyses, TCGA database showed that the low miR-210-3p expression group had poor survival in comparison with the high group, and the high TWIST1 expression group had poor overall (P = 0.00054) and disease-free survival (P = 0.00347) compared to the low expression group significantly. Conclusions We utilized the CRISPR/Cas9 system to analyze an upregulated miRNA in cancer. CRISPR/Cas9 successfully suppressed miR-210-3p expression in RCC cells. Moreover, by using CRISPR/Cas9 techniques, we found that tumorigenesis was acquired through enhanced expression of oncogenic TWIST1 due to the suppression of miR-210-3p expression via CRISPR/Cas9 techniques. The introduction of the CRISPR/Cas9 methodologies into studies of miRNAs as well as other non-coding RNAs should provide new possibilities in cancer research. Funding none
Authors
Hirofumi Yoshino
Masaya Yonemori Kazutaka Miyamoto Satoshi Kofuji Nijiro Nohata Hideki Enokida Masayuki Nakagawa |
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MP60-17 |
Overexpression of CYP1B1 mediated by loss of miR-200c promotes renal cell carcinoma tumorigenesis via altered expressions of CDC20 and DAPK1 |
Kidney Cancer: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP60-17 Sources of Funding: none Introduction Cytochrome P450 1B1 (CYP1B1) has been shown to be up-regulated in many types of cancer including renal cell carcinoma (RCC), while several reports have shown that CYP1B1 influences regulation of tumor development. However, its role in RCC development has not been elucidated. Here, we explored the functional role and regulatory mechanism of CYP1B1 in RCC. Methods CYP1B1 expression was determined in RCC cell lines, and microarray findings of 96 RCC and 25 normal tissues were obtained. To examine the biological significance of CYP1B1 in RCC progression, we silenced the gene in Caki-1 and 769-P cells by RNA interference, and performed various functional analyses. Furthermore, we evaluated whether miR-200c expression, significantly down-regulated in RCC, is associated with CYP1B1 level in both clinical samples and cell lines. Results First, we confirmed that CYP1B1 protein expression was significantly higher in RCC cell lines as compared to normal kidney tissues, a trend that was also observed in RCC tumor samples (p<0.01). Furthermore, CYP1B1 expression was associated with tumor grade and stage. Next, we silenced the gene in Caki-1 and 769-P cells by RNA interference, and performed various functional analyses to determine the biological significance of CYP1B1 in RCC progression. Inhibition of CYP1B1 expression resulted in decreased cell proliferation, and migration and invasion of RCC cells, while that also induced apoptosis of Caki-1 cells. In addition, gene microarray findings indicated that the anti-tumor effects on RCC cells caused by CYP1B1 depletion might have been due to alteration of CDC20 and DAPK1 expressions, which was confirmed by real-time PCR. Interestingly, CYP1B1 expression was associated with CDC20 and DAPK1 expressions in the clinical samples. Finally, we found that CYP1B1 level was inversely correlated with miR-200c expression in RCC, and miR-200c directly targets the CYP1B1 3&[prime]-UTR and regulates its expression. Conclusions CYP1B1 up-regulation mediated by reduced expression of miR-200C may promote RCC development by inducing CDC20 expression and inhibiting apoptosis via down-regulation of DAPK1. Our results demonstrate that CYP1B1 and miR-200c are potential tumor biomarkers and targets for anticancer therapy in RCC patients. Funding none
Authors
Yozo Mitsui
Inik Chang Koji Tamura Toshihiro Tai Masato Nagata Fumito Yamabe Kuri Suzuki Hideyuki Kobayashi Koichi Nagao Koichi Nakajima Rajvir Dahiya Yuichiro Tanaka |
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MP60-18 |
Long non-coding RNA HOTAIR promotes cell migration via up-regulation of insulin growth factor binding protein 2 in clear cell renal carcinoma |
Kidney Cancer: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP60-18 Sources of Funding: none Introduction The renal cell carcinoma (RCC) is one of the most lethal urologic cancers and about 30% of patients have distal metastasis at the time of diagnosis. Despite great improvement in therapeutic treatment including molecular targeted therapy, the prognosis of patients with distant metastases remains unfavorable. HOX transcript antisense RNA (HOTAIR) is one of the long non-coding RNAs (lncRNAs). Accumulating evidence demonstrates that HOTAIR plays essential roles in cancer development and metastasis in several types of cancer such as lung cancer and gastric cancer. However, the precise mechanism by which HOTAIR enhances cancer malignancy is still unknown, especially in RCC. The object of this study is to elucidate the function of HOTAIR in RCC. Methods The tumor and adjacent normal renal tissues were obtained with informed consent from 64 patients who underwent radical or partial nephrectomy in Miyagi Cancer Center. All tumor tissues were diagnosed pathologically as clear cell renal cell carcinoma. We evaluated the clinical correlates of HOTAIR expression determined by real-time PCR using RNA extracted from the tumor and normal tissues. The functional role of HOTAIR was examined using HOTAIR-overexpressing or knockdown human renal cell carcinoma cell lines (ACHN, A498 and Caki-1). Results The expression of HOTAIR was significantly correlated with tumor nuclear grade, lymph node metastasis, lung metastasis, and AJCC stage. Migration capacity was enhanced in a HOTAIR-depending manner in vitro. Overexpression of HOTAIR in human renal cell carcinoma accelerated tumorigenicity in immunodeficient mice. Microarray analysis revealed that Insulin Growth Factor Binding Protein 2 (IGFBP2) gene was up-regulated in HOTAIR-overexpressing cells, which was validated by real-time PCR and Western blotting. Co-expression of IGFBP2 and HOTAIR was observed in clinical samples (P = 0.04, Fisher&[prime]s exact test). Enhanced migration activity in HOTAIR-expressing cells was attenuated by IGFBP2-knockdown. Conclusions We newly identified IGFBP2 as a downstream molecule of HOTAIR, which is involved in migration capacity. Our findings suggest that a HOTAIR-IGFBP2 axis plays critical roles in RCC progression, and serves as a novel therapeutic target for advanced RCC treatment. Funding none
Authors
Hiromichi Katayama
Keiichi Tamai Sadafumi Kawamura Tatsuo Tochigi Yoichi Arai Kennichi Satoh |
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MP60-19 |
Long noncoding RNA BX357664 regulates cell proliferation and epithelial-to-mesenchymal transition via inhibiting TGF-beta 1/p38/HSP27 signaling in renal cell carcinoma |
Kidney Cancer: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP60-19 Sources of Funding: none Introduction Long noncoding RNAs (lncRNAs) are reported to serve as regulating role in carcinogenesis of various human malignancies. However, the function of lncRNAs and their underlying mechanism in renal cell carcinoma ( RCC ) is still unraveled. The aims of this study were to investigate the expression of lncRNA BX357664 in RCC and explore its function in RCC cell lines. Methods Previous microarray analysis was used to screen potential deregulated lncRNA. Real-time qualitative PCR (qRT-PCR) was used to further confirm the deregulation of BX357664 in 40 paired human RCC samples. Ability of migration, invasion and proliferation in RCC cells were detected by cell migration and invasion assay, cell proliferation assay and cell cycle assay. Western blot was performed to identify the influence of BX357664 on epithelial-mesenchymal transition (EMT), MMP9 and TGF-beta 1/p38/HSP27 signaling pathway in RCC. Results BX357664 was downregulated in tumor tissues in previous microarray analysis (P < 0.05), qRT-PCR was further performed to validate the BX357664 expression in 40 paired RCC tissues and adjacent normal tissues. The result was consistent with the microarray data(P < 0.05). Meanwhile, BX357664 expression was significantly lower in RCC cell lines (Caki-1 and Caki-2) compared with normal renal cell line HK-2(P < 0.05). After upregulation of BX357664 in RCC celllines, ability of migration, invasion and proliferation in RCC cells were significantly inhibited(P < 0.05). In addition, overexpression of BX357664 could block EMT, MMP9 through inhibiting TGF-beta 1/p38/HSP27 signaling pathway. Subsequently, upregulating the protein level of TGF-beta 1 with the present of BX357664 could rescue the malignant cell behaviors inhibited by BX357664 which indicated that BX357664 was attributed its inhibitory role to suppression of TGF-beta 1. Conclusions We have revealed a novel lncRNA BX357664, which might exhibit its inhibitory role in RCC metastasis and progression via block TGF-beta 1/p38/HSP27 pathway. Funding none
Authors
Yiyang Liu
Zengjun Wang |
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MP60-20 |
Identification of microRNA regulating sunitinib resistance in renal cell carcinoma cells |
Kidney Cancer: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP60-20 Sources of Funding: none Introduction Sunitinib is indicated as first-line treatment of metastatic renal cell carcinoma (mRCC) and suppress angiogenesis and tumor cell proliferation through binding to vascular endothelial growth factor receptor and platelet-derived growth factor receptor. However, the clinical benefit in progression free survival is limited and almost patients have a relapse of disease due to acquired resistance. MicroRNA, which are non-protein-coding small RNAs, are involved in cancer progression and regulate gene expression at the post-transcriptional level by binding to the untranslated region (3`UTR) of target mRNAs. The purposes of this study were to generate sunitinib resistant RCC cell lines and to detect candidate miRNAs for regulating sunitinib resistance. Methods The renal cell carcinoma cell line ACHN and RCC23 were cultured in RPMI1640 with 10% Fetal Bovine Serum and 1% of Penicillin-Streptomycin. Sunitinib resistant cells were generated by continuous exposure for three months and gradually increasing doses of sunitinib up to IC50% (inhibitory concentration) of each cell. We used these cells as sunitinib resistant ACHN and RCC23 cell lines (SR-ACHN, SR-RCC23) for the subsequent verification. For microarray analysis, total RNA was labeled using a 3D-Gene miRNA labeling kit. Reverse transcription was performed with a stem-loop RT Megaplex Primer Pool and the Taqman MicroRNA Reverse Transcription Kit. Results According to previous MTT assay, the IC50% of ACHN cell was 10µM and that of RCC23 cell was 14µM. SR-ACHN and SR-RCC23 cells exhibited significantly higher resistance to sunitinib treatment compared with that of these sunitinib sensitive cells. Microarray analysis was performed comparing ACHN vs SR-ACHN and RCC23 vs SR-RCC23, respectively, to evaluate the miRNA profiles of each cells. In SR-ACHN and SR-RCC23 cells as compared with ACHN and RCC23 cells, the CT values of miR-575, -642b-3p and -4430 have significantly increased, while the CT values of miR-18a-5p, -29b-1-5p, -431-3p and -4521 have significantly decreased with real-time RT-PCR. Conclusions We created sunitinib resistant cell lines SR-ACHN and SR-RCC23 and identified microRNAs considering related with sunitnib resistant by performing microarray. By regulating these microRNAs may contribute to the improvement of sunitinib resistance. Funding none
Authors
Noriya Yamaguchi
Tetsuya Yumioka Kunishige Onuma Hideto Iwamoto Toshihiko Masago Shuichi Morizane Masashi Honda Mitsuhiko Osaki Futoshi Okada Atsushi Takenaka |
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MP61-01 |
Impact of positive preoperative urine cultures before pediatric lower urinary tract reconstructive surgery utilizing bowel |
Pediatrics: Urinary Tract Infection and Vesicoureteral Reflux | 17BOS |
Abstract: MP61-01 Sources of Funding: None Introduction Preoperative urinary tract infections (UTIs) have been shown to correlate with postoperative complications including sepsis, surgical site infections (SSI), and kidney failure. Children who undergo lower urinary tract reconstruction (LUTR) for congenital malformations or neurogenic bladder often have asymptomatic bacteriuria due to chronic colonization. We studied the prevalence and impact of positive preoperative urine cultures (PPUC) before pediatric LUTR. Methods We retrospectively reviewed all pediatric LUTR procedures utilizing bowel segments performed by a single surgeon from 2/2014 to 7/2016. Preoperative urine cultures were analyzed 1-2 days before surgery. Baseline characteristics and 90-day infection/readmission rates were compared between patients with and without PPUC. Fischer's exact, Mann-Whitney, and univariate logistic regression analyses were performed to compare groups with significance p<0.05._x000D_ Results Overall, 54 patients underwent LUTR (including 85% catheterizable channel, 56% bladder augmentation and 9% continent diversion with concurrent 54% ureteral reimplantation and 37% bladder neck reconstruction/division). Mean age was 10±6 years. . None were symptomatic. All started antibiotics at the time of surgery and continued while inpatient. The most common isolated organisms were Enterococcus (n=8), E. coli (n=7), Pseudomonas (n=4), and Klebsiella (n=4). Postoperatively, 20% of the cohort had inpatient infections (8 urine, 4 wound, 2 blood). Infection rates did not differ between groups (9% PPUC vs. 11% negative culture, p=0.69). Median length of stay was also the same in both groups (11 days, p=0.96). Within 90 days of discharge, 27% of patients were readmitted (11% PPUC vs. 16% negative, OR 1.83, p=0.32), 18% experienced a symptomatic UTI (7% PPUC vs. 11% negative, OR 0.58, p=0.45), and 4% developed SSI (2% PPUC vs. 2% negative, OR=0.96, p=0.96). Two patients experienced major complications requiring re-operation (bowel obstruction and ureteral obstruction) and both had negative preoperative urine cultures. Conclusions There is a high prevalence of PPUC in patients presenting for LUTR with bowel segments, but this factor did not appear to impact postoperative infection risk or hospital readmissions. This study supports the safety of performing complex LUTR in patients with PPUC and may provide rationale for the use of broad-spectrum perioperative antibiotics._x000D_ Funding None
Authors
Alexander C Small
Alejandra Perez Stanley Desire Michael J Lipsky Justin T Matulay Lisa Creelman Pasquale Casale Shumyle Alam |
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MP61-02 |
MINIMALLY INVASIVE VERSUS OPEN URETERAL REIMPLANTATION: IS THERE A DIFFERENCE IN RATES OF REOPERATION? COMPARISON FROM A LARGE NATIONAL DATABASE |
Pediatrics: Urinary Tract Infection and Vesicoureteral Reflux | 17BOS |
Abstract: MP61-02 Sources of Funding: University of Chicago Section of Urology Introduction Minimally invasive surgical (MIS) approaches to ureteral reimplantation (UR) for vesicoureteral reflux (VUR) are being used with increasing frequency, despite variability in published rates of complications and reoperation. We assessed rates of secondary procedures following ureteral reimplantation in a prospectively maintained national database. Methods We queried MarketScan, a national employer based insurance database, to identify patients less than 18 years of age who underwent an open or MIS UR between 2008 and 2014. Rates of secondary procedures related to ureteral obstruction (placement of stent or nephrostomy tube, or dilation of ureteral stricture) within 120 days of UR and rates of repeat UR at any time point were assessed. Statistical analysis was performed using t-test, chi-square test, Wilcoxon rank-sum test, and multivariate regression. Results Between 2008 and 2014, 2,752 patients underwent UR with an open approach in 2,601 (94.5%) and MIS in 151 (5.5%). There was a trend toward increased utilization of MIS, with MIS comprising 2.5% of cases in 2008 and 9.3% in 2014 (p=0.026). Relative to the open group, mean age in years was higher in the MIS group (5.6 vs 4.3, p<0.01) and mean length of stay in days was shorter (1.44 vs 2.15, p<0.01). Mean inpatient hospital charges did not differ between the groups ($21,660 vs $20,621, p=0.59). The rate of secondary ureteral procedures within 120 days did not differ between the MIS and open groups (0.7% vs 0.3%%, p=0.76), but rate of subsequent open UR at any time was higher in the MIS group (3.97% vs 0.69%, p<0.01). On univariate analysis, patient age, gender, LOS, and surgical approach did not predict subsequent secondary procedures within 120 days (Table 1). Conclusions From 2008 to 2014 there has been a trend toward increased utilization of MIS UR. Relative to the open approach, MIS approach is associated with a shorter length of hospital stay with no difference in inpatient hospital charges. The rate of secondary ureteral procedure within 120 days of UR did not differ by approach, but patients treated with MIS UR had a higher rate of subsequent open UR. Funding University of Chicago Section of Urology
Authors
Eric D. Schadler
William R. Boysen Christopher Lyttle Vignesh T. Packiam Charles U. Nottingham Mohan S. Gundeti |
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MP61-03 |
QUALITY OF REPORTING AND FRAGILITY INDEX FOR RANDOMIZED CONTROLLED TRIALS IN THE VESICOURETERAL REFLUX LITERATURE – WHERE DO WE STAND? |
Pediatrics: Urinary Tract Infection and Vesicoureteral Reflux | 17BOS |
Abstract: MP61-03 Sources of Funding: None Introduction Randomized controlled trials (RCTs) are the "gold standard" methodology for determining whether treatment effects are due to chance. The fragility index (FI) is used to determine the number of events that would be required to change significant positive results to non-significant (p>0.05). Herein, we assess the quality of reporting of RCTs in vesicoureteral reflux (VUR) literature using the 2010 CONSORT statement, and for studies with significant positive findings, calculate the FI as a measure of robustness of the results. Methods A comprehensive search was conducted through MEDLINE® and Embase® to identify RCTs in VUR literature from 2000-16. Two reviewers independently selected articles, and evaluated them using the 2010 CONSORT checklist. An overall quality of reporting score (OQR) was calculated by dividing the number of checklist items present in each study by the maximum possible score (34) and expressed as a percentage. Studies were classified as low (<40%), moderate (40-70%) and high quality (>70%). A methodological index score (MIS) out of 4 was assigned based on: sample size justification, allocation concealment, randomization method, and blinding of outcome assessors. Of 2052 initial results, 2003 (98%) were excluded because they did not focus on VUR/were not RCTs. After full text screening of 50 articles, we excluded 28 (56%) that did not meet our criteria. For studies reporting significant positive results, we calculated the FI by manually adding events to the group with fewest events until the p value was no longer significant. Results Of the 22 included studies, the mean OQR was 45±16% with 9 (41%) identified as low, 11 (50%) as moderate and 2 (9%) as high quality (Table 1). The mean MIS was 1.95±1. There was no difference in OQR between studies published from 2007-16 (n=15) versus those before 2007 (n=7) (41±15% vs. 44±20%, p=0.70) or RCTs with a sample size >100 (n=15) vs. <100 (n=7) (40±15% vs. 46±17%, p=0.41). However, we noted a difference when we compared RCTs with biostatistician support (n=4) vs. those without (n=18) (62±9% vs. 40±14%, p<0.01). 7 studies reported significant positive results making calculation of FI possible. The mean FI was 5.8±5.1 indicating that most studies were fragile. There was no correlation between the OQS and FI. _x000D_ Conclusions The current OQR in VUR literature is suboptimal. In addition, most FI scores were between 1-5 indicating that only a few events would be required to completely change the results of these studies. Implementation of the CONSORT checklist as a prerequisite for submission of manuscripts may improve the quality of reporting, and calculation of the FI could provide readers with an objective measure of robustness for the reported results. Funding None
Authors
Michele Gnech
Mandy Rickard Armando J. Lorenzo Stephanie Sanger Luis Braga |
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MP61-04 |
THE IPSILATERAL URETERO-URETEROSTOMY: DOES FUNCTION OF THE OBSTRUCTED MOIETY MATTER? |
Pediatrics: Urinary Tract Infection and Vesicoureteral Reflux | 17BOS |
Abstract: MP61-04 Sources of Funding: None Introduction Upper pole nephrectomy has been the traditional surgical management of children with poorly functioning upper pole moieties in duplex renal collecting systems having ureteral ectopia or ureterocele. However, ablative surgery confers a risk of functional loss to the remnant moiety due to vasospasm or vascular injury. We hypothesized that Ipsilateral ureteroureterostomy (IUU) is a safe and feasible approach for the management of these patients, and that residual function in the obstructed upper pole does not affect surgical outcomes. Methods All patients who underwent IUU were entered into an IRB approved registry between 2010 to 2016. Only patients with duplex collecting systems were included in the study. Patients were sorted into two groups based on pre-operative imaging: those having < 10% upper pole moiety function (UPMF) and those having ≥10%. Outcomes assessed were post-operative complications (Clavien-Dindo classification), need for secondary surgery and radiological outcomes. Results A total of 62 patients underwent IUU between 2010-2016 (43 robotic, 19 open). Study cohort comprised 56 children with ectopia or ureterocele affecting the upper pole in a duplex system, 23 with upper pole moiety function (UPMF) <10% (median function 0%, median age 1.49 years) and 33 with UPMF ≥10% function (median function 15%, median age 0.91 years). Median follow up was 27.4 months and 27.6 months respectively. In both groups, prenatal hydronephrosis was the most common presentation (54.4% and 54.8% respectively) followed by UTI. Mann-Whitney U test comparing the two groups revealed no significant differences in any of the outcomes assessed. Overall, no patient required secondary surgery. In the UPMF <10% group, complete resolution of urinary tract dilation was seen in 85.7% of patients while 14.3% of cases had resolution of hydroureter with near complete resolution of hydronephrosis. In the UPMF ≥10% group these outcomes were 84.6% and 15.4% respectively. Complications occurred in 13.6% of the UPMF<10% group (Clavien grade 2) and 16.1% of the UPMF ≥10% group (Clavien grades 2 and 3). Conclusions IUU is a safe, definitive surgical intervention which preserves the renal architecture in children with duplex collecting systems regardless of upper pole function. Funding None
Authors
Arun Srinivasan
Trudy Kawal Douglas Canning Thomas Kolon Stephen Zderic Aseem Shukla |
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MP61-05 |
URINARY CARBOHYDRATE ANTIGEN 19-9 LEVEL AS A NOVEL BIOMARKER FOR EARLY DETECTION OF ACUTE PYELONEPHRITIS |
Pediatrics: Urinary Tract Infection and Vesicoureteral Reflux | 17BOS |
Abstract: MP61-05 Sources of Funding: none Introduction The aim of this study is to evaluate urinary Carbohydrate Antigen 19-9 (CA19-9) levels in early detection of pyelonephritis and its relation with clinical course of the infection and inflammatory changes detected by DMSA. Methods Thirty-five patients with febrile UTI were included in this study as the case group and 30 children who had negative urine culture were nominated as the control group. Urine samples were collected from all participants. Children in case group also underwent complete history and physical examination, kidney and bladder ultrasonography, DMSA, urine analysis and culture. Urine CA19-9 was measured by an electrochemiluminescence enzyme immunometric kit and expressed in U/ml. That level was correlated with clinical factors during statistical analysis. Results A total of 65 children were included in this study (mean age: 3 ± 2.8, 12 male and 53 female). CA19-9 levels were significantly greater in the case group than controls (334.30 ± 308 versus 11.68 ± 5.68, P < 0.000). Urine cultures showed that E. coli was the cause of UTI in most cases. CA19-9 levels were significantly higher in the acute phase of febrile UTI and in children with recurrent febrile UTIs and kidney damage. A correlation was found between CA19-9 levels and temperature. No significant association was found regarding age, sex and urinary CA-19-9 levels. Conclusions This study suggests that urine CA19-9 level is markedly increased in pyelonephritis and has potential utility as a predictive biomarker. Also urine CA19-9 levels can be used as an early detection marker for pyelonephritis in children with UTI._x000D_ _x000D_ Funding none
Authors
Seyedeh Sanam Ladi-Seyedian
Seyedeh Maryam Kameli Mastaneh Moghtaderi Abdol-Mohammad Kajbafzadeh |
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MP61-06 |
Clinical and Patient-Centered Outcomes Associated with Chronic Intermittent Catheterization in the Chronic Kidney Disease in Children Cohort Study |
Pediatrics: Urinary Tract Infection and Vesicoureteral Reflux | 17BOS |
Abstract: MP61-06 Sources of Funding: Data is this study were collected by the Chronic Kidney Disease in children prospective cohort study (CKiD) with clinical coordinating centers (Principal Investigators) at Children's Mercy Hospital and the University of Missouri - Kansas City (Bradley Warady, MD) and Children's Hospital of Philadelphia (Susan Furth, MD, Ph.D.), Central Biochemistry Laboratory (George Schwartz, MD) at the University of Rochester Medical Center, and data coordinating center (Alvaro Muñoz, Ph.D). at the Johns Hopkins Bloomberg School of Public Health. The CKiD is funded by the National Institute of Diabetes and Digestive Kidney Diseases, with additional funding from the National Institute of Child Health and Human Development, and the National Heart, Lung, and Blood Institute (U01-DK-66143, U01-DK-66174, U01-DK-082194, U01-DK-66116). _x000D_ _x000D_ _x000D_ Introduction Urological anomalies are a well-established cause of chronic kidney disease (CKD) in children. The standard treatment for some patients with abnormal bladder function is clean intermittent catheterization (CIC). The goal of this study was to determine the prevalence of urinary tract infections and hospitalizations among children who catheterize the bladder, as compared to children who do not. Methods The prospective, observational Chronic Kidney Disease in Children (CKiD) study cohort is composed of children, ages 1 to 16, with mild to moderate CKD recruited from 47 North American pediatric nephrology centers. CIC status, hospitalizations and infections were determined using a parent completed questionnaire at study entry or any point along the follow-up for a one-year period. We determined baseline characteristics for this subset and used longitudinal mixed logistic regression models to identify predictors of kidney infections, urinary tract infections and hospitalizations. Results A total of 416 CKiD children were included with an underlying urological diagnosis, of whom 105 were on CIC and 311 were not. Median age was 11.9 for CIC and 10.0 for non-CIC patients. Baseline median GFRs were worse in catheter users compared to non-catheter users (53.8 vs 45.6 ml/min/1.73m^2, respectively). Among CIC users, 63% were male, while 71% of non-catheter users were male. Children who catheterized via urethra had on average 3.40-fold odds of hospitalization (95% CI 2.07-5.59, p<0.0001), 4.35-fold odds of bladder infection (95% CI 2.55-7.44, p<0.0001) and 2.56-fold odds of kidney infection (95% CI 1.57-4.17, p=0.0002) compared to children who did not catheterize. Children who performed catheter use via stoma had 6.48-fold odds of hospitalization (95% CI 3.79-11.11, p<0.0001), 7.69-fold odds of bladder infection (95% CI 4.21-14.05, p<0.0001) and 4.19-fold odds of kidney infection (95% CI 2.55-6.87, p<0.0001) compared to children who did not catheterize. A higher percentage of catheter users were seen by a mental health professional at 33% compared to non-catheter users at 14%. Conclusions Children with CKD who perform CIC of the bladder via urethra or stoma comprise a clinically distinct subset with increased risk of negative health outcomes and reported more frequent visits to a mental health provider. Recognizing the needs of this vulnerable population can allow for improved care coordination and ultimately improved long term renal function._x000D_ _x000D_ _x000D_ Funding Data is this study were collected by the Chronic Kidney Disease in children prospective cohort study (CKiD) with clinical coordinating centers (Principal Investigators) at Children's Mercy Hospital and the University of Missouri - Kansas City (Bradley Warady, MD) and Children's Hospital of Philadelphia (Susan Furth, MD, Ph.D.), Central Biochemistry Laboratory (George Schwartz, MD) at the University of Rochester Medical Center, and data coordinating center (Alvaro Muñoz, Ph.D). at the Johns Hopkins Bloomberg School of Public Health. The CKiD is funded by the National Institute of Diabetes and Digestive Kidney Diseases, with additional funding from the National Institute of Child Health and Human Development, and the National Heart, Lung, and Blood Institute (U01-DK-66143, U01-DK-66174, U01-DK-082194, U01-DK-66116). _x000D_ _x000D_ _x000D_
Authors
J Michael Winer
Matthew Matheson Arlene C. Gerson Jessica Ming Bradley A. Warady Susan L. Furth Craig S. Wong Jennifer L. Dodson |
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MP61-07 |
National Trends in VCUG Utilization After the Release of the 2011 AAP Guidelines |
Pediatrics: Urinary Tract Infection and Vesicoureteral Reflux | 17BOS |
Abstract: MP61-07 Sources of Funding: Bomalaski Scholarship: Institutional grant to help support urology residents and pediatric urology fellows Introduction The evaluation of children with a febrile urinary tract infection (UTI) has continued to evolve. A significant paradigm shift occurred in 2011, when the American Academy of Pediatrics (AAP) Guidelines on UTI diagnosis and evaluation recommended against voiding cystourethrogram (VCUG) after a first-time diagnosis of febrile UTI in children aged 2 to 24 months. The objective of this study was to assess national trends in VCUG utilization over the past 15 years. Methods We performed analysis using Optum Labs Data Warehouse administrative claims data from January 2001 - June 2015. Our cohort included all children age ≤ 10 yrs who underwent VCUG for UTI, vesicoureteral reflux, or pyelonephritis. We excluded patients with co-existing diagnoses that involves VCUG as part of standard evaluation. Multiple group interrupted time series analysis (ITSA) with two intervention periods was used to evaluate the impact of the 2011 AAP Guideline on standardized rates of VCUG (Linden, Liden & Yarnold). We designated ages 0 - 2 yr as treatment and 6 - 10 yr as control groups. Results There were 49,311 children identified in our cohort. Post AAP Guideline VCUG rates were significantly decreased compared to pre-intervention VCUG rates for both the 0-2 and 6-10 yr groups (p = <0.0001 and 0.009, respectively). From 2011 to 2015, absolute VCUG utilization rates decreased from 115.8 to 56.5 per 100,000. There was a significant decreasing trend in VCUG utilization rates in the post AAP period (2nd quarter of 2011 - 2nd quarter of 2015) for both age groups (p = <0.0001 and <0.0001, respectively). We also identified a significant decrease in VCUG utilization rates between periods 2001 - 2007 and 2007 - 2011 for both age groups (p = <0.0001 and <0.0001, respectively). Conclusions There was a significant reduction in VCUG utilization rates following publication of the 2011 AAP Guidelines. We also observed a significant decrease in VCUG utilization rates in 2007, the year in which the National Institute for Health and Clinical Excellence (NICE) UTI Guidelines recommended the &[Prime]top-down approach&[Prime] and against routine VCUG testing after febrile UTI. How these changes impacted VUR diagnosis, rates of pyelonephritis, and overall healthcare costs remains to be answered. Funding Bomalaski Scholarship: Institutional grant to help support urology residents and pediatric urology fellows
Authors
Ted Lee
Chandy Ellimmoottil John Park Kate Kraft Vesna Ivancic Kathryn Marchetti Tanima Banerjee David Bloom Julian Wan |
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MP61-08 |
VOIDING CYSTOURETHROGRAM AND ANTIBIOTIC PROPHYLAXIS FOR PRENATAL HYDRONEPHROSIS: SURPRISING RESULTS FROM A SURVEY OF SFU MEMBERS' PRACTICE PATTERNS |
Pediatrics: Urinary Tract Infection and Vesicoureteral Reflux | 17BOS |
Abstract: MP61-08 Sources of Funding: None Introduction Voiding cystourethrogram (VCUG) may be ordered in infants during workup of prenatal hydronephrosis (HN) or after febrile urinary tract infection (fUTI). Definitive guidelines regarding VCUG indications and prescription of continuous antibiotic prophylaxis (CAP) are lacking, resulting in a diverse clinical practice. This study aimed to explore current practice patterns amongst pediatric urologists. Methods An online survey was distributed to members of the Society for Fetal Urology (SFU) to assess practice patterns surrounding VCUG and CAP use in infants. To ensure face and content validity, the survey was developed by experts in the field and piloted locally. Anonymized responses were analyzed according to HN etiology (isolated HN vs. hydroureteronephrosis [HUN]) and grade (low vs. high SFU), gender and circumcision status, as well as the use of antibiotics for prevention of post-VCUG UTI. Results Response rate was 37% (109/297), with 86 (79%) respondents coming from an academic setting. No difference was observed regarding use of CAP or VCUG indications for unilateral vs. bilateral HN or between genders/circumcision status. In contrast, regardless of HN etiology and gender, an expected difference in CAP use was observed between low grade HN (SFU I/II) vs. high grade HN (SFU III/IV) (p<0.001). Most respondents recommended CAP and VCUG to infants with high grade HUN (Table 1). For infants with their 1st fUTI and a normal ultrasound (US), we observed that more respondents would order VCUG for males (74%) and females (77%) 0-2 mos. compared to male (54%) and female (53%) infants 2-24 mos. (p<0.01). No significant difference was found when comparing VCUG indications for a 1st fUTI for male and female infants 0-2 and 2-24 mos. with abnormal US. Over 90% of respondents indicated that they would order VCUG regardless of gender or age for this cohort. Despite 85% of clinicians reporting that they had observed a UTI after VCUG, only 31 (28%) empirically treated to avoid a potential post-VCUG UTI. Conclusions This is the largest study to date assessing pediatric urology practice patterns in evaluating subtypes of prenatal HN. Despite being a common condition, our study demonstrates VCUG and CAP practice patterns vary substantially. Surprisingly, CAP use and VCUG indications were minimally affected by gender and HN laterality. However, their use was much more common in infants with high vs. low grade HN, as well as those with HUN compared to isolated HN. Funding None
Authors
Adriana Dekirmendjian
Mandy Rickard CD Anthony Herndon Christopher S. Cooper Armando J. Lorenzo Bethany Easterbrook Rebecca S. Zee Natasha Brownrigg Luis H. Braga |
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MP61-09 |
Distal Ureteral Diameter Ratio is an Independent Risk Factor for Breakthrough Febrile Urinary Tract Infection |
Pediatrics: Urinary Tract Infection and Vesicoureteral Reflux | 17BOS |
Abstract: MP61-09 Sources of Funding: None Introduction Previous reports have demonstrated that distal ureteral diameter ratio (UDR) is an objective and reliable measure predictive of spontaneous resolution in children with primary vesicoureteral reflux (VUR). Improved identification of children at risk for recurrent febrile urinary tract infections (fUTI), along with likelihood of spontaneous resolution, may impact management decisions. We evaluated the effect of UDR as a predictive factor for breakthrough fUTI. Methods Children with primary VUR and detailed voiding cystourethrogram (VCUG) were identified. Children were prescribed daily prophylactic antibiotics and followed with annual cystograms until reflux resolution or operative repair. UDR was computed by measuring largest ureteral diameter within the pelvis and dividing by the distance between the L1-L3 vertebral bodies. Demographics, VUR grade, laterality, presence/absence of bladder bowel dysfunction (BBD), and UDR were tested in uni and multivariate analysis. Primary outcome was breakthrough fUTI. Results One hundred and forty children (112 girls, 28 boys) met inclusion criteria. Mean age at diagnosis was 2.5±2.3 years, and mean length of follow-up was 3.2±2.7 years. VUR was grade 1-2 (n = 64, 45.7%), grade 3 (n = 50; 35.7%), grade 4 (n = 16; 11.4%) and grade 5 (n = 10; 7.2%). Forty children (28.6%) experienced breakthrough fUTI events. Children with breakthrough fUTI had significantly higher UDR than those without (0.25 versus 0.36; p = 0.004). Controlling for VUR grade, every 0.1 unit increase in UDR resulted in 1.7 times increased odds of breakthrough fUTI (95% CI 1.24-2.26; p<0.0001). Increased probability of breakthrough fUTI was observed with increased UDR; however increasing grade alone was not [Figure]. Forty-five children (32.1%) experienced spontaneous VUR resolution at a mean of 2.7±2.7 years. Ninety-five patients (67.9%) underwent surgical correction of VUR at a mean of 3.4±2.6 years from initial diagnosis. Conclusions Children with elevated distal ureteral diameter ratio are at increased risk for breakthrough fUTI independent of reflux grade. UDR was more predictive of breakthrough fUTI than either VUR grade or UDR combined with grade. UDR provides valuable prognostic information about risk of recurrent pyelonephritis and may assist with clinical decision-making. Funding None
Authors
Angela M. Arlen
Siobhan E. Alexander Paul J. Guidos Traci Leong Christopher S. Cooper |
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MP61-10 |
Use of single point dosimeter to evaluate radiation dose with fluoroscopic voiding cystourethrogram in pediatric patients: a prospective pilot study |
Pediatrics: Urinary Tract Infection and Vesicoureteral Reflux | 17BOS |
Abstract: MP61-10 Sources of Funding: None Introduction A voiding cystourethrogram (VCUG) is a source of ionizing radiation exposure to pediatric patients. The actual radiation dose absorbed by the patient has not been accurately reported, and concerns for radiation exposure using this conventional imaging modality has spurred the development of less accurate means to diagnose and characterize vesicoureteral reflux (VUR). We prospectively measure radiation dose during VCUG using a single point dosimeter in pediatric patients. Methods Pediatric patients undergoing conventional VCUG were prospectively enrolled in the study. Dosimeters (nanoDot®OSL) were affixed to the skin overlying the sacrum. Siemens® Axiom Luminos TF fluoroscopic machine was used, and skin-to-source distance was fixed at 60 cm, beam collimated to the smallest area possible, low dose setting applied, and fluoroscopy pulsed at 3 frames/sec. Dose area product (mGy*m2) and fluoroscopic time (sec) was determined by the xray source. Air kerma (mGy), which is the radiation dose delivered by the source to a single point in air, was calculated. The absorbed dose received by dosimeter (mGy) was measured. Results Thirty-eight patients were prospectively enrolled in our study with a median age of 12.5 months (IQR 4-39), median body mass index (BMI) of 17 (IQR 16.4-18.6), and predominantly female (68%). Median fluoroscopic time was 54 seconds (IQR 36-72). The median dose area product (mGy*m2) was 4.4 (IQR 2.6-7.5) and median radiation dose absorbed at the skin entrance per dosimeter (mGy) was 0.33 (IQR 0.13-0.5, range .01-2.9) (p=0.01). There was a positive correlation between the air kerma, 0.2 mGy (IQR 0.17-0.39) and absorbed dose measured by dosimeter, 0.33 mGy (IQR 0.13-0.5) (r = 0.67, p < 0.001). There was no correlation between absorbed dose and BMI (r = 0.14, p = 0.4), and fluoroscopy time and BMI (r = 0.24, p = 0.15). There was a positive correlation between fluoroscopy time and absorbed dose (r = 0.64, p < 0.001). Conclusions The radiation dose absorbed at skin entrance is low for a single VCUG when employing tight collimation, low dose settings and pulsed fluoroscopy without compromising the quality of the image. As newer non-ionizing technologies to diagnoses VUR continue to emerge, this study provides reassurance that a single VCUG is still safe with low radiation doses. Funding None
Authors
Rajeev Chaudhry
Patrick J Fox Pankaj Dangle Wael Abdalla Helen Bradley Mark Duranko Michael Sheetz Francis X Schneck Glenn M Cannon Michael C Ost Heidi A Stephany |
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MP61-11 |
A Reevaluation of the RIVUR trial with a Validated Risk Stratification Model |
Pediatrics: Urinary Tract Infection and Vesicoureteral Reflux | 17BOS |
Abstract: MP61-11 Sources of Funding: None Introduction The Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) trial showed a 50% reduction in the risk for recurrent urinary tract infection (UTI) in children who received prophylaxis compared to placebo. This conclusion is heavily debated. We reevaluated the RIVUR data using a validated risk stratification model. Methods Data from all 607 children were used. We stratified the children into low, intermediate and high risk categories based on gender, circumcision status, VUR grade and bladder bowel dysfunction. Febrile or symptomatic UTI recurrence in our stratified placebo and prophylaxis groups were compared using Fisher's exact test. Kaplan-Meier curves and a log-rank test was used for time-to-event analysis. Results There were 389 (65%), 132 (22%) and 50 (8%) children stratified into low, intermediate and high risk categories. The rate of recurrent UTI was not significantly different in low risk children receiving either placebo or prophylaxis (Table 1). Whereas intermediate risk children receiving prophylaxis had a 20% absolute reduction in recurrence compared to placebo. Similarly, there were half as many recurrent UTIs in high risk children on prophylaxis; however this was not significant due to the small sample size. Time-to-event analysis showed no difference in recurrence between the stratified categories with placebo or prophylaxis (p=0.045). Conclusions The majority (65%) of the children in the RIVUR trial fell into the low risk category and do not benefit from prophylaxis, while intermediate risk children receiving prophylaxis showed a 20% absolute reduction in recurrence. These results favor an individualized approach for the optimal management of children with vesicoureteral reflux. Funding None
Authors
Zhan Tao (Peter) Wang
Yasaman Alam Irene McAleer Ahmed Ali Josh Chamberlin Guy Hidas Antoine Khoury |
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MP61-12 |
A critical review of recent clinical practice guidelines on the diagnosis and management of paediatric urinary tract infection using the AGREE lI TooL |
Pediatrics: Urinary Tract Infection and Vesicoureteral Reflux | 17BOS |
Abstract: MP61-12 Sources of Funding: none Introduction There are many clinical practice guidelines (CPGs) published recently pertaining to the management of pediatric urinary tract infection (pUTI). Concerns regarding the quality, credibility and applicability of these CPGs have been raised due to the inconsistencies of recommendations between them. We hypothesized that these differences may be due to variation in the quality of the guideline development process therefore the aim of this project was to determine the quality of the CPGs on pUTI using AGREE II (Appraisal of Guidelines Research and Evaluation) instrument. Methods A systematic literature search was performed to identify CPGs for pUTI published from 2007-2016. Eligible CPGs were independently assessed and appraised by 5 physician reviewers using AGREE II tool. The CPGs were assessed for domains and summarized for overall quality by each reviewer. The appraisal score for each guideline was extrapolated for each AGREE domain and in overall total. CPGs were then ranked accordingly and domains were assessed for quality. Domain score less than 70 is considered low. Inter-rater reliability was assessed using Inter-class coefficient (ICC) and statistical significance was set at 0.5. Results A total of 13 CPGs were critically reviewed. Amongst the 5 reviewers, there was a high degree of inter-rater reliability. The average measure ICC was 0.922 with a 95% confidence interval from 0.826 to .0.973 (F(12,48)= 12.806, p<.0001). The Spanish guideline for pediatric UTI, American Association of Pediatrics (AAP) and National Institute for Health and Clinical Excellence (NICE) guidelines consistently scored high on all AGREE domains. 10/13 CPGs had scores <70 for the domains of applicability, while the domains of stakeholder involvement and rigor of development were low in 9 CPGs. Conclusions The CPGs from Spain, AAP and NICE scored highly on the AGREE II indicators of quality of the CPG development process. Domains of applicability, stakeholder involvement and rigor of development were suboptimal quality wise in the majority of the most recently available CPGs for pUTI. This leads to potential confusion for the intended audience for whom these guidelines have been developed. Clinicians are recommended to consider these findings when selecting pUTI guidelines for use in practice. Funding none
Authors
Michael Chua
Jessica Ming Joana Dos Santos Shang-Jen Chang Jan Michael Silangcruz Mark Bayley Martin Koyle |
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MP61-13 |
Compliance with the 2011 AAP UTI Guidelines for VCUG Ordering by Provider Specialty |
Pediatrics: Urinary Tract Infection and Vesicoureteral Reflux | 17BOS |
Abstract: MP61-13 Sources of Funding: None Introduction Controversy exists regarding the 2011 AAP guidelines for voiding cystourethrogram (VCUG) ordering in the setting of febrile urinary tract infection (UTI) in children aged 2-24 months. We aimed to (1) determine rates of provider compliance by specialty and (2) evaluate the association between guideline adherence and VCUG result. Methods We completed a retrospective review of all patients undergoing VCUG at our institution from 1/12-12/13. Patients with neurogenic bladder, known genitourinary abnormality, known vesicoureteral reflux, or those >18 years of age were excluded. The primary outcome was adherence to the 2011 guidelines for VCUG acquisition. Relationships between provider specialty (urology vs pediatrics), patient demographics, VCUG outcome, and guideline adherence were evaluated with bivariate statistics and logistic regression. Subgroup analysis of patients 2-24 months was completed. Results VCUGs from 1,115 consecutive patients were reviewed. 747 patients were excluded (243 for known genitourinary anomalies, 262 for known VUR, 171 for antenatal hydronephrosis without UTI, and 71 for incomplete records). 368 patients (67% female, median age 12.5 months [range 4.6-49]) were included in the primary analysis. 188 patients (51%) were aged 2-24 months. VCUG ordering patterns were similar among urologists and nephrologists (35% of VCUGs) and among pediatricians and other specialists (65% of VCUGs). Thus, these specialties were grouped for analysis. 61% of VCUGs were ordered in accordance with the 2011 AAP guidelines; urologists/nephrologists were more likely to adhere to ordering guidelines than pediatricians/other specialists (76% vs 52%, OR 2.93 [1.8-4.7], p<0.0001). Subgroup analysis in patients 2-24 months revealed similar findings (76% vs 52%, OR 3.0 [1.5-6.1], p=0.002). VCUGs were abnormal in 117/368 patients (32%) overall and 49/188 (26%) patients 2-24 months. Guideline adherence was associated with increased likelihood of abnormal VCUG among all patients (36% of appropriately ordered vs. 25% of inappropriately ordered studies were abnormal, p=0.03), but there was no association in patients 2-24 months (26% of studies were abnormal in each group, p=0.98). Conclusions At our institution, 2011 AAP UTI guideline adherence for VCUG ordering was more likely among urologists/nephrologists than pediatricians. While adherence increased the diagnostic yield of VCUG studies in the full cohort, there was no association in children 2-24 months. Further multi-center evaluation is necessary to determine whether ordering recommendations should be revised. Funding None
Authors
Deborah L Jacobson
Rachel Shannon Jared R Green Cynthia L Rigsby Sangeeta K Schroeder Neha R Malhotra Ilina Rosoklija Jane L Holl Earl Y Cheng Emilie K Johnson |
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MP61-14 |
Effect of Newborn Circumcision on Urinary Tract Infections in Patients with an Early Diagnosis of Hydronephrosis. |
Pediatrics: Urinary Tract Infection and Vesicoureteral Reflux | 17BOS |
Abstract: MP61-14 Sources of Funding: None Introduction Boys with known urinary tract abnormalities may derive a greater benefit of newborn circumcision for prevention of urinary tract infection (UTI) than the general population. However, the effect of newborn circumcision on UTI in this population is not well characterized across the spectrum of etiologies for hydronephrosis (HN). We hypothesized that in boys with an early diagnosis of HN rates of UTI will be reduced by newborn circumcision while patients with vesicoureteral reflux (VUR) and posterior urethral valves (PUV) will realize the greatest benefit of the intervention. Methods Claims from MarketScan®, an employer-based dataset of privately insured patients, were used to identify boys with HN or HN-related diagnoses (PUV, VUR, ureteropelvic junction obstruction [UPJO], ureterocele) within the first 30 days of life. Patients with severe urologic comorbidities were excluded as were children with inadequate longitudinal enrollment for follow-up and/or UTI within the first 30 days of life. The primary outcome was the rate of UTIs within the first year of life, comparing circumcised to uncircumcised boys as an entire group and across diagnostic sub-groups, adjusting for region, insurance type, year of birth, and infant comorbidity. Results A total of 5561 boys met inclusion criteria, including 2386 (42.9%) undergoing newborn circumcision and 3175 (57.1%) uncircumcised boys. Boys with > 2 comorbidities were more frequently uncircumcised (6.1% vs 2.5%, p < 0.001). Overall rates of UTI were lower in circumcised boys as compared to uncircumcised boys (5.9% vs 16.1%, p < 0.001) with an adjusted odds ratio for a UTI of 0.35 (0.29-0.43) in the circumcised population. Circumcision was associated with a decreased odds of UTI across several diagnostic subgroups including general HN, VUR, and UPJO, as seen in the Table. Conclusions Newborn circumcision is associated with a 35% lower rate of UTI in boys with an early diagnosis of HN. This association is seen for across all most diagnostic sub-groups for HN, adjusting for measurable confounding variables. Lack of significant association in boys with PUV and ureterocele may be due to low rates of these diagnosis in this cohort. Future work to prospectively evaluate the benefit of circumcision in this population at a granular level is needed. Funding None
Authors
Jonathan Ellison
Geolani Dy Ben Fu Sarah Holt John Gore Paul Merguerian |
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MP61-15 |
Technical Variability in Robot-Assisted Laparoscopic Ureteral Reimplantation: Feasibility of a Multi-Institutional Collaborative |
Pediatrics: Urinary Tract Infection and Vesicoureteral Reflux | 17BOS |
Abstract: MP61-15 Sources of Funding: None Introduction Robot-assisted laparoscopic ureteral reimplantation (RALUR) has been criticized due to concerns about technique and success rates. Within a 4-site Robotic Research Collaborative (RRC) we aimed to: (1) determine if sufficient technical variability exists to conduct a prospective study, and (2) evaluate the association between RALUR technical factors and patient outcomes._x000D_ Methods A retrospective study of children undergoing RALUR for 1° vesicoureteral reflux (VUR) from 1/2013-5/2015 was conducted. Exclusions: neurogenic bladder, megaureter, or follow-up <30 days. Clinical failure definition: persistent VUR Grade ≥II, febrile urinary tract infection (fUTI) within 1 year of RALUR, or complication requiring reoperation. Fisher&[prime]s exact test was used for bivariate comparisons. Results 98 patients (143 ureters, 85% single system, 79% female, median age 5 years) underwent RALUR by 9 surgeons. Indications included VUR non-resolution (43%), renal scarring (37%), and breakthrough UTI (27%). Highest VUR grade was I/II in 15%, III in 45%, IV/V in 38%, and ungraded in 2%. Bowel/bladder dysfunction was noted in 45%. Variability in multiple technical details was identified (Table 1). 17 patients (17%) had clinical failure: 9 (9%) VUR Grade ≥II, 9 (9%) fUTI, 2 (2%) fUTI + persistent VUR, and 2 (2%) required reoperation. None of the technical factors in Table 1 were associated with clinical failure (e.g., Table 2). Conclusions Patients undergoing RALUR at 4 RRC sites had an 83% clinical success rate, comparable to historical open surgery rates. It was feasible to collect some technical details retrospectively; technique variability was documented. This initial series found no association between technical factors and clinical outcomes. Future plans include prospectively evaluating associations between technical factors and RALUR outcomes, and developing standardized technique recommendations. Funding None
Authors
Emilie Johnson
Michael Kurtz Ilina Rosoklija Edward Gong Duong Tu Sheila Ryan Trudy Kawal Aseem Shukla Arun Srinivasan Richard Yu Bruce Lindgren Chester Koh |
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MP61-16 |
Variations in Adherence to AUA Guidelines for Vesicoureteral Reflux |
Pediatrics: Urinary Tract Infection and Vesicoureteral Reflux | 17BOS |
Abstract: MP61-16 Sources of Funding: 2016 AUA Data Grant Introduction Although the American Urologic Association (AUA) has established clinical guidelines addressing the evaluation of children with vesicoureteral reflux (VUR), the extent of adoption of these guidelines is unclear. The purpose of this study was to assess adherence to AUA recommendations for annual follow up of children with VUR and to identify demographic and clinical factors associated with increased adherence across multiple sites. Methods We conducted a multicenter cohort study utilizing data embedded in the Epic electronic health record (EMR) across three pediatric urology practices. Patients were included if they had been seen between 9/1/2015 and 2/28/2016, were age < 18 years, and had a diagnosis of VUR. Data regarding patient demographics, initial and one year follow up evaluation with vital signs, urinalysis (UA), and ultrasound (US) were captured. Chi-squared was used for univariate analyses and logistic regression models were created for univariate and multivariable analyses. Results 837 patients were identified. Most patients were female (69%), white (67.2%), and non-Hispanic (61.5%) with a mean age of 2.3 years (st. dev. 3). Initial evaluation with vital signs and UA varied significantly across sites (p<0.001). In patients who had at least one year of follow up (n=439), follow up vital signs and US were associated with treatment with prophylaxis and age (p<0.01). Site was associated with follow up blood pressure (BP), height, and UA (p<0.001); US and weight did not vary by site. Initial evaluation was also associated with follow up BP, height, and UA (p<0.001). On multivariate analysis, location, initial evaluation with BP, treatment plan, and age remained significantly associated with follow up BP (all p<=0.02). Location and height at initial visit were associated with follow up height (p<0.001); similarly, location and UA at initial visit were associated with follow up UA (p<0.001). Weight and US did not seem to be associated with location but did vary by treatment plan (p<0.05). Conclusions We found significant variations in adherence to AUA recommendations for annual vital signs, US, and UA. While many of these appear to be based on site of care, follow up studies were also associated with patient age, initial evaluation, and treatment plan. Further work is needed to better understand the etiology of these variations and the role of additional clinical factors, such as VUR grade and renal impairment, on adherence to AUA recommendations for VUR. Funding 2016 AUA Data Grant
Authors
Vijaya Vemulakonda
Nicolette Janzen Carter Sevick George Chiang |
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MP61-17 |
Split-cuff nipple ureteroneocystotomy for repair of primary obstructed megaureter in small capacity bladder of infants |
Pediatrics: Urinary Tract Infection and Vesicoureteral Reflux | 17BOS |
Abstract: MP61-17 Sources of Funding: None Introduction The majority of congenital megaureters who present with prenatal dilation are managed conservatively by periodic monitoring with or without antibacterial prophylaxis. In some cases of break through infections, renal function deterioration and/or worsening of the dilation surgical intervention is contemplated. Surgery ranges from temporary stenting, refluxing re-implantation to cutaneous ureterostomy. Herein is a report on the results of the split-cuff nipple technique uretero-neocystotomy in the infantile small capacity bladder Methods Between 1996 and 2015 seventeen infants (12 males and 5 females) with 21 megaureters presented with breakthrough pyelonephritis(9), and worsening hydroureternephrosis (8). the ages varied between 14-34 weeks at the time of surgery. The ureteral diameter on ultrasonography was 12-30 mm(mean 16 mm). All underwent excision of the distal narrow ureteral segment and non-tapered transvesical reimplantation by a combination of a short submucosal tunnel (1-2 cm)and creation of a splt-cuff nipple ureteral orifice. 16/21 ureters were stented and the stents were removed 4-6 weeks postoperatvely. Follow up studies with ultrasonography(US)at 1,3,6 and 12 months and voiding cystouretherography (VCUG) were performed in all children at 4-6 months post surgery. Results Renal dilation improved in 15, resolved in5 and unchanged in 1 renal unit. The VCUG showed no vsicoureteral reflux in 19/21 (90%), Grade III and Grade I reflux in two ureters. Postoperative urinary infection occurred in 2 children. Conclusions In 1969 Lyon et al. suggested that the shape of the ureteral orifice played an important role in reflux prevention. In a parametric simulation model Villanueva et al studied the mechanics of the ureterovesical valve and challenged the time honored Paquin length/diameter rule of 5/1.Their model suggested that the shape of the ureteral orifice making it protrude into the bladder like a volcano or creating a nipple contributed to an efficient antireflux mechanism._x000D_ The simple split cuff nipple technique without ureteral tapering combined with a modest submucosal tunneling was highly successful for the management of dilated ureters and small capacity bladders when there is a limited space for conventional tapered long tunnel ureteroneocystotomy. Funding None
Authors
Moneer Hanna
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MP61-18 |
Evolution in Endoscopic Management of Ureterocele: Long-Term Outcomes of Ureterocele Double Puncture as a Promising Technique |
Pediatrics: Urinary Tract Infection and Vesicoureteral Reflux | 17BOS |
Abstract: MP61-18 Sources of Funding: none Introduction We aim to present long-term outcomes of patients with ureterocele, treated by an innovative technique. To date the optimal surgical technique for ureterocele complex remains unclear and treatment options are extremely variable in this regard. These techniques mostly share major drawbacks including de novo vesicoureteral reflux (VUR) into ureterocele moiety and mandatory secondary surgery. A feasible and minimally invasive method for treatment of ureterocele using concomitant ureterocele double puncture and intraureterocele fulguration has been previously introduced (Kajbafzadeh et al. J Urol 2007; 177: 1118-23). Herein, we present long-term outcomes of this technique. Methods After obtaining institutional ethical approval, a retrospective chart review was performed to gather records of patients undergone this technique between 1999 and 2014. Patients with history of previous ureterocele surgery or follow up period of less than two years were excluded from the study. In this technique, after maintaining two punctures into the poles of ureterocele using the stylet of a 3Fr ureteral stent and cutting current, a Double-J stent was inserted into the both punctured sites. Afterwards, fulguration of anterior and posterior ureterocele walls at multiple sites was performed under direct vision in order to create anterior and posterior wall surface welding of urine channel. Results During the study period, 48 patients (51 ureteroceles) underwent this technique. From these, 31 (64.6%) patients were female. Two patients had single system ureteroceles. Three patients (6.2%) underwent bilateral ureterocele double puncture. Mean (range) age at the time of surgery was 2.9 (2 months – 13 years) years. The mean follow up period was 6.1 (2-15.2) years. Mode of presentation was febrile UTI (52%). Ureterocele was successfully decompressed in all except two kids (success rate=96%). Secondary ureterocele surgery was performed successfully in two aforementioned patients. De novo VUR was diagnosed in another two patients in upper pole ureter (one grade II, one grade III) which was endoscopically treated with success in both cases. No febrile UTI was encountered postoperatively. Conclusions The present study suggests that double puncture ureterocele surgery is highly successful in decompressing ureterocele without incurring major complications, further partial nephroureterectomy or common sheet double ureteric reimplatation. We believe that, this technique could serve as a promising minimally invasive alternative in ureterocele management. Funding none
Authors
Behnam Nabavizadeh
Reza Nabavizadeh Abdol-Mohammad Kajbafzadeh |
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MP61-19 |
An Inguinal Approach To Complex Extravesical Ureteral Reimplantation |
Pediatrics: Urinary Tract Infection and Vesicoureteral Reflux | 17BOS |
Abstract: MP61-19 Sources of Funding: none Introduction The modified Lich-Gregoir extravesical technique (EVR) via a Pfannenstiel incision avoids opening the bladder and dissection of the trigone, and carries exceptional success. Minimally invasiveness endoscopic injections and laparoscopic/robotic approaches carry inferior results and are uncommonly used in more complex cases (megaureter, duplex systems). Consistent with the goal of minimizing invasiveness, we previously reported our positive experience with EVR through a 2 cm inguinal incision. Herein, we report our experience applying this approach to complex cases of ureteral reimplantation. Methods We reviewed the records of all patients who underwent common sheath and/or tapered EVR through an inguinal incision by a single surgeon. Patient characteristics of age, gender, and reflux grade were obtained, and outcomes were assessed. The technique involved a 2 cm incision made in the lowest inguinal skin crease, standard cord exposure and lateral retraction, opening the floor of the inguinal canal to isolate the ureter. Excisional tapering was performed with the ureter dismembered from the bladder and then reimplanted via detrussorhaphy while the common sheath reimplantation was performed with advancement fixation sutures and the ureters in situ. Results There were 28 patients (15 males and 13 females) with a median age of 1.7 years (range 0.9-4.8 yr) included in the series. 15 patients had ureteral tapering, 12 underwent common sheath reimplantation, and 1 child had both. Indications for surgery were VUR in 19 (average - grade IV), UVJ obstruction in 8, and both in 1 patient. The majority of cases were left-sided (22, 78.6%). One case was a redo surgery from a prior failed reimplantation. Mean hospital length of stay was 1.8 days. Success was seen in 93% (two patients had persistent VUR, one required re-operation). There were no postoperative obstructions, urinary leaks, or wound infections. Conclusions Extravesical ureteral tapering and common sheath reimplantation can safely and effectively be performed through a 2 cm inguinal approach. Funding none
Authors
Adam S. Howe
Lane S. Palmer |
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MP61-20 |
Acute Ureteral Jet Angled Measured by Preoperative Ultrasound Correlates With Resolution of Vesicoureteral Reflux Treated With Endoscopic Injection of Subureteric Bulking Agents |
Pediatrics: Urinary Tract Infection and Vesicoureteral Reflux | 17BOS |
Abstract: MP61-20 Sources of Funding: None Introduction Endoscopic injection of subureteric bulking agents (SBAs) provides a minimally invasive surgical option for the treatment of vesicoureteral reflux. We evaluated the correlation between ureteral jet angle (UJA) demonstrated by preoperative ultrasound and the successful treatment of vesicoureteral reflux with SBAs. Methods This is a retrospective study of pediatric patients treated with SBAs for vesicoureteral reflux. Inclusion criteria were preoperative and postoperative voiding cystourethrogram (VCUG) and preoperative ultrasound that demonstrated ureteral jets. Resolution of reflux was defined as complete absence of reflux on postoperative VCUG. Patients with missing radiographic studies, repeat SBAs, or patients with duplicated collecting systems were excluded. Preoperative UJAs were measured by ultrasound in the transverse plane as the angle between the ureteral jet and the trigonal ridge. Mean UJAs were compared using the t-test. The electronic medical record was reviewed for pertinent clinical and radiographic parameters. Results We identified 68 refluxing renal units in 48 patients. Median age was 6 years old (range 2-11). Majority of patients were female (89.5%). 70.7% of patients were dysfunctional voiders. 47 renal units had low-grade reflux (grade 1 and 2) while 21 had high-grade reflux (grades 3, 4, and 5). The mean preoperative UJA in patients with resolution of reflux after SBA was 60.4° (std. 24.7) compared to a preoperative UJA of 85.4° (std. 45.6) with persistent reflux postoperative, p=0.0097 (Figure 1). When stratified by grade of reflux, resolution of low-grade reflux demonstrated an acute preoperative ureteral jet angle (64.4° +/-27.7) compared to patients with persistent reflux (98.15° +/- 45.33), p=0.0039. This effect was not seen in children with high-grade reflux (21 renal units). Dysfunctional voiders displayed the same trend in mean preoperative UJA. Mean preoperative UJA with resolution of reflux was 61.9° (SD+/- 26.1) and 100.6° with persistent reflux (SD +/- 50.3) in this subpopulation, p=0.0004. No significant difference was seen in nondysfunctional voiding children (20 renal units). No association was seen with UJA and the development of febrile UTI postoperatively. Conclusions In our study sample, an acute preoperative UJA measured by renal US was associated with resolution of reflux with SBAs. Further investigation into the prognostic utility of UJA is warranted. Funding None
Authors
Kevin Ginsburg
Jesse Jacobs Kahlil Saad Theodore Barber Brian Roelof Kirstan Meldrum George Steinhardt |
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MP62-01 |
Prediction for success rate of shock wave lithotripsy using mean stone densitystone heterogeneity index ratio calculating Hounsfield unit on noncontrast computed tomography |
Stone Disease: Shock Wave Lithotripsy | 17BOS |
Abstract: MP62-01 Sources of Funding: None Introduction The mean stone density (MSD) and stone heterogeneity index (SHI), was defined as the mean of Hounsfield unit (HU) and the standard deviation of a HU on non-contrast computed tomography (NCCT), are already reported independent predictor of SWL outcomes. We investigated whether MSD-SHI ratio can be a significant predictor for SWL outcomes in patients with ureteral stones. Methods Medical records were obtained from a consecutive database of patients (n = 1,824) who had undergone the first session of SWL between November 2005 and December 2014 in the Severance Hospital, Seoul, Korea. Ultimately, 700 patients with ureter calculi were eligible for the current analyses. Stone related variables including mean stone length (MSL), MSD, skin-to-stone distance (SSD), and SHI were obtained on NCCT. Results The mean age of total patients was 52.55±13.88 years. The distribution of ureteral stone locations was comprised of 573 cases of upper ureter stones (81.9%), 48 cases of mid-ureter stones (6.9%), and 79 cases of lower ureter stones (11.2%). The MSL was 9.12±3.89 mm, and the mean MSD and SHI were 707.04±272.10 HU and 244.90±110.16 HU, respectively. The mean SSD was 110.81±18.98 mm. The one-session success and one-session stone-free rates were 69.6%. The univariate logistic regression models revealed the following predictive factors of one-session success following SWL for ureteral stones: shorter MSL, lower MSD, higher SHI, and lower MSD-SHI ratio. The multivariate analyses also demonstrated that a shorter MSL, lower MSD, higher SHI, and lower MSD-SHI were independent predictors of one-session success after SWL for ureteral calculi. For one-session success rates, the AUC of ROC curves in total cohort were 0.725 for MSD, 0.661 for MSL, and 0.749 for MSD-SHI ratio and there were no significant differences between MSD and MSD-SHI ratio (P = 0.348). In patients with upper 50% MSL, the AUC of ROC curves were 0.676 for MSD, 0.661 for MSL, and 0.764 for MSD-SHI ratio and there were significant differences between MSD and MSD-SHI ratio (P = 0.011) (Fig. 1). Conclusions MSL, MSD, SHI, and MSD-SHI were independent predictors of one-session success after SWL for ureteral calculi. MSD-SHI showed higher predictive value compared to MSD or MSL in patients with relatively large stone. Funding None
Authors
Jong Kyou Kwon
Dong Hyuk Kang Kang Su Cho Won Sik Ham Seung Hwan Lee Young Deuk Choi Joo Yong Lee |
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MP62-02 |
Variation coefficient of stone density: a novel predictor of treatment outcome following extracorporeal shockwave lithotripsy. |
Stone Disease: Shock Wave Lithotripsy | 17BOS |
Abstract: MP62-02 Sources of Funding: none. Introduction Although previous studies have indicated that stone heterogeneity can affect shock wave lithotripsy (SWL) outcomes, there is no established measurement of stone heterogeneity on non-contrast computed tomography (NCCT) imagery. We investigated whether variation coefficient of stone density (VCSD) can predict shock wave success. Methods We conducted a retrospective review of 245 patients with urinary calculi who had undergone SWL for upper urinary tract calculi. We compared discriminative powers for treatment success using receiver operating characteristics ROC analyses among three indices based on CT attenuation of the stone, i.e., mean stone density (MSD), standard deviation of stone density (SDSD) and VCSD. We also performed logistic regression analysis to identify factors contributing to treatment success. Treatment success was determined as absence or residual fragments <4mm using NCCT within three months after a first session of SWL. Results Treatment success rate was 47.8% (117/245 cases). From ROC analyses for treatment success, AUC of VCSD (0.71) was larger than that of MSD (0.64, p=0.09) and SDSD (0.54, p<0.01) (Figure). Multivariate analysis revealed that MDS (p=0.028) and VCSD (p<0.001) independently predicted the outcome (Table). Categorized by stone location, VCSD was the independent significant predictor for SWL outcomes in both kidney (p=0.047) and ureteral calculi (p<0.001). Conclusions We found that variation coefficient of stone density can be a novel predictor of SWL success. The development of nomograms or scoring systems including VCSD can assist in the decision process for patients and minimize unnecessary delay in treatment of urolithiasis. Funding none.
Authors
Shimpei Yamashita
Yasuo Kohjimoto Takashi Iguchi Akinori Iba Isao Hara |
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MP62-03 |
Predicting ESWL outcome using classification and regression tree (CART) analysis |
Stone Disease: Shock Wave Lithotripsy | 17BOS |
Abstract: MP62-03 Sources of Funding: None Introduction Previous studies have developed various predictive models for stone-free rate following extracorporeal shock wave lithotripsy (ESWL). However, these models have several limitations such as difficulty in usage and lack of information derived from CT imaging. In this study, we sought to develop a user-friendly predictive model for ESWL outcome using the classification and regression tree (CART) analysis._x000D_ Methods We retrospectively reviewed charts of 245 patients who underwent ESWL for upper urinary tract calculi between January 2008 and January 2016. To create the CART decision tree, predictor variables were entered into the software (R version 3.2.2) to classify patients who achieved stone-free after a first session of ESWL. Variables included age, sex, hydronephrosis, urinary drainage, stone location, stone volume, number of stones and three indices based on CT attenuation of the stone, i.e., mean stone density (MSD), standard deviation of stone density (SDSD) and variation coefficient of stone density (VCSD). Stone-free status was determined as absence or residual fragments <4mm using NCCT within three months after a first session of ESWL._x000D_ Results Overall stone-free rate was 47.8%. In CART analysis, VCSD had the greatest variable importance (100%) followed by MSD (56.7%), stone volume (52.7%) and SDSD (49.3%). A total of five subgroups of patients with distinct stone-free rate were produced by three predictive variables (Figure). Conclusions We have generated a first CART decision tree for ESWL outcome that included VCSD as a novel and most important factor, as well as previously reported predictors such as MSD and stone volume. This model provides clinician with practical bedside tool for predicting stone-free following ESWL._x000D_ Funding None
Authors
Yasuo Kohjimoto
Shimpei Yamashita Takashi Iguchi Satoshi Nishizawa Akinori Iba Kazuro Kikkawa Isao Hara |
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MP62-04 |
Identification of the recommended techniques, case selection, and invention to improve extracorporeal shock wave lithotripsy success rates |
Stone Disease: Shock Wave Lithotripsy | 17BOS |
Abstract: MP62-04 Sources of Funding: None Introduction We previously reported that the success rates of extracorporeal shock wave lithotripsy (ESWL) were increased from 66.3% to 87.2% by technical training (Okada et al. Urolithiasis 2013). In the present study, we analyzed how the technical skills acquired by this training directly affected subsequent ESWL results. Methods Among 335 ESWL treatments performed at Nagoya City University Hospital from December 2011 to August 2016, we analyzed the 324 cases that could be evaluated by CT three months post-ESWL treatment. All 17 urologists in charge of treatment attended the technical training. We analyzed associations between success rate and the following parameters: patient factors (age and body mass index), kidney stone factors (size, CT value, constituents, intervening period and skin-to-stone distance), conformity to the recommended techniques from training, number of ESWL sessions, grade of hydronephrosis, indwelling of ureteral stents, therapeutic position, use of stretcher wedges, targeting methods, air removal between cushion and skin, type of ESWL apparatus (Gemini or Lithotripter S, Dornier MedTech, Japan), shock wave frequency, and period from apparatus adjustment (stone model tests). The techniques recommended in training were 1) combined use of fluoroscopy and ultrasonography for targeting renal and proximal ureter stones, 2) use of stretcher wedges for middle ureter stones, and 3) semi-supine position with stretcher wedges for distal ureter stones. Results The average total success rate was 84.3% over the study period. Average conformity to the training techniques was 80.2%, and the average success rates of the conformity and nonconformity groups were 86.2% and 76.6%, respectively (p<0.0001). There was a significant difference in the success rates between the types of apparatuses used, where the Gemini group success rate was 90.1% and the Lithotripter S group success rate was 82.0% (p<0.0001). The number of the selected cases with conformity of the recommended techniques, air removal, low CT values (≤1000HU), appropriate stone size (≤10mm), and the first therapy were 90 and their success rate was 95.6%. Conclusions Conforming to recommended techniques, air removal, and appropriate case selection can all lead to higher success rates in ESWL. Funding None
Authors
Atsushi Okada
Teruaki Sugino Rei Unno Kazumi Taguchi Shuzo Hamamoto Ryosuke Ando Keiichi Tozawa Takahiro Yasui |
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MP62-05 |
Does bowel preparation or fasting improve stone visualisation and clearance in those undergoing Shock Wave Lithotripsy for intra-renal calculi? |
Stone Disease: Shock Wave Lithotripsy | 17BOS |
Abstract: MP62-05 Sources of Funding: None Introduction Extracorporeal Shock Wave Lithotripsy (SWL) is performed in only few centres across Australia including Monash Health. Currently patients fast for 2 hours prior to the procedure. On the day of procedure, bowel gas can obscure visualisation of the calculus resulting in 8% of cases being cancelled. This study aims to review whether bowel preparation or fasting for six hours prior to SWL will improve stone visualisation on the day of treatment, reduce cancellations and improve calculi clearance rates. Methods This is a single centre, randomised controlled trial, with ethics approval granted from Monash Health Human Research and Ethics Committee (approval number: 16324A). Patients who were selected for SWL were then consented for participation in the trial. Patients were randomly allocated to one of the three arms of the trial; 1. Two sachets of Sodium Picosulphate, 2. Six hours of fasting or 3. Fasting for two hours. Sodium Picosulphate sachets were provided by Fresenius-Kabi. Patients were included into the study if they had intra-renal calculi measuring between 8-12mm. Patients were excluded from the study, if they were over 75 years of age, had more than three medical co-morbidities or had any cardiac/renal conditions. At six weeks post SWL, all patients had a CT KUB to assess stone clearance and completed a survey on their subjective experience of the trial. Statistical analysis was performed using SPSS, t-test. Results Sixty patients were recruited in total, twenty into each of the three arms. In the bowel preparation group, there were no cancellations on the day of SWL treatment. All stones were fragmented, with one patient needing a repeat treatment for a 5mm intra-renal fragment. Of the patients who were fasting for either the six hours or the two hours, each group had two cancellations on the day of the procedure for poor visualisation of the calculus. This was a statistically significant difference of p = 0.03 between the bowel preparation and fasting groups. There were no complications related to the bowel preparation or fasting. There was no loss to follow-up. Patient satisfaction was high across all three groups, including those who received bowel preparation. Conclusions Giving bowel preparation within twelve hours of SWL appears to be an effective method of reducing bowel gas interference and improving the calculi visualisation at the time of SWL, resulting in fewer cancellations. Fasting for extended periods of time does not seem to make a significant difference. We are in the process of recruiting more patients to the study. Funding None
Authors
Athina Pirpiris
Debbie Siew Antonio de Sousa Shekib Shahbaz Philip McCahy |
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MP62-06 |
Advancements in ultrasonic propulsion technology for pushing kidney stones |
Stone Disease: Shock Wave Lithotripsy | 17BOS |
Abstract: MP62-06 Sources of Funding: Work support by NIH NIDDK grants DK043881 and the National Space Biomedical Research Institute through NASA NCC 9-58. Introduction In our first-in-human trial with ultrasonic propulsion (UP), we moved stones in 14 of 15 subjects and 4 post-lithotripsy subjects passed an aggregate of over 30 stone fragments. Our experience suggested probe heating would limit the duration of the push pulse and the rate at which treatment could be delivered with the clinical C5-2 probe. We have developed a new UP probe (SC-50) that provides a more uniform beam design with greater focal extent in depth and reduced probe heating. Methods The calyx phantom consisted of a pipette (12 mm x 30 mm) embedded in a block of tissue mimicking material at two skin-to-stone depths (4.2 cm and 9.5 cm). Three separate targets were placed into the pipette: a single 7 mm x 4 mm calcium oxalate stone, ten 1-2 mm calcium oxalate fragments, and ten 2-3 mm calcium oxalate fragments. The original C5-2 probe or the new SC-50 probe was positioned below the phantom pushing against gravity. Ten pushes at maximum focal intensity were applied, The C5-2 probe was tested with a push duration of 50 ms, the maximum used in human clinical trial, while the SC-50 probe was tested with push durations of 50 ms and 3000 ms. The capability of the two probes to expel the stone or fragments with each push was summed over the ten push attempts. Results Stone expulsion was similar for the C5-2 and the new SC-50 probe with a push duration of 50 ms. No stones or fragments were expelled the full 30 mm distance with the C5-2 probe and only 2-3% of the stone fragments were expelled with the SC-50 probe. Extending the total Push duration to 3000 ms, available only with the SC-50 probe, results in 100% of stones and all fragments expelled independent of depth from 4.5 cm to 9.5 cm and with less temperature rise within the probe. Conclusions We have developed a new custom designed probe for ultrasonic propulsion that allows for longer duration pushes and reduced probe heating than the commercial probe used in our first-in-human clinical trial, and thus allows for longer duration pushes, than the first-in-human clinical system. The new probe provides similar focal intensity up to 10 cm depth and is significantly more efficient at clearing single stones and stone fragments of various sizes at a range of skin to stone distances. The longer duration push has been shown safe in preclinical studies . Future work is currently in progess for FDA approval of the new probe. Funding Work support by NIH NIDDK grants DK043881 and the National Space Biomedical Research Institute through NASA NCC 9-58.
Authors
Karmon Janssen
Barbrina Dunmire Mike Bailey Bryan Cunitz Lei Kapaku Mathew Sorensen Jonathan Harper Timothy Brand |
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MP62-07 |
Identification of factors affecting in vitro lithotripsy experiments towards an improved model |
Stone Disease: Shock Wave Lithotripsy | 17BOS |
Abstract: MP62-07 Sources of Funding: Acknowledge NIH DK043881, DK104854 Introduction In vitro lithotripsy experiments are often conducted in conditions that do not realistically reflect those in vivo. New lithotripsy devices and modalities for nephrolithiasis such as Burst Wave Lithotripsy (BWL) will require in vitro testing to identify appropriate output parameters. To create a more clinically relevant model, we investigated the effects of fluid gas concentration, temperature, stone holder, and model stone composition on fragmentation. Methods We performed experiments in an acrylic tank with 53-gallons of deionized water. A motorized 3-axis positioning arm was used to position the stone holder. A BWL transducer was positioned in the tank with a targeting P4-2 ultrasound probe. Water gas concentration was controlled by recirculating water through an evacuated membrane contactor. Water temperature was controlled by an immersion heater. We compared three different kidney phantoms as stone holders including open wire basket, polyvinyl chloride (PVC) open-ended gel, and a Blue Phantom anatomic kidney phantom. Artificial and human stones from 5-9 mm were compared, including Begostone at 2 different mixture ratios, calcite, calcium oxalate monohydrate (COM), and uric acid (UA) stones. At least 3 stones were treated for each condition with BWL for 30 min, and assessed every 10 min as percentage of stone treated to fragments < 2mm. Results Begostone(2:1 powder:water ratio) treated in water at room temperature (20°C) vs. body temperature (37°C) showed 75±13% vs. 62±6% breakage at completion, respectively. The same stone type showed a water-gas concentration dependent response with 23±4%, 55±8%, and 82±16% breakage at 60, 30, and 15% O2 respectively. Kidney phantoms with greater enclosure showed decreasing lithotripsy efficacy with 94±11%, 64±21%, and 13±2% breakage in basket, PVC, and anatomic phantom models, respectively. The time course of stone breakage was linear for all stone types except calcite, which demonstrated rapid breakage in the first 10 min followed by a prolonged delay to treatment completion. Stone breakage in 2:1 Begostone more closely mimicked COM stones compared to 4:1 Begostone, despite the latter having closer reported acoustic properties to COM. All UA stones were completely treated in 10 min. Conclusions The choice of model and environmental conditions can significantly affect lithotripsy results, and should be considered in in vitro lithotripsy studies. Partial water degassing at body temperature, realistic kidney phantoms, and appropriate stone models will help in vitro results better reflect clinical outcomes. Funding Acknowledge NIH DK043881, DK104854
Authors
Justin Ahn
Wayne Kreider Christopher Hunter Theresa Zwaschka Michael Bailey Mathew Sorensen Jonathan Harper Adam Maxwell |
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MP62-08 |
Markers of Renal Injury During Shock Wave Lithotripsy with Narrow vs. Wide Focal Zones |
Stone Disease: Shock Wave Lithotripsy | 17BOS |
Abstract: MP62-08 Sources of Funding: "None" Introduction The Modulith SLK-F2 Electromagnatic lithotripter (Storz Medical AG, Tägerwilen, Switzerland) is the first lithotripter on the market with a unique design that allows for a dual focus system with the option of either a narrow or wide focal zone. Ex vivo data on the SLK-F2 lithotripter shows that the disintegration capacity and the renal vascular injury are independent of the focal diameter of the SW generator at the same peak positive pressure and disintegration power. We report on a subset of patients from our larger randomized trial for whom data on markers of renal injury were available. _x000D_ _x000D_ Methods A subset of 134 patients (out of 263 total patients randomized in the trial) with previously untreated radio-opaque solitary stone located within the renal collecting system, measuring at least 5mm, were randomized to receive narrow or wide focus lithotripsy while maintaining a constant overall energy level, and also collected urinary markers of renal injury. Patients were followed with renal ultrasound at 2 weeks post lithotripsy to assess for the development of perinephric hematoma. Urinary markers of renal cellular damage (microalbulin, creatinine, beta 2-microglobulin, microalbumin/creatinine ratio and Beta 2-microglobulin/creatinine ratio) were measured pre-SWL, immediately post-procedure in the recovery room, 24 hours post-SWL and 7 days post-treatment. Data was analyzed using ANOVA and repeated measures ANOVA, Chi-square statistic and linear regression where appropriate, controlling for presence of diabetes as a confounder._x000D_ _x000D_ Results 68 patients were randomized to narrow focus lithotripsy versus 66 patients to wide focus. The groups were similar in baseline characteristics including age, gender, BMI, stone size and density, skin to stone distance and diagnosis of diabetes. Overall complication rates were comparable between the two groups (Narrow: 23.5% vs Wide: 12.1% P=0.085) including similar rates of perinephric hematoma (Narrow: 2.9% vs Wide: 4.5%; P = 0.624) and Steinstrasse (Narrow: 7.4% vs Wide: 4.5%; P = 0.493). Urinary markers of renal injury did change after SWL, and then normalized within 7days, however there were no differences in the magnitude, timing or degree of change between the narrow and wide focal zone groups. Conclusions The degree of renal injury as assessed by renal cellular markers and by ultrasound assessment of perinephric hematoma are comparable when using the narrow or wide focal zone of the Modulith SLX-F2. Funding "None"
Authors
RJD'A Honey
Daniela Ghiculete Monica A. Farcas Kenneth T. Pace |
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MP62-09 |
Randomized Control Trial Comparing Narrow versus Wide Focal Zones for Shock Wave Lithotripsy of Renal Calculi |
Stone Disease: Shock Wave Lithotripsy | 17BOS |
Abstract: MP62-09 Sources of Funding: "None" Introduction The Modulith SLK-F2 Electromagnatic lithotripter (Storz Medical AG, Tägerwilen, Switzerland) is the first lithotripter on the market with a unique design that allows for a dual focus system with the option of either a narrow or wide focal zone. Ex vivo data on the SLK-F2 lithotripter shows that disintegration capacity and renal vascular injury are independent of the focal diameter of the SW generator at the same peak positive pressure and disintegration power. The objective of this study is to compare the single-treatment success rates of narrow and wide focal zones for shock wave lithotripsy of renal stones. Methods 263 patients, with a previously untreated >= 5 mm radio-opaque solitary stone located within the collecting system, were randomized to receive narrow or wide focus lithotripsy, while maintaining a constant overall energy level of 6. Patients were followed with KUB x-rays and renal ultrasound at 2 and 12 weeks post lithotripsy to assess stone area and stone free status. Primary outcome was success rate, defined as stone-free or adequate fragmentation (sand or asymptomatic fragments <=4 mm) at 3 months following a single SWL treatment. Results 130 patients were randomized to narrow focus lithotripsy versus 133 to wide focus lithotripsy. The groups were similar in baseline characteristics. The overall success rates were statistically different at 2 weeks post treatment (Narrow: 69.2% vs Wide: 57.1%; P = 0.042) and also at 3 months (Narrow: 69.2% vs Wide: 57.1%; P = 0.042). For smaller stones (area < 100 mm2) there was a greater benefit with narrow focus lithotripsy (72.6% vs 60.3%; P=0.05). The SWL retreatment rate for the same stone within 3 months was significantly higher when Wide focus was used (44.4% vs 30.8%; P=0.023). Overall the complication rates were comparable in both groups (Narrow: 23.3% vs Wide: 15.9%; P = 0.135). However, the narrow group required significantly fewer ancillary procedures within the initial 3 month follow-up period (Narrow: 30.8% vs Wide: 42.9 %; P = 0.042). Conclusions Narrow focus lithotripsy yields better outcomes than wide focus lithotripsy, particularly for stones < 100 mm2, with lower retreatment rates and without increased in morbidity. Funding "None"
Authors
RJ D'A Honey
Daniela Ghiculete Monica A. Farcas Kenneth T. Pace |
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MP62-10 |
PRELIMINARY REPORT ON STONE BREAKAGE AND LESION SIZE EVALUATION OF A NEW ELECTROHYDRAULIC (SPARKER ARRAY) DISCHARGE DEVICE |
Stone Disease: Shock Wave Lithotripsy | 17BOS |
Abstract: MP62-10 Sources of Funding: NIH grants PO1 DK-43881, and R44 DK-089703 Introduction An innovative electrohydraulic discharge device has been developed to fracture kidney stones. This device is composed of an array of 18 sparker units, each generating an acoustic pulse, which coalesce to produce a single shock wave front. We report on preliminary tests to determine if the sparker array can fracture stones (in vitro) and if sparker array treatment produces a renal hemorrhagic lesion in our pig model of lithotripsy injury (in vivo). Methods U-30 model stones were placed at the focus of the sparker array in a holder with 2-mm mesh openings. 600 shock waves (SWs) were then administered to each stone using a charging voltage of 21.6 kV at 60 SWs/min. All large stone fragments (≥ 2-mm) retained in the holder were collected, dried and weighed to determine percent of stone breakage. The renal lesion analysis portion of the study consisted of treating the left kidney of anesthetized female pigs (35-40 kg) with 2400 SWs using 21.6 kV at 60 SWs/min. Immediately after sparker array treatment the kidneys were perfusion fixed with glutaraldehyde, excised and processed to quantitate the parenchymal hemorrhagic lesion of that kidney. Results On average, 71.3±1.9% (mean±S.E., n=6) of each model stone was fractured to < 2-mm in size. Renal injury analysis revealed that none of the kidneys treated with 2400 SWs (n=3) showed evidence of hemorrhagic injury. Conclusions The sparker array consistently comminuted model stones demonstrating its ability to fracture stones similar to other lithotripters. However, unlike most other lithotripters, the sparker array did not cause renal injury at the settings used in this study. These findings suggest further research is warranted to determine the potential of this device. Funding NIH grants PO1 DK-43881, and R44 DK-089703
Authors
Bret Connors
Ray Schaefer John Gallagher Cynthia Johnson Andrew Evan |
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MP62-11 |
Extracorporeal shock-wave lithotripsy (ESWL) for renal stones is associated with decreased kidney function after long term follow-up |
Stone Disease: Shock Wave Lithotripsy | 17BOS |
Abstract: MP62-11 Sources of Funding: none Introduction Beside well characterized short term adverse effects of extracorporeal shock wave lithotripsy (ESWL) for the treatment of renal stones, concerns regarding long term adverse effects to the kidneys or adjacent organs (e.g. pancreas) were raised. We aimed to analyze whether ESWL applied to the kidneys is associated with decreased kidney function, hypertension or diabetes during long term follow-up. Methods All patients with urolithiasis treated by ESWL at our tertiary care center between 1992 and 2013 were retrospectively identified. Cases consisted of patients treated by ESWL because of kidney stones (kidney group). Patients with distal ureter stones treated by ESWL served as a control group. Patients treated by ESWL for upper or middle ureter stones or patients treated for both, kidney and distal ureter stones were excluded. In 2016, a questionnaire was sent to all patients to assess the prevalence of decreased kidney function, hypertension and diabetes. The Swiss Health Survey data set (n=21,597) providing population data for hypertension and diabetes but not decreased kidney function was used as an additional comparison group. Results Of 7108 identified patients, 2,776 (39%) met the inclusion criteria. Follow-up questionnaires were returned by 764 (28%) patients of which 585 (77%) questionnaires belonged to the kidney group, and 179 (23%) to the distal ureter group. Median time between first ESWL and returned questionnaire was 12 years (8-18 years) for the kidney group and 16 years (IQR 11-20 years) for the control group._x000D_ There was no significant difference between the kidney group and the control group regarding age (mean 62+-14 vs. 64+-14, p=0.252), gender (female 34% vs. 28%, p=0.123) and BMI (mean 26+-4 vs. 26+-4, p=0.687). However, in the kidney group more number of ESWL sessions were observed compared to the control group (1 [IQR 1-2] vs. 1 [IQR 1-1], p<0.001). Furthermore the prevalence of decreased kidney function in the kidney group was significantly higher compared to the control group (8.3% vs. 2.9%, p=0.015). The kidney group, control group and general population showed significant differences regarding prevalence of hypertension (47.5% vs. 49.4% vs. 27.5%, p<0.001) and diabetes (14.1% vs. 11.9% vs. 4.9%, p<0.001)._x000D_ In multivariable regression analyses controlling for age, gender and BMI, number of applied ESWL sessions to the kidneys was an independent predictor for decreased kidney function (OR 1.28, 95% CI 1.010 to 1.623, p=0.041) but not for hypertension or diabetes._x000D_ Conclusions ESWL for renal stones may lead to decreased kidney function during long term follow-up. The association between increasing number of applied ESWL sessions and decreased kidney function at long-term follow-up supports a causal relationship. Funding none
Authors
Christian Fankhauser
Josias Grogg Alexander Holenstein Qing Zhong Johann Steurer Thomas Hermanns Tullio Sulser Cédric Poyet |
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MP62-12 |
Ureteroscopy and Shockwave Lithotripsy Utilization Patterns in Wisconsin: An Analysis of Sociodemographic Factors |
Stone Disease: Shock Wave Lithotripsy | 17BOS |
Abstract: MP62-12 Sources of Funding: None Introduction Recent data is showing a rise in the use of Ureteroscopy (URS) compared to Shockwave Lithotripsy (SWL), which is attributed to more widely available equipment and expertise as well as higher stone-free rates. We compared the sociodemographics of patients who underwent URS vs SWL to evaluate for URS utilization trends based on age, gender, race and location. Methods The State Ambulatory Surgery and Service Database (SASD) for the state of Wisconsin for the years 2012 and 2013 was accessed which contains information regarding outpatient encounters and was queried for Current Procedural Terminology (CPT) codes pertaining to URS and SWL. We evaluated the data for usage of URS and SWL based on age, gender, race and Rural Urban Commuting Area (RUCA) code (indicating population of patient residence location). Univariate and Chi-Square analyses was used to compare the rate of URS vs SWL encounters based on gender, age, race, and location. Results A total of 16,587 encounters were identified for URS and SWL. 10,077 (62%) encounters contained a CPT code for URS vs 6,207 (38%) for SWL. URS utilization varied based on age, specifically pediatric patients were more likely to undergo URS vs SWL when compared to adults (73% vs 62%, OR 1.8 (1.23 - 2.64), p = 0.002). Adults 80 years old and older were also more likely to undergo URS compared to other adult ages (73.4% vs 61%, OR 1.75 (1.49 - 2.06), p < 0.001). We found no difference in the rates of URS encounters according to gender (p = 0.863). Caucasian patients were more likely to have URS vs Black patients (OR 1.58, 1.32 - 1.88, p < 0.001). Hispanic patients were more likely to undergo URS compared to Caucasian patients (OR 1.32, 0.61 - 0.928, p = 0.008). Patients living in a large town (10,000 - 50,000 people) were more likely to have URS compared to those living in a metropolitan area (>50,000 people) (66% vs 61%, OR 1.25, CI 1.13 - 1.38, p < 0.001) or a rural area (<2,500 people) (66% vs 60%, OR 1.30, CI 1.14 - 1.50, p < 0.001). Conclusions URS encounters are more common than SWL (62% vs 38%). Pediatric patients and those 80 years old and older were more likely to undergo URS. No difference was seen in relation to gender. Hispanic patients had the highest percentage of URS encounters followed by White, then Black patients. Patients living in a large town had the highest percentage of URS encounters. Funding None
Authors
John Roger Bell
Brett Johnson Kristina Penniston Stephen Y Nakada |
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MP62-13 |
COMPARISON OF PATIENT SATISFACTION FOR TREATMENT EFFICACY AND ASSOCIATED FACTORS BETWEEN SWL AND URS FOR URINARY STONE: ANALYSIS FROM PATIENTS’ VIEW |
Stone Disease: Shock Wave Lithotripsy | 17BOS |
Abstract: MP62-13 Sources of Funding: none Introduction Goals of this study were to compare satisfaction for treatment efficacy and associated factors in treatment for upper urinary stone with shock wave lithotripsy (SWL) and ureteroscopic surgery (URS) and to clarify significant factors for desirable treatment from patients view. Methods In current study, 294 consecutive patients who underwent SWL (n=194) or URS (n=71) and both surgical procedures (n=29) for upper urinary stone in one treatment period were enrolled. We evaluated satisfaction for treatment outcomes and significant factors for desirable treatment used a self-administered ad-hock questionnaire. Satisfaction for treatment were analyzed in five domains (overall satisfaction, pain during treatment and after treatment, voiding symptom, and overall difficulty) using a visual analog scale. Results There is no significant differences in age and sex distribution between the SWL and URS group (a mean age of 50.7years, range 21-76). There were no significant difference in overall satisfaction values between both groups. However, other objective outcomes from patients’ view (pain during treatment and after treatment, voiding symptom, and overall difficulty) were significantly better in the SWL group compared to those in the URS group. The patients considered many factors to decide for counseling treatment options, such as efficacy of treatment, cost, safety, hospitalization, kind of anesthesia, pain associated with treatment. Rate of patients who selected SWL as a next desirable treatment in the SWL group, the URS group and both treatment group were 61.5, 81.0, and 93.5%, respectively. Conclusions Overall satisfaction were not significantly different between SWL and URS. However, pain and convenience associated treatment around operative period are better in SWL than TUL. The patients considered many factors to decide for counseling treatment options in addition to treatment efficacy. Consequently, significantly higher percentage of patients selected SWL treatment as a desirable treatment option. Funding none
Authors
Yoshikazu Sato
Musashi Tobe Kosuke Uchida Kazunori Haga Ichiya Honma Keigo Akagashi Toshikazu Nitta Hisao Nakajima Tatsuo Hanzawa |
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MP62-14 |
Ureteral stenting can be a negative predictor for successful outcome following shock wave lithotripsy in patients with ureteral stones |
Stone Disease: Shock Wave Lithotripsy | 17BOS |
Abstract: MP62-14 Sources of Funding: None Introduction According to the European Association of Urology Urolithiasis Guidelines, ureteral stenting reduces the risk of renal colic and obstruction, and many physicians consider inserting ureteral stents before SWL to create an artificial chamber with an improved stone-fluid interface for better fragmentation during SWL and to reduce the risk of obstruction. Accordingly, several studies have been performed to determine whether routine pre-SWL ureteral stenting is helpful in preventing obstructive complications, but the issue remains somewhat controversial. Thus, the current study was conducted to evaluate the effects of ureteral stenting and stone characteristics on ureteral stone clearance and to estimate the probability of one-session success in SWL patients with ureteral calculi according to whether they underwent ureteral stenting or exhibited various other factors. Methods We retrospectively reviewed the medical records of 1,651 patients who underwent their first SWL. Among these patients, 680 had a ureteral stone measuring 4-20 mm and were thus eligible for our study. The 57 patients who underwent ureteral stenting during SWL were identified. Maximal stone length (MSL), mean stone density (MSD), skin-to-stone distance (SSD), and stone heterogeneity index (SHI) were determined by pre-SWL non-contrast computed tomography. Results After propensity score matching, 399 patients were extracted from the total patient cohort. There were no significant differences between stenting and stentless groups after matching, except for a higher one-session success rate in the stentless group (78.6% versus 49.1%; P=0.026). In multivariate analysis, shorter MSL, lower MSD, higher SHI, and absence of a stent were positive predictors for one-session success in patients who underwent SWL. Using cut-off values of MSL and MSD obtained from receiver operator curve analysis, in patients with a lower MSD (≤784 HU), the success rate was lower in those with a stent (61.1%) than in those without (83.5%) (P=0.001). However, in patients with a higher MSL (>10 mm), the success rate was lower in those with a stent (23.6%) than in those without (52.2%) (P=0.002). Conclusions Ureteral stenting during SWL was a negative predictor of one-session success in patients with a ureteral stone. Funding None
Authors
Dong Hyuk Kang
Kang Su Cho Won Sik Ham Jong Kyou Kwon Seung Hwan Lee Young Deuk Choi Joo Yong Lee |
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MP62-15 |
Emergency Extracorporeal Shock Wave Lithotripsy For Upper Ureteric Stones With or Without Pre-stenting: A Randomized Clinical Trial |
Stone Disease: Shock Wave Lithotripsy | 17BOS |
Abstract: MP62-15 Sources of Funding: none Introduction Extracorpreal Shock Wave Lithotripsy (ESWL) is an attractive non-invasive therapeutic modality for urolithiasis typically reserved for elective cases in a controlled setting. Proceeding directly to ESWL without pre-stenting in patients presenting to the emergency room with acute renal colic secondary to upper ureteric calculi can spare patients multiple anesthesia-requiring procedures. In this study, we aim to compare upper ureteric stone clearance with and without pre-stenting in patients undergoing ESWL within 48 hours of their initial presentation. Methods Between July 2012 and July 2015, 124 patients who had presented to emergency with renal colic secondary to upper ureteric calculi were recruited for this study. Criteria for exclusion included abnormally elevated renal parameters, signs of a concomitant infectious process (fever, leukocytosis, or a positive urine dipstick), pain poorly responding to analgesia, radiolucent stones, or stones smaller than 4-mm or larger than 15-mm in size. 72 patients had been randomly assigned to undergo ESWL directly without pre-stenting (Group A), while 52 patients were assigned for pre-stenting (Group B), with their data and outcomes prospectively collected. Mean patient BMI in both groups was 26.1 and 26.7 kg/m2 (p = 0.49), mean skin-to-stone distance was 11 and 10.1 cm (p = 0.03), mean stone size was 7.3 and 7.8 mm (p = 0.114), and mean stone density was 902 and 1078 Hounsfield units (p = 0.005) respectively. Results 72 patients had undergone emergency ESWL directly without pre-stenting (Group A), while 52 patients had undergone pre-stenting before emergency ESWL (Group B). All 124 patients had their first session of ESWL done within 48 hours of their initial presentation. 8 patients were lost to follow up in Group A, while one patient was lost to follow up in Group B. Four patients' stones had migrated to the kidney with stenting and were excluded from the study. Stone clearance in both groups was 61% and 44% (p = 0.068) after one session, 91% vs 59% (p = <0.001) by the second session, and 95% and 73% (p = 0.001) by the third and last session. No patients in Group A crossed over to Group B or required stenting at any point. Conclusions Emergency ESWL for upper ureteric calculi offers excellent stone clearance outcomes for properly selected patients with an acute presentation of renal colic that has subsided. Proceeding directly for ESWL without pre-stenting was associated with significantly enhanced stone clearance while sparing the patient multiple invasive interventions and their potential morbidity. Funding none
Authors
Tarek El-Ghazaly
Shameem Vita Salam Hussain Abdulkader Al-Obaidy |
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MP62-16 |
Shock Wave Lithotripsy is Efficacious for Treating Obese Patients with Upper Ureteric Calculi : 5 year prospective outcomes from a dedicated centre treating patients with a skin-to-stone distance of more than 14cm |
Stone Disease: Shock Wave Lithotripsy | 17BOS |
Abstract: MP62-16 Sources of Funding: none Introduction Obesity is increasingly common and often a predisposing factor in stone formation. Clinical reviews and guidelines indicate that SWL outcomes are poor for treating stones in patients with skin-to-stone distance (SSD) of >10-14cm, and regard a large SSD as an adverse predictor for SWL success (EAU Urolithiasis Guidelines 2016). There is a paucity of literature on treating such patients with SWL, and given the higher recognised perioperative morbidity of surgery in such a population, and the potential benefits of sedo-analgesia and short length of stay with ambulatory SWL, it is germane to re-evaluate the efficacy of SWL for treating such patients using a lithotriptor with a focal length of >14cm. Methods Consecutive patients with a solitary radio-opaque upper ureteric calculus diagnosed on CT scan with a SSD ≥14cm were identified from a prospective database (2011-2016). Out-patient SWL was performed under sedo-analgesia (diclofenac ± alfentanil) using a Sonolith I-Sys, EDAP-TMS (focal depth 17cm). Outcome was assessed with an XRKUB at 2 weeks. Those with significant fragments (>3mm) received further treatment. Success was defined as patients being free of stones on XRKUB or as having asymptomatic clinically insignificant stone fragments (CISF) ≤3mm. Failure was defined as residual fragments >3mm (treated with ureteroscopy). Results 182 patients met the inclusion criteria. 4 were lost to follow up. Median age was 54 years. Median stone size was 8mm (range 3-21). Overall stone-free rate (SFR) was 81% after mean 1.3 sessions. 63% were stone-free after a single session. 9% had CISF≤3mm. 11% required ureteroscopy. Conclusions SWL can provide efficacious treatment of upper ureteric stones in obese patients, traditionally thought to be poor candidates for such treatment due to their high SSD. The upper threshold of SSD for SWL selection should be revised, as such patients can receive the benefits of effective SWL treatment, without the need for general anaesthesia, when referred to a dedicated stone centre. Funding none
Authors
William K M Gietzmann
Abishek Sharma Edward Mains ismail El-Mokadem Ben G Thomas Simon Phipps David A Tolley Mark L Cutress |
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MP62-17 |
Listening to music during shock wave lithotripsy decreases anxiety, pain and dissatisfaction: A randomized controlled study |
Stone Disease: Shock Wave Lithotripsy | 17BOS |
Abstract: MP62-17 Sources of Funding: None Introduction We analyzed the effects of music on pain, anxiety and overall satisfaction in patients undergoing shock wave lithotripsy (SWL) procedure. Methods Two hundred patients scheduled for SWL were prospectively enrolled in this study. Group 1 consisted of 95 patients who listened music during the SWL procedure while 105 patients in group 2 did not listen music during the treatment. Anxiety of the patients were measured according to State-Trait Anxiety Inventory (STAI). STAI-T (Trait) was completed only before the procedure, whereas STAI-S (State) was completed both before and after SWL. Pain, patient satisfaction and willingness to repeat procedure were evaluated after SWL using a visual analog scale (VAS). Hemodynamic parameters including sistolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) were measured before and after procedure. Results Group 1 consisted of 95 (47.5%) patients while group 2 included 105 (52.5%) patients. No statistically significant difference was found between two groups in terms of stone characteristics, SWL parameters, STAI-T and STAI-S scores and hemodynamic parameters before SWL. Pre-SWL hemodynamic parameters, STAI-S and STAI-T scores of the study groups are displayed in Table 1. After SWL completed, STAI-S scores were found to be lower in patients who listened music (p=0.006). At the end of the SWL, VAS scores of pain, satisfaction and willingness to repeat procedure were significantly different in favour of music group (p=0.007, p=0.001, p=0.015, respectively). SBP, DBP and HR were found significantly higher in patients who did not listened music (p=0.002, p=0.024, p<0.001, respectively). Post-SWL hemodynamic parameters, STAI-S scores and VAS scores are shown in Table 2. Conclusions Music can be an ideal adjunctive treatment modality for patients undergoing SWL treatment. It has the potential to enhance patient compliance and treatment satisfaction by reducing the procedure-related anxiety and pain perception. Funding None
Authors
Ozgur Cakmak
Sertac Cimen Huseyin Tarhan Rahmi Gokhan Ekin Batuhan Ergani Taha Cetin Volkan Ulker Ilker Akarken Zafer Kozacioglu |
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MP62-18 |
Ambulatory Shock Wave Lithotripsy is an efficacious and cost-effective treatment for lower pole renal stones between 10-20mm in size: a prospective large single centre study |
Stone Disease: Shock Wave Lithotripsy | 17BOS |
Abstract: MP62-18 Sources of Funding: None Introduction There is clinical equipoise as to the most cost effective approach for the treatment of lower pole stones between 10-20mm. _x000D_ We aimed to assess the clinical features, outcomes, complications, and cost-effectiveness of ambulatory SWL, FURS and PCNL in the treatment of lower pole (LP) stones (10-20mm) in a large tertiary referral stone centre. Methods Consecutive patients treated for solitary LP stones (10-20mm) between 2008-13 were identified from a prospective database. Ambulatory SWL under sedo-analgesia (diclofenac +/- alfentanyl) was used as primary treatment in all cases (following a stone MDT assessment), with FURS and PCNL reserved for SWL contraindications, failure or patient choice. “Success” was defined as stone free and/or clinically insignificant stone fragments (?3mm) at 1 and 3 months follow-up. Effect of anatomy on SWL success was determined from using CT images and regression analysis. Average cost per treatment modality (including additional second-line treatments) was calculated using the NHS England 2014/15 National Tariff HRG codes. Results 225 patients were included (mean age 54.9; median stone size 12mm). 198 (88%), 21 (9.3%) and 6 (2.7%) patients underwent SWL, FURS and PCNL as primary treatments respectively; for median stone sizes of 12mm, 12mm, and 20mm. Overall success rates were 82.8%, 76.1% and 66.7% respectively (p < 0.05). 63% of patients undergoing primary SWL were successfully treated after one session. Anatomical analysis determined infundibulopelvic angle and infundibular length to be significantly different in patients successfully treated with SWL (p = 0.04. SWL was performed with superior length of stay and complication rates compared to FURS or PCNL (p<05), and with a low auxiliary treatment rate (7%). SWL was significantly more cost-effective (mean £751/patient) than FURS (mean £1261) or PCNL (mean £2658) (p < 0.01). Conclusions SWL is a cost-effective, and efficacious primary treatment for patients with solitary LP stones (10-20mm). The majority of patients can be successfully treated with primary SWL in a dedicated stone centre, with the benefits of a short length of stay, low complication and auxiliary treatment rates, and without the need for general anaesthesia. The referral of such patients to high-volume lithotripsy centres with demonstrable outcomes should be given due consideration. Funding None
Authors
Daniel Good
Luke Chan Karina Laing Simon Phipps Ben Thomas Julian Keanie David Tolley Mark Cutress |
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MP62-19 |
Cross validation of a predictive analytic model which predicts success and complications of shockwave lithotripsy |
Stone Disease: Shock Wave Lithotripsy | 17BOS |
Abstract: MP62-19 Sources of Funding: NextMed, Inc. Introduction Shockwave lithotripsy (SWL) is a primary treatment for nephrolithiasis that has been used widely for the past 3 decades. Recently, this technology has come under fire because of declining outcomes in the face of improving alternative technologies. Multiple authors have described pre-operative parameters that improve the success of SWL, including stone size, location, density, and skin-to-stone distance. Using these and other parameters, we present a predictive analytic model to help urologists select the most effective treatment modality with the highest likelihood of success and lowest likelihood of complication. Methods We performed a random 70/30 split of 7,000 SWL treatment records for renal and ureteral stones from 2010-2016 to train and validate a generalized linear mixed model (GLMM) using statistical software (PROC GLIMMIX in SAS 9.4). This model uses 9 parameters: stone size, Hounsfield Units (HU), body mass index (BMI), stone location, anesthesia type, SWL machine type, anticoagulant use, age, and gender to predict treatment success, defined as stone free or fragments ? 4mm, and to predict treatment complications. Actual treatment success and complications were obtained from self-reported physician follow-up surveys tied to the original SWL treatment record. Both treatment and follow-up data are housed in The Stone Disease Registry. Results The training model was significantly related to treatment success, Likelihood Ratio (LR) Chi-square = 1136.02 , p < .0001, Area under the curve (AUC) = .82. This model was in turn a good predictor of success in the validation dataset, AUC = .81. The training model was also significantly related to complications, Likelihood Ratio Chi-square = 538.75, p < .0001, AUC = .91. This model was a fair predictor of complication rate in the validation dataset, AUC = .77. Conclusions This novel predictive analytic model provides accurate prediction of treatment success and complications for SWL. Given the robust model fit to the validation data, we conclude that this model will be useful in prospectively predicting success for the treatment of urinary stones with SWL. This has the potential to assist urologists in prospectively making evidence-based decisions on which treatment modality will be most effective in maximizing success and minimizing complications and costs for treatment of urinary stones. Funding NextMed, Inc.
Authors
Blake Hamilton
Ryan Seltzer Donald Gleason Stephen Nakada Glenn Gerber |
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MP62-20 |
Effect of stone size and composition on ultrasonic propulsion in vitro |
Stone Disease: Shock Wave Lithotripsy | 17BOS |
Abstract: MP62-20 Sources of Funding: Work support by NIH NIDDK grants DK043881 and the National Space Biomedical Research Institute through NASA NCC 9-58. Introduction Ultrasonic propulsion (UP) has been successfully demonstrated in a human clinical trial to reposition stones and facilitate spontaneous passage of fragments. Given the prevalence of kidney stones, and the cost related to symptomatic relief of a patient in acute renal colic, a non-invasive ultrasound treatment for immediate pain relief would be of great benefit. Repositioning an obstructing stone and alleviating the acute pain would allow for temporization and a delayed elective vist. The purpose of this study was to use a phantom model to evaluate the effect of stone size and composition on the potential limits of UP to expel stones and fragments using a phantom model. Methods The phantom consisted of a 12 mm x 30 mm cylindrical pipette bulb embedded in a tissue mimicking material at 10 cm depth, simulating the uretero-pelvic junction (UPJ) or a calyx within the kidney. Four different stone compositions were tested. Three stones of each type with varying size and weight were treated at the maximum probe intensity and push duration from 0.5 s to 5 s. Stone composition (average weight) included Ammonium acid urate (0.16 g), Struvite (0.62 g), Calcium Phosphate (0.28 g), and Calcium Monohydrate (0.26 g). The aggregate maximal size of the three stones was 8-12 mm. The average number of times a stone was expelled over 10 attempts was assessed for each stone type and over the range of stone sizes. If the stone became trapped within the calyx, two additional push attempts were performed. Results The only stones expelled less than 100% of the time were the heaviest stone (Struvite, 0.68 g) that was never lifted high enough for expulsion with a single 0.5 s pulse and the largest stone (CAP, 12 mm x 7 mm), which occasionally became stuck at the 12 mm orifice of the pipette. Multiple pushes did not result in further expulsion of the stuck stone. Conclusions This phantom study showed UP of large stones was rather insensitive to stone size or composition. Exceptions occurred with the heaviest and largest stones. Struvite required push durations longer than 0.5 s to move the stone out of the phantom. Also, a stone presenting with a wider aspect than the width of the calyx could not be forced through the smaller opening. A limitation of the study is the force was always optimally aligned with the pipette opening, which may be challenging for stones in the UPJ. Funding Work support by NIH NIDDK grants DK043881 and the National Space Biomedical Research Institute through NASA NCC 9-58.
Authors
Karmon Janssen
Barbrina Dunmire Mike Bailey Bryan Cunitz Mathew Sorensen Jonathan Harper Timothy Brand |
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MP63-01 |
Advanced maternal age at first delivery does not affect patient-reported urinary outcomes: results from a nationwide sample |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Incontinence: Evaluation (Urodynamic Testing) | 17BOS |
Abstract: MP63-01 Sources of Funding: none Introduction Urinary incontinence (UI) is a prevalent condition that affects women’s quality of life. The female pelvic floor experiences trauma and strain during pregnancy and childbirth that can predispose women to UI. As the average age of pregnancies increases, more women are giving birth at an advanced maternal age (AMA). However, it is unclear what affect childbirth and pregnancy might have on the pelvic floor and UI in women of AMA. We aim to evaluate patient-reported UI outcomes in US women that have undergone a single childbirth at younger ages and those of AMA. Methods The NHANES database was queried for all primiparous women during the years 2005-2012. Women were excluded that had multiple deliveries, prior hysterectomy, pelvic organ prolapse, had given birth greater than 20 years from the time of survey and had given birth less than 2 years from time of survey. Nulliparous women (NP) aged 20-65 years were used for baseline incontinence rates. Women that had undergone childbirth were stratified by type of delivery and age at time of delivery with women 35 years or older classified as AMA. Cohorts were created composed of NP, young cesarean (YC), young vaginal (YV), AMA cesarean (AMAC), and AMA vaginal (AMAV). Multivariable logistic regression was performed to assess the effect of delivery type and AMA on urinary outcomes when adjusting for age and BMI. Results A total of 4,270 women met our inclusion criteria. AMAV had the highest rate of any UI (62.7%) and stress UI (50.6%), compared to all other groups. When adjusting for age and BMI; women undergoing vaginal deliveries (YV and AMAV) had increased UI and SUI. There were no differences seen in urge UI between all groups. YV and AMAV also had increased bother with UI and an increased severity of incontinence. When looking between groups, there were no differences in UI between YC and AMAC (OR 1.1). In addition, there was no difference in UI between YV and AMAV (OR 1.2). Conclusions It appears that AMA does not have an effect on UI when stratified by delivery type. Any differences seen in patient-reported UI are driven by a vaginal delivery, regardless of age at time of childbirth. Primiparous women undergoing a cesarean delivery have similar UI outcomes to nulliparous women. Funding none
Authors
Michael Daugherty
Natasha Ginzburg |
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MP63-02 |
PURE STRESS URINARY INCONTINENCE: ANALYSIS OF THE PREVALENCE, ESTIMATION OF COSTS AND FINANCIAL IMPACT |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Incontinence: Evaluation (Urodynamic Testing) | 17BOS |
Abstract: MP63-02 Sources of Funding: None Introduction Aim of our study was to evaluate the prevalence of 'pure' SUI (P-SUI), in a cohort underwent urodynamic test (UD) for urinary incontinence (UI), and the correspondence with UD findings. We also estimated the amount of costs of UD, and if the UD data could change the surgical indications. Methods We did a retrospective evaluation of the UD-database selecting 544 women with UI between January 2012 and July 2016. Pure SUI was defined by the International Continence Society criteria (table 1). Two very experienced urologists evaluated data. _x000D_ Data researched were: _x000D_ - Prevalence of clinical and UD P-SUI _x000D_ - Correspondence between clinical P-SUI and UD findings_x000D_ - Accurate estimation in € of a single UD examination, including the human resources and materials used_x000D_ - Total amount of UD costs in € in P-SUI patients_x000D_ - Number of surgical procedures avoided due to UD results_x000D_ - Related avoided surgical costs in € in P-SUI patients_x000D_ Results SUI was present in 323/544 (59.4%), in this group the prevalence of P-SUI was 20.7% (67/323) while the prevalence of complicated SUI was 79.3% (256/323). _x000D_ The correspondence between the clinical diagnosis of P-SUI and the UD findings was 88% (59/67 patients). For this reason after UD the number of patients with diagnosis of P-SUI decreased to 59/323 with a rate of 18.3%._x000D_ The cost of each UD study was 383 € and the total amount for this cohort of patients was 25.661 €. As consequence of a change of the therapeutic treatment after UD findings we did not performed the scheduled middle urethral sling in 6 patients with a total amount saved of 10.800 €. Conclusions UD study detected a relevant prevalence of P-SUI as 1/5 of the amount of the SUI women. The correspondence between clinical and UD findings was high. A total amount cost of P-SUI patients is not negligible respect to the total UD budget. Nevertheless, UD was able to avoid an inappropriate procedure in 9% of the patients. Funding None
Authors
Emanuele Rubilotta
Matteo Balzarro Silvia Bassi Paolo Corsi Marco Pirozzi Trabacchin Nicolò Antonio Benito Porcaro Antonio D'Amico Walter Artibani |
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MP63-03 |
The Timed Assessment of Mobility for Urinary function (TAM-U): A Measure for Functional Incontinence in the Elderly |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Incontinence: Evaluation (Urodynamic Testing) | 17BOS |
Abstract: MP63-03 Sources of Funding: none Introduction Functional incontinence is recognized as leakage of urine associated with restrictions in mobility and / or cognition resulting in urinary incontinence (UI); however, it lacks a validated instrument to measure its presence and to quantify its severity. In orthopedics, the timed get up and go test (TGUG test) is a validated method to determine timed functional mobility. Functional UI needs to take into account actions including undressing and/ or transition to the seated position for toileting. The objective of this study was to extend the concept of the TGUG to incorporate actions required for continent toileting for measurement of functional continence status in the elderly. Methods A volunteer sample of community dwelling adult women with UI and controls. Subjects completed the TAM-U sequence of: sit to stand, walk 10 m, turn, return 10 m, turn to sit, undress sufficient to sit on the urodynamics chair and void. Initiation of voiding (uroflow start) ends the sequence. Test retest of the full sequence in triplicate, kinematic subsequences, International Physical Activity Questionnaires (IPAQ short form) Urogenital Distress Inventory 6, Colorectal Anal Distress Inventory 8 and Pelvic Organ Prolapse Distress Inventory scores were compared. Uroflow parameters and post void residual by ultrasound were completed. Results 10 controls and 20 UI subjects completed the TAM-U, mean age 70 years range 55 to 85, BMI mean 30 kg/m2, history of reduced mobility due to arthritis in 15, hip fracture in 5. IPAQ scores included inactive, minimally active and HEPA active in subjects and minimally active and HEPA active in controls, UGDI scores ranged from 12 to 30 in subjects and 0 to 3 in controls. Prolongations in gait or undress-sit-void sequences were associated with UI. Mean voided volumes in controls were 253cc (range 190cc-340cc), mean Qmax 22 cc/s (range 19-38) all with continuous flow patterns compared to incontinent subjects (180cc (range 140-250cc), mean Qmax 18 cc/s (range 15-30), PVR mean 45 (range 0 to 70). Test re test correlations were 0.84 in controls and 0.78 in incontinent subjects. Conclusions The TAM-U was developed as a physical function assessment tool that incorporates the actions required for seated voiding in the elderly. It is reproducible within subjects and total speeds for completion were statistically different between cases and controls. Further development will include incorporation of mobility aids and examination of the influence of clothing and hand function on undressing for voiding as part of self-care in the elderly. Funding none
Authors
Lynn Stothers
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MP63-04 |
OAB SCORE. A CLINICAL MODEL THAT OPTIMAZES THE PROBABILITY OF PRESENTING OVERACTIVE DETRUSOR IN URODYNIMIC STUDY |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Incontinence: Evaluation (Urodynamic Testing) | 17BOS |
Abstract: MP63-04 Sources of Funding: none Introduction overactive bladder (OAB) is a weakening condition that affects an important group of people, altering their quality of life. Traditionally this syndrome has been associated with the presence of involuntary detrusor contractions (IDC) in the filling phase of the cystomanometry; this urodynamic observation is called overactive detrusor (OAD). IDC identification in the urodynamic study in patients with OAB is around 50%. In this way, the association between OAB and OAD is not yet clear. Taking into account the above-mentioned information, the creation of a model that improves the predictive ability of OAB symptoms by itself is essential._x000D_ PURPOSE: to create a predictive model of IDC (OAB score) in order to improve the diagnostic accuracy of OAD, associating OAB symptoms with other clinical parameters in the female population._x000D_ _x000D_ Methods A total of 727 women who underwent urodynamic studies for urogynecological causes were evaluated. Demographics data, personal pathological background, as well as surgical, symptoms, physical exam, mictionary record (micturition chart) and urinary culture, were collected in all patients who previously underwent uroflowmetry and urodynamic studies. A logistic regression model was carried out in order to determine independent predictors of presence of involuntary detrusor contraction (IDC). OR estimation was use to assign a score to each one of the significant variables (p<0.05) in the logistic regression model. To conclude, we performed a ROC curve in order to determine the predictive ability of the score in relation to the presence of OAD. Results presence of OAD was evident in 210 women (29%). In the logistic regression analysis, independent predictors of OAD were micturition urgency, UUI, nicturia, absence of SUI symptoms, presence of diabetes, reduction of vaginal trophism and vesical capacity under 150 mL. The IDC diagnosis probability increases directly as the score raises (Score 0: 4% until Score ?10: 88%). Sensitivity is 71% and specificity 72%. The area under the curve of OAB score was 0.784 (p>0.001). Conclusions OAB score is a clinical tool that shows higher diagnostic accuracy than OAB symptoms alone when predicting overactive detrusor (OAD). Funding none
Authors
Leandro Arribillaga
Ariel Montedoro Rubén Guillermo Bengió Marta Ledesma Florencia Pisano Aldana Pierantozzi Ruben Hugo Bengió |
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MP63-05 |
Novel Urodynamic Findings in Female Patients With Urgency Urinary Incontinence |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Incontinence: Evaluation (Urodynamic Testing) | 17BOS |
Abstract: MP63-05 Sources of Funding: None Introduction The purpose of this study is to analyze the urodynamic features of female patients with urge urinary incontinence (UUI). The study tries to classify female UUI types according to their urodynamic features, so as to improve the level of personalized clinical diagnosis and treatment for female UUI. Methods A retrospective urodynamic study was performed among 102 female patients diagnosed with UUI who presented to our center between June 2015 and June 2016. All recruited patients were required to complete several examinations besides history taking, including urine analysis, ultrasound of KUB, and PVR. After that, 44 patients with urinary tract infection (UTI), cancer, stone disease, neurogenic bladder or different kinds of cystitis were excluded. The remained 58 patients were evaluated by UDS, collecting data of bladder compliance, detrusor involuntary contraction and urethra response in storage phase. The study focused on whether there were detrusor overactivity and coexsisted urethral pressures changes in storage phase. Results The mean age of the studied patients was 63 years (SD 10.1). All patients had normal bladder compliance in storage phase. No obvious abnormal in voiding phase were found except for 2 cases failing to induce automatic micturition. According to whether there was involuntary detrusor contraction or not in storage phase, patients were divided into two types. No involuntary detrusor contractions were demonstrated in 22 patients (37.9%), though having a strong micturition desire during UDS. Involuntary detrusor contractions were demonstrated in 36 patients?62.1%?which could be further divided into two types. Among 36 patients, simultaneous decrease of urethra pressure was demonstrated in 19 patients?32.8%?while 17 others did not(29.3%). Conclusions UUI often pose a negative impact on the quality of life in female patients. UDS is an excellent choice to show the pathophysiological changes of lower urinary tract in female patients with UUI. This study shows that UUI in female patients could be classified into three different types based on UDS. Type I: involuntary detrusor contractions with simultaneous decrease of urethra pressure; type II: involuntary detrusor contractions without simultaneous decrease of urethra pressure; type III: no involuntary detrusor contractions, neither simultaneous decrease of urethra pressure. These three different types of UUI shows there could be a potential difference with the underlying mechanisms, which may benefit the development of personalized treatment for UUI. Funding None
Authors
Liang Dong
Jiayi Li Jianwei Lv Jing Leng Wei Xue Yiran Huang |
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MP63-06 |
Categorization of Real-Time Sensation Patterns During Urodynamics |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Incontinence: Evaluation (Urodynamic Testing) | 17BOS |
Abstract: MP63-06 Sources of Funding: Support provided by NIH grant R01DK101719 and the VCU Presidential Research Quest Fund. Introduction The objective of this study was to identify and categorize sensation patterns during urodynamics using a novel &[Prime]sensation meter.&[Prime] Methods Twenty one patients with voiding dysfunction of various types completed pre-procedure ICIq-OAB surveys. Then patients recorded real-time unprompted sensation on a 0 to 100% scale using a touch-screen &[Prime]sensation meter&[Prime] throughout urodynamics testing. Data were sampled at 5% increments of cystometric capacity, and percent capacity vs. sensation curves were generated. Gender and age were recorded, and sensation-capacity curves were compared in patients with low urgency (ICIq-OAB 5a = 0 to 1) or high urgency (ICIq-OAB = 2 to 3). Results Individual normalized sensation-capacity curves showed distinct trends for the two groups (Fig 1A) and the average curves were significantly different at 5 points between 50% and 90% capacity (Fig 1B, * = p<0.05, n=11 low & 10 high). The low urgency pattern was generally r-shaped with a rapid increase in urgency at low capacity and then a leveling off after 50% capacity. The high urgency group was generally J-shaped with a slow increase in urgency at low capacity and then a rapid increase after 50% capacity. Average bladder capacities and ages for the low urgency group (285±38 ml, 71±4 years) and high urgency group (315±47 ml, 62±4 years) were not different (p>0.05). The low urgency group included 7 men and 4 women while the high urgency group included 4 men and 6 women. Conclusions Real-time sensation data collected using the sensation meter during urodynamics identified patients with distinct r-shaped and J-shaped sensation-capacity curves which generally corresponded to individuals with low and high urgency, based on standardized survey scores. The study highlights that collection of real-time sensation data during urodynamics has the potential to identify novel bladder sensory patterns that could be used for sub-typing of patients for future therapies and trials. Additional studies are needed to potentially correlate patterns with specific pathologies. Funding Support provided by NIH grant R01DK101719 and the VCU Presidential Research Quest Fund.
Authors
Zachary Cullingsworth
Adam Klausner Anna Nagle William Simmons Jacqueline Morin Randy Vince David Rapp John Speich |
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MP63-07 |
Characterization of Low Amplitude Rhythmic Contractions During Urodynamics |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Incontinence: Evaluation (Urodynamic Testing) | 17BOS |
Abstract: MP63-07 Sources of Funding: Support provided by NIH grant R01DK101719 and the VCU Presidential Research Quest Fund. Introduction Human detrusor smooth muscle (DSM) can exhibit low amplitude rhythmic contractions (LARC) which may contribute to overactive bladder (OAB) in some patients. The aim of this study was to develop an objective method to identify LARC during urodynamics (UD), categorize patients with significant LARC, and potentially begin to characterize a LARC-mediated OAB/detrusor overactivity subtype. Methods An algorithm was developed to analyze UD filling data in low volume (1st 410 seconds) and high volume (final 410s) regions. Fast Fourier Transform (FFT) analysis identified the frequency (F) in the 1-6 cycle/min range associated with the maximum amplitude of the vesical pressure (Pves) in each region (Fig 1). A patient-specific range of interest corresponding to F ± 0.5 cycles/min was determined. Pves and Pabd amplitudes were analyzed separately to identify both significant (higher than average) and independent (distinct from Pabd) Pves signals. To be significant, Pves amplitude must be > 1.35 standard deviations (SD) above average Pves amplitude. To be independent, the Pabd amplitude must be < 1.35 SD above the average Pabd amplitude. SD of 1.35 was chosen using an iterative process in 0.05 SD increments to identify the maximum number of significant and independent signals. Results This algorithm was used to retrospectively analyze 43 consecutive UD studies which included 25 (14 neurogenic, 11 idiopathic) with detrusor overactivity (58%). The average age of the entire group was 55±2 years and included 14 men and 29 women. FFT analysis identified a significant and independent Pves signal in 12/43 patients (28%) of which 8/12 (67%, 5 neurogenic, 3 idiopathic) had detrusor overactivity. The average age of patients with significant and independent signals was 54±5 years and included 6 men and 6 women. Conclusions Analysis of LARC during UD testing identified a subset of patients with a significant and independent slow wave frequency in Pves. Further refinements of this technique may help identify subsets of individuals with LARC-mediated OAB/detrusor overactivity. Funding Support provided by NIH grant R01DK101719 and the VCU Presidential Research Quest Fund.
Authors
Zachary Cullingsworth
Brooks Kelly William Simmons Andrew Colhoun Anna Nagle Randy Vince John Speich Adam Klausner |
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MP63-08 |
Can Urodynamic Parameters Predict Sling Revision for Voiding Dysfunction in Women Undergoing Synthetic Midurethral Sling Placement? |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Incontinence: Evaluation (Urodynamic Testing) | 17BOS |
Abstract: MP63-08 Sources of Funding: None Introduction To evaluate the utility of urodynamic studies, performed before primary midurethral sling placement for stress urinary incontinence, in predicting the need for subsequent sling release for voiding dysfunction. Methods The health records of women managed with primary synthetic midurethral sling placement at Mayo Clinic (Rochester, Minnesota) from January 1, 2002, through December 31, 2012, were reviewed. The primary outcome was surgical sling release for postoperative voiding dysfunction (ie, prolonged retention, elevated postvoid residual volumes with new voiding symptoms, or de novo onset or worsening of overactive bladder symptoms). Logistic regression models were used to evaluate associations between potential clinical risk factors and the primary outcome. Results Overall, 1,629 women underwent primary synthetic midurethral sling placement during the study timeframe, including 1,081 patients (66%) who underwent a preoperative multichannel urodynamic evaluation. A sling release for voiding dysfunction was performed for 51 patients (3.1%) at a median of 1.9 months postoperatively (interquartile range, 1.3-9.3 months). Patients undergoing sling release were significantly more likely to have had retropubic sling placement (P=.003) and concomitant prolapse surgery (P=.005). On univariate analysis, no urodynamic parameters were associated with the risk of sling release; evaluated parameters included peak flow rate (P=.20), postvoid residual volume (P=.37), voiding without detrusor contraction (P=.96), and detrusor pressure at maximal flow (P=.23). Conclusions Sling release for voiding dysfunction was rare in our cohort. No urodynamic parameters were associated with the risk of sling release. Funding None
Authors
Brian Linder
Emanuel Trabuco John Gebhart Christopher Klingele John Occhino Daniel Elliott Deborah Lightner |
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MP63-09 |
Prediction of the long-term durability of suburethral sling based on postoperative urodynamics |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Incontinence: Evaluation (Urodynamic Testing) | 17BOS |
Abstract: MP63-09 Sources of Funding: none Introduction Although a high success rate has been achieved in the early follow-up after suburethral sling for stress urinary incontinence(SUI), there are limited data about long-term effects. The objective of this study is to survey the long-term durability of suburethral sling for SUI and to identify urodynamic changes that are correlated with successful outcomes. Methods Totally 309 women underwent 331 retropubic suburethral slings for SUI between 1989 and 2014 in this survey. Patients received standardized urodynamic testing preoperatively as the baseline and postoperatively within 6 months. Surgical results, demographic characteristics, urodynamic parameters, and postoperative clinical manifestation were retrospectively analyzed. Results The median follow-up period was 86.6 months. The overall subjective cure rate was 82.5%. Previous SUI surgery has negative influence on cure rate (P .048). 6.2% de novo urge urinary incontinence (UUI) in the successes, but none in the failure group (P .049). Persistent UUI after sling surgery was noted in 66 (24.2%) in the successes and 40 (69%) in the failures (P<.001). 107 women (39.2%) experienced UUI resolution in the successes, and 10 (17.2%) in the failures (P .001). Among successes, a significant interaction (P<.001) was detected between the baseline and postoperative urodynamic parameters, including Qmax, corrected Qmax, postvoid residual (PVR), voiding volume, voiding efficiency(VE), and bladder outlet obstruction index (BOOI). Significantly increased PdetQmax was also observed after surgery (P .015). A significant interaction (P .034) is detected from the baseline to 6 months between successes and failures for BOOI. Conclusions Suburethral sling has a durable long-term effect in our study. There is a trend suggesting that the decreased Qmax, corrected Qmax and VE are associated with surgical success, while increased Pdet.Qmax, BOOI, and PVR are also associated with success. Slight obstruction makes efficacious sling surgery. The increased outlet resistance is essential for achieving dryness. Funding none
Authors
Hsin-Ho Liu
Hann-Chorng Kuo |
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MP63-10 |
DO URODYNAMICS PREDICT URINARY RETENTION AFTER SLING PLACEMENT IN THE COMPLEX PATIENT: VALUE OF REPRODUCING SYMPTOMS OF URODYNAMICS |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Incontinence: Evaluation (Urodynamic Testing) | 17BOS |
Abstract: MP63-10 Sources of Funding: none Introduction The risk factors for urinary retention (UR) after sling in women with detrusor underactivity (DU)/Valsalva voiding is not well established. There is limited evidence that increasing outlet resistance in those with poor contractility would be a risk factor for urinary retention (UR). Symptoms of DU are often manifest as hesitancy and straining during the voiding phase and urodynamics (UDS) may overestimate this condition due to a number of factors during UDS including: psychogenic inhibition and pain from urethral catheterization. This study examined UR after sling in patients with or without DU/Valsalva voiding to determine if the reproduction of voiding symptoms on UDS in those with DU is predictive of UR after sling. Methods Following IRB approval, we performed a review of patients undergoing sling looking specifically at the occurrence of short and long term urinary retention. Preoperative incontinence symptom score questionnaire and UDS data were obtained from a prospective UDS database in which patients are directly queried at the time of the UDS study whether the filling/storage, and voiding phases of the study reproduced their usual symptoms. Urinary retention was defined as failed void trial requiring prolonged suprapubic catheter drainage or initiation of intermittent catheterization and was assessed at 1 week, 1 month and 3 months. Results Of the 96 women who had a sling procedure, 77 (80%) had preoperative UDS. Of those who had UDS, 27 (43%) had de-novo UR at some point post-operatively; 5 at 1 week, 7 at 1 month, and 15 at 3 months or longer. 26/27 (96.3%) patients who had UR had APVS versus MUS sling. As compared to those without DU, patients with DU were more likely to have UR (81% vs 56%, p=0.025). A positive symptom score of incomplete emptying did not increase risk of UR (p=0.58). 63/77 (82%) patients had UDS which reproduced their voiding symptoms, 23 (37%) of whom had UR. There was no difference in risk of UR in patients with DU/Valsalva voiding whose UDS reproduced voiding symptoms compared to those with DU/Valsalva voiding whose UDS did not reproduce symptoms (OR 0.98, CI 0.23-4.18, p= 0.98). _x000D_ Conclusions Patients with DU/Valsalva voiding have an increased risk of UR following sling, however reproduction of symptoms on UDS or symptom score do not correlate with risk of UR in either those with DU/Valsalva voiding or those with normal bladder contractility. Funding none
Authors
Alyssa Greiman
Lauren Rittenberg Lindsey Cox Ross Rames Eric Rovner |
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MP63-11 |
Is it mandatory to perform urodynamics to identify occult stress urinary incontinence? |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Incontinence: Evaluation (Urodynamic Testing) | 17BOS |
Abstract: MP63-11 Sources of Funding: None Introduction Occult stress urinary incontinece (OSUI) is defined as the stress incontinence only observed after the reduction of co-existent prolapse. The objective of this study was to investigate OSUI by physical examination and urodynamic study, comparing both methods. Methods This study enrolled 105 women with pelvic organ prolapse stage III and IV, according to the Pelvic Organ Prolapse Quantificaton (POP-Q) system, evaluated prospectively between January and December 2015. The study was reviewed and approved by the school´s Institutional Review Board and all included subjects signed informed consent before participating in the study. A standard history and physical examination was carried out and the investigaton of the OSUI was performed on supine standing and lithotomy position, reducing the prolapse using gauze and a Cheron dressing forceps. During physical examination, the patients were requested to cough and to do valsalva maneuver. Afterwords, they were asked to do the same maneuvers during multichannel urodynamics. Both evaluation were perfomed with 300ml bladder filling. The OSUI was defined when there was urine leakage only after the reduction of the prolapse. Results The mean patient age was 65.7 years, ranging from 40 to 89 years, mean parity 5.1 and mean body mass index 27.4. From a total of 105 patients, 70 (66.7%) presented with POP-Q stage III and 35 (33.3%) stage IV. Sixty three (60%) women were identified as occult stress incontinent, twenty seven (25.7%) as continent, and 15 (14.3%) as stress urinary incontinent (leaked without prolapse reduction). From the 63 OSUI subjects, 48 (76.2%) were identified in both evaluations, and 8 were identified only during physical examination, and 7 only during urodynamics. The sensitivity to detect OSUI during physical examination and urodynamics was 88.9% and 87.3% respectively (p=0.783). The value of Kappa to measure the agreement between both tests was 0.648 (95% CI, 0.441- 0.854). Anterior (p=0.006) and posterior (p<0.001) compartment stage IV prolapse showed increased risk of OSUI. Despite 86 (81.9%) patients mentioned storage symptoms, only 8 (7.6%) had urodynamic demonstrated detrusor overactivity. Conclusions Urodynamic study and physical examination are equivalent and concordant to demonstrate OSUI, thus it´s not mandatory to perform urodynamics to identify OSUI. Funding None
Authors
Susane Hwang
LuÃs Gustavo Toledo Silvia Carramao Armando Frade Raquel Richetti Andre Matos Antonio Auge |
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MP63-12 |
Reliability of valsalva leak point pressure in female stress urinary incontinence |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Incontinence: Evaluation (Urodynamic Testing) | 17BOS |
Abstract: MP63-12 Sources of Funding: none Introduction The valsalva leak point pressure (VLPP) on urodynamic study (UDS) is measured to evaluate the severity and characteristic of incontinence. The aim of this study was to investigate the test-retest reliability of VLPP in female stress urinary incontinence (SUI). Methods Our study included 80 women who underwent UDS to evaluate SUI. The UDS was performed by a single operator consecutively within a 30 minutes period. Intra-class Correlation Coefficient (ICC) was used to investigate the test-retest reliability. All definitions of urinary incontinence corresponded to recommendations of the International Continence Society. Results The mean age was 58.9 ± 7.4 years. Among enrolled patients, 34 had only SUI; 46 patients had mixed urinary incontinence (MUI). The 32 patients had underline diseases such as diabetes mellitus (DM), cerebrovascular disease or spinal disease. Overall, test-retest reliability of VLPP on UDS is excellent (ICC 0.94, P < 0.01). When enrolled patients were divided into several groups by incontinence type and presence of underline diseases, test-retest reliability of VLPP is excellent in each group (ICC 0.96, P < 0.01 in a SUI group; ICC 0.93, P < 0.01 in a MUI group; ICC 0.95, P < 0.01 in a group without underline diseases; ICC 0.92, P < 0.01 in a group with underline diseases). Conclusions The test-retest reliability of urodynamic VLPP in female SUI is excellent regardless of comorbid factors such as MUI, DM, cerebrovascular disease or spinal disease. The VLPP on UDS is a reliable data in female SUI. Funding none
Authors
Jun Seok Kim
Dong Hoon Yoo Dong Hoon Lim Myung Ki Kim Hee Jong Jeong Eun Mi Yang Seong Woon Park Joon Hwa Noh |
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MP63-13 |
Does videourodynamic classification depend on patient positioning in patients with stress urinary incontinence? |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Incontinence: Evaluation (Urodynamic Testing) | 17BOS |
Abstract: MP63-13 Sources of Funding: none Introduction Videourodynamic studies (VUDS) are often used to assess stress urinary incontinence (SUI). Treatment options are based on the degree of hypermobility and intrinsic sphincter deficiency. The most common classification on VUDS of SUI by Blaivas-Olsson is described in the semi-oblique position. However, most urodynamics are performed supine or standing with advocates of standing position suggesting that this stance permits gravity to enhance prolapse and aid diagnosis. We assessed the difference in Blaivas-Olsson grading in either positions. Methods 121 consecutive women with SUI underwent videourodynamic study prior to operative intervention. SUI was assessed in both supine and standing positions and the extent of descent was classified according to Blaivas-Olsson criteria. Differences between the positions was assessed using Fisher's exact test with p <0.05 being significant. _x000D_ Results 72 of 121 SUI classifications remained the same in both lying and standing positions. 49 gradings were upgraded with position (40%); no patients were downgraded. Of the 49 patients whose grading changed, 20 (16.5%) had non-demonstrable SUI converted to demonstrable (i.e. grade 0 converted to I, IIa, IIb or III); 22 patients with SUI in the supine position were upgraded by one grade (I –IIa (10) and IIa-IIb (12)) and 7 were upgraded by two grades from I to IIb (Figure).The difference in the distribution of SUI grading between supine and standing positions was statistically significant (p < 0.01)_x000D_ Conclusions 16.5% of patients only had SUI demonstrable in the standing position. 40% Blaivas-Olsson classifications were upgraded with patients in the standing position. This has important implications for practice. To best replicate symptoms, and minimise the chance of underestimating both incontinence and the degree of descent, we suggest that videourodynamics are performed using standardised methodology in both lying and standing positions. Funding none
Authors
Hazel Ecclestone
Eskinder Solomon Rizwan Hamid Mahreen Paksad Daniel Wood Tamsin Greenwell Jeremy Ockrim |
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MP63-14 |
Overnight ambulatory urodynamics findings in patients with nocturia and/or nocturnal enuresis |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Incontinence: Evaluation (Urodynamic Testing) | 17BOS |
Abstract: MP63-14 Sources of Funding: None Introduction Nocturnal symptoms are very troublesome to patients, yet objective methods to assess night time bladder function are limited. We aimed to determine the prevalence of detrusor overactivity in patients with nocturia and nocturnal enuresis during overnight ambulatory urodynamics Methods Twenty patients whose most bothersome symptoms were nocturia and/or nocturnal enuresis underwent overnight ambulatory urodynamic studies. All patients had undergone prior undiagnostic standard filling cystometry. Traces were reviewed and it was documented if detrusor overactivity (DO) +/-leakage was demonstrated, as well as the maximum voided volume and nocturnal urine output. Results The mean ( SD) agewas 45.1 ± 19.9 years, comprising 14 female and 6 male patients All patients presented with nocturia with 17 patients additionally complaining of nocturnal enuresis. Only 5 patients reported bothersome day time symptoms. The mean duration for the overnight ambulatory urodynamic studies was 14.5 hours (range 12 to 16.6 hours). DO was demonstrated in 80% (n=16) of patients. 15 out of the 17 (88.3%) patients with nocturnal enuresis demonstrated DO. Small volume SUI was demonstrated in 4 out the 17 (23.5%) patients with nocturnal enuresis. The mean and median peak DO pressure was 68.3 (± 50.9) and 50 cmH2O. There appears to be no significant difference in the maximum voided volume and nocturnal urine output between the two DO groups (NB: small sample DO -ve patients). Incontinence was observed in 15 out of 16 (93%) patients with DO. Conclusions 80.0% of patients who present with nocturia and 88% with nocturnal enuresis demonstrate detrusor overactivity on overnight ambulatory urodynamics tests. The DO pressures demonstrated were large amplitude and resulted in incontinence by overcoming in most cases an otherwise competent outlet. Nocturnal ambulatory urodynamics are a useful clinical adjunct for assessing night time urinary symptoms. Funding None
Authors
Eskinder Solomon
Megan Duffy Sachin Malde Hazel Ecclestone Mahreen Paksad Rizwan Hamid Tamsin Greenwell Jeremy Ockrim |
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MP63-15 |
Concordance Of Urodynamic Definitions Of Female Bladder Outlet Obstruction |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Incontinence: Evaluation (Urodynamic Testing) | 17BOS |
Abstract: MP63-15 Sources of Funding: None Introduction Unlike the diagnosis of bladder outlet obstruction (BOO) in men, BOO in women has neither a standard definition nor well-accepted defining diagnostic criteria. The aim of this study is to assess the level of agreement between seven diagnostic criteria for female BOO based on voiding pressure and/or flowrates with radiographic evidence of BOO. Methods We reviewed the video-urodynamics and clinical data of 535 women. We categorised the women as obstructed or unobstructed based on Farrar (1), Massey and Abrams (2), Chassagne (3), Lemack (4), Defreitas (5), Blavais and Groutz (6), Solomon-Greenwell (7) definitions of BOO. We also assessed if there was radiographical evidence of BOO in the presence of a sustained voiding pressure as per Nitti (8). We then assessed the level of agreement between urodynamics and radiographic data using Cohen&[prime]s kappa coefficient. Results Radiographic evidence of BOO was observed in 124 (23.2%) of patients. Of these patients; 104, 105, 94, 71, 82, 121 and 106 women were classified as obstructed according to (1) to (7) definitions of BOO respectively. Out of the 411 patients without radiographic evidence of BOO; 115, 35, 43, 8, 42, 156 and 18 patients were classified as obstructed according to (1) to (7) definitions of BOO respectively. The Blaivis-Groutz nomogram (6) is the most sensitive but least specific. Conversely, Lemack et al&[prime]s (4) definition of BOO is the least sensitive but the most specific. The highest Cohen&[prime]s Kappa coefficient of 0.81 (p<0.01), thus best level of agreement, was between the Solomon-Greenwell nomogram (7) and radiographic evidence of BOO (8). Conclusions The various urodynamic definitions of female BOO have wide ranging sensitivity and specificity when compared to radiographic evidence of obstruction. The Solomon-Greenwell nomogram cut off of Pdet.Qmax >2.2Qmax+5 demonstrated an excellent level of agreement with radiographic evidence of BOO. Funding None
Authors
Eskinder Solomon
Habiba Yasmin Megan Duffy Sachin Malde Jeremy Ockrim Tamsin Greenwell |
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MP63-16 |
Effects of radiation on male stress incontinence |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Incontinence: Evaluation (Urodynamic Testing) | 17BOS |
Abstract: MP63-16 Sources of Funding: none Introduction The aim of this study is assess the utility of preoperative urodynamic testing in men with stress urinary incontinence (SUI) and to identify urodynamic parameters that correlate to clinical variables and outcomes after surgery for SUI. Methods A retrospective chart review of all male patients with stress urinary incontinence (SUI) who underwent urodynamic testing (UDS) from 2010 until 2016 was performed. Clinical variables were correlated with urodynamic parameters such as maximum cystometric capacity (MCC), presence of detrusor overactivity (DO), and end filling pressure (EFP) as a measure of impaired compliance. _x000D_ Results 207 men were identified that underwent UDS with a presumed diagnosis of SUI. 73 (35.5%) men developed SUI after they underwent robotic prostatectomy, 48 (23.2%) had open prostatectomy, 21 (10.1%) had external beam radiotherapy (EBRT) only and 8 (3.9%) had brachytherapy. 41 (19.8%) had salvage radiotherapy. 65/207 (31.4%) were exposed to radiation as a treatment modality. All patients that underwent urodynamic testing moved on to surgical correction of SUI, 155 men had artificial urinary sphincter (AUS) and 52 men had male sling. _x000D_ Table 1 and 2. _x000D_ Conclusions Radiation was predictive of having lower MCC (p=.03) and DO on UDS (p<0.0001) when compared to non-radiated (NR) men. Patients who have been radiated have a higher incidence of DO and high pressure DO(>40cmH20) when compared to NR men. Radiated patients with these urodynamic findings were associated to have increased need for anticholinergic use and progression to third line therapy. Interestingly, impaired compliance was not predictive. UDS did not change the decision to surgically treat SUI in any patient, however UDS may be helpful in counseling as having DO on UDS was predictive of requiring anticholinergic use post operatively (p=0.001) and having refractory OAB requiring third line therapy (p=0.01). _x000D_ Funding none
Authors
Daniel Hoffman
Benjamin Brucker Nirit Rosenblum Varun Vijay Victor Nitti |
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MP63-17 |
Roles of urodynamics in the assessment of post radical prostatectomy incontinence: do findings change patient management? |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Incontinence: Evaluation (Urodynamic Testing) | 17BOS |
Abstract: MP63-17 Sources of Funding: None Introduction Urinary incontinence after radical prostatectomy is aetiologically diverse, and not solely confined to post-surgical stress urinary incontinence (SUI). Previous studies have shown overall incidence of detrusor overactivity (DO) in this group ranging between 25-63%. With increasing treatment options for overactive bladder and new surgical procedures for male SUI, we aimed to evaluate the impact of urodynamic study findings on subsequent management in a contemporary cohort of patients with post prostatectomy incontinence. Methods Prostate cancer patients with urinary incontinence post open radical prostatectomy, who had failed conservative management and being considered for surgical treatment underwent multichannel urodynamic studies between 2011 and 2015. Patients with adjuvant or salvage radiotherapy, as well as those who have undergone previous surgical treatments for SUI were also included. Urodynamic findings were reviewed and subsequent patient management outcomes obtained from medical records. Patients who had laparoscopic or robotic radical prostatectomies were excluded, as were patients treated with radiotherapy alone. Results 145 patients (age 50-87, median 69) were included. Prior to urodynamic study, 41 patients had adjuvant or salvage external beam radiotherapy, 20 had prior SUI surgery, and 5 had both. Overall, DO was demonstrated in 59 patients and 57 had reduced compliance on filling. DO was found in 55.0% (11/20) of patients with persistent incontinence following previous SUI surgery. DO was present in 48.8% (20/41) of patients with previous radiotherapy and 37.5% (39/104) of patients without previous radiotherapy. In patients with DO, 42.4% (25/59) were treated with anticholinergics, mirabegron or intravesical onabotulinumtoxinA, and did not proceed to SUI surgery. 22.0% (13/59) of patients with DO were managed with SUI surgery alone and 13.6% (8/59) received treatment for DO prior to undergoing SUI surgery. In contrast, only 4.6% (4/87) of patients without DO required treatment with anticholinergics, mirabegron or onabotulinumtoxinA, either in isolation or combined with SUI surgery. Conclusions Bladder dysfunction is an important cause of post prostatectomy incontinence in addition to sphincter insufficiency. A significant proportion of such patients can be successfully treated without requiring surgical treatment. Urodynamic study plays an important role in patient evaluation, and helps to optimise the opportunity for successful treatment outcome by guiding individual patient management. Funding None
Authors
Janice Cheng
Ameet Patel Vincent Tse Lewis Chan |
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MP63-18 |
DO SYMPTOMS CORRELATE WITH URODYNAMIC FINDINGS FOR MEN WITH POST-PROSTATECTOMY INCONTINENCE? |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Incontinence: Evaluation (Urodynamic Testing) | 17BOS |
Abstract: MP63-18 Sources of Funding: Source of Funding: None Introduction Persistent bothersome urinary incontinence occurs in up to 10-15% of men after radical prostatectomy (RP). Urodynamics (UDS) are often utilized in the assessment of men with post-prostatectomy incontinence (PPI). Our objective is to determine how well patient symptoms correlate with UDS in men with PPI. Methods Retrospective review of a cohort of 496 men referred to our institution with PPI over a 20-year period. All patients with a history of RP were included in the study. All patients had a standardized history as well as the original multichannel UDS and interpretation. Results 496 patients with an average age of 64 were reviewed accounting for 513 studies. UDS were performed on average 3 years after RP. On history, 471 (91%) patients complained of stress urinary incontinence (SUI), 249 (48%) urgency urinary incontinence (UUI) and 207 (40%) had mixed urinary incontinence (MUI). 264 (52%) of patients had only SUI and 42 (8%) only UUI symptoms. 356 of the 471 patients with a history of SUI symptoms had SUI on UDS for a positive predictive value (PPV) of 75%. Negative predictive value (NPV) for SUI symptoms was 78%. 6% of men complaining of SUI symptoms on history had only detrusor overactivity incontinence (DOI) on UDS, and 18% of men with SUI symptoms demonstrated no incontinence on UDS. 108 of the 249 patients with symptoms of UUI had DOI on UDS for a PPV of 43%. NPV for UUI symptoms was 85%. Of the 42 men complaining only of UUI symptoms, 14% had only SUI, 50% had only DOI and 17% had both SUI and DOI on UDS. 19% of men with only UUI symptoms demonstrated no incontinence on UDS. 77% of patients with MUI symptoms had SUI on UDS. Conclusions 91% of men in this study with PPI presented with some element of SUI symptoms on history. SUI symptoms on history accurately predicts SUI on UDS and rarely identifies only DOI. These data question the routine use of UDS in the workup of men presenting with SUI symptoms after RP prior to treatment. Men complaining only of UUI symptoms on history also predicts for DOI on UDS. UDS may be helpful in this patient group to further guide treatment decisions if initial treatment fails and to rule out SUI. Most men with MUI symptoms will have SUI identified on UDS. Funding Source of Funding: None
Authors
Joseph LaBossiere
Sender Herschorn |
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MP63-19 |
The value of urodynamics prior to sacral neuromodulation in men |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Incontinence: Evaluation (Urodynamic Testing) | 17BOS |
Abstract: MP63-19 Sources of Funding: None Introduction Sacral neuromodulation (SNM) is an effective therapy for non-obstructive urinary retention, refractory urgency/frequency and urgency incontinence, however it may be underutilized in men. There is a dearth of literature on SNM in men, as most male lower urinary tract symptoms (LUTS) research focuses on medical therapy and bladder outlet procedures, offering little guidance about SNM in men. To what extent UDS can yield diagnostic clarity in male LUTS and its role in predicting SNM success in men is unknown. Herein, we analyze how UDS findings relate to SNS utilization in men._x000D_ Methods A retrospective review of men undergoing SNM procedures from 2011-2015 at our institution was performed. Demographics, comorbidities, prior urologic treatments, SNM indication, and SNM utilization were assessed. Patients were stratified according to UDS ≤12 months before SNM (+UDS) vs. no UDS testing (-UDS). Descriptive statistics characterized the groups, T-test or chi-square tests were used where appropriate, and logistic regression was used to identify clinical and UDS parameters related to SNM outcomes. Results 56 men underwent SNM therapy and 28 had UDS within the prior year. UDS+ and UDS- men were similar in age and co-morbid conditions. On average, +UDS men had a greater BMI (30.4+6.5 v 27.3+4.6, p 0.045). Rates of prior transurethral prostate procedures were not significantly different (17.9% v 25%) between the groups. _x000D_ Most (N=53) men underwent staged implant, though 3 (+UDS N=2, -UDS N=1) had peripheral nerve evaluation (PNE). All PNE trials were successful, while rates of Stage 1 success (80.8% v 63.0%, p 0.22) and Stage 2 completion (95.2% v 94.1%, p 1.00) did not differ between +UDS or -UDS men. Device revision (21.4% vs. 25%, p 0.75) and explant (17.9% v 14.5%, p 1.00) rates also did not differ by +UDS or -UDS. _x000D_ No stress urinary incontinence (N=0) was noted on UDS in any patient, but detrusor overactivity was present in 50% (N=14) with urgency urinary incontinence in 25% (N=7).UDS findings of obstruction (N=1), poor compliance (N=1), and hypocontracility (N=1) were rare. Rates of Stage 1 success, Stage 2 completion, device revision, and device explant did not differ in the presence or absence of UDS-proven pathology_x000D_ Conclusions Sacral nerve stimulation is a feasible treatment for men with refractory lower urinary tract symptoms. Neither the performance of urodynamics nor the presence of urodynamically-proven pathology was associated with greater likelihood of progression to stage 2, device revision or explant. Our findings suggest that SNM may be safely and effectively utilized in men without preoperative urodynamics. Funding None
Authors
Elodi Dielubanza
Bradley Gill Shree Agrawal Henry Okafor Jessica Lloyd Juan Guzman Courtenay Moore Howard B. Goldman Sandip Vasavada Raymond Rackley |
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MP63-20 |
Symptomatic Urinary Tract Infections' Rate Post-Urodynamic Studies and Risk Factors |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Incontinence: Evaluation (Urodynamic Testing) | 17BOS |
Abstract: MP63-20 Sources of Funding: none Introduction Urodynamic study (UDS) is an invasive ambulatory procedure that carries a risk for urinary tract infection (UTI). AUA statement justifies antimicrobial prophylaxis before UDS only in patients with certain risk factors based on studies that used a rate of all types of bacteriuria as a measure of post-UDS UTI. The aim of the study was to verify a symptomatic post-UDS UTI rate and identify possible risk factors for post-UDS symptomatic UTI._x000D_ Methods 398 patients in an IRB-approved retrospective review of UDS clinic electronic charts' database. Anyone with symptoms of: dysuria, urinary frequency, urgency or fever and a positive urine culture within 15 days after UDS considered as post-UDS symptomatic UTI. Following variables: age >70, male gender, past or current smoking, diabetes mellitus, neuropathic pathologies, indwelling or intermittent catheters, time interval between urine culture (UC) and a day of UDS, presence of asymptomatic bacteriuria pre-UDS were verified as possible risk factors for post-UDS UTI. Results Mean age of a study population was 65.7 (range=19-95) years old. 243/398(61.1%) were male. 320(80.4%) patients had a negative UC prior to UDS with a significantly lower symptomatic UTI rate of 5% compared to 14.7% symptomatic UTI rate among patients who had prior to UDS appropriately treated positive UC (p<0.02). There was no significant difference in a time interval between UC and a date of UDS in a group that developed UTI compared to an asymptomatic group (p=0.1). In a univariate analysis, age >70, appropriately treated UC before UDS, time interval between UC and UDS more than a week, male gender, diabetes mellitus and neuropathic conditions were found as a significant variables predicting post-UDS symptomatic UTI (p<0.0001). However, in a multivariate analyses, only an appropriately treated positive UC before UDS (OR=2.75, 95%CI=1.04-7.27, p=0.04) and an interval of more than a week between pre-UDS UC and UDS (OR=2.83, 95%CI=1.16-6.91, p=0.022) were found as significant variables predicting symptomatic post-UDS UTI. Conclusions The first study to verify a symptomatic post-UDS UTI rate and identify possible risk factors for post-UDS symptomatic UTI. This study supports our antimicrobial prophylaxis protocol before UDS to minimize post-UDS UTI rate. However, a retrospective design and a relatively small number of patients in each group of proposed risk factors might cause that only few risk factors were with significance were found in a multivariate analysis. Funding none
Authors
Michael Vainrib
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MP64-01 |
External validation of the CAPRA-S score to predict biochemical recurrence after radical prostatectomy: Results from the K-CaP database |
Prostate Cancer: Localized: Surgical Therapy V | 17BOS |
Abstract: MP64-01 Sources of Funding: None Introduction The CAPRA-S score uses pathologic data from radical prostatectomy to predict biochemical recurrence and mortality. Recently, external validation was performed using the American and European cohorts, however, it has not previously been validated in a large, multi-institutional Asian cohort. Thus, we independently validated CAPRA-S score in an independent multi-institutional Korean (K-CaP) database. Methods The study cohort comprised 3,274 patients treated with radical prostatectomy between March 2005 and December 2014. Prediction of biochemical recurrence was assessed by Kaplan-Meier analysis and the concordance index (c-index). Performance of CAPRA-S in predicting biochemical recurrence was assessed by calibration plots, and decision curve analysis. Results During the median follow-up duration of 43.0 months, biochemical recurrence developed in 697 patients (21.3%). When stratifying patients with a CAPRA-S of 0-2, 3-5, and 6-12 (defining low, intermediate and high risk group), 39.4%, 35.9%, and 24.7% of patients were in a CAPRA-S low, intermediate and high risk group, respectively. Also, estimated 5-year biochemical recurrence-free survival was 91.2%, 71.3% and 30.7%, respectively. The c-index of the CAPRA-S to predict biochemical recurrence was 0.782 (Fig. 1). The calibration plot at 5-year generally showed a good fit. Decision curve analysis revealed a greater net benefit (net increase in the proportion of patients appropriately identified for adjuvant treatment) of the CAPRA-S score for the threshold probabilities of treating all men or no men with adjuvant therapy (Fig. 2). Conclusions The CAPRA-S score was accurate when applied in a multi-institutional Korean database. It predicted biochemical recurrence after radical prostatectomy with a c-index of 0.782. The CAPRA-S score can be valuable that may aid in determining the need for adjuvant therapy. Funding None
Authors
Yong Hyun Park
Jin Bong Choi U-Syn Ha Sung-Hoo Hong Sae Woong Kim Ji Youl Lee |
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MP64-02 |
Oncological Outcomes of Salvage Radical Prostatectomy: a multicentre series of 243 patients. |
Prostate Cancer: Localized: Surgical Therapy V | 17BOS |
Abstract: MP64-02 Sources of Funding: None Introduction Salvage radical prostatectomy (sRP) represents a valid treatment option with curative intent, in men with biochemical recurrence (BCR). We evaluated oncological outcomes of a contemporary series of sRP. Methods Three hundred seventy-six men with biochemical recurrence (BCR), who underwent sRP between 2000 and 2015 at 13 Tertiary referral centres, were retrospectively analysed. Age, PSA, clinical and pathological TNM, primary and pre-sRP biopsy and sRP gleason score (GS), surgical margins, imaging type and positive sites, lymphadenectomy template used, number of lymph-nodes removed and positive, ASA score and ECOG performance status and use of hormonal treatment (HT) were collected for each patient. Exclusion criteria were a follow up <12 months or unavailability of the data. Continuous variables were tested for normal distribution and then compared using Wilcoxon-Mann-Whitney test; differences in categorical variables were assessed by Chi-square or Fisher's exact tests. Results Two hundred forty-three men were included. Primary treatments were external beam radiation therapy in 69.5%, cryotherapy in 3.7%, HIFU in 4.1%, brachytherapy in 21.4% and other primary treatments in 1.2% of the patients. Mean PSA and age pre-sRP were 6.32 ±8.23ng/mL and 64.7 ±8.35 years, respectively. Pre-operatively, 1 men had radiological evidence of retroperitoneal nodal involvement, no extra-nodal metastasis were present, 88 men (37.13%) were on HT whereas 15 (6.22%) had castration resistant prostate cancer (CRPC). ASA score was 3 in 63 (26%) patients. A super-extended lymphadenectomy, including retroperitoneal nodes was performed in 6 cases (2.49%). At final pathology, 85 patients (38.6%) had a GS ≥8, whereas local extra-prostatic extension (T stage≥3) was diagnosed in 118 patients (48.96%). Surgical margins were positive in 89 patients (37.09%). Mean number of nodes removed and positive were 11.6 ±9.27 and 0.68 ±2.55, respectively. After a median follow up of 36.8 months (IQ range 22.7-61.4), BCR had occurred in 104 patients (44.07%) and 16 patients (6.5%) developed CRPC. Overall survival (OS) was 92.95% and cancer specific survival (CSS) 95.85%. Conclusions Promising oncological outcomes can be achieved by salvage radical prostatectomy. Although significant rates of BCR and positive surgical margins are observed, OS and CSS prove relatively high on a short-medium term follow-up. To validate the present findings, longer follow-up and higher number of patients are needed. Funding None
Authors
Giancarlo Marra
Paolo Gontero Paolo Alessio Marco Oderda Michele Brattoli Giorgio Calleris Anna Palazzetti Francesca Pisano Antonino Battaglia Stefania Munegato Bruno Frea Fernando Munoz Claudia Filippini Estefania Linares Rafael Sanchez-Salas Sanchia Goonewardene Prokar Dasgupta Declan Cahill Ben Challacombe Rick Popert David Gillatt Raj Persad Juan Palou Steven Joniau Salvatore Smelzo Thierry Piechaud Alexandre De La Taille Morgan Roupret Simone Albissini Roland Van Velthoven Alessandro Morlacco Sharma Vidit Giorgio Gandaglia Alexander Mottrie Joseph Smith Shreyas Joshi Gabriel Fiscus Robert Jeffrey Karnes |
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MP64-03 |
TUMOR AND MRI FEATURES PREDICTIVE OF EXTRACAPSULAR EXTENSION IN HIGH RISK PROSTATE CANCER |
Prostate Cancer: Localized: Surgical Therapy V | 17BOS |
Abstract: MP64-03 Sources of Funding: None. Introduction Advancements in prostate imaging have improved prostate cancer detection, localization and staging. Prediction of tumor capsular breaches on multiparametric MRI (mpMRI) may assist with surgical planning as well as improve prostate cancer prognostication. The objective of this study was to determine what tumor and MRI characteristics are suggestive of extracapsular extension (ECE) on pathologic prostate specimens. Methods High risk prostate cancer patients who underwent mpMRI and radical prostatectomy from January 2011 to April 2015 were retrospectively reviewed. Clinicopathological characteristics (PSA, PSA density, clinical stage, biopsy Gleason score and percent positive core), MRI features and pathology results were analyzed. Univariate and multivariate logistic regression analyses were performed to determine odds ratios predictive of ECE on pathology. Results Among 93 patients that underwent radical prostatectomy, 55 had ECE on final pathology. On univariate analysis, PSA (OR=1.1, 26.1 vs 10.9, p=0.03) was predictive of pathologic ECE while biopsy Gleason score (OR=1.2, p=0.62), percent positive cores (OR=2.6, p=0.27) and lowest ADC value on MRI (OR=1, p=0.27) were not. On multivariate analysis, gross ECE on MRI was the only factor associated with pathologic ECE (OR=1.9,p=0.03). PSA (p=0.07) and other MRI features were not suggestive of pathologic ECE. The sensitivity and specificity of MRI for identifying pathologic ECE was 52.6% and 65.8%, respectively; the associated positive and negative predictive values were 84.3% and 28%, respectively. Conclusions The presence of ECE on mpMRI was the most reliable predictor of pathological ECE in this high-risk cohort. mpMRI is a valuable adjunct in surgical planning and stage prognostication. Funding None.
Authors
Pooya Banapour
Andrew Schumacher Rex Parker David Finley |
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MP64-04 |
Prostate Specific Antigen Nadir: The Optimal Level to Define Biochemical Failure after Radical Prostatectomy |
Prostate Cancer: Localized: Surgical Therapy V | 17BOS |
Abstract: MP64-04 Sources of Funding: None Introduction Biochemical failure after radical prostatectomy (RP) is defined by two consecutive serum prostate specific antigen (PSA)values of >0.2ng/mL. This value has been determined based on retrospective studies in men who had undergone RP for localized prostate cancer. However retrospective design and probability of extra-prostatic extension affect the accuracy of the aforesaid cut-off value. To determine a more accurate PSA nadir value we measured serum PSA after cystoprostatectomy in patients with bladder urothelial cancer and no evidence of prostatic malignancy. Methods Fifty two consecutive patients underwent radical cystoprostatectomy for muscle invasive bladder cancer in our institution between December 2010 and December 2013. Histopathological evaluation of prostatic tissue was performed in slices with 3 micrometers in thickness. Any evidence of prostatic adenocarcinoma and/or high grade prostatic intraepithelial neoplasia were considered as exclusion criteria. Additional exclusion criteria were prostatic involvement with urothelial carcinoma, neoadjuvant or adjuvant chemotherapy and radiation therapy. Among all patients, 41 were eligible for study. Serum PSA level was measured using immunochemiluminescence technique between 6 month and 3 years after surgery in study participants. Results Forty one patients with mean age of 66.4±8.9 were evaluated in this study. Mean serum PSA level after radical cystoprostatectomy was 0.037±0.031 ng/mL (ranging from 0.002 to 0.1). Serum PSA level was not affected by either surgical technique or interval between surgery and PSA measurement. Mean serum PSA level in our study was significantly lower than 0.2 ng/mL which is considered as PSA nadir value after RP. Conclusions Serum PSA level of 0.2 ng/mL which is considered as PSA nadir level may be inaccurate and delay salvage treatment. Our results showed that cut off value of ≤0.1 ng/mL may be more accurate. Funding None
Authors
Seyed Yousef Hosseini
Erfan Amini Naser Riazi Mohsen Ayati |
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MP64-05 |
Contemporary extended pelvic lymph node dissection for prostate cancer in the UK – an analysis of national practice and lymph node invasion rates |
Prostate Cancer: Localized: Surgical Therapy V | 17BOS |
Abstract: MP64-05 Sources of Funding: None Introduction Extended pelvic lymph node dissection (ePLND) is the optimal method of lymph node staging in prostate cancer. In the UK, radical prostatectomy has been performed in specialist centres since 2002. Since 2014 as part of a NHS transparency drive, a national registry collating outcomes after radical prostatectomy was set up and managed by the British Association of Urological Surgeons (BAUS). We report a detailed analysis of UK ePLND practice and lymph node invasion rates stratified by the 2016 WHO-approved new prostate cancer grading system. Methods All preoperative clinical N0 (cN0) patients undergoing radical prostatectomy with ePLND between January 1, 2014 and December 31, 2015 with surgeon/institution-reported data recorded in the BAUS registry were analysed. Results In total over the two year period 12857 radical prostatectomy cases were reported. Of these, 11462/12857 (89.1%) met the inclusion criteria and were cN0; 4591/11462 (40.1%) underwent pelvic lymph node dissection. In total 2224/4591 (48.4%) underwent ePLND, median age 65 years, median lymph node yield 13 nodes._x000D_ _x000D_ The surgical technique of ePLND was open 504 (22.6%), laparoscopic 467 (20.9%) or robotic 1253 (56.3%). Lymph node invasion rate stratified by pre-operative PSA 0-10ug/L,11-20ug/L and >20ug/L was 46/656(7.0%), 45/425(10.6%) and 24/153(15.7%) respectively. Lymph node invasion rate stratified by pre-operative clinical stage cT2 and cT3 was 92/829(11.1%) and 155/572(27.1%) respectively._x000D_ _x000D_ Table 1 Describes lymph node invasion rates stratified by the new grading system risk groups (p=ns) _x000D_ Conclusions This UK-wide analysis demonstrates that ePLND is done increasingly commonly as the risk group grading increases in localised prostate cancer. However, lymph node invasion rates are not significantly different between the new grading classification risk groups, suggesting inaccuracy in staging for ePLND and/or limitations of current risk stratification methods. Funding None
Authors
Edward Calleja
Sarah Fowler John McGrath Prasanna Sooriakumaran Jonathan Aning |
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MP64-06 |
Lymphadenectomy in Gleason 7 Prostate Cancer: Utilization and Adherence to Guidelines |
Prostate Cancer: Localized: Surgical Therapy V | 17BOS |
Abstract: MP64-06 Sources of Funding: None Introduction The current evidence for lymphadenectomy (LND) at the time of radical prostatectomy (RP) for Gleason 7 intermediate-risk prostate cancer (PCa) is not as robust as for high-risk prostate cancer. Current guidelines defer to various nomograms regarding the risk of lymph node involvement to dictate the need for LND. The objective of this study was to examine utilization trends and survival data for patients who underwent LND for Gleason 7 PCa. Methods The SEER database was queried for all patients with either Gleason 3+4 (G34) or 4+3 (G43) PCa from 2004-2013, limited to patients with no evidence of metastatic disease or prior radiotherapy. Distributions and trends of LND, cancer-specific survival (CSS) and overall-survival (OS) were calculated. Memorial-Sloan Kettering Cancer Center (MSKCC) nomogram was applied to stratify patients based on risk of nodal disease at time of RP (<5% risk or >5% risk). Finally, multivariate logistic regression analyses (MVA) were performed to determine covariates associated with the likelihood of receiving LND. Results A total of 78641 patients with either G34 or G43 PCa underwent RP (59194 and 19447, respectively) with mean follow-up of 57.9 months. Of these patients, 61.2% of G34 and 73.5% of G43 patients underwent LND. During this time, the proportion of G43 patients undergoing LND remained relatively stable. The proportion of G34 patients undergoing LND varied between 55.9% in 2008 and 67.9% in 2013 despite decreasing RP rates in that same time frame. On MVA, the primary contributor to the variability in LND completion was socioeconomic status (SES): patients with higher SES were less likely to receive LND when indicated (OR 0.82, p < 0.05) and more likely to receive LND when not indicated (OR 1.15, p < 0.05). Age, race and insurance status were not significant predictors of LND. The incidence of pN+ disease was 1.5% and 5.2% in the <5% and >5% risk groups, respectively. Completion of LND at time of RP did not significantly change CSS in patients with G34 PCa (99.50% with LND and 99.59% without LND, p = 0.14.) In G43 patients, however, CSS was better in patients who did not undergo LND (98.81% with LND and 99.33% without LND, p = 0.002), the difference primarily driven by pN1 patients. Conclusions The role of LND for Gleason 7 prostate adenocarcinoma is not yet standardized, as indicated by the variability of LND dissection rates over an 11-year period in the United States. SES was the primary predictor of LND completion at time of RP. As CSS was not affected by completion of LND for G34 PCa, further evaluation of oncologic benefit in this patient population is warranted. Funding None
Authors
Thenappan Chandrasekar
Hanan Goldberg Zachary Klaassen Robert J. Hamilton Girish S. Kulkarni Neil E. Fleshner |
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MP64-07 |
Lymph node yield and positivity rate by location in 1000 robotic prostatectomy patients that underwent extended pelvic lymph node dissections at a single institution. |
Prostate Cancer: Localized: Surgical Therapy V | 17BOS |
Abstract: MP64-07 Sources of Funding: none Introduction For intermediate- and high-risk prostate cancer patients, an extended pelvic lymph node dissection (ePLND) template is recommended by NCCN and EAU guidelines at the time of prostatectomy. We report on 1000 robotic assisted-laparoscopic prostatectomy (RALP) patients who underwent an ePLND at a single institution. Methods From August 2010 to September 2016, 1000 patients underwent an ePLND during RALP. Our ELND technique includes as boundaries the ureteral crossing over the common iliac bifurcation proximally, the lateral border of the external iliac artery laterally, the node of Cloquet distally, as well as the obturator fossa. LNs were sent in 11 packets (bilateral common, external and internal iliacs, node of Cloquet, obturator and anterior bladder fat). Clinicopathological and lymph node (LN) data were obtained from our prospectively collected institutional database. Results 61.9% patients were D’Amico intermediate-risk and 30.8% were high-risk. Median age was 64 years. Median PSA was 6.4. 33% were ? pT3. 24.7% had positive margins. The median LN yield was 20 and 2.1% of LNs removed were positive. LNs were positive in 17.4% of all patients including 9.7% of the intermediate- and 35.4% of the high-risk groups. Figure 1 illustrates the median LN yields. Figure 2 demonstrates the percentage of LN that were positive by packet location. 1.4% of patients received blood transfusion. 90-day complications were low and similar between risk groups with 2.2% having symptomatic lymphoceles requiring intervention and 0.8% having DVTs overall. Conclusions 17.4% of 1000 RALP had positive LNs with an ePLND and complications were rare. Most common locations for metastasis were the obturator (39.8%) followed by external iliac packets (29.3%). To our knowledge, this is the largest series of robotic ePLND during RALP. Funding none
Authors
Paul Gellhaus
Nora Ruel Avinash Chennamsetty William Chu Justin Emtage Jonathan Yamzon Clayton Lau Timothy Wilson Bertram Yuh |
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MP64-08 |
Symptomatic Lymphocele Formation after Extraperitoneal vs. Transperitoneal Robot Assisted Radical Prostatectomy and Bilateral Pelvic Lymphadenectomy |
Prostate Cancer: Localized: Surgical Therapy V | 17BOS |
Abstract: MP64-08 Sources of Funding: none Introduction With the peritoneum acting as a natural surface for lymphatic reabsorption, many Urologists believe that a transperitoneal approach to robot assisted radical prostatectomy (tRARP) results in a lower incidence of symptomatic lymphocele (SL) formation compared extraperitoneal robot assisted radical prostatectomy (eRARP) when bilateral pelvic lymph node dissection (BPLND) is performed. There remains a paucity of evidence in support of this claim and no group has directly compared the two approaches for this outcome. Herein, we aim to determine if there is a difference in SL formation and characteristics between the two approaches. Methods A chart review of patients undergoing RARP and BPLND at a single tertiary care academic center from July 1, 2003 to May 31, 2016 was undertaken. Patients who underwent prior pelvic radiotherapy, concomitant inguinal hernia repair, did not undergo BPLND, or had non-adenocarcinoma of the prostate were excluded. The resulting eRARP and tRARP groups were propensity matched for age, BMI, ASA, D'Amico risk classification and total number of lymph nodes (LN) removed. SL was defined as pelvic fluid collections diagnosed by US, CT or MRI, at least 3 cm in maximal diameter, located directly adjacent to the site of the PLND and associated with pelvic pain or pressure, urinary retention, weakness/malaise, high drain output, leg edema/pain/weakness or infection in patients who underwent PLND. Results 3183 RARP procedures were performed during this time period and after exclusions and propensity matching, 662 and 666 patients remained in the tRARP and eRARP groups respectively. No differences were noted between the groups with regards to age, BMI, operating room time, pathological stage, positive margin rate, pathological Gleason score or pathological stage. The eRARP group had higher ASA scores (p=0.0028) and estimated blood loss (EBL, 218.5±152.4 vs. 182.8±218.5, p<0.0001). The tRARP group had higher D'Amico scores (p=0.22), total number of LN removed (7.3±5.49 vs. 5.8±4.18, p<0.0001), rate of positive LN (p=0.001). SL were identified in 19/666 (2.85%) vs. 11/662 (1.69%) but this was not statistically significant. Of these 30 SL, no differences were noted between the groups with regard to initial presentation, laterality, maximal axial area on CT, hospital admission rate, treatment of SL or drain removal time. Conclusions The clinical characteristics of SL are similar amongst patients treated with eRARP or tRARP and BPLND. A transperitoneal approach was not associated with lower rates of SL when compared to the extraperitoneal approach. Funding none
Authors
David Horovitz
Xiang Lu Changyong Feng Edward Messing Jean Joseph |
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MP64-09 |
The Impact of of lymph nodes count and adjuvant therapy on oncologic outcomes in men with lymph node metastasis at the time of radical prostatectomy |
Prostate Cancer: Localized: Surgical Therapy V | 17BOS |
Abstract: MP64-09 Sources of Funding: none Introduction While pelvic lymph node dissection (PLND) offers prognostic value at time of diagnosis for patients with intermediate and high risk prostate cancer, the survival benefit of PLND at radical prostatectomy (RP) is still unclear. In addition, data is limited regarding the value of adding adjuvant radiotherapy in the setting of positive lymph node metastasis._x000D_ Objective: To evaluate associations between oncologic outcomes and nodal count in patients with positive nodes at RP (pN1). Secondary objective is to determine any association between adding adjuvant therapy in patients with lymph node metastasis (pN1+) and improved oncologic outcomes._x000D_ Methods We analyzed 10,733 men who underwent RP between 1990-2015 at multiple institutions (43 CAPSURE study sites and UCSF Department of Urology), 6,789 of whom had PLND. Median follow up after RP was 56 months. Outcomes after RP were biochemical recurrence-free survival (RFS), bone metastasis-free survival (MFS) and cancer-specific survival (CSS). The associations between adjuvant treatment (none, radiation, ADT), number of nodes dissected, and surgical CAPRA risk score and oncologic outcomes were analyzed using Cox regression models. Analyses were repeated for the subgroup of 254 patients with pN1+. Results Among the 6,789 men who had PLND, men with positive nodes had worse pathological staging, cancer grade (Gleason score) and oncological outcomes at 5 years after RP compared to those with pN0 (BCR: 96% vs 80%, MFS: 99% vs 90%, CSS: 99% vs 97%, all log rank p<0.01). Of the 254 men (4%) who had positive lymph node at RP, the median number of LN removed was 12 (interquartile range (IQR) 7-18) and the median number of positive LN was 1 (IQR 1-2). The nodal count as a continuous variable or with cutoff of less or more than 14 did not show any significant association with oncologic outcomes in node positive men. BCR, MFS and CSS for pN1+ patients who received adjuvant therapy in the forms of ADT, XRT or combination did not differ significantly from patients without adjuvant therapy. Main limitation was the small sample size of pN1 patients and retrospective nature of the analysis._x000D_ Conclusions In a multi-institutional analysis, we found that patients with positive lymph nodes had worse outcomes. In patients with lymph node metastasis, neither nodal count nor adjuvant therapy was associated with better outcomes. _x000D_ Funding none
Authors
Hao Nguyen
Janet Cowan Matthew Cooperberg Peter Carroll |
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MP64-10 |
Is there an age limit for the indication of extended pelvic lymph node dissection during radical prostatectomy in patients with clinically localized prostate cancer? |
Prostate Cancer: Localized: Surgical Therapy V | 17BOS |
Abstract: MP64-10 Sources of Funding: none Introduction Available recommendations for extended lymph node dissection [eLND] at radical prostatectomy [RP] do not consider patient age, but rely on cancer characteristics only. However, for patients with limited life-expectancy, eLND might be an overtreatment. We hypothesized that limited life-expectancy of older RP candidates might dilute any beneficial effect of eLND in terms of cancer staging and outcomes. Therefore, we aimed at assessing the differential effect of age on the risk of lymph node invasion [LNI] and mortality due to cause other than prostate cancer [OCM] in order to define an age limit above which eLND might be avoided. Methods We included 3,906 patients diagnosed with prostate cancer and treated with RP and an anatomically defined eLND at a single Institution. Logistic and Cox regression analyses were used to compute the risk of LNI at eLND and the risk of OCM 10 years after RP. Predictors of LNI were chosen in compliance with guidelines-recommended models and were PSA, primary and secondary biopsy Gleason score and clinical stage. Predictors of OCM were age at surgery, Charlson comorbidity index [CCI] and year of surgery. Locally weighted scatterplot smoothing method was used to graphically examine the differential effect of age on the risk of LNI and OCM. Results Median age was 65 years. LNI rate was 12%. 10-year OCM rate was 5%. PSA (odd ratio [OR] 1.06; p<0.001), primary (OR 5.32; p<0.001) and secondary (OR 2.27; p<0.001) biopsy Gleason score ≥4 as well as clinical stage cT2 (OR 2.4; p<0.001) and cT3 (OR 3.24; p<0.001) were associated with higher LNI risk. Age (hazard ratio [HR] 1.11; p<0.001) and CCI (HR 1.28; p=0.03) were associated with higher OCM risk. Year of surgery (HR 0.92; p<0.001) was associated with lower OCM risk. For patients aged 75 or younger, the risk of LNI (8-11%) was higher than the risk of OCM (<1-10%; Figure 1). Conversely, for patients aged 76 or older the risk of LNI (11-17%) was equal or lower than the risk of OCM (11-26%). Conclusions For RP candidates older than 75 years, the risk of OCM equals or exceeds the risk of LNI. Such relatively high risk of OCM compared to the relatively low risk of LNI casts relevant doubts on any potential benefit related to eLND at RP. These findings argue against the routine use of eLND for older patients in clinical practice. Funding none
Authors
Alessandro Larcher
Nicola Fossati Giorgio Gandaglia Umberto Capitanio Paolo Dell’Oglio Emanuele Zaffuto Nazareno Suardi Marco Bandini Shahrokh Shariat Francesco Montorsi Alberto Briganti |
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MP64-11 |
Zonal distribution of prostate cancer is important prognostic factor in patients with clinically localized prostate cancer treated robot assisted radical prostatectomy(RARP). |
Prostate Cancer: Localized: Surgical Therapy V | 17BOS |
Abstract: MP64-11 Sources of Funding: None Introduction Because of the spread of saturation biopsy and MRI guided needle biopsy, we may often see a cancer in transition zone (TZ). To assess whether there is a difference in prognosis in TZ and peripheral zone (PZ) prostate cancer, we studied the patients with clinically localized prostate cancers who had RARP. Methods We studied retrospectively the clinical and pathological features of 404 consecutive patients with prostate cancer treated with RARP by one surgeon at Tokyo Medical University. We categorized the patients into predominantly PZ cancer, TZ cancer and both TZPZ cancer based on the area of cancer on whole-mount step sections of RARP specimens. Biochemical recurrence (BCR) was evaluated using the Kaplan-Meier method. With a Cox hazard regression analysis, we identified significant preoperative factors that predict BCR, and based on these results, we developed a nomogram to predict the non-BCR at 5 years after RARP. A concordance index was used to assess the value of a nomogram, and a calibration plot was used to compare the predicted values to actual values. Results PZ, TZ and both cancer was identified in 64%, 33% and 3% of the patients, respectively. Non-BCR rates at 2 and 5 year for patients with PZ were 88% and 78%, respectively, compared to 97% and 97% for patients with TZ cancer (p=0.0072). Also, none of 10 patients with both cancer had a BCR. While the frequency of positive surgical margins was similar between PZ and TZ groups (28% for both), the patients with PZ were more likely to have seminal vesicle invasion compared to patients with TZ (10% vs. 1%, p=0.001) and to have >=4+3/4+4 Gleason score (52% vs.40%, p=0.37). In fact, in the absence of seminal vesicle invasion and >=4+3/4+4 Gleason score, non-BCR rate at 3 year was 95% for patients with PZ and 99% for patients with TZ (p=0.40). A Cox hazard regression analysis showed that zonal distribution of cancer (p=0.004) was significantly associated with BCR after controlled with PSA, pathological stage, Gleason score and surgical margins. Based on this analysis, the postoperative momogram to predict non-BCR was constructed with an excellent concordance index of 0.89. The calibration plots also appeared to be good. Conclusions We concluded that the prognosis of a patient with prostate cancer is significantly more dependent upon the features of cancer in the PZ than in the TZ. Assessment of zonal distribution of cancer is important to gauge prognosis. Funding None
Authors
Makoto Ohori
Tatsuo Gondo Yosuke Hirasawa Takeshi Hashimoto Yoshihiro Nakagami Rie Inoue Takashi Nagao |
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MP64-12 |
Assessing Decipher for predicting lymph node positive disease among men diagnosed with intermediate risk disease treated with prostatectomy and ePLND |
Prostate Cancer: Localized: Surgical Therapy V | 17BOS |
Abstract: MP64-12 Sources of Funding: GenomeDx Biosciences Introduction Radical prostatectomy (RP) is a primary treatment option for men with intermediate risk (IR) prostate cancer (PCa). Though many will be effectively cured with local therapy alone, these men are by definition at higher risk of disease recurrence. In this study, we evaluated whether a genomic signature of metastasis risk (Decipher PCa classifier) could improve pre-operative staging for predicting lymph node invasion (LNI). Methods We examined 263 NCCN intermediate men treated with RP and extended template pelvic lymph node dissection (ePLND) from 2007-2015 at MD Anderson Cancer Center, Houston, Texas. Patients were categorized into three risk groups: 1) men with N1 disease (N1), 2) men without N0, but who had either ≥pT3 stage, RP Gleason score ≥8, lymphovascular invasion or tertiary Gleason 5 pattern (N0 high-risk [HR]) and 3) men with no high-risk features at RP (N0IR). Decipher scores were obtained from 263 RP specimens and 25 matching biopsy specimens. Fisher's exact test was used to compare the difference in patient risk groups. Logistic regression analysis was used to evaluate performance of Decipher for prediction of LNI. Discrimination of the Partin tables (≥2%) and combined model of Partin tables (≥2%) and Decipher (>0.6) was assessed using c-index. Concordance of biopsy and RP Decipher (low- and intermediate- vs high-risk) was also assessed. Results Of the 263 men, 42 (16.0%), 98 (37.2%) and 123 (46.8%) men were categorized as N1, N0HR and N0IR risk groups, respectively. Partin tables classified 34/42 (81%) N1, 70/98 (71%) N0HR and 66/123 (54%) N0IR men as high clinical risk (≥2%) for LNI (p=0.0012). Decipher classified 23/42 (55%) N1, 34/98 (35%) N0HR and 35/123 (29%) N0IR as high genomic risk (>0.6) for metastasis (p=0.013). After adjusting for Partin Tables, Decipher high genomic risk had an odds ratio of 2.3 (95% CI 1.2-4.5) as a predictor of LNI (p=0.02). Addition of Decipher to Partin Tables improved the c-index from 0.60 (95%CI 0.53-0.67) to 0.66 (95%CI 0.57-0.75). The concordance of Decipher risk groups between matched Biopsy and RP specimens was 84%. Conclusions Decipher may be an important adjunct tool to improve preoperative staging that may be useful for prioritizing intermediate risk patients to ePLND. Further investigation of Decipher biopsy specimens is required to validate these findings. Funding GenomeDx Biosciences
Authors
Mary Achim
Surena Matin Brian Chapin Patricia Troncoso Elsa Li Ning Tapia Mireya Guerrero Ina Prokhorova Anders Olson Zaid Haddad Jennifer Margrave Jijumon Chelliserry Lucia Lam Kasra Yousefi Christine Buerki Elai Davicioni John Davis |
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MP64-13 |
Decreasing Overtreatment of Localized Prostate Cancer with Radical Prostatectomy: 10-year Trends |
Prostate Cancer: Localized: Surgical Therapy V | 17BOS |
Abstract: MP64-13 Sources of Funding: none Introduction There has been increasing emphasis on active surveillance to limit overtreatment of prostate cancer (PC). However, the actual effect that such emphasis has on the selection of patients for radical prostatectomy (RP) has not been well studied. In this study, we investigated the trends in PC pathology at yearly intervals over the past decade to verify any changes in the RP population. Methods We retrospectively reviewed information from 1034 patients who underwent open RP between October 2004 and August 2015 by a single surgeon at a high-volume tertiary care center. Information was cataloged into one-year intervals. Chi-squared, Fisher's Exact test, ANOVA, and Kruskal-Wallis test were used for data analysis. Results There was significant in-group differences among the one-year intervals regarding pathological Gleason score (p<0.01), pathological staging (p<0.04), extracapsular extension (p <0.001), and positive margins (p=0.0001), with trends in increasing percentages of prostate glands with adverse pathological features over time. There was significant in-group differences in Gleason upgrading (p<0.01), with decreasing pathology upgrading over time. There was significant in-group differences in pre-RP D'Amico risk stratification over time (p<0.01). The percent of patients with pre-RP low-risk D'Amico pathology decreased from 42.9% in 2004 to 24.3% in 2009, increased to 50.9% between 2009 and 2011, then decreased again to 27.8% from 2011 to 2015. There were no significant in-group differences in age, race, or seminal vesicle invasion. Conclusions Over the last 10 years, we have increasingly targeted RP to patients with adverse pathology who have greater need for treatment while also reducing Gleason upgrading at RP. Our results indicate decreasing overtreatment and validate the effect that active surveillance emphasis has on changing the population undergoing RP. Funding none
Authors
Ilhan Gokhan
Tracy Han Ghalib Jibara Robert Qi Judd Moul |
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MP64-14 |
Simple prognostic model for high-risk prostate cancer after radical prostatectomy |
Prostate Cancer: Localized: Surgical Therapy V | 17BOS |
Abstract: MP64-14 Sources of Funding: None Introduction Since high-risk prostate cancer is an extremely heterogeneous disease, it is necessary to further stratify this group of patients. The aim of the present study was to substratify surgically treated patients with high-risk prostate cancer according to combination of accepted risk factors. _x000D_ Methods We identified 239 consecutive patients with NCCN high-risk prostate cancer treated with radical prostatectomy and pelvic lymph node dissection between March 2000 and December 2015 at Wakayama Medical University Hospital. Probabilities of specimen-confined disease (SCD; ?pT3aN0 and RM0) and biochemical recurrence (BCR) were examined with preoperative risk factors (PSA cT stage, biopsy Gleason score [GS]) using multivariable logistic regression and Cox proportional hazard models, respectively. Patients were then classified according to the combination of preoperative risk factors (PSA > 20ng/mL, cT3a, biopsy GS ?8) and probability of SCD and BCR-free survival were compared among groups. Results SCD was observed in 139 patients (58.2%). Five-year BCR-free survival rate was 61.7%. Multivariable analyses identified PSA as the only independent predictor of SCD and BCR after adjustment for age and type of surgery (Table). Based on the BCR-free survival rates for seven subgroups according to the combination of three preoperative risk factors, simple model with three subgroups were constructed, i.e., group 1: risk factor(s) other than PSA > 20ngmL; group 2: PSA > 20ng/mL only; group 3: PSA ? 20ng/mL and other risk factor(s). BCR-free survival rates were significantly different among three groups (p < 0.01, Figure). In addition, probabilities of SCD were also significantly different among groups (64.2% vs. 51.1% vs. 34.5%, p<0.01). Conclusions This study identified PSA as the most important preoperative risk factor in patients with high-risk prostate cancer and generated simple prognostic model according to PSA-based combination of three risk factors. Funding None
Authors
Yasuo Kohjimoto
Takahito Wakamiya Takashi Iguchi Shimpei Yamashita Satoshi Nishizawa Akinori Iba Kazuro Kikkawa Isao Hara |
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MP64-15 |
Robotic Assisted Laparoscopic Radical Prostatectomy in ISUP Grade 5 Prostate Cancer: Oncological Outcomes |
Prostate Cancer: Localized: Surgical Therapy V | 17BOS |
Abstract: MP64-15 Sources of Funding: none Introduction We present here oncological outcome for patients with International Society of Urological Pathology (ISUP) Grade 5 prostate cancer (PC) who underwent primary treatment with robotic assisted laparoscopic radical prostatectomy (RALP). Methods Using a prospectively collected institutional registry, we identified patients with clinically organ confined and locally advanced (cT1-T3N0M0) ISUP Grade 5 PC who underwent RALP with bilateral pelvic lymphadenectomy as primary treatment between 2005 and 2013. Results We included 106 patients with median age of 65 years (IQR 58.5-68). The majority of patients had clinically organ-confined disease (90%). Following surgery, 71 patients (67%) were upstaged to pT3 and 40 patients (38%) were downgraded to Gleason score 8 or 7. With median follow-up of 63.5 months (IQR 34-85), 50 patients (48%) had biochemical failure: 24 patients (23%) had PSA persistence and 26 patients (24%) had biochemical recurrence (BCR). Adjuvant and salvage RT were administered to 12 (11%) and 34 (32%) patients, respectively; adjuvant and salvage ADT were given to two (2%) and 31 (29%) patients, respectively; 9 patients (8%) received subsequent therapies. Eleven patients (10%) had systemic failure and 10 patients (9.5%) died: 3 (3%) from prostate cancer and 7 (7%) from other causes. Using Kaplan-Meier estimate, the 5-year overall, disease specific, metastasis-free and disease-free survivals are 91%, 96%, 88%, and 59% respectively. Using univariate analysis, pre-operative PSA, number of cores involved with ISUP grade 5 PC on biopsy, percentage of positive cores on biopsy, and pathological T stage were all correlated with both biochemical and systemic failure. Conclusions The disease volume on pre-operative biopsy and specifically the amount of Gleason 5 pattern predicted both biochemical and systemic failure. RALP in ISUP grade 5 PC is a viable treatment option in the multimodality management of PC, it affords local control and might improve long-term oncologic outcomes. Funding none
Authors
Itay Sagy
Charles Nottingham Shay Golan Matt Galocy Arieh Shalhav |
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MP64-16 |
Adverse Features and Competing Risk Mortality in Patients With High-Risk Prostate Cancer |
Prostate Cancer: Localized: Surgical Therapy V | 17BOS |
Abstract: MP64-16 Sources of Funding: none Introduction To assess survival and competing causes of mortality in prostate cancer (PCa) patients referred to radical prostatectomy (RP) through a combination of pathologic adverse features (AFs). Methods A single Tertiary Referral academic institution cohort of 2886 consecutive patients who underwent open or laparoscopic RP and pelvic lymph node dissection (PLND) for PCa between November 1995 and April 2015 was evaluated. Patients referred to neoadjuvant therapy and those lacking clinical, pathologic, and follow-up data were excluded. The final population consisted of 615 patients with at least one AF: preoperative PSA ?20 ng/mL, pathologic Gleason score ?8 and no organ-confined disease at final pathology (seminal vesicle involvement, and/or positive surgical margins, and/or lymph node invasion). Kaplan-Meier analyses were used to assess cancer-specific mortality (CSM)-free survival rates by stratifying patients into 3 risk categories according to the number of AFs (namely, 1, 2, and 3 AFs). Multivariable competing risk Cox regression analyses were used to assess CSM. The study was performed in line with the Helsinki Declaration. Results Overall, 420 (68.2%) men had 1 AF, 156 (25.3%) had 2 AFs and 39 had 3 AFs (6.3%): among these different risk categories, significant differences in terms of preoperative and pathologic tumor characteristics, adjuvant therapies and biochemical recurrence were found (all p?0.01); overall, 44 (7.1%) of 615 patients died of PCa. Men with 1 AF had higher CSM-free survival estimates compared to those with 2 and 3 AFs (92.8% vs. 84.2% vs. 27.7% at 10 years’ follow-up, p<0.001 – Figure). At multivariate competing risk Cox regression analyses, the presence of 3 AFs (hazard ratio [HR]: 2.59), postoperative treatment status, namely adjuvant androgen deprivation therapy (aADT) alone/aADT plus adjuvant radiotherapy (aRT; HR: 2.44) and time to BCR (HR: 0.96), were all independent predictors of CSM (all p<0.04). In the subgroup of individuals referred to aADT alone, men with 2 AFs (HR: 3.11) and 3 AFs (HR: 5.14) had a higher risk of cancer-related death compared to those with 1 AF (all P?0.04). Conclusions The risk group stratification according to the number of AFs could help physicians to accurately predict oncologic outcomes selecting PCa patients for the most appropriate postoperative strategies. _x000D_ Funding none
Authors
Valerio Vagnoni
Lorenzo Bianchi Marco Borghesi Cristian Vincenzo Pultrone Hussam Dababneh Marco Giampaoli Martina Sofia Rossi Francesco Chessa Daniele Romagnoli Andrea Angiolini Giuseppe Martorana Riccardo Schiavina Eugenio Brunocilla |
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MP64-17 |
Reduction of positive surgical margins due to a simplified NeuroSafe technique |
Prostate Cancer: Localized: Surgical Therapy V | 17BOS |
Abstract: MP64-17 Sources of Funding: none Introduction Positive surgical margins (PSM) are a known risk factor for biochemical recurrence (BC) after radical prostatectomy (RP). The relevance for the survival remains unclear. Frozen section is a possible approach to reduce the risk for PSM. The aim of the present study is to compare the oncologic outcome of patients treated by open radical prostatectomy and robot assisted laparoscopic prostatectomy (RALP) using standard frozen section and a new procedure of frozen section named Tue-Safe. Methods We included 111 and 180 patients with intermediate and high risk prostate cancer undergoing radical prostatectomy with standard frozen section and a new approach between 2014 and 2016. Clinical, pathological and perioperative parameters were obtained retrospectively. The Tue-safe approach included assessment of the whole circumference separated in the apical and basal section and both sided layer corresponding to the neurovascular bundle. In the standard frozen section group number and region of specimen was decided individually on behalf of the surgeon. Pathologic outcome was compared in the whole cohort and in the subgroups of intermediate and high risk. Results The two groups did not differ in terms of Age, PSA value, D Amico-Risk-Score, Gleason-score. In the whole cohort there was no significant difference, but a clear trend in reduced postoperative surgical margin between the Tue-Safe-technique and standard frozen section (20.72% and 29.83%; p=0.0561). In the high risk group we could show a trend towards reduction in PSM with Tue-Safe compared to standard frozen section (26.09% and 39.39%; p=0.1032) In the intermediate risk group we found a significant reduction in PSM at the base of the prostate in the Tue-Safe group compared to standard frozen section (1.54% and 8.70%; p=0.0335). Conclusions Due to the Tue-Safe technique the rate of PSM showed a trend towards a reduction, thereby lowering the rate of potential subsequent therapies like adjuvant radiotherapy. This trend was also present in the high risk cohort. This shows that RPx is a valid option in the treatment of high-risk patients and is thereby able to avoid the concomitant use of ADT which is required if radiotherapy is chosen as a therapy in this high-risk population. In addition, within a concept of multimodal therapy of high-risk patients, a negative residual margin may decrease the rate of bi or trimodal treatments in this patient cohort. Further investigation in a bigger cohort is needed to prove the benefit of the Tue-Safe technique. Funding none
Authors
Niklas Harland
Bence Sipos Jörg Hennenlotter Bastian Amend Marcus Scharpf Arnulf Stenzl Jens Bedke |
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MP64-18 |
Long-term impact of positive surgical margins after radical prostatectomy: An analysis of a large prospective cohort |
Prostate Cancer: Localized: Surgical Therapy V | 17BOS |
Abstract: MP64-18 Sources of Funding: none Introduction Management of prostate cancer is complicated by positive surgical margins (PSM) after prostatectomy. We present risk factors for and impact of PSM in a large prospective cohort. Methods The Heidelberg prospective tumour data base was searched data on PSM including Gleason pattern of PSM, age, BMI, preop.-PSA, Gleason score(GS), Specimen T- and N-stage, PSA up to 10 yrs. after RP etc. RT regime and HT were considered. Recurrence free(RFS) and cancer specific survival(CSS) were evaluated. Analysis was made with the IBM-SPSS software and Chi2-, Students´- t-test and Fischer´s test, Kaplan meier and multivariate analyses. Results 2383 men were investigated. Approx. 45% had locally advanced disease and 44% had PSM. Significantly higher PSM rates were noted in men with suspicious digital-rectal examination (DRE), pT>2, GS>7 and preop.-PSA>10ng/ml. PSM-rate was also significantly influenced by the surgeon and BMI>25. PT>2, suspicious DRE and preop. PSA>10ng/ml were associated with Gleason-pattern >3 at PSM. Gleason-pattern at PSM did not influence postop. PSA. PSM significantly influenced biochemical recurrence (BCR). Men with PSM had significantly higher PSA at 3, 6, 12, 24, 36, 48 and 60 months. The chance of BCR at 3, 6, 12 and 24 months significantly correlated to preop. PSA. _x000D_ Multivariate analyses revealed significantly higher PSMs only in pT>2 (p<0.001), GS>7(p=0.001), preop. PSA>10ng/ml(p<0.001), BMI>25(p=0.02) and suspicious DRE(p=0.05). Preop. PSA significantly correlated to pT>2 (p<0.001), GS>7(p=0.001), pN+(p=0.001), PSM(p<0.001), and BCR(p=0.05) in the multivariate analysis. _x000D_ 24% received RT; significantly more men with PSM(p<0.001) or GS>7(p<0.001) received RT. pT-stage, GS, PSM and pattern at PSM (à p<0.001) influenced RT-regime significantly. BCR at 12(p<0.001) months was significantly lower after ART; there was no significant correlation between RT-regime and BCR afterwards. RDE(p=0.02), ECOG-Score(p=0.02), pT-stage(p<0.001), GS(p<0.001), PSM (p=0.01) significantly affected CSS. _x000D_ RFS was significantly influenced by pT-stage(p<0.001), PSM(p=0.001), GS (p=0.002), preop. PSA(p<0.001) and suspicious DRE(p=0.001) in the multivariate investigation_x000D_ Conclusions Aggressive tumour specific characteristics like preop. PSA>10, pT>2 and GS>7 and BMI significantly increased risk for PSM. PSM also considerably influenced BCR. These results underline the importance of early cancer detection enabling prompt therapy. Techniques to reduce PSM-rate especially in advanced prostate cancer should be concurrently explored. Funding none
Authors
Joanne Nyarangi-Dix
Gencay Hatiboglu Dogu Teber Stefan Duensing Markus Hohenfellner |
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MP64-19 |
Factors predicting persistently elevated prostate-specific antigen after radical prostatectomy: Results from a high-volume single institution over 10 years |
Prostate Cancer: Localized: Surgical Therapy V | 17BOS |
Abstract: MP64-19 Sources of Funding: None Introduction Persistently elevated prostate-specific antigen (PSA) after radical prostatectomy (RP) is associated with recurrent disease and poor prognosis. Predictors that may be associated with persistent PSA need to be evaluated in order to better counsel patients and gauge postoperative outcomes. We sought to assess independent clinical and pathologic predictors of persistently elevated PSA after RP in a contemporary cohort. Methods We identified a cohort of patients with non-metastatic prostate cancer who underwent RP from 2006-2016 at the Cleveland Clinic Foundation. Independent predictors of persistently elevated PSA were identified using chi-square and multivariate logistic regression analyses, accounting for patient demographic and clinicopathologic factors. Persistently elevated PSA was defined as ≥0.1 six weeks after RP. Results Of a total 2,710 patients undergoing RP, 158 patients had persistently elevated PSA after surgery (5.8%). On multivariate analysis, clinicopathologic factors associated with persistently elevated PSA included initial PSA >20 ng/mL (OR 2.8; p<0.01), extra-prostatic extension (OR 3.3; p<0.01), seminal vesicle invasion (OR 1.6; p=0.048), positive surgical margin (OR 2.0; p<0.01), lymph node involvement (OR 2.5; p<0.01), and pathologic Gleason score ≥8 (OR 4.5; p<0.01). Conclusions With persistently elevated PSA after RP recognized as a marker of continued disease progression, clinicopathologic factors that predicted persistently elevated PSA were characterized in a contemporary cohort. These results highlight factors that can assist with determination of necessity for adjuvant therapy and help with better patient counseling prior to and following prostatectomy. Funding None
Authors
Victor Chen
Onder Kara Pascal Mouracade Jaya Chavali Robert Stein |
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MP64-20 |
PATHOLOGICAL UPGRADING AND UPSTAGING AT RADICAL PROSTATECTOMY IN JAMAICAN MEN WITH LOW RISK PROSTATE CANCER |
Prostate Cancer: Localized: Surgical Therapy V | 17BOS |
Abstract: MP64-20 Sources of Funding: None Introduction Several studies suggest race-based health disparities in men with low-risk prostate cancer (PCa), with African-American males having poorer oncological outcomes. We sought to determine the predictors of pathological upgrading and upstaging in a cohort of black Jamaican males with low-risk PCa who underwent radical prostatectomy (RP) between 2000 and 2015._x000D_ Methods We studied 141 men who met National Comprehensive Cancer Network criteria for low-risk PCa and underwent RP at the University Hospital of the West Indies, Kingston, Jamaica. All men had a minimum of a 12 core trans-rectal ultrasound-guided biopsy. Pre-operative clinical and final pathological data were obtained. Data were summarized as means and standard deviations or percentages as appropriate. Bivariate analyses such as independent samples t tests and chi square tables were conducted and logistic regression models were estimated to predict upgrading (> Gleason 6) and upstaging (≥ pT3)._x000D_ _x000D_ Results Mean age was 59.5 ± 7.8 years with mean PSA of 6.6 ± 2 ng/ml. A total of 48.3% of men were upgraded and 30.8% were upstaged. Bivariate analyses indicated that PSA levels (p=0.008) and percentage of cancer found on biopsy (p=0.002) were associated with upgrading. Clinical T stage (p=0.020), number of positive cores found (p=0.024) and the percentage of cancer found on biopsy (p=0.004) were significantly associated with upstaging. The odds of upgrading increased with increased PSA levels (OR = 1.40; p= 0.021) or increased percentages of cancer found (OR = 8.27; p = 0.002). The odds of upstaging increased with increased percentages of cancer found (OR = 3.62; p = 0.039). Conclusions Jamaican males with low-risk PCa have high rates of poor pathological outcomes. Percentage cancer found on biopsy is significantly associated with upgrading and upstaging. These findings should be taken into consideration when discussing treatment options for these patients._x000D_ Funding None
Authors
Belinda Morrison
Gareth Reid Richard Mayhew William Aiken Barrie Hanchard |
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MP65-01 |
Extracellular vesicles as a possible mechanism for Bacillus Calmette-Guérin immunotherapy |
Bladder Cancer: Basic Research & Pathophysiology III | 17BOS |
Abstract: MP65-01 Sources of Funding: None Introduction Intravesical Bacillus Calmette-Guérin (BCG) immunotherapy has been used to treat non-muscle invasive bladder cancer (BC) for nearly 40 years but its underlying mechanism remains largely unknown. It is generally believed that BCG adheres to integrin ?5?1 in the urothelial lining by interacting with fibronectin, then triggers an immune response cascade. Extracellular vesicles (EVs), small membrane-bound vesicles, act as immune modulators by transferring molecular cargos to recipient cells. We hypothesize that EVs derived from BC cells play key roles in mediating BCG-induced anti-tumor host immune responses, and the patient derived EVs may serve as predictive biomarkers that can differentiate BCG responders from non-responders. Methods BC cell lines, human T24 and murine MB49, and immortalized bladder SV-HUC cells were treated with 1-4x106 CFU/ml live BCG. After 12-72 hours, secreted EVs were isolated by serial ultracentrifugation and analyzed by Nanoparticle Tracking Analysis. Cell lysate and total RNA was collected for immuno-molecular profiling by quantitative PCR and Western blotting analyses. The alterations in EV secretion, gene and protein expression, and molecules from BC derived EVs in response to BCG were compared. Urinary EVs were collected and purified before and after BCG patients’ 1st and 3rd BCG instillations and EV secretion profiles were compared. Results In response to BCG, SV-HUC cells showed decreased EV secretion and their immuno- molecules were significantly reduced compared with EVs from naïve SV-HUC cells. In contrast, in BC cells the EV secretion rate was significantly induced by BCG as well as the expression of the key molecules in modulating immune response, such as MHC and co-stimulatory molecules at gene and protein levels. Critically, we found that BC cells, but not SV-HUC cells, released immuno-molecules containing EVs in response to BCG. Importantly, we found that urinary EV numbers were increased significantly after the 3rd BCG instillation in BCG responders, but not in BCG-non-responders in a pilot study. Conclusions We conclude that BCG treatment resulted in increased EV release from BC cells as well as in increased EVs in urine of BC patients. In addition, BCG induced expression of key immuno-modulatory molecules in BC cells and within the EVs. This up-regulated expression of immuno-molecules in response to BCG supports the hypothesis that EVs have a role in activating the immune system during BCG immunotherapy. The immunologically active EVs detected in patients’ urine can be further explored as predictive biomarkers. Funding None
Authors
Carlos Ortiz-Bonilla
Christopher Silvers Peng-Nien Yin Edward Messing Yi-Fen Lee |
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MP65-02 |
Cancer extracellular vesicles promote bladder tumorigenesis by inducing chronic endoplasmic reticulum stress and inflammation: a novel mechanism for field cancerization |
Bladder Cancer: Basic Research & Pathophysiology III | 17BOS |
Abstract: MP65-02 Sources of Funding: NCI RO1CA173986 Introduction Cancer field effect describes the predisposition of a field of tissue with histological anomalies or molecular alterations to a high incidence of tumor initiation and has been proposed to explain bladder cancer’s (BC’s) multifocal and recurrence nature, yet its mechanisms remain unknown. Extracellular vesicles (EVs) are small, membrane-bound vesicles with functions in cell-cell communication. We hypothesize that EVs derived from BC cells transfer bioactive cargo to reprogram recipient cells in the field and induce malignant transformation. Methods EVs from TCC-SUP, a BC line, were collected and purified. SV-HUC cells, a non-malignant immortalized urothelial line, were used as recipients. Tumorigenicity was determined by an in vitro anchorage-independent colony formation assay and an in vivo xenograft mouse model. Hallmarks of cancer such as loss of contact inhibition, genome instability, and invasion were studied. Molecular alterations in EV-transformed cells were assayed by qPCR and Western blot. Pro-inflammatory cytokines were compared by multiplex ELISA assays. Results Bladder cancer EVs induced malignant transformation of SV-HUC cells in vitro and in vivo. Molecular profiling revealed abnormal levels of endoplasmic reticulum (ER) stress sensors/effectors and pro-inflammatory cytokines in transformed cells. Moreover, the expression of ER chaperone protein Grp78 and two ER resident sensors, PERK and IRE1, was induced. Pro-apoptotic ER stress effector CHOP was absent, suggesting cancer EVs promote tumorigenesis by activating tumor-promoting signals while inhibiting pro-apoptotic signals. Conclusions Our data support a novel mechanism whereby cancer EVs and their cargo molecules play key roles in the malignant field of BC. Our study reveals that cancer EVs promote malignant transformation of predisposed cells by inhibiting pro-apoptotic signals and activating tumor-promoting ER stress induced unfolded protein response and inflammation. This study provides insight into mechanism of BC’s field effect and suggests EV as potential markers of disease recurrence and progression Funding NCI RO1CA173986
Authors
Chia-Hao Wu
Christopher Silvers Edward Messing Yi-Fen Lee |
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MP65-03 |
Inhibition of PEG10 may be a novel treatment strategy for a subset of bladder cancer. |
Bladder Cancer: Basic Research & Pathophysiology III | 17BOS |
Abstract: MP65-03 Sources of Funding: none Introduction Paternally expressed gene-10 (PEG10) is required for placental development. There is currently intense interest in the reactivation of placental and developmental genes in cancer, given the inherently ‘‘oncogenic’’ tissue invasion and immune evasion properties of the placenta. Although transposon ability was lost 120 million years ago, PEG10 retains the ability to self-cleave, in an apparently homologous manner, to HIV. We have recently identified that PEG10 promotes cell cycle progression in the context of TP53 and RB1 loss in neuroendocrine prostate cancer. Based on the evidence that TP53 mutations and RB1 inactivation are more prevalent in muscle invasive bladder cancer (MIBC), we hypothesized that PEG10 may be concerned to the poor prognosis of MIBC. To test this hypothesis, we characterized PEG10 function in bladder cancer and evaluated if PEG10 can be a novel therapeutic target for bladder cancer. We also investigated whether Ritonavir, which is an antiretroviral medication used to treat HIV/AIDS, suppresses the expression of PEG10 and induced growth suppression in T24 cells. Methods PEG10 gene expression of tumor samples was analyzed using the cancer genome atlas (TCGA) cohort. The PEG10 expression in several bladder cancer cell lines was assessed by Western blot analysis and quantitative reverse transcription-PCR (qRT-PCR). Silencing of PEG10 in vitro was achieved using siRNA. The in vivo effect of PEG10 antisense oligonucleotide (ASO) treatment was assessed in the T24 orthotopic bladder cancer model. Results Higher mRNA level of PEG10 was significantly associated with poorer disease-free survival after cystectomy in 131 patients in the TCGA, Nature 2014 cohort. We examined PEG10 expression in a panel of 12 bladder cancer cell lines by Western blot. UM-UC14 showed the highest PEG10 expression, and T24 showed higher PEG10 expression than the other bladder cancer cell lines. Similar results were confirmed by qRT-PCR. PEG10 transient knockdown using two independent siRNAs resulted in significant growth suppression in UM-UC14 (RB1inactivatedTP53mut) and T24 (RB1wtTP53mut) cells. PEG10 knockdown induced higher expression of key cell cycle dependent kinase inhibitors p21 and p27 than observed in the control cells. Conversely, forced PEG10 RF1b/2 isoform over-expression induced cell growth in UC14 and T24 cells. Furthermore, UM-UC14 cell invasion was significantly decreased with PEG10 transient knockdown. Using the BrdU incorporation assay after cell cycle synchronization by double-thymidine block, we found that PEG10 drives cell cycle progression from G0/G1. In the orthotopic bladder cancer model, systemic PEG10-ASO administration to athymic nude mice delayed tumor progression in T24 cells. Surprisingly, Ritonavir suppressed the expression of PEG10 and induced growth suppression in T24 cells. Conclusions We have demonstrated that PEG10 promotes bladder cancer progression. Inhibition of PEG10 may be a novel treatment strategy for a subset of bladder cancer. Funding none
Authors
Yoshihisa Kawai
Fan Zhang Shusuke Akamatsu Tetsutaro Hayashi Kenjiro Imada Eliana Beraldi Roland Seiler Jeffrey Leong Htoo Oo Igor Moskalev Ladan Fazli Akinori Sato Hideyasu Matsuyama Peter Black Colin Collins Martin Gleave |
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MP65-04 |
GSTT2 modulates patient response to BCG immunotherapy |
Bladder Cancer: Basic Research & Pathophysiology III | 17BOS |
Abstract: MP65-04 Sources of Funding: NCIS/NMRC Introduction In studies on human bladder cancer cell lines, BCG induced the expression of GST theta 2 (GSTT2) a member of the Glutathione-S-transferase family. The objective of this study was to investigate the cellular function of GSTT2 and its impact on the response to BCG therapy in NMIBC patients. Methods GSTT2B (pseudogene) deletion decreases GSTT2 expression. PCR was performed to identify GSTT2B presence or absence in human bladder cancer and macrophage cell lines, and in patients (n=139) and controls (n=150) (IRB approval, NHG DSRB: 2012/00475) GSTT2 silencing (siRNA) and overexpression (plasmid carrying GSTT2) were performed on selected cell lines. Reactive oxygen species (ROS); BCG induced cytotoxicity and intracellular BCG survival were analyzed. Patient demographic, initial disease characteristics (based on EORTC scoring system) and therapy outcomes were evaluated with respect to the GSTT2B genotypes. The impact of BCG instillation (numbers) on recurrence was analyzed in a subset of patients for whom complete 10y follow-up data was available. Analysis was performed using SPSS 23.0 and p<0.05 was taken to be significant. Results GSTT2 was silenced in MGH cells (GSTT2B homozygous full length (GSTT2Bfl/fl)) and overexpressed in UMUC3 and U937 cells (GSTT2B homozygous deleted (GSTT2Bdel/del)). A 2h exposure to BCG resulted in decreased ROS in GSTT2 silenced cells (p<0.05) and increased ROS in GSTT2 overexpressing cells (p<0.05). There was no difference in cellular cytotoxicity to BCG with respect to GSTT2 expression. However, intracellular BCG survival increased at 2 hours when GSTT2 was silenced (p<0.05) and decreased when GSTT2 was overexpressed (p<0.05). There was no significant difference between these groups at 24h. The majority of patients with complete 10y follow-up data, completed a 6+3 BCG schedule (n=63) and n=22 had less than 8 instillations. Patients with GSTT2Bdel/del genotype (n=6) who received 8 or less BCG instillations, were recurrence free (Likelihood ratio = 0.040, p=0.054). In the group that received at least 9 instillations of BCG, the GSTT2Bdel/del was associated with earlier recurrence. Conclusions GSTT2 expression decreases cellular ROS and BCG survival. GSTT2Bdel/del was associated with lower likelihood of recurrence for patients who received 8 or less BCG instillations. In contrast patients with GSTT2Bdel/del who received 9 or more instillations of BCG had earlier recurrences. Hence GSTT2Bdel/del could be used as a marker for patients who will do well with less BCG therapy. Funding NCIS/NMRC
Authors
Juwita Norasmara Rahmat
Kah Wei Tan Yiong Huak Chan Lata Raman Ma Zin Mar Wai Edmund Chiong Kesavan Esuvaranathan Ratha Mahendran |
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MP65-05 |
IFNα modulates the response to BCG immunotherapy in bladder cancer patients with specific CTLA4 Single nucleotide polymorphisms |
Bladder Cancer: Basic Research & Pathophysiology III | 17BOS |
Abstract: MP65-05 Sources of Funding: NCIS/NMRC Introduction Though BCG immunotherapy reduces the incidence of recurrence and progression there are still patients who fail therapy. This could be due to an inability to generate activated antigen specific T cells. CLTA4 modulates the activation of T cells. The objective of this study was to determine if CTLA4 (Rs733618, Rs4553808, Rs5742909, Rs231775, Rs3087243, Rs565213 and Rs960792) Single Nucleotide Polymorphisms (SNPs) modulate the incidence and outcomes to BCG immunotherapy. Methods DNA was obtained from bladder cancer patients attending the National University Hospital (n=139) and healthy controls (n=150) (IRB approval, NHG DSRB: 2012/00475). SNPs were evaluated using PCR followed by high resolution melt analysis. Patients received either standard or low dose BCG or low dose BCG+IFNα. The median length of follow up was 97 months (range 2.4 - 205.2 months). Time to events are presented as mean±standard error (95% confidence intervals) in months. Multivariate Cox & Logistic regressions were performed to assess the impact of the genotypes, treatment, tumor stage, grade, age, smoking history and gender on time to clinical outcomes (recurrence, progression and death) and their incidences, respectively. Analysis was performed using SPSS 23.0 and p<0.05 was taken to be significant. Results There was no statistical difference between the 3 treatment groups, therefore standard BCG and low BCG (B) were combined and compared to low dose BCG+IFNα (BI). BI therapy significantly improved outcomes for patients with Rs733618CC (B vs BI, 13 patients, p=0.019), Rs7565213GG (B vs BI, 52 patients, p=0.015) and Rs960792TT (B vs BI, 52 patients, p=0.04) in terms of time to recurrence and with Rs231775GG (B vs BI, 41 patients, p=0.039) and Rs7565213GG (B vs BI, 53 patients, p=0.032) in terms of time to progression. Patients with Rs960792CC had earlier recurrences with BI therapy (B:10 vs BI:11 patients, p=0.08). In subjects with the combination of genotypes: Rs3087243GG, Rs7565213GG and Rs960792TT (B:22 vs BI:18 patients), treatment with BI resulted in increased recurrence free survival time (97.51±20.44 (57.45 - 137.57) months vs 154.64±16.94 (121.45 - 187.83) months, p=0.025) and increased time to cancer specific death (75.13±14.31 (47.07 - 103.18) months vs 150.00±19.09 (112.58 - 187.42) months, p=0.047). Conclusions IFNα modulates response to BCG positively in subjects with CTLA4 genotypes Rs3087243GG, Rs7565213GG and Rs960792TT. Funding NCIS/NMRC
Authors
Ratha Mahendran
Juwita Norasmara Rahmat Sin Mun Tham Yew Koon Lim Jen Hwei Sng Lata Raman Ma Zin Mar Wai Yiong Huak Chan Woon Chau Tsang Edmund Chiong Kesavan Esuvaranathan |
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MP65-06 |
Intravesical BCG induces CD4+ T Cell Expansion but not Activation in a Clinically Relevant Immune Competent Model of Bladder Cancer |
Bladder Cancer: Basic Research & Pathophysiology III | 17BOS |
Abstract: MP65-06 Sources of Funding: Greenberg Bladder Cancer Institute Introduction Intravesical BCG Immunotherapy is the standard of care in treating non-muscle invasive bladder cancer, yet its mechanism of action remains elusive. While prior research has indirectly demonstrated the importance of T cells and shown a rise in CD4+ T cells in bladder tissue after BCG, the role of T cells in BCG anti-tumor activity has not been characterized. We investigated T cell recruitment and differentiation after BCG in an immune competent, clinically relevant rodent model of bladder cancer. Methods Fischer 344 rats aged 7 weeks received 1.5mg/kg N-Nitroso-N-methylurea (MNU) every other week for 6 weeks (4 doses). Dysplasia begins by week 8 and by week 16 the majority of rats have a NMIBC phenotype. Beginning week 8 following the first MNU dose, rats were intravesically administered 0.3ml of BCG (Tice®), cisplatin (1mg/ml), Mitomycin C (2mg/ml), MMC+ BCG, or saline (n=10 for all groups) weekly for 6 total doses. Animals were sacrificed at week 16, and bladders were processed for histopathology and digested into single cell suspensions for flow cytometry. Whole transcriptome expression profiling was then performed on sorted CD4 and CD8 cells of post-BCG tumors vs untreated tumors to assess T cell differentiation after BCG. Results Our data demonstrate that cancer progression in the MNU rat model of bladder cancer is characterized by a decline in the CD8/FoxP3 ratio, consistent with decreased adaptive immunity. By contrast, treatment with intravesical BCG leads to a large, transient rise in the CD4+ T cell population in the urothelium, and is both more effective and immunogenic compared to intravesical chemotherapy. Interestingly, whole transcriptome expression profiling of post-treatment intravesical CD4+ and CD8+ T cells revealed minimal differences in gene expression after BCG treatment. Conclusions Together, our results suggest that while BCG induces T cell recruitment to the bladder, the T cell phenotype does not markedly change, implying that combining T cell activating agents with BCG might improve clinical activity. Funding Greenberg Bladder Cancer Institute
Authors
Max Kates
Thomas Nirschl Niklai Sopko Hotaka Matsui Alexander Baras George Netto Noah Hahn David McConkey Charles Drake Trinity Bivalacqua |
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MP65-07 |
Treatment with the Histone Deacetylase Inhibitor, CI-994, in Combination with PD-1 Blockade Leads to Regression of Intravesical Murine Tumors |
Bladder Cancer: Basic Research & Pathophysiology III | 17BOS |
Abstract: MP65-07 Sources of Funding: None Introduction HDACs constitute a family of enzymes that deacetylate histones and cellular proteins resulting in regulation of transcription and cellular processes. HDAC inhibition has been shown to induce genes coding for MHC class I and class II molecules and immunologic activation molecules. Tissue microarray analysis of bladder cancer cell lines has demonstrated high HDAC expression in 40-60% of urothelial tumors. _x000D_ Our objective was to investigate the use of HDAC inhibitors on bladder tumors to stimulate immune mediated tumor cell destruction. Methods In vitro human bladder cancer cell lines were cultured with exposure to various HDAC inhibitors and HLA matched human T cells. The murine urothelial cell line, MB49 was also cultured with HDAC inhibitors and activated murine splenocytes. MTT assay was performed to measure cell viability. _x000D_ We transduced the murine tumor line to carry Firefly luciferase to allow for bioluminescence monitoring post implantation and then implanted the cells intra-vesically using a 24Fr angiocatheter delivery method. Following implantation bioluminescence signals were monitored using IVIS Lumina imaging system. _x000D_ Our treatment arm consisted of a single intra-vesical instillation of CI-994 for 60 minutes on post-implantation Day 6 with intraperitoneal injection of PD-1 blockade, appropriate controls were also performed. Total flux was monitored by IVIS in the treatment and control arms. _x000D_ Results In Vitro analysis showed a statistically significant decrease in viable tumor cells when treated with a short course of CI-994 and then exposed to activated human T cells (p 0.0025). There was an even greater response when the T cells had received PD-1 blockade (p 0.0003). MTT assay analysis of MB49 yielded similar positive results with CI-994 treatment and T cell exposure. _x000D_ In vivo mice who received intravesical CI-994 in combination with intraperitoneal PD-1 blockade showed a more immediate and durable response than mice in the control arms. The average bioluminescence signal for our combination treatment arm indicates minimal to no retained tumor burden._x000D_ Conclusions HDACs are widely expressed in urothelial cancer and inhibition of the selective HDAC inhibitor CI-994 has shown promising results in vitro and in an in vivo orthotopic model at reducing tumor burden. Funding None
Authors
Catherine Eden
Cynthia Perez-Fournier Gopal Gupta Jose Guevara-Patino |
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MP65-08 |
HEAT-TARGETED DRUG DELIVERY USING THE COMBAT BRS DEVICE FOR TREATING BLADDER CANCER |
Bladder Cancer: Basic Research & Pathophysiology III | 17BOS |
Abstract: MP65-08 Sources of Funding: Duke University Introduction Mild bladder hyperthermia (~43°C) can be used to improve intravesical drug delivery, to trigger payload release from systemically-administered thermally-sensitive liposomes, and to elicit immune responses. In this study we assess a novel conductive bladder heater, the Combat BRS device, in a live porcine bladder model to assess its ability to function as a heat-targeted drug delivery platform for use in bladder cancer. Methods Eleven 60 kg female swine were anesthestized and catheterized with a 3-way 16 French catheter. A multidimensional and multiparametric thermal monitoring system (fiberoptic microprobes, semiconductor germanium thermistors, custom designed/fabricated thermistor strips, and infrared cameras) was surgically implanted for high resolution 3D bladder temperature mapping. The Combat BRS device was used to heat the bladders to ~43°C for 2 hours. Pigs received intravesical mitomycin C (MMC, 2 mg/mL), systemic thermally-sensitive liposomes containing doxorubicin (Dox), or both. Pharmacokinetic testing was done by measuring MMC and Dox levels in blood and tissues (bladder, lymph nodes, liver, kidney, spleen, heart, and lung) by liquid chromatography tandem-mass spectrometry (Agilent 1200 - Applied Biosciences/SCIEX API 5500 QTrap). Data acquisition and quantification was performed by Analyst 1.6.2 software. Results Heat mapping showed consistent intravesical temperatures of 42.9°C (±0.14) and a transmural gradient of 1.5°C across the detrusor, resulting in full thickness bladder heating >41°C. Adjacent organ and core body temperature increased only minimally, well below safety thresholds. Mean bladder tissue MMC level was 0.9 μM. Mean tissue Dox level was 117.2 μM in the bladder and 6.7 μM in the heart, a 17-fold difference. Liver, kidney, spleen, lung, and LN tissue all contained significantly lower Dox levels than the bladder. Conclusions The Combat BRS device effectively heated the entire bladder wall to acceptable target temperatures and with excellent temperature safety parameters. Combat BRS was able to effectively trigger the release of Dox from systemically-administered thermally-sensitive liposomes, resulting in bladder Dox levels far exceeding levels required for anti-neoplastic effects, while concurrently minimizing unwanted drug delivery to other organ sites. Heat-targeted drug delivery has the potential to make systemic chemotherapy much more effective while also dramatically improving safety. Funding Duke University
Authors
Steven C. Brousell
Thomas A. Longo Joseph J. Fantony Wiguins Etienne David Needham Mark W. Dewhirst Paolo F. Maccarini Ivan Spasojevic Brant A. Inman |
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MP65-09 |
Molecular Tumour Grading and Outcome Prognostication of Non Muscle Invasive Bladder Cancer Based on Whole Transcriptome Analysis |
Bladder Cancer: Basic Research & Pathophysiology III | 17BOS |
Abstract: MP65-09 Sources of Funding: Canadian Cancer Society - Impact Grant Introduction Non muscle invasive bladder cancer (NMIBC) has a highly variable clinical behaviour not adequately predicted by their histological grade and clinical parameters. Some are indolent; others quickly progress to muscle-invasive disease. The discrepancy between phenotype and genotype is compounded further by interobserver variability in pathological grading. Methods Whole transcriptomic (WT) analysis of 178 bladder tumours (158 NMIBC and 20 MIBC or metastatic) was performed from formalin fixed paraffin embedded (FFPE) tissues incorporating messenger RNA expression, splice variants, gene fusion and mutation detection. In NMIBC, we used a discovery (n=38) and 2 validation cohorts (n= 40 and 80). These data were integrated and tested for correlations with both pathological grading and clinical outcomes. Conventional pathological grading for both WHO 1973 (grade 1, 2 and 3) and 2004 (low grade-LG vs high grade-HG) classifications was reviewed by 3 different expert uro-pathologists and kappa statistic for interobserver variability was calculated. Results Unsupervised clustering of data from RNA sequencing revealed classification of three robust-non-overlapping molecular subtypes of NMIBC termed Grade Related Index (GRI) 1, GRI2 and GRI3. GRI1 comprised of almost exclusively LG tumours, while GRI3 clustered with HG MIBC tumours. After assessment by expert pathologists, kappa for interobserver variability in 1973 WHO histological grading was 0.40 whereas it reached 0.78 for the 2004 classification. Most discrepant cases clustered in molecular subtype GRI2. GRI subclassification independently predicted disease progression in NMIBC (p=0.004, gray test). FGFR3 mutations, FGFR3::TACC3 fusion events and Hedgehog were strongly enriched in GRI1. GRI3 disease was associated with a germ stem cell-like phenotype and upregulation in APOBEC3B. Conclusions WT sequencing data delineated three molecular classes of NMIBC, and improved prediction of disease progression from NMIBC to MI compared to conventional histologic grading. WT analysis could be integrated to a new WHO classification. Funding Canadian Cancer Society - Impact Grant
Authors
Alexandre R Zlotta
Jess Shen Aidan P Noon Haiyan Jiang Cynthia Kuk Ruoyu Ni Balram Sukhu Kin Chan Annette Erlich Morgan Roupret Thomas Seisen Eva Comparat Joan Sweet Girish S Kulkarni Neil E Fleshner Azar Azad Theodorus H van der Kwast Jeffrey Wrana |
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MP65-10 |
Recurrent non-muscle invasive urothelial carcinoma tumors have common ancestral clone |
Bladder Cancer: Basic Research & Pathophysiology III | 17BOS |
Abstract: MP65-10 Sources of Funding: none Introduction Studies of genetic and DNA methylation changes in urothelial carcinoma of the bladder (BC) have been largely in muscle invasive disease. Herein we studied the genetic and epigenetic changes in tumors of patients with recurrent, non-muscle invasive (NMI) BC to identify clonal composition. Methods 30 tumors from 13 patients with recurrent NMIBC were examined from an IRB approved database. The median follow-up was 26 months (range=6-180). Whole-exome sequencing (WES) was used to identify mutated genes; 450K DNA methylation array was used to detect genome-wide DNA methylation alterations. Metachronous tumors were analyzed for a common ancestral clone. Mutations seen in 2 or more tumors in a given patient were defined as public. Results 13 patients (100%) showed clonal evolution from an ancestral clone with a mean of 38% (0.3-68%) of the total mutations per patient in the public mutations branch (Figure 1). 30 genes were publically mutated in at least 2 patients and present in all tumors for a given patient including MLL2 (54%), MUC16 (38%), ATN1 (23%), HRNR (23%), SRCAP (23%), TP53 (23%), and WNK1 (23%). Public DNA hypermethylation (36% of alterations per patient) and hypomethylation (29% of alterations per patient) occurred more frequently than genetic mutations, and occurred independent of genetic mutations (see Figure 2). 64 genes showed promoter hypermethylation in ≥60% of tumors (18); pathway analysis revealed cadherin signaling pathway members PCDH8 (83%), PCDHAC1 (80%), PDCHB7 *80%), PCDHB15 (77%) and PCDHB4 (73%), implicating the potential silencing of multiple genes in this pathway. FASSF1 hypermethylation was seen in 66% of tumors. 43 genes with hypomethylated promoters occurring in ≥60% of tumors were identified without specific associated pathways. Conclusions Recurrent NMIBC tumors arise from an ancestral clone. Public epigenetic mutations are more common than public genetic mutations in this setting, suggesting that both genetic and epigenetic alterations are involved in tumor initiation and are potential targets for therapies. Funding none
Authors
Christopher Duymich
Sumeet Syan-Bhanvadia Yong June Kim Jessica Charlet Hung-Yoon Yoon Won Tae Kim Wun-Jae Kim Peter Jones Siamak Daneshmand Gangning Liang |
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MP65-11 |
Mucin 16 is a mutational hotspot for non-muscle invasive urothelial carcinoma of the bladder |
Bladder Cancer: Basic Research & Pathophysiology III | 17BOS |
Abstract: MP65-11 Sources of Funding: none Introduction Our previous work has demonstrated that 30 genes are publically mutated in a cohort of patients with recurrence of non-muscle invasive urothelial carcinoma tumors of the bladder (NMIBC). The most common of these were MLL2 (54%) and MUC16 (38%), which have demonstrated a role during tumoriogenesis. Herein we examine both to identify mutational hotspots for NMIUC of the bladder. Methods 30 tumors from 13 patients with recurrent NMI UC bladder were examined from an IRB approved database. The median follow-up was 26 months (range=6-180). Whole-exome sequencing (WES) was used to identify mutated genes. Public mutation was defined as that seen in 2 or more tumors in a given patient. Tumors were then compared to samples from the TCGA cohort, both in UC where the majority of samples are in muscle-invasive disease, as well as to other cancers. Results No mutation hotspot was found for MLL2 but one for MUC16 in the coding region for tandem SEA domains was seen (p<0.0001) (Figure 1). No MUC16 hotspot was found in lung, colorectal or kidney cancer samples from TCGA; neither was it found in the cohort&[prime]s UC samples. No MLL2 hotspot was found in any cancer from the TCGA samples. Analysis of other identified genes within the mucin family did not show mutational hotspots (see Figure 2). Conclusions MUC16 of the mucin family of genes represents a unique mutational hotspot in recurrent, NMIBC of the bladder that is not seen in muscle invasive disease. In addition, several studies have demonstrated that MUC16-as part of focal adhesion signaling could play a critical role in facilitating tumor growth and metastasis. Our finding indicates MUC16 may potentially drive NMIBC and its recurrence and represent a potential therapeutic target for recurrence of NMIBC. Funding none
Authors
Sumeet Syan-Bhanvadia
Christopher Duymich Yong June Kim Jessica Charlet Hung-Yoon Yoon Won Tae Kim Wun-Jae Kim Peter Jones Siamak Daneshmand Gangning Liang |
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MP65-12 |
Targeting estrogen/estrogen receptor signal pathways to enhance the efficacy of Bacillus Calmette-Guérin treatment in bladder cancer |
Bladder Cancer: Basic Research & Pathophysiology III | 17BOS |
Abstract: MP65-12 Sources of Funding: none Introduction Although Bacillus Calmette-Guerin (BCG) is the most effective agent for non-muscle-invasive bladder cancers, approximately 30% of patients treated with intravesical BCG fail to respond to this agent. Previous studies from our lab showed the potential linkage of estrogen/estrogen receptor signaling with the efficacy of BCG, yet the detailed mechanisms remain unclear. Our new data showed the combination of BCG and the anti-estrogen ICI 182,780 (ICI) or tamoxifen could lead to a better suppression of bladder cancer (BCa) than BCG alone. Methods We first applied PCR to detect BCG internalization in two ERα positive BCa cell lines to investigate the potential effect of anti-estrogen ICI. Then, we used Q-PCR and western blot and examined the E2/ER effects on the integrin-α5β1 expression and the BCG attachment/internalization to BCa cells. To examine whether ICI can help the recruitment of macrophages toward BCa cells, we applied the transwell migration assay and in vivo mouse BCG model. Q-PCR, Elisa assay and MTT assay were used to detect the cytokine profile changes and BCa cell viability. For our in vivo studies, we applied the BBN-induced mouse BCa model, HE staining, BrdU and F4/80 staining to show the changes of macrophage infiltration and to prove the better efficacy of combining BCG plus anti-estrogen. Results We found treatment with either 1 μM ICI or tamoxifen significantly increased the BCG attachment/internalization, and the neutralization of integrin-α5β1 could reduce the ability of the ICI enhanced BCG attachment/internalization to BCa cells (Figure 1). Mechanism dissection revealed ICI could promote BCG attachment/internalization to the BCa cells through targeting ERα and increased the integrin-α5β1 expression and IL-6 secretion. The increased cytokine production may enhance BCG-mediated suppression of BCa cell growth and TNF-α production via recruiting more monocytes/macrophages to BCa cells (Figure 2-3). Consistently, in vivo studies found ICI could potentiate the anti-BCa effects of BCG in the carcinogen-induced mouse BCa models (Figure 4). Conclusions Taken together, these in vitro and in vivo results suggest that combining BCG with the anti-estrogen may become a new therapeutic approach with better efficacy to suppress BCa progression and recurrence. Funding none
Authors
Zhiqun Shang
Yang Yang Matthew Truong Yanjun Li Iawen Hsu Jing Tian Simeng Wen Ruifa Han Edward M. Messing Chawnshang Chang Yuanjie Niu Shuyuan Yeh |
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MP65-13 |
Flavopiridol as a Novel Agent for Bladder Cancer |
Bladder Cancer: Basic Research & Pathophysiology III | 17BOS |
Abstract: MP65-13 Sources of Funding: NIH intramural support Introduction Bladder cancer (CaB) is the 4th most common cancer among men in the US. It is among the most expensive malignancies to treat from diagnosis to death. There is an urgent need for the development of new treatment therapies. We utilized a quantitative high throughput screening (qHTS) technique to identify new therapies in two primary bladder cancer cell lines (T24 and UMUC3) and their metastatic lines (T24T, SLT3 and FL3 of T24 and LUL-2 for UMUC3) and further characterized one novel inhibitor: flavopiridol. Methods We screened 7 bladder cancer cell lines (including RT4, T24, and UMUC3) against 1,912 oncology drugs using a 48-hour cell proliferation assay with an ATP?based readout (CellTiterGlo) to determine activity and potency of compounds in a dose response manner. One of the candidate drugs inhibitory in all cell lines tested was flavopiridol, a pan-CDK inhibitor. We further characterized the mechanism of action and in vivo effects of flavopiridol using various cell based assays and mouse xenograft studies. Results The initial screen identified 95 compounds active in 7 cell lines. The top 50 compounds were further analyzed for molecular size of >200 g/mol and TPSA<90. This identified mitomycin C and 8 novel compounds. One of these compounds was flavopiridol which had an IC50 of 100-300nM in additional cell lines. Flavopiridol induces G2/M arrest; however, very little apoptosis was seen suggesting cytostatic rather than cytotoxic mechanism of action. Flavopiridol demonstrated dose dependent inhibition of migration, invasion and colony formation in CaB cell lines tested. Xenograft studies in rapidly growing UMUC-3 cells showed slowing of tumor growth but not complete reduction indicating cytostatic mechanism of flavopiridol. However, in slow growing cells, 5637, 5/8 treated mice showed complete tumor reduction. Conclusions qHTS can identify novel compounds. Flavopiridol seems to be a very effective inhibitor both in vitro and in vivo. Physical properties of Flavopiridol are most suited for intravesical use which may lead to it being an effective inhibitor of CaB in the bladder at higher doses without any/few systemic toxicities. Studies are underway to elucidate the use of flavopiridol as a single intravesical agent. Finally, combination therapy with intravesical chemotherapeutics shown to be effective in bladder cancer (e.g. paclitaxel, gemcitabine) can also be considered if intravesical therapy of flavopiridol is feasible. Funding NIH intramural support
Authors
Reema Railkar
Thomas Sanford Mohammed Siddiqui Spencer Krane Piyush Agarwal |
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MP65-14 |
Long-term validation of a molecular progression–related gene classifier for prediction of muscle invasion in primary non–muscle-invasive bladder cancer |
Bladder Cancer: Basic Research & Pathophysiology III | 17BOS |
Abstract: MP65-14 Sources of Funding: none Introduction Previously, we reported a clinically applicable prognostic gene classifier for primary non-muscle-invasive bladder cancer (NMIBC). In the present study, we sought to perform long-term validation of this classifier in the prediction of muscle-invasive disease. Methods We used previously published gene expression profiles from 176 NMIBC patients with extended follow-up. Progression was defined as development of muscle invasion or metastasis, and the progression risk score was calculated using the previously developed eight-gene progression classifier. Results During median follow-up of 72.8 (interquartile range, 37.0-118.7) months, 26 (14.8%) patients progressed to muscle-invasive bladder cancer. The molecular progression risk score was significantly associated with clinicopathological variables, including tumor number, stage, grade, and multivariate risk assessment tools (P < 0.05 in each case). Multivariate Cox regression analysis revealed that molecular progression risk score was an independent predictor of development of invasive tumor, either as a continuous variable (hazard ratio, 1.489; 95% CI, 1.216-1.823; P < 0.001) or as a categorical variable (hazard ratio, 5.026; 95% CI, 1.619-15.608; P = 0.005). Conclusions Our results confirm the clinical utility of the progression-related gene classifier for prediction of development of muscle invasion in NMIBC. The molecular progression risk score could aid in selecting patients who could benefit from more aggressive therapeutic intervention. Funding none
Authors
Ho Won Kang
Sung Pil Seo Pildu Jeong Yun-Sok Ha In-Chang Cho Won Tae Kim Yong-June Kim Seok-Joong Yun Sang-Cheol Lee Wun-Jae Kim |
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MP65-15 |
Comparison of genomic alterations in bladder urothelial tumors with and without telomerase reverse transcriptase promoter mutation using a next-generation sequencing assay |
Bladder Cancer: Basic Research & Pathophysiology III | 17BOS |
Abstract: MP65-15 Sources of Funding: Ruth L. Kirschstein National Research Service Award T32CA082088, Marie-Josee and Henry R. Kravis Center for Molecular Oncology and the National Cancer Institute Cancer Center Core Grant No. P30-CA008748 Introduction Telomerase reverse transcriptase (TERT) is the most frequently altered gene in urothelial cancer (UC), detected across all grades and stages of disease. We sought to characterize TERT alterations within a prospective cohort of UC treated at our institute and compare the frequency of genomic alterations in TERT promoter mutant vs wild-type UC specimens. Methods Patients diagnosed with bladder urothelial tumors were enrolled onto an institutional review board approved prospective sequencing protocol. Tumor and matched germline DNA were analyzed for somatic point mutations, truncations, copy number alterations, and insertions/deletions using the MSK-IMPACT NGS assay that detects alterations in all exons and select introns of 410 oncogenes and tumor suppressor genes as well as the entire TERT promoter region. Results 329 UC were sequenced of which 236 (71.7%) harbored TERT mutations, the majority being promoter region hotspots (chr5: 1295228 G>A [81%] and chr5:1295250 G>A [16%]). Patients with TERT promoter mutations were significantly older than those without (69.01 ± 10.70 years vs. 65.44 ± 11.78 years, p=0.0317). UC with TERT promoter mutations had significantly higher mutation count [median 10 (range: 2-76) vs median 5 (range: 0-119)] as well as copy number alterations [median 0.11 (range: 0-0.68) vs median 0.047 (range: 0-0.65)]. In non-invasive UC, TERT promoter mutations were identified in 14 of 23 low grade (61%) and in 26 of 30 high grade (87%) tumors. Between UC with and without TERT promoter mutations, there was a very significant difference in mutation frequencies of ARID1A(34% vs 11%), PIK3CA(27% vs 13%), FGFR3(33% vs 16%), CREBBP(19% vs 4%), CDKN1A(17% vs 2%), ERBB2(26% vs 9%), ERCC2(15% vs 3%), TSC1(11% vs 0%), KMT2C(17% vs 9%) (all with p < 0.005). Conclusions TERT is the most frequently altered gene in bladder cancer with the majority of TERT alterations comprised of two hotspot mutations. UC with TERT promoter mutations tends to occur in older patients and is associated with overall higher mutation count and copy number alterations. A number of genes are differentially mutated in UC with and without TERT promoter mutations and may suggest a link between TERT promoter mutations and distinct mutations profiles in UC. Funding Ruth L. Kirschstein National Research Service Award T32CA082088, Marie-Josee and Henry R. Kravis Center for Molecular Oncology and the National Cancer Institute Cancer Center Core Grant No. P30-CA008748
Authors
Sumit Isharwal
François Audenet Eugene Pietzak Eugene Cha Gopakumar Iyer Ahmet Zehir Barry Taylor Michael Berger Satish Tickoo Victor Reuter Jonathan Rosenberg Dean Bajorin Guido Dalbagni Bernard Bochner David Solit Hikmat Al-Ahmadie |
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MP65-16 |
Inactivation of Foxa1 and Pten results in development of carcinoma in situ and the basal subtype of muscle invasive bladder cancer following carcinogen exposure |
Bladder Cancer: Basic Research & Pathophysiology III | 17BOS |
Abstract: MP65-16 Sources of Funding: NIH/NCI CA172122, BCAN Young Investigator Award Introduction Muscle invasive bladder cancer (MI BLCa) often consists of conventional urothelial cell carcinoma with mixed squamous cell differentiation (SqD). Presence of SqD is associated with a basal molecular subtype and poor prognosis. Previous work identified decreased expression of the transcription factor Forkhead box A1 (FOXA1) in the urothelium as a marker of SqD, and that genetic ablation of Foxa1 in the bladders of mice results in SqD. However, it is unclear how FOXA1 loss cooperates with other oncogenic changes to promote urothelial tumorigenesis and progression. Inactivation of the tumor suppressor phosphatase and tensin homolog on chromosome ten (PTEN) is associated with squamous cancers independent of anatomic site, and found in a subset of MI BLCa. Therefore, we undertook studies to identify the extent to which FOXA1 and PTEN inactivation cooperate to promote progression to MI BLCa. Methods We utilized the urothelial-specific uroplakin 2 promoter to drive Cre recombinase (UpII-Cre) expression, enabling us to knockout (KO) Foxa1 and/or Pten in a bladder-specific manner. Following Foxa1 and/or Pten KO, experimental mice and appropriate controls were exposed to the carcinogen N-butyl-(4-hydroxybutyl)nitrosamine (BBN) for 12, 16 and 24 weeks, followed by morphologic and immunohistochemical analyses. Results Similar to control mice, mice with urothelial-specific KO of one or two alleles of Foxa1 and/or Pten develop marked inflammation and proliferative hyperplasia following 12 weeks of BBN exposure, and do not develop MI BLCa until 24 weeks of exposure. However, homozygous KO of Foxa1 combined with Pten haploinsufficiency, or homozygous KO of Pten combined with Foxa1 haploinsufficency resulted in the development of carcinoma in situ and MI BLCa with squamous features following just 12 weeks of BBN exposure. In addition, MI BLCa arising in these genetically engineered mice express several markers of the basal molecular subtype, which is extremely aggressive in humans. Conclusions Our work indicates combined loss of Foxa1 and Pten dramatically increases sensitivity to environmental carcinogens, which is consistent with previous studies identifying an important role for these factors in BLCa. In addition, our work suggests combined FOXA1 and PTEN inactivation may be important in basal BLCa. Future studies will define the mechanism by which FOXA1 and PTEN inactivation promote tumor progression and the emergence of a basal molecular subtype of disease in the setting of carcinogen exposure. Funding NIH/NCI CA172122, BCAN Young Investigator Award
Authors
Vasty Osei-Amponsa
Zongyu Zheng Soumar Bouza Joshua Warrick Cathy Mendelsohn Klaus Kaestner Xue-Ru Wu David DeGraff |
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MP65-17 |
INTRAVESICAL THALIDOMIDE BOOSTS BACILLUS CALMETE- GUÉRIN (BCG) IN NON-MUSCLE INVASIVE BLADDER CANCER TREATMENT |
Bladder Cancer: Basic Research & Pathophysiology III | 17BOS |
Abstract: MP65-17 Sources of Funding: None Introduction BCG immunomodulatory effect has proven effective in high-grade non-muscle invasive bladder cancer (NMIBC), but refractory patients are at risk of muscle-invasive disease. We explored the efficacy of intravesical Thalidomide (immune-modulatory, anti-inflammatory, and anti-angiogenic) added to BCG using an immune competent autochthonous orthotopic NMIBC animal model. Methods Female Fischer 344 rats, 7 weeks of age, received once every 15 days, for 4 times, a dose of 1.5 mg/kg of n-methyl-n-nitrosourea (MNU) intravesically. The rats were randomized in 4 groups (n=10 per group) to receive intravesical treatment once a week for 6 weeks as follows: MNU cancer (0.2 ml vehicle), BCG (2 x 106 CFU of Moreau strain in 0.2 ml), Thalidomide (20mg/kg in 0.2 ml) and BCG-Thalidomide in 0.2 ml. At week 16, bladders were collected for histopathology, cell turnover index by immunohistochemistry and immunoblotting quantification of 4E-BP1 and p70S6K1 for downstream mTOR proliferation signaling and HIF and VEGF for angiogenesis pathway. Results Treatments were responsible for favorable histopathology, cell turn over and down-regulation of p70S6K1, HIF-1 and VEGF. Optimal histopathology and cell turnover index was seen in Thalidomide-BCG association. All treatments reduced the action of p70S6K1 but not 4E-BP1 supporting that these proteins regulation occur independently on mTOR pathway in NMIBC. Conclusions Intravesical BCG-Thalidomide might represent a significant increment in NMIBC treatment, suggesting p70S6K1, HIF-1 and VEGF as potential molecular target candidates in a clinically relevant immune competent NMIBC model. Funding None
Authors
Gabriela R. Passos
Juliana A. Camargo Karen L. Ferrari Mário J. A. Saad Amilcar Castro Leonardo O. Reis |
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MP65-18 |
Early detection of urinary bladder cancer by assessment of urine protein markers (ApoA1 and ApoA2 proteins) |
Bladder Cancer: Basic Research & Pathophysiology III | 17BOS |
Abstract: MP65-18 Sources of Funding: none Introduction Proteomic patterns in body fluids gain increasing importance as a new tool for the identification of novel, highly sensitive diagnostic markers for the detection of cancer. One promising approach in the search for useful bladder cancer biomarkers is to study the urine proteome during the occurrence of the disease. _x000D_ No previous reports on assessment of ApoA1 and ApoA2 protein in serum or tissue of bladder cancer patients._x000D_ The aim of our study to Identify and assess the expression of ApoA1 and ApoA2 protein in urine samples of bladder cancer patients and to validate results by correlations with analysis of urinary bladder tissue and blood samples._x000D_ Also to Correlate the results with histopathology findings, and the clinical picture_x000D_ Methods Thirty two patients admitted to the urology department were enrolled in the study; 22 were histologically diagnosed as bladder cancer patient whereas the remaining 10 patient were diagnosed as cystitis. Ten healthy control subjects were also included in the study. Morning voided urine sample and Ten ml blood sample were collected from each patient. Urine and blood samples were transported to the laboratory on ice., and were separated by centrifugation and stored at -80°C till the time of laboratory assays. One gm from suspected tissue lesions were collected during cystoscopy from suspected bladder cancer patients._x000D_ Western blot technique was used to measure ApoA1 and ApoA2 protein in the serum and urine of the three groups in addition to the tissue of bladder cancer._x000D_ Results ApoA1 & ApoA2 expression in voided urine was significantly higher in malignant group than cystitis (benign) group than normal healthy group (P < 0.05). ApoA1 & ApoA2 expression in the serum of cancer patients showing no significant difference from normal control group._x000D_ ApoA1 &ApoA2 in urine and tissue of the malignant groups were nearly expressed in the same ratio. _x000D_ There was no significant correlation between the two markers. _x000D_ Receiver operating characteristics curves were carried out to assess the diagnostic performance of ApoA1 and ApoA2 and their Sensitivity (true positive fraction) and Specificity (false positive fraction) showing 100% sensitivity and specificity for both ApoA1 &ApoA2 in urine._x000D_ No significant correlation was detected between both markers and histopathological types, presence of bilharziasis, stage, grade or gender._x000D_ Conclusions Our study demonstrated that ApoA1 and ApoA2 protein levels in urine could serve as a non-invasive highly sensitive diagnostic and screening biomarker for bladder cancer._x000D_ The present study showed that ApoA1 and ApoA2 were expressed in bladder cancer tissue in ratios similar to their urine ratios indicating that the only source of ApoA1 and ApoA2 protein levels in urine came from bladder cancer tissue._x000D_ To our best knowledge, this study is the first to report on these markers in serum and tissue of bladder cancer patients._x000D_ Further studies of these markers on large number of patients along with follow-up of the patients for tumor recurrence are recommended._x000D_ Funding none
Authors
Hosni Salem
Mona Abdel Hamid Doha El-Sayed Ellakwa Hanan Fouad |
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MP65-19 |
Expression of FGFR 3 protein and gene amplification (FISH) in different stages and grades of bladder cancer |
Bladder Cancer: Basic Research & Pathophysiology III | 17BOS |
Abstract: MP65-19 Sources of Funding: none Introduction Aim:Evaluation of the expression of FGFR3 protein and gene amplification (FISH) in the urothelial cells of neoplastic and non-neoplastic urothelial lesions of the urinary bladder, and correlation with,hitopathological typpes tumor grade, stage and associated bilharziasis. Methods One hundred and five different urinary bladder lesions were studied. Data concerning age, sex, tumor grade, stage, and associated bilharziasis were obtained. Each case was studied using monoclonal antibodies for FGFR3 and examined for detection of immunostaining in urothelial cells_x000D_ and FISH(Flourescent insitu hybridization technique ) technique was applied on 40 malignant cases that shows FGFR3 protein over expression ( more than50% expression og FGFR 3 protien) by immunohitochemistry._x000D_ Results Histologically, 15 of the cases were diagnosed as chronic cystitis, and the other 90 cases had malignant lesions. Totally, 29.7% of all examined lesions had bilharzial affection._x000D_ Urothelial lesions were more predominant in males (75.6%), Malignant cases comprised TCC (75cases), SCC (15 cases). Sixty percent of TCC cases presented in non muscle invasive stage, while all SCC cases were in muscle invasive stages,62% of TCC cases were of high grades (grade II and grade III) while all cases of SCC are of high grade. ._x000D_ Bilharzial associated malignant lesions were muscle invasive (T2 and T3) in 75.7 % of cases and of high grade (grade II and III) in 84.8 % of cases, while non muscle invasive tumors and low grade tumors presented in 24.3% and 15.2% of non bilharzial malignant tumors respectively._x000D_ Bilharzial association in TCC cases was in 24% of cases, While all cases of SCC were associated with bilharziasis._x000D_ All five control cases were negative for FGFR3 immunostaining. Sixty six percent of chronic cystitis cases were positive for FGFR3immunostaining, while in malignant cases 67.8% were FGFR3positive with significant increase in staining extent versus chronic cystitis cases. _x000D_ Non bilharzial chronic cystitis cases were 66.6% positive for FGFR3 immunostaining and 66.6% of bilharzial cystitis cases expressed FGFR3 . This incidence of FGFR3 expression raised significantly in malignant cases to involve 54.5% of them. _x000D_ Seventy two percent of TCC cases were positive for FGFR3 while 7 cases of SCC were positive for FGFR3 ._x000D_ Staining intensity of FGFR3 in bilharzial associated malignant lesions were mainly of mild and moderate intensity(36% and 15% ), while in non bilharzial malignant lesions it was mainly of mild intensity (66.6% )._x000D_ FISH technique was applied on forty cases in malignant group with overexpression of FGFR3 protein. There are 36 malignant cases out of 40 cases show amplified FGFR3 gene, There were 88.2% of TCC cases show FGFR3 gene amplification most were of low grade (70%) and show significant difference at p value < 0.01 compared to high grade, and in NMIBC group (80%) ( p value <0.01)._x000D_ Conclusions Estimation of FGFR3 expression can serve as a prognostic indicator in follow up of cancer bladder patients , especially in bilharzial associated malignant cases._x000D_ Expression of FGFR3 could be utilized for molecular targeted therapy in urinary bladder cancer._x000D_ To our knowledge,this is the first study to assess FGFR 3 protein gene amplification (FISH)in SCC of the bladder._x000D_ _x000D_ Funding none
Authors
Hosni Salem
Amira kamel Tarek Aboushousha Olfat Hammam Ali El-Hindawi |
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MP65-20 |
Epigenetic priming with 5-azacitidine increases sensitivity of bladder cancer cells to chemotherapeutic agents |
Bladder Cancer: Basic Research & Pathophysiology III | 17BOS |
Abstract: MP65-20 Sources of Funding: none Introduction Bladder cancer is characterized by high prevalence of mutations in chromatin regulatory genes. Therefore, the epigenome presents multiple candidate targets for drug development. In this study, we assessed the effects of 5-azacitidine (AZA), which is a DNA methyltransferase inhibitor, on DNA methylation in luminal and basal bladder cancer cells. We also tested the priming effect of AZA on sensitivity of cells to cisplatin and gemcitabine Methods Bladder cancer cell lines RT4 (luminal), 5637 (basal, _x000D_ &[Prime]epithelial&[Prime]), and J82 (basal, &[Prime]mesenchymal&[Prime]/claudin-low) were treated with AZA in various conditions to determine optimal demethylation dosing schedules. Methylation levels were evaluated by pyrosequencing 11 CpG islands in long interspersed nucleotide elements-1 (LINE-1) repetitive element. To test priming effect of AZA, cell lines were pretreated with AZA at a dose that had no cytotoxic effects (500 and 1000 nM) for 5 days. Demethylation was confirmed and cells were subsequently subjected to cisplatin and gemcitabine treatment. Cell viability was evaluated using the CellTiter-Glo® assay. IC50’s were calculated based on the results of the viability assays. _x000D_ Results CpG islands in LINE-1 in the cell lines were demethylated by AZA treatment in a dose- and time-dependent manner. Although AZA suppressed proliferation of cell lines during treatment, it did not affect subsequent proliferation of cells after withdrawal of AZA. Pretreatment with AZA significantly decreased the IC50&[prime]s of cisplatin in the RT4 and 5637 cells from 2.82 to 0.78 and 0.67 to 0.37 µg/ml, respectively (Figure 1). The IC50‘s of gemcitabine were also significantly decreased in the RT4 and 5637 cells with pretreatment from 1.01 to 0.59 and 3.53 to 2.32 ng/ml, respectively (Figure 1). The IC50&[prime]s for cisplatin and gemcitabine did not change with AZA pretreatment in the J82 cell line. Conclusions AZA efficiently demethylated DNA in both luminal and basal bladder cancer cell lines. Pretreatment of AZA sensitized &[Prime]epithelial&[Prime] bladder cancer cells (RT4 and 5637) to cisplatin and gemcitabine. Combination of AZA epigenetic priming with chemotherapeutic agents warrants further investigation to delineate the mechanism of cytotoxic effect with priming in both NMIBC and MIBC. Funding none
Authors
Takahiro Yoshida
Anup Sharma Max Kates Niklai Sopko Xiaopu Liu Noah Hahn David McConkey Nita Ahuja Trinity Bivalacqua |
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MP66-01 |
Emergency Department Revisits for Children following an Acute Urinary Stone Episode |
Pediatrics: Testis, Varicocele & Stones | 17BOS |
Abstract: MP66-01 Sources of Funding: None Introduction Revisiting the emergency department (ED) after discharge is an undesired clinical outcome that remains unstudied in children with kidney stones. We sought to determine the rate of stone-related ED revisits among children, to characterize the reasons for revisiting and to identify patient-, hospital- and clinical characteristics associated with ED revisit. _x000D_ Methods In a retrospective population-based cohort study of patients ≤18 years with urinary stone disease, ED revisits within 180 days of the index visit were identified in the South Carolina Medical Encounter database. This database includes all ED visits in the state from December 30, 1995 to September 30, 2015. We used discrete time failure models to describe the rate of ED revisit risk over the 180-day period following the index visit. Multivariable logistic regression models were used to estimate the association between patient, hospital and clinical characteristics and ED revisit. Results Among 5,642 index stone episodes, 11% led to a stone-related ED revisit within 180 days of discharge. Nearly 60% of these revisits occurred within 30 days of discharge. The odds of revisit within the first 2 days after discharge were 23 times higher than the odds of revisit after 2 weeks from discharge (OR 22.6, 95% CI 18.0 - 28.5, Figure 1). The most common documented symptom at revisit was pain, which occurred in 40% of patients. Nearly 40% of patients underwent surgery and/or hospital admission at the time of revisit. Each year increase in age (OR 1.06, 95% CI 1.03 - 1.10) and public insurance (OR 1.46, 95% CI 1.21 - 1.77) were associated with an increased risk of ED revisit. Patients with a history of stone disease were two times more likely to revisit than patients with no prior history (OR 2.1, 95% CI 1.74 - 2.56). Patients evaluated by a urologist were 40% less likely to revisit the hospital than those who were not (OR 0.6, 95% CI .42 - 0.86). Conclusions Children who present to the ED with kidney stones are at most likely to return to the ED within 48 hours of discharge. Older children, publicly insured patients and repeat stone-formers are at greatest risk of ED revisit. Urology consultation is associated with a decreased risk of revisit. Future studies should seek to identify processes of care that decrease ED revisits among high-risk patients. Funding None
Authors
Jane Kurtzman
Lihai Song Michelle Ross Charles Scales Jr. Gregory Tasian |
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MP66-02 |
Pre-Operative Tamsulosin and Ureteral Orifice Navigation in Pediatric Patients: Is there any benefit? |
Pediatrics: Testis, Varicocele & Stones | 17BOS |
Abstract: MP66-02 Sources of Funding: None Introduction Alpha-1 adrenergic receptors are densely located in the intramural ureter, which can be too narrow to navigate during ureteroscopy (URS). Balloon dilation of the ureteral orifice (UO) is not recommended in pediatric patients, as it may lead to vesicoureteral reflux, ureteral stricture, or rupture. Therefore, ureteral stents (US) are usually placed for passive dilation resulting in another procedure. We aim to evaluate whether pre-operative tamsulosin increases the rate of ureteral navigation for URS. Methods We retrospectively reviewed all pediatric patients who underwent URS at our institution from January 2013 to October 2016. Procedures were identified by searching the electronic medical records for cases billed as URS. All cases were performed by a single surgeon using a standard approach for UO navigation based on location of the stone, semi-rigid ureteroscope (Wolf 4.5 Fr) for distal and mid ureteral stones, and flexible ureteroscope (Storz 7.5 Fr) with or without a ureteral access sheath (Cook 9.5 Fr) for proximal ureteral and kidney stones. Patients were separated into 2 groups: those who took tamsulosin 0.4 mg daily for at least 48 hours pre-operatively and those who did not take tamsulosin pre-operatively. Exclusion criteria included any patient who had a US placed previously. The student T test, Z test, and chi square test were used for statistical analysis. Results A total of 55 patients underwent URS with 22 taking pre-operative tamsulosin, 19 without tamsulosin, and 14 patients were excluded. There was no significant difference between the groups with consideration to age and weight of the patients and size or location of the stones. We were able to navigate the ureter in 19 of 22 patients (86.4%) who took tamsulosin and 10 of 19 patients (52.6%) who did not take tamsulosin (p = 0.018). Further stratification was made between distal and proximal stone location. We were able to navigate the ureter in 9 of 10 patients (90.0%) in the tamsulosin group and 1 of 4 patients (25.0%) in the no tamsulosin group for mid and distal stones (p = 0.015). For proximal ureteral and renal stones, we were able to navigate the ureter in 10 of 12 patients (83.3%) in the tamsulosin group and 9 of 15 patients (60.0%) in the no tamsulosin group (p = 0.187). We did not observe any adverse effect from tamsulosin. Conclusions Pre-operative tamsulosin did significantly increase the success rate of ureteral navigation for URS, particularly during semi-rigid ureteroscopy for distal or mid ureteral stones, thus decreasing the number of surgeries in our pediatric patients. Funding None
Authors
Chad Morley
Ali Hajiran Morris Jessop Osama AL-Omar |
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MP66-03 |
Prescribing Narcotic Should be Selective After Many Pediatric Urologic Surgeries |
Pediatrics: Testis, Varicocele & Stones | 17BOS |
Abstract: MP66-03 Sources of Funding: none Introduction Morrison’s survey of SPU members reported no clear consensus in managing peri-operative pain in pediatric patients undergoing common urological procedures. We posit that non-narcotic analgesia allows withholding narcotic use following simple urologic surgery in out-patient surgery in most patients. _x000D_ Methods We prospectively tracked analgesic use and pain scales of patients undergoing outpatient penile (non-hypospadias) or groin surgery (hernia, orchidopexy). Parents marked an analgesic usage form and Wong-Baker FACES pain scale on the day of surgery (DOS) and post-operative day 1 (POD1). Patients received a caudal nerve block, unless contraindicated or refused by parents, or a penile block. Postoperative analgesics were either non-narcotic agents or narcotics prescribed at surgeon’s discretion. Descriptive statistics, contingency table analyses, and t-test were performed. _x000D_ Results 249 male patients, median age 36 mo (2-216mo) underwent penile (64%) or groin (36%) surgery. Caudal (92) or local block (147) was used in 96% of cases. Narcotics prescribed in 152 (61%) was associated with older age (74mo vs 47mo; p =0.0002). Overall, no difference in analgesic use was noted (p=NS) on DOS (72%) and POD (62%) and were not affected by surgery or block type._x000D_ Among patients prescribed narcotics, 76% used any analgesic on DOS and 66% on POD 1 (p=NS); narcotic use on DOS (91 cases - 65 took 1 dose) declined on POD1 (57; p=0.0001) and was unaffected by surgery type or block type. Analgesic type used was similar between surgery types and between DOS and POD1 regardless of block used. Among patients not prescribed narcotics, 72% took 1+ doses of analgesics on DOS which declined to 59% on POD 1 (p=NS); usage was similar based on surgery type and from DOS to POD1 for both surgery and block types. Pain scale differences were not significant on DOS between non-narcotics and narcotic users (3.2 v 3.6, p=NS) but were on POD 1 (2.8 v 3.6, p=0.0003). Pain significantly decreased for those using non-narcotics between DOS and POD1 (p=0.004) but not for those using narcotics, perhaps due to pain perception in older children._x000D_ Conclusions Narcotic availability leads to its usage following uncomplicated urologic surgery. Given the efficacy of non-narcotic analgesics, and the associated costs and potential side effects, prescribing narcotics should be highly selective. Funding none
Authors
Bradley Morganstern
Sandeep Mehta Shannon Smith Adam Howe Wayland Wu Vinaya Vasudevan Ronnie Fine Jordan Gitlin Lane S. Palmer |
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MP66-04 |
GONADAL FUNCTION AND REPRODUCTIVE SYSTEM ANATOMY IN POST PUBERAL PRUNE BELLY SYNDROME PATIENTS |
Pediatrics: Testis, Varicocele & Stones | 17BOS |
Abstract: MP66-04 Sources of Funding: None. Introduction Prune belly syndrome (PBS) is characterized by abdominal wall muscle hypoplasia, urinary tract dilatation and bilateral intra-abdominal testis. No spontaneous paternity has been reported to date and infertility is usually taken for granted. Our purpose was to gain insight on the causes of infertility in PBS by evaluating reproductive system anatomy and gonadal function in a cohort of post puberal PBS patients. Methods We contacted all patients 14 years-old or older that had undergone surgical reconstruction at our Institution since 1987. Age at orchidopexy, type of orchidopexy (with or without ligation of gonadal vessels), testicular volumes and positions and last serum creatinin were recorded. A pelvic MRI to evaluate prostate size, seminal vesicles and vas and serum FSH, LH and testosterone were ordered. Sperm analysis and analysis of urine after masturbation were performed when the patient and family consented. Results Fifteen patients had data from physical examination and hormonal profile and were included in this study. Mean age was 18.2 years. Mean age at orchidopexy was 17 months. Fourteen (93.3%) patients had both testes in scrotum. Mean testicular volume was 6.9 cc (2.1 to 9.4 cc). Eight patients collected semen. Mean concentration was 5.07 million/mL. Motile sperm was found in 5 patients (62.5%): 3 (37.5%) in the ejaculate a 2 (25%) in urine after masturbation. Mean hormone levels were LH: 5.3 mg/dL, FSH:6.9 mg/dL, testosterone 531 mg/dL. MRI revealed prostates hypoplastic in 55.6% and absent in 22.3%. Absence of at least one seminal vesicle was seen in 55.6%. No vasal abnormality was noted. Mean Cr=1.64 mg/dL. Conclusions Patients with PBS may have normal sexual hormonal levels and motile sperm in the ejaculate or post masturbation urine. Our study highlights a high prevalence of prostate and seminal vesical abnormalities that may represent an important cause for their infertility. Funding None.
Authors
Francisco Tibor-Dénes
Alessandro Tavares Marcello Cocuzza Bruno Tiseu Marcos Gianetti Machado Amilcar Martins Giron Miguel Srougi |
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MP66-05 |
Testicular histology in infants with Prader-Willi syndrome |
Pediatrics: Testis, Varicocele & Stones | 17BOS |
Abstract: MP66-05 Sources of Funding: none Introduction Hypogonadism is a prominent feature of Prader-Willi syndrome (PWS); cryptorchism occurs in approximately 90% of male cases. Hypogonadism in PWS has long been believed to be hypothalamus-related, resulting in low gonadotropin levels. Recent studies have suggested that hypothalamic and primary testicular dysfunction contribute to hypogonadism in PWS (Human Reproduction, 2015). No men with PWS have been reported to have fathered children. This is attributed to dysfunctional spermatogenesis secondary to cryptorchism, hypogonadism, or decreased libido in adulthood; however, a clear cause has not been identified. Further, only a few testicular histopathology reports have been published regarding males with PWS. Here, we present a report comparing the testicular histopathologies and endocrinologies of boys with PWS and cryptorchism with boys having isolated cryptorchism ._x000D_ Methods This study included 9 boys, 14–32-months-old (mean age, 21 months), with PWS who underwent orchidopexy at Nagoya City University Hospital between April 2002 and February 2016. The testes were position in the abdomen (2 cases), inguinal canal (7), high scrotal(7), or were retractile (2). Testicular biopsies were performed in 8 cases (15 testes). Sixteen cases (32 testes) of a corresponding age and testis position were included in a control group. The histological findings were evaluated to determine the seminiferous tubule fertility index. “Decreasing spermatogonia� was defined as <60% of the seminiferous tubules being positive for spermatogonia (J Urol, 2008). Serum levels of LH, FSH, testosterone (T), Inhibin B, and anti-mullerian hormone (AMH) were determined immediately before orchidopexy. Results Boys with PWS had significantly smaller testicular volumes than did the controls (mean values, 0.25 mL vs 0.62 mL; p < 0.05), and also had significantly fewer spermatogonia (87% vs 47%, p = 0.01). The endocrinological results were as follows: the laboratory data for the PWS boys (mean age, 23 months) showed LH at 0.1 IU/L (range, less than 0.2), FSH at 0.94 IU/L (0.5-1.8), T at <0.05 ng/mL(less than 0.1), AMH at 56 ng/mL, and Inhibin B at 38.2 pg/mL; those of the control group (mean age, 21 months) showed LH at 0.1 IU/L, FSH at 1.75 IU/L, T at <0.05 ng/mL, AMH at 234 ng/ml, and Inhibin B at 183 pg/mL. Conclusions Boys with PWS-associated cryptorchism show a reduced number of spermatogonia, beginning in infancy, suggesting that spermatogenic dysfunction is one cause of patient infertility. Low Inhibin B levels also suggest that boys with PWS have primary testicular dysfunction. Funding none
Authors
Taiki Kato
Kentaro Mizuno Hidenori Nishio Yoshinobu Moritoki Akihiro Nakane Hideyuki Kamisawa Satoshi Kurokawa Tetsuji Maruyama Takahiro Yasui Yutaro Hayashi |
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MP66-06 |
Is Surgical Antibiotic Prophylaxis Necessary for Pediatric Orchiopexy? |
Pediatrics: Testis, Varicocele & Stones | 17BOS |
Abstract: MP66-06 Sources of Funding: None Introduction Surgeons frequently use surgical antibiotic prophylaxis (SAP) despite limited evidence to support its efficacy. We hypothesized that children who received SAP prior to orchiopexy would have no reduction in surgical site infection (SSI) risk but an increased risk of antibiotic-associated adverse events. Methods We performed a retrospective cohort study of all males between 30 days and 18 years of age who underwent an orchiopexy (ICD-9 CM 62.5) with or without herniorraphy (ICD-9 CM 53.0 or 53.1) in an ambulatory or observation setting from January 2004 to December 2015 using the Pediatric Health Information System database. We excluded inpatients and those with any concomitant procedures. We used Chi-square or Fisher's exact tests to determine the association between SAP and allergic reaction (defined as a charge for epinephrine or ICD-9 diagnosis code for allergic reaction on the date of surgery) and any of the following within 30 days: SSI, hospital readmission or any repeat hospital encounter. We performed mixed effects logistic regression controlling for age, race, insurance and clustering of similar practice patterns by hospital. Results A total of 71,767 patients were included: median age 4.6 years; 61.4% white; 49.3% with public insurance. 33.5% received SAP. A total of 1.4% of patients had a perioperative allergic reaction and <0.1% of patients were diagnosed with a SSI. On mixed effects logistic regression, patients who received SAP had 1.2 times the odds of a perioperative allergic reaction compared to those who did not receive SAP (p=0.005). SAP was not associated with SSI, hospital readmission, or any repeat encounter within 30 days. Conclusions In patients undergoing orchiopexy we found that SAP did not reduce the risk of postoperative SSI, readmissions or hospital visits. Patients who received SAP, however, had significantly increased odds of perioperative allergic reaction. This suggests that the risks of SAP may outweigh the benefits in children undergoing orchiopexy. Funding None
Authors
Adam J Rensing
Benjamin M Whittam Katherine H Chan Mark P Cain Aaron E Caroll William E Bennett, Jr. |
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MP66-07 |
Testicular torsion in minors: does point-of-care influence testicular salvage rates? A population-based study |
Pediatrics: Testis, Varicocele & Stones | 17BOS |
Abstract: MP66-07 Sources of Funding: Dalhousie Clinical Scholar Award Introduction Testicular torsion (TT) in minors is afflicted by delays in treatment due to inappropriate referrals to tertiary pediatric centers. We sought to determine whether point-of-care (community hospitals vs. tertiary centers) or other treatment delaying variables such as transfer, emergency room (ER) wait times and distance travelled affect testicular salvage rates in minors with TT using a National database. Methods Data prospectively collected by the Canadian Institute of Health Information (CIHI) between January 2010-December 2014 were obtained; all Canadian males <18 years of age with TT based on ICD codes were included, except for the province of Quebec. Variables collected were: age, complexity level of surgical center based on case mix (community small/medium, community large, or tertiary/academic), if patient was transferred for definitive treatment, road distance travelled to the point-of-care based on postal codes, ER wait time in hours. Outcome was testicular salvage based on intervention codes used by CIHI for orchiectomy/orchidopexy. Uni and multivariate analyses were performed using logistic regression. Results Complete data were available for 1736 out of 1935 TT patients <18 years of age. Overall testicular salvage rate was 70%. Most patients (52%) were treated at tertiary hospitals. On univariate analysis, there was no difference in testicular salvage rates between tertiary and large community hospitals (70% vs 66%); treatment at small/medium community hospitals was associated with higher salvage rates (77%) compared to large community ones (OR=0.59, CI 0.39-0.85, p<0.05). ER wait time longer than 1 hour was associated with a significant increase in testicular loss (OR=1.89, CI 1.41-2.52, p<0.0001). Transfer and distance travelled were not associated with higher orchiectomy rates, even on stratified analysis by type of hospital. On multivariate analysis, age 12-17 years, treatment at community small/medium or tertiary/academic hospitals and shorter ER wait times were significantly associated with higher salvage rates. Conclusions Point-of-care affects testicular salvage rates in minors with TT. Small/medium community hospitals depict the lowest orchiectomy rates; while academic centers had better outcomes than large community hospitals on multivariate analysis, it is unclear if this of clinical significance. Transfer to another facility for definitive care and distance travelled did not affect orchiectomy rates. Longer ER wait time and younger age were the most consistent risk factors associated with orchiectomy. Funding Dalhousie Clinical Scholar Award
Authors
Katherine H Anderson
Bryan Maguire Dawn L MacLellan Peter AM Anderson Rodrigo LP Romao |
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MP66-08 |
The Impact of the Choosing Wisely&[copy] Campaign on Rates of Scrotal Ultrasound for Children Born with Cryptorchidism before and after Guideline Implementation |
Pediatrics: Testis, Varicocele & Stones | 17BOS |
Abstract: MP66-08 Sources of Funding: None Introduction Cryptorchidism is the most common genitourinary disorder identified in neonates affecting up to 3.7% of males. Ultrasound (US) is often used inappropriately following clinical diagnosis in attempts to locate the testis. Extensive evidence based research demonstrates the unreliability and poor sensitivity/specificity of scrotal US in cryptorchid males. The American Urologic Association in conjunction with the Choosing Wisely&[copy] initiative released a statement against ordering of US in males with cryptorchidism on February 21st, 2013. Our objective is to assess trends in the rates of US use after publication of the 2013 recommendation. Methods We utilized the Truven Health Analytics MarketScan® Research Database of commercially insured children to identify a cohort of children with a diagnosis code for undescended (752.51) and retractile testes (752.52) during an outpatient encounter in 2010-2014. Using CPT codes for scrotal US (76870) and for duplex scan of scrotal contents (93975/93976), males aged 0-12 were identified to isolate a primarily pre-pubertal population. The primary outcome measured was rate of US usage before and after the guideline release date. Cases were subcategorized according to geographic region. Out of pocket costs were determined and the average additional expense for US visits were calculated. Results We identified 52,804 outpatient encounters for undescended or retractile testes, of which, 9771 (19%) were associated with a scrotal US between 2010-2014. From 2010-2012 US was used in 6367/33,995 patients (18.7%). Following the guideline implementation the rate was 18.7% (1666/8890) in 2013 and 17.5% (1738/9919) in 2014. In this time period, the highest rate of visits associated with US were found in the West (22%), while the remaining regions had frequencies of 15-19%. Patients received an average of 1.8 tests (±1), with a range of 1 to 16. The average out-of-pocket cost for an US was $115 (±$202). Conclusions Following release of the Choosing Wisely&[copy] initiative, there was a small national reduction in rates of inappropriate US imaging for commercially insured pre-pubertal boys with the diagnosis of undescended or retractile testes. A significant proportion of the population continues to receive unnecessary imaging studies without clinical indication resulting in significant financial burden to the consumer and to the healthcare system as a whole. Continued efforts should be made to educate primary physicians on the poor utility of scrotal US in cryptorchid males. Funding None
Authors
Bryce Wyatt
Anne Andrews Andrew Stec Kit Simpson Michaella Prasad |
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MP66-09 |
Is having a sibling with undescended testis or hypospadias your biggest risk factor for being born with these anomalies: A multivariable analyses of known risk factors for undescended testis and hypospadias adjusted for clustering in mothers who have a previous child with these anomalies |
Pediatrics: Testis, Varicocele & Stones | 17BOS |
Abstract: MP66-09 Sources of Funding: None Introduction Several studies have identified risk factors for undescended testis (UDT) and hypospadias (HYP), but few have adjusted their estimates using multivariate modeling techniques. The objective of this study was to utilize an administrative database to measure the adjusted estimates of known maternal and fetal risk factors for UDT and HYP, while accounting for the effect of having a previous sibling with these anomalies. Methods This retrospective population-based cohort study used several linked provincial databases held at the Institute for Clinical Evaluative Sciences, in the province of Ontario, Canada, to identify all males born between 1997-2007 with a diagnosis of UDT and HYP. To ensure validity of the diagnosis, the cohort only included patients who had a surgical procedure for UDT or HYP on follow up. Baseline maternal and fetal risk factors obtained using ICD 9-10 codes, were assessed using generalized estimating equations with a logit link, adjusting for clustering amongst mothers with previous children with UDT or HYP. Results In 5830 boys with UDT, multivariable analysis identified prematurity and small for gestational age, associated HYP, multiple gestation, gestational hypertension, use of assisted fertility techniques, increased maternal age, babies born to immigrant mothers and a need for caesarean section as significant risk factors. In 2722 boys with HYP, significant risk factors included small for gestational age and prematurity, associated UDT, multiple gestation and babies born to immigrant mothers. After adjusting for a previous sibling with UDT, all these maternal and fetal risk factors lost statistical significance, except associated anomalies like DSD (OR: 82.3 95% CI 54.4-124.5 p<0.01) or HYP (OR: 2.04 95% CI 1.0-4.1 p= 0.04). After adjusting for a previous sibling with HYP, only small for gestational age (OR: 1.80 95% CI 1.03-3.1 p=0.03) and associated UDT (OR: 7.09 95% CI 4.87- 10.33 p<0.01) remained as significant risk factors. Conclusions While a combination of maternal and fetal factors were identified as risk factors for UDT and HYP in our multivariable analysis, after adjusting our analysis for individuals with a previous sibling with these conditions, only few fetal factors remained as significant risk factors. These results indicate that an underlying genetic predisposition for HYP and UDT could be a confounding factor when analyzing studies, which estimate risk factors for UDT and HYP without accounting for clustering in mothers who have had children with these anomalies Funding None
Authors
Roderick Clark
Kuan Liu Adiel Mamut Amit Garg Salimah Shariff Sumit Dave |
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MP66-10 |
Contralateral metachronous undescended testis: Is it predictable? |
Pediatrics: Testis, Varicocele & Stones | 17BOS |
Abstract: MP66-10 Sources of Funding: None Introduction Undescended testis (UDT) is usually congenital, but can be acquired in a boy with a prior documented descended testis. Some boys develop metachronous acquired UDT (mcUDT), requiring two separate orchiopexies. Our hypothesis was there may be characteristics evident at the time of initial orchiopexy which could predict the development of contralateral metachronous UDT. Methods By database query using CPT code for inguinal orchiopexy (54640), we identified all patients with UDT between the dates of 1/1997 to 10/2015. We included all patients who underwent orchiopexy for the indication of unilateral UDT. Our study population were patients who had undergone metachronous orchiopexies, while controls were patients who were 17 years old at time of data collection and had a unilateral orchiopexy (uUDT). Statistical analysis was completed with SAS Software 9.4. Results From a pool of 1035 eligible patients we identified 38 with mcUDT and 207 controls (uUDT). Comparing mcUDT to uUDT, median age at the first orchiopexy of patients who had a subsequent orchiopexy was 2.5 yrs (min/max, 0.50, 10.4) and 8.2 yrs (min/max 0.70, 12.8) for those who did not, p<0.0001 (Table 1). Contralateral testicular exam was significantly predictive of a subsequent UDT, p<.0001. Specifically, subjects who had a retractile testis on preoperative physical exam had a 4.2 times higher rate of subsequent UDT than patients who had a descended testis (95% CI [2.077, 8.353]). Subjects who had a retractile testis under anesthesia had a 6.7 times higher rate of subsequent UDT than patients who had a descended testis (95% CI [2.7, 16.5]). No relationship was found for side of initial UDT (p=.4947), acquired vs. congenital UDT (p=.40), procedure type (p=.52), ipsilateral testicular position (p=.71), size of ipsilateral UDT (p=.21), and patency of the processus vaginalis (p=.08). Conclusions Patients with a contralateral retractile testis at time of orchiopexy have an increased rate of requiring a contralateral orchiopexy in the future. A discussion of risks and benefits regarding about preforming bilateral orchiopexies should be undertaken with the parents prior to surgery. Funding None
Authors
Madeline Cancian
Anthony Caldamone |
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MP66-11 |
Follow-up Imaging Patterns After Emergency Department Visits for Pediatric Nephrolithiasis |
Pediatrics: Testis, Varicocele & Stones | 17BOS |
Abstract: MP66-11 Sources of Funding: None Introduction Concern exists regarding overuse of computed tomography (CT) children with nephrolithiasis. While guidelines for pediatric nephrolithiasis call for imaging such as plain film of the kidney-ureter-bladder (KUB) or renal ultrasound (US) to minimize ionizing radiation in both initial and follow-up management, little is known regarding follow-up imaging practices. We explored nationwide imaging patterns in children following emergency department (ED) evaluations for nephrolithiasis, hypothesizing that initial imaging choice and need for admission or readmission increase the risk of follow-up CT scans. Methods Claims from MarketScan (2007-2013), an employer-based dataset of privately insured patients, were used to assess children 1-18 presenting to the ED an acute nephrolithiasis event, defined as no prior ED visits or surgical interventions for nephrolithiasis within 6 months. Independent variables were age, gender, region of care and insurance status, initial imaging modality, need for hospital admission, and return ED visits. Primary outcome was imaging modality 90 days following an encounter. Appropriate imaging was defined as either KUB or US. Using logistic regression, odds for receiving CT or appropriate imaging in follow-up were calculated. Results A total of 871 children with an ED visit for nephrolithiasis met inclusion criteria. Median age was 16 (range 1-18) and the majority of patients were female (550, 63.0%). KUB was the most common initial modality (520, 59.7%) followed by CT (196, 22.5%) and US (150, 17.2%). A total of 282 (30.9%) children received no follow-up imaging. Of children receiving any follow-up imaging, appropriate imaging was obtained in 306 (51.9%) and CT obtained in 283 (48.0%) children. Of children initially receiving a CT, 79 (40.3%) had a CT in follow-up. Predictors for imaging patterns are shown in the Table. Conclusions Overuse of CT in children with nephrolithiasis is not limited to initial presentation as one third of all children presenting to the ED received a CT in follow-up. Identifiable risk factors for follow-up CT include younger age, complexity of stone event, and region of care. Clinical pathways directing imaging strategies for pediatric nephrolithiasis should focus on follow-up imaging as well as initial evaluation. Funding None
Authors
Jonathan Ellison
Paul Merguerian Ben Fu Sarah Holt Thomas Lendvay John Gore Margarett Shnorhavorian |
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MP66-12 |
PERCUTANEOUS EXTERNALLY ASSEMBLED LAPAROSCOPIC INSTRUMENTS FOR FOWLER-STEPHENS ORCHIOPEXY: THE FEASIBILITY OF A NEW SURGICAL SYSTEM |
Pediatrics: Testis, Varicocele & Stones | 17BOS |
Abstract: MP66-12 Sources of Funding: None Introduction Conventional laparoscopy is routinely used for the evaluation and management of the non-palpable testis but routinely requires three 5 mm ports that result in 9-10 mm scars. We have developed novel percutaneous externally assembled laparoscopic (PEAL) instruments which allow for nearly scarless laparoscopy. We present here a clinical series of six pediatric patients who underwent a Fowler-Stephens orchiopexy using these instruments. Methods Using the PEAL instruments, one patient underwent a single stage, four patients underwent a first stage and one patient underwent a second stage Fowler-Stephens orchiopexy. In all cases, a 5 mm port was placed at the umbilicus for the camera. The PEAL instrument, which consists of a reusable handle and a 2.96 mm shaft was then introduced lateral to the rectus sheath at the level of the umbilicus using a special introducer tip under direct visualization. The introducer was then brought out through the camera port and switched to a 5 mm grasper tip. An additional 5 mm port was placed on the right at the same level for insertion of a hook electrode and clip applier. Results The PEAL instruments functioned well for all dissection and grasping tasks, similar to 5 mm conventional instruments. Using these innovative new instruments, all patients underwent successful Fowler-Stephens procedures. Median operative time was 66 minutes (45-180 minutes). Blood loss was less then 5 mL in all cases. All six patients were discharged the day of surgery. The procedures were well tolerated without any perioperative or postoperative complications. At follow up, the average length of the PEAL scars was 3.25 mm, while the 5 mm port scars were 10 mm. Conclusions We describe a novel instrument paradigm for performing a pediatric laparoscopic Fowler-Stephens orchiopexy. These instruments offer improved cosmesis compared to conventional laparoscopy, and may show promise in other laparoscopic applications. Funding None
Authors
Isaac Kelly
Samuel Abourbih Minh Chau Nazih Khater Mohamed Keheila Salim Cheriyan Patrick Yang Jim Shen Matthew Pierce D. Duane Baldwin |
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MP66-13 |
Novel Sonographic Evaluation of Adolescent Varicoceles |
Pediatrics: Testis, Varicocele & Stones | 17BOS |
Abstract: MP66-13 Sources of Funding: None Introduction The adolescent varicocele poses several intriguing conundrums regarding the management and treatment of the varicocele. Correlations do exist between testicular hypotrophy and altered semen parameters; however, currently we have limited methods helping guide us as when to intervene or surveille these patients. We posit that there may be differences in heterogeneity as seen on sonography (SG) of patients with varicoceles compared to normal testicles. _x000D_ Methods The testes of adolescents with grade 2-3 varicoceles were compared to unaffected testes of adolescents with confirmed testicular torsion (controls). Representative static transverse sonographic images were examined using a novel program where the pixels of gray-scale SG images were transformed into a binary map to determine heterogeneity index (HI) values. Comparisons were made using T-tests, paired t-tests and Pearson correlations (p<0.05). _x000D_ _x000D_ Results We compared testes of 50 patients (mean age 17.7 years) with clinically significant varicoceles to 27 control testes. There was no significant difference in HI between the right and left testes of varicocele patients (p=0.25). However, the HI's of both the right and left testis of varicocele patients were significantly different compared to controls (p<0.0001). _x000D_ _x000D_ Varicocele patients who had surgery had smaller total testis volume (p <0.0001), and lower sperm count than non-surgical patients (p < 0.006). Testis volume increased significantly after surgery (p <0 .028) entirely due to change in left testis volume (p <0.017). At presentation, HI of the right testis was negatively correlated with both right (p <0.001) and left testis volume (p < 0.001). Post-op, right testis HI was negatively correlated with right (p<0.017) and left (p<0.022) testis volume, while the left testis HI negatively correlated with left testis volume (p<0.019). _x000D_ _x000D_ Conclusions Subtle differences in testicular heterogeneity exist in patients with varicoceles compared to normals. Moreover, we demonstrated that the unilateral process appears to affect the both testes and hence these subtle bilateral changes may correlate to global abnormal semen analysis sometimes seen in these patients. Further investigation may allow to develop a novel method to help manage and advise these patients. _x000D_ _x000D_ _x000D_ _x000D_ Funding None
Authors
Bradley Morganstern
Samir Derisavifard Matthew Elmasri Megan Murphy Bruce Rapkin Lane S. Palmer Sleiman R. Ghorayeb |
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MP66-14 |
Testicular Microlithiasis: A Case-Based, Multinational Survey of Clinical Management Practices |
Pediatrics: Testis, Varicocele & Stones | 17BOS |
Abstract: MP66-14 Sources of Funding: None Introduction Testicular microlithiasis (TM) is a condition characterised by calcium deposits within the testis, mostly detected incidentally. TM has been postulated to increase the risk of developing testicular malignancy. Our aim was to document international clinical management practices of post-pubertal adolescent patients with TM, and to analyze what factors and perception of risk influence conservative versus active management and follow-up patterns. Methods European Society for Paediatric Urology (ESPU) and Society for Pediatric Urology (SPU) members were invited to complete an online case-based survey of clinical management practices of testicular microlithiasis. Eight cases were presented, each based on a 15-year-old post-pubescent male. These assessed three variables (classic versus limited patterns of TM, unilateral versus bilateral TM, prior cryptorchidism versus no cryptorchidism) to ascertain the provider's perception of risk. The respondents completed multiple choice questions on initial management and follow-up plan, as well as length and duration of follow-up. Results There were 265 respondents to the survey from 35 countries. Median time in practice was 13.0 yrs (range 0-45 yrs). Median number of TM cases encountered per year was 4.5 (range 0-75). Factors significantly correlated on multivariate logistic regression analysis (p<0.05) with more aggressive initial management (more than counselling and teaching testicular self-examinations) included: not yet in independent practice, low volume of TM cases seen per year, those practicing pediatric and adult urology (vs. pediatric urology alone), classic pattern of TM and prior history of cryptorchidism. Factors that significantly correlated (p<0.05) with recommending urology follow-up and active investigation included: European practitioners, low volume of TM cases seen per year, those practicing combined pediatric urology and pediatric surgery, classic pattern of TM and prior history of cryptorchism_x000D_ Interval and length of follow-up were wide-ranging, with annual follow-up favoured by a majority. Conclusions The management of TM varies widely among those surveyed and a variety of surgeon and case-specific factors significantly affected selection of management strategies. Guidelines are much needed to recommend management and surveillance of adolescent patients with TM. These data on surgeons' perceptions of TM are important in informing the development of such guidelines. Funding None
Authors
Katie Brodie
Amanda Saltzman Nicholas Cost |
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MP66-15 |
Effectiveness of Surgical Management for Pediatric Ureteral Stones: Systematic review and Meta-analysis |
Pediatrics: Testis, Varicocele & Stones | 17BOS |
Abstract: MP66-15 Sources of Funding: None Introduction With the rising incidence of pediatric nephrolithiasis, the management debate between ureteroscopy (URS) and shockwave lithotripsy (SWL) has become more important. To date, success and complication rates for both have been based on single-institution reports. The aim of this study was to analyze the reported data on the effectiveness of SWL and URS for ureteral stones in children. Methods We searched Cochrane Controlled Trials Register, clinicaltrials.gov, MEDLINE, and EMBASE for reports in any language. Inclusion criteria were age <18 yrs with ureteral stones who underwent surgical treatment (URS vs SWL) with clearly defined success and complication rate. Manuscripts were then assessed and data abstracted in duplicate, with differences resolved by the senior author. Bias was assessed using standardized instruments. Pooled success and complication rates were estimated. Results We identified a total of 3,356 studies: 99 met inclusion criteria. The overall success rate was 0.80 (95% CI: 0.76-0.83) for SWL and 0.89 (95% CI: 0.86-0.91) for URS. The success rate for URS increased with more distal location: 0.83 (95% CI: 0.73-0.90) for proximal; 0.96 (95% CI: 0.87-0.99) for mid; and 0.94 (95% CI: 0.91-0.97) for distal ureteral stones. By contrast, SWL success decreased more distally: proximal 0.90 (95%CI: 0.83-0.95), mid 0.87 (95% CI: 0.79-0.92), and distal ureter 0.83 (95% CI: 0.72-0.90), respectively. _x000D_ _x000D_ The overall complication rate was not significantly different between the two modalities (SWL 0.04 (95% CI: 0.03-0.06) vs URS 0.06 (95% CI: 0.04-0.09)). Statistically significant heterogeneity was detected in all groups and subgroups of studies (p<0.001). However, little significant publication bias was detected._x000D_ _x000D_ _x000D_ Conclusions Compared to SWL, URS was associated with higher overall success rate and similar risk of complications. URS was associated with higher success in treating mid-distal ureteral stones. By contrast, SWL was most successful in treating proximal ureteral stones. Funding None
Authors
Hsin-Hsiao S. Wang
Ruiyang Jiang J. Todd Purves John S. Wiener Jonathan C. Routh |
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MP66-16 |
Immediate Post-Operative Course Following Open and Laparoscopic Orchiopexy of Abdominal Testes: Is There A Difference? |
Pediatrics: Testis, Varicocele & Stones | 17BOS |
Abstract: MP66-16 Sources of Funding: None Introduction The 2014 American Urologic Association cryptorchidism guidelines recommend abdominal orchiopexy for testes remaining non-palpable when examined under anesthesia after 6 months of age. Laparoscopic and open approaches are considered equivalent and dependent upon surgeon preference. We questioned whether immediate post-operative complications were comparable. Methods The American College of Surgeons National Surgical Quality Improvement Program data file was queried for laparoscopic (lap) and open orchiopexies of abdominal testes from 2012 - 2014. Data points included: age, ASA class, surgeon type, length of stay, operative time, complications, reoperation, and readmission. Statistical analyses included Student&[prime]s t-test and chi-square. Results A total of 1039 lap and 489 open abdominal orchiopexies were performed. Lap orchiopexy was performed even more commonly in 2013 (p=0.018) and 2014 (p<0.001) than in 2012. There was no difference in ASA class between approaches. Pediatric urology performed the most orchiopexies (822 lap, 414 open), followed by pediatric surgery (126 lap, 52 open). Urology (63 lap, 19 open) and general surgery (23 lap, 0 open) performed fewer procedures. There was no difference in approach among the pediatric subspecialists (p=0.294). Patients undergoing the lap approach were younger (mean 919.8±34.9 vs 1266.0±62.5 days, p<0.001). There was a trend towards lap surgeries being more commonly performed as outpatient (94.3% vs 91.2%, p=0.08). The mean length of stay was shorter for lap patients (0.17±0.04 vs 0.48±0.20 days, p=0.035), however open surgeries were shorter (73.7±3.0 vs 85.9±1.6 minutes, p<0.001). While the complication rate was low for both approaches (presented in the table), they were more than twice as likely to occur with the open approach (p=0.03). There was no statistical difference in reoperation rate (0.3% lap vs 0.6% open) or readmission rate (1.2% lap vs 1.8% open). Conclusions Although the open approach to abdominal orchiopexy takes less time to perform, the length of stay is longer. Immediate post-operative complications occur more commonly with the open approach, however the rate is low for both. Population studies into long term outcomes, such as failure or testicular loss, may offer further insight as to whether one approach is superior to the other. Funding None
Authors
Kristina Suson
Yegappan Lakshmanan |
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MP66-17 |
Risk Factors for Repeat Surgical Intervention in Pediatric Nephrolithiasis: A Pediatric Health Information System® Database Study. |
Pediatrics: Testis, Varicocele & Stones | 17BOS |
Abstract: MP66-17 Sources of Funding: None Introduction While successful surgery for pediatric nephrolithiasis minimizes the need for repeat interventions, staged procedures are sometimes necessary. We assessed predictors of repeat intervention for ureteroscopy (URS) and shock wave lithotripsy (SWL) in children utilizing a nationwide pediatric-specific administrative dataset, hypothesizing that repeat procedures would be higher for patients undergoing SWL. Methods Using the Pediatric Health Information System® dataset, we assessed all patients with nephrolithiasis from 2010 to August 2015 undergoing SWL or URS for an index stone surgery. Primary outcome was need for a repeat stone-related procedure, excluding cystoscopy with stent removal. Index treatment, stone location, presence of chronic comorbidity, use of ureteral stenting, presence of post-operative complications, age, gender, race, and insurance coverage were assessed as possible risk factors for repeat stone-related interventions. Statistical analyses with univariate and multi-variate modeling for mixed effects were performed. Results A total of 2788 patients undergoing URS (2216, 79.5%) and SWL (572, 20.5%) were identified. As compared to the SWL cohort, URS patients had higher rates of ureteral calculi (55.1 vs 17.1%, p < 0.001), were more frequently female (61.1% vs 53.5%, p = 0.0012) and older than 6 years of age (14.9% vs 5.2%, p < 0.001). Children undergoing URS had a higher rate of chronic comorbidity (27.1% vs 22.2%, p = 0.0163). Multivariate analysis with a mixed effects model is shown in the Table, assessing factors associated with repeat stone-related interventions. Conclusions Within the PHIS dataset, URS is performed more commonly than SWL for children with nephrolithiasis, especially for older children and those with ureteral calculi. SWL is associated with a 2.6-fold higher risk of repeat stone-related interventions. Intra-operative stent placement, younger age, chronic comorbidity and renal calculi are also associated with higher risks of repeat intervention on multivariate analysis. Prospective studies are needed to assess comparative effectiveness of SWL and URS in children and reduce risk for repeat surgical interventions in pediatric stone disease. Funding None
Authors
Jonathan Ellison
Thomas Lendvay Kathleen Kieran Assaf Oron Margarett Shnorhavorian Paul Merguerian |
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MP66-18 |
DECELLULARIZED WHOLE TESTIS AS A POTENTIAL BIOSCAFFOLD FOR TESTIS TISSUE-ENGINEERING |
Pediatrics: Testis, Varicocele & Stones | 17BOS |
Abstract: MP66-18 Sources of Funding: none Introduction Bilateral Vanishing Testis Syndrome is one of the most challenging problems of pediatric and adolescent urology. There are at least two major problems for patients with congenital or acquired anorchia: Long-life androgen replacement therapy and possible hepatic cancer occurrence as well as fertility issue. The purpose of present study was to describe a method to produce human sized decellularized testis scaffold as a primitive step for testis tissue engineering in such complex situation._x000D_ Methods A total of 32 sheep testes were classified in 8 groups of 4. Seven decellularization protocols were proposed which were tested on groups 1-7, respectively and group 8 was left intact as the control group. The protocols consisted of 0.5%, 1%, 2% solution of sodium dodecyl sulfate (SDS), Trypsin-EDTA 0.5%, 1%, Triton X-100 1% and 2%, respectively. Then, using the best protocol obtained in phase I, the optimal timing was evaluated; ovine testes were decellularized by arterial perfusion and specimen were collected for evaluation at 4-6-8-10-12 hours after initiation of the procedure, respectively. _x000D_ To evaluate the efficacy of the protocol, histological examinations, scanning electron microscopy (SEM), magnetic resonance imaging (MRI) biochemical assays and evaluation of mechanical properties were performed. The patency of vascular network of the decellularized scaffold was examined by angiography. The cytotoxicity analyses of samples was performed by tetrazolium salt MTT (3-[4,5- dimethylthiazol- 2-yl]-2,5-diphenyltetrazolium bromide) assay. _x000D_ Results Histological exams depict that treating the tissues with SDS 1% for 6-8 hours was found to be the best protocol for cell removal and preserving the extracellular matrix (ECM) components. The microstructure, ultrastructure and vascular integrity of the decellularized testis scaffold were well-preserved and confirmed by scaffold angiography, SEM and MRI. Moreover, MTT assay showed that the decellularized testis was not cytotoxic to cells and it is ready for recellularization Conclusions The SDS 1% with 6-8 hours perfusion based protocol is the best, effective, minimally invasive technique for creation of whole testis bioscaffold with well-preserved extra-cellular matrix structure and vascular network integrity. To the best of our knowledge the whole large size testis decellularization by this novel protocol has not been reported previously. This preliminary step may pave the road for slowing these problems in future. _x000D_ Funding none
Authors
Aram AKBARZADEH
Maral KIANIMANESH Maryam EBADI Ahmad MASOOMI Fereshteh GHAZISAEEDI Reza Seyed Hosein BEIGI Arash FALLAHI Reyhane SHEIKH Abdol-Mohammad KAJBAFZADEH |
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MP66-19 |
The Declining Rate of Pediatric Varicocelectomy in New York State |
Pediatrics: Testis, Varicocele & Stones | 17BOS |
Abstract: MP66-19 Sources of Funding: None Introduction Treatment of pediatric varicoceles remains controversial. Generally, observation is the preferred approach, with surgery reserved for patients with pain, testicular hypotrophy or abnormal semen parameters. However, the utility of varicocelectomy has been disputed due to studies showing spontaneous improvement in testicular size with observation and unreliability of semen studies in adolescents. This uncertainty may have affected surgical practice patterns and we sought to analyze trends of varicocelectomy in New York State over the past 12 years. Methods The New York Statewide Planning and Research Cooperative System (SPARCS) database was queried for boys <18 years-old who underwent varicocelectomy from 2003 to 2014. Patients were identified using ICD-9-CM procedural codes (631) and CPT codes (55530, 55535, 55540, and 55550), and were then divided by approach (inguinal, abdominal, laparoscopic). Rates of surgery were adjusted by yearly state population of boys <18 years-old using census data (census.gov). Trends were estimated using the method of least squares, and goodness of fit was determined using the R2 coefficient. Results A total of 3,927 patients were identified who underwent varicocele repair between 2003 and 2014 in New York State. Median age at surgery was 15 years. 68.6% of patients were white. Most procedures were done in New York City (54.4%), and almost all were by inguinal (57.3%) or laparoscopic (30.9%) approaches. Annual rate of varicocelectomy declined by 0.57 cases per 100,000 boys per year (slope = -0.57, R2 = 0.72; Figure 1) from 16 cases/100,000 in 2003 to 9 cases/100,000 in 2014. The decrease in inguinal approach accounted for the majority of this trend (slope = -0.55, R2=0.94), from 11 cases/100,000 in 2003 to 4 cases/100,000 in 2014. Laparoscopic and abdominal approaches remained stable. Conclusions The rate of pediatric varicocelectomy performed in New York State significantly dropped over the last 12 years, particularly the inguinal approach. Contrary to studies showing stable rates of varicocelectomy performed at Children&[prime]s Hospitals (Harel, 2015), we found a consistent decline across academic and community centers. Further study is required to identify factors that have driven the nearly 50% decline in surgery and to better define indications for intervention. Funding None
Authors
Michael J Lipsky
Wilson Sui Julia B Finkelstein Alexander C Small Dennis J Robins Sarah M Lambert Pasquale Casale |
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MP66-20 |
Pediatric Modified Supine Percutaneous Nephrolithotomy: An Australian case series. |
Pediatrics: Testis, Varicocele & Stones | 17BOS |
Abstract: MP66-20 Sources of Funding: None Introduction The modified supine Percutaneous Nephrolithotomy (PCNL) is an attractive alternative option to the prone PCNL for the management of large (>2cm) intra-renal calculi. This technique has shorter operative times, similar complication rates and length of hospital stays to the prone position. There are only two studies in the pediatric population. This study aims to evaluate the safety and efficacy of the supine PCNL in the pediatric population. Methods This is a single-center, prospective study, conducted at Monash Health, Australia. It includes patients under the age of 18 years who underwent a supine PCNL between April 2007 and June 2015. The Monash Health Human Research Ethics Committee approved this as a Quality and Service improvement activity. Data was collated on patient age, number, size and composition of stones, technique used, equipment used, length of surgery and complications. Results Thirteen patients (3 girls and 10 boys) with a mean age of 8.2 years were included. Of these, 12 had at least one renal calculus with the largest calculi having a mean size of 15mm and the procedure took 114 minutes. The stone clearance rate was 69%, three patients had residual stones on follow-up imaging. The mean length of stay was 3 days. One patient required ICU post-operatively for sepsis and two patients required blood transfusions. These results are comparable to prone PCNL. Conclusions The Modified supine PCNL is a safe and effective and method of retrieving large calculi in the pediatric population and is comparable to the prone PCNL. Funding None
Authors
Athina Pirpiris
Debbie Siew Antonio de Sousa Shekib Shahbaz Philip McCahy Nathalie Webb |
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MP67-01 |
Telomere length and genetic anticipation in a large cohort of Chinese von Hipple-Lindau disease |
Kidney Cancer: Epidemiology & Evaluation/Staging II | 17BOS |
Abstract: MP67-01 Sources of Funding: Supported by National Natural Science Foundation of China(Grand number 81572506) Introduction von Hipple-Lindau(VHL) disease is an autosomal dominant familial cancer syndrome with a birth incidence of around 1/36000. Renal cell carcinoma(RCC) occurs in 35% of VHL patients, and is one of the main death causes. In order to describe the genetic characteristics of Chinese VHL patients, we have evaluated the telomere length and genetic anticipation in a large cohort of Chinese von Hipple-Lindau disease. Methods We recruited 140 patients from 70 families with VHL disease and 51 normal controls. Onset age was defined as the age when any symptom or sign of VHL disease first appeared. Genomic DNA was extracted from peripheral blood and age-adjusted relative telomere length(aRTL) was measured with qRT-PCR method. 101 parent-child pairs were analysed for genetic anticipation by paired t test. Results The mean onset age in our cohort was 29.5±11.6 years, and RCC occurred in 48.6%(68/140) VHL patients. Onset age was 16.8 years earlier for child than parent in the parent-child pairs(p<0.001). Patients in the next generation had younger onset age with shorter age-adjusted relative telomere length (p=0.018) in the 27 parent-child pairs. In addition, age-adjusted relative telomere length was shorter in the 140 VHL patients than in the normal controls(p=0.038). Conclusions This study provide evidence that telomere shortening is associated with genetic anticipation in a large Chinese cohort of VHL disease, suggesting that it might be a mechanism for pathogenesis of VHL-associated tumors. Funding Supported by National Natural Science Foundation of China(Grand number 81572506)
Authors
Jiangyi Wang
Shuanghe Peng Xianghui Ning Teng Li Jiayuan Liu Shengjie Liu Kan Gong |
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MP67-02 |
Increased Hp1-gamma expression associates with adverse outcome in patients with non-metastatic clear cell renal cell carcinoma |
Kidney Cancer: Epidemiology & Evaluation/Staging II | 17BOS |
Abstract: MP67-02 Sources of Funding: none Introduction Heterochromatin protein 1 gamma (HP1?) is a non-histone heterochromatic protein, which plays an important role in maintaining the stability of chromatin and embryonic development. Recently, HP1? has been implied to be involved in the development and progression of cancer. Here, we investgated the association of HP1? expression with oncologic outcome of patients with non-metastatic clear cell renal cell carcinoma (ccRCC). Methods In this retrospective study, we enrolled 721 patients with non-metastatic ccRCC performed partial or radical nephrectomy at two academic medical centers between 2005 and 2009. The first cohort with 521 patients was treated as training cohort and the other as validation cohort. Tissue microarrays (TMAs) were built on triplicate from formalin-fixed, paraffin embedded specimens. Immunohistochemistry (IHC) was performed and the association of HP1? expression with standard pathologic features and clinical outcomes were evaluated. Results High HP1? expression were remarkably correlated with shortened survival time (P = 0.001 and P < 0.001, respectively) and increased risk of recurrence (P = 0.037 and P = 0.001, respectively) in both cohorts. HP1? could also offer a better prognostic stratification based on traditional histologic factors. Furthermore, multivariate analyses confirmed HP1? to be an independent adverse prognostic factor for post-operative survival of patients. A predictive nomogram was generated based on identified independent risk factors to for a better prognosis of patients’ survival at 5 and 10 years. Conclusions HP1? expression emerges as an independent prognostic factor for non-metastatic ccRCC patients after surgical treatment Funding none
Authors
Yu Zhu
Zewei Wang Dingwei Ye |
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MP67-03 |
Differential Activity of Immune System Pathways and the PI3K/AKT/mTOR Pathway in Black and White Patients with Papillary Renal Cell Carcinoma |
Kidney Cancer: Epidemiology & Evaluation/Staging II | 17BOS |
Abstract: MP67-03 Sources of Funding: None Introduction Significant disparities in survival, incidence and possibly response to current therapies exist between black and white patients with renal cell carcinoma (RCC). Recent genomic evidence to account for these disparities has been reported for clear cell RCC. However, racial disparities at the genomic level for papillary RCC (pRCC) which is a genetically distinct and less responsive histologic subtype of RCC have not been reported. Using The Cancer Genome Atlas (TCGA) data, the present study assessed differences in gene-level expression and pathway activity between black and white patients with pRCC. Methods The TCGA dataset was used to identify 235 (54 black, 181 white) of 290 patients with an initial diagnosis of pRCC from 2001-2013. Black and white patients were propensity matched on age, gender and pathologic TNM stage. Supervised whole genome expression analysis using the SAMSeq package in R was conducted to identify genes differentially expressed genes (FDR<0.05). Gene Set Enrichment Analysis (GSEA) to evaluate differential activity of pathways and gene sets in white and black patient groups was also conducted. Results There were 167 genes and 47 genes identified as overexpressed in black and white patients, respectively (FDR<0.05). Gene Set Enrichment Analysis identified 111 gene sets enriched (p<0.05) in black patients, with differences in PI3K/AKT/mTOR signaling (p<.001) and immune system pathways being the most prevalent including T cell signal transduction (p<0.001), Interferon ?/? signaling (p=.004), Interferon gamma response (p=.018), B cell antigen receptor (p=.018), IL-2 signaling (p=.015) and MHC class II antigen presentation (p=.012). PTPN20B and CRYBB2 associated with the PAK and WNT pathways were overexpressed in Black patients, respectively. Conclusions Distinct tumor biology between black and white patients was identified with differential activity of immune related pathways and signaling of the PI3K/AKT/mTOR pathway. While our data requires validation, these findings suggests that race may have implications for distinct immune responses to cancer and that the use of immunotherapies, VEGFR, mTOR, MEK and PI3K inhibitors to target these pathways may improve survival in black patients with advanced pRCC. Funding None
Authors
David Paulucci
John Sfakianos Anders Skanderup Kathleen Kan Che-Kai Tsao Matthew Galsky A Ari Hakimi Ketan Badani |
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MP67-04 |
Evaluation of the De Ritis (aspartate transaminase/alanine transaminase) ratio as a predictor of oncological outcomes in patients with upper urinary tract urothelial carcinoma after surgery |
Kidney Cancer: Epidemiology & Evaluation/Staging II | 17BOS |
Abstract: MP67-04 Sources of Funding: none Introduction Recently, several studies have shown that the De Ritis (aspartate transaminase/alanine transaminase) ratio can be a useful prognostic biomarker in patients with certain types of malignant tumors. However, the prognostic value of the De Ritis ratio in patients with upper tract urothelial carcinoma remains largely unknown. The aim of the present study was to evaluate the prognostic significance of the De Ritis ratio in patients with upper urinary tract urothelial carcinoma after radical nephroureterectomy (RNU). Methods One thousand forty-nine patients who underwent RNU at eight institutions from 2004 to 2015 were retrospectively reviewed. The effect of the De Ritis ratio and conventional clinicopathological parameters were analyzed. Survival analysis was performed using the Kaplan-Meier method and log-rank test. Multivariable analysis was performed using the Cox proportional hazard regression model. Cutoff values of the De Ritis ratio were calculated using a receiver operating characteristic curve (ROC). Results According to the ROC curve, the cutoff value for overall death was 1.6 (p=0.002). The cancer-specific survival (CSS) and overall survival (OS) were significantly shorter for patients with a high De Ritis ratio (>1.6). Results of multivariable analysis identified an increased De Ritis ratio (>1.6) as independently related to worse CSS (hazard ratio [HR] 2.49, 95% confidence interval [CI] 1.70-3.64; p=0.001) and OS (HR 1.84, 95% CI 1.34-2.52; p=0.001). Conclusions Our results suggest that the De Ritis ratio can be a significant predictor of oncological outcomes in patients with upper urinary tract urothelial carcinoma after surgery. Funding none
Authors
Eu Chang Hwang
Yang Hyun Cho Ho Seok Chung Seung Il Jung Taek Won Kang Dong Deuk Kwon Myung Ki Kim Sung Gu Kang Jun Cheon Ja Yoon Ku Hong Koo Ha Chang Wook Jeong Ja Hyeon Ku Cheol Kwak Tae Gyun Kwon Tae-Hwan Kim Seock Hwan Choi |
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MP67-05 |
Clinicopathologic Analysis of Renal Epithelioid Angiomyolipoma: A Single Institute Experience of 21 Cases |
Kidney Cancer: Epidemiology & Evaluation/Staging II | 17BOS |
Abstract: MP67-05 Sources of Funding: NSC 105-2314-B-182-024-MY3 Introduction Epithelioid angiomyolipoma (eAML) has been considered a malignant variant of angiomyolipoma (AML) since it was classified by World Health Organization in 2004. Recent studies have argued that the actual metastatic rate of eAML is very low. This retrospective study aims to analyze the aggressive behavior rate and describe the vast clinicopathalogical variety of eAML. Methods In Chang Gung Memorial Hospital, Taiwan, a total of 887 patients were diagnosed with AML from 2001 to 2016 according to the healthcare information system archive, including 21 cases of renal eAML. All of the cases were diagnosed according to tissue proof and immunohistochemical studies. The images, pathology and medical records of these 21 eAML cases were reviewed and summarized._x000D_ Results In these 21 eAML cases, the average age was 43.1 (ranges from 18 to 64), including 6 males and 15 females. All 21 cases are not associated with tuberous sclerosis complex. The longest diameter of the tumors ranges from 1.3 to 20 centimeters (average 9.8 cm). Three of these cases had multiple tumors (single eAML and single AML coexist on the left kidney, clear cell renal cell carcinoma on the right and single eAML on the left, multiple AML on bilateral kidneys with single eAML on the left). Only one patient suffered from spontaneous haemorrhage. Two cases developed distant metastasis: one had nodules over bilateral lungs and left anterior mediastinum; the other had recurrence over liver and retroperitoneum one year after surgical intervention. Three cases had venous thrombus (two in renal vein and one in inferior vena cava) and received thrombectomy. All 21 cases received surgical intervention: 13 radical nephrectomy, 7 partial nephrectomy, one was found with retroperitoneal eAML arising from renal capsule thus undergone tumor excision without kidney involvement. The follow up period ranges from 1 to 143 months (average 51 months). Only 2 cases died from unrelated cause._x000D_ Conclusions In our study, the rate of aggressive behavior is 24% (2 distant metastasis and 3 venous invasion in the 21 cases). Some noticeable accompanying characteristics including haemorrhage, coexisting with AML, coexisting with renal cell carcinoma are also seen in this series. The incidence of renal vein and inferior vena cava thrombus formation in our series is high (3 out of 21), therefore, detailed preoperative image evaluation is necessary. Funding NSC 105-2314-B-182-024-MY3
Authors
Han-Yu Tsai
Cheng-Keng Chuang Kwai-Fong Ng Kun-Han Lee |
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MP67-06 |
COLLECTING (BELLINI) DUCT CARCINOMA: DISEASE CHARACTERISTICS AND TREATMENT OUTCOMES |
Kidney Cancer: Epidemiology & Evaluation/Staging II | 17BOS |
Abstract: MP67-06 Sources of Funding: none Introduction Collecting (Bellini) Duct renal cell carcinoma (CDRCC) is a rare type of renal cell cancer (RCC), estimated to represent 0.4-2.0% of all RCCs. This subtype has been predominantly studied in single-institution datasets and little is known about treatment patterns and outcomes. We sought to utilize a large, population-level database to assess survival outcomes for this rare disease. Methods The national cancer database (NCDB) was queried for all cases of CDRCC and clear cell RCC (CCRCC) from 2004-13. After patients with other cancer diagnoses were removed, the analytic cohort was composed of 202,263 CCRCC and 577 CDRCC cases. Kaplan-Meier and cox proportional hazards analysis were employed to model survival. Results Compared to CCRCC, patients with CDRCC presented with higher grade and stage, node-positive and metastatic disease (70.7% versus 30.0% with metastasis). Overall median survival for CDRCC was 13.2 months (95% CI 11.0-15.5) compared to the 122.5-month (121.0-123.9) for CCRCC. On multivariate analysis of the CDRCC cohort, increasing T stage, high-grade disease and metastasis were predictors of mortality. Of 184 patients with metastatic CDRCC, 113 underwent cytoreductive nephrectomy (CNx) while the rest were treated with multimodal therapy (MMT) alone or observed. Survival outcomes were improved in patients who received both CNx with MMT compared to surgery alone (HR 0.51, 95% CI 0.32-0.79) or MMT alone (HR 0.57, 95% CI 0.37-0.89) on multivariate analysis. Conclusions Collecting (Bellini) Duct carcinoma is an aggressive subtype of RCC. Median survival is 13 months after diagnosis, drastically lower than for CCRCC. Over 70% of patients are diagnosed with metastatic disease. Multimodal therapy in addition to cytoreductive nephrectomy is associated with a survival benefit over single mode therapy. Funding none
Authors
Wilson Sui
Justin Matulay Dennis Robins Maxwell James Ifeanyi Onyeji Marissa Theofanides Arindam RoyChoudhury Sven Wenske Guarionex DeCastro |
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MP67-07 |
Pathological Determinants of Oncologic Outcomes in Stage II Renal Cell Carcinoma: An International Multicenter Analysis |
Kidney Cancer: Epidemiology & Evaluation/Staging II | 17BOS |
Abstract: MP67-07 Sources of Funding: Stephen Weissman Kidney Cancer Research Fund. NIH grants UL1TR000100 and UL1TR001442. Introduction Stage II Renal Cell Carcinoma (RCC) is characterized by varied oncological outcomes, as the risk of progression and recurrence can vary widely. We analyzed clinical and pathological risk factors associated with oncological outcomes in a multicenter, international cohort. Methods Retrospective multicenter analysis of patients who underwent surgical excision of clinically localized stage 2 (T2) renal mass from 1987-2015. Patients with tumors amenable to nephron-sparing surgery, baseline chronic kidney disease, or bilateral renal masses were provided an option for partial nephrectomy (PN), otherwise radical nephrectomy (RN) was performed. Lymphadenectomy (LND) was performed when clinically indicated. Primary endpoint was Recurrence Free Survival (RFS). Secondary outcome was overall survival (OS). Kaplan-Meier (KM) log-rank test and multivariable analysis (MVA) for factors related to RFS and OS were performed. Results 1328 patients were analyzed (mean age 59.2 years, median follow up 62.7 months, 66.4% male/33.6% female, 20% PN/80% RN). Overall recurrence rate was 22.3%. MVA for factors associated with recurrence was significant for RN (OR 4.68, p=0.010), positive margin (OR 34.19, p=0.012), tumor grade 3/4 (OR 2.35, p=0.001), and lymphovascular invasion (LVI, OR 2.03, p=0.018). MVA for tumor related factors associated with worsened OS was significant only for RN (OR 4.16, p=0.001). KM analysis revealed 5 year RFS of 78.7% for LVI negative and 49.9% for LVI positive patients (p<0.001), as well as a 5 year RFS of 81.8% for tumor grade 1/2 and 62.1% for tumor grade 3/4 (p<0.001, figure). Conclusions For Stage II RCC, LVI and tumor grade 3/4 are independently associated with increased risk of recurrence. Stage II RCC patients with these pathological findings represent a high risk subgroup that requires close follow up and has implications for clinical trial design. Funding Stephen Weissman Kidney Cancer Research Fund. NIH grants UL1TR000100 and UL1TR001442.
Authors
Zachary Hamilton
Daniel Han Alp Tuna Beksac Sean Berquist Abd?elrahma Hassan Charles Field Aaron Bloch Sumi Dey Adam Bezinque Samer Kirmiz Fang Wan James Proudfoot Anthony Patterson Bulent Akdogan Haluk Ozen Brian Lane Ithaar Derweesh |
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MP67-08 |
Preoperative systemic inflammatory markers in upper tract urothelial cell carcinoma: Which is better as a prognostic factor? |
Kidney Cancer: Epidemiology & Evaluation/Staging II | 17BOS |
Abstract: MP67-08 Sources of Funding: none Introduction Systemic inflammatory prognostic markers have been identified for several types of cancer. However, it remains unclear which markers are best for determining prognosis. The aim of this study was to investigate the prognostic value of preoperative systemic inflammatory markers in upper tract urothelial carcinoma (UTUC). Methods A total of 1,137 patients who underwent radical nephroureterectomy with bladder cuff excision at 9 institutions from 2004 to 2015 were retrospectively reviewed. The Glasgow prognostic score (GPS), modified GPS (mGPS), neutrophil to lymphocyte ratio (NLR), and platelet to lymphocyte ratio (PLR) for each patient were calculated. Multivariable analysis was performed using a Cox proportional hazards regression model. Cut-off values for NLR and PLR were calculated using a receiver operating characteristic curve (ROC). Results Median follow-up period was 39.1 (interquartile range: 18.3-63.8) months. Univariable analysis revealed that GPS, mGPS, PLR, and NLR (all, p = 0.001) were significantly associated with recurrence-free survival (RFS) and cancer-specific survival, (CSS). Multivariable analysis revealed that GPS (p = 0.001), PLR (hazard ratio [HR] = 1.34; 95% confidence interval [CI]: 1.10-1.63, p = 0.003 and HR = 1.81; 95% CI: 1.17-2.78, p = 0.002), and NLR (HR = 1.39; 95% CI: 1.14-1.72, p = 0.001 and HR = 1.70; 95% CI: 1.13-2.58, p = 0.011) were significantly associated with RFS and CSS. Conclusions Our results suggest that preoperative systemic inflammatory markers such as GPS, PLR, and NLR are independent prognostic factors in patients with UTUC after surgery Funding none
Authors
Eu Chang Hwang
Yang Hyun Cho Ho Seok Chung Seung Il Jung Taek Won Kang Dong Deuk Kwon Myung Ki Kim Sung Gu Kang Seok Ho Kang Jun Cheon Ja Yoon Ku Hong Koo Ha Chang Wook Jeong Ja Hyeon Ku Cheol Kwak Tae Gyun Kwon Tae-Hwan Kim Seock Hwan Choi Ill Young Seo |
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MP67-09 |
Surveillance strategy and outcome after partial nephrectomy |
Kidney Cancer: Epidemiology & Evaluation/Staging II | 17BOS |
Abstract: MP67-09 Sources of Funding: None Introduction After partial nephrectomy (PN), recurrent disease may develop in the remaining kidney, renal fossa, retroperitoneal lymph node, and in distant organs. The aim of the study was to analyze the characteristics of recurrence, the relevance of imaging studies in detecting recurrence, and the outcomes of surveillance after PN in a single institution. _x000D_ Methods Retrospective study of 1060 patients who underwent PN for localized renal cell carcinoma between 2007 and 2015 at a single institution. We studied the characteristics of recurrence according to pathological and clinical features and elaborated risk groups. The type and the total numbers of imaging studies performed during surveillance or until recurrence were evaluated. Outcomes of surveillance were analyzed._x000D_ _x000D_ Results There were 48 patients diagnosed with recurrence after median 36 months follow up. The sites of recurrence were abdominal in 62.5%, and chest in 27%. All relapses were initially detected at a single site. The recurrence was symptomatic in 10.4%. Chest x-ray and abdominal ultrasound detected 7.7% and 3.4% of all recurrences respectively. During this surveillance period, 1888 CT scans, 118 abdominal MRI, 236 abdominal US, 472 chest CT scans and 1770 chest x-rays were obtained. The number of patients to follow, and imaging studies needed in order to detect 1 recurrence were 19 and 104 respectively._x000D_ When studying the recurrence rate, and time-to-recurrence, 2 risk groups emerged. Tumors with >pT1a stage or high grade tumor or positive surgical margin status, and/or High R.E.N.A.L score had high recurrence rate with the majority of tumors recurring in the first 36 months after PN. Of the 48 patients diagnosed with recurrence, 44 (91.6%) were suitable for secondary active treatment, including 26 (54.2%) patients suitable for metastasectomy. The rate of relapse after secondary treatment was 43.5% (16.6% for the local recurrence group and 60.7% for the metastasis group). _x000D_ _x000D_ _x000D_ _x000D_ _x000D_ _x000D_ Conclusions Patients with any adverse pathological or clinical features should be considered as high risk group and followed closely in the first 36 months with only cross-sectional studies. Chest x-ray and abdominal ultrasound have low utility in detecting recurrence and should not be considered for surveillance. Secondary active treatment is suitable for most patients with recurrence while metastasectomy fits less patients. Local recurrence is associated with increased rates of metastatic progression. Funding None
Authors
Pascal Mouracade
Julien Dagenais Matthew Maurice Onder Kara Ryan Nelson Jaya Sai Chavali Jihad Kaouk |
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MP67-10 |
Accurate Risk Assessment of Patients with Localized Pathologic T3a Renal Cell Carcinoma |
Kidney Cancer: Epidemiology & Evaluation/Staging II | 17BOS |
Abstract: MP67-10 Sources of Funding: none Introduction The accurate risk assessment of pathologic T3a renal cell carcinoma (RCC) remains a challenge. To develop a more precise risk stratification system, we investigated the prognostic impact of tumor growing into fatty tissue around kidney or renal vein. Methods We retrospectively reviewed the medical records of 211 patients with a pathologic diagnosis of T3aN0M0 RCC. Recurrence free survival was estimated using the Kaplan-Meier method. Factors associated with survival outcome were studied using multivariable Cox regression analysis. Results Overall 59% of patients had isolated fat invasion, 19% had isolated renal vein involvement, and 23% had both histologic features. Patients were divided in 2 groups: fat invasion or renal vein involvement (group A) and fat invasion plus renal vein involvement (group B). Group B had a significantly worse recurrence free survival than group A on Kaplan-Meier curve (p = 0.001). At multivariable Cox regression analysis, this new stratified group B was found to be an independent prognostic predictor of recurrence free survival (HR = 1.964, 95% CI = 1.059-3.632, p = 0.032) after adjusting for gender, tumor size, tumor necrosis, angoilymphatic invasion, and sarcomatoid differentiation. Conclusions Patients with pathologic T3a RCC with both fat invasion and renal vein involvement increased risk of recurrence after nephrectomy. According to fat invasion and renal vein involvement, the pathologic T3a RCC should be sub-divided into those with favorable and unfavorable disease. Funding none
Authors
Jung Keun Lee
In Jae Lee Tae Jin Kim Hakmin Lee Jong Jin Oh Sangchul Lee Seong Jin Jeong Seok-Soo Byun Sang Eun Lee Sung Kyu Hong |
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MP67-11 |
The impact of modified International Metastatic Renal Cell Carcinoma Database Consortium model using a two-step stratification process |
Kidney Cancer: Epidemiology & Evaluation/Staging II | 17BOS |
Abstract: MP67-11 Sources of Funding: none Introduction The International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model predicts prognosis in metastatic renal cell carcinoma (mRCC) patients, who are stratified into favorable-, intermediate-, and poor-risk groups (FG, IG, and PG, respectively), based on six clinical parameters, in which about half of mRCCs are classified as IG. We aimed to substratify IG as more favorable (fIG), poorer (pIG), and others (intermediate IG: iIG), as well as generate better risk model: [FG&fIG], iIG, and [PG&pIG] as modified IMDC model. Methods We analyzed the records of 213 consecutive mRCC patients who underwent molecular targeted therapy (MTT). Age, gender, histology (clear vs non-clear cell), type of initial MTT medications (tyrosine kinase inhibitors [TKIs] vs mammalian target of rapamycin inhibitors [mTORIs]), serum laboratory data (albumin [ALB], sodium, and C-reactive protein [CRP]), prior nephrectomy, immunotherapy, and metastatic sites (lung, liver, and bone) were used for IG sub-stratification. Overall survival (OS) was defined as the duration from the initial MTT. Modified and original models were compared using concordance correlation coefficient analysis. Results Median follow-up after the initial MTT was 17.8 months. According to the original criteria, total cohort were classified into FG (n=41 [19.2%], median OS=58.5 months), IG (n=109 [51.2%], median OS=33.5 months), and PG (n=63 [29.6%], median OS=17.1 months), respectively. Among IG cohort, multivariate analysis revealed that ALB <4 g/dL (hazard ratio [HR] =2.65), CRP ≥0.3 mg/dL (HR=2.86), and bone metastases (HR=2.73) were independent predictors of OS, although the remaining factors were not. IG was sub-stratified as fIG, pIG, and iIG, according to the number of predictors present: 0, 3, or other, respectively. Thus, the modified IMDC model was developed: FG&fIG (n=62 [29.1%], median OS=58.5 months) vs iIG (n=70 [32.9%], median OS=34.9 months) vs PG&pIG (n=81 [38.0%]; median OS=14.8 months). The concordance indices for the original and modified models were 0.68 and 0.73, respectively (p<0.001). Conclusions We successfully developed a modified IMDC model using a two-step process: original IMDC plus IG sub-stratification. Our preliminary data showed that PG&pIG group treated with mTORIs in second-line setting had significantly longer OS than with TKIs, based on modified model but not original model. In addition, we are seeking molecular markers for FG&fIG, iIG, and PG&pIG in the modified model, which may contribute to select of MTT as well as newly immunotherapy agents. Funding none
Authors
Suguru Shirotake
Hideyuki Kondo Yota Yasumizu Koshiro Nishimoto Nobuyuki Tanaka Keiichi Ito Kent Kanao Mototsugu Oya Masafumi Oyama |
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MP67-12 |
Clinicopathological characteristics of patients with acquired cystic disease-associated renal cell carcinoma: Central pathology results according to the 2016 WHO classification in a multi-institutional study |
Kidney Cancer: Epidemiology & Evaluation/Staging II | 17BOS |
Abstract: MP67-12 Sources of Funding: None Introduction According to the 2016 WHO classification, new entities were designated for characteristic patterns in renal cell carcinoma (RCC) in patients with end stage renal disease (ESRD), such as acquired cystic disease (ACD)-associated and clear cell papillary RCC. In this study, a central pathologist reanalyzed the pathological findings of RCC in patients with ESRD from multiple institutions, based on the new classification. Methods This study included 315 patients who underwent radical nephrectomy in 3 Japanese institutes from 1987 to 2015. A central pathologist reviewed sections from all patients according to the 2016 WHO classification. Results Based on the new classification, clear cell was diagnosed in 144 patients (46%), ACD-associated in 100 (31%), papillary in 41 (13%), chromophobe in 10 (3%), clear cell papillary in 3 (1%), MiT family translocation in 2 (1%), and unclassified in 15 (5%). We next compared clinicopathological findings of ACD-associated RCC with those of non-ACD-associated RCC. Multivariate analysis showed that independent prognostic clinical factors for occurrence of ACD-associated RCC were the presence of acquired cystic disease of the kidney (ACDK) (hazard ratio [HR]: 2×109, p<0.01), age (HR: 0.97, p=0.03), and duration of dialysis (HR: 1.06, p<0.01). We further compared pathological features in ACD-associated and other RCCs. ACD-associated included more Furman grade 3/4 (90 vs. 47%, p<0.01). In contrast, other unfavorable findings was less frequent in ACD-associated RCC, including the presence of sarcomatoid features (2 vs. 7%, p=0.04), lymphovascular invasion (3 vs. 11%, p<0.01), and necrosis (7 vs. 13%, p=0.18). Conclusions ACD-associated RCC accounts for 31% of RCC in patients with ESRD, and prognostic clinical factors for occurrence include young age, long dialysis duration, and presence of ACDK. In addition, ACD-associated RCC showed higher Furman grade, but fewer cases with other unfavorable pathological features, suggesting the need for an independent nuclear grading system for ACD-associated RCC. Funding None
Authors
Tsunenori Kondo
Toyoori Tsuzuki Naoto Sassa Hiroshi Yamada Toshio Takagi Kenji Omae Junpei Iizuka Kazuhiko Yoshida Hironori Fukuda Kazunari Tanabe |
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MP67-13 |
Pure host-related risk factors for adherent perinephric fat in healthy individuals during laparoscopic renal surgery |
Kidney Cancer: Epidemiology & Evaluation/Staging II | 17BOS |
Abstract: MP67-13 Sources of Funding: None Introduction Adherent perinephric fat (APF) is a risk factor for surgical difficulty during partial nephrectomy. No previous report has analyzed pure host-related risk factors of APF among individuals without cancer. Here, we assessed risk factors and characteristics of APF in healthy individuals. Methods Men who underwent laparoscopic donor nephrectomy between 2009 and 2014 were included in the present study. Based on retrospective review of video-recorded surgical procedures during anterior perinephric fat dissection, the severity of APF was categorized into the following three groups: non-APF (0), APF (1), and severe APF (2). The relationship between APF severity and clinical/radiographic features was evaluated. The relationship between cytokine expression in perinephric fat tissue (PAT)-conditioned medium and APF severity was also assessed using SearchLight Multiplex assays. Results Of the 92 patients, 43 (46.7%) and 8 (8.7%) were categorized as having APF and severe APF, respectively. Mean operative duration was significantly associated with APF severity (trend, P = 0.00248), and patients with severe APF had a significantly higher estimated blood loss than those without (P = 0.002). No difference in postoperative serum creatinine levels or rates of delayed graft function in recipients was observed among the three groups. Gender, body mass index, perinephric fat area, stranding, and thickness were significantly associated with severe APF. On multivariate analysis, perinephric fat area (OR, 1.189; P = 0.005) and the presence of renal stranding (OR, 14.450; P = 0.037) were identified as independent risk factors for severe APF. Of the 44 analyzed cytokines, mean levels of sIL-6R in PAT-conditioned medium were found to be significantly higher in the APF groups than in the non-APF group (P = 0.049). In a validation study with a larger number of donors (n = 48), mean sIL-6R levels remained significantly higher in both groups with APF compared to the non-APF group (P = 0.042). Conclusions Several radiographic features, such as perinephric fat area and stranding, were found to be pure host-related risk factors for severe APF. sIL-6R secreted from adipose tissues may have utility in predicting the severity of APF in patients undergoing renal surgery. Pure host-related risk factors for APF may predict difficulty during perinephric fat dissection. Funding None
Authors
Shintaro Narita
Takamitsu Inoue Mitsuru Saito Taketoshi Nara Koichiro Takayama Kazuyuki Numakura Hiroshi Tsuruta Atsushi Maeno Shigeru Satoh Tomonori Habuchi |
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MP67-14 |
Characterization of Renal Cell Carcinoma in Patients with Gastrointestinal Stromal Tumors Compared to Other Soft Tissue Sarcomas |
Kidney Cancer: Epidemiology & Evaluation/Staging II | 17BOS |
Abstract: MP67-14 Sources of Funding: Funded in part by the Sidney Kimmel Center for Prostate and Urologic Cancers and the National Cancer Institute Training Grant T32 CA082088 (MG) Introduction Prior case reports and observational studies have shown that patients with gastrointestinal stromal tumors (GISTs), a subtype of soft tissue sarcomas (STSs), are at increased risk of other malignancies, including renal cell carcinoma (RCC). The association between RCC and other subtypes of STSs has not been studied; thus, we aim to assess this relationship and report our experience on patients with RCC and GISTs. Methods We retrospectively reviewed our institutional database to identify patients with pathologically confirmed STSs and co-occurring RCC between January 1980 and June 2016. Clinical and pathologic characteristics of patients with RCC and STS subtypes were collected. Chi square analysis and Fisher’s exact test were used to compare RCC in GIST to other STSs. Results We identified 5371 patients with STSs and 402 with GISTs. Mean follow-up time was 11.4 [3.6–23.6] years. RCC had a statistically significant (p=0.009) higher co-occurrence in GIST (n=6, 1.6%) compared to other STSs (n=20, 0.40%). The GIST cohort compared with the other STS cohort had a higher proportion of metachronous occurrence (66.7% vs. 40%). In addition, when analyzing the pathologic characteristics of GISTs compared with other STSs, a higher proportion of papillary carcinoma was noted in the GIST cohort (33.3% vs. 10%). The prevalence of RCC differentiated by STS subtype was observed to be: GIST (n=6, 23%), liposarcoma (n=6, 23%), leiomyosarcoma (n=4, 15%), fibrosarcoma (n=3, 12%), and other (n=7, 27%). Clinical and pathologic characteristics of the GIST and other STS cohorts are shown in Table 1. Conclusions Diagnosis of RCC in patients with GISTs is significantly higher than those with other STS subtypes. Additionally, a higher proportion of papillary carcinoma compared with other histologies in RCC is observed in patients with GISTs, which is consistent with other reports in the literature. While the incidence of RCC in our GIST cohort is similar to the reported incidence in the general population, the differences in incidence and pathologic characteristics compared to other STSs warrant further investigation into clinical and genetic associations of GISTs and RCC. Funding Funded in part by the Sidney Kimmel Center for Prostate and Urologic Cancers and the National Cancer Institute Training Grant T32 CA082088 (MG)
Authors
Shawn Mendonca
Mazyar Ghanaat Mahyar Kashan Maria Becerra Brandon Manley Nicole Benfante Paul Russo Jonathan Coleman Aimee Crago A. Ari Hakimi |
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MP67-15 |
Surgical Treatment for Stage I Renal Cell Carcinoma: Does Treatment Facility Matter? |
Kidney Cancer: Epidemiology & Evaluation/Staging II | 17BOS |
Abstract: MP67-15 Sources of Funding: none Introduction While the use of partial nephrectomy (PN) has increased over the last decade, it is unclear if the shift has been uniform across the different types of cancer treatment facilities. This study seeks to compare the use of RN across types of Commission on Cancer (CoC)-accredited cancer programs in the United States from 2004-2013. Methods Cases of RCC were identified from the Commission on Cancer’s (CoC) National Cancer Data Base (NCDB) Participant User File (PUF) from 2004-2013. Patients with clinical stage I RCC who received either RN or PN as the primary surgical treatment at a CoC-accredited facility were included. Facility types were grouped by case volume (HV= high volume; LV=low volume) and multivariable logistic regression was used to estimate odds ratios for RN overall and stratified by tumor size across types of CoC-accredited cancer programs. Kaplan-Meier curves, Cox regression, and log-rank tests were used to characterize patient survival. Results The study population consisted of 114,057 cases (PN=52,654; RN=61,403). Academic/Research Cancer programs (ACAD) performed the most PNs (52.0%), while Comprehensive Community Cancer Programs (CCCP) performed the most RNs (50.1%). Multivariable analysis indicated that when compared to ACAD-HV facilities, cases were more likely to be treated with RN if they received care at a Community Cancer Program (CCP) (OR= 3.082, 95%CI: 2.916-3.257), Integrated Network Cancer Program (INCP) (OR= 1.629, 95%CI: 1.542-1.722), CCCP-LV (OR=3.241, 95%CI: 3.084-3.405), CCCP-HV (OR=2.115, 95%CI: 2.047-2.185), or ACAD-LV (0R= 1.771, 95%CI: 1.682-1.865). The survival curves indicate that the overall risk of death was higher for RN compared to PN across all treatment facility types. Conclusions Stage I RCC patients receiving surgical treatment at CoC-accredited cancer programs are more likely to have a RN when receiving care at facilities that are not ACAD-HV. Survival analysis indicates that the benefits associated with PN still remain, regardless of the different treatment facility types. These findings indicate variability in how stage I RCC is surgically treated across CoC-accredited treatment facilities within the United States. Research is required to further explore these differences. Funding none
Authors
Kyle plante
Telisa Stewart Dongliang Wang Thomas Schwaab Gennady Bratslavsky Margaret Formica |
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MP67-16 |
Utility of preoperative MRI in characterizing the parenchymal-tumor interface of renal masses prior to surgical intervention |
Kidney Cancer: Epidemiology & Evaluation/Staging II | 17BOS |
Abstract: MP67-16 Sources of Funding: None Introduction The optimal surgical margin for small renal masses is contested. Recognition of a circumferential, intact radiographic pseudocapsule using MRI is a novel approach to determine if minimal parenchymal resection can be performed while to maximize nephron sparing and to achieve negative margins. Our goal was to characterize the parenchymal-tumor interface (PTI) using preoperative MRI imaging and to correlate with histopathology. _x000D_ Methods We identified 42 of 200 patients who underwent preoperative MRI imaging and subsequent robotic partial nephrectomy. We characterized each RCC by defining the MRI sequence that best illustrated the PTI. We then commented on the capsule, its intactness, shape, and abutting of the collecting system. Finally, positive surgical margin status was correlated to the MRI findings. Results 14 tumors were primarily cystic, while 28 were primarily solid. Tumors that were primarily cystic most clearly showed a traditional hypointense band on T2 Haste/SSFSE (13/14). However, we found that the patients with solid masses exhibited a pseudocapsule best on T2 Postcontrast scans (15/28) (Fig. 1). A capsule of some sort was noted in all cases. The outline was circumferential around the mass in 39/42 cases and a smooth parenchymal/tumor interface was seen in 36/42 cases. Of three cases with preoperative MRI infiltration, 2 resulted in positive surgical margins. The average pseudocapsule score was a 1.92, indicating that the pseudocapsule was focally infiltrated, but not fully penetrated._x000D_ Conclusions The findings of this study suggests that both T2 Haste/SSFSE and T2 Postcontrast scans are efficacious in characterizing the PTI, but the latter is particularly helpful for solid masses. Other histological findings display that most parenchymal/tumor interfaces are smooth, circumferential, and often abutting the collecting system. The histological findings suggest that most tumors are not fully infiltrating the surrounding parenchyma, and the vast majority demonstrated negative margins when analyzed. _x000D_ These findings suggest that preoperative MRI is useful in characterizing the PTI in patients with RCC, and can provide surgeons with useful information to guide surgical technique._x000D_ Funding None
Authors
Shalin Desai
Connor Snarskis Gopal Gupta |
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MP67-17 |
Is a preoperative low ejection fraction a risk factor for complications and impaired survival in renal cancer patients who undergo surgery? Results from a propensity-score matching with non cardiopathic counterparts |
Kidney Cancer: Epidemiology & Evaluation/Staging II | 17BOS |
Abstract: MP67-17 Sources of Funding: None Introduction Little is known about the impact of reduced left ventricular ejection fraction (rLVEF) on outcomes of patients undergoing surgery for renal cell carcinoma (RCC). The aim of our study was to compare complication rate, perioperative mortality, other-cause mortality (OCM) and overall mortality (OM) between cardiopathic patients (rLVEF) and matched controls. Methods Between 1990 and 2016, 2,974 consecutive patients treated with surgery for RCC were collected into an institutional database. When LVEF was <50% at preoperative transthoracic cardiac ultrasound, patients were classified as rLVEF, according to European Society of Cardiology Guidelines. Propensity-score matching was performed between patients with rLVEF and controls without rLVEF with a 1-to-4 ratio, after adjusting for age, body mass index, comorbidities (diabetes, hypertension and Charlson Comorbidity Index) and tumour characteristics (TNM classification). Results After matching 1:4, 175 patients (35 rLVEF vs. 140 controls) were included in the analyses. In the matched cohort, no differences were recorded in terms of baseline clinical features and tumor characteristics. Low grade complications (Clavien-Dindo I-II) were reported in 20% of controls vs. 41% of rLVEF patients (p<0.01). High grade complications (Clavien-Dindo III-IV) were reported in 4% vs. 2.5% (p=0.6) in the control vs. rLVEF groups, respectively. Thirty-day and 90-day mortality rates were 1.3% and 1.4% in the control group vs. 0% and 0% in rLVEF counterparts (all p=0.9). At 1, 5 and 10 years after surgery, OCM resulted 3.2%, 12.5% and 26% vs. 0%, 17.8% and 38.3% in controls vs. rLVEF (p=0.2). Correspondingly, at 1, 5 and 10 years after surgery, OM resulted 4.9%, 22.8% and 40.4% vs. 3.3%, 34.2% and 76.7% in controls vs. rLVEF (p=0.6). Conclusions After matching, patients with rLVEF experienced more frequently minor complications (Clavien-Dindo I-II) relative to controls. However, no differences in terms of high grade complications (Clavien-Dindo III-IV) and perioperative mortality were observed after surgery when patients with preoperative rLVEF were compared to equivalent non cardiopathic counterparts. When long-term survival outcomes were taken into consideration, no difference was recorded according to cardiopathic status. Funding None
Authors
Alessandro Nini
Alessandro Larcher Fabio Muttin Emanuele Zaffuto Paolo Dell'Oglio Francesco Ripa Cristina Carenzi Giovanni La Croce Gabriele Fragasso Francesco Montorsi Umberto Capitanio Roberto Bertini |
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MP67-18 |
The Comprehensive Complication Index (CCI) is superior to the Clavien-Dindo grading system in predicting length of stay and hospital readmission following radical nephroureterectomy |
Kidney Cancer: Epidemiology & Evaluation/Staging II | 17BOS |
Abstract: MP67-18 Sources of Funding: None Introduction Complication rates following radical nephroureterectomy (RNU) are reported to occur in 20-30% of patients. The Clavien-Dindo (CD) grading system is a well-known categorical classification of complication severity. The Comprehensive Complications Index (CCI) is an alternative grading system that aggregrates all complications experienced by a patient expressed on a continuous 0-100 scale. We investigate whether the cumulative nature of CCI renders it superior to CD in predicting perioperative course after RNU. Methods The records of 532 consecutive patents who underwent RNU at 7 academic medical centers between 2005-2015 were reviewed. Complications occurring within 30 days of RNU were annotated with grading both by the CD and CCI classification systems. Logistic regression was used to determined associations between CD and CCI with perioperative covariates as well as with hospital length of stay (LOS) and readmission. Results 377 men and 219 women with a median age of 71, BMI of 27, and Charlson comorbidy score of 4 were included. 60% had an ASA score > 2, 22% were ECOG > 2, and 59% had baseline CKD stage III or greater. Approximately 75% underwent a minimally invasive RNU. Median LOS following RNU was 6.0 days (range, 1-37) and readmission within 30 days occurred in 45 (7%) patients. Overall, 136 patients (23%) experienced a post-operative complication with 91 having a single complication and 45 with multiple (range, 2-6). 44 (7%) patients had Clavien III or greater complications, and the median CCI for those patients experiencing a complication was 20.9 (range, 8.7-100). Both the upper quartile of CCI (> 75th %) and major CD complications were associated with higher Charlson score, ECOG > 2, and CKD stage > III (p for all < 0.05). However, only the upper quartile of CCI was associated with LOS (8.9 vs. 5.4 days, p<0.01) and hospital readmission (OR 3.2, p =0.02) after RNU whilst major CD complications were not (LOS 7.4 vs. 5.6 days, p=0.14; Readmission OR 1.4, p=0.21)._x000D_ Conclusions The CD and CCI classification systems both have their utility in evaluating baseline and perioperative characteristics for RNU patients. However, the continuous and cumulative nature of the CCI that accounts for complications severity appears to allow for superior prediction of perioperative course including LOS and readmission._x000D_ Funding None
Authors
Scott Geiger
Neil Kocher Dan Ilinsky Evanguelos Xylinas Peter Chang Lauren Dewey Andrew A. Wagner Firas Petros Surena F. Matin Conrad Tobert Chad Tracy Patard Pierre-Marie Mathieu Roumiguie Leonardo Lima Monteiro Wassim Kassouf Jay D. Raman |
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MP67-19 |
The nuclear grade and prognosis are unrelated to the TNM stage in multilocular cystic renal cell neoplasm of low malignant potential |
Kidney Cancer: Epidemiology & Evaluation/Staging II | 17BOS |
Abstract: MP67-19 Sources of Funding: National Natural Science Foundation of China (Grant 81172418) and Beijing Municipal Natural Science Foundation (Grant 7142160). Introduction Multilocular cystic clear cell renal cell neoplasm of low malignant potential or multilocular cystic renal cell carcinoma (MCRCC) is a rare distinct subtype of clear cell renal cell carcinoma (RCC). As a rare subtype of renal cell carcinoma, this disease was mostly reported in literature as small cases series, some features about this disease remains unclear, an unresolved issue is whether this disease should be staged as other types of RCCs due to its low nuclear grade and minimal tumor burden. The present study aimed to characterize the clinical and pathologic features of MCRCC. Methods From January 2006 to December 2014, 76 cases were identified as MCRCC among 4345 patients with RCC at our institution. Their clinical and characteristics, surgical management, pathologic features, and outcomes were retrospectively reviewed. Results The incidence of MCRCC in our patients with RCC was 1.7%. The mean age at diagnosis was 46.7±10.5 years (range,18 to 80 years). Most cases showed no symptoms. Nuclear grade was unrelated to the TNM stage (P=0.451). Of these 76 patients, 66 (86.8%) were followed up for a median of 52 months, and no tumor recurrence or metastasis was found, no differences were found in the prognosis of different TNM groups. Conclusions The incidence of MCRCC in patients with RCC is low. The nuclear grade and prognosis of MCRCC cases was unrelated to the TNM stage, suggesting that the current stage criteria might not suitable for this lesion. Patients with MCRCC have an excellent prognosis; thus, the follow-up interval after surgery can be longer to minimize unnecessary examinations. Funding National Natural Science Foundation of China (Grant 81172418) and Beijing Municipal Natural Science Foundation (Grant 7142160).
Authors
Teng Li
Kan Gong Xianghui Ning Shuanghe Peng Jiangyi Wang Qun He Xinyu Yang |
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MP67-20 |
Identifying barriers to the adoption of percutaneous renal tumour biopsy in the management of small renal masses |
Kidney Cancer: Epidemiology & Evaluation/Staging II | 17BOS |
Abstract: MP67-20 Sources of Funding: CUA Scholarship Foundation, Kidney Cancer Research Network of Canada Introduction Although the majority of small renal masses (SRMs) are malignant, up to 30% are benign. Additionally, most malignant ones have low-metastatic potential. Therefore, their management has been associated with considerable overtreatment. To reduce the associated burden of care, renal tumor biopsies (RTBs) have been proposed as a safe, accurate and reliable alternative to identify the histology of SRMs prior to treatment. However, many urologists are still reluctant to adopt RTB; consequently, most SRMs are still being managed with upfront treatment. Thus, we designed a survey study with the objectives to better characterize the uptake of RTB in the management of SRMs and to identify the barriers to a more widespread adoption of RTB. Methods The link to a web-based survey was sent to all registered email addresses of members (n=767) of the Canadian Urological Association and the Quebec Urological Association in June 2016. The survey contained questions regarding the physicians practice patterns, RTB utilization and potential barriers of RTB. Chi-squared tests were used to assess for differences between specific groups of responders (per type of fellowship training). Results In total 223 members responded to the survey (response rate of 29%). Of these, 35 were excluded because of incomplete demographic responses or because they did not manage SRMs. Of the responders, 38 (20%) practiced in an academic center, 72 (38%) in a university-affiliated center and 78 (41%) in a community/rural hospital. Only a minority of responders (12%) requested RTB in >75% of cases while 53% never performed or performed RTB in less than 25% of cases. Physicians with urologic oncology fellowship-training were more likely to request a biopsy than endourologists (p=0.01) and physicians with no fellowship-training (p=0.003). The greatest management-related barrier was the perception that biopsy won&[prime]t alter management (36%) while the risk of obtaining a false-negative or a non-diagnostic biopsy was reported as the greatest pathology-related barrier to a more widespread adoption of RTB in the management of SRMs. Conclusions RTBs continue to be under-utilized in Canada with urologic oncology fellowship-trained physicians being more likely to request them than endourologists and physicians with no fellowship-training. Despite existing evidence that RTB is a safe and useful diagnostic test, concerns about its accuracy and its ability to change clinical practice continue to be barriers to its adoption. A knowledge translation strategy is needed to address these concerns and increase the use of RTB as the first step in managing patients with SRMs. Funding CUA Scholarship Foundation, Kidney Cancer Research Network of Canada
Authors
Patrick O. Richard
Lisa Martin Luke Lavallée Phil Violette Maria Komisarenko Kunal Jain Michael Jewett Antonio Finelli |
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MP68-01 |
Effects and outcomes of ureteral stenting prior to ureteroscopy versus primary ureteroscopy in urinary stone treatment |
Stone Disease: Surgical Therapy VI | 17BOS |
Abstract: MP68-01 Sources of Funding: none Introduction Currently, only a few studies investigate the effects of ureteral stenting (JJ catheter) prior to ureteroscopy (URS). This retrospective single-center study is intended to demonstrate the role of preoperative ureter stenting in ureteroscopy in treatment for ureteral stones and to compare the stone-free rate (SFR) and therapy-associated complications of the primary URS to the URS after ureter stenting Methods We retrospectively evaluated 197 URS in our clinic from 2014 to 2015. The patients were classified into two groups, depending on whether they had a stent placed before URS. 46 patients undergo primary URS and 151 URS were pre-stented prior to URS. The intra- and postoperative results were analyzed with complications as well as stone-free rates depending on treatment details according to adapted Clavien-Dindo classification. We investigate the retrospective data from patient records, imaging and surgical reports Results 73% of the patients were pre-stented before URS, compared to 24% which were treated primarily ureteroscopically. The mean operation time in the pre-stented group was slightly longer (27.7 vs. 27.2 min). The totally stone-free rate (SFR) of the pre-stented patients was 81%, compared with 94% without preoperative stenting. The rate of minor intraoperative complications was 4.6% for pre-stented patients versus 2% without stent (adapted for Clavien-Dindo I-II classification). Major complications of the IIIb-V degree were not observed in both groups. The intraoperative complication of the primary URS group consisted of perforation of the ureter. The intraoperative complications of the pre-stented URS group consisted of 57% ureteral lesion and 43% of slight bleeding. The rate of postoperative complications was 12% for pre-stenting group versus 6.5% without stent. The postoperative complications for the primary URS group consisted of 100% of urinary tract infections. The postoperative complications for the secondary URS group consist of urinary tract infections 53% and hydronephrosis 47% Conclusions Ureteroscopic stone extraction resulted in good stone-free rates with low morbidity. Ureteral stenting before URS does not improve the stone-free rate. The few ureteral lesions could be treated without consequences by urethral stenting. The most of postoperative complications consisted of urinary tract infections and hydronephrosis. Limitations of the study include short follow-up and non-standardized treatment approach. The highest incidence of postoperative complications occurred at stone size larger from 7-8 mm. Funding none
Authors
Ilgar Akbarov
Mustafa Al-Mahmid Ali Tok Vahudin Zugor Melanie Von Brandenstein David Pfister Axel Heidenreich |
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MP68-02 |
Ureteral stricture rates associated with ureteral access sheath use for retrograde renal stone surgery |
Stone Disease: Surgical Therapy VI | 17BOS |
Abstract: MP68-02 Sources of Funding: None Introduction Ureteral access sheaths (UAS) are commonly used adjuncts to assist with stone retrieval. Despite their common use, there is limited data on long-term safety of UAS use. We sought to evaluate the observed rates of ureteral stricture following ureteroscopy with UAS compared to cases without UAS. Methods In a retrospective review, we identified 378 consecutive patients with a new diagnosis of nephrolithiasis managed with ureteroscopy between January 2014 and May 2015. Both the use of UAS and the specific sheath size were assessed (12/14 Fr or 14/16 Fr). The Cook Flexor® sheath was used in all cases. Patients were evaluated for ureteral stricture based on post-operative imaging including ultrasound, CT, MRI, and/or renal scan up to one year after surgery. Patients were excluded from the study if they underwent a concurrent percutaneous or open stone surgery, did not have appropriate follow-up imaging, or had post-operative hydronephrosis or obstruction due to another etiology. Results Of the 378 patients, 141 were excluded, primarily for inadequate post-operative imaging; 237 patients were included in the final analysis. The mean age was 54 years, with 106 women and 131 men. Of these, 81 (34.1%) cases included the use of an access sheath, with 12/14 UAS used in 39 cases and 14/16 UAS used in the remaining 42 cases. There were three (1.2 %) ureteral strictures, with mean time to diagnosis of 11 weeks. All cases occurred in the UAS group (p = 0.039) along the proximal ureter/ureteropelvic junction. When stratified by sheath size, two of the 39 cases using a 12/14 sheath developed a stricture, compared with one stricture in the 14/16 group (p = 0.6). Of the three patients with stricture, two were managed with prolonged stenting whereas the last one was lost to follow-up. Conclusions While the overall ureteral stricture rate was low (1.2 %) after ureteroscopy, there was a statistically significant increase in stricture rate with UAS. Limitations of this study include the low sample size and lack of control of confounders such as pre-stent status. Large, prospective, randomized studies are required to definitively evaluate the effect of UAS on stricture formation. Funding None
Authors
Brian Jordan
Sang Gune Yoo Aziz Khambati Kent Perry Robert Nadler |
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MP68-03 |
Urosepsis Following Ureterorenoscopy for the Treatment of Urolithiasis or Upper Urinary Tract Transitional Cell Carcinoma: A Focus on Underestimated and Harmful Postoperative Complication |
Stone Disease: Surgical Therapy VI | 17BOS |
Abstract: MP68-03 Sources of Funding: none Introduction The reported rate of infectious complications following ureterorenoscopy (URS) for the treatment of patients with either urinary stones or low-risk upper urinary tract transitional cell carcinoma (UUT-TCC) is reasonably low. We investigated the rate of urosepsis following URS in our series and looked for predictors of postoperative infectious events._x000D_ Methods We identified 99 patients submitted to URS with intracorporeal holmium:YAG laser lithotripsy for ureteral and/or renal stones (n=71) or with laser tumour photoablation for suspicion of UUT-TCC (n=28) throughout the last 12 consecutive months. A preoperative urine culture was routinely obtained and any concomitant urinary tract infection (UTI) was treated prior surgery. Antibiotic prophylaxis (i.e., second generation cephalosporin) was offered preoperatively. A ureteral access sheath 10/12 Fr was used when an intrarenal procedure was scheduled. Descriptive statistics was used to detail clinical features of the whole cohort of patients. Urosepsis was defined using the Third International Consensus Definitions for Sepsis and Septic Shock. Chi-square and independent T-test assessed differences among patients with and without urosepsis following URS. All tests were two-sided with a significance level set at p < 0.05._x000D_ Results 89 patients (89.9%) had elective admission to our department, and 10 patients (10.1%) were admitted through the emergency room. Seven patients (7.1%) developed urosepsis, four (4%) advanced to septic shock, and one (1%) eventually died. Patients who developed urosepsis compared with their counterparts who did not develop urosepsis more frequently had a stone or tumour in the intrarenal cavities rather than in the ureter (100% vs. 50%, respectively), a previous history of UTI (57.1 % vs. 13%, respectively), access to our department through the emergency room (42.8% vs. 7.6%, respectively), longer hospital stay prior to surgery (mean = 6 vs. 0.5 days, respectively), and higher burden of comorbid conditions (Charlson Comorbidity Index ≥3 = 43.8% vs. 18.4%, respectively) (all p< 0.01). Conversely, the rate of urosepsis following URS for the treatment of stones and UUT-TCC did not vary significantly (5.6% and 10.7%, respectively; p=0.4). _x000D_ Conclusions Proper counselling of patients candidate to URS for either ureteral/renal stones or UUT-TCC who have comorbid conditions or certain clinical features is mandatory, as the risk of severe urosepsis in these categories of patients is not negligible._x000D_ Funding none
Authors
Luca Villa
Filippo Pederzoli Francesco Trevisani Alberto Briganti Andrea Salonia Francesco Montorsi |
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MP68-04 |
Suctioning flexible ureteroscopic lithotripsy in the oblique supine lithotomy position and supine lithotomy position: a comparative study |
Stone Disease: Surgical Therapy VI | 17BOS |
Abstract: MP68-04 Sources of Funding: None Introduction There is no research report to compare clinical outcomes of flexible ureteroscopic lithotripsy (URS) at different body positions. We sought to compare the safety and efficacy of oblique supine lithotomy position and supine lithotomy position in suctioning flexible URS. Methods A total of 82 patients with upper urinary calculi were divided into two groups. Group 1 included 47 patients who were treated by suctioning flexible URS in oblique supine lithotomy position. Group 2 included 35 patients who were treated in supine lithotomy position. There were no significant statistical differences in the age, gender and rate of comorbidities between the two groups before surgery (p>0.05). The operative time, stone-free rates at postoperative day 30, renal pelvic pressure (RPP) ?postoperative complications (graded by the Clavien system) and length of stay were compared. Results Retrograde intrarenal surgery was successful in 73 patients in the first surgery; it was also completed successfully in other 9 patients after indwelling a double-J stent for 2 weeks. Compared with supine lithotomy position, a significantly greater stone-free rate on postoperative day 30 and a significantly shorter operative time were noted (p<0.05 each). There were no differences in complication rates of Clavien grade I and Clavien grade II, RPP and length of hospital stay (p> 0.05). Conclusions Suctioning flexible URS in the oblique supine lithotomy position is safe and more effective than the supine lithotomy position. Funding None
Authors
Leming Song
Xiaolin Deng Donghua Xie Jianrong Huang |
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MP68-05 |
SINGLE SURGEON EXPERIENCE WITH RETAINED ENCRUSTED STENTS: COMBINED ENDOUROLOGICAL APPROACH AND MODIFIED GRADING SYSTEM |
Stone Disease: Surgical Therapy VI | 17BOS |
Abstract: MP68-05 Sources of Funding: none Introduction The encrusted and retained ureteral stent represents the most challenging complication associated with ureteral stents. The aim of our study is to describe our experience in the management of retained encrusted stents using a combined endourological approach and also to suggest a modified grading system for stent encrustation._x000D_ Methods All of the procedures were carried out by the same first surgeon, who is experienced in prone and supine PCNL, retrograde ureteroscopy and retrograde intrarenal surgery. Surgical management was based on the location and the stone burden of cases (considering encrusted stents and associated stones) and of course renal function._x000D_ Between June 2010 and June 2015, all patients referred with retained and encrusted ureteral stents to our hospital were submitted to a combined endourological approach with a Galdakao-modified Valdivia positioning supine removal of the stents without need of bolster below the patient. Results Fifty patients were evaluated. Two groups were created additionaly to the grading system proposed by Acosta-Miranda et al: calcified and broken stent (stage VI - 9 cases) and isolated ureteral calcification (stage VII - 5 cases)._x000D_ Percutaneous nephrolithotripsy was common for stages III to VI and rare or not performed in stage I, II and VII, as these encrustations were usually minor and not located in the kidney and therefore did not hinder stent extraction (p=0.004). Ureterolithotripsy was commonly used for ureteral stent encrustation, especially in groups with lower stone burden (stages I and II) and stage VII (ureteral only). Length of operation was higher for groups with severe stone burden (stages III and IV - 158.1±64.8 min) when compared to moderate stone burden (stage III - 110.0±64min) and low stone burden (stages I, II, VI and VII - 78.6±29.8 min) - p value 0,0012._x000D_ Number of procedures, length of stay, blood transfusion, complications and stone analysis were similar between groups. Stone-free was worse in stages III to V, as expected, due to higher stone burden, even though not statistically significant. All stents were successfully removed in all cases (100%) by our combined endourological approach, which was the primary objective of our study._x000D_ Conclusions Galdakao-modified Valdivia positioning supine removal of retained and encrusted stents is a safe and feasible technique, with all catheters removed in a single procedure. A modified classification of the encrusted stones might help urologists to advise their patients on expected surgical outcomes. _x000D_ Funding none
Authors
Roberto Lopes
Carlos Watanabe-Silva Fabricio Beltrame Alexandre Danilovic Joaquim Claro Fabio Vicentini |
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MP68-06 |
A prospective randomized study evaluating safety and efficacy of bilateral simultaneous retrograde intrarenal surgery for endoscopic management of bilateral renal calculi. |
Stone Disease: Surgical Therapy VI | 17BOS |
Abstract: MP68-06 Sources of Funding: none Introduction To prospectively evaluate safety and efficacy of bilateral simultaneous retrograde intrarenal surgery (RIRS) for endoscopic management of bilateral renal calculi. Methods We prospectively evaluated 56 patients with bilateral renal calculi who underwent bilateral simultaneous RIRS for endoscopic management of bilateral renal calculi between June 2003 & May 2016 (study group). Placement of ureteral access sheath was preferred in all patients. 100 W holmium laser machine with 200-micron laser fiber was used with intention of stone dusting and fragmentation. A DJ stent was placed in all patients postoperatively. Stone free rate were evaluated 2-6 weeks postoperatively by combination of x-ray and ultrasonography of Kidneys. In patients who had tight ureter needing staged procedure, the data from second definitive procedure was used for analysis. Patient’s demographics, intra and postoperative data was entered in IBM SPSS Statistics 24 software and compared with 56 randomly selected patients who underwent unilateral RIRS for unilateral renal calculi at our institute (control group). Each control group patient was the one who underwent RIRS immediately after the study group patient in the sequence of RIRS patients at our institute. Results Patients demographics are shown in table 1. Study group patients had higher overall stone burden than control group. The mean duration of surgery was significantly longer in study group (P= 0.000). Despite longer operation time, the duration of postoperative catheterization and hospital stay was comparable in both groups (table 2). The intra and postoperative complications were comparable in both groups. Complete stone free rate was 78.5 % of patients in control group and 67.85 % of patients in study group (p= 0.436). Conclusions Bilateral simultaneous RIRS is safe and effective in patients with bilateral renal calculi. Funding none
Authors
Hemendra Shah
Rashmi Shah |
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MP68-07 |
1-Bilateral simultaneous retrograde intrarenal surgery in children: Is it safe and feasible? |
Stone Disease: Surgical Therapy VI | 17BOS |
Abstract: MP68-07 Sources of Funding: None Introduction Bilateral simultaneous retrograde intrarenal surgery in children has the potential advantages of omitting the need for second intervention together with reducing cost and length of hospital stay. Aim of the current study is to assess the safety and feasibility of this approach in children. Methods Twenty four children with a mean age of 11.5 years were prospectively enrolled in this study. Technique of simultaneous removal of the upper urinary tract stones on both sides consisted of removal of the stone from the kidney or the ureter of the technically less complicated side followed by the removal of the stone on the contralateral side. Stones were arranged in renal collecting system in both side (n=8), and in ureters on both sides (n=10) and the remaining (n=6 pts) on one side in the kidney, another side in the ureter. Results Mean stone size of both renal unit and ureter ranged from 8 to 22 (14.6 mm) and 5-12 (7.2 mm) respectively. Mean operating time was 98 minutes. Mean hospital stay was 2.4 days. Stone free rate was 83.3% after a single session. Complications included ureteric perforation and extravasation (n=2), postoperatively, moderate hematuria (n=4) and febrile UTI (n=2) requiring intravenous antibiotics. Four patients (16.6%) needed auxiliary procedures for complete recovery of the residual stones in the form of ESWL (n=3) and PCNL (n=1) Conclusions Bilateral simultaneous retrograde intrarenal surgery in children is safe and feasible with good stone clearance and low morbidities. It eliminates the need for repeated anesthesia and psychological stress associated with multiple interventions. However, this practice should be restricted to tertiary referral centers with high stone volume. Funding None
Authors
Ahmed fahmy
Moustafa Elsawy Amr Kamal hazem Rhasad |
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MP68-08 |
Positional manipulations to facilitate success during retrograde intrarenal surgery in children using semi rigid ureteroscopy |
Stone Disease: Surgical Therapy VI | 17BOS |
Abstract: MP68-08 Sources of Funding: None Introduction The use of retrograde intrarenal surgery (RIRS) in children for management of upper tract urinary stones is on the rise. This is best accomplished by flexible ureteroscopy and laser lithotripsy; however, this might not be feasible in centers of limited resources. We present our experience with RIRS using semirigid ureteroscopy with the help of positional maneuvers to facilitate success of RIRS Methods Fifty children underwent RIRS and laser lithotripsy with the aid of series of kidney position manipulations including: manually uplifting the kidney by flank elevation, pushing the kidney down by anterior abdominal wall pressure, rotating the kidney medially or laterally by manual pressure in the lateral flank or midline, placing the patient in Trendelenburg or reverse Trendelenburg position, altering respiratory rate and tidal volume and use of syringe pressurized irrigation or suction to alter stone position and help getting stone in the target zone of the ureteroscopy. Results Twenty seven children had a renal pelvic stone, 12 with upper calyceal stones, 7 with middle calyceal stones and 4 with lower calyceal stones. Forty two (84%) patients were rendered stone free with the help of positional manipulation described. No intraoperative complication except for mild extravasation in two cases. Mean operative time was 52 minutes. Five patients of febrile UTI and two cases of moderate hematuria successfully managed conservatively in postoperative period. Conclusions Positional manipulation for RIRS using semirigid ureteroscopy in children is a successful and cost effective approach with low complication rates. However, this approach might not be possible when ureteric or pelvicalyceal anatomy is unfavorable. Funding None
Authors
Ahmed fahmy
Moustafa Elsawy Amr Kamal hazem Rhasad Abdelrahman Zahran |
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MP68-09 |
Continuing Aspirin Does Not Increase Blood Loss From Percutaneous Nephrolithotomy |
Stone Disease: Surgical Therapy VI | 17BOS |
Abstract: MP68-09 Sources of Funding: None Introduction Patients with vascular or cardiac disease may benefit from continuing antiplatelet therapy during surgery. Percutaneous nephrolithotomy (PCNL) is a transparenchymal procedure that can be associated with significant bleeding. Recent studies have demonstrated safety with continuing aspirin during PCNL. However, these studies were notable for patients having large postoperative nephrostomy tubes that may have provided additional hemostatic control. Here, we evaluated our experience with continuing aspirin in patients undergoing PCNL. Methods All patients that underwent PCNL over the last 3 years were evaluated. Hematocrit levels were recorded preoperatively, one hour after surgery and on postoperative day 1. Clinical and demographic parameters were recorded. Statistical difference was assessed using Student’s t-test and chi-square test._x000D_ Results 218 patients underwent PCNL during this time period. 20 patients continued aspirin through surgery and an additional 20 stopped aspirin one week prior to their procedure. No difference in mean hematocrit decrease was noted between patients that never took aspirin, those that stopped and those that continued on postoperative day 0 (-2.40% vs. -2.62% vs. -2.38%, respectively, p = 0.86) or postoperative day 1 (-2.37% vs. -2.94% vs. -2.11%, p = 0.34). No significant difference in preoperative platelet count, operating room time, estimated blood loss, and postoperative nephrostomy tube size (16 French) was noted between the groups._x000D_ Conclusions Continuing aspirin through PCNL does not appear to lead to increased bleeding. _x000D_ Funding None
Authors
Timothy Tran
Egor Parkhomenko Julie Thai Kyle Blum Mantu Gupta |
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MP68-10 |
Perioperative aspirin use during percutaneous nephrolithotomy (PCNL): our single center experience. |
Stone Disease: Surgical Therapy VI | 17BOS |
Abstract: MP68-10 Sources of Funding: none Introduction The rates of heart disease and nephrolithiasis continue to increase in the United States. As more patients on aspirin for secondary prevention present with large kidney stones, urologists are increasingly faced with the decision to proceed with the less effective but lower risk ureteroscopy or the higher risk but more effective percutaneous nephrolithotomy (PCNL). Leavitt, Smith, and Okeke recently published their experience performing PCNLs on seventeen patients continued on aspirin perioperatively and concluded that the procedure was safe. We wish to add our center's experience to this body of knowledge. Methods We retrospectively reviewed our single center, single surgeon, experience of 199 PCNLs performed between January 2013 and September 2016. Hemoglobin pre- and post-operatively was recorded as were the relevant related variables of age, sex, BMI, operative duration, skin-to-stone distance, stone size, aspirin dose, aspirin indication, number of blood transfusions, and Clavien-Dindo complication classification. Correlations between hemoglobin and explanatory variables were then explored with linear regression and the Wilcoxon rank-sum test. Results Of the 199 PCNLs performed at our institution in the range of our study, 27 procedures on 23 patients were conducted without discontinuing aspirin perioperatively. Coronary artery disease was the most common indication for aspirin use. In 24 cases, the patient was on 81 mg of aspirin perioperatively with the remaining three patients on 325 mg of aspirin daily. The average patient experienced a 1.3 g/dl drop in hemoglobin perioperatively. The largest drop was 4.1 g/dl, but the lowest post-operative hemoglobin was 8.2 g/dl. No significant associations were found between hemoglobin decline and age, sex, BMI, operative duration, skin-to-stone distance, or stone size. There were no Clavien-Dindo grade III or higher complications in the course of our review, and no patients required a blood transfusion or embolization. In one case, a patient required a three day inpatient stay following stent removal for continuous bladder irrigation after developing gross hematuria but this resolved spontaneously. Conclusions In our single center experience, PCNLs performed on patients taking aspirin perioperatively were not associated with the need for blood transfusion nor the occurrence of high-grade complications. It is our experience that this practice is safe when performed by expert hands. Funding none
Authors
Joshua Ebel
Bodo Knudsen |
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MP68-11 |
A prospective, Randomized Trial evaluating the efficacy of two different Hemostatic sealant in Tubeless Percutaneous Nephrolithotomy |
Stone Disease: Surgical Therapy VI | 17BOS |
Abstract: MP68-11 Sources of Funding: none Introduction We performed a prospective, randomized trial to assess the safety and efficacy of Tisseel®, Tachosil® in tubeless percutaneous nephrolithotomy. Methods A total of 75 patients undergoing tubeless percutaneous nephrolithotomy(PCNL) were randomized to receive Tisseel®, Tachosil® and control at the end of the procedure. _x000D_ The three groups were comparable in age, sex, height, weight, body mass index, stone size and in metabolic and anatomic features. (Table 1) After stone clearance, at the end of the procedure, the nephrostomy tract was closed with a deep #1-0 silk stitch in group 1 patients. Tisseel sealant was loaded and introduced into nephrostomy tract in group 2 patients. In group 3 patients, Tachosil was dipped in contrast medium, rolled like a cigarette and inserted through the nephrostomy tract. The primary end of this study was to evaluate the efficacy of sealants in PCNL. And, the secondary end was compliance of sealants by pain and hospital stay._x000D_ Results There were no differences in the hemoglobin decrease and blood transfusion requirement among the groups during the operation. (Table 2) Serial changes in hemoglobin were comparable among the groups during the hospital stay. (Table 3) There was no significant difference in the extent of postoperative perirenal hematoma formation. (p=0.694) (Table 4) The average visual analog scale pain score on postoperative 1 day were 1.92±2.47, 1.72±1.67 and 1.48±1.73 respectively in each group. (p=0.378) The hospital stay were 2.28±0.93, 2.00±0.96, and 2.04±0.99 (p=0.579) in each group. No long-term sequelae were observed in the median follow up period of 24 months in any patient. Conclusions This study indicates that the hemostatic agents in standard tubeless PCNL were not expected to be effective or mandatory. Additional wide, prospective, randomized studies are required to get more fine clinical evidence for the hemostatic agent usage in tubeless PCNL. Funding none
Authors
YONG SUN CHOI
Kyu Won Lee Woong Jin Bae Sung-Dae Kim Sung-Hoo Hong Ji Youl Lee Sae Woong Kim Hyuk Jin Cho |
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MP68-12 |
STONE MORPHOMETRY: TRACT (S) AND STAGE (S) PREDICTOR FOR PERCUTANEOUS NEPHROLITHOTOMY |
Stone Disease: Surgical Therapy VI | 17BOS |
Abstract: MP68-12 Sources of Funding: None Introduction There is no consensus for the term "staghorn calculi", "partial" or "complete", are designations that do not imply any volume judgment. "Staghorn morphometry", is defined as the stone volumetric burden distribution in the collecting system. Objective. Determine "stone morphometry" by preoperative computed tomography (CT). Methods Retrospective-analytical study. 46 patients, 2012-2016, CT at all. Using OsiriX Software, measurement of: Total stone volume (TSV: volume calculated with the reconstruction of the entire image of the stone), entry calix stone volume (ECSV: component of stone in entry calix), favorable calix stone volume (FCSV: component of stone in favorable calix). Results It was observe: TSV: 2753 ± 1423 mm3 and 56867 ± 26781 mm3 (p=<0,001), ECSV: 580 ± 474 mm3 and 17586 ± 13150 mm3 (p=<0,001), FCSV: 589 ± 569 mm3 and 17900 ± 13717 mm3 (p=<0,001), in cases with single and those with ≥ 2 tracts, respectively. TSV >5000 mm3, has 8 and 60 times greater risk for ≥2 stages and/or tracts, necessaries for stone free rates (CI 95: 2,05-33,16 and 9,01-40,16). Conclusions Stone morphometry, provides the volumetric stone distribution to be treated, and significantly influences to determine the number of tracts and/or stages necessary to achieve a stone free rate in patients with staghorn calculi who underwent percutaneous nephrolithotomy. Funding None
Authors
Jorge Sedano-Basilio
LUIS TRUJILLO-ORTIZ CARLOS MARTÍNEZ-ARROYO CARLOS PACHECO-GAHBLER |
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MP68-13 |
Outcomes of patients with radiographic xanthogranulomatous pyelonephritis managed with percutaneous nephrolithotomy |
Stone Disease: Surgical Therapy VI | 17BOS |
Abstract: MP68-13 Sources of Funding: none Introduction Xanthogranulomatous pyelonephritis (XGP) presents an imaging challenge, as the true diagnosis is usually confirmed histologically after nephrectomy. Patients with radiographically diagnosed XGP but with other circumstances that make nephrectomy an undesirable choice can include those with a solitary kidney, poor overall renal function, or the rare case of bilateral disease. Herein we describe our experience managing these types of patients with percutaneous nephrolithotomy (PCNL). Methods We reviewed the charts of all patients diagnosed with radiographic or pathologic XGP (n=32) at a single institution from 2009 to 2015. Patient demographics, stone characteristics, and laboratory data including renal function and microbiology were recorded. Outcomes of patients treated with PCNL including surgical complications and post-operative renal function were analyzed. Results We identified 11 patients (34.4%) who were diagnosed with XGP and managed with PCNL, including 2 patients with bilateral findings (total 13 renal units). Mean age was 39.1 ± 12.6 years, 91% were female, mean body mass index was 27.7 ± 8.0 kg/m2, and 55% were diabetic. Median follow up was 38.5 months (IQR 12.9-64.1). A pre-operative nephrostomy tube was placed in 82% of patients and all patients had pre-operative urinary tract infections (UTI), although there was only 45% concordance between pre-operative urine and stone cultures. The mean operative time was 4.1 hours. Table 1 lists post-operative outcomes. The majority of patients (91%) had residual stones, although residual stone growth or new stone formation was rare (8%). Recurrent UTIs were seen in the majority of patients (55%). One kidney (8%) in a patient with bilateral findings was removed due to poor function. Four patients (36%) had post-operative complications: 2 Clavien grade II for additional antibiotics, and 2 Clavien grade IV for intensive care unit admissions due to infection. Conclusions For select patients with radiographically diagnosed XGP, PCNL is a feasible alternative to nephrectomy to preserve ipsilateral renal function, although post-operative infectious complications are common. A larger series of patients with longer-term follow-up will further elucidate the outcomes for this selective management strategy. Funding none
Authors
Noah Canvasser
Aaron Lay Shuvro De Arthi Satyanarayan Elysha Kolitz Margaret Pearle Jodi Antonelli |
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MP68-14 |
SUPINE MINI PCNL – ARE WE LOOKING AT A RECOURSE TO STANDARD PCNL? - A SINGLE CENTER EXPERIENCE |
Stone Disease: Surgical Therapy VI | 17BOS |
Abstract: MP68-14 Sources of Funding: none Introduction _x000D_ _x000D_ A standard Percutaneous Nephrolithotomy is the standard of care for renal calculus especially those more than 2 cm, which involves the patient in prone position with percutaneous access. In addition to this technique various techniques of using miniaturised scopes and instruments have been described in both prone and supine position.We present our series of mini PCNL in supine postion._x000D_ _x000D_ _x000D_ _x000D_ A observational study was done to evaluate the efficacy, safety and outcomes of supine mini PCNL(smPCNL) in our patients Methods 200 patients underwent smPCNL over a period of 3 years including both retrsospective and prospective cohorts were analysed. Data collection included stone size & location, anaesthesia & operative time, use of stent/ureteric catheter, length of hospital stay, stone clearance & complications.Cases were performed using mini PCNL set, in Galdakao-modified Supine Valdivia / modified supine position using fluoroscopy. Success was defined as patients free of stones or with residual stone fragments <5mm. Results The mean stone size was 2.7 cm. There were 36 cases with stone located in a single calyx, while 4 case with stones in multiple calyces . Pelvic stones were 50 in number, while pelvi-calyceal/pelvi-uretric stones were 61 in number. 28 upper uretric stones with 17 bilateral renal unit stones were present; while there were 4 each of upper calyceal diverticulum stone and upper ureter plus calyceal stone. 93% of the cases required a single puncture while frequency of lower calyceal and middle calyceal puncture was 53% and 42 % respectively. Complete stone clearance was achieved in 190 cases (95%) with 10 cases having residual fragments which were treated with ESWL. 30 cases had simultaneous PCNL & URS for stone clearance. 75% cases were totally tubeless. Mean hospital stay was 2.15 days & overall complication rate was 9% which included bleeding, sepsis etc.5% of patients were discharged from the day care room. Conclusions smPCNL is safe and effective in suitable patients and offers good stone clearance with minimal morbidity. Funding none
Authors
Arunkumar Balakrishnan
Kulthe Ramesh Seetharam Bhat Priyank Shah R Gaurav Gyvi |
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MP68-15 |
Supine percutaneous nephrolithotomy for staghorn calculi – prospectively recorded experience in a single tertiary referral endourology unit |
Stone Disease: Surgical Therapy VI | 17BOS |
Abstract: MP68-15 Sources of Funding: none Introduction Clearing staghorn calculi can take multiple procedures and multiple modalities with significant associated morbidity. In order to evaluate the safety and effectiveness of sPCNL for staghorn stones, we prospectively recorded patient characteristics, operative details and outcomes of these cases over a nine-year period. _x000D_ Methods We present our experience of supine percutaneous nephrolithotomy (sPNCL) for staghorn calculi performed at a single tertiary referral endourology unit, by two senior endourologists. Data were prospectively recorded in a pre-designed anonymised database._x000D_ Basic demographic information, detailed radiological information regarding stone size, number and position and comorbid information were entered, followed by post-operative entry of operative detail, stone clearance, following CT imaging, within 3 months post-sPCNL and complications, were graded according to the Clavien-Dindo classification._x000D_ Results 74 patients underwent sPCNL for staghorn calculi between February 2007 and August 2016. These included 32 (43%) female and 42 (57%) male patients, with a median age of 58 (range 18-82), median BMI of 27 (20-46) and median Charlson Comorbidity Index of 2.5 (0-8)._x000D_ 13 (18%) of patients had partial staghorn and 61 (82%) had complete staghorn calculi. Median stone density on CT was 970 Hounsfield Units (306-2032). _x000D_ Multiple access tracts were used in 9 (12%) patients. 43 (58%) had primary access in the lower pole, 17 (23%) in the interpolar region and 14 (19%) in the upper pole. Median operative time was 90 minutes (35-240). 50 (68%) patients had a ureteric stent placed intraoperatively._x000D_ After a single procedure, stone clearance (residual fragments <2mm on CT, within 3 months postoperatively) was achieved in 39 (53%) of patients. 15 (20%) complications (Clavien-Dindo Grade II or above) were recorded, including 7 (10%) UTI or sepsis and 2 (3%) bleeding requiring transfusion._x000D_ Conclusions sPCNL for staghorn calculi is safe and effective in appropriately selected and counselled patients. In particular, patients should be advised that multiple procedures may be required in order to achieve clearance and that complication rates, including bleeding and infection are higher than for less complex stones. _x000D_ Funding none
Authors
John Withington
David Curry Sarah Tang Asheesh Kaul Helena Gresty Anthony Goode Nick Woodward Dominic Yu Anuj Goyal Rajesh Kucheria Darrell Allen Leye Ajayi |
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MP68-16 |
Percutaneous Nephrolithotomy Accessed by SVOF Two-step Dilation with Ultrasound-guided Prone Position Puncture for 11 507 Patients |
Stone Disease: Surgical Therapy VI | 17BOS |
Abstract: MP68-16 Sources of Funding: none Introduction Objective: To evaluate the efficiency and validity of type-B ultrasound guided prone position percutaneous nephrolithotomy (PCNL) accessed by two-step dilation. Methods Methods: A total of 11 507 patients with 12 203 kidneys or upper ureter calculi underwent PCNL accessed by two-step dilation percutaneous nephrolithotomy between June 2006 to Sept 2016, including 524 patients with solitary kidney, 204 with kidney cysts, 132 with horseshoe kidney, 78 with vertebral column deformity, 84 with medullary sponge kidney and 12 transplanted kidney. Stone burdens were (46.1± 34.5) mm in length. Results Results: 98.1% of 12 203 operations were successful in one-session access, in which 10 922 PCNLs were accessed by single tract (89.5%), 1 048 by double tracts (8.5%) and 87 by triple-tracts (0.7%). The mean operating time was (65.4± 31.8) min, the mean first accessing time were (16.5±12.0) min and the mean calculi-dealing time were (36.1± 52.4) min. The stone-free rate after one session operation was 98.2% for single calculus and 71.4% for multiple or staghorn calculi. Of all the kidneys, 1 122 (9.2%) accepted another PCNL to remove the residual calculi, and the last stone-free rate of PCNL was 87.5%. During and after operation, 156 cases (1.2%) needed transfusion, 89 (0.7%) underwent selective embolization of renal artery. No injury of organs occurred except for 9 (0.07%) cases with pneumatothorax and 9 (0.07%) with septic shock. Conclusions Conclusion: PCNL accessed by SVOF two-step dilation with ultrasound-guided prone position puncture is effective and safe. Funding none
Authors
xiao yu
ejun peng shaogang wang zhangqun ye |
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MP68-17 |
The clinical safety and feasibility for ultrasound guided paravertebral block anesthesia of percutaneous nephrolithotomy |
Stone Disease: Surgical Therapy VI | 17BOS |
Abstract: MP68-17 Sources of Funding: none Introduction To evaluate the clinical safety and feasibility for ultrasound guided paravertebral block anesthesia of percutaneous nephrolithotomy Methods Between December 2015 to May 2015, 58patients with renal or ureteral calculi came to our department and performed percutaneous nephrolithotomy. Men 33 cases, women 25 cases, aged 23-66, an average of 38.7 years. Stone of maximum diameter of 1.2 ~ 4.3 cm, the average (2.35 + 0.43) cm. 7 cases of previous ipsilateral renal surgery. All of the 58 patients were performedT10/T11?T11/T12 and T12/L1paravertebral block anesthesia guided by ultrasound. The time to identify the exact vertebra level and perform block were recorded. Subjective symptoms were monitored during operation. Muscular strength and pain score was checked after the operation Results Ultrasound guided thoracic-lumbar paravertebral block was performed successfully in all of the 58 patients with no complications. The time to identify the exact vertebra levelwas30±12s. The time to perform nerve block was 7±2min.None of the 58 patients complained pain during surgery. Operation time was 67 + 39min. After operation, ipsilateral lower extremity muscle strength grade IV in 9 cases, grade III in 46 cases, grade II in 3 cases. Postoperative hospital stay was 3 ~ 7 d, with an average (3.4 + 1.3) d. Stone-free rate84.5% (49/58). Conclusions Ultrasound guided paravertebral block can provide safe and reliable surgical anesthesia for percutaneous nephrolithotomy, which is worth widely clinical application and spread. Funding none
Authors
jia hu
xiao yu shaogang wang |
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MP68-18 |
“DOES SPLITTING OF PAPILLA MATTER DURING PCNL?” A PROSPECTIVE STUDY |
Stone Disease: Surgical Therapy VI | 17BOS |
Abstract: MP68-18 Sources of Funding: none Introduction The ideal puncture provides the shortest and straightest access to all calculi, avoids major vessels, bowel and lung, follows the axis of the calyx, causes minimal parenchymal damage and is bloodless. It is well accepted that best way to access the pelvicalyceal system is through the tip of the papilla. We describe the ‘split papilla’ which provides endoscopic evidence of a correct puncture. _x000D_ _x000D_ The objective was to study the hemoglobin fall and blood transfusion rate between split papilla group versus non split papilla group. Methods _x000D_ All punctures were done by using the triangulation technique using fluoroscopy. Tracts were dilated using a balloon dilator. Once the stone was cleared the Amplatz was withdrawn into the tract to visualize the split papilla. Which appeared as triangular flaps with straight lines converging towards the apex. We compared endoscopic time, drop in hemoglobin and transfusion rate in those patients in whom the split papilla( Group A) was demonstrable versus those in whom it was not( Group B). _x000D_ Results During the study period 123 patients underwent PCNL. 45 patients did not have split papilla, 78 patents had split papilla. All the parameters were matched in both groups. The average fall in hemoglobin in Group A was 1.4 (SD1.06) and in group B was 2.2( SD 0.9), p-value 0.001. None required blood transfusion in both the group. Conclusions Blood loss was significantly lesser in patients where a split papilla could be demonstrated. A careful search for this finding can provide the surgeon with a quality control tool to assess the PCNL puncture. Funding none
Authors
Venkatesh Krishnamoorthy
MG Pradeepa Maneesh Sinha |
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MP68-19 |
Bilateral single session percutaneous nephrolithotomy: Is it worth the risk? |
Stone Disease: Surgical Therapy VI | 17BOS |
Abstract: MP68-19 Sources of Funding: none Introduction We wanted to evaluate our outcomes of a single-session bilateral PCNL procedure during 16 years of practice. Methods Between 2000 and 2016, 85 patients underwent 89 bilateral Percutaneous Nephrolithotomy (PCNL) procedures. In this study we collected the epidemiological and clinical data of the patients and the intervention results. A successful treatment was defined as a stone free kidney or with a stone fragment of less than 5 mm and no need for an additional procedure within 1 year of initial treatment. Results Patients' age range was 1.5-87 years (mean 53.2, median 54), 42 women and 43 men. The mean and median hospitalization days ware 11. Seventeen patients (19%) were known to suffer from metabolic disorders. There was one patient with abnormal anatomy in both kidneys and five patients with abnormal anatomy in one kidney. The mean stone burden per kidney was 23 cm3 and the median was 8 cm 3. The mean and median operating time was 198 and 185 minutes respectively. Postoperative complications were noted in 64 patients divided by Clavien score: grade I - 20 % (13), grade II - 44% (28), grade III - 33% (21), grade IV - 0%, grade V - 3% (2). The most serious complications included: bleeding that required blood transfusion in 25% (21), pneumothorax that required drainage in 6% (5), pleural effusion that required drainage in 13% (11), sepsis 4.7% (4), two patients died during their hospital stay (one aged 74 had urosepsis, the other aged 88 died of pulmonary emboli). Overall, 75% of the operated kidneys, and 63% of the procedures achieved either a stone free state or insignificant stone without the need for further intervention. Conclusions Bilateral PCNL allows most patients with a very large stone burden to be fully treated in one session and achieve complete recovery. However, these procedures have a high rate of complications, including death. Therefore, patient selection and meticulous technique is of paramount importance. Funding none
Authors
Oleg Goldin
Sergiu Bistritchi Tareq Aro Ariel Zisman Gilad E. Amiel Michael Mullerad |
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MP68-20 |
Interobserver variability among surgeons and radiologists in assessment of Guy’s stone score and S.T.O.N.E. nephrolithometric score: a prospective evaluation. |
Stone Disease: Surgical Therapy VI | 17BOS |
Abstract: MP68-20 Sources of Funding: None Introduction Several scoring systems have been developed to assess stone complexity in patients undergoing percutaneous nephrolithotomy (PCNL) which may help in preoperative patient counselling, surgical planning and stratification of outcomes . Their precise role is yet to be established; moreover, the associated interobserver variability may lead to poor reproducibility of these scoring systems. The present study aims at assessing the interobserver variability among the surgeons performing the PCNL and compares with scoring done by the radiologists for the Guy’s stone score and S.T.O.N.E. nephrolithometry score. Methods Patients undergoing PCNL between February 2016 and September 2016 were prospectively enrolled. Preoperative computed tomography was done in all patients. The Guy’s stone score and S.T.O.N.E. nephrolithometry score were independently calculated by 8 surgeons (5 consultants and 3 residents) and 4 radiologists (2 consultants and 2 residents). All patients underwent either standard PCNL or mini PCNL by one of the 5 surgeons (consultants). Consistency among the scores was assessed using Cronbach’s alpha. Receiver operative characteristic (ROC) curve was used to predict the stone free rate (SFR) using average scores of the surgeons as well as the radiologists individually. Results 157 patients underwent PCNL during this period. The SFR was 71.3% (112/157 patients). Cronbach’s alpha among the 8 surgeons and 4 radiologists was 0.957 and 0.994 respectively. ROC curve revealed that the S.T.O.N.E. nephrolithometry score of the surgeons (AUC = 0.806) as well as the radiologists (AUC = 0.810) had better predictive accuracy as compared to Guy’s stone score by surgeons (AUC = 0.738) and the radiologists (AUC = 0.747). Conclusions The S.T.O.N.E. nephrolithometry score has superior reproducibility among the surgeons and radiologists and is a better indicator of SFR compared to the Guy’s stone score. Funding None
Authors
Aneesh Srivastava
Priyank Yadav Sanjoy Sureka Uday Singh Rakesh Kapoor M S Ansari Hira Lal Prabhakar Mishra |
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MP69-01 |
Antimuscarinic use in the elderly: a poisoned apple? |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making III | 17BOS |
Abstract: MP69-01 Sources of Funding: none Introduction Overactive bladder (OAB) is characterized by urinary urgency, frequency, nocturia, and urinary incontinence (UI). The prevalence of OAB increases significantly with age. The first-line therapy for OAB is antimuscarinic medication, some of which have deleterious side-effects, including cognitive decline. We sought to examine the incidence and prevalence of antimuscarinic prescriptions among elderly persons ? age 65._x000D_ Methods The 2006-12 National Ambulatory Medical Care Survey (NAMCS) were queried for patients with newly given or renewed prescriptions for any of 6 antimuscarinics: oxybutynin, tolterodine, fesoterodine, darifenacin, solifenacin, and trospium. Within these cohorts, frequencies of patient/physician attributes and annual trends in drug prescription were determined utilizing drug-mention weighting methodology. Results A weighted estimate of 47.68 million individuals (unweighted n=1,968) had their antimuscarinics renewed, and 12.77 million patients (unweighted n=641) received a new prescription (Table 1). The majority of new antimuscarinics were prescribed in elderly (? age 65) (55.2%), female (69.2%), white (61.7%), and Medicare insured (84.1%) individuals. Oxybutynin was a frequently prescribed (incidence 27.3%) and continued (prevalence 33.2 %) antimuscarinic among elderly patients. In 2010, there was a sharp decrease in the number of all continued antimuscarinic prescriptions, followed by annual increases in oxybutynin continuation versus continued decline in other antimuscarinic continuation (Figure 1).Figure 1: Continued Antimuscarinic Prescriptions in Patients > 65 Years of Age, NAMCS 2006-2012_x000D_ Conclusions We found alarmingly high prescription rates of oxybutynin (27.3%), pharmacologically the least suitable antimuscarinic, for which studies have consistently demonstrated higher rates of cognitive impairment in the elderly. Frequent oxybutynin prescription is likely driven by tiered Medicare formularies which require patients to trial oxybutynin, a cheaper, generic antimuscarinic, before allowing access to newer, more costly yet safer, antimuscarinics. This work is the first population-based study demonstrating both the alarming rate of oxybutynin prescription and the lack of a proper safety net for a growing and vulnerable elderly population. Our work demands an increased consideration of the possible deleterious effects of unmonitored antimuscarinic use in elderly patients. Funding none
Authors
Daniel Pucheril
Christian P. Meyer Patrick Karabon Humphrey Atiemo Mani Menon Quoc-Dien Trinh Bilal Chughtai |
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MP69-02 |
Variation in Care Intensity for Overactive Bladder Symptoms Among Medicare Beneficiaries |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making III | 17BOS |
Abstract: MP69-02 Sources of Funding: NIH/NIA GEMSSTAR program (R03AG048130) and American Geriatric Society Dennis W. Jahnigen Career Development Award (Scales). Introduction Overactive bladder (OAB) affects up to 40-50% of older men and women. OAB diminishes quality of life through its impact on daily living and emotional well-being, even in the absence of urine loss. The economic costs of treating patients with OAB are projected to exceed $80 billion annually by 2020, more than half incurred by Medicare beneficiaries. Our objective was to describe variation in downstream care intensity after initial treatment of OAB symptoms among Medicare Part D beneficiaries. Methods We performed a retrospective cohort study of beneficiaries using the Medicare 5% sample. Between 2007-2013, we identified beneficiaries with an outpatient encounter consistent with OAB symptoms and a Medicare Part D drug claim for pharmacotherapy. Subjects with urinary tract infection within 30 days, neurogenic bladder, and prostate cancer diagnoses were excluded. No subject had a prior OAB drug claim. We followed beneficiaries for two years after initial treatment. We used OAB-specific expenditures as a proxy for care intensity. Using a multivariable Poisson regression model with a log link, we identified associations between patient and provider characteristics and downstream OAB Medicare costs. All expenditures were inflation-adjusted to 2013 dollars. Results During the study period, 5,337 beneficiaries had an initial drug claim and 2 years of continuous follow up. The average beneficiary was aged 78 ± 7.1 years, 80% were female, and 89% were white. In multivariable models, expenditures for Medicaid-eligible beneficiaries were 35% higher (95% CI 20-52%, p<0.001). Expenditures for individuals initially treated by urologists were 23% higher (95% CI, 11-37%, p<0.001) than those initially treated by primary care, even after controlling for urinary incontinence. Urodynamic evaluation was much more likely under the treatment of urology or gynecology specialists. Once individuals initiated treatment with a given specialty (e.g., gynecology), the vast majority continued treatment within that specialty, rather than returning to primary care. Conclusions Downstream OAB treatment costs vary by both patient and provider characteristics, and particularly by provider specialty, even after controlling for the presence of incontinence. Individuals are unlikely to change between specialties once treatment is initiated. To the extent that these data represent unwarranted variation in care intensity, an opportunity to improve efficiency and value of care may exist. Funding NIH/NIA GEMSSTAR program (R03AG048130) and American Geriatric Society Dennis W. Jahnigen Career Development Award (Scales).
Authors
Charles Scales Jr
Melissa Greiner Lesley Curtis Brad Hammill Andrew Peterson Cindy Amundsen Kenneth Schmader |
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MP69-03 |
Use of pelvic floor rehabilitation in a statewide quality improvement collaborative: Patient and cost characteristics |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making III | 17BOS |
Abstract: MP69-03 Sources of Funding: Blue Cross and Blue Shield of Michigan Introduction Clinical trials have suggested that pelvic floor rehab (PFR) can improve early urinary control following radical prostatectomy. However, the details surrounding its use in clinical practice and its contribution to cost and value are not well understood. In this context, we examined the use of PFR in a diverse statewide quality improvement collaborative, including patient characteristics, implementation patterns, and costs. Methods Using registry data from the Michigan Urological Surgery Improvement Collaborative and claims data from Michigan Value Collaborative, we identified all men who underwent a laparoscopic radical prostatectomy from 04/2014 through 11/2015 with insurance from Medicare or a large commercial payer. All men reported pre-operative urinary function using the STAR questionnaire with scores ranging from 0 (worst) to 21 (best). We compared patient demographics, cancer characteristics, pre-operative urinary function, and 90-day total episode costs of patients who did and did not receive PFR. Results 142 men met our inclusion criteria, of whom 53 (37%) received pelvic floor rehab. There were no differences in patient or cancer characteristics among patients who did and did not receive PFR. Patients initiated PFR an average of 34 days after discharge (range 15-83 days). Mean baseline urinary function scores were worse for PFR patients (17.8 vs 19.3, p=0.01). Ninety-day episode costs were similar in the two cohorts, with PFR contributing an average of $422, or 3% of total episode costs. Conclusions In a statewide collaborative, PFR is used in the minority of cases, but its use appears to be concentrated among patients with worse baseline urinary function. Incremental costs from PFR are modest, accounting for 3% of 90-day episode costs. In the era of value-based care, decisions about further expanding this therapy will depend on studying its comparative impact on post-operative patient reported outcomes in large groups of non-clinical trial patients. Funding Blue Cross and Blue Shield of Michigan
Authors
Deborah R. Kaye
John Syrjamaki Chad Ellimootil M Hugh Solomon Take Kim Susan Linsell Khurshid R. Ghani David C. Miller James E. Montie James M. Dupree for the Michigan Urological Surgery Improvement Collaborative |
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MP69-04 |
Identification of Modifiable Risk Factors Associated with Patient-Reported Erectile Dysfunction to Enhance Patient Health Counseling and Sexual Quality of Life |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making III | 17BOS |
Abstract: MP69-04 Sources of Funding: none Introduction Many lifestyle factors and comorbidities that may contribute to the development of erectile dysfunction (ED) are potentially modifiable. Therefore, the ability to predict ED severity based on associated comorbidities would be of value in counseling patients about early lifestyle modifications to prevent future dysfunction. We sought to identify patient risk factors that predict worse patient-reported Sexual Health Inventory for Men (SHIM) scores. Methods We retrospectively reviewed 25,388 men who participated in a nationwide men's health screening program in 2003, 2011, and 2012. All men completed a questionnaire, which included exercise frequency, fat content of diet, urinary symptoms, sexual function, medical comorbidities, and body mass index (BMI). Testosterone (T) was available in 10,130. SHIM scores were stratified by severity: none (21-25), mild (17-21), moderate (8-16), or severe (1-7). Associations between SHIM and patient factors were assessed by Chi-squared test and ANOVA. Statistically significant variables from univariate analyses (p<.05) were included in a multivariable linear regression model for patient-reported SHIM score. Results Median age was 61.2 years (IQR 54-68) with racial distribution of 75.6% Caucasian, 17.1% African American, 5.2% Hispanic, and 2.0% Asian. On linear regression, age (HR .28 95% CI .31-.24; p<.0001), BMI (HR .08 95% CI .13-.04, p=.001), prostatic enlargement (HR 1.87 95% CI 2.58-1.16; p<.0001), heart disease (HR 1.34 95% CI 2.26-.428; p=.004), diabetes (HR 1.99 95% CI 2.78-1.20, p=.0001), and total AUA symptom score (HR .12 95% CI .16-.07, p<.0001) were associated with a lower SHIM score. Factors that did not reach statistical significance were race (p=.36), history of heart attack (p=.09), exercise level (p=.07), fat content of diet (p=.74), and testosterone level (p=.27). Conclusions There are several health issues and lifestyle behaviors that predict the development and worsening of ED. Increased awareness of such modifiable factors may be useful in counseling patients to improve overall health and prevent potentially irreversible damage on erectile function. Likewise, worse SHIM scores should alert the physician to investigate comorbidities that may be inadequately managed. Funding none
Authors
Jaime A. Cavallo
Jared S. Winoker Kyle A. Blum Wendy L. Poage E. David Crawford Steven A. Kaplan Nelson N. Stone |
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MP69-05 |
Twitter Mentions and Academic Citations in Urology Literature |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making III | 17BOS |
Abstract: MP69-05 Sources of Funding: None Introduction Social media use has dramatically increased in academic medicine with over 70% of journals now using Twitter accounts. This calls into question if there is a measurable association between academic impact and Twitter use. We sought to quantify the relationship between the number of Twitter mentions and the number of academic citations a urology publication receives. Methods 213 papers from 7 prominent urology journals were examined 18 months after publication from December 2014-January 2015. Articles were evaluated with 2 citation based "bibliometrics"(Scopus, Google Scholar) and 1 social media based metric (Altmetric). Altmetric software allowed for individual tweets regarding an article to be examined. Scores and Twitter mentions were compared using one way ANOVA and bivariate fit analysis. Results 73% of articles had at least 1 twitter mention. These articles were found to have 2.0 fold more Scopus citations (p < 0.01), 2.1 fold more Google Scholar citations (p < 0.01), and 27.8 fold higher Altmetric scores (p < 0.001) compared to articles with no Twitter mentions. There was a positive correlation between the number of Twitter mentions and the number of citations on Scopus (R= 0.328, p<0.01) and Google Scholar (R=0.348, p<0.01). This relationship remained significant when controlling for journal impact factor. 9% of authors self-tweeted their own publications. Authors self-tweeting articles was associated with an increased number of citations, with a 6.5 and 4.6 mean citation increase in Google Scholar and Scopus scores (p = 0.02 and p < 0.01) compared to non-self-tweeted articles. Conclusions The majority of urology publications are being shared on Twitter. The number of citations a urologic publication receives is associated with the number of mentions it has on Twitter. Authors self-tweeting articles may be a factor that increases paper visibility and academic impact. Funding None
Authors
Solomon Hayon
Ian Stormont Meagan Dunne Michael Naslund Mohummad Minhaj Siddiqui |
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MP69-06 |
AUTHOR SELF-CITATION IN THE UROLOGY LITERATURE |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making III | 17BOS |
Abstract: MP69-06 Sources of Funding: None Introduction The h-index, introduced by Hirsch in 2005, quantifies an individual's contribution to the literature using the author's total number of publications and how frequently those publications have been cited. Author self-citation is commonly used when expanding on previous research; however, there is concern that self-citation practices may be used to artificially inflate one's h-index. The objective of our study was to determine the frequency and patterns of author self-citation in the urology literature. Methods A retrospective review of bibliographic references was performed of consecutive publications in three high-impact urology journals published between October and December 2015. Data included number of authors, total references, author self-citations, self-cited references, journal self-citations, urology topic, and country of origin. Chi-square and Fisher's exact tests were used to evaluate categorical variables while nonparametric Wilcoxon rank sum tests and Kruskal-Wallis tests were used for continuous variables. Results A total of 215 articles were analyzed from Journal of Urology, European Urology, and British Journal of Urology. The median number of authors per article was 8 (IQR 6-11) and median number of references was 27 (IQR 20-30). Articles in European Urology generally had more authors than Journal of Urology or British Journal of Urology (median = 12, 7, and 7, respectively, p<0.001). Overall, 180 articles (84%) had at least one self-cited reference. The median number of references with at least one self-citation was 4 (IQR 1-7), corresponding to an overall self-citation rate of 14% (IQR 5-25). Articles in European Urology were significantly more likely than those in Journal of Urology (98% vs. 79%, p<0.001) or British Journal of Urology (98% vs. 81%, p<0.001) to include at least one self-citation. This translated to a significantly higher rate of self-citation in European Urology compared to both Journal of Urology and British Journal of Urology that had equal rates (median 25% vs. 12%, p<0.001). Conclusions This study found that author self-citation in the urology literature is common, seen in greater than 80% of articles reviewed. Our study is the first to show the practice of self-citation varies significantly between journals and was more common by authors published in European Urology versus Journal of Urology and British Journal of Urology. The effect of self-citation on an individual's h-index, however, remains to be elucidated and warrants further study. Funding None
Authors
Katherine Carlisle
Joseph Sterbis Phuong Do Leah McMann |
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MP69-07 |
Hashtag Peer-Review: Does Early Social Media Success Correlate with Conventional Metrics of Publication Impact? |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making III | 17BOS |
Abstract: MP69-07 Sources of Funding: None Introduction Social media is increasingly utilized as a means to disseminate information, including scientific study. In contrast to the conventional academic peer-review process, social media may serve as an efficient vehicle to both vet and widely broadcast research. To test this hypothesis, we evaluated whether Twitter activity at a national urology meeting mirrors subsequent journal impact factor (IF), a traditional measure of academic impact._x000D_ Methods We retrospectively reviewed historical Twitter data obtained through the Keyhole archiving platform using the hashtag “#aua15” between May 1 and June 1, 2015 reflecting the widely utilized hashtag of the 2015 American Urological Association (AUA) meeting. We analyzed all tweets receiving ? 4 likes/retweets (RT). Among tweets reporting on newly presented studies with discernable attribution, we evaluated subsequent publication status within 18 months, including IF. Published studies with multiple tweets were grouped, and RTs were summed. We assessed the relationship between social media reception (likes/RT) and subsequent journal IF using Pearson’s correlation. Results A total of 15,303 posts were associated with “#aua15” drawing from 2,015 users, reaching 2,263,438 unique twitter users, and culminated in 27,327,075 impressions (number of times users have seen posts containing “#aua15”). 451 of the most promoted tweets were analyzed, including 74 related to discernable data with author attribution. The most common categories of tweets included references to data or studies without discrete author or study attribution (18.8%), generalized comments (17.5%), and meeting-related announcements (16.6%). At 18 months following the AUA, 44 studies were identifiable on PubMed (59%). Among published studies there was a modest, positive correlation between number of likes/RT and IF (r=0.59)._x000D_ Conclusions Measures of social media engagement with data presented at a national medical meeting positively correlated with subsequent publication impact factor within 18 months of presentation. _x000D_ _x000D_ Funding None
Authors
Kevin Nguyen
Cary Gross Matthew Cooperberg Matthew Katz Adam Hittelman Jamil Syed Peter Schulam Michael Leapman |
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MP69-08 |
Pharmaceutical industry payments and physician prescribing of urologic drugs |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making III | 17BOS |
Abstract: MP69-08 Sources of Funding: none Introduction The effects of industry payments to physicians on prescribing habits are not well understood. We aimed to determine the association between the receipt of industry payments and the prescribing of alpha-blockers and overactive bladder (OAB) medications. Methods The Open Payments Program (OPP) database and Medicare Part D claims database for 2014 were linked. This provided industry payment information and prescription information for individual physicians in the US. We identified all physicians who prescribed any alpha-blocker or OAB drug. We also identified actively promoted drug (based on payments) within each group. Silodosin was the only actively promoted alpha-blocker. Fesoterodine, solifenacin, and mirabegron were the actively promoted OAB drugs. For each promoted drug, we calculated the proportion of physicians who &[Prime]preferred&[Prime] the promoted drug, i.e. prescribed the promoted drug more often than all other drugs in that class combined. Regression analysis was performed to quantify the effect of industry payment on &[Prime]preferred&[Prime] prescribing. Analysis was conducted for any payment, greater than the median payment, and high payment (>$100). Prescribing physicians were categorized as urologists or non-urologists. Results In 2014, among the 108,680 physicians who prescribed an alpha blocker or an overactive bladder medication through Medicare Part D, 66,726 received at least one industry payment by the manufacturer of that drug. For each promoted drug, physicians who received any payment from its manufacturer prescribed that drug more often, relative to all drugs in its class. Receipt of payment from the promoting company was associated with significantly increased odds of preferentially prescribing that drug (Table 1). This effect was significant when considering all physicians and non-urologists. However, when considering urologists alone, no significant effect was noted. Sensitivity analyses conducted using median payment and high payment thresholds confirmed these findings. Conclusions Receipt of industry payment is associated with increased prescribing of promoted urologic drugs. This effect varies according to specialty, possibly reflecting the strength of established prescribing patterns or close familiarity with these drugs for urologists as compared to other physicians. Funding none
Authors
Parth Modi
Matthew Ingham Eric Singer Steven Chang |
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MP69-09 |
Survival outcomes of organ sparing surgery, partial penectomy and total penectomy in T1/T2 penile cancer |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making III | 17BOS |
Abstract: MP69-09 Sources of Funding: None Introduction In the United States, the most common presentation for penile cancer (PC) is a distal, organ confined squamous cell cancer. Traditional treatment of PC in the form of total penectomy (TP) carries devastating functional and psychological outcomes. There is evidence that organ sparing surgery (OSS) has a higher rate of recurrence though that may not impact survival. We utilize the national cancer database to asses for a difference in survival among the different surgical options commonly used to treat T1/T2 penile cancer. Methods Patients underwent OSS, partial penectomy (PP) and TP were identified. Demographic data including differences among the 3 groups were assessed using Chi-square test. Survival estimates were assessed using Kaplan-Meier estimate. Results Between 2004 and 2014, 1,539 patients underwent surgery for T1/T2 penile cancer. There were 477 patients in the OSS group, 802 in the PP group and 202 in the TP group. Mean follow up in months was 44.6, 41.6 and 38.4 in the OSS, PP and TP groups respectively (p=0.002). There was no difference in age or racial distribution among the 3 groups (p=0.75 and 0.54 respectively). Overall, the three groups were more likely to receive treatment in an academic center, Medicare was the prevailing insurance type and most patients reside in Urban areas (p=<0.001, <0.001 and 0.04 respectively). The incidence of T1/T2 in the OSS, PP and TP groups were 85.9/14.1, 39.8/50.2 and 37.7/62.3 respectively (p= <0.001). The 1,5 and 10 years survival rates for the 3 groups is illustrated in Table 1. Predictors of poor survival were older age, black race and T2 disease. The type of surgery offered was not predictor of poor survival. Conclusions In the early stage penile cancer, which is the most common presenting stage in the United States, the degree of aggressiveness of initial surgical treatment did not alter the long term patient survival. Consideration for penile organ sparing surgery, which has better functional and psychological outcomes, should always be discussed with the patient. Funding None
Authors
Benjamin Schurhamer
Jun Tao Mark Campbell Judy Farias Alfred Hall Rodney Davis Joseph Su Mohamed Kamel |
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MP69-10 |
Trends in Stage I Non-Seminomatous Germ Cell Tumors in the United States |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making III | 17BOS |
Abstract: MP69-10 Sources of Funding: None Introduction Testicular malignancies are the most common solid tumor in men 15-34 years and affect approximately 8400 men in the United States each year. Almost half can be classified as non-seminomatous germ cell tumors (NSGCT). Treatment options for stage I include surveillance, chemotherapy, or retroperitoneal lymph node dissection (RPLND). Our study aimed to examine demographic and socioeconomic trends around treatment patterns. _x000D_ Methods Using the National Cancer Database, we retrospectively examined 55,756 patients between January 1, 2004 and December 31, 2013. Data was extracted on 7,657 individuals with ICD histology diagnosis for stage I NSGCT. We obtained data on various demographic and socioeconomic variables including race, education, income, location and health insurance. We used multivariable logistic regression models to estimate odds ratios with 95% confidence intervals._x000D_ _x000D_ Results Throughout 2004-2013 fewer patients received RPLND (OR 0.65 [0.55-0.76] p<0.01), and more received chemotherapy (OR 1.26 [1.10-1.43] p<0.01). Compared to other treatments, RPLND was less commonly seen in non-academic centers (OR 0.47 [0.33-0.66] p<0.01), more commonly in the highest volume institutions compared to the lowest volume institutions (OR 4.57 [2.47-8.46] p<0.01), and more commonly seen in those with low income (OR 1.24 [1.06-1.46] p<0.01). Patients living in rural counties compared to metro counties were more likely to receive chemotherapy (OR 1.72 [1.08-2.75] p=0.03). As distance from hospital increased, individuals were more likely to receive any form of treatment versus observation for their disease (OR 1.51 for the greatest vs. the lowest quartile [1.31-1.74] p<0.01). Low income and Medicaid predicted greater chance for any treatment (OR 1.17 [1.04-1.32] p=0.01 and OR 1.45 [1.20-1.74] p<0.01, respectively). No trends were seen for race or education status. Conclusions Our study illustrates that fewer patients are undergoing RPLND, which may be due to increased surveillance. RPLND is more commonly practiced at higher volume and academic centers. Education and race do not predict choice of treatment, whereas distance, income and insurance type do predict increased likelihood for receiving treatment overall._x000D_ Funding None
Authors
Nahid Punjani
Thomas Seisen Claire Beard Christoper Sweeney Quoc-Dien Trinh Jennifer Rider Mark Preston |
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MP69-11 |
Patterns of Surveillance Intensity in Kidney Cancer |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making III | 17BOS |
Abstract: MP69-11 Sources of Funding: None Introduction Multiple surveillance guidelines exist for kidney cancer following surgical intervention. Although these recommendations lack conformity, the majority do use stage as well as surgery type to stratify surveillance intensity. Due to guideline heterogeneity, it remains unclear what factors influence surveillance intensity in current practice. Our objective was to assess the patterns of surveillance intensity in kidney cancer after primary surgical intervention among patients ≥66 years. Methods Using SEER-Medicare, we identified patients diagnosed with non-metastatic kidney cancer who had undergone primary surgical intervention (n = 2433) from 2007 to 2011. Surveillance intensity was measured as the number of unique inpatient and outpatient claims made for kidney cancer (ICD-9 diagnosis code 189.0) starting 60 days after primary intervention. Using multivariable linear regression, we assessed the relationships between patient related factors and surveillance intensity (log-transformed). Parameters from the model were reported using risk ratios (RRs). Results Patients diagnosed in later years experienced more surveillance with an estimated 10% greater number of visits/12months occurring with each subsequent calendar year (RR 1.10 for every 1-year increase, 95% CI 1.07-1.13, p<0.001). As compared to pT1 stage, patients with pT2-4 disease experienced 108% more surveillance visits/12 months (RR 2.08, 95%CI 1.90-2.27, p<0.001). Both older age and living in a metro/urban area, as compared to a big metropolitan location, were associated with significantly fewer follow-up visits (10-year increase in age: RR 0.89, 95%CI 0.83-0.95, p<0.001; metro/urban: RR 0.86, 95%CI 0.79-0.93, p<0.001). Surgery type (radical, partial or ablation), gender, race and Charlson comorbidity score were not significantly associated with surveillance. Conclusions Similar to guidelines, surveillance intensity in current practice was found to correlate with disease stage. However, surgery type played less of a role. Other factors such as year of diagnosis, location and younger patient age were associated with more surveillance administered. Further analysis is warranted to understand the reasons for this variation in current surveillance practice and its impact on oncologic care. Funding None
Authors
Suzanne Merrill
Eric Schaefer Chris Hollenbeak |
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MP69-12 |
Underutilization of Palliative Services in Advanced Genitourinary Malignancies |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making III | 17BOS |
Abstract: MP69-12 Sources of Funding: none Introduction Comprehensive cancer care aims to reduce disease mortality while simultaneously maximizing patient quality of life. Palliative care addresses the morbidity of cancer and cancer treatments and should be offered in conjunction with traditional therapy. Recent randomized trials demonstrate that early referral to palliative care for advanced malignancy is associated with not only improved quality of life, but survival as well. Despite these findings, their services may remain underutilized. The aim of this study was to assess patterns of care in the use of palliative care services for advanced genitourinary malignancies. Methods Data from the National Cancer Database was queried for Stage III and IV genitourinary malignancies (prostate, renal, bladder, penile, and testicular). Patient and facility characteristics were compared in those who received palliative care treatments versus those who did not. Comorbidities were stratified by Charlson-Deyo score. Logistic regression models were used to identify factors associated with palliative care. Results We identified 377,248 patients with advanced GU malignancies between 2004-2014. Only 24,224 (6%) were referred to palliative care and 12,284 (15%) died within 1 year of diagnosis. Multivariable analysis revealed that advanced disease and death within one year of diagnosis were most strongly associated with palliative care. Additionally, older age, more co-morbidities, uninsured, female gender, lower income and decreased education and treatment at low volume and academic centers were associated with utilization of palliative care, p<0.05, respectively (Table). Over the study period there was a significant, although, modest increase in the utilization of palliative services (5.5% in 2004 to 7.7% in 2014, p<.001). Conclusions Relatively few patients with advanced GU malignancies receive palliative care. While referrals increased in recent years, palliative care remains under-utilized and remains an opportunity for educational engagement with patients and physicians alike. Funding none
Authors
Adrien Bernstein
Ron Golan Brian Dinerman Jonathan Fainberg Bashir Al Hussein Al Awamlh Jim C. Hu |
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MP69-13 |
Patient reported health and quality of life after neoadjuvant chemotherapy and cystectomy: results from Bladder Cancer Outcomes and Impact Study |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making III | 17BOS |
Abstract: MP69-13 Sources of Funding: Florida Bankhead-Coley Research Program Introduction Prior quality of life (QOL) research in bladder cancer has predominantly focused on differences between patients treated with radical cystectomy (RC) and different forms of urinary diversion. Other aspects of bladder cancer treatment, such as receipt of neoadjuvant chemotherapy (NAC), have gone unexamined. Using validated health questionnaires, we sought to determine the relationship between receipt of NAC and patient QOL. Methods 124 patients were enrolled in a prospective complication and QOL assessment study between 2013 and 2015. Patients were surveyed longitudinally with a panel of health questionnaires, including the SF-36, a measure of general quality of life. The SF-36 contains 36 questions that assess several health domains, including physical functioning, physical health problems, pain, general health perception, emotional well-being, emotional health problems, social functioning and energy/fatigue. Patients surveyed in this study completed the SF-36 prior to cystectomy and at 3, 6 and 12-months following RC. Generalized linear models were used to examine differences in SF-36 scores by the primary exposure of interest (receipt of NAC) and adjusted for clinical and demographic factors. Results 87 patients completed the SF-36 at both baseline and 6 months. The mean age was 68 years and 66 (75.8%) were men. More than half (46, 52.9%) received NAC. Patients who were not treated with NAC had lower SF-36 scores 6 months after RC (change in physical composite score (PCS) -1.47 vs. +1.95 and mental composite score (MCS) -1.96 vs. +3.68) compared to those who did. After adjusting for age, gender, diversion type and stage, receipt of NAC was significantly associated with higher general health perceptions (PE 5.29, p=0.012), emotional well-being (PE 5.41, p=0.012), and mental composite score (PE 6.02, p=0.005). There was no difference with NAC in PCS after controlling for confounders (p=0.10). Conclusions Receipt of NAC is a significant predictor of better quality of life 6 months after cystectomy as measured by SF-36. We found significant differences between patients treated with and without NAC in several domains, including mental composite score, general health perception, and emotional well-being. The exact mediators of this association need to be examined in larger studies. Funding Florida Bankhead-Coley Research Program
Authors
Dominic Tang
Andrew Leone Juan Chipollini Paul Crispen Carl Henriksen Michael Poch Wade Sexton Scott Gilbert |
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MP69-14 |
Academic and High-Volume Hospitals Are Associated with Improved Outcomes in the Management of Retroperitoneal Sarcoma |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making III | 17BOS |
Abstract: MP69-14 Sources of Funding: none Introduction Retroperitoneal sarcoma (RPS) is a rare malignancy. Principles of management include surgical management (SM) and complete resection (CR) with negative microscopic margins (NMM). We aimed to evaluate the role of provider characteristics on RPS outcomes. Methods Adult patients diagnosed with non-metastatic RPS from 2004-2013 were identified from the National Cancer Database. Volume was classified based on average annual number of RPS cases as low (<5) or high (>=5), with high-volume hospitals (HVH) corresponding to top 10th percentile. Univariate and multivariable statistical methods were used to examine the association between hospitals volume and academic status on SM, CR, NMM and OS, adjusted for other covariates. Results We identified 3,093 patients with RPS (median age 61 years). Histologic subtypes included liposarcoma (49.6%), leiomyosarcoma (26.3%), and other subtypes (24.1%). SM offered improved overall survival (OS) compared to non-surgical management (84.2 vs. 43.2 months, p<.001). CR improved OS compared to incomplete resection (85.9 vs. 39.9 months, p<.01). In patients who had CR, achieving NMM improved OS (97.6 vs. 71.1 months, p<.01). Surgery was used to treat 2,168 (70.0%) patients, and the odds of SM were 1.5-fold higher at academic hospitals (OR 1.5, 95%CI 1.2-1.7) and 2-fold higher at HVH (OR 2, 95%CI 1.4-2.8). CR was achieved in 2,058 (95.0%) of surgical patients, with odds of CR 1.8-fold higher at academic hospitals (OR 1.8, 95% CI 1.2-2.7) and 3.8-fold higher at HVH (OR 3.8, 95%CI 1.2-12.4). NMM was obtained in 1,361 (33.9%) patients with CR, with 1.8-fold higher odds of NMM at HVH (OR 1.8, 95%CI 1.3-2.4). Conclusions Quality measures (SM, CR, NMM) associated with improved OS are achieved more readily at academic and high-volume hospitals. Consideration should be given to centralization of RPS care. Funding none
Authors
Jessica Yih
Matthew Maurice Robert Abouassaly John Ammori |
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MP69-15 |
Receipt of Mannitol Use in Partial Nephrectomy and Rates of Conversion to Radical Nephrectomy After Mannitol Administration |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making III | 17BOS |
Abstract: MP69-15 Sources of Funding: None Introduction Accurate rates of mannitol use for partial nephrectomy (PN) and subsequent intra-operative conversion from PN to radical nephrectomy (RN) are unknown. Understanding factors predictive for conversion and ascertaining surgical outcomes of these converted nephrectomies would contribute greatly to the literature and also allow clinicians to better counsel prospective patients. Thus, we sought to calculate conversion rates of both open and minimally invasive PN using mannitol usage as an indicator for PN intent and to identify factors associated with the conversion from PN to RN. Methods A total of 136,298 patients undergoing PN (open: n=68,580, laparoscopic: n=17,549, robotic: n=50,169) and 423,759 undergoing RN (open: n=237,411, laparoscopic: n=143,179, robotic: n=43,169) were identified from the Premier Perspective Database, an all-payer hospital clinical and economic database in the U.S. capturing patients from 2003 to 2015. An algorithm utilizing a variety of charge and billing codes based on the use of mannitol osmotic diuretic in RN was used to calculate rates of conversion. Results Overall, mannitol was used in 41.7% of the total PN cohort (open: 32.4%, laparoscopic: 21.7%, robotic: 59.9%, p <0.001). After adjusting for the use of mannitol, the conversion rate of PN to RN was 27.9% for open, 42.6% for laparoscopic, and 14.2% for the robotic approach (p <0.001). Multivariate analysis found that age, gender, charlson comorbidity index, surgical approach, surgery year, and annual surgeon and hospital volume were independent factors associated with conversion from PN to RN (all p<0.001). After adjusting for patient, surgeon and hospital demographics, laparoscopic approach had higher odds (OR=1.77, 95% CI 1.5 to 2.2, p=<0.001) and the robotic-approach had lower odds (OR=0.62, 95% CI 0.54-0.71, p<0.001) of conversion compared to open surgery. Conclusions Robot-assisted PN had higher usage rates of mannitol compared to laparoscopic and open approaches. Also, robotic PN had the lowest odds of PN to RN conversion while the laparoscopic approach had the highest odds of conversion. Clinicians should be aware of these conversion rates especially prior to undertaking technically difficult nephron sparing procedures irrespective of approach. Funding None
Authors
Yash Khandwala
In Gab Jeong Ye Wang Deok Hyun Han Jae Heon Kim Shufeng Li Steven L Chang Benjamin Chung |
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MP69-16 |
The Association of Health Literacy and Numeracy on Understanding of Prostate Cancer Terminology |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making III | 17BOS |
Abstract: MP69-16 Sources of Funding: National Cancer Institute 5K12CA090625-14 (KM) Introduction A source of treatment regret and less engaged treatment decision making may be lack of health literacy and numeracy regarding terms commonly associated with prostate cancer treatment. The objective of this study was to determine community levels of health literacy and numeracy and their association with terminology commonly used when discussing prostate cancer treatment. Methods A total of 52 men from the outpatient clinics of Nashville General Hospital (n=41), which primarily serves the uninsured, Medicaid/Medicare, and indigent populations in the greater Nashville area, and Vanderbilt University Medical Center (n=11) participated. Demographic information was collected, and health literacy and numeracy were assessed using the revised Rapid Estimate of Adult Literacy in Medicine (REALM-R), the Brief Health Literacy Screen (BHLS), the Subjective Numeracy Scale (SNS-3), and Schwartz-Woloshin (S-W) questionnaires. Men were asked to identify the location of the prostate on a standardized model of the male pelvis. They were then asked to complete a 29-term questionnaire which asks men to define terms associated with sexual, bowel and urinary function. Adequate health literacy (AHL) was defined as a REALM-R score >=6, and inadequate health literacy (IHL) was REALM-R <6. Results Median age of the cohort was 55y, 57.7% were Black, 75% had annual household income <$20,000, and 28.8% had less than 12th grade education. Median REALM-R score was 8 (IQR 2-8), median BHLS score was 11 (IQR 9-14.25), median SNS-3 score was 11 (IQR 8-14), and median S-W score was 1 (IQR 1-2). Overall, 40.4% of men were able to identify the location of the prostate. For the 29-item questionnaire, the median number of correct responses was 23.5. Men with AHL had significantly higher percent of correct responses compared to men with IHL (89.5% vs 54.5%, p<0.005). There was a significant, positive linear relationship with amount of formal education and total correct responses (p=0.002). Men with annual incomes <$20,000 had significantly lower correct scores (19.5 vs 25.3 for >$20,000, p <0.02). Each of the measures of health literacy and numeracy were strongly related to understanding of the functional terms (Spearman correlation REALM-R r=0.72, BHLS r=0.72, SNS-3 r=0.62; all p<0.001). Conclusions The rates of low health literacy and numeracy are high and are associated with lack of knowledge of prostate cancer related terminology. Efforts to improve effective communication regardless of patient health literacy level are needed. Funding National Cancer Institute 5K12CA090625-14 (KM)
Authors
Jeremiah Umoh
Shaquille Brown Daniel Heslop Ken Wallston Kelvin Moses |
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MP69-17 |
Incidence of Prostate Cancer Stratified by County Education, Poverty, and Urbanization Levels: A Population Based Analysis of SEER |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making III | 17BOS |
Abstract: MP69-17 Sources of Funding: None Introduction A decline in prostate cancer incidence was reported after USPSTF recommendations in 2008 and 2012. It is unknown if this decline is uniformly present among various education and socioeconomic levels within the US population. Methods Age-adjusted prostate cancer incidence from Surveillance Epidemiology and End Results (SEER) data were studied from 2008-2013. Utilizing American Community Survey (ACS) 2009-2013 and US Census 2010, 3142 counties were stratified by education (percent county pop. >= 25 years with >= high school degree or equivalent), poverty (percent county pop. >= 200% federal poverty line), and urbanization (percent county pop. living in an urban area) categories to set national quintile cut points. SEER county incidence data were matched with their corresponding national education, poverty, and urbanization quintiles. The highest, middle, and lowest quintiles were compared over time using incidence rate ratio (IRR) and between quintiles by absolute disparity (AD; highest and lowest quintile range difference) and relative disparity (RD; highest and lowest quintile range ratio). Analysis was performed to 95% confidence intervals (CI) using the Tiwari et al. method. Results Counties with highest education, economic, and urbanization levels had the highest prostate cancer incidence, 112.7, 108.7, and 108.1 per 100,000 respectively in 2013. Counties with the lowest education, economic, and urbanization levels had the lowest prostate cancer incidence, 97.9, 104.0, 97.2 per 100,000 respectively in 2013. The AD demonstrated a convergence in incidence rate between highest and lowest quintiles. From 2008-2013 the percentage change in absolute disparity declined -39.2%, -34.3%, -46.2%, for education, economic, and urbanization categories respectively. IRR declined equally across all quintiles within each category ranging 0.69-0.71. Equivalent IRRs among quintiles indicates decline in incidence was homogenous across counties and not weighted to county educational, poverty, or urbanization level. Conclusions Incidence rate is positively correlated with higher county education, wealth, and urbanization levels. The incidence absolutely converged between highest, middle, and lowest education, poverty and urbanization quintiles in all categories after USPSTF recommendations, relative disparity remained unchanged. Statistically equivalent IRRs suggest prostate cancer incidence has declined uniformly among counties of varying education, poverty, and urbanization levels between 2008 and 2013. Funding None
Authors
Daniel Au
Johar Syed Sameer Siddiqui |
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MP69-18 |
A patient-centered practice change: Finding the best approach for prostate cancer decision support |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making III | 17BOS |
Abstract: MP69-18 Sources of Funding: NIH 5R01NR009692 Introduction Implementation of evidenced-based patient-centered care is challenging in clinical settings. Success of such practice changes varies. The purpose of our study was to evaluate implementation strategies to deploy a shared decision aid for localized prostate cancer (LPC). Methods The Personal Patient Profile-Prostate (P3P) is a web-based decision aid with demonstrated efficacy in reducing decisional conflict among men choosing a care plan for LPC. Implementation strategies were co-designed with leaders in six geographically-diverse urology clinics. As part of routine care, men were informed of P3P and offered access via a variety of methods. Physicians received 1-page summaries of P3P patient-generated reports of current symptoms and factors influencing the care decision. Focus groups including physicians, clinic staff and administrators were held at each site to solicit feedback after the implementation period. Access metrics were monitored for up to 6 months. General impressions, common barriers and promoters were identified and synthesized from the focus group data. Results Two sites chose written information only to inform men of P3P, 1 site chose email only, 1 site chose email plus phone contact, 1 site chose MD instruction to use, followed by phone and email follow up and 1 site chose in clinic only. Barriers common to all settings included creating new workflows on top of heavy workloads, and staff and administrator misunderstanding of P3P context and resources. Staff inability to identify men with new LPC (vs follow up visits) hampered access. Promoters to successful implementation included an identified clinical lead, physician engagement and phone combined with email contact. Of all men with LPC seen in the clinics, 51% (range 15-98%) were informed of P3P. The highest rates of P3P access outside of clinic and prior to the consult visit (82, 73%) were observed when 2-3 modes of informing were implemented: physician, email and phone invitations. Clinic sites that chose to only provide written material with instruction to access P3P had the lowest access rates (range 0-14%). Physicians appraised the summaries as useful and helpful. Conclusions Despite challenges for clinic staff to add strategies to implement P3P to already heavy workloads, success was realized when physicians engaged and when staff provided follow up contacts to encourage P3P access. New practice changes to implement an evidence-based intervention require multi-modal strategies for early success. Future trials evaluating methods to reduce clinical workload may be of value. Funding NIH 5R01NR009692
Authors
Donna Berry
Barbara Halpenny Meghan Underhill Martin Sanda Viraj Master Christopher Filson Peter Chang Gary Chien Seth Wolpin |
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MP69-19 |
The Impact of Race on Perceptions of Anxiety after Local Therapy for Prostate Cancer |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making III | 17BOS |
Abstract: MP69-19 Sources of Funding: none Introduction Despite the potential side effects associated with treating prostate cancer, many men choose treatment over observation. The relative treatment benefits and harms to health related quality of life outcomes (HRQOL) remain poorly understood. In particular, there is a paucity of data detailing the differences in perceived treatment outcomes in African American (AA) and Hispanic men. We prospectively evaluated the functional and psychosocial effects of prostate cancer treatment in men and hypothesize that there may be differences in outcomes in Caucasian men vs. AA/Hispanic men. Methods We enrolled 105 men with recently diagnosed prostate cancer at our institution in an internet-based study which used validated questionnaires to longitudinally assess HRQOL domains such as sexual and urinary function, bowel function, anxiety, and depression, at 1, 3, 6, and 12 months following treatment. Linear mixed models were used to examine changes in self-reported measures at enrollment (pre-treatment) and at each post-treatment follow-up assessment. We focused our analysis on the 70 patients who chose radical prostatectomy or radiation therapy as treatment: 55 of these men were non-Hispanic white; 15 were AA or Hispanic. Results Despite significant declines in functional outcomes such as erectile function (P<.001 for both groups), anxiety was significantly lowered post-treatment in both groups. Significant reductions in anxiety were noted for Caucasian men (3.9 points , P<0.001) and were even greater for AA/Hispanic men (5.7 points, P<.001). When controlling for differences in income, marital status, education, and improvements in urinary score, the impact on anxiety remained significant (P<0.05) at 3, 6, and 12 months. Based on previous analyses, these improvements are both statistically and clinically significant. Conclusions We found significant reductions in anxiety after local therapy. While these reductions were found in all men, AA and Hispanic men reported a greater reduction in anxiety compared to Caucasians. This suggests that AA/Hispanic men may have a different perspective regarding prostate cancer and treatment outcomes. Further work is necessary to elucidate this difference in perspective. Funding none
Authors
Shilajit Kundu
Vincent Wong Channa Amarasekera Kevin Lewis Edward Schaeffer Anthony Schaeffer Joshua Meeks David Victorson James Burns Sandra Gutierrez Kevin McVary Sarah Psutka David Cella |
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MP69-20 |
The Impact of State Laws Limiting Malpractice Awards on Diffusion of Surgical Innovation: The Case of Minimally Invasive Radical Prostatectomy |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making III | 17BOS |
Abstract: MP69-20 Sources of Funding: None Introduction While previous studies have evaluated the impact of malpractice caps on health care utilization and physician density, their effect on the adoption of innovative technology is unknown. We examined whether such caps impacted the national diffusion of minimally invasive radical prostatectomy (MIRP) for prostate cancer (PCa). For comparison we also examined trends in the diffusion of two technologies that antedate MIRP and are in their post-dissemination era: laparoscopic radical nephrectomy (LRN) and laparoscopic partial nephrectomy (LPN) for renal cell carcinoma (RCC). Methods We identified patients ≥66 years with non-metastatic PCa between 2003-2011 in the SEER-Medicare database. Our cohort (n=129,793) was classified based on the existence of a limit on non-economic damages in their geographical locations: states with a cap before and through our study period (cap states), states without cap before and through the study (non-cap states) and states whose cap was introduced during our study period (late-cap states). Multivariable logistic regression models were fitted to examine the influence of &[prime]cap&[prime] status on MIRP adoption while controlling for demographic and tumor characteristics. A similar analysis was performed for patients with non-metastatic RCC undergoing LRN and LPN. Results Median age (IQR) of our PCa cohort was 74 years (70-79 years). 84% were White; 97% had T1/ T2 disease and 52% had high-grade disease. 17% were treated with radical prostatectomy (RP): 8.1% with MIRP and 8% with open RP (0.9%-unknown). Adoption of MIRP was quicker in cap-states than in non-cap and late-cap states (p<0.0001, Figure 1). On multivariable analysis, there was a 70% higher likelihood of receipt of MIRP in patients in a cap-state compared to a non-cap state (OR: 1.7, P<0.0001). In contrast to MIRP, the diffusion of LPN and LRN were not different between cap and non-cap states on multivariable modeling (P≥0.05). Conclusions In a contemporary national cohort of PCa patients, states with malpractice caps had higher MIRP adoption rates. Diffusion rates of background technologies (LRN, LPN) in their post dissemination phase were not different in such states, highlighting the primacy of malpractice caps in explaining the differential effect on MIRP diffusion rates. Funding None
Authors
Shyam Sukumar
Oluwakayode Adejoro Badrinath Konety |
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MP70-01 |
Utility of multiparametric MRI on patient selection for focal therapy in intermediate risk prostate cancer |
Prostate Cancer: Localized: Ablative Therapy I | 17BOS |
Abstract: MP70-01 Sources of Funding: This research was made possible through the NIH Medical Research Scholars Program, a public-private partnership supported jointly by the NIH and generous contributions to the Foundation for the NIH by the Doris Duke Charitable Foundation (Grant #2014194), the American Association for Dental Research, the Colgate-Palmolive Company, Genentech, and other private donors. For a complete list, visit the foundation website at http://www.fnih.org. Introduction Intermediate risk prostate cancer (IRPCa, Gleason 7 with PSA<20) patients often receive whole gland therapy, potentially exposing them to overtreatment and side effects associated with treatment. Focal therapy (FT) minimizes these risks while treating all clinically significant cancer. We aimed to determine the accuracy of multiparametric MRI (mpMRI) and fusion biopsy (Fbx) in selecting candidates for FT. Methods Clinical and pathology data was prospectively collected from IRPCa patients who underwent prostate MpMRI prior to radical prostatectomy (RP) (2010-16). Patients were analyzed in two cohorts: those who received mpMRI with Systematic Biopsy (Sbx) alone and those who received combination mpMRI Fbx/Sbx. Patients were considered suitable for FT if they had IRPCa in only one lobe of the prostate with a corresponding mpMRI visible lesion on the same side. Poor candidates were patients found to have high risk cancer (Gleason 8-10), IRPCa bilaterally, or PCa lesions that crossed the midline. Good candidates were confirmed with whole mount pathology analysis performed. Results 185 patients with IRPCA (median age of 61 (IQR 10) years and PSA 5.67 (IQR 4.5 ng/dl) were included in the study. 129 (69.7%) had MRI and combination Fbx/Sbx. There was no difference in age, PSA and race distribution between the two cohorts. 98 (53.0%) patients were considered good FT candidates based on preoperative MpMRI and biopsy findings. Whole mount pathology analysis confirmed 67.1% of FT candidates determined from pre RP information (31.9% of total IRPCa patients). A higher proportion of FT candidates determined by mpMRI and Fbx/Sbx was confirmed on whole mount than FT candidates determined by mpMRI and Sbx alone (73.8% vs 44.4%; p=0.026). Failure on whole mount was due to Gleason upgrade in 25.0% of patients and due to presence of bilateral IRPCa in the rest. On regression analysis, low PSA was the sole predictor of confirmed FT candidates on final pathology (p=0.021). Conclusions MpMRI Fbx/Sbx is a more accurate tool than mpMRI with Sbx alone for predicting FT candidates. However, the application of mpMRI and Fbx/Sbx criteria to predict FT candidates may result in undertreatment of approximately one quarter of the patients with significant cancer. More accurate predictive capability is needed before FT can be offered to all patients with IRPCa. Funding This research was made possible through the NIH Medical Research Scholars Program, a public-private partnership supported jointly by the NIH and generous contributions to the Foundation for the NIH by the Doris Duke Charitable Foundation (Grant #2014194), the American Association for Dental Research, the Colgate-Palmolive Company, Genentech, and other private donors. For a complete list, visit the foundation website at http://www.fnih.org.
Authors
Brian Calio
Abhinav Sidana Dordaneh Sugano Sonia Gaur Amit Jain Mahir Maruf Maria Merino Baris Turkbey Peter Choyke Bradford Wood Peter Pinto |
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MP70-02 |
Correlation of mpMRI contours with 3-Dimensional 5mm Transperineal Prostate Mapping biopsy within the PROMIS trial pilot: what margins are required? |
Prostate Cancer: Localized: Ablative Therapy I | 17BOS |
Abstract: MP70-02 Sources of Funding: Medical Research Council UK Introduction mpMRI offers the possibility to locate cancer in 3-Dimensions and aid surgical planning. We investigated the margin needed around an mpMRI lesion for complete disease control in a prospectively enrolled biopsy naïve population who underwent mpMRI followed by Transperineal Prostate Mapping with biopsies taken every 5mm(5TPM)._x000D_ _x000D_ Methods 94 patients included in this analysis were part of the pilot phase of Prostate MRI Imaging Study (NCT01292291) investigating accuracy of mpMRI against standard of care with TPM as a reference test. All patients were biopsy-naïve with a PSA below 15ng/ml. All patients underwent 1.5T mpMRI with standardized protocol (T2W, Diffusion, DCE), blinded reported using Likert scoring. Each core was separately labelled and oriented in space. Each prostate and MRI lesion was contoured on T2W-imaging, blinded to pathology. A 3D digital map of the TPM was reconstructed using an in-house software. Correlation between mpMRI and biopsy findings was automatically carried out using a platform generating the registration based on landmarks. We report the margin ‘M’ around the MRI lesion as the maximum distance within a set of negative biopsy location surrounding the MRI lesion. Results are also stratified by MRI score, Gleason Score, lesion eligibility to focal therapy and significance. Results 41 patients (median PSA 6.5ng/ml, median age 62) were found to harbour cancer at 5TPM in this cohort, yielding 75 MRI lesions that corresponded to cancer at 5TPM. The median number of MRI lesions per patient was 1.5. As a control of registration, correlation between MRI volume and TPM volume was ?=0.92 (p<0.001). Lesion characteristics are summarized in Table 1. The mean margin (enclosing a perimeter of negative cores) for MRI lesions corresponding the cancer at 5TPM was 7.0 mm (SD 4.6mm). For lesion eligible for focal therapy (n= 35), the mean margin was 7.3 (SD 4.3mm). The mean Gleason score of biopsy core outside the MRI lesion was 6.7 (+/- 0.5)._x000D_ _x000D_ _x000D_ Conclusions Our study is the first to report a margin around a mpMRI lesion when based on prostates that have not been removed using surgery and evaluated against a very accurate 3-dimensional 5mm mapping biopsy. These findings have implications for focal therapy and nerve-sparing surgery._x000D_ _x000D_ Funding Medical Research Council UK
Authors
Clement Orczyk
Yi Peng Hu Ahmed El-Shater Bosaily Eli Gibson Alex Kirkham Shonit Punwani Esther Bonmati Louise Brown Yolana Coraco-Moraes Katie Ward Rick Kaplan Dean Barratt Mark Emberton Hashim U Ahmed |
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MP70-03 |
Clinical performance of Multi parametric Magnetic Resonance Imaging in the follow-up of Partial gland ablation for Prostate Cancer |
Prostate Cancer: Localized: Ablative Therapy I | 17BOS |
Abstract: MP70-03 Sources of Funding: None Introduction Multi parametric Magnetic Resonance Imaging (mp-MRI) is the most common imaging modality used for detecting residual cancer following Partial Gland Ablation (PGA) for Prostate Cancer. The aim of this study was to assess the diagnostic accuracy of mp-MRI to detect residual cancer in the ablated area following PGA and to assess whether a biopsy of the ablated area may be avoided based on MRI. Methods Prospectively maintained institutional database was queried to identify 65 patients with primary PGA from May 2010 to February 2016 and had a postoperative MRI and a control biopsy within 18 months after the procedure. All the MRIs were reviewed by a single radiologist blinded to the biopsy results and visible abnormalities in the ablated area were scored based on a 5-point Likert scale and PIRADS V2. Univariate generalized estimating equation regression with an exchangeable correlation structure to account for within patient correlation was used to test the association between a high MRI score (Likert or PIRADS score ?3) and any- (Gleason ?6) and high-grade (Gleason ?7) disease detected on biopsy of the ablated area. Results After exclusions, we identified 38 post-PGA MRI and biopsy pairs with 6 patients having 2 MRI/biopsy combinations. Any-grade disease was detected on 15 biopsies (39%; 95% CI 24%, 57%) and high-grade on 2 biopsies (5.3%; 95% CI 0.6%, 18%). Patient with MRI lesion of Likert and PIRADS score ?3 in the ablated area were 8 (21%) and 7 (18%) respectively. Both the 2 instances of high-grade disease detected on biopsy occurred among the 8 MRIs with a Likert score ?3 (25%; 95% CI 3.2%, 65%) and 7 MRIs with a PIRADS score ?3. No high-grade disease was detected among participants with a Likert or PIRADS score <3, the upper bound of a 97.5% exact confidence interval was 11.6% and 11.2% based on Likert score (n=30) and PIRADS Score (n=31) respectively. One patient had a PIRADS score of 5 and had a Gleason 6 disease detected on biopsy. We did not find sufficient evidence to suggest an association between a PIRADS score and any-grade disease (p = 0.6) nor between Likert score and any-grade disease (p = 0.9), the association was not estimable as we had no participants with high-grade disease with an MRI score less than 3. Conclusions This preliminary study was unable to identify an association between MRI scores and presence of prostate cancer in the treated area following PGA therapy. Men with MRI scores of <3 should not be precluded from biopsy given that it is plausible that the rate of high-grade disease is meaningfully high. Funding None
Authors
Arjun Sivaraman
Melissa Assel Andreas Hoetker Govindarajan Srimathveeravalli Behfar Ehdaie Oguz Akin Jonathan Coleman |
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MP70-04 |
3-T Multiparametric MRI Characteristics of Prostate Cancer Patients Suspicious for Biochemical Recurrence after Primary Focal Cryosurgery. |
Prostate Cancer: Localized: Ablative Therapy I | 17BOS |
Abstract: MP70-04 Sources of Funding: Department of Urology, Winthrop University Hospital Introduction Biochemical recurrence (BCR) after primary focal cryosurgery (PFC) is determined using criteria (Phoenix, ASTRO) designed for post radiation patients. These criteria are limiting, hence the need for PFC-specific BCR criteria. We report on MRI characteristics of post-PFC patients with suspected BCR. Methods We retrospectively reviewed patients who underwent PFC. Prostate specific antigen (PSA) nadir was determined using ≥2 PSA values. BCR was determined using Phoenix criteria (nadir + 2 ng/ml). Pre- and post-PFC multiparametric MRIs (mpMRI) were obtained and biopsies were performed. Results Ninety (51.1%) of 176 patients who underwent PFC had more than 2 post-PFC PSAs. Of those who experienced BCR (41.1%) (median time to BCR 19.9 months), 27 (73.0%) underwent mpMRI (Table 1). Seventeen (45.9%) mpMRIs were found with a suspicious lesion, 58.8% were ipsilateral compared to pre-PFC mpMRI and location of pre-PFC positive cores. 35.3% of lesions were located in the central gland of the prostate. Five of 11 patients with positive post-PFC MRI were positive on biopsy. Seven of 17 patients with positive MRIs received definitive treatment. Conclusions Post-PFC MRI at suspected BCR may help identify a significant number of patients failing PFC. Funding Department of Urology, Winthrop University Hospital
Authors
Daniel Halpern
Michael Kongnyuy Kaitlin Kosinski Jeffrey Schiff Anthony Corcoran Aaron Katz |
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MP70-05 |
Defining the Index Lesion for Salvage Partial Gland Ablation after Radiation Therapy for Localized Prostate Cancer |
Prostate Cancer: Localized: Ablative Therapy I | 17BOS |
Abstract: MP70-05 Sources of Funding: None Introduction Partial gland ablation (PGA) is a promising treatment for selected patients with recurrent localized prostate cancer after radiation therapy. Our objective was to evaluate the impact of MRI and systematic biopsy characteristics to identify the index lesion for salvage partial gland ablation using tumor maps from whole mount slides of salvage radical prostatectomy (sRP) specimen. Methods We identified 225 patients who underwent sRP between 2000 and 2014 and a tumor map was created from whole-mount slides in 77 patients. Among these patients, we selected men with a priori pre-treatment criteria considered eligible for PGA, including, biopsy proven unilateral disease concordant with a region of interest (ROI) on MRI, and excluding men with imaging suspicious for extra-capsular extension (ECE), seminal vesicle Invasion (SVI) or lymph node involvement (LNI). We describe the correlation between pre-treatment clinical characteristics and final radical prostatectomy whole mount specimen to select men eligible for PGA defined as hemi-gland ablation. Results Among 77 patients with a tumor map of entirely-submitted and whole-mounted specimens, 15 patients were determined to be eligible for partial gland ablation based on pre-treatment clinical characteristics. The mean age was 60 years and median time from primary RT was 48 months. The median (IQR) tumor volume of the index lesion was 0.3 (0.4) cc. The location of the index lesion was determined to be the apex, mid-gland and base in 77%, 100% and 15% of patients, respectively. The median distance of the index tumor to the urethra was 0.5 (0.2) cm. The index tumor was confined to one lobe and concordant to the biopsy pathology and MRI data in all 15 patients (100%). There was no ECE, LNI or SVI identified in the sRP specimens. To account for those patients who did not have a tumor map of the whole-mount specimen, a sensitivity analysis was performed and determined that the clinical characteristics of the 77 patients with tumor maps were comparable to the entire 225 sRP cohort. Conclusions Clinical characteristics guided by biopsy findings and MRI data can be used to select men for PGA with recurrent localized prostate cancer after radiation therapy. Based on tumor maps from whole-mount slides of sRP specimen, we propose that salvage hemi-gland ablation including periurethral tissue is feasible in select patients with biopsy proven unilateral disease concordant with MRI data. Funding None
Authors
Arjun Sivaraman
Toshikazu Takeda Hebert Alberto Vargas Samson Fine James Eastham Behfar Ehdaie |
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MP70-06 |
Predicting Oncological Control Following Focal Ablation(FA) of Prostate Cancer(PCa) |
Prostate Cancer: Localized: Ablative Therapy I | 17BOS |
Abstract: MP70-06 Sources of Funding: None Introduction There is increasing interest in FA for select cases of PCa. The objective of this study is to provide insights into oncological control following FA. Methods 59 men who underwent radical prostatectomy (RP) between 2012 and 2016 fulfilled criteria for FA: a single MRI lesion (MRI-L) concordant with biopsy Gleason score (GS) <8, no gross extra-prostatic extension on MRI, no GS>6 or GS 6 core length>5mm contralateral to the single MRI-L on 12 core systematic biopsy. All RP surgical specimens were sectioned transversely every 3mm. The greatest linear dimension, GS and extent of Gleason pattern (GP) 4 of all tumor foci were recorded and related to scale on corresponding 3 mm transverse slice prostate maps. Clinically significant secondary cancers (CSSC) were defined as GS 6>5mm or any GP 4 not detected by mpMRI. The location of these CSSC relative to the MRI-L and the distance from the peripheries of the CSSC and the MRI-L were recorded and used to predict oncological control following theoretic ablation templates (TAT) of MRI-L + 10mm margin or hemi-ablation. Results Overall, 29 (49%) of the prostates had at least one CSSC. Of the total 50 CSSC, 15 (30%), 34 (68%) and 1 (2%) were ipsilateral, contralateral and midline to the MRI-L. Of the 50 CSSC, 30 (60%), 16 (32%), and 4(8%) were GS 6 > 5mm, GS 3 +4, and GS >3 + 4 respectively. The median greatest linear dimensions (MGLD) of the GS 6, GS 3 + 4, and GS > 3 + 4 PCa were 7.5mm, 5mm, and 2mm, respectively. The MGLD of the ipsilateral vs contralateral CSSC were not significantly different. Of the 20 CSSC with any GP 4, 10 (50%) exhibited a MGLD < 5 mm. The median GP 4 length in missed CSSCs was 0.8mm (range 0.1-2.4mm). A MRI-L + 10mm margin vs hemi-ablation would leave residual GP4 CSSC in 14 (23.7%) vs. 10 (16.9%) cases (p=.36), respectively Conclusions Approximately half of candidates meeting our criteria for FA have CSSC. Since 50% of these CSSC were <5mm, many were not detected by MRI. In addition, the median GP 4 length was only 0.8mm, suggesting that many of these CSSC were of equivocal biological significance. Of the CSSC, 68% were contralateral to MRI-L suggesting similar oncological limitations of TAT of MRI-L + 10mm margin and hemi-ablation. Our study provides compelling evidence that all men undergoing FA require active surveillance for disease both within and outside the AT._x000D_ Funding None
Authors
Alexander Kenigsberg
Elton Llukani Fang-Ming Deng Jonathan Melamed Herbert Lepor |
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MP70-07 |
A multivariable model and risk score for biochemical failure after whole-gland salvage cryosurgery at 10 years follow-up. |
Prostate Cancer: Localized: Ablative Therapy I | 17BOS |
Abstract: MP70-07 Sources of Funding: None Introduction Whole-gland salvage cryosurgery (SCS) is a potential curative treatment for organ-confined radiorecurrent prostate cancer (PCa). To enhance patient selection and optimize follow-up, a prediction model was created for biochemical failure (BF). Methods Data on patients (pts) treated (1995-2004) with salvage SCS at one centre was prospectively collected. Recurrences were biopsy proven and metastatic disease was excluded with pelvic/abdominal CT and radionuclide bone scan. Cox regression was adopted to assess the influence of clinical characteristics on BF. Missing data was imputed 20 times. Factors with a p-valueÿ0.25 were left in the model. The model was internally validated using bootstrap resampling (500 times) after which the C-statistic and hazard ratios could be adjusted for optimism. Calibration at different time points was performed and a risk score were created to assess different prognostic groups. Results 152 pts had follow-up data. A total of 89 pts experienced BF according to the Phoenix-definition (PSA-nadir+2 ng/ml). Median follow-up was 117 months (interquartile range 56-154). Five and ten year biochemical disease free survival (BDFS) was 45% (95%-CI 37-54%) and 35% (95%-CI 27-45%). Age at SCS, pre-salvage PSA, Gleason score and PSA-nadir after treatment were associated with BF after multivariable regression (table 1), adjusted C-statistic 0.76. The model was well calibrated up to 10 years. Four risk groups were created (score <22, 22-25, 25-30 and >30, see table 1). BDFS estimates at ten years were 68%, 41%, 27% and 12%, respectively (log-rank p<0.0001)(fig.1). Conclusions Selection of salvage pts is challenging, since guidance in the literature is scarce as to prognostic value of clinical characteristics. The presented model can guide patient selection and individualize follow-up. The model is not externally validation. Applicability might therefore be limited for other centres performing SCS. Funding None
Authors
Max Peters
Khurram Siddiqui Jochem van der Voort van Zyp Philippe Violette Glenn Bauman Robbert Tersteeg Joseph Chin |
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MP70-08 |
A Nomogram for Prediction of Local Cancer Recurrence after Primary Prostate Cryoablation |
Prostate Cancer: Localized: Ablative Therapy I | 17BOS |
Abstract: MP70-08 Sources of Funding: none Introduction The purpose of this study is to create a pre-treatment and post-treatment model for prediction of local recurrence in men who underwent primary full gland cryoablation of the prostate. Methods We studied 961 patients from the Cryo On-Line Data (COLD) registry who underwent primary full gland cryoablation for prostate cancer and subsequently received post-treatment prostate biopsy. Pre- and post-treatment variables of interest were identified and fit in a Cox regression model to predict time to positive biopsy using backward stepwise elimination of variables, knots and interactions of p>0.1 to accept the model with maximum AIC. The pre-treatment and post-treatment regression models were each internally validated and calibrated using 500 bootstraps and then constructed into nomograms. Results Mean age was 69.2 (± 7.9) years old. The median pre-treatment PSA was 6.8 ng/ml (IQR 4.6-9.8). Biopsy prognostic grade group (PGG) ranged from 1 to 5 in 70%, 12%, 6%, 8% and 3% of men respectively and 14% had a clinical stage ≥cT3. Post-treatment biopsy was positive in 28.2% of patients. The pre-operative nomogram included: PSA, PGG, ≥cT3 and use of neoadjuvant androgen deprivation therapy (nADT) (Figure 1). The post-operative nomogram included: PGG, ≥cT3, nADT, PSA nadir, biochemical recurrence (BCR, Phoenix), time till undetectable PSA, time on undetectable PSA and various interaction terms (Figure 2). The pre-operative nomogram achieved a corrected C-index of 61% while the post-operative nomogram achieved a corrected C-index of 71%. Conclusions We developed the predictive models for time to local cancer recurrence before and after primary full gland cryoablation of the prostate. Addition of post-treatment factors appears to improve predictive ability. These models can guide the urologist in selecting the appropriate candidate for cryoablation and determining the intensity of post-treatment follow-up._x000D_ _x000D_ Funding none
Authors
Ahmed El Shafei
Kae Jack Tay Ashley Ross Thomas Polascik Robert Given Vladimir Mouraviev J. Kellogg Parsons J Stephen Jones |
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MP70-09 |
Predictors of Biochemical Recurrence after Primary Focal Cryotherapy for Localized Prostate Cancer: A Multi-Institutional Analytic Comparison of the Phoenix and Stuttgart Criteria. |
Prostate Cancer: Localized: Ablative Therapy I | 17BOS |
Abstract: MP70-09 Sources of Funding: Department of Urology, Winthrop University Hospital Introduction The Phoenix (PD) and Stuttgart definitions (SD) are used to define biochemical recurrence (BCR) in patients after radiotherapy and High Intensity Focused Ultrasound treatment of organ-confined prostate cancer (PCa) respectively. However, these definitions have also been applied to follow patients who have undergone cryosurgery. We sought to identify predictors of BCR using the PD and SD criteria and evaluate each criterion&[prime]s ability to predict biopsy-proven recurrence in primary focal cryosurgery (PFC) patients. Methods We performed a retrospective review of patients who underwent PFC at two tertiary care centers. Patients were followed with serial prostate specific antigen (PSA) tests. PSA levels, pre- and post-PFC biopsy Gleason scores, number of positive cores, and BCR (defined as: PD = [PSA nadir + 2 ng/mL] and SD = [PSA nadir + 1.2 ng/mL]) were recorded. Patients who experienced BCR were biopsied, monitored carefully or treated at the discretion of the treating urologist. Cox proportional regression and survival analyses were performed to assess time to BCR using the PD and SD criteria. Results Of 162 patients included [median (range) follow up: 36.6 (2.8-109.4) months] in the study, 64 (39.5%) and 98 (60.5%) experienced BCR based on PD and SD, respectively. On multivariate Cox regression analysis, the number of positive pre-PFC biopsy cores was an independent predictor of both PD (Hazard Ratio [HR]: 1.4, p=0.001) and SD (HR: 1.3, p=0.006) BCRs. Post-PFC PSA nadir was an independent predictor of BCR using the PD (HR: 2.2, p=0.024) but not SD (HR: 1.4, p=0.181) BCR. Survival analysis showed a 3-year BCR free survival of 55% and 36% for PD and SD respectively. Of those biopsied after BCR, 14/26 (53.8%) using the PD and 18/35 (51.4%) using the SD were found to have cancer (57.1% PD and 66.7% SD were clinically significant PCa). Conclusions Both the PD and the SD showed about a 50% biopsy-proven rate of recurrence after PFC. The number of positive cores on pretreatment biopsy appears to be a significant predictor of failure after PFC. The ideal definition of BCR after PFC remains to be elucidated. Funding Department of Urology, Winthrop University Hospital
Authors
Michael Kongnyuy
Michael Lipsky Shahidul Islam Dennis Robins Kaitlin Kosinski Daniel Halpern Shaun Hager Jeffrey Schiff Anthony Corcoran Sven Wenske Aaron Katz |
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MP70-10 |
New approach to focal therapy of localized prostate cancer with “fusion” integrated path and high intensity focused ultrasound (HIFU): initial experience |
Prostate Cancer: Localized: Ablative Therapy I | 17BOS |
Abstract: MP70-10 Sources of Funding: none Introduction Focal therapy is an emerging mini-invasive treatment modality for localized prostate cancer (PCa) aimed to reduce the morbidity associated with radical therapy while maintaining optimal cancer control. The technological improvement of multiparametric magnetic resonance imaging (mpMRI), 3D-ultrasound and software for image fusion in order to locate more accurately PCa foci provides an optimal technology combination for the ideal focal efficacy. We report the 6-months oncological and functional results of primary focal ablation high-intensity focused ultrasound (HIFU) after fusion biopsy diagnosis of PCa in a prospective cohort of patients. Methods Single-center prospective evaluation of focal therapy for organ-confined PCa was performed from November 2015 through April 2016 using Focal-One® device (EDAP TMS). PCa diagnosis and localization was done based on mpMRI and -3D ultrasound-targeted fusion biopsy (Trinity, Koelis) plus standard biopsy. HIFU focal ablation using Focal-One® device was carried out under general anesthesia to immobilize the target lesion. The MRI/US imaging fusion of the target area was transported directely from Trinity to Focal One through specific software for the treatment. Treatment oncologic outcomes were evaluated with PSA and mpMRI 6 months after treatment. Targeted fusion biopsy after HIFU treatment was performed only in mpMRI positive patients. Functional outcomes were assessed with validated questionnaires for genitourinary symptoms. Results Forty-one patients underwent focal therapy and were included in the study. Mean age was 70 yr (55-79 yr). Mean PSA was 6.8 ng/ml (0.5-18). National Comprehensive Cancer Network low-, intermediate-, and high-risk disease was 29 (70,8%), 10 (24,4%), and 2 (5,8%), respectively. Mean pre-treatment prostate volume was 39,7 ml (14-66); Mean volume of tissue treated was 13,5 ml (4-30). In three patients a ThuLEP procedure was performed 2 months before HIFU. In thirty-three patients (80,3%) the catheter was removed in day 7 after HIFU; in eight patients (19,5%) the catheter was maintained until day 15. Nine men (21,9%) had self-resolving, mild to moderate, dysuria (median duration 7 days). Urinary tract infection was noted in 5 men (12,2%). Mean 6-months PSA was 2,4 ng/ml (0,2-9). Forthy patients (97,6%) had normal mpMRI findings 6-months after HIFU. One patient showed focal abnormal signal at mpMRI around the treated area: fusion biopsies confirmed the persistence of microfocal PCa with Gleason score 3+3 (treatment failure); in this patients a retreatment was performed. No major complication was observed. IPSS score showed no significant difference before and 6-months after HIFU. At 6 months, all patients were completely continent, and potency was maintained in 30 of 31 preoperatively potent patients. Conclusions The integration between fusion biopsy and Focal One device allows to date the most accurate detection and treatment of index focus of PCa. This preliminary experience with 6-months follow-up time indicates that HIFU focal ablation of prostate cancer leads to &[Prime]Trifecta&[Prime] outcomes (cancer control, continence, sexual potency) in 91,5% of 41 men. The integration of new technologies enables the accurate and early diagnosis of recurrence after focal ablative treatment, leaving the possibility of a precise HIFU retreatment. Funding none
Authors
Alessandro Branchi
Giulio Milanese Luca Gasparri Redi Claudini Michele Pucci Andrea Benedetto Galosi Tiziana Pierangeli Marco Dellabella |
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MP70-11 |
Medium term outcomes following Focal HIFU for the treatment of Localised Prostate Cancer: a single centre experience. |
Prostate Cancer: Localized: Ablative Therapy I | 17BOS |
Abstract: MP70-11 Sources of Funding: None Introduction Focal therapy using High Intensity Focused Ultrasound (HIFU) in the treatment of non-metastatic prostate cancer has been shown to confer a low risk of genitourinary side-effects with encouraging early disease control. We present our single centre experience over a 7 year period (2009-2016) of 164 cases. Here we report on medium term functional and oncological outcomes in this group of patients. Methods 164 patients with (T1c-T3a) localised prostate cancer were treated with focal-HIFU. Multi-parametric MRI followed by transperineal mapping biopsies and/or MR-targeted biopsies was used as the standard diagnostic tool. Focal-HIFU was carried out according to disease location and Surgeon planning but usually involved a hemi or quadrant ablation. Patient follow up included regular PSA, MRI and further prostate biopsies if indicated. Results 32 (20%), 117 (71%) and 15 (9%) had low, intermediate and high-risk disease, respectively. Median PSA at diagnosis was 7 (range 2.6-21.4). Median follow-up was 50 (range 2-78) months._x000D_ _x000D_ 100% of patients who were pad free prior to treatment maintained pad free status by 3 months post procedure while 82% of patients who was had satisfactory pre-operative erection maintained their potency post-operatively. There were no major complications and 1 developed a stricture which required intervention._x000D_ _x000D_ Median PSA nadir was 1.2ng /L by 4.5 months. 7 patients had a further focal-HIFU treatment, whilst 5 had radical prostatectomy and 1 had Radiotherapy. 1 patient underwent cryotherapy and 1 HIFU for contralateral disease. 1 patient required systemic hormones for metastatic disease. Metastasis-free survival and overall cancer specific survival at 5 years was 99.4% and 100% respectively. Conclusions Our single centre focal HIFU experience supports the place for a focal ablative therapy in the management of prostate cancer in carefully selected cases. We have demonstrated good oncological results with minimal morbidity and a favourable side-effect profile. Funding None
Authors
Kiki Mistry
Utsav Reddy Simon Bott Amr Emara Richard Hindley |
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MP70-12 |
Predicting extensive disease among potential candidates for hemi-ablative focal therapy for prostate cancer |
Prostate Cancer: Localized: Ablative Therapy I | 17BOS |
Abstract: MP70-12 Sources of Funding: none Introduction Although there is increasing interest in focal therapy for prostate cancer as an alternative treatment option to whole-gland therapy, it remains difficult to select eligible candidates. We sought to identify preoperative factors that can predict extensive disease after radical prostatectomy (RP) in potential candidates for hemi-ablative focal therapy. Methods We identified 770 patients who were diagnosed with unilateral prostate cancer by biopsy, met the focal therapy consensus meeting criteria (PSA<15 ng/mL, clinical stage T1c-T2a, Gleason score 3+3 or 3+4), and had undergone RP at our institution between 2000 and 2014. Among these 770 patients, 98 had tumor maps from whole-mount slides and magnetic resonance imaging (MRI) data. Extensive disease was defined as having Gleason pattern 4 or 5 in bilateral lobes, extracapsular extension, seminal vesicle involvement, or lymph node involvement on the tumor map and RP pathology. Both lobes of the prostate were scored using the standardized 5-point Prostate Imaging Reporting and Data System version 2 on MRI. Extracapsular extension and seminal vesicle involvement were also scored using a 5-point scale. Preoperative characteristics including biopsy and MRI data were evaluated. Selected predictors of extensive disease were analyzed by multivariable logistic regression. Decision curve analysis was performed to evaluate the clinical utility of our model. Results Among our cohort, 39 patients (40%; 95% CI 30%, 50%) had extensive disease. The Kattan nomogram score (p=0.020) and a MRI extracapsular extension score ≥3 (p=0.002) were independent predictors of extensive disease. Our model exhibited a discrimination of 0.698 after 10-fold cross-validation. However, decision curve analysis demonstrated that our multivariable model does not add value for threshold probabilities of having extensive disease below 20%, with no increase in net benefits compared to a treat-all strategy._x000D_ _x000D_ Conclusions Although the variables in our model are significantly associated with extensive disease, it was not able to place patients into a low enough risk of extensive disease where hemi-ablative therapy would be indicated. Funding none
Authors
Toshikazu Takeda
Amy Tin Renato Corradi Maha Mamoor Nicola Robertson Hebert Vargas Nicole Benfante Daniel Sjoberg Samson Fine James Eastham Peter Scardino Karim Touijer |
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MP70-13 |
Cryosurgical Ablation of the Prostate: Local Disease Control for Intermediate /High-grade Gleason Prostate Cancer |
Prostate Cancer: Localized: Ablative Therapy I | 17BOS |
Abstract: MP70-13 Sources of Funding: None Introduction Our objective is to report local disease control after primary whole gland cryoablation when used to treat Gleason ≥ 7 localized prostate cancers at our institution. Methods We analyzed 134 prostate cryoablation patients who had a Gleason score of ≥ 7 who underwent primary whole gland cryoablation. Progression free survival (PFS) was defined according to Phoenix definition of PSA nadir +2 ng/ml. Among the biochemical failure (BF) patients, we assessed local disease control by postoperative prostate biopsy, pelvic MRI or CT. BS was used to assess metastatic disease. We defined local treatment failure by a positive post cryoablation prostate biopsy and/or MRI/CT scan findings suggesting local recurrence within the prostate. Results PFS was noted in 101 patients (75%) with median follow up time of 31.5 months. Among the 33 patients who showed BF, 3 patients did not have a metastatic workup. Of the remaining 30 patients, 15 (11.2% of treated patients) showed only local treatment failure as indicated by positive post cryoablation prostate biopsy and/or MRI/CT scan findings suggesting local recurrence within the prostatic gland. The other 15 patients (11.2%) showed metastatic disease with no evidence of local treatment failure. (Table 1) Conclusions Cryoablation is a successful primary treatment option for patients with intermediate/high grade prostate cancer. Up to half of patients who showed biochemical failure had good local disease control but had distant failure as evident by post cryoablation prostate biopsy and/or MRI/CT scans; this suggests patient selection failing to identify micro metastasis present at the time of treatment rather than local treatment failure. Funding None
Authors
Ahmed El Shafei
Mohamed Eltemamy Yaw Nyame Hans Arora J Stephen Jones |
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MP70-14 |
PSA nadir and PSA flare are the predictors of biochemical failure after High-Intensity Focused Ultrasound treatment of localized prostate cancer |
Prostate Cancer: Localized: Ablative Therapy I | 17BOS |
Abstract: MP70-14 Sources of Funding: none Introduction High-Intensity Focused Ultrasound (HIFU) is an emerging treatment for localized prostate cancer patients. HIFU is a noninvasive technique that induces coagulative necrosis in tumors without surgical exposure or insertion of instruments into the lesion. We evaluated the association between clinical outcomes and biochemical failure (BCR). Methods From June 2006 to November 2014, 259 consecutive patients with T1-2 prostate cancer were treated with Sonablate? (SB) devices. After HIFU, prostate-specific antigen (PSA) was measured every 3 months. BCR was defined according to the Stuttgart definition (a rise of 1.2 ng/ml or more above the nadir PSA). Serum PSA level was increased rapidly after HIFU. Then, PSA flare was determined an increase of 3.0 ng/ml with a spontaneous return to the pre-flare level or lower. Predictors for BCR was identified using the Cox-proportional hazard method. Results A total of 259 patients with a median age of 67.6 years were followed for median duration of 59 months. Mean pretreatment PSA was 9.6 ng/ml. Mean pretreatment prostate volume was 28.7ml. Stratification according to D’Amico’s risk group was low, intermediate, high in 23.6%, 30.5%, 45.9% of patients, respectively. Neoadjuvant hormone therapy was administered in 45.1% of patients. Transurethral resection of prostate (TURP) at the time of HIFU was performed in 34.4% of patients. Mean PSA nadir was 0.3 ? 0.8 ng/ml with 77.6% reaching nadir of ? 0.3 ng/ml. The overall survival rate at 5 year was 99.6%. The 3- and 5- BCR free survival rates were 72.3-62.6%, 89.1-78.1%, 72.7-65.0%, 62.6-51.1% for all patients, low- intermediate-, and high risk patients. 44.1% of patients had urinary structure, 29.7% of patients had self-resolving lower urinary tract syndrome (LUTS). Cox multivariate analysis revealed Preoperative PSA (PSA cut off = 10 ng/ml: Hazard ratio (HR) = 2.369, 95% CI 1.518–3.735, p<0.001), D’Amico risk group (Low & intermediate vs high: HR = 2.359, 95% CI 1.066-3.086, p=0.028), PSA nadir (PSA cut off = 0.3 ng/ml: HR = 3.248, 95% CI 1.943-5.427, p<0.001), and PSA flare (PSA cut off = 3.0ng/ml: HR = 2.063, 95% CI 1.014-4.194, p=0.046) were a predictor for BCR. Conclusions HIFU represents an effective, minimally invasive treatment for prostate cancer. The PSA nadir and PSA flare correlate significantly with BCR, and can be applied in daily clinical practice. Funding none
Authors
Naokazu Ibuki
Teruo Inamoto Yudai Nishimoto Kiyoshi Takahara Toshikazu Watsuji Haruhito Azuma |
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MP70-15 |
Intra-prostatic PRX302 focal therapy in treating clinically significant low-intermediate prostate cancer: an open label, proof-of-concept study |
Prostate Cancer: Localized: Ablative Therapy I | 17BOS |
Abstract: MP70-15 Sources of Funding: Sophiris Bio Corp. Introduction Intra-prostatic injection of PRX302 may provide a targeted approach to focally lysing tumor cells, avoiding the side-effects of radical treatment. It is a genetically modified pore-forming protein (aerolysin) activated by enzymatically active PSA. Our proof-of-concept IRB-approved study aimed to determine toxicity, side-effects and early efficacy as well as to determine optimum treatment delivery of MRI-ultrasound fusion-guided intra-prostatic injection of PRX302. Methods 18 men with histologically proven, clinically significant, localized low-intermediate risk prostate cancer associated with an MRI lesion were recruited (PSA =15, T2aN0Mo, Gleason =4+3 with a maximum cancer core length [MCCL] =10mm, or Gleason 3+3 with MCCL >/=4mm (May/2015-Nov/2015). Patients had a single lesion injected transperineally using MRI-ultrasound image-fusion software (SmartTarget®), under general anaesthetic with up to 5mL of a standard dosing solution (20ug/mL) of PRX302. Follow-up occurred at 2 days and at 2, 6, 12, 24 and 26 weeks. A mpMRI-targeted transperineal biopsy of the treated area was performed at 24 weeks. All men who enrolled completed the study. Results Median age and PSA were 66.50 years (IQR 13.00) and 6.25ng/ml (IQR 2.45). 4 patients (22%) had high volume Gleason 6 and 14 (78%) had Gleason 7 cancer with median lesion size 0.3mL (IQR 0.2-0.5). The administration of PRX302 was well tolerated with no serious adverse events and no new safety signals. At 24 weeks following treatment, 2 had complete tumour ablation (no histological evidence of cancer). These 2 showed reductions in PSA of 3.0 to 2.2ng/mL (26.7%) and 5.7 to 4.8ng/mL (15.8%), respectively. Seven had partial response defined as reductions in MCCL or Gleason grade. 9 had no histological response, with some experiencing increases in MCCL or grade. Conclusions Our proof-of-concept study shows that a single intraprostatic administration of PRX302 has a biological effect on prostate tumor cells when focally injected with low side-effect profile. Optimizing the dosing and delivery of PRX302 based on tumour size may increase response rates and will be tested in a multicenter phase 2 study. Funding Sophiris Bio Corp.
Authors
Edward Bass
Yaalini Shanmugabavan Allison Hulme Alex Freeman Chris Brew-Graves Ingrid Potyka Navin Ramachandran Mark Emberton Hashim Ahmed |
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MP70-16 |
Safety and feasibility of real-time MRI-guided focused ultrasound for focal therapy of localized prostate cancer using the ExAblate 2100 device: Phase 1 study |
Prostate Cancer: Localized: Ablative Therapy I | 17BOS |
Abstract: MP70-16 Sources of Funding: _x000D_ InSightec, Inc. Haifa, Israel; the Ontario Research Fund; and the Canadian Foundation for Innovation._x000D_ Introduction Organ preserving therapy is emerging as an option for localized prostate cancer to minimize the morbidity associated with whole-gland therapy. We examine the short-term oncologic and functional data of the initial phase 1 trial of patients treated with focal transrectal MRI-guided focused ultrasound (MRgFUS) in North America._x000D_ Methods This phase 1 prospective study was approved by institutional review board. Eight patients with organ-confined PC visible on multiparametric MRI (mpMRI) and confirmed by the MRI-fusion biopsy (Artemis, Eigen) were enrolled. Patients were eligible with PSA ≤10ng/mL and Gleason score (GS) ≤ 7(4+3). Tumors larger than 1.5 cm in any dimension, too peripheral for a 5mm ablation margin or with concern for extraprostatic extension were excluded. Under MRI-guidance and real-time MR thermography, focal lesions were ablated using high frequency ultrasound energy delivered via an endorectal transducer with 990 elements (ExAblate 2100, InSightec). Incidence and severity of treatment-related adverse events were recorded at 6 months. _x000D_ Results Eight patients with 10 peripheral zone lesions were treated. Prostate volume ranged from 25 to 50 cc with mean target volume of 2.7cc (range 0.4 - 5.7cc). Mean procedure time was 248 minutes. Based on pre-treatment biopsy, six lesions were GS6(3+3), two were GS7(3+4) and two others were GS7(4+3). Treatments were all completed as planned without major technical delays or surgical complications. Mean post treatment non-perfused volume was 4.3cc (range 2.2 - 7.6cc). Quality of life parameters were similar between baseline and 6-months in 6 of 8 patients. One patient with bilateral ablation had significantly worse storage symptoms while a second patient developed self-limiting acute prostatitis with erectile dysfunction. Mean PSA decreased from 5.06 to 3.4 ng/ml at 6 months. All patients were MRI negative in their treated regions. On biopsy, five patients were disease-free in treated regions (7 of 10 lesions). In one patient with a presumed GS7(4+3) tumor, a 2mm MRI-invisible focus of GS8(4+4) PC was seen in 1 of 5 cores from the ablation site. He underwent prostatectomy with negative surgical margins. Conclusions MRgFUS is a feasible and safe method of ablating localized PC. Further work is required to improve patient selection and address causes of failed ablation. Our study is limited by small sample size and brief follow-up. More meaningful oncologic and functional outcomes for MRgFUS can be assessed with larger trials with longer follow-up. _x000D_ Funding _x000D_ InSightec, Inc. Haifa, Israel; the Ontario Research Fund; and the Canadian Foundation for Innovation._x000D_
Authors
Nathan Perlis
Eugen Hlasny Walter Kucharczyk Masoom Haider Antonio Finelli Alexandre Zlotta Girish Kulkarni John Trachtenberg Sangeet Ghai |
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MP70-17 |
Does Prior Interventional Therapy for BPH Increase the Risk of Complications after Primary Whole Gland Prostate Cryoablation? |
Prostate Cancer: Localized: Ablative Therapy I | 17BOS |
Abstract: MP70-17 Sources of Funding: None Introduction To assess whether prior interventional treatment for benign prostatic hyperplasia (BPH) increases the risk of complications of primary whole gland prostate cryoablation. Methods Among 3955 men who underwent primary whole gland prostate cryoablation, we identified 156 who had undergone prior therapy for BPH including transurethral needle ablation (n=6), transurethral microwave thermotherapy (n=11), and transurethral resection of the prostate (n = 139). Patients with a history of medical or unspecified BPH therapy were excluded from the study. Primary outcomes included post-treatment urinary incontinence, urinary retention, erectile dysfunction (ED), and recto-urethral fistulae. Results Median age was 71 years (IQR 66-76), median Gleason sum 6 (IQR6-7) and median PSA 6.6 ng/mL (IQR 4.8-9.8). Men who received prior BPH therapy were older with median age (74 vs 71, p<0.001), were more likely to have pretreatment Gleason sum ≥7 disease (50% vs 41.5%, p=0.04) and have undergone neoadjuvant androgen deprivation therapy (50% vs.36%, p<0.001). In unadjusted analyses, prior interventional BPH therapy was associated with higher risks of post-operative urinary retention 22 of 149 (14.8%) vs. 325 of 3560 (9.1%), p=0.02 and new-onset urinary incontinence 20 of 144(13.9%) vs. 251/3371 (7.5%), p=0.005 compared to no prior therapy. Interventional BPH therapy was not correlated with the risk of development of recto-urethral fistula 2 of 149 (1.3%) vs. 46 of 3560 (1.3%), p=0.9 or new onset ED 23 of 34 (67.7%) vs. 631 of 1195 (52.8%), p=0.09 following surgery. On multivariable regression, prior interventional BPH therapy was associated with an 83% increased risk of urinary retention (OR 1.83, 95% CI 1.02-3.09, p=0.03) and a 73% increased risk of new-onset urinary incontinence (OR 1.73, 95% CI 1.03-2.78, p=0.03) (Table 1). _x000D_ Conclusions Prior interventional therapy for BPH is associated with increased risks of urinary retention and incontinence after whole gland prostate cryoablation. Nevertheless, in properly selected patients, prior bladder outlet procedures are not an absolute contraindication to cryotherapy. Consideration should be given to management protocol in those men including but not limited to time for catheter removal postoperatively and continuing BPH medical treatment Funding None
Authors
Ahmed El Shafei
Kae Jack Tay Asmaa Hatem Thomas Polascik Ashley Ross J. Kellogg Parsons Vladimir Mouraviev Robert Given J Stephen Jones |
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MP70-18 |
Prostate Radiofrequency Ablation Focal Treatment (proRAFT) : interim results of a prospective development study |
Prostate Cancer: Localized: Ablative Therapy I | 17BOS |
Abstract: MP70-18 Sources of Funding: TROD MEDICAL Introduction Radiofrequency ablation (RFA) using a bipolar coil design (Encage™ device) which acts as a Faraday cage offer the versatility needed to perform focal treatment of localised prostate cancer whilst sparing critical anatomical and functional structures. We report preliminary outcomes of our ethics approved prospective development study investigating focal Encage™ ablation (NCT02294903). Our primary objective was to determine the ablative efficacy 6 months after bipolar RFA. Secondary objectives included the assessment of genito-urinary toxicity._x000D_ Methods 21 men who had multi-parametric MR-visible index lesion concordant with transperineal biopsies and absence of clinically significant disease elsewhere with PSA =15ng/ml underwent day-case bipolar RFA with margins around the lesion of >/=5mm using elastic image-fusion (SmartTarget® platform). mpMRI transperineal targeted biopsies of the ablated zone and any new suspicious areas were carried out at 6 months._x000D_ Results 20 men were treated,none were eligible for active surveillance. Data are available for 15 patients treated and followed up to 6 months. Patient characteristics are presented in Tab1. No significant residual disease was found in 13/15 patients. Two had clinically significant cancer of 6mm Gleason 7 (3+4) and 4mm Gleason 6, with one of these undergoing a retreatment. One harboured insignificant disease (1mm Gleason 6; pre-RFA 8 mm Gleason 7). Median PSA (IQR) at 6 months post RFA was 3.1 (1.2 to 4.8) ng/mL_x000D_ _x000D_ 2 patients showed decrease function in term of leakage (1 patient needed a urethral dilatation for stricture). For pad use, 3/15 patients started to use pad. IPSS changed from 9.2 to 8.9 and IPSS quality-of-life from 1.86 to 1.8. Across the 11 patients declaring in IIEF questionnaires some sexual stimulation, 2 patients with already poor erectile function had some decrease at the point to not be sufficient for penetrations._x000D_ Erectile and bowel functions remained stable, as measured by the IIEF-15 and UCLA-EPIC bowel domain, respectively. EQ-5D and the FACT-P remained stable. There were 4 serious adverse events, none related to the procedure. Conclusions RFA using a bipolar device (Encage™) showed promising early disease control and a low profile of genito-urinary toxicity. Trial completion to one-year follow-up is awaited and further phase II multicentre trials will be needed. Funding TROD MEDICAL
Authors
Clement Orczyk
Chris Brew-graves Norman Williams Ingrid Potika Navin Ramachandran Alex Freeman Mark Emberton Hashim U Ahmed |
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MP70-19 |
Local Immune Modulation by Increasing T cytotoxic / T helper ratio after Prostate Cancer Hemi-Cryoablation |
Prostate Cancer: Localized: Ablative Therapy I | 17BOS |
Abstract: MP70-19 Sources of Funding: None Introduction While thermal ablation might activate tumor-specific T cells by raising the presentation of tumor antigens to the immune system, there is no information about prostate hemi-cryoablation impact on local immunology. Methods Prostate biopsies were collected from 10 very low risk prostate cancer patients (T1c, PSA density <0.15 ng / dL, Gleason ≤6, ≤2 cancer biopsy cores and ≤50% involvement any core with cancer) at diagnosis and 12 months after hemi-cryoablation. Cancer positive and negative lobes at diagnosis and the same areas 12 months after hemi-cryoablation (Diag+, Diag-, Cryo+ and Cryo-, respectively) were explored using immunohistochemistry for tumor infiltrating CD4+ T helper and CD8+ T cytotoxic cells (counted in 45 fields per patient with a 40x objective). The quantitative analysis of cells/mm2 and CD8+/CD4+ ratio were performed using ImageJ software. Results There was a significant increase in tumor infiltrating CD8+ T cytotoxic cells/mm2 in post Cryo+ prostatic tissue (mean ± SD: 0.31 ± 0.30) compared to Diag+ (0.18 ± 0.15), p=0.015. In contrast, tumor infiltrating CD4+ T helper cells/mm2 showed a tendency to decrease in Cryo+ (0.26 ± 0.27) compared to Diag + (0.38 ± 0.52). Tumor infiltrating T cytotoxic / T helper cells ratio increased after hemi-cryoablation, with conceivable anti-tumor immunity and favorable prognosis._x000D_ _x000D_ Conclusions This is the first study to show positive local immune modulation after prostate cancer cryoablation, characterized by increasing T cytotoxic / T helper cells ratio with potential to boost antitumor immune response. Long term follow-up and wider cohorts might confirm potential clinical impact and if such modulation occurs for any ablation or for cryoablation only._x000D_ _x000D_ Funding None
Authors
Karen L. Ferrari
Michael Cerqueira Athanase Billis Mário J. A. Saad Amilcar Castro Leonardo O. Reis |
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MP70-20 |
Predictors and Utilization of Ablative Therapies in New York State |
Prostate Cancer: Localized: Ablative Therapy I | 17BOS |
Abstract: MP70-20 Sources of Funding: none Introduction With the increased incidence of low-risk prostate and renal cancer, minimally invasive treatment options have become more desirable. In selected patients, focal ablative therapies offer less morbidity while achieving comparable outcomes to extirpative surgery. We describe patterns of usage of such therapies within a statewide database. Methods We queried the New York Statewide Planning and Research Cooperative System database to identify patients who underwent any focal ablative treatment for prostate or renal malignancy from 2001-2014 using CPT codes (55873, 53852, 53850, 50593, 50250, 50592, 50542), ICD-9-CM procedure codes (5532-5535, 6096, 6097), and ICD-9-CM diagnosis codes (185, 189.0, 189.1, 198.0). Medical comorbidities are also available. Hospital specific characteristics were obtained using available information from the New York Department of Health and the American Hospital Association. High volume centers were defined as the five highest volume hospitals according to number of ablative procedures. Logistic regression was performed to determine independent predictors of utilization. Results The final cohort included 1872 prostate ablations and 989 renal ablations. The five highest volume prostate and renal ablation centers performed 1173 (62.7%) and 376 (38.0%) cases, respectively. Demographic information is displayed in Table 1. On multivariate analysis, treatment with prostate ablation was associated with black race (OR 0.27, 95%CI 0.19-0.39, p<0.001), increasing age (OR 0.98, 95%CI 0.967-0.998, p=0.03), teaching hospital status (OR 3.32, 95%CI 2.34-4.71, p<0.001), and number of beds (OR 1.002, 95%CI 1.001-1.002, p<0.001). For renal ablation, significant predictors on multivariate analysis were black race (OR 0.46, 95%CI 0.25-0.84, p=0.012), other non-white race (OR 0.48, 95%CI 0.29-0.79, p=0.004), number of beds (OR 1.001, 95%CI 1.000-1.001, p<0.001), and higher Elixhauser comorbidity index (OR 1.017, 95%CI 1.002-1.033, p=0.025). Conclusions In New York State, the use of ablative therapies is largely limited to academic institutions in urban areas, yet minority populations are significantly less likely to undergo such procedures. Future study should focus on identifying the barriers to treatment and what impact this might have on disease outcomes among different populations. Funding none
Authors
Maxwell B James
Dennis J Robins Wilson Sui Ifeanyi C Onyeji Justin T Matulay Marissa C Theofanides Sven Wenske |
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MP71-01 |
Comprehensive Genomic Characterization of Upper Tract Urothelial Carcinoma (UTUC) |
Bladder Cancer: Upper Tract Transitional Cell Carcinoma I | 17BOS |
Abstract: MP71-01 Sources of Funding: Kleberg Center for Molecular Markers and the Institute for Personalized Cancer Therapy; Eleanor and Scott Petty Fund for Study of Upper Tract Urothelial Carcinoma; Monteleone Family Foundation for Research in Bladder and Kidney Cancers. Introduction Upper urinary tract urothelial cancer has many similarities to lower urinary tract cancer but also has many unique etiologic and genomic factors. We performed a comprehensive integrated genomic analysis of UTUC in order to characterize the genomic landscape of UTUC and provide insights into biology. Methods We obtained 31 untreated fresh snap frozen UTUCs under approved IRB approved protocols from 2 academic institutions. Following histologic confirmation and quality control for adequate viable tumor, DNA, RNA and protein underwent WES, RNAseq, and RPPA analysis. After adjusting for batch effects, consensus mutation calls from independent pipelines from each center identified gene expression clusters using unsupervised consensus hierarchical clustering (UCHC). Results Clinical data are shown in the Table. WES identified mutations in FGFR3 (74.1%), enriched not only in low grade tumors (92%), but also high grade (60%); KMT2D (44.4%), PIK3CA (25.9%), TP53 (22.2%). APOBEC and CpG signatures were identified. UCHC of RNAseq segregated samples into 4 molecular subtypes, not all of which resembled bladder TCGA subtypes. Cluster 1: no PIK3CA mutations; enriched for nonsmokers, high grade non-muscle invasive tumors, high recurrence rates and favorable survival. Cluster 2: 100% FGFR3 mutations; enriched for low grade, noninvasive disease, no bladder recurrences. Cluster 3: 100% FGFR3 mutations, 71% PIK3CA, no TP53 mutations; high tobacco use and bladder recurrence (62.5%); tumors all non-muscle invasive. Cluster 4: KMT2D (62.5%), FGFR3 (50%), TP53 (50%) mutations, no PIK3CA mutations; enriched for high grade, muscle-invasive disease, tobacco use, CIS, reduced survival; novel fusion of SH3KBP1-CNTNAP5 was identified, with high expression levels in the sample. Conclusions We show mutations in UTUC occurring at differing frequencies and subtypes that differ from high grade invasive bladder cancer. Novel fusion SH3KBP1 regulates RTK signaling and acts to recycle TGF? receptors. Further studies are needed to validate the described subtypes, explore their responses to therapy, and better define the novel fusion mutation. Funding Kleberg Center for Molecular Markers and the Institute for Personalized Cancer Therapy; Eleanor and Scott Petty Fund for Study of Upper Tract Urothelial Carcinoma; Monteleone Family Foundation for Research in Bladder and Kidney Cancers.
Authors
Tyler Moss
Yuan Qi Bo Peng Liu Xi Maribel Mosqueda Charles Guo Michael Ittmann David Wheeler Seth Lerner Surena Matin |
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MP71-02 |
Distinct Genomic Landscape of Upper Urinary Tract Urothelial Carcinoma |
Bladder Cancer: Upper Tract Transitional Cell Carcinoma I | 17BOS |
Abstract: MP71-02 Sources of Funding: none Introduction Upper urinary tract urothelial carcinoma (UTUC) is relatively rare and its molecular biology is poorly understood. To clarify distinct characteristics of UTUC, we comprehensively investigated the genetic alterations of this disease. Methods Surgical specimens of UTUC and matched normal samples were obtained from 99 patients with various stages and subjected to whole exome and RNA sequencing. Apparently normal urothelial epithelia and preoperative urine sediments were also analysed in 5 cases. Results Genetic alterations were most frequently observed in TERT promoter (51% of cases), followed by KMT2D (48%), FGFR3 (44%), CDKN2A (42%), TP53 (31%), and RAS pathway (HRAS/KRAS/NRAS, 21%). More than 95% of cases harbored either TP53/MDM2, FGFR3, or RAS pathway mutations in an almost mutually exclusive manner, based on which UTUCs are classified into 3 distinct subgroups with unique molecular and clinical features; FGFR3-mutated tumors showed a significantly better prognosis than those with TP53/MDM2 (p<0.001) and RAS pathway (p=0.010) lesions. We also found 4 hypermutated cases which harbored biallelic mutations in mismatch repair genes._x000D_ To further clarify the unique feature of mutations in UTUC, the mutation patterns were compared with those of bladder urothelial carcinoma (BUC) using previously reported datasets. Although altered genes in UTUC were almost same as those of BUC, frequencies were substantially different in some genes such as KMT2D and RB1. In addition, mutation spectrum in UTUC were also different depending on the anatomical location; Most of the RAS pathway mutations were found in renal pelvis (p=0.0013) while KMT2D mutations were observed more frequently in ureter (p<0.0001). _x000D_ In the analysis of normal epithelia, some epithelia and primary tumors harbored shared mutations as well as their private ones, indicating that clonal precancerous area expands in normal epithelia. By contrast, in other epithelia, we also found driver gene mutations that were not shared by primary tumors, suggesting the presence of a mutagenic field effect on urothelial multiple occurence. _x000D_ We also detected mutations in urine sediments identical to primary tumors with similar allele frequencies, suggesting that sequencing urine may be useful for disease monitoring._x000D_ Conclusions UTUC tumors are classified into 3 molecularly and clinically distinct subtypes based on the status of mutations in TP53/MDM2, FGFR3, and RAS pathway. Depending on their location, urothlial cancers have different genetic backgrounds, where a field effect and clonal expansion might contribute to multifocal occurrence of UTUC. Funding none
Authors
Yoichi Fujii
Yusuke Sato Hiromichi Suzuki Tetsuichi Yoshizato Yusuke Shiozawa Kenichi Yoshida Yuichi Shiraishi Tohru Nakagawa Haruki Kume Hiroaki Nishimatsu Toshikazu Okaneya Masashi Sanada Hideki Makishima Satoru Miyano Seishi Ogawa Yukio Homma |
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MP71-03 |
PROGNOSTIC VALUE OF PD-1 AND PD-L1 EXPRESSION IN PATIENTS WITH HIGH-GRADE UROTHELIAL CARCINOMA OF THE UPPER URINARY TRACT |
Bladder Cancer: Upper Tract Transitional Cell Carcinoma I | 17BOS |
Abstract: MP71-03 Sources of Funding: none Introduction To investigate the prognostic value of PD-1 and PD-L1 expression in patients with high-grade upper tract urothelial carcinoma (UTUC). Methods Tissue microarrays were created using 448 patients from the International UTUC collaboration who underwent extirpative surgery for high-grade UTUC and stained for PD-1 (antibody (AB): NAT105, diluted 1:250 from Ventana) and PD-L1 (AB: E1L3N&[copy] prediluted from Cell Signaling). PD-1 and PD-L1 expression was assessed in a semi-quantitative fashion and any percentage of staining of the tumor cells (PD-L1) and tumor-infiltrating lymphocytes (PD-1) was considered positive. Univariate (UVA) and multivariate analyses (MVA) were performed to assess independent prognosticators of oncological outcomes. No funding was received. Results Median age of the cohort was 69.2 years and 56.5% of patients were male. PD-L1 and PD-1 were positive in 24.1% and 37.5% of patients. PD-L1 positivity was associated with favorable pathological stage, where as PD-1 positivity was significantly associated with pelvicalyceal location, lymph node metastases, non-organ confined disease, presence of lymphovascular invasion, sessile architecture, necrosis, concomitant CIS, and history of non-muscle invasive bladder cancer. PD-L1 positivity was not significantly associated with survival outcomes. In Cox regression UVA, PD-1 positivity was associated with worse recurrence-free survival (RFS) (HR 1.5 (95%CI 1.08-2.14, p=0.016)), cancer-specific survival (CSS) (HR 1.5 (95%CI 1.07-2.19, p=0.021)), and overall survival (OS) (HR 1.5 (95%CI 1.10-1.97, p=0.009)) (see figure for KM curves). However in MVA, PD-1 positivity was not found to be an independent predictor of RFS, CSS or OS. Conclusions PD-1 positivity of tumor-infiltrating lymphocytes was associated with adverse pathological criteria and was a significant prognosticator for RFS, CSS and OS on UVA in patients treated with extirpative surgery for high-grade UTUC in a large, multi-institutional cohort. In MVA, the independent prognostic value of PD-1 was not confirmed. PD-L1 positivity was associated with lower tumor stage, but not with other pathological characteristics or survival outcomes. Funding none
Authors
Laura-Maria Krabbe
Barbara Heitzplatz Ryan Hutchinson Solomon Woldu Nirmish Singla Sina Preuss Martin Boegemann Christopher Wood Jose Karam Alon Weizer Jay Raman Mesut Remzi Nathalie Rioux-Leclercq Andrea Haitel Marco Roscigno Christian Bolenz Karim Bensalah Arthur Sagalowsky Shahrokh Shariat Yair Lotan Evanguelos Xylinas Vitaly Margulis |
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MP71-04 |
GATA3 immunohistochemistry in urothelial carcinoma of the upper urinary tract as a urothelial marker as well as a prognosticator |
Bladder Cancer: Upper Tract Transitional Cell Carcinoma I | 17BOS |
Abstract: MP71-04 Sources of Funding: None Introduction A transcription factor, GATA3, has been one of the most useful urothelial markers in diagnostic surgical pathology practice. However, previous studies have assessed the utility of GATA3 immunohistochemistry often in bladder specimens. Moreover, the prognostic significance of GATA3 expression in upper urinary tract urothelial carcinomas (UUTUCs) has not been fully investigated. Meanwhile, using cell line and animal models, we have demonstrated that GATA3 functions as a tumor suppressor for urothelial cancer. The current study aims to determine the expression status of GATA3 in UUTUC and its prognostic significance. Methods We immunohistochemically stained for GATA3 in the tissue microarrays consisting of 99 UUTUC samples and paired non-neoplastic urothelium from each case. We then evaluated the associations between GATA3 expression and clinicopathologic features available for our patient cohort. Results GATA3 was positive in 51 [52%; 32 (32%) weak, 11 (11%) moderate, 8 (8%) strong] of 99 UUTUCs, which was significantly lower than in benign urothelium [79 (96%) of 82; 33 (40%) weak, 35 (43%) moderate, 11 (13%) strong] (P < 0.001). Ten (67%) of 15 low-grade versus 41 (48%) of 84 high-grade UUTUCs (P = 0.266) and 20 (54%) of 37 non-muscle-invasive versus 31 (50%) of 62 muscle-invasive UUTUCs (P = 0.836) were immunoreactive for GATA3. There were also no statistically significant associations between GATA3 expression and pN status, distant metastasis, gender of the patients, or the side of UUTUC. However, the rate of GATA3 positivity was significantly higher (P = 0.004) in ureteral tumors (66%) than in renal pelvic tumors (36%). Kaplan-Meier and log-rank tests revealed that GATA3 negativity significantly correlated with lower recurrence-free survival (P = 0.040 for all cases; P = 0.030 for muscle-invasive tumors) and cancer-specific survival (P = 0.007 for all cases; P = 0.012 for muscle-invasive tumors) rates. Multivariate analysis further identified strong correlations of GATA3 expression with cancer-specific mortality of all cases [hazard ratio (HR) = 0.399, 95% confidence interval (CI) = 0.179-0.890, P = 0.025] or muscle-invasive tumors (HR = 0.374, 95% CI = 0.169-0.831, P = 0.016). Conclusions Compared with non-neoplastic urothelium, a significant decrease in the expression of GATA3 in UUTUC was seen. Of note was that GATA3 was immunohistochemically detected only in roughly half of high-grade and/or muscle-invasive UUTUCs. In addition, loss of GATA3 expression was found to be an independent predictor of poor patient outcomes. Funding None
Authors
Satoshi Inoue
Kazutoshi Fujita Hiroki Ide Seiji Yamaguchi Hiroaki Fushimi George Netto Norio Nonomura Hiroshi Miyamoto |
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MP71-05 |
Prognostic significance of BAP1 expression in upper tract urothelial carcinoma |
Bladder Cancer: Upper Tract Transitional Cell Carcinoma I | 17BOS |
Abstract: MP71-05 Sources of Funding: none Introduction BRCA1-associated protein-1 is a deubiquitinase encoded by the BAP1 tumor suppressor gene. BAP1 mutations have been associated with prognostic implications in renal cell carcinoma, uveal melanoma and mesothelioma. Its role in urothelial carcinoma remains poorly elucidated. We sought to evaluate the prognostic value of BAP1 expression in upper tract urothelial carcinoma (UTUC). Methods We reviewed a multi-institutional cohort of patients who underwent radical nephroureterectomy (RNU) for high-grade UTUC from 1990-2008. Immunohistochemistry for BAP1 was performed on tissue microarrays from RNU specimens. BAP1 nuclear staining intensity was graded from 0-3, with positivity defined as average intensity >1. Clinicopathologic characteristics and oncologic outcomes including recurrence-free (RFS), cancer-specific (CSS), and overall survival (OS) were stratified by BAP1 positivity. Prognostic role of BAP1 was assessed using Kaplan-Meier (KM) and Cox regression analysis. Significance was defined as p<0.05. Results 373 patients were included for analysis, with median follow-up 36 months. 180 (48.3%) patients were BAP1-negative and 193 (51.7%) were BAP1-positive. While pT stage, lymphovascular invasion (LVI), and pN stage were similar between groups, BAP1 expression was more often associated with sessile architecture, necrosis, and CIS (Table). On multivariable analysis (MVA) adjusted for pT, pN, and LVI, positive BAP1 expression was a significant predictor for worse RFS (HR 1.56, p=0.026) and CSS (HR 1.56, p=0.035). On univariable analysis, BAP1 expression was predictive of worse OS (HR 1.43, p=0.030), though significance was lost on MVA (HR 1.30, p=0.116). KM curves are shown (Figure). Conclusions BAP1 expression is associated with adverse pathologic features and worse oncologic outcomes in patients with high-grade UTUC. Although loss of BAP1 is frequently associated with worse outcomes in other malignancies, our findings parallel those of mesothelioma, in which BAP1 loss confers a better prognosis. The role of BAP1 pathways in UTUC pathogenesis remains to be further elucidated. Funding none
Authors
Nirmish Singla
Ahmet Aydin Vandana Panwar Ryan Hutchinson Solomon Woldu Christopher Wood Jose Karam Alon Weizer Jay Raman Mesut Remzi Nathalie Rioux-Leclercq Andrea Haitel Marco Roscigno Christian Bolenz Karim Bensalah Arthur Sagalowsky Shahrokh Shariat Yair Lotan Aditya Bagrodia Payal Kapur Vitaly Margulis Laura-Maria Krabbe |
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MP71-06 |
Prognostic significance of EZH2 expression in upper tract urothelial carcinoma |
Bladder Cancer: Upper Tract Transitional Cell Carcinoma I | 17BOS |
Abstract: MP71-06 Sources of Funding: none Introduction Enhancer of zeste homolog 2 is a methyltransferase encoded by the EZH2 gene. The role of EZH2 upregulation has been studied in several malignancies, including bladder cancer, though its role in upper tract urothelial carcinoma (UTUC) is poorly understood. We sought to evaluate the prognostic value of EZH2 expression in UTUC. Methods We reviewed a multi-institutional cohort of patients who underwent radical nephroureterectomy (RNU) for high-grade UTUC from 1990-2008. Immunohistochemistry for EZH2 was performed on tissue microarrays from RNU specimens. The percentage of staining was evaluated, with EZH2 positivity defined as >20% staining present. Clinicopathologic characteristics and oncologic outcomes including recurrence-free (RFS), cancer-specific (CSS), and overall survival (OS) were compared between patients stratified by EZH2 positivity. Prognostic role of EZH2 was assessed using Kaplan-Meier (KM) analysis. Predictors of oncologic outcomes were identified using univariate (UVA) and multivariate (MVA) Cox regression analysis. Significance was defined for p<0.05. Results 402 patients were included for analysis, with median follow-up 35.5 months. 313 (77.9%) patients were EZH2-negative and 89 (22.1%) were EZH2-positive. While gender, pT stage, pN stage, and prior bladder cancer were similar between groups, EZH2 expression was more often associated with ureteral location, sessile architecture, necrosis, and CIS (Table). On UVA, EZH2 was a significant predictor for worse RFS (HR 1.63, p=0.019), CSS (HR 1.87, p=0.004), and OS (HR 1.97, p<0.001). On MVA adjusted for age, pT, pN, and LVI, EZH2 remained a significant predictor for worse OS (HR 1.65, p=0.005), while significance was lost for RFS and CSS. KM curves are shown (Figure). Conclusions EZH2 expression appears to be associated with adverse pathologic features and may predict worse oncologic outcomes in patients with high-grade UTUC. The role of EZH2 pathways in UTUC pathogenesis remains to be further elucidated. Funding none
Authors
Ahmet Aydin
Nirmish Singla Vandana Panwar Ryan Hutchinson Solomon Woldu Christopher Wood Jose Karam Alon Weizer Jay Raman Mesut Remzi Nathalie Rioux-Leclercq Andrea Haitel Marco Roscigno Christian Bolenz Karim Bensalah Arthur Sagalowsky Shahrokh Shariat Yair Lotan Aditya Bagrodia Payal Kapur Vitaly Margulis Laura-Maria Krabbe |
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MP71-07 |
Serum core fucosylated N-glycan carrying immunoglobrin is a diagnostic and pre-operative prognostic marker of upper tract urothelial carcinoma |
Bladder Cancer: Upper Tract Transitional Cell Carcinoma I | 17BOS |
Abstract: MP71-07 Sources of Funding: none Introduction Although hematuria and urine cytology is a powerful indicator for diagnosis of upper tract urothelial carcinoma (UTUC), there is a need to identify more powerful predictive biomarkers of UTUC to improve diagnostic accuracy. Prognostic biomarkers were also required to decide on therapeutic strategy of UTUC. The use of N-glycans of immunoglobrins (Igs) as a biomarkers of UTUC has not yet been tested. In the present study, we performed serum N-glycomics between healthy volunteer (HLT) and UTUC patients and evaluated its potential as a diagnostic and prognostic serum-based biomarkers of UTUC. Methods N-glycomics in Igs fraction were performed in randomly selected 78 HLT and 73 UTUC (preoperative serum, n=52 and post-operative serum, n=21, respectively) patients. The putative structure of N-glycans was analyzed by MALDI-TOF-MS analysis. To confirm the result of N-glycomics of Igs, We performed lectin-array analysis utilizing recombinant lectin-array chip and evanescent fluorescence scanner. Results N-glycomics of Igs reveled that preoperative serum core fucosylated biantennary (m/z 1590, 2073, and 2524) and core fucosylated bisecting (m/z 1647, 1793, 2955 and 2727) N-glycans of Igs levels in UTUC patients was significantly higher in HLT group. Receiver-operating characteristic area under the curve (AUC) for prediction of UTUC in significant core fucoslyalted N-glycans was 0.7290-0.8728 in contrast to hematuria positive status (AUC 0.8627) and urine cytology class ?IV (AUC 0.7745), respectively. In post-operative serum analysis, we found that the level of serum core fucosylated N-glycans in cancer death group was tend to higher than that of surviving group. Furthermore, lectin-array analysis revealed that fucoslyted IgG (Fuc-IgG) level of UTUC was tend to higher than HLT. In post-operative serum analysis, we also found serum fuc-IgG levels in cancer death group was significantly higher than that of surviving group. Conclusions The serum core fucosylated N-glycans levels and Fuc-IgG levels may be a promising diagnostic and post-operative prognostic markers of UTUC. Funding none
Authors
Toshikazu Tanaka
Yuki Tobisawa Shingo Hatakeyama Kazuyuki Mori Yasuhiro Hashimoto Takuya Koie Chikara Ohyama Tohru Yoneyama |
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MP71-08 |
Expression of transcription factors, ELK1, FOXO1, NFATc1, and ZKSCAN3, in urothelial carcinoma of the upper urinary tract as prognosticators |
Bladder Cancer: Upper Tract Transitional Cell Carcinoma I | 17BOS |
Abstract: MP71-08 Sources of Funding: None Introduction Various transcription factors, including ELK1, FOXO1, NFAT, and ZKSCAN3, have been shown to contribute to bladder tumorigenesis and cancer progression. Meanwhile, we have demonstrated that androgens promote bladder cancer outgrowth via modulating the activity of some of these transcription factors. In contrast, little is known about their role in the development and growth of upper urinary tract urothelial carcinoma (UUTUC). This study aims to determine the expression status of phospho-ELK1 (pELK1) and phospho-FOXO1 (pFOXO1), their activated and inactivated forms, respectively, as well as NFATc1 and ZKSCAN3, in UUTUC and its prognostic significance. Methods We immunohistochemically stained for pELK1, pFOXO1, NFATc1, and ZKSCAN3 in the tissue microarrays consisting of 99 UUTUC samples and paired non-neoplastic urothelium from each case. We then evaluated the relationship between the expression of each transcription factor and clinicopathologic features available for our patient cohort. Results pELK1, pFOXO1, NFATc1, and ZKSCAN3 were positive in 47% [37% weak (1+), 10% moderate (2+), 0% strong (3+)], 100% (12% 1+, 46% 2+, 41% 3+), 51% (40% 1+, 9% 2+, 3% 3+), and 42% (26% 1+, 13% 2+, 3% 3+) of UUTUCs, respectively, which were significantly higher (pELK1: 25%, P=0.002; pFOXO1: 94%, P=0.018; NFATc1: 24%, P=0.038) or lower (ZKSCAN3: 86%, P<0.001) than in benign urothelial tissues. Five (33%) of 15 low-grade versus 42 (50%) of 84 high-grade UUTUCs (P=0.036) and 13 (35%) of 37 non-muscle-invasive (NMI) versus 34 (55%) of 62 muscle-invasive (MI) UUTUCs (P=0.065) were immunoreactive for pELK1. Similarly, 29 (78%) NMI versus 58 (94%) MI UUTUCs (P=0.031) were moderately or strongly positive for pFOXO1. However, there were no statistically significant associations between pELK1/pFOXO1/NFATc1/ZKSCAN3 expression and pN/M status. Kaplan-Meier and log-rank tests revealed that patients with high (2+) pELK1 tumor (P=0.008), high (3+) pFOXO1 tumor (P=0.059), high (2+/3+) NFATc1 tumor (P=0.005), or high (3+) ZKSCAN3 MI tumor (P=0.069) had higher risks of cancer-specific mortality. Conclusions Compared with non-neoplastic urothelium, significant increases and a decrease in the expression of pELK1/pFOXO1/NFATc1 and ZKSCAN3, respectively, in UUTUC were seen. The current results also support our preclinical findings indicating correlations of ELK1/FOXO1 activation with urothelial tumor progression/regression, respectively. Furthermore, pELK1/NFATc1 overexpression was found to serve as predictors of poor prognosis. Funding None
Authors
Taichi Mizushima
Kazutoshi Fujita Satoshi Inoue Hiroki Ide Takashi Kawahara Mehrsa Jalalizadeh Seiji Yamaguchi Hiroaki Fushimi Eiji Kashiwagi George Netto Norio Nonomura Hiroshi Miyamoto |
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MP71-09 |
Effectiveness of adjuvant chemotherapy after radical nephroureterectomy for locally advanced and/or positive regional lymph node upper tract urothelial carcinoma |
Bladder Cancer: Upper Tract Transitional Cell Carcinoma I | 17BOS |
Abstract: MP71-09 Sources of Funding: None Introduction There is limited evidence supporting the use of adjuvant chemotherapy (AC) after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). Against this backdrop, we hypothesized that such treatment is associated with an overall survival (OS) benefit in patients with locally advanced and/or positive regional lymph node disease._x000D_ Methods Within the National Cancer Data Base (2004-2012), we identified 3,253 individuals who received AC or observation after RNU for pT3/T4 and/or pN+ UTUC. Inverse probability of treatment weighting (IPTW)-adjusted Kaplan-Meier curves and Cox regression analyses were used to compare OS of patients in the two treatment groups. Additionally, we performed exploratory analyses of treatment effect according to age, gender, Charlson comorbidity index, pathological stage (pT3/T4N0, pT3/T4Nx and pTanyN+) and surgical margin status. Results Overall, 762 (23.42%) and 2,491 (76.58%) patients with pT3/T4 and/or pN+ UTUC received AC and observation after RNU, respectively. IPTW-adjusted Kaplan-Meier curves showed that median OS was significantly longer for AC vs. observation (47.41[IQR,19.88-112.39] vs. 35.78 [IQR,14.09-99.22] months; P<0.001; Figure 1). The 5-year IPTW-adjusted rates of OS for AC vs. observation were 43.90% vs. 35.85%, respectively. In IPTW-adjusted Cox regression analysis, AC was associated with a significant OS benefit (HR=0.77; 95%CI=[0.68-0.88]; P<0.001). This benefit was consistent across all subgroups examined (all P<0.05) and no significant heterogeneity of treatment effect was observed (all Pinteraction>0.05; Figure 2)._x000D_ _x000D_ _x000D_ Conclusions We report an OS benefit in patients who received AC vs. observation after RNU for pT3/T4 and/or pN+ UTUC. Although our results are limited by the usual biases related to the observational study design, we believe that the present findings should be considered when advising post-RNU management of advanced UTUC, pending level I evidence. Funding None
Authors
Thomas Seisen
Ross E. Krasnow Joaquim Bellmunt Morgan Rouprêt Jeffrey J. Leow Stuart R. Lipsitz Malte Vetterlein Mark A. Preston Nawar Hanna Adam S. Kibel Maxine Sun Toni K. Choueiri Quoc-Dien Trinh Steven Lee Chang |
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MP71-10 |
Adjuvant Therapy for T3b of the Upper Tract Urothelial Carcinoma |
Bladder Cancer: Upper Tract Transitional Cell Carcinoma I | 17BOS |
Abstract: MP71-10 Sources of Funding: none Introduction We reported that tumor invades peripelvic fat or periureteral fat (pT3b) had worse prognosis than tumor invades renal parenchyma (pT3a)1. We evaluated the disease recurrence and cancer specific survival of patients with pT3b urothelial carcinoma of the upper urinary tract who received adjuvant treatment._x000D_ _x000D_ Reference_x000D_ 1. Park, J., et al., Peripelvic/periureteral fat invasion is independently associated with worse prognosis in pT3 upper tract urothelial carcinoma. World J Urol, 2014. 32(1): p. 157-63._x000D_ Methods The data from a total of the 128 pT3b patients after radical nephroureterectomy were analyzed. The patients were divided into 4groups; 60 without adjuvant therapy (Group 1), 22 with adjuvant radiotherapy (Group 2), 27 with adjuvant chemotherapy (Group 3) and 19 with adjuvant radiotherapy plus adjuvant chemotherapy (Group 4). Recurrence-free survival and cancer specific survival rates were compared among these groups. Results The median follow-up duration was 43.7 months. The patients who received adjuvant radiotherapy (Group 2 and 4) were more likely to have high pathologic grade (p=0.036) and more frequent positive surgical margin (p=0.010), but were no differences by gender, age, tumor location, status of lymphovascular invasion. 5-year recurrence-free survival rates of group 1, group 2, group 3 and group 4 were 31.3%, 66.3%, 26.1% and 57.9%, respectively. The patients who received adjuvant radiotherapy (Group 2 and 4) showed significantly higher recurrence free survival than those who did not. Low recurrence rates after adjuvant radiotherapy may be due to decreased local recurrence (HR 0.129, p=0.005). 5-year cancer specific survival rates in group 1, group 2, group 3 and group 4 were 51.6%, 50.6%, 50.6% and 72.7%, respectively. Higher cancer specific survival was noted in group 4, but didn&[prime]t reach statistical significance (p=0.119). Conclusions The Adjuvant radiotherapy in pT3b patients significantly reduced disease recurrence. Adjuvant radiotherapy plus chemotherapy seem to increase the cancer specific survival. The adjuvant radiotherapy plus chemotherapy should be considered in patients with pT3bN0/Nx. Funding none
Authors
Jong Keun Kim
Myungchan Park Myong Kim Dalsan You In Gab Jeoung Cheryn Song Bumsik Hong Young Seok Kim Seong-Ho Lee Sang Hyun Park Choung-Soo Kim Tai Young Ahn Hanjong Ahn |
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MP71-11 |
CLINICAL RESPONSE RATES OF NEOADJUVANT CHEMOTHERAPY IN HIGH GRADE UPPER TRACT UROTHELIAL CARCINOMA: A SINGLE INSTITUTIONAL EXPERIENCE |
Bladder Cancer: Upper Tract Transitional Cell Carcinoma I | 17BOS |
Abstract: MP71-11 Sources of Funding: none Introduction Upper tract urothelial carcinoma (UTUC) is histologically similar to urothelial carcinoma of the bladder, but frequently associated with high grade (HG) invasive disease at diagnosis, resulting in poor outcomes. Although Level I evidence supports the use of cisplatin based neoadjuvant chemotherapy (NAC) for patients with muscle invasive bladder cancer, there is currently no level 1 data supporting the use of peri-operative chemotherapy for patients with HG UTUC. Given the inability to accurately stage UTUC, some speculate that NAC for patients undergoing nephroureterectomy (NU) for HG UTUC may improve outcomes, considering their limited eligibility for adjuvant chemotherapy due to renal impairment. Our study objective was to evaluate the impact of NAC in patients who underwent NU for pathologically proven HG UTUC. Methods A retrospective review was conducted of patients with HG UTUC at our institution from 2012 to 2016 who underwent NU. As per department protocol, all patients scheduled for NU with pre-op estimated glomerular filtration rate (eGFR) > 45 mL/min per 1.73 m2 were referred for evaluation of NAC. Clinical and pathologic response rates were noted, with pre- and post-operative kidney function defined by eGFR. Results A total of 58 patients met inclusion criteria, with a median age was 75 years (range: 35-92) and a pre-op and post-op eGFR of 54.45 and 47.6 mL/min per 1.73 m2 respectively. 26 patients were considered eligible for NAC, of which 18 (69%) received NAC. The rate of utilization increased over time (Figure 1). 13/18 (72%) demonstrated a clinical response including 6 (33%) with a complete clinical response. Final pathology demonstrated pT0N0 in 2 patients (11%) and pTisN0 in 2 patients (11%). No patients suffered a delay or were deemed ineligible for surgery due to NAC. Conclusions Cisplatin based NAC demonstrated a clinical response rate in the majority of patients with HG UTUC without compromising definitive surgical treatment. Since NU significantly reduces kidney function and eligibility for cisplatin based chemotherapy, patients with HG UTUC may be considered candidates for NAC. Longer follow-up data is needed to further assess the impact of NAC on survival rates. Funding none
Authors
Hayley R. Silver
Marc A. Bjurlin William C. Huang |
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MP71-12 |
Clinical benefit of platinum-based neoadjuvant chemotherapy for locally advanced upper tract urothelial carcinoma |
Bladder Cancer: Upper Tract Transitional Cell Carcinoma I | 17BOS |
Abstract: MP71-12 Sources of Funding: none Introduction The benefit of neoadjuvant chemotherapy (NAC) for patients with locally advanced upper tract urothelial carcinoma (UTUC) remain unclear. The purpose of this study was to access safety and effectiveness of platinum-based NAC for locally advanced UTUC. Methods From Feb 1995 to Sep 2016, we underwent radical nephroureterectomy for consecutive 229 patients with UTUC at a single institute. Of these, we identified 50 patients who received NAC and 179 patients without NAC. We selected pair-matched patients from with and without NAC using propensity score by logistic analysis. We retrospectively evaluated the tumor response, post-therapy pathological down staging and toxicity between pair-matched patients. Variables for propensity score matching included age, sex, clinical TNM stage, diabetes, tumor location. Disease free and overall survivals were evaluated using Kaplan – Meier methods with log – lank test between two groups: those with and without NAC. Multivariate Cox regression analysis was performed for independent factor for overall survival. Results We statistically selected pair-matched 45 patients in each group. The regimens in the NAC group were gemcitabine and carboplatin for 31 cases, gemcitabine and cisplatin for 13 cases, or docetaxel, ifosfamide and nedaplatin for 1 cases. There were no significant differences in patient characteristics between the groups. Median follow up periods in NAC and control group were 21 and 39 months. No severe adverse event associated with NAC was observed. The median response rate in NAC group was 39%. Pathological down staging in primary tumor was achieved in 29 (64%) patients, and it was significantly higher compared with control group (n = 11, 24%). Platinum-based NAC for locally advanced UTUC significantly prolonged progression free survival (P = 0.015) and overall survival (P = 0.025).?In multivariate Cox regression analysis, NAC was selected as an independent predictor for prolonged overall survival (P = 0.008, HR: 0.25, 95%CI: 0.90-0.70) Conclusions Although present data are preliminary, the platinum-based NAC for advanced UTUC seems to have a potential to improve outcomes. Further prospective randomized studies are needed to confirm the benefit of NAC in patients with locally advanced UTUC. Funding none
Authors
Shingo Hatakeyama
Shogo Hosogoe Masaki Momota Koichi Kido Hayato Yamamoto Yasuhiro Hashimoto Takahiro Yoneyama Takuya Koie Chikara Ohyama |
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MP71-13 |
Efficacy of Chemotherapy Administration in Elderly Patients with Metastatic Upper Tract Urothelial Carcinoma after Radical Nephroureterectomy. |
Bladder Cancer: Upper Tract Transitional Cell Carcinoma I | 17BOS |
Abstract: MP71-13 Sources of Funding: none Introduction Our recent findings from a multi-institutional study showed that up to one-third of upper tract urothelial carcinoma (UTUC) patients did not receive any chemotherapeutic treatment (CTx) for disease recurrence after radical nephroureterectomy (RNU) due to their high age, poor performance status (PS), and comorbidity. However, some patients may not have the chance to receive effective systemic CTx simply because of their advanced age. In this study, we attempted to determine the influence of age on the outcomes of CTx in UTUC patients with disease recurrence following RNU. Methods We identified a study population of 226 patients who developed disease recurrence after RNU during the past 15 years at our 14 Japanese institutions. To identify factors that were related to cancer-specific survival (CSS) and overall survival (OS), we performed multivariate analysis using a Cox proportional hazards regression model that included clinicopathological variables. We also analyzed the efficacy of systemic CTx in a subgroup of patients aged >75 years (yr). Results After disease recurrence, 145 patients underwent systemic CTx while the remaining 81 received no systemic treatment. Patients aged >75 yr (n=81) tended to have poor PS (P<0.001) and bone metastasis at the time of disease relapse (P=0.028) compared with the younger patients (n=145), while the administration of adjuvant CTx was less frequent (14.8% in patients aged >75 yr vs. 42.1% in those <75 yr, P<0.001). Multivariate analysis in the overall population revealed that the salvage CTx setting was independently related to CSS as well as OS along with poor PS, the presence of liver metastasis, number of recurrence sites, and lymph node involvement in RNU specimens. Meanwhile, age was not selected as an independent factor. In the subgroup analysis on patients >75 yr, we found no significant difference in the clinicopathological backgrounds among patients who received systemic CTx (n=38) and their counterparts (n=43). However, CSS rates in patients with systemic CTx were 41.8% at 1 year and 18.6% at 2 years, while those without were significantly decreased to 10.2% and 6.8% (P=0.001), respectively. A similar difference could be observed in the estimated probability of OS among patients aged >75 yr. _x000D_ _x000D_ Conclusions Survival rates are significantly higher in patients receiving salvage systemic CTx regardless of their age. Age is not a key indicator for selecting candidates for systemic CTx with disease recurrence after RNU. Funding none
Authors
Keisuke Shigeta
Eiji Kikuchi Keishiro Fukumoto Nozomi Hayakawa Takeo Kosaka Akira Miyajima Mototsugu Oya |
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MP71-14 |
Significance of buttyrylcholinesterase before chemotherapy as an independent predictor of over-all survival in patients with advanced upper-tract urothelial cancer |
Bladder Cancer: Upper Tract Transitional Cell Carcinoma I | 17BOS |
Abstract: MP71-14 Sources of Funding: none Introduction Systemic inflammation is a common host reaction to cancer progression. Serum level of buttyrylcholinesterase (BChE) have been reported to reflect the presence of inflammation and other clinical conditions. BChE is an alphaglycoprotein found in the nervous system and liver. Its serum level is reduced in many clinical conditions, such as liver damage, injury, infection, and malignant disease. We retrospectively evaluated the potential prognostic significance of buttyrylcholinesterase before chemotherapy as an independent predictor of overall survival in patients with advanced upper-tract urothelial cancer. Methods We treated seventy-four patients (52 men and 22 women) with advanced upper-tract urothelial cancer (UTUC) at our clinic between August 2004 and December 2015. The average age was 69.3 (43–89), and average eGFR was 50.5 (11.6–99.3) ml/minute/1.73m2. Mean observation period was 24.0 (3–96) months. Levels of serum BChE (normal range 168-470 U/L) were measured 1 week before chemotherapy. The average serum level of BChE were 240.6 U/L (53-509). The patients received 2 courses of GCarbo consisted of 800mg/m2 gemcitabine on days 1, 8, and 15 and carboplatin (AUC 4) on day 2. If this regimen was effective, another 2 courses of GCcarbo was performed. If this regimen did not induce any tumor size reduction, we switched to 2 courses of GCarboD (D; 70mg/m2) treatment as second-line treatment. Results GCarbo regimen yielded 5 cases (6.8%) of CR, 32 (43.2%) of PR, and the average duration of response of 11.4 (2–29) months. GCarboD treatment was administered in 21 cases, and yielded 2 (9.5%) PR and a duration of response was 31.5(7-50) months. The median over-all survival period was 14.3 months. When analyzed by serum BChE level, the over-all survival were 22.0 months in the BChE >168 U/L group and 12.0 months in the BChE <168 group (p=0.036). The level of serum BChE showed no association with treatment effect. Conclusions Serum BChE level before chemotherapy may have the potential to predict over-all survival in patients with advanced upper-tract urothelial cancer. Funding none
Authors
Takahiro Yoneyama
Masaaki Oikawa Kazuhisa Hagiwara Takuma Narita Toshikazu Tanaka Kengo Imanishi Tohru Yoneyama Kazuyuki Mori Atsushi Imai Shingo Hatakeyama Yasuhiro Hashimoto Takuya Koie Chikara Ohyama |
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MP71-15 |
Predictive ability of renal cortex enhancement in dynamic CT for residual renal function after nephroureterectomy: Comparative study with renography |
Bladder Cancer: Upper Tract Transitional Cell Carcinoma I | 17BOS |
Abstract: MP71-15 Sources of Funding: none Introduction The precise prediction of perioperative change in renal function would enable the appropriate management including perioperative systemic chemotherapy for patients with upper tract urothelial carcinoma (UTUC). The renal cortex enhancement in CT could reflect renal function. We have reported the usefulness of renal cortex enhancement to predict residual single kidney function after nephroureterectomy (NU) [AUA 2015]. The predictive ability of renal cortex enhancement in CT was evaluated in comparison with that of nuclear renography. Methods Forty-seven patients with UTUC in whom both dynamic CT and Tc-99m diethylenetriamine pentaacetic acid renography were performed before NU were subjects of this study. Pre- and postoperative estimated glomerular filtration rates (eGFRs) were calculated using serum creatinine measured before and 1-3 months after NU, respectively. Renal cortex radiodensity was measured in Hounsfield units (HU) from a round region of interest placed over the highest enhancing area on corticomedullary images. CT-based split renal function (SRF) of the intact contralateral kidney was calculated by splitting pre-eGFR: pre-eGFR × percent of total HU. The same formula was used for nuclear SRF. The correlations between observed and calculated post-eGFR using CT and nuclear renography were assessed with a calibration plot. Results The median pre-eGFR was 77 (range: 41-124) ml/min/1.73 m2, and decreased to 53 (27-89) after NU. The median percent of total HU for the contralateral kidney was 52% (48-68), and that of the total nuclear SRF was 56% (43-100). CT-based SRF showed linear correlation with the observed post-eGFR (r = 0.80), which was equivalent to the nuclear SRF (r = 0.78). From the conversion factors derived from a linear regression, an updated prediction formula was developed by parallel translation, adding 11.7 to the CT-based SRF and 8.8 to the nuclear SRF. The calibration plot in which the observed post-eGFR was plotted against each updated SRF showed equally good agreement (Fig.). Conclusions The predictive ability of CT enhancement for postoperative renal function is feasible and comparable to that of renography. This CT model could be useful in clinical practice because CT is an essential diagnostic tool for patients with UTUC. Funding none
Authors
Yuma Waseda
Kazutaka Saito Masaharu Inoue Masaya Ito Toshiki Kijima Soichiro Yoshida Minato Yokoyama Junichiro Ishioka Yoh Matsuoka Kazunori Kihara Yasuhisa Fujii |
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MP71-16 |
Risk stratification by means of the biological age related factors better predicts cancer-specific survival than the chronological age in patients with upper tract urothelial carcinoma (UTUC): a multi-institutional database study |
Bladder Cancer: Upper Tract Transitional Cell Carcinoma I | 17BOS |
Abstract: MP71-16 Sources of Funding: none Introduction Chronological age is an important factor in in determining the treatment option and clinical response of patients with upper-tract urothelial carcinoma (UTUC). Much evidence suggests that chronological age alone is an inadequate indicator to predict the clinical response to radical nephroureterecyomy (RNU). On the other hand, prognostic impact of biological age has not been reported previously. Defining the biological age consists of the determination of a number of biological age markers including telomeres, chromatin, and some blood sampling data which is commonly measured in clinical practice. Therefore, the aim of our study was the validation of the prognostic significance of biological age related factors in a large cohort of UTUC patients. Methods We retrospectively reviewed the data from 1349 patients with localized UTUC (Ta-4N0M0) treated by RNU. WBC, NLR, Hb, PLT, CRP, Alb, ALP, LDH, Cr, corrected Ca were tested by the Spearman correlation to indicate the direction of association to chronological age. The test yielded significant, negative associations of Hb (P<0.001) and WBC (P=0.010) with chronological age. Hb (g/dl) and WBC (counts/?l) were analyzed to compare the 10-year cancer-specific survival (CSS) by Cox regression analysis as categorical variables (>14, 13-13.9, 12-12.9, 11-11.9, and <11), and (9200-8500, 8499-6000, 5999-4500, 4499-3200, <3200, and >9200), respectively. To establish the scoring system, we assigned points for these categories, and then correlated the total points to predicted probability of the surviving outcome as follows; point &[Prime]0&[Prime] for Hb >14 (reference) and 13-13.9 (OR: 1.533), point &[Prime]1&[Prime] for 12-12.9 (OR: 2.391), point &[Prime]2&[Prime] for 11-11.9 (OR: 3.015), and point &[Prime]3&[Prime] for <11 (OR: 3.584). For WBC, point &[Prime]1&[Prime] was assigned for >9200 (OR: 2.541) and &[Prime]0&[Prime] was assigned for the rest; 9200-8500 (reference), 8499-6000 (OR: 0.873), 5999-4500 (OR: 0.772), 4499-3200 (OR: 0.486), and <3200 (OR: 1.277). Results 10-year CSS in higher risk group with score 4 or larger in age<60 was worse than score-0, or 1 in age >80 (mean estimated survival 69.7 months, CI: 33.3-106 v.s. 103.5. CI: 91-115.9). Concordance index between biological age scoring and chronological age was 0.704 for CSS and 0.798 for recurrence-free survival. Conclusions The biological age scoring developed for patients with UTUC undergoing RNU. It was applicable to those with localized disease, and performed well in diverse age populations Funding none
Authors
Teruo Inamoto
Kiyoshi Takahara Naokazu Ibuki Hideyasu Matsuyama Kiyohide Fujimoto Hiroaki Shiina Shigeru Sakano Kazuhiro Nagao Yoshihiro Tatsumi Hiroaki Yasumoto Haruhito Azuma Nishinihon Uro-Oncology Collaborative Group |
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MP71-17 |
Comparative study of oncological outcomes of laparoscopic and open radical nephroureterectomy for patients with urothelial carcinoma of the upper urinary tract undergoing regional lymph node dissection |
Bladder Cancer: Upper Tract Transitional Cell Carcinoma I | 17BOS |
Abstract: MP71-17 Sources of Funding: none Introduction Laparoscopic radical nephroureterectomy (LRNU) has now emerged as an alternative treatment method to open radical nephroureterectomy (ORNU). However, in terms of cancer control, there are conflicting data. In most reported studies, regional lymph node dissection (LND) was frequently skipped, which might have caused staging migration. Our group and Tokyo Women&[prime]s Medical University (TWMU) have been actively performing regional LND. Our group has preferred LRNU (J Endourol 2015) while ORNU has been preferred in TWMU (J Urol 2007). The aim of the present study was to compare survival outcomes between LRNU and ORNU in patients (pts) undergoing regional LND. Methods We retrospectively analyzed the data of 214 cTanyN0M0 pts undergoing radical nephroureterectomy with regional LND at 3 hospitals between 2000-15. The pts undergoing neoadjuvant chemotherapy were not included. The template of LND was previously reported. Briefly, LNs around great vessels were removed in pelvic/upper ureteral tumors and endopelvic LNs in lower ureteral tumors. In LRNU for pelvic/upper ureteral tumors, LND was also performed laparoscopically. The survival outcomes included overall survival (OS) and cancer-specific survival (CSS). The Kaplan-Meier method and Cox-hazard model were used for analyses. Results A total of 114 pts underwent LRNU and 100 received ORNU. There was no significant difference in the pT stage, pN stage, tumor grade, or LNs count removed (median: 11.5) between the two groups, but lower ureteral tumors were more frequent in the LRNU group. LN metastasis was pathologically identified in 19 pts (8.9%). The 5-year OS (75.9 vs. 72.8%, log-rank p=0.346) and CSS (80 vs. 77.8%, p=0.8441) did not differ significantly between the LRNU and ORNU groups. Multivariate analyses showed that the age, pT3/4 and pN+ were adverse prognostic factors. In the sub-analysis of pT3/4 pts (n=83), the 5-year OS (42.6 vs. 60.9%, log-rank p=0.2181) and CSS (48.4 vs. 62.4%, p=0.3763) did not differ significantly between the LRNU and ORNU groups. The multivariate model of OS revealed that the age, a lower ureteral tumor, and pN+ were independent adverse factors, while pN+ was significant and the other two were marginal in the univariate model of CSS. After adjusting for those three factors, LRNU continued to show no association with a poorer OS or CSS in pT3/4 pts. Conclusions Our data support the non-inferior oncological outcome of LNU compared with ORNU when regional LND is performed. Funding none
Authors
Takashige Abe
Tsunenori Kondo Toru Harabayashi Norikata Takada Ryuji Matsumoto Ataru Sazawa Takahiro Osawa Keita Minami Satoshi Nagamori Naoto Miyajima Kunihiko Tsuchiya Satoru Maruyama Sachiyo Murai Kazunari Tanabe Nobuo Shinohara |
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MP71-18 |
Distribution of lymph node metastasis in upper urinary tract urothelial cancer, sub-analysis of JCOG1110A study |
Bladder Cancer: Upper Tract Transitional Cell Carcinoma I | 17BOS |
Abstract: MP71-18 Sources of Funding: This study was supported in part by the National Cancer Center Research and Development Fund (23-A-20, 26-A-4). Introduction Information on distribution of regional lymph node metastasis (LNM) in upper urinary tract urothelial cancer (UTUC) are sparse, and the appropriate extent of lymph node dissection (LND) remains unclear. The objective of the present study was to investigate the distribution of LNM in a large multicenter case series of the Urologic Oncology Group of the Japan Clinical Oncology Group (JCOG). Methods The multicenter study, JCOG1110A, included 2,744 patients with non-metastatic UTUC who underwent radical nepheroureterectomy in 30 institutions in Japan between 1995 and 2009. In this analysis, patients with previous or simultaneous bladder cancer, patients who received neoadjuvant treatment, and patients without data of primary tumor site were excluded. The indication and extent of LND were determined by each surgeon or institution. Anatomical locations of primary tumor and number of patinets with positive lymph nodes (LNs) in each LN region were analyzed and descriptive statistics were performed. Results Of 1932 patients, we identified 188 (9.7%) pathologically node positive patients. On the right and left side, primary tumor location was documented as 51 and 76 patients with renal pelvis, 2 and 5 with upper ureter, 7 and 9 with middle ureter, 20 and 18 with lower ureter. The distribution of LNM in upper ureteral cancer was similar to that in renal pelvic caner, and the distribution in middle ureteral cancer was similar to that in lower ureteral cancer. Wherein we classified UTUC into two groups, upper UTUC (renal pelvis to upper ureter) and lower UTUC (middle to lower ureter). On right side, upper UTUC of 53 patients had LNM to renal hilar, paracaval and interaortocaval regions in 59%, 23% and 13%. Lower UTUC of 27 patients had LNM to common iliac, obturator, external and internal iliac regions in 22%, 33%, 19% and 11%, and also to renal hilar and interaortocaval region in 7% and 7%. On left side, upper UTUC of 81 patients had LNM to the renal hilar, paraaortic, interaortocaval regions in 54%, 37% and 5%. Lower UTUC of 27 patients had LNM to the common iliac, obturator, external and internal iliac regions in 19%, 26%, 11% and 7%, and also to renal hilar and paraaortic region in 11% and 26%. Conclusions UTUC has characteristic distribution of regional LNM depending on the side and location of primary cancer. LNM of lower UTUC was detected not only in pelvic region but also in upper abdominal region. These results support to establish the standardized dissection extent, which is necessary for evaluating potential clinical benefit of LND. Funding This study was supported in part by the National Cancer Center Research and Development Fund (23-A-20, 26-A-4).
Authors
Junichi Inokuchi
Kentaro Kuroiwa Yoshiyuki Kakehi Mikio Sugimoto Toshiki Tanikawa Hiroyuki Fujimoto Momokazu Gotoh Naoya Masumori Osamu Ogawa Masatoshi Eto Chikara Ohyama Akito Yamaguchi Hideyasu Matsuyama Tomohiko Ichikawa Tomohiko Asano Atsushi Takenaka Kiyohide Fujimoto Raizo Yamaguchi Tomonori Habuchi Katsuyoshi Hashine Yoichi Arai Norihiko Tsuchiya Hiroyuki Nishiyama Nobuo Shinohara Masashi Niwakawa Shin Egawa Seiichiro Ozono Tomomi Kamba Osamu Ishizuka Kazuo Nishimura Tatsuo Tochigi Yoshiki Sugimura Junki Mizusawa Kenichi Miyamoto Seiji Naito |
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MP71-19 |
Preoperative Predictors of Muscle Invasion in Upper Tract Urothelial Carcinoma |
Bladder Cancer: Upper Tract Transitional Cell Carcinoma I | 17BOS |
Abstract: MP71-19 Sources of Funding: None Introduction Clinical staging of upper tract urothelial carcinoma (UTUC) is often inaccurate given the limitations of ureteroscopic biopsy. The ability to identify patients with invasive disease would help select those who may benefit from more aggressive treatments. We sought to describe the prevalence of and identify preoperative risk factors for muscle invasive (MI)-UTUC. Methods We performed a retrospective review using a combined institutional cohort of all patients who underwent definitive surgical management for UTUC from 2000-2016. Patients were only included in the analysis if they underwent preoperative ureteroscopic biopsy. We identified several preoperative tumor and patient characteristics, including the details of biopsy. Our primary outcome was MI-UTUC at final surgical pathology. We used logistic regression to identify predictors of MI-UTUC and all p-values <0.05 were considered statistically significant. Results We identified 259 patients meeting selection criteria with median age at biopsy of 72 years (IQR 64-79). On biopsy, 63% of tumors were high-grade (HG) and lamina propria (LP) invasion was seen in 24%. 88% of patients were treated with radical nephroureterectomy and 12% had a segmental ureterectomy. On final surgical pathology, 46% of tumors had MI-UTUC. On multivariate analysis, HG and LP invasion on biopsy were each independently associated with presence of MI-UTUC (table). The combined presence of both LP and HG on biopsy (n=61) had a positive predictive value (PPV) of 85% and a negative predictive value of 66% for MI-UTUC. While HG and LP invasion had a high specificity (94%), it was relatively insensitive (43%). We conducted a separate analysis to identify risk factors for absence of HG and LP invasion on biopsy for patients with MI-UTUC. On multivariate logistic regression, absence of HG and LP invasion for patients with MI-UTUC was associated with biopsy tissue samples ≤ 1 mm in length (OR 4.0, 95% CI 1.2-13.1; p=0.02). Conclusions Findings of HG disease and LP invasion on ureteroscopic biopsy are independent risk factors for MI-UTUC and combine for a high PPV. Additionally, invasive tumors may be missed when ureteroscopic biopsy only captures small tissue samples. There are likely additional radiographic or ureterscopic tumor characteristics that are associated with MI-UTUC that we were unable to quantify. Funding None
Authors
Ezra J. Margolin
Justin T. Matulay Xiaosong Meng Brian Chao Varun Vijay Hayley Silver William C. Huang Marc A. Bjurlin Ojas Shah Christopher B. Anderson |
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MP71-20 |
Prognostic Significance of Erythrocyte protein band 4.1-like5 Expression in Upper Urinary Tract Urothelial Carcinoma |
Bladder Cancer: Upper Tract Transitional Cell Carcinoma I | 17BOS |
Abstract: MP71-20 Sources of Funding: none Introduction The erythrocyte protein band 4.1-like5 (EPB4.1L5) regulates E-cadherin in cancer invasion and metastasis inducing epithelial to mesenchymal transition (EMT). EPB4.1L5 coordinates the downregulation of E-cadherin-mediated cell-cell adhesion in a posttranscriptional manner by binding to p120 catenin, inhibiting p120 catenin-E-cadherin binding, and relocalizing E-cadherin by endocytosis. Recently, it is reported that in the breast cancer cells ZEB1, one of EMT transcriptional factors, induces EPB4.1L5 and promotes tumor invasion and metastasis. This study aimed to investigate the biological significance of EPB4.1L5 in upper urinary tract urothelial carcinoma (UTUC). Methods Retrospective analysis of the clinical records of 165 patients with UTUC (Ta-4N0M0) subjected to radical nephroureterectomy and immunohistochemical examination of EPB4.1L5 expression in those tissues. Results The median follow-up period was 62.2 months. The score of EPB4.1L5 significantly correlated with tumor grade, pathological T stage, and lymphovascular invasion (all p<0.001). The 5-year Kaplan–Meier recurrence-free survival and cancer-specific survival rates were 59.5% and 54.1% in patients with high EPB4.1L5 expression, compared with 81.6% and 87.2%,(all p<0.001) in their counterparts. Multivariate analyses revealed that high expression of EPB4.1L5 was one of the independent prognostic factors for tumor recurrence (p = 0.022, HR = 2.40) and cancer specific survival (p = 0.015, HR = 2.94). Conclusions High EPB4.1L5 expression related to worse clinical outcome in patients with UTUC. These results indicated that EPB4.1L5 could provide prognostic information in patients with UTUC regarding EMT. Funding none
Authors
Tatsuaki Daimon
Takeo Kosaka Eiji Kikuchi Shuji Mikami Yasumasa Miyazaki Ryuchi Mizuno Akira Miyajima Yasunori Okada Hisataka Sabe Mototsugu Oya |
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MP72-01 |
Predicting Renal Cell Carcinoma Progression after Surgery |
Kidney Cancer: Localized: Surgical Therapy V | 17BOS |
Abstract: MP72-01 Sources of Funding: None Introduction Multiple algorithms exist for the prediction of progression after surgical treatment of localized renal cell carcinoma (RCC); however, most are limited to clear cell (ccRCC) only, and have not been updated with contemporary pathologic assessment. We therefore sought to develop predictive models for progression in ccRCC, papillary RCC (papRCC), and chromophobe RCC (chrRCC). Methods Binephric patients treated with radical or partial nephrectomy for sporadic, unilateral M0 ccRCC, papRCC, or chrRCC between 1980 and 2010 were identified. All patients had their pathology slides re-reviewed by one pathologist, blinded to patient outcome. Associations with time to progression (defined as local recurrence, distant metastasis, or death from RCC) were evaluated with multivariable Cox proportional hazards regression with stepwise selection using a 500-sample bootstrap resampling approach. Results In total, 3,549 patients were identified: 2,726 (76.8%) with ccRCC, 601 (16.9%) with papRCC, and 222 (6.3%) with chrRCC. For patients with ccRCC, median follow-up was 9.9 years during which time 862 progressed. Features independently associated with ccRCC progression were constitutional symptoms, grade, coagulative necrosis, sarcomatoid differentiation, tumor size, fat invasion, tumor thrombus level, extension beyond Gerota's fascia, and pN classification. The c-index of this model was 0.83. For papRCC patients, median follow-up was 10.3 years during which time 66 had progressed. Features associated with papRCC progression were grade, fat invasion, and tumor thrombus level, resulting in a c-index of 0.77. For chrRCC patients, median follow-up was 9.1 years during which time 35 had progressed. Features associated with progression included sarcomatoid differentiation, fat invasion, and pN classification, resulting in a c-index of 0.77. Predicted 10-year progression-free survivals for patients without any risk factors were 96%, 96%, and 91% for ccRCC, papRCC, and chrRCC, respectively. Conclusions Using routine clinical and pathologic data, we generated 3 histology-specific predictive models for progression after surgical management of RCC. These models have excellent discrimination and may prove important in patient counseling and follow-up planning after surgical intervention. Funding None
Authors
William Parker
Christine Lohse John Cheville Harras Zaid Stephen Boorjian Igor Frank R. Houston Thompson Bradley Leibovich |
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MP72-02 |
Favorable prognosis of patients with end-stage renal disease patients and renal cell carcinoma: a long-term follow-up study at a single institution |
Kidney Cancer: Localized: Surgical Therapy V | 17BOS |
Abstract: MP72-02 Sources of Funding: None Introduction We aimed to define the clinical features of renal cell carcinoma (RCC) arising in patients with end-stage renal disease (ESRD). Methods A total of 261 patients (male, n=221; female, n=40; median age, 56 years; range 21 - 81 years) with ESRD and RCC who underwent radical nephrectomy at our institute between November 1985 and June 2016. The dialysis status of all patients at the time of diagnosis was chronic renal failure. Information was collected about age, sex, symptoms, duration of dialysis therapy, tumor staging and grading, histological subtype and outcome, and the median post-surgical follow up was 78 (range 1 - 368) months. Results The median duration of dialysis before surgery was 146 (range 1 - 400) months. Symptomatic RCC was evident in 24 (9.1%) patients, and gross hematuria was the most frequent complaint (12 patients). Renal cell carcinoma was incidentally diagnosed in 237 (90.9%) patients by ultrasonography or computed tomography screening. Bilateral RCC was observed in 56 patients (21%). Thus, radical nephrectomy was performed in 317 kidneys. Mean maximum tumor size was 2.45 cm. Organ-confined cancer was pathologically proven after radical nephrectomy in 98% of the patients, including 86% of those with pT1 (tumors < 7cm). Only four patients had advanced RCC (pT3). The histological subtypes were clear cell, papillary in 76 (24%) and dialysis-related renal tumors in 233 (74%), 76 (24%) and 8 (3%) patients, respectively. Three patients died of renal cancer and 31 died due to other causes. The estimated 5- and 10-year overall survival rates were 95% and 89%, respectively. Especially, the estimated 5- and 10-year cancer-specific survival rates were both 98.8%. Conclusions Long-term outcomes for patients with RCC and ESRD were favorable in this study. Therefore, the early detection of tumors is particularly important for the optimal survival of patients with RCC and ESRD. This can be achieved through regular monitoring by abdominal ultrasonography or computed tomography. Funding None
Authors
Shunichi Namiki
Yoshihiro Ikeda Takashi Kudo Masataka Aizawa Naaomasa Ioritani |
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MP72-03 |
Comparative Analysis of Radical and Partial Nephrectomy in Patients with Preoperative Stage 2 Chronic Kidney Disease: A Multicenter Study |
Kidney Cancer: Localized: Surgical Therapy V | 17BOS |
Abstract: MP72-03 Sources of Funding: Stephen Weissman Kidney Cancer Research Fund. NIH grants UL1TR000100 and UL1TR001442. Introduction Partial nephrectomy (PN) is considered a strong (imperative/relative) indication for patients with stage 3 chronic kidney disease [(CKD), estimated glomerular filtration rate (eGFR)<60 ml/min/1.73m2] and is considered elective for patients with higher GFR. Change in GFR (δGFR) is less for PN compared to radical nephrectomy (RN), and patients with stage 2 CKD (eGFR 60-89) may be at increased risk for postoperative renal decline to thresholds of increased risk. We compared renal function and survival outcomes in patients with baseline stage 2 CKD who underwent PN or RN. Methods International multicenter retrospective analysis of patients with baseline stage 2 CKD who underwent PN or RN from 1987-2015. Demographics, disease characteristics, survival and renal function outcomes were recorded. Patients were stratified into baseline Stage 2a CKD (GFR 75-89) and Stage 2b CKD (GFR 60-74.9) for analysis. Primary outcome was δGFR at last follow up. Secondary outcomes included occurrence of GFR<45, a risk factor for poor survival outcomes, and overall survival (OS). Cox proportional hazard regression, Kaplan Meier analysis, and multivariable (MV) regression for risk factors associated with outcomes was performed. Results 1460 patients were analyzed (mean age 61.9 years, median follow up 46 months). 49.3% underwent PN/50.7% underwent RN, and 49.5% were Stage 2a CKD (n=723) while 50.5% were Stage 2b CKD (n=737). Mean δGFR was greater for RN than PN overall (-12.5 vs. -6.5, p<0.001), in stage 2a CKD (-12.9 vs. -10.0, p<0.001), and stage 2b CKD (-11.9 vs. -2.9, p<0.001). Cox proportional hazard regression for GFR<45 noted negative effect for RN overall (HR 1.78, p<0.001), in Stage 2a CKD (HR 1.88, p=0.019), and in Stage 2b CKD (HR 1.74, p=0.002). On MV regression for GFR<45, Stage 2b CKD (OR 1.70, p<0.001) and RN (OR 1.47, p=0.028) were independent risk factors. MV regression for OS was worse for RN overall (OR 2.93, p<0.001), in Stage 2a CKD (OR 3.12, p<0.001), and in 2b CKD (OR 2.77, p<0.001). Conclusions Patients with baseline Stage 2 CKD undergoing RN are at increased risk of GFR decline, including the threshold of GFR<45, and worsened OS. For patients with Stage 2 CKD, PN may be considered a relative indication and should be prioritized when appropriate. Funding Stephen Weissman Kidney Cancer Research Fund. NIH grants UL1TR000100 and UL1TR001442.
Authors
Zachary Hamilton
Alessandro Larcher Brian Lane Umberto Capitanio Sumi Dey Aaron Bloch Charles Field Samer Kirmiz Daniel Han Adam Bezinque Alp Tuna Beksac Cristina Carenzi Fang Wan James Proudfoot Francesco Montorsi Ithaar Derweesh |
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MP72-04 |
Can partial nephrectomy provide equal oncological efficiency and safety compared with radical nephrectomy in patients with renal cell carcinoma (? 4 cm)? A propensity score matched study |
Kidney Cancer: Localized: Surgical Therapy V | 17BOS |
Abstract: MP72-04 Sources of Funding: none Introduction Although partial nephrectomy is the standard treatment for localized clinical T1a renal cell carcinoma, treatment of larger renal tumors is controversial. We evaluated the oncological outcomes and perioperative complications after radical and partial nephrectomy for renal cell carcinoma ≥ 4 cm. Methods We retrospectively analyzed the data of 2,373 patients surgically treated for non-metastatic RCC with clinical T1b or T2 (≥ 4 cm). The propensity scores for surgery type were calculated and the partial group was matched to the radical group in a 1:3 ratio. The oncological outcomes were compared using Kaplan-Meier analysis and multivariate Cox regression models were utilized to identify the independent predictors of progression-free, cancer-specific, and overall survival. Results All differences in preoperative clinical characteristics disappeared after matching. There were no significant differences in progression-free, cancer-specific, or overall survival between the partial and radical groups in the matched cohort. The patients&[prime] age, tumor size, cellular grade, and pathologic stage were independent predictors for all three survival outcomes. However, early complications (< 30 days postoperative) were significantly more common in the partial group (p < 0.001). In a subgroup analysis of the patients with clinical T2 stage, there were no significant differences in all three survival outcomes. Conclusions The partial and radical nephrectomy groups had equivalent oncological outcomes. Although the early complication rate was significantly higher after partial nephrectomy, it should be considered as a valuable treatment option even in patients with clinical T1b or higher renal cell carcinoma. Funding none
Authors
Hakmin Lee
Ohseong Kwon Jong Jin Oh Seok-Soo Byun Chang Wook Jeong Cheol Kwak Hwang Gyun Jeon Byong Chang Jeong Seong Soo Jeon Hyun Moo Lee Han-Yong Choi Seong Il Seo |
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MP72-05 |
Patterns and predictors of recurrence after partial nephrectomy for kidney tumors |
Kidney Cancer: Localized: Surgical Therapy V | 17BOS |
Abstract: MP72-05 Sources of Funding: none Introduction The last years have been marked by a growth in the use of partial nephrectomy (PN) for complex renal masses. This has led to an overall increase in the number of tumors found to have adverse pathological features. The aim of this study was to identify patterns and predictors of recurrence in patients with clinically localized renal cell carcinoma managed with PN._x000D_ Methods Retrospective study of 830 consecutive cases of PN done between 2007 and 2015 at a single institution. Patient demographics, and pathological characteristics were correlated with recurrence patterns (overall, local and distant) and overall survival (OS) using Kaplan-Meier and cox regression analyses. Differences in the recurrence patterns were evaluated. Results Median age was 61 years, and median tumor size was 3.1 cm. Overall, 11.6% of tumors were pT3 stage, 39.3% were high grade, 2.9% had lymphovascular invasion, and 7.1% had positive margins. Median follow up was 36 months. There were 5.8% of patients diagnosed with recurrence. Grade, stage, surgical margins, and R.E.N.A.L score were associated with shorter disease-free survival (DFS). In multivariable regression pT (p<0.01), grade (p<0.01), and R.EN.A.L score (p=0.02) remain independent predictors of DFS. pT stage (HR 4.9, p<0.01) and grade (HR 3.9, p<0.01) were predictors of metastasis, while R.E.N.A.L score (HR 3.86, p=0.03) was the single predictor of local recurrence. Positive surgical margin did not predict recurrence. Five-year DFS and OS probabilities were 91% and 94%, respectively. Local recurrence emerged and developed earlier than metastasis (median 13 vs. 22 months, p<0.01). Conclusions High pT stage, high grade, and high R.E.N.A.L. score increase the risk of disease recurrence after partial nephrectomy. pT stage and grade are predictors of metastasis while R.E.N.A.L. score predicts local recurrence. Surgical margin status did not predict disease recurrence. The relapse features and risk factors are different between the 2 recurrence patterns. Funding none
Authors
Pascal Mouracade
Onder Kara Matthew Maurice Julien Dagenais Ercan Malkoc Jaya Sai Chavali Ryan Nelson Khaled Fareed Robert Stein Amr Fergany Jihad Kaouk |
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MP72-06 |
MULTI-INSTITUTIONAL SURVIVAL ANALYSIS OF INCIDENTAL PATHOLOGIC T3a UPSTAGING IN CLINICAL T1 RENAL CELL CARCINOMA FOLLOWING PARTIAL NEPHRECTOMY |
Kidney Cancer: Localized: Surgical Therapy V | 17BOS |
Abstract: MP72-06 Sources of Funding: None Introduction pT3a disease is known to represent a poor prognostic factor in renal cell carcinoma (RCC) with an approximate four-fold increased risk for recurrence regardless of size when compared to pT1 disease. The impact of incidental pT3a upstaging in patients undergoing partial nephrectomy (PNx) for cT1 disease, however, is not well defined. Methods A retrospective chart review was completed at the University of Michigan and Moffitt Cancer Center to identify patients who underwent PNx between 1996-2015 for cT1 RCC with subsequent pathologic upstaging to pT3a disease. Patients with pT3a disease were compared to controls who underwent PNx for cT1 disease with final pathology confirming pT1 disease. Recurrence-free survival (RFS) and cancer-specific survival (CSS) were estimated using the Kaplan-Meier method. Results A total of 95 patients with pT3a upstaging were identified and compared to 1164 controls. Median follow up in our series was 38.2 (IQR 11.6-56.8) months. Following PNx, 20 (21%) patients with incidental pT3a upstaging suffered disease recurrence at a median of 28.7 months (IQR 10.3-43.5), consisting of 4 (4%) local recurrences and 17 (18%) distant metastases. In comparison, 8 (0.7%) controls suffered disease recurrence at a median of 46.6 months (IQR 17.7-74.2). In patients with pT3a disease, the 5- and 8-year RFS was 71% and 59%, compared to 88% and 78% in controls (p<0.0001). CSS was also significantly different between cohorts, with pT3a patients experiencing a 5- and 8-year CSS of 92% and 79%, compared to 99% and 98% in controls (p=0.001). Kaplan-Meijer curves are depicted in Figure 1. There were a total of 7 (7%) RCC related deaths, which occurred at a median of 28.5 months (IQR 9.3-54.3) in the pT3a cohort, while there were 5 (0.4%) RCC related deaths at a median of 96.5 months (IQR 56.9-96.9) in those with final pT1 disease. Conclusions The data presented here suggests that patients with cT1 disease and incidental pT3a upstaging following PNx experience a significantly reduced RFS and CSS compared to those with final pT1 disease, and thus may benefit from modified follow up protocols or early adjuvant therapies. Funding None
Authors
Christopher M. Russell
Amir H. Lebastchi Juan Chipollini Adam Niemann Rohit Mehra Todd M. Morgan David C. Miller Ganesh S. Palapattu Khaled S. Hafez J. Stuart Wolf Wade J. Sexton Philippe E. Spiess Alon Z. Weizer |
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MP72-07 |
Histopathologic Analysis of Tumor Bed after in vitro Tumor Enucleation on Radical Nephrectomy Specimen |
Kidney Cancer: Localized: Surgical Therapy V | 17BOS |
Abstract: MP72-07 Sources of Funding: none Introduction In recent years, large series of tumor enucleation (TE) for renal masses have showed equivalent functional and oncological results compared with standard partial nephrectomy. However, few objective assessments and pathologic evidence of enucleation tumor bed have been reported. This study was designed to assess the feasibility and histopathologic safety of tumor enucleation for renal cell carcinoma, through histopathologic analysis of the tumor bed after in vitro tumor enucleation. Methods We studied 246 radical nephrectomy specimens for clinical T1 RCC in our institution, from January 2013 to December 2015. Immediately after the kidney was excised, the tumor of radical specimen was enucleated in vitro in the same fashion as open or laparoscopic kidney tumor enucleation. The tumor bed parenchyma of 15 mm beyond the pseudocapsule were continuously sectioned and examined to investigate the possible presence of tumor invasion or satellite lesions. Results The study involved 246 patients, consisting of 148 men (60.2%) and 98 women (39.8%), with a mean age of 60.9±10.3 years. The average tumor size was 5.3±1.7 cm. The histopathologic evaluation revealed that 82.5% of tumors were clear cell RCC, 7.7% were papillary, and 6.5% were chromophobe. The pathological staging showed that 23.2% of tumors were pT1a, 68.3% were pT1b, 3.7% were pT2, and 4.9% were pT3a.On the basis of Fuhrman nuclear grading, 171 lesions (69.5%) were grade 1-2 and 75 (30.5%) were grade 3-4. The incidence of positive surgical margins was 3.3%. For the pathological characteristics of tumor bed, tumor infiltration was detected in 5 cases (2.0%) and satellite lesion was detected in 4 cases (1.6%). In the group of 60 primary tumors 4 cm or less in diameter, 3 (5.0%) were found with residual tumor, 1 with tumor infiltration and 2 with satellite lesion. In the group of 186 primary tumors larger than 4 cm, 6 (3.2%) were found with residual tumor, 4 with tumor infiltration and 2 with satellite lesion. Statistically, there was no significant difference (p=0.809). In the group of grade 1-2, 4 (2.3%) were found with residual tumor, and 5 (6.7%) in the group of grade 3-4 (p=0.195). Median follow-up was 24 months (range 8-43) with a recurrence rate of 4.1% (10 of 246) and a cancer specific mortality rate of 2.4% (6 of 246). Conclusions The risks of tumor infiltration and/or satellite lesions of enucleation tumor bed are relatively low. Tumor enucleation is a histopathologically safe technique for patients undergoing partial nephrectomy. Funding none
Authors
Qun Lu
Changwei Ji Xiaozhi Zhao Guangxiang Liu Hongqian Guo |
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MP72-08 |
Severity of Preoperative Proteinuria is a Risk Factor for Overall Mortality in Patients Undergoing Nephrectomy |
Kidney Cancer: Localized: Surgical Therapy V | 17BOS |
Abstract: MP72-08 Sources of Funding: none Introduction Chronic kidney disease has significant implications on patient outcomes. Proteinuria along with glomerular filtration rate is increasing used as a marker for kidney disease. The relationship between pre-operative proteinuria and survival following nephrectomy is incompletely characterized. Herein, we evaluated the association of preoperative proteinuria with overall and cancer-specific survival in our institutional nephrectomy registry. Methods We identified patients with clear cell renal cell carcinoma treated for curative intent from 1995 to 2010. Patients were categorized based on KDIGO (Kidney Disease Improving Global Outcomes) 2012 guidelines. Overall and cancer-specific survivals were evaluated using Kaplan-Meier methodology. Cox proportional hazards regression models were used to assess for variables associated with overall and cancer-specific mortality. Results Between 1995 and 2010, 1,846 patients underwent radical or partial nephrectomy. Of these, 1,347 (73%) underwent preoperative predicted 24-hour urine protein testing. Patients with and without predicted 24-hour urine protein had no difference in overall survival (p=0.73) or cancer-specific survival (p=0.85). There were 804 (60%) patients classified with mild (<150 mg/day), 332 (25%) classified with moderate (150-500 mg/day), and 211 (16%) classified with severe proteinuria (>500 mg/day). Kaplan-Meier overall survival curves stratified by pre-operative proteinuria severity are depicted in the Figure (p<0.001). Multivariate analysis demonstrated severe proteinuria was associated with worse overall survival (HR 1.61 95%CI 1.26-2.07 p<0.001). Proteinuria level was not associated with worse cancer-specific survival. Conclusions Severe pre-operative proteinuria is associated with worse overall survival. During patient counseling, pre-operative proteinuria should be considered when estimating a patient&[prime]s overall health risk. Funding none
Authors
David Y Yang MD
R Houston Thompson MD Harras B Zaid MD Christine M Lohse MS Andrew D Rule MD Bradley C Leibovich MD John C Cheville MD Matthew K Tollefson MD |
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MP72-09 |
Trends in Utilization and Quality Outcomes of Partial Nephrectomy in cT1b and cT2a Renal Cell Carcinoma: Analysis of the National Cancer Database |
Kidney Cancer: Localized: Surgical Therapy V | 17BOS |
Abstract: MP72-09 Sources of Funding: none Introduction Emerging data from centers of excellence suggests that partial nephrectomy (PN) for cT1b and cT2a Renal Cell Carcinoma (RCC) are oncologically safe and may confer renal functional benefit. We sought to study trends in utilization and short term quality outcomes of PN among patients with cT1b and cT2a RCC using the National Cancer Database (NCDB). Methods We identified 39,561 patients with localized cT1b or cT2a RCC who underwent PN from 2004-2013. Primary outcome was utilization of PN over time. Secondary outcomes included hospital length of stay (LOS, short hospitalization: 0-4 days), margin status and 30-day readmissions. Cochrane-Armitage test was used to describe trends over time. Multivariable (MVA) logistic regression models were used to investigate associations between tumor stage and outcomes. Results The study consisted of 28,620 (72.3%) patients with cT1b and 10,941 (27.7%) with cT2a masses. Overall, 8,953 (22.6%) patients underwent PN. More patients with cT1b vs. cT2a tumors underwent PN (28.1% vs. 8.34%; p<0.01). PN increased over the study period (cT1b: 13.7% to 37.1%, p<0.01; cT2a: 3.2% to 11.0%, p<0.01; Figure). For all PN, positive margin rates increased from 4.3% in 2004 to 6.8% in 2013, (p<0.01); 30-day readmission was not significantly changed (2.2% in 2004 to 5.1% in 2013, p=0.76). Proportion of short LOS increased, from 51.6% in 2004 to 75.2% in 2013 (p<0.01). MVA for positive margins was notable for increasing age (OR 1.01, p=0.012), year of diagnosis (OR 1.07, p=0.01), and facility type (comprehensive community OR 1.362, p=0.002, integrated network cancer program OR 1.53, p=0.009, free standing cancer center program OR 3.44, p=0.003). MVA for 30-day readmission demonstrated high Charlson score (OR 1.38, p=0.046), and facility type (integrated network cancer program OR 0.56, p=0.022) as being significant. On MVA, patients with cT2a tumors were no more likely than those with cT1b to require 30-day readmission (OR 0.86, p=0.36) or have positive margins (OR 0.96, p=0.75). Conclusions Utilization of PN for cT1b and cT2a renal mass has increased over time. While length of hospital stay has shortened and 30-day readmission rates are not significantly different, an increase in positive margin rates has been noted, with predictive factors including patient age and facility type. PN in cT2a does not confer increased risk compared to PN in cT1b RCC. Focused emphasis and strategies to reduce positive margin rates in this higher risk population of localized renal masses should be considered. Funding none
Authors
Katherine Fero
Zachary Hamilton Daniel Han Aaron Bloch Charles Field Ithaar Derweesh |
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MP72-10 |
The prognostic implication of body mass index on postoperative survival outcomes in non-metastatic renal cell carcinoma |
Kidney Cancer: Localized: Surgical Therapy V | 17BOS |
Abstract: MP72-10 Sources of Funding: none Introduction To evaluate the association between body mass index (BMI) and survival outcomes in patients with non-metastatic RCC. Methods A single-institutional retrospective analysis was implemented on 2329 patients who underwent radical or partial nephrectomy for non-metastatic RCC from 2000 to 2014. Enrolled patients were grouped into normal (BMI <23kg/m2, n=705), overweight (BMI 23-24.9 kg/m2, n=648), and obese (BMI ?25kg/m2, n=976) according to BMI cut-offs for Asian population. Outcomes of interest included recurrence free survival (RFS), overall survival (OS), and cancer-specific survival (CSS). Survival curves for each BMI category were estimated and compared using the Kaplan-Meier method with log-rank test. The impact of BMI as continuous or categorical variables on survival outcomes was assessed with multivariable Cox proportional hazard models. Results Several clinico-pathological factors, including asymptomatic presentation, being female, lower transfusion rate, higher proportion of clear cell histology, and lower frequency of nodal invasion, were observed in association with obese group (all p<0.05). Obese group showed significantly better 5-year RFS (90.7% vs 84.9%, p<0.001), OS (91.8% vs 86.8%, p=0.002), and CSS (94.8% vs 89.4%, p=0.002) rates than normal patients. On multivariable analysis, BMI as continuous variable independently correlated with favorable RFS (hazard ratio [HR] 0.93; 95% confidence interval [CI] 0.89-0.97, p=0.002), OS (HR 0.95; 95% CI 0.91-0.99, p=0.033) and CSS (HR 0.91; 95% CI 0.86-0.97, p=0.002). In addition, multivariable analysis revealed overweight (HR 0.57; 95% CI 0.37-0.87, p=0.009) and obese patients (HR 0.58; 95% CI 0.39-0.87, p=0.009) were associated with significantly reduced risk of RCC related death compared to normal patients. Conclusions Our data suggest overweight and obesity defined as increasing BMI are generally related to favorable survival outcomes after nephrectomy for non-metastatic RCC. Further basic research will be required to discover the biological mechanisms explaining the positive correlation between high BMI and improved RCC survival. Funding none
Authors
Hyung Suk Kim
Chang Wook Jeong Cheol Kwak Ja Hyeon Ku Hyeon Hoe Kim Hae Won Lee |
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MP72-11 |
Modified 5-item frailty index is associated with increased healthcare resource utilization following elective minimally invasive radical nephrectomy |
Kidney Cancer: Localized: Surgical Therapy V | 17BOS |
Abstract: MP72-11 Sources of Funding: None Introduction To evaluate the condensed 5-item frailty index (FFI) based on contemporary National Surgical Quality Improvement Program (NSQIP) database as a predictor of increased healthcare resource utilization (HRU) after elective minimally invasive radical nephrectomy (MIRN). Methods The NSQIP database (2012 - 2015) was used to identify patients with renal cell carcinoma who had elective MIRN. The primary outcome of interest was increased HRU, which was pre-defined as prolonged length of hospital stay (PLOS) (> 4 d), discharged to continued care (DCC), and unplanned readmission (UR) within 30 days of surgery. FFI was modified from the previously reported 11-item frailty index and based on 6 variables were not collected in recent NSQIP database possibly because of infrequent occurrence. FFI was calculated by scoring following items (full score of 6): diabetes (1 if on oral agents, 2 if on insulin), impaired functional status (1), chronic obstructive pulmonary disease (1), hypertension requiring medication (1), and congestive heart failure in 30 days before surgery (1). Patients were stratified into 4 groups by FFI (0, 1, 2, and ≥ 3) and outcomes were compared. Multivariable logistic regression was performed to determine whether FFI could independently predict increased HRU outcomes. Results A total of 2,321 patients were included. Increased HRU outcomes stratified by FFI were shown in Figure 1 and there was increasing likelihood with increasing FFI. Multivariable logistic regression showed that FFI = 2 (OR = 1.96 [1.36-2.81], P <0.001) and FFI ≥ 3 (OR = 3.10 [2.08-4.62], P <0.001) were independent predictors of overall increased HRU. When the outcomes of PLOS, DCC, and UR were analyzed separately, FFI = 2 (OR = 1.78, P = 0.006 for PLOS, OR = 4.61, P = 0.008 for DCC, and OR = 1.93, P = 0.042 for UR) and FFI≥ 3 (OR = 2.73, P < 0.001 for PLOS, OR = 7.85, P < 0.001 for DCC, and OR = 2.47, P = 0.009 for UR) were still independently associated with each individual outcome. Conclusions The readily available and easily reproducible FFI correlates with increased HRU after MIRN. FFI might be a useful tool to patients, providers, and healthcare policy makers in terms of surgical safety as well as cost outcomes. Further studies are needed to validate our findings. Funding None
Authors
Benjamin Taylor
Leilei Xia Jose Pulido Jeremy Bonzo George Drach Thomas Guzzo |
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MP72-12 |
Surveillance after Surgery for Renal Cell Carcinoma: A Risk-Adapted Approach |
Kidney Cancer: Localized: Surgical Therapy V | 17BOS |
Abstract: MP72-12 Sources of Funding: None Introduction The risk of recurrence following surgical excision of clear cell renal cell carcinoma (ccRCC) varies based on clinical and pathologic features, while risk of non-cancer death evolves as a function of age and comorbidities. Despite these differences in how these competing risks mature over time, current guidelines recommend surveillance based on stage alone. We therefore sought to develop risk adapted postoperative surveillance recommendations. Methods Patients with ccRCC managed surgically between 1990 and 2008 (n=2,511) were identified from the Mayo Clinic Nephrectomy registry and risks of abdominal and chest recurrence estimated using accelerated failure-time (AFT) models by pathology stage (pT1a, pT1b, pT2, pT3/4, or pTanyN+). Similarly, risk of non-cancer death was estimated by age (<50, 51-59, 60-69, 70-79, and ≥80) and comorbidity index (CCI: ≤1 versus >1). Recommended surveillance schedules balance estimated risk of non-cancer death with recurrence risk where allowable recurrence is up to the risk of non-cancer death. Surveillance intervals were calculated based on each 1%, 3%, and 5% recurrence risk increase to a maximum 10 years. Intervals shorter than 3 months were not allowed, with the next risk increase calculated from the date of the adjusted interval. Results AFT models for recurrence and death for stage, age, and comorbidity risk groups were generated (tables). Recommended interval schedules (e.g. 1%, 3%, or 5%) are based on the predicted risk of non-cancer death for a given age and CCI group. For example, patients <70 years with a CCI score ≤1 would be followed on a 1% risk of recurrence schedule for the duration of 10 years of follow-up regardless of stage. Conversely, patients 60-69 years old with a CCI >1, would follow a 1% interval for the first year only, then switch to 3% interval until year 6, at which point they would follow a 5% schedule. Conclusions Using an AFT model for estimating risk of recurrence and risk of death we were able to generate risk-adapted screening intervals for surgical managed patients with RCC. Funding None
Authors
William Parker
Suzanne Merrill Phillip Schulte Ross Mason R. Houston Thompson Christine Lohse Igor Frank |
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MP72-13 |
Modified robot-assisted simple enucleation with single layer suture technique in localized renal tumors?a propensity score-matching analysis |
Kidney Cancer: Localized: Surgical Therapy V | 17BOS |
Abstract: MP72-13 Sources of Funding: none Introduction Simple enucleation has been proved oncologically safe. The aim of the present study is to compare perioperative results and early oncological outcomes of modified robot-assisted simple enucleation (MRASE) with laparoscopic simple enucleation (MLSE) for treating localized renal tumors in our large institutional experience. Methods We evaluated 581 consecutive patients who underwent MRASE or MLSE for renal tumors in our institution from November 2012 to October 2016 in terms of perioperative and oncologic outcome variables. Propensity score matching was performed on age, gender, ECOG score, tumor size, preoperative estimated glomerular filtration rate and PADUA score. Modified simple enucleation was performed with robotic or laparoscopic system. The surgeon used the pseudocapsule as the anatomical landmark to enucleate the tumor by combining sharp and blunt dissection. Single layer suture technique was performed for renal reconstruction. The parenchymal defect was closed with horizontal interrupted 2-0 monocryl sutures with Hem-o-lok clips placed on the kidney capsule. Results In total, 299 patients underwent MRASE and 282 underwent MLSE. After matching, mean operative time and warm ischemic time was significantly lower in the MRASE than MLSE group (172.2 min vs.184.3 min; p=0.003 and 20.6 min vs. 25.2 min; p=0.000, respectively). The estimated blood loss was similar. Tumor bed suturing was performed in only 7.2% and 9.1% of MRASE and MLSE patients, respectively ( p=0.437). Postoperative complication rates were similar for MRASE and MLSE (8.7% vs. 13.0%, p=0.101). The incidence of positive surgical margins was comparable between the MRASE and MLSE group (1.4% vs. 1.8%, p=0.737). The decline in postoperative eGFR did not differ between the two groups (p=0.328). The median follow-up period was 13 (1-25) months for MRASE versus 30 (2-47) months for MLSE patients. Recurrence did not differ between the two groups (2.2% vs. 2.9%, p=0.588). Conclusions MRASE is a safe and acceptable alternative to MLSE, providing comparable morbidity and equivalent early oncological outcomes. MRASE appears to confer shorter operative time and warm ischemic time than MLSE. Moreover, MRASE is more likely to be used for complex renal tumors. Funding none
Authors
Xiaozhi Zhao
Qun Lu Guangxiang Liu Gutian Zhang Xiaogong Li Weidong Gan Hongqian Guo |
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MP72-14 |
Impact of chronic kidney disease and hypertension on decline in remaining kidney function after radical nephrectomy |
Kidney Cancer: Localized: Surgical Therapy V | 17BOS |
Abstract: MP72-14 Sources of Funding: None Introduction We previously reported on the long-term recovery of renal function after radical nephrectomy (RN) (J Urol 2011, Int J Urol 2016). Atypically, some patients experience longitudinal decline in post-nephrectomy renal function, and a few eventually develop end-stage renal disease (ESRD). A >30% decrease in estimated glomerular filtration rate (eGFR) has been shown to be a risk factor for ESRD and all-cause mortality in chronic kidney disease (CKD) patients. Here, we investigated the incidence and risk factors of a >30% eGFR decline from the postoperative baseline in patients undergoing radical nephrectomy (RN). Methods This multicenter study included 894 patients who had undergone RN between 1994 and 2014. Patients with bilateral renal tumors, metastases, preoperative ESRD, and follow-up <1 year were excluded. The primary endpoint was a >30% eGFR decrease from the postoperative baseline, which was defined as eGFR at 1 month after RN. We identified the preoperative risk factors for a >30% eGFR decrease using the Cox proportional hazard model. A risk-stratification model incorporating independent risk factors was then generated. Results The median age, preoperative eGFR, and postoperative baseline eGFR of the 894 patients (593 men, 301 women) were 65 years, 70.5, and 45.1 ml/min/1.73 m2, respectively. Of these, 235, 351, 126, and 131 patients had preoperative CKD defined as eGFR <60 ml/min/1.73 m2, hypertension (HT), diabetes mellitus, and cardiovascular disease, respectively. During the median follow-up of 48 months, a >30% eGFR decrease from the postoperative baseline was observed in 47 patients (5.3%). ESRD requiring dialysis developed in 10 of the 47 patients. Multivariate analysis revealed that preoperative CKD and HT were independent risk factors for a >30% eGFR decrease. Five-year >30% eGFR decrease-free survival rates were 98%, 94%, and 84% in patients with 0, 1, and 2 risk factors, respectively (p < 0.001, Figure). Of the 10 patients who developed ESRD, 8 had both risk factors and the remaining 2 had 1 risk factor. Conclusions Approximately 5% of patients undergoing RN experienced a >30% eGFR decrease from the postoperative baseline, and one-fifth of these patients eventually developed ESRD. Preoperative CKD and HT were the risk factors for a >30% decline in eGFR. Funding None
Authors
Minato Yokoyama
Fumitaka Koga Yukihiro Otsuka Tetsuro Tsukamoto Tetsuo Okuno Katsushi Nagahama Yukio Kageyama Akira Noro Toshihiko Tsujii Shinji Morimoto Satoshi Kitahara Kazunori Kihara Yasuhisa Fujii |
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MP72-15 |
Robotic Partial Nephrectomy in Patients with Chronic Kidney Disease: Objective measurement of Short and Long Term Renal Functional Outcomes |
Kidney Cancer: Localized: Surgical Therapy V | 17BOS |
Abstract: MP72-15 Sources of Funding: none Introduction There is paucity of literature regarding short and long-term renal functional outcomes in patients with chronic kidney disease (CKD) undergoing robotic partial nephrectomy (RPN). We sought to objectively assess short and long term renal functional outcomes in patients with CKD undergoing RPN for suspicious renal masses. Methods We reviewed a prospectively maintained single surgeon database of patients who underwent RPN between 2010 - 2015. 182 patients who had pre- and post-operative (2 and 12 months post-op) MAG-3 renal scans comprised the study cohort. eGFR (in mL/min/1.73m2) preop and post-op (1 year) was calculated using the MDRD equation. CKD was defined as an eGFR <60 mL/min/1.73m2 (CKD category III & IV). Changes in creatinine, eGFR, and split renal function on renal scan were compared between patients with and without pre-operative CKD. Correlations between pre-op and post-op creatinine and eGFR were also calculated. Results Of 182 patients, 30 (16.5%) had CKD. Preop eGFR was 48.5 and 99.0 in the CKD and non-CKD groups, respectively (p <0.001; Table 2). Patients with CKD were more likely to have a malignant tumor on pathology (93.3% vs. 73.2%, p=0.02) and a higher Furhman Grade (3 or more: 49.7% vs 28.1 %, p<0.001). From pre-op to 12 months post-op, eGFR decreased by 2.8 and 1.1 mL/min/1.73m2 (p = 0.6) and the contribution of the surgical kidney on MAG3 renal scan decreased by 5.0 and 4.8% (p = 0.9) in the CKD and non-CKD cohorts, respectively (table 2). When comparing renal scans at 2 months 12 months of the cohort (figure1), the resected kidney recovered significantly (p<0.001) in both groups in a similar fashion (2.0% in CKD, 1.4% in no CKD p=0.6)_x000D_ Long-term follow up (median of 2.5 and 3.0 years for CKD and non-CKD groups, respectively) of eGFR change also did not show any difference compared to patients with normal kidney function (-2.8 vs -1.1 mL/min/1.73m2, p=0.6)._x000D_ _x000D_ Conclusions RPN is a reasonable treatment option in patients with CKD as they did not experience a greater decline in renal function after RPN compared to patients without CKD. The long-term renal functional recovery parallels that of patients without CKD undergoing RPN. Of interest, CKD patients were more likely to have a malignant tumor with a higher Fuhrman grade; a factor to be considered when counseling patients regarding treatment options. Funding none
Authors
charbel chalouhy
Jessica Ruck Tian Cheng Zhou abhishek Srivastava lucas policastro kara watts Reza Ghavamian |
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MP72-16 |
Predictors of Positive Surgical Margins in Patients Undergoing Partial Nephrectomy: A Single-Center Experience |
Kidney Cancer: Localized: Surgical Therapy V | 17BOS |
Abstract: MP72-16 Sources of Funding: None Introduction Several risk factors for positive surgical margin (PSM) have been suggested, including age, tumor location, tumor size, tumor stage, tumor grade, and tumor invasion into the perinephric fat. The aim of this study was to identify predictors of PSM in partial nephrectomy (PN) while taking into account surgeon factors, namely approach and volume. Only preoperative characteristics were assessed in order to inform patient counseling and PSM prevention. _x000D_ Methods Using our institutional partial nephrectomy database, we identified patients who underwent PN for malignant tumors between January 2011 and December 2015. Patient, tumor, surgeon characteristics were compared by surgical margin status. Multivariable logistic regression was used to identify independent predictors of positive surgical margins._x000D_ Results A total of 1025 cases were available for analysis, of which 65 and 960 had positive and negative surgical margins, respectively. On univariate analysis, positive margins were associated with older age (64.3 vs. 59.6, <0.01), history of prior ipsilateral kidney surgery (13.8% vs. 5.6%, <0.01), lower preoperative eGFR (74.7 vs. 81.2, p=0.01), high tumor complexity (31.8% vs. 19.0%, p=0.03), hilar tumor location (23.1% vs. 12.5%, p=0.01), and lower surgeon volume (p<0.01). Robotic versus open approach was not associated with the risk of positive margins (p=0.79). On multivariable analysis (Table), lower preoperative eGFR (p=0.01), hilar tumor location (p=0.01), and lower surgeon volume (<0.01) were found to be independent predictors of positive margins._x000D_ Conclusions In our series of PN cases, patient, tumor, and surgeon factors influence the risk of positive margins. Of these, surgeon’s volume is the primary and only modifiable predictor of surgical margin status. Funding None
Authors
Ercan Malkoc
Matthew J. Maurice Onder Kara Pascal Mouracade Daniel Ramirez Ryan J. Nelson Julien Dagenais Khaled Fareed Amr Fergany Robert J. Stein Jihad H. Kaouk |
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MP72-17 |
ROBOT-ASSISTED PARTIAL NEPHRECTOMY FOR COMPLEX CASES (PADUA SCORE ? 10): RESULTS FROM A MULTICENTER EXPERIENCE AT THREE HIGH-VOLUME CENTERS |
Kidney Cancer: Localized: Surgical Therapy V | 17BOS |
Abstract: MP72-17 Sources of Funding: None Introduction We assessed the feasibility of robot-assisted partial nephrectomy (RAPN) in a contemporary series of patients with highly-complex tumors (PADUA score≥ 10) treated at three high-volume robotic surgery institutions. Methods Data from a multi-institutional database on patients subjected to RAPN for clinically-localized kidney cancer between 2010 and 2016 were reviewed. Overall, 198 patients with highly-complex renal tumors, defined as a PADUA score≥ 10, were included. Complications, functional and oncological outcomes were assessed. Optimal surgical outcomes, defined according to the Margin Ischemia and Complications (MIC) binary system (absence of Clavien-Dindo >2 complications, warm ischemia time [WIT] <20 minutes and absence of positive surgical margins) were assessed. Finally, predictors of optimal surgical outcomes were determined using logistic regression models (LRMs). Results Median patient age was 61.5 years (IQR: 53-68), median preoperative tumor size was 43 mm (IQR 28-54), and median preoperative creatinine was 0.92 mg/dL (IQR: 0.80-1.13). Overall, 91 (46.0%) patients had a PADUA score 10, followed by 65 (32.8%) with a score of 11, 33 (16.7%) with a score of 12 and 9 (4.5%) with a score of 13. Median operative time was 180 minutes (IQR: 131-221), median WIT was 18 minutes (IQR: 15-22), and median estimated blood loss was 150 ml (IQR: 100-300). WIT was > 20 minutes in 62 (31.3%) patients, while a Clavien-Dindo >2 complication and positive surgical margins were observed in 12 patients (5.0%) and 4 (2.0%) individuals, respectively. Optimal surgical outcomes were achieved in 126 (63.6%) patients. Median creatinine the day after surgery was 1.10 mg/dL and remained stable 2 weeks later (median: 1.10 mg/dL. At a median follow-up of 22 months, no local or distant recurrence of the disease was observed. In multivariable LRMs, after adjustment for patient age, gender, BMI, side, CCI, and tumor size, extremely complex tumors (PADUA score 12-13) were associated with a 2.7 -fold higher risk of not achieving optimal outcomes (OR: 1.03-7.02; p=0.044). In addition, males showed a 2.31-fold higher risk of not achieving optimal surgical outcomes (95%CI: 1.04-5.14; p=0.040) relative to their female counterparts. Conclusions In experienced hands, RAPN can be considered as an effective treatment option even for complex renal lesions. Increasing tumor complexity may affect the surgical outcomes even in this highly-selected patient population. Funding None
Authors
Giovanni Lughezzani
Nicolo' Buffi Giuliana Lista Davide Maffei Giovanni Forni Nicola Fossati Alessandro Larcher Massimo Lazzeri Alberto Saita Paolo Casale Giorgio Guazzoni Jim Porter Alex Mottrie |
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MP72-18 |
Oncological outcomes of positive surgical margins in patients who underwent partial nephrectomy for renal cell carcinoma. |
Kidney Cancer: Localized: Surgical Therapy V | 17BOS |
Abstract: MP72-18 Sources of Funding: none Introduction The prognostic significance and optimal management of positive surgical margins following partial nephrectomy remain controversial. The association between positive margin and risk of disease recurrence in patients with clinically localized renal neoplasm undergoing partial nephrectomy was evaluated. Methods We analyzed the records of 429 patients cases of non-metastatic renal cell carcinoma who underwent partial nephrectomy (PN) at our institution, from 2001 to 2016. Recurrence-free survival was evaluated using Kaplan-Meier method, log rank test and Cox models adjusting for tumor size, grade, histology, pathological stage, focality and laterality. The relationship between positive margin and risk of relapse was evaluated independently for pathological high risk (Fuhrman grades III-IV) and low risk (Fuhrman grades I-II) groups. Results A positive surgical margin was found in 55 (12.8%) patients. Recurrence developed in 26 (6%) patients during a median follow-up of 39 months. A positive margin was associated with an increased risk of relapse on multivariable analysis (HR 3.34, CI95%: 1.24 - 8.10, p= 0.01) Graph 1. In a stratified analysis based on pathological features, a positive surgical margin was significantly associated with a higher risk of recurrence in cases of high risk (Fuhrmann III-IV) (HR 13.8, CI95%: 4.19 - 45.9, p= 0.0005) Graph 2. Conclusions Positive surgical margins after partial nephrectomy increase the risk of disease recurrence, primarily in patients with high-risk pathological features. _x000D_ Funding none
Authors
Henrique Nonemacher
Mauricio Cordeiro George Lins de Albuquerque Joao Brunhara Paulo Afonso Carvalho Fabio Gallucci Leornardo Borges Rafael Coelho Vipul Patel Willian Nahas |
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MP72-19 |
PHASE II STUDY OF AXITINIB FOR DOWNSTAGING cT2a to cT1 RENAL TUMORS FOR ALLOWING PARTIAL NEPHRECTOMY (AXIPAN) |
Kidney Cancer: Localized: Surgical Therapy V | 17BOS |
Abstract: MP72-19 Sources of Funding: none Introduction Laparoscopic Radical Nephrectomy (RN) is the current standard of care for large organ confined renal tumors while Partial Nephrectomy (PN) is recommanded for tumor sizes up to 7 cm. PN preserves long term renal function with possible effect on overall survival. Axitinib, a potent VEGFR TKI can reduce the size of primary tumor in metastatic setting. Our primary objective was to test the ability of axitinib to reduce the size of large tumors for shifting from a RN to a PN indication. Methods Patients with localized (cT2N0M0) RCCs were enrolled in a prospective phase II trial assessing the effect of neoadjuvant axitinib prior to surgery (PN or RN). Main inclusion criteria were: age ≥ 18, histologically proven clear cell RCC, MDRD creatinin clearance ≥ 60 ml/min, cT2a N0NxM0 tumors (&[null]> 7cm; ≤ 10 cm). Medical treatment consisted in axitinib 5 mg up to 10 mg tw/d during 2 to 6 months prior surgery according to radiological response. Results A total of 18 patients including 11 men (61%) and 7 women (39%) with a median age of 60 yrs were enrolled. Median baseline tumor size, RENAL score, serum creatinine and MDRD estimated GFR were: 7.6 cm, 11, 0.8 mg/dl and 96.5 ml/min respectively. Duration of treatment was 2, 4 and 6 months in 12 (66%), 3 (17%) and 3 cases (17%), respectively. Median interval from treatment stop to surgery was 6 days. After neoadjuvant treatment median tumor size and RENAL score decreased to 6.2 cm and 10. 89% of patients presented a decrease in maximum tumor diameter, with median size reduction of 19%. Out of the 17 patients who were operated, 16 (94%) underwent a PN (9 robotic & 7 open), including 67% of the cases which were performed for tumors ≤ 7cm. At 1 month from surgery, median serum creatinin and MDRD estimated GFR were 0.9 mg/dl and 87 ml/min, respectively. Medical and surgical complications included 1 embolization for severe bleeding and 1 Clavien V complication at 1 month after surgery due to massive myocardial infarction. Conclusions Neoadjuvant axitinib in cT2 renal tumors allowed cT1 downstaging and nephron sparing surgery in almost 70% of the cases. However, PN procedures remained high complexity cases requiring adequate surgeon expertise and information of the patients for possible morbidity of these procedures. Funding none
Authors
Cedric Lebacle
Jean Christophe Bernhard Karim Bensalah Herve Baumert Herve Lang Didier Jacqmin Brigitte Duclos Alain Ravaud Brigitte Laguerre Laurence Albiges Armelle Arnoux Bernard Escudier Jean Jacques Patard |
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MP72-20 |
Differential Hemodynamic and Antihypertensive Changes after Partial Nephrectomy versus Radical Nephrectomy |
Kidney Cancer: Localized: Surgical Therapy V | 17BOS |
Abstract: MP72-20 Sources of Funding: None Introduction Partial nephrectomy is a common therapy for small renal masses and is associated with improved postoperative renal function when compared to radical nephrectomy. The highest quality prospective study of partial versus radical nephrectomy demonstrated worse overall survival in patients undergoing partial nephrectomy which appeared to be driven by cardiovascular outcomes. We examined patients undergoing partial and radical nephrectomy to assess for possible differential postsurgical hemodynamic effects. Methods An institutional renal mass database was queried for patients undergoing partial or radical nephrectomy between 2006 and 2012. Serial blood pressure followup, clinicopathologic variables and changes in medications including antihypertensives were collected. Patients were excluded for inadequate data, non-curative-intent surgery, non-cancer surgical indication and absence of medication information. Time-dependent changes in blood pressure were compared by split-plot ANOVA and addition or modification of antihypertensive regimen were studied as time-to-event survival analyses with Kaplan-Meier curves and a Cox proportional hazards model. Results Between 2006 and 2012, 402 partial nephrectomies and 205 radical nephrectomies were performed and a final cohort of 264 partial nephrectomy and 130 radical nephrectomy cases was identified with evaluable data. Patients undergoing partial nephrectomy were significantly younger, more likely to have T1 tumors, and had lower preoperative creatinine values (p < 0.001 for all). No differences were noted on postoperative systolic blood pressures, diastolic blood pressures and heart rates (p > 0.05) however, these analyses were underpowered on post-hoc analysis. Significantly more patients who underwent partial nephrectomy started new antihypertensive medications postoperatively (p = <0.001) and surgical treatment remained as a significant independent predictor on multivariate Cox regression (HR 2.51, p = 0.002). Conclusions Hemodynamic parameters after radical or partial nephrectomy may be different. The etiology of this observation, if any, is currently unexplored. Additional prospective mechanistic investigations are warranted. Funding None
Authors
Ryan Hutchinson
Nirmish Singla Laura-Maria Krabbe Solomon Woldu Gong Chen Charles Rew Isamu Tachibana Yair Lotan Jeffrey A. Cadeddu Vitaly Margulis |
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MP73-01 |
IMMUNE CHECKPOINT INHIBITOR COMBINED WITH THE GROWTH INHIBITOR LYCORINE SYNERGISTICALLY FUNCTION TO MEDIATE ANTI-TUMOR EFFECTS IN A MOUSE MODEL OF RENAL CELL CARCINOMA |
Kidney Cancer: Basic Research & Pathophysiology III | 17BOS |
Abstract: MP73-01 Sources of Funding: Pearl River Nova Program of Guangzhou (No. 2013J2200044); and the Ministry of Education, Culture, Sports, Science and Technology of Japan (No. KAKENHI 25861425, 15K20093). Introduction Immune checkpoint inhibitors-based therapy is rapidly developing into an effective treatment option for a surprising range of cancers. Despite the autoimmune or inflammatory immune-mediated adverse effects which have been seen, the responses and overall survival benefits exhibited thus far warrant further clinical development. Lycorine, an alkaloid extracted from plants in the Amaryllidaceae family, which showed a strong anticancer effect by inducing cell lysis of various carcinomas. This study investigated the effectiveness of a combination therapy of lycorine and anti-CTLA-4 in a mouse model of renal cell carcinoma (RCC). Methods We investigated the anti-tumor efficacy of lycorine in various RCC cell lines including Caki-1, ACHN, KPK-1 and Renca through XTT proliferation, scratch motility, migration and invasion assays. We also discuss that mechanism underlying this anticancer potential with flow cytometry and western blot. Furthermore, luciferase-expressing Renca cells were implanted in the left kidney and the lung of BALB/c mice to develop a RCC metastatic mouse model for investigated the combination therapy effect of lycorine and anti-CTLA-4. Results We confirmed the anticancer potential of lycorine in vitro as observed time-dependent inhibition in several RCC cell lines. Moreover, lycorine suppressed the migratory and invasive abilities of Renca cells. The possible mechanism underlying this anticancer potential was cell cycle profile arrest. Lycorine and anti-CTLA-4 additively decreased tumor weight, lung metastasis, and luciferin-stained tumor images. Importantly, these effects were dependent on significantly suppressing regulatory T-cells while upregulating effector T-cells. Conclusions Herein, as we know, it’s the first report that lycorine in combination with anti-CTLA-4 inhibited orthotopic and metastatic tumors by downregulating Treg, which was accompanied with upregulation of effector T-cells. Our findings suggest and indicate lycorine as a potent candidate for treating RCC and will serve as an excellent aid for developing a better treatment strategy for the use of immune checkpoint inhibitors in RCC. Funding Pearl River Nova Program of Guangzhou (No. 2013J2200044); and the Ministry of Education, Culture, Sports, Science and Technology of Japan (No. KAKENHI 25861425, 15K20093).
Authors
Xiezhao Li
Naijin Xu Aibai Xu Masami Watanabe Peng Huang Yasutomo Nasu Chunxiao Liu |
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MP73-02 |
Immunological Classification in Renal Cell Carcinoma Based on Immunocheckpoint Molecules: The relationship with tumor aggressiveness and the presence of intra-tumor diversity |
Kidney Cancer: Basic Research & Pathophysiology III | 17BOS |
Abstract: MP73-02 Sources of Funding: Shionogi Co. Ltd. (Osaka, Japan) (H.W.) _x000D_ Osaka Kidney Bank (Osaka, Japan) (A.K.) _x000D_ The Public Trust Surgery Research Fund (Tokyo, Japan) (A.K.). Introduction Renal cell carcinoma (RCC) is considered an immunogenic tumor, and novel immune checkpoint inhibitors have impressive antitumor responses. However, little is known about comprehensive immunological signature patterns of tumor-infiltrating lymphocytes (TILs) in RCC patients. We investigated the surface marker expressions of TILs and classified them based on their functional populations. Moreover, we explored the presence of intra-tumor diversity of surface marker expressions of TILs in each individual. Methods We extracted 109 TILs from 80 patients who underwent surgical resection of RCC, of which 44 TILs were multiply extracted from 15 patients. Each TIL was characterized on the basis of functional T-cell populations using 10 surface marker expressions measured by flow cytometry. Immunological classification was performed by unsupervised clustering analysis of TILs. Comparisons between the surface marker expressions and clinical features were evaluated by logistic regression analysis. Distributions of overall metastasis free survival (MFS) time and recurrence free survival (RFS) was estimated with Kaplan-Meier method and immunological classification was assessed with the log-rank test. Results All of the TILs were classified into three groups, which correlated significantly with a substantial number of TILs (p<0.001) and the population of circulating T-cell subsets. Also 35 patients (81.4%) within Group III had lower Fuhrman Grade tumor (G1, 2) whereas 19 patients (47.5%) within Group I, II had higher Fuhrman Grade tumor (G3, 4) (p=0.028). In multivariate analysis, only Fuhrman grade was also significantly correlated with this immunological classification (odds ratio: 0.253, 95% Confidence Interval (CI): 0.094-0.678, p=0.006). Importantly, this classification was significantly correlated with overall MFS (hazard ratio (HR): 0.449, 95% CI: 0.243-0.832, p=0.011) and RFS (HR: 0.475, 95%CI: 0.238-0.948, p=0.035) in multivariate analysis. Also, we discovered the presence of intra-tumoral diversity in the classification of 3 (20%) of the 15 patients. Conclusions This study showed the presence of classable diversity in the immunological signature of TILs correlated with tumor aggressiveness and prognosis that is observed even within the individual tumor in some patients with RCC. Funding Shionogi Co. Ltd. (Osaka, Japan) (H.W.) _x000D_ Osaka Kidney Bank (Osaka, Japan) (A.K.) _x000D_ The Public Trust Surgery Research Fund (Tokyo, Japan) (A.K.).
Authors
Atsunari Kawashima
Takayuki Kanazawa Kumiko Goto Mitsunobu Matsumoto Yu Ishizuya Cong Wang Yoshiyuki Yamamoto Takuji Hayashi Toshiro Kinouchi Kyosuke Matsuzaki Norihiko Kawamura Takeshi Ujike Akira Nagahara Kazutoshi Fujita Motohide Uemura Hisashi Wada Norio Nonomura |
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MP73-03 |
PD-L1 expression in Xp11.2 translocation renal cell carcinoma: Indicator of tumor aggressiveness |
Kidney Cancer: Basic Research & Pathophysiology III | 17BOS |
Abstract: MP73-03 Sources of Funding: none Introduction Programmed death ligand-1 (PD-L1), as a promising anti-tumor target, has proved its significant clinical value in many malignancies. However, the expression of PD-L1 in Xp11.2 translocation renal cell carcinoma (Xp11.2 RCC) and association with clinical outcomes remains unclear. This study amid to investigate the expression of PD-L1 in Xp11.2 RCC and to assess its prognostic value. Methods Immunohistochemistry was conducted on formalin-fixed paraffin-embedded specimens from 36 adult Xp11.2 RCC patients who were histologically confirmed by FISH analysis. Students’s t-test and Chi-square test were used to evaluate the relationship between PD-L1 expression and clinicopathological parameters. Cox regression models were used to evaluate the prognostic value of all parameters. Results Among 36 assessed Xp11.2 RCC patients, 9 (25.0%) patients showed high expression of PD-L1 and 27 (75.0%) patients showed low PD-L1 expression. High PD-L1 expression was correlated with the presence of advanced tumor stage (P=0.001), regional lymph node metastasis (P<0.001) and distant metastasis (P<0.001). In the multivariate analysis, N stage (HR: 4.316, P = 0.032), M stage (HR: 16.561, P = 0.009) and high PD-L1 expression (HR: 4.236, P = 0.007) were independent prognostic factors of PFS. Moreover, high PD-L1 expression (HR: 6.479, P = 0.006), along with distant metastasis (HR: 9.215, P = 0.016), was independent prognostic factors after adjusting for covariates. Conclusions High PD-L1 expression is independently associated with tumor progression and predictive of adverse prognosis for Xp11.2 RCC patients. Importantly, our findings may provide a basis for the use of immunotherapy targeting the PD-1/PD-L1 pathway as a potential novel treatment for Xp11.2 RCC patients. Funding none
Authors
Yuan-Yuan Qu
Kun Chang Bo Dai Yao Zhu Hai-Liang Zhang Ding-Wei Ye |
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MP73-04 |
Tumor Infiltrating Mast Cells (TIMs) Confers a Marked Survival Advantage in Non-Metastasis Clear-Cell Renal Cell Carcinoma |
Kidney Cancer: Basic Research & Pathophysiology III | 17BOS |
Abstract: MP73-04 Sources of Funding: This study was funded by grants from National Key Projects for Infectious Diseases of China (2012ZX10002012-007, 2016ZX10002018-008), National Natural Science Foundation of China (31100629, 31270863, 81372755, 31470794, 81402082, 81402085, 81471621, 81472227, 81472376, 31570803, 81501999, 81671628 and 81672324), Program for New Century Excellent Talents in University (NCET-13-0146) and Shanghai Municipal Commission of Health and Family Planning Program (20144Y0223). All these study sponsors have no roles in the study design, in the collection, analysis, and interpretation of data. Introduction The role played by the innate immune system in determining the clinical outcome of clear-cell renal cell carcinoma (ccRCC) was still blurred. This study aims to investigate the prognostic significance of tumor infiltrating mast cells (TIMs) in ccRCC. Methods The study retrospectively enrolled a training set (474 patients) and a validation set (188 patients) with non-metastasis (pT1-4N0M0) ccRCC from two institutional medical centers of China. TIMs was evaluated by immunohistochemical staining of tryptase and its association with clinicopathologic features and prognosis were evaluated. Results In ccRCC tissues, TIMs ranged from zero to 103 cells/mm2 and zero to 113 cells/mm2 in the training set and validation set, respectively. TIMs was negatively correlated with tumor size (P < 0.001 and P < 0.001, respectively), pathological T stage (P = 0.005 and P = 0.007, respectively) and Fuhrman grade (P < 0.001 and P < 0.001, respectively). Patients with abundant TIMs infiltration showed significantly longer cancer-specific survival in the training cohort and the validation cohort (P < 0.001 and P < 0.001). Patients with abundant mast cell infiltration showed significantly longer overall survival in the TCGA cohort (P<0.001). Moreover, multivariate analysis identified TIMs as an independent prognostic factor for cancer-specific survival (CSS) and relapse-free survival (RFS). Also, TIMs was significantly correlated with CSS and RFS of the mediate and high risk patients in the training cohort and the validation cohort. Conclusions TIMs density is a powerful independent prognostic factor for CSS and RFS in patients with non-metastasis (pT1-4N0M0) ccRCC. Funding This study was funded by grants from National Key Projects for Infectious Diseases of China (2012ZX10002012-007, 2016ZX10002018-008), National Natural Science Foundation of China (31100629, 31270863, 81372755, 31470794, 81402082, 81402085, 81471621, 81472227, 81472376, 31570803, 81501999, 81671628 and 81672324), Program for New Century Excellent Talents in University (NCET-13-0146) and Shanghai Municipal Commission of Health and Family Planning Program (20144Y0223). All these study sponsors have no roles in the study design, in the collection, analysis, and interpretation of data.
Authors
Hangcheng Fu
Yu Zhu Dingwei Ye |
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MP73-05 |
Activation of serine biosynthesis pathway in HIF2? antagonist-resistant renal cell carcinoma cells after acquiring sunitinib resistance: results from the genome editing technology |
Kidney Cancer: Basic Research & Pathophysiology III | 17BOS |
Abstract: MP73-05 Sources of Funding: none Introduction ontinuous activation of hypoxia-inducible factor (HIF) is important for renal cell carcinoma (RCC) progression as well as resistance acquisition against mTOR and VEGFR inhibitors. Recently a HIF2α antagonist (PT2385) has been developed, and is currently being investigated in a phase I clinical trial for advanced or metastatic clear cell RCC (ccRCC) patients who had prior tyrosine kinase inhibitors. However, resistant mechanisms against the HIF2α antagonist seems to be a next problem in the near future. The aim of this study was to find activated signals involved in the HIF2α antagonist-resistance after acquiring sunitinib resistance. Methods First, we established sunitinib resistant 786-o (SU-R-786-o) cells in vivo by oral gavage treatment. Instead of the HIF2α antagonist administration, we completely knocked out the HIF2α gene expression in SU-R-786-o cells by using a recent genome editing technology, CRISPR/Cas9 system, with two different single guide RNAs against HIF2α. We identified their characteristics in cell proliferation assay and western blot. These cells were also analyzed in proteomics and RNA sequence analyses to elucidate their activated signals. Results By using CRISPR/Cas9 system, we succeeded in establishing HIF2α knockout sunitinib resistant 786-o (HIF2α-KO-SU-R-786-o) cells. Cell morphology was changed from spindle to round shape in HIF2α-KO-SU-R-786-o cells. In addition, cell proliferation in HIF2α-KO-SU-R-786-o cells became significantly slower than in the parental cells as well as SU-R-786-o cells (P < 0.01). After recovering cell proliferation in HIF2α-KO-SU-R-786-o cells, proteomics and RNA sequence revealed that CXCR4 expression was dramatically up-regulated in SU-R-786-o cells compared to the parental cells, however, it was decreased in HIF2α-KO-SU-R-786-o cells compared to SU-R-786-o cells. Another surprise was that serine biosynthesis pathway was accelerated in HIF2α-KO-SU-R-786-o cells compared to SU-R-786-o cells. Conclusions Based on the proteomics and RNA sequence analyses, we found that CXCR4 upregulation or serine biosynthesis might be critical for acquiring resistance against multi kinase inhibitors or HIF2α antagonist. Even though both drugs target angiogenesis pathway, the activated signals were altered in the different therapeutic stage by the different drugs administration. The inhibitions of serine biosynthesis pathways might be potential targeted therapy for advanced or metastatic ccRCC which shows resistance to HIF2α agonist after acquiring resistance to multi kinase inhibitors. Funding none
Authors
Hideki Enokida
Hirofumi Yoshino Kazutaka Miyamoto Masaya Yonemori Satoru Sugita Takashi Sakaguchi Masayuki Nakagawa |
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MP73-06 |
Drug Resistance Consequences of Tumor Heterogeneity in Metastatic Renal Cell Carcinoma using Ultra-Fast Patient Derived Xenografts and Multiregional Genomic Sequencing |
Kidney Cancer: Basic Research & Pathophysiology III | 17BOS |
Abstract: MP73-06 Sources of Funding: AMOSO, CUASF Introduction Next generation preclinical models of renal cell carcinoma (RCC) now offer the ability to pre-determine de novo drug resistance in fresh patient tumor samples prior to targeted therapy. Implantation of tumor specimens into the chorioallantoic membrane (CAM) of the chicken embryo results in high engraftment efficiencies within two days, permitting large scale &[Prime]tumor avatar&[Prime] studies. Functional tumor heterogeneity studies, which can be performed in context of drug resistance within two weeks, can guide the selection of drugs and predict drug resistance outcomes for RCC patients. This ultrafast PDX model is mirrored by high-frequency ultrasound imaging that permits quantification of tumor volume and tumor vascularity in a high-throughput manner. _x000D_ Methods Several core biopsies were extracted from primary tumors and metastases from clear cell RCC, chromophobe RCC, and type 1/2 papillary RCC patients and submitted to xenografting into the CAM of chick embryos. At least 6 regions of the primary tumor were xenografted and 3 metastases were xenografted. At least N>36 per region was submitted to xenografting with half of these treated with sunitinib or vehicle (DMSO). At T=10 days post-implantation, high frequency ultrasound imaging was used to quantitate tumor vascularity, tumor volume, tumor blood flow and and tumor blood volume. After imaging, total exome sequencing was performed to identify any genetic mutations for correlation to drug resistance. Results Using this &[Prime]tumor avatar&[Prime] model paired with a prospective RCC patient cohort, we observe intratumoral functional heterogeneity in the context of sunitinib treatment, as determined by high-frequency ultrasound imaging, highlighting its potential interventional role in the clinic. Exome sequencing and gene copy number variation analysis did not reveal DNA mutation signatures that were associated with resistance to sunitinib treatment within this intratumoral set of PDX biopsies. Conclusions These findings suggest that genetic tumor heterogeneity exists, but evidence for a direct relationship to the drug resistant phenotype was not manifest in DNA mutations. Therefore, these results support a phenotype based readout to predict drug resistance within 10 days as opposed to a genotype signature, and that drug resistance to targeted therapy is heterogeneous across the primary tumor. Funding AMOSO, CUASF
Authors
Matt Lowerison
Slavic Fedyshyn Stephenie Prokopec Paul Boutros Ann Chambers James Lacefield Nicholas Power Hon Leong |
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MP73-07 |
Involvement of angiogenin in sunitinib resistance in human renal cell carcinoma |
Kidney Cancer: Basic Research & Pathophysiology III | 17BOS |
Abstract: MP73-07 Sources of Funding: INSERM, University of Strasbourg Introduction Clear cell renal cell carcinoma (CCC), the main subtype of kidney cancer, represents 250 000 cases and 110 000 deaths worldwide/year. In 75% of cases there is a loss of the von Hippel-Lindau (VHL) tumor suppressor gene that is involved in hypoxia inducible factors (HIF) degradation. Current targeted therapies for advanced CCC arise from the knowledge of the VHL/HIF system. These include sunitinib, sorafenib and everolimus. Their efficiency is however limited due to acquired resistance. Since the classical mechanisms of resistance are not involved in CCC, we hypothesized that signalling pathways and/or markers are involved in such resistance. We focused here on sunitinib. Methods We used a panel of CCC cell lines expressing VHL (Caki-1, Caki-2, ACHN) or not (786-0, A498) and tumor/normal tissues pairs from 50 CCC patients. We analyzed tumor growth in response to sunitinib both in vitro using Cristal Violet assay and in vivo using the xenografted nude mice tumor model (40 mg/kg, 3 times/week, 4 weeks, per os). We analyzed protein expression and signaling pathways by RT-qPCR, Western blot, proteome arrays specific for phosphokinases, apoptosis and angiogenesis and with the HTG EdgeSeq oncology biomarker panel assay (2560 genes of 24 signaling pathways). Results In vitro, sunitinib inhibited cell growth of all cell lines tested by up to 85%. In vivo, however, xenografted 786-0 and A498 tumors were resistant to sunitinib. By analyzing A498 tumors we identified, among others, angiogenin (Ang), a pro-angiogenic factor, as being stimulated more than 10 fold by sunitinib. The stimulation of Ang by sunitinib was also observed in all cell lines. Interestingly, in tissue pairs, the expression of Ang was found to be deregulated in 75% of tumors, regardless of tumor stage and grade. Ang stimulates rRNA transcription after nuclear translocation and activates oncogenic signaling pathways (Akt, JunK, MAPK) through a uncharacterized transmembrane receptor. Ang expression and activity has never been functionally linked to sunitinib. In 786-0 tumors-bearing nude mice, tumoral growth was inhibited by 30% by neamine, an inhibitor of Ang nuclear translocation, but it had no effect on sunitinib resistance. Akt and GSK-3 were also activated in vitro and in vivo by sunitinib. We are now performing in vivo studies using siRNA targeting Ang allowing to also inhibit its effect on oncogenic pathways, alone and in combination with sunitinib. Conclusions Taken together, these results strongly suggest that Ang is involved in sunitinib resistance in human CCC, opening new therapeutic option for this refractory disease. Funding INSERM, University of Strasbourg
Authors
Laure Pierard
Sébastien Bergerat Claire Béraud Pascal Mouracade Imène Hamaidi Catherine Coquard Sylvie Rothhut Véronique Lindner Hervé Lang Thierry Massfelder |
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MP73-08 |
Metformin drives synergistic effect and overcomes the treatment resistance of molecular targeted drugs for renal cell carcinoma |
Kidney Cancer: Basic Research & Pathophysiology III | 17BOS |
Abstract: MP73-08 Sources of Funding: Grant-in-Aid for Scientific Research (KAKENHI) 25464281 Introduction Molecular targeted drugs have shown clinical benefit and improvement of their QOL for patients with advanced renal cell carcinoma. However, conquest of primary or acquired drug resistance is urgent problem in clinical practice. The previous reports have shown that Metformin is promising treatment approach for several cancers by regulating AMPK-mTOR pathway. In this study, we assessed whether combination of Metformin synergized molecular targeted drugs and repressed the progression of renal cancer model. Methods We tested synergy effect of Metformin combined with molecular targeted drugs, Everolimus and Axitinib. We assessed cell proliferation and apoptosis by WST-1 assay or a crystal violet assay and flow cytometry. We examined the gene expression profile of parental and molecular targeted drug resistant cells by microarray analysis. And protein expression of the AMPK-mTOR pathway by Western blot. The effects of combination treatment on A498 tumor growth was assessed in orthotropic renal cell carcinoma model. Results Combination of Metformin + Axitinib showed synergistic effect and more potently suppressed A498 cell growth rates in a dose and time dependent manner compared to Metformin or Axitinib monotherapy. Apoptosis detected by flow cytometry with Annexin V was most enhanced with combination treatment. We compared gene expression profile between parental and Axitinib resistant cell line, several pathways enhanced to survive from cellar stress. Metformin induced AMPK expression and suppressed Akt and mTOR expression in Axitinib treatment. In vivo, combination of Metformin + Axitinib therapy significantly repressed tumor growth compared with their mono therapy. In addition, micro vessel density and VEGF immunostaining were significantly reduced in tumor tissue of combination treatment. Conclusions Metformin showed synergistic effect for renal cell carcinoma growth combined with Axitinib in vitro and in vivo. Combination treatment of Metformin + Axitinib is providing pre-clinical proof-of-principle as a promising approach against drug resistance for renal cell carcinoma. Funding Grant-in-Aid for Scientific Research (KAKENHI) 25464281
Authors
Hiroaki Matsumoto
Juiichi Mori Kosuke Shimizu Nakanori Fujii Yoshihisa Kawai Ryo Inoue Yoshiaki Yamamoto Hiroshi Hirata Tomoaki Shimabukuro Hideyasu Matsuyama |
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MP73-09 |
Nelfinavir acts synergistically with panobinostat to induce endoplasmic reticulum stress and inhibit renal cancer growth |
Kidney Cancer: Basic Research & Pathophysiology III | 17BOS |
Abstract: MP73-09 Sources of Funding: none Introduction Inducing endoplasmic reticulum (ER) stress is a novel approach to cancer treatment. The pan-deacetylase inhibitor panobinostat inhibits molecular chaperones and increases the amount of unfolded proteins. The antiretroviral drug nelfinavir suppresses proteasomes and inhibits degradation of unfolded proteins. We postulated that combining nelfinavir with panobinostat would kill renal cancer cells effectively by inhibiting degradation of panobinostat-increased unfolded proteins and thereby inducing ER stress. Methods After renal cancer cells (769-P, 786-O, Caki-2) were treated with clinically feasible concentrations of panobinostat (15-60 nM) and/or nelfinavir (10-20 µM), their viability and clonogenicity were assessed by MTS assay and colony formation assay. Apoptosis was evaluated by annexin-V assay. Cell cycle analysis was done using flow cytometry. Western blotting was used to evaluate the induction of ER stress (increased expression of ER stress markers) and the expression of cyclin D1, cyclin-dependent kinase (CDK) 4, AMP-activated protein kinase (AMPK), S6 ribosomal protein, and ERK1/2. Results The combination of panobinostat and nelfinavir was demonstrated by isobologram analysis to inhibit cancer cell growth synergistically. It also suppressed colony formation significantly (p <0.05). The combination decreased the expression of cyclin D1 and CDK4, leading to the accumulation of the cells in the sub-G1 fraction. It also induced robust apoptosis synergistically: 60 nM panobinostat alone caused slight to moderate increases in the amount of annexin-V positive cells but in combination with 20 µM nelfinavir increased it drastically (up to 100-fold). Mechanistically, the combination induced ER stress synergistically. This ER stress caused dephosphorylation of S6 ribosomal protein by increasing the expression of mammalian target of rapamycin (mTOR) inhibitor AMPK, showing that the combination also inhibited the mTOR pathway. The combination also inhibited the ERK pathway. Conclusions The combination of panobinostat and nelfinavir inhibits renal cancer growth by inducing ER stress synergistically. Inhibiting the mTOR and ERK pathways are also important mechanisms of action. Funding none
Authors
Kazuki Okubo
Akinori Sato Takako Asano Makoto Isono Tomohiko Asano |
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MP73-10 |
Ritonavir, a potent inhibitor of CYP3A4, enhances the anticancer effects of entinostat in renal cancer cells in vitro and in vivo |
Kidney Cancer: Basic Research & Pathophysiology III | 17BOS |
Abstract: MP73-10 Sources of Funding: none Introduction Histone deacetylase (HDAC) inhibitors not only induce histone acetylation but also inhibit molecular chaperones, causing unfolded proteins to accumulate and thereby inducing endoplasmic reticulum (ER) stress. However, the efficacy of HDAC inhibitors as anticancer agents is limited, especially in solid tumors. The HDAC inhibitor entinostat is partly metabolized by CYP3A4, and the human immunodeficiency virus protease inhibitor ritonavir also inhibits CYP3A4. We therefore thought that combining ritonavir with entinostat would kill cancer cells effectively by enhancing entinostat's activity. Methods Renal cancer cells (769-P, 786-O, Caki-2) were treated with ritonavir (20-40 µM) and entinostat (10-20 µM). Cell viability and clonogenicity were assessed by MTS assay and colony formation assay. A murine subcutaneous tumor model was used to evaluate in vivo efficacy. Flow cytometry was used for cell cycle analysis and annexin-V assay. Western blotting was used to evaluate the induction of histone acetylation and ER stress and the expression of cleaved poly(ADP-ribose) polymerase and the autophagy marker light chain (LC) 3-II. Combination indexes were calculated by the Chou-Talalay method. Results The combination of entinostat and ritonavir inhibited cancer cell growth synergistically (combination indexes <1) and suppressed colony formation significantly (p <0.05). The combination perturbed the cell cycle, increasing the number of the cells in the sub-G1 fraction (up to 98.2%). Drastic increases in the number of annexin-V positive cells (up to 98.6%) confirmed that the combination induced apoptosis. In murine subcutaneous tumor models using Caki-2 cells, a 10-day treatment with a combination of entinostat (2 mg/kg) and ritonavir (50 mg/kg) was well tolerated and inhibited tumor growth significantly (p <0.05). As expected, entinostat induced histone acetylation in a dose-dependent fashion, and ritonavir enhanced this acetylation synergistically. The combination also synergistically induced ER stress evidenced by increased expression of glucose-regulated protein 78 and endoplasmic reticulum resident protein 44. Interestingly, we also found that entinostat-ritonavir combination increased the expression of LC3-II, confirming that the unfolded protein accumulation due to the combination induced autophagy. Conclusions Ritonavir enhanced entinostat's activity, and the combination inhibited renal cancer growth synergistically. Funding none
Authors
Takako Asano
Akinori Sato Kazuki Okubo Makoto Isono Tomohiko Asano |
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MP73-11 |
Ginsenoside compound K enhances TRAIL-mediated renal cancer cell apoptosis through CHOP signaling |
Kidney Cancer: Basic Research & Pathophysiology III | 17BOS |
Abstract: MP73-11 Sources of Funding: none Introduction Molecular target therapy is a new approach to cure renal carcinoma. In the process of cell apoptosis, TRAIL binds to the death receptor 4 (DR4) and 5(DR5), forming a death inducing signaling complex (DISC) complex, thus leading to a subsequent apoptosis process. However, drug resistance of TRAIL is a major roadblock for the application of TRAIL-based cancer therapy, and the mechanisms are poorly understood. Reports have shown Ginsenoside compound K (CK) acted as potential anti-tumor drug in many cancer types. In our study, we investigate the influence of CK on renal cancer cell apoptosis induced by TRAIL, and further explore the potential mechanisms. Methods Cell viability was measured by MTs, with TRAIL treated alone or combined used of CK. Cell apoptosis was evaluated by PI/Annexin V staining and flow cytometer. Furthermore, we use western blot to measure the target protein changes. Results In this study, we treated CK alone or in combination with TRAIL in Caki, A498 and ACHN cell lines. We found combined treatment of CK and TRAIL significantly increased cell apoptosis rate compared with TRAIL treated alone (Figure. 1A, B, C, D). Furthermore, CK induced DR5 (death receptor 5) expression in a time and concentration manner (Figure. 1E, F, G). To our surprise, the CK-enhanced TRAIL-mediated cell apoptosis was abrogated by addition of DR5siRNA or CHOP siRNA, but not DR4 siRNA (Figure. 1H-O). In addition, we found CK markly inhibited XIAP, surviving, Mcl-1 expression, but have no influence on c-IAP1, c-IAP2, Bcl-2 and Bcl-xl levels (Figure. 1P, Q). Conclusions Our results indicate that CK inhibits the aiti-tumor proteins and up-regulates DR5 expression through CHOP signaling, thus enhancing TRAIL-mediated renal cancer cell apoptosis. Funding none
Authors
Yu Ren
Shuaishuai Huang Xue Wang Xuping Yao Guobin Weng |
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MP73-12 |
Lopinavir synergizes with ritonavir to cause renal cancer apoptosis via inducing endoplasmic reticulum stress |
Kidney Cancer: Basic Research & Pathophysiology III | 17BOS |
Abstract: MP73-12 Sources of Funding: none Introduction The combination of the human immunodeficiency virus (HIV) protease inhibitors lopinavir and ritonavir has been a standard regimen used to treat HIV infection. Ritonavir acts as a chemical booster to enhance lopinavir's activity. Lopinavir has recently been shown to act against cancer by inducing endoplasmic reticulum (ER) stress, and we thought that the combination would kill renal cancer cells by inducing robust ER stress. Methods The viability and clonogenicity of renal cancer cells (769-P, 786-O, Caki-2) treated with clinically feasible concentrations of lopinavir (10-40 µM) and/or ritonavir (5-10 µM) were assessed by MTS assay and colony formation assay. Apoptosis was evaluated by annexin-V assay. Cell cycle analysis was done using flow cytometry. Induction of ER stress and the expression of cell-cycle regulators, apoptosis-associated proteins, NOXA, Akt, BCL-2, and survivin were evaluated by western blot analysis. Drug synergism was assessed by the Chou-Talalay method. Results Lopinavir in combination with ritonavir inhibited renal cancer growth synergistically (combination index <1). The combination also inhibited clonogenic survival of cancer cells significantly (p <0.05). It perturbed the cell cycle by inhibiting the expression of cyclin D1 and cyclin-dependent kinase 4, increasing the cells in the sub-G1 fraction. The combination caused apoptosis synergistically: 10-20 µM lopinavir increased the number of annexin-V positive cells and the expression of cleaved poly(ADP-ribose) polymerase slightly but in combination with 10 µM ritonavir increased both drastically. As expected, the combination induced ER stress evidenced by the increased expression of the ER stress markers glucose-regulated protein 78 and endoplasmic reticulum resident protein 44. Furthermore, increased expression of NOXA confirmed that the combination-induced apoptosis was a result of ER stress. We also found that the combination decreased the expression of the anti-apoptotic proteins BCL-2 and survivin by inhibiting the Akt signaling pathway. Conclusions The combination of lopinavir and ritonavir induces ER stress and causes renal cancer apoptosis synergistically. Inhibition of the Akt pathway is another important mechanism of its action. Funding none
Authors
Kazuki Okubo
Akinori Sato Takako Asano Makoto Isono Tomohiko Asano |
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MP73-13 |
Phenoxodiol, a novel soy isoflavone analog, inhibits Akt pathway and induces renal cancer apoptosis |
Kidney Cancer: Basic Research & Pathophysiology III | 17BOS |
Abstract: MP73-13 Sources of Funding: none Introduction There are no curative agents for advanced renal cancer, and a novel treatment approach is urgently needed. Soy isoflavones are dietary nutrients that have been shown to inhibit cancer development and progression, and phenoxodiol is a novel isoflavone analog being tested in clinical trials. Because its efficacy in renal cancer is unknown, in the present study we investigated its antineoplastic activity and mechanism of action in renal cancer cells. Methods A panel of renal cancer cells (769-P, 786-O, Caki-2) was treated with phenoxodiol (5-20 µM). The cell viability and clonogenicity were assessed by MTS assay and colony formation assay. Cell cycle analysis was done using flow cytometry. Apoptosis and necrosis were detected by flow cytometry after staining the cells with annexin V and 7-amino-actinomycin D (7-AAD). The expression of cyclin D1, cyclin-dependent kinase (CDK) 4, cleaved poly(ADP-ribose) polymerase (PARP), FLICE inhibitory protein (FLIP), and Akt was evaluated by western blotting. Results MTS assay results showed that phenoxodiol decreased renal cancer viability in a time- and dose-dependent manner (IC50: 19.9-28.8 µM). It also inhibited colony formation significantly (p <0.05) and perturbed the cell cycle: 24-hour treatment with 20 µM phenoxodiol induced marked G1-S arrest but prolonged treatment (48-72 hours) increased the number of cells in the sub-G1 fraction, suggesting that phenoxodiol disrupted cell cycle checkpoints. These changes were associated with decreased expression of the cell-cycle regulators cyclin D1 and CDK4. Treatment with phenoxodiol increased the numbers of 7-AAD-positive cells as well as annexin-V positive cells and increased the expression of cleaved PARP, demonstrating that the phenoxodiol-induced apoptosis was late apoptosis. Phenoxodiol also inhibited the Akt pathway by causing dephosphorylation of Akt. This inhibition of the Akt pathway inhibited expression of the apoptosis inhibitor FLIP and thus led to renal cancer apoptosis. Conclusions Phenoxodiol induces apoptosis of renal cancer cells by inhibiting the Akt pathway. Funding none
Authors
Makoto Isono
Akinori Sato Takako Asano Kazuki Okubo Tomohiko Asano |
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MP73-14 |
Capability of Electrical Impedance Spectroscopy Sensor on a Needle as a Novel Tool to Estimate Malignant Renal Tumor Margin: Ex-Vivo Demarcation of tumor and surgical margin |
Kidney Cancer: Basic Research & Pathophysiology III | 17BOS |
Abstract: MP73-14 Sources of Funding: None. Introduction To estimate tumor margin during partial nephrectomy, we developed a needle having electrochemical impedance spectroscopy (EIS) sensor on the tip of a needle which we named &[Prime]EoN (EIS-on-a needle)&[Prime]. In this study, the impedances of renal parenchyma in accordance with the distance from the tumor were measured by using EoN to evaluate the capability of the device in detecting the tumor margin. Methods Microelectromechanical-system technology was applied to fabricate EoN, which is a 22-gauge needle with interdigitated electrodes on its tip. For the experiment, 10 renal specimen consisted of tumor and its surgical margin resected by partial nephrectomy were used. EoN was inserted into the surgical margin of the specimens and the impedance was measured while the device was accessing toward the tumor at the frequency range from 0.1 kHz to 1 MHz. The areas within the specimens where the impedance was measured were categorized into five sections according to the distance from the tumor: 1) surgical margin at > 6 mm and ≤ 8 mm from the tumor as section I; 2) between > 4 mm and ≤ 6 mm as section II; 3) between > 2 mm and ≤ 4 mm as section III; 4) between > 0 mm and ≤ 2 mm as section IV; and 5) within the tumor as section V. The magnitude and phase angle of impedance between each sections were compared by using repeated-measures analysis of variance at each single frequency. Results The mean magnitude and phase angle of the impedances were proved to have a statistically significant variation (p <0.05) in accordance with the distance from the tumor at the frequency from 10.08 kHz to 1MHz and at 39.89 kHz, respectively. At these frequencies, the mean magnitude and phase angle of section V was significantly different (p <0.05) to that of at least one other section of the specimen. However, the mean impedance differences between each respective sections other than section V did not show any statistical significance. Conclusions The present thesis has proved the capability of EoN in detecting the tumor when EoN was inserted from the normal renal parenchyma. The depth of tumor margin beneath the renal surface is assumed to be measurable by estimating the inserted length of EoN which has reached an area showing significant change of impedance values at specific frequencies. Funding None.
Authors
Hyeon Woo Kim
Joho Yun Dong Gil Shin Jeong Zoo Lee Tae Nam Kim Wan Lee Chang Yell Lee Chul Soo Yoon Seong Choi Jong-Hyun Lee |
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MP73-15 |
Protective Effect of Ethyl Pyruvate on Oxidative Renal Cell Injury: Implication in Prevention of Renal Ischemia/Reperfusion Injury |
Kidney Cancer: Basic Research & Pathophysiology III | 17BOS |
Abstract: MP73-15 Sources of Funding: Departmental Introduction Various renal cell injuries, including renal ischemia/reperfusion injury (RIRI), have been shown to be primarily attributed to oxidative stress. Particularly, to protect the kidneys from RIRI, the perioperative interventions have been routinely employed but the outcomes remain elusive. To improve the efficacy of renoprotection, certain antioxidant such as ethyl pyruvate (EPy) may more effectively prevent RIRI as its safety or beneficial and therapeutic effects have been well documented. Accordingly, we investigated the protective effects of EPy and mannitol (Mann), one of perioperative agents often used, on renal cells against oxidative stress in vitro. Methods Oxidative stress was exerted by hydrogen peroxide (H2O2) on the renal proximal tubular MDCK cells. Severity of oxidative stress was determined by malondialdehyde (MDA) assay and protective effects of EPy and Mann against H2O2 were assessed by cell viability test. To explore the cytotoxic mechanism of H2O2, the status of glycolytic parameters, cell cycle, and metabolic signaling pathways as well as induction of apoptosis was also examined. Results H2O2 (500 µM) increased the MDA level by ~3.5 times of controls, but PE (1 mM) nearly completely reduced it to the basal level. Although cell viability was reduced to merely 10% by H2O2 in 24 h, EPy yet maintained >90% cell viability. Two glycolytic parameters, hexokinase activity and ATP level, declined to ~45% and ~30% (compared to controls) by H2O2, respectively. This decline significantly (80-90%) went up with EPy. H2O2 also induced a G1 cell cycle arrest and the modulations of metabolic signaling regulators such as AMP-activated protein kinase (AMPK), protein kinase B (Akt), and mammalian target of rapamycin (mTOR). EPy utterly reversed a cell cycle arrest and prevented those modulations. Analysis of two key apoptosis regulators, bcl-2 and Bax, further indicated induction of apoptosis by H2O2, which was yet fully prevented with EPy. Unlike EPy, Mann had little effects on any H2O2-induced adverse cellular effects. Conclusions Oxidative stress exerted by H2O2 can cause cell injury and death in MDCK cells. It involves the cell viability reduction, the glycolysis inhibition, a cell cycle arrest, the modulations of metabolic signaling pathways, and ultimately induction of apoptosis. However, all these adverse effects through oxidative stress were effectively and nearly completely prevented or reversed with EPy, not with Mann. Therefore, EPy should be considered as a more effective prophylactic and perioperative renoprotective agent (compared with Mann) against oxidative renal cell injury including RIRI. Funding Departmental
Authors
Jonathan Bloom
Mark Ferretti Matthew Chaimowitz Muhammad Choudhury Majid Eshghi Sensuke Konno |
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MP73-16 |
An evaluation of the protective effect of Esomeprazole in an experimental model of renal ischemia reperfusion |
Kidney Cancer: Basic Research & Pathophysiology III | 17BOS |
Abstract: MP73-16 Sources of Funding: None Introduction The ischaemia and subsequent reperfusion (IR) which occurs in partial nephrectomy used in the treatment of renal tumours causes loss of parenchyma in the damaged kidney. The aim of this study was to investigate the protective effect of Esomeprazole, which is used in the suppression of gastric acid, on a rat model of IR. Methods The 21 rats were separated into 3 groups of 7. In Group 1 (sham), only laparotomy was applied and no renal ischaemia was formed. In Group 2 (control), ischaemia was formed by applying a cross-clamp to the left renal artery. In Group 3 (PPI), Esomeprazole was administered 1 hour before the procedure, then ischaemia was formed. All the animals were sacrificed 24 hours after the procedure. Biochemical analyses were applied for evaluation of oxidant and antioxidant agents in the blood and left kidney of each subject (oxidative markers: malondialdehyde, myeloperoxidase; antioxidant marker: superoxidedismutase). In the histological examination of the kidney tissues stained with haematoxylin-eosin, the TUNEL method was applied in the evaluation of apoptosis. Results No statistically significant biochemical difference was determined in the blood and tissue samples. In the histological and apoptosis evaluations, a statistically significant difference was determined between the sham, control and PPI groups. The median (interquartile range) values of the TUNEL positive cells were counted as 1.50 (4) in the Sham group, 11.50 (12) in the Control group and 6.00 (9) in the PPI group (p<0.001). Conclusions A protective effect of Esomeprazole was confirmed in renal ischaemia-reperfusion damage created in an experimental rat model.None Funding None
Authors
Nihat Karakoyunlu
Reyhan Polat Sanem Saribas Nevzat Sener Seyda Ozdemir Kevser Peker Dilek Unal Can Tuygun |
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MP73-17 |
Benign and Tumor Parenchyma Metabolomic Profiles Affect Compensatory Renal Growth in Renal Cell Carcinoma Surgical Patients |
Kidney Cancer: Basic Research & Pathophysiology III | 17BOS |
Abstract: MP73-17 Sources of Funding: P30 Grant Introduction Pre-operative kidney volume is an independent predictor of glomerular filtration rate in renal cell carcinoma patients. Compensatory renal growth (CRG) can ensue prior to nephrectomy in parallel to tumor growth and benign parenchyma loss. We aimed to test whether renal metabolite abundances significantly associate with CRG, suggesting a causative relationship. Methods Tissue metabolomics data from 49 patients, with a median age of 60 years, were previously collected and the pre-operative fold-change of their contra to ipsi-lateral benign kidney volume served as a surrogate for their CRG. Contra-lateral kidney volume fold-change within a 3.3 +/- 2.1 years follow-up interval was used as a surrogate for long-term CRG. Using a multivariable statistical model we identified metabolites whose abundances significantly associate with CRG. Results We identified 13 metabolites in the benign (e.g. L-urobilin) and 163 metabolites in the malignant (e.g. 3-indoxyl-sulfate) tissues to significantly associate with CRG. Benign/tumor fold change in metabolite abundances revealed three additional metabolites with a significant positive association with CRG (e.g. p-cresol sulfate)(Fig. 1). At the pathway level, we show that fatty-acid oxidation is highly enriched with metabolites whose benign tissue abundances strongly positively associate with CRG, whereas in the tumor tissue significant enrichment of dipeptides (positive association) and benzoate, glycolysis/gluconeogenesis, lysolipid and nucleotide sugar pentose (negative associations) sub-pathways were observed(Fig. 2). The effect of metabolite abundances in the benign tissue on long term CRG provided further support for positive association of fatty-acid metabolism sub-pathway enrichment, where sphingolipid, monoacylglycerol, long chain fatty acids, and mid chain fatty acids were enriched for a negative association. Conclusions These data suggest that specific biological processes in the benign as well as in the tumor parenchyma strongly influence compensatory renal growth. Funding P30 Grant
Authors
Barak Rosenzweig
Nimrod Daniel Rubinstein Ed Reznik Piotr Zareba Roman Shingarev Krishna Juluru Oguz Akin James J Hsieh Edgar Jaimes Paul Russo Katalin Susztak Jonathan A Coleman A Ari Hakimi |
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MP73-18 |
Histologic Abnormalities in Non-neoplastic Renal Parenchyma after Radical Nephrectomy: A Nomogram to Predict Chronic Kidney Disease |
Kidney Cancer: Basic Research & Pathophysiology III | 17BOS |
Abstract: MP73-18 Sources of Funding: none Introduction The current evaluation of nephrectomy specimens centers on the pathological diagnosis, grade, and stage of the neoplasm._x000D_ The evaluation of the non-neoplastic renal parenchyma is often overlooked. The remnant renal parenchyma can suffer the long-term effects of comorbidities, compromising functional outcomes. These changes can be assessed by histopathological analysis of non-neoplastic tissue of the nephrectomy specimen and can be used to predict the extent of future renal function compromise. In this study, we aim to evaluate changes in the non-neoplastic renal parenchyma in patients who were submitted to radical nephrectomy, as well as demographic and clinical parameters as predictors of decrease in renal function and development of new-onset CKD after surgery._x000D_ Methods Data were extracted from 222 patients who underwent radical nephrectomy. The MDRD formula was used. The study end point was development of CKD, defined as an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73 m2. A renal pathologist assessed three histologic features in the non-neoplastic parenchyma, namely global glomerulosclerosis (GS), arteriosclerosis (AS), and interstitial fibrosis (IF). For GS assessment, the percent of affected glomeruli was determined. AS was graded and divided into three groups, namely 1—0%-25%, 2—26%-50%, and 3—greater than 50%. IF was evaluated as absent or present. _x000D_ A nomogram was created to predict CKD following radical nephrectomy._x000D_ Results After a mean follow-up of 49.06 months, the mean eGFR rate decrease was 26.5% after radical nephrectomy. Almost half of the patients (53.8%) developed CKD. For each 2.5% increase in GS, each point increase in Charlson comorbidity index, and each 10-year increase in patient’s age, the eGFR decreased 28%, 33%, and 39%, respectively. In a univariate analysis, age, CCI, GS, AS, IF, hypertension, and DM were associated with new-onset CKD after radical nephrectomy. After multivariate logistic regression, CCI, GS, and baseline eGFR were associated with new-onset CKD after radical nephrectomy. Conclusions Histopathological evaluation of non-neoplastic renal parenchyma in patients who undergo radical nephrectomy can be used to predict the development of new-onset CKD. Funding none
Authors
Ricardo Brandina
Miguel Srougi Katia Ramos Moreira Leite Emerson Pereira Gregório |
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MP73-19 |
Preoperative Proteinuria Predicts Increased Rates of Acute Kidney Injury After Partial Nephrectomy |
Kidney Cancer: Basic Research & Pathophysiology III | 17BOS |
Abstract: MP73-19 Sources of Funding: none Introduction Proteinuria reflects structural damage to glomeruli and/or renal tubules and is considered an important prognostic indicator of chronic kidney disease (CKD) and possibly acute kidney injury (AKI). We examined the significance of preoperative proteinuria on postoperative kidney function after robotic partial nephrectomy (RPN). Methods We retrospectively reviewed 1121 consecutive RPN cases at a single academic center from 2006 to 2016. Patients without pre-existing CKD (eGFR≥60 mL/min/1.73m2) who had a urinalysis within 1-month prior to RPN were included. The cohort was categorized by the presence or absence of preoperative proteinuria (≥30 mg/dL), and groups were compared in terms of clinical and functional outcomes. The incidence of AKI was assessed using RIFLE criteria. Univariate and multivariable models were used to identify predictors of postoperative AKI. Results Of 947 patients, 97 (10.5%) had preoperative proteinuria. Characteristics associated with preoperative proteinuria included non-white race (p<0.01), preoperative diabetes (p<0.01) and hypertension (HTN) (p<0.01), higher ASA (p<0.01), higher BMI (p<0.01), and higher Charlson score (p<0.01). The incidence of AKI was higher in patients with preoperative proteinuria (10.3% vs. 4.6%, p=0.01). The median eGFR preservation measured within one month after surgery was lower (83.6% vs. 91%, p=0.04) in those with proteinuria; however, there were no significant differences by 3 months after surgery or last follow-up visit. Independent predictors of AKI were high BMI (p<0.01), longer ischemia time (p<0.01), and preoperative proteinuria (p=0.02). Conclusions Preoperative proteinuria by urine dipstick is an independent predictor of postoperative AKI after RPN. This test may be used to identify patients, especially those without overt CKD, who are at increased risk for developing AKI after RPN. Funding none
Authors
Önder Kara
Matthew J. Maurice Pascal Mouracade Ercan Malkoç Julien Dagenais Ryan J. Nelson Jaya Sai Chavali Jihad H. Kaouk |
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MP73-20 |
Novel culture method for renal cell carcinoma: modified organoid culture |
Kidney Cancer: Basic Research & Pathophysiology III | 17BOS |
Abstract: MP73-20 Sources of Funding: none Introduction In our study, we aim to present a primary culture model of renal cell carcinoma using an organoid culture method which preserves primary tissue characteristics. Methods Renal cell carcinoma tissues were obtained from advanced cancer patients and were degraded through 1 hour of incubation at 37? using collagenase. Separated cells were mixed with matrigel (3D culture) or applied on top of a large amount of previously harden matrigel (3D on-top culture). The cells were replaced with fresh medium containing EGF, Hydrocortisone, insulin, Noggin, and Leucin in DMEM/F12 every 2 days. The cells grown in general cell culture dish were used as a control after being subcultured 4 times. To investigate whether the original characteristics of the primary cancer were preserved, the expressions of carbonic anhydrase IX (CA9), vimentin (VIM), and BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP-3) were compared using immunohistochemistry, western blotting, and confocal microscopy. Results Early stage renal cell carcinoma contained abundant clear cytoplasm within the cells. After being subcultured, in the cells grown in the normal culture dish, clear cytoplasm was dramatically reduced, and the size of nuclear and cytoplasm was increased, while the dendritic change was observed (Fig. 1A). However, the initial appearance of renal cell carcinoma was maintained in the 3D culture and 3D on-top culture incubated over the same period (Fig. 1B). Moreover, the expression for CA9, VIM and BNIP-3, which are the major genes for renal cell carcinoma, are also well-maintained compared to the control group. Conclusions In this study, we present a new primary 3D culture method appropriate for cancer cells using a modification of the pre-existing organoid culture method. This culture is characterized by its preservation of primary tumor characteristics in cancer tissue through progenitor cell growth. The methodology described here should enable the procurement of cells which maintain primary cancer properties, a major issue in personalized medicine research. Furthermore, it can be presented as a new alternative to replace the patient-derived xenograft model in the new anti-cancer drug selection stage which offers advantages regarding both time and cost. Funding none
Authors
Hyung Ho Lee
Sook Young Kim Young Eun Yoon Sung Ku Kang Jae Yong Jeong Kwang Hyun Kim Kyung Hwa Choi Joong Shik Lee Koon Ho Rha Young Deuk Choi Sung Joon Hong Woong Kyu Han |
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MP74-01 |
Arteriolar hyalinization predicts clinical outcome in renal transplantation from donors after cardiac death. |
Transplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery III | 17BOS |
Abstract: MP74-01 Sources of Funding: none Introduction The shortage of organ donation has led to increasing use of kidneys from marginal deceased donors. The number of kidney transplantation from donors after cardiac death (DCD) has increased even in the United State. More than 90% of all deceased kidney transplantation (DKT) in Japan had been obtained from DCD before 2009. The objectives of this study are to elucidate the clinic-pathological factors that predict outcomes after DKT from DCD. Methods We retrospectively analyzed 59 recipients who received DKT from DCD between 1995 and 2013 in Niigata University Hospital. Graft function was assessed using estimated glomerular filtration rate (eGFR). The recipients were divided into two groups, stable graft function (Group 1. N=44) and poor graft function that eGFR decreased ≥ 25% after transplantation (Group 2. N=15). We performed histologic analysis of preimplantation biopsies. Expanded criteria donor (ECD) is defined as all deceased donors older than 60 years and donors older than 50 years with 2 of the following: hypertension, stroke as the cause of death, or preretrieval serum creatinine greater than 1.5 mg/dl. Results 5, and 10 years graft survival before 2001 were 61.9%, and 54.2%, respectively. In contrast, graft survivals were dramatically improved since 2002, such as 5, and 10 years graft survival were 87.4%, and 83.0%, respectively. Multivariate analysis revealed that arteriolar hyalinization (P=0.046) and ECD (P=0.046) were significantly associated with poor graft function and graft survival (Figure 1). When the recipients were divided into 4 groups according to graft function after transplantation (Improved: eGFR increased ≥ 25% after transplantation / Stable / Decreased: eGFR decreased ≥ 25% after transplantation / Primary non-function), degree of severity of arteriolar hyalinization was associated with renal function (Figure 2). Conclusions Arteriolar hyalinization predicts clinical outcome after DKT from DCD. This histologic factor may guide clinical decisions regarding use, allocation, or minimization of immunosuppression. Funding none
Authors
Masayuki Tasaki
Kazuhide Saito Yuki Nakagawa Naofumi Imai Yumi Ito Masato Akiyama Kota Takahashi Yoshihiko Tomita |
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MP74-02 |
Role of early povidone iodine instillation in post renal transplant lymphorrhoea: a prospective randomized study |
Transplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery III | 17BOS |
Abstract: MP74-02 Sources of Funding: None Introduction Lymphatic collections commonly develop after renal transplantation although most of them are asymptomatic and resolve spontaneously. Persistent drain output is one of the earliest signs of lymphatic leak. An encysted collection or lymphocoele if symptomatic, can lead to complications as grave as the graft dysfunction itself. This study aimed at prospectively evaluating the role of early povidone iodine instillation in the management of post renal transplant lymphorrhoea. Methods A prospective evaluation of live related renal transplant recipients was done from Jan 2002 to Dec 2015. Significant lymphorrhoea was defined as >50 mL lymph from drain beyond POD 5. Such patients were randomized into 2 groups: Group A (received 0.5% povidone iodine instillation) and Group B (no instillation). Povidone iodine instillation was done for upto three weeks. The drain was removed if the output decreased to <50ml/day or at three weeks drainage persisted. Absolute risk reduction and NNT were calculated to estimate effect of povidone iodine instillation for the treatment of lymphorrhoea. Fisher exact test or chi square test for categorical data descriptive statistics and t test was used for continuous data SPSS version 20.0. Armonk, NY: IBM Corp. Results 1766 patients underwent renal transplant during this period. 117 patients with lymphorrhoea through the drain underwent randomization into group A (n=61) and group B (n=56). In group A, 58(95%) patients had successful resolution within two weeks while in group B, 34(60%) patients had successful resolution within two weeks. Symptomatic lymphocoele was present in 1 patient in group A and 7 patients in group B on follow up. Absolute risk reduction was 10.8% and for every symptomatic lymphocoele prevented, 10 patients needed povidone iodine instillation. Conclusions Povidone iodine instillation helps in early resolution of post renal transplantation lymphorrhoea as well as reduces the incidence of lymphocoele formation. Funding None
Authors
Sanjoy Sureka
Aneesh Srivastava Priyank Yadav Rakesh Kapoor M S Ansari Uday Singh |
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MP74-03 |
Transplant kidney retrograde ureteral stent placement and exchange: overcoming the challenge |
Transplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery III | 17BOS |
Abstract: MP74-03 Sources of Funding: none Introduction Ureteral stricture is the most common urologic complication following renal transplantation. In patients who are poor candidates for open or endoscopic repair or in patients who failed repair attempts, an indwelling ureteral stent (DJS) may be the only option. The ureterovesical anastomosis in kidney transplant patients is often placed at the dome of the urinary bladder; thus, DJS placement or exchange can be challenging._x000D_ The loss of access during the procedure could be deleterious, necessitating insertion of a percutaneous nephrostomy tube to the transplanted kidney in patients who are often treated with antiaggregants or anticoagulants. _x000D_ Herein we describe a safe and reproducible technique for the exchange or initial placement of DJS in transplant kidneys in cases where direct cystoscopic approach may be difficult and fluoroscopic control insertion is required._x000D_ Methods Tecnique: During cystoscopy the DJS, if present and the neo-orifice are identified. A hydrophilic coated guide wire (GW) is placed alongside the ureteral stent into the transplant renal pelvis. A 5Fr ureteral catheter (UC) is then negotiated over the guide. A super stiff (SS) wire is passed through the UC and the indwelling ureteral stent is withdrawn. An access sheath (AS) is then passed over the SS wire and advanced up to the proximal ureter. The SS wire is now exchanged for the GW that passing through the AS allowing easy and smooth passage of the DJS into the upper pole calix. In most cases, particularly after dilation of a ueretero-vesical stricture a unique 8/12Fr 16cm silicone DJ stent is used. _x000D_ A total of 32 stent replacement or insertion were performed during the study period with a median stent indwelling time and follow-up time of 12.8 and 32 months, respectively._x000D_ Results Successful stent placement or exchange in the first attempt was achieved in 31/32 renal units with an overall success rate of 96.9%. No intraoperative or postoperative complications occurred. No patient developed hydronephrosis on a follow-up ultrasound. Renal function remained stable in 11 patients and in 3 patients function declined due to non-urological etiology. Conclusions Our results indicate that the standardized transplant stent placement technique is almost always successful despite technical challenges with an overall success rate of 96.8%. In this group of patients, periodic replacement of indwelling ureteral stent using our novel technique is effective, reproducible and safe with stable renal function during a long follow-up. Funding none
Authors
Daniel Halstuch
Roy Mano Chen Shenhar Ronen Holland Jack Baniel David Lifshitz |
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MP74-04 |
IMPACT OF PACKAGE AND STORAGE TECHNIQUES ON KIDNEY TEMPERATURE ENVIROMENT |
Transplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery III | 17BOS |
Abstract: MP74-04 Sources of Funding: none Introduction Static or dynamic cold storage of organs for transplantation are key steps to its success, as they have a significant impact on its short- and long-term results. The ideal temperature range for preservation is between 2 and 6ºC. This study aims to compare temperature variation among six organ package techniques (plastic bag and thermal transport container). Methods Six technical variations were tested: 1- Renal standard storage: set of packages placed in a polystyrene thermal container (average size 34 liters) covered with ice cubes; 2- Renal standard + Plastic vessel: standard storage including plastic vessel wrapping plastic bags before placed in ice; 3- Renal standard + Metal case: standard storage including metal case wrapping plastic bags before placed in ice; 4- Renal standard + Crushed Ice: standard storage using crushed ice instead of cubes; 5- Renal Standard + Bar of ice: standard storage using bar of ice instead of cubes; 6- Liver Standard: standard storage in 50-liter thermal container. Variables were analysed using one-way ANOVA with post-hoc Tukey test: A) temperature mean area under the curve inside the packages (TAUCp); B) mean time to reach the temperature nadir (Tnadir); C) duration of temperature within the ideal range (Tideal); D) temperature mean area under the curve inside the thermal container (TAUCt). The temperatures were measured every 30 minutes for 48 hours. Results Each of the technical variations were tested five times. There were no differences between groups regarding TAUCp and Tideal (p = 0.550 and p=0,053, respectively). The median Tideal in all groups was 0.5h (0-47.5h). Group 3 had longer Tnadir than groups 5 and 6 (p = 0.018). The group 5 presented temperature mean area under the curve inside the thermal container (TAUCt) higher than groups 1, 2 and 6 (p = 0.008). Conclusions Cold storage, regardless of tested technique, results in temperatures outside the ideal range most of the time. The use of a metal case may delay the time to reach ideal temperature. Although the use of bars of ice causes higher temperatures within the thermal container, this may represent a greater approximation to the ideal temperature range. Funding none
Authors
Luã Souza Cunha
Gabriela Yale Lima de Oliveira Laila Gabriely Souza Mota Diego Henrique Gomes Sobrinho Leonardo Oliveira Reis Alessandro Prudente |
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MP74-05 |
Donor Age is the Most Important Predictor of Longterm Graft Function in Simultaneous Pancreas-Kidney Transplantation from Donors after Cardiac Death |
Transplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery III | 17BOS |
Abstract: MP74-05 Sources of Funding: Schulich Research Opportunities Program, Schulich School of Medicine & Dentistry, Western University, London, ON, Canada Introduction In efforts to bridge the gap between the increasing numbers of patients on the waiting list for simultaneous pancreas-kidney (SPK) transplantation, there has been an increase in the use of organs from donors after cardiac death (DCD). DCD allografts represent the fastest growing source of deceased donor organs globally. Although studies have shown that longterm outcomes of DCD-SPK grafts are inferior to those of neurologically deceased SPK grafts, specific information is lacking on which donor factors impact a DCD-SPK organ&[prime]s longterm outcome. The predictive tool PDRI (Pancreas Donor Risk Index) is only proven for short term outcomes and does not heavily weigh factors such as donor age or organ cold ischemic time. Here, we analyzed data from UNOS (United Network for Organ Sharing) to determine the effects of donor age, donor BMI, and cold ischemic time on DCD-SPK graft outcomes. Methods We evaluated all DCD-SPK transplants performed in the United States from 1988 to 2013. We excluded transplants with incomplete values required to calculate PDRI and KDRI (Kidney Donor Risk Index). The effects of donor characteristics on graft and recipient survival were evaluated using Cox Regression and the Kaplan-Meier method. Logistic regression was used to evaluate the effects on delayed graft function (DGF). Results We analyzed 189 DCD transplants with donors ≤40 years old, and 38 with donors >40. Overall, SPK grafts from donors >40 displayed significantly higher rates of kidney failure (HR 2.10, 95%CI 1.15-3.83, p<0.05) and pancreas failure (HR 2.07, 95%CI 1.16-3.70, p<0.05) compared to grafts from donors ≤40. One year (88.2% ± 2.4% vs 73.4% ± 7.2%) and 10 year (66.3% ± 6.9% vs 50.3% ± 10%) pancreas graft survival were greater in donors ≤40. A similar trend was also observed for both short and longterm kidney graft survival. Importantly, increasing donor age was associated with increased DGF (OR 1.030, 95%CI 1.003-1.057, p<0.05). Increasing donor BMI was also predictive of pancreas failure (HR 1.024, 95% CI 1.007-1.042, p<0.01), recipient mortality (HR 1.022, 95% CI 1.003-1.041, p<0.05), and DGF (OR1.119, 95%CI, 1.035-1.208, p<.005). Donor age was equally as predictive of 1 year graft outcomes as PDRI or KDRI. We did not observe an effect of cold ischemic time on graft or recipient outcomes. Conclusions Donor age and donor BMI are significant predictors of DCD-SPK graft failure, DGF, and recipient mortality. Organs from donors >40 are up to twice as likely to result in kidney failure and pancreas failure compared to grafts from donors ≤40. Funding Schulich Research Opportunities Program, Schulich School of Medicine & Dentistry, Western University, London, ON, Canada
Authors
Jingwen Chen
David Mikhail Hemant Sharma Larry Stitt Jeffrey Jevnikar Patrick Luke Alp Sener |
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MP74-06 |
Fabrication of Biomimetic Vascular Scaffolds Using Vascular Corrosion Casts for Reconstruction of Kidney Tissues |
Transplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery III | 17BOS |
Abstract: MP74-06 Sources of Funding: Grant from the State of North Carolina Introduction Vascularization is among the most pressing technical challenges facing tissue engineering of 3D organs. While small engineered tissue constructs can rely solely on vascular infiltration and diffusion from host tissues following implantation, larger avascular constructs do not survive long enough for vessel ingrowth to occur. To address this challenge, strategies for pre-vascularization of engineered constructs have been developed. To this end, we developed a simple and novel fabrication method to create biomimetic microvascular scaffolds using vascular corrosion casting as a template for pre-vascularization of engineered kidney tissue constructs. Methods Vascular corrosion casts were made of the left kidney of adult rats. To create polycaprolactone (PCL) casts, the kidney was perfused with with 10% w/v PCL dissolved in acetone. To fabricate collagen-based vascular scaffolds from the PCL cast, the cast were dip-coated with Type 1 rat tail collagen and cross-linked. Warm acetone was used to remove the PCL casts from inside the collagen, leaving a hollow collagen vascular scaffold. To test endothelialization of the vascular scaffolds, endothelial cells labeled with green fluorescent protein (GFP) were seeded. Morphological and structural analyses were performed. Results Gross and electron microscopic analysis demonstrated that polycaprolactone (PCL)-derived kidney vascular corrosion casts are able to capture the architecture of normal renal tissue and can serve as a sacrificial template for the creation of a collagen-based vascular scaffold. Histological analysis demonstrates that the collagen vascular scaffolds are biomimetic in structure and can be perfused, endothelialized, and embedded in hydrogel tissue constructs. Conclusions Our scaffold creation method is simple, cost effective, and provides a biomimetic, tissue-specific option for pre- vascularization that may be used for reconstruction of kidney tissues. Funding Grant from the State of North Carolina
Authors
Jennifer Huling
In Kap Ko John Jackson James Yoo Anthony Atala |
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MP74-07 |
Renal protection by applying ischemic preconditioning. |
Transplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery III | 17BOS |
Abstract: MP74-07 Sources of Funding: none Introduction Surgical techniques that apply temporary kidney ischemia are currently widely used. Post ischemia-reperfusion (IR) is essential for ischemic tissue survival.The term ischemic preconditioning (IPC) is defined as the short ischemic period followed by a brief period of reperfusion that typically precede a longer period of definitive ischemia. _x000D_ This study aimed to evaluate the effect of IPC on kidney subjected to IR by using dosing markers of oxidative damage in the kidney tissue._x000D_ _x000D_ Methods Seventeen Wistar male rats were randomized into group 1 (n=6), animals subjected to IR; group 2 (n=6), animals subjected to preconditioning before IR; and group 3 (n=5), subjected to sham._x000D_ We performed the following procedure for each group:_x000D_ a) in the IR group, the animals were subjected to 45-min left renal ischemia and 60-min reperfusion._x000D_ b) in the IPC group, we conducted three periods of 3 min (each time) of renal blood flow interruption with the use of a bulldog vascular clamp on the left renal pedicle, interposed with 5 min of reperfusion. Shortly thereafter, the left kidney was subjected to 45-min ischemia and, later, to 60-min reperfusion._x000D_ c) In the sham group, we conducted only left renal pedicle manipulation and killed the animals after 105 min. (45+60)._x000D_ _x000D_ Were evaluated markers of stress oxidative. _x000D_ _x000D_ Results _x000D_ The total antioxidant capacity and total content of the sulfhydryl groups showed similar values in the sham group (24.44±1.90 and 1.41±0.12, respectively) compared with the group IR and PIC group (18.48±1.77 and 1.20±0.08, respectively). These values were higher when compared with those in the IR group (9.22±2.16 and 1.01±0.07)._x000D_ The enzymes that comprise the endogenous antioxidant system (glutathione peroxidase and glutathione reductase), the activities were reduced in the IR and IPC groups compared with the sham group. IPC group showed higher values compared with the ischemic reperfusion group._x000D_ The malondialdehyde increased in the IR group compared with the animal of sham group and IPC group. _x000D_ The carbonyl protein and caspase-3 contents were higher in the IR group than in the sham group. The PIC group demonstrated similar averages for both protein carbonyls and caspase 3 as those in the IR group._x000D_ Conclusions IPC contributed to reducing cell damage by kidney IR in animals subjected to brief periods of vascular pedicle clamping._x000D_ Funding none
Authors
VALTER TOREZAN GOUVÊA JUNIOR
CERVANTES CAPOROSSI RAFAEL MORAIS DE ASSIS MAISA PAVANI DOS SANTOS THIAGO RACHID JAUDY LUIZ MOLINA RAFAEL AMARAL AMANDA MARTINS BAVIERA, NAIR HONDA KAWASHITA DAMIANA LUISA PEREIRA SOUZA CLAUDIA BONADIMAN DE LIMA MAIKON ADRIANO TICIANEL FELIPE DE SOUZA BOURET NICOLLE GABRIELLE HERNANDES THULIO FERNANDES DE SOUZA GABRIEL SILVA DE LIMA JOÃO HENRIQUE ALEIXO |
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MP74-08 |
Glucocorticoid receptor polymorphism affects recipients’ susceptibility to dyslipidemia 1 year after kidney transplantation |
Transplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery III | 17BOS |
Abstract: MP74-08 Sources of Funding: None Introduction Dyslipidemia (DL) is a critical comorbidity that occurs after renal transplantation and can lead to cardiovascular diseases. The relationship between the development of DL and glucocorticoid receptor (NR3C1) polymorphism was previously reported by the authors. However, a confirmation study of the implication of DL in polymorphism and the effect of DL on allograft prognosis has not been conducted yet. In this study, we validated the clinical implications of the NR3C1 Bcl I G allele and assessed risk factors for developing DL and graft survival. Methods Two hundred forty-seven consequent renal allograft recipients (153 men and 94 women) who underwent transplantation under tacrolimus (TAC)-based immunosuppression between February 2002 and August 2015 were evaluated. Susceptibility to DL was validated in 76 recipients who underwent transplantation between September 2011 and August 2015. Risk factors for developing DL and allograft prognosis were assessed in all the 247 patients. Results In the validation study, the incidence of DL was significantly higher in the patients with the NR3C1 Bcl I G allele than in those with the CC genotype (p = 0.009). After validation, 92 recipients (37.2%) were diagnosed as having DL after transplantation. No significant differences in mean body mass index, acute rejection rate, ABO incompatibility, and the incidence of diabetes mellitus or hyperuricemia were observed. The occurrence of DL was associated with female sex and older age (p = 0.002 and 0.026, respectively). No significant differences were observed in the immunosuppressant pharmacokinetic parameters. The incidence of DL was significantly higher in the patients with the NR3C1 Bcl I G allele than in those with the CC genotype (p = 0.002). The multivariate analysis revealed that the NR3C1 Bcl I G allele, female sex, and age of >47 years were significant risk factors for developing DL (odds ratios, 2.16, 2.43, and 1.78, respectively; 95% confidence intervals, 1.24-3.76, 1.39-4.24, and 1.07-3.26, respectively; Table 1). No significant difference in graft survival was found between the two groups. Conclusions The incidence of DL in our cohort was 37.2%. The NR3C1 Bcl I G allele may allow prediction of the occurrence of DL. These findings may aid in predicting patients&[prime] risk of developing DL. Funding None
Authors
Kazuyuki Numakura
Hideaki Kagaya Naoki Komine Nobuhiro Fujiyama Mitsuru Saito Takamitsu Inoue Hiroshi Tsuruta Atsushi Maeno Shintaro Narita Takenori Niioka Masatomo Miura Tomonori Habuchi Shigeru Satoh |
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MP74-09 |
Focal Ablative Therapy for Solid Renal Masses in Transplant Allograft Kidneys |
Transplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery III | 17BOS |
Abstract: MP74-09 Sources of Funding: None Introduction Renal transplantation is the gold-standard treatment for end-stage renal disease (ESRD). It is known that transplant patients are at an increased risk of developing de-novo malignancy, with initial evidence showing an increased risk of solid renal masses (SRMs) in the transplant allograft kidney compared to the overall population. Definitive management of SRMs in transplanted allograft kidneys is a difficult clinical scenario due to complex surgical anatomy, postoperative adhesions, and need for renal preservation. The aim of this study was to review a single institutional experience with focal ablative therapies for SRMS in transplant allograft kidneys. Methods After institutional review board approval, patients with a history of SRM in transplanted allograft kidneys who underwent focal ablative therapy were identified. Complete chart review was performed with relevant data extracted for cumulative analysis. Results Five patients treated with focal ablative therapy of a SRM in a transplanted allograft kidney were identified from 2010-2015 at our institution. Two underwent percutaneous microwave ablation, one percutaneous irreversible electroporation ablation, one laparoscopic cryoablation, and one open cryoablation. Median mass size was 2.8cm (range 1.6-3.4cm). SRMs were diagnosed at a median of 96 months (range 1-96 months) after transplantation, with three patients having undergone living donor transplantation and two receiving cadaveric grafts. Tumor histology included 3 clear cell renal cell carcinoma (RCC), 1 papillary RCC, and 1 had no available pathology. One mass had a Furhman grade of 3 and the other three available histologies were classified as Fuhrman grade 1-2. Two patients experienced postoperative complications, with one patient developing a hematoma requiring drainage (Clavien IIIa), and another patient developing a hematoma managed conservatively (Clavien I). Four patients had no evidence of disease at a median follow up of 30 months (range 9-60 months). One patient developed metastatic disease 48 months following ablation. All patients had stable GFR after ablation, with none requiring a return to dialysis. Conclusions Our single institution case series presents the largest reported series of focal ablative therapies for SRMs in transplant allograft kidneys. Our experience shows, with intermediate term follow up that focal ablative therapies are a feasible renal-sparing intervention for management of SRMs in transplant allograft kidneys. Funding None
Authors
John Griffith
Aaron Fischman Nikhil Waingankar Michael Palese John Sfakianos Ketan Badani Reza Mehrazin |
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MP74-10 |
The Fate of Postoperative Peri-nephric Fluid Collections within 1 Month after Pediatric Renal Transplantation: Etiology and Therapeutic Interventions |
Transplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery III | 17BOS |
Abstract: MP74-10 Sources of Funding: None. Introduction Postoperative peri-nephric fluid collections are common after pediatric renal transplantation (RT), and may be caused by clinical entities such as urinoma, hematoma, and lymphocele. These collections are usually monitored with serial ultrasounds. Size, etiology, extrinsic ureteral obstruction and/or the presence of symptoms dictate management. We hypothesized that these fluid collections rarely require intervention, and gain little benefit from close follow-up with imaging in the presence of stable clinical status (asymptomatic with stable renal function) and absence of hydronephrosis. Methods Retrospective review was performed of all children who underwent pediatric RT at our institution within the last five years (2010-2014) and monitored at least 1 month postoperatively. Peri-nephric fluid collections on postoperative renal ultrasounds were measured in 3 axes and correlated with clinical parameters and symptomatology. Indicated interventions including image-guided drainage and surgery were captured. Results 103 children underwent RT (59 deceased and 44 living-related donor) over this period, at a mean age of 10.6±5.4 years. Only 37 patients (36%) had no peri-nephric collections on ultrasound at two weeks postoperatively. Sixty-six patients (64%) had fluid collections, 14 of which underwent intervention: 9 lymphoceles (8.7%), 3 infected hematomas (2.9%), and 2 urinomas (1.9%). Four patients with lymphoceles underwent laparoscopic marsupialization after failed drainage and/or sclerotherapy. The average fluid collection volume was 169 cm3; 618 cm3 in the intervention group compared to 46 cm3 in those observed. Conclusions Peri-nephric fluid collections are common after pediatric renal transplantation, the majority of which do not require intervention. Larger volume fluid collections were associated with intervention and are usually secondary to lymphoceles. Funding None.
Authors
Frank J. Penna
Armando J. Lorenzo Walid A. Farhat Martin A. Koyle |
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MP74-11 |
Adverse events in therapeutic plasma exchange using fresh-frozen plasma in kidney transplant recipients |
Transplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery III | 17BOS |
Abstract: MP74-11 Sources of Funding: None Introduction For successful kidney transplantation, patients who are at immunological high risk, such as those who have an ABO blood type incompatibility with the donor and/or who are positive for donor specific anti-HLA antibodies, should undergo apheresis therapy. For apheresis therapy, immunoadsorption, double filtration plasmapheresis (DFPP), or plasma exchange is often performed. Plasma exchange using fresh-frozen plasma (FFP) often causes unpleasant adverse events. However, there are few reports on the incidence and profile of adverse events during therapeutic plasma exchange in kidney transplant recipients. Methods From April 2005, 53 kidney transplant recipients (including 6 preemptive cases) at immunological high risk were enrolled in this study. For desensitization, they underwent three or four sessions of apheresis therapy (two or three sessions of DFPP and one or two sessions of plasma exchange). They also received a single dose of rituximab at 200 mg/body 3 weeks before transplantation. The induction immunosuppressive therapy consisted of tacrolimus, mycophenolate mofetil, steroid, and basiliximab. All patients with antibody-mediated rejection (ABMR) received apheresis therapy (plasma exchange or DFPP), steroid pulse therapy, and administration of low-dose (100 mg/kg) immunoglobulin intravenously for 3 to 5 days. Three liters of FFP equivalent to the total plasma volume in each patient was used during each session of plasma exchange. We evaluated adverse events during 88 sessions of plasma exchange (62 sessions, including 12 sessions combined with hemodialysis preoperatively, and 26 sessions for ABMR). Adverse events were evaluated by the Common Terminology Criteria for Adverse Events Version 4.0. Results The incidence of adverse events was 83% (73/88). The principal events were pruritus 53% (47/88), numbness (hypocalcemic symptoms) 40% (35/88), urticaria 33% (29/88), chill 19% (17/88), nausea and vomiting 13% (11/88), mild dyspnea 5% (4/88), and mild hypotension 3% (3/88). Severe adverse events (grade 3 or over) were not recorded. The incidence of adverse events was significantly higher at pretransplantation than at posttransplantation (p < 0.001). No differences were found in the incidence of adverse events between preemptive cases and patients receiving maintenance dialysis. The incidence of numbness during plasma exchange was significantly less (p = 0.009) in patients receiving combined hemodialysis than in those not receiving hemodialysis. Conclusions During therapeutic plasma exchange using FFP in kidney transplant recipients, pruritus, numbness, and urticaria commonly occur. In patients with chronic renal failure, plasma exchange combined hemodialysis may be useful to prevent numbness. The incidence and severity of adverse events during plasma exchange may be associated with kidney function. Funding None
Authors
Mitsuru Saito
Takamitsu Inoue Shintaro Narita Atsushi Maeno Hiroshi Tsuruta Kazuyuki Numakura Shigeru Satoh Tomonori Habuchi |
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MP74-12 |
Antibody titer against BK polyomavirus of renal transplant recipients' serum and intravenous immunoglobulin 3 products derived from donated blood in Japan and its clinical implications |
Transplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery III | 17BOS |
Abstract: MP74-12 Sources of Funding: None Introduction BK polyomavirus (BKV) is a causative agent of BKV-associated nephropathy (BKVN) and hemorrhagic cystitis, which occur subsequent to the reactivation of BKV. Although the clinical implications of antibodies against BKV have not yet been clarified, intravenous immunoglobulin (IVIg), which is presumed to have significant neutralizing activity, may represent a promising approach for the control of BKV-associated diseases. The objective of this study was to measure anti-BKV antibody titer in an IVIg preparation as well as in renal transplant recipients and to examine its significance as a clinical marker. Methods Three IVIg products derived from donated blood samples in Japan as well as clinical samples from 45 recipients of kidney transplants at Akita University Hospital were used for evaluation of neutralizing titers and antibody titers. A reliable method of measurement using the human lung (carcinoma) cell line A549 and the Gardner strain of BKV was established to quantitatively determine neutralizing activity. Antibody titers in the samples were evaluated by neutralizing capacity and binding capacity, using enzyme-linked immunosorbent assays. Results The mean neutralizing titer against BKV was 2,687-fold (±558) higher in pooled plasma and 12,014-fold (±2,145) higher in IVIg products concentrated from pooled plasma. Stable high antibody titers of all IVIgs were found against BKV subtype I/c, which is the major subtype in Japan. In contrast, the antibody titers among the renal transplant recipients differed, and recipients who had BKVN showed a particular tendency to have low antibody titers before surgery. Conclusions IVIg products derived from more than 10,000 lots of plasma exhibited significant neutralizing activity against BKV, and the neutralizing titers were stable for more than 10 years without appreciable change. Anti-BKV antibody titers of kidney transplant recipients might be a useful clinical marker for a potential risk of BKVN. Funding None
Authors
Mitsuru Saito
Takeru Urayama Kazuyuki Numakura Takamitsu Inoue Shintaro Narita Hiroshi Tsuruta Atsushi Maeno Kaoru Sakai Shigeru Satoh Tomonori Habuchi |
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MP74-13 |
Associaton of PCK2 gene polymorphism with impaired glucose tolerance after kidney transplantation |
Transplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery III | 17BOS |
Abstract: MP74-13 Sources of Funding: none Introduction New-onset diabetes mellitus after kidney transplantation (NODAT) is known to be a risk factor for deterioration of graft function and may also cause various fatal complications, including cardiovascular disease after kidney transplantation (KTx). In this study, we focused on genes encoding proteins responsible for the glucose metabolism and determined their single-nucleotide polymorphisms (SNPs). We also examined the correlation between these SNPs and glucose intolerance after KTx. Methods This study included 38 patients who underwent KTx at Kobe University Hospital and had normal glucose tolerance prior to KTx. We defined patients with plasma glucose level higher than 140mg/dl at 120 minutes in 75g OGTT at 1 year after KTx as new-onset impaired glucose tolerance (NIGT). We identified 8 SNPs in 7 genes, including, GLUT2 and PCK2, which are involved in glucose metabolism in the liver, as well as IGF2BP2, CDKN2A/B, HHEX and SLC30A8, CDKAL1 which are associated with glucose metabolism in other tissues. We compared the prevalence rate of NIGT among SNPs in each gene. Results Out of 38 patients included in this study, 11 patients (28.9%) were diagnosed as NIGT. There was no difference in genotype distribution between transplant and Japanese population samples concerning 8 SNPs in 7 genes. As for rs4982856 in PCK2 gene, the distribution of genotype was, T/T: 11 (28.9 %), T/C: 23 (60.5 %), C/C: 4 (10.5 %) as a whole (table 1). Seven patients out of 11 patients with NIGT had T/T genotype of rs4982856, while only 5 patients out of 27 patients with normal glucose tolerance had T/T genotype of rs4982856. The T allele frequency of the rs4982856 was significantly higher in NIGT than in normal group (81.8 vs. 52.8 %, respectively; p = 0.015; Table 2). Other SNPs were not associated with the risk of glucose intolerance. Conclusions Our study indicates that T allele of the rs4982856 in PCK2 gene may be the risk factor for impaired glucose tolerance after kidney transplantation. Funding none
Authors
Naoki Yokoyama
Teruyuki Oda Satoshi Ogawa Takeshi Ishimura Masato Fujisawa |
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MP74-14 |
Is it Possible to Predict Success of Renal Auto-transplantation for Chronic Kidney Pain? Development of an Algorithm Utilizing Celiac Plexus Block |
Transplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery III | 17BOS |
Abstract: MP74-14 Sources of Funding: none Introduction Chronic kidney pain can be debilitating for patients and frustrating for physicians due to a lack of consensus evaluation or treatment. Chronic narcotics are commonly used with multiple untoward effects often without satisfactory resolution of pain. The celiac plexus provides sensory innervation to multiple intraabdominal organs, including the kidneys. Alleviation of chronic renal pain can be achieved with celiac block, but this is often short-lived. Skeletonizing the renal artery, auto-transplantation and nephrectomy have all been used as last-ditch efforts for relief. We seek here to introduce a practice pattern whereby patients in whom auto-transplant or nephrectomy is considered first undergo celiac block and, if successful, then undergo definitive management. Methods Six patients were retrospectively identified who were considered for auto-transplant for various indications including ureteral stricture disease, chronic pain, and renal vascular disease. A single surgeon performed all procedures. Ultimately, celiac block was performed in 3 patients with chronic flank pain prior to surgery. Age, BMI, Creatinine, length of follow up, subjective pain score and use of narcotics at last visit were assessed. Results Of the 6 patients included in the study, 5 underwent auto-transplant. Of these 5, 2 had celiac block prior to surgery, both of which reported alleviation of pain following the block. Of note, the patient who did not undergo auto-transplant also had a successful celiac block but elected for simple nephrectomy for fear of complications with transplantation. All 3 patients who had celiac block and subsequently underwent surgery had resolution of pain and were not on narcotics at last follow-up. Of the remaining 3 patients, 2 were still taking narcotics at last follow up. Mean age was 36.8 yrs., mean BMI was 26.2 and mean follow up was 11.7 mos. All patients had normal renal function at last follow-up with mean serum Cr of 0.88 mg/dL. Conclusions Chronic pain syndromes are frustrating for patients, their families, and their physicians. Invasive surgical options such as auto transplant or nephrectomy are considered when conservative measures fail, but not even these methods guarantee pain relief, and can result in significant complication.. Based on our experience, we recommend celiac plexus block prior to consideration of more invasive treatment when conservative options fail. Funding none
Authors
TJ Tipton
Hayden Hill Michaella M Prasad Arthur R Smith Kenneth D Chavin Stephen J Savage |
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MP74-15 |
A novel NF-?B inhibitor dehydroxymethylepoxyquinomicin prevents acute rejection of kidney allografts in a rat model |
Transplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery III | 17BOS |
Abstract: MP74-15 Sources of Funding: none Introduction Clinical regimens of immunosuppression involve different types of agents because the targets of each drug are the halfway points of signaling pathways leading to expression of various essential proteins in immune cells activation. Nuclear factor (NF)-?B is one of key transcriptional factors and is located in the down stream of several signaling pathways activated in immune responses. Therefore pharmacological modulation of NF-?B activities may be of great use for the treatment of allograft rejection. In this study, we investigated for an immunosuppressive effect of a novel NF-?B inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), using a rat kidney transplant model between a highly immune reactive combination. Methods We performed kidney allograft transplant in a rat acute rejection model (WKAH to LEWIS rats, age 6-8 weeks). Rats were randomly assigned into 3 groups (A: control group, not administrated DHMEQ, B: administration of 12 mg/kg DHMEQ, C: administration of 20 mg/kg DHMEQ). DHMEQ was administrated i.p. once daily for consecutive 10 days. Urine and blood samples were collected every each day. The date of anuria was determined as the date of rejection. Transplanted kidney allografts were also explanted on the 4th postoperative day and the infiltration rates of T cells and monocytes were investigated by immunohistochemistry. Results DHMEQ significantly prolonged kidney allograft survival. (7.2 ± 1.4 post-transplant days, 13.5 ± 3.4 post-transplant days, 19.4 ± 4.5 post-transplant days, for a control (group A), 12 mg/kg DHMEQ (group B), 20 mg/kg DHMEQ (group C), respectively). There was a reduction of T cell and macrophage infiltration to DHMEQ-treated kidney allografts compared to control allografts. The production of pro-inflammatory cytokines including IL-6, IL-12 p70, TNF-? in the recipients treated with DHMEQ was significantly decreased compared to that in the control group. No remarkable side effects were observed during the experiments. Conclusions DHMEQ is remarkably effective in preventing kidney allograft rejection. DHMEQ can be administrated safely and could be involved in a new immunosuppressive strategy, which allows reducing the dose of current immunosuppressive agents. Funding none
Authors
Kazunobu Shinoda
Shinya Morita Kazuhiro Matsumoto Takeo Kosaka Ryuichi Mizuno Toshiaki Shinojima Eiji Kikkuchi Hiroshi Asanuma Akira Miyajima Kazuo Umezawa Mototsugu Oya |
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MP74-16 |
Transurethral resection or incision of the prostate after renal transplantation: Is there a safer time for the procedure? |
Transplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery III | 17BOS |
Abstract: MP74-16 Sources of Funding: None Introduction The age of patients undergoing renal transplantation has increased in the past decades. Symptoms of benign prostate hyperplasia (BPH) are rare in dialysis patients due to low urine excretion. As BPH is very prevalent in elderly men, urologists often have to address unexpectedly symptomatic patients after their kidneys recover function. The aim of this study is to compare urological outcomes and morbidity related to transurethral resection (TURP) or incision of the prostate (TUIP) performed in either the early or the late post-transplant period. Methods Between 1998 and 2016, 3145 renal allograft transplantations were performed in our institution. Fifty patients developed severe prostatic symptoms with no response to drug treatment after recovery of renal function. The patients were divided into two groups in accordance with the time between transplantation and the prostate procedure and were prospectively studied: group I – 18 patients in which TURP/TUIP was performed less than 90 days after transplantation; and group II – 32 patients in which the prostate procedure was performed more than 90 days after transplantation. Urologic parameters analyzed were International Prostate Symptom Score (IPSS), Prostate Specific Antigen (PSA), prostate measurements and PVR (post void residual urine) before and 6 months after surgery. The morbidity was compared based on need of transfusion, presence of urinary tract infection (UTI), time to home discharge and loss of renal function (elevation of creatinine levels). Results Both groups were comparable in terms of age (59.8 ± 8.6 vs. 58.5 ± 9.3, p=0.744), but not in prostate measurement (55.3 ± 37.5 vs. 37.0 ± 12.7, p=0,001). Furthermore, time of home discharge (9.4 ± 8.5 vs. 4.1 ± 4.5, p=0.026), the UTI incidence (55.6% vs. 18.8%, p<0,017), and loss of renal function (elevation of creatinine levels - p<0,001) were significantly higher in group I. However, there were no differences between the groups in terms of IPSS in the 6 months (5.9 ± 4.3 vs. 5.1 ± 3,8, p=0.560), decrease PSA levels (p=0.568), and PVR in the 6 months (14,2 ± 35,3 ml vs. 26,3 ± 41,4 ml, p=0.309). No patients need receive transfusions. Conclusions Despite the fact that there was no difference in effectiveness, TURP and TUIP should be avoided in the early post transplantation period due to the increasing risk of infection, the loss of graft function and higher time of home discharge. Funding None
Authors
Afonso Celso Piovesan
Rafael Fagionato Locali Marcos Mello Kleiton G R Yamaçake Hideki Kanashiro Gustavo Xavier Ebaid Ioannis Antonopoulos Flavio Jota de Paula William Carlos Nahas |
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MP74-17 |
Renal artery diameter is a surrogate marker for kidney volume in living kidney donors |
Transplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery III | 17BOS |
Abstract: MP74-17 Sources of Funding: None Introduction Donor kidney volume (KV) is an increasingly important parameter evaluated before living kidney donation. It potentially enhances the estimation of glomerular filtration rate before surgery, measures split renal function for selection of the explantation side and prognosticates recipient function following transplantation. However, KV measurements on Computerised Tomographic (CT) scanning requires a manually intensive process of manual or semi-automatic segmentation of kidneys with inter-observer variation. Renal artery diameter (RAD) is an easier marker to measure and this study aims to investigate the relationship between donor RAD and KV. Methods A retrospective review of consecutive patients who underwent living donor nephrectomy between 2010 and 2016 was conducted. In all patients, bilateral kidney volumes were measured based on contrast-enhanced CT scan imaging, using segmentation of functional nephron mass to exclude sinus fat, blood vessels and the pelvi-calyceal system. For the renal artery maximum diameter, we measured the RAD at the vessel cross section just distal to the aortic ostia. Measurements were taken between the tunica intima by direct visualisation on the arterial phase of transverse CT slices. Estimated Glomerular Filtration Rate (eGFR) was determined using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation from serum creatinine levels collected before surgery. Results 92 consecutive living donor nephrectomy patients were reviewed. After excluding 15 patients with multiple arteries, 77 patients (55.8% Female, 58.4% Chinese) were available for this study. The mean age of the donors was 44.4+/-12.7 years. Controlled hypertension, hyperlipidemia and smoking were present in 9(11.7%), 17 (22.1%) and 7 (9.2%) patients with no other significant co-morbidities. All patients had normal blood pressure (BP) measurements pre-operatively with a mean systolic and diastolic BP of 122.4+/-14.4 and 72.4+/-10.4 mmHg respectively. Mean right and left KVs were 132.8+/-25.9 and 138.9+/-24.8 cm3 respectively. Mean right and left RADs were 4.86+/-0.91 and 5.14+/-0.85 mm respectively On regression analysis, there was a significant association between the right and left RADs and their ipsilateral KVs with a regression coefficient of 7.9 (95% C.I. 1.3-14.5, P=0.019) and 9.8 (95% C.I. 3.3-16.3, P=0.004) respectively. Mean eGFR pre-operatively was 105.1+/-14.9 mL/min/1.73 m2. Mean total RAD (the sum of both left and right RAD) was 9.61+/-2.51mm. It was found to be correlated with pre-operative eGFR at 0.095. Patients with pre-operative eGFR of < 100 mL/min/1.73 m2 had a lower total RAD than those with eGFR>100 mL/min/1.73 m2 (9.38+/-3.44 mm vs 9.73+/-1.86 mm, p=n.s.) Conclusions This study demonstrates that renal artery size is positively associated with kidney volume and may be used as a more easily measured surrogate marker for kidney size with its attended implications in living donor transplantation. Funding None
Authors
Arshvin Kesavan
Bee Choo Tai Arun B Benjamin Goh Lata Raman Vathsala Anantharaman Ho Yee Tiong |
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MP74-18 |
The effect of thymoquinone on the renal functions following ischemia-reperfusion injury |
Transplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery III | 17BOS |
Abstract: MP74-18 Sources of Funding: College of Medicine & Health Sciences, United Arab Emirates University Introduction Renal ischemia-reperfusion injury (IRI) is an invariable consequence of several urological conditions and procedures and is associated with alterations in renal functions._x000D_ Recently, there has been a growing interest in using natural phytochemical compounds as treatment alternatives to conventional drugs in several diseases. This is due to their relatively low toxicity and price and to wide availability. Thymoquinone, an antioxidant phytochemical compound found in the plant Nigella sativa which is heavily consumed in some parts of the world, has been shown to have a protective effect in several renal conditions. However, its effect on the IRI-induced renal hemodynamic and tubular dysfunction has not been investigated yet. Thus, the aim of this study was to investigate the effect of thymoquinone on the alterations in renal functional parameters following warm IRI in the rat_x000D_ Methods Wistar rats underwent left renal ischemia for 35 minutes. Group-TQ (n=15) received thymoquinone 10 mg/kg/day (dissolved in a vehicle (corn oil) orally by gavage starting 4 days prior to the IRI and continued 6 days thereafter when the renal functions of the right and left kidneys were measured using clearance techniques. Group-Vx (n=15) underwent similar protocol but received only the vehicle. In addition, gene expression of some markers of kidney injury and cytokines was measured in the kidney tissue using PCR technique Results IRI affected all hemodynamic and tubular parameters in the affected kidney. So in Group-Vx, the left renal blood flow (RBF), six days following IRI, was 22% of the right RBF (1.27±0.21 vs. 5.77±0.54, P=0.0001). Similarly, the left kidney glomerular filtration rate (GFR) was 15% that of the right non-ischemic kidney (0.18±0.03 vs. 1.22±0.07, P=0.0001). On the other hand, the fractional excretion of sodium (FENa) in the left kidney was significantly higher than the right kidney (2.40±0.35 vs. 0.59±0.08, P=0.0001). When the right non-ischemic kidneys in both groups were compared, all the variables were similar._x000D_ Thymoquinone attenuated the IRI-related alteration in renal functions so when the left ischemic kidney in Group-TQ and Group-Vx were compared, the left RBF and GFR were significantly higher in Group-TQ (2.02±0.39 vs. 1.27±0.21, P=0.04 and 0.33±0.08 vs. 0.18±0.03, P=0.03, respectively). On the other hand, the left renal FENa was significantly lower in Group-TQ (1.59±0.28 vs. 2.40±0.35, P=0.04). Thymoquinone also decreased the gene expressions of KIM-1, NGAL, TNF-α, TGF-β1 and PAI-1 (143±20 vs. 358±49, 16±3 vs. 34±6, 1.1±0.2 vs. 2.8±0.4, 1.6±0.1 vs. 2.8±0.1, and 2.4±0.3 vs. 5.8±1.0, P<0.05 for all)._x000D_ Conclusions Thymoquinone ameliorated the IRI effect on the hemodynamic and tubular renal functional parameters as well as the expression of some markers of renal injury and pro-inflammatory and pro-fibrotic cytokines indicating a renoprotective effect of this agent on the IRI-induced renal dysfunction with potential clinical implications. Funding College of Medicine & Health Sciences, United Arab Emirates University
Authors
FAYEZ HAMMAD
Loay Lubbad |
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MP74-19 |
Protective Effects of Regulatory T cells in a murine model of Renal Ischemia-Reperfusion Injury |
Transplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery III | 17BOS |
Abstract: MP74-19 Sources of Funding: none Introduction Solid organ transplantation inevitably leads to ischemia-reperfusion injury (IRI).?Regulatory T cells (Tregs) are involved in immunological tolerance at the transplantation site, especially with respect to natural immunity, and also have anti-inflammatory effects. The present study aimed to evaluate whether Tregs protect the kidney from IRI and to explore the possible underlying mechanism. Methods We established the IRI model in male mice (C57BL/6, 10–12 weeks old). Left renal ischemia was performed for 30 min, and then the right kidney was resected following left renal reperfusion. We administered tricostatin A (TsA) and PC61 (anti-CD25 mAb) to increase and decrease the number of Tregs, respectively. Mice were divided into the four groups: the TsA group, the DMSO (vehicle) group, the TsA + PC61 group, and the DMSO + PC61 group. Splenic Treg fractions (CD4[+]Foxp3[+]) were evaluated by flow cytometry at postoperative day (POD) 7. Serum levels of creatinine and different inflammatory cytokines, such as IL-10, IL-6, IL-2, and TNF, were measured by ELISA. The mRNA expressions of Foxp3, IL-10, IL-6, TGF-B, CD80, CD86, and ICAM-1 in the kidney at POD2 were measured by real-time qRT-PCR. Results The splenic Treg fraction in the TsA group was significantly higher than those in the other three groups (p < 0.001, respectively). At POD2, the mean level of serum creatinine in the TsA group was significantly lower than those in the other three groups (p < 0.001, respectively). The mean level of serum IL-10 in the TsA group was significantly higher than those in the DMSO/DMSO + PC61 groups (p = 0.01), whereas the mean level of serum IL-6 in the TsA group was significantly lower than those in the DMSO/DMSO + PC61 groups (p = 0.003, respectively). The renal expressions of Foxp3 and IL-10 mRNA were significantly higher in the TsA group than those in the DMSO group (p = 0.003 and p = 0.03, respectively). In contrast to the above findings, the IL-6 mRNA expression was significantly lower in the TsA group than that in the DMSO group (p = 0.016). The mRNA expressions of CD80, CD86, and ICAM-1 in the kidney were significantly lower in the TsA group than those in the DMSO group (p < 0.001, p = 0.018, p = 0.004, respectively). Conclusions Facilitation of Treg expansion by TsA might have some roles in the protection of the kidney from IRI by reducing the expression of co-stimulatory molecules. Funding none
Authors
Ryohei Yamamoto
Mitsuru Saito Kazuyuki Numakura Hiroshi Tsuruta Atushi Maeno Takamitsu Inoue Shintaro Narita Shigeru Satoh Tomonori Habuchi |
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MP74-20 |
Necessity of pre-transplant bladder cycling for patients with defunctionalized bladder : a prospective randomized trial |
Transplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery III | 17BOS |
Abstract: MP74-20 Sources of Funding: none Introduction Renal transplantation in patients with lower urinary tract (LUT) dysfunction is a unique challenge, as they are at higher risk of urinary tract infection, sepsis, surgical complications, allograft dysfunction and graft loss. We opt to identify the impact of pre-transplant bladder cycling on the urological complications, graft function and lower urinary tract function Methods The study included patients maintained on hemodialysis for more than 12 months with oliguria or anuria, reduced bladder capacity by ascending cystogram, poor compliance by cystometry, no history of lower urinary tract dysfunction and have no evidence of urological cause of renal failure. Patients were randomly allocated into two groups, group I received direct renal transplantation without bladder recycling. Group II received renal transplant after programmed bladder recycling through bladder instillation of sterile water in amount equal to the estimated bladder capacity to be gradually increased till patient can withstand filling the bladder with 200 cc for 2 hours. Standard renal transplantation was carried out with stented Leich Gregoir ureteroneocystostomy. Urological complications and graft functions were recorded at 3 months. Patients were assessed by IPSS, Cystogram as well as cystometry. To achieve a difference in mean cystometric capacity of 50 cc in favor of bladder training patients, 16 patients in each group are required to achieve a power of 80% and an ? error of 0.05. Results A total of 22 patients were randomized so far including 11 patients in each group. All the cases underwent right iliac renal allotransplantation. Urinary leakage occurred in 2 cases (18%) in group I that was managed conservatively and subsided with prolongation of the internal stent and one case required percutaneous tube drainage. In group II urinary leakage occurred in one case (9%) that was managed by surgical exploration and redo ureterovesical reimplantation (p= 0.07 ). At 3 months, mean serum creatinine was 0.9 mg/dl and 1 mg/dl in both groups respectively (p= 0.4 ). Symptom score was 9 and 11 in both groups respectively (p =0.09 ). Mean cystometric capacity three months after transplant was 382 cc and 397 cc in both groups respectively (p= 0.1) Conclusions Pretransplant programmed bladder recycling for patients with defunctionalized bladder provide no clinical advantage as regard postoperative urological complications, graft function, lower urinary tract symptoms and cystometric capacity. Funding none
Authors
Mohammad Zahran
Yasser Osman Ahmed Elhefnawy Ahmed Harraz Islam Fakhreldin Ahmed Kamal mohammad Nagib Beder Ali-El-Dein Ahmed Shokeir |
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MP75-01 |
Paravertebral Block for Percutaneous Nephrolithotomy: A Prospective, Randomized, Double-Blind Placebo-Controlled Study |
Stone Disease: Surgical Therapy VII | 17BOS |
Abstract: MP75-01 Sources of Funding: None Introduction Percutaneous nephrolithotomy (PCNL) is considered the gold standard minimally invasive treatment for large stone burdens, but post-operative pain control remains challenging. Paravertebral block (PVB) has been described for breast and thoracic surgery as an effective pain control strategy, but is not being utilized for PCNL. The objective of this study was to evaluate the effect of paravertebral block on pain control and opioid use following PCNL. Methods This was a prospective, randomized, double-blind, placebo-controlled study. Willing patients undergoing unilateral PCNL for stone disease were consented and randomized to receive either PVB or placebo intervention in the preoperative area. The PVB consists of a single injection of 20 mL of 0.5% bupivacaine into the T10 paravertebral space under ultrasound guidance. For the placebo intervention, the ultrasound probe is applied, the skin is infiltrated with lidocaine, and pressure is held to mimic injection. The patient, surgeon, and anesthesia team were blinded to the study group. Patients received patient-controlled analgesia (PCA) following surgery. Outcomes were visual analog scale (VAS) pain scores, intra-operative and post-operative opioid use, and anti-emetic use. Statistical analysis was performed using paired t-tests for continuous variables and chi-square tests for categorical variables. Results The 45 patients enrolled in the study had no difference in baseline characteristics. There were no complications attributed to the PVB. The average VAS pain score was lower in the PVB group. Intra-operative opioid use, post-operative opioid use, frequency of opioid use, and anti-emetic use were significantly lower in the PVB group as compared to the control group. The time from the conclusion of surgery to the first administration of opioids was longer in the PVB group Conclusions To our knowledge, this is the first randomized, double-blind, placebo-controlled trial investigating the use of PVB in PCNL. PVB prior to PCNL improved average VAS pain scores and decreased both intra-operative and post-operative opioid use. The reduction in opioid use likely leads to improved nausea as reflected in decreased anti-emetic use. PVB should be considered an effective strategy to reduce pain for patients undergoing PCNL. Funding None
Authors
Kristin G. Baldea
Grace Delos Santos Chandy Ellimoottil Ahmer Farooq Elizabeth R. Mueller Scott Byram Thomas M.T. Turk |
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MP75-02 |
Predictors of ED visits Following Ureteroscopy |
Stone Disease: Surgical Therapy VII | 17BOS |
Abstract: MP75-02 Sources of Funding: none Introduction Ureteroscopy is one of the most common ambulatory procedures performed by urologists to manage a variety of different pathologies, including nephrolithiasis and urothelial cancers. As a high volume endourologic center, the vast majority of our emergency department visits occur after ureteroscopy. The affordable care act and centers for Medicare and Medicaid services have recently instituted several quality improvement initiatives, one of which includes decreased hospital reimbursement for re-admissions within 30 days. We attempted to identify trends surrounding outpatient ureteroscopy in hopes of decreasing future ED visits._x000D_ Methods A retrospective chart review from 7/1/2015 to 12/31/2015 was performed to identify patients who returned to the ED within 30 days of elective ureteroscopy. CPT codes 52351-6 and 52344-6 were used as search parameters. Patient demographics, operative characteristics, and ED presentation data were collected and analyzed. _x000D_ Results A total of 330 ureteroscopies were performed, resulting in 47 ED visits (14.2%) occurring an average of 8.4 days [1–28] postoperatively. 29 were female and 18 male with an average age of 48.2 [16-86]. 27 (57.4%) were pre-stented an average of 11.5 days preoperatively. All patients were discharged with a stent in place, and 26 (55.3%) with a string attached with instructions to remove at home. 40 (85.1%) were discharged with either Tylenol#3 or Tramadol for pain control. The most common presenting complaint was flank pain (59.6%). Of these patients, 13 (46.4%) presented after the stent was self-pulled, 3 (10.7%) presented after the stent was inadvertently removed, 4 (14.3%) after it was removed via cystoscopy in clinic, and 8 (28.6%) with the stent in place._x000D_ Conclusions The rate of ED visits following ureteroscopy is estimated to be from 5% to 16%. Our results were in line with previous data demonstrating pain as the most common presenting complaint in the ED following ambulatory surgery. The cause of the pain may be due to issues with self-removal of stents and inadequate postoperative pain management. Some evidence exists that pre-stenting improves stone free rates, which intuitively would lead to decreased ED visits. However, this was not the case in our data as a majority of patients had been pre-stented. This hypothesis-generating study elicits the need to explore potential methods, including improved pain management and expectations, particularly with self-pulled stents, in order to possibly decrease ED visit rates._x000D_ Funding none
Authors
Graham Machen
Lawrence Tsai Patrick Lowry Erin Bird Marawan El Tayeb |
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MP75-03 |
Unplanned 30-day encounters after uretero-renoscopy for urolithiasis |
Stone Disease: Surgical Therapy VII | 17BOS |
Abstract: MP75-03 Sources of Funding: None Introduction While stone treatment by ureteroscopy is increasingly performed, it incurs frequent unplanned encounters. We aim to identify avoidable predictors to minimize 30-day encounters. Methods We performed retrospective chart review on 157 patients who underwent ureteroscopy for urolithiasis between January and June 2016. Patient demographics, stone characteristics, operative details, and 30-day postoperative unplanned patient-initiated phone calls, emergency department (ED) visits, and readmissions were collected. Administrative patient phone calls were excluded. In order to obtain the most accurate ED and readmission rates, questionnaires were delivered to patients via telephone or email and supplemented chart review data. Fisher&[prime]s exact and Wilcoxon rank-sum tests were used for qualitative and quantitative variables, respectively. Results There were 44 (28%) unplanned patient-initiated phone calls, 23 (14.6%) ED visits, and 8 (5.1%) readmissions postoperatively. The most common chief complaints and ED diagnoses are listed in Table 1. Factors associated with a higher rate of phone calls include first time stone procedure (37% vs 21%, p = 0.03), outpatient status (30% vs 0%, p = 0.02), intraoperative stent placement (31% vs 0%, p = 0.01), and stent removal at home (59% vs 29%, p = 0.01). Factors associated with increased rate of ED visits were first time stone procedure (23% vs 8%, p = 0.01) and ureteral access sheath usage (30% vs 12%, p = 0.02). Factors associated with a higher rate of readmissions were bilateral procedure (20% vs 3%, p = 0.01) and ureteral access sheath usage (15% vs 3%, p = 0.03). Interestingly, of the 16 patients who had no intraoperative stenting, none had unplanned phone call, ED visit or readmission. Stone number and location, operative time, Charleston comorbidity, and history of preoperative urinary tract infection were not significantly associated with postoperative encounters. Conclusions Pain, first time stone treatment, and presence of a ureteral stent were common reasons for postoperative encounters after ureteroscopy. Development of a clinical care pathway for ureteroscopic stone treatment including patient education and pain management may minimize these encounters and improve treatment quality and cost. Funding None
Authors
Kefu Du
Robert Wang Joel Vetter Alethea Paradis Alana Desai Robert Figenshau Ramakrishna Venkatesh |
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MP75-04 |
Variation in national opioid prescribing patterns following outpatient nephrolithiasis procedures |
Stone Disease: Surgical Therapy VII | 17BOS |
Abstract: MP75-04 Sources of Funding: T32-CA180984 from the National Cancer Institute Introduction Opioid abuse has become an epidemic in the United States. Surgical episodes account for 40% of all opioids prescribed and thus, surgeons are uniquely positioned to control the supply of available opioids. Given the high incidence of nephrolithiasis, we sought to characterize the variation in opioid prescribing among a national cohort following extracorporeal shock wave lithotripsy (ESWL) and ureteroscopy with lithotripsy (URS). Methods We identified patients who underwent outpatient ESWL and URS between 2012 and 2014 using the de-identified ClinformaticsTM Data Mart Database (OptumInsight, Eden Prairie, MN). The database contains administrative health and pharmacy claims from a large, national US health insurer. We limited our cohort to patients that had no concurrent procedures and had not filled an opioid prescription in the 6 months prior to their procedure. We calculated the dose and type of opioids, standardized to morphine milligram equivalents (MME), prescribed within 7 days of the procedure. For urologists with a minimum of 10 cases and 3 opioid prescriptions we quantified the variation in surgeon prescribing patterns. Results We identified 22,577 patients (12,942 ESWL, 9,635 URS) treated during our study period. Forty percent of ESWL and 43% of URS patients filled an opioid prescription following their procedure. Among those patients, the median dose was 150 MME (interquartile range [IQR] 128-225). This corresponds to twenty 5mg oxycodone tablets with a range of 17 to 30 tablets. Hydrocodone (57%) was the most frequently prescribed opioid for ESWL and oxycodone (59%) for URS. Surgeons varied widely in the average dose of opioids prescribed, ranging from 89 to 675 MME (p<0.001), or eleven to ninety 5mg oxycodone tablets (Figure). Conclusions Most patients did not fill an opioid prescription after ESWL or URS. There was no significant difference between ESWL and URS in terms of frequency or amount of opioids prescribed. There was wide variation in opioid prescribing at both the patient and urologist level. Given that these patients were opioid naive, patient variables are not likely to account for this variation. As such, urologists appear to be well positioned to reduce excess opioid prescribing. _x000D_ Funding T32-CA180984 from the National Cancer Institute
Authors
Tudor Borza
Rodney L. Dunn Yongmei Qui Tyler N. Winkelman Ted A. Skolarus David C. Miller Brent K. Hollenbeck Gregory B. Auffenberg |
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MP75-05 |
Fast track stent study (FaST): Short term external ureter stenting shows significant benefit in comparison to routine DJ stent placement after ureterorenoscopic stone extraction – a prospective-randomized trail |
Stone Disease: Surgical Therapy VII | 17BOS |
Abstract: MP75-05 Sources of Funding: None Introduction Does short-term ureter stenting using an external ureter catheter (UC) for 6 hours following ureterorenoscopic stone extraction (URS) provide an equivalent outcome in comparison to postoperative double-J (DJ) ureter stenting? Methods Between 08/2014 and 08/2015, 141 patients initially treated with a DJ insertion for 7 days were prospectively randomized to UC for 6 hours vs DJ insertion for 3-5 days after stone extraction via URS (incl. flexible URS) in a single academic center. Exclusion criteria were acute urinary tract infection, a solitary kidney or a stone mass more than 25mm. Study endpoints were ureter-stent related symptoms and pain assessed by a validated questionnaire (USSQ) and visual analogue scale (VAS) before and 3-5 weeks after surgery. Parameters of both groups were compared using unpaired t-test. Level of significance was p<0.05. BMI, stone size, age, and need for analgetics, reintervention rate and comorbidities were recorded. Results Endoscopic procedures performed by 9 surgeons resulted in more than 90% stone removal in all cases (n=141) in a mean operation time of 24 minutes (range 5-63 min). Groups did not differ in mean age (48 years), mean BMI (28.1) and stone size (5.4 mm). Patients, who received short-term UC, showed a significant higher quality of life (USSQ) compared to patients with a long-term DJ: In the UC group the urinary index score was significantly lower (16.8 vs. 27.8; p <0.0001) as well as the pain score (9.7 ± 1.3 vs. 20.2 ± 1.5; p<0.0001) and general health index (15.3 ± 0.7 vs. 8.5 ± 0.6; p<0.0001). Consultation of a physician and antibiotic treatment were rarely needed (1.3 ± 0.1 vs. 1.6 ± 0.1; p=0.027). The UC study group returned to work earlier (3.0 ± 0.8 days) compared to the DJ study group (7.0 ± 0.9 days; p<0.0009). Furthermore, most of the UC population (88.3%) recommended treatment and would prefer an UC in case of another stone treatment in the future. Only two patients of the UC study group reported prolonged complaints lasting 2 days. No re-intervention was needed in both groups during the follow-up of 6 weeks. Conclusions In patients who had a DJ prior to secondary ureteroscopic stone removal postoperative short-term ureteral stenting should be standard of care rather than routine DJ insertion. Funding None
Authors
Peter Bach
Alina Reicherz Lisa Dahlkamp Nicolas von Landenberg Rein-Jueri Palisaar Joachim Noldus Christian von Bodman |
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MP75-06 |
A prospective observational study about stent-related symptoms after ureteroscopy assessed through a validated questionnaire. |
Stone Disease: Surgical Therapy VII | 17BOS |
Abstract: MP75-06 Sources of Funding: None Introduction Double J ureteral stents can cause major discomfort. Nevertheless, they are still often used at the end of ureteroscopy. The Ureteric Stent Symptoms Questionnaire (USSQ) is a specific validated tool to evaluate the impact of ureteral stents on different aspects of life._x000D_ The objective of our study was to evaluate how patients tolerate ureteral stent after ureteroscopy using the USSQ. Methods A prospective single-institutional observational study was organized. Since January 2010 to October 2015, after a semirigid or flexible ureteroscopy with double J positioning, patients were asked to complete the validated Italian version of the USSQ. The USSQ consists of 6 sections exploring urinary symptoms, body pain, general health, work performance, sexual matters, additional problems and general satisfaction._x000D_ Endpoint of the study was to assess the true extent of stent-related symptoms in the population and their impact on quality of life. Results 232 patients completed the USSQ. 59% experienced a daily urinary frequency ≥ 1 hour. 90% had ≥ 1 micturition during the night. 87% complained of urgency, 37% of urge incontinence. 82% experienced burning at voiding and 81% sensation of incomplete bladder emptying. 69% had episodes of macroscopic hematuria. Urinary symptoms represented a problem for 88%. 79% would feel unhappy if they had to spend the rest of their life with their urinary symptoms. The stent was cause of pain or discomfort in 83%. Median Visual Analogue Scale (VAS) score was 5 (range 0-10). Pain was felt in the kidney back area by 31%, in the kidney front/side area by 26% and in the bladder area by 31%. 73% complained of pain during physical activities. Pain caused sleep interruption in 44%, occurred at voiding in 77% and interfered with everyday life in 77%. 47% used painkillers. General health, working and sexual activity were also negatively influenced by the stent: patients needed bed rest for a median of 2 days and reduced their daily activities for a median of 5 half days, 45% reduced their usual working hours and 46% stopped sexual life after stent insertion. 62% of patients would be unsatisfied (52% unhappy or terrible) if further ureteral stenting would be proposed in future._x000D_ Conclusions Double J ureteral stents after ureteroscopy heavily affect all USSQ domains and patients&[prime] quality of life. Pain, urinary and sexual symptoms adversely influence daily life and working activity in the majority of patients. Stents should be placed only when absolutely needed and should be left in place as short as possible. Funding None
Authors
Andrea Bosio
Eugenio Alessandria Ettore Dalmasso Dario Peretti Alessandro Bisconti Paolo Destefanis Paolo Gontero |
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MP75-07 |
INTRAVESICAL INSTILLATION OF LEVOBUPIVACAINE AS AN ADJUNCT TO REDUCE THE URETERAL STENT ASSOCIATED DISCOMFORT: A DOUBLE BLIND RANDOMIZED CONTROLLED TRIAL. |
Stone Disease: Surgical Therapy VII | 17BOS |
Abstract: MP75-07 Sources of Funding: Chilean Association of Urology Introduction The insertion of double J ureteral catheters is a common practice in modern urology. Unfortunately, different symptoms may occur with indwelling stents, such as dysuria, hematuria, flank and suprapubic pain. The objective of the present study was to evaluate the safety and efficacy of levobupivacaine as an intravesical instillation in the control of pain and urinary symptoms generated by the ureteral stent. Methods 77 patients with double J catheter (Percuflex 26/6 TM, Boston Scientific) after endoscopic treatment of an ureteral stone were randomized into 2 groups. Both groups received standard therapy for catheter discomfort management (paracetamol, ketorolac and tamsulosine). At the end of the procedure group 1 received instillation of 30 cc of saline and group 2 received a dose of 150 mg (30 cc) of intravesical levobupivacaine. Surgeon and patient were blinded for type of instillation received. Symptomatology was evaluate at 4 and 24 hours after the procedure and at the moment of catheter removal. The USSQ survey, in its Spanish-validated version, was used for this purpose. Plasma levels of levobupivacaine were measured at 5, 10, 15 and 20 minutes after instillation in both groups._x000D_ Results Both groups were comparable in terms of age, location and size of stone treated , duration of procedure, stone free rate and days of catheter permanence. Statistical analysis showed significant reduction in group 2 regarding the intensity of pain at 4 hours post-operatively (p = 0.02). In addition, during the catheter carrying period, those patients in whom the levobupivacaine solution was applied had less alteration in work activities (p = 0.03), and less discomfort in the sexual sphere (p = 0.01) Plasma levels of levobupivacaine in the 40 patients exposed to the drug were undetectable (<0.1 mg / dL). There were no side effects attributable to intravesical levobupivacaine_x000D_ Conclusions To our knowledge this is the first clinical trial using levobupivacaine in bladder instillation, which demonstrate better pain control in the immediate postoperative period. There is a significant effect on daily life parameters that could allow better tolerance to the catheter during the time it should remain installed. Also, the use of this substance does not imply a higher cost and its safe, without side effects. Funding Chilean Association of Urology
Authors
José A. Salvadó
Gaston Astroza Alvaro Saavedra |
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MP75-08 |
Use of Non-Metallic Long Term Stents for Ureteral Obstruction |
Stone Disease: Surgical Therapy VII | 17BOS |
Abstract: MP75-08 Sources of Funding: None Introduction Metallic stents have been shown to be advantageous for chronic ureteral obstruction. Non-metallic stents have historically been used for short term applications due to their propensity to encrust and obstruct. We present our 8-year experience with a novel non-metallic stent with a 365-day dwell time. Methods Since 2008 we placed Bard Optima (Covington, GA) stents for ureteral obstruction in patients not deemed suitable for definitive surgical management. Goal was to exchange stents annually. Indications included – malignant obstruction (11), calculus stricture (10), retroperitoneal fibrosis (5), radiation injury (3), ileal-ureter anastomotic stricture (2) and ureteral pelvic junction (2). Patients underwent initial cystoscopy and placement of 7F stent with subsequent upsizing to 8F. Initially stents were exchanged every 6-9 months, but with experience we exchanged them annually, unless the patient became symptomatic. Patency was evaluated by passage of wire through the stent lumen. Results From 2008 to 2016, twenty-four patients and 32 renal units were managed by long-term stent placement. Total of 112 stents were exchanged in this time. Shortest and longest dwell times were 70 days and 742 days, respectively. Exterior stent encrustations were noted in 23% of exchanges. Nonetheless, stents remained patent in 93% of exchanges, with mean dwell time of 280 days. Conclusions To our knowledge this is the first long term series evaluating non-metallic ureteral stents for long-term placement for various causes of ureteral obstruction. The Bard Optima stent is a good alternative to long-term metallic stents. Compared the metallic stents, Optima stents are placed easily over a wire to facilitate ease of use and adoption. Additionally, cost is substantially lower and patient comfort has been exceptional._x000D_ Funding None
Authors
Amar P. Patel
Jeffrey Pearl John G. Pattaras |
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MP75-09 |
Risk factors for re-infection in patients drained with DJ stent for ureterolithiasis and sepsis |
Stone Disease: Surgical Therapy VII | 17BOS |
Abstract: MP75-09 Sources of Funding: none Introduction Currently, there are no guidelines defining optimal timing for definitive stone treatment in stented patients after an event of acute infection with ureteral stones and following resolution of infection. Objective: to evaluate risk factors for re-infection and re-admission in this sub-set of patients. Methods The records of 176 patients admitted between 2009-2016 due to ureterolithiasis and sepsis that were primarily drained with a DJ stent, were retrospectively reviewed. A comparison was carried out between 128 patients with no re-infection and 48 patients (27%) re-admitted for re-infection in the presence of a ureteral DJ stent prior to definitive stone treatment. Univariate and multivariate analysis were performed. Results Mean length of hospitalization due to primary septic episode was 7.4 ±5.3 days. 11.4% (20 patients) required ICU admission. Re-infection rate that required admission was 27.3% (48/176). Mean time to definite stone surgery in patients without re-infection was 72.4± 46.2 days and for those who were re-admitted with infection 42.1 ± 37.3 days._x000D_ In multivariate analysis diabetes mellitus (p=0.02) and previous endourological intervention (p=0.046) were found to be independent risk factors for re-infection. 38% of patients re-admitted for re-infection do so within 3 weeks following the primary septic episode. Mortality: one case (0.8%) during the primary septic episode and three cases (6.3%) during re-admission. _x000D_ Conclusions Patients who suffer from diabetes or have a history of previous endourological surgery are at risk for re-infection during the period between drainage and definite stone treatment._x000D_ Re-infection episode is associated with increased risk for mortality._x000D_ Definite stone treatment within 3 weeks following primary sepsis and drainage may eliminate re-infection rate._x000D_ Optimal bacteriological and patient systemic measures at the time of definite stone treatment should be define and taken into consideration._x000D_ Funding none
Authors
Eyal Kord
Yoram Siegel Amir Cooper Sivan Hirsh Galina Goltsman Amnon zisman |
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MP75-10 |
Tailoring Antibiotic Prophylaxis for Ureteroscopic Procedures Based on Local Resistance Profiles May Lead to Reduced Rates of Infections and Urosepsis |
Stone Disease: Surgical Therapy VII | 17BOS |
Abstract: MP75-10 Sources of Funding: None Introduction Post ureteroscopy UTI rate is about 4%. AUA guidelines suggest prophylaxis treatment for proximal or impacted stones. We examined whether a double drug Antibiotic Prophylaxis Treatment (APT), an aminoglycoside and penicillin based on resistant bacteria strains we encounter in our institution may reduce urosepsis post-ureteroscopy. Methods Between February 2015 and March 2016, we performed 344 ureteroscopies. Starting September, 2015 we changed the APT for endo-urological procedures according to the bacterial resistance profile in urine cultures at our institution. Inclusion criteria were adult patients referred to ureteroscopic treatment for a urinary stone, with or without prior stenting. Exclusion Criteria included integrated procedures (with PCNL), biopsies, pediatric or pregnant patients. Sepsis was defined as fever above 38.5 degrees Celsius with additional standard criteria (International Sepsis Definitions Conference). All patients had a urine culture taken prior to APT initiation. Fisher's exact test and T-test with a two-tailed P value < 0.05 denoted statistical significance. Results 57 patients were excluded. Group 1 (n=106) were the last to receive the conventional APT (PO Ciprofloxacin 500mg X 2), while the second group (n=181) were the first to receive the new regimen (IV Gentamycin 240mg & Ampicillin 1gr X 3) prior to ureteroscopy. 65 patients had a preoperative positive culture. A significant percentage of both groups had a preoperative positive urine culture (29%-group 1; 18%-group 2). Seven out of 9 septic events developed in those patients (P<0.001). Patients undergoing RIRS procedures were at increased risk for a septic event when treated with conventional APT (7/9 events; P<0.01). No significant correlation was found between preoperative kidney drainage (stent or nephrostomy tube) and sepsis. Conclusions Our study demonstrates that a significant portion of patients undergoing ureteroscopic treatment for urinary stones have positive preoperative urine culture, despite previous treatment. Standard, 'one size fits all' APT is not sufficient according to our data. A regimen tailored to the local bacterial resistance strains can lower the rate of sepsis significantly. Funding None
Authors
Ariel Zisman
Shadie Badaan Alexander Kastin Alexander Kravtsov David Kakiashvili Gilad E. Amiel Michael Mullerad |
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MP75-11 |
Renal stone culture and sensitivity is a better predictor of potential urosepsis than pelvic or midstream urine culture and sensitivity |
Stone Disease: Surgical Therapy VII | 17BOS |
Abstract: MP75-11 Sources of Funding: none Introduction Septicemia is a serious complication following percutaneous nephrolithotomy(PCNL) and can occur inspite of sterile preoperative urine culture and prophylactic antibiotics. The aim of the study was to analyze the utility of cultures of mid stream urine(MSU), renal pelvic urine and crushed stones for prediction of urosepsis Methods We performed a prospective clinical study in consecutive patients undergoing PCNL between April 2015 and Oct 2015. The samples collected for culture and sensitivity (C&S) were 1) MSU one day before surgery, 2) Urine from pelvicaliceal system during percutaneous puncture, and 3) Stone fragments collected during the procedure.All the patients were monitored in the postoperative period for symptoms and signs of urosepsis. The data collected were divided into 3 main groups MSU C&S, pelvic urine C&S and stone C&S and analyzed to determine association with urosepsis. Results A total of 83 patients were included. The MSU C&S was positive in 10.8%, pelvic C&S in 13.7% and stone C&S in 30.1% patients. 20 patients had systemic inflammatory response syndrome (SIRS) and 3 patients had septic shock. Out of the 20 with SIRS, 17 cases were stone C&S positive, 6 were pelvic urine C&S positive and 2 patients had positive MSU C&S Conclusions Stone C&S is a better predictor of potential urosepsis than pelvic urine and MSUC &S which often fail to grow stone colonizing bacteria. We recommend routine collection of stone for C&S for the diagnosis and management of urosepsis after PCNL. Funding none
Authors
KARTHIK TANNERU
RAHUL DEVRAJ ramreddy ch |
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MP75-12 |
Prospective Evaluation of Stone Free Rates by Computed Tomography After Aggressive Ureteroscopy |
Stone Disease: Surgical Therapy VII | 17BOS |
Abstract: MP75-12 Sources of Funding: None Introduction Previous retrospective and prospective studies have shown surprisingly low stone free rates (SFR) (approximately 50%) after ureteroscopy (URS) using stringent computed tomography (CT) criteria, although the aggressiveness of fragment extraction was not always quantified. Our goal was to determine SFR by CT after URS and aggressive fragment retrieval, quantified by the number of ureteroscope passes through a ureteral access sheath (UAS). Methods We prospectively evaluated patients undergoing URS with laser lithotripsy at our institution from December 2015 to October 2016. UAS were used in all patients except those with distal ureteral stones. Every attempt was made to extract all stone fragments, regardless of size, after fragmentation. Patient demographics, stone number, size, and location, and the number of passes of the ureteroscope were recorded. SFR was determined using non-contrast CT scan approximately 8 weeks after the procedure. Stone free (SF) cohort was compared to the residual fragment (RF) cohort using the student&[prime]s T-test and the chi-squared test, and binary logistic regression identified factors associated with stone free status. Statistical significance was set at p < 0.05. Results In total, 104 patients (141 renal units) underwent URS, with 67 patients (84 renal units) completing radiographic follow up to date. Mean number of stones was 3.3 and mean aggregate stone size was 13mm. Our overall SFR was 55%, with a mean number of ureteroscope passes of 44 (range 1 - 164). On univariate comparison between the SF and RF cohorts, SF patients had fewer numbers of stones (2.4 vs. 4.3, p=0.001), smaller aggregate stone size (11 vs. 15mm, p=0.02), and a smaller proportion of renal or renal and ureteral stones (54% and 15% vs. 66% and 26%, respectively, p=0.003). There were no significant differences in OR time, UAS size, or the number of ureteroscope passes (41 vs. 48, p=0.4) between groups. Binary logistic regression revealed no significant factors predictive of SF status. Conclusions SFRs by CT after URS are disappointingly low even with aggressive manual fragment retrieval. Larger sample size is likely to identify select cohorts of patients that benefit most from URS. Funding None
Authors
Noah Canvasser
Aaron Lay Elysha Kolitz Jodi Antonelli Margaret Pearle |
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MP75-13 |
The C.R.E.A.M. Nephrolithometry Score: A Comprehensive Grading System Based on Non-enhanced CT Scan to Predict Success of Flexible Ureteroscopic Lithotripsy for Renal Calculi |
Stone Disease: Surgical Therapy VII | 17BOS |
Abstract: MP75-13 Sources of Funding: none Introduction To propose a scoring system to standardize and grade the complexity of flexible ureteroscopic lithotripsy (FURL) for renal calculi. The current predict methods available for percutaneous nephrolithotomy (PCNL) are not validated for FURL procedures. Methods The C.R.E.A.M. score comprises 5 reproducible variables from non-enhanced CT: (C)ount of stone number, (R)elationship between stone and parenchyma, (E)ssence of stone density, (A)rea the stone locates in, and (M)easurement of stone burden. Each of components is scored on a 3-grade scale. We first propose a novel method to standardize the stone location without considering the anatomical features of collection system. A vertical axis line through the highest point of lower lip (HPL) of renal pelvis, a horizontal line from HPL to middle parenchyma, and a 45 degree diagonal line from HPL to lower parenchyma are drawn on coronal plane of kidney. The collection system is segmented to 3 areas by the lines (diagram resembles lower case letter &[prime]k&[prime]), which we named K-Segmentation. The C.R.E.A.M. score was validated on 112 consecutive FURL procedures performed by one single experienced surgeon in our tertiary medical center. Results The mean C.R.E.A.M score was 9.6 (range 5-15). The immediate stone-free rate (SFR) was 58.0% confirmed by plain film obtained on first postoperative day. The score correlated with the operation time (P<0.001). The patients with residual stones had significant higher scores than those with stone free (10.7 vs 8.3, P<0.001). Additionally, the SFR of simple (score 5-8), medium (score 9-12), and complex (score 13-15) group were 77.6%, 54.2%, 6.7%, respectively. There was significant difference between groups (P<0.001). 20 complications (17.9%) were recorded. All were postoperative urosepsis including 3 Clavien grade one and 17 Clavien grade two. The distribution was 5 (10.2%) in simple, 10 (20.8%) in medium, and 5 (33.3%) in complex group. Conclusions The C.R.E.A.M. score can be applied to accurately predict the outcome of FURL procedure. For complex renal stones with high C.R.E.A.M scores, the SFR after FURL would be extremely low and other modalities such as PCNL should be considered. Funding none
Authors
Ke Liu
Chunlei Xiao Yichang Hao Lulin Ma |
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MP75-14 |
The Impact of One Week of Pre-operative Tamsulosin on Deployment of 16-French Ureteral Access Sheaths |
Stone Disease: Surgical Therapy VII | 17BOS |
Abstract: MP75-14 Sources of Funding: None Introduction Use of an ureteral access sheath (UAS) has been shown to decrease operative time, improve stone free rates, and lower intrarenal pressures during ureteroscopy. With a bigger UAS, the larger dual lumen ureteroscopes can be passed and stone fragments up to 4 mm can be retrieved. We hypothesized that facilitating ureteral relaxation might aid placement of the 16F UAS. In late 2016, two surgeons (JL and RVC) began to routinely pre-treat patients undergoing percutaneous nephrolithotomy (PCNL) or ureteroscopy (URS) for 1-week with tamsulosin._x000D_ Methods A retrospective chart review was conducted on 84 patients who underwent PCNL or URS in non-stented ureters between January 2015 and September 2016. Demographic data, tamsulosin usage, UAS size (11F, 14F, and 16F), deployment failure, and occurrence of ureteral injuries were reviewed. We performed a univariate and multivariate analysis to assess the impact of tamsulosin administration on the size of the UAS deployed._x000D_ Results There was no difference between the tamsulosin group and non-tamsulosin group with regard to age, sex, BMI, or side of ureter treated (Table 1). The tamsulosin group had a higher percentage of 16F deployment 83% vs 39% (p<.001), and no significant difference in ureteral injuries (4% vs 3%). Univariate and multivariate analysis (Table 2) revealed that tamsulosin pre-treatment statistically significantly increased the odds ratio (16.0 and 22.9, respectively) for successful passage of a 16F UAS vs 14F UAS. _x000D_ Conclusions In this retrospective study, one week of pre-operative tamsulosin was associated with an increase in the successful deployment of a 16F UAS. _x000D_ Funding None
Authors
Kamaljot S. Kaler
Shoaib M. Safiullah Roshan M. Patel Daniel Lama Young H. Ko Zhamshid Okhunov Jaime Landman Ralph V. Clayman |
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MP75-15 |
Real time whole course monitored ultrasound guided percutaneous renal access establishment using balloon dilation?135 cases in a single center |
Stone Disease: Surgical Therapy VII | 17BOS |
Abstract: MP75-15 Sources of Funding: None Introduction Balloon dilation with fluoroscopic guidance when gaining percutaneous renal access is generally regarded as the safest technique in western countries. However, a major drawback of fluoroscopy is the radiation. Herein, we introduce the safety and effectiveness of ultrasound monitored balloon dilation in the establishment of percutaneous renal access, based on our experience. Methods A retrospective study was performed of patients who underwent percutaneous nephrolithotomy (PCNL) by using ultrasound monitored balloon dilation in our center from December 2014 to May 2016. Data of the patients were analyzed, such as age, sex, stone burden, operative time, operation success, and postoperative findings. The severity of surgical complication was determined according to the Modified Clavien Classification System (MCCS). Results 135 patients (69 male and 66 female) with a mean age of 51.6 years (range 34-74 years) were included in this study. Mean size of the largest stone diameter was 36.3mm (range 22.1-48.9mm). A total of 169 percutaneous renal tracts were gained in 142 kidneys. Successful tracts gained by balloon dilation to the collecting system was 94.7% (160/169). All procedures were successfully completed with no major complications during operation. Mean operative duration was 67min (range 51-148min). Mean temperature and mean postoperative hemoglobin drop on the 1st postoperative day were 37.5? (range 36.5-39.6?) and 1.2g/dl (range 0.1-3.2g/dl), respectively. Clavien I complications were noted in 50 cases (transient hematuria in 22 patients, fever in 28 patients), while Clavien II complications were noted in 2 cases (hematuria in 2 patients requiring pharmacological treatment). No major complications (Clavien III-V) occurred. The stone-free rate of PCNL was 82.96% (112/135). Conclusions Our experience demonstrates that real time whole course monitored ultrasound guided percutaneous renal access establishment using balloon dilation was safe and efficient because of its high stone-free rate and low operative time, compared to literatures. It could help to avoid exposition to radiation, not increase the risks of infection, bleeding and postoperative complications. Patients with a hydronephrotic collecting system or target calyx are more suitable for this procedure. Funding None
Authors
Shu Wang
Xin Zhang Bo Xiao Weiguo Hu Song Chen Jianxing Li |
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MP75-16 |
Supracostal Access Tubeless Percutaneous Nephrolithotomy: Minimizing Complications |
Stone Disease: Surgical Therapy VII | 17BOS |
Abstract: MP75-16 Sources of Funding: None Introduction Supracostal access in percutaneous nephrolithotomy (PCNL) may be avoided due to concern for thoracic complications. The objective of the study is to report the safety and efficacy of supracostal access utilizing a tubeless (stent only) PCNL technique. Methods From July 2010 to Oct 2016, 70 patients (76 renal units) underwent a supracostal access tubeless PCNL. The study is a retrospective review of their perioperative and postoperative outcomes. All patients underwent a non-contrast CT prior to the surgery. No nephrostomy tubes were left and all patients had a 7F ureteral stent and Foley catheter placed. The nephrostomy sheath was removed with the patient held in expiration, similar to a chest tube, and the incision closed. Results Median patient age was 62 years. Median BMI and ASA score was 32.9 kg/m2 and 3, respectively. The median stone size was 20 x 21 mm, and 13 patients had complete staghorn stones. The upper calyx was the site of access in 50 cases. The access was above the 12th and 11th rib in 57 and 12 cases, respectively. The median length of hospital stay was 30 hours. Postoperatively, 48 (63%) patients had no residual fragments (<2 mm) on postoperative imaging. 8 patients underwent an ancillary procedure to clear residual stones (7 URS and 1 ESWL), with an additional 6 patients becoming stone-free after this procedure. Thoracic complications occurred in 2 (2.6%) patients: 1 small pneumothorax that resolved with conservative management, and 1 symptomatic ipsilateral pleural effusion requiring thoracocentesis. Other complications occurred in 9 patients (11.8%) which included bleeding requiring transfusion (1), fever (4), urinary retention (2), and syncope (2). Conclusions Compared to historical controls, our approach to upper tract PCNL utilizing a nephrostomy tube free approach resulted in an overall low thoracic complication rate and facilitated hospital discharge. Funding None
Authors
Michael Sourial
Nathaly Francois Hiroko Miyagi Geoffrey Box Bodo Knudsen |
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MP75-17 |
C-Reactive Protein and Erythrocyte Sedimentation Rate Predicts SIRS after Percutaneous Nephrolithotomy |
Stone Disease: Surgical Therapy VII | 17BOS |
Abstract: MP75-17 Sources of Funding: None Introduction To test the hypothesis that high levels of pre-operative C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are associated with an increased risk of systemic inflammatory response syndrome (SIRS) following percutaneous nephrolithotomy (PCNL). Methods Retrospective cohort study of patients who underwent percutaneous nephrolithotomy at our institution between October 2012 and October 2013 when ESR and CRP levels were part of our standard pre-operative order set. The primary endpoint was the development of SIRS postoperatively; defined as having 2 of the following: temperature >38C or <36C, heart rate >90 beats per minute, respiratory rate >20 breaths per minute or WBC count >12,000 cells/uL or <4000 cells/uL. Multivariable logistic regression was used to evaluate the association between ESR, CRP and the development of SIRS while controlling for potential confounders. Receiver operating characteristics curves were used to evaluate the discriminative ability of the test and identify the optimal cut-offs which maximized sensitivity and specificity. _x000D_ _x000D_ Results Among the 107 PCNLs performed during the study period, 35 (33%) of patients had evidence of SIRS during the post-operative stay. Patients who experienced SIRS had a longer operative time (99 min vs. 85 min, p = 0.016), were more likely to have been transferred to the intensive care unit (ICU) (15% vs. 0%, p = 0.002) and experience a longer length of stay (median 2 days vs. 1 day, p < 0.001). On multivariable analysis controlling for operative time and the presence of a positive pre-operative urine culture, both ESR (odds ratio [OR] 1.32, 95% confidence interval [CI], 1.01-1.72, p = 0.04) and CRP (OR 1.59; 95% CI, 1.07-2.37, p = 0.02) were associated with development of SIRS. Among patients without a positive urine culture, an ESR >6.5 mm/hr (AUC 0.62; 95% CI, 0.52-0.78) had sensitivity, specificity, and negative predictive value of 70.4%, 61.5%, and 80.0% respectively, for development of SIRS. Among all patients, a CRP >0.65 mg/dL (AUC 0.63; 95% CI, 0.51 to 0.74) had sensitivity, specificity, and negative predictive value of 51.4%, 69.4%, 74.6%. The combination of a high ESR and CRP using the previously described thresholds demonstrated a lower sensitivity at 31% and higher specificity at 78%. Conclusions A preoperative blood test for ESR and CRP was predictive for the development of SIRS after PCNL. This knowledge could be used to risk-stratify patients and guide duration of antibiotic prophylaxis prior to PCNL, particularly among those without a positive urine culture. Funding None
Authors
Vishnu Ganesan
Robert Brown Juan Jimenez Shubha De Manoj Monga |
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MP75-18 |
Comparison of Costs and Outcomes of Percutaneous Nephrolithotomy Based on Percutaneous Access |
Stone Disease: Surgical Therapy VII | 17BOS |
Abstract: MP75-18 Sources of Funding: none Introduction Establishing access into a kidney is a prerequisite for percutaneous nephrolithotomy (PCNL). Currently, access is urologist-obtained (UOA) or radiologist-obtained. Ancillary services like interventional radiology (IR) add significant cost and delay, impacting hospital profit margin. Methods We performed a retrospective review of our institutional database of consecutive PCNLs from 01/2014 to 09/2015. The study subjects were separated by which group established renal access. Patient characteristics and clinical variables including blood loss, change in laboratory parameters, length of stay, and complications were analyzed. Costs and material expenses were also compared. Statistical analysis was performed using chi-square, Fisher&[prime]s exact test, and t-test. P value < 0.05 was considered significant. Results Of the 76 PCNLs, 23 (30%) cases contained a UOA. These were performed by two fellowship-trained endourologists: one who routinely obtains renal access and the other who routinely has initial access by IR. The operative details, post-operative parameters, and length of stay were not significant (Table 1). No significant differences in overall complications existed between the two groups (p=0.82). The materials cost for the operating room was higher for a UOA, but not significant (Table 2). When factoring ancillary service costs, the difference became significant ($1500.13 vs. $2150.90, p = 0.0001). Average total cost was cheaper for a UOA PCNL, $29,997.12 versus $34,299.39, or a savings of $4,302.27. Analysis using specific operating room and IR staff/facilities costs show that there is about a 20-minute buffer before the cost-benefit of establishing a UOA is erased. Conclusions Either method of access is suitable for PCNL and offers no significant advantage to clinical outcomes. However, the use of IR led to a 14% increase in costs. Funding none
Authors
Rutveej Patel
Kushan Radadia Christopher Han Ephrem Olweny Sammy Elsamra |
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MP75-19 |
National Trends In Imaging Following Ureteroscopy & Shockwave Lithotripsy |
Stone Disease: Surgical Therapy VII | 17BOS |
Abstract: MP75-19 Sources of Funding: none Introduction Imaging after ureteroscopy (URS) and shockwave lithotripsy (SWL) is suggested by the American Urologic Association to ensure stone fragment clearance, resolution of hydronephrosis, and rule out ureteral stricture formation. To our knowledge, no prior studies have examined large-scale national imaging patterns after procedural intervention for nephrolithiasis. We sought to characterize imaging utilization patterns after URS and SWL. Methods Using Marketscan, a private employer-based insurance database, we identified patients 17-64 years old undergoing URS or SWL between 2007-2014. A minimum of 12 months of enrollment was required and patients were excluded if they received more than 1 lithotripsy procedure of any type within 90 days. Imaging modalities identified by CPT and ICD-9 codes included computed tomography (CT), renal ultrasound (US), abdominal X-ray (KUB), and intravenous pyelogram (IVP), and were tracked postoperatively. Utilization patterns by demographic factors were assessed using chi-squared test. Results A total of 100,710 patients met inclusion criteria following URS, with 39% having no post-operative imaging within 12 months. Only 45% underwent imaging within 3 months of URS, most commonly KUB (28%). At 3, 6, and 12 months, only 26%, 33%, and 42%, respectively, of URS patients had any anatomic imaging (US, CT, or IVP). A total of 109,237 patients met inclusion criteria following SWL, with 16% having no postoperative imaging within 12 months. 78% underwent imaging within 3 months; most commonly KUB (69%). By 3, 6, and 12 months, 19%, 26%, and 36%, respectively, of SWL patients had any anatomic imaging. _x000D_ KUB was the most common imaging modality after either intervention type (38% of URS, 74% of SWL) within 12 months, followed by CT (25% of URS, 24% of SWL), then US (23% of URS, 17% of SWL). Over the 7 year study interval US increased by 10% after URS and 6% after SWL, while CT use decreased by 4%. Older age and female sex were independently associated with higher rates of imaging (p<0.001). US use was 13% higher in the Northeast, and more likely to be utilized in patients in metropolitan statistical areas or enrolled in health maintenance organizations._x000D_ Conclusions Despite recommendations for routine imaging after stone procedures, a large proportion of insured patients received none, especially following URS. The majority of URS and SWL patients did not receive any postoperative anatomic imaging, which may raise the risk of undiagnosed ureteral strictures, silent obstruction, and renal function loss. Although RUS use is slowly increasing, it remains underutilized compared to CT. Funding none
Authors
Justin Ahn
Sarah Holt Philip May Jonathan Harper |
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MP75-20 |
Evaluation of the treatment of distal uretral stones causing renal colic in a high intervention setting |
Stone Disease: Surgical Therapy VII | 17BOS |
Abstract: MP75-20 Sources of Funding: MSI Foundation, Edmonton, Alberta Introduction Renal colic is a common condition affecting up to 10% of the population causing significant morbidity. Research has shown that an unsuccessful trial of medical expulsive therapy has no detrimental impact on the patients (Portis et al., Urology 2015). Therefore, we wish to evaluate a large cohort of renal colic patients in a high intervention setting to determine the effect of stone location and treatment on patient outcomes. Methods This multicenter administrative database study retrospectively reviewed the all Calgary patients with an ED diagnosis of renal colic between Jan 1, 2014 and Dec 31, 2014. Demographics were captured from the regional ED database, tests and treatments from the order entry database, and ED revisits, admissions and interventions from the discharge abstract database. Events were collated from all regional hospitals (4 sites). Results 3104 renal colic visits were studied at 4 hospitals, including 921 (29.7%) with an index surgical intervention and 2183 (70.3%) managed medically. 1850 (59.6%) had imaging confirmed ureteral stones with 752 (40.6%) of these patients receiving surgery at an index visit. While proximally located ureteral stones were more likely to receive surgery at the index visit (OR = 2.177, 95% CI 1.80-2.64; P< 0.001), distally located stones were still frequently operated on with 34% of distal stones receiving surgery. Distal stones that are treated surgically at the index visit are more likely to re-visit the emergency department (OR = 2.011, 95% CI 1.535-2.635; p<0.001) and be admitted (OR = 3.103, 95% CI 2.130-4.520; p<0.001). There was no significant difference in patients returning for further surgery within 60 days of the index visit between these two groups (p=0.232). Conclusions Patients that present with acute renal colic and have an imaging confirmed distal ureteral stones are commonly operated on at the sites analyzed. Distal ureteral stones that were managed surgically were more likely than those that received conservative management to re-visit the emergency department and be admitted. These findings suggest that conservatively managing patients with distally located stones does not have a negative effect on these patients. This retrospective study does not consider complicating factors that may have influenced the treatment of these patients. Surgical intervention remains an appropriate treatment for distal ureteral stones depending on the individual contexts of patient cases. Funding MSI Foundation, Edmonton, Alberta
Authors
Bruce Gao
Taylor Remondini Premal Patel Navraj Dhaliwal Ravneet Dhaliwal Adrian Frusescu Anthony Cook Grant Innes Bryce Weber |
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MP76-01 |
Sharp Decrease in Prostate Biopsy Incidence with Wide Geographic Variation Following Task Force Prostate Cancer Screening Recommendations |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making IV | 17BOS |
Abstract: MP76-01 Sources of Funding: Emory Urology Research Scholars Grant; Winship Cancer Institute Prostate Cancer Pilot Grant Introduction Since the United States Preventative Services Task Force (USPSTF) recommendations against routine prostatic specific antigen (PSA) screening in 2012, PSA testing has declined significantly. We hypothesized that prostate biopsy incidence would mimic this pattern. We characterized trends from 2012-2014, and described factors associated with geographic variation in biopsy use. Methods Using Medicare Provider Utilization and Payment data (2012-2014), we captured reimbursements for prostate biopsies (i.e., CPT 55700) performed by physicians performing ≥10 annual biopsies. We calculated annual incidence (i.e., number of biopsies per 1,000 eligible men) across 306 hospital referral regions (HRR). HRR-level factors of interest included % men ≥75 years of age with PSA screening in 2012, % African-Americans, provider density, average hierarchical condition category (HCC) index (for Medicare risk adjustment), and number of male beneficiaries. Multivariable regression adjusted for factors associated with annual incidence of prostate biopsy, and predicted prostate biopsy incidence ratios were generated across all HRRs. Results Overall, we identified 359,698 biopsies performed by physicians, and the annual incidence ratio decreased from 10.95 biopsies/1,000 men in 2012 to 8.74 biopsies/1,000 men in 2014 (p<0.001). In 2014, the strongest associations with incidence of prostate biopsy were seen with % PSA screening (β=+2.25 per 10% screened, p<0.001) and biopsy provider density (β=+2.00 per provider per 1,000 men, p<0.001). There was also a significant associations seen with % African-American population (β=+0.47 per 10% increase, p=0.017) and inverse association with average HCC score (β=-0.07 per 0.01 increase, p=0.006). At the HRR-level in 2014, we noted nearly 40-fold variation across 306 HRRs, from predicted 0.75 to 19.51 biopsies per 1,000 eligible men (Figure, p<0.001)_x000D_ Conclusions The incidence of prostate biopsies has decreased in parallel to drops in PSA screening and prostate cancer incidence after 2012. PSA screening and provider density were strongly associated with prostate biopsy incidence, and unmeasured patient and provider-level factors are likely driving considerable geographic variation in the use of prostate biopsy. Funding Emory Urology Research Scholars Grant; Winship Cancer Institute Prostate Cancer Pilot Grant
Authors
Mark Henry
David Howard Dattatraya Patil Benjamin Davies Christopher Filson |
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MP76-02 |
Urologist practice affiliation and intensity modulated radiation therapy for prostate cancer |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making IV | 17BOS |
Abstract: MP76-02 Sources of Funding: This work was supported by research funding from the NCI (R01 CA168691) to BKH and VBS. FRS is supported by the Department of Veterans Affairs, Veterans Health Administration, VISN1 Career Development Award. Introduction Prostate cancer treatment is a significant source of morbidity and spending. It is widely believed that some men with prostate cancer, particularly those with significant health problems, are unlikely to benefit from treatment. Financial incentives associated with urologist ownership of radiation facilities have the potential to spur utilization despite this understanding about disease biology. Methods Using a 20% sample of national Medicare claims between 2010 and 2013, prostate cancer treatment was measured according to urologist practice affiliation (i.e., single specialty groups by size, multispecialty group). Overall treatment, and intensity modulated radiation therapy (IMRT) in particular, was further assessed by urologist ownership of IMRT and patient risk of non-cancer mortality within 10 years of diagnosis. Generalized estimating equations were used to adjust for patient differences. Results Among the men with newly diagnosed prostate cancer, use of IMRT ranged from 23.5% in multispecialty groups to 37.4% in large urology groups (p < 0.001). In the cohort, 5,133 patients were managed in urology groups with IMRT ownership. Urologists with ownership interest were more likely to use IMRT compared with non-owners practicing in single specialty groups (42.5% vs. 29.5%, p < 0.001), regardless of group size. Among patients with a very high risk (≥ 75%) of non-cancer death within 10 years of diagnosis, both IMRT use (41.6% vs. 26.3%, p < 0.001) and overall treatment with curative intent (52.7% vs. 43.5%, p < 0.001, Figure) were more likely in urology groups with ownership compared with non-owners, respectively. Conclusions Urologists practicing in single-specialty groups with an ownership interest in radiation therapy are more likely to treat men with prostate cancer, including those with a high risk of non-cancer mortality. Funding This work was supported by research funding from the NCI (R01 CA168691) to BKH and VBS. FRS is supported by the Department of Veterans Affairs, Veterans Health Administration, VISN1 Career Development Award.
Authors
Lindsey Herrel
Brent Hollenbeck Samuel Kaufman Phyllis Yan Tudor Borza Florian Schroeck Bruce Jacobs Ted Skolarus Vahakn Shahinian |
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MP76-03 |
Small Effect of Pharmaceutical Industry Payments to Physicians on Medicare Prescription Habits: Using Abiraterone and Enzalutamide |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making IV | 17BOS |
Abstract: MP76-03 Sources of Funding: none Introduction Abiraterone and enzalutamide are both oral chemotherapeutic agents used in metastatic prostate cancer that have been aggressively marketed to physicians since FDA approval in 2011 and 2012, respectively. We sought to investigate if there is an association between pharmaceutical industry payments to physicians and prescriptions for abiraterone and enzalutamide. Methods Using the Open Payments Database from 2014, we determined the number and total dollar amount of payments from industry to each urologist or oncologist who prescribed abiraterone and enzalutamide. These data were merged with the 2013 Medicare Part D Provider and Utilization Data to identify the total claim count ascribed to each physician as well as the total drug cost per prescribing physician. Drug costs (primary outcome) and claim counts (secondary outcome) were compared between prescribers who did and did not receive industry payment using Wilcoxon rank-sum tests. A Spearman Rank correlation was used to assess the relationship between industry payments and total drug costs/total claim counts for each drug. Results For abiraterone, we identified 4918 Open Payment recipients and 1197 prescribers, of whom 615 were both recipients and prescribers. The median payment amount to prescribers was $72 (IQR $26-$114). For enzalutamide, we identified 7820 Open Payment recipients and 412 prescribers, of whom 289 were both recipients and prescribers. The median payment amount to prescribers was 59$ (IQR $25-$148). There was no statistical association between industry payment amount and total drug costs among abiraterone prescribers (ρ = 0.07, p = 0.11) and there was a small association among enzalutamide prescribers (ρ = 0.33, p < 0.001) (Figure). _x000D_ Conclusions Industry payments to prescribers of abiraterone and enzalutamide were common but of low amount. There was a small association between total drug costs and industry payments for prescribers of enzalutamide, but not abiraterone. Continued public reporting of industry payments to physicians will allow for further investigation of this relationship. Funding none
Authors
Omar Ayyash
Jathin Bandari Robert Turner Bruce Jacobs Benjamin Davies |
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MP76-04 |
Recent trends in funding of clinical trials for Urological malignancies. |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making IV | 17BOS |
Abstract: MP76-04 Sources of Funding: none Introduction Clinical trials form the basis for clinical decision making. Most trials are funded by one of several large groups including the National Institute of Health (NIH,) pharmaceutical industry or university or other healthcare organization. In 2005, public reporting became required for major journal publication in 2007 the U.S.F.D.A. mandated registration for a large range of trials. We examine trends in funding for Urological malignancies across the last decade. Methods The publicly available www.clinicaltrials.gov website was individually queried for new trials first received between 2006 and 2015 for the following search terms: "prostate cancer," "kidney cancer" and "bladder cancer." Each category was then stratified by funder type including: NIH, Industry, Other Federal Agency and all others (individuals, universities, organizations.) Trends in funding sources across the decade were examined. Results Newly registered clinical trials from 2006 to 2015 included 2,487 prostate, 901 kidney and 517 bladder trials, with an upward trend in overall, prostate and bladder trials across the decade. Figure 1 reflects the distribution among cancer type. For all three malignancies, the absolute number of NIH-funded trials decreased while industry funded trials increased when comparing 2006 to 2015. Prostate cancer: NIH: 52 &[rarr] 36, Industry: 67 &[rarr] 83 (p=0.043) Kidney cancer: NIH: 37 &[rarr] 15, Industry: 28 &[rarr] 38 (p=0.002) Bladder cancer: NIH 15 &[rarr] 10, Industry 12 &[rarr] 39 (p=0.002). Similarly, the percentage of NIH funded trials showed a progressive decrease across the decade for all three malignancies. Trials run by &[prime]other&[prime] organizations including individuals, universities and organizations displayed the most growth comprising 13-27% of studies in 2006 compared to 43-57% of trials in 2015. Percentage distribution by funder type for each malignancy is reflected in Figure 2. Conclusions The funding of new trials for prostate, kidney and bladder cancer have each exhibited a progressive, sustained decrease in federally-funded trials across the last decade, while there has been in an increase in industry funded trials. It is critical to consider the sources of funding for clinical trials, and strive for balanced distribution of research funds. Funding none
Authors
Ariel Schulman
Ghalib Jibara Christina Sze Kae Jack Tay Efrat Tsivian Thomas Polascik |
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MP76-05 |
Radical Cystectomy: The association between distance to treating facility and quality of care |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making IV | 17BOS |
Abstract: MP76-05 Sources of Funding: None Introduction Overall Survival for Muscle Invasive Bladder Cancer (MIBC) with Radical Cystectomy (RC) is improved with neoadjuvant chemotherapy and surgery in high-volume centers. However, concentration of care inadvertently increases the average travel distance for patients who may have a post-RC complication. Using data from the National Cancer Data Base (NCDB), we evaluated the association between increasing travel distance in patients undergoing RC and the likelihood of receiving high volume care, neoadjuvant chemotherapy and overall survival. Methods Data were obtained from NCDB 2004-13. Patients had MIBC (T2-T4a, N0, M0) treated with RC. Distance to treating facility was examined in 3 categories (<12.5, 12.5-49, 50-250 miles). Multivariate logistic regression analysis was preformed to examine the interaction between distance and overall survival, then to test receipt of neoadjuvant chemotherapy. Multinomial regression examined the interaction between travel distance and RC volume tertiles (<3, 3-6, >6 per year). Results 11,059 patients treated with RC identified, including 2609 that had neoadjuvant chemotherapy. Hazard ratios for overall survival, receipt of neoadjuvant chemotherapy, as well as volume of RC are presented in Table 1. Overall survival was not associated with travel distance. As distance to facility increased, so did the likelihood that a patient received neoadjuvant chemotherapy. Increase in distance was also associated with facilities that had high volumes of RC. Conclusions As distance to treatment facility increased, the likelihood that a patient would receive neoadjuvant chemotherapy or have surgery at a high volume center also increased, supporting the relationship between concentration of care and quality. Nevertheless, overall survival was not affected by distance. Funding None
Authors
Stephen Ryan
Patrick Karabon Gregory Mills Moritz Hansen Matthew Hayn Mani Menon Quoc-Dien Trinh Firas Abdollah Jesse Sammon |
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MP76-06 |
Trends in use of androgen deprivation therapy with radiation in high and very high risk prostate cancer patients |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making IV | 17BOS |
Abstract: MP76-06 Sources of Funding: none Introduction For men with high and very high risk prostate cancer, level I evidence supports the use of androgen deprivation therapy (ADT) with radiation to prolong disease-specific and overall survival. However, not all patients receive ADT with radiotherapy. We sought to evaluate trends and factors associated with ADT use with radiation therapy for clinically localized high and very high risk prostate cancer. Methods We identified patients diagnosed with high or very high risk prostate cancer in the National Cancer Database from 2004-2013 and underwent external beam radiotherapy (EBRT), brachytherapy (BT) or combined EBRT and BT. ADT use was defined as receipt of ADT prior to or at the time of radiation therapy. Trends in ADT use were assessed and multivariable logistic regression was used to evaluate associations between demographic and clinical factors and the receipt of ADT. Results Of 85,442 patients with high or very high risk prostate cancer treated with radiotherapy, the proportion of patients receiving ADT increased from 52.7% in 2004 to 65.6% in 2013 (p for trend <0.001). This proportion increased from 60.1% to 68.7% for EBRT and 45.9 to 65.7% for combination radiotherapy; however use decreased in BT patients from 35.8% to 29.7% (each p for trend <0.001). Controlling for covariates and year, we found decreased odds [OR (95%CI)] of ADT use in patients who underwent BT [0.29 (0.28-0.31)] or combination radiotherapy [0.69 (0.66-72)] (Table 1). We found increased odds of ADT use in very high risk patients [2.01 (1.91-2.10)], those over 75 years old [1.16 (1.11-1.22)], patients from suburban [1.34 (1.28-1.40)] and rural counties [1.71 (1.53-1.91)], those with Medicare or Medicaid insurance [1.14 (1.09-1.18)], and with Charlson-Deyo scores of 1 [1.10 (1.05-1.15)] or greater [1.13 (1.02-1.25)]. Conclusions Use of ADT in patients undergoing radiotherapy for high or very high risk prostate cancer has increased over the past decade in patients undergoing EBRT and combination EBRT and BT. However, more than one third of these patients do not receive ADT, which represents an opportunity for quality improvement initiatives to impact the quality of prostate cancer care. Funding none
Authors
John DeLancey
Richard Matulewicz Oliver Ko Edward Schaeffer |
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MP76-07 |
Predicting Complications Following Robot-Assisted Partial Nephrectomy with the ACS-NSQIP Universal Surgical Risk Calculator |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making IV | 17BOS |
Abstract: MP76-07 Sources of Funding: None Introduction Assessment of surgical risk is integral to patient counseling and shared clinical decision-making. The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) surgical risk calculator is an easily accessible, online tool for predicting surgical outcomes after a variety of procedures. Little is known of the tool's applicability to urologic surgery. We sought to evaluate the predictive value of the calculator in a tertiary referral cohort of patients undergoing robot-assisted partial nephrectomy (RAPN). Methods We queried our prospectively maintained multi-institutional database of RAPN (n=1260) from 2008 to 2016. Preoperative details of 300 randomly selected patients were entered into the calculator. The predicted rates of complications were compared with the actual rates of observed complications. Validation of the calculator was assessed by receiver-operator area under the curve (AUC) for discrimination and Brier score (BS) for calibration. Calculated BS was also compared to a null model (null-BS); a BS lower than the null model indicates stronger predictive power for that individual outcome where a BS of zero indicates perfect prediction. Results The observed rate of any complication in our cohort was 14%, comparable with that reported in the literature, while the mean predicted rate of any complication was 5.42%. The calculated AUC for any complications was 0.51. Our cohort demonstrated a serious complication (Clavien Score ≥ 3) rate of 3.67%, lower than the predicted rate of 4.89% (AUC 0.55). The majority of the captured complications had a low BS, indicative of good calibration. However, the calculated AUC was low for all outcomes, indicating poor discrimination ability. Venous thromboembolism (VTE) and readmission had the highest AUCs - 0.67 and 0.69, respectively. Conclusions The ACS-NSQIP risk calculator poorly predicted most complications after RAPN. The model had marginal accuracy for predicting VTE and readmissions, and good accuracy for predicting the rate of serious complications, but it lacked the power to discriminate which patients were at risk to have such outcomes. These findings suggest the need for a more tailored outcome prediction model to accurately assist surgeons in counseling patients undergoing RAPN. Funding None
Authors
Jared S. Winoker
Harry Anastos David J. Paulucci Nikhil Waingankar John P. Sfakianos Ketan K. Badani |
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MP76-08 |
The impact of pathological risk factors and the management of Stage I Non Seminomatous Germ Cell Testicular Cancer |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making IV | 17BOS |
Abstract: MP76-08 Sources of Funding: None Introduction The preferred method of management for analytic stage I (CS1) Non Seminomatous Germ Cell Tumors (NSGCT) is active surveillance (AS). Approximately 30% of men with CS1 NSGCT are liable to relapse on AS. Pathological risk factors (PRF) may identify men at higher risk for relapse. Our aim was to evaluate trends in managing CS1 NSGCT and to examine the influence of PRF. Methods We used national cancer database (NCDB), 2004 to 2013; we examined AS, adjuvant Chemotherapy (ACT) and adjuvant retroperitoneal lymph node dissection (RPLND) using cross tabulation and trend analysis. We assessed PRF including, lympho-vascular invasion (LVI) and the presence of embryonal carcinoma (EC). We further examined the impact of CS1 sub-staging, IA, IB and IS, as defined by the TNM classification (UICC 2009 7th Ed.). Differences in overall survival (OS) were observed by treatment modality, based on log rank test. Results 12,211 men were classified as CS1 NSGCT in NCDB; of these 2,484 men were LVI +ve, 4,686 were LVI -ve (5041 had missing LVI data); 2,624 men had EC. Trend analyses (Fig.1) showed a stable utilization of AS (p = 0.310), a rising preference for ACT (p <0.001) and a declining utilization of RPLND (p <0.001). Analysis of PRF showed 40% of LVI +ve men had ACT vs 18% of LVI -ve men, Fig 2. The presence of EC increased the chances for ACT (32% vs 22% in those with no EC). Analysis of CS1 sub-staging showed 37% of IB and 29% of IS had ACT vs only 15% of IA sub-group. RPLND use was not influenced by sub-staging or LVI status. Conclusions AS remains underutilized in CS1 NSGCT. We observed a slow but steady rise towards more ACT usage and a declining utilization of RPLND. Utilization of ACT was greatly influenced by PRF. We believe that PRF and subgrouping of CS1 may be influencing decision making for men with CS1 NSGCT disease that is amenable to AS. Funding None
Authors
Mazen Alsinnawi
Sydney Akapame John Burns John Paul Flores Christopher Porter |
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MP76-09 |
PREDICTORS OF METASTASIS AT TIME OF DIAGNOSIS AND OVERALL SURVIVAL IN METASTATIC TESTICULAR CANCER |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making IV | 17BOS |
Abstract: MP76-09 Sources of Funding: none Introduction Few large series in the literature examine predictors of metastatic disease at time of testicular cancer diagnosis. We performed an analysis of the National Cancer Database (NCDB) to examine predictors of metastatic disease at the time of diagnosis and overall survival (OS) based on site of metastatic disease. Methods Utilizing the NCDB, 44,354 patients were identified with data available for metastatic disease at time of diagnosis and tumor histology. Metastases were stratified as either absent, lymph node only, lung, brain, liver or bone metastases. Demographic characteristics, socioeconomic indicators and tumor histology were compared using the chi-squared test. Univariate survival analysis was performed using the Kaplan Meier method. Multivariate survival analysis was performed using cox proportional hazard model. Results Mean age of diagnosis was 35 and mean follow-up was 53 months. On univariate analysis decreased age at diagnosis (p<0.001), non-white race (p=0.002), uninsured status (p=<0.001), <$38,000 annual income (p=<0.001), distance from treating hospital (p<0.001), and pure choriocarcinoma histology (166/202, 82%, p<0.001) were associated with metastases at time of diagnosis. 3,504 (7.9%) patients had metastatic disease at diagnosis. Kaplan Meier survival analysis showed significant differences in OS between metastatic sites at presentation, with 5 yr OS of 87% for lymph node only metastases compared to 48% OS in those with brain metastases (p<0.001). On multivariate analysis while controlling for age, race, insurance status, income, comorbidities, histology, receipt of chemotherapy, and primary tumor size, metastases to any site were associated with worsened survival compared to no metastases (referent): metastasis to lymph nodes (3.4, 95% CI: 2.70-4.50, p<0.001), lung (4.48, 95% CI: 3.69-5.43, p<0.001), liver (10.32, 95% CI: 6.78-15.7), bone (12.99, 95% CI: 7.93-21.29) and brain (14.4, 95% CI: 9.53-21.89). Private insurance status (0.48, 95% CI: 0.40-0.56, p<0.001) and income >$63,000 (0.72, 95% CI: 0.60-0.87, p=0.001) were favorable predictors of OS. Conclusions There are significant differences in OS dependent on site of metastases at time of testicular cancer diagnosis. Several sociodemographic factors likely contribute to likelihood of metastases at presentation as well. Further prospective studies are warranted to better characterize the impact of sociodemographic factors on metastases at presentation and to improve access to care in high-risk populations. Funding none
Authors
Marshall Shaw
Andrew Bachman Alexander Parker Brian Cross Kelly Stratton Michael Cookson Sanjay Patel |
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MP76-10 |
Burnout in Urology: Results from the 2016 AUA Census |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making IV | 17BOS |
Abstract: MP76-10 Sources of Funding: none Introduction Physician burnout is linked to decreased job performance as well as increased medical errors, interpersonal conflicts and depression. Two recent multi-specialty studies showed that compared to other physicians in the 29-65 age group, urologists had the highest rate of burnout (54.4% vs. 63.6%); however, these reports were limited by a low sample size for urologists (n=119). We aimed to establish the prevalence of urologist burnout and to determine factors associated with burnout more comprehensively. Methods In the 2016 AUA Census, Maslach Burnout Inventory (MBI) questions were randomly assigned to half of the respondents. Using matrix sampling, the 1,126 practicing urologists who received and answered the MBI questions represent the entire 2,301 who completed the Census with a sampling weight of 2.04. Burnout was defined as scoring high in either the emotional exhaustion (score≥27) or depersonalization (score≥10) categories. Demographic and practice variables were assessed through both univariate descriptive analysis and multivariate logistic analysis to establish correlating factors to burnout. Results Overall, 38.8% of urologists met the criteria for burnout, of whom 17.2% scored high for emotional exhaustion and 37.1% scored high for depersonalization. Multivariate analysis revealed that urologist burnout is associated with a variety of factors as follows (ranked from most important): greater number of patient visits in a typical week; younger age group; in sub-specialty area other than pediatric or oncology; in either solo or multi-specialty practices; practice size of more than 2; and greater number of work hours in a typical week. (See table.) Conclusions These results suggest that the burnout rate for urologists, 38.8% overall or 41.3% in urologists ages 29-65, is lower than previously reported and is consistent with rates reported in other medical and surgical specialties. Burnout continues to be an important issue for urologists. Higher workload correlated with increased burnout while other practice patterns, such as being a solo owner of a practice or working in an academic center, appear to be protective. Understanding the causes of burnout in urology will help guide future intervention. It is important to keep all urologists in the workforce to help lessen projected shortages. Funding none
Authors
Amanda C. North
Patrick H. McKenna Raymond Fang Alp Sener Brian K. McNeil Julie Franc-Guimond William Meeks Steven Schlossberg Chris M. Gonzalez James Q. Clemens |
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MP76-11 |
Is your Career Hurting You? The Ergonomic Consequences of Surgery Over Time in 701 Global Urologists |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making IV | 17BOS |
Abstract: MP76-11 Sources of Funding: None Introduction Workplace injury has been long recognized; recent attention has turned to the concern that modern surgical volumes and especially laparoscopic techniques put practitioners at risk of these injuries. We surveyed urologists to seek correlations between the type, volume and duration of surgical work performed, surgeon characteristics, and the prevalence of musculoskeletal complaint and injury across career._x000D_ Methods An anonymous web-based multi-national survey of urologists was conducted, with pain as the primary outcome. Student t-test, Fisher exact and Chi-Square tests were used for analysis._x000D_ Results 701 complete responses were received from this multi-national survey (Figure 1). Gender, pain distribution, and private or academic practice did not correlate with pain, while exercise and lower weight and BMI were protective (Table 1). Dose-response of surgical type was assessed with high and low volume density quartiles and frequency of each pain severity (Figure 2). _x000D_ Conclusions To our knowledge, no study has assessed hard endpoints of occupational spinal injury, nor sought surgeon-protective factors. In this, the largest surgical ergonomic study to date: surgical type, duration, volume, setting, and physician gender were unrelated to surgeon pain throughout career. Female practitioners seek invasive therapy less than male counterparts. Exercise appears protective against these complaints in a dose-related fashion; increasing weight and BMI are associated with pain. North Americans report less pain than global counterparts. Practitioners of direct optical cystoscopy report no more neck trouble than others. Although 47% of urologists with spinal pain blame their career, we are unable to identify any dose-response relationship that supports that assumption._x000D_ Funding None
Authors
Granville Lloyd
Amanda Chung Mark Sawyer Steve Steinberg Daniel Williams Douglas Overbey |
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MP76-12 |
The Rising Trend of Advanced Practice Provider Assistance in Urologic Surgery |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making IV | 17BOS |
Abstract: MP76-12 Sources of Funding: AUA data grant Introduction Projections demonstrate a worsening shortage of urologists in the United States in the next decade. Advanced practice providers (APPs) are increasingly used in urology and other fields to improve physician productivity. While APPs have become common in urology clinics, little data exists regarding the use of APPs in the surgical setting. Though in the past, urologists were often assisted by a second surgeon for complicated operations, we hypothesized that APPs are increasingly filling that role. This study aims to quantify the change in surgical assist patterns over time for commonly performed urologic operations. Methods We used data derived from the Medicare Physician/Supplier Procedure Summary Master File to examine the rates of APP-assisted and surgeon-assisted procedures performed by urologists from 2003-2014, as identified by CPT codes and modifiers. The annual frequency is reported by assist type for six common urologic operations: robotic prostatectomy, open prostatectomy, radical cystectomy, open nephrectomy, open partial nephrectomy, and laparoscopic nephrectomy. The average annual rates of change were determined using least squares regression and tested using t-tests (?=0.05). Results Of the 677,111 urologic operations analyzed, 5.0% of cases were assisted by APPs compared to 27.0% assisted by a second surgeon. The proportion of cases assisted by an APP rose significantly for all procedures (Figure 1); conversely, the proportion of cases assisted by a second surgeon declined significantly for all procedures, except for open partial nephrectomy. The largest changes were seen in robotic prostatectomies; similar proportions of robotic prostatectomies are now performed by APPs as by second surgeons. Conclusions Urologists are increasingly using APPs as assistants in surgery, particularly in laparoscopic and robotic cases. This trend will likely continue as the shortage of urologists worsens in coming years. At the same time, surgical assistance is less frequently being performed by a second surgeon, which may decrease opportunities for refining operative skills. APPs can be a valuable part of the surgical team, but further consideration of the impacts of this shift in practice is needed. Funding AUA data grant
Authors
Amanda Swanton
Ahmad Alzubaidi Bradley Erickson |
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MP76-13 |
Scribes in ambulatory urologic practice: Financial analysis and practice management considerations |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making IV | 17BOS |
Abstract: MP76-13 Sources of Funding: None Introduction Usability of the EMR has failed to fulfill its purported promise of increased efficiency in physician documentation. Although primarily used in the ER, medical scribes have been shown to provide high satisfaction rates for both physician and patients during urology office hours. With an aging population and shortage of physicians, urologists face pressure to see an increasing clinical workload in the office and need to maximize office based productivity and efficiency. We hypothesize that medical scribes can increase patient encounters, net revenue, and physician quality of life in the outpatient urology setting. Methods We retrospectively reviewed billable encounters of nine urologists practicing in an urban private and academic urologic practice. Number of billable encounters, scribe expense, revenue, and net revenue were compared between quarter 1 of 2015 (Q1-15) and 2016 (Q1-16). Medical scribes were integrated into the practice following a 6 month trial period and by Q1-16 the scribe – physician interaction had matured. A survey was administered to all physicians after Q1-16. Results Between Q1-15 and Q1-16 the average encounters per physician increased by 152 [range -22-382] and average revenue increased by $15,802.78 [$469 - $37,106]. Average scribe expense per physician for Q1-16 was $6,042.39 [$2,978.39 - $10,899.00] and therefore net change in revenue after accounting for scribe cost was $9,760.39 [-$2,509.39 - $26,207.00]. The average scribe cost per encounter was $8.58 [$6, $11]. We had a 100% response rate to our survey. On a scale of strongly disagree (1) to strongly agree (5), physicians reported an increase in productivity (4.4), increase in quality of life (4.8), and an average decrease in after-hours documentation of 5.9 hours. Conclusions Following incorporation of scribes, an increase in average encounters and net revenue per physician was observed. Self-assessed physician productivity and quality of life greatly increased, leading to an overwhelmingly positive impression of medical scribes within the urologic ambulatory practice. Funding None
Authors
Madeline Cancian
Gyan Pareek Stephen schiff Simone Thavaseelan |
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MP76-14 |
Patient portal usage in pediatric urology: Is it meaningful use to everyone? |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making IV | 17BOS |
Abstract: MP76-14 Sources of Funding: Dr. Bush's time was supported in part by grant number R00 HS022404 from the Agency for Healthcare Research and Quality._x000D_ Introduction As part of the Affordable Care Act, multiple directives for meaningful use of the Electronic Health Record (EHR) have been promoted including the use of a patient/provider portal with the goal of optimizing efficiency of care. Although patient portals are increasingly common, there is little information regarding their use as an engagement tool to connect patients, caregivers, and healthcare teams as partners. Use of the portal by patients and providers for children with chronic illnesses might help alleviate caregiver stresses, and may serve as a potential modality to educate patients and parents on chronic care management. However, portal enrollment patterns have not been fully studied. The Urology Division at a tertiary pediatric academic center provides the necessary patient population to examine adoption patterns. Methods We retrospectively assessed adoption and use of Epic's MyChart patient portal from January 2010- June 2016. We examined EHR data from 10,464 patients aged 2- 18 who fit 4 categories: activated (or caretaker activated) MyChart access code; accepted but did not activate a code; declined activation; or activated and then deactivated their account and who had at least one Urology appointment. Differences in adoption rates were examined using chi-square statistics and one-way Analysis of Variance (ANOVA). Results Overall, 46.5% of patients offered an access code logged into their MyChart account. Males (X2 = 10.2; p=.01); those self-identifying as "Other" (not White, Asian, or African American) (X2 375.0; p<.001); and Hispanic patients (X2= 366.5; p<.001) were less likely to activate their portal account. Patients living in central, urban areas were less likely than those living in suburban areas to activate their accounts (X2= 240.7; p<.001). Using census data for zip code region, patients who activated their account had a significantly higher median household income than those who did not activate, refused, or deactivated their account (F= 135.6; p<.001). Language was significantly associated with adoption. Those who reported their primary language as Spanish were much less likely to activate the portal (X2=895.9; p<.001) (358 of 1704) than English-speaking patients (4405 of 8480). Conclusions Our findings suggest that primary language and socioeconomic factors may be a significant barriers in adopting the portal. Focusing on patient education to reduce these barriers, may increase portal acceptance thereby making the portal a more meaningful tool for patients, parents, and providers. Funding Dr. Bush's time was supported in part by grant number R00 HS022404 from the Agency for Healthcare Research and Quality._x000D_
Authors
Diana Cardona-Grau
Ruth Bush Hena Din Andrew Richardson Cynthia Kuelbs George Chiang |
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MP76-15 |
Surgical Outcomes Center for Kids: A Research Model for Pediatric Urology |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making IV | 17BOS |
Abstract: MP76-15 Sources of Funding: None Introduction Surgical Outcomes Center for Kids (SOCKs) was born out of a need to make research infrastructure available to pediatric surgeon scientists with an interest in improving clinical care using evidenced-based medicine and evaluating patient-centered outcomes. Evolution and impact of our multi-disciplinary, trans-institutional, and multi-institutional research center on our Pediatric Urology Department is described here. Methods The overarching goal of SOCKs is to assess surgical and patient-centered outcomes that can inform future clinical decision making, identifying standards of excellence that can potentially improve resource utilization for the healthcare system. This research infrastructure gives academically-minded clinicians the ability to maintain their level of clinical productivity while establishing an active research agenda. Through internal and external funding, SOCKs supports personnel, referred to as research extenders, used to facilitate clinical research for our surgeon-scientists. These individuals oversee all aspects of the research process from hypothesis generation, data analysis and dissemination of results, allowing the busy clinician to successfully produce relevant works that can be disseminated through national podium talks and peer-reviewed publications. Results Still in infancy, pediatric urologic research has grown from 3 to 16 studies, supporting 4 research fellows, resulting in 15 abstracts (many in manuscript development), and a national clinical research award. Our center has allowed for seamless integration of research into the day-to-day clinical world without disruption. We have seen a multitude of successes since inception including 1) capturing quality of life data to better inform treatment decision making, 2) understanding the variation in interpretation of urodynamics across institutions, 3) initiating prospective patient registries allowing for better evaluation of clinical outcomes, 4) utilizing implementation science methodology to better understand the value of biofeedback therapy, and 5) reducing resource utilization through the development of multi-disciplinary imaging protocols. Conclusions The SOCKs model was created in response to the needs of our surgeon scientists to be more academically successful. This program has created a collaborative, accessible research environment without compromising clinical productivity. Additionally, this model has proven value-added to the healthcare system and has showcased the potential to positively impact on patients. Funding None
Authors
Chelsea Lauderdale
Madison Shultz Douglass Clayton Stacy Tanaka John Thomas John Pope Mark Adams John Brock Chevis Shannon |
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MP76-16 |
PATTERNS OF MEDICAL MANAGEMENT OF OVERACTIVE BLADDER (OAB) AND BENIGN PROSTATIC HYPERPLASIA (BPH) IN THE US: WHO DOES BETTER? |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making IV | 17BOS |
Abstract: MP76-16 Sources of Funding: none Introduction BPH and OAB are highly prevalent conditions that place a large burden on the US health care system. Medical management is the mainstay of therapy for both conditions, but few datasets are available that analyze patterns of medication usage and long-term persistence. This study analyzes patterns of prescription medication usage for incident BPH in men and incident OAB in men and women using US observational data. Methods Truven Health MarketScan® Commercial and Medicare Supplemental Research databases include de-identified medical claims and prescription drug claims for individuals in the US with employer-sponsored health insurance, as well as individuals with Medicare supplemental coverage. The data are pooled from diverse points of care, including large employers, managed care organizations, hospitals, and public organizations, thus providing greater generalizability than single payer databases. Men age 18+ had incident BPH with 2 diagnoses of BPH ?30 days apart and no BPH diagnosis for 1 year prior, based on ICD-9 codes for BPH, bladder neck obstruction, urinary retention, and incomplete bladder emptying. Men and women age 18+ were diagnosed similarly with incident OAB, based on ICD-9 codes for OAB symptoms (urinary frequency, urgency, nocturia, urge incontinence). Other criteria included continuous enrollment for 1 year before and 6 months after the first diagnosis date. Medication continuation (persistence), switching, and discontinuation were analyzed through September 30, 2013. Results 31,701 women and 7,208 men were prescribed OAB medication; 69,079 men were prescribed medication for BPH (Table 1). Medication persistence was much higher overall for BPH than OAB (56% vs 34%, respectively), and was highest among men with BPH age 65+ (62%). Patients age 18-64 were less likely to continue medication than older adults (age 65+) for both BPH and OAB. Conclusions Persistence was higher with BPH than OAB medications overall, likely reflecting a combination of better efficacy and tolerability of BPH medications. Funding none
Authors
Jennifer Anger
Howard Goldman Xuemei Luo Martin Carlsson Douglass Chapman Kelly Zou Fady Ntanios David Russell Canan Esinduy J. Quentin Clemens |
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MP76-17 |
PATTERNS OF CARE FOR THE EVALUATION OF HEMATURIA AMONG INSURED NON?ELDERLY PATIENTS |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making IV | 17BOS |
Abstract: MP76-17 Sources of Funding: none Introduction Fifty percent of patients with hematuria will have demonstrable causes. Full evaluation includes cystoscopy, urine cytology, and imaging. We determined patterns of care for hematuria evaluation in the insured population. _x000D_ _x000D_ Methods Utilizing a national administrative database of privately insured patients (Truven Health Analytics MarketScan® Research Database), we performed a cross-sectional analysis of men and women aged 40-65 years with newly diagnosed gross or microscopic hematuria in the calendar year 2013. Patients with pre-existing genitourinary diagnoses in the previous 12 months were excluded. The primary outcome was hematuria evaluation as assessed by the use of cystoscopy, urine cytology, and/or imaging for 6 months after a hematuria diagnosis identified by claims coding. Results We identified 22,514 and 69,310 patients with gross and microscopic hematuria, respectively; 44% of patients were male and 56% were female. Patients with gross and microscopic hematuria had complete evaluation in 6.3% and 5.2% and had no evaluation in 37.2% and 47.9% of cases, respectively (p<0.001 for all). For patients with gross and microscopic hematuria, 46.1% and 29.0% underwent cystoscopy, respectively (p<0.001). Performance of imaging and cytology are described in Table 1. Conclusions Among men and women with initial presentation of gross or microscopic hematuria, less than 6% of patients receive a complete evaluation with imaging, urine cytology and cystoscopic examination while over 48% have no evaluation. Practice patterns between gross and microscopic hematuria did not differ significantly, raising quality of care concerns that physicians treat these two conditions similarly despite significant differences in the natural history and the risk of urologic malignancies of these entities. Future studies should address causes for the discrepancies observed in the evaluation of hematuria. _x000D_ _x000D_ Funding none
Authors
Alyssa Greiman
Kit Simpson Amit Patel Sandip Prasad |
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MP76-18 |
Variability in Intensive Care Unit Use In Patients With Renal Trauma |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making IV | 17BOS |
Abstract: MP76-18 Sources of Funding: None Introduction Patients with renal trauma are frequently admitted to the intensive care unit (ICU) adding significant cost to the health care system despite lack of evidence suggesting benefit. We aimed to examine the variability of ICU use in patients with isolated renal trauma and assess the factors that may influence admission to a higher level of care. Methods The National Trauma Data Bank was used to identify isolated (Abbreviated Injury Severity Score ? 2 non-kidney regions) renal trauma patients of any age who were admitted to a designated trauma hospital from 2007 – 2014. The primary outcome was initial emergency department (ED) disposition to the ICU. Pre-admission variables assessed were age, gender, ethnicity, hypotension in ED, mechanism of injury, renal injury grade, comorbidities, insurance status, hospital trauma level, and region. Multivariable normal multiple imputation was used to address missing renal injury grade data (29% missing). Adjusted risk ratios (RR) and 95% confidence intervals (95% CI) were estimated from imputations using Poisson regression with robust standard errors and clustering by facility. Results There were 20,755 eligible subjects with a mean age of 34.3 years. Of patients with any ICU stay during hospitalization 50% had low grade renal injuries (AAST grade I/II). Over one-third of high grade injuries (AAST grade IV/V) were managed exclusively on the ward. In multivariable analysis, elderly patients were 33% more likely to be admitted to the ICU (95% CI 1.16, 1.52), as were those injured via firearm (aRR 3.71, 95% CI 3.71, 1.35), were hypotensive in the ED (aRR 2.77, 95% CI 2.13, 3.61), and those with more comorbidities (aRR 1.14; 95% CI 1.09, 1.19). The higher grade renal injuries were more likely to be admitted to the ICU (grade III aRR 1.65, 95% CI 1.49, 1.81; grade IV aRR 2.90, 95% CI 2.46, 3.42; grade V aRR 3.56, 95% CI 2.96, 4.28). Hospital trauma level and region were also significantly associated with ICU admission (Level II trauma facilities: aRR 1.24, 95% CI 1.03, 1.49; Southern region: aRR 1.36, 95% CI 1.02, 1.82). Conclusions We found that older age, more comorbidities, firearm injury, hypotension in the ED, higher grade injury, hospital trauma level II and Southern region were significantly associated with ICU admission in isolated renal trauma. A large proportion of patients admitted to the ICU have low grade renal injuries, whereas a notable portion of high grade injuries are being managed on the floor. The variability in admission patterns suggests a need for disease-specific guidelines for ICU admission in order to provide safe, cost effective, and efficient health care. Funding None
Authors
Judith C. Hagedorn
D. Alex Quistberg Saman Arbabi Monica S. Vavilala Hunter Wessells |
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MP76-19 |
Assessment of physicians' practices in screening and treating women with bacteriuria |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making IV | 17BOS |
Abstract: MP76-19 Sources of Funding: None Introduction Evidence-based screening and treatment for bacteriuria is crucial to prevent antibiotic overuse and increasing antimicrobial resistance. The Infectious Disease Society of America (IDSA) released guidelines in 2005 and 2011 on the management of asymptomatic bacteriuria (ASB) and uncomplicated urinary tract infections (UTIs) in women. We hypothesized that these guidelines have not been widely adopted. This study assessed physicians’ practices in screening and treating women with bacteriuria relative to guideline recommendations. Methods Between 7/2016 and 10/2016, cross-sectional data from physicians in relevant fields were collected using an anonymous questionnaire. Multivariable logistic regression analysis identified independent predictors of adherence to guidelines for ASB and uncomplicated UTIs in women. Results Data were collected from 260 physicians (29.6% internal medicine, 29.6% urology, 25.8% OBGYN, 9.2% emergency medicine, 5.8% family medicine). Over half of physicians surveyed were unfamiliar with the IDSA guidelines (56.9%) and overtreated ASB, or selected to give an antibiotic in a clinical scenario in which antibiotics were not indicated (54.7%). Independent variables associated with overtreating ASB included a non-academic practice (OR 3.23, p= 0.024) and practicing as an OBGYN (OR 3.65, p= 0.006). Urologists were more likely to report prescribing antibiotics in clinical scenarios where treatment is recommended by the IDSA (OR 6.50, p< 0.001). Nearly one third (30.1%) of physicians reported prescribing an antibiotic other than a recommended first-line agent for uncomplicated UTIs, including 8.1% who chose a fluoroquinolone. OBGYNs and urologists were more likely to prescribe a recommended first-line agent to women with uncomplicated UTIs (OBGYNs: OR 21.01, p< 0.001; urologists: OR 2.37, p= 0.044) compared to internists. Of those who correctly selected a first-line agent, 29.8% prescribed a longer than recommended duration of therapy. IDSA guideline awareness was not associated with physicians' practices in managing women with bacteriuria. Conclusions Most physicians surveyed were unfamiliar with guidelines related to managing ASB and uncomplicated UTIs in women, likely contributing to overscreening and overtreatment of ASB and the use of inappropriate antibiotic regimens in treating uncomplicated UTIs. However, superior antibiotic stewardship was not associated with knowledge of IDSA guidelines, suggesting that guideline dissemination alone may not alter practice patterns among physicians managing women with bacteriuria. Funding None
Authors
Erica L. Ditkoff
Carrie Mlynarczyk Casey Kowalik Joshua Cohn Wilson Sui Marissa Theofanides Matthew Rutman Rony Adam Roger Dmochowski Kimberly L. Cooper |
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MP76-20 |
Utilization of Radiation Therapy for T2/T3 Bladder Urothelial Carcinoma: A 25-Year Population-Based Analysis |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making IV | 17BOS |
Abstract: MP76-20 Sources of Funding: None Introduction The gold standard treatment for non-metastatic muscle invasive bladder urothelial carcinoma is radical cystectomy (RC) +/- neoadjuvant chemotherapy. Radiation therapy (RT) has typically been reserved for the adjuvant setting or in combination with chemotherapy when patients are medically unfit for extirpative surgery. The objective of this study was to assess factors associated with the use of RT in T2/T3 stage urothelial carcinomas and to identify utilization trends over time. Methods Patients ≥18 years of age diagnosed with AJCC stage T2/T3 bladder urothelial carcinoma were identified in the SEER database (1988-2012; n=41,448). These patients were categorized as those that received no RT, RT only, neoadjuvant RT, adjuvant RT, or both neo- and adjuvant RT. Temporal trends in utilization of RT were assessed in 5-year increments. Descriptive statistics and multivariable regression models were performed to generate odds ratios (OR) to identify factors associated with receipt of RT. Results There were 6,734 patients (16.2%) that received RT at any point in their treatment. Patients who were less likely to receive RT were younger (median age 72.2 years, no RT vs 76.8 years, RT only; p<0.001), Caucasian (no RT 84.0% vs 80.5% black; p<0.001) and married (no RT 84.6% vs 82.4% unmarried; p<0.001). Patients with T3 disease were less likely to receive only RT (7.4% vs 16.5% T2), however more likely to receive adjuvant RT (4.0% vs 0.8% T2; both p<0.001) compared to patients with T2 disease. Over time, the utilization of RT without extirpative surgery in the treatment of bladder urothelial carcinoma has increased (14.4% to 16.2%), however the utilization of adjuvant RT has declined (2.3% to 1.1%). Only 3.1% of patients that underwent RC received RT during any point in their treatment. The strongest factor associated with receipt of RT was T3 disease (vs T2 OR 1.89, 95%CI 1.73-2.05), in addition to Caucasian race (vs non-Caucasian OR 0.89, 95%CI 0.82-0.97), married status (vs unmarried OR 0.98, 95%CI 0.96-0.99), and RC (vs no RC 0.10, 95%CI 0.09-0.11). Conclusions The use of RT for patients with stage T2/T3 bladder urothelial carcinoma has increased modestly over the past 25-years, with more judicious use of RT in the adjuvant setting typically reserved for T3 disease. Furthermore, poor socioeconomic factors including non-Caucasian race and unmarried status may be associated with receipt of RT and warrants further specific evaluation. Funding None
Authors
Matthew Kaufman
Zachary Klaassen Chris Ellington Alan K. Carnes Michael Kemper Rabii Madi Martha K. Terris Durwood E. Neal, Jr. |
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MP77-01 |
11C-Choline versus 68ga-PSMA PET/CT scan for the detection of nodal recurrence from prostate cancer: results from a large, multi-institutional salvage lymph node dissection series |
Prostate Cancer: Detection & Screening VII | 17BOS |
Abstract: MP77-01 Sources of Funding: none Introduction Positron emission tomography / computed tomography (PET/CT) scan with 11C-choline or 68Ga-prostate-specific-membrane-antigen (PSMA) ligand is used to diagnose nodal recurrence of prostate cancer. However, no previous study directly compared these two tracers in men receiving salvage lymph node dissection (SLND). Methods The study included 266 patients affected by a single nodal recurrence and treated with SLND at eight tertiary referral centers. All patients were diagnosed with PET/CT scan using either 11C-choline (n=196; 74%) or 68Ga-PSMA ligand (n=70; 26%). The study outcomes were the following: (i) rate of negative histologic report at final pathology; (ii) concordance between site of positive imaging and location of positive nodes (iii) biochemical response (BR) defined as PSA ≤0.2 ng/ml at one month after SLND. Results PSA level at SLND was lower in patients diagnosed with PSMA-ligand (2.2 vs. 1.5 ng/ml, p=0.011). The single positive spot at pre-operative imaging was pelvic and retroperitoneal in 178 (91%) and 18 (9%) patients diagnosed with 11C-choline, versus 62 (89%) and 8 (11%) patients diagnosed with PSMA ligand (p=0.6). In the 11C-choline group, 41 out of 178 (23%) patients with a single pelvic spot received also retroperitoneal SLND, compared to 21 out of 62 (34%) patients in the PSMA group. In the 11C-choline group 12 out of 18 (67%) patients with a single retroperitoneal spot received also pelvic SLND, compared to 8 out of 8 (100%) patients in the PSMA group. The median number of lymph nodes removed was not significantly different (18 vs. 16, p=0.3). Overall, 50 (26%) patients diagnosed with 11C-choline and 19 (27%) patients diagnosed with PSMA had negative histologic report at final pathology (p=0.7), whereas 92 (47%) and 20 (30%) patients had ≥2 positive nodes, respectively (p=0.013). The concordance between site of positive imaging and location of positive nodes was not significantly different among groups (72% vs. 69%, p=0.3). 0verall, 93 (47%) and 23 (32%) patients had positive nodes outside the positive sites of PET/CT scan (p=0.013). The BR rate was significantly higher in the PSMA group (33% vs. 43%, p=0.016). Conclusions In patients with a single positive spot at PET/CT scan, the rate of negative histology is not significantly different when 11C-choline or PSMA are used. Moreover, both ligands significantly underestimate the true nodal tumor burden. However, using PSMA ligand tracer, similar diagnostic results may be achieved at lower PSA level. Funding none
Authors
Nicola Fossati
Nazareno Suardi Giorgio Gandaglia Armando Stabile Michele Colicchia R. Jeffrey Karnes Friederike Haidl David Pfister Daniel Porres Axel Heidenreich Christian Gratzke Annika Herlemann Christian Stief Antonino Battaglia Wouter Everaerts Steven Joniau Hein Van Poppel Alexey V. Aksenov Daniar K. Osmonov Klaus-Peter Juenemann ADL Abreu Fabio Almeida C. Fay Inderbir Gill Alexandre Mottrie Francesco Montorsi Alberto Briganti |
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MP77-02 |
First clinical experience of trimodal (18)F-choline-PET/mpMRI/TRUS targeted prostate biopsies: A pilot study for a new concept. |
Prostate Cancer: Detection & Screening VII | 17BOS |
Abstract: MP77-02 Sources of Funding: none Introduction Assess the feasibility and the accuracy of targeted prostate biopsy with standard (systematic 12-core) biopsies after fusion imaging of choline-PET/CT (choline-PET) and multiparametric MRI (mpMRI) with 3D-transrectal ultrasound (TRUS) to detect prostate cancer. The Fusion of the two modality with echography 3d was try to compare the diagnostic performance for localization of primary PCa with (mpMRI) and last generation of PET/CT (Biograph mCT Flow, Siemens). Methods Within a prospective single-center study, from December 2014 to October 2016, 31 patients with a rising PSA ? 10ng/ml or with an history of a negative prostate biopsies were included, and performed a choline-PET and a mpMRI. PET and T2-weighted MR volumes of the prostate were spatially registered using commercially available software. Biopsy targets were selected on both modalities._x000D_ TRUS biopsy using the real-time 3D TRUS-tracking system (Urostation Touch®, Koelis, France), which enabled US-guided and/or MR/US fusion targeted biopsies. _x000D_ The biopsy procedure was performed after registration of real-time TRUS with mpMRI and choline-PET by the same operator, using 3D TRUS-tracking system. At the time of biopsy, volume data of the mpMRI and PET 18-ch was elastically fused with TRUS. Each target was biopsied twice. Histologic results were determined from standard and targeted biopsy cores_x000D_ Results Mean PSA was 13.01 ng/ml (5.32-73). Mean number of biopsy was 16 (13-21) and mean prostate volume was 63.41 cc (25-169). The cancer detection rate was 69%. The cancer detection rate with standard biopsies off target was 42% and with prostate targeted biopsy was 50% using PET, 65% using mpMRI with a sensibility of 72%, 94%, 100% respectively for PET, mpMRI or both . The average number of positive cores was respectively 1.77 (1-7) ,2.74 (3-11) for PET and mpMRI. Conclusions We demonstrated the feasibility and accuracy of multimodal image registration for targeted prostate biopsies with echography 3D to define localization of prostate cancer, compared to standard biopsies. It was very interesting to observe sometimes a great difference in the distribution of PET choline targets and mpMRI targets in the prostate. mpMRI was probably better than PET to detected prostate cancer but it could be complementary. A new study with a novel ligands targeting prostate specific membrane antigen (PSMA) could improve our clinical results. Funding none
Authors
Jean-Louis Bonnal
Arnaud Marien Aurelien ROCK Khaled El maadarani Brigitte Mauroy Delphine Bessard Arnaud Delebarre Pierre Gosset Tanguy Blaire |
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MP77-03 |
Targeted 11C-choline PET/CT/TRUS software fusion?guided prostate biopsy has in men with persistently elevated PSA after previous negative biopsy |
Prostate Cancer: Detection & Screening VII | 17BOS |
Abstract: MP77-03 Sources of Funding: None Introduction Multiparametric MRI (mpMRI) has become the preferred method for detecting prostate cancer (PCa) foci after a negative biopsy and has been incorporated into EAU guidelines. Although the NPV of mpMRI is around 90-95%, some, potentially important, cancers may be mpMRI-invisible. Some men may have contraindications to MRI (i.e. claustrophobic patients or presence of metallic implants). 11C-choline PET is a promising tool for the investigation of PCa but studies have provided equivocal results because of overlap with benign prostate hyperplasia (BPH) and prostatitis. The aim of this study was to assess the potential clinical impact of 11C-choline PET/TRUS fusion-guided prostate biopsy in men with persistently elevated PSA after negative biopsy and negative or contra-indicated mpMRI. Methods Clinical data were acquired as part of a prospective ongoing observational study: MpMRI_ICH_1398; Ethical Committee approval March 2015. Patients with persistently elevated PSA, with or without ASAP and/or HG-PIN and negative DRE, after at least one negative biopsy (at least 12 cores for each biopsy course) and a negative (PI-RADSv.2 <3) or contraindications for mpMRI were the nested cases. The 11C-choline was synthesized using a General Electric TracerLab FXc module and administered in a total activity of 250-400 MBq. Total-body images were obtained with a PET/CT Discovery 690 (GE Healthcare) and acquired using an automated dose modulation (maximal 140 mA, 140 kVp), 64x3.75 mm collimation, 3.75 mm slice thickness, 0.5s rotation time, pitch 0.984:1. Reconstructed images of the pelvis were obtained and displayed for reading on an OsiriX MD Imaging workstation. The Bio-Jet fusion system and software (D&K Technologies, Barum, Germany) were used. Biopsies, transrectal or transperineal according to lesion site, were performed with patients in the dorsal lithotomic position, under antibiotic prophylaxis and local anaesthesia, using 3D triplane transrectal ultrasound system (BK Medical, Analogic Ultrasound Group, Pro Focus, Transducer 8818, 6/9 MHz). The primary endpoint was to assess whether 11C-choline PET/CT was able to determine the presence and the topographical distribution of the tumour foci. Data were complemented by statistical analysis. Results Of 298 consecutive patients enrolled from April 2015 to September 2016, 14 (mean age 65.3±8.3 years; tPSA 12.7±3.9 ng/ml) were cases of interest and underwent. PET documented 26 suspect lesions. The uptake values of ROIs on were: mean SUVmax 5.43 (±1.45; range: 1.9-8.3), mean SUVbackground 3.34 (±0.57; range1.6-5.5), SUVratio to background 1.64 (±0,35; range 1.16-2.51). PET/TRUS fusion biopsy was feasible in all patients. PCa was detected in 6 patients (42.8%). Of 77 cores, 23 (29.8%) were positive. Four patients harboured a significant PCa (GS > 6). The mean extension (length in mm) of PCa was higher in GS>6 patients than GS=6 patients (10,4 mm versus 5.5). We found no significant difference in mean values for SUVmax and SUVratio between benign (BPH + prostatitis) and malignant lesions. Patients with benign lesions presented a mean SUVmax and SUVratio of 5.77 and 1.64; patients with PCa had a mean SUVmax and SUVratio of 4.81 and 1.38 (p> 0.05). Conclusions Our findings showed a relative low accuracy of 11C-choline PET for detection of PCa, although patients with an aggressive PCa (GS>6) had a higher, but not statistically significant, uptake. Further studies using more specific radiotracers (i.e. 68Ga-PSMA PET/CT Imaging) are mandatory before introduction of this technique into clinical practice. Funding None
Authors
Egesta Lopci
Massimo Lazzeri Giovanni Lughezzani NicolòMaria Buffi Paolo Casale Rodolfo Hurle Alberto Saita Giuliana Lista Luisa Pasini Silvia Zandegiacomo Alessio Benetti Roberto Peschechera Pasquale Cardone Arturo Chiti Giorgio Guazzoni |
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MP77-04 |
Implications of Recurrence Sites Identification Following Salvage Treatments for Prostate Cancer Using C-11 Choline PET and Multiparametric MRI |
Prostate Cancer: Detection & Screening VII | 17BOS |
Abstract: MP77-04 Sources of Funding: None Introduction 11C-choline positron emission tomography (PET) and multiparametric MRI (mpMRI) imaging may be considered for evaluation of PSA recurrence. The pattern of failure following salvage therapy after prostatectomy is poorly understood. The objective of this study is to identify sites of cancer recurrence in patients who received hormonal therapy (HT), radiation therapy (RT) or combination of HT and RT following prostatectomy and subsequently developed PSA progression. Methods Between January 2008 and June 2016, 2466 patients underwent imaging for PSA recurrence. From this cohort 216 received RT, HT or RT+HT postoperatively and underwent 11C-choline PET scan and mpMRI. Additionally, clinical factors (ie. PSA at imaging) associated with recurrence were also evaluated. Local recurrence was defined as positive imaging within prostate bed. Metastatic recurrence included recurrent disease of pelvic/distant nodes as well as osseous disease. Results Among 216 patients with PSA progression, 26 (12.0%) patients exhibited local recurrence, 34 (15.8%) had local and distant metastatic disease, and 156 (72.2%) had metastatic disease. Table 1 describes patterns of recurrence. Mean PSA was 4.47, 6.87, and 10.63 in patients with local recurrence, local and metastatic recurrence, and metastatic recurrence, respectively (p=0.21). When recurrence patterns were compared with postoperative treatment-naïve patients (Sobol et al JU 2016), patients receiving postoperative therapy had higher rates of metastatic recurrence (72% vs. 44%) while treatment-naïve patients had higher rates of local recurrence (34% vs 12%; both p<0.0001). Conclusions Utilization of mpMRI and 11C-choline PET imaging in the evaluation of PSA progression after postoperative therapy reveals varied recurrence patterns, with the majority of patients having evidence of metastatic disease, when compared with a treatment-naïve cohort. Approximately 12% of patients who failed postoperative therapy after prostatectomy may be eligible for additional local therapy. Prudent utilization of advanced imaging techniques may optimize and guide therapeutic options among patients who develop PSA progression following postoperative therapy potentially avoiding unnecessary or ineffective treatments. Funding None
Authors
Avinash K. Nehra
Sean S. Park Rimki Haloi Lance A. Mynderse Val Lowe Brian J. Davis Fernando Quevedo Geoffrey B. Johnson Eugene D. Kwon R. Jeffrey Karnes |
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MP77-05 |
Simple Prostate Biopsy Protocol with Augmented Antibiotics Decreases Complications and Admissions in Veterans |
Prostate Cancer: Detection & Screening VII | 17BOS |
Abstract: MP77-05 Sources of Funding: None Introduction Complications following prostate biopsy are rare but can be devastating. The American Urologic Association (AUA) Quality Improvement Summit in 2014 recommended identifying high risk patients and considering augmented antibiotics. We prospectively implemented a biopsy protocol to identify high-risk patients for bleeding or infections and use augmented antibiotics with the objective of reducing complications. Methods Overall, 637 consecutive patients from June 1, 2014 to August 30, 2016, who underwent prostate biopsy at our Veterans Affairs hospital were evaluated. The prostate biopsy protocol required the provider to document infectious risk factors including prior UTI, antibiotic exposure, and/or recent biopsy to alert the prescriber to substitute IM ceftriaxone for oral ciprofloxacin in high-risk patients. Patients were also monitored closer for bleeding after the biopsy, especially those driving ≥2 hours. We defined complications as any deviations from normal post-biopsy activities. Comparisons were made between pre/post protocol cohorts, and logistic regression was used to identify risk factors for admissions or complications. Results The median age was 67 (IQR 64-69, p=0.4) in both groups (pre n=334, post n=303). 45 patients were deemed high infectious risk with the following patient-reported events: 22 patients with antibiotics for recent UTI, 10 patients with history of complicated UTI/prostatitis, 16 patients with prostate biopsies within 6 months and 3 patients with clean intermittent catheterization or indwelling catheter. Pre-protocol, 98.8% patients received ciprofloxacin empirically; post-protocol, 85.7% received ciprofloxacin and 14.3% received ceftriaxone (p<0.001). _x000D_ _x000D_ There were no deaths in either group. The 30-day complication rates pre- and post-protocol were 16.2% and 8.5% (p=0.001) with infectious complication rates of 1.2% and 1.7% (p=0.74). There was a decrease in 30-day hospitalization rate in the post-protocol group vs. the pre-protocol group (1% vs. 3.6%, p=0.04). On logistic regression, there were reduced odds of 30-day complications (OR 0.48, p=0.004) and 30-day hospitalization (OR 0.27, p=0.04) in the post-protocol group. Conclusions A screening protocol for bleeding and infectious risks prior to prostate biopsy provides a more targeted approach for selecting prophylactic antibiotics and closer monitoring post-biopsy for bleeding. Rates of infection overall were quite low. Our results suggest that the protocol has a favorable impact on complication and hospitalization rates. Funding None
Authors
Kimberly A Maciolek
Sara L Best Wade A Bushman David F Jarrard Tracy M Downs E Jason Abel Kyle A Richards |
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MP77-06 |
Antimicrobial lubricant reduces rectal bacteria at transrectal prostate biopsy. Results from a large prospective randomized trial |
Prostate Cancer: Detection & Screening VII | 17BOS |
Abstract: MP77-06 Sources of Funding: The lubricant was provided and the microbiological examinations were sponsored by FarcoPharma. Introduction Antibiotic resistancy may lead to increasing infection rates at transrectal prostate biopsy (PBx). Previous studies showed promising results by using targeted antibiotic therapy by rectal swab culture. Nonetheless, performing rectal swabs may be time- and cost ineffective. In consequence, there is a strong need for agents that can achieve a reduction of bacteria. Aim of our study was to test, if an antimicrobial lubricant can reduce bacteria. Methods Study population consisted of 384 pbx patients who received a rectal swab before and after biopsy in an European single center between March 2013 and June 2015. Patients were randomized for biopsy with pre-interventional instillation of an antimicrobial lubricant (intervention group) or with standard lubricant (control group). Bacteria were semi-quantitatively recorded (≤ 20 colonies: [+]; > 20 colonies, growth only within first streak: +; growth in second streak: ++; growth in third streak: +++). Colonies growing within the ciprofloxacin inhibition zone were identified. Results Overall, 384 patients were included in the study. Out of them, 256 (66.7%) were in the intervention group and received antimicrobial lubricant, 128 (33.3%) were in the control group. Median age at biopsy was 65 years and mean PSA-levels was 7.5 ng/ml. _x000D_ In patients of the intervention group, semi-quantitative bacterial count was statistically significantly lower after instillation of antimicrobial lubricant(p<0.001). In the control group, no statistically significant difference was recorded at the bacteria count of the second rectal swab vs. bacteria count of the first rectal swab(p=0.4). _x000D_ Ciprofloxacin-resistance was shown in overall 30 (7.8%) patients. Instillation of antimicrobial lubricant reduced ciprofloxacin-resistant bacteria from 24 (9.4%) to 15 (5.9%), but reduction did not achieve statistical significance (p=0.5). For the control group, number of ciprofloxacin-resistance bacteria were comparable at first vs. second rectal swab (6 (4.7%) vs. 4 (3.1%); p=0.7)._x000D_ Conclusions Semi-quantitatively colonie count was significantly lower in patients of the intervention group (p<0.001). Preinterventional overall ciprofloxacin resistance rate was 7.8%. This is relatively low compared to other studies. In our study, the antimicrobial lubricant reduced ciprofloxacin resistant bacteria, but due to the low incidence the reduction was not significant. Our results show that antimicrobial lubricants might be helpful in patients with high risk for ciprofloxacin resistancy._x000D_ _x000D_ Funding The lubricant was provided and the microbiological examinations were sponsored by FarcoPharma.
Authors
Katharina Boehm
Sandra Prues Judith Saul Lars Budäus Derya Tilki Axel Haferkamp Markus Graefen Georg Salomon |
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MP77-07 |
Pathologic outcomes of additional 2-cores in prostate apex anterior compared to 12-routine cores: prospective study |
Prostate Cancer: Detection & Screening VII | 17BOS |
Abstract: MP77-07 Sources of Funding: none Introduction Apex prostate cancer is an important prognostic factor related to the biochemical recurrence after a radical prostatectomy. In this study, we have taken a biopsy of additional two cores of both prostate apex anterior along with the 12-routine cores. We evaluated a pathological aggressiveness of the additional both apex anterior cores and compared it to the 12-routine cores. Methods Patients who underwent 14-core prostate biopsy including 2-additional cores of prostate apex anterior for elevated prostate specific antigen from May 2014 to May 2016 were enrolled in this study, prospectively. Those who have had a previous biopsy history or a palpable nodule on the digital rectum examination were excluded. A total of 194 patients clinical data were collected which includes age, prostate specific antigen, prostate volume measured by transrectal ultrasonography, pathological data of prostate cancer including Gleason score, cancer length of core, and the percentage of cancer. Results Cancer detection rate of the 14-core prostate biopsy was 46.6% (91/194). In terms of prostate biopsy specimen, the cancer detection rate of 12-routine cores was higher than additional 2-cores, but was not significant (19.1% (446/2338) vs 15.4% (60/390), p=0.083). The Gleason score of cancer with 12-routine cores was more aggressive than 2-additional cores (table2, p=0.04). The percent of cancer in cancer cores of 12-routine cores was higher than that of 2-additional cores. (table2, p=0.04). Only 3 patients were diagnosed with prostate cancer through 2-additional cores out of 14-cores, all of the patients had 1 cancer core with a Gleason score of 6. 3 patients underwent upgrading of Gleason score by 2-additional cores with 1 Gleason score point. Conclusions There were few patients who had prostate cancer only in anterior apex cores. In apex anterior cores, incidence of cancer was lower than the other cores and pathological feature was similar or indolent. Additional cores of apex anterior was not most aggressive feature to determine the treatment method of patients. Funding none
Authors
Sung Jin Kim
Chang Hoo Park Han Kwon Kim Jong Yeon Park |
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MP77-08 |
Secular trends in prostate biopsy criteria and outcomes: The Dartmouth experience |
Prostate Cancer: Detection & Screening VII | 17BOS |
Abstract: MP77-08 Sources of Funding: None Introduction Changes in PSA guidelines since 2012 have led to both lower rates of screening and lower rates of prostate cancer diagnoses. This has been heralded for reduction in over-diagnosis of low risk cancer and criticized based on concern for missed diagnosis of higher risk disease. It is not clear how regions with stringent screening practices may be affected by changed guidelines; for instance, Dartmouth-Hitchcock Medical Center (DHMC) had the lowest rate of PSA screening among Medicare patients in the United States in 2012. In this study, we evaluated trends in biopsy and diagnosis rates at DHMC to assess the impact of changed guidelines in this environment. Methods Using a data warehouse query and chart review, we retrospectively analyzed patients at DHMC who underwent a trans-rectal ultrasound guided (TRUS) prostate biopsy January 2011 through March 2016. We excluded patients on active surveillance and those with clinical metastatic disease. Demographic and clinical characteristics were collected and analyzed, stratifying on time. Multivariable analysis was conducted using a priori variables to assess factors associated with higher grade cancer diagnoses. Statistical analysis was performed using SAS 9.4 (Cary, NC). Results During the study period, 614 prostate biopsies were performed. The mean age at biopsy was 63.7 (42-87); the mean PSA was 8.2 (0.14-49.9). Pathology results included 44.9% benign, 16.9% Gleason 3+3, and 38.1% ?3+4 disease. The mean PSA at biopsy increased with time (7.2 in 2011 vs 10.1 in 2016; p = 0.0085), while mean age did not (p=0.3645). The proportion of benign results remained stable (46.1% in 2011 vs 45.8% in 2015) however the proportion of low grade disease decreased while intermediate/high grade increased (2011 vs 2015: 21.1% vs 10.8% Gleason 3+3, 32.9% vs 43.3% ?Gleason 3+4, p = 0.0454). On multivariable analysis factors predictive of worse disease included abnormal digital rectal exam (OR 2.19, p-value 0.0076), higher PSA level (OR 1.09, p-value 0.0040), and later biopsy date (OR 1.01, p-value 0.0469). Conclusions In an environment of already austere screening practices, there has been a shift in both prostate biopsy criteria and outcomes, namely a rising PSA threshold for biopsy and a 50% decrease in the rate of diagnosis of low risk disease. There has been a concomitant 30% increase in the rate of higher grade disease. These trends demonstrate the potential benefit of more restrained screening practices. Additional study of the downstream effects of changing screening and biopsy practices is needed to ensure these are favorably impacting the overall quality of care. Funding None
Authors
Lael Reinstatler
Cody Rissman John Seigne Elias Hyams |
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MP77-09 |
Current practice of prostate biopsy in Australia and New Zealand: An updated survey |
Prostate Cancer: Detection & Screening VII | 17BOS |
Abstract: MP77-09 Sources of Funding: None Introduction The diagnostic work-up of prostate cancer has experienced a rapid shift worldwide in recent years. This study aims to provide a current appraisal of the practice of prostate biopsy in Australia and New Zealand in the emerging era of transperineal template biopsy (TPB) and multiparametric MRI (mpMRI). Methods A 36-question online survey was distributed to 545 members of the Urological Society of Australia & New Zealand (USANZ), including consultant urologists and trainees. This was an updated survey, based on a similar questionnaire distributed to USANZ members in 2012, addressing patterns of prostate biopsy practice in 4 domains: transrectal ultrasound-guided (TRUS) biopsy; TPB; mpMRI and peri-operative antibiotic and analgesia use. Survey results were collated and statistical analysis was performed using descriptive statistics and chi-squared test. Results 155 participants completed the survey, with a response rate of 21.1%. 81.9% of respondents were consultant urologists and 66.5% worked in a metropolitan setting. 92.3% perform TRUS biopsy and 91.3% sample between 10-16 cores. 66.9% of respondents perform TPB, increased from 38.4% in 2012 (p<0.001). 59.4% perform mpMRI prior to initial biopsy, increased from 19.6% (p<0.001). 90.1% perform MRI prior to repeat biopsy after an initial negative biopsy. 97.2% use prophylactic oral antibiotics prior to TRUS biopsy, most commonly quinolones. 55.7% use parenteral antibiotics, compared to 69.4% previously (p=0.013). 27.7% routinely use carbapenem prophylaxis in settings of recent overseas travel or quinolone exposure, compared to 27.9% in 2012 (p=0.965). General anaesthetic/IV sedation is used for 60.6% of TRUS biopsies and 97.9% of TPB. Conclusions Our survey demonstrates a shift in practice of biopsy for the diagnosis of prostate cancer among urologists in Australia & New Zealand, when compared with results of our initial study in 2012. More urologists are performing TPB now, and there has been a corresponding increase in the use of pre-initial biopsy mpMRI despite no current guidelines recommending this practice yet. There has been a reduction in the use of parenteral antibiotics overall, prior to TRUS biopsy, however, rates of carbapenem use have remained stable, suggesting ongoing concerns regarding the risk of sepsis due to antibiotic resistance. Funding None
Authors
Arveen Kalapara
Paul Davis Eldho Paul Jeremy Grummet |
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MP77-10 |
The effect of ultrasound-guided compression performed immediately after transrectal ultrasound-guided prostate biopsy on postbiopsy bleeding |
Prostate Cancer: Detection & Screening VII | 17BOS |
Abstract: MP77-10 Sources of Funding: none Introduction The effect of ultrasound-guided compression performed immediately after transrectal ultrasound-guided prostate biopsy on postbiopsy bleeding: a randomized controlled pilot study Methods We prospectively evaluated a total of 148 consecutive patients who underwent TRUS-guided prostate biopsy between March 2015 and July 2016. Systematic 12-cores prostate biopsy was performed in all patients. Of these, 100 patients were randomly assigned to two groups: compression group (n=50) underwent TRUS-guided compression on bleeding biopsy tracts immediately after prostate biopsy; non-compression group (n=50) only underwent TRUS-guided prostate biopsy. The incidence rate and duration of hematuria, hematospermia, and rectal bleeding were compared between two groups. Results The incidence rates of hematuria and hematospermia were not significantly different between two groups (60% vs. 64%, p=0.68; 22% vs. 30%, p=0.362, respectively, for compression vs. non-compression group). Rectal bleeding incidence was significantly lower in compression group than non-compression group (20% vs. 44%, p=0.01). However, there were not significant differences in the median duration of hematuria, hematospermia, and rectal bleeding between two groups (2, 8, and 2 days vs. 2, 10, and 1 days, p > 0.05, respectively, for compression vs. non-compression group) (Tale 1). TRUS-guided compression (p=0.004, odds ratio: OR=0.25) and patient age (p=0.013, OR= 0.93) were significant, protective factors for the occurrence of rectal bleeding after prostate biopsy in multivariable analysis (Table 2). Conclusions Although it has no impact on other complications, ultrasound-guided compression on bleeding biopsy tracts performed immediately after TRUS-guided prostate biopsy is a effective, practical method to treat or decrease rectal bleeding . Funding none
Authors
Bong Hee Park
Sung Hak Kang Joon Se Jung Sang Rak Bae Yong Seok Lee Chang Hee Han |
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MP77-11 |
Assessment of Discomfort and Pain in Patients undergoing Fusion-MRI-guided versus TRUS-guided Prostate Biopsy |
Prostate Cancer: Detection & Screening VII | 17BOS |
Abstract: MP77-11 Sources of Funding: none Introduction The addition of MRI fusion guided prostate biopsy (FusionBx) to transrectal ultrasound guided template biopsy (TRUSBx) has emerged in urology due to its increased sensitivity in detecting clinically relevant prostate cancer (PCa) over TRUSBx alone. FusionBx in conjunction with TRUSBx requires more biopsies in less accessible locations and takes more time than TRUSBx, suggesting that FusionBx+TRUSBx may be less tolerable to patients than TRUSBx alone. The objective of our study was to investigate patient pain associated with FusionBx+TRUSBx versus TRUSBx, which has never been studied before. Methods Patients undergoing FusionBx+TRUSBx or TRUSBx alone from April through September 2016 at Columbia University Medical Center for PCa detection or surveillance were asked to complete a validated pain survey immediately after biopsy. Responses were graded from 0-10 (0: no pain/willing to return for repeat procedure; 10: excruciating pain/not willing to return for repeat procedure). Procedures were performed by a single urologist with a 1% Lidocaine periprostatic nerve block. Pain scores between groups were compared via Mann-Whitney U test. Results A total of 94 patients were included, with 50 FusionBx+TRUSBx and 44 TRUSBx. For each group, median age was 66.5 (range 47-84) and 68 years (range 44-86), and median number of cores was 14 (range 12-22) and 12 (range 6-14), respectively. Prostate biopsy pain questionnaire scores did not differ significantly for any of the questions (Figure 1). Patients in both groups had mild discomfort overall with the procedure (3 out of 10), the probe insertion (2 out of 10) and the biopsy portion of the exam (3 out of 10). If medically necessary, both groups were very willing to come back for the same procedure again (1 out of 10). Conclusions Patients reported no difference in pain or discomfort with added FusionBx relative to TRUSBx alone. Both procedures were mildly painful with patients very willing to return for repeat biopsy if necessary. Patients tolerate the addition of FusionBx to TRUSBx alone. Patients&[prime] pain experience or discomfort does not seem to hinder whether FusionBx of the prostate should be performed, or not. Funding none
Authors
Dennis Robins
Michael Lipsky Sven Wenske |
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MP77-12 |
Head-to-head comparison of commonly used international prostate cancer risk calculators for prostate biopsy |
Prostate Cancer: Detection & Screening VII | 17BOS |
Abstract: MP77-12 Sources of Funding: None Introduction Multivariable risk calculators (RC) predicting prostate cancer (PCa) aim to reduce unnecessary biopsies and improve detection of clinically significant PCa (Gleason ≥7). We aimed to evaluate well-known RCs in a head-to-head comparison. Methods Our multicentre study comprised 7158 men from 10 independent contemporary cohorts in Europe and Australia who underwent prostate biopsy in 2007-2015. We evaluated the performance of the ERSPC, Finne, Chun, ProstataClass, Karakiewicz, Sunnybrook, and PCPT(HG) RCs in predicting the presence of any PCa and clinically significant PCa. Results A total of 3509 (49%) PCa were detected; 1866 (26%) men had clinically significant PCa. In predicting any PCa no particular RC stood out, pooled area under the ROC-curve (AUC) ranged between 0.66 and 0.73 (Fig. 1). Substantial heterogeneity in the AUC was found between the cohorts (range I2 74%-94%). The ERSPC RC had the highest pooled AUC 0.77 (95% CI: 0.73-0.81) in predicting clinically significant PCa, and was statistically significantly better than the other RCs. Conclusions No particular risk calculator stands out to discriminate between men with and without PCa across a range of settings, but the ERSPC is most promising to identify those with clinically significant PCa. Further research is necessary to evaluate the practical usefulness and clinical impact of these RCs. Funding None
Authors
Nuno Pereira-Azevedo*
Jan Verbeek* Daan Nieboer Ewout Steyerberg Monique Roobol |
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MP77-13 |
A prospective evaluation on the effect of inter-observer variability of DRE on the performance of the DRE based Rotterdam Prostate Cancer Risk Calculator |
Prostate Cancer: Detection & Screening VII | 17BOS |
Abstract: MP77-13 Sources of Funding: None. Introduction To reduce overdiagnosis and overtreatment on Prostate Cancer (PCa), a biopsy (Bx) should only be offered to men with an increased risk of having a potentially life-threatening PCa. The Digital Rectal Examination (DRE) version of the Rotterdam PCa Risk Calculator (RPCRC), was developed to include information on prostate volume but to circumvent the need for imaging studies, enabling easier implementation into daily practice of urologists and general practitioners (GPs). Our objective was to assess the level of agreement between DRE findings (irregularities and estimation of volume) of two urologists in men suspicious for PCa and, subsequently, the potential effect on risk prediction using the DRE-based RPCRC. Methods A prospective cohort of asymptomatic and unscreened men with PSA <=50.0 ng/mL and TRUS (transrectal ultrasonography) volume <=110 mL who underwent 16-core TRUS-guided Bx were evaluated. _x000D_ Both urologists’ DRE findings were graded normal or abnormal (i.e. nodularity and/or induration), and volume classified as 25mL, 40mL or 60mL, according to the RPCRC algorithm. Inter-rater agreement analysis using Cohens’s kappa (?) statistic was performed to determine consistency of DRE outcome and volume assessment. Receiver operating characteristic (ROC) curve analysis and calibration plots were constructed per urologist to determine the effect of inter-rater differences. Decision curve analysis (DCA) was applied to evaluate the clinical usefulness of the DRE based model. Results Of the 241 men included in the study, 41% (n = 98) had a positive Bx (81 PCa were clinically significant). There was substantial agreement in the DRE examination (abnormal/normal) (? = 0.78; P < 0.001), and volume estimation (? = 0.79; P < 0.001). _x000D_ ROC analyses showed good discrimination (0.75–0.78) and were highly comparable for both urologists. In our high risk cohort, at a probability threshold of 25%, the DRE-based RPCRC reduces the Bx rate by 9%, without missing cancers. Conclusions This is the first study to validate the DRE-version of the RPCRC. Most crucial in this validation is the effect of the inter observer variability of a subjective predictor like DRE and DRE assessed volume. The slight differences in DRE findings between the two urologists had very little impact on the performance of the RPCRC. The DRE-based RPCRC can be considered a useful Bx outcome prediction tool. Funding None.
Authors
Nuno Pereira-Azevedo
Isaac Braga Jan F.M. Verbeek Luís Osório Vitor Cavadas Avelino Fraga Eduardo Carrasquinho Eduardo Cardoso de Oliveira Daan Nieboer Monique J. Roobol |
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MP77-14 |
Diabetes Mellitus, Metformin and Prostate Cancer: Results of A Prostate Cancer Database Analysis |
Prostate Cancer: Detection & Screening VII | 17BOS |
Abstract: MP77-14 Sources of Funding: None Introduction Chemoprevention of prostate cancer has long been an interesting topic. Data have shown that Metformin is associated with lower prostate specific antigen levels. A recent study showed that Metformin can modify gene expression in prostate cancer cells. Literature is controversial on the role of metformin in prostate cancer prevention. This study was designed to assess relationship of diabetes mellitus and metformin with prostate cancer. Methods A database of patients with prostate cancer was searched for patients with diabetes mellitus taking medications. Patients with diabetes mellitus prior to prostate cancer detection were detected. Data were imported into SPSS v. 21 for analysis. After primary analysis, patients taking metformin were compared to diabetic patients not taking metformin and non-diabetic patients. Results Between March 2003 and October 2016, there were 3,645 patients in the database of which 228 (6.2%) were diagnosed with diabetes mellitus prior to the time of prostate cancer detection. In diabetic group, 139 patients were using metformin products prior to surgery. There were additional 35 patients who were taking metformin for other conditions rather than diabetes mellitus. A general comparison of characteristics of diabetic and non-diabetic patients in the study is shown in table 1. Diabetic patients were more commonly black, had higher BMI, Higher D’Amico risk and higher American Society of Anesthesiologist risk classification (all p<0.05). There was no significant difference between diabetic patients taking metformin and diabetic patients on other treatment plans. Analysis of patients taking metformin with other patients (diabetic and non-diabetic) showed no significant difference in terms of prostate cancer characteristics. Conclusions Diabetes mellitus might impact the course of prostate cancer development. The results of the study does not support the protective effect of metformin on prostate cancers in diabetic or non-diabetic Funding None
Authors
Seyed Behzad Jazayeri
Brittany Weissman David Samadi |
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MP77-15 |
Inclusion of mpMRI into the European Randomized study of Screening for Prostate Cancer (ERSPC) risk calculator: a new proposal to improve the accuracy of prostate cancer detection |
Prostate Cancer: Detection & Screening VII | 17BOS |
Abstract: MP77-15 Sources of Funding: none Introduction The ERSPC risk calculator estimates the risk of positive prostate biopsy. We aimed at evaluating whether the inclusion of mpMRI data might improve the predictive accuracy of this calculator in detecting positive biopsy in patients undergoing mpMRI targeted biopsy Methods 214 consecutive patients underwent mpMRI of the prostate with subsequent targeted and concomitant systematic biopsy at a single centre between 2013 and 2016. A 1.5 T mpMRI study using an endorectal coil was performed in all patients who had also complete data required by ERSPC risk calculator 4. Four multivariable logistic regression analyses (MVA) were performed to assess the predictors of positive biopsy. Predictors included in Model 1 were those of the ERSPC risk calculator, namely transrectal ultra-sonography (normal vs. abnormal), digital rectal examination (normal vs. abnormal), prostate volume (ml), the logarithmic transformation of PSA (ng/ml), previous negative biopsy (no vs. yes). Model 2 included as predictor only by PIRADS v.2 (<4 vs. ≥4). Predictors of Model 3 and Model 4 were the same of Model 1 plus PIRADS (<4 vs. ≥4) for Model 3 and PIRADS (<4 vs. ≥4) + patient age for Model 4. Leave-one-out cross validation (LOOCV) and calibration plots were used to internally validate each model. Decision curve analyses (DCA) were performed to evaluate and compare the net benefit associated with the use of each model Results Overall, 63% had a positive biopsy. At MVA of Model 1, prostate volume (OR: 0.97) and PSA (OR: 2.8), were independent predictors of positive biopsy (all p≤0.001). In all models including mpMRI results (Model 2-4), the presence of PIRADS ≥4 was significantly associated with positive biopsy (OR range: 3-4.6; all p≤0.001). At MVA of Model 3 and 4, prostate volume and PSA also reached the independent predictor status for positive biopsy prediction (all p≤0.009). Moreover, at MVA of Model 4, older age was significantly associated with positive biopsy (OR: 1.08, p<0.001). In LOOCV, inclusion of age and mpMRI results into the ERSPC risk 4 calculator was associated with the highest accuracy (C-index 77.3%) as compared to all other models tested (C-index of model 1, 2, 3: 65.8 vs. 53.7 vs. 73.7%, respectively). At DCA, the combined use of age, mpMRI and ERSPC calculator resulted into higher net-benefit relative to all the other 3 Models Conclusions Our data demonstrated the importance of inclusion of both PIRADS v.2 and patient age into the ERSPC risk calculator to better identify patients with higher risk of positive biopsy Funding none
Authors
Paolo Dell'Oglio
Armando Stabile Giorgio Gandaglia Giorgio Brembilla Tommaso Maga Giulia Cristel Ella Kinzikeeva Andrea Losa Antonio Esposito Gianpiero Cardone Francesco De Cobelli Alessandro Del Maschio Franco Gaboardi Francesco Montorsi Alberto Briganti |
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MP77-16 |
First repeated biopsy represents the most informative predictor of progression-free survival at 3 years follow-up in patients included in an active surveillance protocol for low-risk prostate cancer |
Prostate Cancer: Detection & Screening VII | 17BOS |
Abstract: MP77-16 Sources of Funding: none Introduction Active surveillance (AS) represents a safe management strategy to reduce the risk of overtreatment in men with low risk prostate cancer (PCa). However, patients on AS must undergo PSA testing and repeated biopsies over time in all proposed protocols and patients are subjected to discomfort and anxiety as well as to the complications of repeated biopsies. We tried to identify the predictors of progression-free survival (PFS) at a single institution AS program in order to identify patients in whom repeated biopsies could be avoided or reduced in frequency. Methods Between 2009 and 2016, 235 consecutive patients affected by low-risk PCa according to PRIAS criteria (cT1/T2a; PSA<10 ng/ml; PSA density <0.2; Gleason score <7; <3 positive cores) were enrolled in our AS program. Tumor progression was defined as pathological upgrading (Gleason >6 or >2 positive cores) at repeated yearly biopsies. First, Kaplan-Meier analyses were used to quantify progression-free survival at 1, 3 and 5 years, respectively. Second, we identified patients who were progression-free at 3 years of follow-up. Finally, univariable and multivariable logistic regression analyses were used to predict 3-year PFS. Covariates consisted of age, total PSA, clinical stage (cT) and number of positive cores at the time of enrolment as well as negative (no cancer) 1-year biopsy. Results Progression-free survival rate was 85%, 55%, and 40% at 1, 3 and 5 years, respectively. Median follow-up was 19 months. Overall, 56 (23.8%) patients were progression-free at 3 years of follow-up. Median number of cores at enrolment in AS program was 16 (IQR: 14-20), while median number of cores at first-year biopsy was 18 (IQR: 14-20). At univariable analyses, total PSA and negative 1-year biopsy were significant predictors of 3-year PFS (all p<0.05). Patients with negative biopsy at 1 year had a 3-year PFS of 75.8 vs. 29.0% in those with positive biopsy at 1-year. These results were confirmed at multivariable analyses, where a negative 1-year biopsy represented the only independent predictor of 3-year PFS (OR: 2.47; p=0.04). Conclusions The first biopsy after enrolment in AS program is an important predictor of PCa progression in the first 3 years in men on AS. Negative findings at 1-year biopsy suggest a high chance of 3-year PFS. Patients with negative 1-year biopsy could be followed-up with less stringent biopsy protocol, in order to reduce possible biopsy-related side effects and discomfort. Funding none
Authors
Stefano Luzzago
Nazareno Suardi Paolo Dell'Oglio Nicola Fossati Umberto Capitanio Giorgio Gandaglia Emanuele Zaffuto Vincenzo Mirone Roberto Bertini Rocco Damiano Massimo Freschi Franco Gaboardi Francesco Montorsi Alberto Briganti |
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MP77-17 |
Impact of Time From Biopsy to Surgery on Complications, Functional and Oncologic Outcomes Following Radical Prostatectomy |
Prostate Cancer: Detection & Screening VII | 17BOS |
Abstract: MP77-17 Sources of Funding: none Introduction The optimal interval between prostate biopsy and radical prostatectomy (RP) is unknown. Therefore we sought to determine the impact of time from biopsy to surgery on outcomes following RP._x000D_ Methods 13,265 men who underwent RP at our institution between 1992 and 2012 had a prostate biopsy within one year of surgery. Men were divided into four groups based on the interval between biopsy and surgery: 1) ≤3 weeks (n=2511), 2) 4-6 weeks (n=2493), 3) 7-12 weeks (n=5273), 4) >12 weeks (n=2998) to assess for complications. Oncologic outcomes were compared between those waiting ≤3 weeks (n=2511) versus ≥6 months (n=443), stratified by NCCN risk category. Logistic regression was performed to assess the impact of time on postoperative complications, functional and oncologic outcomes. Results Mean time from biopsy to surgery was 63 days (±51 days) and the overall complication rate for the cohort was 19.8% with a 1.0% intraoperative complication rate. Men undergoing RP within 3 weeks of biopsy were older (63.4 vs 61.7; p<0.001), with higher pre-operative PSA (9.1 vs 7.6; p<0.001) and clinically higher risk disease (3.2% vs 1.9% with ≥2 NCCN high risk criteria; p<0.001) compared to those who waited more than 12 weeks until surgery. On multivariate analysis, waiting at least 7 weeks was associated with a lower likelihood of complications (OR: 0.8, p= 0.01) and higher likelihood of a nerve sparing procedure (OR: 1.6, p<0.001). Men waiting 12 weeks were least likely to have a positive margin (OR: 0.6, p<0.001). There was no significant difference in functional outcomes at 1 year. Finally, there was no clinically significant difference in oncologic outcomes among men undergoing early (≤3 weeks) compared to delayed (≥6 months) RP. Conclusions Waiting at least 6 weeks from biopsy to RP is associated with a lower overall complication and positive margin rate. There appears to be no oncologic harm in waiting 6-12 months between biopsy and RP, even for men with intermediate and high risk disease. Funding none
Authors
Mary E. Westerman
Vidit Sharma George C. Bailey Stephen A. Boorjian Igor Frank Matthew T. Gettman R. Houston Thompson Matthew K. Tollefson R. Jeffrey Karnes |
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MP77-18 |
What False Negative Rate of Non-Invasive Testing Are Active Surveillance Patients and Uro-Oncologists Willing to Accept in Order to Avoid Prostate Biopsy? |
Prostate Cancer: Detection & Screening VII | 17BOS |
Abstract: MP77-18 Sources of Funding: None Introduction Repeat prostate biopsies in active surveillance patients are associated with significant complications. Novel imaging and blood/urine based non-invasive tests are being developed to better predict disease grade and volume progression. We conducted a theoretical study to determine what test performance characteristics and costs would a non-invasive test(s) require in order for patients and their physicians to comfortably avoid biopsy. Methods Surveys were administered to two populations to determine an acceptable false-negative rate and cost for such test(s). AS patients were recruited at time of visit to the prostate cancer clinic at Princess Margaret Cancer Centre, beginning August 2015 for a period of four months. Responses from urologic oncologists worldwide were obtained in March 2016 by circulating an online survey via the Society of Urologic Oncology. Participants were questioned about their demographics and other characteristics that might influence chosen error rates and cost. Differences between patient and physician choices were tested using the Chi-square test. Results 136 patients and 670 physicians were surveyed, with 130 (96%) and 104 (16%) responses obtained, respectively. 90.6% of patients were comfortable with a non-invasive test(s) in place of biopsy, with 64.8% accepting a false-negative rate of 5% or worse. 25.8% of patients requested a FN rate of 1% or lower. 93.3% of physicians were comfortable with a non-invasive test, with 77.9% accepting a rate of 5% or worse. 15.4% of physicians requested a FN rate of 1% or lower. 75% of patients and 77% of physicians felt that a cost of less than $1,000, per administration, would be reasonable. No significant differences existed between patient and physicians choices for FN rate or costs (p>0.05). Conclusions Most patients/physicians are comfortable with a non-invasive test(s). Although a 5% error rate seems acceptable to many, a substantial subset feels that 99% or higher negative predictive value is required. Thus, a personalized approach with shared-decision making between patients and physicians is essential to optimize patient care in such situations. Funding None
Authors
Rashid Sayyid
Dharmendra Dingar Katherine Fleshner Taylor Thorburn Joshua Diamond Erik Yao Karen Hersey Karen Chadwick Nathan Perlis Laurence Klotz Antonio Finelli Alexandre Zlotta Robert Hamilton Girish Kulkarni Neil Fleshner |
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MP77-19 |
Timing of Confirmatory Biopsies Influences Eligibility for Active Surveillance |
Prostate Cancer: Detection & Screening VII | 17BOS |
Abstract: MP77-19 Sources of Funding: none Introduction While serial biopsies are a key component of most active surveillance (AS) programs, surveillance protocols differ as to when the first surveillance biopsy should be performed. Some protocols mandate a confirmatory biopsy while in others, the first surveillance biopsy is performed at 1 year. In the present study we sought to determine differential impact of obtaining the first surveillance biopsy either within 6 months or at 9-15 months after diagnosis. Methods We retrospectively identified patients who enrolled in a prostate cancer active surveillance (AS) program during 2004-2015 and underwent a biopsy either ≤6 months or between 9-15 months after their initial diagnostic biopsy. Eligibility for enrollment in AS was defined according to MSK criteria (biopsy Gleason: ≤6; biopsy T stage: cT1c or cT2a, diagnostic PSA <10, % positive for each core ≤50%, ≤3 positive cores, or if number of total cores >12, then number of positive cores ≤25% of the total cores). We compared MSK-defined eligibility for AS in patients who received a second biopsy at either ≤6 or 9-15 months after their initial diagnostic biopsy. Results A total of 115 patients on AS were identified within the study period. 62 (53.9) and 53 (46.1%) of patients underwent a second biopsy at ≤6 or 9-15 months after their initial diagnostic biopsy, respectively (table). Age, number of biopsy cores and positive cores, serum PSA, and eligibility for AS by MSK criteria were similar between groups. 56(90.3%) and 42 (79.2%) of patients initially met MSK AS criteria. Of these, those rebiopsied at 9-15 months appear more apt to be reclassified as ineligible than patients rebiopsied at ≤6 months (42.9 v. 25.0%, p=0.082). Patients biopsied at ≤6 months had more cores taken at the second biopsy (15(IQR 12-16) vs. 12 (12-12), p<.001) Conclusions Surveillance protocols differ as to when the first surveillance biopsy is performed. In patients initially meeting AS inclusion criteria, a delay in confirmatory biopsy may be associated with a higher rate (42.9% v 25.0%) of AS ineligibility. Just as important, 25% of patients immediately learn they do not meet AS criteria. These findings may be due to disease progression rather than under sampling, as patients who were biopsied at ≤6 months had more biopsies performed. These data may be helpful in patient counseling prior to AS enrollment._x000D_ Funding none
Authors
Jessica Armstrong
Peter Haddock Scott Wiener Ilene Staff Joseph Cusano Joseph Wagner |
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MP77-20 |
Multiparametric MRI represents an added value but not a substitute of follow-up biopsies in patients on active surveillance for low-risk prostate cancer |
Prostate Cancer: Detection & Screening VII | 17BOS |
Abstract: MP77-20 Sources of Funding: none Introduction Some authors proposed the possibility to avoid follow-up biopsies when multiparametric-magnetic resonance (mpMRI) is not suspicious for clinically significant prostate cancer (csPCa) in patients on active surveillance (AS) Methods Between 2009 and 2016, 235 patients were included to AS program for low risk PCa according to the PRIAS criteria. 95 underwent a mpMRI and represent the study population. Number, size, location and grading of mpMRI lesions were recorded. We compared pathologic outcomes in patients submitted to targeted biopsies. csPCa was defined as Gleason score >6. We analyzed the mpMRI performed in patients on AS and correlated mpMRI findings to histopathological results of subsequent biopsies. The rates of csPCa was assessed in patients submitted to prostate biopsy after mpMRI according to PIRADS score, for the biopsy approach (targeted vs. systematic) Results 80 patients underwent more than one mpMRI, resulting in 120 evaluable mpMRI. Median time from protocol entry to mpMRI was 12 months. Overall, 48 (40.0%) and 72 (60.0%) patients had a PIRADS score ≤2 and ≥3, respectively. PIRADS score was 3 in 32 (44.4%), 4 in 31 (43.1%), and 5 in 9 (12.5%) patients. Median and mean lesion size at MRI were 9 and 9.1 mm. 34 (35%) suspicious lesions were localized at the transitional zone of the prostate, while 23 (23.7%), 9 (13.5%), and 27 (27.8%) at the apex, the base and the lateral zone. 18 patients (18.9%) had >1 suspicious lesion. Overall, 75 patients underwent a biopsy after mpMRI, 34 (45.4%) with a targeted approach and 41 (54.6%) with random systematic biopsies. Of 75 patients, 54 (72.5%) had PIRADS ≥3 while the others (n=21) had PIRADS ≤2. Of 54 patients with PIRADS ≥3, 17 (31.4%) had Gleason ≥7. However, patients with PIRADS ≥3 submitted to targeted biopsy (n=34), Gleason 7 or higher was found in 23 (67.6%) vs. 7 (33.3%) in patients with PIRADS score ≥3 submitted to systematic biopsies (p=0.001). Of patients submitted to targeted biopsy (n=34), Gleason ≥7 outside of the targeted area was found in 7 patients (20.1%). Finally, of 21 patients with PIRADS ≤2, 7 (33.3%), 11 (52,3%) and 3 (14.5%) had negative biopsy, Gleason 6 and Gleason ≥7 at systematic biopsy. These figures resulted in 3+7/75 (13%) patients with csPCa that were missed by mpMRI Conclusions 80% of AS patients submitted to mpMRI have suspicious csPCa, especially in areas not normally investigated by means of random biopsies. Therefore, mpMRI should be taken into account when evaluating candidates for AS. However, 13% of clinically significant cancers may be missed by mpMRI Funding none
Authors
Stefano Luzzago
Nazareno Suardi Paolo Dell'Oglio Gianpiero Cardone Giorgio Gandaglia Antonio Esposito Francesco De Cobelli Giulia Cristel Ella Kinzikeeva Massimo Freschi Franco Gaboardi Alessandro Del Maschio Francesco Montorsi Alberto Briganti |
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MP78-01 |
Impact of ureteroscopy before radical nephroureterectomy for upper tract urothelial carcinomas on oncologic outcomes: a meta-analysis |
Bladder Cancer: Upper Tract Transitional Cell Carcinoma II | 17BOS |
Abstract: MP78-01 Sources of Funding: none Introduction In the current era, the ureteroscopy (URS) has become a powerful tool to diagnose and treat patients with upper tract urothelial carcinoma (UTUC). However, there is concern that it may have a negative impact on the patients. We aim to investigate whether the URS before RNU for UTUC has impact on oncologic outcomes. Methods We performed a systematic literature search of PubMed, Embase, and Cochrane library for citations published prior to June 2016, describing URS performed among patients with UTUC and conducted a standard meta-analysis of survival outcomes. Results Our meta-analysis included eight eligible studies containing 2998 patients. The results were as follows: cancer-specific survival(CSS) (Hazard Ratio(HR) = 0.74, 95% confidence interval(CI): 0.59-0.94, P = 0.01), overall survival(OS) (HR = 0.76, 95% CI: 0.48-1.21, P = 0.24), recurrence-free survival(RFS) (HR = 0.89, 95%CI: 0.69-1.14, P = 0.37), metastasis-free survival(MFS) (HR = 1.06, 95% CI: 0.82-1.36, P = 0.66), and intravesical recurrence-free survival(IRFS) (HR = 1.54, 95% CI: 1.31-1.80, P < 0.00001). Besides, excluding the previous bladder tumor history, the results of IRFS were HR = 1.83, 95% CI: 1.55-2.15, and P < 0.00001. Conclusions This meta-analysis indicated that URS before RNU did not have a negative impact on CSS, OS, RFS and MFS in UTUC patients. However, patients are at higher risk for intravesical recurrence after RNU when they have undergone prior URS. Further studies are needed to assess the effects of post-URS intravesical chemotherapy on intravesical recurrence. Funding none
Authors
Run-Qi GUO
Peng HONG Xue-Song LI Li-Qun ZHOU |
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MP78-02 |
RESULTS OF SECOND LINE TOPICAL THERAPY FOR UPPER TRACT UROTHELIAL CARCINOMA (UTUC) |
Bladder Cancer: Upper Tract Transitional Cell Carcinoma II | 17BOS |
Abstract: MP78-02 Sources of Funding: Supported in part by the Monteleone Family Foundation for Research in Kidney and Bladder Cancer and the Eleanor and Scott Petty Fund for UTUC Research Introduction Topical therapy (TT) for UTUC has been explored as a kidney sparing approach to treat carcinoma in situ (CIS) and to decrease recurrence and progression for endoscopically treated Ta-1 tumors. In bladder cancer data supports use of 2nd line TT for repeat induction but this approach has yet to be investigated for UTUC. This study looks at outcomes following a 2nd line use of induction TT for UTUC in patients (Pts) ineligible for or refusing nephroureterectomy. Methods After IRB approval, charts of Pts receiving TT for UTUC from 3/2005-10/2016 at MD Anderson Cancer Center were retrospectively reviewed. Pts received TT via percutaneous nephrostomy tube or cystoscopically placed ureteral catheters per Pt choice. All Pts were offered induction and maintenance TT. Follow up was every 3 months with upper tract imaging or ureteroscopy (URS) in the 1st year and then at a minimum 6 mos interval. Pt outcomes were classified based upon recommendations outlined by the Intl. Bladder Cancer Group. Response after start of TT was defined as no evidence of disease after 6 mos, refractory cases as recurrence within 6 mos, and relapse as recurrence after 6 mos. Salvage TT was defined as therapy reinitiation following primary TT failure. Results 51 Pts with 58 renal units (RUs) received TT. 55% (32/58) of RUs had low grade UTUC, 22% (13/58) had high grade UTUC, 17% (10/58) had CIS, and 5% (3/58) had unknown disease grade due to insufficient tissue but presumed low grade based on URS. Median follow up was 28.5 mos. 18 RUs received 2nd line TT, 8 (44%) as salvage therapy for refractory disease and 10 (56%) as re-induction for relapse or 1st line TT intolerance. Results of 2nd line TT and corresponding responses can be found in Table 1. 60% (6/10) with CIS responded to 1st line TT while 20% (1/5) with refractory/recurrent CIS responded to 2nd line TT. RUs receiving adjuvant TT had a 71% (34/48) response to 1st line TT and 62% (8/13) response to 2nd line TT both as salvage and reinduction. Conclusions Within the limitations of small subgroups, our data suggests that refractory/recurrent UTUC after 1st line adjuvant TT may be associated with response to a 2nd line agent. However, refractory/recurrent CIS was much less responsive to 2nd line TT. 2nd line TT is a potential salvage therapy for select Ta-1 tumors in those with limited treatment options. Funding Supported in part by the Monteleone Family Foundation for Research in Kidney and Bladder Cancer and the Eleanor and Scott Petty Fund for UTUC Research
Authors
Adithya Balasubramanian
Michael J Metcalfe Gavin Wagenheim Lianchun Xiao Firas G Petros John Papadopoulos Neema Navai John W Davis Jose A Karam Ashish M Kamat Christopher G Wood Colin P Dinney Surena F Matin |
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MP78-03 |
Impact of residual peri-orifice urothelium on intravesical recurrence after nephroureterectomy for upper tract urothelial cancer |
Bladder Cancer: Upper Tract Transitional Cell Carcinoma II | 17BOS |
Abstract: MP78-03 Sources of Funding: None Introduction To determine the impact of residual periorifice urothelium after nephroureterectomy for primary upper tract urothelial cancer. (UTUC)_x000D_ Methods We retrospectively reviewed patients with upper UTUC that had undergonenephroureterectomy. Of these 105 patients, 67 of which belonged to the study group with ipsilateral residual peri-ureteral orifice urothelium (RUO), while 38 patients served as controls with no residual peri-ureteral orifice urothelium (NUO) postoperatively by follow up cystoscopy. We analyzed intravesical recurrence, local recurrence, and survival to assess the significance between two groups._x000D_ Results Baseline demographics were comparable in both groups. In comparison with the RUO group, the NUO group was associated with a longer total operative time (150±78 vs.200±115 mins, p=0.03). Bladder recurrence was observed in 40 out of 67 (59.7%) in the RUO group and in 10 out of 38 (26%) in the NUO group (p=0.001) during median 39.7 months follow up. There was a significant difference in bladder cancer recurrence-free rate in the NUO group versus RUO group (p=0.04). Fifty-four percent (24/50) of first intravesical recurrence had a tendency of recurrence occurring near the area of ipsilateral ureteral orifice/scar especially in RUO group. (57.5% vs.40 %, p= 0.04). Most patients (94%) in whom a bladder tumor developed postoperatively were superficial and underwent transurethral resection of the bladder tumor. The cancer specific survival rate was not significantly different when we compared the RUO and NUO groups (p =0.42)._x000D_ _x000D_ _x000D_ Conclusions Residual peri-ureteral orifice urothelium increased the risk of intravesical recurrence, but did not undermine survival after nephroureterectomy for primary UTUC._x000D_ Funding None
Authors
Chia-Wei Cheng
Ze-Hong Lu Weng-Horng Yang Chien-Hui Ou |
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MP78-04 |
Efficacy of early ureteral ligation on prevention of intravesical recurrence after radical nephroureterectomy for upper urinary tract urothelial carcinoma: A prospective single-arm multicenter clinical trial |
Bladder Cancer: Upper Tract Transitional Cell Carcinoma II | 17BOS |
Abstract: MP78-04 Sources of Funding: none Introduction Intravesical recurrence (IVR) after radical nephroureterectomy (RNU) for upper urinary tract urothelial carcinoma (UTUC) occurs at a high rate. We previously reported that most IVR occurs around the site of damage to the bladder mucosa within one year of RNU and that IVR after RNU affects the oncological outcomes of patients with non-muscle invasive UTUC. Seeding of UTUC cells on the damaged bladder wall during RNU is considered to be a cause of IVR. Thus, efficacy of early ureteral ligation (EUL) on prevention of IVR after RNU for UTUC was prospectively evaluated in a multicenter clinical trial. Methods Patients who underwent RNU for UTUC between 2012 and 2013 at 15 institutions participating in the Tohoku Urological Evidence-Based Medicine Study Group were enrolled. Those with bladder cancer before RNU or metastasis at the time of UTUC diagnosis were excluded. We defined EUL as ligating the ureter as soon as possible after expanding the retroperitoneal space and before ligating the renal artery. A historical control was extracted from 454 patients from the same group who underwent RNU for UTUC between 2000 and 2011, using propensity score-matched analysis. The IVR-free survival rates following RNU were prospectively analyzed using Kaplan-Meier curves and the log-rank test. Factors predicting IVR were assessed using multivariate analyses. The Ethics Committee at Tohoku University Hospital approved the study protocol. Results Seventy-four of the 148 patients had EUL and 74 patients in the control group did not undergo ureteral ligation. With a median follow-up of 21 months, 17 (23%) patients in the EUL group had IVR. The 1- and 2-year IVR-free survival rates in the EUL and control groups were 81% and 76%, respectively and 75% and 63%, respectively (p=0.201). The 1- and 2-year IVR-free survival rates among patients with renal pelvic cancer in the EUL and control groups were 89% and 86%, respectively and 74% and 64%, respectively (p=0.032). However, IVR-free survival rates were similar among the patients with ureteral cancer. Multivariate analyses of a subset of patients with renal pelvic cancer selected EUL as an independent predictor of IVR after RNU (hazard ratio, 0.37; p=0.049). Conclusions Early ureteral ligation decreased the rate of IVR after RNU among patients with renal pelvic cancer. This might result from the prevention of floating UTUC cells during RNU. Thus, EUL might contribute to the prevention of IVR after RNU for renal pelvic cancer. Funding none
Authors
Shinichi Yamashita
Akihiro Ito Koji Mitsuzuka Masataka Aizawa Naomasa Ioritani Shigeto Ishidoya Yoshihiro Ikeda Kenji Numahata Kazuhiko Orikasa Tatsuo Tochigi Fumihiko Soma Takashige Namima Hideo Saito Makoto Sato Shinnosuke Katoh Shozo Ota Atsushi Kyan Atsushi Takeda Yasuhiro Kaiho Yoichi Arai |
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MP78-05 |
Intravesical Irrigation Prevents Bladder Carcinoma Recurrence after Nephroureterectomy |
Bladder Cancer: Upper Tract Transitional Cell Carcinoma II | 17BOS |
Abstract: MP78-05 Sources of Funding: none Introduction The effectiveness of intravesical irrigation with physiological saline solution or distilled water for prevention of bladder carcinoma recurrence in upper urinary tract urothelial carcinoma (UUT-UC) was examined. Methods The study involved UUT-UC patients without distant metastasis who underwent laparoscopic nephroureterectomy from 2001 to 2014. Those who had a history of bladder carcinoma, had undergone neoadjuvant therapy and had bladder carcinoma confirmed before surgery were excluded. Cases that did and did not involve intravesical irrigation were compared for bladder carcinoma recurrence rates within 2 years after surgery. Physiological saline solution or distilled water was used for irrigation, which was performed only during surgery. Results Irrigation was performed in 48 (distilled water, 26 cases; physiological saline solution, 22 cases) of the 74 cases in our study. Bladder carcinoma recurrence was observed in 25 patients within 2 years. Comparison between the irrigation and non-irrigation groups revealed that recurrence rates were significantly lower in the irrigation group (irrigation group vs non-irrigation group: 25.0% vs 50.0%, HR0.29, P=0.013). No significant difference in recurrence rate were observed based on the type of irrigation (P=0.96). No adverse event was confirmed in the irrigation group. On multivariate analysis, irrigation was the independent predictive factor involved in the prevention of recurrence (HR0.32, P= 0.0075). Conclusions Intravesical irrigation during laparoscopic nephroureterctomy may be a useful option in preventing postoperative bladder carcinoma recurrence in UUT-UC. Funding none
Authors
Satoshi Yamamoto
Shinichi Sakamoto Tomokazu Sazuka Toshihito Inoue Kazuyoshi Nozumi Kazuto Chiba Kanetaka Miyazaki Atsushi Inoue Maki Nagata Tomohiko Ichikawa |
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MP78-06 |
Phase II study of personalized peptide vaccination for metastatic upper tract urothelial cancer patients refractory to the standard chemotherapy |
Bladder Cancer: Upper Tract Transitional Cell Carcinoma II | 17BOS |
Abstract: MP78-06 Sources of Funding: none Introduction The prognosis of metastatic upper tract urothelial cancer (mUTUC) refractory to the standard chemotherapy is very short. To address the affordability of personalized peptide vaccination (PPV) for mUTUC patients refractory to the standard chemotherapy from views of safety, immune responses, and clinical benefits. Methods A phase II trial of PPV immunotherapy was conducted for patients with mUTUC refractory to the standard chemotherapy. Eligible patients were human leukocyte antigen (HLA) A02, A24, A26, or A03 superfamily positive. A maximum of four HLA-matched peptides was selected based on the preexisting immunoglobulin G (IgG) responses against the 31 warehouse peptides and administered every 1 to 2 week. The overall survival (OS) time was estimated by the Kaplan-Meier method. Association between pre-vaccination biomarkers, including immune responses, and OS were evaluated by univariate and multivariate analyses with the Cox regression model, and by the Kaplan-Meier method with the log-rank test. Results Among 48 patients entered, 28 patients received PPV combined with salvage chemotherapy based on physicians&[prime] choice, and 20 patients received PPV alone since of ineligible due to potential intolerance to chemotherapy. Although no PPV-related severe adverse events were noted, 1 or 12 of 28 patients of the former group dropped before 1st or 2nd cycle due to disease progression, whereas dropped 7 or 16 of 20 patients of the latter group (p=0.002). Peptide-specific cytotoxic T lymphocyte (CTL) activity before PPV was scarcely detectable, but boosted in about half of patients tested after PPV. Median survival time (MST) of all 48 patients was 7.3 months (M) with 13.0 M for 28 patients under PPV and salvage chemotherapy and 4.5 M for 20 patients under PPV alone (p=0.08). Unfavorable prognostic factors by multivariate Cox regression analysis were higher numbers of Bellmunt risk factors (p=0.027) and higher levels of pre-vaccination BAFF (p=0.002). Notably, both peptide-specific CTL and IgG boosting were favorable prognostic factors, suggesting a causal relationship between immune responses and clinical efficacy in PPV. Conclusions Further clinical trials of PPV would be warranted for mUTUC because of the safety, immune boosting, and potential clinical benefits. Our data might provide promising evidence of clinical benefit of PPV for patients with mUTUC refractory to the standard chemotherapy. Funding none
Authors
Shigetaka Suekane
Kousuke Ueda Kiyoaki Nishihara Tsukasa Igawa Masanori Noguchi Tetsuro Sasada Takuto Yamashita Shigeru Yutani Shigeki Shichijo Kyogo Itoh |
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MP78-07 |
Gender-specific differences in cancer-specific survival after nephroureterectomy with bladder cuff for patients with upper tract urothelial carcinoma |
Bladder Cancer: Upper Tract Transitional Cell Carcinoma II | 17BOS |
Abstract: MP78-07 Sources of Funding: none Introduction Upper tract urothelial carcinoma (UTUC) show heterogeneous outcome after nephroureterectomy (NU). Despite gender-specific differences, no comparative studies exist for this tumor. The aim of this investigation was to describe tumor characteristics, and survival in patients with UTUC in a multicenter-based cohort, with special reference to gender-related differences. Methods Cancer-specific survival (CSS) of 1304 UTUC patients without neoadjuvant chemotherapy staged any pT, pN0-1, M0 after NU were analyzed in a retrospective multicenter study. Median follow-up period was 34 months. The influence of different clinical and histopathologic variables on CSS was determined through uni- and multi-variate Cox regression analyses. Results In total, 916 (70.2%) patients were male and 388 (29.8%) were female. Compared to men, women were more likely to have advanced tumor stages (p = 0.007), higher grade (p < 0.001) and lympho-vascular invasion (LVI) (p < 0.001). There was statistical difference in disease recurrence and cancer-specific survival between both genders when analyzed as a group. In LVI status-adjusted analyses, women without LVI were more likely to die of UTUC compared to the male counterparts (p = 0.011). Logistic regression modeling, female gender (HR = 1.42, p = 0.037), LVI (HR = 1.61, p = 0.004), and ECOG performance status (HR = 1.47, p = 0.007) significantly worsened cancer specific deaths. In gender-specific multivariable analyses that adjusted for standard clinico-pathologic features, positive urine cytology at diagnosis (p = 0.001), tumor grade (p = 0.007), LVI (p = 0.005), and pathologic tumor stage (p < 0.001) were independent predictors for CSS. Conclusions In this multicenter-based cohort, female gender was associated with inferior cancer-specific and relative survival. Women present with more aggressive tumor biologic features at NU, this translated into inferior outcomes compared to men in LVI-specific analyses in our cohort. Positive urine cytology at diagnosis, tumor grade, LVI, and pathologic tumor stage, were the factors influencing the course of disease in both genders. Funding none
Authors
Teruo Inamoto
Kiyoshi Takahara Naokazu Ibuki Hideyasu Matsuyama Kiyohide Fujimoto Hiroaki Shiina Shigeru Sakano Kazuhiro Nagao Yoshihiro Tatsumi Haruhito Azuma Nishinihon Uro-Oncology Collaborative Group |
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MP78-08 |
Improved survival of cytoreductive surgery in addition to chemotherapy for metastatic upper tract urothelial carcinoma: results from the National Cancer Data Base |
Bladder Cancer: Upper Tract Transitional Cell Carcinoma II | 17BOS |
Abstract: MP78-08 Sources of Funding: None Introduction Prior studies have shown a possible survival benefit of cytoreductive surgery (CS) in addition to the standard of care for the treatment of major metastatic urologic cancers, including renal cell carcinoma, prostate cancer, and bladder cancer. The objective of our study was to compare the survival outcomes of chemotherapy combined with CS (nephroureterectomy, nephrectomy, and/or ureterectomy) versus chemotherapy alone for the treatment of metastatic upper tract urothelial carcinoma (mUTUC). Methods We identified patients who presented with mUTUC at diagnosis in the National Cancer Data Base (NCDB) from 2004 to 2014. Only patients who had multi-agent systemic chemotherapy with or without CS were included. Multivariable logistic regression was performed to identify the predictors of receiving CS. Kaplan-Meier survival, log-rank test, and multivariable Cox regression controlled for demographics, socioeconomic factors, and tumor characteristics were used to compare the overall survival (OS) between CS and no CS groups. Results We included 657 patients in our study of which 202 (30.75%) underwent CS. Logistic regression showed that patients who were older (OR = 0.98, 95% CI = 0.96-1.00, P =0.038), diagnosed with ureteral cancer (OR = 0.42, 95% CI = 0.27-0.66, P < 0.001), and had cN+ disease (OR = 0.33, 95% CI = 0.21-0.54, P < 0.001) were less likely to receive CS. Patients who were treated at a community hospital (OR = 1.96, 95% CI = 1.35-2.86, P < 0.001) were more likely to receive CS. No difference was found in Charlson comorbidity index between the CS and no CS groups (P = 0.434). CS group had significantly higher median OS than no CS group (13.4 vs. 10.3 months, log-rank test P < 0.001, Figure 1). Cox regression showed that compared with chemotherapy alone, chemotherapy combined with CS was significantly associated with improved OS (HR = 0.57, 95%CI = 0.44-0.74, P < 0.001). Conclusions Consistent with various other malignancies, CS appears to provide a survival benefit for mUTUC. However, our study is limited by the observational study design. Studies with higher level of evidence, especially randomized controlled trials are needed to validate the findings and to better identify the patients who are most likely to benefit from CS. Funding None
Authors
Leilei Xia
Benjamin Taylor Jose Pulido Jeremy Bonzo Thomas Guzzo |
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MP78-09 |
External validation of a preoperative nomogram to predict likelihood of all complications following radical nephroureterectomy |
Bladder Cancer: Upper Tract Transitional Cell Carcinoma II | 17BOS |
Abstract: MP78-09 Sources of Funding: None Introduction A preoperative nomogram to predict complications following radical nephroureterectomy (RNU) has previously been created. This nomogram incorporated 5 variables (patient age, race, ECOG performance status, CKD stage, and Charlson Comorbidity Index [CCI]) with an area under the curve of 72%. We externally validate this nomogram with a distinct international RNU patient population. Methods Amongst 610 RNU patients treated at 7 academic medical centers between 2005 and 2015, 382 (63%) had complete data with all variables reported as the initial nomogram. Logistic regression determined the association between preoperative variables and post-RNU complications. Nomogram validation was performed by analyzing the area under the receiver operating characteristics (AUC-ROC) curve. A calibration plot compared the nomogram-predicted probability of complications with the observed rate of complications within 30 days. Results 225 men and 157 women with a median age of 71 were included. 85% of the patients were Caucasian, 18% has an ECOG ≥ 2, 25% had a CCI score >5 and 52% had baseline chronic kidney disease (CKD) ≥ stage III. Overall, 93 patients (24%) experienced a complication, including 31 (8%) with Clavien grade ≥ III. The performance of the nomogram was evaluated using two methods. Discrimination between individual patients was assessed by analyzing the AUC-ROC curve, which was 67.0% (95% CI 60.3%-73.7%). (Figure 1) A calibration plot compared the performance of the ideal nomogram (indicated by the dotted line), whereas the solid line represents the performance of this specific nomogram. There was a slight underestimation of complications for patients with high nomogram-predicted probabilities. (Figure 2) Conclusions External validation of a preoperative RNU complications nomogram noted an AUC-ROC curve of 67% with underestimation of complications for higher predicted probabilities. These observations may be a result of a lower complication rate observed in the validation versus original cohort (24% vs. 38%). Funding None
Authors
Neil Kocher
Jay D. Raman Evanguelos Xylinas Peter Chang Lauren Dewey Andrew Wagner Firas Petros Surena F. Matin Conrad Tobert Chad Tracy Patard Pierre-Marie Mathieu Roumiguie Leonardo Lima Monteiro Wassim Kassouf Shahrokh F. Shariat Tobias Klatte |
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MP78-10 |
Higher risk of recurrence at extraregional nodes after radical nephroureterectomy in patients with left than in patients with right ureteral cancer |
Bladder Cancer: Upper Tract Transitional Cell Carcinoma II | 17BOS |
Abstract: MP78-10 Sources of Funding: None Introduction We reported the lack of therapeutic effect of lymphadenectomy on lower ureteral cancer (LUC). We further examined this mechanism by analyzing the recurrence pattern and factors influencing the outcome of LUC. Methods From January 1988 to September 2016, we performed radical nephroureterectomy for 83 patients with non-metastatic (clinically N0 M0) LUC at two Japanese institutes. The lower ureter was designated as located below the crossing of the common iliac artery. Metastatic sites were identified with radiological imaging studies or resected specimens. Regional nodes of LUC were identified as ipsilateral pelvic nodes below the aortic bifurcation, according to the description in our previous study. Results The mean age of the 83 patients was 71.2 years (range: 38–90 years), and the mean follow-up period was 48 months (range: 2–225 months). Radical nephroureterectomy was performed for 41 patients with right LUC and for 42 patients with left LUC. No significant difference was found in the patients who underwent template-based lymphadenectomy (34% in the right and 36% in the left LUC, p=0.88). The 5-year recurrence-free and cancer-specific survival rates were respectively 71.9% and 80.1% in the right LUC, and 50.6% and 62.7% in the left LUC. The difference was statistically significant (p=0.02 and 0.03, respectively; Figure 1). The incidence of lymph node recurrence was even higher in the patients with left LUC (24%) than in those with right LUC (2%), and 60% of the lymph node recurrences occurred at the extraregional nodes in the left LUC. The multivariate analysis revealed that the factors that influenced cancer-specific survival were left ureteral tumors (hazard ratio [HR], 3.38; p=0.02) and pathological stage T3 or higher (HR, 28.9; p=0.002). Template-based lymphadenectomy or adjuvant chemotherapy was not a significant factor. Conclusions This multi-institutional study shows a higher risk of extraregional nodes recurrence after nephroureterectomy in patients with left LUC, which is likely to be associated with worse oncological outcome of left LUC than right LUC. Template-based lymphadenectomy alone appears inadequate to improve patient survival in left LUC. Funding None
Authors
Tsunenori Kondo
Isao Hara Toshio Takagi Yoshiki Kodama Kenji Omae Junpei Iizuka Kazuhiko Yoshida Hironori Fukuda Kazunari Tanabe |
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MP78-11 |
Positive Predictive Value of CT Urography for Upper Tract Urothelial Carcinoma Diagnosis using Diagnostic Ureteroscopy as the Reference Standard |
Bladder Cancer: Upper Tract Transitional Cell Carcinoma II | 17BOS |
Abstract: MP78-11 Sources of Funding: None Introduction CT Urography (CTU) is the initial imaging modality of choice for assessing upper urinary tract pathology, including upper tract urothelial carcinoma (UTUC). However, despite abnormal findings on CTU suggestive of UTUC, follow-up diagnostic ureteroscopy (DURS) is frequently negative. We aim to assess the positive predictive value (PPV) of CTU for UTUC using DURS as the reference standard. Methods The study group comprised 79 consecutive patients from 2 academic institutions. They had CTU findings of upper tract wall thickening, hydronephrosis, a filling defect and/or contrast enhancement diagnosed in consensus by 2 radiologists as suspicious for UTUC. DURS, with either wash cytology when endoscopically negative or biopsies when endoscopically positive, was used as the reference standard. The results of DURS were classified as UTUC, benign lesions (BL) and no pathological findings (NPF). Statistical analysis was conducted. Results Solitary CTU suspected findings were reported in 45 (57%) patients, including thickness in 8 (10%), hydronephrosis in 5 (6%), filling defect in 30 (38%) and enhancement in 2 (3%). Combinations of suspected findings were reported in 34 (43%) patients. DURS revealed 41 (52%) UTUC, 14 (18%) BL and 24 (30%) NPF. Table shows the calculated PPV. _x000D_ The combination of CTU findings had higher PPV in comparison to solitary findings for detection of UTUC (65% vs 42%, respectively; p<0.05, OR 2.5, 95% CI 1.007-6.28) as well as for overall endoscopic pathological findings (82% vs 60%, respectively; p<0.05, OR 3.1, 95% CI 1.07-9.02). Arbitrary stratification of solitary CTU findings as minor UTUC predictors (PPV<50%: thickening, hydronephrosis and enhancement) and major UTUC predictors (PPV≥50%: filling defect) resulted in a statistically significant better prediction for the major group (p<0.05; OR 7.2, 95% CI 1.39-38.15). Conclusions The best PPV of CTU diagnosis of UTUC is achieved based on a combination of findings, with filling defect appearing to be the most significant among them. In the absence of filling defect, other CTU findings, such as thickening, hydronephrosis and enhancement, are not predictive for UTUC. We suggest that the need for DURS in these cases should be re-considered in correlation with other data (e.g., cytology, biomarkers, history of heavy smoking, recurrent hematuria, etc.). DURS remains the diagnostic standard for deciding whether or not to proceed to nephroureterectomy. Funding None
Authors
Timothy Chan Chang
Ishay Mintz Yuval Bar-Yosef Simon Conti Sophie Barnes Diego Mercer Nicola Mabjeesh Joseph Liao Mario Sofer |
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MP78-12 |
Preoperative Controlling Nutritional Status (CONUT) score as a novel predictive biomarker of survival in patients with localized urothelial carcinoma of the upper urinary tract treated with radical nephroureterectomy |
Bladder Cancer: Upper Tract Transitional Cell Carcinoma II | 17BOS |
Abstract: MP78-12 Sources of Funding: None. Introduction The purpose of this study was to investigate the correlation between Controlling Nutritional Status (CONUT) score and survival of patients with localized urothelial carcinoma of the upper urinary tract (UCUT) treated with radical nephroureterectomy (RNU). Methods We retrospectively enrolled 109 patients. The CONUT score was based on serum albumin level, lymphocyte count, and total cholesterol level. Receiver-operating characteristic curve analysis for relapse-free survival (RFS) was performed, and the maximum Youden index was used to set the cutoff value of CONUT score. According to this cutoff, patients were classified into two groups (i.e., high and low CONUT score). RFS, cancer-specific survival (CSS), and overall survival (OS) after RNU were compared, and predictors of survival were analyzed. Results For CONUT score, the area under the curve was 0.588 and the optimal cutoff value was 3. Twenty-five patients (22.9%) had high CONUT score. The CONUT score was not associated with the clinicopathological parameters. The patients with high CONUT score had significantly lower 5-year RFS, CSS, and OS than those with low CONUT scores (RFS: 46.7% vs. 66.0%; CSS: 25.7% vs. 71.7%; OS: 24.2% vs. 66.8%, all p < 0.05). Multivariate analyses, after adjustment for factors, including pT stage, pN stage and tumor grade, revealed that CONUT score was an independent predictor of CSS (hazard ratio [HR], 5.03; p = 0.0006) and OS (HR, 3.01; p = 0.0080), and a statistically marginal difference in RFS (HR, 2.15; p = 0.0513). Conclusions Preoperative CONUT score is a novel predictive biomarker in patients with localized UCUT treated with RNU. Funding None.
Authors
Hiroki Ishihara
Tsunenori Kondo Kazuhiko Yoshida Kenji Omae Toshio Takagi Junpei Iizuka Kazunari Tanabe |
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MP78-13 |
Impaired baseline performance status and chronic kidney disease are significantly associated with major complications following radical nephroureterectomy |
Bladder Cancer: Upper Tract Transitional Cell Carcinoma II | 17BOS |
Abstract: MP78-13 Sources of Funding: None Introduction Radical nephroureterectomy (RNU) is the gold standard for management of bulky, invasive, or high grade upper-tract urothelial carcinoma (UTUC). Patients undergoing RNU are elderly and comorbid therefore placing them at risk for complications following surgery. We review an international multi-center cohort of RNU patients to identify the incidence of major complications and risk factors for their occurrence. Methods The charts of 1266 patients undergoing RNU at 14 international academic medical centers between 2002 and 2015 were reviewed. Preoperative clinical, demographic, and comorbidity indices were collected. Complications occurring within 30 days of surgery were graded using the modified Clavien-Dindo scale. Multivariate logistic regression determined the association between preoperative variables and Clavien III or greater post-RNU complications. Results A total of 707 men and 559 women with a median age of 70 years and body mass index of 27 kg/m2 were included. Almost 80% of the cohort was white, 17% had an Eastern Cooperative Oncology Group (ECOG) performance status ≥ 2, 22% had a Charlson comorbidity index (CCI) score > 5 and 50% had baseline chronic disease (CKD) ≥ stage III. Overall, 413 (33%) experienced a complication including 103 (8.1%) with a Clavien grade ≥ III. Specific distribution of major complications included 49 Clavien III, 44 Clavien IV, and 10 Clavien V. On univariate analysis, patient age (p=0.006), ASA score (p=0.02), ECOG (p<0.0001), CCI (p<0.0001), HTN (p=0.002), DM (p=0.02), and CKD stage (p<0.001) all were associated with major complications. A multivariate linear regression model highlighted that ECOG ≥ 2 (OR 2.38, p=0.001), CCI > 5 (OR 3.44, p=0.007), and CKD stage ≥ 3 (OR 3.64, p=0.008) were independently associated with major complications. (Table) Conclusions Major complications occur in 8% of patients undergoing RNU. Impaired preoperative performance status (as determined by ECOG or Charlson comorbidity index) and baseline CKD are associated with a major post-surgical adverse event. These easily measurable indices warrant consideration prior to proceeding with RNU. Funding None
Authors
Neil Kocher
Jay Raman David Canes Karim Bensalah Morgan Roupret Costas Lallas Vitaly Margulis Shahrokh Shariat Pierre Colin Surena Matin Chad Tracy Evanguelos Xylinas Andrew Wagner Mathieu Roumiguie Wassim Kassouf Tobias Klatte |
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MP78-14 |
Importance of Tumor Size as Risk Stratification Parameter in Upper Tract Urothelial Carcinoma (UTUC) |
Bladder Cancer: Upper Tract Transitional Cell Carcinoma II | 17BOS |
Abstract: MP78-14 Sources of Funding: none Introduction One of the major challenges regarding upper tract urothelial carcinoma (UTUC) is to identify patients who can safely be managed by kidney-sparing surgery (KSS). European Association of Urology (EAU) Guidelines proposed criteria for pre-treatment risk stratification includes a tumor diameter >1cm as exclusion criteria for KSS. Our aim was to evaluate the performance of different tumor diameters for identifying advanced pathologic stage after RNU and to assess its prognostic value on survival. Methods A multi-institutional retrospective study was conducted that included 800 patients undergoing radical nephroureterectomy (RNU) for non-metastatic UTUC between 1988 and 2016. Tumor sizes were pathologically assessed and categorized into four groups: ≤1, 1.1-2, 2.1-3, >3 cm. We performed logistic regression analyses to compare different diameter thresholds in predicting advanced pathologic stage. Kaplan-Meier analyses with log rank test for comparison was used for the estimation of survival outcomes. Results Overall, 31 (3.9%) patients had a tumor size ≤1cm, 107 (13.4%) 1.1-2cm, 175 (21.9%) 2.1-3cm and 487 (60.9%) >3cm. In preoperative predictive models, that adjusted for the effects of clinicopathologic features, tumor diameters >2cm versus ≤2cm (OR 1.90, p=0.011) and >3cm versus ≤3 (OR 1.71, p=0.003), were both independently associated with advanced stage (≥pT2). The addition of tumor size improved the accuracy of the model from 59 to 61 %. Previous bladder cancer (p=0.011) and preoperative hydronephrosis (p=0.015) were also associated with ≥pT2 disease. Tumor sizes >2cm or ≤2cm predicted muscle-invasion (≥pT2) with 57% positive predictive value (PPV) and 59% negative predictive value (NPV), respectively. With a threshold of 3cm the PPV was 59% and NPV 54%. Kaplan-Meier curves did not show a prognostic impact of tumor size on recurrence-free and cancer-specific survival after RNU. Conclusions Tumor size of 2cm seems to best identify patients who likely harbor muscle-invasive tumor stage. This puts the current risk stratification of EAU Guidelines based on 1cm into question. Our study is limited by the small sample size of ≤1cm tumors and its design (RNU cohort, retrospective, multi-institutional). Therefore, this area needs further research to better identify the optimal criteria for KSS. Funding none
Authors
Beat Foerster
Thomas Seisen Marco Bandini Kees Hendricksen Anna K. Czech Marco Moschini Mohammad Abufaraj Marco Bianchi Donald Schweitzer Kilian M. Gust Morgan Roupret Alberto Briganti Bas G. van Rhijn Piotr Chlosta Pierre Colin Hubert John Shahrokh F. Shariat |
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MP78-15 |
Robotic radical nephroureterectomy is associated with poorer oncological outcomes than open and laparoscopic radical nephroureterectomy |
Bladder Cancer: Upper Tract Transitional Cell Carcinoma II | 17BOS |
Abstract: MP78-15 Sources of Funding: none Introduction In recent years several teams have reported their techniques of robot-assisted radical nephroureterectomy (RARNU) whose main benefit is to facilitate the laparoscopic resection of the bladder cuff, which was usually performed through a Gibson incision in case of laparoscopic radical nephroureterectomy (LRNU). The objective of this study was to compare the oncological outcomes and and patterns of recurrence after RARNU vs. open RNU (ORNU) vs. LRNU. Methods All patients who underwent a RNU in four centers between 2008 and 2016 were included in a retrospective study. The patients were divided into three groups: RARNU, ORNU, and LRNU. The recurrence-free survival (RFS), cancer-specific (CSS), overall survival (OS) and bladder-recurrence-free survival (BRFS) were estimated using the Kaplan-Meier method and compared using the log-rank test. The prognostic factors associated with RFS, BRFS, OS and CSS were assessed using a multivariate Cox regression model. The chi2 test was used to compare recurrence sites between the three groups. Results In total, 185 patients were included : 50 in the ORNU group, 93 in the LRNU group and 42 in the RARNU group. After a median follow up of 22 months, there were 34 recurrences (18.4%) with similar rates of peritoneal carcinomatosis in the three groups (15.8% vs. 12.5% vs. 14.3%; p=0.98). OS and CSS were similar in the three groups. However RFS was poorer in the robotic group compared to the open and laparoscopic groups (1 year: 57.7% vs. 76.1% vs. 76.7%; p = 0.02) as well as BRFS (1 year: 57.1% vs. 81.6% vs. 74.8%; p = 0.04). In multivariate analysis, the robotic approach was associated with BRFS (OR = 8.7; p = 0.01) but not with RFS (OR = 1.7; p = 0.92). Conclusions In this multicenter study, robot-assisted radical nephroureterectomy was associated with poorer RFS and BRFS than laparoscopic and open radical nephroureterectomy. In multivariate analysis, the robotic approach was associated with poorer BRFS but not RFS. Further studies with long-term follow-up are needed to confirm these findings. Funding none
Authors
benoit peyronnet
nicolas brichart franck bruyere quentin alimi tondut lauranne romain mathieu christophe vaessen thomas seisen benjamin pradere adham rammal victor vanalderwerelt gregory verhoest pierre colin morgan roupret karim bensalah |
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MP78-16 |
Outcomes of Ureteroscopic Management of Upper Tract Urothelial Carcinoma |
Bladder Cancer: Upper Tract Transitional Cell Carcinoma II | 17BOS |
Abstract: MP78-16 Sources of Funding: None Introduction Upper tract urothelial carcinoma (UTUC) is an uncommon malignancy, accounting for only five percent of urothelial cancers. Traditionally, nephroureterectomy (NU) with removal of an ipsilateral bladder cuff has been the standard for treatment of this disease entity. However, less invasive, kidney-sparing techniques are becoming more widely embraced. The use of ureteroscopy for the management of UTUC has been advocated in select circumstances such as in patients with a solitary kidney or bilateral disease. Based on our multiple decade experience with this technique, however, we champion a more robust role for this technique and present here our patient experience and outcomes with the use of endoscopy in the management of UTUC. Methods An extensive retrospective review was performed of over two hundred patients with UTUC initially managed by a single endourologic surgeon. Patients were seen over a 21 year period from 1994-2015 with initial evaluations occurring from 1994-2008.Evaluations were performed on patient and tumor characteristics as well as surgical parameters. Statistical analyses were utilized to determine factors affecting patient outcomes. Results A total of 258 patients diagnosed with UTUC were initially evaluated and managed by a single surgeon. 1486 procedures were performed with mean of 7.0 procedures per patient over the period of evaluation. Average tumor size on initial ureteroscopic excision was 16.8 mm (range 1-60) while average recurrent tumor size was 6.4 mm (range 1-50). Of this patient cohort, 94.2% were white and 66% were male. Patients with low grade tumors were successfully managed long-term, with 70.6% of patients avoiding NU. Even in cases of patients with high tumor volume, ureteroscopic management was associated with relatively long-term patient survival. Seventy patients ultimately underwent NU for reasons including conversion to high grade, tumor burden, patient choice and difficult endoscopic access. Multivariate analysis revealed no association of tumor location with survival. Patients with at least a 5 year follow up had overall survival 46.3% and recurrence free survival (RFS) 22%. In this subpopulation, patients with initial grade 1 tumors had RFS of 37.8%. Their average follow up was 7.1 years (range 5-20). Conclusions We have demonstrated that ureteroscopic management of UTUC is a successful alternative to NU for patients with low grade tumors. This work presents a comprehensive investigation of tumor characteristics as well as patient outcomes over a twenty one year period of management of patients with UTUC by a single initial surgeon. Funding None
Authors
Kymora Scotland
Dillon Cason Logan Hubbard Kelly Healy Scott Hubosky Demetrius Bagley |
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MP78-17 |
EAU guidelines inclusion criteria for conservative endoscopic treatment in upper tract urothelial carcinoma: Are they too strict? |
Bladder Cancer: Upper Tract Transitional Cell Carcinoma II | 17BOS |
Abstract: MP78-17 Sources of Funding: none Introduction Evaluate the role of conservative endoscopic treatment (ET) in patients with high-risk upper tract urothelial carcinoma (UTUC) Methods 42 out of 50 (84%) UTUC patients managed conservatively were included in prospective analysis from January 2011 to October 2016. Inclusion criteria were high-risk UTUC diagnosis (one or more high-risk EAU guidelines features), meanwhile exclusion criteria were pT1 or grade III biopsy in elective cases, invasive tumour aspect on CT-urography or previous radical cystectomy._x000D_ ET was performed both retrograde and anterograde access with rigid and digital flexible ureteroscope or percutaneous access. Endoscopic ablation was performed with Ho: YAG laser._x000D_ The variables analysed were: age, sex, history of bladder cancer, elective/imperative indication, hydronephrosis, urine cytology, tumour grade and stage, tumour size (?1cm/>1cm), tumour location and multifocality. Statistical analysis was performed using Chi square test or categorical variables. Overall Survival (OS) and Cancer Specific Survival (CSS) were calculated using Kaplan-Meier analysis. A p value <0.05 was considered to indicate statistical significance. SPSS 17.0 software was used_x000D_ Results Elective and imperative indications occurred in 20 (47,6%) and 22 (52,4%) cases, respectively. Median age was 65 years (46-83) and 35 (70%) were male. Hydronephrosis on diagnosis was present in 17 (40,5%) and high-grade cytology in 4 cases (9,8%). Multifocality were in 21 (50%) and tumour size was >1cm in 23 (54,8%). Biopsies showed grade I in 23 (54,8%) and grade II in 17 (40,5%). Tumour stage was pTa in 37 (88%)._x000D_ ET was possible in 33 out of 42 (78,6%), where 17 (85%) were elective and 16 (72,7%) were imperative. Renal preservation was possible in 18 (94,7%) ?1cm tumours and in 15 (62,2%) >1cm, being tumour size the only predictive variable of renal preservation._x000D_ At 20 months (1-69) of follow up, recurrence was noted in 26 cases (61,9%) and grade progression in 6 (14,31%). The median OS was 51,8 months (42-61) and the median CSS was 56,7 months (47-65) with significant difference between imperative and elective cases. No death occurred in elective cases. Renal preservation survival (time until nephroureterectomy) was 42 months (33-51)._x000D_ Conclusions According to our results, conservative endoscopic treatment should play a more important role in selected high-risk UTUC patients. It suggests a revision of the EAU guidelines recommendations Funding none
Authors
Marta Trassierra Villa
Alberto Budia Daniel López-Acón Domingo de Guzmán Ordaz Pilar Bahílo Francisco Boronat |
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MP78-18 |
Clinical Outcomes and Impact of Treatment on Renal Function for Patients with Second Primary Urothelial Cancers of the Upper Tract Following Radical Cystectomy |
Bladder Cancer: Upper Tract Transitional Cell Carcinoma II | 17BOS |
Abstract: MP78-18 Sources of Funding: none Introduction Patients with bladder urothelial carcinoma (UC) are at risk for developing second primary tumors (SPTs) in the upper urinary tract (UUT). Peri-operative cisplatin-based therapy (CBT) is a standard of care for muscle invasive bladder UC, but requires adequate renal function which may be a limiting factor after definitive surgery for UUT carcinoma. In this study, we evaluate the outcomes of patients with UUT-SPTs after radical cystectomy (RC), with an emphasis on change in renal function associated with extirpative surgical treatment and eligibility for peri-operative CBT. Methods From January 1996 to October 2016, two surgeons at a high volume academic institution performed 486 consecutive RCs for bladder UC. Excluding patients with prior UUT carcinoma, 26 patients developed UUT-SPTs requiring surgical treatment and were the focus of this study. Patient outcomes were measured using end points of survivorship and estimated glomerular filtration rate (eGFR) in relation to tumor stage, tumor grade and time from RC to SPT. Results The 26 (5.3%) patients who developed UUT-SPTs requiring surgical treatment after RC had predominantly invasive cancers (Ta = 23.1%, Tis = 11.5%, T1 = 26.9%, T2 = 19.2%, T3= 15.4%, T4 = 3.9%) which were also predominantly high grade (G3= 88.5%, G2 = 7.7 %, G1 = 3.8). The mean time from RC to the development of SPT was 33.8 months. In a linear regression analysis that controlled for age, bladder pathologic tumor stage was significantly associated with decreased time to SPT (p= 0.030). Neoadjuvant CBT was given to 11.5 % of bladder UC patients prior to RC and 19.2% received adjuvant CBT after RC . Mean eGFR decreased from 69.3 prior to RC to 55.7 prior to UUT-SPT surgical treatment. UUT-SPTs were managed with nephroureterectomy (92.3%) or ureterectomy (7.7%), and ipsilateral lymphadenectomy (77%). Neoadjuvant CBT prior to UUT surgery was administered to 15.4% of patients. Mean eGFR further decreased after UUT-SPT surgery to 39.5, and 23.1% of patients received adjuvant CBT following UUT surgery. Patient were followed for a mean of 76.1 months and 38.5% of patients died of disease, 29.9% died of unknown/other causes, and 34.6% are alive with no evidence of disease. Conclusions UUT-SPTs manifest as more advanced disease after RC. Decreased renal function occurs frequently post RC and may impair the use of peri-operative CBT for patients with high grade SPTs of the UUT. This warrants further studies to develop novel non-nephrotoxic targeted therapies in the peri-operative setting of surgery for SPTs. Funding none
Authors
Nayan Tiwary
Taylor Kohn Rao Mandalapu Seth Lerner |
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MP78-19 |
Surgical Management Of Urothelial Carcinoma In Patients With Upper Tract And Lower Tract Urothelial Carcinoma: Impact Of Surgical Sequence |
Bladder Cancer: Upper Tract Transitional Cell Carcinoma II | 17BOS |
Abstract: MP78-19 Sources of Funding: None Introduction Urothelial carcinoma can occur in both the upper and lower urinary tract; however, the natural history of disease recurrence and outcomes in patients who ultimately require both radical cystectomy (RC) and radical nephroureterectomy (RNU) is poorly understood. We aim to define outcomes in these populations to better inform surveillance strategies following upper and lower tract resection for urothelial carcinoma. Methods We retrospectively reviewed the medical records of patients who underwent both RC and RNU at the Mayo Clinic between 1995 and 2009. Patients who had undergone both RC and RNU were grouped by resection order. Time between resections and pathology data at the time of resection were determined, and Kaplan-Meier analysis was used to evaluate disease specific and overall survival. Results Of 524 patients who underwent RNU at our institution, 100 (19%) patients also underwent RC. 49/100 (49%) underwent initial RC followed by RNU (RC->RNU), 24/100 (24%) underwent RNU followed by RC (RNU->RC), and 27/100 (27%) underwent simultaneous RC and RNU (RC+RNU). The median time between procedures was shorter for patients undergoing RNU->RC (14.6 months) compared to patients undergoing RC->RNU (42.6 months). Upper tract disease after RC (RC->RNU) was more likely to be Grade 3 (80.0%) and T3 or T4 (22.7%) than bladder cancer after RNU (RNU->RC; Grade 3: 58.3%; T3 or T4: 12.5%). Nevertheless, after the second surgery, there was no significant difference in median disease specific survival (DSS, Log-Rank, P=0.28) or overall survival (OS, Log-Rank, P=0.74) between groups RC->RNU (DSS: 83.7 months; OS: 110.1 months), RNU->RC (DSS: 74.3 months; OS: 149.9 months) and RC+RNU (DSS: 62.5 months; OS: 109.2 months). Conclusions Our data highlight the high frequency of synchronous and metachronous upper and lower tract urothelial carcinoma, with nearly 20% of patients undergoing RNU also requiring RC. Disease recurrence in the bladder after RNU occurred more rapidly than upper tract recurrence after RC. However, patients with upper tract recurrence after RC presented later and with higher grade and stage disease compared to patients presenting with lower tract recurrence after RNU. These data highlight the importance of long-term oncologic surveillance after both RC and RNU. Funding None
Authors
Tanner Miest
Amir Toussi R. Jeffery Karnes Stephen Boorjian R. Houston Thompson Matthew Tollefson Igor Frank Bradley Leibovich |
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MP78-20 |
Confocal laser endomicroscopy in upper tract urothelial cancer (UTUC) |
Bladder Cancer: Upper Tract Transitional Cell Carcinoma II | 17BOS |
Abstract: MP78-20 Sources of Funding: none Introduction Real-time confocal laser endomicroscopy (CLE) provides in vivo microscopic images of tissues using a low-energy laser light source. This has been described to be particularly useful in distinguishing between low-grade (LG) and high-grade (HG) bladder transitional cell carcinoma. However, little is known on its potential utility in upper tract urothelial carcinoma (UTUC). The aim of this study is to describe our initial experience with CLE for the evaluation of UTUC. Methods Between January and September 2016, 15 flexible ureteroscopies (f-URS) were performed at our center with CLE for UTUC. A semirigid and/or a flexible digital ureteroscope [Karl Storz, Tuttlingen, Germany] were used in all the patients. An initial inspection of the ureter and renal collecting system was performed in white light with a “no touch technique” (no wire) to macroscopically identify all potential suspicious lesions. CLE was then performed using the Cellvizio® system (Mauna Kea Technologies, Paris, France) according to the following protocol: 10 mL of fluorescein was injected into the renal cavities and left indwelling for 5 minutes. A 3Fr- diameter probe (UroFlex™ B) was inserted through the working channel of the ureteroscope and then placed in contact with the lesions. The reading of the surgeon (low grade vs high grade) was documented in the operation report. Biopsies using a 3 Fr biopsy forceps or a 1.8 Nitinol Basket (COOK) were then performed. The same dedicated genitourinary pathologist blind to the surgeon reading, examined all specimens. A third person compared the informations obtained with CLE with the corresponding histopathological reports. Results Data on 15 patients (13 males and 2 females) are reported. The mean age was 70 (range 61-81). Mean diameter of tumors at CT scan was 22 mm (range 8-50 mm). Tumor locations were: two in the renal calyxes, three in the renal pelvis, 4 in the proximal ureter and 6 in the distal ureter. A total of 22 biopsies were taken. In 9 patients CLE allowed to obtain images with characteristic features compatible with low-grade (LG) UTUC; in 5 patients with high grade (HG) UTUC and in one case CIS. We found correspondence between the CLE images and the final histopathological results in 7/9 cases of LG UTUC (78%), in 4/5 cases of HG UTUC (80%) and in 1/1 case of CIS (100%). In the LG UTUC group two cases (22%) were up-staged to HG at the final histopathology. In the HG UTUC one case (20%) was down-staged to LG. Conclusions CLE might improve the accuracy of the available current tools to characterize the grade of UTUC, therefore providing a better selection of patients for a conservative endourological treatment. Funding none
Authors
Alberto Breda
Angelo Territo Martina Manfredi Andrea Guttilla Luigi Quaresima José Gaya Ferran Algaba Joan Palou Humberto Villavicencio |
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MP79-01 |
Nephrectomy after high-grade renal trauma: Results from the American Association for the Surgery of Trauma (AAST) Genitourinary Trauma Study |
Trauma/Reconstruction/Diversion: External Genitalia Reconstruction and Urotrauma (including transgender surgery) I | 17BOS |
Abstract: MP79-01 Sources of Funding: This investigation was supported by the University of Utah Study Design and Biostatistics Center, with funding in part from the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant 8UL1TR000105 (formerly UL1RR025764). Introduction AUA urotrauma guidelines for renal injury recommend conservative initial management for all stable patients, however, unstable patients with high-grade injury are often managed with nephrectomy. We hypothesized that there are clinical factors associated with need for nephrectomy. Methods From 2014 to 2016, data on high-grade renal trauma (AAST grade III-V) were gathered from 13 participating trauma centers. Demographics, injury characteristics, and trauma management were collected for patients with high-grade renal injury. Shock was defined as systolic blood pressure < 90 mmHg at the time of admission. Needing >10 packed red blood cell (PRBC) was defined as massive transfusion. Univariate logistic mixed effect models with clustering by facility were used to look at associations between proposed risk factors and nephrectomy._x000D_ Results 242 high-grade renal injuries were identified. The mean age and injury severity score (ISS) were 34.0 and 24.4. 34 (14%) nephrectomies were performed. 13/172 patients with blunt injury and 21/70 with penetrating trauma underwent nephrectomies (8% vs. 30%, P<0.001). The nephrectomy rate was 0/139 (0%), 14/69 (20%) and 20/34 (59%) for grades III, IV and V, respectively. Nephrectomies were performed during immediate laparotomy in 25 and were delayed in 9 at a median of 22 hours (range: 3-65 h). A general / trauma surgeon performed the nephrectomy in 26 (76%) of cases. In univariate analyses, renal AAST grade, ISS, presence of associated injuries, and penetrating injury were significantly associated with the need for nephrectomy. Also, clinical factors at admission such as higher heart rate, shock, higher lactate level, base deficit < -6, and massive transfusion needs were associated with higher odds of nephrectomy (Table-1)_x000D_ Conclusions A considerable number of patients with grades IV and V renal injuries are still treated with nephrectomy. Clinical factors like presence of shock, higher heart rate and surrogates of metabolic acidosis were associated with need for nephrectomy for high grade renal injury._x000D_ Funding This investigation was supported by the University of Utah Study Design and Biostatistics Center, with funding in part from the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant 8UL1TR000105 (formerly UL1RR025764).
Authors
Sorena Keihani
Yizhe Xu Angela P. Presson Brian P. Smith Patrick M. Reilly Xian Luo-Owen Kaushik Mukherjee Bradley J. Morris Sarah Majercik Peter B. Thomsen Bradley A. Erickson Benjamin N. Breyer Gregory Murphy Barbara A. Shaffer Matthew M. Carrick Brandi Miller Richard A. Santucci Timothy Hewitt Frank N. Burks Erik S. DeSoucy Scott A. Zakaluzny LaDonna Allen Jurek F. Kocik Raminder Nirula Jeremy B. Myers |
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MP79-02 |
Long-term complications of renal traumas: a multicenter study |
Trauma/Reconstruction/Diversion: External Genitalia Reconstruction and Urotrauma (including transgender surgery) I | 17BOS |
Abstract: MP79-02 Sources of Funding: none Introduction Renal trauma is the most frequent urological trauma, and occurs in 10 % of abdominal trauma. Data regarding long-term complications of renal trauma in the literature are scarce. The aim of this study was to report long-term complications after renal trauma and to assess their predictive factors. Methods A nationwide multicenter retrospective study was conducted, including all patients treated for renal trauma in 15 centers, from 2005 and 2015. Iatrogenic traumas and patients lost to follow up were excluded. Long-term complications were defined as any complications occurring more than 3 months after the trauma._x000D_ Results Out of 1287 patients treated for renal trauma during the study period, 729 patients had long-term follow-up data available. Out of these 729 patients, 37 (5.1 %) had long-term complications. Mean delay between the initial trauma and the diagnosis of long-term complication was 16.23 months. The most common long-term complications and their prevalence are shown in table 1. Treatment of these long-term complications included four nephrectomies, three angioembolizations for renal artery pseudo-aneurysms, one ureteral stenting and 1 ureteral dilation for a ureteral stenosis. Three patients were under anti-hypertensive medications. Conclusions Long-term complications of renal traumas are rare but must be identified because of their potential severity. Long-term complications rate may be underestimated in this series due to the retrospective study design and the high proportion of patients lost to follow-up. Long-term urological follow-up after renal trauma might be advocated in order to identify long-term complications. Funding none
Authors
Ines Dominique
Gaelle Fiard Xavier Matillon Benjamin Pradere Charles Dariane Lucas Freton Jonathan Olivier Cedric Lebacle Clementine Millet Quentin Langouet Paul Panayatopoulos Reem Betari Ala Chebbi Thomas Caes Pierre Marie Patard Francois Xavier Madec Francois xavier Nouhaud Xavier Rod Martine Hutin marina ruggiero Axelle Bohem jerome rizk Kerem Guleryuz Benoit Peyronnet |
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MP79-03 |
Simultaneous Colon and Renal Trauma in the Era of Conservative Management: A Single Institution Study |
Trauma/Reconstruction/Diversion: External Genitalia Reconstruction and Urotrauma (including transgender surgery) I | 17BOS |
Abstract: MP79-03 Sources of Funding: none Introduction Concurrent colon injury in the setting of renal trauma has historically resulted in concern for increased morbidity from genitourinary complications. Sparse data exist on the management of renal trauma in the setting of colon injury, especially in the era of conservative management. This study investigates the effect of concurrent colon injury on the management and morbidity of renal trauma. Methods An institutional trauma registry was queried between the years of 2005 and 2015. All patients with concurrent renal and colon trauma were retrospectively isolated and reviewed. Patient characteristics such as age, renal injury grade, mechanism, need for immediate exploration and urology consultation was noted. Grade of renal injury was stratified according to AAST criteria and was staged via computed tomography imaging or operative examination. If applicable, the type of genitourinary intervention performed was also noted. Complication rates were compared between patients who underwent genitourinary intervention and those that did not. Results A total of 45 patients were included, with the average age of 33 years (16-71 yrs). The slight majority presented with penetrating injury (53%). Immediate abdominal exploration occurred in 51% of patients. Urologic consultation occurred in only seven (15.5%) patients. However, 20 patients underwent urologic intervention, with nephrectomy and renorrhaphy being most common. In total, 13 nephrectomies (29%) were performed, all for high-grade (Grade 4-5) injuries. All nephrectomies were performed by trauma service without urology involvement. Overall complication rate was 57%. Differences in total complication rate were not found to be statistically significant based on genitourinary intervention. No urology specific complications (urinary tract infection, pyelonephritis, perinephric abscess, urinoma) were observed in low-grade (Grade 1-3) renal injuries that were conservatively managed (N=20). Conclusions Urologic intervention for renal trauma with concurrent colon injury does not reduce the risk of complication. Low-grade renal injuries can still be managed expectantly without increasing risk of genitourinary complication. High-grade injuries are at increased risk for nephrectomy. Larger, multi-institutional studies are warranted to determine viability of expectant management or intraoperative urology consultation in high-grade renal injuries with concurrent colon injury. Funding none
Authors
James Furr
Jared Higley Byron Dubow Babawale Oluborode Tabitha Garwe Sanjay Patel Alisa Cross Brian Cross |
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MP79-04 |
Contemporary Report of a Multi-institutional Experience with Fournier’s Gangrene |
Trauma/Reconstruction/Diversion: External Genitalia Reconstruction and Urotrauma (including transgender surgery) I | 17BOS |
Abstract: MP79-04 Sources of Funding: none Introduction Fournier's gangrene is a rare necrotizing soft tissue infection requiring emergent surgical debridement that is often morbid, disfiguring, and can be fatal. Mortality rates reported in the literature have historically been as high as 20-40%. However, contemporary series suggest survival rates are improved. Our objective was to determine the patient characteristics, clinical course, and outcomes for patients treated for Fournier's gangrene at three large, urban, academic, tertiary care institutions. Methods In this multi-institutional retrospective study, cases of Fournier's gangrene were identified by ICD-9 (608.83) and CPT (11004, 11005, 11006) codes after obtaining institution-specific review board approval. Accurate diagnosis was confirmed on chart review. Data on comorbidities, hospital course, length of stay, and mortality were extracted from the medical record. Results A total of 147 men (ages 24-81, median 52 years) treated for Fournier's gangrene between 2006 and 2016 were identified. Sixty-seven percent of these men had diabetes mellitus. Patients underwent an average of 2.5 (range 1-7, median 2) debridements while hospitalized, with an average length of stay of 19 (range 2-96, median 15) days. Fifty-five percent of patients required multidisciplinary surgical management with some combination of urologic, general, plastic, trauma, and colorectal surgeons, with 22% requiring fecal diversion. Seventy-six percent of men were admitted to the ICU, and 59% required mechanical ventilation. Most wounds were managed with wet to dry dressings, though 27% were covered with a wound vac. Inpatient mortality was 7.4%, which is lower than prior small case series and consistent with contemporary population based studies. Diabetics were significantly more likely to undergo more than one debridement than non-diabetics (p=0.009). Conclusions Great strides have been made in reducing the mortality rate of Fournier's gangrene, but high percentages of patients require multiple operations, fecal diversion, and multidisciplinary surgical management. Patients with diabetes are more likely to return to the operating room for repeat debridements. These findings offer insight into contemporary outcomes for men affected by this devastating condition. Funding none
Authors
Barbara E Kahn
Alexander J Tatem Daniel J Mazur James Wren Marah Hehemann Anuj S Desai Mary Kate Keeter Patrick Hensley Jonathan Walker James B Angel Kevin Lewis Matthew J Mellon Jason R Bylund Nelson E Bennett Robert E Brannigan |
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MP79-05 |
SINGLE-STAGE DELAYED PRIMARY CLOSURE OF FOURNIER’S GANGRENE: OUR EXPERIENCE AT THE UNIVERSITY OF PUERTO RICO MEDICAL CENTER |
Trauma/Reconstruction/Diversion: External Genitalia Reconstruction and Urotrauma (including transgender surgery) I | 17BOS |
Abstract: MP79-05 Sources of Funding: None Introduction Fournier's gangrene (FG) has been a dreadful entity since first described in the late 19th century. Initial management includes hemodynamic stabilization, broad-spectrum antibiotics, and aggressive surgical debridement. Moreover, posterior wound management and closure, which requires multiple surgical procedures and prolonged hospitalizations, has always been a multidisciplinary challenge. We want to report our experience, involving a single-stage delayed primary closure (DPC) of FG, using mattress sutures and a non-slip knot technique, which aims to reduce patient's admission time and necessity for multiple operations. Methods Retrospective analysis of 27 patients who underwent surgical management over the last three years due to FG. All patients underwent wide local debridement and DPC, using the same technique, involving the placement of interrupted Prolene mattresses along the wound edges and sequential wound re-approximation. Patients were analyzed in respect to age, comorbidities, total area and volume of resection, hospitalization time, and WBC at the time of admission. Results Mean patient age was 57.7 years (range 45-82 years). Most prevalent comorbidities were diabetes mellitus and hypertension (55% of cohort). Other comorbidities included alcohol dependence, obesity, and peripheral vascular disease. The average resected area was 89 cm2 (12-225 cm2), with resection volume of 224 cm3 (18-700 cm3). Average hospitalization was 8.2 days (2-19 days). Mean WBC count at the time of admission was 16.7 thousand cells/mcL (6.6-33). Four patients required a secondary procedure, three for revision due to persistent soft tissue defects, and other for a general surgery procedure. Only three patients received supplementary hyperbaric therapy during the delayed closure time. After discharge, all patients were followed at least once, within 2 weeks after discharge, and none required further surgical management or re-hospitalization. When compared to a matched cohort of patients with similar characteristics, the admission time and the need for secondary procedures was diminished, and results were statistically significant. Conclusions Our data show that patients with FG can be safely managed with delayed primary wound closure. Also, the necessity for expensive supportive therapies and reoperation is decreased. This may translate into improved wound healing, cosmesis, and shorter hospitalization time. Moreover, this method may become an option for well-selected patients with defects not requiring tissue grafting. Funding None
Authors
Jose Antonio Saavedra-Belaunde
Timoteo Torres Antonio Puras-Baez Magaly Cabrera-Beauchamp |
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MP79-06 |
Surgical Management of Genitoperineal Hidradenitis Suppurativa: A 12 year experience |
Trauma/Reconstruction/Diversion: External Genitalia Reconstruction and Urotrauma (including transgender surgery) I | 17BOS |
Abstract: MP79-06 Sources of Funding: None Introduction Hidradenitis Supurativa (HS) is a recurrent inflammatory disease of the apocrine glands that causes painful lesions associated with sinus tracts, abscesses and skin fibrosis which can be debilitating. We report our experience with surgical management of genitoperineal HS with complete resection and reconstruction using local skin flaps and grafts in 23 patients, the largest series of which we are aware. Methods We completed a retrospective chart review from June 2004 to June 2016 of patients treated with complete resection of HS in the genital and perineal region. Patient demographics, previous treatment of HS, incidence/nature of recurrence and complications were analyzed. Results From 2004-2016 23 patients underwent hidradenitis excision. 96% were male, 74% were African American. The average age was 46 years old, with an average BMI of 31.5 (19.7-50.7). The most common comorbidities included tobacco use (69%), obesity (57%), HTN (39%) and DM (22%). Prior to definitive excision, 16 patients (76%) had at least one incision and drainage. STSG was required in 30% of patients, but the rest were covered with local thigh, scrotal or perineal flaps. Average length of hospital stay was 3.5 days (0-22 days). Follow-up interval was 13 months (0-45 mo). The 30-day complication rate was 48% (11/23 patients) for minor complications (Grade 1-2) which included wound infection and dehiscence. 3 patients (13%) had a Grade 3B complication with no grade 4 or 5 complications. Recurrence of HS outside of the borders of previous excision occurred 1-42 months after surgery in 8 (35%) patients, most requiring limited re-excision. Conclusions Genitoperineal HS can be a debilitating, painful and disfiguring disease. Conservative treatments or incision and drainage of lesions is ineffective in curing the root cause of the problem, and persistence or worsening is the rule over time. Complete surgical resection followed by local flap or skin graft closure is possible, curative and most often successful, at the cost of a unsurprisingly high number of self limited wound complications. Urologists should endeavor to fix instead of merely manage this difficult problem. Funding None
Authors
Brandi Miller
Sarah Martin Richard Santucci |
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MP79-07 |
Indications for novel interposition myocutaneous flap for the repair of recto-urinary fistula |
Trauma/Reconstruction/Diversion: External Genitalia Reconstruction and Urotrauma (including transgender surgery) I | 17BOS |
Abstract: MP79-07 Sources of Funding: none Introduction Recto-urinary fistula (RUF) is a rare complication following pelvic surgery, radiation or trauma. We report our experience using a perineal approach with a cremasteric myocutaneous interposition flap (CIF) for the treatment of symptomatic RUF and sought to compare their outcomes with patients undergoing repair with other interpositions. _x000D_ _x000D_ _x000D_ Methods We identified all patients undergoing RUF repair at a single institution from January 2001 to June 2014. Demographics, fistula etiology, surgical approach and outcomes were reviewed. Successful RUF repair was defined based on a post-operative voiding cystourethrogram without evidence of contrast extravasation. Results 26 patients underwent RUF repair by a single surgeon at our institution. All patients underwent colonic diversion prior to repair. Initial repair was performed at the median age of 63 (21-83) years using a cremasteric interposition flap (CIF) in 12 patients, gracilis interposition flap (GIF) in 13 and a rectus myocutaneos flap (RMF) in one. Median follow-up was 8.8 (1-44) months. Fistulas were categorized as complex where radiation therapy, salvage cryoablation or APR was performed (69.2%), and simple when they occurred in the setting of radical prostatectomy, hemorrhoidectomy or trauma (30.8%). Pre-repair hyperbaric oxygen was performed in 57.7% of patients and was not associated with improved success in initial closure for either complex or simple fistulas (p=0.16, 0.69). In the CIF group, 9 (75%) patients failed the initial repair with 2 subsequently undergoing successful second CIF, 4 with successful subsequent GIF and 2 lost to follow-up. One patient failed a repeat CIF. The majority of patients (88%) who failed initial repair with CIF had radiation-induced fistulas, whereas only 33% of patients with a successful initial repair had prior radiation exposure (p=0.12). In the GIF group, 11(84.6%) had successful repair with initial surgery. Initial repair of simple fistulas was more successful than complex fistulas (p=0.04). The use of GIF or rectus myocutaneous flap resulted in improved success in complex fistula repair as compared to CIF (p=0.004). There was no difference seen in success of simple fistula repair when comparing GIF and CIF (p=0.17). Conclusions Perineal repair of RUF using CIF is a novel approach with potentially less morbidity than larger muscle interposition flaps. However, the CIF is less effective in complex fistulas and thus should only be considered in patients with simple fistulas. For complex fistulas, a more vascularized flap such as GIF or rectus myocutaneous flap is effective. Funding none
Authors
Alyssa Greiman
Lawrence Dagrosa Nima Baradaran Eric Rovner Harry Clarke |
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MP79-08 |
Updated Outcomes of Early Endoscopic Realignment for Pelvic Fracture Urethral Injuries at a Level 1 Trauma Center |
Trauma/Reconstruction/Diversion: External Genitalia Reconstruction and Urotrauma (including transgender surgery) I | 17BOS |
Abstract: MP79-08 Sources of Funding: None Introduction The initial management of pelvic fracture urethral injuries (PFUI) with early endoscopic realignment (EER) versus suprapubic tube (SPT) placement is controversial. At our institution, early endoscopic realignment (EER) is performed for all patients who undergo pelvic fracture repair. In our initial analysis from 2011, we evaluated 19 patients and reported a 21% success rate for EER. We sought to update our experience with EER following PFUI. Methods A retrospective review was performed of patients treated at our level 1 trauma center with EER for PFUI secondary to blunt pelvic trauma. EER was performed with a retrograde or a combined antegrade/retrograde approach with a cystoscope through the SPT tract. Failures of EER were defined as requiring a secondary procedure, permanent SPT management, or lost to follow up (LTF). Treatment success was defined as no secondary procedure or the ability to pass a cystoscope across the area of injury or surgical anastomosis. Results Thirty patients underwent EER at our institution between 2004-2016 with a mean follow up of 27 months (range 0-105). Mean time to realignment was 2 days (range 0-6). Delayed EER was scheduled with another surgical service in 22 patients (81%). Average operative time for EER was 46 minutes (range 6-100). No patient experienced complications from endoscopic realignment (i.e. pelvic abscess or orthopedic hardware infection). The catheter was removed on average 35 days (range 12-98) after EER. 26 patients (87%) returned with obstructive voiding symptoms (mean 27 days, range 2-109) requiring delayed surgical treatment and 1 patient was LTF. Using an intent-to-treat analysis, 27 patients (90%) failed EER (Figure). 15 patients underwent primary urethroplasty with 100% success. 2 patients elected permanent SPT management. 9 patients underwent primary endoscopic management with dilation or DVIU with 22% success (2/9). Of the 7 patients who failed endoscopic management, 6 patients underwent urethroplasty with 100% success and 1 patient was LTF. Conclusions Our updated overall success rate for EER was 10%. The low long term success rates of EER should be balanced with potential benefits such as decreased orthopedic hardware infection after SPT removal and improved alignment in the case a subsequent urethroplasty is required. Funding None
Authors
Paul H Chung
Hunter Wessells Bryan B Voelzke |
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MP79-09 |
Title: Robot Assisted Penile Inversion Vaginoplasty a Description of a Novel Technique |
Trauma/Reconstruction/Diversion: External Genitalia Reconstruction and Urotrauma (including transgender surgery) I | 17BOS |
Abstract: MP79-09 Sources of Funding: None Introduction Gender confirmation surgery represents an essential component in the management of gender identity disorder. The perineal dissection and creation of the neovaginal canal is the most challenging aspect of the penile inversion vaginoplasty (PiV) and poor visualization can lead to surgical complications. An incomplete dissection also results in a foreshortened neovagina, increased risk for vaginal stenosis and need for excessive postoperative dilations. Here we present the results of our first 15 patients performed at our intuition utilizing our robot assisted PiV (RAPiV). Methods 15 transgender patients who were already living as females presented to our institution from 1/2016 to 10/2016, and underwent our previously defined RAPiV. Briefly, the RAPiv is performed in the low lithotomy position and the penis is degloved through a circumcision incision. An additional perineal incision is made to the bulbar urethra. The dissected penis, urethra, neurovascular bundle, glans and corpora are delivered through the perineal incision (Figure 1a). We spare the dorsal aspect of the tunica of the corpora cavernosa to reduce risk of glans necrosis. Four robotic ports were placed and the abdomen was insufflated (1b) and robot docked. Denonviller’s fascia is opened (1c) and the abdominal dissection is continued to the peritoneal one (1d), the neovagina is passed into robotic field (1e) and pexed to the anterior reflection of the posterior peritoneum (1f). The peritoneal reflection is then closed (1g). We then complete the labioplasty and clitoroplasty. Results The average operative time for RAPiV was 5.8 hours (5-7), 8/15 (53%) required mobilization of additional tissue flaps (4/15, 27%) or underwent concomitant abdominoplasty and skin graft harvest (4/15 27%) to supplement penile skin. EBL was 386cc (100-600) and LOS was 3.7 (2-6). Average postoperative vaginal depth was 11.3cm (10.2-12.7). Two patients had complications, 1 dehiscence of labioplasty treated with conservative therapy and 1 had loss of neovagina depth and distal urethral stenosis secondary to wound infection requiring debridement. Conclusions We have performed 15 cases utilizing our novel method for robot assisted penile inversion vaginoplasty. Under direct visualization the neovaginal canal is created. This technique achieves maximal vaginal length in a reproducible manner. Funding None
Authors
Brenton Armstrong
Aaron Weinberg Kiranpreet Khurana Jamie Levine Lee Zhao |
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MP79-10 |
URINARY?CUTANEOUS FISTULAE: A RARE BUT MORBID COMPLICATION OF NON-OPERATIVELY MANAGED EXTRAPERITONEAL BLADDER RUPTURES |
Trauma/Reconstruction/Diversion: External Genitalia Reconstruction and Urotrauma (including transgender surgery) I | 17BOS |
Abstract: MP79-10 Sources of Funding: None Introduction Non-operative management of uncomplicated traumatic extraperitoneal (EP) bladder ruptures has become the standard of care. However, a number of these patients still develop significant complications. We sought to evaluate our experience with urinary-cutaneous fistulae (UCF) in conservatively managed EP rupture patients. Methods Review of our institutional trauma registry identified all patients admitted with blunt-trauma EP bladder ruptures from 2000 to 2014. Patients with concomitant urethral, bladder neck, or ureteral injuries were excluded. All patients who underwent primary management with catheter drainage alone were included in the analysis. Patient characteristics, urologic complications (specifically UCF) and management strategies were evaluated. Results 162 traumatic bladder injuries were identified during the study period. 96/162 (59%) of these bladder injuries were classified as EP. 56/96 (58%) of EP ruptures were managed conservatively with catheter drainage, of which 10 (18%) developed major urologic complications (Clavien Dindo-Grade ≥ III), with 6/10 (60%) developing UCF (6/56 [11%]). Of the patients with UCF, mean age was 47.9 years with 50% of patients female. All injuries were a result of motor vehicle accidents, with a mean injury severity score at presentation of 43.7. Four patients (66.7%) underwent non-urologic operations without cystorrhaphy at presentation, while one was taken to the operating room for cystoscopy and catheter placement alone. Mean time to diagnosis of EP rupture was three days, while mean time to diagnosis of UCF was 13.5 days. Two patients developed UCF to the perineum, while four were to the medial aspect of the thigh. One patient died without resolution of her fistula. Of the remaining five, all subsequently required operative repair for fistula resolution, with none healing spontaneously. Mean time to repair from diagnosis was 30 days (range 2 to 106). One patient required a second operation after fistula recurrence. Mean time to resolution from initial diagnosis for all patients was 90 days. _x000D_ Conclusions UCF are an underreported but significantly morbid complication of non-operative management of EP bladder ruptures. Though our numbers preclude the ability to analyze specific predictors of UCF, the occurrence of UCF following non-operative management of EP bladder rupture should prompt surgical intervention given the potential for prolonged convalescence and low likelihood of spontaneous resolution. Funding None
Authors
Niels Johnsen
Rachel Sosland Jason Young Joshua Cohn W. Stuart Reynolds Melissa Kaufman Doug Milam Oscar Guillamondegui Roger Dmochowski |
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MP79-11 |
Comparison of Outcomes between Ulnar and Radial Free Flaps for Neophallus Construction |
Trauma/Reconstruction/Diversion: External Genitalia Reconstruction and Urotrauma (including transgender surgery) I | 17BOS |
Abstract: MP79-11 Sources of Funding: None Introduction Forearm free flaps are a well-known modality for total phallic reconstruction. Both ulnar and radial artery flaps have been described, however there is a paucity of literature comparing outcomes between these two methods. Methods A retrospective chart review was performed using 64 patients (65 total phalloplasties) who met inclusion criteria. All procedures were performed at our institution between 1983 and 2015. Demographics were compared using student's T-test (age) and Fisher's exact test (all other demographic variables). Outcomes were compared using Fisher's exact test to investigate for statistically significant differences in stricture rate, fistula rate and flap loss for ulnar vs. radial free flaps. Results Of the 65 procedures performed, there were 7 flap losses, 26 fistulas and 27 strictures. Mean follow-up was 78 months (range 0.4-395). One patient who experienced radial flap loss went on to have a successful ulnar flap neophallus created. No statistical demographical difference existed between the two groups. Of the 58 successful procedures, there was a statistically significant difference (p = <0.01) in the number of fistula formations, with ulnar flaps being superior to radial flaps. Ulnar flaps also showed a trend towards decreased stricture formation, but this failed to reach significance (p=0.059). There was no difference in the number of flap losses between the ulnar and radial groups (4 vs. 3 respectively, p=1.0). Conclusions Ulnar forearm free flaps are associated with a significantly decreased fistula rate when compared to radial free flaps. There was also a trend towards decreased urethral stricture rate, however this failed to reach significance. There was no difference in flap loss between the two groups. Funding None
Authors
Katherine Smentkowski
Jack Zuckerman Oscar Suarez Fernadez de Lara David Gilbert Ramon Virasoro Jessica Delong Jeremy Tonkin Kurt McCammon |
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MP79-12 |
Skin Graft Glanuloplasty after Total Glansectomy or Partial Penectomy. |
Trauma/Reconstruction/Diversion: External Genitalia Reconstruction and Urotrauma (including transgender surgery) I | 17BOS |
Abstract: MP79-12 Sources of Funding: none Introduction The importance of psychosocial and sexual outcomes for patients after glansectomy or partial penectomy cannot be overstated. Penile lenght preservation and a good cosmetic apearence are essential for good functional outcomes. Despite the popular use of different skin flaps to cover the distal penile shaft, the use of grafts have been increasing during the last years. The objective of this study is to evaluate the experience with skin graft glanuloplasty. Methods The charts of 17 patients submitted to a total glansectomy or a partial penectomy and to a glanuloplasty with a skin graft were analysed. The age of the patients ranged from 58 to 76 years (mean of 67 years). The mean follow-up time was 16 months (minimal follow-up of 6 months). The group included 15 patients with diagnosis of penile cancer (stages I or II) and 02 patients with complications after malleable penile implants. In all patients with penile cancer the disassembly technique principle (proposed to treat distal penile deformities) was used to achieve the maximum penile lenght preservation (organ sparing surgery) . After the mobilization of the complex urethra, glans, tumor, skin and dorsal plexus, a partial penectomy was performed in 4/15 patients (26,7%) and a total glansectomy in 11/15 (73,3%). After the oncological ressection, the glanuloplasty was performed. First, a corporoplasty to modify the shape of the distal penile shat ( to become more cylindrical) . After, the fixation of the spatulated urethra on the top penile shaft, the dorsal plexus and the penile skin creating an area for neoglans . A split-tickness skin grafts harvest from the thigh was used to the glanuloplasty in 14/17 patients ( 82,3%) and a full tickness skin graft in 3/17 cases (17,7%) Additional cosmetic procedures was used in 5 patients (29,4%) - suspensory ligament release, ventral phaloplasty, and suprapubic lipectomy. Results None patients had local recurrences during the follow-up period. None urethral complications (meatal stenosis) were observed. All patients are able to urinate in a standing position. Erection was preserved in 12/17 patients (70,6%) and 8/12 (66,7%) refered sexual intercourse. The patients satisfaction was excellent and all patients were satisfied with the cosmetic results and considered that they expected a penile lenght lower and a worse cosmetic result than was observed in the postoperative period. Conclusions The use skin graft glanuplasty in the scenario of the organ sparing glasectomy or partial penectomy seems to be a safe option for the treatment of penile cancer with involvement of the distal portion of the penile shaft, offering the high functional and cosmetic outcomes. Funding none
Authors
André Cavalcanti
Carlos Felipe Restreppo Henrique Florindo Roberto Medeiros Túlio Rojas Neildo Chaves |
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MP79-13 |
Genitourinary Injury in Male Veterans Receiving VA Health Care: The Importance of Linking DoD and VA Data |
Trauma/Reconstruction/Diversion: External Genitalia Reconstruction and Urotrauma (including transgender surgery) I | 17BOS |
Abstract: MP79-13 Sources of Funding: VA Health Services Research and Development Service Project # I01 HX000329-05; The view(s) expressed herein are those of the author(s) and do not reflect the official policy or position of Brooke Army Medical Center, the U.S. Army Medical Department, the U.S. Army Office of the Surgeon General, the Department of the Army or the Department of Defense or the U.S. Government. Introduction Outcomes of military genitourinary injuries (GUI) have not been well-studied. Although US servicemen with GUI sustained during Operations Iraqi and Enduring Freedom (OIF/OEF) have been identified separately in the Department of Defense Trauma Registry (DoDTR) and VA electronic medical records, no previous studies have linked DoD and VA data to investigate outcomes in the population of Veterans with combat deployment-related GUI. Methods VA electronic medical records were searched for male OIF/OEF Veterans receiving VA care at least once between 1 October 2001 and 30 September 2011. VA records were linked with DoDTR records for male US service members injured while deployed to OIF/OEF during the same time period. Variables extracted from the DoDTR included type of GUI, severity of GUI, and Injury Severity Scores (ISS). Outcome diagnoses from VA electronic medical records included sexual dysfunction, urinary symptoms, and neuropsychiatric conditions. Injury characteristics and prevalence of outcomes among those with and without GUI were compared. Results Of the 12,923 injured male OIF/OEF Veterans identified in both VA electronic medical records and the DoDTR, n=591 (4.6%) had a diagnosis of combat deployment-related GUI in the DoDTR. Of note, only 3.0% of patients with a GUI diagnosis in the DoDTR also had a GUI diagnosis documented in VA medical records. The 591 patients with GUI were injured early in OIF/OEF, with 80.0% injured before 2008. A total of 30.3% had severe GUI. Overall injury severity was greater (ISS ≥ 16: 58.5% vs. 14.9%; p<0.01) and the prevalence of both urinary symptoms (6.3% vs. 3.1%; p<0.01) and sexual dysfunction (13.5% vs. 7.1%; p<0.01) higher among those with GUI vs. without GUI, respectively. Traumatic brain injury prevalence was higher among those with vs. without GUI (48.0 % vs. 40.0%; p<0.01) and post-traumatic stress disorder (PTSD) was common among both groups (51.6% vs. 50.6%; p=0.64). Conclusions A minority of VA patients with GUI sustained during OIF/OEF have GUI documented in their VA medical record. However, VA patients with GUI have substantially higher rates of urinary and sexual problems treated at VA facilities. Thus, comprehensive care for OIF/OEF Veterans could be improved with better documentation of GUI upon transfer from DoD to VA care. Funding VA Health Services Research and Development Service Project # I01 HX000329-05; The view(s) expressed herein are those of the author(s) and do not reflect the official policy or position of Brooke Army Medical Center, the U.S. Army Medical Department, the U.S. Army Office of the Surgeon General, the Department of the Army or the Department of Defense or the U.S. Government.
Authors
Steven Hudak
Jean Orman Megan Amuan Mary Jo Pugh Nina Nnamani Douglas Soderdahl Judson Janak Michael Liss |
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MP79-14 |
Penile Fracture Incidence and Physician Compliance with Urotrauma Guidelines in New York State |
Trauma/Reconstruction/Diversion: External Genitalia Reconstruction and Urotrauma (including transgender surgery) I | 17BOS |
Abstract: MP79-14 Sources of Funding: None Introduction Penile fracture (PFx) is a rare form of genital trauma (GT) that can impact long term penile health and sexual quality of life. Population data describing real world incidence and management of PFx are scarce. We describe the management of PFx in relation to American Urological Association (AUA) urotrauma guidelines using a large statewide database. Methods We queried the New York Statewide Planning and Research Cooperative System database for men presenting to an Emergency Room with PFx from 2003-2014. Patients were identified with ICD-9-CM diagnosis 95913. Management was defined as surgical or nonsurgical by concomitant procedural codes for any penile or urethral surgery. Use of diagnostic tests for urethral evaluation was determined by CPT codes. Guideline compliance was defined as surgical management or non-surgical management only if imaging was performed. Incidence was calculated from New York census data. Patients were tracked for PFx sequelae. Results 711 men presented with PFx with mean age 38 years (Range 18-81). PFx accounted for 6.2% of all GT over this time. The incidence rate was 0.83 cases/100,000 person-years (p-y) with a peak in men 30-39 years old (1.31 cases/100,000 p-y). Eighty men (11.3%) underwent urethral evaluation, 15 (2.1%) had diagnostic ultrasound and 397 (55.8%) underwent surgery (Figure 1). All men with ultrasound were managed conservatively. The AUA guideline compliance rate was 58%. On multivariate logistic regression, high comorbidity burden was associated with low compliance (OR [95% CI]: 0.35 [0.16-0.73], p<0.01) whereas non-White race (1.58 [1.16-2.16], p<0.01) and academic centers (1.53 [1.11-2.11], p=0.01) were associated with high compliance. PFx sequelae (erectile dysfunction, urethral stricture, Peyronie&[prime]s disease) developed in 12 patients (1.7%). Conclusions This is the largest report of PFx incidence and management in the literature to date. PFx is rare with peak rate in men 30-39 years old. About half of cases were managed surgically with overall guideline compliance rate of only 58%. This may reflect suboptimal management or incorrect diagnostic coding of non-fracture injuries. Efforts to improve physician education on the management of suspected PFx is crucial given its potential for long term morbidity. Funding None
Authors
Michael J Lipsky
Wilson Sui Alexander C Small Dennis J Robins Carrie M Mlynarczyk Steven B Brandes Peter J Stahl |
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MP79-15 |
Development of Hypertension after Renal Trauma |
Trauma/Reconstruction/Diversion: External Genitalia Reconstruction and Urotrauma (including transgender surgery) I | 17BOS |
Abstract: MP79-15 Sources of Funding: none Introduction Traumatic renal injuries are often managed conservatively without the need for operative exploration or embolization. Complications following non-operative management for renal trauma are low; however, post-traumatic hypertension (HTN) has been reported. We sought to determine if traumatic renal injuries, renal trauma grade, and/or computed tomography (CT) findings are predictive of developing long-term HTN. Methods We performed a retrospective review of a prospectively maintained renal trauma database at Zuckerberg San Francisco General Hospital from 1995-2015. Renal injuries were categorized using the American Association for the Surgery of Trauma grading system. Isolated non-renal genitourinary trauma patients were selected as controls. Patient charts were reviewed for a diagnosis of HTN on follow-up and/or initiation of anti-hypertensive medication(s). Renal CT scans were obtained for patients having renal trauma after July of 2004 and reviewed for injury characteristics. Patients with HTN prior to their trauma or lack of follow up were excluded. Results In total, 390 patients had renal injuries and 163 (42%) met our inclusion criteria. 142 controls were identified with traumatic non-renal, genitourinary injuries, and 60 (42%) met our inclusion criteria. The median age of patients at the time of their trauma was 31 years (interquartile range, IQR 23-43) with median follow up of 4.7 years (IQR 1.9-8.5). 23/163 (14%) of renal trauma patients were newly diagnosed with HTN on follow-up, compared to 2/60 (3%) in the control group (p=0.02). After adjusting for age, sex, race, history of nephrectomy, and follow-up time, the odds of developing HTN after a high grade renal trauma was 15.6 (95% confidence interval, CI 2.3-107.1) (Table 1). Patients with a mid-pole medial laceration with medial blood on CT had higher odds of developing HTN compared to patients without these characteristics (odds ratio, OR 5.36, 95% CI 1.3-22.6). Nephrectomy, or any renal procedures were not associated with developing HTN. Conclusions Increasing renal trauma grade is a risk factor for future development of HTN. CT findings at trauma presentation suggest mid-pole medial laceration with medial blood may be useful in stratifying patients who are at risk. Routine follow-up for the development of HTN is warranted following high grade renal trauma. Funding none
Authors
E. Charles Osterberg
Mohannad Awad Gregory Murphy Thomas Gaither Jennie Yoo Thanabhudee Chumnarnsongkhroh Benjamin Breyer |
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MP79-16 |
Complications of Genital Enlargement Surgery |
Trauma/Reconstruction/Diversion: External Genitalia Reconstruction and Urotrauma (including transgender surgery) I | 17BOS |
Abstract: MP79-16 Sources of Funding: none Introduction The objective of genital enlargement surgery is to increase length and/or girth for cosmetic reasons. These surgeries have been recently reported to be associated with only minor complications in a small percentage of patients. However, we continue to see and treat patients with major complications from these procedures and present our experience to date. Methods Institutional Review Board approval was obtained. We reviewed our prospectively maintained database for all patients who presented with complications of genital enlargement surgery from 2002-2016. Results Eight patients were identified. Mean age was 49 years (29-70). Prior procedures included subcutaneous penile and/or scrotal implants, dermal grafts, subcutaneous autologous or silicone injections, and suspensory ligament ligation. Three patients underwent multiple of these techniques. All patients who underwent subcutaneous penile implant underwent removal prior to presentation. _x000D_ _x000D_ Adverse changes included sexually disabling penile deformity, curvature, edema, subcutaneous masses, infection, non-healing wounds, and scarring. Seven patients underwent corrective surgery, with 2 requiring multiple procedures and 2 requiring split thickness skin grafting. All 7 patients had an improved cosmetic appearance. Postoperative Sexual Health Inventory for Men (SHIM) scores were available for half of these patients, with a mean of 18 (2-25). _x000D_ Conclusions Penile and scrotal enhancement surgery can be associated with major disabling complications, leading to deformity and functional compromise in men with prior normal anatomy. Patients should be aware of these risks. According to the Sexual Medicine Society of North America, these surgeries should be considered experimental. Funding none
Authors
Kristi Hebert
Eric Wisenbaugh Joel Gelman |
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MP79-17 |
IDIOPATHIC URETHRAL STRICTURES -- SIMILAR CHARACTERISTICS TO THOSE FOLLOWING RECOGNIZED TRAUMA |
Trauma/Reconstruction/Diversion: External Genitalia Reconstruction and Urotrauma (including transgender surgery) I | 17BOS |
Abstract: MP79-17 Sources of Funding: none Introduction Up to one-third of men undergoing urethroplasty have strictures of unknown etiology. Little data exists defining the clinical characteristics and outcomes of urethroplasty in this population. We hypothesized that idiopathic strictures may be the result of unrecognized remote urethral trauma. The aim of this study was to compare stricture characteristics and surgical outcomes of men with idiopathic strictures to those with an identified etiology in an effort to delineate the nature of this common, yet poorly understood entity. Methods We retrospectively reviewed our urethroplasty database of over 1200 cases performed from 2007-2016 to identify those men undergoing first-time urethroplasty. Patients were stratified by urethral stricture etiology including radiation, trauma/iatrogenic, hypospadias, balanitis xerotica obliterans, and idiopathic. Idiopathic strictures were defined by absence of any identified etiology. Only cases with at least 2 years follow-up were included in this analysis. Results Of the 434 patients with urethral strictures undergoing first-time urethroplasty having complete data available, more than one-third were identified as being idiopathic (165/434, 38%). When compared to other stricture etiologies (Table 1), men with idiopathic strictures were remarkably similar to traumatic/iatrogenic strictures in terms of age, stricture length, location, and surgery. The majority of idiopathic strictures presented in younger men (median 48 years), were confined to the bulbar urethra (153/166, 92%), and had a median length of 2 cm. The most common procedure was excision and primary anastomosis (EPA) (123/165, 74%) and only 19 (11%) men with idiopathic strictures experienced primary urethroplasty failure. Compared to strictures with identified etiology, men with idiopathic strictures underwent more pre-urethroplasty endoscopic interventions and had a greater delay between diagnosis and surgery. Estimated 24-month stricture recurrence-free survival was similar to traumatic strictures (79% vs 77%) with radiation and hypospadias having a much higher risk of failure. Conclusions Stricture characteristics and outcomes of idiopathic urethral strictures are similar to those of traumatic strictures, suggesting that unrecognized trauma may contribute to idiopathic stricture formation. Although definitive treatment of idiopathic strictures tends to be delayed, they have a high rate of urethroplasty success because most are short bulbar strictures amenable to EPA. Funding none
Authors
Boyd Viers
Travis Pagliara Charles Rew Lauren Folgosa-Cooley Christine Shiang Jeremy Scott Allen Morey |
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MP79-18 |
Injury Severity Score Associated with Concurrent Bladder Injury in Patients with Blunt Urethral Injury |
Trauma/Reconstruction/Diversion: External Genitalia Reconstruction and Urotrauma (including transgender surgery) I | 17BOS |
Abstract: MP79-18 Sources of Funding: This research was supported in part by the Proposed Research Initiated by Students and Mentors (PRISM) Program, University of Maryland School of Medicine Office of Student Research. Introduction Missed or delayed diagnoses of concurrent bladder damage in a patient with blunt urethral trauma can lead to a high rate of morbidity. A proven prognostic indicator to evaluate the likelihood of bladder injury in this patient population has not yet been established, but would be beneficial in determining care. The aim of this study was to determine if there was a clinically useful association between the Injury Severity Score (ISS) and bladder involvement among patients with blunt urethral trauma. Methods Retrospective analysis was performed on a cohort of 98 patients who had presented with blunt urethral trauma to R. Adams Cowley Shock Trauma Center between the years of 2002-2014. Univariate analysis was performed to determine if there was an association between concurrent bladder injuries and a variety of factors including ISS, Trauma Injury Severity Score (TRISS), age, pelvic fracture, and complete urethral distraction. A receiver operating characteristic plot was also performed to analyze the association between ISS and bladder involvement. Results Of the 98 patients with blunt urethral trauma, 28 of them had concurrent bladder injury. ISS was shown to have a significant correlation with concurrent bladder injury with and odds ratio of 2.2 for every 10 point increase in ISS (p=0.0001). Receiver operating characteristics curve analysis showed an area under the curve of 0.76 as shown in Figure 1. Furthermore, patients with an ISS ≥34 had a 54% chance of bladder involvement, while patients with an ISS <34 had a 13% chance of involvement. None of the other factors analyzed showed significance (p>0.05). Conclusions An ISS≥34 may be a reliable clinical indicator of bladder injury in patients presenting with blunt urethral trauma. This added information could be used in determining which patients receive additional imaging. Advantages of using ISS in this manner include high utility and ease of implementation. Funding This research was supported in part by the Proposed Research Initiated by Students and Mentors (PRISM) Program, University of Maryland School of Medicine Office of Student Research.
Authors
Eric Eidelman
Ian Stormont Gauthami Churukanti Deborah M Stein Mohummad Minhaj Siddiqui |
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MP79-19 |
The walking patient with grade IV – V renal injury |
Trauma/Reconstruction/Diversion: External Genitalia Reconstruction and Urotrauma (including transgender surgery) I | 17BOS |
Abstract: MP79-19 Sources of Funding: none Introduction High grade renal injuries are usually diagnosed in multitrauma patients following traffic accidents, assault or penetrating trauma. In recent years, conservative management in hemodynamically stable patients is the preferred strategy. The primary aim of the study was to compare the characteristics of ambulatory Grade IV – V trauma patients (Group A) with patients transferred by prehospital emergency units (Group B). Methods Data were retrieved from emergency cases presented between 2000 and 2015. Rec-ords were reviewed for all patients hospitalised after a diagnosed renal injury. Trauma resulted from motor accidents, assault and falls. The same mode of diagnostic evalua-tion (clinical assessment, laboratory tests and radiographic staging) was followed in all patients. They were reviewed with respect to type of injury, age, gender, time of ac-ceptance from injury, physical and radiographic findings, renal function, associated injuries, comorbidities and outcome. All hemodynamically stable patients were selected for non-operative managed and were supported under close monitoring. Results One hundred and twenty-six patients (mean age: 44 years) were diagnosed with a Grade IV – V renal injury. Group B patients (n:102) had lower hemoglobin (9.5g/dl vs 13.5g/dl) and Glascow Coma Scale (8 vs 14) at presentation and higher ISS (21 vs 13). Renal injuries in Group A patients were due to falls and contact sports while most Group B patients (90%) had traffic accidents. Age, gender and radiographic findings were similar in both groups. Hematuria and pain were the main complains in Group A patients (n:24) who were admitted with 6 hours delay after the injury, did not have seri-ous associated injuries, were hospitalized for a mean of 4 days and only 2 had surgical intervention resulting in nephrectomy. Most Group B patients (80%) had multiple inju-ries and 70% had an early exploration resulting in 60 nephrectomies and 10 renal unit reconstructions. Genitourinary related complications included transient renal insuffi-ciency (9%), abscess formation (3%), and reoperation were observed in Group B pa-tients while coagulopathy (25%), respiratory infections (30%) and gastrointestinal dis-orders (52%) were similar in both groups. No late deaths were reported. Most patients were lost at long term follow up. Conclusions Ambulatory patients with high grade renal injury have minor signs and symptoms, not serious associated injuries and a better prognosis in regard of conservative manage-ment and outcome. Funding none
Authors
Efraim Serafetinides
Graham Haesketh Georgia Galani Alexia Balanika Andreas Fildisis Nikolaos Mourmouras Ahilleas Karafotias Dimitrios Delakas |
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MP79-20 |
Risk Stratification for Erectile Dysfunction after Pelvic Fracture Urethral Injuries: A Pilot Study |
Trauma/Reconstruction/Diversion: External Genitalia Reconstruction and Urotrauma (including transgender surgery) I | 17BOS |
Abstract: MP79-20 Sources of Funding: None Introduction Pelvic fractures with associated urethral injuries are associated with a high risk of erectile dysfunction (ED) perhaps due to the proximity of the cavernosal nerve to the bulbomembranous junction. We sought to compare the frequency and severity of new onset ED in pelvic fracture patients with and without urethral injuries and to identify potential risk factors for ED in the setting of pelvic injury. Methods A retrospective analysis was conducted evaluating male patients treated for pelvic fractures with and without urethral injury at a level 1 trauma center between 2005 and 2016. The International Index of Erectile Function (IIEF) questionnaire was administered by telephone to assess post-injury ED. Additional questions regarding pre-injury sexual function, glans vascular symptoms, glans sensitivity, and an updated past medical history were also administered. A diagnosis of new onset ED was defined as the patient having no recollection of ED prior to injury and subsequently having an IIEF score of <22 after injury. Glans vascular symptoms were defined as having a cold glans during an erection. Penile sensitivity was described as either decreased or increased sensitivity of the glans penis. Results Of the 118 patients, 42% (50/118) patients responded to the questionnaire: 21 (42%) with pelvic fracture urethral injuries (PFUI) and 29 (58%) with pelvic fractures alone. We observed a numerical increase in new-onset ED in the PFUI group (n=12, 57%) when compared to the pelvic fracture alone group (n=11, 38%, p=0.29). The mean post-injury IIEF score was higher for the PFUI group (18 ± 7.6) than the pelvic fracture alone group (13 ± 8.7, p=0.05), with the PFUI patients more frequently developing severe ED (IIEF <7) (p<0.05). There were no significant differences in glans vascular symptoms (p=0.33) or penile sensitivity (p=0.17) between the two groups. Age, comorbidities, concomitant injuries, pelvic fracture pattern, and need for pelvic angioembolization were not risk factors for developing ED in either cohort. Conclusions ED was more severe in patients with PFUI compared to patients with pelvic fractures alone. Based on our results, a larger prospective analysis is warranted to better characterize ED in pelvic fracture patients. Funding None
Authors
Paul H Chung
Cody Gehring Reza Firoozabadi Bryan B Voelzke |
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MP80-01 |
The use of intra-operative frozen section during organ sparing surgery for penile cancer greatly reduces the local recurrence rate. Long term follow up data |
Sexual Function/Dysfunction: Penis/Testis/Urethra: Benign Disease & Malignant Disease III | 17BOS |
Abstract: MP80-01 Sources of Funding: none Introduction Local recurrence rate of penile cancer following surgical excision is reported in many series to be between 6 and-29%. Intra-operative Frozen Section (FS) is a useful tool to ensure safe microscopic margins in organ sparing procedures in penile cancer. In this series, we evaluated the impact of intra-operative surgical margin assessment by FS examination during penile-cancer preserving surgery on the local recurrence rate. Methods We analysed all those patients in which intra-operative FS was employed during penile preserving surgery in a single tertiary referral centre (catchment of 6.5 million) from 2007-2014. The tissue analysed for margins was the Urethral “donut�, corporal and/or glandular tissue proximal to the resection margin. We looked to see if this technique altered the surgical technique and what affect it had on recurrence rates. Median follow-up was 28 (1-114) months. Results Of the total number of 93 patients, 39 (41.9%) had a total glansectomy, 44 (47.3%) a partial penectomy, 7 (7.5%) a wide local excision, 2 (2.2%) a total penectomy and one (1%) a circumcision. Intra-operative histological FS examination of the surgical margin was positive in 16 (17.2%) cases mandating further resection under the same anaesthetic. Final paraffin histological examination confirmed cancer-free margins in 100%. At follow-up, none of the 16 patients with initial positive FS had local recurrence. Only 1 (1%) patient with negative intra-operative FS developed local recurrence at 23 months. This patient’s histology was initially G3pT4. Conclusions The use of intra-operative frozen section analysis during organ preserving surgery for penile cancer facilitates conservative surgery, reduces the need, distress and expense of further surgery and in this series contributed to a very low rate (1%) of local recurrence. Funding none
Authors
Ayman Younis
Dawn Cave John Dormer Timothy Terry Jonathan Goddard Duncan Summerton |
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MP80-02 |
Increasing age of patients with testicular cancer: 1980-2016 single-center experience |
Sexual Function/Dysfunction: Penis/Testis/Urethra: Benign Disease & Malignant Disease III | 17BOS |
Abstract: MP80-02 Sources of Funding: none Introduction Testicular germ cell tumor is the most common cancer in young men, and its incidence has been increasing. The standard therapy for advanced testicular cancer is multi-agent chemotherapy comprising bleomycin, etoposide, and cisplatin. However, opportunities for a regimen consisting of etoposide, ifosfamide, and cisplatin increase in consideration of the risk of pulmonary toxicity from bleomycin, particularly among older men. This study therefore retrospectively examined trends over time in the age at diagnosis of testicular cancer. Methods A total of 478 patients were diagnosed with and underwent treatment for testicular cancer at our institution between January 1980 and May 2016. Patients were divided into 4 groups according to the year of diagnosis: 1980 to 1989; 1990 to 1999; 2000 to 2009; and 2010 to 2016. Results Median age at diagnosis continuously increased, from 27 years (n=53) to 31 years (n=135), 34 years (n=179) and 38 years (n=111) in each period, respectively. Next, patients were divided by pathological type into 2 groups: a seminoma group with pure seminoma (n=227; 47.5%); and a non-seminoma group with non-seminoma or mixed germ cell tumor (n=251; 52.5%). In the seminoma group, median age increased constantly from 31 years (n=20) to 34 years (n=54), 36 years (n=93) and 41 years (n=60) in each period, respectively. Median age in the non-seminoma group also increased constantly from 26 years (n=33) to 28 years (n=81), 29 years (n=86) and 35 years (n=51) in each period, respectively. Interestingly, a continuous increase was also seen in the relative proportion of seminomas, from 37.7% to 40.0%, 52.0%, and 54.0% in each period, respectively. Conclusions The age at diagnosis is rising for patients with testicular cancer, and the age of patients with testicular cancer may increase in future. This should be kept in mind for the decision-making process leading to chemotherapy for testicular cancer. Funding none
Authors
Shinichi Yamashita
Shinji Fujii Shigeyuki Yamada Yoshihide Kawasaki Hideaki Izumi Naoki Kawamorita Koji Mitsuzuka Hisanobu Adachi Yasuhiro Kaiho Akihiro Ito Yoichi Arai |
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MP80-03 |
Distress screening in patients with urogenital malignancies |
Sexual Function/Dysfunction: Penis/Testis/Urethra: Benign Disease & Malignant Disease III | 17BOS |
Abstract: MP80-03 Sources of Funding: none Introduction Malignant tumors do not only have a somatic but also a psychological impact on patients. To date, only a few studies are available which evaluated the potential psychological burden of patients suffering from urogenital cancers. In this prospective, longitudinal study we examine the baseline psychological distress of patients treated for urogenital malignancies focussing on testicular cancer (TC) and prostate cancer (PCA). Methods Psychological distress of 192 inpatients treated for urogenital malignancies was evaluated using the distress thermometer (DT), a well-established clinical tool for the detection of distress, at admission to the hospital prior to any surgical or systemic therapy. The DT consists of a visual analogue scale ranging from 0 to 10 resulting in a low (0-3), moderate (4-6) or high (7-10) stress level. Furthermore, it contains a 36-item list of problems subdivided into 5 categories (practical, family, emotional, spiritual/religious, physical). Results Of the eligible 192 patients, 103 (54%) patients were diagnosed with PCA, 40 (21%) with TC, 22 (11%) with urothelial cancer, 21 (11%) with renal cell cancer and 6 (3%) with penile cancer. The mean DT score was 5 (interquartile range (IQR) 3-7) with the most common stressors being of emotional origin, namely fear (95/192, 50%), worry (85/192, 44%), nervousness (80/192, 42%), sleep disorders (75/192, 39%) and fatigue (61/192, 32%). DT analysis did not reveal any difference between the tumor entities but 64% of all patients displayed a moderate to high stress level requiring psycho-oncological support. The comparison of PCA and TC demonstrated a higher distress level in PCA patients in the subgroups of metastatic disease (median 5.5, IQR 4-8 vs. median 4, IQR 2-6; p = 0.018), secondary therapy (median 6, IQR 5-8 vs. median 4.5, IQR 2.75-6; p = 0.023) and salvage treatment (median 7, IQR 4.5-9 vs. 5, IQR 2.75-6; p = 0.021). Furthermore, PCA patients receiving salvage treatment displayed significantly higher distress levels compared to non-salvage treated patients (median 7, IQR 4.5-9 vs. median 5, IQR 2-7; p 0.028). Conclusions Our study shows that 64% of urological tumor patients should be offered psycho-oncological support. Especially patients suffering from advanced stage PCA seem to have a high stress level. Thus, physicians in the field of urologic oncology should be aware of their patients' psychological distress in order to identify high-risk patients and provide them with an appropriate psycho-oncological support. Funding none
Authors
Pia Paffenholz
Maria Angerer-Shpilenya Johannes Salem David Pfister Axel Heidenreich |
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MP80-04 |
Effect of Alvimopan on Gastrointestinal Recovery and Hospital Length of Stay After Retroperitoneal Lymph Node Dissection For Testicular Cancer |
Sexual Function/Dysfunction: Penis/Testis/Urethra: Benign Disease & Malignant Disease III | 17BOS |
Abstract: MP80-04 Sources of Funding: None Introduction Alvimopan use in enhanced recovery programs has reduced the hospital length of stay (LOS) in patients undergoing major abdominal surgeries. Retroperitoneal lymph node dissection (RPLND) for testicular cancer may be associated with delayed GI recovery prolonging hospital LOS. In this study, we evaluate whether alvimopan is associated with enhanced GI recovery and shorter hospital LOS in men undergoing RPLND for testicular cancer. Methods From 2010 to 2016, 29 patients underwent RPLND by a single surgeon (23 post-chemotherapy). All patients underwent bilateral template dissection. Data for patients who received alvimopan was prospectively collected and compared to a historical cohort of patients who did not receive alvimopan. Primary outcomes measured were hospital LOS and recovery of GI function. Mann-Whitney Wilcoxon and Chi square tests were used to determine statistical significance between the two groups. Kaplan-Meier survival curves were plotted and the log-rank test was utilized to compare treatment effects. Results Of 29 men who underwent RPLND, 8 received alvimopan and 21 did not. There were no differences in preoperative or operative variables between the groups (Table 1). Median hospital LOS for men receiving alvimopan was 4 days compared to 6 days for those who did not (p=0.074). The median time to return of flatus in men receiving alvimopan was 2 days compared to 4 days for those who did not (p=0.0023). The median time to first bowel movement (BM) in men receiving alvimopan was 2.5 days compared to 4 days for those who did not (p=0.0028). Survival curves revealed that treatment intervention decreased both median time to event (time to flatus: 2 days vs. 4 days, log-rank test p-value<0.001; time to BM: 3 days vs. 5 days, log-rank test p-value<0.05; Figure 1) Conclusions Alvimopan significantly reduced the median time to return of flatus and to first BM after RPLND. Furthermore, there was a trend towards shorter hospital LOS in those receiving alvimopan. Funding None
Authors
Kushan Radadia
Nicholas Farber Alexandra Tabakin Wei Wang Lee Milas Thomas Jang |
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MP80-05 |
Is there benefit to adjuvant radiation in stage III penile cancer after lymph node dissection? Findings from the National Cancer Database. |
Sexual Function/Dysfunction: Penis/Testis/Urethra: Benign Disease & Malignant Disease III | 17BOS |
Abstract: MP80-05 Sources of Funding: None Introduction Due to the rarity of penile cancer, there are no randomized studies evaluating the different treatment modalities for high stage disease. We used the National Cancer Database (NCDB) to determine factors associated with receiving adjuvant radiation and the influence on prognosis in men with Stage III (T1-3, N1-2) penile cancer who underwent inguinal lymph node dissection (ILND)._x000D_ Methods The National Cancer Database (NCDB) was queried from 1998-2012 to identify men with penile cancer who had pathologic nodal status available. Clinical and pathologic variables associated with adjuvant radiation therapy were examined using chi square testing. Univariate and multivariate logistic regression was used to evaluate odds of receiving adjuvant radiation therapy, while Cox regression analysis evaluated whether adjuvant radiation influenced overall survival._x000D_ Results A total of 589 patients with stage III disease (T1-3, N1-2) underwent ILND. Adjuvant radiation was given in 23% of patients (N=136). Mean age was 61.8 +/-13.7 years (median age 63, IQR 52-72). Patient age, year of diagnosis, Charlson comorbidity index, insurance status, income, education, stage, grade, tumor size, histology, LVI, extra-nodal extension (ENE), and primary surgery (partial vs. total penectomy) were not associated with receiving adjuvant radiation therapy. Factors associated with adjuvant radiation were higher pathologic nodal stage (OR 1.9, 95%CI 1.1-3.1), greater distance of travel (OR 0.5, 95%CI 0.3-0.9), and treatment in an academic setting (OR 0.5, 95%CI 0.3-0.8). Those receiving adjuvant radiation had a significant improvement in overall survival (HR 0.65, 95%CI 0.43-0.96) in the multivariate Cox regression analysis adjusting for year of diagnosis, age, race, Charlson comorbidity index, stage, grade, nodal status, and primary surgery. This benefit was notably attenuated when limited to N1 disease only (HR 0.86, 95%CI 0.36-2.06) versus to N2 disease only (HR 0.71, 95%CI 0.43-1.18)._x000D_ _x000D_ Conclusions Use of adjuvant radiation for stage III penile cancer is relatively common in the United States. The primary determinants of adjuvant radiation therapy are related to the proximity to cancer centers and greater nodal burden. We find evidence of a benefit with the use of adjuvant radiation, particularly in those with higher nodal disease burden (N2 vs. N1). As penile cancer remains a rare disease, multi-institutional studies are needed to improve treatment algorithms for high-stage disease._x000D_ Funding None
Authors
Brian Winters
James Kearns Sarah Holt Matthew Mossanen Daniel Lin Jonathan Wright |
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MP80-06 |
Evaluation of ‘Programmed Death-1’ / ’Programmed Death Ligand 1 and 2’ pathway in tumor samples of seminoma and non-seminoma, and its prognostic role in testicular cancers |
Sexual Function/Dysfunction: Penis/Testis/Urethra: Benign Disease & Malignant Disease III | 17BOS |
Abstract: MP80-06 Sources of Funding: none Introduction Inhibition of the Programmed Death Receptor 1 (PD-1) and Programmed Death Receptor Ligand 1 (PD-L1) pathway is a promising treatment alterative and improves survival in a number of different cancers, including melanoma and kidney cancer. Recent data showed that evaluation of PD-1 and PD-L1 expression in various tumors could be used for the prognostic value of anti-PD-1 or anti-PD-L1 treatments. We aimed to analyze the expressions of PD-1, PD-L1 and PD-L2 in the testicular germ cell tumors (TGCTs) and evaluate their potential as immunotherapeutic target. Methods Formalin-fixed paraffin-embedded tumor specimens of 60 patients diagnosed with TGCTs were evaluated, where there are 24 pure seminomas and 36 mixed germ cell tumors. Immunohistochemistry was performed to evaluate expression of PD-1 (EH33 antibody), PD-L1 (E1L3N antibody), PD-L2 (D7U8C antibody), CD8 (4B11 antibody) and CD4 (368) using monoclonal antibodies mentioned in the brackets. Results None of seminoma specimens exhibited PD-L1 expression, where PD-L1 expression was found in 19.4% of mixed germ cell tumors. None of seminomas and nonseminomas expressed PD-L2. In mixed germ cell tumors PD-1 negativity or poor expression of PD-1 in both stromal and intra-tumoral lymphocytes was associated with statistically lower overall survival (figure) and high progression and mortality rates. Conclusions The PD-1 expression profiles in mixed germ cell tumors could help to identify patients with poor prognosis potential and those patients could benefit from early therapeutic interventions and immunotherapeutic strategies using anti-PD1 and anti-PDL1 antibodies. Funding none
Authors
Asgar Garayev
Emine Bozkurtlar Deniz Filinte Haydar Kamil Cam Ferruh ?im?ek ?lker Tinay |
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MP80-07 |
Sex Cord-Gonadal Stromal Tumors of the Testicle are Far More Lethal Than Germ Cell Testicular Neoplasms |
Sexual Function/Dysfunction: Penis/Testis/Urethra: Benign Disease & Malignant Disease III | 17BOS |
Abstract: MP80-07 Sources of Funding: none Introduction Sex cord-gonadal stromal tumors (SCGS) of the testicle, primarily made up of Leydig cell and Sertoli cell tumors, are rare testicular neoplasms. Single institutional studies suggest that metastases are rare and survival excellent. We utilized the SEER database to characterize risks of metastasis in patients with SCGS tumors. Methods We interrogated the SEER database from 1973 to 2010 to identify all Leydig cell (code -86503) and Sertoli cell (code -86403) tumors among male patients. Data collected and analyzed included patient age and race; SEER stage including limited to primary site (Localized), the presence of disease in retroperitoneal lymph nodes (Regional) and distant metastases (Distant); as well as cancer-specific and overall survival. Results We identified 53 patients with Leydig cell tumors and 23 with Sertoli cell tumors. Sertoli cell tumors were fairly evenly distributed overall all age groups while Leydig cell tumors were concentrated among ages 30-59. Using SEER extent of disease, 79% were found to be Localized and 21% Distant on initial presentation with equal distribution among patients with Leydig and Sertoli cell tumors. Median survival of patients presenting with metastases was 27 months. Patients with apparently Localized disease had a 13% chance of developing metastases at a median of 17 months. Patients with SCGS tumors of the testicle whether localized or metastatic had a significantly poorer survival compared to patients with germ cell tumors. Conclusions This study represents the largest analysis of outcomes for patients with SCGS tumors. These neoplasms have a high risk of presenting with metastasis (20%) than previously recognized as as well as a significant risk (13%) of patients with Localized tumor developing a recurrence. Patients with metastatic SCGS tumors are at higher risk of dying from their disease than patients with metastatic germ cell neoplasms likely due to inherent resistance to radiation and chemotherapy. Funding none
Authors
Joel Slaton
Jet Li Ngoc Duong Kai Ding |
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MP80-08 |
Diagnostic value of frozen section examination (FSE) during inguinal exploration in patients with inconclusive testicular lesions |
Sexual Function/Dysfunction: Penis/Testis/Urethra: Benign Disease & Malignant Disease III | 17BOS |
Abstract: MP80-08 Sources of Funding: none Introduction In patients with inconclusive testicular lesions, frozen section examination (FSE) during inguinal exploration is recommended by the current European Association of Urology (EAU) guidelines. However, FSE is not available to every urologist, is time consuming, and the diagnostic value of FSE remains poorly defined. The aim of this investigation was to assess the diagnostic value of FSE during inguinal exploration. Methods We reviewed the medical records of patients undergoing inguinal exploration and FSE between 1999 and 2015 in a tertiary care academic center. Patients demographic and clinical information were extracted. The results from FSE and final pathology were compared. Results FSEs were performed on 142 testicular lesions during inguinal exploration of the affected testis. Germ cell tumors (GCT) and non-GCT pathologies were correctly identified in 106 cases (74.6%, 46 non-seminomas, 60 seminomas) and 35 cases (24.6%), respectively. One case was incorrectly classified as non-malignant hypocellular nodule on FSE. However, final pathology revealed a seminoma. The patient underwent a secondary inguinal orchiectomy and remains disease-free 6 years post orchiectomy under active surveillance. No patient underwent unnecessary orchiectomy due to an incorrectly classified testicular GCT. According to our data, FSE has a sensitivity of 99% (95% CI 95%-100%), a specificity of 100% (95% CI 85%-100%), a positive predictive value of 100% (95% CI 95%-100%) and a negative predictive value of 97% (95% CI 85%-100%). Conclusions FSE is a useful diagnostic tool, which reliably predicts the presence or absence of GCT and thus is helpful to guide intraoperative management of testicular lesions particularly in patients with inconclusive preoperative results (i.e. negative tumor markers). To minimize the rate of unnecessary orchiectomies, these patients should only be treated in institutions where FSE is available. Funding none
Authors
Christian Fankhauser
Joerg Beyer Lisa Roth Peter-Karl Bode Holger Moch Tullio Sulser Thomas Hermanns |
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MP80-09 |
2-18fluoro-deoxy-D-glucose positron emission tomography (FDG-PET) in Seminoma: Is an objective scoring system useful? |
Sexual Function/Dysfunction: Penis/Testis/Urethra: Benign Disease & Malignant Disease III | 17BOS |
Abstract: MP80-09 Sources of Funding: none Introduction FDG-PET imaging is a valuable tool to guide additional treatment recommendations in the post-chemotherapy setting for metastatic seminoma. However, false positive results can be a problem. We sought to identify a new methodology to interpret FDG-PET scans using a more objective approach to reduce false positive results. Methods We identified patients who had FDG-PET imaging available for re-review with a diagnosis of germ cell tumor at our institution from 2006 to 2016. Twenty-six scans were identified. All images were re-reviewed by an experienced radiologist who was blinded to patient treatments and outcomes. Radiographic variables recorded were mass size, standard uptake values (SUV), liver and blood pool values, and date of scan. Liver and blood ratios were calculated for each scan by dividing the SUV of the index lesion by the liver and blood pool values, respectively. A ratio of ≤1 would be considered a negative scan. A 5-point scale was assigned to each scan based on the dominant FDG-avid lesion using a similar system to the Deauville scale for lymphoma with 5 representing significant uptake and 1 for no uptake. Results A total of 26 patients were identified. The median follow-up from the PET scan was 21 months (range 1-96). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the original PET scan interpretation was 100%, 81%, 77%, and 100% respectively. If the liver ratio was included as an objective measurement, the sensitivity, specificity, PPV, and NPV would have improved to 100%, 88%, 83%, 100%, respectively. Thus, the increase in specificity would have resulted in a decrease of false positive results. Of the 26 PET studies, 3 (12%) were false positives and 0 (0%) were false negatives. Four patients underwent a RPLND due to positive findings on the PET study. Of these, 3 were found to have seminoma and 1 had necrosis on final pathology. The median SUV value of the 3 PCRPLND patients with seminoma was 6.7, with a liver ratio of 2.68. The patient with necrosis had an SUV of 2.5, with liver ratio of 0.9. The blood ratio and 5-point scoring system did not add additional significant information. Conclusions By including the liver ratio in interpreting PET scans, we believe we can reduce the number of false positive scans. Funding none
Authors
Clint Cary
Antoin Dougwali Ryan Zukerman Costantine Albany Mark Tann Richard Foster |
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MP80-10 |
Midline Extraperitoneal Approach to Retroperitoneal Lymph Node Dissection in Testicular cancer: Minimizing Surgical Morbidity |
Sexual Function/Dysfunction: Penis/Testis/Urethra: Benign Disease & Malignant Disease III | 17BOS |
Abstract: MP80-10 Sources of Funding: none Introduction Retroperitoneal lymph node dissection (RPLND) is an important component of the management of testicular germ cell tumor (GCT) but carries significant morbidity. Herein we describe our updated experience with a midline extraperitoneal (EP) approach to RPLND for seminomatous and non-seminomatous GCT that minimizes perioperative morbidity. Methods 122 consecutive patients from an IRB approved database underwent RPLND from 2010-2015. Patients requiring aortic resection, retrocrural dissection or access to intraperitoneal disease were excluded. The remaining 69 patients underwent midline EP-RPLND. All post-chemotherapy (PC) cases underwent bilateral template dissection; all primary cases underwent extended ipsilateral templates. Perioperative and long-term outcomes were analyzed and a descriptive analysis using SAS was performed. Results 68 patients underwent midline EP-RPLND successfully (98.6%). Median age was 28 years. On pre-operative imaging the size of retroperitoneal mass or lymphadenopathy was <2 cm in 29 patients, 2-5 cm in 15 patients, and >5 cm in 24 patients, of which 19 were >10cm. 3 patients underwent cavectomy. Median EBL was 325 mL (IQR: 200-612.5). Median number of lymph nodes (LN) resected was 36 (IQR: 24.5-49); median number of positive nodes was 1 (IQR: 0-4). Median return of bowel function was 2 days (IQR: 1-2) and LOS was 3 days (IQR: 3-4). There were no cases of ileus. 11 patients (16.2%) had 30-day complications: 6 (55%) were Clavien grade 1, 5 (45%) were grade 2. There was 1 long-term complication (1.5%), which was grade 3b. Antegrade ejaculation rates were 91.6% in the primary group and 96.8% in the PC group. _x000D_ _x000D_ Conclusions Midline EP-RPLND can be performed safely without compromising completeness of resection. This approach is associated with a faster return of bowel function, lower rates of ileus and shorter LOS. Funding none
Authors
Sumeet Syan-Bhanvadia
Soroush Bazargani Thomas Clifford Jie Cai Gus Miranda Hooman Djaladat Anne Schuckman Siamak Daneshmand |
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MP80-11 |
Penile Sparing Surgery for Penile Cancer: A Multicenter International Retrospective Cohort |
Sexual Function/Dysfunction: Penis/Testis/Urethra: Benign Disease & Malignant Disease III | 17BOS |
Abstract: MP80-11 Sources of Funding: None Introduction Penile cancer (PC) is a rare and potentially disfiguring disease. There have been great strides made to improve cancer control, as well as to decrease treatment-associated morbidities. We present our outcomes using penile sparing surgery (PSS) for the treatment of PC in the largest cohort known to date. Methods 1439 patients were retrospectively identified to have undergone PSS for PC from July 2000 to June 2015 at five international institutions of excellence. PSS consisted of laser ablation, wide local excision, circumcision, and partial/total glansectomy. Patient demographics and clinical characteristics were summarized using descriptive statistics. Univariate analyses were performed using the chi-square test for categorical variables. Kaplan Meier survival curves were applied to determine overall recurrence free survival (RFS) as well RFS stratified by pathologic stage and surgical intervention. Results Median patient age of our cohort was 63 years old. Median patient follow up was 40 months. 23.9% of all patients recurred after PSS. 5 year RFS by pT stage was Ta/Tis: 58.0%, T1: 55.5%, and T2: 49.8%. RFS for all patients undergoing PSS was 55.6%( 1 year: 77.3%, 2 year: 67.3%, 5 year: 55.6%). Treatment modality (p=0.056) and pT stage (p=0.99) did not significantly correlate with RFS at 5 years. Patients with higher pT tumors underwent more aggressive interventions (p <0.001). Conclusions PSS is indicated for appropriately selected patients with PC. Treatment modality and pT stage were not significant predictors of RFS. Close follow-up remains a critical component of all treatment considerations. Funding None
Authors
Adam Baumgarten
Sylvia Yan Sarah Ottenhof Juan Chipollini Dominic Tang Barrett McCormick Yao Zhu Ding-Wei Ye Chris Protzel Simon Horenblas Nicholas Watkin Philippe Spiess |
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MP80-12 |
Retinal toxicity after cisplatin-based chemotherapy in patients with testicular cancer |
Sexual Function/Dysfunction: Penis/Testis/Urethra: Benign Disease & Malignant Disease III | 17BOS |
Abstract: MP80-12 Sources of Funding: none Introduction Cisplatin-based chemotherapy (CBC) is a cornerstone in the treatment of advanced stage testicular cancer (TC). Since its introduction it has led to excellent survival rates and as TC usually is a cancer of young men, most patients live to experience significant short- and long-term side effects. These include infertility, cardiovascular disease, and sensomotoric impairment due to oto- and neurotoxicity. Meanwhile little is known on retinal toxicity associated with CBC. We therefore sought to outline potential morphological and functional retinal alterations in CBC treated patients._x000D_ Methods After ethics committee approval was obtained, we enrolled patients who had received at least one cycle of CBC at any of three Hamburg-based TC centers. Furthermore, a matched control group of healthy, untreated patients were included in this study. Subjects were evaluated for functional and morphological retinal dysfunction. This included testing of retinal nerve fiber thickness (RNFL), color vision, and visual acuity testing in CBC recipients. Additionally, full-field electroretinograms (ff-ERG) for CBC recipients and their healthy controls were conducted. Pearson correlation coefficient analysis was carried out to assess a possible correlation between cumulative Cisplatin dose and measured RNFL and ff-ERG. Endpoints of this study were differences in test measures as well as a dose dependency on outcomes. Results Both study groups (CBC recipients vs. healthy controls) consisted of N=14 participants with a median patient age of 30 years (range: 22 - 52 years). Seminomatous and nonseminomatous germ cell tumors were exhibited in 6 (42.85%), and 8 (57.14%) out of 14 patients, respectively. Patients had received between one to seven cycles of a CBC regimen consisting of Cisplatin, Etoposide, and Bleomycin with a median Cisplatin dose of 627mg (range: 216mg - 1,205mg). The median interval between last CBC and diagnostic evaluation was 19.8 month (range: 6 - 61.5 months)._x000D_ Morphological assessment revealed reduced RNFL in 11 of 14 patients (78.6%). While the reduction in RNFL was significantly correlated to the cumulative CBC dose received (?=0.70; P=0.004), it did not correlate with the time since cessation of CBC (?=0.16; P=0.1). ff-ERG showed significant differences between CBC recipients and the control-group in 2 of 5 tested categories (all P<0.001)._x000D_ Functional testing revealed no loss in visual acuity in all 14 CBC recipients, yet impaired color vision was observed in 6 of 14 patients (42.8%)._x000D_ Conclusions Our study is limited in small sample size and short-term follow-up. However, it appears that CBC in TC patients leads to short-term functional and morphological retinal alterations. Future studies should address this circumstance, as there are major implications._x000D_ Funding none
Authors
Philipp Gild
Malte W. Vetterlein Klaus-Peter Dieckmann Cord Matthies Walter Wagner Tim A. Ludwig Christian P. Meyer Armin Soave Simon Dulz Niels H. Asselborn Karin Oechsle Carsten Bokemeyer Andreas Becker Margit Fisch Michael Hartmann Felix K.H. Chun Luis A. Kluth |
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MP80-13 |
Managing the High Incidence of Genital Pain and Pathology in the Male Prison Population with Telemedicine |
Sexual Function/Dysfunction: Penis/Testis/Urethra: Benign Disease & Malignant Disease III | 17BOS |
Abstract: MP80-13 Sources of Funding: NIH Institutional Training Grant T35-HL007485-36 Introduction Stress has been shown to exacerbate testicular pain and likely few personal situations are more stressful than incarceration. Our medical center manages all of the urologic complaints in the state prison population and we have anecdotally noted a large number of incarcerated men reporting genital pain and pathology (GPP). Iowa prisoners with non-emergent urologic complaints are initially evaluated with telemedicine (TM) before an in-person clinic visit. The objective of the study was to evaluate trends in urologic complaints in our male prisoner population and to determine the incidence, management, and outcomes of GPP. Methods We retrospectively reviewed the medical records of all prisoners in our state who were initially evaluated by TM from Jan 2007 – Jul 2014 after obtaining IRB approval. Patient records were evaluated for urologic complaints, diagnoses, initial tests and treatments, outcomes, and eventual need for surgical treatment. GPP was defined as a primary diagnosis at the initial TM encounter of benign testicular lesion, testicular pain, or epididymitis. To determine the incidence of GPP, we queried the Iowa prison database for average numbers of male inmates per year during the study dates and compared to the frequency of prisoner visits for urologic complaints. Results There were 376 prisoners with urologic complaints during the study period (incidence 7 per 1000 prisoner years), of which 29% (n=110) were for GPP. Tests were ordered in 78% of men presenting with GPP on the TM encounter (73% US/radiology, 15% labs, 6% other) and medication was prescribed in 25%. Clinic visits followed TM 49% of the time. In these visits, the TM diagnosis was confirmed in 98%. Follow-up revealed that <1% had worsening of their GPP and only 9 patients (8%) ultimately required surgery (4 hydrocelectomy, 2 varicocelectomy, 1 spermatocelectomy, 1 spermatic cord block, 1 scrotal exploration). No patients were found to have testicular cancer or acute testicular torsion. Conclusions GPP represented nearly a third of all urologic complaints in our male prison population. Most of the GPP resolved with time and few required surgery. For this access-poor population, it appears that TM, combined with local ultrasound, may represent an ideal way to manage the majority of these complaints safely and more cost-effectively. Funding NIH Institutional Training Grant T35-HL007485-36
Authors
Brenton Sherwood
Yu Han Kenneth Nepple Bradley Erickson |
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MP80-14 |
LYMPH NODE YIELD AS A PREDICTOR OF OVERALL SURVIVAL FOLLOWING REGIONAL LYMPHADENECTOMY FOR PENILE CANCER |
Sexual Function/Dysfunction: Penis/Testis/Urethra: Benign Disease & Malignant Disease III | 17BOS |
Abstract: MP80-14 Sources of Funding: None Introduction There is limited data to define an appropriate threshold for lymph node yield (LNY) following regional lymphadenectomy (rND) for penile squamous cell carcinoma (pSCC) and, whether that specific threshold impacts overall survival (OS). We sought to determine whether a specific LNY affects OS following rND for pSCC and, to define the minimum beneficial number of lymph nodes (LN) to retrieve. Methods Using the National Cancer Database (NCDB), we identified men diagnosed with pSCC, who underwent rND, from 2004 to 2013. We excluded men diagnosed on autopsy or at the time of death, with preoperative chemotherapy or radiotherapy, M+ disease, and with < 3 months of follow up. We assessed the statistical distribution of LNY following rND. A multivariable logistic regression model was developed to assess predictors of OS including: age, comorbidity, race, stage, grade, nodal status, and LNY. Kaplan-Meier (KM) survival analysis was performed to compare OS by varying thresholds of LNY. Results 938 men with pSCC underwent rND. Of these 452 met inclusion criteria. Median follow up was 29.9 months. The median number of regional LN retrieved was 16. Based on the statistical distribution of LNY and, sensitivity analysis, a threshold of 15 LNs appeared to be clinically and statistically relevant. There was no significant difference in race, stage, grade for men with LNY ≤15 vs >15. However, men with LNY ≤ 15 were older than those with LNY >15 (64 vs 58 years, p<0.01). On multivariable analysis, significant independent predictors of worse OS were: age (HR: 1.02; CI [1-1.03], p<0.05), N+ disease (HR: 3.06; CI [2.12-4.42], p<0.001), and LNY ≤ 15 (HR: 1.62; CI [1.17-2.24], p<0.01). Men with a LNY ≤ 15 demonstrated a significantly decreased 5-year OS compared to those with LNY > 15 (50% VS 73%, p<0.05). On subgroup analysis of men with T2, N0, LNY >15 trended toward better 5-year OS vs LNY ≤15 (90% VS 71%, p=0.06) (Figure) Conclusions LNY following rND for pSCC appears to have an impact on OS independent of age, stage, nodal status and grade. A minimum LNY >15 following rND may have a beneficial impact on OS and may serve as the quantitative threshold for defining an adequate rND. Funding None
Authors
Chad Ritch
Nachiketh Soodana Prakash Varsha Sinha Diana M Lopategui Katherine Almengo Micheal Ahdoot David Alonzo Mahmoud Alameddine Sanoj Punnen Dipen Parekh Mark Gonzalgo |
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MP80-15 |
Retroperitoneal Lymph Node Dissection for Testicular Seminomas: Population-Based Stage-by-Stage Survival Outcomes |
Sexual Function/Dysfunction: Penis/Testis/Urethra: Benign Disease & Malignant Disease III | 17BOS |
Abstract: MP80-15 Sources of Funding: none Introduction While retroperitoneal lymph node dissection (RPLND) is traditionally reserved for nonseminomatous germ cell tumors, recent efforts to reduce long-term toxicities of radiation and chemotherapy have turned attention to its application for testicular seminomas. Currently, RPLND is reserved for recurrent or residual masses after chemotherapy for stage 2 testicular seminomas. We aimed to describe the current utilization of RPNLD for testicular seminomas by stage and impact on survival outcomes. Methods A national sample of men diagnosed with stage 1A, 1B, 2A, 2B, and 2C testicular seminomas between 1988 and 2013 was evaluated from Surveillance, Epidemiology, and End Results Program registries. Stage-specific utilization of RPLND was determined. Cox proportional hazards models, adjusted for age, race, and radiation therapy, evaluated the impact of RPLND on overall (OS) and cancer-specific survival (CSS). Adjusted models also compared patients receiving only RPLND to those receiving only radiation therapy by stage. Results A total of 14807 men (mean age 37, 76% Caucasian, 15% Hispanic) with testicular seminomas were included with low utilization of RPLND for stage 1 disease (1A and 1B; 1.2% overall) and somewhat higher rates for stage 2 disease (10.4% overall). There were no appreciable trends over time. Adjusted models showed no added OS or CSS advantage for RPLND when adjusted for age, race, and radiation therapy among stage 1 (OS HR 1.27 (0.73-2.20), p=0.40) or stage 2 (OS HR 0.96 (0.43-2.17), p=0.93) disease. For the comparison of patients receiving RPLND only to radiation therapy only, adjusted models showed statistically significant worse OS for RPLND for stage 1 disease (HR 2.15 (1.06-4.34), p=0.033) but a non-significant difference for stage 2 disease (HR 1.85 (0.73-4.73), p=0.196). Timing of RPLND relative to chemotherapy was not available. Conclusions Among men with testicular seminoma, RPLND was not associated with a survival benefit. Higher risk men undergo RPLND compared to radiation therapy as evidenced by differences in survival. Given that current use of RPLND is largely limited to the post-chemotherapy setting, upcoming trials implementing RPLND as a first-line modality for testicular seminoma will help quantify relative recurrence and survival tradeoffs. Funding none
Authors
Hiten Patel
Gregory Joice Zeyad Schwen Alice Semerjian Ridwan Alam Arnav Srivastava Mohamad Allaf Phillip Pierorazio |
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MP80-16 |
Neutrophil-to-Lymphocyte Ratio – A Simple Biomarker in Testicular Cancer |
Sexual Function/Dysfunction: Penis/Testis/Urethra: Benign Disease & Malignant Disease III | 17BOS |
Abstract: MP80-16 Sources of Funding: none Introduction Elevated neutrophil-to-lymphocyte ratio (NLR) has been reported to be a poor prognostic indicator in several malignancies and associated with response to immune checkpoint inhibitors; however the association with testicular cancer has not been evaluated. We explore the association between NLR on staging of testicular germ cell tumors (TGCT). Methods Retrospective review of institutional testicular tumor database from 2010-2016. Patients with non-TGCT were excluded. Patients were categorized as localized or non-localized based on the presence of retroperitoneal or distant metastasis or elevated serum tumor markers following orchiectomy. Pre-and post-orchiectomy mean serum NLR and was calculated for patients and correlated with disease state. NLR > 4 was assessed separately based on previously reported correlation of this cut-point with prognosis in other malignancies. ROC analysis was used to determine accuracy of the NLR to distinguish patients presenting with clinically non-localized disease Results 159 pts with TGCT were identified for analysis: seminoma (n=59), NSGCT (n=97), ITGCN (n=2), unknown (n=1). Pre- and post-orchiectomy NLR was available for 61 and 56 patients, respectively. Mean NLR was significantly higher for patients with non-localized TGCT (Table). ROC analysis (Figure) demonstrated that pre-orchiectomy NLR was associated with the presence of non-localized disease (AUC 0.770, p<0.001), while post-orchiectomy NLR trended toward significance (AUC 0.659, p=0.063) as a factor associated with the presence of non-localized disease. Additionally, mean pre-orchiectomy NLR demonstrated a dose-response relationship with IGCCCG risk grouping for metastatic TGCT: good risk - NLR 4.6±4.0, intermediate risk - NLR 5.7±3.4, poor risk - NLR 13.2±9.8, (p=0.013) Conclusions NLR appears to be predictive of non-localized TGCT. Application of NLR may be useful as a predictive biomarker in a number of settings in which presence or degree of non-localized disease is in question e.g. prior to post-chemotherapy RPLND. Further validation is required. Funding none
Authors
Ahmet Aydin
Solomon Woldu Thomas Lowrey Ryan Hutchinson Laura-Maria Krabbe Nirmish Singla Arthur Sagalowsky Vitaly Margulis Aditya Bagrodia |
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MP80-17 |
CXCL12 is a predictor for disease recurrence in patients with metastatic non-seminoma |
Sexual Function/Dysfunction: Penis/Testis/Urethra: Benign Disease & Malignant Disease III | 17BOS |
Abstract: MP80-17 Sources of Funding: none Introduction In testicular germ cell tumors (GCT) attempts have been made to stratify patients, who are at higher risk for disease recurrence based on certain pathological characteristics or biomarkers. Recently Gilbert et al. (Clin Cancer Res 2016) described an association between immunohistochemical CXCL12 expression and a decreased relapse rate in stage 1 non-seminoma patients. Therefore CXCL12 might be a clinically useful biomarker to allocate patients with stage 1 non-seminoma to adjuvant therapy vs. active surveillance. The aim of our study was to externally validate the results of Gilbert et al. and to assess the utility of CXCL12 as prognostic marker in patients with metastatic disease. Methods A tissue micro array was constructed with tissue cores of 152 seminoma, 113 non-seminoma and 14 non-cancer patients, diagnosed in the period from 2004-2014. All tumor components were represented by two tissue cores (diameter 0.6 mm). If more than one tumor component was present in case of non-seminoma, each component was separately punched and represented on the tissue microarray. Immunohistochemical staining of TMA sections with CXCL12 antibody (Antibody 79018, 1:100; R&D Systems) was performed. The amount and the intensity of positive stained cells were analyzed using a semi-quantitative score. Results Of 267 GCT patients, 31 out of 153 (20.3%) seminoma and 54 out of 114 (47.3%) non-seminoma patients were diagnosed with metastatic disease. Within all 1201 tissue cores CXCL12 expression was found in 0.2% of seminomatous components, 88.2% of yolk sac tumors, 43.3% of teratomas, 100% of choriocarcinomas, 30.6% of embryonal carcinoma, 0% of Germ cell neoplasia in situ (GCNIS) and 0% in normal tissue. With focus on non-seminoma patients, CXCL12 was expressed in 30 out of 60 (50%) localized and 27 out of 54 (50%) metastatic patients._x000D_ After a median follow-up of 5.2 years (IQR 3.2-8.5) follow-up was available for 260 patients (98%) of which 36 (13.8%) recurred. In localized non-seminoma patients 7 out of 29 (24.1%) CXCL12 positive patients recurred compared to 4 out of 23 (14.8%) CXCL12 negative patients (p=0.506). In metastatic non-seminoma patients 11 out of 12 (91.7%) CXCL12 positive patients compared to 1 out of 25 (4.0%) CXCL12 negative patients showed disease relapse after initial chemotherapy (p=0.001). Conclusions CXCL12 is almost exclusively expressed in non-seminoma and absent in seminoma, normal tissue or GCNIS. The reported association between CXCL12 expression and lower recurrence rates in stage 1 non-seminoma patients could not be reproduced in our dataset. However our analysis suggests that CXCL12 expression is a risk factor for recurrence in metastatic non-seminoma patients. Funding none
Authors
Christian Fankhauser
Lisa Roth Joerg Beyer Tullio Sulser Holger Moch Thomas Hermanns Peter-Karl Bode |
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MP80-18 |
Kidney Injury Molecule-1 Staining Helps to Differentiate Mixed Germ Cell Neoplasms of Testis from Classic Seminomas |
Sexual Function/Dysfunction: Penis/Testis/Urethra: Benign Disease & Malignant Disease III | 17BOS |
Abstract: MP80-18 Sources of Funding: None Introduction Embyrologically, gonads are derived from mesonephrons while kidneys are derived from metanephrons. Our previous study demonstrated a positive association between kidney injury molecule-1 (KIM-1) staining and renal cell (papillary/clear cell type), and ovarian carcinoma (clear cell). The preliminary data also revealed positive KIM-1 staining in the tubules of mesonephrons, raising the possibility of KIM-1 expression in various testicular tumors. This study was to investigate whether KIM-1 and CD133 (a progenitor cell marker known to be positive in some renal cell carcinoma) expressions can help predict or differentiate various germ cell neoplasms of testis. Methods A total of 29 cases of seminoma and 31 cases of mixed germ cell neoplasms were identified. Tumors were sectioned and immunohistochemically stained for KIM-1 (AKG7 monoclonal KIM-1 antibody from JV Bonventre, BWH, Boston, at dilution 1:10) and CD133 (AC133 monoclonal antibody, Miltenyi Biotec, at 1:100 dilution). The membranous staining of each marker was graded 0 to 3+ and the percent of expressive distribution was recorded. Results KIM-1 was found to stain 77.4% (24/31, intensity at 1 to 3+, and distribution ranging from 1 % to 90 %) of mixed germ cell neoplasms (predominantly embryonal and yolk sac components), whereas there was no KIM-1 expression in benign seminiferous tubules, mature teratoma, classic seminoma and Leydig cell tumor. Scattered and weak CD133 staining was seen in seminoma and mixed germ cell tumors (10% and 16% respectively) and absent in benign tissue, mature teratoma and Leydig cell tumor. Conclusions Our data suggest that KIM-1 expression can be used to differentiate mixed germ cell neoplasms from pure seminomas (negative for KIM-1 staining). CD133 appears to be not as useful in differentiating various testicular tumors. Funding None
Authors
Chirag Dave
Alia Gupta Mitual Amin Ping Zhang Jason Hafron |
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MP80-19 |
TREATMENT TRENDS AND OUTCOMES FOR LYMPH NODE POSITIVE PENILE CANCER PATIENTS |
Sexual Function/Dysfunction: Penis/Testis/Urethra: Benign Disease & Malignant Disease III | 17BOS |
Abstract: MP80-19 Sources of Funding: none Introduction Penile cancer is an uncommon disease with little level I evidence to guide therapy. The NCCN guidelines advocate a lymph node dissection (LND) with consideration of perioperative chemotherapy (CT) for all lymph node positive (LN+) penile cancer (PC) pts. Using a large national cancer registry, we assessed temporal trends in utilization of CT for LN+M0 PC, and evaluated outcomes between those who did (LND+) and did not (LND-) receive a LND and/or chemotherapy (CT+ vs. CT-). Methods The National Cancer Database (NCDB) was queried for all non-metastatic PC patients with LN+ squamous cell carcinoma of the penis from 2004-2014. Temporal trends were assessed using Cochran-Armitage tests. Adjusting for patient, clinical, and tumor characteristics, multivariable logistic models were used to examine the association between clinicopathologic characteristics and receipt of CT. Kaplan Meier analyses with log-rank tests and multivariable Cox regressions were used to analyze overall survival (OS). Results Of 1123 pts identified, 750 (67%) underwent a LND. Receipt of chemotherapy was similar in both LND+ (40%) and LND- (42%) pts (p=0.53). From 2004-2014, the overall utilization of systemic therapy significantly increased (38% vs. 48%. p=0.0009). However, only 53% of N3 patients received CT (N1 31%, N2 40%). Following adjustment, older patients (76 + years: OR 0.34 [CI 0.19-0.59], p=0.0002) were less likely to receive CT, while N2 (OR 1.62 [CI 1.16-2.27], p=0.005) and N3 (OR 2.32 [CI 1.67-3.22], p<0.0001) pts were more likely to receive CT. High volume centers (≥ 4 cases of PC/year; 29% of all LN+ cases) delivered less CT (OR 0.69 [CI 0.48-1.00], p=0.047). OS varied from 14.9 mo in the LND-/CT- group to 42.6 mo in the LND+/CT+ group. On multivariable analysis, receipt of CT was not associated with OS (HR 0.95 [CI 0.77-1.19], p=0.67). Conclusions In hospitals reporting to the NCDB, only 67% of LN+ PC pts receive a LND. While CT utilization has increased since 2004, rates remain low, even for N3 pts for whom the NCCN clearly recommends systemic therapy. Surprisingly, high volume centers were less likely to deliver CT for LN+ patients. Receipt of CT does not appear to affect OS, which likely reflects the aggressive natural history of PC. Nonetheless, these data highlight opportunities to improve adherence to guideline-recommended care. Funding none
Authors
Shreyas Joshi
Handorf Elizabeth Andres Correa Michael Haifler Benjamin Ristau Robert Uzzo Richard Greenberg David Chen Rosalia Viterbo Alexander Kutikov Marc Smaldone Daniel Geynisman |
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MP80-20 |
Complications and adjunctive surgical procedures in post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) to define a tertial referral center |
Sexual Function/Dysfunction: Penis/Testis/Urethra: Benign Disease & Malignant Disease III | 17BOS |
Abstract: MP80-20 Sources of Funding: None Introduction Post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) is standard of care for patients with advanced germ cell tumors and residual disease. Due to the invasiveness and complexity of the disease additional surgical procedures may be necessary. This analysis aims to quantify the additional procedures in order to define the necessity for other surgical specialties on an ad hoc basis._x000D_ Methods We performed a retrospective analysis of 431 PC-RPLNDs in 382 patients for intra- and postoperative complications as well as additional surgical procedures. Complications were classified by Clavien-Dindo grading. _x000D_ Results 431 RPLNDs with 383 PC-RPLNDs were performed between 2008 und 2016 in a single center. Mean patient age was 35 years with a mean tumor size of 6 cm. PC-RPLND was performed unilaterally in 176 patients (40.8%) and bilaterally in 253 patients (58.7%). Mean OR time was 217 minutes (range 60-510 min) with a mean intra-operative blood loss of 1026 cc (range 0-15000). 128 patients (29.7%) received blood transfusions. A significant vascular intervention during the operation occurred in 78 patients (18.1%) – vena cava procedures including resection and cavotomie were necessary in 24 patients (7.2%) and aortic replacement in 7 patients (1.8%). Nephrectomy was performed in 41 cases (9.7%), 32 patients received partial liver resection (7.4%) and 14 patients needed vertebral resection (3.2%). During the postoperative course 24 patients (4.6%) showed a lymphocele. Complications by Clavien Grading: (including post OP complications) Grade I: 84 (19.4%) (inclusive post OP hematoma and lymphocele), Grade II: 128 (29.6%) (incl. blood transfusion); Grade III: 9 (2.1%); Grade III b: 9 (2.1%); Grade IV a: 4 (0.9%); Grade V: 1 (0.2%)._x000D_ Conclusions PC-RPLND in testis cancer patients is a demanding operation which frequently requires a multivisceral surgical approach in about 30% of cases. Adjunctive surgical procedures which require other surgical specialties such as vascular interventions including cava resection, aortic grafting or extensive liver and vertrebral resections may be ad hoc necessary. Consequently tertial referral centers are defined to provide ad hoc surgical specialty service and this type of surgery should not be perfomed outside of these centers due to the high frequency of a multivisceral approach._x000D_ Funding None
Authors
Achim Lusch
Laura Gerbaulet Christian Winter Peter Albers |
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MP81-01 |
Central Tumor Necrosis Factor-alpha Blockade Increased nNOS Expression in the Hypothalamic Paraventricular Nucleus and Improved Sexual Behavior Disorder in Male Diabetic Rats |
Sexual Function/Dysfunction: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP81-01 Sources of Funding: Guangdong Province Characteristic Innovation Project (China, 2015KTSCX044) (PI, Ting Long). Introduction Sexual dysfunction, including decreased libido, sexual behavior disorder and erectile dysfunction (ED), is common in male patients with diabetes mellitus (DM). We previously demonstrated that increased peripheral tumor necrosis factor alpha (TNF-?) expression, associated with inflammation in DM, contributes to ED in the rat corpus cavernosum. However, the role of TNF-? in the central pathophysiology of DM-associated male sexual dysfunction is unknown. In this study, we examined the effects of TNF-? inhibition, i.e. etanercept (ETN) via chronic intra-cerebroventricular (ICV) infusion on neuronal nitric oxide synthase (nNOS) expression in the hypothalamic paraventricular nucleus (PVN) and sexual behavior disorder in male diabetic rats. Methods Type II male DM rats were divided into 4 groups (G), n= 12/G, and subjected to chronic ICV infusion of artificial cerebrospinal fluid (aCSF) or ETN (10 ?g/kg/day) by Osmotic Pumps, with and without induction of DM: G1: non-diabetic+ICV aCSF as control; G2: non-diabetic+ICV ETN; G3: DM+ICV aCSF; and G4: DM+ICV ETN. After 4 weeks of treatments, sexual behavior, expression of TNF-?, TNFR-1, and nNOS proteins, nNOS activity, and reactive oxygen species (ROS) generation within the PVN were assessed. Results Male diabetic rats with ICV aCSF treatment displayed significantly severe sexual disorder accompanied with blunted nNOS expression and activity in the PVN in addition to local upregulated TNF-? and TNFR-1 expression, and increased ROS generation compared with non-diabetic controls. The sexual behavioral parameters including mounting latency, intromission latency, the number of mountings and the number of intromissions until ejaculation, induced by the introduction of receptive females, were significantly improved in the treated group with ETN. ICV ETN significantly inhibited TNF-? and TNFR-1 expression and reduced ROS generation in the PVN in diabetic rats. In addition, ICV ETN appeared to induce marked increased in nNOS expression in the PVN of diabetic animals compared with ICV aCSF-treated diabetic rats. Activity of nNOS in the PVN was also significantly increased in ICV ETN-treated versus ICV aCSF-treated diabetic rats. Conclusions Increased TNF-? and TNFR1 expression in the hypothalamic PVN associated with DM contributes to male sexual disorder by centrally inhibiting nNOS expression and activity in the PVN via promoting local ROS generation. Central TNF-? blockade may have beneficial effects on the male sexual disorder in diabetes through improvement of NO pathway within the PVN. Funding Guangdong Province Characteristic Innovation Project (China, 2015KTSCX044) (PI, Ting Long).
Authors
Ting Long
Huanhuan Wang Xiaohong Ye Wenwen Lin Yuanyuan Zhang Danian Qin |
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MP81-02 |
Oxygen saturation after vacuum erectile device like important factor in penile rehabilitation. |
Sexual Function/Dysfunction: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP81-02 Sources of Funding: none Introduction Vacuum therapy allows to prevent fibrosis in the corpus cavernosum and penile length loss. But participation of VED in penile rehabilitation (PR) to prevent hypoxia of cavernosal tissue is not completely clear due to lack of data about blood gas (BG) at the time of using VED without constriction ring._x000D_ We assessed some BG analytical parameters at the time of artificial erection induced by VED and then compared it with the results of color-Doppler ultrasonography (CDU) and scores of domain EF of International Index of Erectile Function-15 (IIEF-15). Methods We took corporal blood after VED use from 15 patients before doing nerve-sparing radical prostatectomy (NSRP). We used acid-base parameters of venous and arterial blood of the patient for control. We measured the partial pressure of oxygen (pO2), the partial pressure of carbon dioxide (pCO2) and oxygen saturation (SO2) to determine BG and blood oxygenation. All patients who underwent preoperative comprehensive evaluation of EF with using IIEF questionnaire and CDU. Results 15 patients were divided into three groups based on BG corporal blood after using VED: 4 with a predominance of arterial blood (26.6%), 4 with a predominance of venous blood (26.6%) and 7 with mixed blood (46,6%) respectively. Mean IIEF score and averages of pO2 (mmHg), pCO2 (mmHg) and sO2 (%) obtained during the study are shown in Table._x000D_ IIEF score and values of CDU in patients with a predominance of arterial blood in corpus cavernosum after using VED differed with higher rates comparing patients with venous and mixed blood. According acid-base parameters in the II and III groups corporal blood consists venous and mixed blood after VED therapy, where SO2 is 86.3% and 93.9%, respectively, which corresponds to the high level of oxygenation. Conclusions High level of oxygenation in all investigated groups is an important factor of prevention collagen synthesis and fibrosis and thereby VED can be used in PR in patients who underwent NSPR. Use of expanded opportunities of CDU is very important because it shows real penile length loss. Besides, measurement of RI shows in arterial blood group patients that the high RI (>0.8) indicates sufficient veno-occlusive mechanism. It can be used as a predictor in appointment of VED therapy for PR. Funding none
Authors
Sergey Kotov
Alexander Osadchinsky |
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MP81-03 |
Erectile dysfunction is independently associated with apnea hypopnea index & oxygen desaturation index in elderly, but not younger, community-dwelling men |
Sexual Function/Dysfunction: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP81-03 Sources of Funding: National Health and Medical Research Council (Australia) Introduction This study aimed to examine whether there is an independent association between obstructive sleep apnea (OSA) and other sleep indices using polysomnography data and erectile dysfunction (ED) in a representative cohort of middle-aged to elderly men. Methods Data were drawn from a randomly-selected, community-dwelling cohort of men aged ?35y at recruitment (2002-5). Of these, n=734 men with no prior OSA diagnosis who underwent full in-home polysomnography (Embletta X100; 2010-11) and had complete ED measures (Global Impotence Rating) were selected for the analytic sample (mean age (SD): 60.8 (10.9)). Uni- and multi-adjusted regression models of ED were fitted against PSG measures, along with related covariates. Results Of the men examined, 24.7% (n=181) had ED, most notably in men aged over 65 years (p<0.001). Given an observed age interaction (p=0.005), analyses were repeated in age-stratified samples (<65; 65+ years). In men <65 years, only severe OSA was found to have an association with ED (2.01; 1.13-4.69) in unadjusted models, however this effect was attenuated after adjustment. For men 65+ years, an independent association with ED was found for AHI (1.55;1.02-2.36), moderate (1.79;1.18-2.43) and severe (4.84;2.56-9.93) OSA, and ODI (both continuous (1.48;1.03-1.99) and >16 secs (2.79;1.23-6.32)). The effect of AHI on ED was shown to be primarily mediated through ODI (63.4%, Sobel p value=0.29). Conclusions In younger, community-based men there appeared no independent relationship between objective measures of sleep and ED. However, there appears a strong, independent relationship between OSA, ODI and ED in men aged 65 and over. Funding National Health and Medical Research Council (Australia)
Authors
Sean Martin
Sarah Appleton Robert Adams Anne Taylor Nicholas Brook Peter Catcheside Douglas McEvoy Gary Wittert |
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MP81-04 |
Leydig Stem Cell Isolation and Differentiation From Human Testis Biopsies: Potential Modality To Increase Serum Testosterone |
Sexual Function/Dysfunction: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP81-04 Sources of Funding: This work was supported in part by the Urology Care Foundation Research Scholar Award Program to RR Introduction Impaired testosterone production as a result of Leydig cell loss or dysfunction can occur in men with testicular failure. Testis failure is typically seen in men with Klinefelter syndrome and in men undergoing high dose chemotherapy or hematopoietic stem cell transplant. Currently, these patients are offered long-term testosterone supplementation that can cause infertility. We evaluated an approach for isolation and differentiation of Leydig stem cells from men with infertility that underwent testis biopsies. Methods A total of 6 men with testicular failure underwent testis biopsies for sperm retrieval. Using an IRB approved protocol, about 10mg of testicular tissue from each of these men were processed for Leydig stem cell isolation and culture. Leydig stem cells and Sertoli cells were analyzed by immunofluorescence (IF) and quantitative real time PCR (qPCR) for PDGFR-? and Sox-9 respectively. After stimulation by Luteinizing hormone (LH), we compared the levels of 3?HSD mRNAs (involved in testosterone production) using qPCR, and testosterone production in the media using radioimmunoassay from the adult Leydig cells. Results We successfully isolated and cultured Leydig stem cells from all 6 men with testicular failure who underwent testis biopsies. Leydig stem cells were maintained in the media without LH for up to 30 days. We conducted a minimum of five independent isolations within 30 days. We were able to culture up to 3 million cells / biopsy in 14 days. Of the cells cultured, up to 70% of the cells were Leydig stem cells and 10% of them were Sertoli-cell in origin on day 14. IF and qPCR data showed as the majority of cell population was undifferentiated, the expression of PDGFR-? was high. Upon stimulation by LH, the expression of 3?HSD was induced and that of PDGFR-? was reduced at both RNA as well as at protein levels. Conclusions Our results indicate that Leydig stem cells can be isolated and cultured from men with testicular failure. Leydig stem cells can be differentiated with LH and the adult Leydig cells can be functional. These results suggest that Leydig stem cell therapy can be used to increase serum testosterone without affecting fertility outcomes. Funding This work was supported in part by the Urology Care Foundation Research Scholar Award Program to RR
Authors
HIMANSHU ARORA
Marilia Sanches Santos Rizzo Zutti Bruno Nahar Joshua M. Hare Ranjith Ramasamy |
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MP81-05 |
PELVIC AUTONOMIC DYSFUNCTION: A NEW CONCEPT IN PATIENTS HAVING LOWER URINARY TRACT SYMPTOMS WITH COEXISTENCE OF ERECTILE DYSFUNCTION |
Sexual Function/Dysfunction: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP81-05 Sources of Funding: none Introduction To investigate the answer could CC-EMG recording be used as a diagnostic parameter in pelvic autonomic dysfunction in patients with LUTS. Methods This study was performed in 50 patients having LUTS including erectile dysfunction. Total ‘International Index of Erectile Function’ (IIEF) scores were below 26 and International prostate symptom score (I-PSS) scores were more than 10 point. All patient’s urologic evaluation were performed with penile color Doppler ultrasonography, electromyography of corpus cavernosum (CC-EMG), cavernosometry, urodynamics and transrectal ultrasonography. CC-EMG measurements obtained from patients that were divided into groups according to their degree of relaxation. The degree of relaxation is less than 50% of patients in group 1 (23 patients) (autonomic dysfunction) and more than 50% in group 2 (27 patients) patients. Results IIEF-5 and IIEF-15 scores of group 1 patients were lower than group 2 patients. I-PSS scores of group 2 patients were lower than group 1 patients. The mean amplitude values were 261.41 ± 112.97 in group 1 before papaverine injection and that was reported to be 246 ± 101.28 in group 2 (p<0.05). The mean amplitude after papaverine enjection value was 182.73 ± 60.71 in group 1 and that value was 83.2 ± 29.19 in group 2 (p<0.05). Conclusions Increased electrical bursts and decreased relaxation responses could be the indirect sign of increased contractile status of bladder sphincteric activity and thus CC-EMG could be used in the diagnosing of pelvic autonomic dysfunction as to be used in cavernous autonomic dysfunction analogically. Funding none
Authors
Onder Kayigil
Yucel Altay Emrah Okulu |
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MP81-06 |
Is bariatric surgery the answer to sexual dysfunction in obese men? |
Sexual Function/Dysfunction: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP81-06 Sources of Funding: None Introduction Currently bariatric surgery is the most effective treatment for significant and sustained weight loss. Erectile and endothelial dysfunctions may share some common metabolic and vascular pathways that may be influenced by weight-loss. The aim of this study is to assess the effect of surgically induced weight loss on obese men with sexual dysfunction undergoing laparoscopic sleeve gastrectomy (LSG). We also aimed to analyse the proposed underlying mechanism associated with change in erectile function after weight loss by LSG. Methods Eighty two consecutive obese men who underwent a laparoscopic sleeve gastrectomy were followed for 12 months. All operations were performed by the same surgeon at a single institution. _x000D_ _x000D_ Patients were examined both before and after 12 months of LSG for biochemical tests; total serum cholesterol, triglyceride, C-reactive protein (CRP), interleukin-6 (IL-6) and endothelial nitric oxide synthase (eNOS) and for erectile function tests; International index of erectile function (IIEF) scores. _x000D_ Results Eighty two men (mean age 39±14.6years, range 24–62; mean BMI 41.2± 4.8kg/m2) completed all pre- and postoperative questionnaires and biochemical tests. At 12 months the mean weight loss was 34.8?kg and the mean BMI decrease was 8.6?kg/m2._x000D_ Preoperatively, 67 (77%) men (mean age 40± 12.9 mean, BMI 42.2± 5 kg/m2) were sexually active. Erectile function was significantly improved (p=0.02). Men had a significant decrease in serum cholesterol and triglyceride levels. NOS activity showed a significant increase (P<0.02). In addition, our patients showed a statistically significant decrease in IL-6 levels and CRP compared with preoperative period (P<0.03 and P<0.01 respectively)._x000D_ Conclusions A significant improvement of erectile function was documented among obese young men undergoing bariatric surgery. This improvement was documented both clinically by improvement in IIEF score postoperatively and biochemically through reduction of hyperlipidemia and amelioration of both endothelial function and inflammatory cytokines. Funding None
Authors
Ahmed fahmy
Moustafa Elsawy Amr Kamal Abdelrahman Zahran hazem Rhasad |
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MP81-07 |
Penile carcinoma: genetically engineered models for novel therapeutics identification |
Sexual Function/Dysfunction: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP81-07 Sources of Funding: None Introduction Penile cancer is rare but fatal malignant disease. The predominant histologic type of penile cancer is squamous cell carcinoma. The molecular mechanism of penile cancer has not been extensively studied thus far and remain poorly understood. We present the first genetically engineered penile cancer model in mice that represents a model for studying molecular mechanisms and pathway alterations in penile cancer pathogenesis Methods Two transgenic models that develop penile cancer through tissue-specific deletion of tumor suppressor genes were generated in a background nearly congenic to C57BL/6: deletion of smad4;Apc (model 1) and deletion of smad4;Apc; Pten (model 2). Penile prolapse was the phenotype of penile cancer formation. Tumor histology was confirmed by two pathologists (P.T., P.R.). Established penile tumors were harvested for RNAseq, reverse phase protein array (RPPA) and mass cytometry (CyTOF) for analyses if transcriptome, targeted proteome and immunophenotyping, respectively. In vivo treatment of mouse primary penile tumors was performed in 6 mice/group using cisplatin chemotherapy Results Smad4; Apc mice developed primary penile tumors at 18-20 weeks of age, whereas Smad4; Apc; Pten mice develop tumors at 8-10 weeks. The tumors resembled penile squamous carcinoma by pathologic confirmation. In vivo treatment of mice with cisplatin revealed that that Pten loss could mediate tumor resistance to cisplatin treatment. CyTOF analysis showed a strong inflammatory phenotype of the tumors with massive infiltration of CD11b+ Gr1+ myeloid cells. Transcriptomic analysis indicates that COX-2 may be the master regulator of the inflammatory phenotype. RPPA analysis showed a number of highly regulated proteins and pathways in Smad4;Apc tumors compared with normal penis. Based on RPPA result, we are currently testing sensitivities of isolated penile cancer cell lines to a panel of 50 drugs, targeting molecules involved in pathways such as PI3K/AKT/mTOR, HER2/EGFR, SRC, JAK, STAT3, Bcl-XL, etc. We have also developed 4 penile cancer PDX models, and isolated penile cancer cell lines that grow squamous cell carcinoma in SCID mice from 2 of the 4 models. The PDX and cell lines will help validate our findings from transgenic mouse models. Conclusions A genetically engineered penile cancer mouse model was developed exhibiting a histologic and molecular phenotype that resembles human penile cancer. This model may assist in studying the mechanisms of tumor pathogenesis, progression and novel therapeutic strategies Funding None
Authors
Ahmed Sarhan
Xiaoying Shang Pherose Tamboli Priya Rao Curtis Pettaway Alan Wang Ronald DePinho Xin Lu |
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MP81-08 |
Enclomiphene Citrate vs. Topical Testosterone Gel: Effects on Reproductive Hormones and Sperm Parameters |
Sexual Function/Dysfunction: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP81-08 Sources of Funding: Repros Therapeutics Introduction Objectives: To determine effects of daily oral doses Enclomiphene citrate (EC) in comparison to topical testosterone treatment on total testosterone (TT), LH and FSH changes in semen parameters, changes in testicular volume and cholesterol changes in men with secondary hypogonadism. _x000D_ _x000D_ Methods Patients and Methods: Results of two randomized, double-blind, double-dummy, placebo-controlled, multi-center, Phase III studies (ZA-304/305) to evaluate two doses of EC versus AndroGel (AG) 1.62% on TT, LH and FSH and sperm counts in overweight men 18-60 years of age with secondary hypogonadism. Subjects in this trial exhibited early morning serum TT levels in the low or low normal range (?300 ng/dL; ?10.1 nmol/L) and had low or normal LH (<9.04 IU/L) levels. Semen samples were collected at the beginning and end of the study EOS). Testicular volume was measured at baseline and 16 weeks of treatment as determined by orchidometry. Serum samples, collected at baseline and 16 weeks, were analyzed for hormone and lipid levels. _x000D_ Results Results: TT levels were increased between baseline and after 16 weeks of treatment in all treatment groups. EC administration reestablished a more normal diurnal pattern of secretion. FSH and LH levels increased in the EC groups and decreased in the AG group at 16 weeks. EC maintained sperm concentration in the normal range over the treatment period. In contrast there was a marked reduction in spermatogenesis in the AG group. Combined data from the two studies showed normalized morphology strict was significantly improved with EC administration and decreased with AG administration. All men were similar at baseline in testes volume (p = 0.94, ANOVA) by orchidometry. In both studies men on topical testosterone demonstrated decreases in mean testicular volume (-0.86 cm3) and a significant decrease overall compared to the EC (p<0.05) or placebo (p<0.05). Treatment with daily oral enclomiphene citrate lowered serum cholesterol by 18.1 mg/dL over 16 weeks. _x000D_ Conclusions Conclusions: EC consistently increased serum TT, LH and FSH restoring normal levels of serum testosterone. The effects on TT were also seen with T replacement, via AG, but sperm counts were not maintained and in most cases decreased. EC treatment maintained sperm concentrations in the normal range and morphology strict parameters were improved. EC resulted in a significant increase in testicular volume, whereas treatment with AG resulted in a significant decrease in testicular volume. A significant decrease in cholesterol was seen with EC. Funding Repros Therapeutics
Authors
Greg Fontenot
Joseph Podolski |
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MP81-09 |
The nerves in the glans penis: anatomical and histological study |
Sexual Function/Dysfunction: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP81-09 Sources of Funding: none Introduction The topographical anatomy of the composite nerve fibers in the human glans penis is poorly characterized. Therefore, histological methods were used to analyze nerves to the cavernous tissue at the distal end of the corpus spongiosum. Methods Immunohistochemical techniques were used to detect S100, neuronal nitric oxide synthase, tyrosine hydroxylase, and vasoactive intestinal polypeptide protein expressions in frontal or sagittal penile sections obtained from 20 donated, older male cadavers. Results At or near the coronal sulcus at the dorsal midline, three to seven terminal branches of the unilateral dorsal nerve ran deeply or centrally along the distal dull end of the corpus cavernosum and entered the glans cavernous tissue. Once there, the nerve divided into thinner branches (neuronal nitric oxide synthase or tyrosine hydroxylase positive) and the major nerve section reached the surface skin of the glans. Several thin nerves took highly arduous paths, as evidenced in ventral subcutaneous tissue of the distal third of the penis. Conclusions Histological examination revealed a neurovascular bundle that penetrated the glans cavernous tissue toward the skin covering, with a rich nerve supply to the skin folds at and near the coronal sulcus. Funding none
Authors
Nobuyuki Hinata
Ahmed Aly Hussein Tomoaki Terakawa Yukari Bando Gen Murakami Khurshid Guru Masato Fujisawa |
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MP81-10 |
Erectile dysfunction in 45-year-old German men in association with risk factors and comorbidities; Results of the German Male Sex-Study |
Sexual Function/Dysfunction: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP81-10 Sources of Funding: none Introduction We analyzed erectile dysfunction (ED) in a representative sample of 45-year-old German men and assessed the association with lifestyle risk factors and ED-related comorbidities. Methods Data was collected within the German Male Sex-Study (part of the PROBASE prostate cancer screening trial) between April 2014 and April 2016. _x000D_ 45-year old men living in four German regions (Dusseldorf, Hannover, Heidelberg, Munich) were invited within a screening trial. 10.135 Caucasian, heterosexual and sexually active men were included in this analysis. An anamnesis interview was obtained for all men including information on comorbidities and medication. Weight and waist circumference were measured on site._x000D_ Erectile function was evaluated using the International Index of Erectile Function (IIEF-EF(6)). The presence of ED was defined as IIEF-EF-Score <=25._x000D_ Association of ED and comorbidities/risk factors were analyzed by logistic regression._x000D_ Results The prevalence of ED was 25.2% (IIEF-EF: 6-10: 3.1%, 11-16: 9.2%, 17-21: 4.2%, 22-25: 8.7%). We ascertained a baseline risk of 14.4% for men without ED-related comorbidities and with healthy lifestyle factors: no smoking, waist circumference <94cm, physical activity >=4 days a week, IPSS=0._x000D_ In multiple logistic regression with backward elimination the following factors associated with ED were identified: _x000D_ Comorbidities: Depression [OR 1.87], lower urinary tract symptoms (defined as International Prostate Symptom Score >7) [OR 1.68], diabetes mellitus [OR 1.38], hypertension [OR 1.22]._x000D_ Risk factors: Poor general health status (first question of SF12) [OR 1.72], waist circumference (>=102cm) [OR 1.31], physical activity (<2 days a week minimum 30 minutes per day mild exercise) [OR 1.27], smoking regularly [OR 1.15]._x000D_ The only factor eliminated during variable selection was BMI even though this factor showed a crude OR of 1.42._x000D_ ED-prevalence increased with the number of risk factors (0 factors: 21.9%; 3 factors: 33.4%) and number of comorbidities (0 comorbidities: 22.4%; 3-4 comorbidities: 64.3%)._x000D_ Conclusions ED was found in every fourth 45-year-old German man. Prevalence increased significantly with the number of risk factors and comorbidities. Funding none
Authors
Kathleen Herkommer
Jacqueline Hallanzy Martina Kron F.-M. Köhn Maximilian Schmautz Peter Albers Christian Arsov Boris A. Hadaschik Markus Hohenfellner Florian Imkamp Martin Kuczyk Jürgen E. Gschwend |
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MP81-11 |
Sacubitril/Valsartan (ENTRESTO®) and Valsartran/Sildenafil Combination Improves Functional Responses on Isolated Rat Corpus Cavernosum from Nerve-Crush Injury Model |
Sexual Function/Dysfunction: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP81-11 Sources of Funding: None Introduction Erectile dysfunction (ED) is a frequent complication of radical prostatectomy (RP), with penile neuropathy contributing to the disease process. Angiotensin-II is a known mediator of smooth muscle vasoconstriction and fibrosis after bilateral cavernosal nerve injury (CNI). Sacubitril-valsartan (Entresto®-Novartis), described as an angiotensin receptor neprilysin inhibitor, is a new oral drug combination for the treatment of symptomatic chronic heart failure in adults with reduced ejection fraction. The aim of this study was to compare the combined effects of sacubitril/valsartan and valsartan/ sildenafil on bilateral CNI-induced functional changes in rat cavernosal tissue. Methods Bilateral CNI was produced in anesthetized male rats and cavernosal tissue was removed 2 weeks after CNI. Organ-bath relaxant responses were performed on corpus cavernosum (CC) strips (1×1×6 mm). After phenylephrine-induced contraction (Phe, 10 µM), dose-response curves were evaluated for valsartan (10 nM-0.5 mM), sacubitril (10 nM-0.2 mM), sacubitril/valsartan (10 nM-0.5 mM) and valsartan (10 µM)/ sildenafil (10 µM). Electrical field stimulation (EFS; duration: 15 sec amplitude: 50-80 V; frequency: 1-20 Hz; pulse width: 5msec) of the cavernosal autonomic nerves was accomplished by the use of platinum electrodes positioned on the either side of the tissue strip in the absence and presence of these drugs. Results Valsartan, sacubitril, and sacubitril/valsartan inhibited Phe-evoked CC contractions (maximum relaxation responses: 88.6 ± 8.4; 12.6 ± 5.9; 96.5 ± 3.5 %, respectively) in a dose-dependent manner in CC strips from CNI rats. Sildenafil-induced relaxation (50.5± 5.5 %, at 10µM) was increased by 44.5% in the presence of valsartan (91.0 ± 3.5 %, p=0.0142). EFS-induced relaxation responses (28.8 ± 3.0%, at 20Hz) occurred after Phe-precontraction potentiated by 40.8%, in the presence of valsartan (70.3 ± 6.5 %, p=0.0199). Conclusions Valsartan markedly relaxed isolated CC strips from CNI rats. Combining the sildenafil with valsartan causes greater nitrergic relaxation of CC smooth muscle compared to sildenafil alone. In vitro administration of valsartan combined with sacubitril in the setting of CNI may mitigate ED caused by CNI. Further experimental and clinical studies are required to advance knowledge of combined treatment modality in ED after RP. Funding None
Authors
Serap Gur
Suresh C Sikka Philip J Kadowitz Nora Haney Kenneth DeLay Wayne JG Hellstrom |
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MP81-12 |
Functional brain imaging shows a correlation between distended seminal vesicles and specific brain activity in healthy men |
Sexual Function/Dysfunction: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP81-12 Sources of Funding: none Introduction In a mouse model a positive correlation between occluded and thus congested seminal vesicles and sexual activity has been suggested. No study so far has compared the neural processing of visual sexual stimuli in men as a consequence of the filling state of the seminal vesicles. The objective was to evaluate potential specific cortical activation by visual sexual stimuli in young healthy men with distended and voided seminal vesicles. Methods 6 healthy heterosexual men were included and underwent 2 visits on 2 consecutive days (day 1 and day 2). Ethical Committee approval has been obtained. Both visits took place between 8 and 11 a.m. Before first visit no ejaculation for 3 to 5 days was requested. On both visits hormone analyses (Testosterone, SHBG, Prolactin, Serotonin, TSH), Derogatis Interview for Sexual Functioning (DISF) questionnaire, functional MRI (fMRI), and structural pelvic MRI were performed. During fMRI, subjects viewed alternating blocks of sexual, neutral, positive, and negative emotional pictures. Pictures were presented in 16 blocks in a pseudo-randomized order. One block consisted of 8 pictures, each picture was showed for 3 s resulting in a 6.4 min long fMRI. After each fMRI, subjects had to rate their arousal from 1 (none) to 10 (maximum). After first visit, subjects had to void seminal vesicles by masturbation between 6 and 9 p.m. for re-evaluation the next day. Results Median age was 26 years (range 24-29). Between day 1 and day 2, hormone analyses (all pairwise comparisons p>0.36), DISF questionnaire score (p=0.14), and arousal scoring between fMRI sessions (p=0.61) showed no significant differences. Seminal vesicles volume was significantly lower at day 2 (p=0.003). Significant higher activation was detected in the right precentral gyrus and middle frontal gyrus (Brodmann area (BA) 6) and left cuneus (BA 18, 19) when contrasted for sexual over neutral pictures (p<0.001 at voxel level, family-wise error corrected (p<0.05) at cluster level) at day 1 with full seminal vesicles compared to day 2 with voided seminal vesicles. Conclusions In response to sexual pictures a significant higher activation was detected in brain areas involved in motor preparation (arousal) and visual association areas at day 1 with distended seminal vesicles compared to day 2 with voided seminal vesicles. This suggests that the filling state of the seminal vesicles may have an influence on the brain activation and sexual desire in men. Funding none
Authors
Christian Weisstanner
Manuela Wapp Martin Schmitt Stefan Puig Livio Mordasini Roland Wiest George N. Thalmann Frédéric D. Birkhäuser |
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MP81-13 |
Effect of vaginal estrogen delivery on the vaginal muscularis in a rodent model of vulvovaginal atrophy with menopause. |
Sexual Function/Dysfunction: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP81-13 Sources of Funding: Support provided by a WVCTSI pilot grant. Introduction Vaginal estrogen delivery is the recommended treatment for_x000D_ vulvovaginal atrophy with menopause to minimize systemic estrogen_x000D_ exposure. Both human and animal studies have indicated a_x000D_ restorative effect of local estrogen therapy on the vaginal_x000D_ epithelium however little is known of its effect on other aspects of_x000D_ vaginal physiology. The objective of this study was to determine the_x000D_ effect of vaginal estrogen delivery on vaginal non vascular smooth_x000D_ muscle (vaginal muscularis) structure and function in a rodent model_x000D_ of menopause. Methods Three month old ovariectomized (OVX) and sham ovariectomized (SH)_x000D_ Sprague Dawley rats were ordered from a commercial supplier. Two_x000D_ weeks following surgery, animals were treated vaginally with either_x000D_ a vehicle cream (SHVV,OVXVV) or an 0.002% 17 β estradiol cream_x000D_ (OVXVE). Animals were euthanized after 4 weeks of daily vaginal_x000D_ cream delivery and uterine and vaginal weight were recorded._x000D_ Immmunohistochemical analysis of α actin expression was_x000D_ performed with vaginal tissue(n=3/group). In vitro contractility_x000D_ studies of proximal and distal vaginal strips were conducted (n=3)._x000D_ Dose response curves to carbachol (a muscarinic agonist) were_x000D_ constructed to calculate the EC50 and maximal amplitude of_x000D_ contraction (force normalized to KCl). Data are presented as means ±SEM. Data were statistically analyzed using a one way ANOVA_x000D_ followed by Tukeys test(GraphPad Prism software). Results Vaginal wet weight was decreased (P<0.05) in OVXVV animals compared_x000D_ to SHVV, an effect reversed by local estrogen delivery. Qualitative_x000D_ analysis of vaginal cross sections indicated reversal of ovariectomy_x000D_ induced atrophy of the vaginal muscularis with estrogen treatment._x000D_ In vitro contractility studies with carbachol demonstrated a trend_x000D_ of a lower EC50 (increased sensitivity) of vaginal strips obtained_x000D_ from OVXVV animals compared to SHVV and OVXVE. The amplitude of_x000D_ contraction to 10 uM carbachol was greater of proximal strips from_x000D_ OVXVV animals compared to SHVV and OVXVE (P<0.05). Conclusions Our results indicate that vaginal estrogen is effective at reversing_x000D_ not only OVX induced atrophy of the epithelium but also the_x000D_ vaginal muscularis. We report an increased contractile response to_x000D_ carbachol in OVXVV animals, an effect also reversed by vaginal_x000D_ estrogen. Interestingly, previous studies have shown an increase in_x000D_ vaginal sensory innervation in ovariectomized rodents. More studies_x000D_ are needed to evaluate changes in autonomic innervation with this_x000D_ animal model to identify new therapeutic uses of vaginal estrogen_x000D_ treatment. Funding Support provided by a WVCTSI pilot grant.
Authors
Nicole Pepe
Lauren Doda Sarah Stewart Millie Mattox Maureen Basha |
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MP81-14 |
Human Tissue kallikrein 1 Ameliorates Erectile Function Via Modulating Autophagy and Activating Hif-1?/COX-2 pathway in Aged transgenic rats |
Sexual Function/Dysfunction: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP81-14 Sources of Funding: none Introduction Our previous studies have demonstrated that Human Tissue Kallikrein 1 (hKLK1) improved erectile function via several signaling pathways related to such as oxidative stress or corporal cavernosal fibrosis. However, the potential molecular mechanisms of hKLK1 inhibited age-related erectile dysfunction via modulating autophagy remains unknown. The aim of this article is to partly clarify the mechanisms of hKLK1 improving the erectile function in aged rats._x000D_ Methods Male wild-type Sprague-Dawley rats (WTR) and transgenic rats expressing the hKLK1 gene (TGR) were fed to 4 and 18 months of age, respectively, and divided into three groups: young WTR (yWTR) as the control, aged WTR (aWTR) and aged TGR (aTGR). Cavernous nerve electrostimulation was used to evaluate the erectile function of all rats. Transmission electron microscopy, immunohistochemistry, and western blotting were performed to determine the levels of autophagy. Related signaling pathways were detected by western blot and immunohistochemistry._x000D_ Results Compared with the yWTR group and aTGR group, the aWTR group showed (1)lower erectile function: lower intracavernosal pressure(ICP)/mean arterial pressure(MAP) ratio; (2) reduced expressions of eNOS and nNOS, lower NO level; (3) inhibited autophagy: decreased autophagosomes, lower expressions of BECN1 and LC3-II; and (4) low expression levels of PI3K/Akt/mTOR and Hif-1?/Cox-2 pathways. Conclusions The hKLK1 gene played a potential role of restoring erectile function in aged transgenic rats through modulating autophagy via PI3K/Akt/mTOR and Hif-1?/Cox-2 pathways. This finding provided evidence for hKLK1 being gene therapy method of age-related erectile dysfunction. _x000D_ Funding none
Authors
Zhe Tang
Kai Cui Yang Luan Yajun Ruan Tao Wang Jun Yang Shaogang Wang Jihong Liu |
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MP81-15 |
THE ROLE OF NEUTROPHIL-TO-LYMPHOCYTE RATIO IN MEN WITH ERECTILE DYSFUNCTION – PRELIMINARY FINDINGS OF A REAL-LIFE CROSS-SECTIONAL STUDY |
Sexual Function/Dysfunction: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP81-15 Sources of Funding: none Introduction Erectile dysfunction (ED) has been associated to an overall lower general health status; in this context, systemic inflammation has been considered a potential pathophysiological link between ED and the overall male comorbidity status. We aimed to investigate the role of systemic inflammation by means of the neutrophil-to-lymphocyte ratio (NLR) in men with ED. Methods Complete demographic, clinical and laboratory data from 279 consecutive men with newly-diagnosed ED were analyzed. Health-significant comorbidities were scored with the Charlson Comorbidity Index (CCI). A complete blood count was requested for every man and the NLR was calculated for every individual. Patients were invited to complete the IIEF questionnaire. Logistic regression models tested the odds (OR, 95%CI) of severe ED (defined as IIEF-EF < 11, according to Cappelleri's criteria) after adjusting for age, BMI, comorbidities (CCI>0), NLR, and cigarette smoking. Likewise, LNR values were also dichotomized according to the most informative cut-off predicting severe ED using the minimum p-value approach._x000D_ Results Of all, 87/279 (31%) men had severe ED. Men with severe ED were older (median [IQR] age: 61 [47-67] vs. 49 [39-58] yrs) and showed higher rate of CCI≥1 [46 (53%) vs. 44 (23%) patients]. Thereof, NLR was dichotomized according to the most-informative cut-off (NLR>3); severe ED patients more frequently had NLR>3 as compared with all other ED patients [namely, 18 (21%) vs. 13 (7%)]. At multivariable logistic regression analysis, NLR>3.0 emerged as an independent predictor (OR [CI] 2.41 [1.06; 5.53] of severe ED, after accounting for patients' age, CCI score, cigarette smoking and BMI. Conclusions A NLR>3 increased the risk of having severe ED in our cohort, boosting the already existing evidence linking systemic inflammation to ED. Moreover, this easily obtainable index, can be clinically useful in better risk-stratifying patients with ED. Funding none
Authors
Eugenio Ventimiglia
Walter Cazzaniga Paolo Capogrosso Filippo Pederzoli Luca Boeri Nicola Frego Alberto Briganti Massimo Alfano Federico Dehò Alessandro Palmieri Lorenzo Piemonti Francesco Montorsi Andrea Salonia |
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MP81-16 |
Three- Dimensional Reconstruction of Male Pelvic Anatomy from Magnetic Resonance Imaging |
Sexual Function/Dysfunction: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP81-16 Sources of Funding: None Introduction Perineal muscles such as ischiocavernosus (ICM) and bulbospongiosus (BSM) muscles play an important role in male sexual function and a clear understanding of the anatomy of these muscles is critical. However, the anatomical description of ICM and BSM has undergone several revisions (previous conclusions were mostly derived from cadaveric dissection). These findings have been plagued by distortions of anatomical structures in cadavers. Our objective was to elucidate anatomy of the male pelvic/ perineal muscles by resorting to in vivo, proton-density imaging to improve our understanding by avoiding the errors in cadaveric studies. We used proton-density MR images of young adults and performed computer generated, 3-dimensional reconstruction of the male pelvis from these MR images to investigate the anatomy of these perineal muscles pertinent to male sexual function. Methods Five male young, normal and healthy subjects, (mean age ~25 yrs) were scanned on a 3T GE MR scanner, using a multi-channel cardiac coil, lying supine, feet-first. Axial morphological proton-density scans were acquired extending from a few slices below the base of the bladder to beyond the entry of the urethra into the penis (~18-22 slices depending on the height of the subject). Discrete anatomical structures, including the pelvic bone, bladder/ urethra, corpus cavernosum (CC), BSM and ICM were segmented from the axial proton density images obtained from these healthy male subjects. Using a volume and surface rendering software (Amira), 3-dimensional models of each structure were generated and assembled into composite figures (all images are color coded so that each colored word identifies with the same structure). Results Figure shows important structures of male pelvis. Panels A-D show various structures identified in selected slices that were used to create segmentation and 3D surface rendering. Panel E and F shows 3D reconstruction of important BSM and ISM structures along with the bladder/urethra and bones derived from proton density images Conclusions This is perhaps the first 3-D reconstruction based on in-vivo MR images of healthy male perineal muscles. These observations will form the basis of normal perineal muscle morphology that can be monitored in post-surgery patients and correlated with age/ male sexual function. Funding None
Authors
M. Raj Rajasekaran
Ishika Trivedi Shantanu Sinha Valmik Bhargava |
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MP81-17 |
Developing Improved E-Learning Anatomy Resources for Undergraduate Medical Students: Male Reproductive Anatomy, A Case Study |
Sexual Function/Dysfunction: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP81-17 Sources of Funding: none Introduction The pre-clinical undergraduate Medical Sciences course at the University of Oxford retains its classical structure with gross anatomy rigorously taught in years one and three. Traditionally this teaching was delivered as a combination of lectures and prosection, with limited online material. In the technological age, it is anticipated that students would appreciate comprehensive online resources. We began this project with the aim of modernising anatomical teaching at the University of Oxford – starting with the urogenital tract. Methods We undertook critical analysis of: comparable university online domains (namely those in the US), publicly available websites, and mobile apps. We further conducted a comprehensive student questionnaire. Based on our findings we formed a work group comprising: current third and fourth year medical students, the current Professor of Anatomy, the Emeritus Professor of Anatomy and the Director of Pre-Clinical studies. Together we triangulated our findings with the current syllabus and devised a set of clear objectives to be met by the new module. Results The urogenital anatomy module has been rewritten using a combination of: up to date videos, images, animations, tables and 3D models. This work was conducted in a new web based software package - “moodle�- which boasts an enhanced user friendly interface. Finally, when we conducted comparative analysis of learning outcomes in student study groups we observed a significant increase in performance when using the revised module. Conclusions Our revised teaching module demonstrates a high degree of both student satisfaction and content retention. Therefore, from the perspective of undergraduates and faculty alike this project has been highly successful. It is hoped that we can implement similar changes across the rest of the undergraduate anatomy E-learning resources at the University of Oxford. Funding none
Authors
Matthew A Williams
Jessica Caterson Christopher Horton Tom Cosker |
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MP81-18 |
Effects of sex hormones on cell proliferation in human umbilical vein endothelial cells |
Sexual Function/Dysfunction: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP81-18 Sources of Funding: none Introduction Although sex hormones may play a role in angiogenesis, the direct effects of sex hormones on vascular endothelial cells remain to be characterized. Thus, the aim of this study was to examine the effects of sex hormones and androgen inhibitors on cell proliferation in Human Umbilical Vein Endothelial Cells (HUVECs). Methods We analyzed the expression of androgen receptor (AR) and enzymes relevant to the action of androgens in HUVECs and prostate cancer cell lines. Furthermore, we analyzed the effect of testosterone (T), dehydroepiandrosterone (DHEA), dihydrotestosterone (DHT), and several androgen inhibitors (enzalutamide, abiraterone, dutasteride) in HUVECs. Viability of HUVECs was determined using the WST-1 assay. Results We observed that the protein level of AR in HUVECs was lower than that of the prostate cancer cell lines (LNCap, C4-2). Our results indicated that treatment with T, DHEA, DHT, enzalutamide, and abiraterone (Fig. 1) caused decreased cell proliferation at high doses. Dutasteride did not have an effect on HUVEC viability. Enzalutamide and abiraterone decreased HUVEC proliferation, including when in proliferation-inducing conditions with VEGF. To ascertain their potential androgenic activity, we cultured HUVECs with the steroid precursor 13C-[2,3,4]-progesterone (13C-Prog), and analyzed the subsequent biosynthesis of 13C-[2,3,4]-17-hydroxyprogesterone (13C-17-OHP) and 13C-[2,3,4]-androstenedione (13C-Adione) by liquid chromatography/mass spectrometry (LC/MS/MS). LC/MS/MS analysis enabled detection of 13C-17-OHP and 13C-A-dione in HUVEC cells. Furthermore, we observed that CYP17A1 has dual activities, mediated by 17α-hydroxylase and 17, 20-lyase, in HUVECs. Conclusions The present results demonstrated that HUVECs may undergo apoptosis mediated by sex hormones. Enzalutamide and abiraterone have an in vitro anti-proliferative effect on HUVECs, but not dutasteride. Thus, the anti-angiogenic activity of enzalutamide and abiraterone may have a therapeutic effect on prostate cancer. Funding none
Authors
Yasumasa Miyazaki
Takeo Kosaka Eiji Kikuchi Akira Miyajima Mototsugu Oya |
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MP81-19 |
Androgen receptor CAG repeat length as a risk factor of late onset hypogonadism in a Korean male population |
Sexual Function/Dysfunction: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP81-19 Sources of Funding: This research was supported by Basic Science Research Program through the National Research Foundation of Korea(NRF) funded by the Ministry of Education(R1304182) Introduction Androgen receptor (AR) CAG polymorphism that modulates the effect of testosterone has been found to influence sexual function. However, correlation between AR CAG repeat length and clinical factors of late onset hypogonadism is unclear and there are only few studies from Asian population. In this study we explored the relationship between AR CAG repeat length polymorphism and late onset hypogonadism (LOH) in a Korean male population. Methods The association between AR CAG repeat length was analyzed in a total 263 Korean men from 2014 to 2015. LOH was diagnosed by serum testosterone level of <3.5ng/mL and androgen deficiency in the aging male questionnaire positive. AR CAG repeat length was determined by microsatellite fragment sizing. Clinical factors and questionnaire related with LOH (patient health questionnaire-9 (PHQ), aging male symptom scale (AMS), and international index of erectile function (IIEF-5)) were analyzed with AR CAG repeat length. Results Mean age of the patients was 61.2±10.9 years and mean AR CAG repeat length was 26.2±5.1. Mean serum testosterone levels was 2.6±0.4 in men with LOH and 6.0±2.0 in men without LOH, respectively. A Total of 33 men (12.5%) were diagnosed with LOH. Men with LOH showed significant longer AR CAG repeat length compared with men without LOH (30.1 vs 25.6, p<0.001). As CAG repeat length increased, AMS total and AMS psychotic/somatic/sexual subscore increased(r=0.219 r=0.168, r=0.160, r=0.241) (p=0.001,p=0.006 p=0.001, p=0.001) and IIEF-5 score decreased, significantly (r=-0.187 p=0.002). In multivariate analysis showed that CAG was independently associated with LOH. (OR=1.3, P<0.001) Conclusions AR CAG repeat length was associated with prevalence of LOH and clinical symptoms of LOH in a Korean male population. Longer CAG repeat length was identified as a risk factor of LOH in Korean male. Funding This research was supported by Basic Science Research Program through the National Research Foundation of Korea(NRF) funded by the Ministry of Education(R1304182)
Authors
Sun Tae Ahn
Hyeong Guk Jeong Ji Yun Chae Jong Wook Kim Mi Mi Oh Hong Seok Park Je jong Kim Du Geon Moon |
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MP81-20 |
THE ROLE OF SYSTEMIC INFLAMMATION IN DETERMINING HEALTH STATUS IN MEN WITH SEXUAL DYSFUNCTION – A WORRISOME SCENARIO IN YOUNG MEN |
Sexual Function/Dysfunction: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP81-20 Sources of Funding: none Introduction Sexual dysfunctions (SDs) have been associated with an overall decreased general health status, acquiring significant importance in young men. In this context, systemic inflammation has been considered as the link between SDs and the overall comorbidity status. We aimed to investigate the role of systemic inflammation in determining overall health status in men with SDs._x000D_ Methods Complete demographic, clinical and laboratory data from 585 consecutive men seeking medical help for SD were analyzed. Health-significant comorbidities were scored with the Charlson Comorbidity Index (CCI). A complete blood count was requested and the neutrophil-to-lymphocyte (NLR), lymphocyte-to-monocyte (LMR), and the platelet-to-lymphocyte (PLR) ratios were calculated for every individual. Three different logistic regression models tested the odds (OR, 95%CI) of decreased health status (defined as CCI > 0) after adjusting for age, BMI, erectile dysfunction (ED), cigarette smoking, and NLR in model 1, LMR in model 2, and PLR in model 3, respectively. The same models were implemented in young men (defined as < 40 years of age). Results Of all, 352 (60%) men had ED, 104 (18%) had premature ejaculation, 81 (14%) had Peyronie disease, and 100 (17%) had low sexual desire/interest. Overall, 183 (31%) men were below age 40. Men with CCI≥1 were older (median [IQR] age: 61 [53-68] vs. 43 [32-55]) and had higher BMI (26 kg/m2 [24-28] vs 24 [23-27]). After accounting for other variables known to be associated with reduced health status, NLR (OR [CI]: 1.21 [1.04; 1.4] in model 1), LMR (0.75 [0.64; 0.87] in model 2), and PLR (1.01 [1; 1.01] in model 3) emerged as independent predictors of decreased health status. NLR (1.15 [1; 1.33]), LMR (0.76 [0.65; 0.88], and PLR (1.01 [1; 1.03]) predicted decreased health status in young men as well. Conclusions Higher NLR and PLR, and lower LMR, increased the likelihood of decreased health status in a European-Caucasian sample of men with SDs. Of clinical relevance, systemic inflammation seems to play a role in determining health status even in young men. Funding none
Authors
Eugenio Ventimiglia
Walter Cazzaniga Filippo Pederzoli Paolo Capogrosso Luca Boeri Nicola Frego Federico Dehò Massimo Alfano Lorenzo Piemonti Alessandro Palmieri Francesco Montorsi Andrea Salonia |
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MP82-01 |
A genetic female mouse model with congenital genitourinary anomalies and urinary incontinence |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP82-01 Sources of Funding: None Introduction Hedgehog signaling pathway is known to have important role in the urogenital development. Transcription mediators of the pathway, Gli2 and Gli3, have been shown to be heavily involved in proper urogenital sinus formation. Both Gli2 and Gli3 null mice are non-viable, and display severe urogenital ad hindgut malformations. Here, we have generated a compound genetic mutant, Gli2+/-;Gli3δ699/+, that is viable well into adulthood, and displaying variable urogenital malformations including urinary incontinence in its females. We aim to characterize the urinary incontinence observed in Gli2+/-; Gli3δ699/+ female mice and assess its functional, anatomical, and histological characteristics. Methods Gli2+/- and Gli3δ699/+ mice were crossed to generate the double mutant (Gli2+/-; Gli3δ699/+) female mice and wild type female mice were used as comparison controls; which all were verified via Polymerase Chain Reactions. Void measurements, Cystometrogram (CMG) and leak point pressure (LPP) were performed in all genotypes to assess bladder functions. The mice were then sacrificed to harvest the bladders and urethras for gross characterization via ink injection and histological assays. Differences were reported as mean and standard errors of mean (SEM) and analyzed using univariate analysis. Statistical significance set at 0.05. Results No significant differences between the mutant and wild type mice were detected for 24 hour urinary output [(n= 13) mean 26.5cc±5 vs ( n=7) mean 22.15cc±6, p=0.13]. CMG studies revealed a decrease in peak micturition pressure values and significantly reduced LPP in Gli2+/-; Gli3δ699/+ mice compared to wild type mice [(n=5) 4.28 cmH2O±2.4 vs (n=4) 20.24 cmH2O±6.45, p<0.0001; (n=5) 6.66 cmH2O±1.6 vs (n=5) 26.5cmH2O±5, p<0.05; respectively]. Gross characterization revealed that the ano-genital distance was severely reduced in double mutant mice; however, the urethra, vagina, and anus all remain separate and distinctly identifiable in these mice. Histological analyses revealed Gli2+/-; Gli3δ699/+ mice exhibited a widened urethra and a decrease in smooth muscle layer thickness in the bladder outlet and urethra, with increased mucosal folding. Conclusions Gli2+/-; Gli3δ699/+ female mice display persistent urinary incontinence with evident malformation of the bladder outlet and urethra. This presents a genetic mouse model for female urinary incontinence and alludes to potential genetic factors involved in the human condition. Funding None
Authors
Akbari Pedram
Ali Fathollahi Rong Mo Michael Chua Michael Kavran Nicole Episalla Chi-Chung Hui Walid Farhat Adonis Hijaz |
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MP82-02 |
DECREASED URINARY FUNGAL BURDEN AND DIVERSITY IN OVERACTIVE BLADDER |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP82-02 Sources of Funding: Funding: Urology Care Foundation Grant (ALA) Introduction The urinary bacterial microbiome is altered in overactive bladder (OAB) patients in comparison to controls. As bacteria and fungi frequently have a reciprocal relationship, with fungi expanding and contracting inversely with changes in bacterial burden, we examined if alterations in urinary fungal diversity and community composition accompany these bacterial changes to play a role in OAB pathophysiology. Methods Urinary fungal and bacterial burdens were examined by quantitative polymerase chain reaction of conserved ribosomal RNA (rRNA) regions. Individual bacterial and fungal species were identified using deep sequencing of the 16S and ITS1 loci, respectively, of genomic DNA from catheterized urine obtained from asymptomatic controls (n=14) and OAB patients (n=17). Bacterial and fungal taxa were identified by alignment to multiple sequence databases. The relative abundances of individual species, overall microbial diversity, and total microbial burdens for each urinary microbial community were compared between OAB and controls and correlated with self-reported symptom severity as measured by the OAB questionnaire (OABq). Results OAB was associated with significantly decreased fungal burden, with a nonsignificant increase in overall bacteria. Bacterial community composition at both the species and genus level was not significantly different between OAB patients and healthy controls. In contrast, overall fungal levels were dramatically decreased in OAB, which correlated with a drastically altered mycobiome. Worsening symptom severity (assessed by OABq) was associated with loss of Cladosporium spp. and Malassezia sympodialis and dramatic expansion of Wickerhamomyces anomalus. Conclusions While minimal differences could be observed in urinary bacterial communities, overactive bladder was associated with major shifts in urinary fungi, both in overall levels and community composition and diversity. The observation that the loss of urinary fungi is associated with urinary tract symptomatology suggests a crucial role for fungi in bladder homeostasis and implicates several fungal species, such as Wickerhamomyces, as possible pathobionts in the urinary tract. Funding Funding: Urology Care Foundation Grant (ALA)
Authors
A. Lenore Ackerman
Jie Tang Karyn Eilber Jayoung Kim Jennifer Anger David Underhill Michael Freeman |
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MP82-03 |
Neutralization of brain-derived neurotrophic factor increases synergistic activity of external urethral sphincter with reduction of acid-sensing ion channels in mice with spinal cord injury |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP82-03 Sources of Funding: NIH P01 DK093424 Introduction The role of brain-derived neurotrophic factor (BDNF) in lower urinary tract dysfunction induced by spinal cord injury (SCI) is still unclear. Previous data showed that the neutralization of BDNF in SCI mice increased voided volume and improved the voiding efficiency (2016 AUA). BDNF might involve in the voiding phase via Aδ-fiber afferents, on which the receptor of BDNF (tropomyosin receptor kinase B) is mainly distributed. Acid-sensing ion channels (ASIC), which can function as mechanosensors, are identified as a target of BDNF signaling. We therefore investigated the changes of urethral function and ASIC expression in dorsal root ganglia (DRG) after the neutralization of BDNF in SCI mice. Methods Female C57 BL/6N mice underwent Th8-9 spinal cord transection. Three weeks later, an osmotic pump was placed subcutaneously to administer 10µg/kg/hr of anti-BDNF antibody for 1 week. Four weeks after spinal cord transection, SCI mice were evaluated using single-filling cystometry and external urethral sphincter (EUS)-electromyogram (EMG) under an awake condition. CMG-EMG recordings were used to detect intermittent voiding coincided with reductions in intravesical pressure in CMG traces, which occurred during periods of reduced EUS-EMG activity. We measured voiding contraction time (VT), reduced EMG activity duration (RED) and the ratio of RED to VT. Bladder BDNF was measured and the transcripts of TRPV1 and ASIC1, 2, and 3 of L6/S1 DRG were also evaluated. Results Compared to vehicle-treated SCI mice, voided volume was significantly increased and voiding efficiency was significantly better in anti-BDNF antibody-treated SCI mice. In CMG-EMG recordings, the RED was significantly prolonged, and the ratio of RED to VT was significantly greater in anti-BDNF antibody-treated SCI mice than those in vehicle-treated SCI mice. Bladder BDNF levels of SCI mice were significantly increased compared with spinal intact mice, but decreased after anti-BDNF antibody treatment. The transcripts of TRPV1, ASIC2 and 3 were increased in SCI mice compared to spinal intact mice, and anti-BDNF treatment significantly decreased expressions of ASIC2 and 3, but not TRPV1. Conclusions BDNF upregulation in the bladder is likely to be involved in dyssynergic activity of the EUS during voiding in association with ASIC overexpression in L6/S1 DRG in SCI mice. Thus, BDNF targeting treatments could be effective for voiding problems such as DSD and inefficient voiding after SCI. Funding NIH P01 DK093424
Authors
Naoki Wada
Takahiro Shimizu Nobutaka Shimizu Pradeep Tyagi William de Groat Anthony Kanai Hidehiro Kakizaki Naoki Yoshimura |
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MP82-04 |
TRANSCRIPTIONAL REGULATION OF CORTICOTROPIN RELEASING FACTOR |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP82-04 Sources of Funding: Research reported in this publication was supported by the National Institute Of Allergy And Infectious Diseases of the National Institutes of Health under Award Number F31AI106357. Introduction Interstitial cystitis (IC) patients suffer from chronic pelvic pain and bladder dysfunction. IC patients have altered cortisol levels suggesting dysregulation of the hypothalamic-pituitary adrenal (HPA) axis and suffer from exacerbated symptoms in response to high stress. Corticotropin-releasing factor (CRF) is the initiator of the HPA axis and mediates stress responses and voiding control, where increased CRF levels in Barrington's nucleus induce bladder dysfunction. Arachidonic acid (AA) metabolites have been shown to induce CRF expression, however the transcriptional mediators of this modulation are unknown. Here we identify transcription factors that mediate AA-induced CRF gene expression. Methods We used MIRAGE software to identify candidate transcription factor binding sites in a 1kb region of the human CRF gene promoter. We identified a peroxisome proliferator activated hormone response element (PPRE) and two Xenobiotic Responsive Element (XRE) sites as candidate mediators of AA-dependent CRF induction. Site-directed mutations of the PPRE and XRE sites were generated in a CRF-luciferase reporter plasmid to evaluate responses to AA and the impact of AhR and PPAR gamma expressed in HEK 293T cells. The hypothalamic neuronal cell line N42 was used to evaluate the role of AhR and PPAR gamma in native promoter regulation by RT PCR. We also generated mice that have PPAR gamma and AhR knocked-out in CRF-expressing cells and characterized voiding activity._x000D_ _x000D_ Results AA induction in the PPRE mutant resulted in increased CRF promoter activity compared to WT, whereas XRE1 had decreased activity. The mutation of both XRE1 and XRE2 resulted in decreased responsiveness to AA. Over-expression of PPAR gamma alone showed no change, while over-expression of AhR alone showed a significant increase in AA-induced CRF expression; this was inhibited by over-expression of both AhR and PPAR gamma in HEK 293T cells. Over-expression of AhR in N42 cells resulted in increased CRF mRNA in response to AA induction. AhR conditional knockout mice showed increased voiding frequency. Conclusions These results suggest AhR binding to the XRE sites modulates AA-dependent CRF gene expression. PPAR gamma inhibits AA-dependent CRF gene expression. Continued studies will use mouse models to examine the in vivo role of AhR and PPAR gamma inhibitors to modulate voiding activity. Funding Research reported in this publication was supported by the National Institute Of Allergy And Infectious Diseases of the National Institutes of Health under Award Number F31AI106357.
Authors
Lizath Aguiniga
Anthony Schaeffer David Klumpp |
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MP82-05 |
PSYCHOSOCIAL FACTORS, SLEEP, AND PHYSICAL FUNCTION IN WOMEN WITH LOWER URINARY TRACT SYMPTOMS |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP82-05 Sources of Funding: Funding for the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN) is provided by grants from the NIDDK. Introduction We examined psychosocial health measures in women with lower urinary tract symptoms (LUTS), and compared them in groups of women based on presence and type of urinary incontinence (UI). Methods The Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN) is conducting a prospective observational study in six clinical sites. This is a cross-sectional analysis of baseline information from 510 women seeking treatment for LUTS; those with urologic pain were excluded. The LUTS Tool was used to identify women with and without UI, and to categorize symptoms into: 1) stress (SUI); 2) urgency (UUI); and 3) mixed (MUI) subtypes. Patient-Reported Outcomes Measurement Information System (PROMIS) short forms assessed sleep disturbance, depression, anxiety and physical function. The International Physical Activity Questionnaire (IPAQ-SF), Perceived Stress Scale (PSS), and Childhood Traumatic Events Scale were also administered. Results Mean age was 56±14 years; 82% were Caucasian, 46% were obese, and 15% reported diabetes. Women with UI (n=425) reported more sleep disturbance (54 vs. 52, p<0.01), more depression (50 vs. 47, p=0.03), more anxiety (51 vs. 48, p=0.02), more perceived stress (13 vs. 11, p=0.01), and poorer physical function (47 vs. 51, p<0.01) compared to those without UI (n=85). There were no significant differences in childhood traumatic events (78% vs 70%, p=0.12) or physical activity (1272 vs 1372 MET-minutes, p=0.58) in women with UI compared to those without UI. Among UI subtypes, women with MUI reported the highest depression, anxiety and perceived stress, and the poorest physical function (table). Conclusions Among women with LUTS, those with UI had more emotional distress and sleep disturbance, and worse physical function. Of women with UI, those with MUI reported more severe emotional distress. Frequency of at least one reported childhood traumatic event did not significantly differ across groups. Funding Funding for the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN) is provided by grants from the NIDDK.
Authors
Nazema Y. Siddiqui, MD, MHS
Anne P. Cameron, MD David Cella, PhD Catherine S. Bradley, MD, MSCE H. Henry Lai, MD Margaret E. Helmuth, MA Jonathan Wiseman, MS James W. Griffith, PhD Cindy L. Amundsen, MD Kimberly Kenton, MD, MS J. Quentin Clemens, MD, FACS, MSCI Karl J. Kreder, MD, MBA Robert M. Merion, MD, FACS Ziya Kirkali, MD John W. Kusek PhD, for the LURN |
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MP82-06 |
Detrusor underactivity in an obese-prone rat model |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP82-06 Sources of Funding: 4K12DK100024-04 Introduction Detrusor underactivity (DUA) is an understudied health concern that affects up to 45% of men and women in secondary care. The clinical management of DUA is inadequate and fails to improve the quality of life of these patients. The limited availability of animal models that exhibit the integrated pathophysiology of DUA impedes the development of new therapeutic approaches. The current studies characterized the bladder function of an obesity model of DUA to increase our understanding of the initiation and progression of urinary retention. Methods Animals: Eight-week old female obese-prone (OP) and obese-resistant (OR) rats purchased from Charles River (Boston, MA) were housed two per cage and maintained in standard laboratory conditions with food and water available ad libitum. Experimental procedures were approved by the Duke University IACUC and experimentation was conducted in accordance with the NIH Guide for the Care and Use of Laboratory Animals (8th ed.)._x000D_ High-fat feeding and glucose measurements: OP and OR rats were fed a 45% fat diet (D12451, Research Diets, Inc.) from 9-21 weeks and a 60% fat diet (D12492, Research Diets, Inc.) from 21-24 weeks. Whole blood was collected from the tail vein for glucose analysis at 8 and 24 weeks._x000D_ Surgical preparation and instrumentation: At 24 weeks, OP and OR rats were anesthetized with urethane (1.2 g/kg s.c. and supplemented as needed). The bladder was exposed through a midline abdominal incision and a flared PE-60 catheter was inserted into the bladder dome. The catheter was secured and connected via a 3-way stopcock to a pressure transducer and infusion pump. A paddle with platinum iridium contacts was placed between the pubic symphysis and the EUS to record EMG signals. Pressure and EMG signals were amplified, filtered, and sampled on a PowerLab acquisition unit with LabChart 7 Pro._x000D_ Results OP rats weighed significantly more than OR rats (450 ± 11.1 vs. 270 ± 6.7 g, respectively; p ≤ 0.001); however, blood glucose was not altered between OP (169.1 ± 7.11 mg/dl) or OR (176.5 ± 6.09 mg/dl; p ≥ 0.05) rats. Compared to OR rats, OP rats have significantly increased volume threshold (0.7574 ± 0.07 vs. 0.529 ± 0.04 ml; p ≤ 0.05), decreased maximum micturition pressure (16.62 ± 1.2 vs. 23.94 ± 1.1 cmH2O; p ≤ 0.001), and decreased voiding efficiency (8.743 ± 2.58 vs. 42.19 ± 6.5 %; p ≤ 0.001). Conclusions OP rats exhibit DUA and decreased voiding efficiency. This animal model may be used to understand the pathophysiology underlying DUA and enable the development of novel therapeutic approaches to recover efficient voiding. Funding 4K12DK100024-04
Authors
Eric Gonzalez
Warren Grill |
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MP82-07 |
Urothelial genes modulating micturition behavior induced by a repetitive lipopolysaccharide (LPS) exposure in an ovariectomized (OVX) mouse model |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP82-07 Sources of Funding: SUFU OAB Grant Introduction Menopause increases risk of persistent UTI which manifests with chronic lower urinary tract symptoms (LUTS). While treatment focuses on eradicating pathogens (e.g. antibiotics), we lack an understanding of host responses which can lead to bladder functional changes, including refractory LUTS. In this study, we sought to measure host responses, including voiding behavior, urothelial gene expression, and bladder morphology. We identified urothelial genes influenced by OVX that regulated voiding behavior after repetitive LPS intravesical exposure. Methods Female C57BL6 mice underwent sham (n=10) or OVX (n=10) surgery. Micturition behavior was measured using voiding spot assay (VSA) performed pre-surgery, 4 weeks post-surgery (but prior to LPS exposure) and after each of three consecutive days of intravesical inoculation of LPS. At end of experiment, animals were euthanized and bladders harvested for Gomori trichome staining. A separate experiment, following same LPS exposure protocol, was performed in 18 mice (sham=9, OVX =9) for microarray analysis of urothelial gene expression (pure urothelial sheet dissections) before LPS, 1d and 3d after LPS exposure, using Affymetrix gene chip for entire mouse transcriptome. Results In Fig 1, OVX and sham animals exhibited overactive voiding behavior on day 1 (Fig 1). However, voiding behaviors diverged on days 2 and 3 of LPS treatment with the OVX mice persisting with an overactive voiding phenotype. Gomori trichome staining showed that OVX mice had flattened rugae which was not seen in sham mice. Analysis of microarray data focused on pattern of gene expression changes (cutoff >+10x or <-10x) that mimicked voiding pattern changes for both sham and OVX animals. Six genes (protein) were identified using this focused approach: Nr4a3 (nuclear receptor 4a3), Nr4a1 (nerve growth factor IB), Areg (amphoregulin), Egr1 (early growth response 1), Krt23 (keratin type 1 cytoskeletal 23), and Gm30571 (unknown protein) (Fig 2A, 2B). Conclusions Focused microarray analysis revealed 6 urothelial gene expression changes that paralleled voiding changes. These genes involve inflammation, epithelial growth/repair and cytokines. Treating LUTS secondary to inflammation/UTI might target these host response urothelial genes. Funding SUFU OAB Grant
Authors
Marian Acevedo-Alvarez
Judy Yeh Lery Alvarez-Lugo Ming Lu Nitin Sukumar Warren Hill Toby Chai |
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MP82-08 |
The potential of 2 microRNA clusters in elucidation of biological functions of signalling pathways regulated by microRNAs in underactive bladder |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP82-08 Sources of Funding: SNSF Grant 320030_156161/1, Velux Foundation Grant 895 _x000D_ _x000D_ Introduction MicroRNAs regulate diverse biological processes. Previously we identified miRNA-regulated pathways in bladder outlet obstruction (BOO)-induced bladder dysfunction. MiRNAs in a cluster reside in genomic proximity (<10 kb) and their expression might be mediated by common transcription factors. Here we probed functional associations of BOO phenotype-specific miRNAs and identified several co-expressed miRNA sub-networks. Methods MiRNA sequences and genomic coordinates were extracted from miRBase version 21. Large scale chromosomal mapping of human miRNA structural clusters was done using MIReStruC-1.0 package. Next-generation sequencing datasets of patients&[prime] biopsies with urodynamically established BOO with and without detrusor overactivity (DO and BO groups, respectively) or with detrusor underactivity (UA group) were used to perform miRNA-mRNA integrated analysis and target pairing. Sequences were aligned with MAFFT version 7 and Clustal X 2.1 and manually refined with RALEE-RNA version 0.8. Results In DO group hsa-miR-376c-3p/hsa-miR-409-3p cluster was identified on chromosome 14. In BO group hsa-miR-889-3p/hsa-miR-410-3p/hsa-miR-409-3p cluster was detected on chromosome 14. Three miRNA clusters were detected in UA group: hsa-miR-25-3p/hsa-miR-106b-3p cluster on chromosome 7, and 2 clusters on chromosome 1: hsa-miR-199a-3p/hsa-miR-3120-3p cluster and hsa-miR-429/hsa-miR-200b-3p cluster belonging to miR-200bc/429/548a family. Integrated miRNA-mRNA expression profiling revealed no significant target overlap, and 90% of targets of up-regulated miRNA clusters were also up-regulated. No major contribution of the miRNA clusters to the biological functions of miRNA-regulated pathways was detected in DO and BO groups. In UA group 2 down-regulated hsa-miR-199a-3p/hsa-miR-3120-3p and hsa-miR-429/hsa-miR-200b-3p miRNA clusters were necessary and sufficient to determine the functions of all miRNA-regulated pathways and their targets constituted the majority of miRNA-regulated pathway elements. Conclusions Multiple co-expressed miRNAs may cooperatively influence biological processes and the acontractile urodynamic phenotype in the underactive bladder. Elucidating the down-regulation mechanisms of these miRNA clusters may help determine the &[raquo]point of no return&[laquo] for the loss of bladder function during BOO. Funding SNSF Grant 320030_156161/1, Velux Foundation Grant 895 _x000D_ _x000D_
Authors
Ali Hashemi Gheinani
Fiona C. Burkhard Katia Monastyrskaya |
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MP82-09 |
ENHANCEMENT OF SNEEZE-INDUCED URETHRAL CONTINENCE REFLEX VIA SEROTONIN TYPE 7 RECEPTORS IN RATS |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP82-09 Sources of Funding: NIH R01DK107450_x000D_ Introduction The spinal serotonin (5HT) system is well known to be involved in the control of lower urinary tract function, and we previously reported that 5HT receptors such as 5HT1A or 5HT2C, have respectively inhibit or enhance the urethral continence reflex during sneezing in rats. However, because there are multiple 5HT receptor subtypes, it is often difficult to determine the subtype-specific mechanism. Thus, we examined the role of 5HT7 receptors in the urethral continence mechanism using a rat model of stress urinary incontinence (SUI), in which endogenous 5HT was depleted by p-chlorophenylalanine (PCPA). Methods Female Sprague-Dawley rats were used. PCPA (200 mg/kg/day) was administered intraperitoneally for two days. Thereafter, using a microtransducer-tipped catheter inserted to the mid-urethra, we assessed urethral baseline pressure (UBP), amplitudes of urethral responses during sneezing (AURS) and abdominal pressure during sneezing (Pabd) under urethane anesthesia before and after administration of following drugs. First, we investigated the effects of a 5HT7 and partial 5HT1A agonist (LP 44 = LP, 0.3mg/kg, iv) in PCPA-administered rats. To suppress the partial 5HT1A effect of LP, a 5HT1A antagonist (WAY 100635 = WAY, 0.1 mg/kg, iv) was administered before LP treatment. Secondly, we investigated whether the effects of LP in the presence of WAY were inhibited by a 5HT7 antagonist (SB 269970 = SB, 0.1 mg/kg, iv), which was administered with WAY prior to LP administration. All data are shown in cmH2O. Results After LP administration (n = 6), UBP and AURS were significantly increased compared to the PCPA + WAY (n = 4) or PCPA only group (n = 7) (UBP: 15.2 vs 16.8 vs 26.6, AURS: 30.0 vs 32.2 vs 50.5 [PCPA only vs PCPA + WAY vs PCPA + WAY + LP], respectively) (Figure). However, in the presence of the SB, UBP and AURS were not significantly increased after LP administration (n = 6) compared to the PCPA + WAY (n = 6) or PCPA only group (n = 6). Pabd had no statistical difference among groups. Conclusions The 5HT7 receptor exerts the facilitatory effects on the urethral baseline activity and the urethral continence reflex during stress conditions such as sneezing, which are reportedly attributable to contractions of smooth and striated urethral sphincter muscles, respectively. Thus, 5HT7 agonists could be effective for the treatment of SUI. Funding NIH R01DK107450_x000D_
Authors
Takahisa Suzuki
Takahiro Shimizu Joombeom Kwon Eiichiro Takaoka Shun Takai Nobutaka Shimizu Naoki Wada Seiichiro Ozono Naoki Yoshimura |
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MP82-10 |
Characterization of the “one-pad patient” at long-term follow-up after radical prostatectomy |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP82-10 Sources of Funding: none Introduction Various definitions of continence after radical prostatectomy for prostate cancer exist. Most authors consider patients who use one pad for security as continent. Others argue, only patients without any pads should considered continent. We sought to evaluate functional outcomes and health-related quality of life (HRQOL) in the &[Prime]one-pad patient&[Prime] at long-term follow-up after open retropubic radical prostatectomy (ORRP) in contrast to those patients without pads or ≥2 pads. Methods Patients who underwent ORRP between 2003 and 2010 were followed with standardized questionnaires five years after surgery. The International Consultation on Incontinence Questionnaire (ICIQ), International Prostate Symptom Score (IPSS), European Organization for Research and Treatment of cancer (EORTC) QLQ-C30, EORTC PR-25, and an institutional questionnaire were applied. Patient groups were compared using descriptive, uni- and multivariable analyses to assess impact of pad consumption on functional outcomes and HRQOL. Results A follow-up was available for 60% (1895/3173) patients. Median follow-up was 60 months (IQR 60, 61). Overall, 69% (1303/1895), 9.6% (182/1895), and 18% (349/1895) used 0, 1, or ≥2 pads. Table 1 shows clinical, functional, and HRQOL results of the study population. The majority (46% [84/183]) of patients using one pad considered themselves as continent. Total IPSS score was significantly different between those patients using 0, 1, or ≥2 pads (p<0.001). Mean ICIQ score was significantly different between those patients using 0, 1, or ≥2 pads (p<0.001). Of all, 2.3% (4/171) of the patients using one pad achieved total continence in the ICIQ, whereas 51% (81/171) of these patients had severe incontinence according to the ICIQ. The global health score and the social function score of the EORTC QLQ-C30 did not differ clinically significant between those patients using no or one pad (73.9±19.9 vs. 69.9±18.1 and 82.2±24.6 vs. 78.1±25.5, respectively). Clinically meaningful differences were observed in the prostate-specific module of the EORTC questionnaire. Concerning urinary function no pad patients showed clinically meaningfully differences compared to those using no pad (24.7±15.1 vs. 19.7±15.8; p<0.001). Additionally, a large clinically meaningfully difference was observed considering bother induced by use of an incontinence device. Those patients with no pads vs. those with one pad had significantly lower bother induced by use of an incontinence device (12.9±25.4 vs. 28.8±27.9; p<0.001). Conclusions Our results indicate, at long-term follow-up, &[Prime]one-pad patients&[Prime] cannot be considered as continent. Patient&[prime]s self-estimation, functional, and HRQOL questionnaire-based outcomes indicate these patients are incontinent. Consequently, only patients using no pads should be considered continent. Funding none
Authors
Björn Löppenberg
Guido Müller Peter Bach Christian von Bodman Marko Brock Florian Roghmann Joachim Noldus Jüri Palisaar |
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MP82-11 |
The molecular biologic study about the circadian rhythmic control of micturition function |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP82-11 Sources of Funding: none Introduction We investigate the relationship between circadian rhythm and water metabolism and expression of circadian clock gene in peripheral bladder and central micturition centers. Methods Normal mouse (C57BL/6J male; WT) and circadian gene knock-out mouse (per1-/-per2-/-; PDK) was used. Water intake and urine output according to the circadian rhythm was checked using metabolic cage in 12:12 LD photoperiodic cycle (LD cycle) and constant dark cycle (DD cycle) in both WT and PDK. Circadian clock gene expression rhythm in bladder was evaluated with the activation of Per2 promotor. Circadian expression of representative clock gene was analysed; Bmal1 and Rev-erb? and rhythmic expression of circadian clock gene was analysed according to time in three main functional tissue related with micturition (detrusor smooth muscle, sphincter smooth muscle and urothelium) in both WT and PDK. Expression of clock gene in central micturition center was analysed; lumbar spinal cord, pontine micturition center (PMC) and ventrolateral periaqueductal gray (vlPAG), real-time RT-PCR was used in every 3 hours for 24 hours in DD cycle in both WT and PDK. Results Water intake and urine output was increased in night-time of WT in LD and DD cycle. However this tendency was disappeared to PDK. Water intake and urine output was increased in night-time of WT in LD cycle and DD cycle was disappeared in PDK and this means that circadian rhythm is due to endogenous circadian rhythm not outside environment. We can observe the activation of Per2 promotor approximately 24 hours of rhythm. And this finding represents that bladder peripheral clock was well functioned. In case of WT, characteristic circadian expression pattern of clock gene in all three tissues. On the contrary, 24 hours of promoter activated rhythm was not observed in PDK. In spinal level, unlike PDK, clock gene expression rhythm was observed in WT. But, there was no definite rhythmicity of circadian expression pattern of clock gene in the upper region of central micturition center like PMC and vlPAG. Conclusions Endogenous circadian rhythm in water intake and urine output is exist approximately 24 hours. Bladder peripheral clock gene is existed in main functional tissue related with micturition. But in terms of central micturition center, we can find circadian clock gene expression only in lumbar spinal cord. Further study about the reason why absence of circadian clock in upper central micturition center and finding other circadian control mechanism in upper micturition center is needed. Funding none
Authors
Su Jin Kim
Young Sam Cho Khae Hawn Kim |
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MP82-12 |
The effect of GsMTx4, an inhibitor of stretch-activated channels, on nocturia in mice. |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP82-12 Sources of Funding: none Introduction GsMTx4, an inhibitor of stretch-activated-channels (SACs), showed dose-dependent effect. At EAU2014, we reported that the intraperitoneal administration (i.p) of GsMTx4 1.35mg/kg could reduce voiding frequency (VF) and increase urine volume/voiding (Uvol/v) in mice. Furthermore, we reported at ICS2016 that Clock mutant mouse showed a phenotype of nocturia (NOC) because of the loss of circadian sensation of bladder fullness, which regulated by clock genes. In order to assess the effect of GsMTx4 on NOC, and the differences of these effects according to circadian rhythm of urine sensation, we measured voiding behavior pre and post i.p of GsMTx4 in different time between wild type mice and Clock mutant mice. _x000D_ Methods Male C57BL/6 mice (WT) and C57BL/6 Clock mutant mice (mutant) were bred under 12 h light/dark cycles for 2 week. The light period (sleep phase in mice) started from 6 a.m. [zeitgeber time (ZT) 0]. GsMTx4 0.75 mg/kg diluted with normal saline (NS) 100 ul was administrated by i.p at the peak and nadir of gene expression time of SACs, which consistent with the beginning of active phase (ZT12) and the beginning of sleep phase (ZT0), respectively. In control of each genotype, NS 100 ul was administrated. The changes of following parameters were measured using metabolic cage: VF, urine volume (UV) and Uvol/v. In ZT12 i.p group, during 12hrs voiding behavior in active phase of pre and post i.p, In ZT0 i.p group, during 12hrs voiding behavior in sleep phase of pre and post i.p, were compared between WT and mutant mice. Data were analysed using Wilcoxon signed-rank test and Mann-Whitney u-test. Results UV didn't show differences between WT and mutant mice. In WT, VF after ZT0 i.p (during sleep phase) was significantly decreased. In contrast, mutant showed significant decreasing in VF both ZT0 and ZT12 i.p (Fig. 1). Uvol/v was not increased both ZT0 and ZT12 i.p in WT mice. In contrast, Uvol/v was significantly increased both ZT0 and ZT12 i.p in mutant mice. Conclusions In WT, the lower VF and higher Uvol/v after GsMTx4 1.35 mg/kg i.p was not observed in 0.75mg/kg i.p. These effects seemed to be change with time-dependently, namely to be enhanced during sleep phase in WT when the SACs expression level were lower. In contrast, mutant showed significant effect on the voiding suppression both ZT0 and ZT12 i.p. These results suggested that GsMTx4 may show the improving effect on NOC with the lower dose if appreciate administration time were selected, and be useful for the treatment of NOC caused by the disruption of circadian rhythm in sensation of bladder fullness. Funding none
Authors
Tatsuya Ihara
Takahiko Mitsui Yuki Nakamura Yuki Imai Satoru Kira Hirishi Nakagomi Norifumi Sawada Atushiko Nakao Masayuki Takeda |
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MP82-13 |
Bladder distension regulates Pannexin 1 expression in the bladder urothelium |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP82-13 Sources of Funding: Einstein-Montefiore FPMRS Fellowship Program Introduction Pannexin 1 (Panx1) channels play essential roles in urothelial mechanotransduction and signaling by providing a mechanosensitive conduit for ATP release in response to bladder distension. It has been proposed that urothelial ATP signaling to bladder sensory fibers relays the degree of bladder fullness and modulates detrusor activity, which are essential for proper micturition. Panx1 channels have been implicated in neurogenic bladder and bladder overactivity. However, little is known about the mechanisms that regulate Panx1 in the bladder. Our goal was to investigate the extent to which mechanical stimulation and bladder overdistension, as occurs with polyuria in diabetes, regulates Panx1 expression and function. Methods Studies were performed with a) mouse urothelial cell cultures and b) 10 week old C57BL/6 mice treated for 2 and 4 weeks with 5% sucrose in the drinking water (diuresis mouse model), and non-treated age-match control mice. Urothelial cells cultured on custom made stretchable silicone culture chambers were submitted to uniaxial stretch for 0, 2 and 5 hours (30 sec cycle duration; maximum strain ~10%) and then immediately harvested and processed for quantification of Panx1 mRNA by real-time quantitative PCR (qPCR). Voided urine samples from sucrose-fed and control mice were collected for quantification of ATP levels using the luciferin-luciferase assay. Bladders were then isolated, the urothelium dissected and processed for qPCR analysis of Panx1 mRNA levels. Results Prolonged cyclic mechanical stimulation (5hrs) resulted in significant reduction of Panx1 expression in urothelial cells when compared to non-stimulated cells or to shorter (2hrs) stimulation (5 hrs: 0.66 ± 0.07*; 2 hrs: 1.02 ± 0.05; 0 hrs: 1.01 ± 0.05; mRNA norm. to mean 0 hrs levels; N = 6, *P<0.01). Panx1 expression in the bladder urothelium of mice after 2 and 4 weeks of sucrose-induced diuresis was significantly lower than in control mice (2 wks: 0.88 ± 0.05*; 4 wks: 0.74 ± 0.07*; Ctrl: 1.00 ± 0.03; mRNA norm. to mean Ctrl value; N = 4, *P<0.01). Urine ATP levels (nM) in 2 and 4 weeks diuresis mice were also significantly lower when compared to those in control mice (2 wks: 7.1 ± 0.6*; 4 wks: 6.3 ± 0.5*; Ctrl: 38.7 ± 1.8; N = 4, *P<0.0001), consistent with observed Panx1 downregulation. Conclusions Prolonged mechanical loading and overdistension reduce urothelial Panx1 expression and ATP release. This impairs proper urothelial ATP signaling and bladder mechanosensory activation, and may thereby contribute to development of detrusor underactivity. Funding Einstein-Montefiore FPMRS Fellowship Program
Authors
Melissa Laudano
Marcia Urban-Maldonado Hui Sun Mia Thi Sylvia Suadicani |
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MP82-14 |
Detection of Rac activity and inhibition of smooth muscle contraction by the Rac inhibitor EHT1864 in the human trigone: implications for Rac GTPase in bladder smooth muscle contraction |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP82-14 Sources of Funding: Deutsche Forschungsgemeinschaft (DFG), Chinese Scholarship Council (CSC) Introduction Monomeric GTPases (e. g. RhoA, Rac) are critical mediators of smooth muscle contraction in the lower urinary tract, which is involved in pathophysiology and therapy of lower urinary tract symptoms (LUTS). Rac has been recently identified as a novel intracellular mediator of prostate smooth muscle contraction. A similar role in the bladder appears now possible. Here, we addressed Rac function in the human trigone. Methods Bladder tissues (trigone, dome, wall, mucosa) were obtained from patients undergoing radical cystectomy. Rac isoforms were detected by RT-PCR, Western blot, and immunofluorescence staining. Active Rac1 was detected by pull down assays using a GST/PBD-PAK (glutathione S-transferase/p21 binding domain of p21-activated kinase) fusion protein, immobilized to glutathione-covered agarose beads. Contractility of trigone tissues was examined in an organ bath. Results By RT-PCR, mRNA for Rac1, Rac2 and Rac3 was detectable in trigone tissues (n=5 patients), bladder dome (n=4 patients), and bladder wall (n=2 patients). Western blot analysis for Rac1 revealed bands with expected sizes (ca. 21 kDa), and suggested protein expression in trigone, bladder dome, bladder wall, and mucosa, while Rac2 may lack in the mucosa, and Rac3 may lack in the detrusor. Active Rac1 was detectable in trigone and detrusor tissues by pull down of guanosine triphosphate-loaded Rac1 (GTP-Rac). In the organ bath, the muscarinic agonist carbachol (100 nM-1 mM) induced concentration-dependent contractions of trigone tissues, which were reduced by the Rac inhibitor EHT1864 (30 µM). This inhibition was observed in all included samples (n=5 patients), despite high variations in magnitude of trigone contractions. Reduced contractility after Rac inhibition was reflected by decreased Emax value after curve fitting (111 ±17 % of KCl in the control group; 76 ±16 % of KCl after EHT1864). EHT1864 did not change EC50 values for carbachol, pointing to non-competitive inhibition of carbachol contractions. Conclusions Rac GTPases are active in the human trigone and detrusor. Smooth muscle contraction in the human trigone can be inhibited by the Rac inhibitor EHT1864. Rac-mediated trigone contractions may be involved in bladder outlet obstruction, in parallel to prostate-dependent mechanisms. Rac function in the bladder, including detrusor and overactive bladder merits further consideration. Funding Deutsche Forschungsgemeinschaft (DFG), Chinese Scholarship Council (CSC)
Authors
Yiming Wang
Christian Gratzke Qingfeng Yu Frank Strittmatter Annika Herlemann Beata Rutz Christian G. Stief Martin Hennenberg |
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MP82-15 |
The ameliorative potential of tamsulosin on bladder function in a rat model of chronic pelvic ischemia |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP82-15 Sources of Funding: None. Introduction The exact etiology of LUTS in human is still poorly understood. Alpha1-blockers are widely used in the treatment of LUTS associated with BPH. Tamsulosin has been reported to possess a potential of increasing blood flow in bladder microcirculation. Using a characterized rat model of chronic pelvic ischemia, we have studied the ameliorating potential of tamsulosin on the changes in bladder function caused by chronic ischemia. Methods Chronic pelvic ischemia (CPI) was induced by causing bilateral endothelial injury of both iliac arteries and feeding a 2% cholesterol diet. A total of 60 male Sprague Dawley rats (18 weeks old) were divided into three groups: Control, CPI, and CPI-tamsulosin. The Control group received a regular diet and the CPI-tamsulosin group received tamsulosin (10 mg/kg/day) for 8 weeks. Eight weeks after surgery, half of the rats in the Control, CPI and CPI-tamsulosin groups were examined by cystometry and sacrificed for organ bath study. The other half of the rats from each group was examined 16 weeks after surgery (the CPI-tamsulosin group were continued treatment in the latter half of 8 weeks). Results The iliac arteries from the AI showed neo-intimal proliferation and vascular occlusion. This was not prevented by tamsulosin treatment. After 8 weeks, there was no difference between CPI and CPI-tamsulosin groups in micturition interval (MI), bladder capacity (Bcap), and voiding volume (VV). Those parameters in both groups were significantly less than in the Control group (P<0.05). After 16 weeks, those parameters were improved in CPI-tamsulosin group without changing other parameters. Conclusions Tamsulosin treatment improved voiding function in rats with established chronic pelvic ischemia. The translational impact of this finding would be worth further study for improving the bladder function. Funding None.
Authors
Norifumi Sawada
Satoru Kira Tatsuya Ihara Takanori Mochizuki Yuki Imai Hiroshi Nakagomi Takahiko Mitsui Karl-Erik Andersson Masayuki Takeda |
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MP82-16 |
Bladder smooth muscle contractility is inhibited by HC030031 independently of TRPA1 |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP82-16 Sources of Funding: none Introduction TRPA1, a member of the Transient Receptor Potential (TRP) ion channel superfamily, is expressed in sensory afferents innervating the bladder, and activation of this channel induces urinary frequency in mice and rats. To investigate the role of TRPA1 in bladder physiology, researchers have often used HC030031 as a selective TRPA1 antagonist. In organ bath studies, concentrations between 1 and 100 μM are typically used. Preliminary data from our lab indicated inhibition of detrusor contractility with HC03031 (100 μM) in TRPA1 knock out mice. _x000D_ Our aim is to evaluate if HC030031 (100 μM) inhibits detrusor contractility in a TRPA1-independent manner. Methods The effect of HC030031 on detrusor contractility was examined in an organ bath study in wild type (WT) and TRPA1 knock-out (KO) C57Bl/6 mice. Contractile forces to cold (10°C), KCl (120 mM), carbachol (10 μM) and electrical field stimulation (EFS: 50V, 20Hz, 0,5ms, 10s) were recorded before, and after addition of HC030031 (100 μM), and following wash out. Contractile responses are reported as percentage of the first stimulus with the respective agonist. Statistical analyses were performed using Mann-Whitney U test and Kruskal-Wallis test. Results In WT animals, HC030031 (100 μM) partially inhibited all tested agonist-induced detrusor contractions. We observed a 46 ± 5 % reduction of the contractile response to KCl, a 45 ± 4 % reduction to carbachol and a 32 ± 6 % reduction to EFS. Importantly, similar blocking potency was observed in TRPA1 KO-animals, where HC030031 (100 μM) inhibited the contractile response to KCl by 59 ± 5 % and to carbachol by 61 ± 4 %. Conclusions HC030031 (100 μM) inhibits detrusor contractility independent of TRPA1. Further research is necessary to investigate the target of HC030031. Funding none
Authors
Karel Dewulf
Jan Franken Pieter Uvin Yves Deruyver Wouter Everaerts Dirk De Ridder Thomas Voets |
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MP82-17 |
A neuro-modulative sling improves mixed urinary incontinence in an acute animal model |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP82-17 Sources of Funding: NSF China 81670695; China America Promotion Society for Medical Doctors (CAPs MD) Introduction Clinically, mid-urethral sling procedure has become a regular and popular treatment for stress urinary incontinence (SUI). However, it has limited improvement if intrinsic sphincter deficiency dominantly and/or co-existing serious urgency symptom. We applied a new neuro-modulative sling in an acute urinary incontinence rat model to test if it can improve the urinary incontinence and urinary urgency simultaneously. Methods The neuro-modulative sling made by sling mesh along with small silver wire electrodes which were connected to electrical stimulator with the free ends in the middle of sling for electrical stimulation. An acute mixed urinary incontinence animal model was made by bilaterally pudendual nerve transaction (PNT, n=21) or sham PNT (n=20) followed by potassium chloride (4M, KCl) or saline (control, 0.9% NaCl) bladder perfusion. Urodynamic testing performed to confirm the changing of the bladder contractions. Leak point pressure (LPP) was also tested during filling cytometry. Results With current above 10mA and frequency above 50Hz result in significantly increased LPP during electrical stimulation delivering to the neuro-modulative sling (p<0.05). The continuous electrical stimulation with bi-polar square wave at the parameters of frequency to 5 Hz and pulse duration to 150 ?s may decrease the increased bladder contractions significantly after PNT and KCl perfusion (p<0.01)._x000D_ Conclusions The study demonstrated the neuro-modulative sling with different electrical stimulation parameters may improve mixed urinary incontinence in an acute animal model. Our future direction is studying its effects on a long-term animal model and possible complications if long-term implantation and use. Funding NSF China 81670695; China America Promotion Society for Medical Doctors (CAPs MD)
Authors
Ling Qing
Xiang-xiang Ye Qi Ling Qi-Xiang Song Limin Liao Hai-Yan Li |
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MP82-18 |
SHARED ALTERATIONS IN URINARY BACTERIAL COMMUNITIES IN PATIENTS WITH INTERSTITIAL CYSTITIS AND OVERACTIVE BLADDER |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP82-18 Sources of Funding: Funded by a Urology Care Foundation Grant (ALA) and the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Network (1U01DK103260; JK, JCN, GSE, MRF, JTA) Introduction Despite historical assumptions that urine is sterile, accumulating research demonstrates that adult women have diverse bacterial ecosystems resident in the urine. Changes in these communities are associated with benign lower urinary tract conditions, such as overactive bladder (OAB) and interstitial cystitis/painful bladder syndrome (IC/PBS). As there is significant symptomatic overlap between these two conditions, we sought to characterize changes in the urinary microbiome in a spectrum of patients with these bladder hypersensitivity syndromes to clarify potential shared pathophysiologic mechanisms. Methods We used high-throughput 16S rRNA gene sequencing using an Illumina MiSeq next generation sequencing platform to identify bacterial DNA isolated from catheterized urine specimens obtained from asymptomatic controls (n=14) and subjects with IC/PBS (n=13) or OAB (n=17). After classifying bacterial taxa via alignment to multiple bacterial 16S sequence databases, urinary communities were compared at a population level between experimental groups. Results Women with OAB or IC/PBS demonstrated decreased bacterial diversity at the genus level in comparison to controls, but this difference was more profound in IC/PBS (Figure). Several unique genera were altered in these conditions in comparison to controls. Changes in the levels of Burkholderia, a genus recently identified in association with chronic pelvic pain in males (Nickel et al., 2015), were associated with disease in our population, with a stronger association with OAB than IC/PBS. In addition, alterations in Lactobacillus species were also prevalent in both conditions, but more pronounced in patients with IC/PBS. Conclusions Bacterial communities resident within the lower urinary tract are altered in the presence of lower urinary tract symptoms. The microbiomes of urine from patients with OAB and IC/PBS, however, were similar when analyzed in parallel, varying more with symptom severity than with diagnosis. Regardless of diagnosis, greater symptom severity inversely correlated with bacterial diversity. These results support recent propositions that OAB and IC/PBS may represent points on a spectrum of disease sharing a similar pathophysiology. Funding Funded by a Urology Care Foundation Grant (ALA) and the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Network (1U01DK103260; JK, JCN, GSE, MRF, JTA)
Authors
A. Lenore Ackerman
Jie Tang Karyn Eilber Jayoung Kim J. Curtis Nickel Garth Ehrlich James Ackerman David Underhill Michael Freeman Jennifer Anger MAPP Research Network |
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MP82-19 |
Validation of TNF-? as the top upstream regulator of bladder remodeling during outlet obstruction-induced lower urinary tract dysfunction |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP82-19 Sources of Funding: SNSF Grant 320020_156161/1_x000D_ Velux Foundation Grant 895 Introduction Bladder outlet obstruction (BOO) induces organ remodeling accompanied by changes in bladder function leading to lower urinary tract dysfunction (LUTD). MicroRNAs (miRNAs) may cause molecular changes in the bladder wall. Previously, using next generation sequencing (NGS) of mRNAs and miRNAs in human patients&[prime] biopsies we identified TNF-α as the top upstream regulator of signaling, potentially contributing to organ remodeling. Here we validated the NGS and pathway analysis in cell-based models using bladder smooth muscle (SM) and urothelial (UE) cells exposed to TNF-α. Methods TNF-α-responsive genes were selected based on LUTD patients&[prime] NGS data and in silico analysis. SMC and UE cells were treated with 10 ng/ml TNF-α and RNA isolated. Regulation of TNF-α-induced genes was studied by qRT-PCR and comprehensive transcriptome analysis performed by NGS. NanoString nCounter miRNA assays were used to profile miRNAs, and results validated by qRT-PCR. Cell proliferation assay was performed to evaluate the proliferative effects of TNF-α. Results Primary SM and UE cells express TNF-α receptors TNFR1 and TNFR2 and respond to TNF-α treatment. NFKB2, RelB and TNFAIP3 showed a progressive time- and concentration-dependent up-regulation, and responses were stronger in SM cells compared to UE. TNF-α treatment increased cell proliferation. MiRNA expression profiling identified 17 miRNAs altered in both SMC and UE cells. MiRNAs miR-146a-5p, -21-5p, -1260a, -183-5p, -22-3p, -199a-3p, -199b-3p were similarly regulated in patients and cell-based models. MiR-26b was significantly induced in UE and SMC, but down-regulated in BOO. There was a cell-type dependent difference in miRNA profiles, with SMC-specific miRNAs gown-regulated after TNF-α treatment, in accordance with the down-regulation of SM markers and loss of contractility in human patients. Transcriptome analysis of TNF-treated cells was carried out and expression levels of predicted targets of disease-relevant miRNAs identified. Conclusions Our results confirm an important role of TNF-α in the regulation of BOO-specific miRNAs, and identify miRNAs linking TNF-α signaling and fibrosis. Modulation of expression levels of TNF-α-regulated miRNAs in cell-based models of human bladder using miRNA-overexpression and inhibition will elucidate their role in organ remodeling and lead to novel therapeutic approaches for BOO-induced LUTD. Funding SNSF Grant 320020_156161/1_x000D_ Velux Foundation Grant 895
Authors
Ivonne Köck
Ali Hashemi Gheinani Fiona C. Burkhard Monastyrskaya Katia |
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MP82-20 |
ATP related to VNUT maintains the normal bladder storage function |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP82-20 Sources of Funding: none Introduction ATP is an important substance in bladder function. Vesicular Nucleotide Transporter (VNUT) involved in exocytosis of ATP strongly expressed in the bladder urothelium. VNUT Knock out (KO) mice show frequent urination without a change in voiding function. One of the causes is the reduction of bladder compliance which based on the difficulty of the bladder urothelium surface area expansion. However all mechanism is unclear, here we underwent organ bath studies._x000D_ Methods All experiments were performed by using 8-14 week old male C57BL/6 mice (WT) and VNUTKO mice backcrossed (for eight generations) on a C57BL/6 background. Bladder strips (with or without urothelium) were subjected to a resting tension of 1 g and allowed to stabilize for at least 30 min. Contractions were recorded as changes in tension from baseline in response to 60 mM KCl, carbachol, and electrical field stimulation (EFS). All tissue responses were normalized to gram tissue weight. Results The bladder without urothelium from VNUTKO mice showed a higher contractile response to 60 mM KCl compared with WT, but no change between bladders with urothelium. There was no difference in contractions by carbachol between WT and VNUTKO bladders with the presence of urothelium (Fig1). In the absence of urothelium, the responses to carbachol (Fig1) and EFS were higher in VNUTKO mice than WT mice. Conclusions The contraction of bladder smooth muscle in VNUTKO mice was strongly enhanced that may show the pathological state. Exocytotic ATP released from urothelium could maintain the normal bladder storage function. Funding none
Authors
Hiroshi Nakagomi
Tatsuya Miyamoto Tatsuya Ihara Satoru Kira Norifumi Sawada Takahiko Mitsui Schuichi Koizumi Masayuki Takeda |
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MP83-01 |
High-grade Prostate Cancer has increased mitochondrial content |
Prostate Cancer: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP83-01 Sources of Funding: Australian Prostate Cancer Research Centre New South Wales (APCRC-NSW to V.M.H.) with support to A.M.F.K., W.J. and A-M.H.; Chair support from the Petre Foundation and Sydney Medical School Foundation, Australia to V.M.H.; E.K.F.C. and D.C.P. are partially supported by the Movember Australia and the Prostate Cancer Foundation Australia (PCFA) Prostate Cancer Bone Metastasis (ProMis) Movember Revolutionary Team Award (MRTA) to the Garvan Institute of Medical Research (V.M.H. as a team lead). Introduction Prostate cancer is marked by clinical and pathological heterogeneity. Therefore, there is a critical need to identify biomarkers that predict clinical presentation and outcomes. While much attention has been given to the nuclear genome, less emphasis has been placed on the maternally inherited, circular mitochondrial genome. Alterations in mitochondrial DNA (mtDNA) copy number are common in many human cancers, distinguishing cancer from normal tissue. In contrast, preliminary studies in prostate cancer, have shown no relative difference in mtDNA copy number between matched tumor-normal prostate cells, suggesting a possible field effect. The aim of this study was to test if there is a difference in mtDNA copy number between prostate cancer patients, that could be used to differentiate disease stage and clinical outcome. Methods Fresh prostate cancer biopsies from 115 patients, with a median of 107 months clinical follow-up, were H&E stained and reviewed by pathologists for tumor grade and cellularity and marked for tumor excision. DNA was extracted from tumors and qPCR performed to establish relative mtDNA abundance. Multifocal biopsies were available and examined for seven of the patients. Results Multivariate linear models revealed a significant correlation of decreasing mtDNA copy number with estimated sample tumor cellularity (p = 0.049*) and increasing with tumor pathology ISUP score (p = 0.007**), but no correlation with disease relapse (p = 0.60) or age (p = 0.71). Data from single patient multifocal biopsies showed a similar mtDNA content (average of 1.68-fold difference, range 1.01-2.48), compared to between patient mtDNA content (upper and lower interquartile range 3.23-fold difference, total range 15.99-fold variation) Conclusions We report a positive correlation between mtDNA count and tumor pathology score. Lack of variation in mtDNA abundance between molecular lesions within the same patients adds to accumulating evidence of a field effect contributing to the multifocal presentation of over 70% of prostate cancers. An increase in mtDNA copy number may therefore provide an ideal predictive tool for pathological stage irrespective of tumor purity during prostate diagnostic biopsy. Funding Australian Prostate Cancer Research Centre New South Wales (APCRC-NSW to V.M.H.) with support to A.M.F.K., W.J. and A-M.H.; Chair support from the Petre Foundation and Sydney Medical School Foundation, Australia to V.M.H.; E.K.F.C. and D.C.P. are partially supported by the Movember Australia and the Prostate Cancer Foundation Australia (PCFA) Prostate Cancer Bone Metastasis (ProMis) Movember Revolutionary Team Award (MRTA) to the Garvan Institute of Medical Research (V.M.H. as a team lead).
Authors
Anton Kalsbeek
Eva Chan Judith Grogan Desiree Petersen Weerachai Jaratlerdsiri Ruta Gupta Ruth Lyons Anne-Maree Haynes Lisa Horvath James Kench Phillip Stricker Vanessa Hayes |
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MP83-02 |
Overcoming PI3K/mTOR inhibitor resistance by PIM1 inhibitor through regulation of tyrosine kinase expression. |
Prostate Cancer: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP83-02 Sources of Funding: This work was supported by JSPS KAKENHI Grant Number 15K20109 and 26861299. Introduction Recently we demonstrated that the activated PI3K-Akt-mTOR signaling pathway induced by androgen deprivation therapy or docetaxel explains at least in part the aggressiveness in CRPC. Inhibitors of PI3K-Akt-mTOR signaling pathway have potential as next generation anti-CRPC drug. However, there have been little reports that monotherapy with a PI3K-Akt-mTOR signaling inhibitor was effective to CRPC. PIM1 is a kinase which induces expression of receptor tyrosine kinases and it has been reported to contribute Akt inhibitor resistance in lymphoma. We investigated the anti-tumor effect of PIM1 inhibitor for CRPC. Methods Two cell lines were used: LNCaP, a androgen-dependent PCa cell line with PTEN deficiency; and C4-2AT6, a castration-resistant prostate cancer cell line with PTEN deficiency and elevated Akt signaling pathways. We investigated the therapeutic efficacy of PIM1 inhibitor; AZD1208 and PI3K/mTOR dual inhibitor; BEZ235. Results We compared the cytotoxic effect of docetaxel (DTX) on LNCaP and C4-2AT6 cells by cell viability assay. In LNCaP and C4-2AT6 cells, the relative cell viability treated with 1nM DTX was 68.8 % ± 0.1 % and 87.5% ± 1.9 %, respectively. These results indicated that C4-2AT6 cells showed significantly higher resistance to DTX than LNCaP cells. Next we examined the cytotoxic effect of BEZ235 on LNCaP and C4-2AT6 cells by cell viability assay. In LNCaP and C4-2AT6 cells, the relative cell viability treated with 10nM BEZ235 was 90.2% ± 0.7 % and 89.9% ± 2.3 %, respectively. Western blotting showed increased expression of PIM1 and EGFR in BEZ235 treated cells. These results indicated that PI3K/mTOR inhibitor induced EGFR expression through PIM1 up-regulation. We evaluated the cytotoxic effect of AZD1208 on LNCaP and C4-2AT6. The relative cell viability was 67.9 ± 1.0 % and 67.5 ± 3.1 % with 10µM AZD1208, respectively. AZD1208 significantly inhibited cell proliferation of LNCaP and C4-2AT6. In addition, we examined synergic effect of AZD1208 and DTX/BEZ235. The relative cell viability treated with 10µM AZD1208 and 1nM DTX was 63.8 ± 1.1 % and 48.0 ± 0.6 %. The relative cell viability treated with 10µM AZD1208 and BEZ235 was 55.9 ± 1.6 % and 46.9 ± 1.5 %. We found AZD1208 also had synergic effect with DTX and BEZ235 (Figure). Conclusions PIM1 inhibition can overcome the drug resistant mechanism induced by targeting PI3K/Akt/mTOR pathways in docetaxel resistant CRPC. Funding This work was supported by JSPS KAKENHI Grant Number 15K20109 and 26861299.
Authors
Takeo Kosaka
Hiroshi Hongo Yota Yasumizu Yasumasa Miyazaki Eiji Kikuchi Akira Miyajima Mototsugu Oya |
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MP83-03 |
Novel selective lysine specific demethylase 1 inhibitors effectively impair castration resistant prostate cancer growth |
Prostate Cancer: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP83-03 Sources of Funding: None. Introduction Lysine-specific demethylase 1 (LSD1), the first identified histone demethylase, is a novel target for prostate cancer therapy. Herein we examined the anticancer effects of NCL1 and NCD38, the selective inhibitors of LSD1 that were first discovered at our university. Methods Various tests using LNCaP (a hormone-sensitive prostate cancer cell line) and PCai1 (a castration-resistant prostate cancer [CRPC] cell line established in our institute) cells were used to confirm the anticancer effects of NCL1 and NCD38. Cell viability was assessed by performing a WST assay in the presence of NCL1, NCD38, or a standard vehicle (control). Chromatin immunoprecipitation (ChIP) and PCR were used to confirm the methylation status. For autophagy analysis, LNCaP and PCai1 cells were incubated with or without CQ in the presence or absence of NCL1. Subsequently, transmission electron microscopy (TEM), fluorescent immunocytochemistry, and WST assay were performed with the treated and non-treated cells. A combination index analysis was performed to assess the effects of NCL1 and CQ. Lastly, the effect on xenograft tumors in CRPC mice models was measured by subcutaneously injecting castrated nude mice with PCai1 cells. Mice were injected intraperitoneally with NCL1, NCD38, CQ, or the vehicle, and subsequent growth was recorded. Results WST assay revealed a reduction in the number of viable cells after NCL1 and NCD38 treatment. ChIP showed NCL1-induced H3K9me2 accumulation at the ELK4 and KLK2 promoters, whereas a dose-dependent induction of apoptosis by NCL1 was noted by flow cytometry. Autophagosomes were observed in LNCaP cells treated with NCL1. The expression level of LC3-II was significantly increased in cells treated with NCL1 and CQ. Furthermore, the combination of NCL1 and CQ significantly decreased cell growth in vitro, but had no synergistic effect in vivo. Xenograft tumor volume was reduced in the NCL1 and NCD38-treated mice when compared with the controls; no adverse effects were observed. Conclusions Castration resistant prostate cancer growth was effectively suppressed with NCL1 and NCD38 both in vitro and in vivo, without any adverse events, via regulation of apoptosis and autophagy; thus, indicating the potential use of LSD1 inhibitors as therapeutic agents for prostate cancer. Funding None.
Authors
TOSHIKI ETANI
Taku Naiki Takayoshi Suzuki Takashi Nagai Keitaro Iida Ryosuke Ando Noriyasu Kawai Keiichi Tozawa Tohru Mogami Takahiro Yasui |
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MP83-04 |
Suppression of human prostate cancer (CaP) by adoptive transfer of patient-derived PSMA-specific, TGF-ß-insensitive CD8+ T cells |
Prostate Cancer: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP83-04 Sources of Funding: 1.Walter S. and Lucienne Driskill Immunotherapy Research Program_x000D_ (320-5314000-30026197)_x000D_ 2.Matthews Center for regenerative medicine pilot grants 2014 _x000D_ 3.National Cancer Institute-SPORE in Prostate Cancer (P50 CA90386-01)_x000D_ 4. Developmental Therapeutics Program, FSM Division of Hematology Oncology Introduction It has previously been shown that tumor-derived TGF-β related potent immunosuppression and lack of tumor killing specificity promote CaP progression. Here we report a new immunotherapeutic approach using adoptive transfer of patient-derived PSMA-specific, TGF-β-insensitive human CD8+ T cells to inhibit solid xenograft CaP. Methods Peripheral blood CD8+ T cells were collected from metastatic castration resistant CaP patient by leukapheresis and cultured in the FDA approved Cell Processing Work Station (CPWS, Panasonic) with CD-3 Biotin/CD28/Anti-Biotin Beads (Bead: Cell 1:2) and IL-2 (100units/ml). We developed a TβRIIDN-TK-IRES-PZ1 chimeric T cell receptor retroviral construct using an anti-PSMA IgTCR(&[zeta]) gene (PZ1) and a dominant negative TGF-β type II receptor (TβRIIDN) that could induce CD8+ T cells to be PSMA reactive and insensitive to TGF-β. PC-3 cells (PSMA negative; ATCC) or PSMA positive PC-3-PSMA cells (Cleveland Clinic) were used for target cells. Subcutaneous injection of PC-3 and PC-3-PSMA cells (2x105 cells/each, infected with HSV1-tk-GFP-luciferase reporter) into the left and right flank region respectively in each of 48 immunodeficient RAG-1 mice was performed. One week later, the animals were randomly assigned to one of three adoptive transfer groups (16 mice /each group, 2x106 CD8+ T cells/each mice): Group 1: CD8+ T cells infected with TβRIIDN-TK-IRES-PZ1 (71.1% positive); Group 2: Naive CD8+ T cells; Group 3: No treatment group. Tumor growth was monitored by IVIS luciferase imaging. The animals were provided 2 weekly adoptive transfer treatments and sacrificed after 3 weeks. The size and the weight of the tumor were recorded, and the infiltration of CD8+ T cells and apoptosis was evaluated by immunofluorescence staining and TUNEL. Results In Group 1, the average tumor weight and volume was significantly lower in the PC3-PSMA tumor (0.413g and 514.2mm3) compared to the PC3 tumor (2.75 g and 3165.2 mm3); (~3-6×, P<0.05). There was no difference between the PC3 tumor (2.36g and 2768.5mm3 ) compared to PC3-PSMA tumor (2.45g and 2411.99 mm3) in Group 2 or Group 3. H&E staining showed large amount of nuclear fusion, fragmentation and necrosis were found in PC3-PSMA tumors in Group 1 compared to Group 2 and 3. In Group 1, tumor apoptosis (72.5/1,000 µm2) and CD8+ T cell infiltration (45.5/1,000 µm2 ) in PC3-PSMA tumor parenchyma was significantly higher compared to PC3 tumor (6.7/1,000 µm2 and 3.1/1,000 µm2 respectively). There was no significant apoptosis or CD8+ T cells infiltration observed in either PC3 and PC3-PSMA tumor in Group 2 and Group 3. Conclusions Our approach combines TGF-β insensitive with PSMA selectivity that significantly enhance the specificity and tumor killing ability of patient CD8+ T cells, and simultaneously suppress the tumor derived TGF-βinduced immunosuppression. Therefore, this construct may offer a novel therapeutic intervention for both primary CaP treatment as well as for recurrence after prostatectomy. Funding 1.Walter S. and Lucienne Driskill Immunotherapy Research Program_x000D_ (320-5314000-30026197)_x000D_ 2.Matthews Center for regenerative medicine pilot grants 2014 _x000D_ 3.National Cancer Institute-SPORE in Prostate Cancer (P50 CA90386-01)_x000D_ 4. Developmental Therapeutics Program, FSM Division of Hematology Oncology
Authors
Qiang Zhang
Timothy Kuzel Brian Helfand Ximing J Yang Weijun Qin Chung Lee Benebito Carneiro Francis J Giles |
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MP83-05 |
27-hydroxycholesterol inhibits prostate cancer growth by reducing STAT3 signaling |
Prostate Cancer: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP83-05 Sources of Funding: None Introduction We conducted a bioinformatic study querying genes involved in cholesterol homeostasis and prostate cancer (PC) outcomes. We found sterol hydroxylase CYP27A1 is correlated with PC progression and is consistently lower in PC vs. normal tissue. Preclinically, we found CYP27A1 overexpression, which metabolizes cholesterol to 27-hydroxycholesterol (27HC), decreased intracellular cholesterol and inhibited PC cell growth in vitro and in vivo. Likewise, treating PC cells with 27HC reduced intracellular cholesterol and decreased in vitro cell proliferation. This has not been tested in vivo. Cellular cholesterol is predominantly concentrated in plasma membrane micro-domains known as lipid rafts, which localize various membrane receptors and facilitate cellular signaling. Preliminarily, we found 27HC causes lipid raft depletion and disorganization reducing JAK2/STAT3 signaling. We hypothesize 27HC mediates its anti-PC activity by inhibiting STAT3-driven PC. Methods In vitro : Cell proliferation, immunoblots, immunoprecipitation, immunofluorescence (IF), matrigel based prostasphere assays and fluorescence activated cell sorting (FACS) techniques were used. In vivo : DU145 PC cells were injected subQ in mice fed a high fat high cholesterol diet for 6 weeks. After tumors grew to an average of 200mm3, mice were randomized on tumor size and serum cholesterol into two groups and injected daily with vehicle (cyclodextrin) or 27HC (40mg/kg) for 40 days. Results 27HC reduced active phosphorylated STAT3 (p-STAT3) levels in DU145 PC cells in vitro. 27HC inhibited STAT3 dimerization and reduced nuclear STAT3 levels. Adding exogenous cholesterol rescued p-STAT3 levels. Likewise, upstream of STAT3, phosphorylation of JAK2 was reduced by 27HC. Assessment of lipid rafts by IF and FACS showed a decrease and disorganization of lipid rafts after 27HC treatment. 27HC also reduced the number of PC cell-derived prostaspheres, which was rescued by cholesterol addback. Finally, our in vivo study showed that 27HC reduced tumor volume over time in a DU145 xenograft model. Conclusions 27HC reduced STAT3 signaling in PC cells by inhibiting STAT3 phosphorylation, dimerization and nuclear localization, likely due to reduced lipid raft JAK/STAT signaling. We also observed that 27HC reduces prostasphere numbers in vitro. These 27HC-mediated effects were rescued by cholesterol addback. Lastly, our in vivo study showed that 27HC treatment slowed tumor growth. These data suggest that 27HC may be a novel treatment for STAT3-driven PC. Funding None
Authors
Shweta Dambal
Everardo Macias Sergio Sanders Stephen Freedland |
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MP83-06 |
Combination therapy with EPI-002 and PARP inhibitor for castration-resistant prostate cancer |
Prostate Cancer: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP83-06 Sources of Funding: 2R01CA105304 Introduction Following the results of the TOPARP-A Phase II trial, Olaparib, an oral PARP inhibitor was recently recognized as a FDA breakthrough therapy for metastatic castration recurrent prostate cancer (mCRPC) patients who have germline mutations in DNA repair genes. Although these results are noteworthy, the problem remains of how to treat the remaining mCRPC patients who do not have detectable germline mutations of DNA repair genes. Androgen receptor (AR) signaling regulates DNA repair in prostate cancer and AR modulating drugs induce DNA damage. Thus a combination approach using AR modulating drugs with a PARP inhibitor could be a promising option for the treatment of mCRPC. All currently approved AR modulating drugs, such as enzalutamide and abiraterone, either directly or indirectly target the AR C-terminus ligand-binding domain (LBD). Such drugs are often unsuccessful due to the emergence of AR splice variants (ARV-7, ARv567es) that are constitutively active and lack a LBD. EPI-002 is a first-in-class AR antagonist that targets both full-length AR and AR splice variants. Here we present data to support that a combination of Olaparib, a PARP inhibitor, and EPI-002 have beneficial effects in vitro. Methods Combination therapy using EPI-002 and Olaparib were evaluated in vitro using human prostate cancer cells, LNCaP (androgen sensitive and expresses full-length AR) and LNCaP95, an androgen-independent cell line that expresses full-length AR and AR-V7 and is resistant to enzalutamide. The effects of monotherapy and combination therapy on cell cycle and DNA damage were analysed using FACS and Western blot. Results Unexpectedly, EPI-002 caused an enormous decrease of Checkpoint kinase 1 (Chk1) protein levels in LNCaP and LNCaP95 cells. Chk1 is one of the important mediators in cell cycle checkpoint during the DNA damage response. Whereas, enzalutamide also decreased the expression of Chk1 in LNCaP, it had no effect on Chk1 levels in LNCaP95 cells. Consistent with these data, AR knockdown in LNCaP cells also decreased Chk1 levels. The PARP inhibitor, Olaparib, induced phosphorylation of Chk1. EPI-002 induced G1 cell cycle arrest whereas Olaparib induced G2/M cell cycle arrest. FACS analysis of γH2AX showed increased DNA damage with combination therapy compared to monotherapies. Conclusions EPI-002 decreased the expression of Chk1 in prostate cancer cells that expressed both full-length AR and AR-V7. Combination therapy of EPI-002 plus Olaparib may provide a therapeutic approach for prostate cancer that expresses AR-V7. Funding 2R01CA105304
Authors
Yusuke Ito
C. Adriana Banuelos Marianne D. Sadar |
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MP83-07 |
N-terminal targeting of androgen receptor by EPI-001 in combination with autophagy inhibitors enhances the anti-tumor effect in LNCaP prostate cancer cells |
Prostate Cancer: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP83-07 Sources of Funding: none Introduction Multiple androgen receptor (AR) dependent and independent resistance mechanisms limit the efficacy of current castration resistant prostate cancer (CRPC) treatment modalities. EPI-001 is a novel N-terminal domain (NTD) binding AR targeting component with the promising ability to block constitutively active splice variants; a major resistance mechanism in CRPC. Autophagy a conserved lysosomal degradation pathway, is a survival mechanism in cells exposed to anti-cancer treatment. We hypothesized that also a promising NTD-AR treatment may lead to up-regulation of autophagy, which can be targeted by a combination therapy with autophagy inhibitors. Methods The human prostate cancer cell line LNCaP was cultured in steroid-free medium. Cells were treated with different concentrations of EPI-001 (10, 25, 50uM) and in combination with autophagy inhibitors chloroquine (CHQ, 20uM) or 3-methyladenine (3MA, 5mM). Viability was assessed by WST-1-assays after 1, 3 and 7 days. AnnexinV and Propidium Iodide were used to measure apoptosis and necrosis on day 7 after treatment. Autophagic activity was monitored on protein levels by western blot (WB) and immunocytochemistry for the expression of LC3-I/II, Atg5 and Beclin1. In addition, autophagosome increase was detected by Autodot staining. Results Treatment with EPI-001 resulted in a dose dependent reduction of cell viability up to 50% with 50uM EPI-001 on day 7. At the same time apoptosis increased by 11.53% and necrosis by 3.74% compared to the control. Combination of 50 uM EPI-001 with autophagy inhibitors led to a further significant reduction of cell viability up to 40% for CHQ and 28% for 3MA. Assessment of autophagy levels in EPI-001 treated cells by WB showed an increase of LC3-II in a dose dependent manner. No Change in Beclin1 expression was seen. Immuncytochemistry detected a significant increase of Atg5 and pronounced LC3-II punctuation in EPI-001 treated cells. This was supported by an increase in autophagosome punctuation observed by Autodot staining. Conclusions Our data demonstrate that the treatment with EPI-001 leads to increased autophagic activity in LNCaP prostate cancer cells. Combination of N-terminal androgen receptor blockage with simultaneous autophagy inhibition increases the antitumor effect of EPI-001 in vitro. This may offer a promising strategy to overcome resistance mechanisms in castration resistant prostate cancer. Funding none
Authors
Benedikt Kranzbühler
Souzan Salemi Tullio Sulser Daniel Eberli |
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MP83-08 |
Combination of metformin and sodium valproate for prostate cancer: a rapid approach from bench to clinical trial. |
Prostate Cancer: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP83-08 Sources of Funding: - Flinders Centre for Innovation in Cancer and Faculty Heath Science, Flinders University._x000D_ - Flinders Faculty of Health Sciences Seeding grant._x000D_ Introduction The anti-diabetic drug metformin (MET) and the anti-epileptic drug sodium valproate (VPA), when used alone, have shown anti-cancer effects in prostate cancer (PCa). However high doses are required which results in unacceptable toxicity. Here, we aimed to determine if the combination of MET and VPA (MET+VPA) at clinically relevant doses would (1) induce a synergistic anti-tumor effect in human PCa cell lines and patient-derived PCa explants, (2) cause minimal toxicity to normal tissues in vivo, (3) identify prognostic molecular markers for MET+VPA responses and (4) lead to rapid clinical application. Methods Human PCa cell lines (PC-3 and LNCaP) and radical prostatectomy explants from 8 patients were analyzed for response to MET+VPA. Ki67, cleaved caspase-3, the androgen receptor (AR), and p53 expression in explants were analyzed using immunohistochemistry. The combinatorial effects of MET+VPA were calculated using the Drug Combination Index (CI). The role of p53 and AR in response to MET+VPA was determined using TP53 gene knock-down in LNCaP and TP53 ectopic expression in PC3, and AR was chemically inhibited using Enzalutamide in LNCaP. The toxicity of MET+VPA was determined using histological scoring systems for kidney and liver toxicity in nude mice. Results MET+VPA synergistically inhibited proliferation in both PC-3 and LNCaP and synergistically induced apoptosis in LNCaP cells (CI<0.9). All PCa explants (pathological stage pT2C-pT3A and Gleason score 7-9) demonstrated a significant reduction (90%, p<0.001) in proliferation and a significant dose-dependent increase in apoptosis (300%, p<0.001) compared to vehicle. The p53 protein plays a role in MET+VPA as depletion of TP53 in LNCaP significantly reduced the apoptotic response by 58% (p=0.001) and the ectopic expression of TP53 in PC3 significantly increased the apoptotic response by 15% (p=0.047). The AR signaling pathway was also confirmed to play an important role in the apoptotic response to MET+VPA as Enzalutamide significantly reduced apoptosis by 28.5% (p=0.029) in LNCaP cells. No kidney or liver toxicity was detected in nude mice after 8 weeks administration of MET+VPA. These results support evaluation in a Phase I clinical trial which will start early in 2017 (Trial ID: ACTRN12616001021460p). Conclusions Our study has only taken 2 years from the first experiment to a phase I clinical trial. Although MET+VPA with an AR inhibitor may not show benefit, MET+VPA has potential to control clinically localized or metastatic PCa, particularly in tumors with functional p53 and/or AR signaling. Funding - Flinders Centre for Innovation in Cancer and Faculty Heath Science, Flinders University._x000D_ - Flinders Faculty of Health Sciences Seeding grant._x000D_
Authors
Linh N.K. Tran
Ganessan Kichenadasse Rebecca J. Ormsby Katherine L. Morel Lisa M. Butler Margaret M. Centenera Pamela J. Sykes |
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MP83-09 |
Elucidating Cross-Resistance Between Docetaxel and Cabazitaxel in Castration Resistant Prostate Cancer |
Prostate Cancer: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP83-09 Sources of Funding: This work is supported in part by grants NIH/NCI CA140468, CA168601, CA179970, DOD PC130062, and US Department of Veterans Affairs, ORD VA Merits I01BX0002653. Introduction Castration resistant prostate cancer (CRPC) is an incurable disease with few durable treatment options. Understanding the mechanisms of disease resistance will allow for the creation of more efficacious therapeutic options. Cabazitaxel is a next-generation taxane drug which is approved for the treatment of CRPC post docetaxel. However, cabazitaxel leads only to a modest survival benefit underlying the need to better understand the mechanisms of resistance to this drug. Whether there exists cross-resistance between docetaxel and cabazitaxel in the CRPC setting is unknown. Here we sought to investigate whether docetaxel resistance leads to the development of cabazitaxel resistance and how this effect may be mediated. _x000D_ _x000D_ Methods TaxR and DTXR docetaxel-resistant cell line derivatives were created by chronically exposing C4-2B and DU145 cells respectively to increasing doses of docetaxel. Cell growth assays utilizing a coulter cell counter to attain cell numbers were used to assess cellular response to treatment. Colony formation assays were used to support cell growth assay data. Apoptosis was assessed using western blots for cleaved-PARP. TaxR cells stably expressing a plasmid containing a shRNA targeting ABCB1 were used to test the role of ABCB1 in mediating resistance to cabazitaxel. Results Cell growth and colony formation assays demonstrated that docetaxel resistant prostate cancer cells are cross-resistant to cabazitaxel. We further show that apoptosis is blunted in docetaxel resistant cells in response to cabazitaxel treatment. Interestingly, both resistant cell lines were completely resistant to high dose docetaxel. Our previous work showed that increased expression of ABCB1 was largely responsible for mediating resistance to docetaxel. Thus, we sought to test whether this would alter cellular response to cabazitaxel. Using either a shRNA to decrease the expression of ABCB1 or elacridar, a small molecule inhibitor of ABCB1, re-sensitizes these cells to cabazitaxel treatment and restores the cell death response. We additionally show that inhibition of ABCB1 function using the anti-androgen drugs bicalutamide and enzalutamide effectively re-sensitizes cells to cabazitaxel treatment. Conclusions Our work suggests that docetaxel and cabazitaxel resistance is mediated by similar mechanisms. Evidence from other groups demonstrates that cabazitaxel is a better drug in the pre-docetaxel setting. This in conjunction with our work indicates that it may be more beneficial to move cabazitaxel into the docetaxel treatment space. Our study also highlights the potential of combination therapies with anti-androgen drugs to enhance cabazitaxel effectiveness in the docetaxel resistant setting. Funding This work is supported in part by grants NIH/NCI CA140468, CA168601, CA179970, DOD PC130062, and US Department of Veterans Affairs, ORD VA Merits I01BX0002653.
Authors
Alan Lombard
Chengfei Liu Cameron Armstrong Wei Lou Christopher Evans Allen Gao |
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MP83-10 |
Correlation between Cabazitaxel resistance and EMT in metastatic castration resistant prostate cancer |
Prostate Cancer: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP83-10 Sources of Funding: This work was supported by JSPS KAKENHI Grant Number 15K20109 and 26861299. Introduction Recently, cabazitaxel (CBZ) was identified as the most effective cytotoxic agent to demonstrate an improvement in survival in men with docetaxel-refractory CRPC. Accumulating evidence suggests EMT induced by androgen-deprivation therapy or docetaxel explains in part the aggressiveness of CRPC. The aim of this study was to screen for EMT inhibitory drugs by bioinformatic analysis and exploring the antitumor effect of CBZ for resistant CRPC. Methods PC3 and DU145 were used in this study. We incubated the cell lines with gradually increasing concentrations of CBZ to establish CBZ-resistant cell lines. In addition, we performed screening tests for candidate drugs to inhibit EMT of metastatic CRPC. The combined effect of CBZ and a candidate EMT inhibitor for CBZ-resistant cell lines was determined using a cell viability assay._x000D_ Results We established a CBZ-resistant cell line, PC3-CBZR (Figure). PC3-CBZR cells underwent cell division with 3 nM CBZ. We compared the cytotoxic effect of CBZ on PC3 and PC3-CBZR cells using a cell viability assay. The IC50 of CBZ in PC3 and PC3-CBZR cells were 16.0 nM and 2.5 nM, respectively. Real-time PCR showed up-regulation of ZEB family and Vimentin and down-regulation of E-cadherin expression, suggesting PC3-CBZR cells had elevated metastatic potential. We screened for EMT inhibitors using The Broad institute&[prime]s connectivity map (CMAP) analysis, with human whole genome array data and identified a candidate drug, KOH513. The relative cell viabilities treated with 10 μM KOH513 in PC3 and PC3-CBZR cells were 60.0 ± 1.7%, 58.7 ± 0.7%, respectively. KOH513 was suggested to have an antitumor effect on CBZ-resistant prostate cancer. Real time PCR and immune fluorescence assay showed that KOH513 down-regulated ZEB family and Vimentin in PC3-CBZR cells at the protein and mRNA levels. We tested the efficacy of KOH513 in CBZ resistance using a cell viability assay. Single-agent administration of 6 nM CBZ or 3 μM KOH513 did not have an antitumor effect in PC3-CBZ cells. However, when treated with 6 nM CBZ and 3 µM KOH513 in combination, PC3-CBZ cell proliferation was significantly suppressed (relative cell viability 77.0 ± 1.7%). In the same manner, we established CBZ-resistant DU145 cells, DU145-CBZR. DU145-CBZR cells had also had an up-regulated EMT pathway, and cell proliferation was suppressed by EMT inhibitor KOH513. These results suggested that KOH513 had potential for reprogramming CBZ resistant CRPC cell lines into sensitive cell lines._x000D_ Conclusions Targeting EMT signaling pathways with KOH513 can overcome CBZ resistance in CRPC. Funding This work was supported by JSPS KAKENHI Grant Number 15K20109 and 26861299.
Authors
Hiroshi Hongo
Takeo Kosaka Yota Yasumizu Yasumasa Miyazaki Eiji Kikuchi Akira Miyajima Mototsugu Oya |
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MP83-11 |
y+LAT2 (SLC7A6) expression in castration resistant prostate cancer |
Prostate Cancer: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP83-11 Sources of Funding: none Introduction Leucine stimulates cancer cell proliferation through the mTOR pathway, therefore, inhibiting leucine transporters can be a novel therapeutic strategy. One of leucine transporters, L-type amino acid transporter (LAT) 1 (SLC7A5), a Na+-independent amino acid transporter, has been reported to be selectively expressed in many cancer cells. Recently it has been shown that primary prostate cancer expresses LAT3 (SLC43A1), while castration resistant or highly aggressive prostate cancer expresses LAT1 as a main leucine transporter. In this study, we examine leucine transporters during acquisition of hormone independence. Methods A new &[Prime]LN-abl&[Prime] cell line was established after culturing LNCaP cells for 6 months under androgen-free conditions, which is a model of castration resistant prostate cancer (CRPC) with androgen receptor expression. Uptake of 14C leucine was examined in the presence or absence of LAT inhibitors or Na+. Expression of a major leucine transporter was inhibited by siRNA in LN-abl cells. In silico analysis of leucine transporter expression was examined using Oncomine for different progression status of prostate cancers in clinical data sets. Results Cell viability was decreased to 10% in the absence of leucine. LNCaP cells principally expressed LAT3, and their leucine uptake was more than 90% Na+-independent. In LN-abl cells, Na+-dependent uptake of leucine was 3.8 pmol/mgprotein/min, while, Na+-independent uptake was only 0.52, therefore, leucine uptake of LN-abl was largely (~85%) Na+-dependent. y+LAT2 (SLC7A6) expression was confirmed in LN-abl, however, expression of LAT1, LAT3, y+LAT1 (SLC7A7), ATB0+ (SLC6A14), B0AT1 (SLC6A19), B0AT2 (SLC6A15) or b0+AT (SLC7A9) were not observed. Knockdown of y+LAT2 lead to significant leucine uptake inhibition (40%) and cell growth inhibition (20%) in LN-abl cells. In silico analysis revealed that more frequent up-regulation of SLC7A6 (y+LAT2) was observed in hormone resistant or metastatic samples in 2 data sets. In addition, some advanced prostate cancer appeared to express high levels of LAT3, suggesting heterogeneity in leucine transporter expression among different prostate cancers. Conclusions New CRPC cell line with increased expression of y+LAT2 was established in vitro. This is consistent with the fact that at least some advanced stage prostate cancers express y+LAT2 in Oncomine data. Considering the diversity of leucine transporter expression, target of anti-leucine transporter therapy should be individualized. Funding none
Authors
Hideo Otsuki
Toru Kimura Takeo Kosaka Takashi Yamaga Jun-ichi Suehiro Hiroyuki Sakurai |
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MP83-12 |
Tissue-Specific Radiation Sensitization of Prostate Cancer by Aptamer Targeted siRNA Knock-Down of DNA Repair Pathway |
Prostate Cancer: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP83-12 Sources of Funding: NIH grant 5P50CA058236-15 (to T.L. DeWeese and S.E._x000D_ Lupold), the David H. Koch Charitable Foundation (to S.E. Lupold)_x000D_ Introduction Radiosensitizing agents can improve ionizing radiation (IR) potency. We have previously reported that an A10-3-DNAPK chimera can deliver radiation-sensitizing short interfering RNA (anti-DNA-PK siRNA) to prostate cancer cells and subcutaneous tumors through the PSMA-targeting RNA aptamer, A10-3. Here we describe the DNA-PK knock-down and radiation-sensitizing effect of the A10-3-DNAPK chimera on a human prostate cancer xenograft model in the mouse tibia, and its evaluation by bioluminescent imaging, immunohistochemistry and micro-CT. Methods Five to six-week-old male athymic nude mice were anesthetized by isoflurane, then luciferase expressing human prostate cancer cells (LNCaP-luc) were inoculated into tibias. Tumors were evaluated by IVIS bioluminescent imaging 6 weeks after implantation, then IVIS positive mice were separated into three groups and treated by PBS, A103-ctrl and A103-DNAPK via tail vein injection. For the confirmation of DNAPK knock-down, tibias were harvested 72hrs post injection and evaluated by HE staining and immunohistochemistry. In order to confirm radiation-sensitizing effect, half of the tumors received IR therapy (6 Gy) directly to the tumored leg. Four weeks after IR, the tibias were harvested and tumor burden assessed ex vivo by nanoScan PET/CT and VivoQuant software. The CT value (HU) from these images were applied to automatically assign regions of interest for bone (red, HU 5,000-10,000) and marrow (green, HU <5,000) (Fig 1B). The sum HU were then calculated for each treatment group to estimate tumor burden four weeks after treatment. Results Immunohistochemistry demonstrated reduction of DNAPK protein after A103-DNAPK treatment (Fig 1A: 50%, 38% less than PBS, A103-ctrl, respectively). The results of CT indicate significantly reduced tumor volume in A103-DNAPK pre-treated animals, with IR, when compared to animals pre-treated with PBS or A103-Ctrl (Fig 1C: p =0.045 and p=0.026, respectively). Conclusions Systemically injected aptamer siDNAPK can induce PSMA specific radiosensitization through DNAPK knock-down in human prostate tumor within mouse tibia. This system could be used to enhance radiation therapy of locally advanced PCa. Funding NIH grant 5P50CA058236-15 (to T.L. DeWeese and S.E._x000D_ Lupold), the David H. Koch Charitable Foundation (to S.E. Lupold)_x000D_
Authors
Kenji Zennami
Yonggang Zhang Haoming Zhou Daniel Thorek Theodore DeWeese Shawn Lupold |
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MP83-13 |
Zoledronic acid sensitizes castration-resistant prostate cancer cells to radiotherapy and chemotherapy by downregulating STAT1 |
Prostate Cancer: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP83-13 Sources of Funding: none Introduction Management of castration-resistant prostate cancer (CPRC) remains challenging due to the inevitable emergence of resistance to treatments including radiotherapy (RT) and chemotherapy (CT). We previously reported that zoledronic acid (ZOL) clinically potentiates the antitumor effects of RT in patients with renal cell carcinoma (Kijima et al, BJU Int 2009) and that this radiosensitization could occur through the osteoclast-independent inhibition of signal transducer and activator of transcription 1 (STAT1) (Kijima et al, PLoS One 2013). As the association between STAT1 overexpression and treatment resistance has been reported in several cancers, we investigated whether STAT1 is associated with resistance to RT and CT in CRPC cells and whether ZOL could overcome this resistance by downregulating STAT1. Methods Baseline expression of STAT1 was compared between androgen-dependent LNCaP cells and androgen-independent LNCaP (LNCaP-CR), PC3, and DU145 cells. The effect of ZOL on STAT1 expression was evaluated by Western blot and real-time PCR. The sensitizing effects of ZOL on RT and CT (docetaxel) were examined by clonogenic assay and MTS assay with combination index analysis. To confirm the importance of STAT1 on radio- and chemo-sensitization by ZOL, both siRNA knockdown and forced expression by cDNA transfection were performed. Results STAT1 levels were higher in androgen-independent cell lines (PC3, DU145) than in LNCaP cells (Figure A). STAT1 was gradually upregulated in LNCaP as these cells acquired androgen independency through continuous androgen ablation (Figure B). ZOL decreased STAT1 at the protein level (Figure C) through proteasome-mediated degradation and sensitized PC3 and DU145 to both RT and CT. Functional siRNA knockdown of STAT1 resulted in the sensitization of DU145 to RT and CT. Forced expression of STAT1 in LNCaP cells rendered them resistant to those therapies. Conclusions ZOL sensitizes CRPC cells to RT and CT by downregulating STAT1. Funding none
Authors
Takayuki Nakayama
Toshiki Kijima Soichiro Yoshida Fumitaka Koga Kazunori Kihara Yasuhisa Fujii |
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MP83-14 |
Combination use of EK2K and VPS34 inhibitors with anti-androgen against drug-resistant castration resistant prostate cancer |
Prostate Cancer: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP83-14 Sources of Funding: none Introduction Modulating the activity of eukaryotic elongation factor 2 kinase (eEF2K) has been suggested to regulate protein elongation to block autophagy in the tumor microenvironment. Among inhibitors of eEF2K, one would also inhibit VPS34, a class III phosphatidylinositol-3 kinase, and abrogate autophage flux to impair the survival escape mechanism. We tested the eEF2K and VPS 34 inhibitors from Janssen alone or in combination with anti-androgens for their effects on proliferation of prostate cancer cell lines, especially some castration resistant PC (CRPC) lines. Methods Cell proliferation was assessed with various concentrations of the EF2K or VPS34 inhibitor on CRPC lines using WST-1 viability assay. Effect of combinations of EF2K or VPS34 inhibitor with anti-androgens abiraterone (Abi) or enzalutamide (Enza) on drug-resistant CRPC cells was further explored. Western blot analysis was performed to examine the response of key autophagic molecules, androgen receptor (AR) and variant. Real time RT-PCR (RT-qPCR) was used to elucidate the effect of EF2K or VPS34 inhibitor alone or together with anti-androgens on AR, AR variant and their downstream molecules. Results EF2K and VPS34 inhibitors suppressed CRPC cell growth in a dose-response manner with IC50 ranging from 1 to 5 µM. These inhibitors displayed synergy with Abi and Enza against drug-resistant CRPC cells; especially on the pair of enza + EF2K inhibitor with p = 0.02 for significant difference when compared to enza or EF2K inhibitor alone. To our surprise, no significant autophagy was induced by these two inhibitors according to the autophagy markers detected by Western blots. VPS34 inhibitor alone and when combined with Abi and Enza showed AR/variant degrading ability. This downregulation was at the expression level with significant change of AR and V7, together with their transactivation markers PSA, TMPRS2, NKx3.1 and FKBP5 detected by RT-qPCR._x000D_ _x000D_ Conclusions EF2K and VPS34 inhibitors when combined with anti-androgens may solicit profound inhibitory effect on drug-resistant CRPC cells. Molecular delineation demonstrated the direct target might be AR and its variants. These combinations offered a new therapeutic option for advanced PC treatments. Funding none
Authors
Joy Yang
Vito Cucchiara Allen Gao Christopher Evans |
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MP83-15 |
A novel therapy for castration-resistant prostate cancer through inhibition of oncogenic microRNAs |
Prostate Cancer: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP83-15 Sources of Funding: This work was supported by National Institutes of Health Grants U01CA166905 and U01CA152758 (to C.C. and D.P.) and the Pelotonia Intramural Research Program (D.P.). Introduction Recent studies have shed light on the role of microRNAs (miRs) in prostate cancer (PCa). miR-21 is among the most frequently deregulated miRs in cancer, and has been implicated in a castration-resistant prostate cancer (CRPC) phenotype. In addition to miR-21's many oncogenic effects, a positive feedback loop between miR-21 and the androgen receptor (AR) has been reported in PCa. Separately, miRs -221 and -222 have been shown to target tumor suppressor p27Kip1, leading to inhibition of apoptosis and aberrant proliferation. Nucleolin (NCL) is a multifunctional protein found in the nucleocytoplasm of most human cells, and is abnormally translocated to the cell membrane in cancer. One of the mechanisms by which NCL exerts its oncogenic activity is through the biogenesis of miRs -21, -221, and -222. 4LB5 is a novel single-chain fragment variable (scFv) antibody that binds preferentially to cancer cell membranes via the RNA-binding domain of NCL and inhibits production of these oncogenic miRs. The therapeutic and diagnostic potential of 4LB5 has been described in breast and hepatocellular carcinoma cells in previous studies. Given the supporting evidence, we aim to characterize the effects of 4LB5 on CRPC and compare its efficacy among androgen-dependent and androgen-independent cells. Methods Levels of NCL expression in PCa cell lines DU145, PC3, and LNCaP were investigated with western blot (WB). Cell surface ELISA was performed to compare 4LB5 binding across PCa cell lines. Cell survival assay was performed using 50 nM 4LB5 or control buffer. Levels of mature and precursor forms of miRs in 4LB5-treated cells were assessed using quantitative real-time polymerase chain reaction. MDA-MB-231 cells were used a positive control in all experiments. Results All cell lines expressed NCL as evidenced by WB, and downregulation of NCL was observed with siNCL transfection. ELISA results showed a strong exponential association between 4LB5 concentration and binding activity in DU145 (R2 = 0.9972), PC3 (R2 = 0.9887), and LNCaP (R2 = 0.9897) cells, with more binding units observed in PC3 and DU145 compared to LNCaP. 4LB5 significantly inhibited proliferation of DU145 (p = 0.000016) and PC3 (p = 0.0074) cells, but not LNCaP (p = 0.45). Treatment with 4LB5 caused downregulation of mature forms of miRs 21, 221, and 222 with expected upregulation of precursor forms in PC3 cells, but LNCaP cells exhibited the opposite effect. Conclusions 4LB5 binds CRPC cells and inhibits proliferation through abrogation of oncogenic miR production. 4LB5 could represent a novel therapeutic option in CRPC patients. Funding This work was supported by National Institutes of Health Grants U01CA166905 and U01CA152758 (to C.C. and D.P.) and the Pelotonia Intramural Research Program (D.P.).
Authors
Tyler Sheetz
Dario Palmieri Vincenzo Coppola Anna Tessari Joseph Mills Ashley Braddom Erika Reese Claudia Foray Kareesma Parbhoo Carlo M. Croce |
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MP83-16 |
Exploring 2D and 3D Culture on Responses to Combinatorial Drug Therapy in Human Prostate Cell Lines |
Prostate Cancer: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP83-16 Sources of Funding: NCI Introduction Prostate cancer (PCa) is commonly overtreated, producing iatrogenic side effects in patients without longevity benefits. Active Surveillance (AS), long term monitoring of patients without intervention until there are clear signs of disease progression is an alternative to the use of surgery or radiation-based approaches. This approach can allow patients with clinically indolent diseases to avoid major interventions for prolonged periods. Two major groups who could benefit from new medical therapies used as an adjuvant to AS are: men resistant to AS because of fear of death, and men who do not meet the current stringent AS criteria. _x000D_ _x000D_ Prostate tumors are surrounded by cell populations that include fibroblasts, immune/inflammatory cells, nerves and endothelium that interact to produce a pro-proliferative local microenvironment that contributes to prostate cancer progression. We hypothesize that coordinated suppression of key signaling pathways within the microenvironment represents a potential approach to render selected prostate tumors functionally indolent. The aim is to develop approaches to combine low dose therapeutics as adjuvants to AS. This should allow more comfort for patients who dislike a &[Prime]passive&[Prime] approach and an expansion of the AS criteria to include more men. _x000D_ Methods We tested the TGF-β receptor kinase inhibitor Galunisertib alone and in combination with the Btk kinase inhibitor Ibrutinib to coordinately suppress SDF1/CXCR4 and TGF-β signaling in benign, initiated and malignant human prostate epithelial cell lines in 2D and 3D culture in control and carcinoma associated fibroblast-conditioned medium (CAF-CM). Results In 2D culture in CAF-CM we showed effects of both drugs individually on inhibiting proliferation of target epithelial cells. We were also able to demonstrate that combining the two drugs at doses that, individually, had minimal effects on proliferation was sufficient to significantly reduce cell growth. Cells were more resistant to the effects of drugs in 3D culture. However this approach has a number of advantages, including the ability to examine phenotypic and organization of the epithelium and the response to drugs in terms of these markers. _x000D_ Conclusions Initial studies demonstrate that benign epithelial cells are much less sensitive to drug effects than cells that have undergone tumor-initiating events. 3D culture provides a better model of the in vivo environment than 2D culture. The differences in response under the culture conditions illustrate important limitations to the 2D cell culture model. Funding NCI
Authors
Yana Filipovich
Omar Franco Simon Hayward |
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MP83-17 |
Effect of Combination therapy of Desmopressin and Docetaxel on prostate cancer cell DU145 proliferation, migration and growth |
Prostate Cancer: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP83-17 Sources of Funding: none Introduction This study was designed to assess the efficacy of the combination of Desmopressin and Docetaxel for prostate cancer. Desmopressin has been demonstrated to inhibit tumor progression and metastasis in in vitro and in vivo models of breast cancer. Docetaxel, an anti-mitotic chemotherapeutic agent, is widely used for the treatment of castration resistant prostate cancer. However, it is associated with adverse effects and eventual drug resistance. This is the first report on the effect of combining Desmopressin and Docetaxel in prostate cancer, both in vitro and in vivo. _x000D_ Methods An established castrate resistant prostate cancer cell line DU145 was used. Cellular proliferation was determined using the MTS assay. The migratory inhibition potential of Desmopressin alone and in combination with Docetaxel was accessed using the wound healing assay. In vivo evaluation was performed by using a prostate cancer xenograft model of athymic nude mouse. Treatment was administered bi- weekly and tumor volume were measured throughout the treatment period. Eventually, after a six-week treatment period, tumors were excised and measured. _x000D_ Results combination therapy of 1 μM Desmopressin with 100nM Docetaxel resulted in inhibition of proliferation of DU145 cells 72 hours post treatment compared to either agent along (Figure 1). Wound healing assay revealed inhibition of cellular migration as well (p<0.05). In the xenograft mouse model, treatment with 5 mg/kg Docetaxel intraperitoneally with concomitant 2 μg/ml/kg Desmopressin administered intravenously 30 minutes before administering chemotherapy and 24 hours later resulted in a significant decrease in tumor volume compared to Docetaxel alone, while not impacting body weight. Conclusions Desmopressin enhanced the anti-proliferative and inhibiting the migratory potential of Docetaxel. Combination treatment had no additional effect on mice weight or mortality. These studies could enhance the efficacy of Docetaxel- based chemotherapy treatment for castrate resistant prostate cancer. Funding none
Authors
Azik Hoffman
Hiroshi Sasaki Domenica Roberto Michelle J Mayer Laurence Klotz Vasundara Venkateswaran |
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MP83-18 |
A 21-carbon steroidal metabolite from progestin, 20β-dihydro-5α-dihydroprogesterone, stimulates the androgen receptor in prostate cancer cells |
Prostate Cancer: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP83-18 Sources of Funding: none. Introduction Under androgen deprivation therapy (ADT), 21-carbon steroids (C21s), such as progesterone (P4) and glucocorticoids, accumulate in men with prostate cancer (PCa). Accumulated C21s could stimulate the progesterone receptor (PGR) or glucocorticoid receptor (GR) on PCa cells, and a relationship between these stimulations and castration resistance in PCa has been suggested. However, although the intra-tumoral metabolism of C21s in PCa cells exists, it is not known whether intracrine C21s are implicated in PCa progression. In this study, we showed that 20β-dihydro-5α-dihydroprogesterone (20β-OHDHP), a C21 and a metabolite of P4, was synthesized in PCa cells and was able to directly stimulate the androgen receptor. Methods LNCaP cells expressing mutant AR (mAR) and VCaP cells expressing wild-type AR (wAR) were incubated in the presence of several agents. After incubation, cell growth was determined by the MTS assay, PSA levels were determined by an enzyme immunoassay, C21 and androgen levels were measured by LC-MS, gene expression was analyzed by qRT-PCR, and AR-related signaling was determined by a reporter assay. Results The presence of 20β-OHDHP synthesis from pregnenolone (P5) and the absence of androgen synthesis from P5 or 20β-OHDHP were observed in both cells. With the addition of 20β-OHDHP to the medium, both cells were promoted in a concentration-dependent manner and were able to continuously proliferate or simply survive. In both cells, the expression of AR-related genes, such as KLK3, TMPRSS2, and FKBP5, increased in the presence of 20β-OHDHP and RLU increased in a concentration-dependent manner; however, the expression of GR-related genes, such as SGK1, NR3C1 and PGR, decreased. The stimulation of 20β-OHDHP was inhibited by the addition of bicalutamide, which blocks androgens from binding to AR. Conclusions Under ADT, 20β-OHDHP synthesized in PCa cells accelerates their own growth due to the stimulation of both wAR and mAR. This pathway may be an interesting candidate for targeted therapy. Funding none.
Authors
Takashi Ando
Itsuhiro Takizawa Tatsuhiko Hoshii Yoshimichi Miyashiro Noboru Hara Tsutomu Nishiyama Yoshihiko Tomita |
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MP83-19 |
Co-treatment with L-methadone significantly increases the efficacy of cytostatic drugs in prostate cancer cells |
Prostate Cancer: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP83-19 Sources of Funding: Sanofi-Aventis GmbH, Frankfurt, Germany Introduction In leukemia and glioblastoma cells, a significant increase of apoptosis rates has been observed in vitro under cytostatic therapy by activation of the µ-opioid receptor with methadone. This study investigated the effect of opioid receptor activation in prostate cancer cells in presence of different cytotoxic drugs. Methods The prostate cancer cell lines PC-3, DU145 and LNCaP as well as control cell lines RCC-26 and A172 (renal cell carcinoma and glioblastoma) were incubated with different concentrations of the cytostatic drugs cabazitaxel and doxorubicin and the number of cells in apoptosis after 3 and 5 days was analyzed using flow cytometry (with annexin V-APC and 7AAD staining). In addition, the cells were incubated with various concentrations of L-methadone (0-100 µg/ml). Furthermore, gene expression analysis was performed using microarrays (Affymetrix GeneChip Prime View, ca. 49,000 transcripts) to detect changes in cell biology caused by methadone treatment. Results Incubation of PC-3 cells with 10 nM cabazitaxel resulted in 53% apoptosis after 5 days. This rate remained constant under co-incubation with L-methadone. Incubation with 0.3 µM doxorubicin resulted in 37% apoptosis after 5 days. In this setting, co-incubation with L-methadone showed a dose-dependent increase of apoptosis rate up to 88% (2.4-fold increase). Control experiments with fentanyl and naloxone instead of methadone showed no influence on apoptosis rate. Comparable and partly even clearer results were achieved with DU145, LNCaP, RCC-26 and A172 cells: the cabazitaxel-induced apoptosis rates remained stable under L-methadone, the doxorubicin-induced apoptosis was significantly increased by L-methadone (up to 3.8-fold increase). Microarray analysis revealed 128 upregulated and 398 downregulated genes (≥2-fold change of expression level, p<0.05) caused by L-methadone in PC-3 cells. Conclusions Stimulation of the µ-opioid receptors by L-methadone enhances the therapeutic effect of cytostatic drugs in prostate carcinoma cells and in other tumor cell lines. The increase of cytostatic effect depends on the combination of cell line and cytostatic agent. The combination of L-methadone with certain cytotoxic drugs can be a promising new approach to increase the therapeutic efficacy in hormone-refractory prostate carcinoma. Funding Sanofi-Aventis GmbH, Frankfurt, Germany
Authors
Birgit Stadlbauer
Detlef Kozian Christian Stief Alexander Buchner |
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MP83-20 |
Endogenous sulfur dioxide, a novel gasotransmitter, plays tumor suppressor role in prostate cancer |
Prostate Cancer: Basic Research & Pathophysiology II | 17BOS |
Abstract: MP83-20 Sources of Funding: National Natural Science Foundation of China (No.81370858 and 81570683), and grant from Beijing Natural Science Foundation (No.7142161) Introduction Recently, sulfur dioxide (SO2), similar to nitric oxide and hydrogen sulfide, has been recognized as a new kind of gasotransmitter. It can be endogenously produced from metabolism of the sulfur-containing amino acid L-cysteine by SO2 synthase, aspartate aminotransferase (AAT), in mammal tissues including urogenital system. Besides, studies proved SO2 had physiological and pathophysiological significance among humans. Here, we'd like to explore the effects of endogenous SO2 on prostate cancer (PCa). Methods The expression of AAT1 in human PCa and benign prostatic hyperplasia (BPH), is detected by immunohistochemistry. The SO2 concentrations of prostate from transgenic adenocarcinoma of the mouse prostate (TRAMP) model and that from parental C57BL/6 mouse were measured using high-performance liquid chromatography (HPLC). Bisulfite and sulfite were regarded as SO2 donors. The silenced or overexpressed AAT1/AAT2 PCa cell lines were conducted to further study the role of endogenous SO2. Cell proliferation was determined by Cell Counting Kits-8. And cyclins and cyclin-dependent kinases were analyzed by western blot. Results Compared with human BPH, PCa displayed less AAT1 expression (A). Besides, HPLC showed a lower level of SO2 concentration in prostate from TRAMP mouse than that from parental C57BL/6 mouse (B). Silenced/overexpressed AAT1 in PCa cell lines, C4-2 or CWR22Rv1, could promote/suppress their proliferation (C). Furthermore, cyclin, cyclinD1, and cyclin-dependent kinase, CDK6, were reduced/increased among AAT1/AAT2 overexpressed/silenced PCa cell lines (D). Conclusions SO2, a novel gasotransmitter, and its synthesis enzyme AAT are frequently downregulated in PCa. Endogenous SO2 could function as a tumor suppressor via regulating the proliferation of PCa. Moreover, CyclinD1 and CDK6 would be involved in the regulation of SO2. Funding National Natural Science Foundation of China (No.81370858 and 81570683), and grant from Beijing Natural Science Foundation (No.7142161)
Authors
Yun Cui
Shuai Hu Yang Yang Lu Wang Jindong Sheng Yu Fan Junbao Du Hongfang Jin Jie Jin |
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MP84-01 |
Predictors of Increased Intracavernosal Injection Requirements at Penile Ultrasound |
Sexual Function/Dysfunction: Evaluation II | 17BOS |
Abstract: MP84-01 Sources of Funding: NONE Introduction Penile duplex Doppler ultrasound (PDDU) with intracavernosal injection (ICI) with erectogenic agents is commonly used to evaluate vascular parameters in men with erectile dysfunction (ED). Recent studies have suggested significant variability in outcomes based on ICI dosing protocols, suggesting a need for standardization of injection protocols. Given a lack of literature on this topic, we sought to identify predictors for increased need of ICI dosing to achieve adequate rigidity at the time of PDDU. Methods A retrospective chart review was performed of all patients undergoing PDDU for evaluation of ED from January 2014 to November 2015. At the time of PDDU, men received a combination of papaverine(30 mg/mL), phentolamine(1 mg/mL), and alprostadil(10 mcg/mL) in 0.1 mL increments until an erection sufficient for penetration was achieved or 1.0 cc was administered. Clinicopathologic and demographic variables were reviewed, and univariate and multivariate analyses were used to identify characteristics associated with increased erectogenic requirements. Results A total of 262 men (mean age 53;) underwent PDDU during the study period. Mean IIEF-6 score was 12.4 (SD 10.2), and a mean 2.1 injections (SD 1.1) with 0.34 cc (SD 0.34) were administered. On multivariate analysis, lower IIEF-ED domain score (p<0.01), coronary disease (p=0.03), and diabetes (p=0.01) were associated with increased requirement for erectogenic medications. Conclusions Patients with lower IIEF scores, coronary disease, and diabetes mellitus may require higher volumes of erectogenic medications at the time of PDDU. This information may help to create standardized and efficient protocols for repeated dosing regimen. Funding NONE
Authors
Ross Avant
Matthew Ziegelmann Joshua Savage Landon Trost |
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MP84-02 |
Utility of 2D Photography in The Assessment of Penile Curvature in Men With Peyronie’s Disease (PD): The GoSoft Study |
Sexual Function/Dysfunction: Evaluation II | 17BOS |
Abstract: MP84-02 Sources of Funding: none Introduction Curvature assessment (CA) in Peyronie's disease (PD) is a critical step in the evaluation of the PD patient. Assessment using combined intracavernosal injection and goniometry (IG) is the standard approach. _x000D_ Aim: to evaluate the utility of novel software (GoSoft) for the measurement of the PD deformity. Methods Population: men with PD, who had a CA using IG. A rigid erection was an inclusion criterion for inclusion in this analysis. Degree of curvature was measured with a goniometer, simultaneously a photograph was taken. The photo was analyzed using GoSoft software by three observers at different time points, each being blinded to the goniometer assessment. The primary outcome was to compare the inter-observer and intra-observer reliability of GoSoft. We also aimed to compare the concordance between GoSoft and goniometry. We compare correlation for curvature ≤ 45 degrees and for > 45 degrees. We accepted a variability of 5 degrees and considered an under and over-estimation if the difference was >5 degrees. Results 53 subjects were included. The intra-observer reliability was excellent, representing a high correlation ( r=0.96 to 0.98, p<0.001) with a variance between means of 1.3±0.6 degrees. The inter-observer reliability was also high (r=0.89 to 0.95, p<0.001) (Figure 1) with a variance between means of 2.2±1 degrees. The Pearson correlation coefficients (r) between the goniometer and GoSoft for each rater were: Rater 1: r=0.75, p<0.001; Rater 2: r=0.73, p<0.001; and Rater 3: r=0.80, p<0.001. This indicates strong agreement, but also suggests variability between the types of measurement. For the three raters, when comparing GoSoft to the goniometer, GoSoft accurately measured (within ±5 degrees) 45% of the curvatures, underestimated it by >5 degrees in 25% of the curvatures, and overestimated it by >5 degrees in 30% of the curvatures. The correlation appears to be higher for greater curvatures. For curvature ≤ 45 degrees, the correlations between goniometer and GoSoft ranged from: r=0.41-0.47, p=0.03; while, for curvatures > 45 degrees, the correlations ranged from: r=0.59-0.65, p<0.01. Conclusions GoSoft assessment is consistent with goniometry. The excellent reliability and reproducibility might provide a more standardized instrument for CA in men with PD. Funding none
Authors
Jean-Etienne Terrier
Leonardo Florez Valencia Maciej Orkisz Christian J Nelson Lawrence C Jenkins Phil Vu Bach Eduardo P Miranda Bruno Nascimento John P Mulhall |
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MP84-03 |
Development of a Cut-off for the Peyronie’s Disease Questionnaire (PDQ) Bother Score |
Sexual Function/Dysfunction: Evaluation II | 17BOS |
Abstract: MP84-03 Sources of Funding: none Introduction The Peyronie's Disease Questionnaire (PDQ is a validated self-reported questionnaire that measures the impact and severity of Peyronie's Disease (PD) in 3 domains, including Symptom Bother (6 items, score range 0-16). Mean baseline bother score in the IMPRESS trials was 8 (7.8±3.7). However, the clinical significance of the PDQ bother score has not been evaluated. We aimed to find the optimal PDQ symptom bother score cut-off predicting the presence of clinical bother and distress. Methods Men with PD completed a series of validated questionnaires at initial consultation, including the PDQ, the Center for Epidemiological Studies-Depression scale (CESD), and the Self-Esteem and Relationship questionnaire (SEAR). We used a receiver operating characteristic (ROC) curve to determine the optimal cutoff score of PDQ bother by separately predicting: (1) depressive symptoms as defined as a score of ≥16 on the CESD (2) low sexual self-esteem defined as a score of ≤35 on the SEAR (the score reported by those with severe ED) and (3) the combination of depressive symptoms and low sexual self-esteem. The Youden index was used to determine the optimal cut-off maximizing both sensitivity and specificity. Results The mean age of the 204 men was 56±12 years of age. 82% of the sample had a partner, with an average length of relationship of 16±14 years. The mean duration of PD was 16±21 months and the average curvature was 39±20 degrees. When using depressive symptoms (CESD) as the criterion, the ROC curve analysis produced an area under the curve (AUC) of 0.61 (p=0.04), indicating a cut-off score of 8, which produced the best sensitivity (0.61) and specificity (0.58). When using low sexual self-esteem (SEAR) as the criterion, the ROC curve analysis produced an AUC of 0.70 (p=0.001), and indicated a cut-off score of 9 producing the optimum sensitivity (0.67) and specificity (0.69). The combination of both criteria failed to produce a significant AUC (0.48, p=0.56). Since using sexual self-esteem as the criterion produced better AUC and higher sensitivity and specificity, the cut-off score of 9 is suggested. Conclusions A bother score of 9 on the PDQ appears to represent the optimal cut-off score indicating clinically significant bother. In our opinion, such a score warrants a consideration to refer the patient to a mental health professional. Funding none
Authors
Jean-Etienne Terrier
Christian J Nelson John P Mulhall |
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MP84-04 |
Prediction of Future Erectile Dysfunction Using Comorbid Disease and Medication Profiles |
Sexual Function/Dysfunction: Evaluation II | 17BOS |
Abstract: MP84-04 Sources of Funding: None Introduction Multiple disease states and medications have been correlated with erectile dysfunction (ED). There are currently no methods to predict future erectile function or to determine the impact of multiple comorbidities and medication use on loss of erectile function over time. Methods The Olmstead County Study of Urinary Symptoms and Health Status among Men represents prospective, ongoing study of men aged 40 and older and living in Olmsted County, Minnesota. The database includes detailed information on demographics, laboratory testing, medications, and comorbid conditions as well as assessments of ED using the Brief Male Sexual Inventory (BMSI) beginning in 2002. Subsequent BMSI questionnaires were completed in 2004, 2006, and 2009. Men without a sexual partner or those with prior pelvic surgery were excluded. Multivariable modeling was performed to determine factors associated with BMSI scores at the 2002 time point. Significant variables were then included in a weighted, step-wise scoring system to assess the predictability of loss of erectile function over time. Results 937 patients met inclusion criteria, with a mean age of 61 years (SD 8.7). Mean BMSI scores in 2002, 2004, 2006, and 2009 were 7.4 (3.6), 6.9 (3.7), 6.6 (3.8), and 6.0 (3.9), respectively. Multivariate analysis revealed that increasing age (parameter estimate [PE] -0.2 / year over age 40), arterial disease (myocardial infarction, stroke, coronary artery disease; PE -0.7), diabetes (PE -0.7), insulin use (PE -2.0), and beta blocker (PE -0.6) were all associated with a decreased BMSI score (p<.05). The combination of significant factors into a predictive model demonstrated an overall r-squared value of 0.30, suggesting that only 30% of the variability in BMSI scores over time could be accounted for using these factors. In contrast, the use of the BMSI 2002 results demonstrated an r-squared value of 0.50, suggesting that baseline erectile function is a superior predictor for future ED compared to assessments of comorbid conditions and medication use. Conclusions While multiple comorbidities and medications are associated with ED, they fail to produce a predictive model superior to baseline assessment of erectile function. These findings suggest that despite the known association between select comorbid conditions, medications, and ED, the presence of these conditions does not result in a more rapid deterioration in erectile function over time compared to cases with no comorbid conditions. This information provides a significant addition to our current understanding of the natural history of ED progression. Funding None
Authors
George Bailey
Joshua Piotrowski Tanner Miest Francisco Maldonado Ziegelmann Matthew Brian Montgomery Landon Trost |
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MP84-05 |
HOW LONG SHOULD PATIENTS WAIT BEFORE RESUMING SEXUAL ACTIVITY AFTER BPH SURGERY? |
Sexual Function/Dysfunction: Evaluation II | 17BOS |
Abstract: MP84-05 Sources of Funding: None Introduction Surgical therapy for benign prostatic hyperplasia (BPH) is amongst the most common urological procedures. While most patients are expected to resume sexual activity postoperatively, data pertaining to the required time of abstinence is lacking. Methods Following IRB approval, we prospectively enrolled sexually active men referred for BPH surgery in a questionnaire-based study. Patients were asked to complete an IPSS, IIEF and the sexual part of the EPIC questionnaires (assessing BPH severity, erectile and sexual function) a month before and after their surgery. Upon discharge, patients were advised to resume sexual activity whenever they desired without indicating a specific period of abstinence. _x000D_ To study urologists' perspectives in this context, we approached board certified urologists, asking them to complete a short questionnaire assessing their current practice and recommendations. _x000D_ Results Of the 71 participating patients, roughly half underwent endoscopic surgery (Table 1). Over 80% of patients were older than 60 and over 90% were married. The postoperative IPSS improved significantly, while no difference was detected in the IIEF and EPIC scores. Almost all patients (94%) patients reported on resuming sexual activity less than a month postoperatively and more than 40% within 2 weeks. Two thirds reported on retrograde ejaculation and 11 % reported on mild bleeding. Although more than 20% experienced some pain during orgasm, only 10% decided to refrain temporarily from further sexual activity. _x000D_ Overall, 70 urologists completed the questionnaire (table 2). More than 94% worked at academic centers, most had more than 10 years experience, and over 50% indicated performing at least 60 surgeries yearly. More than 50% would recommend abstaining from any sexual activity for at least 1 month postoperatively._x000D_ Conclusions While most urologists recommend refraining from sexual activity for at least one month following BPH surgery, our study suggests that over 94% of patients may resume sexual activity shortly after surgery, expecting minimal adverse side effects. Funding None
Authors
Hanan Goldberg
Liat WEINZVIEG Marc Lubin Yariv Shtabholtz Amihai Nevo Chen Shenhar Paz Lotan Roy Mano Daniel Halstuch Dov Lask Yaron Erlich David Margel Daniel Kedar Jack Baniel Ofer Yosseopowitch |
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MP84-06 |
Tertiary referral hospital experiences of men presenting with painless post-coital gross hematuria and a suggestion for tentative management algorithm |
Sexual Function/Dysfunction: Evaluation II | 17BOS |
Abstract: MP84-06 Sources of Funding: None Introduction Post-coital gross hematuria (PCGH) is rare clinical symptom, but its clinical significance is still unclear with lack of standardization in the diagnosis and treatment. Herein, we introduced tertiary referral hospital experiences of men presenting with painless PCGH and tried to suggest a tentative management algorithm. Methods Between 2009 and July 2016, data from 20 first-visit patients with PCGH were reviewed. After checking present illness and past history, further studies were performed by our tentative management algorithm for painless PCGH (Figure 1). At first, the general work-up for painless gross hematuria including laboratory test, CT, and urethrocystoscopy was performed. If no discernable reason for PCGH was identified, the focused work-up of PCGH for pelvic vasculatures was carried out as follows. Transrectal and penile ultrasonogrphay (USG) with Doppler study were performed for the evaluation of prostate, penis, and their relevant vasculatures. Diagnostic pelvic angiography and subsequent angioembolization were recommended at the physician&[prime]s discretion. Results The median age was 47 years (31 ~ 67). After following of our tentative algorithm, there was no abnormal finding in 9 (45.0%), urological malignancies were found in 2 (10.0%; 1 bladder, 1 kidney). On urethrocystoscopy, urethral mucosal bulging suggestive of hemangioma was found in 3 (15.0%) (Figure 2A). Doppler USG revealed pelvic varicosities in 3 (15.0%), and pelvic arteriovenous malformation (AVM) in 3 (15.0%) (Figure 2B, C). Pelvic angiography was recommended to the latter 3 patients for confirmatory diagnosis. One refused angiography, but the other 2 patients underwent angiography and subsequent angioembolization for AVM (Figure 2D ~ F). Conclusions PCGH is a different disease entity from painless GH. The focused work-up for the pelvic vasculatures seems to be mandatory for the evaluation of these patients. The feasibility of our tentative algorithm should be evaluated by well designed clinical studies. Funding None
Authors
Dong Hyuk Kang
Jongsoo Lee Jong Won Kim Jae Yong Jeong Sung Ku Kang Jong Kyu Kwon Joo Yong Lee Dae Chul Jung Young Deuk Choi Kang Su Cho |
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MP84-07 |
Performance and Correlation of Efficacy Endpoints in a Clinical Trial of Premature Ejaculation |
Sexual Function/Dysfunction: Evaluation II | 17BOS |
Abstract: MP84-07 Sources of Funding: Ixchelsis Ltd. Introduction Efficacy Assessments in trials of Premature Ejaculation (PE) include intravaginal ejaculatory latency time (IELT), Clinical Global Impression of Change (CGIC) and the Premature Ejaculation Profile (PEP). The objective of this paper is to systematically compare and correlate the IELT, CGIC and PEP data from a clinical trial recruiting men with lifelong PE. Methods Patients in Trial NCT02232425 recorded IELT measured by stopwatch and 2 PEP questions (ejaculation control and ejaculation-related distress) using an e-diary daily during 4 weeks prior to treatment and 8 weeks of study drug treatment. Patients also completed all 4 PEP questions every 4 weeks, and the CGIC at end of treatment. PEP questions on control and distress were scored 0 (worst) to 4 (best response). Treatment groups were analyzed together. IELT, CGIC and PEP results were systematically compared. Descriptive statistics, correlation coefficients (Pearson and Spearman) and Bland-Altman plots were produced for each treatment interval. Box and whisker plots were produced by category of improvement in PEP question scales. Results Data collected daily via e-Diary and based on 4-week recall showed equivalent results (Figure 1 shows results for distress). Each endpoint was sensitive to treatment-related change, and all measures showed a high degree of concordance with one another. For example, improvements in IELT correlated with improved control and reduction in ejaculation-related distress (Figure 2). Men with lifelong PE generally perceived improvement in their condition when their IELT increased by approximately 40 seconds or more, or the fold increase in IELT was 2.5 or greater. Conclusions The results strongly support the use of these efficacy instruments in PE studies. The combination of objective (IELT) and subjective (PEP, CGIC) measures is necessary and appropriate for assessing treatment benefit in men with PE. Funding Ixchelsis Ltd.
Authors
Ray Rosen
Stanley Althof Ian Osterloh Gary Muirhead Christopher McMahon Brian Harty Francois Giuliano |
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MP84-08 |
Impact of metabolic syndrome on the occurrence of premature ejaculation |
Sexual Function/Dysfunction: Evaluation II | 17BOS |
Abstract: MP84-08 Sources of Funding: none Introduction Despite the association between erectile dysfunction and metabolic syndrome (MetS), few reports describe the relationship between premature ejaculation (PE) and MetS. This study investigated the effect of MetS in the pathogenesis of ejaculatory symptoms, and the risk factors associated with PE. Methods Records of 1,029 men who visited our clinic for male health screening between January 2010 and July 2014 were analyzed. Multivariate analyses included the covariates of age, International Prostate Symptom Score (IPSS), International Index of Erectile Function (IIEF) score, National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI) score, body mass index, Androgen Deficiency in the Aging Male (ADAM) score, serum testosterone levels, and all components of MetS. PE was defined as self-reported intravaginal ejaculation latency time (IELT) <1 minute, and MetS was diagnosed by using the modified National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria. The Male Sexual Health Questionnaire for Ejaculatory Dysfunction (MSHQ-EjD) was used to analyze ejaculation anxiety and other dysfunctions. Results Of 1,029 men, 74 (7.2%) had PE (ejaculation within 1 min) and 111 (10.8%) had MetS. Multivariate logistic regression analysis showed that IIEF overall satisfaction score, NIH-CPSI pain score, NIH-CPSI voiding score, and presence of MetS were significantly correlated with prevalence of PE. MSHQ-EjD and ejaculation anxiety scores progressively decreased as the number of components of MetS increased. Conclusions MetS may be an important factor predisposing to development of PE; effective prevention and treatment of MetS could also be important for the prevention of PE. Funding none
Authors
Seong Uk Jeh
See Min Choi Sin Woo Lee sol Yoon Jae Seog Hyun Deok Ha Seo Chunwoo Lee Sung Chul Kam Ky Hyun Chung Jeong Seok Hwa |
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MP84-09 |
Symptoms of Depression and Sexual Dysfunction |
Sexual Function/Dysfunction: Evaluation II | 17BOS |
Abstract: MP84-09 Sources of Funding: none Introduction Patient reported depression is a common data point on sexual health intake surveys. However, limited data are available on correlation between depressive symptoms and sexual dysfunction. We therefore sought to evaluate for relevant associations among a cohort of men presenting to a sexual health clinic with concomitant depressive symptoms. Methods We collected data on all consecutive men undergoing evaluation for sexual health concerns in a men's sexual health clinic between March 2014 and October 2016 at our institution. Detailed information was obtained on topics including relationships, libido, erectile dysfunction, premature and delayed ejaculation and International Index of Erectile Function (IIEF) scores. Data regarding pertinent medical, surgical and social history was also collected. Statistical analysis was performed to evaluate for significant associations between patients reporting depressive symptoms and information on other sexual dysfunctions. Results A total of 884 patients had data available on depressive symptoms and complete sexual function information. Of the cohort, mean IIEF scores were 29.3, and 207 (23%) endorsed depressive symptoms. Among patients reporting depressive symptoms, the most common presenting concerns included erectile dysfunction (75%), penile curvature (28%), low libido/hypogonadism (24%), low testosterone (20%) and ejaculatory dysfunction (10%)(>100% due to more than one concern permitted). Univariate analysis identified lower total IIEF scores (mean 25.9) in men with depressive symptoms compared to those without (mean 30.3, p=0.008). Interestingly, on subgroup analysis, depressive symptoms failed to significantly correlate with the erectile function domain (p=0.10), but did correlate with the orgasmic function (p<0.01), sexual desire(p<0.01), intercourse satisfaction (p<0.01), and the overall satisfaction domains (p<0.0001). Additionally, patients with depressive symptoms were more likely to report that their sexual dysfunction negatively impacted their relationships (p<0.01) and had significantly shorter relationships than those without similar symptoms (20.7 years vs. 25.3 years, respectively, p<0.01).Patients reporting depressive symptoms also reported significantly lower intercourse frequency per month (3.4 vs. 4.5, respectively, p=0.01). Conclusions Patients who reported depressive symptoms had significantly lower IIEF scores, including reduced orgasmic function, sexual desire, intercourse satisfaction, and overall satisfaction domains without significant differences in the erectile function domain. Additionally, these patients had shorter relationships, lower intercourse frequency and were more likely to report that their sexual dysfunction negatively impacted their relationships. These intriguing findings highlight novel areas of potential future research for the impact of mental health on sexual dysfunctions. Funding none
Authors
Jack Andrews M.D.
Matthew Ziegelmann M.D. Manaf Alom M.B.B.S Kevin Hebert M.D. Mary E. Westerman M.D. Landon Trost M.D. |
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MP84-10 |
Prevalence of Hormonal Abnormalities in Young Men with Erectile Dysfunction |
Sexual Function/Dysfunction: Evaluation II | 17BOS |
Abstract: MP84-10 Sources of Funding: None Introduction The risk of erectile dysfunction (ED) increases with age and typically occurs in middle and older aged men. Recently, we have experienced an increase in young men referred to our practice for ED, with many of these men also complaining of symptoms of low testosterone. Given the paucity of data on this subject, we sought to describe the hormonal profiles of young men with the chief complaint of ED. We hypothesize that the majority of young men with ED will have normal hormonal evaluations. _x000D_ Methods Institutional Review Board (IRB) approval was obtained for a retrospective chart review of men aged 18-40 years who presented with the complaint of ED and had a hormonal evaluation from January 2002-October 2016 at a tertiary care institution. We obtained data on demographics, co-morbidities, medications, and hormonal evaluations. Hypogonadism was defined as a testosterone level <200 ng/dL and hyperprolactinemia as a prolactin level >13.1 ng/mL. Results A total of 2,292 men were identified. The median age was 32.7 years with more men complaining of ED as they neared age 40 compared to younger ages. 42.9% of men were White, 8.6% Black or African American, 4% Asian, 0.9% Hispanic, and 43.6% other or unknown. Median BMI was 26.8. The most common comorbidities are listed in Table 1. Men were being actively treated for these medical conditions. Additionally, 9% of men were taking antihistamines, 6.10% using H2-receptor antagonists, and 9.9% taking muscle relaxants. _x000D_ _x000D_ The average total testosterone level was 368 ± 160 ng/dL. 10.6% of men had hypogonadism. Abnormalities of LH and FSH were noted in 10% and 9.1% of men, respectively. 8.5% of men had hyperprolactinemia. _x000D_ _x000D_ For treatment of ED, 68.7% of men were given a phosphodiesterase type 5 inhibitor (PDE5i) and 2.4% were given alprostadil. 12.9% of men were started on testosterone therapy. _x000D_ _x000D_ _x000D_ Conclusions The majority of men under age 40 with ED exhibit a normal hormonal milieu. Men of this cohort that endorsed symptoms of low testosterone may in fact be experiencing symptoms which could be attributed to life stressors or associated comorbidities such as depression, anxiety, or diabetes. Additionally, many men were using medications that have been linked to ED including antihypertensives, antihistamines, and H2-receptor antagonists. A majority of these men with ED were treated with a PDE5i. Funding None
Authors
Daniel J. Mazur
Barbara E. Kahn Mary Kate Keeter Anuj S. Desai Kevin Lewis Alexander J. Tatem Marah C. Hehemann Robert E. Brannigan Nelson E. Bennett |
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MP84-11 |
Calculated Free T and T:E Ratio but not Total Testosterone and Estradiol Predict Low Libido |
Sexual Function/Dysfunction: Evaluation II | 17BOS |
Abstract: MP84-11 Sources of Funding: None Introduction Libido is thought to be influenced by hormonal milieu, particularly testosterone. The role of estradiol in male sexual function has grown in importance, with estradiol cut- point of 5 ng/dL in hypogonadal men thought to directly affect libido. We sought to assess the impact of sex hormones on libido in a cardiac patient population. Methods 200 men in a cardiology practice completed IIEF-15, ADAM, and previous ED treatment questionnaires and had serum total testosterone (T), estradiol (E), and sex hormone binding globulin (SHBG) measured via morning lab draws. Free testosterone (CFT) was calculated using an online ISSM calculator. Patients previously treated for hypogonadism or who were on medications that could affect T were excluded. Answers to IIEF questions 11 and 12 (IIEF11, IIEF12), which concern libido, on a 5-point Likert scale were compared with hormone levels. Spearman correlations and multivariate logistic regression were performed to analyze end points. Results Mean total T was 310 ng/dL, CFT was 5.4 ng/dL, mean E was 4.4 ng/dL, mean T:E ratio was 8.2. 55% of subjects had T < 300 ng/dL. 74% of subjects had CFT < 6.5 ng/dL. Negative correlation was found between estradiol and IIEF11 and IIEF12, which did not reach statistical significance (p=0.08). Positive correlation was found between IIEF11 and IIEF12 and CFT and T:E ratio (p=0.007, p=0.009) At a cutoff of E=5ng/dL, no difference was found for either hypogonadal or eugonadal men on IIEF11 or IIEF12 (p=0.50, p=0.71). Conclusions Only CFT and T:E ratio were predictive of positive libido response on IIEF11 & 12 questionnaire in our cohort. Estradiol, even at a cutoff of 5 ng/dL, was not independently associated with improved libido. Surprisingly total testosterone did not associate with IIEF11 (desire frequency). The effect of testosterone and estradiol administration on libido requires further prospective study. Funding None
Authors
Nikhil Gupta
Bradley Holland Georgia Mueller Tobias Köhler |
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MP84-12 |
DOES CALCULATED FREE TESTOSTERONE OVERCOME TOTAL TESTOSTERONE IN PROTECTING FROM SEXUAL SYMPTOMS IMPAIRMENT? FINDINGS OF A CROSS-SECTIONAL STUDY |
Sexual Function/Dysfunction: Evaluation II | 17BOS |
Abstract: MP84-12 Sources of Funding: none Introduction Erectile dysfunction (ED) has been associated to lower serum total testosterone (TT) levels. The utility of free T over TT is debatable. Calculated empirical estimates of free testosterone (cFT) also are commonly used and accepted. We aimed to assess the relative impact of low TT and low cFT on androgen-related sexual symptoms in men with ED as a primary compliant. Methods Data from 485 consecutive men were analysed. Comorbidities were scored with the Charlson Comorbidity Index (CCI). Patients completed the International Index of Erectile Function (IIEF) and the Beck's inventory for Depression (BDI). Descriptive statistics tested the differences between the referent group of patients with normal TT (defined as TT>3ng/ml according to the Endocrine Society) and normal cFT (>0.065 ng/ml) (Group 1) with those who had normal TT/low cFT (Group 2); low TT/normal cFT (Group 3); and, low TT/low cFT (Group 4). Logistic regression models tested the association between clinical predictors and pathologic psychometric scores. Results Overall, 338 (69.6%), 44 (9.1%), 34 (7.0%) and 69 (14.3%) patients were in Group 1, 2, 3 and 4, respectively. Compared to Group 1, Group 2 patients were older (p<0.001), had higher BMI (p<0.01) and a greater proportion of CCI>=1 (p=0.006). Likewise, Group 2 presented lower IIEF-EF (p=0.07), IIEF-SD (p=0.04), IIEF-OF (p=0.007) and lower BDI scores (p=0.02) than Group 1. Similar findings were found for Group 4 vs. Group 1. Conversely, Group 3 patients were older (p<0.001) than in Group 1, but had similar psychometric scores. At multivariable analysis, low cFT, either with normal or low TT, achieved independent predictor status for pathologic IIEF domains and BDI scores, after accounting for age, CCI, and BMI. Conversely, low TT/normal cFT was not associated with pathological psychometric scores. Conclusions Low cFT, even with normal TT, was associated with a worse clinical profile and impaired sexual and depressive parameters compared to normal TT/normal cFT in a cohort of ED patients. Of clinical relevance, normal cFT, irrespective of low TT, was not associated with signs and symptoms suggestive for testosterone deficiency. Funding none
Authors
Luca Boeri
Paolo Capogrosso Eugenio Ventimiglia Walter Cazzaniga Filippo Pederzoli Davide Oreggia Nicola Frego Donatella Moretti Franco Gaboardi Emanuele Montanari Vincenzo Mirone Francesco Montorsi Andrea Salonia |
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MP84-13 |
Risk Factors for Erectile Dysfunction in a Population Based Cohort |
Sexual Function/Dysfunction: Evaluation II | 17BOS |
Abstract: MP84-13 Sources of Funding: None Introduction Multiple disease states and medications have been correlated with erectile dysfunction, however, few studies have evaluated risk factors in a population-based model. We sought to evaluate risk factors for erectile dysfunction using a population-based database. Methods The Olmstead County Study of Urinary Symptoms and Health Status among Men represents a prospective, ongoing study of men aged 40 and older and living in Olmsted County, Minnesota. The database includes detailed information on demographics, laboratory testing, medications, and comorbid conditions as well as assessments of erectile function using the Brief Male Sexual Inventory (BMSI) beginning in 2002. Men without a sexual partner or those with prior pelvic surgery were excluded. Univariate and multivariate analyses were performed of medical conditions and medication use to assess relationships with BMSI scores. Additional models were used to compare the impact of severity of disease as indirectly measured by the number of medications used for that condition (i.e. hypertension with one, two, three, or more medications) Results 937 men met inclusion criteria, with a mean age of 61 years (SD 8.7). Mean BMSI score was 7.4 (3.6). Univariate analysis demonstrated age, hypertension, hyperlipidemia, diabetes, chronic kidney disease, myocardial infarction (MI), stroke, coronary artery disease (CAD), and benign prostatic hyperplasia were all associated with lower BMSI scores (p<0.05). When controlling for all significant univariate risk factors, only age (parameter estimate [PE] -0.2/year over age 40), cardiovascular disease (MI, stroke, CAD; PE -0.7), diabetes (PE -0.7), insulin (PE -2.0), and beta-blocker use (PE -0.6) maintained significance (p<0.05). In terms of equivalence for factors contributing to erectile dysfunction, this data suggests that cardiovascular disease is equivalent to 3.5 years of aging, diabetes to 3.5 years of aging, insulin use to 10 years of aging, and beta-blocker use to 3 years of aging. Conclusions Multiple risk factors are associated with erectile dysfunction. This data can help guide patient counseling regarding modifiable risk factors in the hopes of delaying erectile dysfunction over time. Funding None
Authors
George Bailey
Joshua Piotrowski Tanner Miest Francisco Maldonado Ziegelmann Matthew Brian Montgomery Landon Trost |
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MP84-14 |
The relationships between lifestyle and testosterone; Night waking, smoking history, drink habit and the length of time using internet and playing games are associated with testosterone level |
Sexual Function/Dysfunction: Evaluation II | 17BOS |
Abstract: MP84-14 Sources of Funding: none Introduction Evaluation and treatment of men with low testosterone have become an important part of urological practice. However prevalence of symptoms associated with low testosterone in healthy men especially aged <50 years were still unclear. We have reported the association between testosterone levels and symptoms related to low testosterone using aging male symptom score (AMS score) in healthy young men. Also the association between lifestyle and testosterone level in healthy young men was still unclear. The objective of this study was to examine the association between lifestyle and total testosterone levels in healthy young and elderly adult. Methods This study included 1557 healthy men who were working for our university and taking annual medical check-up between the ages of 22-73; 145 in 20&[prime]s, 582 in 30&[prime]s, 446 in 40&[prime]s, 291 in 50&[prime]s and 93 over 60. Serum testosterone was measured by electro-chemiluminescence immunoassay. The number of waking time during night, smoking history, drink habit, the length of time using the internet and playing game, the times of night shift per month and the number of taking breakfast per week were obtained from questionnaire. Each items were dichotomized into more than one time night waking and none, having smoking history and none, drinking every day and not every day, more than thirty minutes and less, more than five times night shift and less, taking breakfast every day and not every day, respectively. The relationships between testosterone and lifestyles were analyzed by locally weighted linear regression. Results More than one time waking up during night, the habit drinking every day, having smoking history were related to lower testosterone level. About the length of time using internet and playing game, there was the relationship that lower testosterone was related to low probability of using internet more than thirty minutes (Figure). There was no relationship between testosterone level and the times of night shift per month and the number of taking breakfast per week. Conclusions Lifestyles such as internet use, night waking, drinking habit and smoking in healthy young and elderly adults are associated with testosterone levels. Funding none
Authors
Shinichiro Fukuhara
Norichika Ueda Tetsuji Soda Hiroshi Kiuchi Yasushi Miyagawa Akira Tsujimura Norio Nonomura |
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MP84-15 |
A New Method of Quantitatively Measuring Penile Erection Hardness in Erectile Dysfunction Patients: Real-Time Ultrasonic Shear Wave Elastography |
Sexual Function/Dysfunction: Evaluation II | 17BOS |
Abstract: MP84-15 Sources of Funding: none Introduction Penile erection hardness (EH), according to the Erectile Hardness Grading Scale (EHS), is an important indicator for evaluating penile erectile function. In this study, we provided a new method of real-time quantitative measurement of penile EH for erectile dysfunction (ED) patients using ultrasonic shear wave elastography (SWE). Methods Sixty ED patients diagnosed using the IIEF-5 questionnaire and the presence of nocturnal penile tumescence underwent real-time SWE to measure Young's modulus of the penile corpus cavernosum and albuginea while resting and at various grades of EH. Prostaglandin injection into the corpus cavernosum was used to induce penile erection. Results Young's modulus for the corpus cavernosum (resting) and EH grades 1, 2, 3, and 4 were, ?12.16±1.97?kPa,(10.97±1.98)kPa?(9.06±1.71)kPa?(9.38±1.68)kPa?(9.36±1.34)kPa respectively; Corresponding Young's modulus values for the albuginea (resting) and EH grades 1, 2, 3, and 4 were?21.97±4.68?kPa??32.71±3.71?kPa??54.12±10.09?kPa ??127.81±18.10?kPa ??223.99±26.73?kPa respectively. These Young's modulus values were grouped respectively to draw the receiver operating characteristics curve. The area under the albuginea curve was significantly better than that of the cavernosum (?2 = 61.10). Cutoff point of albuginea at grade 3 hardness was 81.60kPa. Conclusions Quantitatively measuring Young's modulus of penile albuginea using SWE is a novel, noninvasive, objective technique for quantitatively assessing the EH of ED patients. We proved that albuginea hardness, not cavernous tissue hardness, was a good clinical imaging index for penile EH evaluating. Funding none
Authors
Lin Yang
Hao Cheng Litao Ruan |
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MP84-16 |
Baseline Characteristics of Young Men with Erectile Dysfunction: A Single Center Experience |
Sexual Function/Dysfunction: Evaluation II | 17BOS |
Abstract: MP84-16 Sources of Funding: none Introduction Young men presenting with a chief complaint of erectile dysfunction (ED) present a unique challenge to the practicing urologist. The aim of this study was to evaluate the baseline characteristics of a cohort of young men who presented with ED. Methods A list of 185 men from a single urology practice was generated by using a diagnosis code of erectile dysfunction and excluding all men over the age of 40 and men with Peyronie&[prime]s Disease. These men were asked to fill out a detailed survey about their erectile health and medical history, including an International Index of Erectile Function (IIEF) score, on their initial evaluation. 73 men completely filled out this survey. Results The mean age in this series was 32 years (range 18-40). 62/73 (85%) reported problems obtaining an erection while 72/73 (98%) reported problems maintaining an erection. 21/73 (29%) associated the onset of their ED with a specific event such as surgery, injury, relationship difficulties, or an illness in themselves or a family member. 47/73 (64%) men experienced morning erections. 26/73 (36%) reported diminished desire. 72/73 (98%) were able to ejaculate, but 20/73 (27%) complained of premature ejaculation. Overall, 52/73 (71%) were able to produce an erection firm enough for penetration under some circumstances. 46/73 (63%) were in a relationship, and 36/73 (49%) had previously been treated for ED prior to presentation. 3/73 (4%) men had vascular risk factors for ED and 4/73 (5%) men were diabetic. 46/73 (63%) had never smoked, 11/73 (15%) were former smokers, and 13/73 (18%) were current smokers. On average, IIEF scores were in the mild to moderate range for erectile function, orgasmic function, sexual desire, and intercourse satisfaction. Overall satisfaction, however, was in the moderate range. See Graph 1._x000D_ Conclusions There is a limited amount of data on young men with ED. We have collected baseline data on a cohort of these men. Their presentations can vary, but the most common complaint is inability to maintain an erection. The vast majority of these men lack traditional risk factors for ED. An understanding of the baseline characteristics of these patients will be critical to evaluating the efficacy of treatment strategies in this population. Funding none
Authors
Peter Tsambarlis
Mark Ehlers Adam Wiggins Laurence Levine |
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MP84-17 |
Exploring The Association Between Obstructive Sleep Apnea And Venous Leak |
Sexual Function/Dysfunction: Evaluation II | 17BOS |
Abstract: MP84-17 Sources of Funding: none Introduction Literature supports a bi-directional relationship between obstructive sleep apnea (OSA) and erection dysfunction (ED). The Eppworth Sleepiness Scale (ESS) is used to make a clinical diagnosis of OSA. The fragmentation of sleep and loss of REM sleep in OSA has been purported to lead to venous leak. No study has to date addressed the link between OSA and the presence of venous leak (VL). Methods Patients who had ED, completed the international index of erectile function (IIEF) and underwent a penile duplex Doppler ultrasound constituted the study group. All completed the ESS. A score of >10 was used to define OSA and >16 severe OSA. All PDDU studies were done using a redosing injection agent schedule. Peak systolic velocity (PSV) >30cm/s and end diastolic velocity (EDV) <5cm/s were considered normal. Comorbidity and erectile hemodynamics data were recorded. Data were compared between those with and without OSA. Pearson correlation coefficient was generated for he association between IIEF and ESS scores. Multivariable analysis was performed to define predictors of VL in the study cohort. Potential predictors included: patient age, diabetes, number of vascular comorbidities, history of radical prostatectomy (RP) and ESS. Results 758 patients were included in the study. 91 (12%) men has an ESS>10 indicating OSA. Mean age: OSA 62±13 vs non-OSA 64±19 years (p=0.03). Vascular comorbidity profile between the 2 groups was similar except for: coronary artery disease 17% vs 11% (p=0.03); BMI 29±6 vs 22±1 (p=0.015); RP history 16% vs 23% (0.02). The percentage of men with abnormal PSV: 26% vs 17% (p<0.01); abnormal EDV 17% vs 4% (p<0.01). There was a good correlation between IIEF erectile function domain score and ESS (r=0.72). Predictors of the presence of VL are shown in the table. Conclusions There is a clear association between OSA and ED with greater degrees of OSA translating into poorer erectile function. OSA is a predictor of the presence of VL. Funding none
Authors
Patrick Teloken
Eduardo Miranda Coskun Kagacan John Mullhal |
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MP84-18 |
Erectile dysfunction after prostatic radiotherapy: why measurement matters, a systematic review and meta-analysis |
Sexual Function/Dysfunction: Evaluation II | 17BOS |
Abstract: MP84-18 Sources of Funding: None Introduction Rates of erectile dysfunction (ED) following the treatment of prostate cancer with radiotherapy (RT) vary. Pooled estimates of ED after RT will promote accurate patient counseling and shared decision-making. We systematically evaluated the development of ED in potent men after prostate RT. Methods We performed a critical review of PubMed/Medline, Embase, the Cochrane Library, and Web of Science in April 2016 according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. We identified prospective measures of ED before and after prostate RT. 278 abstracts were screened and 105 publications met the criteria for inclusion. Only men who were potent before RT were included in the analysis. We used meta-regression to determine associations with ED. Results In total, 17,057 men underwent brachytherapy (BT) (65%), 8,166 men underwent external beam radiation therapy (EBRT) (31%), and 1046 men underwent BT + EBRT (4%). The median follow-up time for all studies was 3 years (range 0.2-15 years). Seven common instruments were used to measure ED, with 23 different cut-offs for ED. The Sexual Health Inventory for Men (SHIM) was used in 31 studies (30%). Pooled estimates of SHIM-confirmed ED (<10-17), suggest the prevalence of ED after RT is 34% of men (95% confidence interval, CI 0.29-0.39) at 1 year, 39% (95% CI 0.33-0.44) at 2 years, 44% (95% CI 0.34-0.53) at 3 years, and 57% (95% CI 0.53-0.61) at 5.5 years. After controlling for median age in the study and percent of patients on androgen deprivation therapy, meta-regression showed that compared to BT alone, BT+EBRT increased the proportion of men with ED by 12.5% (95% CI 0.01-0.24). No differences were observed in the proportion of men with ED between studies of BT and EBRT. As the loss to follow-up increased by 10% within any of the studies, on average, the proportion of men with ED increased by 2.3% (95% CI 0.6-4.8). Conclusions Measurements of ED vary significantly in published series following RT. ED is common regardless of RT modality. Using the most objective measures, ED is found in approximately 50% of previously potent patients at 5 years. Loss to follow-up in studies may bias the results to overestimate ED. Funding None
Authors
Thomas Gaither
Mohannad Awad E. Charles Osterberg Gregory Murphy Isabel Allen Albert Chang Raymond Rosen Benjamin Breyer |
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MP84-19 |
Bother Associated With Climacturia After Radical Prostatectomy: Prevalence, Degree And Predictors |
Sexual Function/Dysfunction: Evaluation II | 17BOS |
Abstract: MP84-19 Sources of Funding: PB was supported by The Frederick J. and Theresa Dow Wallace Fund of the New York Community Trust. Introduction While erectile dysfunction (ED) and incontinence are well-understood complications of radical prostatectomy (RP), climacturia remains under-appreciated despite its prevalence in this population. Clinical experience suggests that many men and partners are bothered by this RP sequela. Our objective was to characterize and define predictors of climacturia-associated bother in men and their partners after RP. Methods The study was a retrospective review of all men presenting to a single center for management of sexual dysfunction following RP. Patients were queried on various domains of sexual dysfunction including ED, orgasmic and ejaculatory dysfunction, sexual incontinence, and penile deformity. Patients were specifically asked to quantify the amount and frequency of climacturia as well to report their level of bother and to quantify the degree of partner bother. Predictors of bother in patients with climacturia were determined using multivariable analysis (MVA). Results 252 patients post-RP were included. Mean patient and partner ages were 60±8 years and 55±9 years, respectively. 81% of patients were white and 82% of patients were in stable relationships with a mean duration of 24±14 years. 59% of patients reported at least one occurrence of climacturia. Significantly more men reported bother related to climacturia than partner bother related to OAI (39% vs 13%, respectively; RR=2.95, 95% CI: 2.29-3.80, p<0.01). Patient and reported partner bother were related (r=0.31, p<0.001). Both patient and partner bother were negatively related to length of relationship (r=-0.14, p=0.05; r=-0.18, p=0.02). In MVA predicting patient bother, only perceived partner bother remained significant (OR=4.49, 95% CI: 1.64-12.27, p<0.01). In MVA predicting reported partner bother, both patient bother (OR=4.49, 95% CI: 1.64-12.27, p<0.01) and duration of relationship (OR=0.96, 95% CI: 0.92-1.00, p=0.05) were significant predictors. Conclusions Climacturia is highly prevalent (59% of men) and bothersome in men and their partners following RP. While patient and partner bother from climacturia are related and more commonly seen in shorter relationships, patients are more bothered by climacturia than are their partners. Physicians treating patients with RP should both counsel patients about climacturia pre-operatively and specifically inquire about climacturia post-operatively. Funding PB was supported by The Frederick J. and Theresa Dow Wallace Fund of the New York Community Trust.
Authors
Phil V. Bach
Eduardo P. Miranda Lawrence C. Jenkins Christian J. Nelson John P. Mulhall |
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MP84-20 |
Relation between seventeen symptom of Aging Male Symptoms rating scale and serum concentration of IGF-1, DHEA-S, cortisol and testosterone in patients with late onset hypogonadism |
Sexual Function/Dysfunction: Evaluation II | 17BOS |
Abstract: MP84-20 Sources of Funding: none Introduction The concept of late-onset hypogonadism (LOH), defined as “a clinical and biochemical syndrome associated with advancing age and characterized by typical symptoms and a deficiency in serum testosterone levels,” has recently gained increased attention. However, it is already apparent that there are many eugonadal patients who complain of LOH symptoms, that are erectile dysfunction ED in sexual dysfunction, changes in mood and depression, sleep disturbances, decrease in lean body mass, increase in visceral fat, decrease in body hair and skin alterations, and decreased bone mineral density. The study regarding the relation between seventeen symptom of Aging Male Symptoms rating scale (AMS) questionnaire and serum hormonal profiles has not been fully understood. Methods The study comprised 896 outpatients (mean age, 50.2 ± 10.6 years) who visited our clinic with symptom of LOH. The total score of AMS questionnaire was 40.9 ± 11.8. We measured serum concentration of insulin-like growth factor-1 (IGF-1), dehydroepiandrosterone sulfate (DHEA-S), cortisol and total testosterone as the endocrinologic examination and assessed LOH symptom by AMS questionnaire. The associations between seventeen symptoms of AMS and hormonal profile were evaluated by multivariate linear regression model after adjustment for age._x000D_ RESULTS: Significant association was found in question 3 (P=0.049), 7 (P=0.007), and 11 (P=0.010) in IGF-1, only question 2 in DHEA-S (P=0.035), question 6 (P=0.023), 8 (P=0.002), 10 (P=0.002), and 15 (P=0.022) in cortisol, and only question 17 (P=0.033) in testosterone, respectively._x000D_ Results Significant association was found in question 3 (P=0.049), 7 (P=0.007), and 11 (P=0.010) in IGF-1, only question 2 in DHEA-S (P=0.035), question 6 (P=0.023), 8 (P=0.002), 10 (P=0.002), and 15 (P=0.022) in cortisol, and only question 17 (P=0.033) in testosterone, respectively. Conclusions Serum testosterone concentration is only associated with question 17 (Decrease in sexual desire/libido). Other endocrinologic examinations such as IGF-1, DHEA-S and cortisol may be necessary for the diagnosis of LOH. Funding none
Authors
Akira Tsujimura
Ippei Hiramatsu Yusuke Aoki Hirofumi Shimoyama Taiki Mizuno Taiji Nozaki Masato Shirai Yoshiaki Kumamoto Kazuhiro Kobayashi Shigeo Horie |
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MP85-01 |
Roles of nerve growth factor in bladder storage dysfunction due to detrusor overactivity in spinal cord injured mice – analysis of time-dependent responses |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Neurogenic Voiding Dysfunction I | 17BOS |
Abstract: MP85-01 Sources of Funding: NIH P01 DK093424 Introduction We previously reported the urodynamic effect of 1-week anti-nerve growth factor (NGF) treatment in mice with spinal cord injury (SCI), but failed to show the reduction in NGF expression in the bladder (2016 AUA). Therefore, we investigated the time-dependency of the efficacy of anti-NGF treatment in SCI mice. Methods SCI was induced by Th8/9 spinal cord transection in female C57BL/6N mice. SCI mice were divided into 3 groups. Group A did not receive any treatments. Groups B and C respectively received 1-week and 2-weeks anti-NGF antibody treatments (10µg/kg/hr) using an osmotic pump placed subcutaneously before the final evaluation. Four weeks after SCI, animals were evaluated using single-filling cystometry under an awaken condition. NGF levels in the bladder and spinal cord were measured, and the mRNA expression of P2X2, P2X3, TRPA1 and TRPV1 was also evaluated in L6/S1 dorsal root ganglia (DRG). Results There were no significant differences in micturition pressure, threshold pressure, voided volume, post-void residual, bladder capacity or voiding efficiency among 3 groups. The number of non-voiding contractions (NVCs) per a voiding cycle in groups B and C were significantly lower than that of group A. NGF levels of the bladder mucosa and spinal cord of SCI mice (group A) were significantly increased compared with spinal intact mice. Two-weeks (group C), but not one-week (group B), anti-NGF treatment significantly decreased bladder mucosal and spinal NGF expression. The mRNA levels of TRPA1 and TRPV1 were increased in SCI mice compared to spinal intact mice, and significantly decreased after both 1 week and 2 weeks of anti-NGF treatment. Conclusions One-week and 2-week treatments similarly improved NVCs in association with the reduction of the expression of TRPA1 and TRPV1 in L6/S1 DRG although 2-weeks anti-NGF treatment was required to significantly decrease bladder mucosal and spinal NGF. Thus, NGF overexpression is likely to play a significant role in storage dysfunction to induce DO in SCI mice. Funding NIH P01 DK093424
Authors
Naoki Wada
Takahiro Shimizu Nobutaka Shimizu Pradeep Tyagi William de Groat Anthony Kanai Hidehiro Kakizaki Naoki Yoshimura |
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MP85-02 |
Aberrant bladder reflexes can drive hind limb locomotor activity following complete suprasacral spinal cord injury |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Neurogenic Voiding Dysfunction I | 17BOS |
Abstract: MP85-02 Sources of Funding: This work was funded by a grant from the VA RRD SPiRE RX-001749-01 Introduction Many rats with chronic suprasacral spinal cord injury (SCI) demonstrate hind limb locomotor activity (HLLA) in response to external crede or high pressure contractions during cystometry. We propose that this aberrant, pressure-driven bladder reflex pathway may be harnessed to facilitate walking in SCI patients. As a first step in exploring this possibility, we examined the relationship between intravesical pressure (IVP) and HLLA in chronic suprasacral SCI rats. Methods Female rats (4 weeks post-SCI at T9-10, n=16) were anesthetized with isoflurane and fitted with transvesical catheters and right quadriceps EMG electrodes to monitor bladder and hind limb locomotor activities, respectively. The animals were mounted in Ballman restraint cages to which they had been previously acclimated. The catheter was connected to a pressure transducer, an infusion pump, and a saline-filled reservoir mounted on a metered vertical pole (pressure clamp). After 30 min of recovery from anesthesia, the bladder was filled at 0.1 ml/min with saline to verify bladder-to-bladder reflex activity for 30 min. IVP was then increased in an interrupted stepwise fashion from 0-120 cmH2O at 10 cmH2O increments. Each step consisted of five minutes: 3 minutes at the new pressure followed by 2 minutes at 0 cmH2O. IVP and the number of HLLA events (as defined by rhythmic EMG discharges of 3-10 cycles/event) were recorded for each pressure step. This process was repeated for two more trials for each rat to assess the durability of the reflex. Data were analyzed using ANOVA with repeated measures both within and across pressure escalation trials. P<0.05 was considered significant. Results ANOVA revealed that locomotor events increased with increasing intravesical pressure and decreased with the number of escalation trials (P<0.0001 for both effects). The increase in the number of locomotor events with increasing intravesical pressure appeared to plateau at ~50-60 cmH2O (P<0.05 for all). The average of the maximal number of locomotor events for each animal decreased steadily from ~3.0, 2.5 and 1.75 over the three trials. Conclusions There is a positive relationship between IVP and HLLA that suggests the emergence of an aberrant bladder-to-hind limb locomotor reflex pathway following SCI. It may be possible to harness this reflex pathway independently of the state of the bladder to facilitate walking in SCI patients. Funding This work was funded by a grant from the VA RRD SPiRE RX-001749-01
Authors
Brian M. Inouye
Jillene M. Brooks Danielle J. Degoski Francis M. Hughes Jr. J. Todd Purves Matthew O. Fraser |
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MP85-03 |
The therapeutic effect of TRPV4 activation in the bladder on underactive bladder in rats with pelvic nerve crush |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Neurogenic Voiding Dysfunction I | 17BOS |
Abstract: MP85-03 Sources of Funding: none Introduction Incomplete bladder emptying due to detrusor underactivity (DU) is a significant urological problem underlying underactive bladder (UAB). Also, TRPV4 has been reported to be one of the mechanosensitive channels expressed in the bladder. In this study, we sought to produce a consistent rat model of UAB with the modification of our previous model of pelvic nerve crush (PNC) (2016 AUA) and evaluated the therapeutic effect of intravesical application of a TRPV4 agonist on the UAB condition. Methods In female Sprague-Dawley rats, the visceral branches of bilateral pelvic nerves were identified near the internal iliac vessels and bilateral PNC was made by two times of nerve compression of either side with each 20-seconds duration using sharp forceps. After 10 days, awake cystometrograms (CMG) were recorded in sham control and PNC rats. Then, in both groups, a TRPV4 agonist (GSK1016790A) was continuously administered into the bladder and the CMG parameters were compared before and after intravesical drug administration. Results The bladder weight was significantly increased in PNC rats vs. control rats. In CMG, PNC rats showed significant increases in voided volume, post-void residual urine volume, and residual urine rate compared to control rats. PNC rats also revealed the significant increases in intercontraction intervals (ICI), a number of non-voiding contractions, and threshold pressure while the amplitude during voiding was significantly decreased (table). In the TRPV4 administration study, intravesical application of 1.5µM of GSK 1016790A significantly decreased ICI, voided volume, and post-void residual urine volume in PNC rats while it did not significantly affect any CMG parameters in control rats._x000D_ _x000D_ Conclusions Rats with pelvic nerve injury induced by the modified PNC method, which showed the characteristics of DU, seem to be an appropriate model for evaluation of peripheral neurogenic mechanisms of UAB. Also TRPV4 that reduced the bladder capacity and residual urine volume could be a potential target for the treatment of UAB. Funding none
Authors
Ei-ichiro Takaoka
Shun Takai Takahisa Suzuki Nobutaka Shimizu Joonbeom Kwon Hiroki Okada Hiroyuki Nishiyama Naoki Yoshimura Christopher J. Chermansky |
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MP85-04 |
Development of an Underactive Syndrome of Pelvic Targets in Long-Term Studies after a Unilateral Avulsion Injury of Lumbosacral Ventral Roots in Rhesus Macaques |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Neurogenic Voiding Dysfunction I | 17BOS |
Abstract: MP85-04 Sources of Funding: LAH (California Institute for Regenerative Medicine RT3-07616; Department of Defense SC090273; Adelson Medical Research Foundation; NIH P51 OD011107); HHC (NIH DK106181) Introduction A conus medullaris syndrome results from an Injury to the conus medullaris and cauda equine portions of the spinal cord. The clinical presentation is characterized by a lower motor neuron weakness affecting both skeletal muscles and pelvic organs with signs of paralysis, sensory disturbance and impairments of bladder, bowel, and sexual functions. The goal of the present study was to translate the unilateral lumbosacral ventral root avulsion (VRA) injury model from the rat to rhesus macaques, and to determine early and late effects of pelvic target denervation on lower urinary tract and external anal sphincter (EAS) function. Methods A total of 6 female rhesus macaques were included. A unilateral L6-S3 VRA injury was performed and resulted in a lesion of all preganglionic parasympathetic fibers of the ipsilateral pelvic nerve and all somatic motor fibers of the ipsilateral pudendal nerve. Urodynamic studies and EAS electromyography (EMG) were performed under ketamine anesthesia in control subjects (n=6), and at 1 month and 6 months after the unilateral VRA injury (n=4). Results The bladder infusion rate was between 85 and 120 mL/min to partially fill the bladder and induce reflex voiding. Poor voiding efficiency and compliance, and a slower urine flow rate were found in VRA subjects. The EAS guarding reflex was tested using a rectal probe. The maximum amplitude and area under the curve of EAS EMG were significantly decreased at 1 month after injury, but recovered at 6 months. Power spectrum (Fig. 1) showed that the peak frequency increased at 1 month after injury, but it was reduced to normal state at 6 month. The mean frequency was decreased at 1 and 6 months after injury. Conclusions This model eliminated the parasympathetic fibers of pelvic nerve and the somatic motor fibers of pudendal nerve, which resulted in detrusor underactivity and poor EAS contractility. Power spectrum analysis indicated that fewer motor units fired during EAS contraction after injury. This model in rhesus macaques mimics the clinical phenotype of conus medullaris syndrome using a lumbosacral VRA injury approach in long-term studies. It may provide a useful model to test the utility of emerging treatments after denervation of pelvic targets. Funding LAH (California Institute for Regenerative Medicine RT3-07616; Department of Defense SC090273; Adelson Medical Research Foundation; NIH P51 OD011107); HHC (NIH DK106181)
Authors
Huiyi Harriet Chang
Jih-Chao Yeh Robecca Do Jaime H Nieto Kari L Christe Leif A. Havton |
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MP85-05 |
Long-term follow-up reveals differential phenotypes of neurologic impairment and bladder function in a murine model of neurodegeneration |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Neurogenic Voiding Dysfunction I | 17BOS |
Abstract: MP85-05 Sources of Funding: This work was supported by P20 DK097819 grant (to A.M.P.), and AUA Scholar Award (to S.L.). Introduction Patients with multiple sclerosis (MS) develop a variety of lower urinary tract (LUT) symptoms. We recently characterized a murine model of coronavirus-induced encephalomyelitis (CIE model), and confirmed that CIE mice develop neurogenic bladder dysfunction that was comparable with neurogenic LUTS observed in MS patients. Identified mechanisms were morphological changes in the centers controlling micturition, spinal cord gliosis, and increased expression of pro-inflammatory cytokines. In the current study, we aimed to understand the long-term effects of neurodegenerative changes on micturition patterns and bladder physiology, as well as uncover the mechanisms of long-lasting neurogenic bladder dysfunction. Methods Adult C57BL/6J mice were inoculated with 20 µl of mouse hepatitis virus (MHV, N=44, CIE mice) or PBS (N=19). Neurological symptoms and mouse weight were recorded daily, and voiding behavior weekly up to 8 wks pi. Neurologic symptoms were evaluated by the Clinical Symptoms Score (CSS) on a scale from 0 (asymptomatic) to 4 (quadriparesis/paralysis). Detrusor contractility was evaluated in vitro at 10 wks. Based on CSS, CIE mice were assigned to 2 groups: recovery (REC group), and relapse (RELAP group). RELAP group was defined based on: (1) presence of symptom-free period at least for 24 hrs after initial rise in CSS, (2) presence of 2 symptom-free periods (24 h duration each), and (3) CSS>2 during the relapse. Results Long-term follow up of CIE mice revealed two different neurological phenotypes: 1-recovery from initial acute neurological impairment (REC, 73.5% of all CIE mice, N=25); and 2-relapse in symptoms (RELAP, 26.5% of all CIE mice, N=9). Eight percent of mice in REC group still had CSS≥2 at 8 wks in comparison to 22.2% in RELAP group. Animals in both REC and RELAP groups showed the most significant weight loss at 1wk. (22.3±0.28g at baseline vs 16.5±0.3g in REC group, and 9.2±0.86g in RELAP group, p<0.05). Isolated bladder strips from CIE mice did not have significant differences in muscarinic responses to EFS, however, RELAP group showed significantly decreased M3 responses along with increased micturition frequency at 5-6 wks. Conclusions Long-term follow up of CIE mice revealed two differential phenotypes of neurologic impairment mimicking two forms of MS in humans: relapsing-remissive MS and chronic inflammatory type of MS. Mice in RELAP group had a decreased response to M3 agonists suggesting that anti-muscarinic drugs may have limited effects on neurogenic bladder in this type of MS. Funding This work was supported by P20 DK097819 grant (to A.M.P.), and AUA Scholar Award (to S.L.).
Authors
Sanghee Lee
Balachandar Nedumaran Joseph Hypolite Randall Meacham Anna Malykhina |
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MP85-06 |
Brain Networks Controlling Bladder Filling and Voiding |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Neurogenic Voiding Dysfunction I | 17BOS |
Abstract: MP85-06 Sources of Funding: P20 DK103086 Introduction Lower urinary tract symptoms (LUTS) are common and poorly understood; treatment is often ineffective. Failure of neural control of bladder function likely contributes to LUTS symptoms in many patients. Prior studies have shown that the pontine micturition center (PMC) directly controls voiding. Within the PMC corticotropin releasing hormone neurons (PMCCRH) project axons directly to spinal sacral cord nuclei that control bladder contraction. Here we show that PMCCRH neurons are critical for voiding, and identify neurons, particularly in the ventrolateral periaqueductal gray (PAGVL) which directly modulate PMCCRH and alter voiding. Methods We inject adeno-associated viruses expressing proteins in a Cre-dependent fashion into anatomically defined regions of mice expressing Cre recombinase in specific neural types, to cause highly selective expression of these probes in target neuron populations. We monitor conscious voiding with micturition video thermography (MVT), and CMG under anesthesia while monitoring/stimulating specific neuron groups. Results Stimulating PMCCRH neurons using designer receptors exclusively activated by designer drugs (DREADDs) produces urinary frequency in awake mice and on anesthetized CMG. Also, ablating PMCCRH neurons by selective expression of diphtheria toxin A disrupts normal voiding and the normal CMG voiding reflex. To identify neurons which provide input to PMCCRH, we used modified rabies virus and cholera toxin B labeling of PMCCRH and confirmed our results with viral anterograde tracing. Afferents to PMCCRH are located in PAGVL, the preoptic area, the lateral hypothalamic area, and other sites. Because sacral afferents sensing bladder filling project to PAGVL we determined the impact of stimulating Glutamatergic or GABA-ergic neurons (PAGVLGLUT or PAGVLGABA) in this region. Chemogenetic or optogenetic stimulation of PAGVLGLUT neurons leads to voiding and detrusor contraction. By contrast, chemogenetic or optogenetic activation of PAGVLGABA inhibits voiding and delays detrusor contraction on CMG. Conclusions 1. PMCCRH are driver neurons for detrusor contraction/voiding. 2. PAGVLGLUT project to PMCCRH, and when fired drive voiding/detrusor contraction. 3. PAGVLGABA project to PMCCRH and inhibit voiding/detrusor contraction. PAGVL, which receives bladder-based sacral afferents, likely controls bladder filling, and is a potential target in efforts to control urge incontinence and urgency symptoms of LUTS. Funding P20 DK103086
Authors
Hanneke Verstegen
John Mathai Mark Zeidel Joel Geerling |
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MP85-07 |
Functional Neuroimaging of Urine Storage and Voiding in Mice |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Neurogenic Voiding Dysfunction I | 17BOS |
Abstract: MP85-07 Sources of Funding: P20 DK108276 Introduction Lower urinary tract symptoms (LUTS) are common and poorly understood; treatment is often ineffective. Failure of neural control of bladder function likely contributes to LUTS symptoms in many patients. Mice are continent and serve as excellent models of LUTS, in part because they can be manipulated genetically. To relate what is learned in mice to humans, we have developed functional MRI methods for mice which mirror those in humans. Such methods will allow us to compare directly the activation patterns of mouse and human brains during bladder filling and voiding, in normal and disease states. Methods Mice are anesthetized with urethane and a catheter is implanted in the bladder dome. Blood Oxygen Level Detection Magnetic Resonance Imaging (BOLD-MRI) is carried out in a Bruker 9.4T magnet with a 4 element mouse brain phased array coil. A series of 2D multislice gradient echo-planar images are acquired every 2s, while the mouse undergoes cystometry. 25 slices are acquired with slices of 500µm, interslice distance 600µm and in-plane resolution of 250µm. Imaging occurs over a 45 minute time frame during which the mouse undergoes 10-15 voiding cycles (CMG). Data are analyzed with Statistical Parameter Mapping (SPM12) software using mouse brain adaptations. Linear modeling proceeds in 2 stages; first by providing a statistical map of the brain of individual animals and second by combining results across all animals in a group. Results Preliminary results on female C57BL6/J (n =5) with a fixed effects analysis identified candidate regions across the brain with clear activation in the right Pontine Micturition Center (PMC) observed, which was confirmed by a region based random effects analysis. Negative contrast identified more extensive regions such as the periaqueductal gray and inferior colliculus with an indication that these regions are &[Prime]switched off&[Prime] during the transition to voiding. Conclusions Although technically challenging due to the small size, BOLD-MRI on mice is feasible and reveals regions of brain activation related to voiding cycles. Development of this technique along with fine mapping of brain circuits related to voiding will help define mechanisms of LUTS in mouse models that should be translatable to human disease. Funding P20 DK108276
Authors
Bryce MacIver
Aaron Grant Timothy Pagliaro David Alsop John Mathai Mark Zeidel |
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MP85-08 |
NON-SURGICAL MANAGEMENT OF DETRUSOR LEAK POINT PRESSURES ABOVE 40 CM H20 IN ADULTS WITH CONGENITAL NEUROGENIC BLADDER |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Neurogenic Voiding Dysfunction I | 17BOS |
Abstract: MP85-08 Sources of Funding: None Introduction Poorly compliant neurogenic bladders (NGB) with detrusor leak point pressures above 40 cm H2O (dLPP>40) have been associated with deterioration of renal function in children. As such, dLPP>40, despite clean intermittent catheterization (CIC) and anticholinergics, often mandates augmentation or diversion. While we recommend augmentation cystoplasty or diversion to appropriate patients, many elect for non-surgical management. Non-surgical management consists of rigorous urodynamic (UDS) and renal ultrasound (RUS) follow-up, paired with adjustments to CIC routine to keep bladder volumes below that volume at which dLPP>40, adjustments to anticholinergics, and intradetrusor botulinum toxin Type A (BTX). We describe the renal function outcomes of non-surgical management of adults with poorly compliant (dLPP>40) NGB. Methods We retrospectively reviewed the charts of all patients at our Gillette Lifetime adult congenital urology clinic undergoing UDS from January 2011 to June 2016. Patients with dLPP>40 who opted for non-surgical management were included; this study was noted as their &[Prime]index UDS&[Prime] for calculation of follow-up. The primary endpoint was deterioration of renal function as evidenced by change in chronic kidney disease (CKD) stage, progression to CKD-III, or new/worsening hydronephrosis. Results Of 210 patients who underwent UDS, 45 had dLPP>40. After exclusions for incomplete data (n=7) or augmentation cystoplasty (n=11), 27 were the subject of study. 15/27 (56%) were women and all 27 were Caucasian. Median age was 29 years (IQR 25, 35). 21 (78%) had NGB due to spina bifida. Median dLPP on index UDS was 47 cm H2O (IQR 42, 60). The most common interventions for dLPP>40 were adjustment to anticholinergics (n=17, 63%), modification of CIC schedule (n=14, 52%), and BTX (n=4, 15%). Last median follow-up was 1.2 years for repeat UDS, 2.5 years for glomerular filtration rate (GFR), and 2.4 years for RUS. There was a median 2.3 mL/min/1.73 m2 decrease in GFR (IQR -17, 7.5). No patients advanced their CKD stage. Repeat UDS demonstrated dLPP>40 resolved in 16/27 (59%) patients. New, mild hydronephrosis was seen in 1 patient. Conclusions At interim follow up of 2.4 years, a carefully tailored non-surgical treatment protocol for patients with NGB and dLPP>40 is safe and effective in patients with rigorous follow-up. Selecting patients for augmentation cystoplasty requires a balanced assessment of a multitude of patient-specific factors. Funding None
Authors
Giulia Lane
Ronak Gor Jenna Katorski Sean Elliott |
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MP85-09 |
Comparison of neurogenic lower urinary tract dysfunctions in open vs. closed spinal dysraphism : results observed in a prospective cohort of 395 patients |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Neurogenic Voiding Dysfunction I | 17BOS |
Abstract: MP85-09 Sources of Funding: French referral center for spina bifida Introduction Spinal dysraphism is the first congenital cause of neurogenic bladder. Open spinal dysraphism (mainly myelomeningocele) being in the vast majority of cases diagnosed in the neonatal period, neurogenic lower urinary tract dysfunctions (NULTD) it causes are well-known as they have been described for decades in many series. Conversely, closed spinal dysraphism is not always associated with cutaneous markers and are often diagnosed later in the patient's life thanks to modern imaging such as MRI. Hence, little data exist regarding NULTD due to closed spinal dysraphism._x000D_ The aim of this study was to compare the NULTD observed in patients with closed dysraphism (CD) to those observed in patients with open dysraphism (OD)._x000D_ Methods A prospective study was conducted between 2007 and 2016 including all spina bifida patients seen in a multidisciplinary national referral center. At the first visit, lower urinary tract function was assessed wether the patient reported lower urinary tract symptoms or not. This assessement included: history of past urological surgery, type of spinal dysraphism (open or closed), Abbreviated Injury Scale, method of bladder emptying, Urinary Symptom Profil (USP) and Qualiveen scores and urodynamic parameters. Quantitative variables were expressed as mean and standard deviation and categorical variables as numbers and proportions. Patients’ characteristics were compared using the Chi-2 test for categorical variables and the Mann-Whitney test for quantitative variables. Results Three-hundred and ninety-five patients were included : 274 with an OD (69.4%) and 121 had with a CD (30.6%). Patients in the CD group were older (35.9 vs. 29.5 years, p <0.0001), and had lower BMI (23.8 vs. 28 years, p = 0.0002). The method of bladder emptying was spontaneous voiding, clean intermittent catheterization and transileal cutaneous ureterostomy in 47.1% vs. 29.3% ; 47.1% vs. 59.4% and 5.7% vs. 11.2% of CD and OD patients respectively (p = 0.01). The prevalence of urinary incontinence did not differ significantly between the two groups (44.7% vs. 53.5%; p = 0.23), as well as the mean Qualiveen score (76.6 vs. 81.7 , p = 0.19). The main medical and / or social concern was NLUTD in 26% of patients with CD and in 27.8% of patients with OD (p = 0.73). Augmentation cystoplasty was more common in patients with OD (29.2% vs. 10.2%; p <0.0001) as was artificial urinary sphincter (13.2% vs. 4.6 %; p = 0.01) and continent cystostomy (10.2% vs. 0.9%, p = 0.002). Conclusions In this prospective cohort, NLUTD were as frequent and troublesome in patients with open vs. Closed spinal dysraphism. However the need for a surgical treatment of NLUTD was more common in patients open spinal dysraphism. Funding French referral center for spina bifida
Authors
benoit peyronnet
charlene brochard juliette hascoet magali jezequel nelly senal isabelle bonan alexis arnaud benjamin fremond jacques kerdraon helene menard laurent siprdouhis xavier gamé andrea manunta |
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MP85-10 |
High rates of admission seen with adult spina bifida patients presenting to the emergency room |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Neurogenic Voiding Dysfunction I | 17BOS |
Abstract: MP85-10 Sources of Funding: None Introduction The majority of spina bifida patients are now living to adulthood, but finding adult providers to care for these patients is a known transitional challenge. We evaluated the use of the emergency room (ER) by these patients, the presenting complaint, rates of admission, and admitting diagnosis._x000D_ Methods A retrospective review of all patients with a diagnosis of spina bifida (SB) and neurogenic bladder presenting to the Northwestern University Hospital ER from 2008-2015 was conducted. Information on chief complaint, admitting diagnosis, admission disposition, and imaging utilization was collected._x000D_ Results 231 patients were identified that met study criteria. The chief complaint was abdominal pain/nausea/vomiting/diarrhea in 33, headache/shunt issues in 30, skin issues or pressure sores in 25, chills/fevers of unknown origin in 22, urinary tract infection (upper or lower) in 22, back/flank pain in 16 (with known nephrolithiasis in 5), catheter issues in 13, chest pain/cough in 12, post-operative complications in 8, and dialysis complications in 7, with the remainder comprising a variety of complaints. Of the 231 SB patients, 199 (90%) were kept overnight, 179 (77%) for inpatient hospitalization and 13% for overnight observation. The most common admitting diagnoses were urinary tract infection, abdominal pain, cellulitis, and osteomyelitis. Of these 231 patients, 154 (68%) had a urine culture sent regardless of chief complaint._x000D_ Conclusions Adult spina bifida patients present to the emergency with varied chief complaints. The overwhelming majority are admitted for in-patient management. The most common chief complaints were abdominal pain, headache/shunt issues, and skin issues/pressure sores. The majority of patients had a urine culture sent despite often non-urologic chief complaints._x000D_ Funding None
Authors
Stephanie Kielb
Richard Matulewicz Oluwarotimi Nettey |
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MP85-11 |
Predictors of a Return of Volitional Voiding After Spinal Cord Injury |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Neurogenic Voiding Dysfunction I | 17BOS |
Abstract: MP85-11 Sources of Funding: None Introduction Impaired bladder function after spinal cord injury (SCI) is common, with over 75% of patients unable to volitionally void at the time of discharge from rehabilitation. A significant number of patients with SCI have dissatisfaction related to their bladder care and for many improving their bladder condition is more important than improving their motor function. The ability to predict a return to volitional voiding would be useful. Methods Data for the years 2000 to 2013 within the National Spinal Cord Injury Database was assessed. Each patient’s bladder management method was determined at discharge from inpatient rehabilitation and at 1-year followup. Patient variables most likely to affect return of volitional voiding were evaluated: patient age, gender, American Spinal Injury Association Impairment Scale (AIS) classification, presence of deep rectal sphincter sensation/contraction, lowest sensory level, and a composite bilateral lower extremity motor score for L2-S1 (range 0-50). Given the large variance between AIS A-D for voiding return, the models were run separately for each AIS classification. Results Of the 3307 persons evaluated, 681 (20.7%) were volitionally voiding at discharge from inpatient rehabilitation. This increased to 29.9% at 1-year followup. AIS classification and composite lower extremity motor score were the largest predictors of volitional voiding (p<.001) (Figure 1). Persons in the AIS A and B categories rarely had return of voiding at 1-year follow-up (1.4% and 4.5% respectively) as compared to AIS C and D (27.7% and 74.4% respectively). Several predictors of volitional voiding based on AIS Class were identified. For those with AIS C, younger age and higher composite lower extremity motor score were significant predictors of volitional voiding. These were also significant in the AIS D population, in addition to female gender and the combination of deep rectal sensory and motor function (as compared to sensory alone). Conclusions Volitional voiding after SCI is predicted well by AIS Class and lower motor extremity function composite score. In neurologically less impaired patients, female gender and the combination of deep rectal sensory and motor function also help to predict future voiding. Funding None
Authors
Dimitar V. Zlatev
Kazuko Shem Christopher S. Elliott |
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MP85-12 |
Urological management and complications in spinal cord injury patients: a 40- to 50-year follow-up study |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Neurogenic Voiding Dysfunction I | 17BOS |
Abstract: MP85-12 Sources of Funding: None Introduction To assess the management and types of urological complications in spinal cord injury (SCI) patients and to explore the risk factors for these complications. Methods 43 SCI patients with a median follow-up of 45 (range 40 to 50) years were included in this retrospective study (Table 1). All medical charts were reviewed for demographics, urological complications and bladder management. Results Recurrent urinary tract infection (UTI) was noted in all patients, with an average incidence of 6.1 cases/5-year per person. UTI incidence peaked in the 1st and the 10th 5-year intervals (Figure 1). After UTI, bladder stone occurred earliest with a median follow-up of 4 years, followed by autonomic dysreflexia (10 years) and urethral injury (10.5 years). Beside UTI the most common complications were: bladder stone (49%), hydronephrosis (47%), vesicoureteral reflux (33%). Most complications initially occurred during the first 25 years post injury. Male gender, cervical injury and condom catheter use were closely related to complications, particularly UTI and renal insufficiency. The bladder managements used for the longest period were condom catheter in males (79%) and clean intermittent catheterization in females (33%), with an average maintenance of 23.6 and 38 years, respectively. Conclusions With long follow-up, a wide and complex range of urologic complications occurred in SCI patients and continue to do so throughout the period of follow-up. A greater risk for urologic complications may be seen with certain factors (male gender, cervical SCI, condom catheter use); however, all patients with SCI are at risk for urinary complications over time. Thus, even long-term patients that are thought to be &[Prime]stable&[Prime] require regular follow-up and surveillance. Funding None
Authors
Yunliang Gao
Teresa Danforth David Ginsberg |
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MP85-13 |
Severity of lower urinary tract symptoms predict overall neurologic quality of life among patients with multiple sclerosis |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Neurogenic Voiding Dysfunction I | 17BOS |
Abstract: MP85-13 Sources of Funding: None Introduction Lower urinary tract symptoms, while common, are under reported in patients with multiple sclerosis. It is unclear what the impact of lower urinary tract symptoms due to MS is on the overall quality of life. We aim to define the incidence of lower urinary tract symptoms in patients with MS and their effect on neurologic quality of life. Methods We identified patients presenting to neurology clinic for routine follow up for multiple sclerosis. Each patient responded to validated questionnaires regarding urinary quality of life (MSQLI) and overall neurologic quality of life (NeuroQOL). Medical records were reviewed to assess for the presence of lower urinary tract symptoms. Overall neurologic quality of life was measured in the presence and absence of lower urinary tract symptoms and p-values were calculated using student&[prime]s t-test. Urinary quality of life score was correlated to overall neurologic quality of life score by calculating the Spearman&[prime]s rank correlation coefficient. Results 91 patients were included in the study. All 91 patients completed the validated questionnaires. 85 patients (93%) described the presence of at least one lower urinary tract symptom. The most common urinary tract symptoms were urgency (84%), frequency (69%), incontinence (54%), and retention (38%). 72 patients reported urologic symptoms negatively impacted urinary quality of life. Presence of lower urinary tract symptoms negatively impacted overall neurologic quality of life (Figure 1). Urinary quality of life was predictive of the overall neurologic quality of life (-0.24, p=0.02). Conclusions Lower urinary tract symptoms are very common in patients with multiple sclerosis. These symptoms greatly impact and importantly predict the overall neurologic quality of life in patients with multiple sclerosis. Funding None
Authors
Aleksandar Blubaum
Stephen Blakely Nicholas Westfall Augusto Miravalle Brian Flynn |
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MP85-14 |
Peristeen transanal irrigation system for the treatment of neuropathic bowel dysfunction and abdominal pain |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Neurogenic Voiding Dysfunction I | 17BOS |
Abstract: MP85-14 Sources of Funding: None Introduction Transanal irrigation of the rectum (TAI) and colon is designed to assist the evacuation of faeces fromthe bowel by introducing water into these compartments via the anus. Patients with neurologic bowel disease experience not only the discomfort of an irregular bowel clearance but also very often chronic abdominal pain which limits social activities.Data fromliterature have already shown the efficacy of TAI on improving bowel emptying but there is a lack regarding the contribute of this system on reducing abdominal pain. The aim of this study was to evaluate if the use of TAI for neuropathic constipation could also relief symptoms in those subjects with associated chronic abdominal pain. Methods A prospective study was conducted on the first cohort of adult patients affected with spinal cord lesions and neuropathic bowel dysfunction referred to our centre for Peristeen TAI treatment between July 2013 and November 2014. Patients with neurogenic bowel disturbance who did not satisfactorily respond to conventional bowel management were enroled. In particular, patients were selected following the directions of consensus review of best practice of TAI in adults. After providing informed written consent, a previously described and validated Neurogenic Bowel Dysfunction score (NBD) was used to assess bowel function. Abdominal pain was evaluated by a Visual Analogic Scale (VAS), from0¼no discomfort to 10¼severe discomfort. This questionnaires were administered before and after treatment. Peristeen TAI composed of a coated rectal balloon catheter, manual pump and water container. After the first visit in which it was determined if the patients could receive treatment and trained, they performed treatment every day per 10 days, then on alternate days. Results Twenty patients were referred for Peristeen TAI during the study period. Mean time of using Peristeen TAI was 10 months and mean length of follow-up was about 3 months. All patients were noted to have an improvement in their chronic neuropathic constipation and abdominal pain, increasing in quality of life scores. VAS and NBD score were significantly different before and after. In particular, before treatment patients scored at VAS a mean value of 7.64± 0.29, while aftertreatment they scored a mean 3.64± 0.29 ; NBD score before treatment showed a mean value of 23.28± 3.14 and post-treatment of 1,92± 0.76. Conclusions In this study, TAI appears to be a safe and effective bowel management system, which improves bowel function and quality of life in patients affected with chronic neuropathic constipation. Abdominal pain, evaluated through VAS, decreases significantly with satisfaction of the patients. Comprehensive training of the patient is central to a safe and efficient long term use of TAI. Funding None
Authors
Giovanni Palleschi
Antonio Luigi Pastore Yazan Al Salhi Andrea Fuschi Gennaro Velotti Antonino Leto Vincenzo Petrozza Antonio Carbone |
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MP85-15 |
Intravesical injection of highly purified botulinum toxin [Incobotulinumtoxin A (Xeomin)] for neurogenic bladder |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Neurogenic Voiding Dysfunction I | 17BOS |
Abstract: MP85-15 Sources of Funding: none Introduction Currently onabotulinumtoxin A (Botox®) is the only FDA-approved form of botulinum toxin for use in the bladder. However there are now alternative toxins on the market approved for muscle spasticity and cosmetics. Incobotulinumtoxin A (Xeomin®) is a highly purified toxin with no complexing proteins, decreased immunogenicity, improved storage and lower cost. The safety and efficacy of incobotulinumtoxin A use in the bladder has not previously been studied. Methods Patients who received intravesical incobotulinumtoxin A injections for neurogenic or idiopathic detrusor overactivity between 2013 and 2016 were identified. Those who previously received onabotulinumtoxin A had minimum washout interval of 3 months. Baseline characteristics were collected. Outcomes analyzed included UDI-6 scores, IIQ-7 scores, daily incontinence episodes, catheterized volume, pad use, and complications. Analysis with summary statistics and paired t-tests were done with significance p<0.05. Results 14 male patients underwent incobotulinumtoxin A injection. Mean age was 59.8±16.9 years. All patients had neurogenic (n=12, 86%) or idiopathic (n=2, 14%) detrusor overactivity on urodynamics. At baseline, 79% were on oral anticholinergic therapy, 50% were performing CIC, 21% had indwelling catheters and 29% had received previous onabotulinumtoxin A. Initial injection doses were 300 units for 29%, 200 units for 64% and 100 units for 7%. 5 patients (36%) received multiple treatments (2.8±0.4 times) with mean 9.0±4.1 months between sessions. After treatment there were trends toward improvement in mean daily pad use (5.0±6.5 to 2.6±6.3, p=0.33), incontinence episodes (2.7±1.9 to 1.6±2.3, p=0.74), episodes of daytime frequency (7.8±2.7 to 6.6±7.0, p=0.60), CIC volumes (341.7±67.1 to 45070.7 mL, p=0.05) and UDI-6 scores (43.0±30.2 to 18.0±28.1, p=0.19). IIQ-7 scores significantly decreased after treatment (46.4±34.6 to 10.1±18.2, p=0.03). 2 patients (14%) experienced culture-proven urinary tract infections within 30 days of treatment and 1 patient (7%) developed new urinary retention. Conclusions This is the first study to demonstrate safety and efficacy of intravesical incobotulinumtoxin A in patients with neurogenic or idiopathic detrusor overactivity. Incobotulinumtoxin A may be an attractive alternative to onabotulinumtoxin A, especially given its lower cost. Small sample size limits this data, however early results suggest improvements in quality of life and bladder dynamics. A larger, prospective study will be required to validate these findings. Funding none
Authors
Denise Asafu-Adjei
Alex Small Doreen Chung Glen McWilliams Cory Harris |
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MP85-16 |
Comparison of urodynamic parameters following injection of two different botulinum toxin A preparations in management of neurogenic detrusor over-activity following spinal cord injury |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Neurogenic Voiding Dysfunction I | 17BOS |
Abstract: MP85-16 Sources of Funding: None Introduction Following spinal cord injury (SCI), disruption to neuronal pathways of the bladder can lead to neurogenic detrusor over-activity (NDO) causing reduced capacity, high pressure and incontinence. Intra-detrusor injections of botulinum toxin A (BTX-A) are commonly used to manage these complications. Between 2013-2014 our department changed from using abobotulinum toxin (aboBTX) (750-1000 u) to onabotulinum toxin (onaBTX) (200 u). We have analysed the urodynamic outcomes and patient satisfaction to determine the relative efficacy of the two drugs on NDO following SCI. Methods The medical notes of 171 patients receiving consecutive doses of aboBTX and onaBTX during 2013-2014 were reviewed. 36 SCI patients with NDO and urodynamics within 6 months of injection of both aboBTX and onaBTX were included. The maximum cystometric capacity (MCC) and maximum detrusor pressure (MDP) were recorded. Paired t-tests were performed to test difference in bladder function between the two BTX-A drugs. Results The post-injection mean (± SD) MCC for aboBTX was 375 ± 178 ml and for onaBTX was 378 ± 212 ml. The post injection mean (± SD) MDP for aboBTX was 25 ± 21 cmH2O and for onaBTX was 27 ± 18 cmH2O. There was no significant difference between MCC (p=0.5) and MDP (p=0.86) for each drug. The scatter graphs demonstrate the relationship between the preparations with respect to MCC and MDP. The solid line represents the linear regression and the dashed line represents a 1:1 relationship. The linear regression for MCC had a slope of 1 demonstrating a clear correlation between the bladder capacity after aboBTX and onaBTX. There was not such a clear correlation between the MDP data. 12 out of 36 patients reported worse satisfaction with onaBTX than aboBTX, though interestingly this did not correlate with worse urodynamic outcomes. Conclusions There was no statistically significant difference in objectively measured urodynamic parameters of bladder function between aboBTX and onaBTX in patients with NDO following SCI. However 1/3 of patients reported worse satisfaction with onaBTX. The data will be further analysed to compare the efficacy of repeated injections and the effect of prior exposure to each agent. Funding None
Authors
Jason Gan
Sarah Rasip Sarah Knight Mohamed Helal Frank Lee Julian Shah Rizwan Hamid |
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MP85-17 |
FACTORS ASSOCIATED WITH DURABILITY OF THERAPEUTIC BOTULINUM TOXIN A INJECTION FOR OVERACTIVE BLADDER |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Neurogenic Voiding Dysfunction I | 17BOS |
Abstract: MP85-17 Sources of Funding: None Introduction Patients suffering from overactive bladder (OAB) without response to behavioral and pharmaceutical intervention may opt for third?line therapy with botulinum toxin A injection. Botulinum injections have shown success in treating OAB urinary symptoms, but require repeat injections at an interval of 4?12 months. This study seeks to identify factors associated with the durability of this therapeutic effect. Methods Patients undergoing treatment for OAB at Lahey Hospital and Medical Center between 2004 and 2016 were identified. Demographic, clinical and treatment data were extracted from patient charts. Patients were included if they had at least 1 botulinum injections. Time from initial to second botulinum injection was defined as therapeutic durability; time from initial injection to last clinic follow?up was defined and time to event analyses were employed: univariate analysis via log?rank method and multivariate Cox proportional hazards were used to identify associations with therapeutic durability. The multivariate Cox model comprised univariate factors with p values below 0.1 and a priori clinical variables. Significance was defined at the ?= 0.05 level. Results Of the available patients, 54 patients met inclusion criteria. Median time to repeat injection for those who had a second injection was 259 days (8.6 months). Kaplan?Meier survival estimated that 50% of patients required reinjection at 330 days (11 months). On univariate analysis, history of spinal cord injury (p = 0.041), prostate cancer (p < 0.001), history of stroke/CVA (p=0.037), and history of UTI (p=0.013) were significantly associated with lower therapeutic durability. On multivariate analysis, only prostate cancer (OR 50.2, 95% CI 2.95?854, p = 0.0068) and history of UTI (OR 4.11, 95% CI 1.10?15.3, p = 0.035) were associated with lower therapeutic durability. Conclusions Botulinum injection showed a median durability of roughly 9 months. Patients with prostate cancer or a history of UTI had a statistically significantly lower durability of botulinum injection. Further study is warranted to identify further etiologic origins of these connections or elucidate other associated cofactors. Funding None
Authors
Kristian Stensland
Jay Vance Bennett Sluis Jared Schober Arthur Mourtzinos Lara Maclachlan |
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MP85-18 |
GENDER DIFFERENCES IN THE SUCCESS OF SACRAL NERVE STIMULATION IN PATIENTS WITH OVERACTIVE BLADDER |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Neurogenic Voiding Dysfunction I | 17BOS |
Abstract: MP85-18 Sources of Funding: None Introduction Patient suffering from overactive bladder (OAB) may be offered sacral nerve stimulation (SNS). Successful SNS implantation may rely on factors at baseline that differ according to gender. The purpose of the present study is to identify factors within male or female gender which are associated with successful SNS implantation and identify possible effect modification associated with gender. Methods Patients undergoing treatment for OAB at Lahey Hospital and Medical Center between 2004 and 2016 were identified. Relevant data were extracted from patient charts. Patients were stratified by gender. Within groups, univariate analyses were conducted to identify factors associated with SNS treatment success. A multivariate model to predict SNS treatment success was also created within each group. The factors significantly associated with SNS treatment success were compared between groups to assess for effect modification. Results Of 268 patients in the OAB database, 128 patients met inclusion criteria. Within the male subgroup, 26 of 47 men (44.7%) had successful treatment, compared to 73 of 81 women (90.1%). Within the male group, the factors significantly associated with SNS failure were mean volume at first urge on UDS (80.5ml in SNS failure vs. 126.5ml in SNS success) and smoking (SNS failure more likely to be current smokers, p = 0.039). Similarly, on multivariate analysis only lower volume at first urge was statistically significantly associated with SNS failure (OR=.97, 95%CI 0.94?0.99). Within the female group, there were no statistically significant associations between measured variables and SNS success. Notably, mean volume at first urge on UDS was not statistically significantly associated with SNS failure, though there was a similarly large difference between groups (97.5ml in SNS failure compared to 136.0ml in SNS success). On multivariate analysis in the female group, there were no significant factors associated with SNS success. Conclusions SNS is frequently successful at relieving OAB symptoms. The rate of success in men is significantly lower than in women, suggesting that SNS implantation is more effective in woman than men. The best predictor of success for male patients in this study was higher volume at first urge on UDS. Further study is needed to evaluate other predictors of SNS success and to further characterize differentiating characteristics between male and female patients with respect to overactive bladder treatment. Funding None
Authors
Kristian Stensland
Bennett Sluis Jay Vance Jared Schober Lara Maclachlan Arthur Mourtzinos |
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MP85-19 |
Side matters: Sacral neuromodulation lead placement on the less versatile side offers greater benefit in patients with asymmetry |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Neurogenic Voiding Dysfunction I | 17BOS |
Abstract: MP85-19 Sources of Funding: none Introduction Sacral neuromodulation with InterstimTM (Medtronic) is a highly successful treatment for both non-obstructive urinary retention as well as for overactive bladder (OAB) symptoms, but the mechanism of action is not yet defined. Importantly, attempts to predict and improve outcomes have been inconsistent. In this study we assessed the association between laterality of lead placement and patient asymmetry. We have recognized patterns of asymmetry in our patients with severe voiding symptoms. We hypothesize a higher success with lead placement on the less formed side. Methods We performed an IRB approved retrospective chart review of InterstimTM placements from 2003 to 2013. A total of 57 patients were identified, and who had undergone first-stage lead placement for non-obstructive urinary retention or OAB._x000D_ Patient symmetry was assessed by preoperative physical examination findings of bilateral sacral sensory function, gluteal muscle mass, intrinsic muscles of the feet, and pelvic floor muscle strength. Asymmetry was defined as a significant, consistent lateralized difference in findings based on one observer. Among asymmetric patients the side determined to have diminished function was deemed less versatile. Subtle findings were considered symmetric. Successful lead placement was regarded as a 50% or greater improvement in urinary symptoms and transition to second stage InterstimTM placement._x000D_ Results Of the 57 patients reviewed, 47 (82%) progressed to successful second stage InterStimTM placement while 10 (18%) failed. A majority, 39/57(67%) of patients were deemed asymmetric and of these 33 (84%) progressed to second stage. Of the 18 symmetric patients success was achieved in 14 (78%). In a subgroup analysis of 19 asymmetric patients who underwent an initial trial of bilateral lead placements, 13 reported greater benefit with the lead placed on the less versatile side, 2 were equivocal, and only 4 favored the more versatile side (p=0.003). Conclusions Asymmetry is a very frequent finding in patients with pelvic floor dysfunction. Lead placement on the less versatile side of asymmetric patients correlated with better InterstimTM success. Determination of asymmetry among InterStimTM candidates should be considered during preoperative evaluation to guide the choice of side for lead placement. Funding none
Authors
Usama Al-Qassab
Lindsey Hartsell Joy Butterworth John DeCaro Niall Galloway |
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MP85-20 |
ACYLOXYACYL HYDROLASE MODULATES PELVIC PAIN SEVERITY |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Neurogenic Voiding Dysfunction I | 17BOS |
Abstract: MP85-20 Sources of Funding: These studies are supported by NIH /NIDDK R01 DK066112S1 (D.J. K.) and MAPP U01 DK82342 (D.J.K. and A.J.S.). _x000D_ Introduction Chronic pelvic pain causes significant morbidity to patients and is a bane to clinicians. Using a murine neurogenic cystitis model that recapitulates key aspects of interstitial cystitis/bladder pain syndrome (IC), we recently showed that pseudorabies virus (PRV) induces severe pelvic allodynia BALB/c mice, relative to C57BL/6 mice. Here, we use a genetic strategy to identify a novel modulator of pelvic pain expressed along the bladder-brain axis._x000D_ Methods Mouse SNP genotyping: We generated 96 F2 female mice, infected with PRV, and pelvic pain was scored in response to von Frey filament stimulus. Purified F2 mouse tail DNA was genotyped with Illumina Mouse MD arrays containing 1449 SNPs. We mapped QTL using R/qtl software. Knockout mice were evaluated for pelvic allodynia, and expression was localized by immunofluorescence._x000D_ Results female F1CxB mice exhibit the low-allodynia phenotype of C57BL/6 parental mice in response to PRV, indicating that the severe pelvic pain phenotype of BALB/c mice is recessive. To identify loci modulating pelvic pain, we performed a quantitative trait locus (QTL) analysis on female F2CxB progeny by quantifying PRV-induced allodynia and statistical associations between pelvic pain and recombinant genotypes. Analyses identified a polymorphism on chromosome 13, rs6314295, significantly associated with allodynia (LOD=3.11). Expression analyses revealed that the mouse gene for acyloxyacyl hydrolase (AOAH), encoded near this SNP, was induced in the sacral spinal cord of PRV-infected mice. AOAH-deficient mice exhibited pelvic hypersensitivity compared to wild-type (WT) mice and developed extreme pelvic allodynia both in neurogenic and bacterial cystitis models. AOAH deficiency results in greater bladder pathology in neurogenic cystitis consistent with increased bladder mast cell activation. AOAH expression was detected along the bladder-brain axis, and AOAH-deficient mice have elevated levels of bladder VEGF, a UCPPS biomarker. Conclusions These findings indicate that AOAH is expressed along the bladder-brain axis and modulates pelvic pain severity and UCPPS biomarker expression. Thus, allelic variation in Aoah may mediate susceptibility to UCPPS symptoms. Funding These studies are supported by NIH /NIDDK R01 DK066112S1 (D.J. K.) and MAPP U01 DK82342 (D.J.K. and A.J.S.). _x000D_
Authors
Wenbin Yang
Ryan Yaggie Mingcheng Jiang Charles Rudick Joseph Done Charles Heckman Anthony Schaeffer David Klumpp |
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MP86-01 |
Frailty is common among patients presenting to an academic non-oncologic urology practice |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making V | 17BOS |
Abstract: MP86-01 Sources of Funding: NIDDK K12 DK83021-07 Introduction Frailty, defined as a measure of decreased physiologic reserve, is strongly associated with increased susceptibility to disability and poor outcomes. The purpose of this study was to describe the extent of frailty among patients with various urologic diagnoses and to explore whether or not frailty differed between patients who did and did not undergo urologic surgery. Methods This is a prospective study of men and women ages 65 and older presenting to an academic non-oncologic urology practice between December 2015 and May 2016. Frailty was measured in individuals via the Timed Up and Go Test (TUGT) upon intake. Based on the TUGT, individuals were classified as not frail (?10 sec), intermediately frail (11-14 sec) or frail (?15 sec). The TUGT and other clinical data were abstracted from the electronic medical record using EPIC analytical software into an on-going database. TUGT values were reported overall, by urologic diagnosis, and according to whether or not they were associated with a urologic procedure. Results There were 1089 unique individuals who presented to our practice and had a TUGT during the study period. Among these individuals, the mean age was 73.3 (±6.3) years, 77.6% were male, 64.7% were white and the mean TUGT was 11.6 (±6.0) seconds, with 30.0% and 15.2% classified as intermediately frail and frail, respectively. TUGT time (and hence frailty) increased linearly with increasing age (Figure). TUGT values differed by urologic diagnosis ranging from 9.9 (±3.0) seconds among individuals with general male urology diagnoses to 14.3 (±11.9) seconds among individuals with urinary tract infections (UTIs). There were no statistically significant differences in TUGT values between individuals who did and did not undergo urologic surgery. Conclusions Frailty is common, increases with age, and varies based on urologic diagnosis among individuals presenting to an academic non-oncologic urology practice. Interestingly, frailty did not differ between individuals who did and did not undergo urologic surgery, suggesting that there is a potential opportunity to incorporate frailty into the perioperative decision-making process. Since frailty is prevalent among urologic patients and linked to poor outcomes, consideration of frailty in the surgical decision-making process is warranted and may improve outcomes. Funding NIDDK K12 DK83021-07
Authors
Anne M Suskind
Jayce Pangilinan Kathryn Quanstrom Mark Bridge Louise C Walter Emily Finlayson |
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MP86-02 |
Prevalence of frailty among urological cancer patients in comparison with community-dwelling population |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making V | 17BOS |
Abstract: MP86-02 Sources of Funding: none Introduction The prevalence of frailty is expected to increase due to the worldwide ageing. However, little is known about the prevalence of frailty in urological cancer patients. The aim of this study is to investigate the useful frailty assessment tools for urological cancer patients in comparison with community-dwelling population. Methods From August 2013 to March 2016, we evaluated 486 consecutive urological cancer patients in our hospital. Urological cancers included prostate cancer (PC, n=226), bladder cancer (BC, n=132), upper tract urothelial carcinoma (UTUC, n=42), and renal cell carcinoma (RCC, n=86). We retrospectively compared age and sex adjusted urological cancer patients and 2766 community-dwelling subjects who underwent frailty assessment including physical status (handgrip strength and gait speed), serum test (serum albumin and renal function), and mental status (exhaustion and depression). Gait speed was evaluated by timed get up and go test (TGUG). Independent factors that were significantly associated with tumor-bearing status were evaluated by multivariate regression analysis. Results The number of pair-matched patients in PC, BC, UTUC, and RCC were 212, 130, 41, and 84. TGUG, handgrip strength, and serum albumin were significantly worse in all types of cancers than controls. Renal function was significantly better in PC, whereas it was worse in BC, UTUC, and RCC than controls. The number of patients with exhaustion or depression were significantly higher in PC. Multivariate regression analysis showed TGUG and serum albumin were significantly associated with tumor-bearing status. Conclusions Urological cancer patients were significantly frail compared with community-dwelling older adults. Our results provide a picture of the prevalence of frailty in urological patients. TGUG and serum albumin may be simple and useful tools for frailty assessment in urological cancer patients. Funding none
Authors
Shingo Hatakeyama
Osamu Soma Takuma Narita Kazuhisa Tanaka Toshikazu Tanaka Daisuke Noro Masaaki Oikawa Yoshimi Tanaka Teppei Matsumoto Takahiro Yoneyama Yasuhiro Hashimoto Takuya Koie Chikara Ohyama |
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MP86-03 |
A Predictive Risk Stratification Model for Delirium After Major Urologic Cancer Surgeries |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making V | 17BOS |
Abstract: MP86-03 Sources of Funding: None Introduction Post-operative delirium is a common complication in the elderly and contributes to increased healthcare costs, mortality, cognitive decline, and hospital length of stay. No definitive pre-operative risk prediction model for patients undergoing major urologic cancer surgeries is currently available. Methods Using the Premier Hospital Database, we retrospectively identified patients who had undergone radical prostatectomy (RP), radical nephrectomy (RN), partial nephrectomy (PN), and radical cystectomy (RC) from 2003 to 2013. Post-operative delirium was defined using International Classification of Disease, Ninth Revision (ICD-9) codes, as well as post-operative use of antipsychotics, sitters, and restraints. Potential pre-operative risk factors of delirium were extrapolated from patient, hospital, and surgical characteristics. A pre-operative delirium risk prediction score was developed from our multivariate model. Its performance was quantified using Receiver Operating Characteristic (ROC) analysis. All analyses were survey-weighted and clustered by hospitals to achieve estimates generalizable to the US population. Results We identified 165,387 patients representing a weighted total of 1,097,355 patients from 490 hospitals who had undergone RP, RN, PN, or RC. Our model revealed a wide range of clinical and demographic factors that significantly contribute to the risk for post-operative delirium (Figure A). Our delirium risk score was associated with the development of post-operative delirium (Odds Ratio: 1.31, 95% CI 1.29-1.33, p <0.001, Figure B), and it demonstrated good discrimination in the prediction of delirium (Receiver Operator Characteristic [ROC] area = 0.76, 95% CI, 0.76-0.77, Figure C). The ability of the risk score to predict delirium was consistent across surgical subgroups, and the risk score was also predictive of the duration of delirium (Incidence Rate Ratio = 1.07, 95% CI 1.04-1.11, p<0.001). Conclusions The preliminary results of our pre-operative delirium risk prediction tool are promising given its consistency with published delirium risk factors and ease of use. Further validation of this model will shed insight about its clinical utility to identify patients at high-risk of post-operative delirium who may benefit from early therapeutic intervention. Funding None
Authors
Albert Ha
Ross Krasnow Tammy Hsieh Adam Kibel James Rudolph Benjamin Chung Steven Chang |
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MP86-04 |
New-onset Depression and Mental Health-Related Quality of Life Following Prostate Cancer Diagnosis Without Treatment |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making V | 17BOS |
Abstract: MP86-04 Sources of Funding: Emory Urology Research Scholars Grant_x000D_ Winship Cancer Institute Prostate Cancer Pilot Grant Introduction To examine if men receiving a prostate cancer diagnosis without evidence of treatment had increased risk of new-onset depression and changes in mental health-related quality of life (HRQOL). Methods Using Surveillance, Epidemiology, and End Results - Medicare Health Outcomes Survey (SEER-MHOS) data (2006-2013), we identified localized prostate cancer patients who completed baseline and follow-up HRQOL surveys before/after their cancer diagnosis and were not treated in the interim. Surveys captured major depressive disorder and mental component scores (MCS) of the Veterans RAND 12-item health survey, where higher scores correspond to greater HRQOL. The cohort was divided into 3 subgroups of cases by time between diagnosis and follow-up: <1, 1-3, and >3 years. Cases were matched to controls based on age, marital status, and time between surveys. Bivariate statistics (i.e., Kruskal-Wallis and chi-square tests) were used to evaluate the relationship between incident prostate cancer diagnosis and (a) development of new-onset depression and (b) changes in MCS. Results We identified 221 cases matched to 221 controls (n=126 < 1 yr from diagnosis to follow-up, n=82 1-3 yr, n=13 >3 yr). Mean age for subgroups were 75.4 (< 1 yr f/u), 76.6 (1-3 yr f/u), and 78.2 years (>3 yr f/u). Compared to controls, new-onset depression was not more common among prostate cancer patients followed for 1 yr (11.1% vs 8.3% controls, p= 0.53) but was more common if followed for 1-3 yr (14.6% vs 4.9% controls, p=0.04) after diagnosis. Changes in MCS were not significantly greater for cases compared to controls within 1 yr (-0.1 vs -1.4 control, p=0.27) and from 1-3 yr (-2.5 vs -1.0, p=0.54) (Figure). Among men with <1 yr follow-up, new-onset depression was associated with significant decreases in mental HRQOL (-7.0 vs 0.1 no depression, p=0.0038). However, changes were not more significant for prostate cancer patients compared to controls (-3.0 vs -12.1 controls, p=0.15). Conclusions Though more likely to screen positive for new-onset depression, men diagnosed with prostate cancer not receiving treatment did not experience significant changes in overall mental health-related quality of life over time, compared to men without a prostate cancer diagnosis. _x000D_ Funding Emory Urology Research Scholars Grant_x000D_ Winship Cancer Institute Prostate Cancer Pilot Grant
Authors
Hankyul Kim
Dattatraya Patil Christopher Filson |
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MP86-05 |
The relationship between financial toxicity and quality of life among bladder cancer patients |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making V | 17BOS |
Abstract: MP86-05 Sources of Funding: none Introduction Costly cancer surveillance and treatment can lead to financial toxicity (FT), an adverse financial condition as a consequence of the treatment of a disease. Evidence suggests that FT is associated with worse mortality, which may be related to impaired health-related quality of life (HRQOL). The purpose of this study is to evaluate the association of FT with HRQOL among patients with bladder cancer. Methods Bladder cancer patients were identified from the University of North Carolina Health Registry/Cancer Survivorship Cohort (HR/CSC), which includes patient-reported data on FT and QOL. FT was defined as agreement with the following statement “you have to pay more for medical care than you can afford.� Cancer-specific and general HRQOL was measured using the validated FACT-G, FACT-Bl and PROMIS questionnaires. Bivariate analyses were performed comparing FT and HRQOL scores using Student’s t-test. Results 144 bladder cancer patients were enrolled in HR/CSC, of which 138 completed the baseline questionnaire. Median age was 66.9 years. 75% were male, 89% were white, and 66% had less than a college degree. Half of patients had a stage of cT2 or higher. Thirty-three participants overall (24%) endorsed FT. With regard to general HRQOL using the PROMIS questionnaire, patients with FT had worse physical and mental health scores compared to those without FT (p=0.03 and <0.01, respectively). Patients who endorsed FT also reported lower cancer-specific QOL (72 vs. 81) as well as physical well-being (20.3 vs. 23.0) (p=0.01). Patients who endorsed FT reported lower functional well-being (14.6 vs. 17.8; p=0.05). No differences in social well-being, emotional well-being or bladder-cancer specific QOL were noted. Conclusions FT is negatively associated with physical and mental health-related quality of life among bladder cancer patients. Our future research will investigate the association between FT and HRQOL as affected by patient-specific characteristics such as demographics, disease stage, and comorbidities. Funding none
Authors
Marianne Casilla-Lennon
Seul Ki Cho Allison Deal Gopal Narang Jeannette Bensen Pauline Filippou Benjamin McCormick Raj Pruthi Eric Wallen Michael Woods Hung-Jui (Ray) Tan Matthew Nielsen Angela Smith |
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MP86-06 |
Quality-of-life evaluation during platinum-based neoadjuvant chemotherapies for urothelial carcinoma |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making V | 17BOS |
Abstract: MP86-06 Sources of Funding: none Introduction Although quality of life (QOL) is one of the most important considerations in patients treated with anticancer therapies, desirable regimens for neoadjuvant chemotherapy including QOL in locally advanced urothelial carcinoma remain unclear. The present study evaluated the influence of neoadjuvant platinum-based chemotherapy on QOL in patients with locally advanced urothelial carcinoma. Methods Between June 2013 and March 2016, 83 urothelial carcinoma patients who received two courses of neoadjuvant chemotherapy were enrolled in this prospective observational study. Neoadjuvant regimens included gemcitabine+cisplatin (GCis) or gemcitabine+carboplatin (GCb) therapies. As a primary endpoint, we assessed QOL changes in each group before and after chemotherapy using the QLQ questionnaire on days 1, 3, and 15 of each cycle. Secondary endpoints included toxicity, safety, weight loss, renal function decline, and tumor responses. Results QOL analyses were performed in 39 patients receiving GCis and in 44 patients receiving GCb. The QOL items appetite loss, role functioning, nausea/vomiting, physical, and fatigue deteriorated >10% from baseline in the GCis group but not in the GCb group. Constipation worsened, whereas scores for pain and emotional items improved in both groups. Objective response rates were 38.5% and 43.2% in the GCis and GCb groups, respectively. Conclusions Both GCis and GCb regimens were feasible in terms of QOL. The GCb regimen may be associated with a better QOL status especially in regard to gastrointestinal symptoms. Funding none
Authors
Shingo Hatakeyama
Takuma Narita Ken Fukushi Shogo Hosogoe Ayumu Kusaka Itsuto Hamano Hayato Yamamoto Yasuhiro Hashimoto Takahiro Yoneyama Takuya Koie Chikara Ohyama |
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MP86-07 |
Reduction of Skeletal Muscle Index as a predictive factor in patients with urothelial carcinoma |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making V | 17BOS |
Abstract: MP86-07 Sources of Funding: none Introduction The progression of cancer leads to metabolic disorders and malnutrition, which results in the loss of skeletal muscle mass (sarcopenia). Sarcopenia is an objective indicator of cancer cachexia, and has been previously reported as a predictor of hospitalization, postoperative complications as well as survival in cancer patients. _x000D_ Herein, we analyzed the changes in skeletal muscle mass during chemotherapy using computer tomography (CT) images, and verified whether sarcopenia is a predictive factor of overall survival (OS) or performance status (PS) deterioration._x000D_ Methods We retrospectively reviewed patients with urothelial carcinoma (UC) who had received cisplatin-based chemotherapy as first line and GD (Gemicitabine plus Docetaxel) chemotherapy as second line treatment regimens between 2006 and 2015 in our hospital. Skeletal muscle area (SMA) at the third lumbar vertebrae was measured using CT images. Based on these data, we calculated skeletal muscle index (SMI = SMA/height2), and defined the changes in SMI for months between two points as δSMI (δSMI = SMI/duration). We verified the relationships among δSMI, OS and PS. Mann-Whitney U test, t-tests, Kaplan-Meier method and Log-rank test were used to analyze the data. Results This study included data from 55 UC patients. Due to lack of CT data, 20 patients were excluded at first line and 6 patients were excluded at second line. Median δL3 SMI during the first 2 cycles of first line chemotherapy was -1.66 (range, -5.92-1.62), and median δL3 SMI during the first 2 cycles of second line treatment was 0.042 (range, -1.10-7.42). The PS tended to deteriorate in patients when δL3 SMI was high during the first and second line treatments. By setting a cut-off value of δL3 SMI during the first 2 cycles of the first and second line regimen as -0.1 (first line) and -1 (second line), the Kaplan-Meier log rank analysis showed that patients in high δL3 SMI group (first line:< -0.1, second line< -1) had poorer OS when compared with those in the low δL3 SMI group (fist line:≥ -0.1, second line:≥ -1; P < 0.01; Figure) Conclusions It is possible to predict OS and PS deterioration in chemotherapy-treated UC patients by measuring δL3 SMI and setting proper cutoff of δL3 SMI. Thus, reduction of skeletal muscle mass may be considered as a useful predictor of prognosis in these patients. Funding none
Authors
Takashi Nagai
Taku Naiki Keitaro Iida Toshiki Etani Ryosuke Ando Noriyasu Kawai Hidetoshi Akita Takehiko Okamura Takahiro Yasui |
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MP86-08 |
Use of a Mobile App for Ecological Momentary Assessment of Pain and Other Symptoms in Patients with Urologic Chronic Pelvic Pain Syndrome |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making V | 17BOS |
Abstract: MP86-08 Sources of Funding: MAPP Research Network grants (U01, NIDDK) to the University of Iowa and Northwestern University. Introduction Pain in patients with chronic pelvic pain varies widely by location, intensity, severity and by its intermittency. Static assessment of pain does not allow for a comprehensive description of this inherent heterogeneity of pain, potentially obscuring phenotypic differences in UCPPS patients that could help predict treatment response and disease course. Ecological Momentary Assessment (EMA) of pain is a way to describe pain more comprehensively. Mobile apps can communicate directly with patients at all times of the day in most locations and are thus, perfectly suited to collect EMA pain data. For the Multidisciplinary Approach to Pelvic Pain (MAPP) Research Network, we developed a mobile app to capture pain and associated symptoms in a time-efficient manner. We present the results from the app beta testing herein. We hypothesized that participants would find the app easy to use and that utilization of the app would reveal significant daily pain variability. Methods A total of 22 participants completed beta testing for 14 days, locating and rating their pain and other symptoms. Mobile phone notifications that linked to and opened the app were sent at wake up, 4 and 8 hours after wake-up and bedtime. On Day 15 participants completed the NASA task load index to assess app usability and satisfaction. Participants then completed a qualitative exit interview to give us feedback on all aspects of the app and testing. Thus, we obtained both quantitative and qualitative information during the beta-testing period. Results We created a summary score for pain using the maximum pain rating across different areas of the body at a particular time. Using a linear model with time of day, nested with testing day, we found that pain varied significantly during the day, F (37, 257) = 1.75, p = .007. Qualitative interviews and App ratings (see figure) suggested that the app was simple and easy to use (e.g. low mental demand, high app compliance) Conclusions Our quantitative and qualitative results show that our app is easy to use for participants and is able to capture intra-day variability in pain across multiple areas of the body. Moreover, our participants indicated that they would be willing to use this app going forward both for research and clinical/treatment purposes. Mobile apps appear to be well-suited to study chronic urologic conditions. Utilization of the app for EPA testing is currently underway within the MAPP Research Network. Funding MAPP Research Network grants (U01, NIDDK) to the University of Iowa and Northwestern University.
Authors
James Griffith
Ted Herman Anthony Andrys Michael Bass Bayley Taple Brett Lloyd Bradley Erickson |
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MP86-09 |
CRITERION VALIDATION OF THE NOVEL FLOW QUESTIONNAIRE VERSUS AUA SYMPTOM SCORE IN A COMMUNITY?BASED COHORT |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making V | 17BOS |
Abstract: MP86-09 Sources of Funding: Vanderbilt CTSA grant UL1 TR000445 from NCATS/NIH Introduction The American Urological Association Symptom Score (AUA-SS) has been the gold standard for assessing lower urinary tract symptoms (LUTS); however, it is frequently incorrectly completed or unfinished due to inadequate literacy/numeracy. We developed the novel FLOW questionnaire to assess LUTS regardless of respondents' literacy/numeracy level. We previously showed the FLOW questionnaire is internally consistent and rapidly administered. Our current study objective is to establish criterion validation of FLOW vs AUA-SS, and perform a critical analysis of the AUA-SS via validated literacy and numeracy scales. Methods A total of 161 men were recruited from clinics at Nashville General Hospital, a safety net hospital in Nashville, TN. We collected demographic data and assessed literacy/numeracy using validated tools: the revised Rapid Estimate of Adult Literacy in Medicine (REALM-R), the Brief Health Literacy Screen (BHLS), and the Subjective Numeracy Scale (SNS). Patients were administered the FLOW questionnaire and the AUA-SS. We evaluated the completion rates, completion times, and whether or not patients required assistance to complete either questionnaire. Results Median age was 56 years, 99 men (61.5%) identified as Black/African American, and the median REALM-R score was six. There was a significant correlation between FLOW scores and AUA-SS (r=0.63, p<0.001). Among men with adequate health literacy (REALM-R 6-8; n =87), all were able to complete the FLOW and AUA-SS; however, among men with low literacy (REALM-R <6; n =74) all were able to complete the FLOW but only 81% were able to complete the AUA-SS (p<0.001). For the FLOW, health literacy was unrelated to median completion time (21.5 sec), the median number of prompts needed (0), or median score (2). For the AUA-SS, although the median number of prompts needed to complete the questionnaire (2) and median AUA-SS score (10.5) did not differ as a function of the men's health literacy, men with low health literacy who completed it had a median completion time of 129.5 seconds compared to 92 seconds for those with adequate health literacy (p<0.001). Conclusions The FLOW questionnaire meets criterion validity due to its strong, significant correlation with the AUA-SS for those who were able to complete both measures. However, a critical analysis of the AUA-SS utilizing valid health literacy and numeracy scales reveals the AUA-SS is frequently not completed, required prompting, and/or took longer to complete for men with low health literacy. Further studies of the FLOW questionnaire in a larger cohort in diverse clinical settings are needed. Funding Vanderbilt CTSA grant UL1 TR000445 from NCATS/NIH
Authors
Daniel Heslop
Lisa Sherden Christopher Johnson Arturo Holmes Nia Johnson Lauren Sartor Consuelo Wilkins Ken Wallston Kelvin Moses |
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MP86-10 |
Relationship between overactive bladder and metabolic syndrome: A cross-sectional study among Japanese men and women. |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making V | 17BOS |
Abstract: MP86-10 Sources of Funding: JSPS KAKENHI Introduction Metabolic syndrome (MetS) has been implicated in the aetiology of lower urinary symptoms and a few previous epidemiological studies have suggested a relationship between MetS and overactive bladder (OAB) in women. We thus aimed to evaluate the relationship between OAB and MetS or components of MetS among Japanese men and women. Methods We collected data on 12,478 individuals (5,313 males and 7,165 females) who participated in a multiphasic health screening in 2015, in Fukui, Japan. As part of a multiphasic health screening, waist circumference, blood pressure, fasting blood sugar, triglycerides and HDL-cholesterol were measured. All participants were asked to answer a standardized self-reported questionnaire for OAB screening (SQOAB, Screening Questionnaire for Overactive Bladder) [Int J Urol, 2009]. _x000D_ We analyzed the relationships between OAB and other variables including age, gender, waist circumference, high blood pressure, impaired glucose tolerance, and dyslipidemia. The relationships between OAB and MetS were also analyzed. MetS in the Japanese criteria was diagnosed in individuals who had a high waist circumference (≥ 85 cm in men and ≥ 90 cm in women) plus any 2 of the following: (a) high blood pressure (systolic blood pressure ≥ 130/85 mmHg and/or current use of antihypertensive medicine); (b) impaired glucose tolerance (fasting glucose concentration ≥ 110 mg/dL and/or current use of antidiabetic medication); and (c) dyslipidemia (triglyceride concentration ≥ 150 mg/dL and/or HDL-cholesterol level < 40 mg/dL). The chi-square test and logistic regression modeling were used for statistical analyses. Values of p<0.05 were considered statistically significant._x000D_ Results The median age of participants was 69 (18-95) years. The overall prevalence of OAB and MetS were 13.5% (11.2% for men and 15.2% for women) and 15.2% (24.5% for men and 8.2% for women), respectively. The prevalence was higher in older age groups. A significant association was found between OAB and MetS The age-adjusted odds ratio (95% CI) were 1.22 (1.06-1.39) for men and 1.49 (1.21-1.83) for women, respectively. We also analyzed the relationships between OAB and the number of components of MetS. In the multivariate analysis, a significant association was found between OAB and the following: age (odds ratio = 1.05) and high waist circumference (1.24) for men, and, age (1.04) , high waist circumference (1.42) and hyperglycemia (1.17) for women. Conclusions Our study confirmed the relationship between OAB and MetS in both men and women. These findings suggest that OAB is a facet of the MetS. Funding JSPS KAKENHI
Authors
Yoshitaka Aoki
Chieko Matsumoto Yosuke Matsuta Hideaki Ito Yukinori Kusaka Osamu Yokoyama |
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MP86-11 |
Prospective assessment of psychological symptoms in men with late-onset hypogonadism who received testosterone replacement therapy |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making V | 17BOS |
Abstract: MP86-11 Sources of Funding: none Introduction The objective of this study was to characterize the status of psychological symptoms in Japanese men with late-onset hypogonadism (LOH) treated with testosterone replacement therapy (TRT)._x000D_ _x000D_ _x000D_ Methods The psychological symptoms in 100 consecutive Japanese men with LOH undergoing TRT for at least 6 months were prospectively evaluated before and 6 months after the initiation of TRT using several written questionnaires, including Mini International Neuropsychiatric Interview (M.I.N.I.), Self-rating Depression Scale (SDS), Aging Male Symptom (AMS) score and the Medical Outcomes Study 8-items Short-Form health survey (SF-8). Results In these 100 patients, 69 men consulted our outpatient clinic with a chief complaint of psychological symptoms, such as depressed mood, lack of motivation, anxiety and irritation. The other 31 men were with a chief complaint of physiological or sexual symptoms. Before the introduction of TRT, 62 patients were diagnosed as being complicated with depression by M.I.N.I.. Although there were not significant correlations between serum testosterone level and all evaluated psychological questionnaires scores, including SDS, mind domain of AMS and mental component summary of SF-8, before the initiation of TRT, all these scores at 6 months after TRT significantly improved compared with those before TRT in these 100 patients. When divided these 100 men into 2 groups, with and without depression, there was no significant difference in serum testosterone level between these 2 groups before TRT. The psychological symptoms assessed by several questionnaires in this study were significantly severe in men with depression compared with men without depression. However, all evaluated psychological questionnaires scores at 6 months after TRT significantly improved compared with those before TRT even in men with depression. Conclusions TRT appeared to significantly improve the status of psychological symptoms in men with LOH, regardless of a complication of depression._x000D_ Funding none
Authors
Kenta Sumii
Mikito Tanaka Takaki Ishida Noritoshi Enatsu Koji Chiba Kei Matsushita Masato Fujisawa |
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MP86-12 |
Psychological distress in patients undergoing surgery for urological cancer: a prospective single centre cross-sectional study |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making V | 17BOS |
Abstract: MP86-12 Sources of Funding: None Introduction Interest in disease-specific psychological well-being of patients with cancer has increased, and it has been estimated that less than half of all cancer patients are properly identified and treated for anxiety or depression. The aim of this study was to evaluate psychological health assessment in oncological patients admitted for surgery. Methods We performed a cross-sectional study in consecutively enrolled patients with bladder, kidney or prostate cancer, scheduled for surgery. Demographic data, socioeconomic status, education level and diagnoses were recorded. We evaluated the level of clinically meaningful depression and anxiety assessed by two tools: the Hospital Anxiety and Depression Scale and the State-Trait Anxiety Inventory (STAI). In order to determine variables related to depression and anxiety among the demographic variables, logistic regression analyses were conducted, with p<0.05 considered as statistically significant. Results 207 patients completed the questionnaires and were included in the study. The most frequent procedures were performed for bladder tumours (60.4%), being transurethral resection the most common type of surgery (52.7%) followed by radical prostatectomy (24.6%). The mean STAI-state score was 19.3 (±10.3), and the mean STAI-trait score was 18.4 (±11.9) points. Patients showed HADs depression and anxiety scores of 3.3 (±3) and 5.6 (±3.3) points, respectively. Female patients showed a higher level of anxiety and STAI-trait compared to males. Conclusions Gender, tumour type and surgical approach were significantly related to psychological distress in patients undergoing surgery for urological cancer. Females and patients with kidney tumour undergoing radical nephrectomy presented higher levels of anxiety. Funding None
Authors
Antonio Luigi Pastore
Giovanni Palleschi Antonio Carbone Serena Maruccia Ana Mir Bou Nuria Camps Bellnoch Juan Palou |
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MP86-13 |
Health Related Quality of Life of patients undergoing active surveillance – comparison with prostate cancer active treatments |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making V | 17BOS |
Abstract: MP86-13 Sources of Funding: This work was supported by grants from Instituto de Salud Carlos III FEDER (FIS PI11/01191 y FIS PI13/00412) and DIUE of Generalitat de Catalunya (2014 SGR 748) Introduction Active surveillance in localised prostate cancer is an accepted option in selected cases, but some concerns still needs to be clarified. We pretend to evaluate Health-Related Quality of Life (HRQoL), in a cross-sectional study, in patients with localized prostate cancer undergoing active surveillance (AS) compared with active treatments (radical prostatectomy, external-beam radiotherapy, brachytherapy) and general population. Methods Ninety-nine patients fulfilled the inclusion criteria. This group was compared to different active treatments (n=99 per group) from the ‘Spanish Multicentric Study of Clinically Localized Prostate Cancer’ cohort using prostate-specific (Expanded Prostate Cancer Index Composite [EPIC]) and generic (36-Item Short Form Health Survey, version 2 [SF-36]) QoL instruments. SF-36 results were also compared to US reference population. Results Cross-section analysis was performed at 24 months after initial therapy or AS beginning. AS group presented statistically higher sexual scores [54.4 mean score (28.3 SD)] when compared to all other active treatments and better urinary incontinence scores [87.4 (22.8 SD)] than radical prostatectomy group [65.8 (31.6 SD)]. Patients undergoing AS were more likely to present significant urinary irritative/obstructive symptoms compared to radical prostatectomy group. No statistically significant differences were found among other domains. Patients with localized prostate cancer, regardless of treatment applied, presented slightly higher SF-36 physical and mental dimension scores (except for radical prostatectomy) than US general population reference norm (men aged 65-74). Conclusions AS may be a good treatment option for low or intermediate risk prostate cancer since induces the least impact in QoL. No significant differences were found on Physical and Mental Component Summaries compared to general US population. This study provides cross-sectional information about AS impact on QoL. Funding This work was supported by grants from Instituto de Salud Carlos III FEDER (FIS PI11/01191 y FIS PI13/00412) and DIUE of Generalitat de Catalunya (2014 SGR 748)
Authors
Lluis Fumado
Jose Francisco Suárez Olatz Garín Andrea Sureda Montse Ferrer Manel Castells Jose Maria Abascal Maria Carme Mir Xavier Bonet Helena Vila Lluís Cecchini Francesc Vigués |
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MP86-14 |
Prostate Specific Antigen and Health-Related Quality-of-Life Outcomes in Uninsured Men with Prostate Cancer |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making V | 17BOS |
Abstract: MP86-14 Sources of Funding: none Introduction Prostate Specific Antigen (PSA) continues to be a useful marker of risk strata and disease progression for patients with prostate cancer. While there have been multiple investigations into the relationship between PSA and mortality, there is a dearth in the literature describing the association between PSA and health-related quality-of-life (HRQOL) outcomes. In this study, we hypothesize that PSA is inversely related with HRQOL in patients with prostate cancer. Methods Our cohort consisted of a prospective analysis of men from a state-funded program that provides free prostate cancer care to underinsured and uninsured low-income California residents with prostate cancer. Highest pre-treatment PSA was our primary exposure variable of interest. We created 4 strata: <10, 10-19.9, 20-49.9 and ≥50 PSA. The primary outcome variables were HRQOL at program enrollment using the RAND SF-12 to measure physical and mental health, and the UCLA Prostate Cancer Index Short Form to measure urinary, sexual and bowel habits in two domains: bother and function. Controlling for demographic and clinical variables, we conducted separate multivariable linear regression analysis for each quality of life domain. Results 627 men were eligible for the study. Age, ethnicity, primary language, education and Charlson comorbidity did not differ across PSA strata. Compared to the referent group PSA <10, those with PSA ≥50 were more likely to receive androgen deprivation therapy as their primary form of treatment (p <0.01). Patients with PSAs 10-19.9 were more likely to have sexual bother (β=11.1, p<0.03) compared to the referent group. (See Table) There were no other differences in other HRQOL domains across PSA strata. Conclusions In this population, we found no statistically significant difference in HRQOL outcomes by PSA level. The finding that patients with very elevated PSA levels having outcomes that were no worse than patients with less aggressive disease is important clinically because most quality of life detriments tend to be from treatment of localized disease. Further, these findings will inform physicians on patient symptomatology despite PSA level. Funding none
Authors
Avi Baskin
Joseph Shirk Lorna Kwan Karim Chamie |
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MP86-15 |
EFFECTS OF GROUP REHABILITATION UPON WOMEN UNDERGOING SURGERY FOR OBSTETRIC FISTULA |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making V | 17BOS |
Abstract: MP86-15 Sources of Funding: None Introduction Obstetric fistula due to prolonged obstructed labor is a significant public health concern in the developing world. Fistula patients experience chronically elevated levels of social isolation, stigmatization, and depression. In this qualitative study, we aimed to evaluate the experience of group rehabilitation during postoperative recovery in the setting of a "fistula camp" upon women seeking surgical care for fistula and related birth injuries. As this population is marginalized and ostracized, we predicted that group rehabilitation might be particularly germane. Methods Study participants were women who received surgical care for obstetric fistula and high-grade perineal lacerations at the Mbarara Regional Referral Hospital in Uganda during 2 fistula camps in 2015 and 2016. Using semi-structured interviews, we sought to characterize the lived experiences of these women and their feelings surrounding their medical and surgical care in the setting of a group-based rehabilitative fistula camp. Interviews were conducted via translators who spoke the native dialects. Data was transcribed and analyzed using grounded theory methods, as described by Charmaz. We also directly observed women during their stay and recorded the frequency and types of interpersonal behaviors and interactions. Results Twenty-six women participated in the interviews. Themes of social isolation, depression, shame, and stress were present in women's testimonials of their experiences prior to fistula camp arrival (see Table). When discussing experiences during and after fistula camp stay, themes of social support and hopefulness emerged. Behaviors and interactions indicating social integration with bond formation and social support within the fistula ward were observed. Conclusions Exposure to other women who had obstetric fistula was of therapeutic benefit to women with these same conditions. We found that the impact of shared experience amongst the women played a critical role in their understanding, perception, and outlook towards their condition and their hope for recovery. A group-based model of postoperative care that integrates physical and psychosocial healing may be highly effective for this population. Funding None
Authors
Pooja Parameshwar
Musa Kayondo A. Lenore Ackerman Jennifer Anger Christopher Tarnay |
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MP86-16 |
A multi-center analysis of prostate cancer (PCa) treatment among Veterans following introduction of the 17-gene Genomic Prostate Score (GPS) assay |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making V | 17BOS |
Abstract: MP86-16 Sources of Funding: Genomic Health Inc. Introduction Active Surveillance (AS), a recommended management approach for low risk PCa, has been widely implemented within VA Medical Centers (VAMCs). However, Veteran characteristics such as age, race, and Agent Orange (AO) exposure may limit use of AS in some patients. The GPS test uses tumor biology to predict likelihood of favorable pathology. GPS may improve risk stratification for patients who are perceived as higher risk. To date, no published studies describe treatment patterns for Veterans following use of genomic tests. This study compares treatment patterns before and after introduction of the GPS assay within 6 VAMCs. Methods Men with newly diagnosed, NCCN very low, low, or intermediate risk PCa were eligible. We established treatment patterns in an untested patient cohort by reviewing charts from 2013-2014. From 2015-2016, we introduced the GPS assay within these same VAMCs in a prospective study. Six months after biopsy results, we reviewed charts to establish treatments patterns for both untested and tested Veterans. Results There were 200 men in the untested cohort and 190 men in the tested cohort. Patient characteristics were similar across groups. AS increased by 12% overall. The largest increase was among patients under age 60 (33% increase). AS increased in all NCCN risk groups with the largest increases in NCCN low risk (16%) and across racial subgroups (11% Caucasian, 16% Black, 20% Other). Veterans exposed to AO showed a small decrease in AS, while Veterans without exposure showed a 19% increase in AS. Median GPS was similar across racial groups and between Veterans exposed and not exposed to AO._x000D_ _x000D_ Conclusions In clinically similar cohorts of untested and tested Veterans, implementation of the GPS assay increased use of AS across all age, risk, and racial groups. The assay showed similar biological risk between Caucasians and Blacks and Veterans exposed and not exposed to AO. GPS may be a useful tool to refine risk assessment of PCa and to increase the already high rates of AS among clinically and biologically low risk patients, regardless of their race and AO exposure. Future studies of Black and AO exposed Veterans, including persistence on AS, are needed confirm these findings._x000D_ Funding Genomic Health Inc.
Authors
Julie Lynch
Megan Rothney Raoul Salup Cesar Ercole Sharad Mathur David Duchene Joseph Basler Javier Hernandez Michael Liss Michael Porter Jonathan L. Wright Michael Risk Mark Garzotto Olga Efimova Michael Kemeter Bela Denes Phillip Febbo Atreya Dash |
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MP86-17 |
The 2017 American Joint Committee on Cancer Eighth Edition Cancer Staging Manual: Changes in Staging Guidelines for Cancers of the Kidney, Renal Pelvis and Ureter, Bladder, and Urethra |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making V | 17BOS |
Abstract: MP86-17 Sources of Funding: none Introduction Cancers of the kidney, renal pelvis, ureter, bladder and urethra account for 143,190 new cases and 31,540 deaths in 2016. Accurate cancer staging is critical for predicting prognosis and defining optimal treatments. Cancer stages are defined by the American Joint Committee on Cancer (AJCC) which produces and updates the evidence-based Cancer Staging Manual (CSM). In October, 2016 the AJCC released the CSM 8th edition, which is effective for all cancer cases diagnosed on or after January 1, 2017. The aim of this project is to provide a summary of the changes to the classification of these cancers of the urinary tract. _x000D_ _x000D_ Methods To update the CSM 8th Edition, the AJCC convened an international multispecialty expert panel of leading cancer physicians, population scientists, cancer registrars and statisticians. TNM cancer classification is based primarily on anatomic information regarding extent of the primary tumor (T), regional lymph node status (N), and presence of distant metastases (M). Changes in TNM classification were made by the panel after evidence review and expert consensus. The AJCC Evidence-Based Medicine and Statistics Core determined levels of evidence (1 to 4) for each change through analysis of the number and quality of studies used in decision-making. Results CSM 8th Edition changes in urinary tract cancers are detailed in table 1. In summary, the T3a definition for kidney cancer was modified to include tumors invading the pelvicalyceal system. For cancer of the renal pelvis and ureter, prior categorization of N3 metastasis was collapsed into the N2 category. Changes in bladder cancer staging included reclassification of perivesical lymph node involvement, sub-classification of distant metastases and addition of prognostic subgroups for stages 3 and 4. For urethral cancer, urothelial carcinoma in situ of the prostate was collapsed into single stage (Tis), clarification was made for T1 and T4 disease, and distinction was made between N1 and N2 disease. _x000D_ _x000D_ Conclusions The AJCC CSM reflects the latest evidence and expert consensus for cancer staging. The 8th Edition refines the TNM classifications of urinary tract cancers and represents a further step toward a personalized approach to cancer staging. Funding none
Authors
Dennis J. Robins
Alexander C. Small Mahul B. Amin Bernard H. Bochner Sam S. Chang Toni K. Choueiri Jason A. Efstathiou Mary Gospodarowicz Donna E. Hansel Patrick A. Kenney Badrinath R. Konety Jaime Landman Cheryl T. Lee Bradley C. Leibovich Elizabeth R. Plimack Victor E. Reuter Brian I. Rini Srikala Sridhar Walter M. Stadler Satish K. Tickoo Raghunandan Vikram Ming Zhou James M. McKiernan |
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MP86-18 |
Gender Differences in Urological Subspecialties |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making V | 17BOS |
Abstract: MP86-18 Sources of Funding: None Introduction To examine representation in urological subspecialties in relation to surgeon gender and characterize practice patterns among certifying urologists over the last 13 years. Methods Demographic and case log data of certifying and recertifying urologists (2004 to 2015) was obtained from the American Board of Urology (ABU). We investigated gender-specific trends in self-reported practice type (academic or private practice), sub-specialization, and employment as a full-time versus part-time physician, relative to certification year and cycle. _x000D_ Results Of a total of 9,140 urologists applying for certification or recertification over the study period, 815 (8.9%) were women, with first time certifiers representing the largest proportion of women surgeon candidates at 65.0% of all women certifying and 16.7% of total first time certifying urologists (p<0.001). 23.6% of women surgeons identified their practice as being academic compared to 13.7% of their male colleagues(p<0.001). Women surgeons identify as sub-specialists in greater numbers (46.4%) than their male counterparts (23.4%) across all certification cycle cohorts and certification years (p<0.001). 25.4% of all women urologists requesting certification identify as subspecialists in female urology and 10.4% in pediatrics compared to 4.8% and 3.1% of their male colleagues respectively (both p<0.001). Female and male surgeons request certification in equal proportion in infertility (1.9% women compared to 1.8% men). Female surgeons however lag behind their male colleagues in oncology (4.5% compared to 7.6%) as well as endourology and stone disease (4.0% women compared to 6.1% men) across all certification years. Conclusions A growing proportion of certifying urologists are women surgeons, who are disproportionately first time certifiers. Women surgeons account for a disproportionate volume of urologists who practice in the academic setting and identify as sub-specialists. Funding None
Authors
Oluwarotimi Nettey
Joceline Liu Stephanie Kielb Edward Schaeffer |
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MP86-19 |
Female urology resident representation at sectional meetings – do we have a gender disparity issue? |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making V | 17BOS |
Abstract: MP86-19 Sources of Funding: None Introduction The number of female urology residents in the United States has continued to rise over the past 10 years. The representation of this cohort in an academic meeting setting has not been fully defined. We reviewed abstracts from the Mid-Atlantic American Urological Association (MAAUA) sectional meetings to determine if this increase in female urology residents mirrored an increase in this group&[prime]s abstract authorship. Methods Full text abstracts from the MAAUA meetings were analyzed from 2008-2014 excluding one joint section meeting. The first author&[prime]s gender was ascertained from institutional websites, social media, and U.S. News and World Report. If still uncertain, then the gender was classified as &[Prime]unknown&[Prime] and such abstracts were not included in the analysis. The abstracts were categorized as pertaining to general urology, endourology, oncology, reconstruction/trauma, pediatrics, robotic/laparoscopic, female pelvic medicine, and education/other. Results A total of 484 abstracts were analyzed. Of these, 393 (81%) were first authored by men, 81 (17%) by women, and 10 (2%) having an unknown gender. The disparity between men and women authorship was significant at all years of evaluation (p < 0.0001) with a declining trend of female first authorship across the study years. (Figure 1) Subgroup analysis across urology specialties highlighted significantly greater male first author representation in all topic areas including female pelvic medicine. (Figure 2) Conclusions Despite an increasing number of female urology residents, representation at one AUA sectional meeting over the past 7 years remained disproportionately low. Additionally, analysis of trends revealed a slight decrease over the same time period. While this may be a function of smaller sample size, these data underscore the need for closer evaluation of the reasons underlying this trend. Funding None
Authors
Tony Lin
Adam Klausner Jay Raman |
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MP86-20 |
Impact of Numeracy on Understanding of Prostate Cancer Risk Reduction in PSA Screening |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making V | 17BOS |
Abstract: MP86-20 Sources of Funding: None Introduction Prostate-specific antigen (PSA) screening in men of average risk remains controversial. Results from PSA clinical trials are widely cited in patient education materials, but patients' ability to incorporate probability and risk data into their decision-making may depend on their numeracy, or facility with quantitative concepts. This study assessed men's numeracy and its impact on their understanding of the risk reduction benefits of PSA screening. Methods Cross-sectional survey study. Men 40-75 years old attending a general medicine clinic were invited to complete a survey, which included demographics, personal PSA and prostate cancer (CaP) history, and a validated 3-item numeracy test. Numeracy was scored as the number of items correctly answered (range 0-3). Surveys also presented PSA risk reduction data derived from the European Randomized Study of Screening for Prostate Cancer, framed in 1 of 4 ways: absolute or relative risk reduction (ARR or RRR), with or without baseline risk (BR). Respondents were asked to adjust their perceived risk of CaP mortality using the risk data presented. Accuracy of risk reduction was evaluated relative to how risk data were framed. Results 200 men completed the survey (60% response rate). Mean age was 60 years, 51% had received a PSA test, and 5% reported a CaP diagnosis. Respondents' demographics were not significantly different among the 4 survey formats. Most men incorrectly answered 1 or more of the 3 numeracy items; half could not convert "1 in 1000" to a percentage, and one-quarter could not calculate "1% of 1000." Overall accuracy of perceived risk adjustment based on PSA data was 20% among all groups. Accuracy varied with how data were framed: when presented with RRR, men were 13% accurate without BR and 31% accurate with BR; when presented with ARR, they were 0% accurate without BR and 35% accurate with BR. Including BR data significantly improved accuracy for both RRR (P=0.03) and ARR groups (P<0.01). Accuracy was significantly related to numeracy; numeracy scores of 0, 1, 2, and 3 were associated with accuracy rates of 6%, 5%, 9%, and 36%, respectively (P<0.01). Neither PSA testing history nor CaP history was associated with accuracy. Conclusions Patients' numeracy was significantly associated with the accuracy of interpreting quantitative benefits of PSA screening. Although accuracy improved when the presentation of risk reduction data was framed by baseline risk, numeracy in this screening population of men was poor overall. Alternative methods of communicating concepts of risk to patients may facilitate shared decision-making. Funding None
Authors
Kevin Koo
Charles Brackett Ellen Eisenberg Kelly Kieffer Elias Hyams |
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MP87-01 |
AKT-phosphorylated FOXO1 inhibits PKM2 nuclear localization and Warburg effect in prostate cancer |
Prostate Cancer: Basic Research & Pathophysiology III | 17BOS |
Abstract: MP87-01 Sources of Funding: National Institutes of Health (CA134514 and CA130908 to H.H.), the Department of Defense (W81XWH-09-1-622 and W81XWH-14-1-0486 to H.H.), National Natural Science Foundation of China (81101931 to C.W.P) and Shanghai Municipal Commission of Health and Family Planning (201640041 to C.W.P). Introduction Elevated glucose uptake and lactate production in the availability of oxygen, a phenomenon called the Warburg effect, is important for cancer cell growth. Phosphorylation of Pyruvate kinase isozyme M2 (PKM2) by ERK promotes its nuclear localization and the Warburg effect. O-class forkhead factor 1 (FOXO1) acts as a tumor suppressor in the nucleus. FOXO1 can be phosphorylated by activated AKT and exported to cytoplasm, thereby losing its tumor suppressor function. Here, we revealed that AKT-phosphorylated FOXO1 inhibits IQGAP1-augmented activation of ERK. We also investigated whether AKT-phosphorylated FOXO1 inhibits PKM2 nuclear localization and Warburg effect in prostate cancer. Methods We used co-IP to determine protein interaction, Western-blot to detect the protein level, RT-PCR to detect gene expression level, immunocytochemistry to detect PKM2 cellular localization, immunohistochemistry to analysize FOXO1 and phosphor-ERK level in human prostate cancer using tissue microarray (TMA). Glucose or lactate levels were determined using a glucose assay kit or lactate assay kit. IQBP was a small phosphor-mimicking peptide derived from FOXO1. PC-3-Luc cells were injected into NSG mice to generate xenograft model. Results We identified the scaffold protein IQGAP1 as a binding partner of FOXO1 (Fig. a). We demonstrated that activated AKT is important for FOXO1-IQGAP1 interaction (Fig. b and c), and AKT-phosphorylated FOXO1 at serine-319 is critical for FOXO1 binding to IQGAP1 (Fig. d). Phosphorylated FOXO1 inhibits IQGAP1-augmented phosphorylation of ERK(Fig. e-g). We also found that there is an inverse correlation between FOXO1 and phosphorylated ERK1/2 in human prostate cancer tissues (Fig. h and i). Phosphorylated FOXO1 (cytoplasmic) inhibits PKM2 nuclear localization (Fig. j) and knockdown of FOXO1 promotes PKM2 nuclear localization (Fig. k). We further demonstrated that phosphorylated FOXO1 (cytoplasmic) inhibits expression of PKM2 target gene and induces glucose uptake and lactate production (Fig. l and m). Finally, we demonstrated that IQBP overcomes docetaxel (DTX)-induced chemoresistance through inhibiting Warburg effect in vivo (Fig. n and o). Conclusions AKT-phosphorylated FOXO1 inhibits PKM2 nuclear localization and Warburg effect in prostate cancer. Funding National Institutes of Health (CA134514 and CA130908 to H.H.), the Department of Defense (W81XWH-09-1-622 and W81XWH-14-1-0486 to H.H.), National Natural Science Foundation of China (81101931 to C.W.P) and Shanghai Municipal Commission of Health and Family Planning (201640041 to C.W.P).
Authors
Chun-Wu Pan
Jian An R. Jeffrey Karnes Liguo Wang Jun Zhang Jun Qi Haojie Huang |
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MP87-02 |
Tumor-associated macrophages promote prostate cancer metastasis via CCL2-CCR2 axis-induced CCL22-CCR4 axis |
Prostate Cancer: Basic Research & Pathophysiology III | 17BOS |
Abstract: MP87-02 Sources of Funding: JSPS KAKENHI (Grant No. 25861413 to K. Izumi and Grant No. 26462405 to K. Narimoto) Introduction Early studies have found that tumor-associated macrophages (TAMs) promote cancer progression. We previously reported that TAMs promote prostate cancer metastasis via activation of the CCL2-CCR2 axis. Recently, it was reported that the CCR4 (receptor of CCL17 and CCL22) expression level in breast cancer was associated with lung metastasis. However, the role of CCR4 and the relationship between CCR2 and CCR4 in prostate cancer is unclear. The aim of this study was to elucidate the role of CCR4 and the relationship between CCL2-CCR2 axis and CCL17/CCL22-CCR4 axis in prostate cancer progression. Methods Human prostate cancer cell line cells and monocyte-lineage cells were used. Transwell migration and invasion assays co-cultured with or without macrophages were performed. Chemokines and their receptors in prostate cancer cells were measured. CCR2 and CCR4 in prostate cancer tissue were immunohistochemically analyzed. Results Co-culture of macrophages and prostate cancer cells increased prostate cancer cell migration and invasion and induced secretion of CCL2. CCL2 promoted prostate cancer cell migration in an autocrine manner and induced CCR2, CCR4 expressions, and CCL22 secretion of prostate cancer cells. RT-PCR, western blotting, and immunocytochemical staining revealed both CCR2 and CCR4 expressions in prostate cancer cells. CCL22 also promoted prostate cancer cell migration. Blockade of the CCL2-CCR2 or CCL17/22-CCR4 axis with receptor antagonist inhibited the migration of prostate cancer cells. The CCL2-CCR2 and CCL22-CCR4 axes increased phosphorylation of Akt and Erk1/2. Although both CCR2 and CCR4 antagonists could inhibit phosphorylation of Akt and Erk1/2, the CCR4 antagonist, compared with the CCR2 antagonist, strongly inhibited phosphorylation of Akt. CCR4 may have contributed more to prostate cancer cell migration than did CCR2. CCR4 and CCR2 were increased in prostate cancer tissues by IHC staining. Interestingly, the staining intensities of CCR2 and CCR4 in each specimen were significantly correlated. Moreover, the staining intensity of CCR4 was correlated with the progression of TNM stage. Conclusions This is the first study to show that CCR4 was expressed in prostate cancer cell lines and human prostate cancer tissues and that the CCL22-CCR4 axis contributed to prostate cancer migration and invasion. Targeting of the CCL22-CCR4 axis, which is activated by TAMs, may be a novel therapeutic target and a potential biomarker for prostate cancer. Funding JSPS KAKENHI (Grant No. 25861413 to K. Izumi and Grant No. 26462405 to K. Narimoto)
Authors
Kouji Izumi
Aerken Maolake Ariunbold Natsagdorj Kazutaka Narimoto Yoshifumi Kadono Atsushi Mizokami |
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MP87-03 |
Urinary MMP-9 as candidate for a non-invasive prostate cancer biomarker revealed by quantitative proteomics analysis |
Prostate Cancer: Basic Research & Pathophysiology III | 17BOS |
Abstract: MP87-03 Sources of Funding: CNPq Introduction Novel strategies for candidate biomarker discovery in prostate cancer (PC) are needed to address the lack of specificity of prostate specific antigen (PSA) in PC screening and diagnosis. Urine is a very attractive biological fluid for prostate cancer biomarker discovery and measurement, since it is easy to obtain, non-invasive and may reflect biochemical processes within the prostate. Our aim is to search for proteins in the urine of patients with diagnosis of PC using isobaric labeling combined with high sensitive mass spectrometry-based proteomics. Methods In this study we performed isobaric labeling combined with high sensitive and accurate mass spectrometry-based proteomics to identify proteins that are differentially expressed in the urine of men with PC comparing with those with benign prostate hyperplasia (BPH). Results In total, 725 proteins were identified; amongst them 51 and 73 proteins were up and down regulated respectively in patients with PC. Two peptides from MMP-9 and Ly-6/neurotoxin-like were identified significantly up-regulated in PC and were further validated using a complementary targeted proteomic approach. Furthermore, we also quantified the expression of MMP9 in a set of 10 control and 17 prostate cancer urines, using ELISA, demonstrating that the expression of MMP9 is statistically higher in the urines from prostate cancer patients compared to controls (T-test, p<0.05). The activity of metalloproteinase was measured using zymography but no correlation between expression and activity in the urine samples from BPH and PC was observed. Conclusions Mass spectrometry based proteomics is a powerful method to discover and validate novel noninvasive candidate biomarkers in urine and our results open the potential of novel avenues for PC diagnosis. Funding CNPq
Authors
Rebeca Kawahara
Fabio Ortega Livia Rosa-Fernandes Vanessa Guimaraes Katia Leite Willian Nahas Miguel Srougi Martin Larsen Giuseppe Palmisano |
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MP87-04 |
Meis proteins as predictive markers of metastatic prostate cancer progression |
Prostate Cancer: Basic Research & Pathophysiology III | 17BOS |
Abstract: MP87-04 Sources of Funding: University of Chicago Pritzker Fellowship Program_x000D_ _x000D_ DOD grant PCRP PC130587, PI: Vander Griend Introduction Improvement in prostate cancer (PCa) management requires better understanding of mechanisms of PCa progression. Previous studies identified Meis (myeloid ecotropic viral integration site) as a putative biomarker capable of prognostic prediction in PCa. This study analyzed RNA-sequencing (RNA-seq) of 26 tumors and 90 metastases to identify Meis related genes associated with metastatic progression, and examined the negative predictive value (NPV) of Meis in developing metastatic PCa using tissue microarrays (TMA). Methods Annotated TMAs of patients who underwent radical prostatectomy (RP) for PCa were stained for Meis and scored by a single genitourinary pathologist. NPV was calculated for the ability of Meis positivity (+Meis) to predict clinical metastasis, defined as radiographic or pathologic evidence of metastasis. RNA-seq of 26 tumors, and 90 metastases were obtained from publically available data. The 26 tumors were stratified by Meis expression, and pair-wise analysis to the metastases identified genes in low Meis tumors associated with metastatic progression. Results A total of 99 patients underwent RP for PCa. There was no difference in age, race, stage, or Gleason grade among +Meis and Meis negative (-Meis) patients. 23% (n= 23) of patients had a +Meis score. 10% (n= 10) of patients demonstrated evidence of clinical metastasis. Of the 76 -Meis patients, 13% (n= 10) developed clinical metastasis; 0 +Meis patients developed metastasis (NPV= 100%). RNA-Seq of Meis low tumors had an expression profile closest to metastatic lesions compared to Meis high tumors. Pair wise analysis of tumors compared to metastases identified 1082 differentially expressed genes (DEG) in Meis low tumors associated with metastatic progression. Conclusions +Meis negatively predicted 100% of clinical metastasis in post-RP PCa, supporting its prognostic role in PCa. RNA-Seq identified 1082 DEG associated with Meis low tumors and metastatic progression. Further analysis of these genes can potentially identify novel approaches toward preventing and treating metastatic PCa. Funding University of Chicago Pritzker Fellowship Program_x000D_ _x000D_ DOD grant PCRP PC130587, PI: Vander Griend
Authors
Raj Bhanvadia
Erin McAuley Wen-Ching Chan Hannah Brechka Gladell Paner Donald Vander Griend |
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MP87-05 |
Upregulation of opiorphin is associated with prostate cancer; a potential novel therapeutic target |
Prostate Cancer: Basic Research & Pathophysiology III | 17BOS |
Abstract: MP87-05 Sources of Funding: NY State, Department of Health, Prostate Cancer Research, RFA # 1410200115 Introduction Patients who die from prostate cancer (PrCa) do so as a result of the development of castrate resistant disease. Identification of novel targets not related to androgen biosynthesis may provide useful therapeutic alternatives that could have a positive impact on the long term survival of these patients. Recently, it has been shown that upregulation of the opiorphin gene (encoding an endogenous neutral endopeptidase inhibitor involved in the hypoxic response) is an unfavorable risk factor for the survival of oropharyngeal squamous cell carcinoma patients after surgery. In the present studies we determined whether opiorphin is also upregulated in PrCa, and if it plays a role in the hypoxic response in PrCa cells. Methods We searched the Gene Expression Omnibus (GEO), a public functional genomics data repository administered by the NCBI, for evidence of opiorphin gene (ProL1) expression. Quantitative-(qt)-RT-PCR was used to compare expression of ProL1 in 41 PrCa tissues and 7 control, non-cancerous prostate tissue present on a commercially available tissue array. Two PrCa cell lines (LnCaP, androgen dependent and PC-3, androgen independent) were exposed to hypoxia for various lengths of time (1-24 hours, RNA isolated and expression of opiorphin and other genes involved in the hypoxic response determined by qt-RT-PCR or microarray analysis. Results A search of GEO data demonstrated that the gene encoding opiorphin (ProL1) was significantly upregulated in PrCa. We confirmed a significant upregulation, with a trend for greater upregulation with PrCa stage, on an RNA PrCa tissue array. We found hypoxia resulted in an early (2h) 2-fold upregulation of ProL1 in LnCaP cells. In contrast, in PC3 cells, there was only a significant (3-fold) upregulation of ProL1 after 24h of hypoxia, with other markers of the hypoxic response (Hif1a and VEGF) significantly activated after 5h. Conclusions For the first time we report up-regulation of the opiorphin gene (ProL1) in PrCa. Opiorphin is a mediator of the hypoxic response in certain cell types. We demonstrate hypoxic upregulation of ProL1 in two PrCa cell lines. Early upregulation in LnCaP cells, prior to other known markers of the hypoxic response (Hif1a and VEGF) suggests in certain PrCa cells (androgen dependent) ProL1 may play a role in regulating downstream modulators of the hypoxic response. Taken together, these results suggest opiorphin may play a role in overcoming the hypoxic environment in certain PrCa tumors and might therefore represent a novel therapeutic for PrCa. Funding NY State, Department of Health, Prostate Cancer Research, RFA # 1410200115
Authors
Amarnath Mukherjee
Li Wang Mark Schoenberg Kelvin Davies |
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MP87-06 |
Expression analysis of tumor promoting genes in circulating tumor cells of patients with localized and metastatic prostate cancer |
Prostate Cancer: Basic Research & Pathophysiology III | 17BOS |
Abstract: MP87-06 Sources of Funding: Qiagen GmbH Germany Introduction Different platforms exist for the detection of circulating tumor cells (CTC). The identification of the androgen-receptor variant 7 (AR-V7) as a predictor of drug resistance has shown that the Adnatest® is a promising platform for analysis of prostate cancer (PC) associated mRNAs in CTC. Although it has been recently reported that the Adnatest® shows higher CTC detection rates compared to the CellSearch&[copy] platform in patients with metastatic castration resistant PC (mCRPC) (Danila et al. 2016), there is only limited data on stage-dependant prevalence of CTC using this platform. Moreover, the ability of this platform to analyze disease-relevant transcripts beyond AR-V7 has not been assessed sufficiently yet. The aim of the present study was to evaluate the presence of CTC detected by the Adnatest® in different stages of PC. Moreover, we assessed the expression of transcripts specific for cancer stem cells and epithelial mesenchymal transition (EMT) in CTC and further genes that are known to promote PC progression. Methods In this prospective study, we included 42 patients with clinically localized PC (17 low risk, 25 high risk) and 38 patients with metastatic PC (11 patients with metastatic castration sensitive PC (mCSPC) and 27 with mCRPC) between 07/2014 and 02/2015. CTC were enriched using the Adnatest® System (Qiagen, Hilden, Germany). Presence of CTC was assessed using the Adnatest® ProstateCancerDetect which quantifies the expression of PSA, PSMA and EGFR mRNA in CTC. Moreover, CTC with stem cell or EMT-like phenotypes were analyzed using the Adnatest® StemCell/EMT kit. Expression of the androgen receptor (AR), c-met, c-kit and thymidylate synthase (TYMS) were assessed using specific polymerase chain reaction (PCR) assays. Results were correlated with clinical data. Results The Adnatest® ProstateCancerDetect was positive in 8.0%, 18.8%, 54.6% and 70.4% of patients with low risk cM0 PC, high risk cM0 PC, mCSPC and mCRPC (p<0.001). CTCs with stem cell or EMT-features were found in 36.8% and 7.9% of cM1 patients vs. 20.9% and 0% of patients with cM0 disease (p=0.1 and 0.06). C-kit or c-met expressing CTC were present in only one (2.8%) and two patients (5.4%) with cM1 disease. TYMS positive CTCs were present in 7.1%, 20.8%, 48.1% and 50% of patients with low risk cM0 PC, high risk cM0 PC, mCSPC and mCRPC (p=0.01) whereas AR-positive CTCs were found in 0%, 0%, 27.3% and 44.4% of patients (p<0.001). Conclusions The presence of CTCs expressing PC-associated transcripts detected by the Adnatest® shows a clear correlation with clinical stage. AR and TYMS expression are frequently detected in CTC of patients with metastatic PC, whereas c-kit or c-met expressing CTC are rare events in PC patients. The potential prognostic and predictive impact of gene expression profiles of CTC detected by the Adnatest® is currently under investigation. Funding Qiagen GmbH Germany
Authors
Simone Bier
Jörg Hennenlotter Gunthild Beger Lucretia Pavlenco Nathalie Feniuk Siegfried Hauch Steffen Rausch Arnulf Stenzl Tilman Todenhöfer |
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MP87-07 |
The biological ramifications of prostate cancer associated cell free DNA: effect on platelet function and disease progression |
Prostate Cancer: Basic Research & Pathophysiology III | 17BOS |
Abstract: MP87-07 Sources of Funding: None Introduction The risk of developing venous thromboembolic events (VTE) is increased up to 4-fold in in men diagnosed with metastatic prostate cancer (PCa). While the precise reasons for this are unknown previous work has established the capacity of platelets (clot initiators) to absorb factors from the bloodstream that may alter platelet functions. Notably, one such factor, cell free DNA (cfDNA) has been shown to strongly correlate with disease severity and outcome. In this study, we sought to examine the effects of cfDNA from men with aggressive PCa on platelets in the context of clot formation and disease progression. _x000D_ Methods Platelets were isolated from venous blood of 10 men with metastatic castration resistant prostate cancer (mCRPC). Platelet aggregation in response to agonists (i.e. thrombin and collagen) was established using platelet aggregometer. Platelet ability to bind to cancer cells (in vitro) was determined using flow cytometry. Platelet effect on prostate tumor growth in vivo was assessed using human platelet transfusions into 3 different PCa mouse models (intracardiac, subcutaneous, and orthotopic) in combination with standard bioluminescence techniques._x000D_ Results We assessed the effects of tumor associated nucleic acids on circulating platelets. We found that PCa derived cfDNA - loaded platelets were more reactive to agonists (thrombin and collagen), vs. unloaded platelets, making them more susceptible to spontaneous clot formation. We established that platelets from men with mCRPC (10 men) were significantly (p<0.001) more adherent to cancer cells in vitro as compared to platelets from healthy controls. Addition of nucleic acids (i.e. DNA) to healthy donor platelets in vitro converted them to be more thrombogenic and similar to platelets from men with mCRPC. Finally, we observed that platelets from men with mCRPC strongly induced cell proliferation and tumor growth in vivo (p<0.005), as compared to platelets from healthy controls. Conclusions High levels of cancer associated cfDNA have been previously demonstrated to correlate with poor prognosis and increased risk of VTE in men with PCa. Intriguingly, we found that PCa associated cfDNA modulates platelet behavior, revealing, for the first time, a potential molecular basis for Trousseau syndrome in PCa. Further, our findings also shed new light on how cfDNA may alter cancer growth via modulating platelets in the tumor microenvironment. Taken together, our study provides novel insights into the possible biological consequences of cfDNA seen in the advanced cancer state. _x000D_ Funding None
Authors
Mackenzie Adams
James Henderson Mathew Lee Todd Morgan Ganesh Palapattu Alexander Zaslavsky |
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MP87-08 |
Role of the c-Myc target DNPH1, a new N-hydrolase, in kidney and prostate cancers |
Prostate Cancer: Basic Research & Pathophysiology III | 17BOS |
Abstract: MP87-08 Sources of Funding: INSERM, University of Strasbourg, Fondation pour la Recherche Médicale Introduction Clear cell renal cell carcinoma (CCC), the most lethal urologic tumor (250 000 cases, 110 000 deaths worldwide/year), is the main subtype of kidney cancer. It is characterized in 75% of cases by the loss of the von Hippel-Lindau (VHL) tumor suppressor gene leading to HIF? stabilization. Prostate cancer (PCa) is the most common cancer in men > 50 yo (1 100 000 cases, 300 000 deaths worldwide/year). CCC and PCa are resistant to therapies. DNPH1 (2'-deoxynucleoside 5'-phosphate N-hydrolase 1), a c-Myc target overexpressed in various cancers, regulates cell growth and angiogenesis and may thus behave as a new oncogene. Through alternative splicing, 4 isoforms can be generated with still unknown precise function. Our objective was to define the role of DNPH1 in these cancers. Methods We used a panel of cell lines i.e 786-0, A498 (VHL -) and Caki-1, Caki-2, ACHN (VHL +) for CCC and LNCaP, VCap, PC3, DU145, 22RV1 for PCa. Tumor/normal corresponding tissues pairs from 42 and 41 CCC and PCa patients, respectively, were also used. DNPH1 isoforms expression was measured by RTqPCR and Western blot. Since no specific chemical inhibitors are available, the role of DNPH1 isoforms in vitro and in vivo was evaluated using siRNAs and expressing vectors (wild-type or inactive, dead active site). In vivo, we used the tumor xenografted nude mice model to assess the role and the underlying mechanisms of DNPH1 in tumor growth. Results We show that CCC and PCa express only isoforms 1 and 2. These are 174 and 148 aminoacids long, respectively, and are identical till aminoacid 126. DNPH1 expression was deregulated in 71% of CCC cases but upregulated in 75% of PCa cases, regardless of the stage. Both isoforms behave similarly but isoform 1 represented 80% of total DNPH1 expression. In CCC cell lines, the transfection with wild-type DNPH1 expressing vectors decreased cell growth up to 60% by stimulating cell proliferation and inhibiting apoptosis, while the transfection with the inactive vector had no effect. In PCa cells, siRNAs targeting DNPH1 isoforms 1 and 2 decreased cell growth dose-dependently by up to 50% through inhibition of cell proliferation and induction of apoptosis. We are currently evaluating the effect of both isoforms in nude mice xenografted with CCC cell lines transfected with the DNPH1 expressing vector and in PCa-bearing nude mice treated with in vivo siRNAs. First results corroborate in vitro observations. Conclusions Our results show the opposite tumor suppressor/oncogene properties of DNPH1 in CCC and PCa and should allow to design new therapeutic options for these refractory diseases. Funding INSERM, University of Strasbourg, Fondation pour la Recherche Médicale
Authors
Sabrina Danilin
Claire Amiable Catherine Coquard Pierre-Alexandre Kaminski Julie Paoletti Sylvie Rothhut Imène Hamaidi Claire Béraud Véronique Lindner Hervé Lang Sylvie Pochet Thierry Massfelder |
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MP87-09 |
Distinct Epigenetic and Transcriptomic Variations in African American Men as Compared to Caucasian in Prostate Cancer |
Prostate Cancer: Basic Research & Pathophysiology III | 17BOS |
Abstract: MP87-09 Sources of Funding: Deane Prostate Health, Icahn School of Medicine at Mount Sinai. Both Shalini S Yadav and Kamlesh K Yadav are supported by the Prostate Cancer Foundation Young Investigator Awards. Introduction Prostate Cancer (PCa) is amongst the top five in cancer related death in men worldwide. Epidemiologically it varies with race and ethnicity. African American (AA) men not only have a higher incidence rate (~60%), but also ~2.5-times higher rate of mortality when compared to Caucasian men (CaM). In addition, there is diverse molecular heterogeneity in terms of mutations, gene expression, methylation patterns and copy number alterations in PCa. Therefore, it is of interest to identify the epigenetic and transcriptomic variation in African American and Caucasians. Methods The Cancer Genome Atlas (TCGA) dataset was used to investigate the variation in the biology of prostate cancer patients categorized on the basis of ethnicity. The study included large cohort of 333 primary prostate carcinoma patients that included 43 AA (13%) and 162 CaM (48%). We assessed and analyzed the differential methylation patterns amongst African Americans and Caucasians. Further, the genes that are differentially expressed in each methylation cluster were analyzed to identify the biological pathways that are significantly affected in both the races. Results We identified that out of four methylation clusters, AA predominantly belongs to methylation cluster 1 (20.9%) compared to CaM (9.9%). However, CaM (37%) preferentially belongs to methylation cluster 3 than AA (7%). Interestingly, the pathways involved with upregulated genes in methylation cluster 1 were associated with neuronal related pathway whereas, similar pathways were observed to be downregulated in methylation cluster 3. Comparatively, pathways associated with upregulated genes in cluster 3 include inflammation related pathways and hedgehog signaling pathways. Cell cycle signaling, DNA replication and Wnt signaling were predominantly associated with downregulated genes in methylation cluster 1. Conclusions The disparity in the molecular mechanism involved in the pathogenesis of prostate cancers in AA and CaM suggests diverse heterogeneity among different races. Variation of neuronal related pathway in different methylation clusters and their association with AA indicate its crucial role in racial disparity. Enrichment of neuronal signaling may reflect the more aggressive phenotype observed in prostate cancers of AA men. _x000D_ _x000D_ Funding Deane Prostate Health, Icahn School of Medicine at Mount Sinai. Both Shalini S Yadav and Kamlesh K Yadav are supported by the Prostate Cancer Foundation Young Investigator Awards.
Authors
Richa Rai
Cordelia Elaiho Victoria Hackert Kamlesh K Yadav Ashutosh Tewari Shalini S Yadav |
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MP87-10 |
Genomic Analysis of a Longitudinal Series of Surgical Prostate Cancer Bone Metastases and Xenografts from the Same Patient Revealed Selection of a Progressively Therapy Resistant Metastatic Clone |
Prostate Cancer: Basic Research & Pathophysiology III | 17BOS |
Abstract: MP87-10 Sources of Funding: Leo and Anne Albert Charitable Foundation, Phi Beta Psi Charity Trust Introduction Surgical prostate cancer bone metastasis samples were collected at the time of orthopaedic repair surgery and used to establish four novel patient-derived xenograft (PDX) models for advanced prostate cancer in the bone: PCSD1, PCSD4, PCSD5 and PCSD13. These PDX models closely reproduced bone metastatic disease in prostate cancer patients. In order to understand the changes that occur which may lead to progressive therapy resistance of the prostate cancer bone metastases we investigated and compared the genomic and transcriptomic variation in the longitudinal series of surgical bone metastasis prostate cancer patient samples and the xenografts derived from them._x000D_ _x000D_ Methods We performed copy number variation (CNV) assays on whole genome SNP arrays (Oncoscan, Affymetrix), whole exome DNA sequencing on the Illumina HiSeq 2000 sequencing platform and transcriptome analysis using Affymetrix GeneChip Human Transcriptome Array 2.0 on our PDX models from serial xenograft passages in mice and compared them to their originating patient’s bone metastasis samples. We also established microfluidic enrichment of single cells for RNASeq on our PDXs to detect the lethal metastatic clone evolution in the patient and xenograft tumor cells growing in the bone with and without anti-androgen treatment._x000D_ Results Comparison of genome-wide copy number variation (CNV), and whole exome sequencing (WES) revealed selection of a therapy-resistant sub-population - a metastatic clone - in both the patient bone metastases and in the xenograft, PCSD1, derived from the same patient (PDX). This is the first direct evidence that the therapy resistant sub-clone was already present in the heterogeneous early patient bone metastasis. WES analysis revealed germline alterations in DNA repair genes (BRCA2, ATM and CHEK2) in PCSD1, and PCSD5 as well as tumor suppressor genes (TP53, PTEN) in all four PDXs. Enzalutamide or bicalutamide treatment of castrate-resistant intra-femoral PCSD1 xenografts induced expression of a neuronal gene signature._x000D_ Conclusions We showed for the first time the selection in the patient and in his serially passaged xenografts of a pre-existing, therapy-resistant sub-population in his progressing bone metastatic prostate cancer. We have used our new PDXs for the genomic characterization of the lethal metastatic clones in order to generate a multi-marker signature which may be used to detect and therapeutically target lethal metastases early in the disease. _x000D_ _x000D_ Funding Leo and Anne Albert Charitable Foundation, Phi Beta Psi Charity Trust
Authors
Christina Jamieson
Michelle Muldong Abigail Gallegos Christina Wu Theresa Mendoza Jin Sung Park William Zhu Omer Raheem Seung Chol Park Michael Liss Danielle Burner Lee Edsall Olga Miakicheva Nicholas Cacalano Catriona Jamieson Christopher Kane Anna Kulidjian Terry Gaasterland |
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MP87-11 |
Intrinsic prostate cancer subtypes determined in diagnostic prostate biopsies of men with metastatic disease resemble castration-resistant prostate cancer metastases |
Prostate Cancer: Basic Research & Pathophysiology III | 17BOS |
Abstract: MP87-11 Sources of Funding: DOD PC131996, PCF-Movember GAP1 Unique TMAs Project, Prostate Cancer Foundation (PCF) Creativity Award, Jean Perkins Foundation, NIH/NCI P01 CA098912-09, NIH R01CA131255 and P50CA092131, Stephen Spielberg Team Science Award._x000D_ _x000D_ Introduction We recently identified and validated 3 intrinsic prostate cancer subtypes (PCS) based on a 37-gene expression signature. To evaluate the PCS system as a prognostic tool, we determined the frequencies of PC subtypes in diagnostic prostate needle biopsies (PNBX) collected from men with high-grade localized PC (clinical stage M0) who remained disease-free or progressed to castration-resistant prostate cancer (CRPC) after definitive treatment as well as in PNBX of men who were newly diagnosed with metastatic disease (clinical stage M1). Methods PNBX cases were selected from a cohort of 486 patients with high-grade localized or metastatic prostate cancer (mPC), diagnosed and treated in the Greater Los Angeles VA Healthcare System between 2000 and 2015. RNA sequencing (RNAseq) was performed on 86 tumor foci from 68 formalin-fixed, paraffin-embedded (FFPE) PNBXs: thirty nine cases with de novo metastases (M1), 6 cases who progressed to metastasis (M0-P), and 23 PC cases without progression (M0-NP). Computation of pathway activation profiles, principal component analysis, and application of the 37-gene PCS classifier were performed for assignment of subgroups. The results of this analysis were compared to publically available datasets (PCF and SU2C datasets) of primary PC and CRPC metastases. Results Importantly, analysis of RNAseq data revealed adequate levels of transcriptome coverage (>18,000 genes) in all 68 cases. Significant differences in survival were observed in M1 cases compared to M0-P and M0-NP. The frequency of PCS groups in PNBX specimens of patients with M1 stage (36% PCS1; 21% PCS2; 44% PCS3) was similar to that of biopsies from metastatic CRPC in the PCF and SU2C cohort (35% PCS1; 20% PCS2; 45% PCS3). A high proportion of the poor prognosis PCS1 (n=14 of 15 cases) was identified in PNBX of patients with M1 stage compared to M0 stage. Conclusions Although the subtyping of PNBX and derived staging and prognostic information warrants further confirmation in a larger cohort, the data demonstrate a promising potential for a footprint of concurrent or future metastatic disease in PNBXs obtained at the time of PC diagnosis. Funding DOD PC131996, PCF-Movember GAP1 Unique TMAs Project, Prostate Cancer Foundation (PCF) Creativity Award, Jean Perkins Foundation, NIH/NCI P01 CA098912-09, NIH R01CA131255 and P50CA092131, Stephen Spielberg Team Science Award._x000D_ _x000D_
Authors
Eric Miller
Sungyong You Lorna Kwan Xinmin Li Michael Lewis Beatrice Knudsen Michael Freeman Isla Garraway |
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MP87-12 |
Adrenal Androgens Facilitate Prostate Cancer Cell Resistance to Androgen Deprivation Therapy |
Prostate Cancer: Basic Research & Pathophysiology III | 17BOS |
Abstract: MP87-12 Sources of Funding: P01-CA77739, DoD-W81XWH-15-1-0409 and RPCI-CCSG-C416056 Introduction Prostate Cancer (CaP) growth and survival is dependent on the interaction of androgen receptor (AR) and testicular androgens, testosterone and dihydrotestosterone (DHT). Men that fail potential curative treatment are treated with androgen deprivation therapy (ADT). ADT is palliative and CaP recurs as the lethal phenotype. One mechanism that contributes to CaP recurrence is intratumoral intracrine androgen metabolism, which is the conversion of weak adrenal androgens (androstenedione [ASD] or dehydroepiandrosterone [DHEA]) to T or DHT. Mice lack adrenal androgens and therefore adrenal androgen contribute to CaP xenograft recurrence is overlooked. The hypothesis for these studies is adrenal androgen supplementation will facilitate androgen dependent human CaP CWR22 xenograft resistance to ADT. Methods Mice were castrated, implanted with CWR22 and silastic tubes that contained T and empty silastic tubes that contained ASD or DHEA. T silastic tubes were removed after CWR22 tumor volumes reached 0.5 cc to simulate ADT. Digital calipers were used to measure changes in CWR22 tumor volume. Mouse serum, prostate and CWR22 were harvested at designated time points and liquid chromatography tandem-mass spectrometry (LC-MS/MS) was performed to measure androgen levels. Results CWR22 xenografts treated with no adrenal androgen regressed and began to grow 120 days after T silastic tube removal. ASD treated CWR22 tumors did not regress; CWR22 tumor growth increased and mice were euthanized because tumors grew beyond veterinary limits. DHEA treated CWR22 did not regress and did not grow like ASD treated CWR22. However, CWR22 xenografts recurred faster than control CWR22 xenografts. Serum PSA levels correlated with tumor volume. CWR22 androgen levels decreased in all treatment groups, but T levels remained sufficient to activate AR in ASD treated CWR22, but not control or DHEA treated CWR22 xenografts. Conclusions DHEA and ASD supplementation facilitated CWR22 resistance to ADT. However, CWR22 xenografts responded differently to DHEA and ASD, which suggests that adrenal androgens may play different roles when CaP cells undergo ADT. These studies show that adrenal androgen contributes should be taken into account when in vivo studies are performed to test CaP responses to ADT or therapeutic agents. Funding P01-CA77739, DoD-W81XWH-15-1-0409 and RPCI-CCSG-C416056
Authors
Michael Fiandalo
John Stocking Elena Pop Krystin Mantione John Wilton James Mohler |
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MP87-13 |
Estrogen receptor α in cancer associated fibroblasts suppresses prostate cancer invasion via reducing CCL5, IL6 and macrophage infiltration in the tumor microenvironment. |
Prostate Cancer: Basic Research & Pathophysiology III | 17BOS |
Abstract: MP87-13 Sources of Funding: none Introduction Cancer associated fibroblasts (CAF) play important roles in tumor growth that involves inflammation and epithelial cell differentiation. Early studies suggested that estrogen receptor alpha (ERα) was expressed in stromal cells in normal prostates and prostate cancer (PCa), but the detailed functions of stromal ERα in the PCa remain to be further elucidated. Methods In vitro study, we applied migration and invasion assays to demonstrated whether the levels of ERα in CAF cells (CAF.ERα(+)) could suppress PCa invasion via influencing the infiltration of tumor associated macrophages. Q-PCR, Elisa assay and luciferase assay were used to detect which cytokines may mediate the CAF.ERα(+) suppressed macrophage infiltration and PCa invasion. In vivo study, nude mice were orthotopically implanted with CAF.ERα(+) or CAF.ERα(?) mixed with CWR22Rv1 cells. Then, IHC was used to verify the data in vitro study. We further examined the ERα, CD206, CCL5 and IL6 expressions in 14 human PCa tissue specimens by IHC staining. Results Both in vitro and in vivo mouse PCa model studies demonstrated CAF.ERα(+) led to a reduced macrophage migration toward PCa via inhibiting CAF cells secreted chemokine CCL5 (Figure1 and 3). This CAF.ERα(+) suppressed macrophage infiltration affected the neighboring PCa cells invasion and the reduced invasiveness of PCa cells are at least partly due to reduced IL6 expression in the macrophages and CAF. (Figure 2). In human PCa tissues, our results showed a positive correlation between ERα, M2 macrophages, CCL5 and IL-6. In high stromal ERα expression samples, the expression levels of CD206 (M2 macrophage marker), CCL5 and IL6 were higher than in samples with low stromal ERα expression (Figure 4). Conclusions Our data suggest that CAF ERα could be applied as a prognostic marker to predict the recurrence-free survival, and targeting CCL5 and IL6 may be applied as an alternative therapeutic approach to reduce M2 type macrophages and PCa invasion in PCa patients with low or little ERα expression in CAF cells. Funding none
Authors
Yang Yang
Chiuan-Ren Yeh Spencer Slavin Jie Luo Fu-Ju Chou Keliang Wang Matthew Truong Chawnshang Chang Edward M. Messing Shuyuan Yeh |
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MP87-14 |
Structure-Activity Relationship Studies of ERGi-USU, a Highly Selective Inhibitor for ERG positive Prostate Cancer Cells |
Prostate Cancer: Basic Research & Pathophysiology III | 17BOS |
Abstract: MP87-14 Sources of Funding: This work was supported in part by CPDR Program HU0001?10?2-0002 to D.G.M., NIH Grants RO1 DK065977 to S.S., and HJF JOTT FY15 to S.S, A.M. and Stanford University to SVM. Introduction While new prostate cancer (CaP) treatments (Abiraterone and Enzalutamide) have improved survival in castration resistant prostate cancer (CRPC), their benefits are short-lived and drug resistance develops likely due to numerous adaptive mutations. Accumulating evidence has established the androgen regulated TMPRSS2-ERG fusion as a common oncogenic driver that contributes to the early development and progression of over half of CaP. Therefore, ERG oncoprotein and ERG dependent pathways are promising targets for CaP therapy in early stages when cancer is most responsive to treatment. We previously identified a small molecule inhibitor, ERGi-USU, which selectively inhibits ERG protein and cell growth in ERG positive tumor cell lines and mouse xenograft models. In an effort to further develop ERGi-USU with enhanced efficacy we performed detailed structure-activity relationship (SAR) evaluation of ERGi-USU core structure and developed new derivatives. Methods Based on SAR of the core structure of ERGi-USU, 48 new derivatives were designed and synthesized by substitutions with alkyl, alkoxy, cycloalkyl, heterocycloalkyl, aryl, heteroaryl or hydroxyl groups. The new ERGi-USU derivatives were evaluated for inhibition of cell growth and ERG protein levels in the TMPRSS2-ERG fusion harboring CaP cell line, VCaP. Four of these compounds have been selected for evaluation of ERG selectivity by defining IC50 in ERG positive malignant cells (VCaP, KG1, MOLT-4 and COLO320), ERG negative CaP cell line (LNCaP) or ERG positive normal primary endothelium-derived cells (HUVEC). Results Like parental compound, four new ERGi-USU derivatives exhibited inhibition of cell growth and ERG protein levels in ERG positive VCaP, KG1, MOLT-4 and COLO320 cell lines, with no or minimal effects on LNCaP and HUVEC cells. One of the new derivatives (ERGi-USU#6) showed increased efficacy for cell growth inhibition (IC50=0.074µM) compared to the parental ERGi-USU (IC50=0.200µM). Other three new compounds showed similar IC50 as the ERGi-USU. Conclusions Comprehensive evaluation of ERGi-USU derivatives along with parental compound has continued to underscore selective inhibition of ERG positive tumor cells by these small molecules. Funding This work was supported in part by CPDR Program HU0001?10?2-0002 to D.G.M., NIH Grants RO1 DK065977 to S.S., and HJF JOTT FY15 to S.S, A.M. and Stanford University to SVM.
Authors
Ahmed Mohamed
Charles Xavier Gauthaman Sukumar Samuel Banister Vineet Kumar Shyh-Han Tan Shilpa Katta Lakshmi Ravindranath Muhammad Jamal Taduru Sreenath David McLeod Gyorgy Petrovics Albert Dobi Meera Srivastava Sanjay Malhotra Clifton Dalgard Shiv Srivastava |
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MP87-15 |
Inhibition of RPS6KB1 as a potential adjuvant for prostate cancer radiation therapy |
Prostate Cancer: Basic Research & Pathophysiology III | 17BOS |
Abstract: MP87-15 Sources of Funding: Supported by VA-Merit Award I01 BX 000766-01 (APK) Introduction Radiation therapy (RT) is a standard treatment for prostate cancer (PCA). Although dose escalation increases local control, further escalation hampers toxicity. Further improvement will be possible by addition of adjuvant therapies, which can synergize with radiation and thus improve efficacy. Methods Human prostate cancer cell lines were used to test the combination of radiation and (Nexrutine, Nx). Global transcriptome profiling was used to delineate the mechanism. Transgenic adenocarcinomas of mouse prostate (TRAMP) mice were treated with Nx or radiation alone, or combination of Nx plus radiation to assess Nx as a radiation adjuvant. Histopathology and immunohistochemistry of survival targets were used as primary and secondary outcomes respectively. Contingency table analysis with χ2 tests were used to characterize the differences in categorical factors between experimental groups. Means were compared and tested with independent t-test across experimental groups for continuous outcomes and repeated-measures. General linear modeling was used to examine treatment differences over time. Results We have identified ribosomal protein S6K (RPS6KB1) that is upregulated in prostate tumors and its expression is correlated with pathological stage. Knockdown of RPS6KB1 not only decreased colony forming ability of aggressive prostate cancer cells but also increased their sensitivity toward radiation-induced survival inhibition. Furthermore, we have identified a natural compound (Nexrutine, Nx) but not its biologically active components to inhibit the growth of prostate cancer cells in combination with radiation. Importantly, combination studies demonstrated strong synergistic interaction between Nx and radiation both in vitro in multiple prostate cancer cell lines and in vivo using TRAMP model. Mechanistic investigations including transcriptome analysis showed that RPS6KB1 as an important player in radio-resistance as well as in Nx-mediated radio-sensitization. Furthermore, Nx pretreatment prolongs G2/M checkpoint block following radiation by sustained activation of Wee1 kinase and phosphorylation of cdc2. Importantly cells pretreated with Nx showed increased staining for γ-H2AX relative to radiation alone suggesting that increased DNA damage. Remarkably all of these events lead to induction of apoptosis. Conclusions Taken together, this report provides scientific evidence in support of the use of Nx as an adjuvant in prostate cancer patients receiving radiotherapy and further emphasizes RPS6KB1 as a novel target for prostate cancer treatment. _x000D_ Funding Supported by VA-Merit Award I01 BX 000766-01 (APK)
Authors
Suleman Hussain
Roble Bedolla Hiroshi Miyamoto Paul Rivas Joseph Basler Gregory Swanson Nikos Papanikolaou Robert Reddick Rita Ghosh Addanki Kumar |
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MP87-16 |
Interferon-induced microRNA turnover leading to epithelial-to-mesenchymal transition (EMT) in cancer |
Prostate Cancer: Basic Research & Pathophysiology III | 17BOS |
Abstract: MP87-16 Sources of Funding: DoD postdoc training award (W81XWH-14-1-0249)_x000D_ Urology Care Foundation Research Scholar Award Introduction Despite the role of interferon-γ (IFNγ) in tumor immune surveillance; studies have implicated the dark side of IFNγ based on its pro-tumorigenic activity. IFNγ can induce transcriptional activation of IFN-stimulated genes (ISGs) via JAK-STAT signaling pathway. The most highly induced ISGs are interferon-induced tetratricopeptide repeat (IFIT) family members. By studying a differential regulation on a unique tumor suppressor miR-363 from its polycistronic miR-106a-363 cluster, we unveiled a new microRNA (miRNA) turnover machinery composed of IFIT5, which is first described as a viral RNA binding protein. Up to date, the impact of IFIT5 on cancer metastasis is unclear. Methods Luciferase reporter gene assay was for examining the IFNγ-induced IFIT5 gene activation. Transwell migration assay was for demonstrating the function of IFIT5 with cancer metastasis. Site-directed mutagenesis, in vitro transcription, RNA pull down and in vitro RNA degradation assay were for determining the specificity of miRNA species regulated by IFIT5-mediated turnover machinery. Results IFIT5 gene promoter activity and protein level were significantly elevated by IFNγ. IFIT5 complex represents unique post-transcriptional machinery for turnover of a specific population of tumor suppressor miRNAs. We examined several IFIT5-regulated miRNA candidates, and found IFNγ can suppress miR-101, miR-335, miR-203, and miR-128, and phenocopied the miRNA expression profile of IFIT5-overexpressing cells. Seed regions of miR-101 and miR-128 have sequence-matched target sites at ZEB1 mRNA 3&[prime]UTR, and indeed can suppress ZEB1. Meanwhile, IFIT5 is elevated in higher grade prostatic tumors, and positively correlated with ZEB1, ZEB2 and Slug in prostate cancer. Knockdown of IFIT5 lead to suppression of ZEB1 and Slug, along with decreased migration mobility in cancer cells. On the contrary, IFNγ treatment enhanced cell migration, and this effect is diminished by the loss of IFIT5. We also modified the 5&[prime]end structure of precursor miR-101 and miR-128, and examined its regulation by IFIT5-mediated miRNA turnover machinery. Both pre-miR-101 and pre-miR-128 with mutated blunt end are resistant to degradation in an IFIT5-expressing PC3 cell and show greater impact on suppressing cell migration, compared to the mutant precursor with single stranded overhang. Conclusions We demonstrated that IFNγ potentiate prostate cancer metastasis via IFIT5-mediated miRNA turnover machinery, which regulates specific tumor suppressor miRNAs that target critical EMT factors including ZEB1 and Slug._x000D_ _x000D_ Funding DoD postdoc training award (W81XWH-14-1-0249)_x000D_ Urology Care Foundation Research Scholar Award
Authors
U-Ging Lo
Rey-Chen Pong Elizabeth Hernandez Shi-Hong Ma Jer-Tsong Hsieh |
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MP87-17 |
Prostate MRI Represents Leukocyte Density and Not the Presence of Cancer on Biopsy |
Prostate Cancer: Basic Research & Pathophysiology III | 17BOS |
Abstract: MP87-17 Sources of Funding: Washington University School of Medicine, Division of Urology Introduction Suspicious lesions on prostate MRI have been correlated to prostate cancer (PCa) on prostatectomy specimens. However, targeted biopsies of even highly suspicious prostate MRI lesions (i.e. PIRADS 4 or 5) are found to be benign in multiple reported series. One potential factor leading to this discrepancy is the presence of leukocytes, as they may be present in both a small focus of benign inflammation or present as tumor-infiltrating lymphocytes. Methods Reviewing patients with PIRADS 4 or 5 lesions that received MRI targeted as well as systematic biopsy from December 2014 to December 2015, we developed a study cohort for additional pathologic review. We excluded patients with a clinical history of prostatitis, prior prostate biopsy within 12 months, multiple MRI suspicious regions (MSR), and MSR < 0.25 mL. The MRI targeted biopsy specimen (MRI+) and a systematic biopsy specimen geometrically distant from the MSR (MRI-) were stained for leukocytes (CD45). Blinded to the MRI result, leukocyte density (LD) was measured manually (number per mm) and presence of PCa was noted. The groups were compared using the unpaired t test. Results For the overall study cohort, the mean LD for MRI+ biopsy cores was significantly higher than for MRI- biopsy cores (71.9+25.4 versus 42.1+10.6, p=0.04). Within the subset of only MRI+ biopsy cores, mean LD was not different based on the presence of PCa (71.8+28.0 versus 72.0+53.7, p=0.99). Within the subset of only MRI- biopsy cores, mean LD was not different based on the presence of PCa (39.3+11.2 versus 52.2+28.3, p=0.34). An example of similar LD in two MRI+ biopsy cores, despite PCa in one but not the other is provided. Conclusions The LD was significantly higher for biopsy cores from MRI suspicious areas, irrespective of the presence of PCa. The MRI appearance may be representative of leukocytes (benign inflammation of tumor infiltrating lymphocytes) rather than PCa. Funding Washington University School of Medicine, Division of Urology
Authors
Eric Kim
Dengfeng Cao Russell Pachynski Robert Grubb III Gerald Andriole |
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MP87-18 |
Association of germline genetic variants with TMPRSS2-ERG fusion status in prostate cancer |
Prostate Cancer: Basic Research & Pathophysiology III | 17BOS |
Abstract: MP87-18 Sources of Funding: Work is supported by DoD/PCRP Health Disparity Award; W81XWH-13-2-0096 Introduction Oncogenic activation of ERG resulting from prevalent gene fusions is present in two thirds of prostate cancer (CaP) patients of European Ancestry including Caucasian Americans (CA). Our laboratory and others have recently reported that major cancer driver genes, including ERG, show significant racial/ethnic differences in CaP with lower frequencies in African Americans (AA), Africans and Asians. Racial differences of CaP associated SNPs have also been extensively described. However, there is limited data on germline association with ERG fusion status. The goal of this study is to identify germline molecular determinants associating with ERG status of CaP. Methods Blood derived genomic DNA samples were prepared from 270 AA men and 129 CA men treated by radical prostatectomy at Walter Reed National Military Medical Center. ERG status was determined in whole mounted prostate specimens by immuno-histochemistry (IHC) for ERG protein expression as a surrogate for the TMPRSS2-ERG fusion. Blinded blood samples were genotyped for SNPs on the Illumina Golden Gate platform using Infinium Oncoarray, a 500K genome wide BeadChip kit from Illumina. Data analysis approaches included association analyses based on logistic regression, Principal Component Analysis (PCA) and Efficient Mixed-Model Association eXpedited (EMMAX) analysis. Genotype imputation analysis is being performed by IMPUTE2 program. Results After applying rigorous sample and SNP QC steps on the datasets, SNP genotyping analysis was performed in 321 patients with 478,299 SNPs. Logistic regression, principal component analysis by EIGENSTRAT and a variance component approach, EMMAX analysis were performed to account for population structure. By EMMAX we identified SNPs associated with ERG status. The SNPs most significantly (<10-5) associated with ERG fusion status included rs6698333, an intron variant of Kruppel-like factor 17 (KLF17) and two SNPs (rs1889877, rs3798999) in the intron of adhesion G protein-coupled receptor B3 (ADGRB3). Fine-mapping of SNPs is underway by genotype imputation analysis (IMPUTE2) using the 1000 Genomes reference dataset, followed by independent validation. Conclusions This study identified SNPs differentially associated with ERG status of CaP, a major driver oncogene in CaP. Although the biological significance as it relates to ERG status of CaP still needs to be determined, these SNPs, with independent validation, may help as markers in stratifying patients early (even before CaP is detected) for targeted prevention and treatment options. Funding Work is supported by DoD/PCRP Health Disparity Award; W81XWH-13-2-0096
Authors
Indu Kohaar
Lakshmi Ravindranath Denise Young Amina Ali Qiyuan Li Albert Dobi David McLeod Inger Rosner Isabell Sesterhenn Matthew Freedman Shiv Srivastava Gyorgy Petrovics |
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MP87-19 |
Ets Related Gene (ERG) driven Androgen Receptor Aggregation is a key regulator of Endoplasmic Stress and Cell Survival during Prostate Carcinogenesis |
Prostate Cancer: Basic Research & Pathophysiology III | 17BOS |
Abstract: MP87-19 Sources of Funding: This research in part was supported by the National Cancer Institute R01CA162383 (S. S.) and HU0001-10-2-0002 funds. Introduction Deregulated androgen receptor (AR) signaling due to either mutations or altered expression of the AR and its cofactors (activators or suppressors) has been identified as critical in prostate cancer development and progression. AR regulated oncogenic activation of Ets Related Gene (ERG) represents one of the most common and validated prostate cancer driver gene. In our recent studies using prostate specific ERG transgenic mouse prostate glands, we a observed novel morphological phenotypes of endoplasmic reticulum (ER) stress. Since AR was the critical regulator of ERG expression through TMPRSS2 promoter in human prostate cancer, the present study was aimed towards understanding the post-translational interactions between ERG and AR in ER stress and subsequent cell survival mechanisms in mouse and cell culture models. Understanding such mechanistic insights will potentially have major therapeutic implications. Methods Histological phenotype in the mouse prostate glands were examined by light and electron microscopy. Cell culture models of LNCaP, HEK293 and COS7 cells were utilized to examine the AR aggregations, Co-IP and Proximal Ligation Assay in the presence and absence of ERG. Various domain deletions of AR were utilized to identify specific AR domain interactions with ERG and its contribution in AR aggregation. Luminal cell surface markers on the isolated mouse prostate glands and spontaneously immortalized mouse prostate epithelial cells from ERG transgenic mouse (MoE1) were analyzed by FACS analysis. Results Co-expression of ERG and AR in LNCaP and COS-7 cells showed significant aggregation of AR in filter assays. Co-IP experiments and PLA assays in VCaP, LNCaP and HEK 293 cell revealed that ERG physically interacts with AR. Epithelial cells of ERG-Tg mouse prostates showed ~70% increase in CD49f (low) and Sca-1 (med) population with increased sphere formation capability and resistance to radiation induced cell death. Both epithelial cells grown into spheres and established MoE1 cells displayed increased CD49f (low) and significant increase in the EpCAM negative population. Conclusions Overall, our experiments demonstrate the mechanistic link that the physical interactions between ERG and AR initiate the ER stress in prostate epithelium through AR misfolding/aggregation. Our observation of ERG induced AR aggregation is one of the initial events that lead to ER stress to cell survival indicate a critical function for ERG in the etiology of prostate cancer initiation and progression. Funding This research in part was supported by the National Cancer Institute R01CA162383 (S. S.) and HU0001-10-2-0002 funds.
Authors
Taduru Sreenath
Natallia Mikhalkevich Shashwat Sharad Rishita Gupta Oluwatosin Diaro Kevin Babcock Charles Xavier Ahmed Mohamed Muhammad Jamal Shyh-Han Tan Albert Dobi Gyorgy Petrovics Isabell Sesterhenn David McLeod Inger Rosner Shiv Srivastava |
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MP87-20 |
Therapeutic targeting of transcriptional repressor BCL-6 in enzalutamide-resistant castration-resistant prostate cancer |
Prostate Cancer: Basic Research & Pathophysiology III | 17BOS |
Abstract: MP87-20 Sources of Funding: This work was supported by JSPS KAKENHI Grant Number 15K20109 and 26861299. Introduction Recently, several new drugs have been approved for castration-resistant prostate cancer (CRPC) patients, including the next generation anti-androgen enzalutamide (ENZ). However, survival benefits with ENZ are limited, and progression on ENZ is inevitable. We analyzed the gene expression profile of an ENZ-resistant CRPC cell line and identified BCL-6 as a potential therapeutic target. Methods Three cell lines were used: LNCaP, a human prostate cancer cell line that exhibits androgen-dependent proliferation; C4-2, an ENZ-sensitive CRPC cell line; and C4-2AT6, an ENZ-resistant CRPC cell line which had been established by incubating C4-2 in androgen ablation conditions. We performed whole genome expression analysis and explored gene profile changes among the three cell lines. Results Whole genome expression analysis by CGH array and Exome demonstrated that BCL-6 expression was higher in the order C4-2AT6 > C4-2 > LNCaP. We validated these results using western blotting. The protein expression level of BCL-6 was also higher in C4-2AT6 cells._x000D_ We evaluated the cytotoxic effect of a BCL-6 inhibitor, 79-6, on C4-2AT6 cells. Relative cell viability when treated with 10 ?M 79-6 was 65.7 ± 0.8%. Western blotting revealed that 79-6 promoted p53 expression and PARP cleavage in C4-2AT6 cells. We also examined the effect of BCL-6 inhibition by gene knockdown with siRNA. Knockdown of BCL-6 significantly reduces the cell viability of C4-2AT6 cells (78.4 ± 1.4%)._x000D_ Next, we examined the sensitivity of LNCaP and C4-2AT6 cells to ENZ. Relative cell viability when treated with 1 ?M ENZ was 73.6 ± 1.2% and 93.3 ± 2.7%, respectively. C4-2AT6 cells exhibited ENZ resistance. We examined the synergistic effect of ENZ and 79-6 on C4-2AT6 cells. The relative cell viability when treated with 1 ?M ENZ and 10 ?M 79-6 was 43.5 ± 2.1%._x000D_ Conclusions BCL-6 inhibition was able to overcome ENZ resistance in CRPC cell lines. Funding This work was supported by JSPS KAKENHI Grant Number 15K20109 and 26861299.
Authors
Hiroshi Hongo
Takeo Kosaka Yota Yasumizu Yasumasa Miyazaki Eiji Kikuchi Akira Miyajima Mototsugu Oya |
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MP88-01 |
The prognostic value of pre-cystectomy serum ?-glutamyltransferase levels in patients with invasive bladder cancer |
Bladder Cancer: Basic Research & Pathophysiology IV | 17BOS |
Abstract: MP88-01 Sources of Funding: None Introduction Prior experimental studies have shown that the enzyme γ-glutamyltransferase (γ-GT) is overexpressed during carcinogenetic transformation of urothelial cells. This analysis aimed to elucidate the prognostic value of serum γ-GT, glutamat-pyruvat-transaminase (GPT) and glutamat-oxalat-transaminase (GOT) levels in patients with invasive bladder cancer (BC). Methods Preoperative serum γ-GT, GPT and GOT concentrations were assessed in 324 patients treated with RC for clinically non-metastatic BC between 2002 and 2013. Laboratory values were obtained 1-3 days prior to RC. Uni- and multivariable analyses were carried out to evaluate clinicopathologic features and survival after RC. The median follow-up was 36 months (IQR: 10-55). Results Elevated preoperative γ-GT, GPT and GOT levels were diagnosed in 77 (23.8%), 20 (6.2%) and 18 (5.5%) patients, respectively. Elevated γ-GT levels were significantly associated with advanced tumor stage (≥pT3a; p=0.001), lymph-node tumor involvement (p<0.001), positive surgical margins (p=0.018), lymphovascular invasion (p=0.024), muscle-invasive disease at primary diagnosis (p=0.033), increased tumor size (continuously coded; p=0.035), receipt of neoadjuvant chemotherapy (p=0.006), higher Eastern Cooperative Performance Status (p=0.001), hydronephrosis at RC (p=0.049), increased preoperative serum C-reactive protein levels (p<0.001) and elevated serum GPT and GOT levels (both p<0.001). Patients with elevated γ-GT concentration exhibited inferior 3-year disease-free (52.5% vs. 63.2%; p=0.19), cancer-specific (71.1% vs. 80.9%; p=0.042) and overall survival rates (49.2% vs. 69.6%; p=0.005) compared to patients with normal levels. On multivariable analysis, higher ECOG performance status, hydronephrosis at RC (both p=0.010), positive surgical margin status (p=0.014), lymph node positive disease (p=0.030), advanced tumor stage (p=0.032), and an elevated γ-GT concentration (p=0.043) were independent predictors of all-cause mortality. Conclusions Elevated preoperative γ-GT levels are associated with a significantly increased risk for locally advanced bladder cancer and mortality. These data suggest that γ-GT levels may be a useful prognostic marker for patients after RC for BC. Funding None
Authors
Tina Schubert
Manuel Alexander Schmid Thomas Lütfrenk Markus Renninger Arnulf Stenzl Georgios Gakis |
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MP88-02 |
Expression of class III beta-tubulin predicts prognosis in cisplatin-resistant bladder cancer patients receiving paclitaxel-based second-line chemotherapy |
Bladder Cancer: Basic Research & Pathophysiology IV | 17BOS |
Abstract: MP88-02 Sources of Funding: The authors declare no conflict of interest associated with this manuscript. Introduction Class III beta-tubulin (TUBB3) is associated with malignant aggressiveness and prognosis, in addition, its expression is recognized as a predictive marker for taxane-based chemotherapy (CTx) in several cancers. In urothelial cancer (UC), standard first-line therapy for advanced disease is cisplatin (CDDP)-based CTx. On the other hand, although second-line regimen for CDDP-resistant tumor is not still established, several studies showed paclitaxel (PTX)-based regimens were effective to improve the prognosis. The main aim is to clarify the predictive value of TUBB3 expression for anti-cancer effect by first-line CDDP-based CTx and second-line PTX-based one in patients with UC. Methods We reviewed 116 UC (bladder cancer = 90 and upper urinary tract cancer = 26) patients treated with CDDP-based regimen as first-line CTx. Among these patients, 53 patients were received PTX-based second-line CTx. As PTX-based CTx, the combination of gemcitabine and PTX were performed in 42 patients. TUBB3 expression was evaluated by immunohistochemical technique, and survival analyses were performed by using Kaplan-Meier survival curves and multivariate COX proportional hazard analysis. Results Positively stained ratio of TUBB3 in grade 3 tumors (50 / 74 = 67.6%) was significantly higher (P < 0.001) than that in grade 1 (0 / 5 = 0.0%) and grade 2 (14 / 37 = 37.8%). A similar trend was found in T stage; however, it did not reach the significant level (P = 0.062). No significant relationship was found in age, sex, and metastasis. When the predictive value of TUBB3 expression for CDDP-based first-line CTx was investigated, it is not recognized as a significant predictive factor for progression-free survival (P = 0.796). On the other hand, high expression of TUBB3 is significantly associated with unfavorable overall survival from starting of second-line CTx (P = 0.013). Multivariate analysis model including all pathological features, part of a tumor, and regimen of second-line therapy showed that TUBB3 expression was identified as an independent predictor (hazard ratio = 5.18, 95% confidential intervals = 1.85 - 14.53, P = 0.002). Conclusions The TUBB3 expression is associated with malignant potential in UC. TUBB3 expression was identified as a useful predictive factor for anti-cancer effects of second-line PTX-based CTx in advanced UC patients with CDDP-resistant tumors. Out information is useful to discuss treatment strategies for patients with CDDP-resistant UC. Funding The authors declare no conflict of interest associated with this manuscript.
Authors
Tomohiro Matsuo
Yasuyoshi Miyata Yuichiro Nakamura Takuji Yasuda Kojiro Ohba Hideki Sakai |
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MP88-03 |
Sequencing of a Cancer Cell Subpopulation Identifies Micrometastases in Bladder Cancer |
Bladder Cancer: Basic Research & Pathophysiology IV | 17BOS |
Abstract: MP88-03 Sources of Funding: AMA Foundation, H&H Lee Research Program Introduction Latent recurrences despite favorable pathology has been a longstanding conundrum in surgical oncology. In muscle-invasive urothelial carcinoma of the bladder, patients with clinically localized disease (pT2 N0) have a recurrence rate of 11-35% following radical cystectomy, with recurrence rates in higher stages of localized disease up to 50-69% (pT4 N0). Recurrence with N0 disease may be attributed to lymph node micrometastases, therefore improved pathologic staging of lymph nodes may add precision to selecting adjuvant therapy as well as stratifying patients with metastatic disease. Here, we describe a diagnostic approach combining fluorescence activated cell sorting and next-generation sequencing that identifies micrometastases in a patient with muscle-invasive urothelial carcinoma of the bladder. _x000D_ Methods Tumor specimens from multiple regions of patient’s bladder tumor as well as lymph nodes were obtained and were dissociated into a single cell suspension. Fluorescence activated cell sorting using the surface markers CD44 and CD49f was utilized to isolate a cancer cell subpopulation associated with stemness. Whole-exome sequencing and RNA sequencing of total cells and the CD44+CD49f+ subpopulation in multiple tumor specimens and regional lymph nodes were performed in order to identify micrometastases and evaluate gene expression among the different regions and populations._x000D_ Results Pathology of the lymph nodes resected demonstrated N0 disease. Mean allele frequency analysis demonstrated a significant correlation between tumor cancer cells and cancer cells isolated from the lymph nodes. RNA-sequencing revealed intratumoral heterogeneity as well as enrichment for immune system and lipid metabolism gene sets in the micrometastatic cancer cell subpopulations. _x000D_ Conclusions Although pathology demonstrated no lymph node disease, we were able to isolate a cancer cell subpopulation from the pathologically negative lymph nodes. Whole-exome sequencing verified the cells isolated from the lymph nodes were indeed similar to the primary tumor and RNA-seq demonstrated differences in gene expression among the total population and subpopulation. Our analysis illustrates how next-generation sequencing of cancer cell subpopulations can be utilized to improve pathologic staging, and provide insight into cancer stem cell biology._x000D_ Funding AMA Foundation, H&H Lee Research Program
Authors
Kris Prado
Kelvin Zhang Matteo Pellegrini Arnold Chin |
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MP88-04 |
The adaptor protein CRK-induced ErbB2 expression promotes tumor progression and metastasis of bladder cancer via exosomes |
Bladder Cancer: Basic Research & Pathophysiology IV | 17BOS |
Abstract: MP88-04 Sources of Funding: none Introduction Molecular targeted therapies have been developed for various cancers, however; which have not advanced beyond conventional chemotherapy for the locally advanced and metastatic bladder cancer (BC). Therefore, establishment of more efficient therapeutic strategy is urgently desired. Recently, extracellular exosomes are paid attention as important mediators of intercellular communication. Tumor-derived exosomes have known to transfer proteins and nucleic acids from the cells of origin to target cells and affect tumor progression and metastatic process. We have been reported that signaling adaptor protein CRK promotes cell growth, invasion, and adhesion in various cancers, however; the relationship between CRK and exosomes has remained unknown. Here, we investigated the effects of CRK-mediated exosomes on tumor progression and metastasis of BC. Methods Human BC cell line UM-UC-3 were stably transfected with pCSII-CMV-tdTomato-Luc, and CRK was knocked-down by shRNA technique. The parental and CRK-depleted cells (CRKi) were orthotopically injected into nude mice, and the tumor progression and metastasis were investigated using IVIS Spectrum. In in vitro setting, expression levels of proteins associated with cell growth, survival, and invasion were examined in parental and CRKi UM-UC-3 cells and their exosomes, and the proteins contained in exosomes were identified by LC-TOF/MS. Low grade BC 5637 cells and HUVECs were treated with exosomes from parental UM-UC-3 cells, and the cell proliferation and invasion were analyzed. Furthermore, the metastases in mice pretreated with exosomes from parental and CRKi cells were investigated. Results CRKi UM-UC-3 cells inhibited the tumor progression and metastasis in orthotopic xenograft models. We found that CRK and ErbB2 were contained in exosome from the parental UM-UC-3 cells, and the exosomes-incorporated-5637 and -HUVECs significantly promote the cell proliferation and invasion. In contrast, in exosomes from CRKi cells, the expression levels of ErbB2 were reduced, and the exosome-incorporated recipient cells decreased the growth and invasion. Of note, lung metastasis of UM-UC-3 cells was facilitated in mice educated by the parental UM-UC-3-derived exosomes, but not by CRKi cells-derived exosomes. Conclusions Here, we provide novel findings that CRK-regulated up-regulation of ErbB2 in the exosomes of BC facilitated the tumor progression and metastasis. Therefore, CRK and ErbB2 might be potent therapeutic targets to prevent the locally advanced and metastasis for BC patients. Funding none
Authors
Kazuhiko Yoshida
Masumi Tsuda Ryuji Matsumoto Shingo Semba Taichi Kimura Mishie Tanino Hiroshi Nishihara Tsunenori Kondo Kazunari Tanabe Shinya Tanaka |
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MP88-05 |
Comprehensive immune transcriptomic analysis in bladder cancer reveals subtype specific immune gene expression patterns |
Bladder Cancer: Basic Research & Pathophysiology IV | 17BOS |
Abstract: MP88-05 Sources of Funding: none Introduction Genome wide profiling studies across cancers have been key to the increased understanding of tumour heterogeneity and recent efforts from large muscle invasive bladder cancer (MIBC) cohorts have led to their classification into molecular subtypes displaying distinct genomic and transcriptomic features. Herein, we performed a comprehensive in silico immune transcriptomic profiling using publicly available datasets to identify immune gene expression patterns associated with molecular subtypes of MIBC. Methods We utilized the publicly available global transcriptomic sequencing (RNA-Seq) data from 412 MIBC cases, with the corresponding clinical information downloaded from The Cancer Genome Atlas (TCGA) data Portal. Cases were divided into discovery (n=122) and validation (n=245) cohorts for downstream analysis and were divided into four clusters based on their genomic profiles. To investigate the presence of subtype associated immune signatures we assembled a defined set of 828 immune related genes, consisting of genes involved primarily in Type I and II interferon pathways in addition to other immune response and immune cell phenotype genes. All downstream data analysis was performed in R Bioconductor statistical environment. A one-way ANOVA was utilized to determine significantly differentially expressed genes with a Benjamini and Hochberg correction for false-discovery rate (FDR) correction of q<0.05. Results In the 122 case discovery cohort, we identified a total of 452 genes differentially expressed among the four clusters with an FDR q<0.05. The performance of these differentially expressed genes to accurately distinguish the four TCGA clusters was evaluated by unsupervised clustering of both genes and samples. The 64 top 20% of ranked genes were able to distinguish the four clusters in an unsupervised analysis of both the discovery and validation cohorts. The most enriched biological processes in the 452 gene list were response to IFN-γ, antigen processing and presentation, cytokine mediated signalling, cell proliferation, NK cell and macrophage activation and B cell mediated immunity The top five overrepresented pathways included, JAK/STAT signalling pathway, Toll receptor signalling pathway, interleukin signalling pathway, and T cell activation. Kaplan Meier survival analysis revealed that in combination, higher expression of three genes, SA100A7, S100A8 and SERPINB2 significantly associated with decreased survival only between clusters I and III in both discovery and validation cohorts. Conclusions Recent evolving findings from completed immunotherapy based clinical trials have emphasized the value of pre-existing tumour immune state that potentially determines response to treatment and survival. Our analyses reveal a grouping of immune gene expression patterns using both supervised and unsupervised clustering approaches. Given that specific genetic alterations associate with these molecular subtypes it seems that anti-tumour immune responses could be partly driven by oncogenic drivers. The findings provide further insights into the association between genomic subtypes and immune activation in MIBC and may open novel opportunities for their exploitation towards precise treatment with immunotherapy. Funding none
Authors
D. Siemens
Runhan Ren Kathrin Tyryshkin Madhuri Koti |
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MP88-06 |
Nuclear factor (NF)-&[kappa]B signals promote urothelial tumorigenesis through the androgen receptor (AR) pathway |
Bladder Cancer: Basic Research & Pathophysiology IV | 17BOS |
Abstract: MP88-06 Sources of Funding: None Introduction Emerging preclinical evidence has indicated the involvement of AR signaling in urothelial tumorigenesis. Meanwhile, cross-talk between AR and NF-&[kappa]B, a protein complex of transcriptional factor and its phosphorylation is required for optimal induction of target genes, has been demonstrated in prostate cancer cells. We therefore investigated the role of NF-&[kappa]B in neoplastic transformation of urothelial cells in relation to AR signaling. Methods We immunohistochemically stained for NF-&[kappa]B and phospho-NF-&[kappa]B (p-NF-&[kappa]B) in 149 bladder tumor and paired non-neoplastic bladder tissue specimens. Then, in immortalized human normal urothelial SVHUC sublines stably expressing AR with exposure to a chemical carcinogen 3-methylcholanthrene (MCA), we assessed the effects of NF-&[kappa]B activator (betulinic acid; BA) and inhibitor (parthenolide; PAR) on the expression of AR, NF-&[kappa]B p65 subunit, oncogenes, and tumor suppressors (via RT-PCR or western blot) as well as neoplastic transformation (via cell viability assay and plate/soft agar colony formation assays). Finally, N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) was given to male C57BL/6 mice to induce bladder tumors. Results NF-?B and p-NF-?B were positive in 100% [9% weak (1+), 40% moderate (2+), 51% strong (3+)] and 69% (44% 1+, 24% 2+, 1% 3+) of tumors, which was significantly elevated compared with non-neoplastic urothelial tissues [100% (25% 1+, 40% 2+, 35% 3+), P=0.016 (0/1+/2+ vs. 3+); and 46% (36% 1+, 10% 2+), P<0.001 (0 vs. 1+/2+/3+)]. Significantly higher rates of p-NF-&[kappa]B positivity were also seen in high-grade (76%, P=0.015) or muscle-invasive (78%, P=0.033) tumors than in low-grade (56%) or non-muscle-invasive (62%) tumors. In SVHUC-AR cells, BA induced and PAR reduced the expression of p65 and AR. Notably, BA accelerated and PAR prevented neoplastic transformation of MCA-SVHUC-AR cells, but not that of MCA-SVHUC cells. Additionally, in MCA-SVHUC-AR cells, BA up-regulated the expression of c-myc and down-regulated that of p53, p21, and UGT1A, while PAR showed the opposite results. Moreover, bladder tumors were identified in 56% (mock), 89% (BA), and 22% (PAR) of BBN-treated mice sacrificed at 21 weeks of age. Conclusions Compared with non-neoplastic urothelium, NF-&[kappa]B appeared to be activated in bladder cancer. In addition, NF-&[kappa]B modulators were found to involve the regulation of tumorigenesis in AR-activated urothelial cells. Accordingly, NF-&[kappa]B inhibition, together with AR inactivation, has the potential of being an effective chemopreventive approach for urothelial carcinoma. Funding None
Authors
Hiroki Ide
Satoshi Inoue Taichi Mizushima Mototsugu Oya George Netto Hiroshi Miyamoto |
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MP88-07 |
Androgen receptor activity modulates radiosensitivity in bladder cancer cells |
Bladder Cancer: Basic Research & Pathophysiology IV | 17BOS |
Abstract: MP88-07 Sources of Funding: None Introduction Although radiation therapy often with chemotherapy has been shown to offer survival rates comparable to radical cystectomy in select patients with bladder cancer, the development of radiosensitization may significantly enhance its application. Meanwhile, emerging preclinical evidence has indicated the involvement of androgen receptor (AR) signaling in urothelial cancer progression. In prostate cancer, AR has also been linked to radioresistance involving DNA repair pathways. We therefore assessed whether AR signals contribute to the sensitivity to radiotherapy in bladder cancer cells. Methods We compared the inhibitory effects of irradiation (2 Gy) on bladder cancer cell viability or colony formation between AR-positive [e.g. UMUC3 expressing control-short hairpin RNA (shRNA), 5637 or 647V stably expressing wild-type AR] versus AR-negative lines (e.g. UMUC3 stably expressing AR-shRNA, 5637 or 647V expressing vector only) or between AR-positive lines with versus without treatment with dihydrotestosterone (DHT) or an anti-androgen hydroxyflutamide (HF). We also compared DNA double strand breaks (DSB) via γ-H2AX foci formation in these cells after irradiation. Results Ionizing radiation reduced the numbers of viable cells or colonies of AR-negative lines more significantly than those of AR-positive lines. Similarly, in AR-positive cells cultured in androgen-depleted conditions, DHT treatment lowered the effects of irradiation. In AR-positive cells cultured in the presence of androgens, HF treatment then enhanced the effects of irradiation. Furthermore, the percentage of cells containing >10 γ-H2AX foci in AR-negative lines was significantly higher than that in AR-positive lines after irradiation (4, 8, 12, and 24h). DSB repair was also delayed by HF treatment in AR-positive cells after irradiation (4, 8, 12, and 24h). Conclusions These findings suggest that AR activity correlates with the sensitivity to radiotherapy in bladder cancer cells. Accordingly, anti-androgenic drugs may function as sensitizers of irradiation, especially in patients with AR-positive urothelial cancer. Funding None
Authors
Hiroki Ide
Satoshi Inoue Taichi Mizushima Mototsugu Oya Hiroshi Miyamoto |
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MP88-08 |
Estrogen receptor (ER)-β signals induce urothelial tumorigenesis via down-regulation of a potential tumor suppressor forkhead box protein O1 (FOXO1) |
Bladder Cancer: Basic Research & Pathophysiology IV | 17BOS |
Abstract: MP88-08 Sources of Funding: None Introduction Recent preclinical evidence suggests the involvement of ER signaling in urothelial tumorigenesis, although its underlying mechanisms remain unclear. Meanwhile, cross-talk between FOXO1, a transcriptional factor known to induce apoptosis through the PI3K-Akt pathway, and ERβ has been demonstrated in prostate cancer cells. We therefore investigated the role of FOXO1 in neoplastic transformation of urothelial cells in relation to ERβ signaling. Methods We immunohistochemically stained for ERβ and phospho-FOXO1 (p-FOXO1), an inactive form of FOXO1, in the tissue microarrays consisting of 99 cases of upper urinary tract urothelial carcinoma and paired non-neoplastic urothelium. Then, in ERα(-)/ERβ(+) human normal urothelial SVHUC sublines stably expressing control- or FOXO1-shRNA with or without exposure to a chemical carcinogen 3-methylcholanthrene (MCA), we assessed the expression of FOXO1 and other known tumor suppressors (via RT-PCR and western blot) as well as neoplastic transformation (via MTT assay and mouse xenograft model). Results ERβ and p-FOXO1 were positive in 63% and 100% of urothelial tumors, which were significantly lower and higher than in non-neoplastic urothelial tissues [85% (P=0.001) and 94% (P=0.018)], respectively. In addition, there was a significant correlation between strong (3+) p-FOXO1 expression and ERβ positivity (P=0.002). In SVHUC cells, estradiol reduced FOXO1 expression, which was abolished by an anti-estrogen tamoxifen. FOXO1 knockdown considerably accelerated neoplastic transformation of MCA-SVHUC cells. Moreover, the expression levels of several genes known to inhibit urothelial carcinogenesis (e.g. p21, p27, UGT1A) were significantly lower in MCA-SVHUC-FOXO1-shRNA than in control cells. Notably, tamoxifen treatment resulted in inhibition of neoplastic transformation of control cells, which was abolished by a FOXO1 inhibitor AS1842856. However, no significant effects of tamoxifen on neoplastic transformation were seen in MCA-SVHUC-FOXO1-shRNA cells. Conclusions FOXO1 appeared to function as a tumor suppressor and could strongly prevent urothelial tumorigenesis. In contrast, ERβ signals were found to promote it presumably via down-regulation of FOXO1 expression. Accordingly, FOXO1 stimulation via an activator, together with ERβ inactivation via an anti-estrogen, has the potential of being an effective chemopreventive approach for urothelial carcinoma. Funding None
Authors
Hiroki Ide
Satoshi Inoue Kazutoshi Fujita Yi Li Takashi Kawahara Eiji Kashiwagi Taichi Mizushima Seiji Yamaguchi Hiroaki Fushimi Mototsugu Oya Norio Nonomura Hiroshi Miyamoto |
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MP88-09 |
Androgen receptor activity modulates direct cytotoxicity of bacillus Calmette-Guérin (BCG) in bladder cancer cells |
Bladder Cancer: Basic Research & Pathophysiology IV | 17BOS |
Abstract: MP88-09 Sources of Funding: None Introduction A significant amount of patients with non-muscle-invasive bladder cancer (BC) fail to respond to intravesical BCG immunotherapy. Interestingly, in a few studies, male patients have been shown to be less likely to respond to BCG therapy, compared with female patients. Meanwhile, emerging preclinical evidence suggests the involvement of androgen receptor (AR) signaling in urothelial tumorigenesis and cancer progression. This study aims to assess whether AR signals have an impact on the direct cytotoxic effects of BCG on BC cell growth. Methods We compared the inhibitory effects of BCG on BC cell viability, colony formation, or cell migration, between AR-positive (e.g. UMUC3, 5637/647V stably expressing wild-type AR) versus AR-negative lines (e.g. UMUC3 stably expressing AR-shRNA, 5637/647V) or between AR-positive lines with versus without treatment with a synthetic androgen methytrienolone (R1881) and/or an anti-androgen hydroxyflutamide (HF). We also determined the expression of AR and PTEN (whose knockdown in BC cells has correlated with increased BCG uptake) in these AR-positive/negative lines as well as in "BCG-resistant" UMUC3/5637-AR/647V-AR sublines established following long-term culture with low-doses of BCG, using western blot. Immunohistochemistry (IHC) of AR was then performed in tissue microarrays consisting of BCs from patients who subsequently underwent BCG therapy. Results BCG treatment reduced the numbers of viable cells or colonies of AR-negative lines more significantly than those of AR-positive lines. Similarly, in AR-positive cells cultured in an androgen-depleted condition and in the presence of androgens, R1881 and HF treatments lowered and enhanced the BCG effects, respectively. In addition, BCG more significantly inhibited cell migration of AR-negative lines or AR-positive lines with mock treatment, compared to AR-positive lines without or with R1881 treatment, respectively. Furthermore, the expression levels of AR and PTEN were considerably elevated in R1881-treated AR-positive lines as well as BCG-resistant sublines, compared to respective controls. Finally, IHC showed AR positivity in 2 (14%) of 14 responders versus 8 (57%) of 14 non-responders (P=0.046), and the difference was even more significant in male patients [2/13 (15%) vs. 7/11 (64%); P=0.033]. Conclusions These findings suggest that AR activity correlates with resistance to BCG treatment in BC cells. Accordingly, anti-androgenic drugs may function as sensitizers of BCG therapy especially in male patients with AR-positive BC. Funding None
Authors
Jinbo Chen
Peng Li Taichi Mizushima Bin Han Satoshi Inoue Hiroki Ide Mehrsa Jalalizadeh Leonardo Reis Hiroshi Miyamoto |
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MP88-10 |
Inhibition of LIM and SH3 domain protein 1 delays cisplatin-resistant bladder tumor progression |
Bladder Cancer: Basic Research & Pathophysiology IV | 17BOS |
Abstract: MP88-10 Sources of Funding: none Introduction Bladder cancer is the 6th most common cancer in the USA. The current standard therapy for the first line of metastatic or local advanced bladder cancer is combination therapy with cisplatin (CDDP) and gemcitabine (GEM). However 5-years survival is still below 50%; therefore additional therapy is needed._x000D_ LIM-SH3 domain protein 1 (LASP1), identified from cDNA library of metastatic axillary lymph nodes of breast cancer, has been shown to promote cancer progression and invasion in several malignancies. In bladder cancer, LASP1 expression associates with cell invasion and can be used for detecting bladder cancer. However, the anti-tumor effects of LASP1 knockdown in vivo as well as combination therapy with chemotherapy remain unclear. In this study, we investigated the anti-cancer activity of LASP1 knockdown in bladder cancer._x000D_ Methods LASP1 gene expression of tumor samples is analyzed using the Affymetrix Exon Array. The LASP1 expression in several bladder cancer cell lines was assessed by Western blot analysis and quantitative reverse transcription-PCR. Silencing of LASP1 in vitro was achieved using siRNA. Cell growth was measured by crystal violet assay. Cell cycle distribution was analyzed by flow cytometry after double thymidine block. The In vivo effect of LASP1 antisense oligonucleotide (ASO) treatment was assessed in the T24 CDDP-R (cisplatin-resistant) orthotopic bladder cancer model. Results High LASP1 expression correlated with metastatic recurrence rate between patients. The LASP1 expression is higher in UC1 and T24 cells than in UC13 and UC6 cells. Knockdown of LASP1 using siRNA inhibited cell growth, and was accompanied by an increase in p21 and p27, and a decreased of cyclin D1. Flow cytometry revealed that LASP1 knockdown induced G1 arrest. Conversely, stable LASP1 overexpression drove cell growth with an increase of cyclin D1 in UC6 and UC3 cells. The treatment of CDDP and GEM induced LASP1 expression in Western Blotting. Furthermore, compared with parental cell line, LASP1 is higher in T24 CDDP-R and RT112 CDDP-R cells than in parental cells. LASP1 ASO inhibited cell growth in RT112 CDDP-R and T24 CDDP-R cells._x000D_ In the orthotopic bladder cancer model, systemic LASP1 ASO administration to athymic nude mice delayed tumor progression in T24 CDDP-R cells._x000D_ Conclusions These data revealed that LASP1 inhibition might be as a promising novel therapeutics modality in the treatment of chemoresistant bladder cancer. Funding none
Authors
Takashi Dejima
Ario Takeuchi Masaki Shiota Masatoshi Eto Martin Gleave Christopher Ong |
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MP88-11 |
Immune correlates of pathologic response in bladder cancer patients undergoing neoadjuvant chemotherapy |
Bladder Cancer: Basic Research & Pathophysiology IV | 17BOS |
Abstract: MP88-11 Sources of Funding: PHA-AUA Foundation Research Scholar Award, Kidney Cancer Association Young Investigator Award_x000D_ MHJ-NIES #ES026838_x000D_ WSED-NCI #CA173453, CA176289, CA181419_x000D_ JER- Starr Cancer Consortium_x000D_ EVM-NCI #CA188615, Starr Cancer Consortium_x000D_ Introduction The immune system is increasingly recognized as both a key player in cancer control and as druggable target. We hypothesized that the immune system impacts pathologic response in patients undergoing cisplatin-based neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer though the immune system. Methods Whole exome sequencing (WES) was performed on tumor DNA from patients in two independent cohorts who underwent cisplatin-based NAC. The Memorial Sloan Kettering / Dana Farber Cancer Institute (n=50; 25 responders) and Philadelphia (n=48; 20 responders) cohorts were treated with gemcitabine / cisplatin or methotrexate / vinblastine / doxorubicin / cisplatin. Mutation analysis was performed using standard analytical pipelines. Macrohistocompatibility complex (MHC)-restricted neoantigens were identified with netMHCpan and PolySolver. High affinity neoantigens were defined to have ≤500 nM binding affinity (Kd). Pathologic response was defined as ≤ypTis cystectomy specimen. CIBERSORT was used to infer immune cell infiltrate based on DASL Illumina microarray expression profiles (n=41; 17 responders). Results Chemoresponders had >twice as many putative neoantigens as nonresponders (471 vs 207 neoantigens respectively; p=1x10-6, Wilcoxon). This relationship maintained significance when neoantigens were limited to Kd≤100 nM or ≤50 nM, and when chemoresponse was defined as ypT0-only, or ≤ypT1. ERCC2 loss-of-function mutations were 36% sensitive in identifying chemoresponders but 96% specific. Above-median neoantigen burden was 81% sensitive in identifying chemoresponders and 78% specific. CD8+ cells were enriched in responders (13.5% vs 8.4% of infiltrate; p<0.008, t-test) as were activated NK cells (15.5% vs 12.7%; p=0.05). In 28 samples where WES and CIBERSORT data was available, the neoantigen burden was correlated to the CD8+ infiltrate value (R2=0.33, Pearson). Conclusions Neoantigen burden and CD8+ infiltrate correlate strongly with chemoresponse. Neoantigen burden and CD8+ infiltrate are directly proportional. NAC may therefore exert known tumor cell autonomous effects and an extrinsic effect involving the immune system via neoantigens. Anti-neoantigen responses have been shown to impact immune checkpoint responses and a similar mechanism may mediate cytotoxic chemoresponse. Experiments are underway to directly and functionally characterize the effect of the immune system in chemoresponse. Funding PHA-AUA Foundation Research Scholar Award, Kidney Cancer Association Young Investigator Award_x000D_ MHJ-NIES #ES026838_x000D_ WSED-NCI #CA173453, CA176289, CA181419_x000D_ JER- Starr Cancer Consortium_x000D_ EVM-NCI #CA188615, Starr Cancer Consortium_x000D_
Authors
Philip Abbosh
David Liu Woonyoung Choid Wafik El-Deiry Jonathan Rosenberg David McConkey Elizabeth Plimack Eliezer Van Allen |
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MP88-12 |
CYTOTOXIC T LYMPHOCYTE CD8+, CD3+, AND IMMUNOSCORE AS PROGNOSTIC MARKER IN PATIENTS AFTER RADICAL CYSTECTOMY |
Bladder Cancer: Basic Research & Pathophysiology IV | 17BOS |
Abstract: MP88-12 Sources of Funding: CUA-Pfizer urology resident grant awarded to Alice Yu Introduction It is known that patients with the same TNM stage can have different clinical outcomes. There is increasing evidence that cytotoxic T lymphocytes distribution between the tumour core (CT) and invasive margin (IM) correlates with disease free survival (DFS) and overall survival (OS) in other malignancies. The effect of a particular immune response is determined by the balance between the various T-cell subtypes involved, mainly the cytotoxic lymphocytes CD8+ and CD3+. In this sense, the Immunoscore, a new approach to the classification of cancer using the number, type and distribution of immune cells has been developed. Our objective was to evaluate the the prognostic impact of lymphocyte distribution in bladder cancer. Methods Hematoxylin and eosin (H&E) stained slides of cystectomy permanent sections with tumour involvement and identifiable invasive margin were selected and stained for CD8+ lymphocytes. Three non-contiguous areas of highest lymphocyte density were selected from both CT and IM. The number of CD8+ lymphocytes were calculated using Aperio image analysis software. Nonparametric (Wilcoxon–Mann–Whitney) test was used to identify markers with a significantly different expression among patient groups. Kaplan–Meier curves were used to visualize differences between DFS and OS. Results 67 patients who had cystectomy for T1-T4 bladder cancer were included in the study. High concentration of CD8+ lymphocytes in the tumour margin is associated with better DFS (P=0.005) and OS (P=0.03). Similar results were found for CD3+ lymphocytes with regards to DFS (P=0.05) but results did not meet statistical significance for OS (P=0.07). A higher Immunoscore is also associated with better DFS (P=0.04). After controlling for T stage, lymphovascular invasion, and peri-operative chemotherapy, higher levels of CD8+ in the invasive margin was independently associated with better outcomes (DFS: HR 0.26, 95% CI 0.10-0.68, P=0.006, OS: HR 0.031, 95% CI 0.10-0.97, P=0.04) Conclusions The host’s own immune system plays a valuable role in cancer progression. Our data suggests that a strong immune response against the tumour, as demonstrated by high concentration of CD8+ lymphocytes in the tumour margin, is independently associated with better prognosis. In the future, we plan on evaluating markers other than CD3+ that can be used with CD8+ for more accurate Immunoscore determination for bladder cancer. Funding CUA-Pfizer urology resident grant awarded to Alice Yu
Authors
Alice Yu
Jose Joao Mansure Shraddha Solanki Fadi Brimo Wassim Kassouf |
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MP88-13 |
Does Aggressiveness of Tumor Stage correlate with intra-operative Pelvic Washings & Pneumo-peritoneum during Robot-Assisted radical Cystectomy? |
Bladder Cancer: Basic Research & Pathophysiology IV | 17BOS |
Abstract: MP88-13 Sources of Funding: Roswell Park Alliance Foundation & Friends of Urology Introduction Recurrence following radical cystectomy (RC) is a major cause of cancer-specific mortality, and pelvis remains the main site of local recurrence. We sought to investigate whether aggressiveness of bladder cancer correlated with washings in the pelvis & pneumo-peritoneum at different stages of robot-assisted radical cystectomy (RARC). Methods 20 patients who underwent RARC were prospectively enrolled in the study. 6 samples were collected from each patient: Intra-vesical washing prior to RARC (BW), followed by a series of 3 pelvic irrigations; before RARC (Wash 1), after RARC (Wash 2) and after pelvic lymph node dissection (PLND) (Wash 3). Leftover suction fluid from the whole procedure was also collected (Wash 4). A specialized filter from surgical smoke evacuation device was used to trap any cells circulating in the pneumoperitoneum. Each sample was examined for cytology and the presence of bladder cancer-related markers (CDK1, HOXA13, MDK, IGFBP3). Results were correlated with clinical outcomes. Results 18 patients were included in the study (2 excluded for concomitant malignancies). MDK had the highest detection rate in the study. CDK1 had the lowest detection rate among the four markers and was only detected in 1 intra-vesical wash (pT1). There was no difference in the detection rate of the mRNA markers between muscle invasive and non-invasive tumors. However, mRNA in the pelvic irrigation and suction fluids were only detected in invasive (78%) and metastatic (100%) stages. Cytology results showed atypical cells in 4 patients (1 - Wash 3, 3 - Wash 4). After a median follow-up of 7 months, 2 patients developed distant recurrences (ypT0/N1, pT4a/N2) and 1 patient had pelvic recurrence (T4b/N0). No transmission of tumor cells was seen in the pneumo-peritoneum insufflation CO2 used during RARC. Conclusions This simple novel methodology was able to provide valuable information regarding possible pelvic dissemination. Patients with more advanced disease after RARC may have higher odds of bladder cancer dissemination in the pelvis during RARC. Funding Roswell Park Alliance Foundation & Friends of Urology
Authors
Youssef Ahmed
Ahmed Hussein Yingyu Ma Victoria Cranwell Gissou Azabdaftari Wei Luo Song Liu Sean Glenn Candace Johnson Khurshid Guru |
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MP88-14 |
Evaluation of E-cigarettes Users Urine for Known Bladder Carcinogens |
Bladder Cancer: Basic Research & Pathophysiology IV | 17BOS |
Abstract: MP88-14 Sources of Funding: none Introduction Traditional cigarette smoking is a well-established cause of bladder cancer. E-cigarette use is gaining popularity in part due to the perception it represents a safer alternative to smoking. Initial studies have shown the composition of e-cigarette liquids to be complex and may contain nitrosamines, formaldehyde, acrolein, metals, and acetaldehyde many of which are known bladder carcinogens. We compared the urine of e-cigarette users to non-smoking, non e-cigarette using controls by liquid chromactography-mass spectrometry (LC-MS) for known bladder carcinogens. Methods Urine samples were collected from 13 e-cigarette users and 10 non-smoking, non e-cigarette using controls. Samples were acidified, hydrolyzed, extracted, dried and resuspended for LC-MS analysis. Five molecules known to be bladder carcinogens that are either present in traditional cigarettes or common solvents believed to be used in some e-cigarette formulations were targeted for analysis. These included benz(a)anthracene, benzo(a)pyrene, 1-hydroxypyrene, o-toluidine and 2-naphthylamine (limit of detection 10-100 ng/ml). Results Subjects were predominantly male with a mean age of 39.4 years. All subjects had abstained completely by self-report from traditional cigarettes for at least 6 months prior to specimen collection (Table 1). Analysis of e-cigarette user urine was positive for two of the carcinogenic compounds, o-toluidine and 2-naphthylamine (limits of detection 100 ng/ml and 10 ng/ml respectively), in 12/13 e-cigarette users but none of the ten controls (Fischer's exact = 0.0069). The other 3 tested urinary carcinogens were not identified. Conclusions E-cigarettes are historically unregulated with a wide variety of formulations. Previous studies have identified nitrosamines in low levels in e-cigarette formulations as well as a variety of solvents such as formaldehyde. Twelve of the 13 subjects studied had carcinogenic 2-naphtylamine and 0-toluidine present. Many of these subjects (9/13) were long term nonsmokers (>12 months). Further study is needed to clarify the safety profile of e-cigarettes and their contribution to the development of bladder cancer given the greater concentration of carcinogenic nitrosamines in the urine of e-cigarette users in this pilot study. Funding none
Authors
Thomas Fuller
Abhinav Acharya Godugu Bhaskar Michelle Yu Steven Little Tatum Tarin |
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MP88-15 |
Distinct exosomal miRNA profiles in chemoresistant bladder carcinoma cell lines |
Bladder Cancer: Basic Research & Pathophysiology IV | 17BOS |
Abstract: MP88-15 Sources of Funding: NONE Introduction The development of drug resistance in advanced bladder cancer remains a significant clinical challenge. Recently, there has been immense interest in the role that tumor exosomes play in cancer development, metastasis and drug resistance. Tumor cells have been shown to selectively package certain proteins and RNA material into exosomes for the purpose of cell to cell communication. After internalization, recipient cells show altered gene expression, which in turn, modifies their invasiveness, apoptotic rate and sensitivity to therapeutic drugs. Few studies have examined the role of exosomal microRNAs (miRNA) in transference of drug resistance in bladder cancer. We hypothesize, that specific miRNAs have distinct roles in the establishment of chemoresistance. Here we strive to identify exosomal miRNAs profiles and their roles in Cisplatin, Gemcitabine and Cisplatin/Gemcitabine chemoresistance in bladder cancer. Methods Three resistant sublines of the human CUB III bladder carcinoma cell line were developed by gradually exposing the cells to increasing doses of Gemcitabine, Cisplatin or a combination of Gemcitabine and Cisplatin, over a period of 6 months. Exosomes were harvested and characterized by nanoparticle tracking analysis. Exosomal miRNAs were profiled via qRT-PCR array analysis. These distinct exosomal miRNA signatures were investigated in several additional bladder carcinoma resistant cell lines. Results Chemoresistant CUB III cells exhibit distinct miRNA profiles within their exosomes, which is unique depending on the drug of treatment. Of the 759 miRNA profiled, sixteen were differentially expressed (at least two-fold) across all the CUBIII resistant sublines relative to their parental line. Our data showed that 10 miRs were consistently down-regulated and 6 miRNAs were up regulated. Among the differentially expressed exosomal miRNAs in the resistant sublines, miR-Let-7i-3p was the most significantly down-regulated while miR-21-5p was the highest up-regulated compared to their chemosensitive counterpart._x000D_ Conclusions Our findings demonstrate that for each chemotherapeutic drug, resistant cells had differentially expressed miRNA profiles within their exosomes. Many of these miRNAs have been shown to play a role in oncogenesis or the development of drug resistance in other tumor types. After further validation these exosomal miRNAs may have utility as predictive biomarkers of treatment response and possibly as therapeutic targets to enhance drug response. Funding NONE
Authors
Heba Fanous
Travis Sullivan Kimberly Rieger-Christ |
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MP88-16 |
Targeted exosome-mediated delivery of Survivin siRNA for the treatment of bladder cancer |
Bladder Cancer: Basic Research & Pathophysiology IV | 17BOS |
Abstract: MP88-16 Sources of Funding: China Postdoctoral Science Foundation (2016M591831) Introduction Bladder cancer is the most common malignancy of urogenital system and one of the major causes of death in Chinese cancer patients. Small RNAs (sRNA) are potential therapeutic drugs for bladder cancers. However, it is still difficult to transport sRNAs stably in the body. Cell-derived exosomes have been demonstrated to be efficient carriers of small RNAs to neighbouring or distant cells, highlighting the preponderance of exosomes as carriers for gene therapy over other artificial delivery tools._x000D_ Methods In the present study, we employed modified exosomes expressing the iRGD peptide (a tumor-penetrating peptide) on the membrane surface to deliver Survivin siRNA into bladder cancer in a mouse xenograft tumor model. qPCR and western blotting were used to determine the expression of siRNA and survivin in tumor tissues._x000D_ Results We found that Survivin siRNA could be efficiently packaged into iRGD modified exosomes and was associated with argonaute 2 (AGO2) in exosomes. These exosomes efficiently and specifically delivered Survivin siRNA into 5637 bladder cancer cells and the mouse xenograft tumor. Functionally, Survivin siRNA-loaded iRGD exosomes significantly reduced Survivin mRNA and protein levels in bladder cancer cells. Sebsequently, Survivin siRNA delivered by the iRGD modified exosomes strongly inhibited the growth of the mouse xenograft tumor._x000D_ Conclusions In conclusion, our results demonstrate that targeted iRGD exosomes can efficiently transfer siRNA to bladder cancer and mediate the growth inhibiton of bladder cancer by downregulating Survivin expression levels. Our study provides a brand new strategy to treat bladder cancer._x000D_ Funding China Postdoctoral Science Foundation (2016M591831)
Authors
Rong Yang
Xiang Yan Shiwei Zhang Hongqian Guo |
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MP88-17 |
Patient Derived Xenografts of Upper Tract Urothelial Carcinoma: A Potential Tool for Personalized Medicine |
Bladder Cancer: Basic Research & Pathophysiology IV | 17BOS |
Abstract: MP88-17 Sources of Funding: The Wade Thompson Family Foundation, The Sidney Kimmel Center for Prostate and Urologic Cancers, Support Grant P30 CA008747, Urology Care Foundation, Society of Urologic Oncology Introduction Upper tract urothelial carcinomas (UTUC) are treated similarly to urothelial carcinoma of the bladder (UCB). UTUC demonstrates a more aggressive clinical course which may be explained by significant differences in mutational frequencies between UTUC and UCB that were reported using a customized exon capture sequencing assay (the MSK-IMPACTTM assay). A major limitation in the advancement of UTUC field is the lack of appropriate models. The objective of this study was to develop and evaluate preclinical models that would recapitulate treatment response observed in patients. Methods 35 surgical specimens from nephroureterectomy of patients with UTUC were implanted into immunocompromised NOD-SCID IL2Rg?/? (NSG) mice. The histological and the genomic characterization of patient tumors and PDXs were examined by a board certified pathologist and MSK-IMPACTTM assay, respectively. Cell lines were also established to assess histologic and genetic fidelity. Chemosensitivity of PDX models was assessed using a 4-week cycle of gemcitabine/cisplatin (or carboplatin) administration and analysis of tumor growth was performed using a two-way ANOVA test. Results 12 patient-derived xenograft (PDX) models were established with a success rate of 34% (12/35) and a 14% (3/21) success in developing cell lines. Both models were highly reflective of their original tumors in terms of histology and genomic characteristics as noted in Figure 1 and 2. For a representative PDX, chemosensitivity experiments identified gemcitabine/carboplatin as a potentially effective combination, which was also used in the clinical scenario with a therapeutic response. Conclusions We developed a cohort of stable PDX models and cell lines for UTUC that maintains the genetic characteristics of the patient’s initial tumor. The continued development of these models may facilitate personalized medicine strategies in the treatment of UTUC. Funding The Wade Thompson Family Foundation, The Sidney Kimmel Center for Prostate and Urologic Cancers, Support Grant P30 CA008747, Urology Care Foundation, Society of Urologic Oncology
Authors
Kwanghee Kim
Katie Murray Aditya Bagrodia Francois Audenet Sylvia Jebiwott Benjamin Gordon Alexander Somma Stephen LaRosa Yiyu Dong Ricardo Alvim A Ari Hakimi James Hsieh Hikmat Al-Ahmadie Joanthan Rosenberg David Solit Jonathan Coleman |
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MP88-18 |
A novel, integrated gene expression and drug sensitivity approach reveals unique sensitivity of squamous cell carcinoma-like bladder cancers to PI3Kβ inhibitor AZD6482 |
Bladder Cancer: Basic Research & Pathophysiology IV | 17BOS |
Abstract: MP88-18 Sources of Funding: none Introduction The goal of precision medicine is to predict the best treatment strategy from available genomic information, on a patient-by-patient basis. Bladder cancer genomics has emerged as a new area of research, whereby molecular subtypes of bladder cancer based on gene expression models may have selective therapeutic targets. Here we implement a novel bioinformatics approach integrating gene expression and drug sensitivity analyses to determine molecular subtype-specific therapeutic vulnerabilities in bladder cancer. Methods Gene expression profiles for 26 bladder cancer cell lines were obtained from the Cancer Cell Line Encyclopedia (CCLE) and analyzed by unsupervised hierarchical clustering using Morpheus software (Broad Institute, Cambridge, MA). Cell line clusters were classified according to validated genomic classification systems. Mutational status and drug sensitivity data for 19 bladder cancer cell lines treated with 224 anti-cancer drugs was obtained from the Genomics of Drug Sensitivity in Cancer (GDSC) database (Sanger Institute, Cambridge, UK). Differential sensitivity analyses were performed using Graphpad Prism. Results Unsupervised hierarchical clustering of gene expression data revealed major subgroups that clustered according to classified molecular subtypes: Squamous cell carcinoma-like (SCC-like), Urobasal A, Urobasal B, and Urobasal A/B (Fig 1A). Differential sensitivity analyses revealed that certain subtypes are preferentially sensitive to specific drugs. The most significant drug/subtype combination was the sensitivity of SCC-like cell lines to Phosphatidylinositide 3-kinase beta (PI3Kβ) inhibitor AZD6482, compared to Urobasal A or B lines (Fig 1B; P<0.05 by Kruskal-Wallis test). This unique sensitivity is associated with PTEN loss of function, which was found to be more commonly altered in SCC-like vs Urobasal cell lines (p<0.05). Conclusions Using cell line gene expression profiling and drug sensitivity data, we developed a novel bioinformatics approach and demonstrated sensitivity of SCC-like bladder cancers to the PI3Kβ inhibitor AZD6482, which may represent a novel therapeutic target. Furthermore, PTEN mutational status may represent a biomarker for sensitivity to these agents. Funding none
Authors
Kevin Shee
Kevin Koo Lael S. Reinstatler John D. Seigne Todd W. Miller |
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MP88-19 |
MiR-145 modulates Warburg effect by targeting KLF4/PTB1/PKMs axis in bladder cancer cells. |
Bladder Cancer: Basic Research & Pathophysiology IV | 17BOS |
Abstract: MP88-19 Sources of Funding: Grant-in-aid for scientific research from the Ministry of Education, Science, Sports, and Culture of Japan (YA-24659157). Introduction We previously reported the roles of microRNA (miR)-145 as a tumor-suppressor in human bladder cancer (BC) cells. On the other hand, the Warburg effect is a well-known feature in cancer specific metabolism. The functions of miR-145 in the Warburg effect are still largely unknown. Kruppel-like factor 4 (KLF4) is a transcription factors and is well known as a one of the essential factors of induced pluripotent stem cell. Also, it is possible that KLF4 also regulates the Warburg effect. In this study, we revealed that miR-145 affects the regulation of the Warburg effect through targeting KLF4 in BC cells. Methods The expression levels of miR-145 between normal human urothelial cells (HUC), BC cells, and clinical BC samples were examined by a real-time PCR. Human BC T24 and 253 J-BV cells were transfected with miR-145, and the effects were examined by various experiments such as Western blotting analysis(WB), Hoechst33342 staining and immunostaining. The evaluation of targeting KLF4 by miR-145 was performed by luciferase assay. Moreover, the effects of knockdown of KLF4 on the various phenotypes of BC cells were also examined. Furthermore, the networks involving KLF4/PTBP1/PKMs in the Warburg effect related- molecules were examined by WB even in clinical BC samples. Finally, we examined immunohistochemical staining to evaluate KLF4 expression. Results The expression levels of miR-145 were significantly down-regulated in clinical BC samples and BC cells compared with those in normal tissues and HUC. Luciferase assay showed that miR-145 directly targeted KLF4. Also, the Warburg related affect-genes were modulated by the transfection of miR-145 or siR-KLF4 in BC cells. Moreover, the expression levels of KLF4, PTBP1, and PKM2 is up-regulated in all clinical samples by WB. Finally, we observed KLF4-positive staining in the tumor by immunohistochemical staining. Conclusions In this study, we indicated that miR-145 affect the Warburg effect through targeting KLF4/PTBP1/PKMs axis in BC cells, which exhibited a significant cell growth inhibition. Funding Grant-in-aid for scientific research from the Ministry of Education, Science, Sports, and Culture of Japan (YA-24659157).
Authors
Koichiro Minami
Kohei Taniguchi Teruo Inamoto Kiyoshi Takahara Kazumasa Komura Tomoaki Takai Yuki Yoshikawa Yukihiro Akao Haruhito Azuma |
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MP88-20 |
Establishment of novel mouse bladder cancer cell lines mimicking intrinsic subtype of human invasive bladder cancer |
Bladder Cancer: Basic Research & Pathophysiology IV | 17BOS |
Abstract: MP88-20 Sources of Funding: The Bladder Cancer Advocacy Network Introduction Immune checkpoint inhibitors (ICI), such as anti-PD1/PDL1 antibody, have been proved to be effective in advanced human bladder cancer. But we still don’t know why some patients respond to ICI but others not. In order to answer the question, preclinical mouse models mimicking the genetics of human bladder cancer are essential. We established two unique classes of novel mouse bladder cancer cell lines and examined if the syngeneic cell line tumors are applicable to immunological study of human bladder cancer. Methods We established BBN cell lines from N-Butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced mouse bladder cancer model and UPPL cell lines from Upk3a-CreERT2;Tp53 f/f; Pten f/f; Luciferase mouse model. Whole transcriptome profiling was performed on 12 BBN and 8 UPPL primary tumors. Unsupervised clustering and supervised clustering using BASE47, gene sets for identifying basal and luminal subtype, were performed. We treated the subcutaneous allografts of the established cell lines by anti-mouse Pdl1 antibody (10mg/kg, intraperitoneal injection, weekly) and analyzed the background of responders and non-responders with flow cytometry and T/B cell receptor (TCR/BCR) amplicon sequencing of tumor infiltrating lymphocytes. Results Finally 12 BBN cell lines and 8 UPPL cell lines were established. Unsupervised clustering of BBN and UPPL models demonstrated close clustering with human basal and luminal bladder cancers, respectively. More interestingly, BBN tumors had significant enrichment of immune related genes (Figure). We treated the allograft tumors of BBN963, BBN975 and UPPL1541 cell lines with anti-mouse Pdl1 antibody. Half of the BBN963-derived tumors responded to the treatment but BBN975 and UPPL1541-derived tumors not. Paradoxically BBN975 tumors, the non-responders, showed higher infiltration of CD3+ T cells. Conclusions We established mouse bladder cancer cell lines mimicking human basal and luminal bladder cancer. BBN963 could be used as mixed response model and BBN975 could be used as immune exhaustion model. We are now trying to elucidate the mechanism of differential response of the BBN and UPPL tumors to Pd1/Pdl1 blockade._x000D_ Funding The Bladder Cancer Advocacy Network
Authors
RYOICHI SAITO
Christof Smith Jordan Kardos Lisa Bixby Shengjie Chai Jeffrey Damrauer Takanobu Utsumi Sara Wobker Bhavani Krishnan Osamu Ogawa Benjamin Vincent William Kim |
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MP89-01 |
Time to Improvement in Semen Analysis Parameters after Varicocelectomy |
Infertility: Therapy I | 17BOS |
Abstract: MP89-01 Sources of Funding: None Introduction Varicoceles are the most common identifiable cause of male factor subfertility. The impact of varicocelectomy on pregnancy outcome has been debated. We sought to evaluate the time frame for changes in semen parameters following varicocelectomy and examine the impact on natural conception. Methods We performed a retrospective chart review on all patients who presented to our Reproductive Medicine Center for male factor subfertility and abnormal semen analysis (SA) parameters. Inclusion criteria were limited to men with clinically palpable varicoceles, who had at least one abnormal semen parameter on pre-operative SA, and had post-operative SA data available at both 3 and 6 months. Patients with at least 50% increase in total progressively motile sperm per ejaculate on their post-operative SA were classified as having improved semen parameters after varicocelectomy. Pregnancy outcomes were gathered retrospectively, and successful pregnancy was defined as live birth after intrauterine insemination or spontaneous pregnancy. Results A total of 126 patients who underwent sub-inguinal varicocelectomy between 2006 and 2015 were included in this study. Following varicocelectomy, 72 patients (57%) had improvement in semen parameters. Spontaneous pregnancy or pregnancy from intrauterine insemination was more likely to occur in patients who had improved SA parameters (31% vs 10% p = 0.004). Of the patients that improved, 50 patients (69%) did so by 3 months. Another 22 patients (31%) saw eventual improvement in SA parameters by 6 months post-operative. There was no statistically significant difference in pregnancy outcomes between early improvement and delayed improvement in SA parameters ( 26% vs 41% respectively, p = 0.21). Conclusions Varicocelectomy resulted in a significant improvement in semen parameters in half of our patients. Of these, the majority who improved did so by 3 months post procedure; however, ~30% of patients without improvement at 3 months subsequently improved at 6 months. Pregnancy rates were statistically higher in patients who had >50% increase in total progressive motile sperm, regardless of the time it took to see this improvement. This data may be useful in counseling couples post varicocelectomy as to the time course for improvement and pregnancy outcomes. Funding None
Authors
Melissa St.Aubin
Dane Johnson Kate Cohen Jay Sandlow |
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MP89-02 |
Efficacy of indocyanine green fluorescence angiography for arterial sparing during microsurgical subinguinal varicocelectomy |
Infertility: Therapy I | 17BOS |
Abstract: MP89-02 Sources of Funding: none Introduction Varicoceles are present in 20 to 30% of men with infertility; moreover, up to 10% of men with varicoceles experience scrotal pain. Varicocelectomy improves testicular function and may prevent the accelerated decline in sperm parameters and testosterone levels observed in men with varicoceles. Many studies have indicated that microsurgical subinguinal varicocelectomy is one of the best treatment modalities for varicoceles with regard to spontaneous pregnancy outcomes and complication rates; however, the difficulty in identifying testicular arteries that should be spared is a limitation of this technique. We previously reported the usefulness of intraoperative indocyanine green angiography (ICGA) to detect the thin arteries. In the present study, we assessed the feasibility of ICGA during microsurgical subinguinal varicocelectomy in comparison with standard procedures. Methods Microsurgical subinguinal varicocelectomy using ICGA was performed in 48 patients with infertility or chronic pain associated with varicoceles. After exposure of the spermatic cord blood vessels, ICG was injected intravenously to identify and isolate the testicular artery. Intraoperative Doppler blood flow meter was also performed in 29 cases to compare both procedures for detection of the artery. Thereafter, the varicose veins were repeatedly ligated, while preserving a few lymphatic vessels and the spermatic duct. Seventy-eight cases without ICGA use were included as the control group, to determine the efficacy of the ICGA procedure. Results The testicular artery was clearly identified by ICGA. The average operation time significantly decreased from 81.8 to 66.2 minutes with the use of ICGA. The number of preserved arteries was significantly increased by ICGA from 1.16 to 1.77. In 15 ICGA cases, very thin arteries that were undetectable with normal light view or Doppler study could be preserved. Conclusions Microsurgical subinguinal varicocelectomy using intraoperative ICGA enabled a faster procedure and secure preservation of testicular arteries. We believe that this is a significant surgical procedure for the treatment of varicoceles, especially for infertility patients in whom preservation of maximal blood supply is desired. Funding none
Authors
Yasuhiro Shibata
Sota Kurihara Seiji Arai Takeshi Miyao Yoshiyuki Miyazawa Yoshitaka Sekine Hidekazu Koike Kazuto Ito Tetsuya Nakamura Kazuhiro Suzuki |
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MP89-03 |
NORMAL PREOPERATIVE FOLLICLE?STIMULATING HORMONE LEVEL IS ASSOCIATED WITH IMPROVEMENT IN SEMEN PARAMETERS FOLLOWING MICROSURGICAL VARICOCELECTOMY |
Infertility: Therapy I | 17BOS |
Abstract: MP89-03 Sources of Funding: none Introduction We investigated whether preoperative follicle-stimulating hormone (FSH) level is associated with changes in postoperative semen parameters following microsurgical varicocelectomy. Methods We identified 37 men who had undergone microsurgical varicocelectomy between August 2015 and June 2016. We compared semen parameters in men based on their preoperative FSH level, defined as normal <10 mIU/ml (n=25) and abnormal =>10 mIU/ml (n=12). We compared varicocele grade, testis volume, prevalence of bilateral disease, preoperative, and postoperative semen parameters (at 3 months) between men with normal and abnormal FSH. Results The age, varicocele grade, preoperative testosterone levels were similar between men who underwent microsurgical varicocelectomy with normal and high FSH. Men with higher FSH had higher rates of bilateral disease. In a univariate analysis, men with FSH <10 mIU/mL had higher increases in absolute total sperm count (20.4M vs. 0.8M, p=0.002), sperm concentration (5.2M/mL vs. 1.4M/mL, p=0.05), and total motile count (5.1M vs. 1.4M, p=0.02) postoperatively compared to those with abnormal FSH. As expected, testis volume was smaller in the men with high FSH (12 cc vs. 14 cc, p=0.004). Change in motility was not significantly different between men with abnormal and normal FSH. Conclusions Our study suggested an association between men with normal FSH levels (<10 mIU/ml) and significant improvements in total sperm count, sperm concentration, and total motile count among those who underwent microscopic varicocelectomy. Normal FSH levels can suggest preserved spermatogenesis and greater improvement in semen parameters following varicocele repair. Funding none
Authors
Lunan Ji
Samuel A. Shabtaie Nachiketh Soodana Prakash Ranjith Ramasamy |
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MP89-04 |
Does grade matter? A systematic review of the impact of varicocele grade on response to treatment. |
Infertility: Therapy I | 17BOS |
Abstract: MP89-04 Sources of Funding: None Introduction The treatment options for couples affected by varicocele-associated subfertility include varicocelectomy and assisted reproduction. Our goal was to investigate varicocele grade as a prognostic factor that could be potentially incorporated into shared decision making with affected patients. Methods Pubmed, Embase, and MEDLINE databases were searched for studies evaluating the impact of varicocele grade on response to treatment through May 1, 2016. We analyzed all studies of varicocelectomy in infertile men with palpable varicoceles that reported outcomes stratified by varicocele grade. Heterogeneity of semen quality reporting precluded data compilation and meta-analysis. Therefore the impact of varicocele grade on post-treatment semen quality was analyzed by structured data synthesis. The impact of varicocele grade on pregnancy rates was studied by data extraction and meta-analysis using a binary random effects model. Quality assessment was conducted using the Newcastle-Ottawa Scale (NOS). Results One randomized controlled trial and 11 cohort studies described outcomes of varicocelectomy stratified by varicocele grade in 1,394 infertile men with palpable varicocele. For men with only grade 1 varicocele, only 1 of 5 studies reported improved concentration and just 1 of 6 showed improved motility. In contrast, 5 of 5 studies that evaluated concentration and 4 of 5 studies that evaluated motility after repair of grade 2/3 varicoceles reported positive treatment responses. Four of 6 studies that directly compared concentration response to varicocelectomy in men with grade 1 and grade 2/3 varicoceles reported greater improvements in men with larger varicoceles. Three of 6 studies that directly compared motility response to varicocelectomy in men with grade 1 and grade 2/3 varicoceles reported greater improvements in men with larger varicoceles. Morphology changes were less consistently related to varicocele grade. Meta-analyses of the included studies did not reveal improved pregnancy rates after treatment of either grade 1 or grade 2/3 varicoceles. Quality assessment determined that 4 of the 11 non-randomized studies were of high quality. Conclusions Improved semen quality after varicocelectomy has been consistently reported for men with grade 2/3 varicoceles. In contrast, improvement is uncommon for men with grade 1 varicoceles. Incorporation of varicocele grade into patient counseling may improve our ability to select patients for varicocelectomy that are most likely to benefit from surgery. Funding None
Authors
Clark Judge
Christopher Deibert Doron Stember Peter Stahl |
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MP89-05 |
The assessment of hormone replacement therapy success due to hypogonadotrophic hypogonadism |
Infertility: Therapy I | 17BOS |
Abstract: MP89-05 Sources of Funding: none Introduction Hypogonadatrophic hypogonadism is a rare disease in which medical treatment has high success rates for infertility. The aim of this study was to analyze the efficacy of hormone replacement therapy on the infertile patients with hypogonadotrophic hypogonadism (HH) diagnosis. Methods A total of 250 patients had been diagnosed as HH between years 2002-2016 underwent Cella Pituitary MR imaging to exclude intracranial pathology, genetic and biochemical(hormone) analysis. Patients ,who had been diagnosed as HH with low testosterone and FSH levels but without surgical requirement, were administered LH analogues (Recombinant choriogonadotropin) and Recombinant FSH as hormone replacement therapy. Patient followed up was carried out with quarterly semen analysis and hormonal profiles. Detection of sperm in ejaculate and achievement of pregnancy spontaneously or with assisted reproductive tecniques were the predetermined primary and secondary endpoints. Results The patients with regular follow-ups (135) had been selected out of the HH database with 250 patients and retrospectively investigated. During the treatment period(8-24 months), 94 (70%) patients had sperm appearance in their ejaculate. Out of the 72 married males with sperm appearing on their ejaculate, 40 patients (55%) obtained pregnancy spontaneously; 7 patients (%10) via assisted reproductive techniques. Forty one patients (%30) who had no sperm in their ejaculate yet are under routine control with hormonal treatment. Conclusions The medical approach of males ,with hypogonadotropic hypogonadism and azoospermia, is a successful treatment modality both in terms of sperm presence in ejaculate and pregnancy rates. Funding none
Authors
Emre Salabas
Ebubekir Buyuk Caner Bese Mazhar Ortac Ates Kadioglu |
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MP89-06 |
PRESERVATION OF NORMAL CONCENTRATIONS OF PITUITARY GONADOTROPINS DESPITE ACHIEVEMENT OF NORMAL SERUM TESTOTERONE LEVELS IN HYPOGONADAL MEN TREATED WITH A 4.5% NASAL TESTOSTERONE GEL |
Infertility: Therapy I | 17BOS |
Abstract: MP89-06 Sources of Funding: Support from Trimel/Acerus Pharmaceuticals for Phase 3 clinical trial. Introduction One of the recognized effects of standard forms of testosterone (T) therapy is suppression of the pituitary gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) via negative feedback from sustained increases in serum T concentrations. We report here the results of treatment with a 4.5% testosterone gel administered intranasally (nasal testosterone gel - NTG) on serum total testosterone (TT), LH, and FSH in hypogonadal men. Methods Hypogonadal men were randomized into a 90-day, open-label, dose-ranging study. A 4.5% NTG (125 uL/nostril, 11.0mg testosterone/dose) was self-administered using a multiple-dose dispenser either twice daily (BID, n=122) or 3 times a day (TID, n=151) for a total dose of 22.0mg or 33.0mg, respectively. Titration was performed based on blood levels so as to achieve the eugonadal range (300 -1050 ng/dL). Serum samples were obtained at baseline and after 90 days of treatment to determine relevant hormone levels. Results Total serum testosterone increased from a mean Cavg 200.8 ng/dL at baseline to a mean Cmax 818.49 ng/dL at ~40 minutes. After 90 days, 90% (95% CI = 83-97%) of men in the TID group, and 71% (95% CI = 62-79%) of men in the BID group reached normal T levels, and a mean total testosterone Cavg 421 ng/dL and 375 ng/dL, respectively. Baseline FSH (BID) was 8.49 IU/L, mean at Day 90 was 5.99 IU/L. Baseline FSH (TID) was 6.42 IU/L, mean at Day 90 was 3.12 IU/L. Baseline LH (BID) was 5.42 IU/L, mean at Day 90 was 3.56 IU/L. Baseline LH (TID) was 5.25 IU/L, mean at Day 90 was 2.20 IU/L. Conclusions Treatment with 4.5% NTG restored serum TT to normal levels while FSH and LH levels were reduced but remained well within the normal range mitigating the decline in LH and FSH. This maintenance of normal gonadotropins differs from the usual suppression seen with other exogenous T preparations, particularly injections. The mechanism for this reduced gonadotropin suppression is uncertain, but may be due to return of serum T to baseline between doses. Further studies are needed to determine to what extent this reduced gonadotropin suppression may result in preservation of testicular volume and fertility. Funding Support from Trimel/Acerus Pharmaceuticals for Phase 3 clinical trial.
Authors
William Conners, MD
Abraham Morgentaler, MD Margaux Guidry, PhD Gerwin Westfield, PhD Nathan Bryson, PhD Irwin Goldstein, MD |
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MP89-07 |
ARTIFICIAL REOPRODUCTIVE TECHNIQUE OUTCOMES IN MALE HYPOGONODOTROPIC HYPOGONODISM REGARDING SPERM SOURCE |
Infertility: Therapy I | 17BOS |
Abstract: MP89-07 Sources of Funding: None Introduction Hypogonadotropic hypogonadism is a rare disease for infertile patients. Generally, sperm can be obtained in ejaculate after medical treatment, but some patients can undergo testicular sperm extraction. The aim of the present study was to evaluate ART outcomes in men with hypogonadotropic hypogonadism. Methods A total of 119 ART cycles in 61 patients were evaluated in this study between January 2004 to August 2016. Hormone replacement therapy including human chorionic gonadotropin 5.000-10.000 IU weekly and human menopausal gonadotropin 150-225 IU weekly were given before ART cycles. ART cycles were planned when hormone levels were in eugonadotropic and/or sperm was observed in the ejaculate. ART cycles were divided into two groups according to sperm source as ejaculated (n=94) and testicular spermatozoa used (n=25). Total number of retrieved and metaphase II oocytes, fertilization, clinical pregnancy and life birth rates were compared between two groups. Additionaly, ART cycles were also evaluated in fresh (n=91) and frozen embryo (n=28) cycles. Results Male mean age and duration of infertility were 35.8±5.64 and 6.1±4.16 years, respectively.While ejaculated sperm was used in 94 (79%) cycles, testicular sperm was used in 25 (21%) cycles with persistent azoospermia despite hormonal treatment. Micro TeSe was performed on 16 patients (13.4%), and sperm was found in 13 of them. Therefore, the sperm retrieval rate with micro TeSe was 81.3% in hypogonadotropic hypogonadism. Compared parameters were given in Table 1._x000D_ While there was observed statistically significant difference in clinical pregnancy rate between two groups according to sperm source (p=0.017); there were not observed any statistical differences among other compared parameters. _x000D_ Additionally, the ART outcomes were evaluated in fresh and frozen embryo transfered ART cycles. In fresh and frozen embryo cycles, pregnancy rate was 48.4% and 42.9% and life birth rate was 34.1% and 25%, respectively. There were not observed statistical differences between these parameters (p>0.05). _x000D_ Conclusions Patients with hypogonadotropic hypogonadism have high fertilization and pregnancy rates in both of fresh and frozen ART cycles. Although sperm retrieval rate is higher with micro TeSe, ejaculated spermatozoa can be used effectively for ART. Funding None
Authors
M. Murad BASAR
Caroline Pirkevi-Cetinkaya Yesim Kumtepe-Colakoglu Serkan Selimoglu Semra Kahraman |
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MP89-08 |
Ultrasonographically guided puncture of the rete testis for sperm recovery in non-obstructed azoospermic men |
Infertility: Therapy I | 17BOS |
Abstract: MP89-08 Sources of Funding: none Introduction Ultrasonographically guided puncture (UGUP) of the rete testis (RT) has been proven to be an efficient method for sperm recovery in obstructed azoospermic men (Andrologia 35:85, 2003). In the current study we evaluated the role of UGUP of the RT in sperm recovery from non-obstructed azoospermic (NOA) men. Methods Bilateral UGUP of the RT was performed in 83 NOA-men. Under local anesthesia and ultrasonographical control (mode B, frequency of 7.50 MHz), the hyperdense tip of a 30-gauge needle approached and reached the RT of each NOA-man. When ultrasonographical control demonstrated that the tip of the needle had reached the hyperdense line of the RT negative pressure was applied and cells from the RT were aspirated. All the aspirated samples from the RT were observed via confocal scanning laser microscope and some of them after fluorescent in situ hybridization (FISH) techniques. Men who were negative for spermatozoa after UGUP of the RT underwent microsurgical therapeutic testicular biopsy (MTTB). Recovered spermatozoa subpopulations either from UGUP-RT samples or from MTTB-samples were frozen. Results UGUP of the RT resulted in sperm recovery in 19 men (22.89%). The remaining 64 NOA-men underwent MTTB. Twenty nine men out of the 64 men (45.31%) who underwent MTTB demonstrated testicular spermatozoa. Thus in total, 48 men (57.83%) were positive for spermatozoa either in the UGUP-RT-samples or in the MTTB-samples. There was not a significant difference between the mean value of peripheral serum testosterone three months after UGUP-RT and the respective mean value prior to UGUP-RT. FISH techniques in UGUP-RT samples demonstrated in each of the 19 men at least 81% haploid spermatozoa. Hematomas were not demonstrated by ultrasonography one, three, and nine weeks post-UGUP-RT. Nine couples from the above mentioned 19 NOA-couples participated in assisted reproductive technology programs. Three clinical pregnancies were achieved. Four offspring were delivered. Conclusions Considering that UGUP-RT puncture a) does not reduce the volume of testicular parenchyma, b) is less invasive than MTTB, and c) apparently causes less detrimental effect on testicular vasculature than MTTB, UGUP-RT is recommended as first line approach for the treatment of NOA-men. If UGUP-RT is negative for spermatozoa in non-obstructed men, biopsy is indicated. Funding none
Authors
Athanasios Zachariou
Fotios Dimitriadis Sotiris Skouros Panagiota Tsounapi Irene Matthaiou Atsushi Takenaka Nikolaos Sofikitis |
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MP89-09 |
Salvage mTESE after previous failed mTESE: results and predictors for success. |
Infertility: Therapy I | 17BOS |
Abstract: MP89-09 Sources of Funding: None Introduction Microdissection testicular sperm extraction (mTESE) is considered the gold standard for the retrieval of sperm in men with non-obstructive azoospermia with success rates approaching 50%. However a significant proportion of couples wish to be considered for repeat attempts at sperm retrieval. The aim of this study was to determine the rates of success at our centre. Methods Twenty-three patients with non-obstructive azoospermia were identified from a prospective database between 2011 and 2016. All had undergone previous unsuccessful mTESE with testis biopsy. Data on hormonal profile and testis pathology were collected. Twenty-two men were started on hormonal manipulation prior to a repeat mTESE. Results Overall the mean age of men identified was 37.8 years. The commonest pathological findings from first testis biopsy were maturation arrest (n=11) and Sertoli cell only syndrome (n=7). Twelve men had normal testosterone when started on hormonal manipulation. The success rate of repeat mTESE was 35% (n=8). Three men with initial negative mTESE underwent varicocelectomy and hormone treatment prior to successful repeat mTESE. Maturation arrest was more common in the failure group (n=9; 60%) compared with the success group (n=2; 25%). Conclusions There is limited evidence on the utility of repeat mTESE in men who have previously failed the same procedure. Hormonal manipulation may increase the chance of surgical sperm retrieval. Our data suggests that it is worthwhile repeating mTESE with hormonal manipulation however, counselling of these patients remains vitally important. Funding None
Authors
Amr Moubasher
Odunayo Kalejaiye Giovanni Chiriaco Marco Capece Pippa Sangstar Amr Raheem Nim Christopher Asif Muneer Giulio Garaffa David Ralph |
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MP89-10 |
Critical analysis of medical treatment before surgery in non-obstrutive azoospermia: a systematic review |
Infertility: Therapy I | 17BOS |
Abstract: MP89-10 Sources of Funding: NONE Introduction Currently, treatment of men with nonobstructive azoospermia (NOA) is accomplished through assisted reproduction using testicular sperm retrieval techniques combined with in vitro fertilization (IVF) by intracytoplasmic sperm injection technique (ICSI). Among the sperm retrieval techniques, testicular microdissection (micro-TESE) is presenting the best results, with approximately 50% of success. In order to optimize the spermatogenesis process before the procedure, new therapies are being used towards a better chance of success in the recovery of sperm for IVF, through prior drug treatment. There is no consensus in the literature on the effectiveness of this treatment. The objective of this study was to conduct a systematic review regarding the use of previous clinical treatment for sperm retrieval in men with NOA, comparing sperm retrieval rates (SRR), drug used, levels of FSH / testosterone and the relationship with the testicular histology Methods A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis protocols (PRISMA-P) 2015 statement. A total of 53 analyzed studies were selected 7 for the final analysis Results The SRR with micro-TESE in the treated group ranged from 51.0 to 77.0%, while in the control group ranged from 33.0 to 51.0%. Regarding the medication used, it was not possible to compare the results of the studies, but men with Klinefelter Syndrome (KS), responded better to aromatase inhibitor (AI). With respect to hormone levels, we see improvement with treatment in the group of subjects with normal FSH levels. In the case of KS, with high levels of FSH and low levels of testosterone, SRR was also better when individuals showed an increase in testosterone levels. Regarding the histology of biopsy, the best responses were in patients with hypospermatogenesis (HS) and maturation arrest (MA), except in SK Conclusions The studies analyzed lead to the conclusion that the medical treatment in men with NOA, when the FSH levels are normal, histology showed MA or HS and men with KS, with high FSH levels and low levels of T. New prospectives randomized studies are needed to prove the real benefit of these treatments. Funding NONE
Authors
THIAGO NUNES
RICARDO SAADE EDSON BORGES |
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MP89-11 |
Low sample volume cases have high sperm retrieval rates in microdissection testicular sperm extraction. |
Infertility: Therapy I | 17BOS |
Abstract: MP89-11 Sources of Funding: none Introduction Microdissection testicular sperm extraction (Micro-TESE) is the standard treatment for non-obstructive azoospermia (NOA). However, the amount of tissue that should be extracted has not been reported. This study investigated the relationship between sample volume and sperm retrieval rate in Micro-TESE. Methods The subjects were 208 Asian patients with NOA (mean age: 35.1±5.4 years) who had undergone Micro-TESE at Nagoya City University Hospital or affiliated facilities between July 2007 and December 2014. In this study, testicular volume was measured with a ruler before albugineotomy and after testicular ligature, and the difference in values was set as the sample volume. The subjects were assigned to groups based on sample volume: less than 1.5 mL (group A: n=17), 1.5 mL to 3.0 mL (group B: n=56), 3.0 mL to 4.5 mL (group C: n=91), and more than 4.5 mL (group D: n=44); the groups were then compared. Subjects were also divided into groups based on sampling rate (sample volume/testicular volume before surgery): less than 15% (group a: n=46), 15% to 30% (group b: n=70), 30% to 45% (group c: n=45), and more than 45% (group d: n=37); the groups were again compared. Results Sperm extraction rates in groups A, B, C, and D were 39.3%, 17.1%, 20.0%, and 27.0%, respectively (Figure 1). Sperm retrieval rate in group A was significantly higher (p<0.05) than that in group B. No significant differences were noted between the other groups. Sperm retrieval rates in groups a, b, c, and d were 58.3%, 30.3%, 18.6%, and 22.7%, respectively (Figure 2). Sperm retrieval rate in group a was significantly higher than that in groups c and d (p<0.05). No significant differences were noted among the other groups. Conclusions In Micro-TESE, the sperm retrieval rate in the group with a low sample volume was significantly higher, possibly because seminiferous tubules containing sperms are easily identified during microsurgery. The findings suggest that if sperms cannot be seen in a low sample volume, there will be no change in the sperm retrieval rate if the sample volume is increased. Funding none
Authors
Satoshi Nozaki
Tomoki Takeda Shoichiro Iwatsuki Hamakawa Takashi Kazumi Taguchi Yasuhiro FUjii Hiroki Kubota Hiroyuki Kamiya Yukihiro Umemoto Takahiro Yasui |
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MP89-12 |
Efficacy of Treatment with Pseudoephedrine in Men with Retrograde Ejaculation |
Infertility: Therapy I | 17BOS |
Abstract: MP89-12 Sources of Funding: None Introduction To evaluate the efficacy of pseudoephedrine treatment in patients with retrograde ejaculation._x000D_ Methods A retrospective analysis was performed of men seen at a infertility clinic treated with pseudoephedrine for retrograde ejaculation between January 2010 and May 2016. All patients had a semen analysis and post-ejaculatory urinalysis before and after treatment. The treatment protocol consisted of 60 mg of pseudoephedrine every 6 hours on the day before semen analysis and two more 60 mg doses on the day of the semen analysis._x000D_ Results Twenty men were medically treated with pseudoephedrine for retrograde ejaculation between January 2010 and May 2016 (12 with complete retrograde ejaculation and 8 with partial retrograde ejaculation). Diabetes was the most common etiology for complete retrograde ejaculation (60%), while an idiopathic cause was the most common etiology for partial retrograde ejaculation (82%). Of the 12 complete retrograde ejaculation patients treated with pseudoephedrine prior to semen analysis, 7 (58.3%) recovered sperm in the antegrade ejaculate, with a mean total motile count of 54 ± 20 million. Out of the 8 patients with partial retrograde ejaculation, 5 (62.5%) had a ≥ 50% increase in the antegrade total sperm count. The mean total motile count in this group increased from 6.6 ± 3.2 million before treatment to 31.6 ± 13.9 million after treatment, while the percentage of sperm in the urine declined from 41.9 ± 11.2% to 17 ± 10%, respectively (both p < 0.05). Overall, some improvement in seminal parameters occurred in 14 (70%) patients, with 10 patients (38.5% of all patients) achieving antegrade total sperm counts over 39 million._x000D_ _x000D_ Conclusions In men with retrograde ejaculation, a pseudoephedrine regimen prior to ejaculation confers some improvement in ejaculated semen parameters for approximately two thirds of patients and an ejaculated total motile count of greater than 20 million for approximately one third of patients._x000D_ Funding None
Authors
Nikita Abhyankar
Ohad Shoshany Jason Elyaguov Craig Niederberger |
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MP89-13 |
Presentation and Treatment Outcomes of Ejaculatory Duct Obstruction |
Infertility: Therapy I | 17BOS |
Abstract: MP89-13 Sources of Funding: none Introduction Ejaculatory duct obstruction (EDO), is either complete or partial and it affects 5% of infertile men. Complete obstruction occurs in up to 1% of the infertile male population while incomplete obstruction occurs in up to 4.4% of the infertile male population. _x000D_ _x000D_ EDO often presents with infertility. In some patients EDO is symptomatic and patients may present with: decreased force of ejaculate, pain on or after ejaculation, decreased ejaculate volume, haemospermia, perineal or testicular pain, low back pain and dysuria._x000D_ _x000D_ We set out to determine the presentation and treatment outcome of EDO._x000D_ Methods A retrospective analysis of 54 patients diagnosed with EDO over the past 7 years._x000D_ Patients were evaluated by history, examination, semen analysis and trans-rectal ultrasonography (TRUS). Patients presenting with infertility also had hormonal profile and male reproductive genetic profile._x000D_ _x000D_ All patients had transurethral resection of the ejaculatory ducts (TURED) or TUR cyst deroofing for midline cysts. _x000D_ Results The mean (range) patient age was 38(24-64) years. Twenty three patients (42%) presented with ejaculatory disorders, 20 patients (37%) presented with infertility, and 11 with pelvic pain or urinary symptoms. 9 (16%) of these men presented with both infertility and ejaculatory disorders._x000D_ _x000D_ The cause of EDO was congenital midline cyst in 30 patients (56%), idiopathic in 6 (11%), mullerian duct syndrome in 2 (4%), associated with unilateral vasal aplasia in 5 (9%), and ejaculatory duct obstruction associated with calculi in 11 (20%)._x000D_ Of the 33 patients with symptomatic EDO; 22(68%) had complete cure while 5 (22%) had persistence of symptoms and 6 men did not attend for their follow up appointments._x000D_ _x000D_ Semen parameters pre and post procedure were available for 26 men. Improvements were seen in 16 of these men; Mean (range) sperm count was 12.5 (0-75) x106/cc pre-operatively and 25 x106/cc (4 to 137) post TURED. Average semen volume increased from 0.9 to 3.7 mls and mean motility increased from 10% (0-45%) to 43%(14-68%). 10 men remained azoospermic suggesting an associated proximal obstruction._x000D_ _x000D_ Complications occurred in 7 patients (18%): epididymitis (3), chronic pelvic pain (1), retrograde ejaculation (1) and urine retention (2). _x000D_ Conclusions EDO is an underdiagnosed cause of ejaculatory disorders. Excluding EDO is important in the management of patients presenting with ejaculatory disorders in addition to infertile males. _x000D_ _x000D_ It can be easily diagnosed by TRUS. TURED is an effective and safe treatment for EDO. Funding none
Authors
Pippa Sangster
Ayo Kalejaiye Giovanni Chiriaco Amr Raheem Asif Muneer David Ralph |
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MP89-14 |
Hyperbaric oxygen therapy in the treatment of elevated levels of active oxygen radicals in the semen and sperm DNA fragmentation |
Infertility: Therapy I | 17BOS |
Abstract: MP89-14 Sources of Funding: Botkinsky Hospital Introduction Pathogenic effects of reactive oxygen species (ROS) are realized in their excess formation (oxidative stress). According to one hypothesis, they promote the increase in sperm DNA fragmentation (DNAF) in patients with idiopathic male infertility. The aim of the study is to evaluate the influence of hyperbaric oxygen therapy (HBO) on the content of reactive oxygen species (ROS) in semen and on the level of sperm DNAF. Methods The study included 90 men with idiopathic infertility, the content of ROS in the sperm was above 0.64 mV/sec and the level of sperm DNAF was above 15%. In the main group (n=60) 10 sessions of HBO were performed. In the control group (n=30) HBO sessions were not performed. The age of patients ranged from 25 to 37 years (median - 30.5 years). The level of ROS in semen was studied by chemiluminescence, sperm DNAF was determined by TUNEL. The assessment was made at the time of entry into the study and after 3 months (in the main group - 3 months after HBO). Results In the main group, the median level of ROS in semen decreased from 0.89 mV/sec to 0.39 mV/sec (p<0.05), average sperm DNAF after HBO decreased from 33.2 ± 7.5% to 11.9 ± 5.9% (p<0.05), whereas in the control group these figures remained almost at the same level – 0.86 mV/sec and 0.88 mV/sec (p>0.05), 31.2 ± 6.1% and 31.7 ± 6.3% (p>0.05). Conclusions HBO is an effective method reducing the number of free oxygen radicals and the number of sperm with DNAF, which can potentially lead to an increased fertility in patients with idiopathic male infertility. Funding Botkinsky Hospital
Authors
Alexey Metelev
Andrey Bogdanov Evgeny Ivkin Evgeny Veliev |
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MP89-15 |
PATIENT CHARACTERISTICS OF CHILDLESS MEN UNDERGOING VASECTOMY REVERSAL: RESULTS OF RETROSPECTIVE REVIEW |
Infertility: Therapy I | 17BOS |
Abstract: MP89-15 Sources of Funding: None Introduction Vasectomy is a commonly used method of permanent sterilization in the US. The overwhelming majority of these men have fathered at least one child. However, a small subset of men undergoing elective sterilization have never fathered a child. We sought to describe the clinical and social aspects of the childless male seeking vasectomy reversal and analyze any potential differences from their counterparts. _x000D_ Methods Retrospective chart review was performed for patients presenting for vasectomy reversal from 2011-2015. 1,242 men were identified for analysis. Patient and partner demographics, parity status and reversal type were compared between prior fathers and childless men._x000D_ Results Our database included 1,242 men from 2011 to 2015 whom had previously had a vasectomy and were seeking reversal. Of those, 9% (n=116) had never previously fathered children, and 91% (n=1,126) had at least one prior child. These men were largely similar on comparison of age (41.4 vs 39.8 years), partner age (32.8 years), and known female factor (2.5%). However, childless men were significantly more likely to have a nulliparous female partner; 79% vs 59% (p=<0.001). They were also found to have a slightly longer obstructive interval (8.95 vs 10.02 years, p=0.076), although this point did not reach statistical significance. Comparing type of reversal in childless vs those with children, bilateral VV performed in 74% vs 66%, bilateral VE performed in 10% vs 12% and combination VV/VE in 13% vs 16%; these differences were not significant. Patency was 98% (n=102) for childless men and 94% (n=949) for men with prior children. Conclusions This retrospective review sheds light on a unique population of men for which there is a paucity of data in the literature. To our knowledge this is the first study examining childless men electing vasectomy reversal. This data offers important information that may be included in preoperative counseling targeted specifically to men whom have not fathered children. _x000D_ Funding None
Authors
Christopher Corder
Amy Perkins Matthew Marks Sheldon Marks Christopher Deibert |
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MP89-16 |
Characteristics and Motivations of Men Who Seek Vasectomy Reversal |
Infertility: Therapy I | 17BOS |
Abstract: MP89-16 Sources of Funding: AWP is a K12 scholar supported by a Male Reproductive Health Research (MRHR) Career Development Physician-Scientist Award (Grant # HD073917-01) from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Program_x000D_ Introduction Approximately 20% of men who undergo vasectomy subsequently consider reversal. However, the factors influencing the decision to undergo vasectomy reversal (VR) after vasectomy are poorly understood. Here we examine the characteristics and motivating factors of men who expressed preliminary interest in and subsequently elected to proceed or not to proceed with VR. Methods Between February 2011 and October 2016, 252 men inquired about VR from a single andrology clinic through its website. These men were emailed an electronic survey assessing demographic information and motivations for VR. T-test of means and Chi-square test were used to analyze the data. Results The survey was completed by 45 (17.8%) of the 252 men. The mean(SD) time since vasectomy was 9.8(7.7) years, and number of children was 2.2(1.1). One half (49%) of the respondents had undergone VR with an average of 9.7 years between vasectomy and VR. Table 1 compares factors associated with decision to proceed with VR after initial inquiry. Men with an annual income >$100,000 and with at least a college degree were more likely to undergo VR, while time since vasectomy, number of children, age of current partner, and having a new partner following vasectomy did not influence the decision to proceed. Reasons to forego VR included cost (48%), lack of interest in having children (26%), lack of time (9%), and lack of information about the procedure (9%). Most (74%) men who did not undergo VR plan to pursue VR in the future and reported that speaking to another patient (26%), a brochure (30%), and talking to a doctor (39%) would assist their decision making. Conclusions After initial interest in VR following vasectomy, men with high incomes and education are more likely to undergo VR. Financial burden was the most common reason preventing VR. Most men who did not undergo VR reported continued interest in VR and that receiving additional information would assist their decision making. Funding AWP is a K12 scholar supported by a Male Reproductive Health Research (MRHR) Career Development Physician-Scientist Award (Grant # HD073917-01) from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Program_x000D_
Authors
John Sigalos
Mark Hockenberry Edgar Kirby Jordan Krieger Alexander Pastuszak Larry Lipshultz |
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MP89-17 |
Microscopic Evaluation of the Vasal Fluid for Sperm at the Time of Vasectomy Reversal – Do We Really Need to Check? |
Infertility: Therapy I | 17BOS |
Abstract: MP89-17 Sources of Funding: None Introduction During vasectomy reversal (VR), intra-operative microscopic evaluation of the vasal fluid for sperm presence and quality can inform of the possibility of epididymal obstruction and need for a vasoepididymostomy (VE). Despite its potential utility, the practice of intra-operative microscopic vas fluid evaluation is not universal. Some centers may not have bench microscopy available. Some surgeons may only perform vasovasostomy (VV) and therefore are not influenced by vasal fluid characteristics or alternatively feel that the vasal fluid quality alone can predict the need for a VE. Objective: In an effort to validate the utility of microscopic vasal fluid evaluation, the current initiative correlates vasal fluid characteristics with sperm presence and quality in a large series of VRs. Methods 1108 bilateral vasectomy reversals performed by a single surgeon (EG) yielded a total of 2216 vasal units (right & left sides) for analysis. During VR, vasal fluid was expressed and sampled from the transected testicular end vas and the fluid was characterized (thick-paste/opaque/translucent/clear). The volume of vasal fluid was documented (copious/minimal). Each aspirated sample underwent microscopic evaluation for sperm quality and categorized as: motile sperm/intact non-motile sperm/sperm parts/no sperm. The predictive utility of the gross vasal fluid characteristics with respect to sperm presence and quality was analyzed. Results Table 1 summarizes the relationship between the gross vasal fluid characteristics and the microscopic presence and quality of sperm within the fluid among 2216 vasal units. When thick-pasty fluid was observed, no sperm were seen in the samples in 50% of cases and if present, only non-motile sperm were observed. Importantly, even in the setting of more favorable vasal fluid characteristics (clear, translucent & opaque fluid), no sperm were seen in 7-11% of cases, suggesting the possibility of epididymal obstruction and the need for a VE. Conclusions Intra-operative microscopic evaluation of the vasal fluid for sperm is a necessary practice during vasectomy reversal to optimize surgical outcomes. The gross characteristics of the vasal fluid alone does not universally predict sperm presence and quality. Reliance on vasal fluid characteristics in isolation, without microscopic sperm analysis, may lead to unrecognized epididymal obstruction and the possible need for a VE in approximately 10% of cases of VR. Funding None
Authors
Ethan Grober
Sammi Tobe |
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MP89-18 |
The Effect of Fellowship Training on Operative Times and Outcomes for Microsurgical Cases |
Infertility: Therapy I | 17BOS |
Abstract: MP89-18 Sources of Funding: None Introduction The purpose of our study is to assess the effect of fellow involvement in microsurgical cases with regard to operative time and postoperative outcomes Methods We performed a retrospective review of all patients undergoing microsurgical operations for infertility between July 2014 and September 2017. Utilizing patient electronic charts, operative times as well as resident and fellow surgical assistance were documented. Patient and female partner age, natural pregnancy rates, procedure type, pre- and post-operative semen parameters, time from vasectomy, and postoperative complications were all evaluated. The effects of a fellow surgical assistance on perioperative and postoperative outcomes were then analyzed. Statistical significance, defined as a p-value <0.05, was determined using Student's T, chi square or Fischer exact test. Results We identified 183 patients who underwent sub-inguinal varicocele ligation or vasectomy reversal by a single surgeon at our institution. All patients undergoing surgery for fertility concerns were included for analysis. Vasectomy reversals requiring one or more vaso-epididymostomy were excluded from analysis, due to insufficient numbers for meaningful comparison, as were any patients undergoing combined cases in addition to microsurgical surgery. Compared to when faculty was operating without a fellow (n=72), fellow surgical assistance (n=81) results in a statistically significant prolonged operative time for both unilateral varicocele ligation (1:22 vs 1:01, p<0.01), bilateral varicocele ligation (2:13 vs 1:43, p<0.01), and bilateral vaso-vasostomy (2:49 vs 2:19, p<0.01). Comparing fellow assisted cases to those without a fellow, there were no significant differences in all other outcome measurements or patient demographics. Overall, 69.0% of patients undergoing varicocelectomy experienced a significant improvement in their Total Motile Sperm Count post-operatively, and 100% of patients achieved patency after vasectomy reversal. Conclusions Fellowship training was associated with a ~30% increase in operative time for unilateral and bilateral varicocele ligation, and a ~20% increase in operative time for bilateral vaso-vasostomy, but does not adversely impact outcomes of microsurgical cases. Funding None
Authors
Dane Johnson
Raymond Roewe Jay Sandlow |
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MP89-19 |
Timing of return of sperm to the ejaculate and late failures following vasal reconstruction |
Infertility: Therapy I | 17BOS |
Abstract: MP89-19 Sources of Funding: Frederick J and Theresa Dow Wallace Fund of the New York Community Trust & the Agency for Healthcare Research and Quality_x000D_ This work was supported in part by the Urology Care Foundation Research Scholar Award Program and AUA New York Section Research Scholar Fund Introduction Vasal reconstruction is an effective method of treating obstructive azoospermia, with reported patency rates of 99% for vasovasostomy (VV) and 80% for vasoepididymostomy (VE). When deciding between sperm retrieval with in vitro fertilization or vasal reconstruction, a major consideration is often the length of time it will take for sperm to return to the ejaculate following vasal reconstruction. The objective of this study was to compare the time required for sperm to return to the ejaculate following VV or VE, and if the rate of late failures would be less common in VV compared to VE. Methods We performed a retrospective review of all patients undergoing VV and VE by a single surgeon. Demographic information, surgical details, and postoperative semen analysis (SA) values and dates were reviewed. Late failures were defined as those with sperm return to the ejaculate post-reconstruction who subsequently became azoospermic. Descriptive statistics, student t-test, and Fishers exact tests were used to compare the groups, with significance set at p<0.05. Results 338 and 37 men underwent VV and VE, respectively, and had sperm return to the ejaculate postoperatively. Mean age was 43+/-6.7 years, with a mean obstructive period of 10+/-5.5 years. Mean time to return of sperm in the ejaculate was faster following VV than after VE (Table 1). Initial sperm counts were also higher following VV compared to VE (Table 1). Longitudinally, more men had late failure of vasal reconstruction after VE than after VV (Table 1). Presence of sperm granuloma did not impact time to return of sperm in the ejaculate (p=0.22) after VV. Obstructive interval was not associated with either sperm count in the ejaculate after vasal reconstruction or time to return of sperm to the ejaculate._x000D_ Conclusions Among men undergoing vasal reconstruction, return of sperm to the ejaculate typically occurs at 3 months after VV and at 5 months after VE. A small, but significant, proportion of men undergoing vasal reconstruction will have late failures, especially after VE. Since these late failures typically occur within one year post-operatively, men undergoing vasal reconstruction should be advised to consider sperm cryopreservation as soon as motile sperm appear in the ejaculate. Funding Frederick J and Theresa Dow Wallace Fund of the New York Community Trust & the Agency for Healthcare Research and Quality_x000D_ This work was supported in part by the Urology Care Foundation Research Scholar Award Program and AUA New York Section Research Scholar Fund
Authors
Ryan Flannigan
Phil V. Bach Abimbola Ayangbesan Andrew Gottesdiener Marc Goldstein |
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MP89-20 |
Targeted Robotic Assisted Microsurgical Denervation of the spermatic cord for the treatment of chronic scrotal content pain: Single center, large series review. |
Infertility: Therapy I | 17BOS |
Abstract: MP89-20 Sources of Funding: None Introduction Microsurgical denervation of the spermatic cord (MDSC) is a treatment option for chronic scrotal content pain that is unresponsive to conservative treatments. A recent study has shown specific nerve fiber abnormalities (Wallerian degeneration) in the cord as a potential cause for this pain. Our goal was to assess outcomes of a more targeted technique in ablating only these abnormal nerves when performing MDSC: targeted robotic assisted microsurgical denervation of the spermatic cord (RMDSC). Methods Retrospective review of 772 patients who underwent RMDSC by two fellowship trained microsurgeons from October 2008 to July 2016. Selection criteria were as follows: chronic testicular pain (>3 months), failed standard pain management treatments and negative urologic workup. Targeted ligation of tissues containing the trifecta location of nerves with Wallerian degeneration was performed: the cremasteric muscle fibers, the peri-vasal sheath and the posterior spermatic cord lipomatous tissues. The primary outcome measure was level of pain. Pain was assessed preoperatively and postoperatively using two assessment tools: a) the subjective visual analog scale (VAS) and b) an objective standardized externally validated pain assessment tool (PIQ-6, QualityMetric Inc., Lincoln, RI). Results Median age was 41 years. Median operative duration (robot console time) was 20 minutes (15-80). Median follow up was 24 months. Subjective VAS patient pain outcomes: 84% significant reduction in pain (50% complete resolution – 425 patients, 34% reported a greater than 50% reduction in pain – 291 patients). Objective PIQ-6 outcomes: significant reduction in pain in 67% of patients at 6 months and 68% at 1 year post-op. Conclusions Targeted robotic assisted microsurgical denervation of the spermatic cord is a safe and viable treatment option for patients with chronic scrotal content pain refractory to conservative measures. Further studies are warranted. Funding None
Authors
Nahomy Calixte
Bayo Tojuola Ibrahim Kartal Ahmet Gudeloglu Jamin Brahmbhatt Sijo Parekattil |
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MP90-01 |
Successful Diabetic Control as Measured by Hemoglobin A1c Decreases Urine Risk Factors for Uric Acid Calculi |
Stone Disease: Medical & Dietary Therapy | 17BOS |
Abstract: MP90-01 Sources of Funding: None Introduction Patients with diabetes mellitus (DM) have lower urine pH and a higher prevalence of uric acid calculi. It is unknown if glycemic control by patients with DM improves urinary risk factors for stones. We examined the association of hemoglobin A1c (HgbA1c), a measure of long-term DM control, with 24hr urine risk factors for uric acid and calcium calculi. Methods With IRB approval, we identified 278 stone formers (SF) with 24h urine collections and HgbA1c measures obtained within 3 months of the urine collection. Relative saturation indices (RS) were calculated using EQUIL2. Patients were separated by glycemic status: normoglycemic (NG, HgbA1c<6.5) and hyperglycemic (HG, HgbA1c≥6.5); 24-h urine parameters were compared. The NG cohort was further divided into those with no history of DM and those with well controlled DM, characterized by HgbA1c<6.5 near the time of their 24-h urine collection. Variables were analyzed using chi squared, Welch&[prime]s t-test and multivariate linear regression to adjust for BMI, age, gender, and for thiazide and/or potassium citrate use. Results Patients in the HG group were older (63 vs 60, p<0.01) and had higher BMI (35.1 vs 31.5, p<0.01). Multivariate analysis revealed that, overall, hyperglycemia was associated with lower pH (5.85 vs 6.30, p<0.001), higher uric acid RS (1.39 vs 0.69, p<0.001), and lower brushite RS (0.85 vs 1.60, p<0.001). SFs with history of DM who were well controlled had similar risk factors for uric acid stone to SFs with no history of DM (pH 6.2 vs 6.4, p=0.50, and uric acid RS 0.87 vs 0.56, p=0.85). Patients with a history of DM had a higher median urine calcium (223 mg/d vs 160, p=0.05) and corresponding higher calcium oxalate RS (1.90 vs 1.46, p=0.02) than SFs with normal HgbA1c. Conclusions Our study suggests that successful glycemic control may be associated with reduced urinary risk factors for uric acid stone formation. With good glycemic control, patients with DM had equivalent uric acid risk factors to those with no DM history and a subclinical increase in urinary risk factors for calcium stones. Our findings support promoting glycemic control as a component of the multidisciplinary medical management of stone disease. This provides us with the direction needed to reveal whether glycemic control reduces stone risk factors. Funding None
Authors
Kimberly A Maciolek
Kristina L Penniston Sara L Best |
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MP90-02 |
Oral dissolution therapy (ODT) for lucent renal calculi; Can we predict the outcome? |
Stone Disease: Medical & Dietary Therapy | 17BOS |
Abstract: MP90-02 Sources of Funding: none Introduction Oral dissolution therapy (ODT) for lucent renal calculi is non-invasive effective therapeutic approach however;responders to this approach are not well characterized. Methods After obtaining IRB approval, patients with renal stones of less than 600 HU core attenuation value in non contrast computed tomography (NCCT) and without significant hydronephrosis were counseled for 3 months ODT. ODT entails oral potassium citrate 20 mEq three times daily, 3 liters of daily fluid intake and dietary regimen. Patients were followed up at2,4,8 and12weeks,for assessment of ODT compliance and urine analysis.Patients with poor compliance (> one visit) were excluded from final analysis.Study`s end point was change in stone surface area as measured by NCCT at3 months. At 3 months, ODT non-responders were scheduled for secondary intervention and ODT partial responders (reduced stone SA) were asked to choose between ODT extra 3 months vs.immediate secondary intervention. Predictors for 3months ODT-stone free rate and final ODT-success rate were assessed._x000D_ Results Between February 2015 and January 2016:out of 212 legible patients, 182 patients were compliant for ODT and were included in the final analysis.Figure1 summarizes, ODT responders at3 and 6 months. NCCT depicted 97(45.7%) and 57(31.3%)stone free responders at 3 and 6 months respectively.Table 1,summarizes variables that predict less stone free probability 3 months following start of ODT. On multivariate analysis,only proteinuria at urine dipstick at enrollment(p=0.003), stone density (p=0.01) and uric acid level at 8 weeks after treatment (p=0.03) independently predicts less stone free probability 3 months following start of ODT.Table 2 summarizes variables that predict ODT failure at6months.On multivariate analysis, only higher stone density (p=0.03) and lower urine PH at 12 weeks after treatment (p=0.01) independently predict ODT failure at 6 months.The cut-off point of stone density associated with less probability of successful ODT for is 463.5HU (67.7% Sensitivity, 68.9% Specificity, AUC 0.7,P=0.007). Conclusions Regardless stone size, ODT is an effective treatment approach for renal stones. Key factors in determining potential ODT responders are treatment compliance achieving targeted urine PH and low stone density. Funding none
Authors
Amr Elsawy
Ahmed Elshal Ahmed El-Nahas Mohamed Elbaset Hashim Farag Ahmed Shokeir |
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MP90-03 |
INVESTIGATING SMART WATER BOTTLE TECHNOLOGY AS A CLINICAL TOOL FOR STONE FORMERS |
Stone Disease: Medical & Dietary Therapy | 17BOS |
Abstract: MP90-03 Sources of Funding: None Introduction Improved methods of stone prevention are needed to combat rising rates of nephrolithiasis. Achieving adequate fluid intake is an effective strategy; yet, patient compliance with recommendations is generally poor. Mobile health applications and smart technology show promise as tools to improve compliance with medically indicated dietary treatments; however, have yet to be applied specifically towards stone formers with low urinary volume. Recently, a smart water bottle (HidrateSparkTM, Boulder, CO) was introduced as a noninvasive fluid intake monitoring system. This device could conceivably help patients who form stones from low urine volume achieve sustainable improvements in hydration, but has yet to be validated as a useful instrument. We sought to verify its accuracy prior to considering its potential as a medical aide. Methods HidrateSpark (Figure 1) uses capacitive touch sensing via a sensor extending from the lid to base, which calculates volume measurements by detecting changes in water level. Data from the bottle is sent wirelessly to users&[prime] smartphones through an application. A pilot study was conducted to assess accuracy of measured fluid intake over 24 hour periods when used in a real life setting. Subjects were provided smart bottles to sync with their smartphone and given short tutorials on their use. Accuracy was determined by comparing 24 hour measurements recorded through the smart bottle to hand measurements from the corresponding 24 hour period. Results Eight subjects performed 62 24-hour measurements (range 4-14). Mean 24 hour hand measurement was 57.2 ozs (21-96). Corresponding mean 24 hour smart bottle measurement underestimated true fluid intake by a mean of 0.5 ozs (95% CI -1.9, 0.9). The percent difference between hand and smart bottle measurements was 0.0% (95% CI -3%, 3%). The intraclass correlation coefficient (ICC) was calculated to assess consistency between hand measures and bottle measures. The ICC (95% CI) was found to be 0.97 (0.95,0.98) indicating and extremely high consistency between measures. Conclusions 4 hour fluid intake measurements taken through a novel fluid monitoring system (HidrateSpark) are accurate to within 3%. Such technology may be useful as a behavioral aide and/or research tool particularly among recurrent stone formers with low urinary volume. Funding None
Authors
Michael S. Borofsky
Casey A. Dauw Nadya E. York Colin Terry James E. Lingeman |
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MP90-04 |
A novel use of structured water for the prevention of recurrent stones in idiopathic hypercalciuria. |
Stone Disease: Medical & Dietary Therapy | 17BOS |
Abstract: MP90-04 Sources of Funding: none Introduction The majority of stones (85%) contain primarily calcium oxalate. Most renal stones are idiopathic calcium stones, and the most common predisposing factor in these patients is hypercalciuria. Structured water is a new type of water that has been prepared using different types of energy fields and modulators to produce this structured water that has new and different characteristics from the ordinary water. _x000D_ In this study, we compared the efficacy of the structured water (Magnalife®) with hydrochlorothiazide and with ordinary bottled water in the prevention of recurrent renal stones in patients with idiopathic hypercalciuria._x000D_ Methods We conducted a three-year randomized trial comparing the effect of structured water with the effect of hydrochlorothiazide and ordinary bottled water in 300 patients with recurrent calcium oxalate stones and hypercalciuria. 100 men used structured water (Magnalife®). The other 100 men used 50 mg hydrochlorothiazide, and 100 men used ordinary bottled water._x000D_ Urine analysis with renal ultrasonography and radiology were done at baseline and at yearly intervals and any time of recurrence and at the end of the 3 years (36th month). All patients were informed and signed a written informed consent form._x000D_ Results Of the 300 men included in this study, 95 had recurrent stones, 15 men (15%) in the group of structured water ,31 men (31%) in the hydrochlorothiazide group, and 49 men (49%) in the group of ordinary bottled water. The difference in the recurrence rate between the structured water group and the hydrochlorothiazide group is significant (P=0.007) Also the difference between the difference between the structured water group and the ordinary water group is significant (P<0.001), furthermore the hydrochlorothiazide group and the ordinary bottled water group recurrence rate is significantly different (P=0.009). Conclusions Structured water is a safe, effective, and affordable new way to prevent recurrent urinary stones without the need for medications that are expensive and have many side effects. Furthermore, it is more potent than some preventive measures and drugs as a prophylactic way against recurrent urinary stones. It is far more effective than ordinary bottled water in preventing recurrent stones. Further studies are recommended to explore its role in other fields of urology._x000D_ Funding none
Authors
Ali Sami
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MP90-05 |
The Ins and Outs of Fluid Management in Stone Formers: the Impact of Lower Urinary Tract Symptomatology on Urine Volumes |
Stone Disease: Medical & Dietary Therapy | 17BOS |
Abstract: MP90-05 Sources of Funding: None Introduction The most common lifestyle preventative treatment of stone disease is increasing fluid intake. However, many patients experience lower urinary tract symptoms (LUTS) that may impair their ability to increase fluid intake. The objective of this study is to determine if there is a correlation between International Prostate Symptom Scores (IPSS) and 24-hour urine collection volumes. Methods We retrospectively reviewed all kidney stone patients over a 2 year period who were given IPSS questionnaires at the time of their initial consultation, and their subsequent 24-hr urine collections. Exclusion criteria included symptomatic stone or urinary tract infection at time of IPSS completion, inadequate 24-hour collection, or incomplete IPSS questionnaire. Results Overall, 131 patients met inclusion criteria, with a mean age of 53 years. Stratification by IPSS score into mild (0-7), moderate (8-19), and severe (20-35) yielded groups of N=96, 28, and 7, respectively. Linear regression modelling did not reveal a correlation between IPSS score and volume (p=0.1). There was no difference between urine volumes in the mild, moderate and severe groups (p=0.07). However, when comparing those with severe LUTS to the rest of the population, they showed significantly lower daily urine volumes (mean 1.4 L/day vs 2.0 L/day; p=0.02). _x000D_ _x000D_ When patients with low urine outputs (≤1 L/day) (N=1F:9M, mean age 54 years old), were compared to those adequate urine volumes (≥2 L/day) (N=6F:59M, mean age 52 years old), a significantly higher overall IPSS score was noted (11.7 vs. 6.1; p=0.04). Low output patients reported significantly higher scores on the questions related to incomplete emptying (1.8 vs. 0.7; p=0.03), intermittency (1.7 vs. 0.6; p=0.01), and straining (1.8 vs. 0.4; p=0.002)._x000D_ Conclusions This study is the first to examine the correlation between IPSS score and 24-hour urine volume. Though our data does not show a linear relationship between urine output and IPSS; those with lower urine volumes (≤1 L/day) have significantly worse self reported voiding symptoms when compared to those with adequate volumes (≥2 L/day) for stone prevention. Funding None
Authors
Nathan Hoy
Jeremy Wu Nicholas Dean Timothy Wollin Shubha De |
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MP90-06 |
Does thiazide use for stone prevention affect our patients’ health-related quality of life? |
Stone Disease: Medical & Dietary Therapy | 17BOS |
Abstract: MP90-06 Sources of Funding: None Introduction Patients often express concerns about the burden of chronic medication use for stone prevention despite its association with decreased stone recurrence. Fatigue and sexual side effects are among such concerns of patients starting thiazide diuretics. However, it is unknown how the use of thiazides affects the health-related quality of life (HRQOL) of stone formers. We evaluated the effect of thiazides on patients’ stone-related HRQOL. Methods Utilizing the previously validated Wisconsin Stone QOL questionnaire (WISQOL), we analyzed cross-sectional data from patients both new to and established in stone prevention who were enrolled at sites participating in the North American Stone Quality of Life Consortium. We compared HRQOL in the domains of social impact, emotional impact, disease impact, and vitality in patients prescribed thiazides against those not using student’s t-test. We performed multivariate linear regression controlling for age, gender, BMI, and number of stone events to confirm the significance of any differences. Additionally, we assessed with univariate and multivariate logistic regression the likelihood of complaints of fatigue and reduced sexual interest/activity between those prescribed and not prescribed thiazides. Results 1511 stone formers were included (787 M, 724 F), of whom 207 were on a thiazide at study enrollment. Patients prescribed a thiazide had significantly higher scores (better HRQOL) in each domain compared to those not prescribed a thiazide. These differences maintained significance with multivariate analysis (mean domain scores higher by 1.9, 2.3, 2.1, 1.0 points, respectively, all p<0.01). Patients prescribed thiazides were less likely than those not prescribed to report any fatigue in the last 4 weeks (59% vs 68%, p=0.008). Those on thiazides were less likely to report reduced sexual interest/activity (24% vs 31%, p=0.02). On multivariate logistic regression, patients on thiazides were overall 32% less likely to report fatigue, p=0.02, and 33% less likely to report reduced sexual interest/activity, p=0.026, when controlling for the aforementioned factors. Conclusions Patients prescribed thiazide diuretics for stone prevention demonstrated better HRQOL compared to patients not prescribed one. Specifically, thiazide use was not associated with fatigue or reduced sexual interest/activity. These findings may provide reassurance to patients being counseled on starting thiazides for medical management of stones. Funding None
Authors
Eric Raffin
Kristina Penniston Stephen Nakada Jodi Antonelli Davis Viprakasit Timothy Averch Sri Sivalingam Roger Sur Ben Chew Vincent Bird Lawrence Dagrosa Rebecca Smith Vernon Pais |
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MP90-07 |
The effect of potassium citrate on the health-related quality of life of stone formers |
Stone Disease: Medical & Dietary Therapy | 17BOS |
Abstract: MP90-07 Sources of Funding: None Introduction Potassium citrate has an established role in medical management of stone disease but many patients have reported unwanted side effects, notably gastrointestinal (GI). It is not currently well understood how the benefits of potassium citrate affect patients’ health-related quality of life (HRQOL). We sought to evaluate the effect of potassium citrate on patients’ stone-related HRQOL. Methods Utilizing the previously validated Wisconsin Stone-QOL questionnaire (WISQOL), a kidney stone-specific instrument, we analyzed cross-sectional data from patients both new to and already established in stone prevention who were enrolled at sites participating in the North American Stone Quality of Life Consortium. We compared HRQOL in the WISQOL domains of social impact, emotional impact, disease impact, and vitality between patients prescribed potassium citrate and those not. In addition to student’s t-test, multivariate linear regression controlling for age, gender, BMI, and number of stone events was performed to determine the strength of any differences found. Additionally, univariate and multivariate logistic regression were used to assess the likelihood of complaints of nausea and stomach upset or cramps between those prescribed and not prescribed potassium citrate. Results 1511 stone formers were included (787 male, 724 female), of whom 258 were on potassium citrate at study enrollment. Patients prescribed potassium citrate scored significantly higher (better HRQOL) in each of the domains. With multivariate analysis, these differences maintained their significance (mean domain scores were higher by 2.5, 2.8, 2.8, 1.3 points, respectively, all p<0.0001). In item-level analysis, patients prescribed potassium citrate were less likely than those not prescribed it to report any nausea, stomach upset or cramps (43% vs 55%, p<0.001). Multivariate logistic regression showed a 40% lower likelihood of having GI complaints among patients prescribed potassium citrate, p=0.001, when controlling for the aforementioned factors. Conclusions Among chronic stone forming patients, the use of potassium citrate is associated with higher HRQOL across all domains of the WISQOL. Those prescribed potassium citrate appear less likely to endorse GI complaints compared to those not. These findings may be useful when encouraging patients to consider initiating potassium citrate therapy. Funding None
Authors
Eric Raffin
Kristina Penniston Stephen Nakada Jodi Antonelli Davis Viprakasit Timothy Averch Sri Sivalingam Roger Sur Ben Chew Vincent Bird Lawrence Dagrosa Rebecca Smith Vernon Pais |
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MP90-08 |
Variability in Stone Composition and Metabolic Evaluation Between Kidneys in Patients with Bilateral Nephrolithiasis |
Stone Disease: Medical & Dietary Therapy | 17BOS |
Abstract: MP90-08 Sources of Funding: None Introduction Current American Urological Association (AUA) guidelines do not discuss recommendations in obtaining a stone analysis when a bilateral stone procedure is performed. To date, there is a limited amount of data surrounding discordant stone analysis when performing a simultaneous bilateral stone procedure. Stone analysis results, as well as 24-hour urinalysis are utilized for the medical management of stone disease and could possibly be misrepresented if conflicting stone analysis results were present. Therefore, we aim to describe the rate of discordant stone analysis results in patients undergoing ureteroscopy. Methods A retrospective chart review was performed for all patients undergoing bilateral ureteroscopy with stone removal by a single surgeon at a single hospital between 2013 and 2016. All stones were analyzed at a single stone analysis laboratory using Fourier transform infrared spectroscopy (Beck labs, Indianapolis IN). Stones were then classified unilaterally based upon the dominant present (>50%). The only exception was for brushite where the presence of any brushite led to classification as a brushite stone former. 24-hour urinalysis results were reviewed and statistical analysis performed comparing discordant and concordant patient populations, assessing significant differences that would influence clinical management. Results We identified 89 patients (178 renal units) who had bilateral stones removed at the time of ureteroscopy. The majority of stones were classified as calcium oxalate (CaOx) (59.4%) followed by CaP (30.6%), uric acid (UA) (3.9%), brushite (3.9%) and cystine (2.2%). Discrepancies in stone classifications were present 22% of the time. Evaluation of 24-hour urinalysis results demonstrated striking differences between those with conflicting and similar stone analysis results. Those patients with CaOx:CaP stone discordance compared to CaOx:CaOx concordant stone formers were more likely to have an elevated pH (p<0.001), calcium phosphate supersaturation (p<0.01) and lower uric acid supersaturation (p=0.02). Conclusions Discrepancies in stone classifications are common in patients with bilateral stone disease. When metabolic evaluation was performed in these patients there were significant differences between discordant and concordant groups, especially CaOx only and CaOx:CaP stone formers. Thus, a single stone analysis in the setting of bilateral stone disease is insufficient and may lead to mismanagement when it is utilized in addition to 24-hour urinalysis results. Funding None
Authors
Marcelino Rivera
Michael Borofsky Suzanne Kissel Casey Dauw Nadya York Amy Krambeck James Lingeman |
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MP90-09 |
The Metabolic Syndrome and Its Impact on Calcium Oxalate Stone Type |
Stone Disease: Medical & Dietary Therapy | 17BOS |
Abstract: MP90-09 Sources of Funding: None. Introduction The metabolic syndrome plays an important role in lithogenesis of calcium oxalate stones, but to our knowledge no study has clinically correlated metabolic factors that influence stone subtype. It has been indicated that calcium oxalate monohydrate (COM) stones are more likely of tubular origin as secondary deposits onto calcium apatite whereas calcium oxalate dihydrate (COD) stones are more likely to form in solution. We sought to perform a comprehensive analysis of metabolic and clinical factors in patients who make predominantly one type of calcium oxalate stone. Methods From our prospectively maintained database of 1049 kidney stone formers between 01/2014 - 06/2016, we identified 95 patients with comprehensive medical records including stone analysis who had predominantly (≥80%) COM (75 pts) or COD (20 pts) composition. Another 27 patients had mixed COM and COD stones (<80% of one subtype). Clinical, demographic and laboratory parameters were compared between (>80%) COM or COD stones. Results There were no differences in age, gender or BMI between the COM and COD patients. COM patients were more likely to be hypertensive (46.7% vs. 15% p=0.01) and this difference was more pronounced in males (60% vs. 16.7%, p=0.007). Male COM patients were also more likely to be diabetic (22% vs. 0%, p=0.102). There were no differences in hyperlipidemia, coronary artery disease, gastrointestinal disease, and serum markers of uric acid, calcium, creatinine or HbA1c. COM patients were more likely to have hypocitraturia compared to COD patients (49.3% vs. 25%, p = 0.05). Male COM patients had significantly higher urinary oxalate levels (48 vs. 37 mg/d, p=0.05) compared to male COD formers. COD females showed a trend towards higher calcium levels vs. COM females (213 vs. 140 mg/d, p=0.13). The calcium/oxalate ratio in COD formers was significantly higher compared to COM formers (6.46 vs. 4.84, p < 0.05). No differences were observed for urine uric acid levels, supersaturation of uric acid, CaOx supersaturation, magnesium, and pH. Conclusions Our study suggests that HTN and DM, two components of the metabolic syndrome, are more closely linked to COM stones compared to COD stones. Patients with higher urine oxalate and lower urine citrate levels tend to form COM stones, while those with a higher urine calcium/oxalate ratio tend to form COD stones. This suggests that the two stone subtypes are clinically and metabolically different and thus may have different etiology. Funding None.
Authors
Egor Parkhomenko
Kathleen Kan Timothy Tran Julie Thai Kyle Blum Mantu Gupta |
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MP90-10 |
Thiola impact on clinical outcomes in patients with bilateral versus unilateral cystine stone disease |
Stone Disease: Medical & Dietary Therapy | 17BOS |
Abstract: MP90-10 Sources of Funding: NIH NIDDK K12-DK-07-006: Multidisciplinary K12 Urologic Research Career Development Program (TC)_x000D_ Introduction Cystinuria is a rare systemic genetic disease caused by a defect in an amino acid transporter which results in elevated urinary cystine excretion and severe recurrent stone disease. Interestingly, a subset of patients consistently forms stones unilaterally, despite no evidence of anatomic differences between their two kidneys. This study aimed to determine if bilateral cystine stone formers had different clinical outcomes compared to unilateral stone formers and whether thiola use impacted these outcomes. _x000D_ Methods This was a retrospective case-control study for all cystine stone patients evaluated and treated at the University of California, San Francisco between 1994 and 2015. The presence of unilateral (only formed stones in one kidney alone during their entire lifetime) versus bilateral (formed stones in both kidneys at some point in their lifetime) stone disease was determined with review of all imaging studies, radiology reports, and clinic notes. Demographic data, clinical presentation, current medical treatment and overall renal function were compared between the two groups. _x000D_ Results 42 cystine stone patients were identified and included in the analysis. Mean age at first presentation was 21.7±14.0 years (mean current age 44.2±19.7 years) with women representing 52.4% of all cases. Most patients presented with flank pain (62.1%) following by recently passed stone (24.1%). Of the 42 patients, 28 patients (66.7%) had bilateral stone disease, while 9 patients (21.4%) only experienced left sided stones, and 5 patients (11.9%) right side stones. _x000D_ _x000D_ Bilateral stone formation did not correlate to gender (p = 0.38), age of first presentation (p = 0.89), or family history of stone disease (p = 0.32). Thiola was used by 21.4% of patients with unilateral disease and 35.7% of patients with bilateral disease (p = 0.32). Bilateral cystine stone formation was significantly associated with a higher number of lifetime stone surgeries (7.5 versus 3.7 sessions, p <0.05). Despite this increased number of surgeries for patients with bilateral disease, thiola use and current serum creatinine level (1.05 versus 0.94 mg/dL, p = 0.38) were not significantly different between the two groups. _x000D_ Conclusions The majority of cystinuric patients will form stones bilaterally during their lifetime, and require more surgical interventions than those who only form cystine stone on one side. Despite this, overall renal function (via serum creatinine level) is still well preserved in bilateral and unilateral cystine stone formers and thiola use may not impact laterality or severity of disease. _x000D_ Funding NIH NIDDK K12-DK-07-006: Multidisciplinary K12 Urologic Research Career Development Program (TC)_x000D_
Authors
Manint Usawachintachit
Matthew Hudnall Alexander Rifkind David Tzou Ryan Hsi Benjamin Sherer Marshall Stoller Thomas Chi |
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MP90-11 |
Potassium Citrate Increases Urinary Citrate More Effectively Without Altering Calcium Phosphate Stone Risk in Obese Vs. Non-Obese Patients |
Stone Disease: Medical & Dietary Therapy | 17BOS |
Abstract: MP90-11 Sources of Funding: None Introduction The influence of obesity on the effectiveness of KCit to reduce calcium stone risk is not well-characterized. We evaluated 24h urinary risk factors in both obese (BMI ≥ 30) and non-obese stone formers (SFs) and compared treatment-associated changes after starting KCit. As there is a concern for forming calcium phosphate (Ca Phos) stones while taking KCit, brushite relative saturation (RS) and pH changes were also assessed. Methods With IRB approval, we identified 78 known mixed-calcium SFs from an institutional database (n=78; M:F 34:44; age, 54±15 y; BMI, 31±9). Patients were included in this retrospective analysis if they had stone comprised of >50% calcium and 24-hr urine assays within 3 years before and after initiating KCit, and if BMI at the time of collection was documented. RS indices were calculated with Equil2. Patients were divided into non-obese stone formers (NOSF, BMI<30) and obese stone formers (OSF, BMI ≥ 30). Pre- and post-KCit 24-h urinary parameters were examined using univariate and multivariate analyses with BMI as a covariate. To control for multiple statistical comparisons, the Bonferroni correction revealed that a p value <0.003125 was required for significance. Results Baseline 24-h urine values were similar in both groups, though OSF had a higher uric acid RS (1.45 vs 0.60, p=0.002), likely due to more acidic urine (pH 5.8 vs 6.3, p=0.009). Significant increases in urine potassium in both groups suggested KCit compliance (NOSF: +13, p=0.001; OSF: +28, p<0.0001). Both NOSF and OSF had statistically significant increases in urine citrate (233 to 286, p=0.003; 289 to 575, p<0.0001) and pH (6.3 to 6.6, p=0.001; 5.8 to 6.5, p<0.0001). Post therapy brushite RS was similar in NOSF and OSF (1.85 vs 1.53, p=0.894) and did not exceed the risk cutoff of 2.0. BMI correlated directly with changes in urine calcium and citrate in OSF but not NOSF (-5 vs +17 mg/day, p=0.003; and +63 vs +273, p=0.001, respectively). Changes in urine pH and brushite RS were similar between groups. Conclusions Both obese and non-obese calcium SFs experienced favorable changes in urine pH and citrate excretion. However, obese patients were more likely to achieve normocitraturia. Neither group had significant changes in brushite RS while using KCit, perhaps alleviating concerns of CaPhos risk. Funding None
Authors
Kimberly A Maciolek
Kristina L Penniston Stephen Y Nakada Sara L Best |
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MP90-12 |
Does the timing of magnesium supplementation affect urinary oxalate levels in patients with nephrolithiasis? |
Stone Disease: Medical & Dietary Therapy | 17BOS |
Abstract: MP90-12 Sources of Funding: AUA Northeastern Section Young Investigator Grant Introduction Urinary magnesium has been shown previously to inhibit kidney stone formation in chemical models however, when applied to in vivo human models the results have been conflicting. The purpose of this study is to investigate the timing of magnesium supplementation on the inhibitory effect on nephrolithiasis. We hypothesize that if magnesium is taken with meals, more will be absorbed in the small intestine and excreted in the kidney to allow for better inhibitory effect, specifically by reducing oxalate excretion. Methods We prospectively enrolled known calcium oxalate stone formers with isolated hyperoxaluria identified on 24 hour stone risk testing. Patients were then randomized to take magnesium supplementation either fasting or with food. An initial 24 hour urine collection was obtained on enrollment and then repeated after 7 days of magnesium supplementation to determine the effect on urinary excretion of oxalate. Participants were given a controlled diet during the 7 days of intervention which included adequate fluid intake, low oxalate, low salt, moderate animal protein, and normal calcium intake – the standard dietary treatment for hyperoxaluric kidney stone patients. Results Seven patients were enrolled with 3 patients randomized to each arm of magnesium supplementation. Those taking it with food experienced 41.2mg/d increase in urinary magnesium and a 25.2mg/d decrease in their urinary oxalate over the course of 7 days as compared to a 14.3mg/d increase in magnesium and 13.7mg/d decrease in citrate for those taking magnesium while fasting. There were only modest decreases in calcium oxalate supersaturation and calcium but profound increases in stone protective factors like citrate (Table). Secondary endpoints including sodium (decrease 53mg/d with food vs 84mg/d fasting) also showed improvement with little difference between groups. Conclusions Those taking magnesium supplementation with food experienced a more than 3 fold increase in urinary magnesium and twice the reduction in urinary oxalate as those who took it while fasting. Additionally, secondary endpoints like citrate and sodium showed improvement with modest differences between groups. Our pilot study supports the need for further investigation with a larger sample to establish the significance of these trends. Funding AUA Northeastern Section Young Investigator Grant
Authors
Omar Ayyash
Timothy Averch Michelle Semins |
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MP90-13 |
24 Hour Urine Utilization in Nephrolithiasis Treatment: Results from M-STONE (Multi-center collaboration to Study Treatment Outcomes in Nephrolithiasis Evaluation) |
Stone Disease: Medical & Dietary Therapy | 17BOS |
Abstract: MP90-13 Sources of Funding: None Introduction Medical management of nephrolithiasis is based on 24-hour urine collections (24U) despite limited evidence. We formed a multi-center collaboration to study medical management practices and outcomes in tertiary care stone centers. We hypothesize that those patients managed with dietary and/or pharmacotherapy with 24U will be less likely to recur than those managed without 24U. Methods Four centers collected data on recurrent calcium stone formers with at least 2 years of follow-up. Patients were placed in one of three groups based on recommendations given between initial presentation and first stone recurrence. Stone recurrences occurring within 6 weeks of initial presentation were censored. Groups were defined as diet, only given diet advice; medication, continuously recommended stone-specific pharmacotherapy; and hybrid, distinct periods of diet only and medication recommendations during follow-up. We compared the recurrence rates in these three groups overall and with regard to association with 24U. Results We collected data on 405 patients (58% male) with mean age of 49.9 ± 13.5 SD years and median BMI of 28.3 kg/m2 (IQR 25.1-32.9 kg/m2). Overall 297 (73.3%) patients had a stone recurrence during a median follow-up of 19.9 (range 8.4-36.6) months, with a median time to recurrence of 17.4 (7.6 – 33.2) months. Patients in the diet group (158/198, 80%) were more likely to recur compared to patients in the medication (38/54, 70% p= 0.13) or hybrid groups (101/153, 66% p< 0.004). Overall the majority of patients receiving medication recommendations during follow-up had 24U. Specifically, for the medication and hybrid groups, 79% and 95% respectively of those that recurred and 100% of those that did not recur had 24U collections. However, for the diet group overall fewer patients were managed with 24U (47%) compared to the medication (85%) and hybrid (97%) groups (p <0.0001). Furthermore, in the diet group significantly fewer patients had 24U in those that recurred (36%) compared to those that did not recur (90%) (p< 0.0001). Conclusions Overall recurrence rates were surprisingly high in our multi-center cohort, including for those given pharmacotherapy recommendations based on 24U. However, the highest recurrence rate and the poorest utilization of 24U was seen in those patients receiving diet recommendations only. While our results support 24U they demonstrate that risk stratification to portend severity of stone disease and response to treatment is needed. Funding None
Authors
Jodi Antonelli
Thomas Bentley Sara Best Stephen Nakada Chad Tracy Lewis Thomas Ryan Steinberg Tracy Marien Nicole Miller Adam Cohen Elysha Kolitz Xilong Li Beverley Huet Margaret Pearle Yair Lotan |
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MP90-14 |
Does saturation index predict stone activity in patients with calcium oxalate nephrolithiasis? |
Stone Disease: Medical & Dietary Therapy | 17BOS |
Abstract: MP90-14 Sources of Funding: None Introduction Equil 2 has been the gold standard for estimation of urinary saturation of stone-forming salts (relative saturation ratio, RSR). The Joint Expert Speciation System (JESS) is an alternative, perhaps superior, computer program that takes into account soluble complexes that Equil 2 does not and is thought to be a more accurate estimation of supersaturation (saturation index, SI). While RSR is often provided in 24-hour urine analyses, the clinically relevant impact of these estimations of supersaturation on stone activity is not well studied. Our goal was to determine if SI CaOx correlates with stone activity in calcium oxalate (CaOx) stone formers. Methods We reviewed the charts of 604 patients from our stone clinic between 2005 and 2016 and identified CaOx stone formers who had a baseline 24-hour urine collection and at last one follow-up urine collection after the initiation of drug and/or dietary therapy. Patient demographics, imaging studies, serum chemistries, and 24-hour urine studies were recorded in a timeline for each patient. SI was calculated using JESS for each 24-hour urine study. Stone recurrence (SR) was defined as stone growth or new stone formation and no recurrence (NR) indicated no new stone formation. Absolute SI values were compared between times of SR and times of NR, and change in SI from baseline to time of SR were correlated with SI. Statistical analysis was performed with SAS, and significance was set at p<0.05. Results In total, 255 patients with 358 events were included in the analysis. Mean patient age was 51 ± 13 SD years, with a male:female ratio of 1.3. Comparing NR (98 patients with 97 events) to SR (157 patients with 113) demonstrated no significant difference in mean SI CaOx values (5.6 ± 2.8 versus 5.6 ± 2.9, p=0.6). In addition, in patients who experienced SR (n=157) no significant difference was seen comparing mean SI CaOx values during NR (n=148) or SR (n=113) events (5.9 ± 2.8 versus 5.6 ± 2.9, respectively, p=0.08). For all patients with SR, 65 were identified who experienced both changes from SR to NR (median δSI CaOx 0.20, IQR -1.46-1.21) and NR to SR (median δSI CaOx 0.52, IQR -1.55-1.47). No significant difference was seen (p=0.84). Conclusions At first evaluation, neither absolute nor change in SI correlates with stone recurrence and may not be a reliable way to follow effectiveness of medical therapy. Funding None
Authors
Noah Canvasser
Aaron Lay Elysha Kolitz Beverley Huet Xilong Li John Poindexter Jodi Antonelli Margaret Pearle |
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MP90-15 |
Nonsteroidal anti-inflammatory drugs (NSAIDs) may improve 30-day readmission rates to the ED for acute episodes of renal colic |
Stone Disease: Medical & Dietary Therapy | 17BOS |
Abstract: MP90-15 Sources of Funding: None Introduction NSAIDs should be considered first line for the management of renal colic. Despite numerous RCTs supporting their use in clinical practice, NSAIDs are often inconsistently used in patients with renal colic in the emergency department (ED). We examined the use of NSAIDs and effects on outcomes in patients with renal colic and those with ureteral stones who presented to the ED. Methods A retrospective analysis was conducted on all consecutive patients with an ICD-9 diagnosis of kidney calculus (592.00), ureteral calculus (592.1), and renal colic (788.0) who presented to our ED between October 2011 and August 2013. We only included patients that presented to the ED then were discharged. For our secondary analysis we only included patients with a confirmed ureteral stone based on imaging. Results A total of 330 patients were available for analysis. NSAIDs were the first choice in 49.1% (162/330) of patients and was utilized in 67.1% (221/330) of patients. Those given NSAIDs first were significantly less likely to need additional pain medications than those given narcotics first (p=0.006). When performing a subgroup analysis of patients returning to the ED within 30 days, NSAIDs were used significantly less at discharge (47.6% vs 24%, p=0.015) while there was no difference in narcotic prescriptions. Furthermore, we repeated the analysis for patients returning to the ED within 30 days with a confirmed ureteral stone on imaging and found a significantly less rate of NSAID use at discharge in those that returned (53% vs 17.7%, p=0.006). No other factor was predictive of a return visit to the ED. Conclusions Despite clear evidence towards the use of NSAIDs in the acute setting for renal colic, variability still exists in the way ED practitioners prescribe these medications. NSAID use may contribute to less need for additional pain medications and may decrease early return visits (within 30 days) to the ED. Funding None
Authors
Matthew Sterling
Michael McDonald Justin Ziemba Marshall Strother Alexander Skokan Phillip Mucksavage |
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MP90-16 |
Predictors of failure of spontaneous stone passage after emergency department discharge in patients with renal colic |
Stone Disease: Medical & Dietary Therapy | 17BOS |
Abstract: MP90-16 Sources of Funding: MSI Foundation - Edmonton, Alberta Introduction A majority of patients with acute renal colic are discharged from the emergency department (ED) after initial diagnosis and symptom management. Unfortunately 20-30% of these patients require repeat ED visit for ongoing symptom control and 15%-25% require urgent urological intervention. If these patients destined for outpatient failure could be identified prior to discharge, they may benefit from early intervention to reduce morbidity as well as reduce health care expenditure of a repeat ED visit. Our objective was to identify predictors of outpatient treatment failure, defined as the need for hospitalization or urgent intervention within 60 days of ED discharge. Methods Prospectively gathered administrative data from 4 hospitals in Calgary, Alberta, Canada of patients with an ED diagnosis of renal colic from January 1st, 2014 to December 31st, 2014 was collected. Imaging reports were reviewed for stone characteristics. Data was linked to regional hospital databases to identify ED revisits, hospital admissions and surgical procedures. Patients were excluded if they were non-residents of Calgary or if they had a previous renal colic visit within 30 days. Results Of 3104 patients with first ED visit for acute renal colic, 1081 were discharged without intervention for a trial of spontaneous passage. Median patient age was 50 and 72% were males. As per table 1, on multivariate analysis we demonstrate the only predictor for outpatient treatment failure was proximal and mid-ureteric stone location. We found no association between gender, degree of hydronephrosis or stone size. Conclusions Using a prospectively gathered database we demonstrate patients with stones in their proximal or mid ureter are almost 3 times as likely to require 60-day hospital readmission or urgent intervention. Our results demonstrate treatment options should be considered for these patients prior to discharge. Funding MSI Foundation - Edmonton, Alberta
Authors
PREMAL PATEL
Taylor Remondini Bruce Gao Ravneet Dhaliwal Navraj Dhaliwal Adrian Frusescu Anthony Cook Grant Innes Bryce Weber |
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MP90-17 |
Assessing the Care of Kidney Stone Patients in the Primary Care Setting |
Stone Disease: Medical & Dietary Therapy | 17BOS |
Abstract: MP90-17 Sources of Funding: None Introduction Many patients with symptomatic or recurrent stones are evaluated and treated solely in the primary care setting. While the American College of Physicians and American Urological Association have guidelines to assist in the management of stone patients, substantial differences exist in the recommendations. We sought to characterize the care of stone patients within a cohort of primary care providers to better understand practice patterns and determine factors influencing urologic referral. Methods We surveyed primary care providers attending a regional internal medicine conference in March 2016. Participants were questioned regarding their practice with stone patients in respect to acute symptoms, routine surveillance and metabolic evaluation / prevention. Responses were compared using appropriate statistical measures. Results Of 147 (43%) respondents, the mean age was 52 years (range 27?86). 79% of the cohort were physicians. 87% of providers noted routine treatment of stone patients while 68% expressed comfort with their care delivery. For acute colic, imaging was obtained by 87%. 41% routinely used alpha blockers for medical expulsive therapy which was most associated with physicians and older providers (p<0.007). For recurrent stones, surveillance imaging was ordered in 21%. When available, stone analysis was performed by 39% and most associated with older providers (p<0.002). 24 hour urine studies were ordered by only 12%. Thiazides, alkali citrate and allopurinol were routinely prescribed for preventive measures at equal frequencies by 38% of respondents and more commonly by those with increased comfort treating stone patients (p=0.003). Of providers using preventive medications, therapy was empiric in 79%. However, use of thiazides and allopurinol was associated with those ordering urine studies (p<0.004). Routine urologic referral was cited by 52% for acute symptoms, 31% for routine surveillance and 22% for metabolic prevention. Patient factors most associated with prompting referral included stone size (84%), pain symptoms (74%) and urinary symptoms (68%). Conclusions Kidney stone disease is a common complaint in the primary care setting. In our cohort, there was variable use of routine measures including imaging, stone analyses, urine studies and preventive medications. This highlights the importance of improved collaboration for developing uniform stone guidelines. Future studies are needed to confirm differences in patient care based on specialty and may assist in establishing baseline shared treatment pathways and detailed indications for urologic referral. Funding None
Authors
Matthew D. Lyons
Jacquelyn Greiner Davis P. Viprakasit |
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MP90-18 |
Silodosin for medical expulsive therapy in children with distal ureteral stone: a prospective randomized, Placebo-controlled, single blind study study |
Stone Disease: Medical & Dietary Therapy | 17BOS |
Abstract: MP90-18 Sources of Funding: None Introduction Silodosin, a selective ?1-blocker,has been proposed for medical expulsive therapy (MET) instead of tamsulosin in adulthood urolithiasis with promising outcomes but studies comparing these substances for MET in children are lacking._x000D_ _x000D_ The aim of this study was to verify the safety and efficacy of silodosin (8 mg) compared with tamsulosin (0.4 mg) and placebo as a MET for distal ureteral stones in children._x000D_ Methods A prospective randomized placebo-controlled study including 90 children diagnosed with unilateral, single, radio-opaque distal ureteral stones < 10 mm in size was conducted. Age ranged between 5.8 and 18 years old. Patients were randomized into three groups; silodosin group (n = 30) received 8 mg silodosin daily, tamsulosin group (n = 30) received 0.4 mg tamsulosin daily and placebo group (n = 30) were not given any of the above medications. _x000D_ Patients were offered a closely monitored trial for spontaneous stone passage in the 4-week period prior to definitive therapy. The stone clearance rate, time to stone clearance, number of pain episodes, need for analgesia and potential side effects of medications were observed._x000D_ Results The stone clearance rates for silodosin, tamsulosin and placebo groups were 78.5, 66.6 and 53.3 %, respectively. The time to stone clearance was significantly shorter in silodosin and tamsulosin groups than in placebo group (p = 0.006 and 0.035, respectively). Patients taking silodosin and tamsulosin had fewer pain attacks and lesser analgesic requirement than placebo group patients. Conclusions The current study showed the use of ?-blockers for MET of lower ureteric stones in children to be effective, however, the use of silodosin was associated with higher stone clearance rates and shorter time to stone clearance as compared to tamsulosin. Both of these medications demonstrated a good safety and tolerability profile for MET in children with uncomplicated ureteral stones. Funding None
Authors
Ahmed fahmy
hazem Rhasad Amr Kamal Moustafa Elsawy |
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MP90-19 |
Efficacy of tamsulosin on the spontaneous passage of stone >8mm locate in the proximal ureter above the level of L3 transverse process. A single institution randomised controlled study. |
Stone Disease: Medical & Dietary Therapy | 17BOS |
Abstract: MP90-19 Sources of Funding: none Introduction Urinary stone disease is one of the most common reasons for patients visiting a urology practice, affecting about 5% to 10% of the population. Stone size and location are important predictors of stone passage. Using a selective ?-adrenoceptor blocker for medical expulsive therapy (MET) is an effective treatment approach widely used for ureteral stones. Various studies has proven that the MET is effective in the management of distal ureteric stone. The objective of this study is to assess the efficacy of an alpha-1 adrenergic receptor blocking agent (tamsulosin) on the spontaneous passage of stone (>8mm) locate in the proximal ureter (above the level of L3 transverse process). Methods We evaluated 500 patient diagnosed with acute ureteric colic in the emergency room and in the urology outpatient from January 2013 to December 2015.All of them underwent ultrasound or CT scan as the primary imaging modality. Patients having single radio-opaque proximal ureteral stone >8mm above the level of L3 transverse was only included for the study and were randomized into two groups. Group 1 patients (n = 250) were followed with classical conservative approach and patients in Group 2 (n = 250) additionally received tamsulosin, 0.4 mg/day during 4 weeks follow-up. The stone passage rates, stone expulsion time, change in colic episodes, and hospital re-admission were compared. Results Out of 500 patients, there were 350 males (70 %) and 150 females (30%). Age range was 23-55 years. The two groups were well balanced in terms of baseline patient and stone characteristics. Average stone size was (range 8-1.2 mm) The Stone expulsion rates didn’t showed any significant difference between tamsulosin receivers and non-receivers (35% vs 33%). But the time to stone expulsion period was shortened in those receiving tamsulosin (8.4 +/- 3.3 vs 11.6 +/- 4.1 days). Likewise renal colic episodes during follow-up period were significantly diminished in Group 2 patients (66 vs 36% ) and hospitalisation (25% vs33%). Conclusions Studies have shown that tamsulosin is a safe and effective drug that enhances spontaneous passage of ureteric stones. But our study tamsulosin was not much effective for stone (>8mm) locate in the proximal ureter (above the level of L3 transverse process).though it was effective in controlling the colic pain and shortening the time period for stone expulsion. Our study suggested that patient with stone size >8mm above the level of L3 transverse process if not responded to tamsulsoin after 5 days, then should go for the definitive treatment. Larger prospective trials are needed to make a definite clinical recommendation Funding none
Authors
arun panackal
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MP90-20 |
SHOULD WE SUSPEND MEDICAL EXPULSIVE THERAPY: A PROSPECTIVE RANDOMIZED TRIAL |
Stone Disease: Medical & Dietary Therapy | 17BOS |
Abstract: MP90-20 Sources of Funding: None Introduction In recent years, medical expulsive therapy has been questioned in the management of distal ureteric stones. Therefore, we conducted a prospective randomized study to evaluate the possible role of tadalafil individually and in comparison with proven tamsulosin as well as a placebo therapy in distal ureteric stone expulsion. Methods Between January 2015 and March 2016, 327 patients who presented with distal ureteric stones of size 5–10 mm were randomly divided into three groups: tadalafil (Group A), tamsulosin (Group B), and placebo (Group C). Therapy was given for a maximum of 4 weeks. Stone expulsion rate, time to stone expulsion, analgesic use, number of hospital visits for pain, follow-up, endoscopic treatment and adverse effects of drugs were noted. Results A statistically significant expulsion rate of 86.0% in Group A compared with 66.0% in Group B and 38.0% in Group C was observed. Also a shorter stone expulsion time in Group A (13.5 ± 2.5) in comparison to Group B (16.4 ± 3.5) and Group C (24.8 ± 4.5) was observed. Statistically significant differences were noted in renal colic episodes and analgesic requirement in Group A in comparison to Group B and Group C. No serious adverse effects were noted. Conclusions Tadalafil is safe, efficacious, and well tolerated as medical expulsive therapy for distal ureteric stones. This study showed that tadalafil increases ureteric stone expulsion quite significantly along with better control of pain and significantly lower analgesic requirement. Funding None
Authors
Prarthan Joshi
Prasad Mylarappa Puvvada Sandeep Ramesh Desigowda Arvind Nayak Kuldeep Aggarwal |
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MP91-01 |
Electrohydraulic low-intensity shockwave therapy for PDE5i-refractory erectile dysfunction: A prospective, randomized, placebo-controlled study |
Sexual Function/Dysfunction: Medical, Hormonal & Non-surgical Therapy I | 17BOS |
Abstract: MP91-01 Sources of Funding: None Introduction Animal and human studies have evaluated the role of low-intensity extracorporeal shockwave therapy (LIST) in the management of multiple disorders. LIST is thought to release angiogenic factors and recruit endothelial progenitor cells, inducing neovascularization. The aim of the study is to investigate the effects of penile LIST on erectile function in patients suffering erectile dysfunction (ED) refractory to phosphodiesterase type 5 inhibitors (PDE5i) Methods Prospective, randomized, simple-blind, sham-controlled study. 58 patients with vasculogenic ED refractory to PDE5i were randomized into two groups. 30 were treated with electrohydraulic LIST (1 session/week for 6 weeks; 1,500 pulses of 0.10 mJ/mm2 at 5 Hz) and 28 were treated with a sham probe. 11 patients withdrew from the study and were lost to follow-up. Patients were evaluated at baseline and 1 month after the end of treatment using validated ED questionnaires. Fisher´s exact or Student’s t-test were used. Results were considered statistically significant at p<0.05 Results 27 active-treated patients and 20 sham-treated patients completed the one-month follow-up. There was no significant difference between the two groups in baseline characteristics. Baseline five-item version of the International Index of Erectile Function (IIEF-5) mean scores, in the active and sham groups, were 10.0 ± 3.9 and 10.0 ± 4.5, respectively (p= 0.863). At baseline, 48.1% of patients in the active group and 50.0% of patients in the placebo group had a positive answer to the Sexual Encounter Profile (SEP) 2 question (p=1.000); 11.1% of patients in the active group and 10.0% of patients in the placebo group had a positive answer to the SEP 3 question (p=1.000). One month after treatment IIEF-5 scores mean changes from baseline, in the active and placebo group, were 1.6 ± 4.7 and 0.5 ± 4.4, respectively (p=0.478). SEP 3 positive responders increased by 18.5% in the active group and by 0% in the placebo group (p=0.063) Conclusions Electrohydraulic LIST produced non-significant changes in erectile function at one-month follow up, compared to sham treated patients. Severity of ED, type of energy, intensity, frequency of shockwaves and follow-up length, together with limited sample size, could be in part responsible for this finding. More studies with larger sample size and longer follow-up, comparing different lithotripters and shock wave protocols, are imperative to elucidate the real role of LIST in ED Funding None
Authors
Jose Vinay
Daniel Moreno Alvaro Vives Osvaldo Rajmil Eduardo Ruiz-Castane Josvany Sanchez-Curbelo |
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MP91-02 |
Effects of low-intensity extracorporeal shock wave therapy on erectile dysfunction: a systematic review and meta-analysis |
Sexual Function/Dysfunction: Medical, Hormonal & Non-surgical Therapy I | 17BOS |
Abstract: MP91-02 Sources of Funding: None Introduction Low-intensity extracorporeal shock wave therapy (Li-ESWT) has been proposed as an effective non-invasive treatment option for erectile dysfunction (ED). The objective of this systematic review and meta-analysis is to assess the efficacy of Li-ESWT by comparing change in erectile function as assessed by the Erectile Function domain of the International Index of Erectile Function (IIEF-EF) between men undergoing Li-ESWT versus sham therapy for the treatment of erectile dysfunction. Methods Systematic search of MEDLINE, EMBASE, and ClinicalTrials.gov for randomized controlled trials that had been published in peer-reviewed journals or presented in abstract form of Li-ESWT used for the treatment of erectile dysfunction between January 2010 and March 2016. Randomized controlled trials were eligible for inclusion if they were published in the peer-reviewed literature and assessed erectile function outcomes using the IIEF-EF. Estimates were pooled using random-effects meta-analysis. The main outcome measure was the change in IIEF-EF after treatment with Li-ESWT in patients treated with active treatment and sham LiESWT probes. Results Data were extracted from 7 trials involving 602 participants. The average age was 60.7 years and the average follow-up was 19.8 weeks. There was a statistically significant improvement in pooled change in IIEF-EF from baseline to follow-up in men undergoing Li-ESWT compared to those undergoing sham therapy (6.40 points [95% CI: 1.78 to 11.02; I2 = 98.7%, P < 0.0001] vs. 1.65 points [95% CI: 0.92 to 2.39; I2 = 64.6%, P < 0.0001]; between-group difference, P = 0.047). Significant between-group differences were found for total treatment shocks received by patients (P < 0.0001). Conclusions In this meta-analysis of seven randomized controlled trials, treatment of ED with Li-ESWT resulted in a significant increase in IIEF-EF scores. Funding None
Authors
Raul Clavijo
Taylor Kohn Jaden Kohn Ranjith Ramasamy |
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MP91-03 |
Role of Low-Intensity Shock Wave Therapy In Penile Rehabilitation Post Nerve Sparing Radical Cysto-prostatectomy: A Prospective Randomized Controlled Trial |
Sexual Function/Dysfunction: Medical, Hormonal & Non-surgical Therapy I | 17BOS |
Abstract: MP91-03 Sources of Funding: None Introduction To evaluate role of low-intensity shock wave therapy (LI-SWT) in penile rehabilitation (PR) post nerve sparing radical cysto-prostatectomy (NS-RCP). Methods Eighty seven sexually active men with muscle invasive bladder cancer were enrolled in this prospective study. After bilateral NS-RCP with orthotopic diversion (W-Pouch) by a single expert surgeon between January 2015 & October 2016, patients were randomized into 3 groups (29 patients/group). SWL Group received 12 sessions of penile LI-SWT (2/week for 3 weeks, then 3 weeks free of treatment, then 2/week for another 3 weeks). Phosphodiesterase type-5 inhibitors (PDE5i) Group received oral PDE5i of 50 mg /day for 6 months. Control Group was followed up only without any therapy. Patients were assessed before surgery and at 1 (FU1), 3 (FU2), 6 (FU3) and 9-month (FU4) post operatively. Effectiveness was assessed by IIEF-15 questionnaire and erection hardness score (EHS). Results Mean age was 54.1 ± 5.9 years with mean follow-up period 15.9 ± 4.2 months. There were no statistically significant differences regarding preoperative patients demographic data & tumor criteria._x000D_ At FU1; All patients have insufficient erection for vaginal penetration. EHS < 2; with decrease of preoperative IIEF-EF mean score from 28 to 6.6 ._x000D_ In SWL group; At FU2; 17/29 patients regained potency which is maintained in 15 only at FU3&4. However; 6 of remaining 12 patients regained & maintained potency at FU3&4. Statistical evaluation showed significant increase in IIEF-EF score from 6.6 at FU1 to 23 at FU2, 24 at FU3 and 24.5 at FU4 ( P <0.001). _x000D_ In PDE5i group; At FU2; 16/29 patients regained & maintained potency at FU3&4. However; 7 of remaining 13 patients regained & maintained potency at FU3&4. Statistical evaluation showed significant increase in IIEF-EF score from 6.6 at FU1 to 22.8 at FU2, 24 at FU3 and 24.7 at FU4 ( P <0.001)._x000D_ In Control group; At FU2; 12/29 patients regained & maintained potency at FU3&4. However; 6 of remaining 17 patients regained & maintained potency at FU3&4._x000D_ Statistical evaluation showed no significant difference in potency recovery rates at FU2 & FU3,4 among the groups ( P = 0.14 & P = 0.24 respectively)._x000D_ Potency recovery rates at FU2 were 58.6% vs 55.2% vs 41.4% in SWL, PDE5i and Control group, respectively. While potency recovery rates at FU3,4 were 72.4% vs 79.3% vs 62.1% in SWL, PDE5i and Control group, respectively._x000D_ Conclusions LI-SWT is safe and as effective as oral PDE5i in PR post NS-RCP. A large-scale study is required to determine the value of this treatment modality in ED post NS-RCP. Funding None
Authors
Tamer Zewin
Ahmed El-Assmy Ahmed Harraz Ahmed Mosbah Mahmoud Bazeed Ahmed Shokeir Khaled Sheir |
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MP91-04 |
Adverse effects of testosterone replacement therapy for men, a matched cohort study |
Sexual Function/Dysfunction: Medical, Hormonal & Non-surgical Therapy I | 17BOS |
Abstract: MP91-04 Sources of Funding: none Introduction Determine the association of Testosterone Replacement Therapy (TRT) with event free survival and absolute risk of hepatotoxicity, thromboembolic cardiovascular events, and obstructive sleep apnea (OSA) in a cohort of healthy adult men using TRT. Methods We queried the TRICARE military database, which comprises all retired and active duty men and women and their immediate family members, who receive insurance through the military. Men age 18-65, diagnosed with hypogonadism who received TRT between 2006-2010 were included. We compared event-free survival and absolute risk of hepatotoxicity, thromboembolic and cardiovascular events, and obstructive sleep apnea (OSA) between men using TRT and controls._x000D_ Results Relative to controls, patients using TRT had improved cardiovascular event free survival (p=0.004). There was no significant difference in event free survival for hepatotoxicity (p=0.345), and thromboembolic events (p=0.239). Absolute two-year risk for men using TRT was 0.02 for hepatotoxicity, 0.06 for Cardiac events, 0.02 for thromboembolic events and 0.17 for Sleep Apnea. Absolute 2-year risk was similar with the exception with OSA, which had higher 2-year absolute risk (95% CI: 1.56%-1.84% of TRT users vs. 1.1%-1.4% in controls). Conclusions In our cohort of there was no significant increase in risk of hepatotoxicity, and thromboembolic complications among men using TRT. Additionally, men using TRT had modestly prolonged cardiovascular_x000D_ event-free survival. Prior studies suggesting elevated risk of cardiovascular effects may be less generalizable to healthy young men using TRT in a community setting. Funding none
Authors
Julian Hanske
Nicolas von Landenberg Philipp Gild Alexander P. Cole Wei Jiang Stuart R. Lipsitz Martin N. Kathrins Peter Learn Mani Menon Joachim Noldus Maxine Sun Quoc-Dien Trinh |
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MP91-05 |
Aerobic exercise is better for increasing serum testosterone level than strength exercise in patients with erectile dysfunction |
Sexual Function/Dysfunction: Medical, Hormonal & Non-surgical Therapy I | 17BOS |
Abstract: MP91-05 Sources of Funding: none Introduction According to recent study, exercise can improve efficacy of testosterone treatment and the durability of response after cessation of treatment. _x000D_ However, there is no conclusive information on what type of exercise is better to increase serum testosterone levels or improve testosterone deficiency (TD) symptoms such as erectile dysfunction (ED). Hence, the present study aimed to investigate the correlation of serum testosterone with physical fitness in patients with ED._x000D_ Methods Among patients who had their serum testosterone levels measured after visiting the hospital for ED between January 2014 and June 2015, data were analyzed for 87 patients who underwent body composition and basic exercise testing. Body mass index (BMI) was measured in all patients, and bioelectrical impedance analysis (BIA) was used to test the body composition, including skeletal muscle mass, fat mass, lean body mass, body fat percentage, abdominal fat percentage, and visceral fat mass. The patients performed 7 types of basic exercise testing: cardiorespiratory fitness (cycle ergometer test), flexibility (sit-and-reach test), muscular endurance (curl-up test), muscular strength (grip test, vertical jump test), agility (whole body reaction test), and balance (one-leg Stance test). The correlation of serum testosterone levels with the results of body composition and basic exercise tests was investigated by a partial correlation analysis with age as a confounding factor. A serum testosterone cut-off value was obtained for the body composition and basic exercise test parameters that showed a significant correlation with serum testosterone levels. Results The mean age of subjects was 57 years (36 to 73 years), and the mean serum testosterone level was 342.1ng/dL (83.4 to 1030ng/dL). A correlation analysis between BMI and serum testosterone levels showed a negative correlation with a Pearson correlation coefficient (r) of -0.200, but this was not statistically significant (p=0.082). Among the body composition tests, body and abdominal fat percentage showed a statistically significant negative correlation with serum testosterone levels (r=-0.244, p=0.033, r=-0.254, p=0.026). Among the basic exercise tests, all tests showed a positive correlation, but the majority were not statistically significant, and only the cycle ergometer test for cardiorespiratory fitness showed a statistically significant positive correlation with serum testosterone levels (r=0.292, p=0.010). Cut-off value of serum testosterone which makes difference in body fat percentage, abdominal fat percentage, and cardiorespiratory fitness was 384.9ng/dl. Conclusions In patients with erectile dysfunction, serum TT showed a significant negative correlation with body and abdominal fat percentage, and showed a significant positive correlation with cardiorespiratory fitness. Thus, in these patients, serum TT levels, which are closely related to erectile function, can be increased by reducing fat percentage and improving cardiorespiratory fitness by aerobic exercise. Funding none
Authors
Min Gu Park
Jung Kyun Yeo |
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MP91-06 |
Increased Risk of Hypogonadal Symptoms in Shift Workers with Shift Work Sleep Disorder |
Sexual Function/Dysfunction: Medical, Hormonal & Non-surgical Therapy I | 17BOS |
Abstract: MP91-06 Sources of Funding: AWP is a K12 scholar supported by a Male Reproductive Health Research (MRHR) Career Development Physician-Scientist Award (Grant # HD073917-01) from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Program Introduction Non-standard shift workers, who regularly work hours outside a 7am-6pm workday, may have worse hypogonadal symptoms relative to daytime workers, and are also at increased risk for shift work sleep disorder (SWSD), a primary circadian rhythm disorder characterized by excessive daytime sleepiness associated with shift work. Here we examine the association between SWSD and hypogonadal symptoms in shift workers. Methods Men presenting to a single andrology clinic between July 2014 - September 2016 completed questionnaires assessing shift work schedule, SWSD risk, and hypogonadal symptoms (quantitative Androgen Deficiency in the Aging Male (qADAM) questionnaire). The impact of non-standard shift work and SWSD on responses to qADAM was assessed utilizing ANOVA and linear regression. Results Of the 2,487 men who completed the questionnaires, 766 (30.8%) reported working non-standard shifts in the past month. Of those, 282 (36.8%) were diagnosed with SWSD (Table 1). Controlling for age, comorbidities and testosterone (T) levels, non-standard shift workers had qADAM scores 0.8 points lower than daytime workers (p<0.01). Sub-group analysis of the non-standard shift workers showed that those with SWSD had qADAM scores 3.9 points lower than in men without SWSD (p<0.01). In this same sub-group analysis, SWSD was independently associated with lower testosterone (T) levels (mean decrease 100.4 ng/dL, p<0.01) when controlling for age, comorbidities and history of T supplementation. Conclusions Non-standard shift workers have more severe hypogonadal symptoms than daytime workers, and those non-standard shift workers with SWSD have even worse hypogonadal symptoms and lower T levels than those without. These findings suggest that poor sleep habits, as identified by SWSD, may contribute to the more severe hypogonadal symptoms seen in non-standard shift workers. Funding AWP is a K12 scholar supported by a Male Reproductive Health Research (MRHR) Career Development Physician-Scientist Award (Grant # HD073917-01) from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Program
Authors
Will Kirby
Adithya Balasubramanian Javier Santiago Mark Hockenberry David Skutt Taylor Kohn Stephen Pickett Asad Hasan Alex Pastuszak Larry Lipshultz |
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MP91-07 |
Longterm treatment of hypogonadal men: results from a 9-year-registry |
Sexual Function/Dysfunction: Medical, Hormonal & Non-surgical Therapy I | 17BOS |
Abstract: MP91-07 Sources of Funding: none Introduction Longterm data of Testosterone (T) substitution in hypogonadal men are scarce and the clinical value of this treatment is debated. In order to elucidate outcome and inter-patient variability, we utilized a longterm registry documenting an uniform treatment approach and providing an efficient assessment tool. Methods Registry data from 650 patients with hypogonadism comprised of 266 men with primary forms including 149 Klinefelter (KS) patients, 196 with secondary origin and 188 with non-classical (&[Prime]mixed&[Prime] or &[Prime]metabolic&[Prime]) hypogonadism (overall mean age 41±11 years) receiving intramuscular injections of T undecanoate (1000 mg) during a treatment period of max. 9 years. Results The registry contained 8358 time points with a subset of metabolic and safety parameters each. Serum T concentrations increased from 6.6 ± 2.4 nmol/L to 19.3 ± 3.0 nmol/L. Weight decreased from 99.1 ± 15.2 to 92.4 ± 13.4 kg, body mass index (BMI) from 29.8 ± 5.1 to 27.6 ± 4.4 kg/m2 and waist circumference (WC) from 108.6 ± 13.2 to 100.6 ± 11.6 cm (all p<0.001). Respectively, favourable changes in lipid profiles and glucose metabolism were significant (all p<0.01). Prostate size increased from 17.9 ± 6.3 to 22.9 ± 6.1 mL (p<0.001) and PSA levels from baseline 0.7 ± 0.5 to 0.9 ± 0.5 µg/L, p=0.001, PSA levels of >3 µg/L were measured in 49 and >4 µg/L in 25 subjects). Antibiotic treatment was performed in case of suspected prostatitis and multi-core biopsies were initiated in all other cases. No case of prostate cancer was detected. Haematocrit increased (44.2 ± 2.7% to 46.7 ± 3.2%, p<0.001, 47 subjects >54% required adjustment of T-dose). Stepwise multivariate Cox regression models revealed fundamental differences in inter-individual effects: hazard ratios for loss of BMI/WC were significantly higher in those subjects with younger age, lower baseline T and higher ratios of delta testosterone over delta estradiol levels induced by treatment (all p<0.01). Advanced age, higher baseline BMI and higher delta estradiol levels resulted in significantly higher hazard ratios for prostate growth/increase in PSA or hematocrit (all p<0.01). Overall, effects were attenuated, but still significant, in subjects with androgen receptor gene CAG repeat length >24, in those with KS or men with non-classical hypogonadism (using non-KS primary hypogonadism as referent, all p<0.05). Conclusions Major new findings regarding effects and safety of T substitution in hypogonadal men are provided. This long-term registry on T substitution in hypogonadal men of a wide age-range demonstrates a decrement of weight, factors influencing cardiovascular health and a low, manageable amount of risk factors. Effects are modulated by diagnosis, age and genetic background. Funding none
Authors
Michael Zitzmann
Julia Rohayem Jann-Frederik Cremers Eberhard Nieschlag Abdulmaged Traish Sabine Kliesch |
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MP91-08 |
Combination of Metabolic Syndrome Components to Predict Testosterone Deficiency in Men |
Sexual Function/Dysfunction: Medical, Hormonal & Non-surgical Therapy I | 17BOS |
Abstract: MP91-08 Sources of Funding: None Introduction Studies have demonstrated that metabolic syndrome (MetS) is associated with low testosterone (T) levels. However the incremental effect of every MetS component in predicting testosterone deficiency (TD) has not been well explored in the literature. The primary goal of this study was to investigate the association of MetS and low T levels in men from 40 to 80 years of age, while investigating the cumulative effect of the syndrome components Methods We reviewed records of all men who presented to our men’s health clinic from January 2014 to August 2016. We evaluated age, presence of hypertension, waist circumference (WC), blood glucose level and the serum lipid profile (HDL and triglycerides - TGL), and MetS was considered present when 3 or more factors were present. TD was defined as serum total T <300 ng/dL. Univariable analyses were performed to assess the association variables and T levels. ROC curves analyses were performed to evaluate diagnostic accuracy of each MetS component in predicting TD. Results _x000D_ The study comprised 902 men with a mean age of 57.2 ± 9.85 years. The overall prevalence of low T levels was 23.4% and it was similar across all age subgroups: age 40-49 years (y) 22.7%, 50-59y 23.1%, 60-69y 23.8%, and 70-79y 24.4%, p=0.25. The diagnosis of MetS was established in 27.9% of subjects and was associated with TD (OR=3.1, 95%CI 1.2-4.0, p<0.001). The prevalence of each MetS components was: hypertension = 43.6%, increased WC (>102) = 34.5%%, elevated glucose levels (>100 ng/dl) =33,8%, low HDL (< 40 mg/dL) = 25%, and high TGL (> 150 mg/dL) = 53.2%. Median T levels for patients with 5 MetS components was 293 ± 147 ng/dL, 4 = 306 ± 173 ng/dL, 3 = 356 ± 154 ng/dL, 2 = 387 ± 184 ng/dL, 1 = 421 ± 215 ng/dL, 0 = 460 ± 222 ng/dL. Accordingly, TD prevalence for subjects with none MetS components was 9.6%, 1 = 15.4%, 2 = 24%, 3 = 29%, 4= 48%, and 5= 52%. Increased WC was the most accurate predictor of TD in our population. The overall accuracy estimates by area under ROC curve was 0.716(0.686-0.745)95%CI. Diagnostic accuracy measurements of cumulative MetS components are demonstrated in Table 1. Conclusions There is an increased prevalence of TD with increasing number of MetS components. WC was the best predictor of TD in our population and age was not associated with lower T levels Funding None
Authors
Eduardo P Miranda
Carina Oliveira Evanilda Carvalho Alessandra Rabelo Aline Xavier Ricardo Tiraboschi Victor Paschoalin Jose Murillo Bastos-Netto Cristiano Gomes Jose Bessa Junior |
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MP91-09 |
Low PSA Level In Men Diagnosed With Prostate Cancer Predicts Testosterone Deficiency (TD) |
Sexual Function/Dysfunction: Medical, Hormonal & Non-surgical Therapy I | 17BOS |
Abstract: MP91-09 Sources of Funding: None Introduction PSA secretion is a testosterone (T) dependent process. There is published data suggesting that low serum total T level is an independent predictor of higher stage, higher grade prostate cancer. However, the link between men diagnosed with prostate cancer with low PSA values and T deficiency (TD) has not been explored before. Methods All men diagnosed with prostate cancer since 2000 that had a record of pre-treatment early morning total T level measurement were included in the analysis. We analyzed demographic, clinical and pathological data. Patients were stratified according to pre-treatment PSA levels: 0-2; 2.1-4; >4 ng/ml. TD was defined as total T < 300 ng/dL. We evaluated the relationship between these PSA groups and TD. Age, diabetes, and hyperlipidemia were also included in both univariate and multivariable analyses. Results Mean age of 349 men was 64±8 years. The distribution by PSA group was: 5% 0-2, 16% 2.1-4, and 79% >4. The mean T level across the entire cohort was 358±192 ng/dl. Overall, 38% had a T level < 300 ng/dl; 63% > 300 ng/dl. 9% had diabetes, 10% had hyperlipidemia. The mean T leve by PSA group was: 265±168 0-2; 328±210 2.1-4; and 371±189 >4, p=0.03. The percentage of men with TD by PSA group was: 53% 0-2; 49% 2.1-4; and 35% >4, p=0.05. The percentage of men with extremely low T levels (<200) by PSA group was: 35% 0-2; 22% 2.1-4; and 13% >4, p=0.01. Age, diabetes, and hyperlipidemia were not related to T level grouping on univariate analyses (p=0.35 to p=0.81). On multivariable analysis, PSA 0-2 compared to PSA >4: OR=2.1, 95% CI: 0.82-5.36, p=0.12; PSA 2.1-4 compared to PSA >4: OR=1.9, 95% CI: 1.02-3.34, p=0.04. PSA 0-2 compared to PSA >4 was not significant due to low sample size. Conclusions Low PSA levels predict TD in a cohort of patients with prostate cancer. This finding suggests a possible benefit of adding total T level measurement when a patient with low PSA is diagnosed with prostate cancer. Funding None
Authors
Eduardo P. Miranda
Jean E. Terrier Christian J. Nelson John P. Mulhall |
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MP91-10 |
Testosterone Recovery Profiles after Cessation of Androgen Deprivation Therapy (ADT) |
Sexual Function/Dysfunction: Medical, Hormonal & Non-surgical Therapy I | 17BOS |
Abstract: MP91-10 Sources of Funding: None Introduction It has been demonstrated that the combination use of ADT improves overall and cancer-specific survival in men with unfavorable prostate cancer (PCa). After cessation of ADT, testosterone (T) levels are expected to recover from castrate to normal levels. However, very little is known about T recovery profiles in this population, and many patients remain on castrate levels indefinitely. The aim of this study was to evaluate T recovery after cessation of ADT in PCa patients. Methods We reviewed our prospectively maintained database for PCa patients who received ADT therapy at our institution. Serum early morning total T (TT) levels were measured at baseline and periodically after ADT cessation. Multivariable time-to-event analysis (Cox proportional hazards) was performed to determine predictors of TT recovery after ADT cessation and included the following variables: patient age, baseline T level, and duration of ADT. Results 1641 men with a mean age of 66 (43-94) years were included. Primary treatment for PCa was RP in 36%, while the remainder had either RT or primary ADT. The majority received a GnRH agonist as mainstay for ADT. Mean duration of ADT was 28.8 ± 39 months [0.5 to 324]. Distribution of ADT exposure was: <6 months (m) 33%, 6-12m 19%, 12-24m 16%, >24m 33%. Median follow-up was 47.5 ± 45 months. Mean TT values were: baseline 358 ng/dl, 6-12m post ADT cessation 96 ng/dl, 12-18 174 ng/dl, 18-24m 228 ng/dl, >24m 273 ng/dl. At last follow-up: 77% men had TT level above castrate level, 45% had TT >300ng/dl and 39% returned to pre-treatment TT level. Age over 65 years, ADT duration of 6 months or greater, and baseline T of less than 400 ng/dl were all significantly associated with a slower recovery time. Multivariable analysis data are presented in the Table. Conclusions Approximately one third of patients undergoing ADT for prostate cancer at our center had return of TT level back to pre-treatment level with 23% maintaining castrate TT levels at 24 months after ADT cessation. Funding None
Authors
Eduardo P. Miranda
Christian J. Nelson Elizabeth A. Schofield John P. Mulhall |
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MP91-11 |
Positive effects of long-term treatment with testosterone undecanoate injections (TU) on renal function in hypogonadal men: real-life data from a prospective controlled registry Study |
Sexual Function/Dysfunction: Medical, Hormonal & Non-surgical Therapy I | 17BOS |
Abstract: MP91-11 Sources of Funding: none Introduction A registry was established to assess long-term effectiveness and safety of testosterone undecanoate injections (TU) in a urological setting in comparison to an untreated hypogonadal control group. Parameters related to renal function were measured to gain insight on effects of testosterone therapy (TTh) on renal function. Methods Observational, prospective, cumulative registry study in 505 men (age: 61.4 ± 9.7 years) with total testosterone (T) levels ≤350 ng/dL and symptoms of hypogonadism. 321 men received parenteral TU 1000 mg/12 weeks following an initial 6-week interval for up to 12 years (T-group). 184 men had opted against TTh and served as controls (CTRL). 8-year data were analyzed. Renal profile was assessed by (Creatinine, Urea, Uric acid and Glomerular filtration rate measured according to Mayo Clinic setting) Results Creatinine decreased from 1.14±0.18 to 1.07±0.8 mg/dL in the T-group and increased from 0.99±0.25 to 1.13±0.53 in CTRL._x000D_ Uric acid decreased from 6.8±1.5 to 5.5±1.6 mg/dL in the T-group (p<0.0001) and from 5.7±1.5 to 5.2±1.5 mg/dL in CTRL (p<0.01). _x000D_ Urea was only available for the T-group and decreased from 47.5±12.0 to 31.7±12.9 mg/dL (p<0.0001)._x000D_ Glomerular filtration rate (GFR) increased from 86.6±12.8 to 98.5±8.6 mL/min/1.73 m2 in the T-group and decreased from 90.8±20.2 to 87.0±26.0 mL/min/1.73 m2 in CTRL (p<0.0001 for both)._x000D_ γ-GT decreased from 39.31±11.62 to 28.95±7.57 U/L in the T-group (p<0.0001) and increased from 37.79±29.55 to 39.5±26.71 U/L in CTRL (p<0.0005)._x000D_ Bilirubin decreased from 1.64±4.13 to 1.21±1.89 mg/dL in the T-group (p<0.05) and increased from 1.04±7.08 to 1.12±1.96 mg/dL in CTRL (NS). _x000D_ AST remained stable in both groups, ALT declined slightly in both groups._x000D_ Medication adherence in the T-group was 100 per cent as all injections were administered in the office and documented._x000D_ There were 25 deaths (7.8%) in the T-group of which 11 (44%) were cardiovascular. In CTRL, 28 patients (15.2%) died, and all deaths (100%) were attributed to cardiovascular causes. _x000D_ Conclusions Long-term TTh with TU in an unselected hypogonadal men resulted in improvement of renal function, whereas there was a slight worsening in untreated controls. Since renal function may be related to cardiovascular risk, the observed changes may have contributed to a reduction in mortality. Funding none
Authors
Aksam Yassin
Dany-Jan Yassin Gheorge Doros Abdulmaged Traish |
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MP91-12 |
Erectile function in 656 hypogonadal men improves over 8 years with testosterone undecanoate injections (TU) in comparison to an untreated control group |
Sexual Function/Dysfunction: Medical, Hormonal & Non-surgical Therapy I | 17BOS |
Abstract: MP91-12 Sources of Funding: Bayer Pharma AG partially funded data entry and statistical analyses. Introduction Long-term data for testosterone therapy (TTh) on erectile function in hypogonadal men published so far are from observational studies without a control group. We present registry data including an untreated hypogonadal control group. Methods Registry study in 656 men with testosterone ≤350 ng/dL and hypogonadal symptoms. 360 received TU 1000 mg/12 weeks following an initial 6-week interval (T-group). 296 men opted against TTh and served as controls (CTRL). 8-year data are presented. Changes over time between groups were compared by a mixed effects model for repeated measures with a random effect for intercept and fixed effects for time, group and their interaction. Changes were adjusted for age, weight, waist circumference, blood pressure, fasting glucose, lipids and quality of life to account for baseline differences between groups. In order to further validate results, propensity matching was performed for baseline age, BMI, and waist circumference. 82 men in each group fulfilled criteria. Results Total group: mean age was 57.4±7.3 years in the T-group and 64.8±4.3 in CTRL, median follow-up time 7 years for both._x000D_ In the T-group, T levels rose from 285±37 ng/dL to trough levels (measured prior to the following injection) between 450 and 500 ng/dL (p<0.0001). In CTRL, T levels remained stable between 260 and 280 ng/dL. _x000D_ In the T group, IIEF-EF (maximum score: 30) increased from 19.5±5.0 to 25.9±3.0 with a change from baseline of 6.0 points. The improvement was statistically significant for the first four years and remained statistically significant vs baseline throughout the observation time and stable compared to previous years. In the CTRL group, IIEF-EF decreased from 20.5±3.1 to 11.7±1.6 after 8 years by 9.5 points (p<0.0001 for both)._x000D_ _x000D_ Propensity-matched group: mean age was 61.7±5.1 years in the T-group and 61.6±2.9 in CTRL, median follow-up time 8 years in the T-group and 7 in CTRL._x000D_ In the T-group, T levels rose from 277±41 ng/dL to trough levels between 470 and 515 ng/dL (p<0.0001). In CTRL, T levels remained stable between 250 and 280 ng/dL. _x000D_ In the T group, IIEF-EF (maximum score: 30) increased from 19.5±5.6 to 25.8±3.9 with a change from baseline of 5.9 points. The improvement was statistically significant for the first three years and remained statistically significant vs baseline throughout the observation time and stable compared to previous years. In CTRL, IIEF-EF decreased from 20.2±3.3 to 12.4±1.0 after 8 years by 8.6 points (p<0.0001 for both)._x000D_ Conclusions Erectile function is improved and preserved for a prolonged period of time by TTh in hypogonadal men and deteriorates in untreated hypogonadal men. Funding Bayer Pharma AG partially funded data entry and statistical analyses.
Authors
Ahmad Haider
Karim Sultan Haider Gheorghe Doros Abdulmaged Traish |
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MP91-13 |
The association between testosterone and vitality: the role of genetic variation in the androgen receptor |
Sexual Function/Dysfunction: Medical, Hormonal & Non-surgical Therapy I | 17BOS |
Abstract: MP91-13 Sources of Funding: National Institute on Aging (K08-AG047903, R01-AG018386, R01-AG022381, R01-AG022982, R01-AG018384) Introduction Controversy still exists regarding the efficacy of testosterone replacement therapy (TRT) for symptomatic hypogonadism. A recent multi-site randomized controlled study of men undergoing TRT failed to show an improvement in several symptom domains, among them is vitality. We hypothesized that differences in androgen sensitivity would obscure symptom improvement for a subset of individuals. Androgen sensitivity is related to the number of trinucleotide (CAG) repeats on exon 1 of the androgen receptor (AR) gene. We sought to examine the regulatory role of this genetic polymorphism on the relationship between testosterone and vitality in middle-aged men Methods Participants were men from the Vietnam Era Twin Study of Aging (N=696). Average waking, salivary free-testosterone level was acquired on 3 non-consecutive days. The AR gene CAG repeat length was derived using a combination of PCR fragment analysis and Sanger sequencing. Vitality was evaluated with the SF-36Vitality scale. We tested the interaction between low testosterone (low-T) and CAG repeat length while controlling for age, ethnicity, smoking status, BMI, heart disease, hypertension, diabetes, and the correlated nature of the twin data. Low-T was defined as being ? 1 SD below the mean for the 3-day average value Results Mean age of the participants was 56.4 years (SD = 2.6) with average CAG repeat length of 22 (range: 8-37). We observed a significant interaction effect between low-T and AR CAG repeat length. In men with a short variant of the AR gene (< 21 repeats), representing greater androgen sensitivity, there was a significant effect of low-T on vitality (p < 0.01). Men with low-T and the short AR gene were on average 10 points lower on the Vitality scale relative to men with normal T and the same genotype. This effect was not observed in men with either medium (21-23 repeats) or long (? 24 repeats) variants of the AR gene. Without the interaction effect in the model, neither low-T nor the AR gene had a significant effect on vitality Conclusions These results demonstrate that the relationship between low-T and vitality is regulated, in part, by variation in the AR gene. The effect of low-T on vitality was observed only when the genetically-determined sensitivity of the androgen receptor is at its greatest. Variations in the AR gene, bestowing differential androgen sensitivity, are potential targets for personalized therapy of hypogonadism. Future studies are needed to determine how genetic information can be used to improve the efficacy of TRT Funding National Institute on Aging (K08-AG047903, R01-AG018386, R01-AG022381, R01-AG022982, R01-AG018384)
Authors
Matthew Panizzon
Tung-Chin Hsieh Franz Carol Richard Hauger William Kremen |
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MP91-14 |
Cardiovascular disease (CVD), hypogonadism & ED: Positive effects under long-term treatment with testosterone undecanoate injections (TU) |
Sexual Function/Dysfunction: Medical, Hormonal & Non-surgical Therapy I | 17BOS |
Abstract: MP91-14 Sources of Funding: none Introduction ED is a predictive risk factor for CVD. We monitored effectiveness and safety of long-term Testosterone Therapy (TTh) in hypogonadal men with a history of CVD._x000D_ _x000D_ Methods Two observational registry studies of 622 hypogonadal men from two urological centers: 77 men with a previous diagnosis of coronary artery disease (CAD; n=48) and/or a myocardial infarction (MI; n=40) and/or stroke (n=7) received TU for up to 8 years. Results Mean age was 60.65 ± 4.98 years, mean follow-up time was 7.29 ± 1.20 years. Testosterone (T) levels rose from 9.78 ± 1.56 nmol/L to trough levels (measured prior to the following injection) between 16 and 18 nmol/L. IIEF-EF (maximum score: 30) increased from 19.64 ± 6.34 to 24.49 ± 4.69 with a change from baseline of 5.37±0.36, this improvement was statistically significant for the first three years and remained statistically significant vs baseline throughout the observation time and stable compared to previous years._x000D_ Weight decreased progressively from 114.47 ± 13.41 to 90.42 ± 8.77 by 23.6 ± 0.6 kg, proportion of weight loss: 19.62 ± 5.71%. Waist circumference decreased from 111.78±8.22 to 99.24 ± 6.48 by 12.51 ±0.37 cm. The waist:height ratio improved from 0.64 ± 0.05 to 0.57 ± 0.04 (p<0.0001 for all)._x000D_ Blood pressure (BP, mmHg): Systolic BP decreased from 164.45 ± 14.4 to 132.96 ± 8.71, diastolic BP from 99.48 ± 11.37 to 76.39 ± 4.89, pulse pressure from 64.97 ± 6.48 to 56.57 ± 8.02 (p<0.0001 for all)._x000D_ Lipid pattern and glycaemic control improved significantly and sustainably. C-reactive protein (CRP) declined from 3.69 ± 4.51 to 0.25 ± 0.28 mg/dl._x000D_ In no patient was testosterone therapy discontinued or interrupted. No cardiovascular events were reported during the observation time._x000D_ Conclusions In hypogonadal men with a history of CVD, T therapy may improve and preserve erectile function for a prolonged period of time. No cardiologic or urologic events observed during entire period of T therapy. TTh appears to be well-tolerated and safe Funding none
Authors
Dany-Jan Yassin
Aksam Yassin Karim Haider Ahmad Haider |
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MP91-15 |
Can concomitant dutasteride reduce the effect of testosterone replacement therapy in men with late-onset hypogonadism? A 24-week, randomized, parallel study |
Sexual Function/Dysfunction: Medical, Hormonal & Non-surgical Therapy I | 17BOS |
Abstract: MP91-15 Sources of Funding: none Introduction 5ARIs have sexual side effects, including erectile dysfunction (ED), loss of libido and ejaculatory dysfunction due to their action mechanism which decreases serum DHT levels. We examined whether concomitant dutasteride reduced the efficacy of testosterone replacement therapy (TRT) in men with late-onset hypogonadism. Methods This was a 24-week, randomized, parallel study of the clinical outcomes in men age > 40 years with symptomatic benign prostatic hypertrophy (BPH; International Prostate Symptom Score (IPSS) ≥ 12), prostate volume ≥ 30 mL, and testosterone level < 300 ng/dL with aging male symptoms, who were taking stable doses of alpha-blockers 4 weeks before participation. Eligible patients received a combination of dutasteride 0.5 mg once daily and a transdermal gel containing 10 g testosterone (T) (DT group, n=30) or the transdermal gel alone (T group, n=30). The primary outcomes were the change in the aging male symptom (AMS) score, sexual desire (question 17, AMS score), and erectile function (International Index of Erectile Function-5). Secondary outcomes were the post-treatment IPSS, peak urinary flow rate, post-void residual urine volume (PVR), and prostate volume. Results Both groups showed significant improvements from baseline in all primary outcome parameters. However, there were no significant differences in the changes in the AMS total score (DT -5.2 vs. T -5.0; p=0.55), sexual desire (DT -2.5 vs. T -2.3; p=0.23), and IIEF-5 score (DT -2.1 vs. T -1.9; p=0.13) between groups. The extent of IPSS improvement from baseline to 24 weeks was the same in both groups (DT -1.2 vs. T -1.0; p=0.64). In addition, the changes in Q(max) and PVR from baseline were very similar in both groups. However, prostate volume decreased significantly (p<0.01) in the DT group (DT -2.1 cc vs. T +0.6 cc). Conclusions Concomitant dutasteride did not reduce the effect of testosterone replacement therapy in men with late-onset hypogonadism. Otherwise it would be helpful to prevent the progress of prostate size by TRT. Funding none
Authors
Hyun Jun Park
Tae Nam Kim Jong Kil Nam Du Geon Moon Nam Cheol Park |
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MP91-16 |
Safety and efficacy results from the phase-3, double-blind, multicenter STEADY trial of a novel, pre-filled, subcutaneous auto-injector for testosterone replacement therapy |
Sexual Function/Dysfunction: Medical, Hormonal & Non-surgical Therapy I | 17BOS |
Abstract: MP91-16 Sources of Funding: This study was supported by Antares Pharma Inc. Editorial assistance for this abstract was provided by Axon Communications, funded by Antares Pharma Inc. Introduction Phase 3, double-blind, multicenter Subcutaneous Testosterone Efficacy and Safety in Adult Men Diagnosed with Hypogonadism (STEADY) trial results of a novel, pre-filled auto-injector are presented. Methods This 1-year study enrolled 150 men with hypogonadism with 2 baseline testosterone (T) levels of <300 ng/dL. Starting doses of 75 mg of T enanthate (TE) were administered subcutaneously weekly for 6 weeks. At Week 7, blinded dose adjustments were based on Week-6 pre-dose levels. PK was obtained at Week 12. Success required ≥75% of patients to achieve Cavg of 300 to 1100 ng/dL with a lower limit of a 95% 2-sided confidence interval ≥65%, ≥85% of Week 12 Cmax values of <1500 ng/dL, and ≤5% of Cmax values of >1800 ng/dL. Patients without Cmax determination at Week 12 were treated as ≥1500 ng/dL for analysis. Results 137 patients had complete Week 12 PK profiles; 98 were still receiving treatment at Week 52. At Week 12, 92.7% of patients had total T Cavg 0-168h within the range of 300 to 1100 ng/dL (100% of 50 mg; 90.4% of the 75 mg, and 95.2% of the 100 mg patients). Week 12 Cavg was 553.3 (SD 127.3) ng/dL. All Week 12 total T Cmax was <1500 ng/dL. Concentration was within range on days 1, 2, 3, 4, and 8. Daily mean total T ranged from 483.2 to 741.4 ng/dL. In Week 12, total T concentrations <300 ng/dL were observed in <3% of patients. Treatment was well tolerated. Thirty (20%) patients had treatment-emergent adverse events that led to discontinuation; most frequently reported were elevated PSA and/or hematocrit. Three (2.0%) treatment-emergent serious adverse events (SAEs) were not considered drug-related by investigators. One SAE of death was the result of suicide. Fifteen hundred and ten of 1519 injections were reported as painless. Median compliance was 100%. Conclusions Starting dose of 75 mg TE via the auto-injector achieved T levels within a clinically desirable, pre-defined, physiologically normal range. The TE auto-injector was safe, well tolerated, and pain-free. Funding This study was supported by Antares Pharma Inc. Editorial assistance for this abstract was provided by Axon Communications, funded by Antares Pharma Inc.
Authors
Jed Kaminetsky
Christina Wang Ronald Swerdloff Andrew McCullough |
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MP91-17 |
Do repeat prostate biopsies impact functional outcomes after radical prostatectomy? A long-term analysis of 1015 patients |
Sexual Function/Dysfunction: Medical, Hormonal & Non-surgical Therapy I | 17BOS |
Abstract: MP91-17 Sources of Funding: none Introduction As today many men undergo multiple prostate biopsies before undergoing treatment for prostate cancer, the impact of biopsy on functional outcomes after radical prostatectomy (RP) has been questioned. We compared functional outcomes between patients who underwent a single biopsy versus repeat biopsies prior to RP for localized prostate cancer. Methods 1015 consecutive patients underwent RP and pelvic lymph node dissection from January 1996 to April 2015. Continence and potency were assessed at 3, 6, 12 and 24 months. For evaluation of potency, patients who reported absence of erection sufficient for penetration prior to RP and those who did not receive some form of nerve-sparing were excluded. The Chi-square test and the Mann-Whitney U test were used to compare categorical and continuous variables between patients who underwent a single biopsy versus repeat biopsies prior to RP. Multivariable logistic regression models tested whether repeat biopsies prior to RP were a predictor of continence or potency at different time points. A two-sided p value < 0.05 was considered significant. Results Overall continence rates were 84%, 92%, 96%, and 98% at 3, 6, 12, 24 months, respectively. Repeat biopsies prior to RP were associated with lower continence rates at 3 months compared to single biopsy (p=0.03) (Figure); however, no differences were observed at 6, 12, and 24 months. In multivariable analyses adjusting for age, body mass index and Charlson Comorbidity Index, repeat biopsies were associated with a borderline significant lower risk of continence at 3 months (odds ratio 0.68 [95% confidence interval 0.46-1.00; p=0.051], however not at 6, 12, and 24 months._x000D_ Overall potency rates were 16%, 33%, 51%, and 55% at 3, 6, 12, and 24 months, respectively. No differences in potency rates between single biopsy versus repeat biopsies were seen at all time points (Figure). In univariate and multivariable analyses, repeat biopsies were not predictive of potency at any time point._x000D_ _x000D_ Conclusions Repeat biopsies do not impact mid-term to long-term recovery of continence and potency after RP. These data support the current trend towards active surveillance and delayed local treatment in patients with low- to intermediate-risk prostate cancer._x000D_ _x000D_ Funding none
Authors
Marc-Alain Furrer
Thomas von Ruette George N. Thalmann Daniel P. Nguyen |
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MP91-18 |
The role of vacuum erection devices in penile rehabilitation after posterior urethral anastomotic urethroplasty?a pilot study |
Sexual Function/Dysfunction: Medical, Hormonal & Non-surgical Therapy I | 17BOS |
Abstract: MP91-18 Sources of Funding: none Introduction To assess the efficacy and safety of vacuum erection devices(VED) for the penile rehabilitation in patients with pelvic fracture urethral distraction defects (PFUDD) who underwent posterior urethral anastomotic urethroplasty._x000D_ Methods This prospective study consisted of 60 patients who underwent successfully primary bulboprostatic anastomosis with a perineal approach and developed erectile dysfunction following surgery between Jan 2012 and Jun 2015. The patients were randomized to VED combined with Tadalafil (10mg) once every two days (Group 1, n=28) or Tadalafil (10mg) once every two days (Group 2, N=32) for 6 months. The International Index of Erectile Function-5(IIEF-5), nocturnal penile tumescence (NPT) testing and dynamic color-duplex Doppler ultrasonography (D-CDDU) was used as the evaluation tools. Assessments were made at 2 time points: 1 month and 7 months after urethroplasty._x000D_ Results The mean patient age was 31.4±7.0 years (Group 1) and 33.3±7.2 years (Group 2) repectively (P>0.05). No patients ended the penile rehabilitation program because of treatment-related adverse events in both groups. In Group 1, 57.1% (16/28) patients have erections sufficient to finish the vaginal intercourse compared to 46.9% (14/32) in Group 2 at 7 months after urethroplasty. At 7 months after urethroplasty, the IIEF-5 score is (16.5±4.0) and (13.6±4.3) respectively in Group 1 and Group 2 (P<0.05). According to D-CDDU, the cavernosal artery peak systolic velocity (PSV) is (37.1±7.4) cm/second and (31.6±9.7) cm/second (P<0.05), the cavernosal artery end diastolic velocity(EDV) is (4.1±0.9) cm/second and (4.2±1.2) cm/second (P>0.05), and the penile length change is (3.1±0.9) cm and (2.4±0.9) cm(P<0.05) respectively in Group 1 and Group 2 after drug injection. NPT testing shows that the number of erectile events is (2.4±2.0) and (2.8 ±1.7) (P>0.05), the duration of erectile events is (12.1 ±4.1) min and (11.5±4.7)min (P>0.05), and the penile Avg Event Rigidity is (26.9±10.2) cm and (26.4±11.6) cm (P>0.05)respectively in Group 1 and Group 2. Conclusions This short term study showed that early use of VED is useful and well-tolerated in the penile rehabilitation for the patients after posterior urethral anastomotic urethroplasty because of PFUDD. Funding none
Authors
Lujie Song
Qiang Fu |
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MP91-19 |
Neoclitoris size and location: can they affect transsexual women sexual function? A preliminary pelvic MRI study. |
Sexual Function/Dysfunction: Medical, Hormonal & Non-surgical Therapy I | 17BOS |
Abstract: MP91-19 Sources of Funding: None Introduction Clinical trials have shown that biological women with anorgasmia possess a smaller clitoral glans and clitoral components farther from the vagina lumen than women with normal orgasmic function. The aim of this study is to evaluate neoclitoris size and location with regard to sexual function in patients undergoing male to female (MtF) gender reassignment surgery (GRS). For the evaluation of the normal post-operative changes and presence of complications, in our Centre, patients underwent MtF GRS performed a pelvic non-contrast MRI at 2-4 weeks after surgery. Methods From May to June 2015 we enrolled, during follow up visits, 40 Italian speaking transsexual women underwent MtF GRS and postoperative MRI in our Centre between 2004-2014. Sexual functioning was assessed using the Italian version of the Female Sexual Function Index (FSFI). MR Scans were acquired with a 1.5T superconductive equipment in sagittal and axial planes using a multichannel phased array coil for parallel imaging. TSE T2-weighed images were obtained with 3-4mm thick contiguous sections. The neovagina and the rectum were distended with gel or a vaginal tutor inserted._x000D_ Individual pelvic MRIs were reviewed by blinded investigators, the three axes of the neoclitoris were measured and the volume calculated using the ellipsoid formula. The distance between the neoclitoris and the neovagina was measured. Data included demographics, sexual history, previous surgery, partnership status, body mass index (BMI), past and current medical history, chronic medical treatments, education, job. _x000D_ Results 22 patients completed the study. The mean age was 34 years (SD 7.44). The majority were Caucasians (N=20, 91%) and in a relationship (N=13, 51%). At the MRI neoclitoris mean volume was 1.18 cc (SD 0.43), coronal area 6.80 cm2 (SD 2.4) and 5.33 cm2 (SD 1.34) in sagittal view, the mean distance between neoclitoris and neovagina was 3.38 cm (SD 0.5). There is a statistically significant correlation between the parameter that evaluates the distance between the neoclitoris and the neovagina and the FSFI total score (p < 0.0001). Neoclitoris size did not significantly correlate with FSFI total score (p=0.76). Conclusions This study showed that, even in patients undergoing GRS, neoclitoris localization could be considered a parameter for evaluating sexual function and that a reduction of the distance between neovagina and neoclitoris is associated with greater sexual satisfaction. Neoclitoris size seems not to affect MtF sexual function. Funding None
Authors
Francesca Vedovo
Nicola Pavan Giovanni Liguori Stefano Bucci Michele Bertolotto Carlo Trombetta |
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MP91-20 |
A randomized double-blind, placebo-controlled, cross-over trial assessing the effect of tadalafil (Cialis) on the cardiovascular response in men with complete spinal cord injury above the sixth thoracic level |
Sexual Function/Dysfunction: Medical, Hormonal & Non-surgical Therapy I | 17BOS |
Abstract: MP91-20 Sources of Funding: This study was funded with grants from the Manitoba Medical Services Foundation and the Health Sciences Centre Foundation. Introduction Men with spinal cord injury (SCI) commonly have erectile dysfunction, for which PDE5 inhibitors can have good effect in treating. People with SCI above thoracic-6 (T6) are prone to hypotension. Side effects of PDE5 inhibitors can include hypotension. Thus our goal was to determine the effects of tadalafil 20 mg compared to placebo on blood pressure (BP), heart rate (HR), and dizziness of men with complete American Spinal Injury Association Impairment Scale-A (AIS-A) SCI between cervical-4 (C4) and thoracic-5 (T5), and how long these effects last. Methods This was a double blind, randomized cross-over placebo-controlled study of 20 males with AIS-A SCI, C4-T5. Subjects received either tadalafil or placebo for the first arm, then were crossed-over after 1 week to the second arm. BP, HR, and Visual Analogue Scale (VAS) for dizziness upon sitting up from laying were measured at baseline and again 1, 2, 4, 12, 22, 29, and 36 hours post each dose administration. The change in each outcome measures (systolic BP, HR, VAS) was observed from pre-dose to each time point. A change at any point in VAS of 2cm or greater (scale 0-10cm) was considered positive. Results Systolic BP did not change significantly in either group. However, HR increased significantly in the tadalafil group at several time points (12h p>0.05, 22h p>0.05, 29h p>0.01, and 36h p>0.05), with no change in the placebo group. The VAS for dizziness significantly increased (range 2-6cm change) at some time point in 1/4 of the subjects after tadalafil but not in the placebo group; all reports of dizziness were at 12 hours or later. Conclusions It appears that tadalafil use in people with SCI above T6 is safe with respect to not causing hypotension; hemodynamic changes that occur 12-36 post administration are compensated for by elevations in HR. This should be further investigated with larger sample sizes, focusing on the tetraplegic population, as those without spinal cord sympathetic outflow may not be able to have adaptations in HR to maintain BP. Funding This study was funded with grants from the Manitoba Medical Services Foundation and the Health Sciences Centre Foundation.
Authors
Karen Ethans
Alan Casey Mohamed Tarhoni |
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MP92-01 |
Safety and Efficacy of Post-Operative Extended-Duration Venous Thromboembolism Prophylaxis in High-Risk Urologic Oncology Patients |
General & Epidemiological Trends & Socioeconomics: Quality Improvement & Patient Safety II | 17BOS |
Abstract: MP92-01 Sources of Funding: None Introduction Patients undergoing major urologic oncology surgery are at risk for post-operative venous thromboembolic events (VTE). The development of VTE following surgery often presents clinically after discharge and is associated with potentially significant morbidity and mortality. At present there is little published data on the safety and efficacy of extended duration venous thromboembolism prophylaxis (EDVTP) beyond the time of hospital discharge in urologic oncology patients. In this study, we evaluate the use of EDVTP for post-operative high-risk urologic oncology patients. Methods All patients undergoing major urologic oncology surgery by a single surgeon at our institution from April 2015 to present were evaluated for their risk for VTE using the Caprini risk assessment model. Patients considered high-risk (Caprini score ≥ 5) were discharged on post-operative EDVTP according to 2012 ACCP guidelines. 28 days of postoperative subcutaneous enoxaparin was considered the standard of care in eligible patients. These patients were prospectively monitored for the development of clinically symptomatic VTE within 30 days postoperatively and for adverse effects of EDVTP. Results 150 patients who underwent major urologic oncology surgery were considered to be at high VTE risk based on Caprini score of ≥ 5. Average patient age was 63.3 years and 68% of the patients were male. Surgical procedures performed included 39% radical cystectomy, 29% nephrectomy, 16% partial nephrectomy and 16% other. Average Caprini score was 7. Of these, 75% were candidates to receive a 28 day course of enoxaparin EDVTP. The most common reasons for the 25% of patients not receiving standard enoxaparin EDVTP included renal insufficiency (31%), atrial fibrillation requiring oral anticoagulation (26%), and previously diagnosed VTE requiring therapeutic anticoagulation (16%). Adherence to guidelines was not associated with any VTE prophylaxis complications. There were also no noted complications from the use of enoxaparin. The rate of observed 30-day symptomatic VTE in this population was 0%, with an anticipated rate of >5% based upon Caprini score. Conclusions Post-operative use of EDVTP appears to be a safe and effective way to decrease the risk of VTE in high-risk urologic oncology patients. Additional data from larger registries is needed to evaluate and confirm the benefit gained and need for use of EDVTP in this patient population. Funding None
Authors
Russell Terry
Mohit Gupta Michael Blute Paul Crispen |
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MP92-02 |
BPA Alert effect on CAUTIs hospital-wide at UIHC |
General & Epidemiological Trends & Socioeconomics: Quality Improvement & Patient Safety II | 17BOS |
Abstract: MP92-02 Sources of Funding: None Introduction Catheter associated urinary tract infections (CAUTIs), the most common hospital-acquired infection, increase hospital cost, length of stay, morbidity/mortality and time/wages lost for patients. In an effort to reduce the CAUTI rate, our hospital instituted a Best Practice Alert (BPA) reminder within our inpatient electronic medical record system in 2013. To determine the effect of this BPA, we compared the CAUTI rate and number of urinary catheter days before and after 2013, hypothesizing that this BPA reduced both variables. Methods A retrospective review was performed utilizing our institution&[prime]s inpatient database from 2011-2016. All CAUTIs were defined using the 2013 CDC guidelines. Generalized linear mixed modeling was used to estimate the effects of variables of interest on catheter utilization (CU) and CAUTI rates. CU and CAUTI rates were measured using a binomial distribution with a logit link and were also compared between ICU, general adult and general pediatric wards. Results Data from 1,102,803 patient days accounting for 227,256 catheter days was evaluated. Between 2011 and 2013, there was a 1.9% decrease per month (p value < 0.0001) in CU rates. Comparing the years of 2013 to 2016, there was less significant decrease at 1.3% per month (p value < 0.0001) in CU rates. Between 2012 and 2016, there was not a significant decrease in CAUTIs despite a decrease in CU rates (0.01% per month, p value 0.846). We also found a lower relative rate in overall CU rate in pediatrics (-3.14, p value < 0.001) as compared to adult units and a higher rate in overall CU rates in the ICU setting (2.04, p value 0.003) as compared to the non-ICU setting. Conclusions Our study shows that there is a decrease in CU rates, but no effect on CAUTI rates with the BPA alert. This suggests that factors resulting in CAUTIs are multifactorial and not just limited to length of catheter use. These additional factors may be difficult to control, and perhaps are intrinsic to the patient and their disease process, making some CAUTIs difficult to prevent, despite limiting catheter use. This may result in a plauteau in a hospital&[prime]s overall CAUTI rate, despite following recommended best practices. Funding None
Authors
Colette Gnade
Douglas Storm Patrick Ten Eyck |
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MP92-03 |
Transversus abdominis plane blockade as part of a multimodal postoperative analgesia plan is associated with improved postoperative outcomes in radical cystectomy patients |
General & Epidemiological Trends & Socioeconomics: Quality Improvement & Patient Safety II | 17BOS |
Abstract: MP92-03 Sources of Funding: The Alumnae of Northwestern Grant Introduction Enhanced recovery protocols (ERP) after radical cystectomy (RC) focus heavily on GI recovery since prolonged postoperative ileus is associated with an increased risk of complications and longer length of stay (LOS). Recently, novel multimodal pain management plans have been used in conjunction with ERPs to either reduce the use of narcotics postoperatively or prevent their side effects. We examine the benefits of continuous transversus abdominis plane (TAP) blockade with a local anesthetic as part of a post-RC pain regiment. Methods A retrospective comparison of consecutive patients undergoing RC over a 4-year period was conducted. Patients were designated as having RC during either the pre-TAP or TAP era. Patient demographics, operative details, and perioperative outcomes were compared between the two cohorts. Median days to flatus, bowel movement (BM), LOS, and narcotic usage (converted to milligrams of morphine equivalents) were compared using the Mann-Whitney Test. Results In total, 171 patients were included: 100 pre-TAP and 71 TAP. There were no differences in age, smoking status, operative approach (robot vs. open), or urinary diversion type between the two cohorts. The TAP group had fewer men (69% vs. 83%, p=0.03) and more patients who received neoadjuvant chemotherapy (38% vs. 21%, p=0.015). The TAP cohort had significantly better GI recovery with shorter days to flatus (3 vs 4, p<0.001) and days to BM (4 vs. 5, p<0.001). There were no differences in need for NG tube or reoperation (Table 1). Overall, early (POD0-3), and daily narcotic use was significantly lower in the TAP patients: 62 vs. 297mg (p<0.001), 44 vs. 194mg (p=0.001), and 9.7 vs 30.9mg (p=0.001), respectively. Median LOS was significantly shorter in the TAP group (7 vs. 8.5d, p=0.002). Conclusions TAP blockade as part of a multimodal postoperative pain plan is safely associated with low narcotic usage, and significant improvement in time to flatus, BM, and LOS compared to traditional post-RC management. Funding The Alumnae of Northwestern Grant
Authors
Richard Matulewicz
Mehul Patel Jacqueline Morano Brendan Frainey Yasin Bhanji Anton Nader Shilajit Kundu Joshua Meeks |
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MP92-04 |
IMPROVEMENT OF INFORMED CONSENT IN UROLOGICAL SURGERIES: PORTABLE VIDEO MEDIA VERSUS STANDARD VERBAL COMMUNICATION. A Randomized Controlled Trial |
General & Epidemiological Trends & Socioeconomics: Quality Improvement & Patient Safety II | 17BOS |
Abstract: MP92-04 Sources of Funding: None Introduction Informed consent (IC) is the authorization on a voluntary basis for a medical or surgical procedure. At present, the method for providing this information is non-engaging obsolete and in need of updating. Technology plays an important role and the application (app) allows us to describe the surgery with HD videos and interact with the patient using illustrations._x000D_ The aim of this study is to compare the comprehension of the patient between Standard Verbal Communication (SVC) and Portable Video Media (PVM) as in iURO apps in the IC process. _x000D_ Trial registration number ClinicalTrials.gov ID: NCT02846467. Methods The sample consisted of 158 patients undergoing transurethral resection of the prostate or bladder. They were informed by the written IC and subsequently randomized in two groups: patients informed by PVM (group E) and patients with SVC (group C). A validated questionnaire was used to compare the comprehension immediately and 15 days after the surgery. Questionnaire items: information (1), usefulness of the intervention (2), side effects (3), complications (4), comorbidity (5), usefulness of the information (6), anxiety (7) and risks (8)._x000D_ The study was carried out from December 2013 to March 2016 at the University Hospital in Puerto Real (Spain). The analysis was performed with the statistical package SPSS®._x000D_ Results More than 75% of the patients were male and the average age was 68 and 69 years in groups E and C respectively. _x000D_ Before surgery, the questionnaire results demonstrated 6 of 8 items of information were improved by the app with statistical significance (p<0.05), the items improved were: 1, 2, 5, 6, 7 and 8 (table 1). The results after surgery showed improvement in 7 of the 8 items for the app but only 4 have p<0.05, the items improved were: 1, 6, 7 and 8 (table 2)._x000D_ Conclusions The IC process must advance hand in hand with the technological innovations currently being implemented in medicine. This study demonstrates objectively, that the comprehension of the patient before and after surgery is greatly improved when using the app, as a more effective means of content delivery. The results of our study are very encouraging, there is evidence of benefits to patients and indirectly for the improvement of the quality of services provided within the health system. Funding None
Authors
Sebastian Armijos León
Federico Rodriguez-Rubio Jorge Rioja Zuazu Virginia Sanchez Barrios Juan González Caballero Bandi Sanjeev Elba Canelon |
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MP92-05 |
Calculating Surgical Time for Robot-assisted Radical Cystectomy based on Patient related Metrics & Institutional Experience: Results from the International Robotic Cystectomy Consortium |
General & Epidemiological Trends & Socioeconomics: Quality Improvement & Patient Safety II | 17BOS |
Abstract: MP92-05 Sources of Funding: Vattikuti Foundation Collective Quality Initiative and Roswell Park Cancer Institute Alliance Foundation Introduction Surgeons' estimates for their surgical times can be accurately predicted with feedback and knowledge of the key variables. Our study aimed to utilize the International robotic cystectomy consortium (IRCC) database of robot-assisted radical cystectomy (RARC) to determine patient and institutional variables of importance in scheduling the procedure. Methods 2686 RARCs performed at 23 institutions from 12 countries were utilized from the IRCC database. Variables used for prediction of surgical times were: institutional RARC volume, age at RARC, gender, BMI, ASA Score, history of prior abdominal surgery and radiation, clinical stage of disease, administration of neoadjuvant chemotherapy, approach, and type of diversion. A conditional inference tree method was used to fit a binary decision tree predicting operative time. Permutation tests were performed to determine the variables having the strongest association with RARC surgical time. The data was split at the value of this variable resulting in the largest difference in means for the surgical time across the split. This process was repeated separately on the resultant data sets until the permutation tests showed no significant association. Results 2136 procedures were included in the analysis. The most important determinant of surgical time was the type of diversion (Ileal conduits - 69 minutes shorter than Neobladders, p<0.001). Among patients who received neobladders, BMI was also an important determinant of surgical time (higher BMI—longer by 50 minutes, p<0.001). Among the Ileal conduit patients, institutional RARC volume was an important factor (44 minutes, p<0.001). In the following regression tree, the box plots show the median, interquartile deviation, and ranges of surgical times for each node. Conclusions We developed a methodology to predict operative time for RARC based on patient, disease characteristics and Institutional experience. This model can be used to improve OR efficiency. Funding Vattikuti Foundation Collective Quality Initiative and Roswell Park Cancer Institute Alliance Foundation
Authors
Paul May
Franklin Dexter Ahmed Hussein Youssef Ahmed Abolfazl Hosseini Peter Wiklund James Peabody Koon Ho-Rha Lee Richstone Shamim Khan Carl Wijburg Matthias Saar Abdullah Erdem Canda Jihad Kaouk Andrew Wagner Bertram Yuh Juan Redorta M Derya Balbay Thomas Maatman Geert Smits Mani Menon Michael Stoeckle Omar Kawa Ashok Hemal Giovannalberto Pini Franco Gaboardi Alexandre Mottrie John Kelly Wei Shen Tan Francis Schanne Alon Weizer Taylor C. Peak Khurshid Guru |
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MP92-06 |
Analysis of 30 day readmission to an adult urology service: Assessment of risk factors and basis for a quality index metric |
General & Epidemiological Trends & Socioeconomics: Quality Improvement & Patient Safety II | 17BOS |
Abstract: MP92-06 Sources of Funding: None Introduction Readmission within 30 days of discharge following an in-patient admission is increasingly used as a quality metric. Moreover, the Patient Protection and Affordable Care Act (ACA) has associated surgical outcome and hospital readmission rates with potential reimbursement models. Currently, reported 30 day readmission rates to urology services are largely based on pooled national databases from a wide variety of patient populations and health care settings. We wished to determine a 30 day readmission to the urology service of a tertiary care hospital with high 6 year average case mix index (CMI) of 1.5. Methods We reviewed all readmissions within 30 days for any cause following discharge from our adult urology service between January 2010 and December 2015. We also reviewed all readmissions, demographics, and variables following 10 major urology procedures. Non-parametric univariate and regression analysis was considered with an alpha set at 0.05. Results We found that our 30 day un-planned readmission rate was stable (β=0.2) over a 6 year period with an overall rate of 5.22% (range 3.46-6.76). Excluding cystoprostatectomy which had the highest 30 day readmission rate of 21%, the readmission rate for the remaining 9 index procedures was 2.2% (see table). Readmission was associated with patient age, number of ICD-10 diagnoses, and no medical follow up within 1 week after discharge (P<0.05). Conclusions Our data provides a 30 day readmission rate for 10 index procedures at a major tertiary care urology service with a complex patient population. Planned follow up with urologic evaluation as an outpatient within 1 week after elective discharge may improve readmission rates. Funding None
Authors
Suraj Parikh
Alex E. Ward John L. Phillips, MD Majid A. Eshghi, MD Sean A. Fullerton, MD Gerald J. Matthews, MD Michael Stern, MD Muhammad S. Choudhury, MD |
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MP92-07 |
TAKE ‘NOTES’: IDENTIFYING DRIVERS OF 30 DAY READMISSION AFTER RADICAL PROSTATECTOMY |
General & Epidemiological Trends & Socioeconomics: Quality Improvement & Patient Safety II | 17BOS |
Abstract: MP92-07 Sources of Funding: Blue Cross and Blue Shield of Michigan Introduction A key priority of the Michigan Urological Surgery Improvement Collaborative (MUSIC) is to improve perioperative outcomes after radical prostatectomy (RP). MUSIC has previously developed a novel metric, Notable Outcomes and Trackable Events after Surgery (NOTES) to facilitate objective unambiguous tracking of deviations from an uncomplicated recovery pathway. Readmission within 30 days represents a significant, potentially avoidable morbid deviation for the patient and can have financial implications. This study aims to utilize NOTES to assess the relationship between length of stay (LOS) and readmission and identify the key drivers of 30 day readmission after RP. Methods For men undergoing RP from April 1, 2014 to the present, trained abstractors in 43 MUSIC practices prospectively recorded clinical and peri-operative data in an electronic registry. All cases with a 30 day readmission were identified via deviation from the NOTES pathway. Precipitating events for these deviations were recorded by abstractors. Results A total of 4710 RPs were performed by 209 surgeons in 41 participating MUSIC practices. Thirty day readmission rates were 4.1% overall, 3.8% for those with LOS 0-2 days and 7.1% for those with LOS ≥3 days. The most frequent events driving readmission were gastrointestinal (GI) events such as ileus or bowel injury (24.5%), infection (19.8%), urine leaks (13.0%) and pulmonary embolism (PE)/deep vein thrombosis (DVT) (12.5%) (Table 1). GI events resulted in 56.3% of readmissions within 3 days of discharge (Figure 1). Infection, urine leaks and PE/DVT remained persistent drivers beyond this period (Figure 1). Conclusions GI and urine complications represent the majority of drivers resulting in 30 day readmission. Measures to specifically reduce these by appropriate patient education and close post-discharge surveillance may represent a high impact opportunity for quality improvement efforts after RP. Funding Blue Cross and Blue Shield of Michigan
Authors
Naveen Kachroo
Daniel Pucheril Tae Kim Ji Qi Anna Johnson Edward Schervish Mani Menon James Dupree James Peabody for the Michigan Urological Surgery Improvement Collaborative |
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MP92-08 |
Racial Disparity and Adherence to Quality Measures for Radiation Therapy of Prostate Cancer |
General & Epidemiological Trends & Socioeconomics: Quality Improvement & Patient Safety II | 17BOS |
Abstract: MP92-08 Sources of Funding: none Introduction Racial disparities in health care are apparent in the management and outcomes for prostate cancer, however disparities in compliance to quality measures for radiation therapy for prostate cancer have not been previously studied. Therefore, the goal of the study was to characterize disparities in the compliance rates to quality measures. Methods The Comparative Effectiveness Analysis of Radiation Therapy and Surgery (CEASAR) study is a population-based, prospective cohort study that enrolled 3708 men with clinically localized prostate cancer from 2011-12. Compliance with 4 radiation-specific quality measures endorsed by national consortia as of 2011 was assessed (Table), and compliance was compared by race using logistic regression. _x000D_ _x000D_ Results Overall, 634 men received definitive external beam radiation therapy (EBRT) of which 19% were self-reported African-American (AA), 70% Non-Hispanic White (NHW), and 11% Hispanic, Asian, and other (HAO). The median time from diagnosis to EBRT was significantly longer for AA and HAO then NHW men (3.0, 3.6 months vs. 2.7, p<0.01). Less than two-thirds of AA (64%) and HAO men (62%) received EBRT that adhered to all quality measures, compared to 77% of NHW men (p<0.01 ). The disparity in compliance to quality measures was noted in the proportion receiving dose-escalated (> 75 Gy) EBRT (87% AA, 88% HAO vs. 95% NHW, p<0.01). The proportion of men receiving prostate-only EBRT without nodal EBRT for low-risk disease was lower among AA than NHW or HAO (80% AA vs. 99% NHW, 100% HAO, p<0.01), while the proportion having image-guidance EBRT was lowest among HAO (73%) compared to NHW or AA (87%, 88%, p=0.02). On a logistic regression predicting compliance to all the quality measures, AA and HAO men had almost half the odds of receiving quality EBRT than NHW men (OR 0.54, 0.5 p=0.02), after adjusting for education, insurance status, and D’Amico risk. Conclusions Minority men were less likely to receive dose-escalated EBRT which improves prostate cancer control, and were more likely to receive unnecessary nodal radiation for low-risk prostate cancer that increases treatment side effects. There may be opportunities to improve care by enhancing adherence to quality measures among vulnerable groups via implementation initiatives. Funding none
Authors
Daniel Lee
Joann Alvarez Tatsuki Koyama Matthew Resnick David Penson Daniel Barocas Karen Hoffman Ceasar Investigators |
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MP92-09 |
Implications of Regionalizing Care in the Developing World: Impact of Distance to Referral Center on Compliance to Biopsy Recommendations in a Brazilian Prostate Cancer Screening Cohort |
General & Epidemiological Trends & Socioeconomics: Quality Improvement & Patient Safety II | 17BOS |
Abstract: MP92-09 Sources of Funding: none Introduction In many developing countries, care is regionalized at a few high volume centers. However, unlike Western nations where high percentages live in urban areas, developing countries have a higher percent living in rural areas or small towns. It is unknown if the benefits of regionalization outweigh the barriers this creates for access. We tested the link between distance from screening site to biopsy (bx) referral center and risk of non-compliance with showing up to have a bx in a population-based PC screening cohort in Brazil. _x000D_ Methods We reviewed records from 1,561 men recommended to undergo a bx after an initial PC screen by a medical mobile unit at their local clinic between 2004 and 2007. Bxs were performed at a regional referral center, Barretos Cancer Hospital (BCH). Clinical data between men who complied with the bx vs. not were compared with rank-sum & chi-square. Multivariable logistic regression analysis of distance from screening site to BCH (km) and risk of non-compliance was performed adjusting for age and year of screening. Results Median distance was 257km (IQR 135-718). Non-compliant men were older (68 vs 66 yrs), had a higher PSA (4.9 vs 4.2), were less likely to have an abnormal DRE (20% vs 33%) and lived further from BCH (921 vs 225 km) (all p<0.001). On crude and multivariable analyses, further distance was significantly linked with bx non-compliance (OR/100km 0.83, p<0.001, see figure). Among men who lived within 150km of BCH, distance was unrelated to compliance (OR/100km 1.09, p=0.87). _x000D_ Conclusions In Brazil, where distances from PC screening to bx clinic can be hundreds of kms, greater distance to referral center was related to reduced compliance to bx. However, among men who lived within 150km, distance was unrelated to compliance. While regionalization of care may in theory improve quality, it comes at the cost of reduced compliance and thus reduced access and represents a significant barrier to optimal care if distances are large. In regards to PC screening and bx, our data suggest distances up to 150km do not create barriers for care. Alternative thresholds, however, may apply for other services and in other cultures. Funding none
Authors
Alexis Freedland
Cathrine Hoyo Elizabeth Turner Patricia Moorman Roberto Muller Eliney Faria Gustavo Carvahal Rodolfo Reis Edmundo Mauad Andre Carvalho Stephen Freedland |
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MP92-10 |
A Rectal Swab Guided Prophylaxis Program on the Incidence of Infectious Complications Following Trans-Rectal Ultrasound Guided Prostate Biopsy and Fiducial Marker Placement |
General & Epidemiological Trends & Socioeconomics: Quality Improvement & Patient Safety II | 17BOS |
Abstract: MP92-10 Sources of Funding: none Introduction Trans-Rectal Ultrasound guided prostate biopsy (TRUSBX) and fiducial marker placement (TRUSFM) are noted sources of infectious complications. While data describing the risk of post-TRUSFM infection are lacking, there is an abundance of evidence describing the increasing rate of post-TRUSBX infectious complications. Particularly significant is the rising incidence of more serious infections such as Sepsis and UTIs, which are associated with a high degree of morbidity and cost. Recent evidence links this to a concomitant rise in prevalence of flouroquinolone resistant (FQR) organisms and suggests that use of empirical prophylaxis needs reevaluation. This study aims to make a case for adopting a Rectal Swab (RS) guided prophylaxis by showcasing the effectiveness and feasibility of implementing such a protocol in a large private practice with multiple locations. Additionally, we will be able to better describe the risk of infection associated with TRUSFM. Methods From January 1st, 2011 through May, 30th 2015 we observed the difference in rates of infectious sequelae post-TRUSBX and post-TRUSFM in men who received RS-guided prophylaxis vs empirical prophylaxis with fluoroquinolones per AUA guidelines. RS specimens were collected from patients using a BBL culture swab and plated on selective media containing ciprofloxacin to identify FQR. Standard FQ prophylaxis was prescribed to patients showing FQ sensitivity and patients with cultures positive for FQR organisms received targeted prophylaxis based on further susceptibility testing. Results 5,084 men underwent 1,106 TRUSFM and 5,843 TRUSBX. The prophylactic regimen was prescribed empirically for 2,296 TRUSBXs and 404 TRUSFMs; of these 83 (3.61%) and 21 (5.20%) resulted in infectious complications respectively. A RS-guided prophylactic regimen was used for 3,547 TRUSBXs and 707 TRUSFMs; of these 27 (0.76%) and 7 (1.00%) resulted in infection. 4,248 RS were performed and cultured on 3,294 men. Of these, 472 (11.2%) of the rectal swabs were positive, and 393 men (11.9%) were found to have at least one FQR organism. Of the FQR organisms identified (96.27% being E. coli) 83.7% were multidrug resistant and 37.5% possessed co-resistances to at least 5 other antimicrobials. Co-resistance rates for specific antimicrobials were as high as 70% (Ampicillin). Conclusions The considerably lower infection rates observed in men receiving RS guided prophylaxis along with the significant prevalence of FQR displays the advantage of adopting the practice of a rectal swab program. Additionally, the high prevalence of multidrug resistance suggests that alternative methods such as augmented or multi-drug prophylaxis regimens that are commonly empirically prescribed would likely have limited success. Funding none
Authors
Alexander Van Hoof
Nedim Ruhotina MD Sarah Faisal Bashar Omarbasha MD Christopher Pieczonka MD Yi Yang MD David Albala MD |
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MP92-11 |
Utilization of rectal swab cultures prior to prostate biopsy: an initial survey to assess practice and possible barriers to use |
General & Epidemiological Trends & Socioeconomics: Quality Improvement & Patient Safety II | 17BOS |
Abstract: MP92-11 Sources of Funding: None Introduction Approximately 1 million transrectal ultrasound-guided prostate biopsies are performed each year in the United States alone. The rates of bacterial resistance and sepsis are increasing. Utilization of rectal swab culture to guide antibiotic prophylaxis has been demonstrated to reduce infection rates. We aim to understand the awareness of the test, utilization patterns, barriers to use, and its effect on clinical management. Methods A voluntary, email-based, anonymous survey was conducted of urologists in the New York Section of the AUA. SurveyMonkey® was utilized to power the survey and tabulate the results. The inclusion criterion was membership within the New York Section AUA. Results Eighty-seven urologists responded. 26.4% of responders reported they were in academic practice, while 74.6% were in some form of private practice. Most responders were not fellowship trained (65.5%), and most have been in practice >20 years (60.9%). A plurality of urologists utilize a single oral and an additional intravenous/intramuscular antibiotic (41.4%). The next most common regimen was a single oral agent (27.7%). 97.7% of responders were aware of rectal swab cultures, but 67.1% do not utilize the test. 18.8% state they utilize the test regularly, and 14.1% use it occasionally. The largest barrier to use is lack of confidence that it will improve outcomes (61.4%) followed by the feasibility of performing the test (42.1%). Among users of rectal swab cultures, 50.0% use the test in all patients before biopsy, while 39.3% of users target patients with a history of sepsis. Of responders utilizing the test, 46.4% stated it changed management at least 20% of the time, and 89.3% state it changes their management at least 10% of the time. Practitioners found it very easy to incorporate into practice (53.6%) or somewhat easy (25.0%), while 0% found it very difficult. Conclusions While a majority of urologists are aware of rectal swab cultures, only a small subset regularly uses the test. The major finding is that nearly 50% of users state that it changes prophylaxis at least 20% of the time, and 89% state it changes prophylaxis in at least 10% of patients. Future studies should determine cost-effectiveness and verify a reduction in sepsis rates. Funding None
Authors
John Graham
David Silver Jeffrey Weiss Michael Herman |
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MP92-12 |
Prospective Monitoring of Imaging Guideline Adherence in a Statewide Surgical Collaborative: Use of Statistical Process Methods |
General & Epidemiological Trends & Socioeconomics: Quality Improvement & Patient Safety II | 17BOS |
Abstract: MP92-12 Sources of Funding: Blue Cross Blue Shield of Michigan Introduction Systematic, automated methods for monitoring physician performance are necessary if changes in behavior are to be detected promptly and acted on. In the Michigan Urological Surgery Improvement Collaborative (MUSIC), we evaluated several statistical process control (SPC) methods to determine the sensitivity and ease of interpretation for assessing adherence to imaging guidelines for patients with newly diagnosed prostate cancer. Methods MUSIC is a quality improvement consortium consisting of 43 urology practices in Michigan. Following dissemination of imaging guidelines, MUSIC set a target rate of <10% for non-indicated bone and computed tomography scans. We compared four SPC methods: p chart, Bernoulli cumulative sum (CUSUM), weighted binomial CUSUM, and exponentially weighted moving average (EWMA). We studied non-indicated bone scan rates ranging from 11% (out of control rate) to 6% (in control rate) for the median MUSIC practice using each method. SPC method sensitivity was determined using the average run length (ARL): time taken to signal a change, per quarter. Using the Monte Carlo method (n = 10,000), we determined the ARL at the 11% out of control rate. Statistical analysis was performed using R (v 3.3.1). Non-indicated bone scan rates for a single MUSIC practice were plotted using each SPC method to qualitatively assess interpretation. Results When bone scan rates were in an out of control phase, EWMA and Bernoulli CUSUM methods were each found to have lower out of control ARL values (4.5 and 4.4 respectively) than weighted binomial CUSUM (5.0) or p chart (7.4; p<0.001); thus able to detect significant changes in imaging rates earlier. EWMA and p charts were easier to interpret graphically than CUSUM methods due to ability to display prior imaging rates. EWMA was the most suitable method due to its fast response time and ease of interpretation (Figure). Conclusions For the purposes of assessing adherence to guidelines in a statewide collaborative, we found the EWMA method most suited for detecting changes in imaging rates. This technique may have important implications for prospective automated monitoring of patient safety, such as tracking complications following prostate biopsy. Funding Blue Cross Blue Shield of Michigan
Authors
Michael Inadomi
Yuqing Gao Susan Linsell Matthew Plumlee Patrick Hurley James Montie Khurshid R. Ghani for the Michigan Urological Surgery Improvement Collaborative |
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MP92-13 |
IMPROVING ACCESS TO CARE AND GUIDELINE COMPLIANCE IN A VETERANS AFFAIRS CYSTOSCOPY CLINIC |
General & Epidemiological Trends & Socioeconomics: Quality Improvement & Patient Safety II | 17BOS |
Abstract: MP92-13 Sources of Funding: None Introduction The number of Veterans in the US enrolled in the Veterans Health Administration increased by 52% from 2001 to 2014, leading to well-publicized access issues within the health care system. Wait times for routine cystoscopy were high at our VA. We sought a safe way to decrease this time by addressing cystoscopy appropriateness based on guideline compliance. Methods A chart review was performed on all men and women scheduled for cystoscopy that were over 3 months past their ideal cystoscopy date. Indications for the procedure, wait time and appropriateness of the scheduled appointment were scrutinized. For bladder cancer patients, the 2016 AUA guidelines on surveillance of non-muscle invasive bladder cancer were used. For all other cystoscopy indications, respective best-practice policy statements were utilized when possible. _x000D_ Results There were 152 patients in our system awaiting cystoscopy. Indication for cystoscopy was hematuria work-up in 62 (40.8%), bladder cancer surveillance in 64 (42.1%), neurogenic bladder surveillance in 9 (5.9%), and "other" evaluations (e.g. bladder neck contractures, BPH, AUS erosion, and previous atypical cytology) in 17 (11.2%). Median time between ideal cystoscopy date and scheduled cystoscopy date for new and return patients was 42 (IQR: 31, 61) and 39 (IQR: 31, 49) days, respectively. After review, cystoscopy was deemed inappropriate in 17 (11.1%) patients, the majority of which (n=12; 70.5%) were for overly aggressive bladder cancer surveillance especially for low risk disease (Table 1). Other reasons included neurogenic bladder surveillance in 1 (5.9%) and "other" reasons in 4 (24.6%). Conclusions By systematically reviewing our scheduled cystoscopy appointments, over 10% of our cystoscopies in a 3-month period were safely postponed or cancelled simply by compliance with the most up-to-date published guidelines. Review, and subsequent modification, of our practice patterns has simultaneously led to decreased wait times and improved evidence-based medicine. Funding None
Authors
Conrad Tobert
P. Joseph Guidos Bradley Erickson Kenneth Nepple |
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MP92-14 |
Factors Associated with Stage at Presentation and Survival in Penile Cancer |
General & Epidemiological Trends & Socioeconomics: Quality Improvement & Patient Safety II | 17BOS |
Abstract: MP92-14 Sources of Funding: none Introduction Penile cancer is a highly curable malignancy when clinically localized. Advanced stage is associated with significantly worse survival due to a lack of effective systemic therapies. As penile cancer is rare in the United States, we sought to explore factors associated with stage at presentation and survival using a population-level database. Methods The National Cancer Database (NCDB) was queried from 2004-2014 for patients diagnosed with penile squamous cell carcinoma (SCC). AJCC clinical stage grouping at presentation was correlated with patient age, race, insurance status, income/education level of patient zip code, distance from hospital, Charlson/Deyo comorbidity score, urban vs. rural hospital location, and geographic region. Overall survival was stratified by AJCC clinical stage grouping and dichotomized into localized vs. non-localized disease at presentation. Cox multivariate regression survival analysis was performed to determine predictors of survival. Results 11,112 cases of penile SCC were identified; stage 0 (n=2258), stage I (n=2325), stage II (n=1313) stage III (n=632) and stage IV (n=571). Multivariate logistic regression (Table) for localized (stage 0-II) vs. non-localized disease (stage III-IV) identified that minority (black and Hispanic) patients and those with non-private insurance were independently associated with an increased risk of being diagnosed with non-localized penile SCC. Overall survival was inversely proportional with stage at presentation (Figure). Cox multivariate regression analysis for overall survival demonstrated that AJCC stage (stage 0 - reference; stage I HR 1.53; II HR 2.24; III HR 3.36; IV HR 8.73, p<0.01), lower income level, black race (HR 1.22, p=0.008), and lack of private insurance (HR 1.41-1.80 [depending on type of insurance], p<0.05) were associated with decreased survival. Conclusions Minority patients and those with non-private insurance are significantly more likely to present with higher stage, non-localized penile SCC. Predictably survival was strongly associated with stage at presentation; additionally we found black patients, those from lower income levels, and those without private insurance were also at increased risk of dying during follow-up - independent of stage at presentation. Funding none
Authors
Solomon Woldu
Ryan Hutchinson Nirmish Singla Boyd Viers Laura-Maria Krabbe Arthur Sagalowsky Yair Lotan Aditya Bagrodia Vitaly Margulis |
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MP92-15 |
Predicting Post-operative Readmissions in Pediatric Urology by Using Three Validated Comorbidity Indices |
General & Epidemiological Trends & Socioeconomics: Quality Improvement & Patient Safety II | 17BOS |
Abstract: MP92-15 Sources of Funding: K08-DK100534 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Introduction There is a lack of validated surgical risk assessment scores in pediatric urology to predict mortality and complications. Indices such as Charlson Comorbidity (CCI) and Van Walraven (VWI) were developed using adult cohorts, and the Rhee Index was established for pediatric general surgery patients. To assess their applicability in pediatric urology, we compared how well the three comorbidity indices predict post-operative readmissions to the emergency room and inpatient unit after urological procedures. Methods We analyzed the State Inpatient Databases (SID) from 2007 to 2010. The SID is specifically designed to track ER and inpatient visits. We included pediatric patients (< 18 y) who underwent the following urological procedures: ureteroneocystostomy, ureteroureterostomy, radical/partial nephrectomy, pyeloplasty, appendicovesicostomy, enterocystoplasty, vesicostomy, and bladder neck sling. 30-day ER and inpatient readmissions were extracted. Comorbidity scores were calculated using each index. We used descriptive analysis to describe the patient cohort. To compare the performance on predicting post-operative readmissions, receiver operating characteristics (ROC) were constructed for each index. Results We identified a total of 6,752 patients. The median age was 4 years; males accounted for 43.9% of the cohort, and 52.4% were privately insured. 7.4% had at least one inpatient readmission, and 8.1% had at least one ER admission. The CCI had the best predictability for 30-day inpatient readmissions (AUC=0.63) than VWI (AUC=0.54) and Rhee Index (AUC=0.56); p<0.0001. All three indices performed similarly poor in predicting 30-day ER admissions: CCI (AUC=0.52), VWI (AUC=0.51), and Rhee Index (AUC=0.50); p=0.5. Conclusions The Charlson Index was significantly better at predicting inpatient readmissions than Van Walraven or Rhee Index, but the three scores were equally poor in predicting post-surgical ER admissions. The three indices were designed to predict mortality and, thus, performed significantly less well in predicting readmissions. Our result supports that a new risk index needs to be developed to better predict post-operative readmissions in pediatric urology patients. Funding K08-DK100534 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Authors
Ruiyang Jiang
Steven Wolf J. Todd Purves John S. Wiener Jonathan C. Routh |
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MP92-16 |
Quality Improvement for Urologists: Curricular Keys for Educating Residents (QUICKER) |
General & Epidemiological Trends & Socioeconomics: Quality Improvement & Patient Safety II | 17BOS |
Abstract: MP92-16 Sources of Funding: Grant from the Society of Urologic Program Directors Introduction The healthcare system increasingly links patient safety and explicit quality measures to health outcomes. In addition, under the aegis of the ACGME&[prime]s Next Accreditation System, urology residents must now receive training regarding quality improvement (QI). Competing demands of clinical care, other curricular topics, and lack of resources and faculty expertise pose challenges to QI educational programs. To develop content for a QI curriculum for urology residents, we identified 25 candidate topics. Our objective was to identify appropriateness of the topics using an expert panel. Methods We used a modified Delphi approach to gather consensus among a panel of QI and urology education experts through a novel online interface (ExpertLens). We asked experts to anonymously rate 25 topics across 3 domains: importance, feasibility, and potential impact on patient care if residents received instruction on the topic. Potential ratings ranged from 1 to 9 (1 = of no importance; 9 = extremely important). In Round 1, panelists rated each topic. In Round 2, panelists viewed aggregate ratings and justified their own choices through an online discussion board. In Round 3, panelists provided their final ratings based on the online discussion. Twenty-four experts were initially recruited, and 16 ultimately participated in all three rounds._x000D_ Results Minimization of healthcare waste, use of high value care, and standardization of clinical processes scored the highest on importance and impact, while panelists felt that quality measurement tools (i.e., patient satisfaction measures, Physician Quality Reporting System) were less important to teach and unlikely to substantially improve patient care. Expert panelists clearly distinguish quality measurement (i.e. reporting systems) and quality improvement activities (Table). Conclusions These results broadly support a QI curriculum focused on methods to eliminate waste, standardize care pathways, and strengthen processes of urologic patient care. Educating residents about quality measurement and reporting may not meaningfully improve patient outcomes. Future research will assess methods to improve resident engagement in QI education._x000D_ Funding Grant from the Society of Urologic Program Directors
Authors
Eugene Cone
Jonathan Bergman Tannaz Moin Ashley Wietsma Arlene Fink B Price Kerfoot Charles Scales |
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MP92-17 |
Use of Guidewire During Placement of Prophylactic Ureteral Localization Stents (PULSe) for Colorectal Surgery (CRS) Cases Decreases Urologic-induced Operative Complications |
General & Epidemiological Trends & Socioeconomics: Quality Improvement & Patient Safety II | 17BOS |
Abstract: MP92-17 Sources of Funding: none Introduction Prophylactic Ureteral Localization Stents (PULSe) aid in intraoperative localization and detection of suspected ureteral injury during complex Colorectal Surgery cases. We previously reported the incidence of urologic induced Clavien grade III complications of PULSe placement at our institution from July 2013 to June 2014 is estimated at 4%. As a quality health initiative, we sought to compare a modification of technique, mandatory use of guidewire assistance during PULSe placement to reduce urologic induced complications in this patient cohort. Methods Following results of the above study, we made guidewire usage during PULSe placement mandatory at our institution. We reviewed all patients who underwent cystoscopy and PULSe placement at the time of CRS over a 12 month period (July 2015 to June 2016). Bilateral 5 French x 70 cm TigerTail (Bard Medical Division, Covington, GA) PULSe devices were placed with use of guidewire. Flouroscopy was not used. We compared this patient cohort to our prior cohort from July 2013 to June 2014 with the following variables: age, BMI, American Society of Anesthesiologists (ASA) score, preoperative creatinine, postoperative creatinine, pre/postoperative creatinine difference, and Clavien III urologic induced complications. Results 132 patients with a mean age and BMI of 55.78 (18 to 89) and 27.02, respectively underwent bilateral PULSe placement with mandatory use of guidewire. Mean pre and postprocedural creatinine levels were 0.91 and 1.04, respectively with a mean pre/post procedural creatinine difference of 0.09. No Clavien III complications were encountered in the contemporary cohort, compared to the prior incidence of 4% (p≤0.001). Moreover, postoperative creatinine and pre/postprocedural creatinine difference also favored the contemporary cohort (p≤0.022 and p≤0.003, respectively). Conclusions Mandatory use of guidewire prior to PULSe placement reduced our incidence of urologic induced Clavien III complications to zero. Benefits were also observed in postoperative and pre/post procedural renal function with use of guidewire. Funding none
Authors
Ram Pathak
Gregory Broderick Kasey Cockerill Ciarra Boyne Todd Igel Raymond Pak Steven Petrou Paul Young Ryan Frank Nicolette Chimato David Thiel |
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MP92-18 |
A study of Urology resident sleep patterns in relation to volume and category of overnight pages in a home call system |
General & Epidemiological Trends & Socioeconomics: Quality Improvement & Patient Safety II | 17BOS |
Abstract: MP92-18 Sources of Funding: None Introduction Mitigating resident fatigue is central to the design and implementation of residency programs, especially when using a home call system. Existing studies of resident sleep habits and fatigue are mostly limited to in-house call and rely on self-reporting. We quantified time spent asleep for residents employing a home call system, and examined how the volume and type of pages received affected sleep nightly. Methods Urology residents in a single-institution residency were provided with a FitBit Charge HR device to collect objective sleep data over a six-month period. Each page received during this period after 16:00 and before 08:00 was counted and categorized as either &[Prime]clinic&[Prime] (outpatient calls from the after-hours answering service), &[Prime]floor&[Prime] (calls from the inpatient Urology ward), and &[Prime]other&[Prime] (calls regarding off-floor consults). Data analysis was carried out using IBM® SPSS® Statistics 23 and Numbers. Results Residents received a total of 1068 overnight pages while on call. The least senior resident received 321 pages (avg. 7.0/night), followed by 288 (avg. 6.0/night), 265 (avg. 6.3/night), and 194 (avg. 5.0/night) for the next three more senior residents, respectively. On average, residents slept 400 minutes while on call, compared to 434 minutes while not on call (p<0.05). Increased total volume of pages was associated with 4.71 fewer minutes asleep nightly per page for all residents (r=-0.32, n=145, p<0.05). Pages in the &[Prime]other&[Prime] category were associated with 7.74 fewer minutes asleep per page for all residents (r=-0.24, n=145, p<0.05). On individual analysis, pages to the least senior resident from the &[Prime]floor&[Prime] category were associated with 9.02 fewer minutes asleep (r=-0.35, n=44, p<0.05). This correlation did not reach significance for the other residents. Conclusions The most senior resident received the least average pages and the least senior resident received the most, an interesting finding given that call nights were evenly distributed. Residents slept less on call in general. Time asleep was reduced with increasing page volume, most severely when pages were from the &[Prime]other&[Prime] category, suggesting residents needed more time to address pages regarding patients they were unfamiliar with. Calls from the floor were most detrimental to sleep for the least senior resident, suggesting experience is a factor in efficient overnight call management. Funding None
Authors
Adam Ludvigson
Gregory Mills Stephen Ryan Graham VerLee Moritz Hansen |
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MP92-19 |
Novel, Nontoxic Skin Care Formulation Associated with Lower CAUTI Rates for High-Risk ICU, Neuro, C-V and Trauma Patients When Used for Foley Catheter Insertion and Maintenance |
General & Epidemiological Trends & Socioeconomics: Quality Improvement & Patient Safety II | 17BOS |
Abstract: MP92-19 Sources of Funding: None Introduction Over 1 million CAUTIs occur annually among hospitalized U.S. patients receiving a Foley urinary catheter, accounting for over 13,000 deaths. CAUTI treatment requires antibiotics at a time when hospitals are expected to minimize avoidable antibiotic use. CAUTIs financially burden hospitals. The mean per-incident cost is estimated at $750-$4,823. One facility in this study found its net cost, including longer length of stay, to be $11,419 per case. Most payers do not reimburse these costs. The ACA penalizes hospitals for high CAUTI rates. _x000D_ _x000D_ Data was collected from multiple sites to assess whether an intervention using a novel, non-toxic skin care system/formulation for Foley insertion and maintenance could reduce CAUTI rates._x000D_ Methods Approximately 25 hospitals using the formulation were asked to provide insertion and maintenance details on use, plus pre- and post-implementation CAUTI rates reported to the National Healthcare Safety Network. The formulation was used in high-risk ICU, Neuro, C-V and trauma patient populations with fecal and urinary incontinence, in its foam and moisture-impregnated-cloth forms. Both forms are safe for the perineal area, do not cause antibiotic resistance, and are not associated with adverse events. Clinical protocol was to apply the formulation to the meatus and surrounding tissue to establish a zone of protection, then re-establish after each incidence of fecal incontinence as a maintenance intervention. Results Ten hospitals provided pre- and post-intervention data (average time pre-intervention 21.2 months; average time post-intervention 20 months). Eight reported CAUTI rate reductions, ranging from 22.47% to 100% (with two sites reporting elimination of CAUTI). Two other hospitals noted compliance issues that affected their results and made their data unreliable. One of those two reported no change in CAUTI rates and the other reported a 30.31% increase. The mean pre-implementation CAUTI rate for the eight compliant hospitals was 3.65/1,000 catheter days. The mean post-implementation CAUTI rate for those same hospitals was 1.72/1,000 catheter days. The mean change was a reduction in CAUTI rates of 52.88%. Conclusions Eight of 10 reporting sites found use of the skin care formulation was associated with lower CAUTI rates. Further study of the formulation’s efficacy is warranted._x000D_ _x000D_ Funding None
Authors
George Turini III
Joseph Renzulli II |
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MP92-20 |
Female Genital Mutilation at a Safety-Net Hospital in Denver, CO |
General & Epidemiological Trends & Socioeconomics: Quality Improvement & Patient Safety II | 17BOS |
Abstract: MP92-20 Sources of Funding: None Introduction Female genital mutilation is the alteration of genitalia for cultural, non-medical purposes and may cause numerous medical complications. The purpose of this study was to examine female genital mutilation cases seen at Denver Health Medical Center, a Level 1 Trauma Center and Safety-Net Hospital in Denver, Colorado. Furthermore, we assessed chief complaints that initiated evaluation and possible medical treatment. Methods A retrospective review of Denver Health Medical Center’s database was performed from May 2002 to May 2016. Patients were included in the study when the provider identified female genital mutilation using reference ICD9/10 codes. All patients identified were eligible for this study even if their visit was unrelated to female genital mutilation. Results Ninety-two patients were coded as having some form of female genital mutilation at Denver Health Medical Center and were included in the study (Figure 1). A majority of these patients were from Somalia, had Type 3 mutilation, and were seen for childbirth without prenatal visits (Figure 2). Lacerations (37) were the most prevalent dermal lesions encountered in childbearing female genital mutilation patients (Table 1). Additionally, the mutilation led to frequent Caesarean sections (17) and episiotomies (5) in these patients. Urinary tract infections, dyspareunia, inclusion cysts on incised area, and sexual dysfunction were the most common symptoms in the non-pregnant group. Conclusions Alteration of female genitalia often causes a variety of medical symptoms. A majority of these patients were from Africa and initially seen due to pregnancy. Further understanding of possible complications due to this practice may prevent urological complications as well as emergent interventions like Caesarean section and episiotomies. Funding None
Authors
Diedra Gustafson
Leticia Nogueira Stephanie Gold Elizabeth Berry Rodrigo Donalisio da Silva Fernando J. Kim |
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MP93-01 |
MODIFIED ANASTOMOSIS TECHNIQUE DURING ROBOT ASSISTED RADICAL PROSTATECTOMY: PREVENTION OF URETHRAL RETRACTION AND IMPROVEMENT OF EARLY CONTINENCE |
Prostate Cancer: Localized: Surgical Therapy VII | 17BOS |
Abstract: MP93-01 Sources of Funding: none Introduction To report our new vesicourethral anastomosis technique during robot assisted radical prostatectomy and test its impact on the immediate and early continence rates . Methods Between January-June 2016, 60 patients were enrolled in the study and data collected prospectively. Modified vesicourethral anastomosis was performed by a single surgeon. The new technique was based on stabilizing the posterior urethra with anastomosis sutures before transecting the prostatic urethra. Two 3/0 barbed sutures were passed from the urethra at 5 o clock and 7 o clock positions and then used for vesicourethral anastomosis. This cohort of patients (Group I, 60 pts) was compared with the most recent consecutive patients in whom standard continuous running anastomosis technique was used prior to initiating the new technique (Group II, 60 pts). Post catheter removal 1st week and 1st month continence status were compared with the standard technique using ICIQ-SF form and 1st month overactive bladder questionnaire form. Preoperative ICIQ-SF scores were aslo obtained for both groups but there were no statistical significant distance between groups. Results Groups were compared in terms of Prostate specific antigen (EBL), age, body mass index (BMI), American society of anesthesiology score (ASA), prostate volume, final gleason score, operation and anastomosis time, and estimated blood loss (EBL). Also surgical margin positivity, bladder neck reconstruction rate, lymph node invasion rate were compared. Only statistically significant difference was encountered in modified anastomosis group in terms of age; group II was younger compared to group I. (61+7.5 vs. 64+7.6, p<0.05). For the 1st week of post catheter removal, mean ICIQ-SF scores for group I and -group II were 4.1+5.7 vs. 12.1+4.1 respectively (p<0.001). Recatheterization was needed in ;4 of 60 patients in Group 1 and 1 of 60 patients in Group 2 ;(p>0.05). Similarly; 1st month ICIQ-SF scores for group II and group I were 10.8+4.4 vs. 2.6 +4.3, respectively (p<0.001). Overactive bladder questionnaire scores were also compared. There was a statistically significant difference between two groups in favor of group I (18+7.7 vs. 5.3+6.2) (p<0.001). Conclusions Modified anastomosis technique seems to have better early continence rates compared to the standard technique. Moreover, overactive bladder symptoms were significantly less common with the novel anastomosis technique. Further randomized studies are needed to better evaluate the effect and reproducibility of this new technique. Funding none
Authors
Omer Burak Argun
Mustafa Bilal Tuna Tunkut Salim Doganca Ilter Tufek Panagiotis Mourmouris Can Obek Ali R?za Kural |
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MP93-02 |
Comparison of Oncological Outcomes between Open versus Robot-Assisted Salvage Radical Prostatectomy: A Retrospective Multicentre Series. |
Prostate Cancer: Localized: Surgical Therapy VII | 17BOS |
Abstract: MP93-02 Sources of Funding: None Introduction Salvage radical prostatectomy (sRP) represents a valid treatment option in men with biochemical recurrence (BCR) after primary treatment. Oncological outcomes of Robotic (R) and open (O) approaches have not been compared. We report and compare oncological outcomes of R and OsRP in a large contemporary series. Methods Three hundred seventy-six men with BCR, who underwent sRP between 2000 and 2015 at 13 Tertiary referral centres, were retrospectively analysed. Age, PSA, clinical and pathological TNM, primary and pre-sRP biopsy and sRP gleason score (GS), surgical margins, imaging type and positive sites, lymphadenectomy template used, number of lymph-nodes removed and positive, ASA score and ECOG performance status and use of hormonal treatment (HT) were collected for each patient. Exclusion criteria were a follow up <12 months or unavailability of the aforementioned data. Continuous variables were tested for normal distribution and then compared using Wilcoxon-Mann-Whitney test; differences in categorical variables were assessed by Chi-square or Fisher's exact tests. Results Two hundred forty-three men were included. Primary treatments were: external beam radiation therapy in 69.5% of patients, cryotherapy in 3.7%, HIFU in 4.1%, brachytherapy in 21.4% and other primary treatments in 1.2% of the patients. No differences were observed regarding: pre-operative PSA (p=0.46), age (p=0.053), ASA score (p=0.06), patients receiving HT (p=0.22) and final pTNM (p=0.91) and mean number of pathologically positive nodes (0.9 ±3.0 in the OsRP vs 0.3 ±1.2 in the RsRP group (p=0.1)). However, before sRP castration resistant prostate cancer (CRPC) was higher in the OsRP group (9.5% vs 1.92%; p=0.01), sRP GS was ≥8 in 42% of OsRP vs 32% of RsRP (p=0.04) and median follow up was longer for OsRP (46.7 months, IQ range 30.2-81.1 vs 27.9 months, IQ range 13.5-44.4, in the RsRP group; p<0.01). Surgical margins were focally or extensively positive in 12.59% and 24.4% of the OsRP group versus 24.7% and 12.38% of the RsRP group (p<0.01). No significant differences were detected in BCR (46.62% of OsRP vs 40.8% of RsRP p=0.4) or progression to CRPC (17.7% of OsRP vs 11.5% of RsRP; p=0.31). OS was higher for RsRP (98% vs 88,9% for OsRP (p<0.01)) and CSS was 98% for RsRP and 94.1% for OsRP (p=0.057). Conclusions Promising oncological outcomes can be achieved by salvage radical prostatectomy. The robot-assisted procedure has similar BCR rates compared to the open approach, but can allow lower rates of extensively positive surgical margins and may favour higher OS and CSS trends. To validate the present findings, a longer follow-up and a higher number of patients are needed. Funding None
Authors
Paolo Gontero
Giancarlo Marra Paolo Alessio Marco Oderda Anna Palazzetti Francesca Pisano Antonino Battaglia Stefania Munegato Bruno Frea Fernando Munoz Claudia Filippini Estefania Linares Rafael Sanchez-Salas Sanchia Goonewardene Prokar Dasgupta Declan Cahill Ben Challacombe Rick Popert David Gillatt Raj Persad Juan Palou Steven Joniau Salvatore Smelzo Thierry Piechaud Alexandre De La Taille Morgan Roupret Simone Albissini Roland Van Velthoven Alessandro Morlacco Sharma Vidit Giorgio Gandaglia Alexander Mottrie Joseph Smith Shreyas Joshi Gabriel Fiscus Robert Jeffrey Karnes |
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MP93-03 |
NOMOGRAM PREDICTING BOWEL DYSFUNCTION FOR MEN WITH LOCALIZED PROSTATE CANCER TREATED BY RADICAL PROSTATECTOMY, EXTERNAL-BEAM RADIOTHERAPY, OR BRACHYTHERAPY |
Prostate Cancer: Localized: Surgical Therapy VII | 17BOS |
Abstract: MP93-03 Sources of Funding: NIH R01 CA 95662; NIH 1RC1CA146596 Introduction Radical prostatectomy (RP), external-beam radiotherapy (EBRT), and brachytherapy are standard treatments for localized prostate cancer but each may negatively impact bowel function. We sought to develop a nomogram predicting the probability of treatment-related bowel problems using prospective, patient-reported data. Methods Patient-reported data on treatment-related bowel problems was obtained from four prospective, longitudinal, health-related quality-of-life (HRQOL) protocols comprising 2,668 patients treated between 1999 and 2011 in the United States and Spain. A single HRQOL instrument was not uniformly used for each study, though a similar 5-point scale was used in each protocol to assess bother related to bowel problems. Bowel dysfunction was defined as bowel symptoms identified as a moderate-to-big problem by patients on survey responses before treatment and 2 years post-treatment. Multivariable logistic regression analysis was used to model the clinical information and follow-up data. Internal validation was performed using bootstrapping. Results Overall, 43 patients (2%) with complete data had bowel dysfunction prior to treatment. The rate of bowel dysfunction at 2 years in patients with no bowel dysfunction pretreatment was 2%, 10%, and 4% for patients treated by RP, EBRT, and brachytherapy, respectively (p<0.001). A nomogram based on pretreatment bowel bother, treatment modality, and race had a concordance index of 0.725 and predictions were well-calibrated with observed outcome on cross-validation. The predictive accuracy was not increased by the inclusion of additional demographic, tumor-related, or treatment-related variables, or by the creation of separate treatment-specific models. Conclusions A validated nomogram that predicts 2-year probability of bowel dysfunction after treatment for localized prostate cancer has been developed. The nomogram is anticipated to be useful for patient counseling regarding treatment options for localized prostate cancer. Funding NIH R01 CA 95662; NIH 1RC1CA146596
Authors
Joseph Zabell
Joseph Klink Mark Litwin Martin Sanda Meredith Regan Christopher Saigal Lorna Kwan Herbert Tianming Gao Eric Klein Michael Kattan Andrew J. Stephenson |
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MP93-04 |
The risk of urinary retention following Robot-Assisted Radical Prostatectomy and Its Impact on Early Continence Outcomes |
Prostate Cancer: Localized: Surgical Therapy VII | 17BOS |
Abstract: MP93-04 Sources of Funding: none Introduction To evaluate the risk factors of acute urinary retention (AUR) following robot-assisted radical prostatectomy (RARP) including the timing of catheter removal, and to study the relationship of urinary retention with early continence outcomes following RARP, which has never been mentioned in the literature before._x000D_ Methods 740 consecutive underwent RARP by 2 experienced surgeons at our institute were reviewed retrospectively from a prospectively-collected database. Multiple factors including age, body mass index (BMI), international prostatic symptom score (IPSS), prostate volume, presence of median lobe, nerve preservation, anastomosis time, and catheter removal time (day 4 vs 7) were evaluated as risk factors for AUR using univariate and multivariate analysis. The relation between AUR and early return of continence (1 and 3 months) post-RARP was also evaluated._x000D_ Results The incidence of clinically significant vesicourethral anastomotic leak and AUR following catheter removal were 0.9% and 2.2% (17/740), respectively. In men who developed AUR, there was no significant relationship with regards to age, BMI, IPSS, prostatic volume, median lobe presence, nerve preservation or anastomosis time. Moreover, the incidence of AUR was significantly higher (p=0.004) for men with catheter removal at day 4 (4.5% (16/351)) vs day 7 (0.2% (1/289)). Moreover, patients with early removal of catheter (day 4) whom developed AUR had earlier 1 month return of 0-pad continence 87.5% (14/16) compared to patients without AUR 45.6% (153/335), with no significant deference at 3 months._x000D_ Conclusions While AUR is an uncommon complication of RARP, its incidence is much higher than VUA leakage and often not discussed during patient counseling. Early catheter removal at day 4 post RARP is associated with higher incidence of AUR. Moreover, men experiencing AUR were observed to have a much earlier return of urinary continence. Future studies are warranted to validate the impact of AUR on long term outcome of continence. _x000D_ _x000D_ _x000D_ Funding none
Authors
Mansour alnazari
Marc Zanaty Pierre-Alain Hueber Emad Rajih Assad El-Hakim Kevin C. Zorn |
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MP93-05 |
Comparison of functional outcomes between laparoscopic radical prostatectomy and robot-assisted laparoscopic radical prostatectomy: A propensity score-matched comparison study |
Prostate Cancer: Localized: Surgical Therapy VII | 17BOS |
Abstract: MP93-05 Sources of Funding: none Introduction To compare the functional outcomes after laparoscopic radical prostatectomy (LRP) and robot-assisted laparoscopic radical prostatectomy (RARP). Methods Between September 2008 and January 2016, 712 patients underwent radical prostatectomy (RP; 614 LRP and 98 RARP). Recovery of Incontinence was evaluated through a 24-hour pad test. Urinary and erectile function was evaluated using the International Prostate Symptom Score (IPSS) and the International Index of Erectile Function-5 (IIEF-5). Follow-up interval was 1, 3, 6, and 12 months after the surgery. The propensity score (PS) matching was used to balance the pre-operative characteristics. Results The recovery of incontinence was similar to the two groups at 6 and 12 months after the surgery. However, patients underwent RARP restored the continence sooner than those in the LRP group in 1 and 3 months after the surgery (P <0.001 and 0.001) (Fig.1). For the multivariable analysis, the type of RP procedure was a uniquely meaningful contributing factor (P = 0.001, HR = 1.925; 95% CI = 1.299–2.851). In the case of urinary function, the RARP groups showed a better IPSS score than LRP groups at the 1-, 3-, and 6-month visits, respectively (P = 0.008, 0.026, 0.001), (Fig.2) and the RARP groups early improved compared with LRP groups at the 3-month visit in the case of erectile function (P = 0.018) (Fig.3)._x000D_ _x000D_ Conclusions The RARP tended toward getting back the urinary continence earlier than the LRP. In addition, urinary and erectile function recovered more quickly in the RARP group than in the LRP group. Funding none
Authors
JaYoon Ku
ChanHo Lee Kyoung Lee KyungHwan Kim Sang Don Lee Moon Kee Chung HongKoo Ha |
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MP93-06 |
Technical factors preventing full nerve sparing during robotic-assisted laparoscopic radical prostatectomy in patients that are candidates for full nerve sparing |
Prostate Cancer: Localized: Surgical Therapy VII | 17BOS |
Abstract: MP93-06 Sources of Funding: None Introduction Radical prostatectomy is one of the standard treatments for localized prostate cancer. This procedure can significantly effect the quality of life. Nerve sparing (NS) has been proven to improve functional outcomes after radical prostatectomy. But in published literature, only 50% to 75 % of all eligible candidates get bilateral full NS during robotic-assisted radical prostatectomy (RALP). We planned to analyze factors affecting NS Methods We retrospectively analyzed our IRB approved database for low risk prostate cancer patients who underwent RALP. Men with NCCN low risk prostate cancer (LRPCa: PSA < 10 ng/ml, Gleason score ≤ 6 and Clinical stage T1/ T2a) without preoperative erectile dysfunction (no ED, SHIM score>21) are potentially ideal eligible candidates for full NS radical prostatectomy. Our pre-operative and intra-operative intention was to perform full nerve preservation in these patients. During surgery we noted the amount of nerve sparing performed and the level of difficulty of the nerve sparing. We also noted the reason for the challenge in sparing the nerves. We analyzed patient and tumor characteristics affecting the NS during RALP. Results Complete data was available for 1283 men with LRPCa and no ED that underwent RALP. 1085 (84.6%) of them received full NS and remaining 198 (15.4%) received partial NS. In univariate analysis advanced age, obesity, multiple comorbidity, and prior TURP adversely affected full NS. Low PSA level, less number of positive cores and smaller prostate positively influenced full NS. Multiple prior biopsies, more than 12 cores biopsy and PSA density did not affect NS. In multivariate analysis, technical difficulty in NS, number of positive cores, palpable nodule and age significantly affected the nerve sparing. Conclusions Even in the ideal candidate with an experienced surgeon performing the procedure, full NS during RALP is not always possible. Various anatomic, metabolic or functional reasons can prevent full NS and potentially effect recovery. Neither patient nor the surgeon should go into the operation assuming that low risk patients will have a full NS. It is important to counsel the patient on the possible adverse effects of surgery in this situation and weigh the risks and benefits of active surveillance in these patients. Funding None
Authors
Hariharan Palayapalayam Ganapathi
Gabriel Ogaya-Pinies Eduardo Hernandez Travis Rogers Tracey Woodlief Vipul Patel |
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MP93-07 |
Hospital stay is predictive of functional outcome after surgery for high risk or cT3 prostate cancer |
Prostate Cancer: Localized: Surgical Therapy VII | 17BOS |
Abstract: MP93-07 Sources of Funding: None Introduction Surgical management of high-risk and non-metastatic prostate cancer has received renewed attention since the publication of the Protect study which suggests at best marginal benefits for low and intermediate risk categories._x000D_ Tailor-made wide excision surgery is generally offered as part of combined modality treatment with adjuvant radiotherapy. Functional outcome in this group of patients is rarely publicised and is expected to reflect the extensive nature of the disease._x000D_ We prospectively assess the rate of incontinence at follow up of at least one year and compute independent pre- and perioperative predictive parameters of adverse outcome. Methods A total of 178 patients with high risk CaP (44.6% were cT3a/b) underwent laparoscopic radical prostatectomy with pelvic lymphadenectomy from July 2007 to 2016 at Imperial College NHS Trust, London. Pad-use was assessed independently by a specialist nurse from the surgical team at a minimum follow up of 1 year via a telephone clinic and questionnaires. _x000D_ Pre-op factors assessed were: age, psa, Gleason grade, previous TURP, clinical stage, radiological stage, prostate size, family history of prostate cancer, BMI. _x000D_ Peri-op factors assessed were: operating time, blood loss, any nerve sparing, bladder neck sparing, presence of middle lobe, hospital stay, early complication, late complication, Clavien scale complication. _x000D_ Complications were prospectively assessed and graded meticulously with Clavien classification._x000D_ Univariate and multivariate analysis utilising logistic regression was computed to predict a binary outcome of no versus any pad use._x000D_ Results Pad use at one year after surgery for high risk prostate cancer was 17% and artificial urethral sphincter or advance tape was inserted in 5% of men, a urethral stricture was observed in 1.2%. Only hospital stay was independently predictive of persistent urinary incontinence on multivariate analysis p=0.018 OR 1.78 (95% CI 1.106-2.876). _x000D_ Conclusions Men who stay longer in hospital are more likely to experience incontinence. Hospital stay is a likely surrogate for early complications, more extensive surgery or bleeding. A better classification of postoperative complications after radical prostatectomy for high risk prostate cancer may allow prediction of postoperative continence. Funding None
Authors
Pol Servian Vives
Amit Patel Altaf Shamsuddin Mathias Winkler |
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MP93-08 |
Interpreting patient-reported urinary and sexual function outcomes across multiple validated instruments |
Prostate Cancer: Localized: Surgical Therapy VII | 17BOS |
Abstract: MP93-08 Sources of Funding: This work was supported by David H. Koch provided through the Prostate Cancer Foundation; the Sidney Kimmel Center for Prostate and Urologic Cancers; SPORE grant from the National Cancer Institute to Dr. H. Scher (grant number P50-CA92629); a National Institutes of Health/National Cancer Institute Cancer Center Support Grant to MSKCC (grant number P30-CA008748); a Movember grant to Dr. Vickers; and the Department of Defense Prostate Cancer Research Program (grant number W81XWH-13-2-0074). Introduction For purposes of both research and clinical quality assurance, doctors must be able to report and compare their results. In prostate cancer, comparing critical patient-reported outcomes such as urinary and erectile function is complicated by the use of different questionnaires, with some centers using EPIC, others using PCI and others using separate instruments for urinary and erectile score (e.g. SHIM and IPSS). We aimed to develop a method to convert scores between these four commonly used instruments. Methods Patient-reported data on urinary and sexual function were collected from 1,284 men with localized prostate cancer using the Expanded Prostate Index Composite (EPIC-26), UCLA Prostate Cancer Index (PCI), Sexual Health Inventory for Men (SHIM) and International Prostate Symptom Scale (IPSS) questionnaires. We investigated several methods to convert scores between questionnaires. Results Conversion between EPIC and PCI urinary and sexual function subscales is best achieved using only the subset of questions that were asked on both questionnaires. This means that sexual function focuses on erectile function and does not include libido, which is include only on the PCI. For the conversion between EPIC or PCI erectile function scores and the SHIM scores, we defined equivalent thresholds of poor, intermediate or good function respectively: EPIC/PCI 0 - 40 and SHIM 1-7; EPIC/PCI 41 - 59 and SHIM 8-16; EPIC/PCI 60 - 100 and SHIM 17-25. Urinary continence scores are highly correlated between PCI and EPIC (r=0.94). Multiple attempts were made to compare IPSS with EPIC and PCI, but after investigation, no comparison was possible due to differences in domains addressed by these questionnaires. Therefore, we do not believe a conversion between IPSS and either PCI or EPIC is appropriate. Conclusions We have introduced methods for converting scores between the EPIC, PCI and SHIM questionnaires. While these conversion methods may introduce a minor amount of imprecision, such imprecision is dwarfed by other factors (such as case mix and statistical imprecision). Our methods represent the best available tools for combining and comparing patient-reported outcomes assessed using different instruments. Funding This work was supported by David H. Koch provided through the Prostate Cancer Foundation; the Sidney Kimmel Center for Prostate and Urologic Cancers; SPORE grant from the National Cancer Institute to Dr. H. Scher (grant number P50-CA92629); a National Institutes of Health/National Cancer Institute Cancer Center Support Grant to MSKCC (grant number P30-CA008748); a Movember grant to Dr. Vickers; and the Department of Defense Prostate Cancer Research Program (grant number W81XWH-13-2-0074).
Authors
Emily Vertosick
Andrew Vickers Janet Cowan Jeanette Broering Peter Carroll Matthew Cooperberg |
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MP93-09 |
Predictors of Membranous Urethral Length Measurement Prior to Radical Prostatectomy |
Prostate Cancer: Localized: Surgical Therapy VII | 17BOS |
Abstract: MP93-09 Sources of Funding: None Introduction Patient anatomical factors including the preoperative measurement of the membranous urethral length (MUL) have been reported to affect the time to achieve continence following radical prostatectomy (RP). There is limited data available reporting the relationship between patient anthropometric measures and also the test-retest reliability of MUL measurements from separate MRI investigations. _x000D_ Objectives: We sought to investigate i) if patient related anthropometric factors were associated with MUL measurements in men prior to RP and ii) the test-retest reliability of preoperative MUL measurements from separate MRI investigations. _x000D_ Methods 119 preoperative T2 weighted sagittal prostate MRI‘s were cross-referenced with coronal images for the measurement of MUL. Preoperative MUL was measured three times and the mean of the three measures was recorded for analysis. A linear model was used for the regression of MUL against predictive variables height, body mass, BMI and age. Nine patients who had undergone two separate preoperative prostate MRI investigations were identified to assess the test-retest reliability of MUL measurements. An intra class correlation coefficient (ICC) using a two-way mixed-model was used to assess the reliability of the test-retest preoperative MUL measurements. Results The 119 patients had a mean age of age 65 8yrs, mean height 1.72 0.07m, mean body mass 84 12.8kg and a mean BMI 27.8 4.6 kg.m2. MUL was not associated with height (p=0.713), body mass (p=0.894), BMI (p=0.985) or age (p=0.189). For the 9 patients with two separate prostate MRI investigations, there was excellent test-retest reliability for the preoperative measurement of MUL ICC=0.989 (95%CI: 0.935, 0.998). The average time between MRI investigations was 35 64 days. Conclusions Patient anthropometric measurements are not related to MUL in men prior to RP. The two repeated measurements of MUL from separate MRI investigations indicates that MUL is a stable measurement, but due to the small sample size further investigation is warranted. Funding None
Authors
Sean Mungovan
Petra Graham Jaspreet Sandhu Oguz Akin Manish Patel |
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MP93-10 |
Urinary, Bowel, and Sexual Function at 2 Years Following Management of Localized Prostate Cancer |
Prostate Cancer: Localized: Surgical Therapy VII | 17BOS |
Abstract: MP93-10 Sources of Funding: none Introduction Given the various treatment options available to men diagnosed with prostate cancer, optimal urinary, sexual, and bowel function should be goals of care in addition to disease free survival. This study assesses factors including management decision for localized prostate cancer and their association with urinary, bowel, and sexual function at 2 years following definitive procedural treatment (radical prostatectomy (RP) or brachytherapy (BT)) or active surveillance (AS). Methods An institutional review of 572 patients who underwent definitive procedural treatment or AS and completed a validated Prostate Health Related Quality of Life Questionnaire at both the time of treatment selection and at 2 year follow-up. Urinary, sexual, and bowel function at 2 years were assessed by self-reported responses to 3 separate questions asking, "Overall, how big a problem has your urinary/sexual/bowel function been for you during the last 4 weeks?" Patient and disease characteristics, baseline urinary, sexual and bowel function, and management selection were analyzed on multivariable logistic regression models for 2 year function outcomes. Results The median age in this cohort was 62 years (IQR: 57-68) with 109 (19%) patients who elected BT, 102 (18%) participated in AS, and 361 (63%) received RP. On multivariable logistic regression for urine function at 2 years, BT vs. AS (HR: 5.4, p = 0.011) and RP vs. AS (HR: 4.0, p = 0.026) associated with worse urinary function. Presence of a partner was associated with better preservation of sexual function (HR: 0.4, p = 0.009), while RP vs. AS (HR: 2.2, p = 0.013) was associated with worse sexual function at 2 years. Significant baseline bowel bother associated with worse bowel function at 2 years (HR: 11.7, p <0.0001); however, type of management was not significantly associated with adverse bowel function. Conclusions The 2 year urinary, sexual and bowel functions among patients managed for localized prostate cancer are based on multiple patient characteristics in addition to the shared decision for BT, RP or AS. Additional studies should examine matched function outcomes among men managed for localized prostate cancer. Funding none
Authors
Shree Agrawal
Anna Zampini Bradley Gill Sudhir Isharwal Joseph Zabell Yaw Nyame JJ Haijing Zhang Eric Klein Andrew J Stephenson |
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MP93-11 |
Evaluation of functional and oncologic outcomes after robotic radical prostatectomy: validation of the proposed survival, continence, and potency (SCP) system |
Prostate Cancer: Localized: Surgical Therapy VII | 17BOS |
Abstract: MP93-11 Sources of Funding: none Introduction Primary goals of robot-assisted radical prostatectomy (RARP) are threefold: cancer control, return of urinary continence, and recovery of sexual function that constitute the RARP &[Prime]trifecta&[Prime]. A method to quantifying RARP outcome was developed in Europe that classifies survival (S), continence (C), and potency (P). The SCP mimics the TNM system used for staging. We sought to validate SCP in a large cohort of Americans followed for more than 5 years after RARP. Methods A retrospective review of prospectively collected data from 800 men who underwent RARP from Jan 2006 to Dec 2011 was performed. Total of 637 men were used for analysis after applying inclusion and exclusion criteria. NCCN biochemical failure was used as a proxy for oncologic outcome (S). The UCLA-Prostate Cancer Index Urinary Function and Sexual Function Questionnaires were used to evaluate continence (C) and potency (P), respectively. Continence was refined further by querying medical records for use of a security pad. Results The 5- and 10-year biochemical progression-free survival rates were 93% (95% CI: 0.90-0.95) and 73% (95% CI: 0.67-0.79), respectively. At last follow up, 502 (79%) patients used no pads (C0), 70 (11%) patients used one security pad (C1), 63 (9.8%) patients used one or more pads routinely (C2), and 2 (0.2%) patients were incontinent before RARP (Cx). Of the 522 (82%) patients who had bilateral nerve-sparing RARP, 128 (24.5%) patients were fully potent without use of aids (P0), 74 (14.2%) patients were potent with PDE-5 inhibitor (P1), 320 (61.3%) patients experienced erectile dysfunction (P2). 115 (18%) patients were impotent pre-operatively or did not undergo bilateral nerve sparing (Px). In patients preoperatively continent and potent who underwent bilateral nerve preservation and did not require adjuvant radiation therapy, oncologic and functional perfection (S0C0P0) was achieved in 58 (45%) patients. Oncologic and continence perfection (S0C0) was achieved in 92 (80%) of patients for whom potency was not recoverable (Px). Conclusions SCP classification offers a tool for objective assessment of oncologic and functional outcome after RARP. Funding none
Authors
Nicole Dodge
Alexandr Pinkhasov Ruben Pinkhasov Aarti Agarwal Gaybrielle James Elena Pop James Mohler |
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MP93-12 |
Prostate cancer in men younger than 55: Rates of functional recovery post-Robotic Assisted Laparoscopic Radical Prostatectomy |
Prostate Cancer: Localized: Surgical Therapy VII | 17BOS |
Abstract: MP93-12 Sources of Funding: None Introduction Time to and overall likelihood to achieve recovery of functional outcomes within one year of undergoing a radical prostatectomy are of high importance to many patients post-RP, with return of continence and potency being at the top of the list. Age at surgery, comorbidities, rehabilitation compliance, pre-operative-SHIM and degree of nerve spare during surgery encompass some of the main impactors of recovery outcomes and therefore are utilized in the current retrospective analysis to further subdivided men ≤ 55 yo with a minimal follow-up of 1 year. Methods In a retrospective analysis of our IRB approved database between January 2008 and January 2016, 1411 patients who underwent RARP were 55 years old (yo) or less with an average age of 51 ± 0.1 yo (range 32 to 55 yo). Within this subgroup, 1,087 patients had a minimum of one year of follow-up and therefore were included in this analysis of functional outcomes. Date of return of continence and potency were both self-reported. Return of continence was defined as the use of no-pads each day, while return of potency was defined as the ability to achieve an erection and to have successful intercourse more than 50% of the time. All statistical analysis was completed in JMP 12 utilizing a Tukey all pairs test. Results When subdivided by age, while there was no significant difference in the percentage of men in each age subgroup in return to continence, there was a significant increase in the number of days to return to continence in Group 3 (65 ± 4) versus Group 1 (45 ± 3). While, the percentage of men and the number of days to potency in Group 3 (82%; 159 ± 11) was significantly higher than Group 1 (91%; 122 ± 16). Next, when subdivided by both age and pre-op SHIM, there was no significant difference in the number of days to continence or percentage of patients with return within one year. Lastly when subdivided by all here factors (age, pre-op SHIM, and NS), there were no significant differences in the number of days or percentage of patients whom achieved continence within one year. While, group 3 was most effects by both degree of nerve spare and pre-operative SHIM, with the main significant difference being in Group 3b when subdivided into FNS versus PNS. Conclusions Age, pre-operative SHIM and degree of nerve spare all have a significant effect on the return of continence and potency in men ? 55yo, thereby reinforcing the role of each in return of functional outcomes. Increases in age have a significant impact on recovery of potency. Younger patients with a pre-operative SHIM >20 who underwent a FNS report the fastest return to both continence and potency. Funding None
Authors
Tracey Woodlief
Hariharan Ganapathi Gabriel Ogaya-Pinies Eduardo Hernandez Travis Rogers Vipul Patel |
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MP93-13 |
Exploring positive surgical margins after minimally invasive radical prostatectomy: does body habitus really make a difference? |
Prostate Cancer: Localized: Surgical Therapy VII | 17BOS |
Abstract: MP93-13 Sources of Funding: None Introduction Positive surgical margins (PSMs) at radical prostatectomy (RP) are generally recognized as a surrogate of poor or difficult dissection of the prostatic gland. In open RP cohorts, obesity seems to be associated to an increased risk of PSMs, probably due to the technical challenge that obese men pose to surgical access. Minimally invasive RP has been claimed to possibly reduce PSM rate. Aim of the study was to explore the impact of obesity and body habitus on PSM risk and their localisation during laparoscopic and robotic-assisted RP. Methods We reviewed 539 prospectively enrolled patients undergoing laparoscopic and robotic-assisted RP with pT2 prostate cancer. The outcome measured was rate of PSM according to the BMI and surgical approach (laparoscopic vs robotic-assisted). BMI groups were compared using Kruskall-wallis or ?2 test, as appropriate. Uni- and multivariate logistic regression models were constructed to assess the impact of BMI and surgical technique on PSM risk. Results Overall, 127 (24%) of men had PSMs detected at final specimen evaluation. Mean PSM length was 3.9±3.4mm, and 30 (6%) men presented significant margins ≥4mm. Analysing the rate of PSMs across BMI categories, no significant association between increased BMI and PSM was detected (all p>0.48)(table 1). On uni- and multivariate logistic regression BMI was not a statistically significant risk factor for PSM (p=0.14), nor was the minimally invasive technique (laparoscopic vs robotic-assisted) (p=0.54). Conclusions In this study obese men do not appear to have a significant increase in risk of PSMs at RP compared to lean and overweight men when operated by a minimally invasive approach. The magnified vision and increased access to the pelvis allowed by a laparoscopic and robotic-assisted approach may be accountable for our findings. Larger studies are needed to validate our results. Funding None
Authors
Simone Albisinni
Julien Grosman Fouad Aoun Thierry Quackels Alexandre Peltier Roland van Velthoven Thierry Roumeguère |
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MP93-14 |
Extraperitoneal vs. Transperitoneal Robot-Assisted Radical Prostatectomy in the Morbidly Obese |
Prostate Cancer: Localized: Surgical Therapy VII | 17BOS |
Abstract: MP93-14 Sources of Funding: none Introduction When operating deep in the abdomen and pelvis, excess fat can interfere with accessing key anatomical structures and create difficulty in dissection and reconstruction. Since intraperitoneal fat is avoided during extraperitoneal robot assisted radical prostatectomy (eRARP), some Urologists have advocated this approach over its transperitoneal counterpart (tRARP) when operating on morbidly obese men (BMI>40). Herein, we aim to compare outcomes of eRARP vs. tRARP in the morbidly obese. Methods A chart review of patients who have undergone robot assisted radical prostatectomy (RARP) at a tertiary care academic center from July 1, 2003 through April 30, 2016 was undertaken. Patients with BMI >40 were identified. Those with concomitant inguinal hernia repair were excluded. The resulting eRARP and tRARP groups were compared for demographic, clinical and pathologic characteristics. Regression analysis was performed between the groups with Age, BMI, ASA score and D'Amico classification as selected covariates. Results 3168 patients underwent RARP during this time period, of which 82 patients met our inclusion and exclusion criteria; each group comprised 41 patients. No differences were noted in age, BMI, ASA score or pre-operative PSA. The tRARP group had a higher clinical stage (p=0.016), biopsy Gleason score (p=0.007) and D'Amico risk category (p<0.00001). The tRARP group had a higher rate of pelvic lymph node dissection (PLND, p<0.00001). No differences were noted in rate of nerve sparing. No differences were noted in OR time, estimated blood loss (EBL), length of stay (LOS) or time to catheter removal (TCR). No differences were noted in surgical margin status or overall complications (either calculated as binary or total number). On regression analysis, no differences were noted in complications, OR time, LOS, TCR or EBL. Conclusions In this cohort, surgical approach (eRARP vs. tRARP) did not affect intra- or peri-operative outcomes in morbidly obese men undergoing RARP so surgeons should tailor their approach based on comfort level. Funding none
Authors
David Horovitz
Hao Sun Changyong Feng Edward Messing Jean Joseph |
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MP93-15 |
Feasibility of a weight management program tailored for overweight men with localized prostate cancer: a pilot study |
Prostate Cancer: Localized: Surgical Therapy VII | 17BOS |
Abstract: MP93-15 Sources of Funding: The Prostate Cancer Guys Resilient by Individualized Training (PCaGRIT) trial was supported the University of Kansas Cancer Center Cancer Prevention Pilot Grant program (JHR), and in part by an NIH Clinical and Translational Science Award grant (UL1 TR000001, formerly UL1RR033179), awarded to the University of Kansas Medical Center. Support for J. Hamilton-Reeves was provided by KL2 training grant KL2TR000119 a CTSA grant from NCATS awarded to the University of Kansas Medical Center for Frontiers: The Heartland Institute for Clinical and Translational Research (JHR). The contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH or NCATS. Research reported in this publication was supported by the National Cancer Institute Cancer Center Support Grant P30 CA168524 and used the Biospecimen Shared Resource and the Biostatistics and Informatics Shared Resource. Medifast donated the meal replacements for the study. Introduction Men who are overweight at the time of prostatectomy are more likely to have recurrence and die from prostate cancer than healthy weight men. They also have higher risk for cardiovascular disease, the most common cause of death for prostate cancer survivors. Our study tests the feasibility of weight loss before and maintenance after prostatectomy in overweight men with localized prostate cancer. Methods Men scheduled for prostatectomy received a weight management program (intervention; n=15) or standard of care (non-intervention; n=5). The intervention included behavior coaching, diet including meal replacements, physical activity, and self-monitoring technology. Body weight, body composition, cardiometabolic markers, and quality of life were measured at baseline, 1 week before surgery, and 12 weeks after surgery. Changes within and differences between groups were analyzed using the two-sample t-test. Results The intervention led to 6 kg of weight loss (95%CI, 3-8 kg; P<0.001) and 4 kg of fat loss (95%CI, 2-6 kg; P<0.001) from baseline to surgery (mean=6.6 weeks). Between group differences in weight change and fat loss were significant (P=0.012; P=0.032, respectively). In the intervention group, blood glucose decreased by 11 mg/dL (95%CI, 0.5-22 mg/dL; P=0.04); insulin decreased by 3.4 µIU/mL (95%CI, 0.1-7 µIU/mL; P=0.03); C-peptide decreased by 0.7 ng/L (95%CI, 0.17-1.3 ng/L; P=0.01); systolic blood pressure decreased by 8 mmHg (95%CI, 1-15 mmHg; P=0.03); and leptin:adiponectin ratio decreased (P=0.008) from baseline to surgery. Changes in lipid profiles were not significant. Twelve weeks after surgery, weight was maintained and physical quality of life was better in the intervention group than the non-intervention group (P=0.03). Conclusions The intervention led to significant weight loss and improved cardiometabolic markers. A larger, randomized controlled trial is needed to evaluate efficacy and cancer biomarkers. Funding The Prostate Cancer Guys Resilient by Individualized Training (PCaGRIT) trial was supported the University of Kansas Cancer Center Cancer Prevention Pilot Grant program (JHR), and in part by an NIH Clinical and Translational Science Award grant (UL1 TR000001, formerly UL1RR033179), awarded to the University of Kansas Medical Center. Support for J. Hamilton-Reeves was provided by KL2 training grant KL2TR000119 a CTSA grant from NCATS awarded to the University of Kansas Medical Center for Frontiers: The Heartland Institute for Clinical and Translational Research (JHR). The contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH or NCATS. Research reported in this publication was supported by the National Cancer Institute Cancer Center Support Grant P30 CA168524 and used the Biospecimen Shared Resource and the Biostatistics and Informatics Shared Resource. Medifast donated the meal replacements for the study.
Authors
Meredith Metcalf
Cole Chana Lauren Hand Abigail Stanley Misty Bechtel Prabhakar Chalise Tanner Isaacson Debra K. Sullivan Jennifer Klemp Christie Befort J. Brantley Thrasher Jill M. Hamilton-Reeves |
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MP93-16 |
Impact of Obesity on Prostate Cancer Recurrence after Radical Prostatectomy |
Prostate Cancer: Localized: Surgical Therapy VII | 17BOS |
Abstract: MP93-16 Sources of Funding: none Introduction Conflicting data exist on the association of obesity with the risk of prostate cancer (PCa) recurrence after radical prostatectomy (RP), due in part to underpowered cohorts and limited follow up. Herein, we evaluated the association between obesity and PCa recurrence after RP using a large institutional dataset with long-term follow-up. Methods We reviewed years 1987-2013 of the Mayo Clinic RP Registry to identify men with Body Mass Index (BMI) information available. Men who underwent PCa treatment prior to RP and men with metastatic disease at RP were excluded. Patients were grouped into four BMI categories: < 25, 25-29.9, 30-34.9, and > 35. BMI > 30 was defined as obese. Standard descriptive statistics compared baseline characteristics, while forced entry multivariable cox proportional hazard models assessed the association of BMI with metastasis and prostate cancer mortality (PCM). Multivariable models were adjusted for pre-RP PSA, pathologic Gleason Score, pT stage, pN stage, margin status, age, adjuvant hormone therapy, adjuvant radiation, year of surgery, and open vs robotic approach. Results In our cohort of 18,039 men (median follow-up 9.3 years after RP), 20.6% (3,707), 51.9% (9,348), 21.9% (3,936) and 5.6% (1,016) had a BMI < 25, 25-29.9, 30-34.9, and > 35, respectively. Higher BMI categories had higher rates of pathologic Gleason Score 7-10 disease: 38.7%, 40.7%, 46.1%, 54.0%, respectively (p<0.001). Obese patients also had higher positive margin rates: 23.4%, 26.3%, 30.1%, 31.9%, respectively (p<0.001). PSA, pT stage, pN stage, and adjuvant therapy did not significantly differ between BMI categories (p>0.05). Log Rank comparisons found higher Kaplan-Meier rates of metastasis and PCM for patients with a BMI of 30-34.9 and > 35 (p<0.05 for all). On multivariable cox regression for metastasis, patients with a BMI 30-34.9 (HR 1.307, 95% CI 1.073-1.592, p=0.008) and BMI > 35 (HR 1.421, 95% CI 1.071-1.886, p=0.015) had an increased risk of metastasis relative to patients with a BMI < 25. Similarly, patients with a BMI 30-34.9 (HR 1.323, 95% 1.010-1.733, p=0.042) and BMI > 35 (HR 1.620, 95% CI 1.098-2.392, p=0.015) had higher PCM rates relative to patients with BMI < 25 on multivariable analysis. Conclusions Our data supports an independent association between BMI and PCa metastasis and cancer-specific mortality after RP. There was a direct increase in the odds of metastasis and PCM between the BMI 30-34.9 and BMI > 35 groups, further strengthening this link. Further study is warranted to determine if weight loss can abrogate this effect of obesity on PCa recurrence after RP. Funding none
Authors
Vidit Sharma
Mary E Westerman Michele Colicchia Alessandro Morlacco Matthew K. Tollefson Stephen A Boorjian R. Houston Thompson Igor Frank Matthew T Gettman R. Jeffrey Karnes |
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MP93-17 |
Assessment of health related quality of life (HRQOL) in patients submitted to extraperitoneal endoscopic radical prostatectomy (EERP) and transperitoneal endoscopic radical prostatectomy (TERP) with extended pelvic lymph node dissection |
Prostate Cancer: Localized: Surgical Therapy VII | 17BOS |
Abstract: MP93-17 Sources of Funding: none Introduction Radical prostatectomy (RP) remains the mainstay therapy in localized disease. In recent years, minimally invasive, endoscopic RP (ERP) gained widespread use although its influence on patients reported health related quality of life (HRQOL) was not fully established._x000D_ _x000D_ To assess HRQOL in men subjected to extraperitoneal, endoscopic radical prostatectomy (EERP) and transperitoneal endoscopic radical prostatectomy (TERP) with extended pelvic lymph node dissection. Methods HRQOL surveys were completed at baseline, 3 and 12 months after surgery. The general and prostate-specific sections of HRQOL were assessed with Medical Outcomes Study 36 – Item Short Form (SF-36) and University of California, Los Angeles Prostate Cancer Index (UCLA – PCI) respectively._x000D_ Results The surveys were returned by 126 (76%) and 111 (67%) men after 3 and 12 months, respectively. Adjuvant radiotherapy was performed in 10 (9%) patients. Only patients without adjuvant treatment (radiotherapy or hormonotherapy) were included in the analysis, resulting in a final study cohort of 101 patients (71 and 30 for the TERP and EERP, respectively). The median patients age in TERP and EERP group was 62.0 and 64 years, respectively. There is no significant difference QOL scores for the baseline, after 3 months and 12 months after operation in each group._x000D_ In the EERP group Mental Health improved over the baseline after 12 months. In the TERP group Mental health and Social functioning improved over the baseline after 12 months._x000D_ In the rest of domains QOL scores did not change after 12 months in both groups. For the baseline score, at 3 months and 12 months there was no significant difference between the EERP and TERP groups except for sexual function that was worse in the EERP group at baseline._x000D_ Urinary function, urinary bother, sexual function and sexual bother had not returned to baseline at 12 months in both groups. Bowel function and bother was not different after 12 months in each group. At 12 months after ERP 41 (58%) and 17 (54%) men did not use any pads for 24 hours in TERP and EERP group, respectively_x000D_ Conclusions Endoscopic, extraperitoneal and transperitoneal radical prostatectomies with extended pelvic lymph node dissection do not alter patients reported health related quality of life. No significant differences were found between the two treatment groups. We could attributed that aggressive treatment of PCa do not more compromise HRQOL. Funding none
Authors
Sebastian Piotrowicz
?ukasz Nyk Mieszko Kozikowski Jan Powro?nik Jakub Dobruch |
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MP93-18 |
Cavernous Nerve Reconstruction by Processed Nerve Allograft during Robot-Assisted Radical Prostatectomy |
Prostate Cancer: Localized: Surgical Therapy VII | 17BOS |
Abstract: MP93-18 Sources of Funding: none Introduction To explore the technical feasibility of using processed nerve allograft in cavernous nerve repair during robot-assisted radical prostatectomy (RARP). Methods Twelve prostate cancer patients with normal pre-operative erectile and urinary function were enrolled in an IRB approved single arm pilot study to receive RARP with unilateral cavernous nerve reconstruction using processed nerve allograft. Patients were followed for 24 months after surgery. Erectile and urinary functional recovery was measured using the International Index of Erectile Function-EF domain (IIEF-6) and the Expanded Prostate cancer Index Composite (EPIC, Version 2.2002) questionnaires. Possible adverse events related to nerve graft implantation were assessed. Results Planned surgery was successfully performed in all 12 patients by a single surgeon without any attributed complications or adverse events. The implantation procedure extended operation time by16 ± 4.3 minutes. Two patients received androgen deprivation therapy post-operatively and were excluded from analysis. Partial recovery of erectile function (IIEF ≥13) was seen in 50% and 70% of patients by 12 and 24 months after surgery respectively, while recovery of potency (erection firm enough for intercourse, IIEF ≥22) was achieved in 50% of patients 24 months after surgery. Urinary continence (0-1 pad used per day) was restored in 75%, 83.3% and 91.7% of patients by 6, 12 and 24 months after surgery, respectively. Conclusions Cavernous nerve reconstruction using processed nerve allograft during robot-assisted radical prostatectomy is technically feasible and shows promise in recovery of desirable functional outcomes. Funding none
Authors
Svetlana Avulova MD
Kirk K Keegan MD Kristen R Scarpato MD Mark D Tyson MD William Sohn MD John Eifler MD Brock O'Neil MD |
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MP93-19 |
Prostate MRI Prior to Prostatectomy Does Not Impact Surgical Outcomes |
Prostate Cancer: Localized: Surgical Therapy VII | 17BOS |
Abstract: MP93-19 Sources of Funding: None Introduction Multiparametric magnetic resonance imaging (MRI) of the prostate has been increasingly utilized for both diagnosis and staging of prostate cancer (PCa). Studies have suggested that pre-prostatectomy MRI is predictive of extracapsular extension and lymph node involvement. However, the impact of this additional information on surgical outcomes has not been well defined. We examined our institutional experience of prostatectomy with or without preoperative MRI. Methods We identified patients at our institution who received prostate MRI within 6 months of prostatectomy for PCa between January 2012 and December 2015 (n=491). Using propensity scoring analysis, patients who had received MRI prior to prostatectomy were matched 1:1 to patients who did not receive preoperative MRI (based on age, race, body-mass index, comorbidity, PSA, Gleason score, and surgeon performing prostatectomy). The final matched cohort included 192 patients with preoperative MRI and 192 patients without. Multivariate regression analysis was performed for operative time, estimated blood loss (EBL), perioperative complication, and positive surgical margin. Results When controlling for all measured variables between the propensity matched cohorts, preoperative MRI was not predictive of operative time, EBL, complications, or positive surgical margins. Operative time and EBL were significantly associated with preoperative PSA and surgeon performing prostatectomy (p<0.01). Comorbidity (Charlson comorbidity index >2) was the only predictor of 30-day complication (p<0.01). The only predictor of positive surgical margin was increasing biopsy Gleason score (OR 2.3, p=0.04). Conclusions Although prostate MRI has become increasingly utilized in the diagnosis and staging of PCa, preoperative MRI does not impact technical prostatectomy outcomes in our institutional experience. Our findings do not support the routine use of preoperative MRI for surgical planning in patients with clinically localized PCa. Effects of preoperative MRI on patient self-reported outcomes after prostatectomy will be examined in the future. Funding None
Authors
Eric Kim
Joel Vetter Michael Glamore Seth Strope Robert Grubb III Gerald Andriole |
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MP93-20 |
Tumor contact length with prostate capsule on magnetic resonance imaging as a potential predictor for biochemical recurrence after robotic-assisted radical prostatectomy |
Prostate Cancer: Localized: Surgical Therapy VII | 17BOS |
Abstract: MP93-20 Sources of Funding: none Introduction Tumor contact length (TCL) on multiparametric magnetic resonance imaging (mpMRI), defined as the length of a lesion in contact with the prostatic capsule, is a novel marker with promising early results. We aimed to evaluate TCL as a predictor of pathological extracapsular extension (ECE), and biochemical recurrence (BCR) in patients undergoing robotic-assisted radical prostatectomy (RARP). Methods We retrospectively analyzed the records of 230 consecutive patients who underwent prostate mpMRI followed by RARP from April 2013 to July 2016. TCL was measured using T2-weighted magnetic resonance images. Logistic and Cox regression analysis were used to assess associations of clinical, imaging, and histopathological variables with ECE and BCR. Receiver operating characteristic curves were used to characterize and compare TCL performance with biopsy Gleason score (bGS) and Partin tables. Results There were 61/230 (26.5%) ECE and 18/230 (7.8%) BCR patients. Patients with adverse pathology/oncologic outcomes had longer TCL compared to those without adverse outcomes (ECE: 16.6 vs. 7.2mm, p<0.0001 and BCR: 13.4 vs. 9.3mm, p=0.0334). On multivariate analysis, TCL and bGS were the independent predictors of ECE (TCL odds ratio: 1.23, p<0.0001 and bGS odds ratio: 1.75, p=0.0202). Cox regression analysis demonstrated both TCL and bGS was significant predictors of BCR (TCL hazard ratio: 1.05, p=0.0423 and bGS hazard ratio: 1.96, p=0.0030). TCL alone was found to have good predictive ability for ECE (AUC: 0.84) and the best TCL thresholds for predicting ECE was 13.5 mm (sensitivity 70%, specificity 86%). Kaplan-Meier survival analysis was used to compare BCR-free survival between patients with TCL less vs. more than 13.5 mm (Fig). Patients with TCL >13.5 mm had significantly poor BCR-free survival compared to patients with TCL ?13.5mm (log-rank test, p=0.0059). Conclusions We demonstrate that TCL is an independent predictor of ECE. The longer the TCL, the more biochemical recurrence likely occur. Funding none
Authors
Kazumi Kamoi
Koji Okihara Fumiya Hongo Yasuyuki Naitoh Atsuko Iwata Motohiro Kanazawa So Ushijima Osamu Ukimura |
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MP94-01 |
Protective effect of platelet-rich plasma on urethral stricture model of male rats |
Bladder & Urethra: Anatomy, Physiology & Pharmacology II | 17BOS |
Abstract: MP94-01 Sources of Funding: Istanbul Bilim University Introduction Urethral stricture formation is caused by fibrosis after excessive collagen formation to the any injury or trauma to the urethra. We evaluated the affects of platelet-rich plasma (PRP) on urethral stricture model of male rats Methods Urethral stricture model was performed by coagulation current to the male urethra. There were 4 groups of 6 rats in each one: control (C), C+PRP applied, urethral stricture (US), US+PRP applied. PRP was applied to the urethra after coagulation current induced injury as soon as possible. On 14th day all rats were sacrified and urethral tissues investigated for collagen type I (col I), collagen type III (col III), platelet-derived growth factor-A (PDGF-A), platelet-derived growth factor-B (PDGF-B) and transforming growth factor-B (TGF-B) with quantative real-time polymerase chain reaction (RT-PCR) and Western-Blot analysis. The efffect of urethral damage and healing was investigated for col I/col III ratio. Results Collagen type I increase in fibrosis process in US is well defined. Collagen type I/ collagen type III ratio was significantly high in US group (*, p=0,000) than others while US+PRP group had comparable results with the control group (p=0,999). (Graphic 1) RT-PCR analysis of col I, col III, PDGF-A, PDGF-B and TGF-B was shown in table 1._x000D_ Graphic 1: Col I/Col III type ratio of each group._x000D_ Table 1: Results of RT-PCR analysis of col I, col III, PDGF-A, PDGF-B and TGF-B.(* Significant between US and US+PRP groups; & not significant between C and US+PRP groups; ** significant between C and US+PRP groups; )_x000D_ _x000D_ _x000D_ _x000D_ Conclusions Our results show that PRP has a preventive effect on stricture formation in US rat model shown by its effect on collagen synthesis, especially in recurrent cases. Further studies that eventually show the effects of PRP on human tissues is necessary and promising. Funding Istanbul Bilim University
Authors
HASAN TAVUKCU
OMER AYTAÇ FAT?H ATU? BURÇ?N ALEV OZGE CEV?K AY?EN YARAT SULE CET?NEL GÖKSEL SENER HALUK KULAKSIZO?LU |
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MP94-02 |
Analysis of intravesical hyaluronic acid effectiveness on avoiding the development of actinic cystitis in patients during pelvic radiation therapy |
Bladder & Urethra: Anatomy, Physiology & Pharmacology II | 17BOS |
Abstract: MP94-02 Sources of Funding: Foundation Center of Amazonas State Oncology Control . Introduction Actinic cystitis is a common manifestation resulting from radiotherapy treatment of pelvic malignancies. Exposure to radiation causes bladder histopathological changes, thus the urothelium of the bladder is replaced by an unusual layer of cells with eosinophilic infiltration. The main symptoms of actinic cystitis are urinary urgency, dysuria, urinary frequency and hematuria. The objectives of this study were to determine whether the hyaluronic acid intravesical instillation reduces the acute and late toxicity of radiotherapy and to assess the existence of side effects with the use of hyaluronic acid. Methods The research is a randomised clinical trial, was conducted at the Foundation Center of Amazonas State Oncology Control between August 2015 and July 2016. The patients participating in the study were divided into two groups: the control group and the group receiving the drug, random and randomly, all had begun to radiation treatment for cervical cancer. The monitoring included the evaluation of the toxicity of the bladder with 3, 6 and 9 months after the end of radiotherapy. The project was approved by the ethics committee of Foundation Center of Amazonas State Oncology Control in the opinion 1.456.189. Results We followed 35 patients, 18 in the control group and 17 in the intervention group. None of the patients who received instillations of hyaluronic acid had urinary symptoms of actinic cystitis, three patients (16.67%) of the control group showed acute cystitis (symptoms develop during or within three months after radiotherapy) and five (27.7%) had subacute cystitis (symptoms develop between 3-6 months after radiotherapy). No case of late actinic cystitis (symptoms develop 6 months after radiotherapy) was reported in either group, neither was reported any urinary infection or allergic reactions in the group where there was intervention. Conclusions The hyaluronic acid has shown effectiveness in the prophylaxis of actinic cystitis and its secure his administration. Funding Foundation Center of Amazonas State Oncology Control .
Authors
Giuseppe Figiuolo
William Leal Etelvina Karditsa Moreno |
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MP94-03 |
ANTI-VEGF TREATMENT DECREASES BLADDER PAIN IN CYCLOPHOSPHAMIDE CYSTITIS IN MICE |
Bladder & Urethra: Anatomy, Physiology & Pharmacology II | 17BOS |
Abstract: MP94-03 Sources of Funding: NIH/NIDDK MAPP (Multi-disciplinary Approach to the Study of Chronic Pelvic Pain) Research Network Introduction Vascular endothelial growth factor (VEGF) is a pleiotropic cytokine known for its angiogenesic activity. Clinical studies have shown that tissue and urinary levels of VEGF are elevated among patients with interstitial cystitis/bladder pain syndrome (IC/BPS). We investigated whether treatment with anti-VEGF neutralizing antibodies reduced pain and voiding dysfunction in the cyclophosphamide (CYP) cystitis model of bladder pain in mice. Methods Adult female mice received anti-VEGF neutralizing antibodies (10 mg/kg intraperitoneal B20-4.1.1 VEGF mAb) or saline (control) prior to receiving CYP (150 mg/kg intraperitoneal). Pelvic nociceptive responses were assessed 5, 48, and 96 hours later by applying von Frey filaments to the lower abdominal/pelvic area. Spontaneous micturition was assessed using the void spot assay. A second paradigm where anti-VEGF treatment was given after CYP cystitis was also investigated. Results Systemic anti-VEGF pre-treatment in mice prior to CYP-induced cystitis significantly reduced the pelvic nociceptive response compared to saline pre-treatment (control). As shown in the figure, pelvic hypersensitivity decreased significantly between 5 and 48 hours post-CYP in the anti-VEGF pre-treatment group (p=0.0051, n=7). By 96 hours post-CYP, pelvic hypersensitivity had decreased by 47.2% from its peak, and was no longer significantly different from the baseline level in mice pre-treated with anti-VEGF (p=0.17). In contrast, pelvic hypersensitivity remained elevated at 5, 48 and 96 hours in the saline pre-treatment group. There was no difference in urinary frequency and mean voided volume between the two groups at 5, 48, and 96 hours. In the second paradigm where anti-VEGF treatment was given after CYP cystitis has been established, pelvic hypersensitivity was still significantly increased at 96 hours compared to baseline (p=0.0007, n=7). Conclusions Administration of anti-VEGF neutralizing antibodies reduced pelvic/bladder pain in the CYP cystitis model of bladder pain compared to controls. Further investigation of the use of anti-VEGF antibodies to manage bladder pain or visceral pain in humans is warranted. Funding NIH/NIDDK MAPP (Multi-disciplinary Approach to the Study of Chronic Pelvic Pain) Research Network
Authors
H Lai
Baixin Shen Pooja Vijairania Xiaowei Zhang Sherri K. Vogt Robert W. Gereau IV |
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MP94-04 |
Mechanical characterisation and rupture pressure of human urethras: A feasibility study performed in explanted tissue from patients undergoing gender reassignment surgery |
Bladder & Urethra: Anatomy, Physiology & Pharmacology II | 17BOS |
Abstract: MP94-04 Sources of Funding: None Introduction Knowledge of the mechanical properties of human urethral tissue is required to provide an accurate baseline for urethral graft materials. However, previous studies that characterise urethral tissue under intraluminal pressure are limited to animal models. This is the first study to characterise the baseline passive mechanical properties of human urethral tissue in order to better inform the design of tissue engineered biomaterials intended for use as urethral grafts. Furthermore, this group has previously employed porcine urethras as a rupture model to improve the safety of urinary catheterisation. This study also allows for the validation of such porcine models by determining the threshold inflation pressure of urinary catheter anchoring balloons pertaining to rupture in human urethras. Methods Following hospital ethical research committee approval, human urethras were obtained from 9 consenting patients undergoing male to female gender reassignment surgery. The elastic mechanical response of the tissue was characterised by subjecting samples to dynamic cyclical intraluminal pressure (0-10 kPa). The viscoelastic response was characterised by subjecting samples to a static pressure head range (0-10 kPa) and maintaining each pressure increment (1 kPa) for 300s. 12 Fr urinary catheters were then inflated with 10 ml of saline in the bulbar portion of the urethras. Tissue damage was assessed following inflation. Results Pressure-diameter testing reveals a nonlinear mechanical response typical of biological tissue whereby the urethral tissue becomes less compliant at higher intraluminal pressures. The mean compliance in the high pressure range (6-10 kPa) under dynamic and static loading was 0.57±0.38 and 1.34±0.55 %/kPa respectively. The increased compliance during static loading demonstrates the pronounced viscoelastic behavior of the urethral tissue. Furthermore, the mean inflation pressure pertaining to urethral rupture during catheter balloon inflation was 165±57 kPa. This is similar to the values obtained from testing of porcine tissue (150 kPa). Conclusions This study provides pertinent mechanical data that can be employed to improve the mechanics of tissue engineered urethral graft biomaterials by providing a baseline for both the elastic and viscoelastic response of the native tissue. It also validates an existing porcine urethral rupture model that is aimed at improving the safety of urinary catheterisation. Funding None
Authors
Eoghan Cunnane
Niall Davis Jochen Hess Michael Walsh |
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MP94-05 |
Chronic Rat Model for Testing New Therapies for Stress Urinary Incontinence |
Bladder & Urethra: Anatomy, Physiology & Pharmacology II | 17BOS |
Abstract: MP94-05 Sources of Funding: The Danish Council for Independent Research and Odense University Hospital Introduction Urethral sphincter function in a rat is assessed by measuring the leak point pressure (LPP). The current model uses urethane anesthesia and spinal cord injury, making the experiments terminal procedures. This study describes a new method, which allows repeated testing on the same animal. _x000D_ Methods Through a small skin incision, a modified 22G needle opened on one side to form a groove, was used to access the spinal canal between the L6 and S1 vertebrae. A 32G catheter was then inserted into the intrathecal (IT) space and the tip advanced to the level of T12. After minimum of 2 days, the rat was placed vertical on a tilt table and three micturition cycles were recorded under light isoflurane anesthesia (1.2 - 2%). Subsequently, an IT injection of lidocaine was used to suppress the micturition reflex. The pressure at which overflow incontinence started was recorded followed by manually evacuating the bladder and filling it to 50% of its capacity. Then the LPP was assessed using the Crede maneuver (CM). _x000D_ Results IT catheter insertion success rate was ~90%. Position of the IT catheter was confirmed by injection of lidocaine causing transient paraplegia in awake rat. Cystometry under light isoflurane anesthesia produced full micturition cycles with mean maximal pressure of 30.9 cm/H2O, (min. 18.6, max. 37.4) and mean intermicturition oscillatory pressure of 8.0 cm/H2O (min. 4.6, max. 11.9). IT administration of lidocaine completely blocked micturition contractions. The intravesical pressure at which overflow incontinence ensued was 29.6 cm/H2O (min. 24.0, max. 34.6). LPP using the CM was 31.0 cm/H2O (min. 18.5, max. 36.3)._x000D_ Conclusions In low concentration, isoflurane anesthesia preserves continence, bladder contraction and coordinated function between the bladder and sphincter. This makes it appropriate for testing LPP. Isoflurane anesthesia allows placing the animal vertical on the tilt table, and IT injection of lidocaine blocks micturition. The learning curve for IT catheter placement is steep. In most cases, the intravesical pressure at which overflow incontinence coincided closely with the LPP measured using the CM. This experimental design allows repeated evaluation of LPP in a single animal. Funding The Danish Council for Independent Research and Odense University Hospital
Authors
Chrissie T. Wøien
Thomas M. Andersen Travis K. Mann-Gow Peter Zvara |
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MP94-06 |
Morphological and functional restoration comparison between a novel bilayer chitosan and bladder acellular matrix graft as scaffolds in a rat bladder augmentation model. |
Bladder & Urethra: Anatomy, Physiology & Pharmacology II | 17BOS |
Abstract: MP94-06 Sources of Funding: National Natural Science Foundation of China?81370860?81670622? Introduction Confronted by the limitations of current biomaterials applied in bladder augmentation and urgent clinic needs of alternatives for traditional enterocystoplasty, this study compared the performance of a novel asymmetric bilayer chitosan scaffold with conventional bladder acellular matrix graft (BAMG) in the purpose to assess the feasibility of this strategy as a supplement or replacement for current bladder biomaterials. Methods Twenty-four 4-week-old male Sprague-Dawley rats were randomly divided into 3 groups which were subjected to augmentation cystoplasty with BAMG, bilayer chitosan scaffolds and sham operation respectively, with 8 rats in each group. At the time-points of 21 days and 70 days post-implantation, basic epidemiological data, morphological, histological (hematoxylin and eosin, Masson’s trichrome and immunofluorescence analyses) and functional evaluations were carried out to compare bladder regeneration comprehensively. Results Bilayer chitosan scaffold exhibited an excellent combination of mechanical strength and flexibility, with minimal fibrosis and contracture after integrated into bladder defect. All rats survived during the experimental period, recovered to normal activities and were able to void spontaneously without significant difference in body weight, except that one rat in BAMG group (70 days group) died of urinary ascites within first week post-op. It was proved that bilayer chitosan scaffold had a better performance in both histological staining and morphological analyses of cystography. While the de novo cytokeratin positive urothelia appeared more abundant in BAMG group than chitosan group when compared to control group, the regeneration of ?-smooth muscle actin (?-SMA) and SM22-? positive smooth muscle bundles, NeuN positive neural buttons, the mean number of CD31 positive vessels were more favorable in chitosan group than BAMG group, but still did not catch up with the normal level. The mean diameter of CD31 positive vessels revealed that the neo-vessels in BAMG and chitosan group were relatively immature. For both BAMG and chitosan groups, urodynamic analyses demonstrated that the bladder compliance was improved after augmentation, and the interval void cycle time, void volume and bladder capacity were elevated correspondingly, while the peak void pressure of BAMG was exceptionally high. Conclusions The asymmetric bilayer chitosan scaffold displayed a high potential in facilitating defect regeneration in the rat model of bladder augmentation, which still need further modifications in enhancing the regeneration of urothelia, accelerating re-innervation and promoting neo-angiogenesis. Funding National Natural Science Foundation of China?81370860?81670622?
Authors
Dongdong Xiao
Qiong Wang Mujun LU |
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MP94-07 |
Patients with nocturnal polyuria presented a different night-time and day-time bladder capacity: implication for nocturia |
Bladder & Urethra: Anatomy, Physiology & Pharmacology II | 17BOS |
Abstract: MP94-07 Sources of Funding: none Introduction To subtype patients with nocturia according to daily variations in the urine production and in the bladder capacity (BC). Methods Patients with ≥1 nocturia par day, both gender, were prospectively enrolled. Detailed medical history, body mass index (BMI), sonographic Post Void Residual (PVR) and a 3 days-FVC were collected. Patients with a PVR > 50 ml were excluded. Based on 3 days-FVC, frequency (24 hours, day-time, night-time), mean/minimum/maximum BC (24 hours, day-time, night-time), total voided volume (24 hours, day-time, night-time), Nocturia index (Ni) and Nocturnal Polyuria index (NPi) were assessed. Nocturnal Polyuria (NP) was defined as NPi > 20% in patients ≤ 35 years; > 33% in patients > 65 years; >20% + 2% every 5 years in patients between 35 and 65 years of age. BC was calculated by adding mean PVR to the micturition volume. Reduced BC was defined as a mean 24 hours BC < 200 ml. Severe nocturia was defined as ≥3 episodes per night. Patients were categorised in 4 subgroups according the presence/absence of NP and reduced BC. Results 84 patients were enrolled with a mean age of 62.6±13.5 years. 50/84 patients (59.5%) suffered from NP, and 50/84 patients (59.5%) had decreased BC. No gender difference in the incidence of NP and reduced BC were found. Patients with a reduced BC and NP presented a significant larger mean BC (p = 0.002) at night-time when compared to day-time and the highest number of nocturia episodes (3.2±1.6); patients with a normal BC and with NP presented a significant larger mean and maximum BC at night-time (p = 0.033 and p = 0.016, respectively) when compared to day-time (Table 1). In patients with reduced BC and without NP no significant variations in BC was observed between day-time and night-time (Table 1). On multivariate analysis BMI (OR: 1.28 per unit, 95%CI: 1.04-1.58; p = 0.019) and severe nocturia (6.26, 95%CI: 1.71-22.92, p = 0.006) were independent predictive factors for NP, while only severe nocturia (3.77, 95%CI: 1.20-11.83, p = 0.023) was an independent predictive factor for a reduced BC. Conclusions Patients with NP presented a different BC between day-time and night-time. Severe nocturia (≥3 episodes per night) predicts the presence of NP and a reduced BC. Our data suggest that in patients with severe nocturia both conditions should be considered and managed. Funding none
Authors
Fabrizio Presicce
Cosimo De Nunzio Federica Puccini Alberto Melchionna Riccardo Lombardo Andrea Tubaro |
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MP94-08 |
GROUP III METABOTROPIC GLUTAMATE RECEPTOR-MEDIATED REGULATION OF MICTURITION REFLEX IN URETHANE-ANESTHETIZED RATS |
Bladder & Urethra: Anatomy, Physiology & Pharmacology II | 17BOS |
Abstract: MP94-08 Sources of Funding: None Introduction The modulatory actions of glutamate, the main excitatory neurotransmitter in the central nervous system, are exerted via activation of metabotropic glutamate receptors (mGluRs). Eight distinct mGluRs (mGluR1-8) have been classified into three groups (I-III) based on their sequence homology. Group III mGluRs (mGluRIII; mGluR4, mGluR6, mGluR7 and mGluR8) are widely distributed throughout the central nervous system. However, it is unknown whether mGluRIII plays a role in the regulation of neural mechanisms controlling the micturition reflex. In the present study, we assessed whether L-(+)-2-amino-4-phosphonobutyric acid (L-AP4), a selective mGluRIII agonist, affects the micturition reflex in urethane-anesthetized rats. Methods Adult female Sprague-Dawley rats weighing 238 to 261 g were used. Continuous cystometrograms (CMG, 0.04 ml/min infusion rate) were performed in two groups of urethane-anesthetized rats. A group of 24 rats was used for intracerebroventricular administration of 1-10 µg of L-AP4 via a catheter inserted into the lateral ventricle. Using a stereotaxic micro-injector, a 30 gauge needle attached to a 10 µl Hamilton syringe was inserted into the lateral ventricle and single doses of drugs were administered in a volume of 2 µl during 2 minutes. In the second group of 24 rats, 1-10 µg of L-AP4 were administered intrathecally via an intrathecal catheter. Intrathecal injections were made through a polyethylene-10 (PE-10) catheter positioned at the level of the L6-S1 spinal cord. A PE-10 intrathecal catheter was implanted using isoflurane anesthesia 3 days before the experiments. Cystometric parameters were recorded and compared before and after drug administration. Results Intracerebroventricular administration of L-AP4 at doses of 1, 3 and 10 μg (n=8 per dose) increased intercontraction intervals in a dose dependent fashion to 117.1 ± 12.3%, 132.5 ± 10.5% and 137.1 ± 15.6% of the control value, respectively (p <0.01), but did not affect residual urine or baseline pressure at any of the doses tested. Intrathecal administration of L-AP4 at doses of 1, 3 and 10 μg (n=8 per dose) also increased intercontraction intervals in a dose dependent fashion to 125.3 ± 8.2%, 136.9 ± 7.1% and 142.7 ± 12.6% of the control value, respectively (p <0.01), but did not affect residual urine or baseline pressure at any of the doses tested. Conclusions The results of our study indicate that in urethane-anesthetized rats activation of mGluRIII can inhibit the micturition reflex at supraspinal and spinal sites. Thus, mGluRIII could be a potential target for the treatment of bladder dysfunction, such as overactive bladder. Funding None
Authors
Masashi Honda
Yusuke Kimura Bunya Kawamoto Panagiota Tsounapi Katsuya Hikita Shogo Shimizu Takahiro Shimizu Motoaki Saito Atsushi Takenaka |
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MP94-09 |
ROLE OF THE SEROTONERGIC SYSTEM IN URETHRAL CONTINENCE REFLEXES DURING SNEEZING IN RATS |
Bladder & Urethra: Anatomy, Physiology & Pharmacology II | 17BOS |
Abstract: MP94-09 Sources of Funding: NIH R01DK107450 Introduction The spinal serotonergic pathways are reportedly involved in the control of urethral continence reflexes that prevent stress urinary incontinence (SUI). We previously demonstrated that serotonin (5HT) receptor subtypes, 5HT1A and 5HT2C, respectively reduce and enhance the urethral continence reflex during sneezing in rats. However, because there are other multiple excitatory and inhibitory 5HT receptors, the overall effects of the 5HT system on the urethral function are not well elucidated. Therefore, in this study, we examined the effects of 5HT depletion induced by p-chlorophenylalanine (PCPA) that inhibits 5HT synthesis, on urethral baseline activity and reflex contractions during sneezing in rats. Methods We used female 12-week-aged Sprague-Dawley rats, which were divided into two groups; vehicle-administered (Normal, n = 6) and PCPA-administered groups (PCPA, n = 5). PCPA (200 mg/kg/day) was administered intraperitoneally for two days. Thereafter, using a microtransducer-tipped catheter inserted to the mid-urethra, we assessed urethral baseline pressure (UBP) and the amplitude of urethral responses during sneezing (AURS) under urethane anesthesia. UBP was determined from a plateau section of pressure recordings just before inducing sneezing, which was induced by intranasal stimulation with a whisker. AURS values were measured as the urethral maximal pressure change from baseline during sneezing. To evaluate induced sneeze intensity, abdominal pressure during sneezing (Pabd) was also measured via an intraabdominal balloon catheter. All data are shown in cmH2O. Results UBP and AURS were both significantly decreased in the PCPA group (17.8 and 36.7) compared to the Normal group (31.1 and 71.8), respectively (Figure). There was no statistical difference in Pabd between two groups (Normal; 18.2, PCPA; 28.3). Conclusions This result indicates that activation of the serotonergic system contributes to maintaining the urethral baseline activity and the urethral continence reflex during stress conditions such as sneezing, which are reportedly attributable to contractions of smooth and striated urethral sphincter muscles, respectively. Also, 5HT-depleted rats could be a suitable SUI model to investigate the effects of 5HT receptor subtype-selective agonists on urethral continence function._x000D_ Funding NIH R01DK107450
Authors
Takahisa Suzuki
Takahiro Shimizu Joombeom Kwon Eiichiro Takaoka Shun Takai Nobutaka Shimizu Naoki Wada Seiichiro Ozono Naoki Yoshimura |
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MP94-10 |
The Viscoelastic, Reversibly Plastic, Behavior of Detrusor Smooth Muscle Explains Bladder High Compliance. |
Bladder & Urethra: Anatomy, Physiology & Pharmacology II | 17BOS |
Abstract: MP94-10 Sources of Funding: None Introduction : Biological soft tissues are viscoelastic materials because they display time-independent pseudo-elasticity and time-dependent viscosity. Upon an imposed ramp increase then decrease in strain, the resultant increase and decrease in stress, termed loading and unloading respectively, produce nonlinear stress-strain curves, and a reversible reduction in the stress-strain work area that identifies the viscous component. However, there is evidence that bladder tissue may also display plastic behavior, defined as an increase in strain that is unrecoverable unless work is done by the material. In the present study, an electronic lever was used to induce controlled changes in stress and strain to determine whether the material properties of rabbit detrusor smooth muscle (rDSM) represent a viscoelastic or viscoelastic-plastic material. Methods Strips of DSM free from underlying mucosa were removed from rabbit bladders. Each tissue was placed in an organ bath connected to an electronic lever and length-adjuster and subjected to a length-tension protocol to identify the length (Lref) that produced the strongest active force induced by KCl. Each ring was subsequently set to 80% Lref and subjected to sequential ramp loading and unloading cycles, stress-strain and stiffness-stress analyses, and a step-loading, load-clamp, step-unloading (creep) protocol. Results Ramp loading-unloading cycles revealed that rDSM displayed reversible viscoelasticity. The viscous component was responsible for establishing a high stiffness at low stresses that increased only modestly with increasing stress compared to the large increase produced when the viscosity was absent and only pseudo-elasticity governed tissue behavior. The creep protocol revealed that rDSM underwent extensive softening correlating with plastic deformation and creep that was reversible upon activation of muscle contraction. Softening reversal was prevented by inhibitors of actomyosin crossbridge cycling. Conclusions Together, the data support a model of DSM as exhibiting not only viscoelasticity, but also plasticity, the degree of which is controlled by the degree of motor protein activation. This model explains the mechanism of instrinsic bladder compliance as “slipping� crossbridges, predicts that wall tension is dependent not only on vesicle pressure and radius but also on actomyosin crossbridge activity, and identifies a novel molecular target for compliance regulation both physiologically and therapeutically. Funding None
Authors
Randy Vince
John Speich Adam Klausner Christopher Neal Amy Miner Paul Ratz |
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MP94-11 |
AUTOPHAGY, APOPTOSIS AND CELL PROLIFERATION IN EXTROPHY-EPISPADIAS COMPLEX |
Bladder & Urethra: Anatomy, Physiology & Pharmacology II | 17BOS |
Abstract: MP94-11 Sources of Funding: None Introduction Very few pathophysiological mechanisms have been proposed as the etiology of bladder exstrophy (BE). Autophagy, or type II programmed cell death pathway, is an evolutionary conserved process involving intracellular degradation and recycling of cytoplasmic organelles. A basal level of autophagy is detected in most tissues, maintaining cellular homeostasis and viability through development and differentiation of eukaryotic organisms. Impairment of protein degradation pathways such as autophagy has been described in disorders relating to several organs and tissues including, neural defects acute, diseases of skeletal and cardiac muscles, and congenital ureteropelvic junction obstruction. However, it&[prime]s alteration in bladder smooth muscle cells of BE patients has not yet been reported. Herein, the authors investigated the state of autophagy and its interactions with cells apoptosis and proliferation in patients with BE. Methods Primary cultures of bladder smooth muscle cells were established from patients with successful neonatal bladder closure (group 1, N=5), delayed closure due to small bladder template (group 2, N=5) and vesicoureteral reflux as control (group3, N=5). The myogenicity of the cultures was determined using anti-desmin antibody. Immunofluorescence staining for LC3 was used to detect autophagy. Cells apoptosis was assessed using TUNEL assay, 4&[prime], 6-diamidino-2-phenylindole staining. Cellular proliferation was assessed by image analysis of immunofluorescence staining for Ki-67. Results Immunohistochemical staining revealed consistent positivity (greater than 95%) for Desmin in all cultures that confirms the myogenicity of them. Apoptosis was significantly higher in delayed closure group compared to other groups. Autophagy marker (LC3) was more expressed in delayed closure group compared to the other groups. Cellular proliferation was significantly lower in delayed closure group compared with control and successful neonatal closure groups. _x000D_ Conclusions Our results confirms that there are distinct differences in bladder smooth muscle cell function between control, successful neonatal closure and delayed closure cases due to small bladder template which persist in culture. Children with slower bladder growth and small bladder templates showed up-regulated autophagic process and increased apoptotic indices while experiencing a dramatic decrease in their bladder smooth muscle cells proliferation. Finally the concept of manipulating autophagy may lead to promising outcomes for BE patients in future. Funding None
Authors
Mahsa Shabaninia
Ali Tourchi Heather Di Carlo John Gearhart |
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MP94-12 |
Bladder Outlet Obstruction induced remodeling of extracellular matrix of human bladder smooth muscle cells via IL-6 |
Bladder & Urethra: Anatomy, Physiology & Pharmacology II | 17BOS |
Abstract: MP94-12 Sources of Funding: This study was supported by Grant No. 31170907, No. 31370951, No. 81470927 and No.81300579 from the National Natural Science Foundation of China, Grant No. 2014SCU04B21 from Fund for Distinguished Young Scholars of Sichuan University, Grant No.JH2014053 from Academic Leader Traning Fund of Sichuan Province and Grant No. JH2015017 from Application-oriented Foundation of Committee Organization Department of Sichuan Provincial Party. _x000D_ Introduction Bladder Outlet Obstruction(BOO) is one of the pathological changes resulted from abnormal intravesical pressure. We investigated the effects of hydrostatic pressure and mechanic strain on the release of inflammatory cytokines in rat and human bladder smooth muscle cells (HBSMCs) and tried to explore the relationship of Il-6 and the remodeling of of extracellular matrix of human bladder smooth muscle cells. Methods Animal model of bladder outlet obstruction was induced by urethra ligation. HBSMCs were subjected to elevated hydrostatic pressure and mechanic strain. The expression of inflammatory genes were analysed using DNA microarrays. IL-6 was confirmed by quantitative RT–PCR and immunohistochemical staining. Specificity of the IL-6 was determined with qRT-PCR with small interfering ribonucleic acid transfection and iL-6 receptor inhibitor (SC144). And specificity of the downstream was determined with qRT-PCR with small interfering ribonucleic acid transfection and STAT3 inhibitor(S31-201)._x000D_ Results In BOO, inflammatory genes were remarkably induced. in vitro, the expressions of IL-6 were significantly increased. Hydrostatic pressure and mechanic strain both promoted the IL-6 mRNA expression. Additionally, IL-6 increased the mRNA expression of MMP7 and TIMP1, decreased the mRNA expression of collagen and fibronectin. The “knock- down” of activation of IL-6 receptor using target small interfering ribonucleic acid transfection and inhibitor iL-6 receptor(SC144) significantly decreased the expression of MMP7 ,TIMP1 and partially increased the collagen and fibronectin. Additionally, pressure-induced MMP7 andTIMP1 were partially suppressed by STAT3 pathway using target small interfering ribonucleic acid transfection and inhibitor STAT3 (S31-201). Conclusions IL-6 was involved in the remodeling of extracellular matrix in HBSMCs under mechanic strain and hydrostatic pressure, indicating that IL-6 play an important role under in BOO. Funding This study was supported by Grant No. 31170907, No. 31370951, No. 81470927 and No.81300579 from the National Natural Science Foundation of China, Grant No. 2014SCU04B21 from Fund for Distinguished Young Scholars of Sichuan University, Grant No.JH2014053 from Academic Leader Traning Fund of Sichuan Province and Grant No. JH2015017 from Application-oriented Foundation of Committee Organization Department of Sichuan Provincial Party. _x000D_
Authors
Yifei Lin
Kunjie Wang |
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MP94-13 |
The effect of free radical scavenger on the oxidation stress in partial bladder outlet obstruction and its relief in rat model |
Bladder & Urethra: Anatomy, Physiology & Pharmacology II | 17BOS |
Abstract: MP94-13 Sources of Funding: none Introduction In patients with BPH, de novo UI developed in 7.1-44.0% after HoLEP. Urodynamic involuntary detrusor contraction (IDC) was often observed in these patients. Ischemia reperfusion injury that occurs after de-obstruction has been proposed as a main cause of post-operative IDC. We investigated the effect of free radical scavenger (tempol) after relief of partial bladder outlet obstruction (pBOO) on bladder function in a rat model. Methods Eight-week-old female Sprague Dawley of 40 rats (200-250g) were induced pBOO, and relieved it 3 weeks later. Rats were divided randomly 4 groups: tempol treated for 1 week (T1 group) and 3 weeks (T3 group), and no treated for 1 week (nT1 group) and 3 weeks (nT3 group). Cystometrograms were obtained in unanesthetized, unrestrained rats in metabolic cages at 1 or 3 weeks after relief, according to grouping, respectively. After completion of the investigation, the bladder was isolated and weighted. H&E, Masson trichrome and TUNEL staining were used to analyze the change of histology of the bladder. Results Tempol treated groups decreased significantly in the number of IDC per voiding cycle (nT1 vs. T1, 1.18±0.82 vs. 0.36±0.40, P=0.010; nT3 vs. T3, 1.51±0.69 vs. 0.23±0.25, P=0.002). In the H&E staining, treated groups decreased significantly in thickness of the detrusor muscle layer (nT1 vs. T1, 1164.17±190.58 vs. 776.45±140.78, P<0.001; nT3 vs. T3, 905.82±161.16 vs. 726.26±162.76, P=0.043). In the Masson Chrome staining, the rates of collagen fiber were significantly lower in the treated groups. Apoptosis detected by TUNEL was observed in the urothelial cell layer mainly. The treated groups decreased significantly in the rate of apoptosis in urothelial cell layer (nT1 vs. T1, 48.9±3.36% vs. 32.7±11.10%, P=0.024; nT3 vs. T3, 25.8±4.67% vs. 15.7±9.83%, P=0.314). Conclusions Ischemia reperfusion injury that occurred after de-obstruction caused histologic and functional change of the bladder. Free radical scavenger could prevent this oxidative stress. Funding none
Authors
Min Soo Choo
Songzhe Piao Seung-June Oh |
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MP94-14 |
Urodynamic evaluation of DA-8010 in conscious rats with partial bladder outlet obstruction |
Bladder & Urethra: Anatomy, Physiology & Pharmacology II | 17BOS |
Abstract: MP94-14 Sources of Funding: none Introduction DA-8010 is a novel, bladder-selective muscarinic receptor 3 antagonist being developed for the treatment of overactive bladder (OAB). The objectives of this study were to investigate the urodynamic effects of DA-8010 on detrusor overactivity (DO) in awake rats with partial bladder outlet obstruction (pBOO) and to compare its effect with that of a currently used antimuscarinic agent, solifenacin. Methods A total of 40 female Sprague-Dawley rats were subjected to sham operated controls (n=8) and pBOO. DO was induced by partial urethral ligation for 5 weeks. Rats with DO were divided randomly into 4 groups, treated with DA-8010 0.03 mg/kg, DA-8010 0.1 mg/kg, solifenacin 0.2 mg/kg, and solifenacin 1 mg/kg. Cystometrograms were obtained before and after intravenous administration of test compounds in unanesthetized, unrestrained rats in metabolic cages. After completion of the investigation, the bladder was isolated and weighted. Results Results of 37 rats were analyzed. Compared with sham controls, pBOO animals induced DO including shorter micturition intervals, smaller voided volume and reduced bladder capacity. After the administration of DA-8010, DO rats significantly showed longer micturition intervals, larger micturition volume and bladder capacity. In particular, there were no significant differences in residual volume. DA-8010 at 0.1 mg/kg also decreased the peak micturition pressure and basal pressure, whereas a dose of 0.03 mg/kg did not. Solifenacin increased the micturition interval, but did not affect micturition volume. At the higher dose, solifenacin significantly increased the residual volume. Conclusions DA-8010, a novel antimuscarinic agent exerts beneficial effects on the DO induced by pBOO in awake rats, demonstrating that DA-8010 increased both micturition intervals and micturition volume. Furthermore, whereas solifenacin exhibited increasing residual volume in rats with pBOO, DA-8010 did not affect it. These findings suggest that DA-8010 may be a urodynamically effective and safe agent for treatment of OAB and DO. Funding none
Authors
Min Soo Choo
Jun-Hwan Moon Hyung Keun Lee Min Jung Lee Seong Ho Lee Jun Hyun Han Sung Hak Choi |
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MP94-15 |
Muscarinic M3- and M2- Receptor-Activated Signaling in the Bladder is Inversely Regulated by Caveolae. |
Bladder & Urethra: Anatomy, Physiology & Pharmacology II | 17BOS |
Abstract: MP94-15 Sources of Funding: Department of Veterans Affairs, Research Service BX001790 Introduction Bladder smooth muscle (BSM) caveolae are cholesterol-enriched membrane microdomains that augment or attenuate detrusor functional responses by differentially regulating specific receptor-activated signaling pathways. However, BSM contractions induced by cholinergic activation in the rat are not altered by depletion of caveolae, unlike other smooth muscle systems in which muscarinic receptor signaling is evidently mediated by caveolae. Although this discrepancy may reflect the highly specific regulation imparted by caveolae among different tissues and species, a differential regulation of muscarinic M3 and M2 receptor subtypes in the bladder cannot be excluded. This study examined the functional and molecular relationship between caveolae and muscarinic acetylcholine receptor (mAChR) subtypes M3 and M2. Methods BSM tissue strips were prepared from Sprague Dawley rat bladders after removing the mucosa. Tissue was suspended in organ baths for isometric tension studies. Dose response curves to carbachol (CCh, 1nM-10μM) were generated at baseline, as well as in the presence of 4-DAMP (10nM) or AFDX (0.1μM) to inactive M3 or M2 receptors respectively. Responses to CCh were repeated after incubation with methyl-β-cyclodextrin (mβCD, 15mM), an agent that disrupts caveolae by depleting membrane cholesterol. Interaction between caveolin-1 (Cav-1, a protein required for caveolae biogenesis) and M3 or M2 mAChR subtype were investigated by co-immunoprecipitation. Results Compared to baseline responses, 4-DAMP decreased CCh-induced contractions at each dose. After mβCD treatment and in the presence of 4-DAMP, contractile responses to CCh were significantly enhanced. AFDX had little effect on CCh dose-response curves. However, the subsequent disruption of caveolae in the presence of AFDX attenuated significantly contractions induced by CCh. Immunoreactive bands corresponding to M3 and M2 mAChR subtypes were detected in Cav-1 immunoprecipitates. Conclusions The opposite effect of mβCD on CCh responses in the presence of M2 or M3 antagonists suggests that caveolae negatively regulate M2- and positively regulate M3-mediated signaling respectively, but this interaction is masked when only the aggregate effect of CCh is examined. Molecular interaction of Cav-1 and mAChRs is consistent with their localization within caveolae. Changes in the balance among caveolin-mAChR interactions, due to loss of caveolae or changes in mAChR subtype expression, may alter responses to cholinergic activation or the efficacy of anti-muscarinic agents in the bladder. Funding Department of Veterans Affairs, Research Service BX001790
Authors
Vivian Cristofaro
Maryrose P. Sullivan |
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MP94-16 |
Oxidative stress-related alterations in the bladder of a short-period diabetes type-2 rat model. |
Bladder & Urethra: Anatomy, Physiology & Pharmacology II | 17BOS |
Abstract: MP94-16 Sources of Funding: None Introduction Diabetes type-2 accounts for almost 90% of diabetes cases worldwide. Diabetes among other complications induces bladder dysfunction. In the current study we aimed to create a short-period diabetes type-2 model in order to investigate oxidative stress-related alterations in the bladder in the initiation of the disease. Additionally antioxidant treatment with resveratrol or taurine was provided in order to examine whether it is possible to prevent these alterations in the very beginning of the disease. Methods Diabetes was induced in 8-week-old male Wistar rats with a single dose of streptozotocin (40mg/kg) intraperitoneally (i.p.). The next day they were randomly separated into 3 groups and 14 days feeding with a high fat diet followed. One group received no treatment (DM group), another group received orally resveratrol (10mg/Kg; Resv group) and the third one received taurine i.p. (1g/Kg; Tau group). Age matched control animals were used and were fed with normal diet (Control group). Two weeks later animals were sacrificed and bladder were processed for histological evaluation, measurements of malondialdehyde (MDA) and immunohistochemistry (IHC) for oxidative stress markers. Results At the end of 2 weeks all diabetic groups had significantly lower body weight compared to the Control group. DM group demonstrated significantly higher ratio of bladder weight to body weight compared to the Control (Figure 1). Histological evaluation demonstrated mild damage of the bladder tissue in the DM group such as abruption of the mucosa from the muscularis as well as edema in the transitional epithelium. All these alterations were not observed in the treatment groups. MDA levels in the bladder were significantly larger in the DM group compared with Control, Resv or Tau group (Figure 1). Fourteen days of diabetes without treatment in the DM group induced moderate to strong intensity and positivity for oxidative stress marker MDA, 4-Hydroxynonenal and DNA oxidative stress marker 8-deoxyguanosine compared with the other three groups. Conclusions The prompt diagnosis of diabetes can be crucial for the progression of the disease. Specifically in the bladder, it appears that both mild damage in structural level as well as oxidative damage in molecular level can be prevented by resveratrol or taurine treatment. Funding None
Authors
Panagiota Tsounapi
Masashi Honda Fotios Dimitriadis Yusuke Kimura Shogo Shimizu Bunya Kawamoto Katsuya Hikita Motoaki Saito Nikolaos Sofikitis Atsushi Takenaka |
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MP94-17 |
Dynamic imaging of urine flow at bladder neck in rabitt during voiding using tracer by wreless capsule endoscope |
Bladder & Urethra: Anatomy, Physiology & Pharmacology II | 17BOS |
Abstract: MP94-17 Sources of Funding: none Introduction There was not yet report on visualizing flow at voiding from baldder neck in vivo. We vizualized urine flow from internal vew of baldder neck. using by wireless capsule endoscopes (WCEs) for cystoscopy at voiding in vivo. Methods Experimental evaluation of capsule cystoscopy was performed in a 5-kg farm rabbits(n=6). The capsule was inserted after incision of bladder. Images were continuously transmitted at a rate of four frames per second to a laptop computer and processed using proprietary software. Manipulation of the WCE within the bladder was performed using a set protocol. We measured the ability to deploy and manipulate the capsule within the bladder. Feasibility of capturing and retrieving images in real time was also assessed. We used air bubble(injection by syringe) and dye(intravenous administration of indigocarmine) as urine flow tracer. Results The WCE was efficiently deployed and manipulated within the bladder passively by manual. The entire bladder mucosa real-time image transmission and capture was visualized. The urine flow rotated clockwise from ventral to visceral at bladder neck during voiding. _x000D_ Fig.a): closed bladder neck before voiding, b)c) :air bubble rotated fom 12 to 3 at clock and d)sucked to internal urethra,no apparent of the air bubble._x000D_ Fig(A) :the dye was visualized on closed bladder neck before voiding_x000D_ Fig(B) :when bladder neck begun to open , the dye visualized a vortex with rotation clockwise like crescent moom._x000D_ Conclusions By this device, urine flow could be visualized a vortex with rotation clockwise from ventral to visceral at the bladder neck mucosa during voiding. Funding none
Authors
Tokunori Yamamoto
Hideki Mizuno Shigehiro Soh Yasuhito Funahashi Yoshihisa Matsukawa Masanao Nakamura Momokazu Gotoh |
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MP94-18 |
Urothelial cells express a functional succinate receptor GPR91 |
Bladder & Urethra: Anatomy, Physiology & Pharmacology II | 17BOS |
Abstract: MP94-18 Sources of Funding: FRQS Introduction Overactive bladder is associated with the metabolic syndrome. Increased succinate production is detected in the presence of hyperglycemia and hypoxemia, as with diabetes mellitus and metabolic syndrome. Succinate was recently identified as a major metabolic switch controlling metabolic functions in the body through its receptor GPR91 (SUCNR1). The aim of our study is to determine how succinate interacts with urothelial cells through its receptor. Methods Urothelial cells were isolated from female Sprague-Dawley rat bladder using a collagenase IV method. After confluency, cells were exposed to succinate then treated for microscopy and immunoblotting. Cyclic AMP and PGE2 were measured using an Elisa kit from Cayman Chemical Company. Nitric oxide was assessed by an colorimetric method. Retroviruses were generated for shRNA-mediated knockdown of GPR91. Results Urothelial cells were characterized using Cytokeratin 17 and the AE1/AE3 antibody. RT-PCR confirmed expression of GPR91. Short-term incubation of cells with succinate (200 µM) results in phosphorylation of Erk and c-Jun amino-terminal kinases (JNKs). Inhibition of the MAPK pathway by PD98059 (10 µM) inhibited increases of Erk-P elicited by succinic acid. On the other hand, pre-incubation of cells with succinate dose-dependently decreased the concentrations of intracellular cyclic AMP stimulated by forskolin. Succinate triggers entry of calcium inside urothelial cells as visualized by confocal microscopy. Long-term incubation of cells with succinate increased secretion of nitric oxide and decreased PGE2 release.Cells infected with shRNA retrovirus targeting GPR91 displayed a strong decrease in GPR91 expression. This was associated with a loss of succinate-stimulated Erk phosphorylation. Moreover, inhibition of cyclic AMP synthesis, increases in intracellular calcium and release of nitric oxide were all dramatically prevented. Conclusions GPR91 is expressed in urothelial cells. Binding of succinate to its receptor triggers phosphorylation of Erk and JNK, a process that requires the MAPK pathway. Inhibition of cyclic AMP production suggests the receptor is bound to protein Gi. Release of nitric oxide and decrease of PGE2 are under succinic acid control suggesting a potential cross-talk between urothelium and detrusor muscle. Funding FRQS
Authors
Abubakr Mossa
Monica Velasquez-Flores Philippe Cammisotto Lysanne Campeau |
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MP94-19 |
A POTENTIAL NOVEL MECHANISM FOR DETRUSOR UNDER-ACTIVITY MEDIATED BY MYOSIN LIGHT CHAIN PHOSPHORYLATION AND AMP-DEPENDENT KINASE |
Bladder & Urethra: Anatomy, Physiology & Pharmacology II | 17BOS |
Abstract: MP94-19 Sources of Funding: none Introduction Muscarinic receptor stimuli such as carbachol (CCh) cause increases in detrusor smooth muscle (DSM) myosin light chain (MLC) phosphorylation and contraction. Notably, upon stimulation with CCh, DSM force rises rapidly to a peak value, then gradually declines (fades) despite the continued presence of CCh. The mechanism behind the fade in force s not understood. There is evidence that, in addition to causing contraction, muscarinic receptor stimulation can activate AMPK, and AMPK has been shown to negatively regulate smooth muscle contraction. The purpose of this study was to test the hypothesis that DSM contraction fade is due to the delayed activation of AMPK Methods Mouse bladder with mucosa were cut into rings ~3 mm wide, and strips of DSM free from underlying mucosa were removed from rabbit bladders. Each tissue was placed in an organ bath connected to a force transducer and length-adjuster and subjected to a length-tension protocol to identify the length (Lref) that produced the strongest active force induced by KCl. Each ring was subsequently set to 95% Lref. Three tissues were then contracted by exposure to 10 microM CCh and quick-frozen at 5, 30 and 180 seconds. A fourth tissue was not contracted and quick-frozen to assess the basal-state. Tissues were subsequently processed to quantify the level of phosphoproteins that are indices of activation of AMPK (ACC-pS79 and AMPK-p172) and of actomyosin crossbridges (MLC-pS19 and MYPT1-pT853). Results Compared to the basal-state, CCh induced a strong increase in force in mouse bladder and rabbit DSM that peaked at, respectively, 60 sec and 20 sec, before declining to ~50% of the peak values within 180 sec (n=3). MLC-p also displayed a biphasic response. AMPK-pand ACC-p displayed a delayed increase corresponding with the decrease in contractile force. Conclusions Muscarinic receptor stimulus CCh caused a rapid increase in force in mouse bladder and rabbit DSM that faded with time despite the presence of CCh. This fade in force correlated with a delayed increase in AMPK activity as assessed by increases in the phosphoproteins, ACC-p and AMPK-p. Because AMPK has been shown to inhibit smooth muscle contraction, the correlation of an increase in AMPK activity with the decrease in force supports the hypothesis that AMPK may be responsible for fade in DSM force. Because AMPK activity is also elevated during ischemia/hypoxia, a condition known to cause bladder underactivity, these data warrant further studies to investigate the potential role of AMPK in bladder underactivity Funding none
Authors
Randy Vince
Ramanan Remesh John Speich Adam Klausner Amy Miner Paul Ratz |
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MP95-01 |
Association Between Oral Antibiotics and Incident Kidney Stones |
Stone Disease: Epidemiology & Evaluation II | 17BOS |
Abstract: MP95-01 Sources of Funding: NIH K23DK106428 Introduction Composition of the gut microbiome has been associated with recurrent kidney stones, but the impact of antibiotics on developing new kidney stones is unclear. The objective of this study was to evaluate the association between antibiotic exposure and incident kidney stones. Methods In a nested case-control study using THIN, a primary care electronic medical records database, we identified patients with an incident diagnosis of nephrolithiasis and randomly selected age, sex, and practice-matched individuals without kidney stones (10:1). Conditional logistic regression models were used to estimate the odds ratio (OR) between prior oral antibiotic exposure (≤1, 1-5, and >5 years) and kidney stones, adjusting for urinary tract infection, diabetes, cystic fibrosis, inflammatory bowel disease, immobility, and gout and using a Bonferroni corrected p of <0.001 for significance. Results Among 26,466 cases and 265,658 matched controls, most, but not all, antibiotics were associated with an increased odds of incident kidney stones (Figure). The magnitude of association varied by antibiotic class, recentness of exposure, and age at exposure. The highest risk of incident kidney stones occurred within 1 year of treatment with sulfas (OR 4.2, 95% CI 4.0, 4.4), and when exposure occurred before 4 years of age (OR 4.52, 95% CI 2.91, 7.03). The risk of nephrolithiasis was greater with more recent antibiotic exposure; there was a 10%, 26%, and 32% increased odds of incident nephrolithiasis at >5 years, 1-5 years, and <1 year from penicillin treatment (p<0.001). H. pylori treatment, which includes macrolides, was also associated with an increased odds of incident kidney stones within 1 year of treatment (OR 2.13, 95% CI 1.51, 3.02). Prior exposure to clindamycin, anti-mycobacterial agents, and vancomycin was not associated with incident kidney stones. Conclusions Prior antibiotic exposure was strongly associated with an increased odds of incident kidney stones, with the greatest risk for more recent and early life exposures. Exposure to antibiotics may alter the intestinal microbiome, leading to changes in urinary solute excretion. These results are another reason to limit unnecessary antibiotic exposure and may help explain the rapidly rising incidence of nephrolithiasis in the United States. Funding NIH K23DK106428
Authors
Gregory Tasian
Thomas Jemelieta David Goldfarb Qufei Wu Lawrence Copelovitch Jeffrey Gerber Michelle Denburg |
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MP95-02 |
Heterogeneity in Calcium-based Nephrolithiasis from a Materials Perspective |
Stone Disease: Epidemiology & Evaluation II | 17BOS |
Abstract: MP95-02 Sources of Funding: None Introduction Routine clinical stone analytics fail to accurately characterize nuances in structure, composition, and mechanical properties of stone specimens. Using analytical approaches not routinely used in clinical setting, we sought to uncover similarities and differences in structure, chemical composition, and mechanical properties of the most common forms of calcium nephrolithiasis. Methods After endoscopic extraction, human calcium-based stones deemed "pure" (100% calcium oxalate or 100% calcium apatite) by routine clinical Fourier Transmission Infrared stone analysis were selected for further analysis. All stones were then subjected to light microscopy, micro-computed tomography (CT), digital segmentation mineral density analysis, Knoop microindentation, energy dispersive x-ray analysis, and inductively coupled plasma mass spectroscopy (ICP-MS). Results All CaOx and apatite stones demonstrated highly variable regions of mineral density. In CaOx stones, mineral density distributions revealed areas of low (593.3 ± 84.6 mg/cc), medium (842.0 ± 139.4 mg/cc), and high (1127 ± 244.9 mg/cc) density regions. Apatite stones also contained regions of low (694.8 ± 232.5 mg/cc), medium (1096.1 ± 174.6 mg/cc) and high (1420.3 ± 141.8 mg/cc) density which varied within layers extending from single or multiple nucleation sites. Microindentation revealed that, despite having lower average mineral density, CaOx stones demonstrated higher material hardness compared to apatite stones. Energy dispersive x-ray analysis detected organic matter (carbon concentration) between distinct morphologic layers in CaOx stones, whereas apatite stones contained organic material within stratified layers. ICP revealed numerous trace elements in both stone types. Conclusions Using advanced analytic techniques, calcium based calculi were found to have significant heterogeneity in structure, density, material hardness, and mineral composition that is not elucidated by routine clinical testing. Despite traditional thinking, stone density does not directly correlate with mechanical hardness. Underlying stone heterogeneity may help explain why historical approaches have failed in predicting stone types and response to lithotripsy. Funding None
Authors
Benjamin Sherer
Ling Chen Ryan Hsi David Killilea Sunita Ho Marshall Stoller |
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MP95-03 |
Patient Rurality Influences Treatment Modality for Urinary Stone Disease |
Stone Disease: Epidemiology & Evaluation II | 17BOS |
Abstract: MP95-03 Sources of Funding: AUA Data Grant Introduction We have previously demonstrated that outreach centers increase access to urologic procedural care (UPC) in rural settings, but the quality and type of care in these centers has not been explored. Kidney stones affect both sexes of all ages and extracorporeal shock wave lithotripsy (ESWL) and ureteroscopy (URS) are the two most common modalities for treating urinary calculi. However, their treatment equivalency has been questioned. The purpose of this study was to assess whether treatment modality patterns differ in outreach centers versus primary center and by patient rurality. Methods We retrospectively evaluated ESWL and URS procedural data from the Iowa Office of Statewide Clinical Education Programs (OSCEP) and Iowa Hospital Association (IHA) databases from 2007-2014. These two databases provide hospital level information on all outpatient procedures performed across the state, by whom they were performed, and whether the hospital represented a primary or outreach center for the urologist. CPT codes for URS (52320, 52325, 52352, 52353) and ESWL (50590) were compared to the type of hospital and the rurality of the patient based on rural-urban commuting area (RUCA) codes. Geographical data was used to analyze travel distances to sites of closest and actual stone treatments for all patients. Results During the study period, 21,093 outpatient stone procedures were performed in Iowa (12,007 URS; 9086 ESWL), of which 2932 (13.9%) were performed at outreach centers. Ureteroscopy was significantly more common in primary centers versus outreach centers (60.9% v. 32.1%; OR 3.3; 95% CI 3.0-3.6). Average distance traveled to procedures did not differ significantly between ureteroscopy (31.3 ± 37 miles) and ESWL (25.7 ± 25.7 miles; p = 0.3). Comparing the most rural quartile of rurality as assessed by RUCA coding to the least rural, the likelihood of ESWL was significantly more common in for the rural patients (50.6% vs 37.6; p<0.0001). Conclusions Stone and patient characteristics are assumed to be similar in our state&[prime]s rural and urban populations though treatment options and modalities differ widely. Our rural patients were significantly more likely to receive ESWL for their stones and were more likely to receive their care at outreach centers. The clinical and societal significance of this rural disparity is unknown. Funding AUA Data Grant
Authors
Paul Morrison
George Ghareeb Thomas Gruca Craig Jarvie Bradley Erickson |
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MP95-04 |
Urbanization may affect the incidence of urolithiasis in South Korea |
Stone Disease: Epidemiology & Evaluation II | 17BOS |
Abstract: MP95-04 Sources of Funding: This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology, Republic of Korea (2015R1A1A1A0500110), and (2015R1A2A1A15054364). Introduction We evaluated the different climatic factors in urban and rural areas that may affect the incidence of urolithiasis. Methods Nationwide data on urolithiasis were acquired from Health Insurance Review and Assessment Service between 2009 and 2013. Information on age, gender, date of diagnosis, geographic region and daily weather data from all weather stations was collected. The data were grouped by population density and substituted into the lag period model. The primary outcome was the incidence rate in each region. The secondary outcomes were differences between groups and relative risks (RRs) of climatic factors. The tertiary outcome was RRs of urolithiasis presentation cumulated over a 20-day lag period associated with the mean daily temperature. Results The incidence rates of urolithiasis tended to increase annually in most regions from 2009 to 2013. The urban group showed a higher mean temperature, lower amount of rainfall, higher wind speed and lower mean relative humidity than the rural group (p <0.001). The urban group showed significant RRs of temperature (1.013, 95% confidence interval [CI] 1.009-1.017, p <0.001), wind speed (0.979, CI 0.973-0.986, p <0.001), humidity (0.995, CI 0.994-0.996, p <0.001), and sunshine (0.992, CI 0.988-0.996, p <0.001). The rural group showed significant RRs of wind speed (0.980, CI 0.968-0.992, p =0.002) and humidity (0.998, CI 0.996-0.999, p =0.007). In the urban area, RRs increased gradually with increasing temperature. Conclusions Regional differences in climatic factors, especially temperature, may provoke a gap in urolithiasis events between the urban and rural areas. Funding This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology, Republic of Korea (2015R1A1A1A0500110), and (2015R1A2A1A15054364).
Authors
Se Young Choi
Seo Yeon Lee Byung Hoon Chi Seung Hyun Ahn Jae Duck Choi Shin Young Lee In Ho Chang |
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MP95-05 |
Increasing Utilization of Care for Urinary Stone Disease in Older Adults |
Stone Disease: Epidemiology & Evaluation II | 17BOS |
Abstract: MP95-05 Sources of Funding: Departmental Introduction Urinary stone disease (USD) has long been considered a condition afflicting those of working age. As the US population ages, however, it is unclear what impact changing population dynamics may have on care utilization. The objective of our research was to examine trends in health care utilization for USD in the United States by age, with a particular emphasis on older adults. Methods We used data from the Nationwide Inpatient Sample (NIS) and the Nationwide Emergency Department Sample (NEDS) to estimate trends for inpatient and emergency department care utilization from 2006 to 2013. Older adults were defined as individuals aged at least 65 years. Encounters for USD were identified using diagnostic codes and established algorithms. We calculated annual number of ED visits and hospitalizations for stones by age group. Linear regression was used to assess changes in utilization over time. Results An estimated 1.77 million ED visits and 1 million inpatient discharges for USD occurred during the study period for older adults (≥65 years). ED visits with principal diagnosis of USD increased 66% (p <.001) for ages 65-84 and 72% (p <.001) for ages 85+, whereas younger adults (ages 18-64 years) only increased 19% (p <.001) (Figure). Similar trends were observed for inpatient discharges, with an increase of 15% (p = .0014) for ages 65-84 and 34% (p = .0049) for ages 85+. Inpatient discharges for younger adults decreased during the study period. In sensitivity analyses examining any diagnosis of USD, similar increases in utilization by older adults were noted. Conclusions Health care utilization for USD is growing rapidly among older adults, and faster than any other age group. Further research is required to determine the extent to which this trend reflects changing population dynamics, changing risk of stones among older individuals, or both. Regardless of the underlying causes, it will be imperative to develop approaches for medical and surgical stone care for these older and often frail adults. Funding Departmental
Authors
Kevin T. Hobbs
Brad Hammill Daniel Wollin Glenn M. Preminger Michael E. Lipkin Kenneth E. Schmader Charles D. Scales, Jr. |
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MP95-06 |
Patients with urolithiasis are more like to develop fracture: a nation-wide population-based and with an 8-year follow-up study |
Stone Disease: Epidemiology & Evaluation II | 17BOS |
Abstract: MP95-06 Sources of Funding: none Introduction Urolithiasis has been reported to be a cause of decreased bone marrow density. Decreased bone marrow density has also been found to be closely linked to fracture. It is interesting and also important to know whether there is a relevant association between urinary stone and fracture. Methods We used data sourced from Longitudinal Health Insurance Database, which consists of one million randomly selected subjects from the National Health Insurance Research Database of Taiwan. Health Insurance System of Taiwan covers approximately 23 million people (98% of population). From 1997 to 2001, a total of 27237 subjects, 16346 males and 10891 females, with age 18-year-old or older were diagnosed with upper urinary track stone. All subjects did not have previous diagnosis of fracture. A cohort of 136185 (5 for each subject with upper urinary track stone) age and gender matched subjects without the diagnosis of upper urinary track stone in anytime of follow-up were enrolled as the control group. All subjects were followed up to the end of 2009 with a minimal follow-up of 8 years. A Cox shared frailty regression model was used to calculate the risk of fracture between study and control groups. Results At the end of follow-up, 5252 (19.3%) of the 27237 study subjects and 22018 (16.2%) of the 136185 control subjects developed fractures. Upper urinary track stone was associated with a significantly increased risk of fracture (hazard ratio 1.20, 95% confidence interval, 1.16 - 1.24, p < 0.0001) when metabolic syndrome was not taken into account. After adjusting for age, gender and metabolic syndrome status, the Cox shared frailty regression analysis still showed that patients with upper urinary track stone were more likely to develop fracture than the patients without urinary stone (hazard ratio 1.18, 95% confidence interval, 1.14 - 1.21, p < 0.0001). Conclusions The findings of this study indicate that urolithiasis is an independent risk factor for fracture. Patients, especially elderly, with urolithiasis should be advised about appropriate steps to take with respect to fracture prevention. Funding none
Authors
Hsiao-Jen Chung
Alex Tong-Long Lin Yi-Hsiu Huang Chih-Chieh Lin Tzeng-Ji Chen Kuang-Kuo Chen |
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MP95-07 |
Sleep apnea : an independent risk factor for nephrolithiasis |
Stone Disease: Epidemiology & Evaluation II | 17BOS |
Abstract: MP95-07 Sources of Funding: none Introduction Nephrolithiasis and sleep apnea (SA) share known risk factors, namely obesity and metabolic syndrome and both have been linked to states of systemic insulin resistance and oxidative stress. However, a direct relationship between nephrolithiasis and SA has not been thoroughly investigated. This study aims to determine whether SA is an independent risk factor for nephrolithiasis. Methods From January 1, 2000 to December 31, 2012, a nationwide population-based retrospective cohort analysis was performed on a representative sample of 1,000,000 participants from the National Health Insurance Research Database (NHIRD) in Taiwan. 7,831 adult patients with SA were identified and were directly compared to an age and gender-matched control group of 31,293 participants without SA. The diagnosis of disease was confirmed by International Classification of Disease, 9th revision. Cox proportional hazard regression models were used to evaluate the association between SA and the risk of subsequent nephrolithiasis. Results SA patients have an 8.9% incidence of nephrolithiasis, compared to 5.5% of the non-SA control (p<0.001). SA patients also have higher rates of metabolic comorbidities (p<0.001). After adjusting for age, gender and comorbidities, the risk of nephrolithiasis remained significantly increased in the SA group (hazard ratio [HR]=1.35; 95% confidence interval [CI]=1.23-1.47; p<0.001). Greater HRs of nephrolithiasis were observed for male patients (1.21; 95% CI=1.09-1.35; p<0.001) and those aged 20-39 years (1.25; 95% CI=1.06-1.46; p<0.01) in the SA cohort. Risk of nephrolithiasis in SA patients increased significantly with concomitant diabetes mellitus, hypertension, hyperlipidemia, and morbid obesity. Conclusions The study provides evidence that patients with SA have an increased risk of subsequent nephrolithiasis compared with patients without SA. Young male SA patients with concomitant comorbidities are at the greatest risk for nephrolithiasis formation. Funding none
Authors
Sheng-Han Tsai
Marshall Stoller Benjamin Sherer Zi-Hao Chao Tao-Hsin Tong |
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MP95-08 |
Primary Hyperparathyroidism: A Sometimes Elusive Diagnosis |
Stone Disease: Epidemiology & Evaluation II | 17BOS |
Abstract: MP95-08 Sources of Funding: none Introduction Higher serum calcium (Ca) and/or parathyroid hormone (PTH) in patients with kidney stones raises the suspicion for primary hyperparathyroidism (PHPT), however the diagnosis can be challenging to confirm. We sought to determine if patients can be risk stratified regarding likelihood of PHPT based on blood and urine studies. Methods We queried our electronic medical record for patients with ICD-9 codes for both PHPT and kidney or ureteral stones. In an effort to identify patients with a suspicion of PHPT we also included patients with a serum Ca >9.9 mg/dL, PTH >50 pg/ml, and kidney or ureteral stones. Patients with kidney transplant or prior parathyroidectomy were excluded. From the medical record we extracted demographics, lab and urine values at presentation and at follow-up visits, parathyroid Imaging, details of parathyroidectomy, and post-operative lab values when appropriate. Results We divided the 147 patients into three groups based on serum Ca and PTH: classic, suspicious, and not suspicious for PHPT. The classic group (n=30) had high Ca (>10.2mg/dL) and high PTH >65 (pg/ml) simultaneously during follow-up. The suspicious group (n=53) had a Ca ≥9.9 and a PTH ≥50 simultaneously during follow-up. The non-suspicious group (n=64) never had a Ca ≥9.9 and a PTH ≥50 simultaneously during follow-up. We further subdivided the suspicious group into three groups: Group S1 (n=20) with high normal Ca (9.9-10.1mg/dL) and high normal PTH (50-64pg/ml), Group S2 with high normal Ca and high PTH (n=22), and Group S3 (n=11) with high Ca and high normal PTH. There was no significant difference in the maximum urine Ca across groups. In the classic group 100% had parathyroid imaging, 80% of which was positive. In the suspicious group 47% had imaging 52% of which was positive. Parathyroidectomy was performed in 83.3% of classic, 30% of S1, 27%, of S2, 45% of S3 and 9.4% of the not suspicious groups. Serum Ca normalized in 100% of patients who underwent surgery. The classic group had the shortest time to imaging and surgery but this did not reach significance (p=0.2). Conclusions Half of patients who undergo parathyroidectomy had a non-classic presentation, suggesting that we are underdiagnosing PHPT. Although both Ca and PTH are considered when making the diagnosis of PHPT, in our study group serum Ca seemed to more frequently drive the diagnosis supporting the AUA guidelines on the selective use of PTH. Efforts should be made to pursue a better diagnostic algorithm for the diagnosis of PHPT. Funding none
Authors
Jodi Antonelli
Niccolo Passoni Elysha Kolitz Aaron Lay Naim Maalouf Margaret Pearle |
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MP95-09 |
Decreasing Trend in Stone Disease: Are Men Doing Something Right? |
Stone Disease: Epidemiology & Evaluation II | 17BOS |
Abstract: MP95-09 Sources of Funding: none Introduction Demographic studies on renal calculi have suggested an increasing incidence of nephrolithiasis. Although these studies have used large national databases, none have examined data from within the last decade and have suggested that the closing gender gap is due to an increased incidence of calculi in females. The purpose of this study was to examine the most recent data from the Nationwide Inpatient Sample database to investigate the recent trends of gender and race in this pervasive disease. Methods Patient data of 459,823 discharges from 2000 to 2013, with a primary International Classification of Diseases, 9th revision principal diagnosis code of 592.0 (calculus of kidney) or 592.1 (calculus of ureter) were included in the study. Only patients with a designation of either “male” or “female” were included in the study. Racial groups were divided into White, Black, Hispanic, Asian, Native American, or other/not recorded. Trend analysis was performed, and fit lines were generated using a linear regression model to compute statistical significance. A subgroup analysis, with respect to gender, was performed for each race. Results The 459,823 discharges included 243,223 from men and 216,600 from women. Within the 13-year study period, total discharges for renal and ureteral calculi decreased by 19.1% with a statistically significant, 1.7% decrease in incidence per year (p =0.0001). Calculi in men decreased by an average of 2.2% per year for a total of 30.5% decrease in incidence in the study period (p <0.0001). However, the incidence of calculi in women was variable without any significant trend. Sub-group analysis by race revealed that renal and ureteral calculi were more common in Black females and Hispanic females when compared to their male counterparts. The incidence of stones grew by an average of 2.7% per year in Black women (p< 0.002) and 4.6% per year in Hispanic women (p< 0.0001). This resulted in a 50.4% increase in incidence in each group between 2000 and 2013. Conclusions While data from earlier years had suggested that the incidence of stone disease was increasing, our analysis of recent data show that the incidence of renal and ureteral calculi resulting in medical intervention (evaluation by a physician, admission, etc.) is decreasing. This trend is attributable to a decrease in stone disease in men, resulting also in a decreased male-to-female ratio of stone disease from 1.3:1 to about 1:1. This study also reveals interesting trends in the racial demographics of stones with Black and Hispanic women now experiencing up to 50% more stone disease than their male counterparts. Funding none
Authors
Alan Carnes
Zach Klaassen Michael Kemper Durwood Neal Vinata Lokeshwar |
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MP95-10 |
Association of pregnancy with stone formation among US women: A National Health and Nutrition Examination Survey analysis 2007-2012. |
Stone Disease: Epidemiology & Evaluation II | 17BOS |
Abstract: MP95-10 Sources of Funding: None Introduction Lithogenic urinary changes occur during pregnancy. Such changes may increase stone proclivity in working and child rearing aged women thereafter. However, such an association has not been previously identified. Methods We analyzed nationally representative data from the 2007-2012 National Health and Nutrition Examination Survey to assess for an association between pregnancy and nephrolithiasis. Results The weighted national prevalence of nephrolithiasis among women ?50 was 6.4% (95% Confidence Interval (CI) 5.4%-7.6%). The prevalence of nephrolithiasis was significantly higher among women who had been pregnant compared with those who had never been pregnant (7.5% vs 3.2%, p=0.0004). On univariate regression, those who had been pregnant had over twice the odds of having had kidney stones (OR 2.44, 95% CI 1.50-3.98). An increased likelihood of nephrolithiasis among those with history of pregnancy persisted on multivariable logistic regression adjusting for age, ethnicity, obesity, history of diabetes, gout, hormone use, water intake and high sodium diet (OR 2.13, 95% CI 1.31-3.45). Finally, the adjusted prevalence of nephrolithiasis increased significantly with increasing number of pregnancies, from 5.2% in those with 0 reported pregnancies to 12.4% in those with 3 or more pregnancies (p=0.001). Conclusions Nephrolithiasis is strongly associated with prior pregnancies. Among women of reproductive age, the odds of stones are greater than doubled in those who had been pregnant compared with those never pregnant. Nephrolithiasis prevalence also increases with increasing number of pregnancies. Future investigation and identification of modifiable risk factors among pregnant patients may allow reduction in burden of stone disease in women. Funding None
Authors
Lael Reinstatler
Sari Khaleel Vernon Pais |
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MP95-11 |
Evaluation, Management, and Outcomes of Pregnant Patients with Clinically Symptomatic Nephrolithiasis at a Large Women’s Hospital |
Stone Disease: Epidemiology & Evaluation II | 17BOS |
Abstract: MP95-11 Sources of Funding: None Introduction To review the evaluation and management of pregnant patients with clinically symptomatic nephrolithiasis evaluated at a single institution over a 14-year period. Methods A retrospective chart review was performed to identify pregnant patients admitted with a diagnosis of nephrolithiasis at a single institution from 2002-2016. Admission rates, lengths of stay, rates of sepsis, utilization of imaging, administration of MET, rates and type of surgical intervention, and gestational outcomes were analyzed through the patient&[prime]s gestational period. Results 695 pregnant patients with symptomatic nephrolithiasis were identified, 304 of whom delivered at our institution and were included in the analysis. Average maternal age was 30.4 years (range 17-48). Of these, 262 (86.2%) had imaging interpreted as consistent with nephrolithiasis. 261 (85.9%) underwent US, 16 (5.3%) CT scan, and 4 (1.3%) MRI. The remaining 42/304 patients (13.8%) were diagnosed based on history and symptoms alone. 40 patients (13.2%) were started on tamsulosin during their pregnancy. 242 (80%) patients had culture data, 33/242 (13.6%) which were positive. 32 (10.5%) patients underwent surgical management, 2 in the first trimester, 17 in the second, and 13 in the third. Patients were more likely to receive definitive surgical management in the first trimester (2/2, 100%) versus 10/30 (33.3%) later in pregnancy (p<0.05). 6/32 (18.8%) of patients in the surgical group presented with ≥ 2 SIRS criteria. Patients in the MET group were more likely to undergo surgical management (p<0.05). There was a statistically significant correlation between the rate of operative intervention and the number of hospital encounters (p<0.05) as well as length of stay (p<0.05). No statistically significant correlation was seen in the rates of preterm labor or APGAR scores in patients who underwent surgery versus those who did not._x000D_ Conclusions To our knowledge, this is the largest study focused on the management of symptomatic nephrolithiasis in pregnant women. The majority of patients had a diagnosis confirmed by imaging, primarily with ultrasound. Definitive surgical management was more likely to occur in the first trimester. Patients receiving MET were more likely to require surgical intervention. Surgical intervention was not associated with preterm labor or low APGAR scores. Funding None
Authors
Nabeel Hamoui
Emily Yura Mary Kate Keeter Kaitly Sacotte Beverely Onyekwuluje Nirali Shah Granville Lloyd Stephanie J. Kielb |
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MP95-12 |
Changing Lithogenic Trends in Patients with Neurologically Derived Musculoskeletal Deficiencies (NDMD) |
Stone Disease: Epidemiology & Evaluation II | 17BOS |
Abstract: MP95-12 Sources of Funding: None Introduction Patients with neurologically derived musculoskeletal deficiencies (NDMD), like spinal cord injury and spina bifida, are high risk for chronic complicated urolithiasis. Recent studies suggest that stone etiology in this population has shifted from purely infectious to mixed infectious/metabolic. We assess a cohort of NDMD patients for metabolic lithogenic risk factors, trends across etiology of NDMD, as well as trends across primary stone type. Methods We conducted a retrospective cohort study of NDMD patients presenting to our dedicated &[prime]stone clinic&[prime] from 2000-2015. Patients with chemical stone and 24-hour urine analysis were included. Demographics, neurological deficiency, bladder management strategy, urine cultures, 24-hour urine, and stone composition were reviewed. Results Seventy eight patients with NDMD and nephrolithiasis were identified. Of these, 26 had both chemical stone and 24 hour urine analysis. Positive urine cultures prior to treatment were present in 77%. Eighty-five percent of these cultures were positive for urea splitting organisms. The most common stone type categorized by primary composition was carbonate apatite (53.8%) followed by mixed apatite/oxalate (19.2%). When categorized by primary etiology, 61.5% were pure pH dependent (presumed to be infectious), 27% mixed pH dependent/metabolic, and 11.5% pure metabolic. Urinary citrate was significantly lower in patients with carbonate apatite, or pH dependent, calculi. Those with primarily calcium oxalate stones were significantly more likely to be obese (p=0.003), with a mean body mass index of 37. When stratified by gender, males were more likely to have hyperoxaluria. There was a trend toward positive cultures for urea splitting organisms and carbonate apatite stones in catheterized patients. Otherwise, there were no statistically significant differences in 24-hour urine parameters when stratified by gender, neurological deficiency, or bladder management strategy. _x000D_ Conclusions Among NDMD patients, metabolic factors may play a more significant role in stone formation than previously believed. There is still a high incidence of carbonate apatite stones, which could be attributed to bacteriuria and elevated pH. In addition to this, obesity, low volumes, low citrate, and elevated oxalate suggest a metabolic etiology. Identifying metabolic risk factors in NDMD patients is challenging but important; as it may significantly impact stone recurrence and the need for repeat surgery. Funding None
Authors
Lee Hugar
Ilan Kafka Sara Sprauer Michelle Yu Thomas Fuller Hassan Taan Timothy Averch Michelle Semins |
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MP95-13 |
Correlation of Stress in Kidney Stone Patients with the Wisconsin Stone Quality of Life Questionnaire |
Stone Disease: Epidemiology & Evaluation II | 17BOS |
Abstract: MP95-13 Sources of Funding: None Introduction Stress may play a role in endocrinologic causes of kidney stones, be a consequence of stones, or both. We sought to determine if stress was correlated with health-related quality of life (HRQOL) in kidney stone patients with a multi-institutional, prospective approach. Methods With IRB approval at participating sites, a subset of patients from the North American Stone Quality of Life Consortium were administered the Perceived Stress Scale (PSS-10) and the Wisconsin Stone Quality of Life (WISQOL) questionnaires. Both are validated, but WISQOL is a stone-specific, patient-reported outcome to assess HRQOL. WISQOL total and domain scores were compared with PSS-10 scores. WISQOL and PSS-10 scores were also compared by patients’ stone and symptom statuses. Results Patients (n=114; M 56, F 58; age 55±15 y) from 3 centers participated; 78% were white Caucasian, 6% Hispanic/Latino, 11% Asian, and 4% Black/African American. Most (90%) were mixed calcium stone formers. Duration of stone disease varied (mean 10 y; median 4.5 y) as did patients’ estimated number of lifetime stone events (mean 4.6; median 2.0). Among patients with active stone symptoms (27% of sample), total WISQOL and PSS-10 scores were inversely correlated (Pearson correlation coefficient, -0.235; P=0.014), demonstrating that lower HRQOL was associated with more stress. Domain-level analysis revealed that lower HRQOL scores in domains 1 (emotional impact) and 4 (vitality) were also associated with more stress (P=0.011 and 0.0065, respectively). While the WISQOL discriminated patients with stones at survey completion from patients without (P=0.019 for difference in total scores), the PSS-10 did not (P=0.73 for difference in PSS-10 scores). Similarly, the WISQOL distinguished symptomatic patients from asymptomatic (P<0.0001 for difference) while the PSS-10 could not (P=0.46). Conclusions The inverse relationship between the PSS-10 and WISQOL showed overall that patients with higher levels of stress had lower HRQOL. Patients with stone-related symptoms scored lower on the WISQOL for emotional impact and vitality than asymptomatic patients and had significantly more stress. Despite the association of stress and lower HRQOL in patients with stones and symptoms, stress alone did not explain the HRQOL differences between these groups. This study showed that stone patients with a lower HRQOL had more stress. A future comparison of stress levels in stone patients compared to non-stone forming controls may help us determine if stress has a reactive or causative role in kidney stone disease. Funding None
Authors
Ben H. Chew
Thomas Chi Stephen Y. Nakada Kristina L. Penniston |
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MP95-14 |
Impact of race and socioeconomic status on stone characteristics: results from ReSKU – the Registry for Stones of the Kidney and Ureter |
Stone Disease: Epidemiology & Evaluation II | 17BOS |
Abstract: MP95-14 Sources of Funding: NIH P20-DK-100863 (TC), NIH R21-DK-109433 (TC), and NIH K12-DK-07-006: Multidisciplinary K12 Urologic Research Career Development Program (TC) Introduction Socioeconomic status reflects a combination of education, income, and occupation for individuals. It is known to significantly impact several health conditions, but the relationship to kidney stones remains unknown. This study aims to examine the association between race, income, and education on urinary stone presentation._x000D_ Methods ReSKU - the Registry for Stones of the Kidney and Ureter - is a prospective stone registry centered at the University of California, San Francisco. From November 2015 to October 2016, all new nephrolithiasis patients were enrolled. Patient demographics, presentation, and stone characteristics are automatically extracted from the electronic health record and stored in a secure data warehouse. Gross household income for postal address was obtained from Census Bureau data and divided into quartiles. Patient factors were correlated to stone characteristics using univariate and multivariate models. _x000D_ Results 411 new stone patients were enrolled. The most common race was Caucasian (71.8%), following by Asian and Hispanic/Latino. Most patients reported their highest education level as &[Prime]some college or college degree&[Prime] (48.2%), following by &[Prime]high school or less&[Prime] and &[Prime]graduate school&[Prime], and their mean annual income was $77,944.4±34,841.4. Staghorn stone was present in 10.4%. The overall mean total stone burden at presentation was 19.8±25.5 mm. _x000D_ _x000D_ No association existed between race and the presence of staghorn stone (p = 0.47), or stone burden (p = 0.29). Education level was significantly associated with the presence of staghorn stone (p <0.01). Similarly, mean stone burden was significantly higher in patients with high school education level (p <0.01). Patients with the lowest income quartile presented with staghorn stones five times more often than the highest quartile (16.8% versus 3%, p <0.01), and income status was inversely correlated to total stone burden (p <0.01). Multivariate analysis demonstrated a strong correlation between education level and the presence of staghorn stone and total stone burden. Comparing patients with graduate school education to high school or less levels of education, the odds ratio for having a staghorn stone was 0.13 (p <0.01), and coefficient for total stone burden was a 13.8 mm decrease for every incremental increase in education level (p <0.01). _x000D_ Conclusions Lower education level and annual household income were strongly associated with higher total stone burden and the presence of staghorn stones, independent of race. Data collection in ReSKU is continuously ongoing to validate these findings. _x000D_ Funding NIH P20-DK-100863 (TC), NIH R21-DK-109433 (TC), and NIH K12-DK-07-006: Multidisciplinary K12 Urologic Research Career Development Program (TC)
Authors
Manint Usawachintachit
David Tzou Kazumi Taguchi Benjamin Sherer Brian Duty Jonathan Harper Mathew Sorensen Roger Sur Robert Sweet Marshall Stoller Thomas Chi |
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MP95-15 |
Population management kidney stone care approach improves compliance with the American Urological Association (AUA) recommendations on medical management of kidney stones |
Stone Disease: Epidemiology & Evaluation II | 17BOS |
Abstract: MP95-15 Sources of Funding: None Introduction Nephrolithiasis is a chronic disease and stone recurrence rates can be reduced by implementing the AUA kidney stone medical management guidelines. Patient compliance to completion of the necessary laboratory studies has been low. This investigation assessed the impact of a population management program on patient compliance rate for completing the recommend serum and 24-hour urine exams. Methods A 3-year period (2013-2015) retrospective review of electronic medical records of patients at high risk for kidney stone recurrence was performed. The high risk patient group was defined as: stone at young age, bilateral stones, multiple stones, stones over 2 cm, recurrent stones, and malabsorptive gastrointestinal disorders. Patients at high risk for stone recurrence were referred to a registered nurse case manager who followed these individuals under this program. All patients had metabolic evaluation studies ordered by the case manager and were contacted if the test was not completed. Patient compliance rate on completion of the studies was measured annually. Results A total of 4,853 patients were identified with kidney stones. Of these patients, 1,302 patients were identified to be at high risk for kidney stone recurrence. Compliance with the studies were measured and summarized in Table 1. Conclusions Compliance to the recommended preventive kidney stone studies remains a significant challenge. A population management program can effectively improve patient compliance and improve care outcomes in patients at high risk for kidney stone recurrence. Funding None
Authors
Reza Z. Goharderakhshan
Casey K. NG Catherine Guerrero Ronald K. Loo |
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MP95-16 |
Racial differences in urinary metabolic risk factors for nephrolithiasis |
Stone Disease: Epidemiology & Evaluation II | 17BOS |
Abstract: MP95-16 Sources of Funding: None Introduction Over the past two decades, the prevalence of kidney stones in black non-Hispanics has increased by 150%, yet there is a paucity of literature regarding African American (AA) stone-formers. Small studies suggest certain urinary parameters do not significantly differ between racial groups. We asked whether AA stone formers have any meaningful differences in urine and serum metabolic parameters when compared to Caucasians (C). Methods AA patients with known stone composition undergoing metabolic stone evaluation (at least three 24-hour urine collections per patient and paired serum studies) were retrospectively identified by self-reported race from 1995-2016 and sex and age-matched 1:2 to C patients with known stone composition from the same years. Metabolic data were compared between groups by stone type and race using ANOVA. Majority stone type was defined as >50% of composition._x000D_ Results Fifty-five AA (calcium oxalate (CaOx)=29, Ca phosphate (CaP)=9, Uric acid=17) and 125 matched C (CaOx=81, CaP=27, Uric acid=17) had complete pre-treatment metabolic data. Despite similar supersaturation (SS) for their stone type, AA had significantly lower 24-hr urine volumes than C (1.5 vs. 1.9L, p<0.001). Likewise, 24-hr calcium (Ca) levels, were significantly lower than those for C (135 vs. 225 mg, p<0.0001). Urine oxalate and citrate did not differ by ANOVA. Significant differences between races persisted in volume when analyzed by stone type. CaOx AA had lower urine Ca than C, but oxalate and citrate excretions did not differ. Urine Ca did not differ for CaP stone formers by race. For uric acid stones, AA had lower uric acid excretion and uric acid SS but higher urine pH. Serum phosphate also differed by race, and was lower in AA males than in C males; for women this did not differ. Conclusions While physical chemistry dictates that SS drives risk for stone formation, we demonstrate racial differences in determinants of SS. Previously unknown and significant metabolic differences exist between AA and Caucasian stone formers. Funding None
Authors
Andrew Cohen
Melanie Adamsky James McGinnis Kristin Bergsland Fredric ? Coe Elaine Worcester Anna Zisman |
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MP95-17 |
Management of Acute Renal Colic in the Emergency Department: Applying Guidelines |
Stone Disease: Epidemiology & Evaluation II | 17BOS |
Abstract: MP95-17 Sources of Funding: None Introduction Applying guidelines to management of acute renal colic in the Emergency Department (ED) is challenging due to need to incorporate multi-specialty recommendations. A collaboration of urology and ED providers sought to better incorporate guidelines in the management of acute renal colic in the ED through resident education and initiation of algorithms. We hypothesized that these interventions would increase: use of ultrasound in appropriate patients, use of Tamsulosin for distal ureteral stones, and ambulatory referral to urology. Methods We conducted a study prior to and following introduction of the algorithm (Figure 1) and education session via retrospective chart review of patients diagnosed with nephrolithiasis in the ED at one academic institution. Results The pre-intervention and post-intervention cohorts included 469 and 80 patients respectively. Results summarized in Figure 2. Referrals to urology increased by 39% (p<0.05). Use of Tamsulosin for patients with distal ureteral stone and/or hydronephrosis had no significant change. Within the pre-intervention and post-intervention group there were 167 and 37 patients respectively, who met criteria to be evaluated by ultrasound. Use of bedside ultrasound in this group increased by 29% (p<0.05). Conclusions Collaborative resident education and joint development of management algorithms with urology and ED input, improve management of renal colic. We incorporated guidelines, including the American College of Emergency Physician’s “Choosing Wisely� campaign advocating ultrasound for evaluation of acute renal colic in patients < 50 years old with history of nephrolithiasis. The ED utilization of bedside ultrasound in this group rose significantly following the intervention. Additionally the intervention increased the ambulatory referral rate to urology. We did not impact the prescribing rate for Tamsulosin, however prescribing rates remained higher than published studies. Multidisciplinary collaboration can enhance utilization of guidelines and improve patient care. Funding None
Authors
Jessica Jackson
Jacques Farhi Noah Schenkman |
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MP95-18 |
Virtual Stone Clinic – Future of Stone Management? |
Stone Disease: Epidemiology & Evaluation II | 17BOS |
Abstract: MP95-18 Sources of Funding: None Introduction NHS outpatient waiting lists are ever increasing. In January 2016, 976 patients were awaiting a Urology appointment in Brighton. Urgent referrals to a dedicated stone clinic were seen after 12-14 weeks, with routine referrals seen after 6 months. Patient experience was poor, with stone clinic DNA rates of 14%. Innovative changes were needed and a virtual stone clinic (VSC) was set up to improve the service. Methods VSC set up was based on Brighton&[prime]s award-winning virtual fracture clinic. A consultant-led once-weekly VSC was supported by a MDT of the stone registrar, ESWL radiographer and stone nurse. Referrals were triaged direct from source (ED, GPs, in-patient teams, post-lithotripsy). A target of 20-30 patients per week was set and a tariff of £64 agreed. We aimed to assess the effectiveness following the first 2 months of running the service. Results 212 patients were seen. 90 (42.5%) were discharged without any further investigations after the first VSC. Of the 122 (57.5%) who required follow up, 89 were brought back to the VSC, and only 33 patients (15%) were invited to attend face-to-face outpatient appointment, to either discuss more invasive treatment (PCNL) or for metabolic evaluation. 83% were discharged following a second virtual clinic review._x000D_ _x000D_ Treatment was offered to 38 patients (18%); 23 had ESWL, 10 URS, 3 PCNL, and 2 stent/stent removal. _x000D_ _x000D_ Total income, over 2 months, from the 1h-long weekly VSC was £13 568, vs. £24 960 from 4h-long comparable outpatients clinics. The projected income, had the VSC run for 4h, would have however been £54 272._x000D_ _x000D_ The 6 month waiting list was cleared in the 2 months period. All new referrals are now reviewed by a Consultant in less than 1 week. Feedback from patients was good with only 1 complaint (0.5%) and 8 DNAs (3.8%)._x000D_ _x000D_ We expect to see nearer a 1000 patients by May 2017, and will present updated results. _x000D_ Conclusions VSC is a viable and appropriate way for managing patients&[prime] stones. It is cost effective and has a clear advantage with regards to reducing waiting lists. VSCs avoid the time consuming telephone follow-up clinic and free-up traditional outpatient appointments for other activity or complex metabolic stone patients. Early experience suggests patients enjoy the service._x000D_ _x000D_ Virtual clinics have been gaining popularity across the world, improving the quality and access to care for patients. To the best of our knowledge, this is the first virtual clinic dedicated to patients with urolithiasis in the world. Given the encouraging preliminary results of our study, VSC has the scope to be introduced on a much wider scale._x000D_ Funding None
Authors
Ola Blach
Thomas Smith Stephania Baker Leeanne Newman Andrew Symes |
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MP95-19 |
IMPACT OF A CLINICAL PATHWAY FOR ACUTE NEPHROLITHIASIS IN A PEDIATRIC EMERGENCY DEPARTMENT |
Stone Disease: Epidemiology & Evaluation II | 17BOS |
Abstract: MP95-19 Sources of Funding: none Introduction Pediatric nephrolithiasis is increasingly more common in the acute care setting. Variations in diagnostic evaluation and management may result in differing resource utilization and outcomes. Our institution developed a clinical pathway for the care of nephrolithiasis in the emergency department (ED) and inpatient settings. We describe the impact of the acute nephrolithiasis pathway on children who presented to our hospital with suspected or confirmed acute nephrolithiasis. Methods An evidence-based acute nephrolithiasis clinical pathway was developed by a multidisciplinary clinical working group, which guides decisions on usage of appropriate imaging, medical expulsive therapy, antibiotics, and urologic consultation. Electronic medical record (EMR) integration of the pathway allowed data on metrics of interest to be prospectively collected which could then be compared between pre-implementation and post-implementation periods. Results A total of 158 patients (114 pre-pathway & 44 post-pathway) were included, of which there were 124 (83 pre-pathway & 41 post-pathway) patients evaluated in the ED. There were no significant demographic differences in pre- and post-implementation groups in regards to age, race, medical complexity, or insurance status. Since October 2015, ED length of stay decreased from 359.3 minutes to 305.0 minutes (p-value 0.02), and admissions from the ED decreased from 41.0% to 24.4% (p-value 0.076). 30-day readmission rates following implementation of the pathway decreased from 14.3% to 9.7% (p-value 0.732). CT utilization in the ED decreased from 21.2% to 3.2 % (p-value 0.012). When inpatient CT utilization was added to analysis, the rate decreased from 23.7% to 9.1% (p-value 0.04), as shown in Table 1. Conclusions Implementation of a standardized, evidence-based pathway for pediatric nephrolithiasis management can improve quality without sacrificing patient safety. Our hospital saw significantly decreased CT scan utilization, and decreased ED length of stay and trends towards decreased admission rates with pathway implementation. 30-day readmission rates did not differ significantly, suggesting pathways can be implemented without negatively impacting short-term outcomes. There is additional room for optimization as process improvement continues. Funding none
Authors
Tony Chen
Paul A. Merguerian Russell T. Migita Surabhi B. Vora Jonathan S. Ellison |
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MP95-20 |
The Persistence of Open Stone Surgery in the United States in the 21st Century |
Stone Disease: Epidemiology & Evaluation II | 17BOS |
Abstract: MP95-20 Sources of Funding: none Introduction In the era of minimally-invasive surgery, endoscopic and percutaneous interventions for urinary tract stones have become a mainstay. As such, the need for open stone removing procedures has decreased. We sought to determine the contemporary incidence of open stone surgery among urologists in the United States. Methods Case logs submitted for certification and recertification to the American Board of Urology from 2005-2015 were queried for Current Procedural Terminology codes relevant to open stone-related procedures (50060, 50065, 50070, 50075). Cases were then analyzed for the associated practice type, practice area population, geographic region, provider subspecialty, and certifying or recertifying status of the reporting urologist. Results 334 cases of open stone surgery were identified with the majority (245/334; 73.4%) performed by urologists self-identified as generalists. The most common subspecialtists performing open stone surgery were endourologists (41/334; 12.3%). Most cases were done in the private practice setting (255/317; 80.4%) and in practice areas with populations exceeding 1,000,000 people (126/292; 43.2%). Open stone removal was more commonly reported by urologists applying for recertification (55%) than initial certification (45%). On average, 30 open stone cases were reported each year during the study period. Open stone removal was most commonly performed in the Western Section of the American Urological Association (AUA) (84/334; 25.1%) and least commonly performed in the Northeastern Section (5/334; 1.5%). A Chi-square analysis was performed comparing the number of open stone surgeries performed in each AUA section versus the number expected based on current AUA sectional membership data. The Western Section not only had the highest number of open stone cases reported, but it had a significantly higher number than expected as its urologists represent only 17% of the total AUA membership (p<0.01). The Northeastern section comprises 7% of the total AUA membership but only performed 1.5% of open stone cases which was significantly lower than anticipated (p<0.001). Conclusions Open stone surgery is still performed in the United States, typically by private practice general urologists. Open stone removal is more likely to be reported from the Western Section and in practice areas of the highest population density. This data may prove useful in determining the need and optimal location for future courses highlighting minimally-invasive stone removing strategies. Funding none
Authors
Jessica Lange
Ryan Terlecki |
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MP96-01 |
Surgeon Leadership in the OR: The Effects of Positive and Negative Behaviors on Surgical Team Performance |
General & Epidemiological Trends & Socioeconomics: Quality Improvement & Patient Safety III | 17BOS |
Abstract: MP96-01 Sources of Funding: none Introduction Leadership in the operating room has been widely studied, yet the effects of surgeons' leadership on team performance are not well understood. The purpose of this study was to examine the simultaneous effects of transformational, passive, abusive supervision and over-controlling leadership behaviors by surgeons on surgical team performance. We hypothesized that transformational leadership and the three negative leadership behaviors would positively and negatively influence surgical team performance, respectively. Methods Trained observers attended 150 randomly selected operations at a tertiary care teaching hospital, including 20 urology cases. Observers recorded instances of the four leadership behaviors enacted by the surgeon. Postoperatively, team members (nurses, anesthetists, surgeons and their trainees) completed validated questionnaires rating team cohesion and collective efficacy. To test our hypotheses, multiple regression analyses were computed with psychological safety and collective efficacy as separate outcome variables. Data were analyzed using the complex modeling function in MPlus. Results Surgeons' abusive supervision was negatively associated with psychological safety (unstandardized b = -.352, p < .01). There were no significant associations between the other 3 leadership types and psychological safety (p > .05). Both surgeons' abusive supervision (unstandardized b = -.237, p < .01), and over-controlling leadership (unstandardized b = -.230, p < .05) were negatively associated with collective efficacy. Neither transformational leadership nor passive leadership were linked with collective effective. Conclusions This study is the first to assess the simultaneous effects of surgeons' positive and negative leadership behaviors on intraoperative team performance. Significant effects only surfaced for negative leadership behaviors; transformational leadership did not positively influence team performance. Surgeons' intraoperative negative leadership behaviors appear to suppress the effects of transformational leadership behaviors. Educating surgeons about both positive and negative leadership behaviors offers the opportunity to enhance intraoperative team performance. Funding none
Authors
Julian Barling
Amy Akers Michael Di Lena Darren Beiko |
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MP96-02 |
THE REACH CLINIC: USE OF THE T STAGING SYSTEM FOR THE TRANSITION OF PEDIATRIC PATIENTS WITH NEUROGENIC BLADDER INTO ADULT CLINICS |
General & Epidemiological Trends & Socioeconomics: Quality Improvement & Patient Safety III | 17BOS |
Abstract: MP96-02 Sources of Funding: None Introduction Due to advances in medical management, most patients with congenital bladder diseases survive into adulthood. These patients are managed by pediatric urology teams, often into adulthood. However, this practice is challenged by policies at children's hospitals, unfamiliarity of pediatric providers with adult disease processes, and increasing patient numbers. Subsequently, many affected young adults fall into a care gap, are lost to follow up, and ultimately resurface in adult emergency rooms with acute problems. We propose a transition clinic for patients with neurogenic bladder disease, using a T-staging system for the transition process, to ensure long term quality care. Methods The REACH clinic for neurogenic bladder disease was established in 2014. Patients are categorized according to their transition stage, from T0 to T4. Data collected includes diagnosis, age, gender, T-stage, continence, bladder/bowel management, and previous surgeries. Stages T0 and T1 are seen by pediatric urologists only, T2 and T3 by pediatric and adult urologists, and T4 by adult urologists only. T0 patients are not participating in the transition process yet, T1 patients are being introduced, and T4x are adult patients who did not go through a transition process (Figure 1). Results A total of 285 patients have been seen to date. The etiology of neurogenic bladder was spina bifida in approximately 80% of the patients. There were 110 patients in the T0 stage, 26 in T1, 15 in T2, 3 in T3, 19 in T4, and 112 for T4x. Gender distribution was 160:125 female to male. Median ages in years for the stages ranged from 6.2 for T0 to 27 for T4x. Patients in the transition process T0-T4 had significantly less stones and lower rates of bladder augmentation compared with T4x patients._x000D_ Conclusions Published data confirm that successful transition is linked to early initiation of the process. Successful transition allows for continuation of care, less episodes of preventable emergencies, and establishment of a comprehensive long-term plan. Future studies will evaluate the influence of the REACH clinic on patient follow up, prevention of medical emergencies, and patient and caretaker satisfaction. Questionnaires will determine patient and caretaker priorities and will help focus resources. Funding None
Authors
Bhalaajee Meenakshi-Sundaram
Jake Klein Jennifer Lewis Emily Haddad Dominic Frimberger Gennady Slobodov |
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MP96-03 |
Functional outcomes after “minor” urologic surgery among nursing home residents; a national study |
General & Epidemiological Trends & Socioeconomics: Quality Improvement & Patient Safety III | 17BOS |
Abstract: MP96-03 Sources of Funding: NIA R03AG050872-01; NIDDK K12DK83021-07 Introduction Surgery is commonly performed in frail older individuals seeking care for urologic conditions. While it is known that major urologic surgery is associated with increased morbidity and mortality, outcomes of minor urologic surgery among frail older adults remain unknown. The objective of this study is to explore the long-term functional outcomes associated with minor urologic surgery among nursing home residents. Methods Using inpatient Medicare claims and the Minimum Data Set (MDS) for Nursing Homes, we identified all nursing home residents who underwent the following minor urologic procedures between 2004 and 2012: cystoscopy, cystoscopy with bladder biopsy, transurethral resection of bladder tumor (TURBT), prostate biopsy, transurethral resection of the prostate (TURP), removal of ureteral obstruction, and suprapubic tube placement. We examined changes in activities of daily living (ADL) and mortality up to 12 months after surgery and examined factors associated with ADL decline and mortality over this time period. Results We identified 37,671 individuals residing in nursing homes who underwent minor urologic surgery during the study period. Mean age was 81.5 (±7.4) years, 63.7% were male and 78.2% of procedures were elective. At baseline, 29.2% experienced declines in ADLs in the past 6 months and 60.3% had cognitive impairment. Following surgery, 11.5% and 48.7% of individuals were dead within 1 and 12 months, respectively, while ADLs declined steadily over this time period (Figure). Poorer baseline ADL status and ADL decline at baseline were both predictors for death or ADL decline in the 12 months following surgery [adjusted HR 1.40 (95% CI 1.28-1.53) for worst quartile of ADL status compared to best quartile] and [adjusted HR 1.38 (95% CI 1.29-1.47)], respectively. Conclusions Patients undergoing relatively minor urologic surgery experience detriments in function and high rates of mortality in the year following surgery. This information is important to weigh the risks and benefits of any type of surgery, no matter how small, in this vulnerable population. Funding NIA R03AG050872-01; NIDDK K12DK83021-07
Authors
Anne M Suskind
Shoujun Zhao Louise C Walter Emily Finlayson |
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MP96-04 |
Does Allowing Residents to Operate Worsen the Outcome of an Open Radical Prostatectomy? |
General & Epidemiological Trends & Socioeconomics: Quality Improvement & Patient Safety III | 17BOS |
Abstract: MP96-04 Sources of Funding: None Introduction It is documented that the level of experience and number of operations that a consultant does affects the outcome for the patient. Is this also true when a resident or fellow operates on a patient under direct consultant supervision?_x000D_ The aim of this study is to compare the perioperative, cancer and continence outcomes for men undergoing an open radical prostatectomy performed by either a training surgeon or a consultant urologist in a teaching hospital._x000D_ Methods We prospectively collected data from radical prostatectomies performed by four consultants and all urology residents and fellows between January 2010 and February 2015._x000D_ The outcome measures presented in this paper are length of operation, blood loss, incidence of positive margins and pad usage at one year. Results were analysed using the unpaired student's t test and Fishers exact test. Results 428 men underwent radical prostatectomy at Christchurch Hospital during this time. Age ranged from 41-76 year with a median of 65 years._x000D_ 351(82%) completed the pad usage surveys at one year._x000D_ Overall 73% were performed completely by the consultants and the trainee performed 27%. _x000D_ Median operating time was 105 minutes (range 42-184 mins)_x000D_ Median blood loss was 500mls (range 100-3000mls)_x000D_ Table one shows comparison of the operating times and blood loss between consultants and trainees performing the operations._x000D_ 14 men (4%) used 2 pads a day, only two had had their surgery performed by the trainees. 12 men (3.4%) used 3 or more pads a day at one year. These patients were evenly split between the consultant and the trainees. (Table 2) The overall continence status of the two groups showed no significant difference (p = 0.6298)_x000D_ 32.6 % of men undergoing surgery by a training surgeon had a positive margin compared with 36.6% of those operated on by a qualified urologist (p=0.8673)_x000D_ _x000D_ Table 1 Blood loss and operating time_x000D_ Operator status Consultant Trainee P value_x000D_ Length of operation mins 100 (42-180) 120 (61-184) <0.0001_x000D_ Blood loss mls 500 (100-3000) 600 (100-1700) 0.9081_x000D_ _x000D_ Table 2 Continence Outcomes_x000D_ Operator status Consultant Trainee_x000D_ n (%) n (%)_x000D_ Dry 163 (64) 63 (66)_x000D_ One pad 75 (29) 24 (25)_x000D_ Two pads 12 (5) 2 (2)_x000D_ Three or more pads 6 (2) 6 (6)_x000D_ Conclusions Surgeries performed by a supervised trainee surgeon have the same outcomes as those performed by a qualified urologist. Funding None
Authors
Sharon English
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MP96-05 |
Pre-discharge predictors of readmissions and post-discharge complications in robot-assisted radical prostatectomy |
General & Epidemiological Trends & Socioeconomics: Quality Improvement & Patient Safety III | 17BOS |
Abstract: MP96-05 Sources of Funding: None Introduction Robot-assisted radical prostatectomy (RARP) has become the main surgical treatment for localized prostate cancer in the United States. Little is reported about the association between pre-discharge complications and post-discharge outcomes following RARP. The objective of this study was to explore the pre-discharge predictors of readmissions and post-discharge complications in RARP. Methods The National Surgery Quality Improvement Program (NSQIP) database was used to identify prostate cancer patients who underwent elective RARP from 2012 to 2014. Additional exclusion criteria were utilized to control heterogeneity. Multivariable logistic regression was performed to assess potential pre-discharge predictors of readmissions and post-discharge complications within 30 days of RARP. Results A total of 9,975 patients were included. The readmission rate in the cohort was 3.3% (n = 332), and 4.4% (n = 441) had at least 1 complication. Figure 1 shows the causes of readmissions and distributions of 30-days complications. Multivariable logistic regression showed that increased operative time (OT) (OR = 1.002, 95%CI = 1.001-1.003, P = 0.007), increased length of stay (LOS) (OR = 1.35, 95%CI = 1.23-1.48, P < 0.001), and a pre-discharge complication (OR = 2.24, 95%CI = 1.33-3.76, P = 0.002) were associated with readmission. Increased OT (OR = 1.002, 95%CI = 1.001-1.004, P = 0.003) and increased LOS (OR = 1.16, 95%CI = 1.02-1.30, P = 0.019) were associated with post-discharge complications. Logistic regression in patients without pre-discharge complications (n = 9,804) confirmed that increased OT (OR = 1.002, 95%CI = 1.000-1.003, P = 0.014) and increased LOS (OR = 1.34, 95%CI = 1.20-1.48, P < 0.001) were associated with readmissions. The results also confirmed that increased OT (OR = 1.002, 95%CI = 1.001-1.004, P = 0.003) and increased LOS (OR = 1.18, 95%CI = 1.04-1.34, P = 0.010) were associated with post-discharge complications. Conclusions Pre-discharge complications, OT, and LOS, appear to be associated with post-discharge morbidity outcomes in RARP. Identifying modifiable risk factors for complications and readmissions as well as developing post-operative surgical pathways is a high priority in delivering quality care. Further prospective studies are needed to validate our findings. Funding None
Authors
Leilei Xia
Benjamin Taylor Jeremy Bonzo Jose Pulido Thomas Guzzo |
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MP96-06 |
Topical rectal antiseptic at time of prostate biopsy: how a resident patient safety project evolved into institutional practice |
General & Epidemiological Trends & Socioeconomics: Quality Improvement & Patient Safety III | 17BOS |
Abstract: MP96-06 Sources of Funding: None Introduction Infectious complications following transrectal ultrasound guided prostate needle biopsy (TRUS PNB) has steadily increased owing to rising rates of quinolone resistance. Topical cleansing agents such as povidone iodine or chlorhexidine can decrease the rectal vault bacterial load thereby potentially reducing risk of infection. In 2012, a resident quality improvement project was initiated at our hospital to investigate the impact of topical rectal vault cleansing on infection rates following TRUS PNB. We report outcomes four years after initiating this quality measure. Methods A retrospective chart review was conducted on 982 men who underwent TRUS PNB between 2010 and 2016. Comparison groups includes those who received a topical rectal antiseptic (n=400) compared to those who did not (n=582). Povidone-iodine (n=302) or 4% chlorhexidine solution without alcohol (n=98) were topical antiseptic agents. Outcomes of interest included post-biopsy infection (urinary tract infection and/or sepsis), hospital admission, and need for ICU monitoring. Results Median age and PSA of men included in this study were 64 years and 12ng/mL. Almost 90% of patients were Caucasian, 13% had diabetes, 3% were on chronic immunosuppression, 32% had undergone at least one prior biopsy, 14% had received antibiotics in the past 6 months, and 7% were hospitalized in this same time frame. Almost 30% of men had a prior prostate biopsy. Baseline clinical and demographic variables were similar between the two groups (Table) except for perioperative IV antibiotics use which was higher in the group not receiving topical rectal antiseptic (16% vs. 6%, p<0.0001). Overall, 22 patients (2.2%) developed a post-biopsy infection with a significant reduction in the group receiving topical rectal antiseptic (0.8% vs. 3.3%, p=0.01). Post-biopsy UTI rates (p=0.04) and hospital admission (p=0.03) were also lower in the topical antiseptic group with trends to reduction in blood culture positive sepsis and need for ICU monitoring. Conclusions What started as a resident quality safety project 4 years ago has clearly demonstrated a reduction in infections and hospital admission follow TRUS PNB. Our institutional practice now routinely uses povidone-iodine or chlorhexidine as an adjunct to oral quinolones for TRUS PNB perioperative prophylaxis. Funding None
Authors
Rosa Park
Kalyan Dewan Girish Kirimanjeswara Joseph Clark Matthew Kaag Kathleen Lehman Jay Raman |
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MP96-07 |
Patient Travel Distances To High-Volume Cystectomy Centers Follow A Complex Relationship |
General & Epidemiological Trends & Socioeconomics: Quality Improvement & Patient Safety III | 17BOS |
Abstract: MP96-07 Sources of Funding: none Introduction Regionalization of cystectomy has been associated with improved outcomes but it may exacerbate geographic disparity by increasing travel distance. We sought to examine the association between travel distance to a high-volume cystectomy center and the probability of receiving a cystectomy among patients with muscle-invasive bladder cancer._x000D_ Methods Using Surveillance, Epidemiology, and End Results (SEER)-Medicare data, we identified patients diagnosed with non-metastatic muscle-invasive bladder cancer between 2004 and 2011. We further identified patient treatment (i.e, cystectomy, bladder-sparing alternative) using the inpatient, outpatient, and carrier files. Patients were then grouped into quartiles according to travel distance to the nearest high-volume cystectomy center (<=8, 9-22, 23-53, and >53 miles). High-volume cystectomy centers included those with cystectomy volumes in the top quartile. The relationship between distance to a high-volume cystectomy center and treatment was assessed using a multivariable logistic regression model, adjusting for age, sex, race, comorbidity, marital status, county population, education level and median household income in ZIP code of residence, grade, and stage. Results Among 5149 patients with non-metastatic muscle-invasive bladder cancer, 1998 (39%) underwent a radical cystectomy. The adjusted probability of receiving a cystectomy according to travel distance to a high-volume cystectomy center is summarized in Figure 1. Compared to patients with a travel distance of 8 miles or less, those with a travel distance of 9-22 miles were less likely to receive a cystectomy (adjusted OR 0.79, 95% CI 0.66-0.96). However, this difference was mitigated in those with travel distances beyond 22 miles Conclusions Our findings demonstrated a complex relationship between travel distances to a high-volume cystectomy center and the probability of receiving a radical cystectomy. While increasing distance decreased the likelihood of receiving a cystectomy for patients that live easily commutable distance, this disparity dissipated once the travel distance increased beyond 22 miles. Funding none
Authors
Nathan Hale
Jonathan Yabes Robert Turner Mina Fam Benjamin Davies Bruce Jacobs |
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MP96-08 |
Is Gross Hematuria More Likely Than Microscopic Hematuria to Be Evaluated in a Timely Fashion? |
General & Epidemiological Trends & Socioeconomics: Quality Improvement & Patient Safety III | 17BOS |
Abstract: MP96-08 Sources of Funding: None Introduction Painless gross hematuria (GH) is more likely to be associated urologic malignancy when compared to asymptomatic microscopic hematuria (AMH). However, the presence of either GH or AMH should prompt timely urologic evaluation in the absence of an obvious benign cause. The objective of our study is to evaluate whether presentation with GH or AMH was associated with a timely evaluation of patients that present with hematuria. Methods We performed a retrospective electronic health record (EHR) review of 190 consecutive patients who presented with new onset hematuria to a Veterans Affairs (VA) facility between 10/1/2011 and 12/31/2012. The VA&[prime]s EHR offers a comprehensive longitudinal picture of the patient&[prime]s diagnostic journey. We excluded patients who sought diagnostic care outside the institution (n=22), patients with cystoscopy within 3 years prior (n=9), patients with hematuria in the setting of active urinary tract infection (n=3), and patients with terminal illness (n=1). We collected detailed patient demographic data, medical/psychiatric history, and times to diagnostic evaluation (abdominal imaging, urologic referral, and cystoscopy). We defined &[prime]delay&[prime] when diagnostic evaluation was not completed within 60 days from new onset hematuria. Multivariable logistic regression was performed to identify predictors of delay._x000D_ Results After exclusions, 76 (50.7%) patients were found to have new AMH and 74 (49.3%) new GH. Patients with GH had higher rate of urology referral than AMH (83.8% vs. 57.9%; p<0.001) and were more likely to undergo cystoscopy (75.7% vs. 50%; p=0.001). Delays occurred in 65.8% of AMH patients and 64.9% of GH patients (p=0.9). There was no difference in median days to abdominal imaging completion (33 vs. 27.5, p=0.07), urology referral completion (30 vs. 23.5, p=0.12), or time to cystoscopy completion (71.5 vs. 69, p=0.73) between those presenting with AMH vs. GH. On multivariable logistic regression, there were no variables that predicted lack of action within 60 days. Within one year-post presentation, 1.3% of patients with AMH and 20.3% of patients with GH were found to have bladder neoplasms. _x000D_ Conclusions GH is approximately 20 times more likely to be associated with bladder cancer compared to AMH. Approximately 2/3 of patients with any hematuria were not evaluated within 60 days of presentation. Strategies to reduce these delays are warranted._x000D_ Funding None
Authors
Kyle Richards
Daniel Murphy Vania Lopez Tracy Downs Jason Abel David Jarrard Hardeep Singh |
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MP96-09 |
Predicting Probability of Missed Clinic Visits at an Academic Multi-Provider Urology Clinic |
General & Epidemiological Trends & Socioeconomics: Quality Improvement & Patient Safety III | 17BOS |
Abstract: MP96-09 Sources of Funding: none Introduction With the predicted shortage of urologists nationwide, efficiency in outpatient urology clinics is crucial. Our previous study demonstrated predictable patient demographics and diagnoses associated with missed clinic appointments. The significant characteristics of our study included: age, new versus established patient, and patient diagnoses. This study aims to utilize our previous data to develop a model to predict patient missed clinic appointments. Methods Utilizing our previous data, logarithmic regression analysis was performed to formulate an equation to predict the probability of a patient missing their appointment. Variables included age, new versus established patient, and groupings of 27 patient diagnoses. Using this equation, a retrospective analysis of clinic patient data was performed for four full-time academic urologists over a six-month period comparing predicted versus actual missed visits. Results A total of 2486 clinic appointments were compiled for four providers in the adult urology clinic over six months. Of the total, 408 were actual missed clinic visits at an overall no-show rate of 16.4%. The calculated number of patients missing their appointments was 488. Of the predicted 488 missed visits, the calculated number of patients was over by 130 with an average of 1.19 patients over per day, and under by 50 with an average of 0.46 patients under per day. The number of perfect days where the predicted number matched the actual number was 26/109 (23.9%), within +/- 1 patients 61/109 (56.0%), and within +/- 2 patients 87/109 (79.8%). Conversely, the model over predicted 4 or greater patient no-shows on 6/109 (5.5%) of days. Over-predicted patients per day ranged from 0.01-6.5 with a mean of 1.58. Conclusions This review further characterizes the predictable patient characteristics associated with missed clinic visits for an under-served academic urology patient population. This model works well over a large number of patients with a 79.8% efficacy within 2 patients. Applying this to a clinical setting would be limited by overestimating the number of patients that would be scheduled. The model still will require validation when put to test on data from different practice settings and larger patient data sets. Additionally, we predict there may be confounding factors (type of insurance, distance to appointment, previous missed appointments) that we plan to study in order to add to the accuracy of the model. Funding none
Authors
Jordan Foreman
Bryan Wilson Julie Riley |
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MP96-10 |
Initial validation of automated data extraction methods in urologic oncology practice |
General & Epidemiological Trends & Socioeconomics: Quality Improvement & Patient Safety III | 17BOS |
Abstract: MP96-10 Sources of Funding: None. Introduction The Urological Outcomes Data Base (UODB) has existed for 15 years and contains data on over 6,000 patients treated for prostate cancer at University of California, San Francisco (UCSF). Until recently, clinical data in UODB have been manually abstracted from patient records. We are now implementing automated data extraction from the EPIC electronic health record system. EPIC is supported by a research database that automatically extracts patient data. We aim to study a set of chosen variables and compare the types and degrees of miscorrelation between automated and manual data extraction, to see if manual data extraction can be minimized or eliminated. Methods In early 2016 we developed a set of Smart Data Elements (SDEs) for urologic oncology, including SDEs for men with prostate cancer. These SDEs are populated automatically from the EPIC clinician interface during routine clinical documentation, using either SmartForms or SmartLists embedded within a dozen new standardized templates. SDEs are available immediately in EPIC's Clarity database, and can be populated in future documentation notes. We selected 15 core sample SDEs for validation against manually abstracted data in UODB for patients seen in 2016. Manually abstracted values were compared directly to SDEs values to assess match frequency. Results The 15 SDEs encompassed a wide range of variables from diagnosis to pathologic staging, including clinical risk characteristics at diagnosis, biopsy Gleason score and surgical pathology findings. The median number of patients per variable was 37 (IQR 17-39). Median number of matches per variable was was 14% (IQR 5-37) with median match rate of 70.6% (IQR 35.7-97.4%). Detailed match rates are shown in the table. Conclusions Next steps include expanding validation rules across a larger set of variables and exploring the limitations of the match strategy. In some cases, data sources such as a computerized system may prove more accurate than manual entry. Working with the AUA Quality (AQUA) registry, we plan to transfer subsets of SDEs to the EPIC Foundation repository, allowing access to any EPIC center. Automated data extraction can improve clinical workflow and streamline data collection within urologic oncology. Funding None.
Authors
Renu Eapen
Samuel Washington III Annika Herlemann David Tat Mark Bridge Niloufar Ameli Janet Cowan Frank Stauf Peter Carroll Matthew Cooperberg |
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MP96-11 |
In patients with microhematuria, a follow up urinalysis adds information about the risk of benign and malignant diagnoses |
General & Epidemiological Trends & Socioeconomics: Quality Improvement & Patient Safety III | 17BOS |
Abstract: MP96-11 Sources of Funding: This was funded in part by the 2016 AAMC Clinical Care Innovation Pilot Award Introduction Concerns about the intermittency of microhematuria (MH) have led to changes in management guidelines. Currently, a single positive urinalysis (≥3 RBC/hpf) is considered enough to warrant a diagnostic evaluation. However, this practice is supported by low-level evidence. It was our hypothesis that a follow up urinalysis (FUUA) adds prognostic information to the work up of MH. Methods Using a multicenter electronic data warehouse, we retrospectively identified all patients from 2012-2015 with a new diagnosis of MH. Characteristics of those who did and did not complete a FUUA were compared. Severity of MH on FUUA was related and compared to severity on the initial sample. In patients who had a FUUA, regression modeling was used to determine the association of a positive FUUA with a diagnosis of bladder cancer, kidney cancer, and nephrolithiasis after adjusting for age, sex, and degree of MH on index UA. Results _x000D_ Of the 7,879 patients identified with MH, 4,270 (54.1%) had a FUUA at a median time of 71 days after initial UA. Patients who had a FUUA were older (57 vs 53, p<0.001), more commonly female (57% vs. 53%, p=0.001), but had no differences among races (p=0.45). Degree of MH on index UA did not relate to completion of a FUUA (p=0.08). Most FUUA (65.8%) were negative and there was a weak correlation between degree of MH on initial UA and FUUA (rs=0.19, p<0.001), (Figure 1). After adjusting for age, gender and severity of MH on index UA, positive FUUAs were associated with increased odds of being diagnosed with bladder cancer, kidney cancer, and nephrolithiasis compared to a negative FUUA (Table 1). Any FUUA with 11 or more RBC/hpf increased the risk of bladder cancer diagnosis significantly over a negative FUUA. Conversely, in kidney cancer and urolithiasis, compared to a negative FUUA, only a FUUA with 100+ RBC/hpf increased the odds of diagnosis. Conclusions A positive FUUA may help to better identify patients with bladder cancer, kidney cancer, and urolithiasis-- but only at severe thresholds of RBC/hpf. Funding This was funded in part by the 2016 AAMC Clinical Care Innovation Pilot Award
Authors
Richard Matulewicz
John Oliver DeLancey Joshua Meeks |
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MP96-12 |
Does Routine Overnight Stay after Robotic Partial Nephrectomy Increase Complications? |
General & Epidemiological Trends & Socioeconomics: Quality Improvement & Patient Safety III | 17BOS |
Abstract: MP96-12 Sources of Funding: None Introduction Minimally-invasive surgery is known to reduce postoperative length of stay (LOS) for many procedures, but published LOS after robotic partial nephrectomy (RPN) remain similar to what is achieved with contemporary open PN (2-3 days). With increasing experience, some surgeons have transitioned to overnight stay after RPN, postulating that RPN is not so materially different from robotic prostatectomy, where routinely, LOS is overnight. Critics suggest that RPN has risks and complications inherent to nephron-sparing surgery that mandate longer LOS. We investigated whether RPN surgeons who instituted a routine overnight stay protocol had more complications than those who did not. Methods We reviewed a multi-institutional database of 1,868 patients who underwent RPN by 6 surgeons from 2006-2016. Exclusions included 117 patients for stage >cT1b, multiple tumors, metastatic disease, or incomplete complication data. During the selected study period of 9/13-9/16, three surgeons used routine discharge on postoperative day (POD) #1, defined as >80%, while the others discharged patients without a protocol targeting POD#1. A total of 655 patients met inclusion criteria during the 3-year period, including 455 with a POD#1 protocol surgeon and 210 patients without. Complication rates were compared between groups using Chi-squared tests of independence. Results Among surgeons using a POD#1 protocol, 410 of 455 patients (90.2%) were discharged on POD#1 with 97.6%, 82.1% and 80.0% of patients discharged on POD#1 by each of the 3 surgeons. Mean LOS overall was 1.13d with mean LOS for the others being 2.02d (p<.001) and 91.1% of patients discharged by POD#3. Patients of POD#1 protocol surgeons had higher Charlson comorbidity score (4 vs. 2, p=.033) and were less likely to have a hilar tumor (15.9% vs. 23.1%, p=.03). There were no differences in age (p=.10), BMI (p=.164), tumor size (p=.502), or Nephrometry score (p=.974). Between the POD#1 protocol group and the others, there were no significant differences in overall complications (9.5% vs. 8.6%, p=.715), major complications (2.0% vs. 3.8%, p=.164), medical complications (5.9% vs. 2.8%, p=.089), surgical complications (4.0% vs. 5.7%, p=.310), or complications by Clavien grade (p=.130). Conclusions Use of a protocol targeting discharge on POD#1 after RPN did not increase complications. Surgeons performing RPN should assess whether such a practice is implementable among their patients to take advantage of the minimally-invasive nature of the operation and reduce LOS. Funding None
Authors
Ronney Abaza
David Paulucci Ashok Hemal James Porter Daniel Eun Akshay Bhandari Ketan Badani |
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MP96-13 |
Consultant outcome publication: patients’ opinions of a new mandatory health policy |
General & Epidemiological Trends & Socioeconomics: Quality Improvement & Patient Safety III | 17BOS |
Abstract: MP96-13 Sources of Funding: none Introduction Consultant Outcome Publication (COP) regarding outcomes of operations performed by individual surgeons was introduced to UK Urology in 2012 and was championed as a policy to increase transparency of surgical outcomes for patients. Research assessing patient opinion on the introduction of the mandatory health policy is restricted to experience of COP from cardiothoracic surgery in both the US and UK with no research to date from the field of urology. _x000D_ We interviewed patients awaiting surgery to assess if patients are using COP and to evaluate opinion towards the health policy._x000D_ Methods Patient use of and opinions towards COP were explored through one-on-one concept elicitation interviews. Patients awaiting nephrectomy (radical or partial) were invited to take part in the study following explanation of their diagnosis. Interviews were carried out until thematic saturation was reached (n=15). Results Six key topics were identified by the analysis of interview transcripts: _x000D_ (i) Patients are not aware that consultant surgical outcomes are accessible. _x000D_ (ii) Patients welcome a policy to help ensure surgical quality but some voice concern that published data may not be accurate and could lead to risk averse behavior._x000D_ (iii) Investigating the performance of their surgeon is a low priority for patients compared to other stresses at the time of diagnosis including likely presence of cancer, concern for future risk of chronic kidney disease and any problems surgery may cause for their families._x000D_ (iv) Patients regard their own interaction with their surgeon as the most important factor for establishing confidence in their surgeon. _x000D_ (v) Patients take significant reassurance from being referred to a tertiary level service._x000D_ (vi) Patients may base decisions regarding surgery on their own previous experiences of healthcare and also those of family and friends._x000D_ Conclusions For reassurance prior to surgery patients rely primarily on confidence and trust in their surgeon which are gained from the one-on-one interaction and may only use COP to validate their initial impressions of their surgeon. Our data suggests that although COP was in part introduced to increase transparency of surgical outcomes for patients, patients themselves are not aware that the data is available. Furthermore, even after being informed of COP, patients were still reluctant to access the published data suggesting that the type of information currently being published may not be what patients want, and requires review. Funding none
Authors
Marc Williams
Nikki Cotterill Marcus Drake Francis Keeley |
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MP96-14 |
Analysis of National Trends in Hospital Acquired Conditions Following Major Urologic Surgery Before and After Implementation of the Hospital Acquired Condition Reduction Program |
General & Epidemiological Trends & Socioeconomics: Quality Improvement & Patient Safety III | 17BOS |
Abstract: MP96-14 Sources of Funding: none Introduction Hospital acquired conditions are a significant source of patient morbidity and mortality and have been targeted by recent legislation as achievable target for quality improvement. Here, we aim to define the rates of 3 most of the most common hospital acquired conditions (HACs); surgical site infection (SSI) , urinary tract infection (UTI) , and venous thromboembolism (VTE) in patients who undergo major urologic surgery over a period of time encompassing the implementation of the Hospital Acquired Condition Reduction program. Methods Using American College of Surgeons National Surgical Quality Improvement Program data, we determined rates of HACs in patients undergoing major inpatient urologic surgery from 2005 to 2012. Rates were stratified by procedure type and approach (open vs. laparoscopic/robotic). Multivariable logistic regression was used to determine the association between [insert independent variable of interest] and HACs. Results We identified 39,257 patients undergoing major urologic surgery, of whom 2300 (5.8%) had at least one hospital acquired condition. UTI (2.58%) was the most common, followed by SSI (2.46%) and VTE (0.68%). Multivariable logistic regression analysis demonstrated that open surgical approach, diabetes, obesity, hypertension, congestive heart failure, BMI>30, and length of stay were associated with higher likelihood of HAC. When controlling for surgical approach, patients undergoing prostatectomy had the lowest predicted probability of HAC (PP 0.04, p<0.05) compared to patients undergoing upper tract surgery (PP 0.06) or cystectomy and retroperitoneal lymph node dissection (PP 0.02) We observed a non-significant secular trend of decreasing rates of HAC from 7.4% to 5.8% HAC’s during the study period, which encompassed the implementation of the CMS Hospital Acquired Condition Reduction Program. Conclusions HACs occurred at a rate of 5.8% during major urologic surgery, and are significantly affected by procedure type and patient health status. The rate of HAC appeared unaffected by national reduction program in this cohort. Better understanding of the non-modifiable factors associated with HACs is critical in developing effective reduction programs. Funding none
Authors
Temitope Rude
Nicholas Donin Matthew Cohn William Meeks Scott Gulig James Wysock Danil Makarov Marc Bjurlin |
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MP96-15 |
SURGICAL PROCEDURAL VOLUME MAY NOT BE SOLE DRIVER OF URINARY FUNCTION OUTCOME FOLLOWING RADICAL PROSTATECTOMY |
General & Epidemiological Trends & Socioeconomics: Quality Improvement & Patient Safety III | 17BOS |
Abstract: MP96-15 Sources of Funding: Blue Cross and Blue Shield of Michigan Introduction A broad base of surgical literature supports the notion that surgeons with high procedural volume attain superior surgical outcomes. Nonetheless, the practical application of this concept, the referral of all patients to a few select surgeons, is not feasible in our current healthcare framework. Within the context of the Michigan Urologic Surgery Improvement Collaborative (MUSIC), we sought to further explore the relationship between annual prostatectomy volume (APV) and patient reported urinary function (UF) following radical prostatectomy (RP). _x000D_ Methods The MUSIC patient reported outcomes (PRO) project assesses urinary and erectile functional status for men undergoing RP via surveys collected before and at 3, 6, 12, and 24 months after surgery. Surgeons included for analysis had ≥50% patient enrollment in PRO and ≥10 patient responses at 3 and 6 months. Within this cohort of surgeons, we evaluated the relationship between surgical volume and patient reported UF score by calculating the correlation coefficient. Results Of 61 PRO surgeons, 56 had ≥50% patient enrollment and 21 had ≥10 patients respond at 3 and 6 months. APV ranged from 10 to 153. Analysis, after controlling for age, race, BMI, grade, stage, comorbidity, and PSA, demonstrated poor correlation between UF score and APV at both 3 (r = 0.13) and 6 months (r = 0.21). Figure 1, the scatter plot of UF score at 6 months vs. surgeon APV, demonstrates some clustering of low volume surgeons to lower scores, however, no clearly discernable trend towards improved UF score with increasing surgical volume. Conclusions In contrast to much of the surgical literature that associates increasing surgeon volume with improved surgical outcomes, we did not demonstrate significant correlation between surgeon APV and UF score following RP. Notably, our work is limited by our inability to control for significant patient level factors, which may affect early return of UF. Despite this limitation, our work suggests that surgeon factors, other than surgical volume, affect UF. Therefore, as the collaborative seeks to identify best practices, attention should be given to high performers regardless of APV. Further, patients and surgeons should be encouraged that superb outcomes are attainable even in smaller practices. Funding Blue Cross and Blue Shield of Michigan
Authors
Daniel Pucheril
Naveen Kachroo Tae Kim Rodney Dunn Greg Auffenberg James Peabody for the Michigan Urological Surgery Improvement Collaborative |
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MP96-16 |
Association of travel distance, socioeconomic status, and referral institution on delay to definitive surgery in patients with bladder cancer |
General & Epidemiological Trends & Socioeconomics: Quality Improvement & Patient Safety III | 17BOS |
Abstract: MP96-16 Sources of Funding: None Introduction Treatment delay in patients with invasive bladder cancer negatively impacts survival. In rural settings, delays to definitive surgery are often associated with travel distance/burden. We examine factors associated with delay to radical cystectomy (RC) at an urban, tertiary referral center, where travel burden is less likely to represent a barrier to timely care. Methods IRB approved, retrospective review was performed on 383 consecutive non-metastatic patients who underwent definitive RC at a single National Cancer Institute (NCI) designated comprehensive care center between 2001-2014. Zip code derived proxies of socioeconomic status were collected in reference to patient primary residence using US Census data, in addition to characteristics of referring facilities including size, teaching status, and cancer center designation. Travel distance was estimated via straight line distance calculated from latitude and longitude. Multivariable logistic regression analysis was performed to identify factors associated with delay to cystectomy, defined as > 12 weeks from diagnosis of muscle invasive disease to RC. Patients residing outside the US were excluded from analysis. Results Twenty-two patients residing outside the US were excluded, leaving 363 patients for final analysis. Median travel distance was 15.1 miles, and median time from diagnosis to RC was 8 weeks. On multivariable analysis, referral from a non-NCI designated comprehensive care center (OR 3.1 95% CI [1.04 - 9.15] p=0.042), diagnosis outside of our hospital network (OR 5.5 95% CI [1.66 - 18.01] p=0.005), and receipt of neoadjuvant chemotherapy (OR 28 95% CI [14.1 - 56.2] p<0.001) were associated delay to RC. Patient age (p=.842), size of referring hospital (p=0.53), median household income (p=0.16) and estimated patient travel distance (p=0.41) were not associated with delay. Conclusions In an urban environment, distance to treatment facility was not associated with delay to RC. Delay was associated with characteristics referring institutions, including cancer center designation. Further investigation is warranted to determine if consolidation of care to designated centers for complex disease processes such as bladder cancer may improve patient outcomes. Funding None
Authors
David Golombos
Padraic O'Malley Patrick Lewicki Abimbola Ayangbesan LaMont Barlow Douglas Scherr |
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MP96-17 |
Lower Serum Albumin Levels are Associated with Longer Lengths of Stay (LOS) Following Cystectomy: The National Surgical Quality Improvement Program |
General & Epidemiological Trends & Socioeconomics: Quality Improvement & Patient Safety III | 17BOS |
Abstract: MP96-17 Sources of Funding: The project described was supported by the National Center for Research Resources, Grant UL1 RR024975-01, and is now at the National Center for Advancing Translational Sciences, Grant 2 UL1 TR000445-06. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Introduction Serum albumin levels have been reported to be a valid measure of nutritional status for epidemiologic studies. However, contemporary population-based epidemiologic data evaluating the effect of preoperative albumin levels on LOS after cystectomy and urinary diversion is limited. In this study, we measure the relationship between preoperative serum albumin level and hospital LOS and hypothesized that decreasing preoperative albumin levels would be associated with increasing LOS. Such an association would strengthen the importance of preoperative nutritional optimization prior to cystectomy. Methods Data was acquired from the 2014-2015 National Surgical Quality Improvement Program database. We identified 2,469 adult patients who underwent a cystectomy between January 1st 2014 and December 31st 2015. The primary outcome was hospital LOS and the primary exposure was preoperative albumin. We fit proportional odds logistic model with patient-level variables that were either known to be associated with increased LOS or that we had hypothesized would be prior to model fitting. We allowed all continuous variables to have a nonlinear relationship with the primary outcome using restricted cubic spline with 5 knots. Results Multivariable proportional odds logistic regression determined that preoperative serum albumin was independently associated with LOS (OR: 0.81; 95% CI: 0.64-1.02; p<0.001). Figure 1 demonstrates that LOS increases significantly for patients with a serum albumin level of less than 4 g/dl. Other significant predictors include older age (OR 1.56; 95% CI 1.21-2.01; p<0.001), elevated BMI (OR 1.48; 95% CI 1.17-1.86; p<0.001), and non-Caucasian patients (OR 1.7; 95% CI 1.34-2.18; p<0.001). Conclusions This study provides evidence that lower preoperative serum albumin levels are associated with increasing LOS. Efforts to optimize a patient's nutritional status prior to cystectomy undoubtedly have many benefits, including a shorter LOS. Funding The project described was supported by the National Center for Research Resources, Grant UL1 RR024975-01, and is now at the National Center for Advancing Translational Sciences, Grant 2 UL1 TR000445-06. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
Authors
Rohan Bhalla
Li Wang Sam Chang Mark Tyson |
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MP96-18 |
Impact of Prostate Cancer Therapy on Urinary Incontinence and Quality of Life |
General & Epidemiological Trends & Socioeconomics: Quality Improvement & Patient Safety III | 17BOS |
Abstract: MP96-18 Sources of Funding: none Introduction Prostate cancer therapy is known to affect urinary symptoms in men, and its effect on quality of life can depend upon which type of treatment is received. This study is a retrospective review of a large database of men who underwent surgical prostate cancer treatment to assess the impact of therapy on quality of life in prostate cancer patients. Methods A total of 501 patients who underwent treatment for prostate cancer at a single institution from 2004-2014 were reviewed. The patients in this database were stratified into three groups with respect to the type of therapy received--robot-assisted laparoscopic radical prostatectomy (RLP), brachytherapy, and cryotherapy. Urinary incontinence related quality of life (HRQoL) was assessed at baseline and again at 1-60 months after therapy using the Expanded Prostate Cancer Index Composite (EPIC) questionnaire. Preoperative and postoperative urinary incontinence scores were compared using a Student's t-test. Results Baseline patient characteristics were similar between each treatment group. Diabetes was the only comorbidity correlated with urinary symptoms. Baseline urinary incontinence scores were 93.3, 94.5, and 88.2 in the RLP, brachytherapy, and cryotherapy groups, respectively with a significant difference between the RLP and cryotherapy groups (p = 0.046). Urinary incontinence worsened in all three groups at the first follow-up (2.2 months) after treatment (p < 0.0001). The corresponding scores at long term follow-up were 72.0 (p < 0.0001), 78.1 (p < 0.0001), and 83.1 (p = 0.165). The RLP group urinary incontinence improved over time, while the brachytherapy group incontinence did not change significantly after short term follow-up. Only the cryotherapy group achieved a return to baseline at mean follow-up of 17.3 months. No significant difference was found between mean urinary incontinence for RLP and brachytherapy at long-term follow-up (p = 0.128)._x000D_ Conclusions Due to the high survival of patients who receive treatment for prostate cancer, quality of life is a major concern when choosing therapy. All three types of prostate cancer treatment studied above cause a short-term worsening of urinary incontinence. Long term, RLP and brachytherapy are associated with worsening of urinary incontinence, whereas cryotherapy is associated with the least impact. Comparatively, RLP and brachytherapy yield similar post-therapy urinary incontinence outcomes. Funding none
Authors
Andrew Wang
Paul McClain Robert Given |
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MP96-19 |
RETURN TO EMERGENCY DEPARTMENT AFTER PEDIATRIC UROLOGY PROCEDURES |
General & Epidemiological Trends & Socioeconomics: Quality Improvement & Patient Safety III | 17BOS |
Abstract: MP96-19 Sources of Funding: none Introduction Unplanned postoperative return to emergency department (ED) and readmission represent a quality bench outcome and pose a considerable cost burden for health care systems. Here we evaluate a free-standing tertiary care children&[prime]s hospital to identify potential causes and explore areas for improvement. Methods A Quality Improvement Board approved retrospective study was performed in our institution identifying all surgical cases done under the service of Urology from October 2012 to September 2015. Baseline demographics, surgeon, operation type and duration, ASA class, and type of admission were evaluated. Patients who returned to ED within 30 days from surgery date were identified. The ED records were reviewed for time of ED return, reason for visit, and treatment received. Univariate and multivariate statistical analysis were done to identify variables that are associated with ED return. Odds ratio (OR) and 95% confidence Intervals (95%CI) were generated to determine the magnitude of relationships. Results A total of 4125 surgical cases were performed. Overall mean age was 59.9 months (SEM 0.94); with 85.1% of the patients were males. Three hundred forty-nine (8.5%) had unplanned return to the ED within 30 days from the surgery. 15.2% (53) of these returned patients required readmission and 4.3% (15) of them needed further surgical interventions, which were mainly urinary drainage procedures. Penile surgeries accounted for 34.9% of the returns. The most common reason for the ED visit was urinary tract infection in 17.2%, followed by issues related to urethral catheters and wounds (14.3% each). Univariate analysis and multivariate analysis revealed that, the directly associated variables to ED returns were patients younger than 3 yr old (OR 1.48 95%CI 1.18 to 1.87), those lived in the same city with our institution (OR 2.16 95%CI 1.69 -2.76) , procedure time > 150mins (OR 1.5 95%CI 1.12 to 2.00) and in-patient procedures (OR 1.4 95%CI 1.06 to 1.84). The Inguino-scrotal surgery types have significantly lesser ED returns (OR 0.30 95%CI 0.22 to 0.43). Conclusions This study shows that the majority of ED returns can be managed conservatively, and probably are preventable. This offers an opportunity for quality improvement by highlighting the importance of optimizing peri-operative family / patient education, reinforcing post-operative instructions and assures an understanding of family expectations. Funding none
Authors
Naimet K Naoum Alsaigh
Michael Chua Jessica Ming Joana Dos Santos Megan Saunders Roberto I Lopes Martin Koyle Walid Farhat |
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MP96-20 |
Challenging the Paradigm of Mandatory Overnight Observation after Elective Percutaneous Nephrostomy Tube Placement |
General & Epidemiological Trends & Socioeconomics: Quality Improvement & Patient Safety III | 17BOS |
Abstract: MP96-20 Sources of Funding: none Introduction The typical paradigm for patients who undergo elective percutaneous nephrostomy tube placement (PCN) is 23-hr observation to monitor for post-procedure complications such as sepsis or bleeding. However, many similar Interventional Radiology (IR) procedures such as biopsies or abscess drainage are done on an outpatient basis. This maximizes patient and provider satisfaction while reducing medical costs and resource utilization. Our objective is to evaluate the safety of elective PCN placement and to identify which groups should be considered for outpatient PCN placement. Methods We performed a retrospective chart review of 374 patients at our institution who underwent PCN or nephroureteral tube placement by IR from 1/2014 - 1/2016. We excluded inpatients, patients with suspected urosepsis, pregnancy, age <18 yrs or pelvic kidneys. All patients were admitted for observation. We collected data on demographics, clinical characteristics, procedural details and post-PCN clinical course. T-test and Chi-squared analysis were used to assess risk factors for statistical significance. Results We identified 94 patients who underwent electively scheduled PCN placement (see Table 1). There were no major (Clavien Gr III-IV) complications, episodes of sepsis or hemorrhage. There were 8 patients (9%) with systemic inflammatory response syndrome (SIRS): tachycardia (6), fevers (5) and chills (2). Excluding a patient with pancytopenia due to chemotherapy, 100% of patients with SIRS had stones, 6/7 had staghorn stones (p=0.001) and 5/7 had been treated for positive cultures pre-PCN. They were also statistically more likely to have had difficult procedures & positive PCN cultures. Neither chronically colonized or purulent-appearing urine were associated with complications. Conclusions Our data suggests that most patients do not require admission for observation after elective PCN placement. Risk factors for post-PCN complications include large stone burden, longer fluoroscopy time, and difficult PCN access. One-third of patients with staghorn stones developed SIRS and they accounted for the majority of complications despite pre-PCN antibiotic treatment, highlighting the importance of renal pelvic urine cultures and close post-procedural observation for this high-risk group. Funding none
Authors
Jennifer Robles
Nicole Miller |
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MP97-01 |
Efficacy of a neoadjuvant luteinizing hormone-releasing hormone antagonist plus low-dose estramustine phosphate in high-risk prostate cancer |
Prostate Cancer: Localized: Surgical Therapy VIII | 17BOS |
Abstract: MP97-01 Sources of Funding: none Introduction The optimal treatment for high-risk prostate cancer (Pca) remains to be established. We previously reported favorable biochemical recurrence-free survival (BRFS) for high-risk Pca patients treated with neoadjuvant therapy comprising a luteinizing hormone-releasing hormone (LHRH) agonist plus low-dose estramustine (EMP) (LHRH agonist + EMP) prior to radical prostatectomy (RP) (Koie T et al. Int J Clin Oncol 2015). In the present study, we evaluated the efficacy of neoadjuvant therapy comprising a LHRH antagonist plus low-dose EMP (LHRH antagonist + EMP) in patients with high-risk Pca. Methods Between September 2005 and March 2016, we identified 406 high-risk Pca patients of whom 136 received neoadjuvant LHRH antagonist + EMP and 270 received LHRH agonist + EMP before RP. We retrospectively evaluated the clinical and pathological covariates between the two groups. The primary endpoint was the rate of pathological ?T2 status, and the secondary endpoint was BRFS. Results The rates of pathological ?T2 status were 80.2% and 61.5% in the LHRH antagonist + EMP and LHRH agonist + EMP groups, respectively (P < 0.001). The 2-year BRFS rates were 97.8% and 87.8% in the LHRH antagonist + EMP and LHRH agonist + EMP groups, respectively (P = 0.027). Multivariate analysis revealed that biopsy Gleason score, LHRH antagonist + EMP, and clinical T stage were independent predictors of pathological ?T2 status in surgical specimens. Conclusions Our findings suggest that neoadjuvant LHRH antagonist + EMP followed by RP may improve the pathological outcomes and reduce the risk of biochemical recurrence in patients with high-risk Pca. Further prospective studies to confirm these findings are warranted. Funding none
Authors
Kazuhisa Hagiwara
Takuya Koie Yuki Tobisawa Tohru Yoneyama Hayato Yamamoto Atsushi Imai Shingo Hatakeyama Takahiro Yoneyama Yasuhiro Hashimoto Chikara Ohyama |
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MP97-02 |
Robotic Assisted Radical Prostatectomy in Metabolic Syndrome Patients. Stratification by number of Metabolic Risk factors. |
Prostate Cancer: Localized: Surgical Therapy VIII | 17BOS |
Abstract: MP97-02 Sources of Funding: None Introduction Metabolic Syndrome (MetS) is widely accepted in the U.S as a critical health epidemic, as MetS has been linked to a significant increase in the risk of developing prostate cancer in recent literature, yet the number of studies analyzing this ever growing percentage of the population remains underdeveloped._x000D_ _x000D_ To assess the variation in preoperative features, operative, oncological and functional outcomes in patients who underwent RARP for a prostate cancer (PC), stratifying them by number of Metabolic Risk Factors (MRF) in a cumulative stepwise fashion. Methods In our IRB approved retrospective analysis, between January 2008 and March 2016, 6954 patients underwent Robot Assisted Radical Prostatectomy (RARP) for localized PC by one single surgeon (V.P) at our institution. Patients were then divided into 5 groups depending on the number of MRF(s) and obesity status: (I) 1488 non-obese (BMI <30 kg/m2) +0 MRF, (II) 439 obese + 0 MRF, (III) 671 obese + 1 MRF, (IV) 619 obesity + 2 MRFs, (V) 206 obesity + 3 MRFs. Demographic, clinical, operative, oncological and functional results were analyzed and compared. Morbidity was reported using Clavien-Dindo Classification. Results There were no significant differences in preoperative PSA (p>0.05). Charlson Score Index increased significantly increased from Group 1-5 while age and BMI decreased through them (p<0.001). The proportion of High Risk patients increased overall as the number of MRF(s) increased (from 12.9%, GI to 21.0% GV; p=0.003). While operative time and estimated blood loss rates increased with increasing MRF(s) (p<0.001), full nerve-sparing technique decreased through them. No differences were found in complication rate among groups (p>0.05). While adverse pathological features (tumor volume, percentage, positive surgical margins and extraprostatic extension) were found as more MRF were present (p<0.05), overall and disease specific survival were similar among them (p>0.05). Lastly, in terms of functional results; a stepwise decrease of potency and continence rates were observed through the groups (67.4 to 36.9%, and 91.9 to 80.1%, respectively), while no differences in the average time to potency and continence was observed (p>0.05). Conclusions In our study, despite an additive number of MRF(s) was associated with an increased risk of aggressive prostate cancer, final oncological outcomes were similar. Furthermore, an increasing number of MRF’s also was associated with a step-wise decrease recovery in functional outcomes. Funding None
Authors
Xavier Bonet
Gabriel Ogaya Tracey Woodlief Eduardo Hernández-Cardona Hariharan Ganapathi Travis Rogers Renzo diNatale Rafael Coelho Bernardo Rocco Vipul Patel |
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MP97-03 |
Application of local 18F-fluoro-2-deoxyglucose uptake by the prostate to assess perioperative results of robot-assisted laparoscopic radical prostatectomy. |
Prostate Cancer: Localized: Surgical Therapy VIII | 17BOS |
Abstract: MP97-03 Sources of Funding: none Introduction Little glucose metabolism is generally thought to occur in prostate cancer, leading to low diagnostic accuracy of 18F-fluoro-2-deoxyglucose (FDG) positron emission tomography-computed tomography (PET/CT). Nevertheless, this modality is reportedly useful for identifying high-risk local cancers. We therefore investigated whether local FDG uptake by the prostate reflects the perioperative results of robot-assisted laparoscopic radical prostatectomy (RALP). Methods Between November 2012 and August 2016, a total of 248 patients underwent RALP at our institution. Of these, subjects in this study comprised 116 patients in whom FDG-PET/CT was employed for preoperative staging. We retrospectively compared perioperative results between patients, stratified for local FDG uptake in the prostate. Patients who had received preoperative hormone therapy were excluded from the study. FDG uptake was rated based on clinical reports prepared by two radiation diagnosticians. Patient background characteristics, perioperative results and postoperative pathological results were compared between subjects divided into PET-positive and -negative groups. Results Participants comprised 40 PET-positive subjects and 76 PET-negative subjects. Among the patient background characteristics, mean age was slightly but significantly higher in the PET-positive group (66 years) than in the PET-negative group (64 years; p=0.0485). No significant differences were seen in PSA level, clinical T stage or Gleason Score (GS). Operative time, console time and volume of blood loss also showed no differences between groups, and no patients in either group suffered rectal perforation or required blood transfusion. Postoperative urethral balloon retention time and urinary continence rate at 3 months postoperatively were comparable between groups. Postoperative pathological results showed significantly higher values for the following parameters in the PET-positive group than in the PET-negative group: extraprostatic invasion (45.0% vs 22.4%; p=0.0185); positive margin (30.0% vs 13.2%; p=0.0445); and GS ?8 (52.5% vs 23.7%; p=0.00343). Multivariate analysis also showed that PET positivity tended to be associated with positive margins (odds ratio (OR), 2.45; p=0.0819) and extraprostatic invasion (OR, 2.34; p=0.0529), while GS ?8 was a significant predictor (OR, 3.08; p=0.0208). Conclusions In RALP, FDG uptake should be considered a predictor of high-grade disease and a risk factor for positive margins. Funding none
Authors
Hiroyuki Iio
Ryotaro Tomida Kosuke Seto Takuya Tsujioka Kenichi Nishimura Kensuke Shinomori Shiro Fujikata Syuji Tanimoto Kenjiro Okamoto Sadamu Yamashi Masaharu Kan |
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MP97-04 |
Urinary continence, sexual function and biochemical recurrence 12 months following robot-assisted radical prostatectomy: a randomized controlled study comparing the ‘Bocciardi’ and ‘Menon’ techniques |
Prostate Cancer: Localized: Surgical Therapy VIII | 17BOS |
Abstract: MP97-04 Sources of Funding: none Introduction Retzius-sparing (posterior or &[prime]Bocciardi&[prime] approach) of robot-assisted radical prostatectomy (RARP) has been recently suggested as a feasible alternative to the standard (anterior or &[prime]Menon&[prime] approach) RARP. We compared urinary continence (UC), sexual function (SF), oncological outcomes, and postoperative complications over a short term (~1-year) follow up for patients undergoing posterior vs. anterior approach RARP in a randomized trial. Methods 120 patients with low-intermediate risk prostate cancer (PCa) undergoing RARP by a single surgeon were randomized to posterior (n=60) or anterior RARP (n=60). Recovery of SF was defined as a) erections sufficient for penetrative intercourse (ESI), and b) Sexual Health Inventory for Men (SHIM) score≥ 17. UC recovery was defined as use of 0 pad/one security pad per day. Both UC and SF recovery data were collected by an independent third party (MUSIC registry) using validated patient-reported questionnaires. Oncologic outcomes consisted of positive surgical margins (PSM) and short term (~1 year) biochemical recurrence-free survival (BCRFS). Results There were no significant differences in UC at 6- or 12-months post-RARP (98.4% in posterior vs. 95% in anterior RARP) or urinary function scores in the two arms (figure 1). Amongst preoperatively potent men (SHIM≥ 17), 72.4% in anterior and 83.7% in posterior RARP group were able to have ESI one year after surgery (p=0.6); 46.2% and 59.2% had regained SHIM≥ 17 by the same time point (figure 2). There were no significant differences in the incidence of PSM (25% in posterior vs. 13.3% in anterior RARP), BCRFS (91.5% vs. 94.4% respectively) or postoperative complications over a median follow-up of 13.5 months. Conclusions In this randomized trial of patients with low-intermediate risk PCa, UC, SF, postoperative complications, and BCR rates were comparable at 12 months in patients undergoing &[prime]Bocciardi&[prime] vs. &[prime]Menon&[prime] approach RARP. Funding none
Authors
Mani Menon
Deepansh Dalela Madhu Ashni-Prasad Marcus Jamil Firas Abdollah Akshay Sood Patrick Karabon Mireya Diaz Sriram Eleswarapu Jesse Sammon Brad Baize Andrea Simone Wooju Jeong |
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MP97-05 |
Outcomes of preventive vs delayed ligation of dorsal vascular complex during RARP: preliminary results of a randomized trial |
Prostate Cancer: Localized: Surgical Therapy VIII | 17BOS |
Abstract: MP97-05 Sources of Funding: None Introduction The ligation of the dorsal vascular complex (DVC) during robot-assisted radical prostatectomy (RARP) can be done both before (preventive ligation, PL) or after (delayed ligation, DL) its transection, given the haemostatic effect exerted by the pneumoperitoneum. _x000D_ The aim of this study is to compare outcomes of RARP with preventive ligation versus delayed ligation of the DVC in a phase III randomized controlled trial. Methods After IRB approval, a prospective randomized controlled trail is recruiting patients submitted to RARP at our institution since February 2015. Exclusion criteria are: congenital or acquired coagulation disorders and salvage radical prostatectomy. After obtaining an informed consent, patients are randomized into treatment arms on a 1:1 ratio. _x000D_ RARP is performed according to the Patel technique, by 2 experienced robotic surgeons, with PL (1-0 Monocryl® CT-1, after the opening of endopelvic fascia and before bladder neck dissection) or DL (3-0 Monocryl® UR-6, once the prostatectomy is completed). _x000D_ Patients&[prime] characteristics and data are recorded in a prospective maintained database._x000D_ The primary endpoint is estimated blood loss (EBL) during prostatectomy (considering significant a difference of 30 ml or higher). Secondary endpoints are: transfusion rate, positive surgical margins (PSMs) in general and apical PSMs in particular and 1-month PSA and continence (defined as the use of 0 pad or 1 security pad per day). Pearson&[prime]s chi-square test was applied to all variables, with a chi-square probability of 0.05 or less considered statistically significant. Results Overall, 154 patients were randomized from February 2015 to August 2016 (86 patients with PL and 68 with DL). The two groups had comparable preoperative features and no statistically significant differences were found in term of primary and secondary endpoints with the exception of the rate of apical PSMs, higher in the PL group (table 1). Conclusions A DL of the DVC is associated to a greater blood loss, even without any clinical significance, and seems to be protective on the risk of apical PSMs, with no detrimental effects on perioperative course and functional outcomes. Funding None
Authors
Carlotta Palumbo
Alessandro Antonelli Irene Mittino Simone Francavilla Marco Lattarulo Mario Sodano Maria Furlan Angelo Peroni Claudio Simeone |
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MP97-06 |
Inguinal hernia after radical prostatectomy: incidence and risks factors. |
Prostate Cancer: Localized: Surgical Therapy VIII | 17BOS |
Abstract: MP97-06 Sources of Funding: none Introduction The number of patients (pts.) undergoing radical prostatectomy has increased due to early detection of prostate cancer. The two most frequently occurring and well descrbed complications of radical prostatectomy are incontinence and impotence. Inguinal hernia (IH) has emerged as an additional complication with an estimated incidence of 15-20% after radical retropubic prostatectomy (RRP), 7,4% after laparoscopic prostatectomy and 5,8% after robotic prostatectomy. The internal inguinal ring is composed of transversalis fascia and suspended by the transversus abdomen muscle, so that injury to these structures or their nerve supply during surgery could be associated with the development of an indirect IH. The objective of the study is to assess the incidence and the risk factors for an IH development in a series of pts. undergone RRP._x000D_ _x000D_ _x000D_ Methods 360 pts. age ranged from 51 to 73 years, underwent RRP by a single surgeon. During the follow up many pts. complained the development of an IH not detected before surgery. This finding stimulated the Authors to screen all pts. for a post surgical IH by means of physical examination, upstanding ultrasonography and a questionnaire designed to capture the development of clinical IH. 86 pts. responded or were evaluable for the study. The potential risk factors for IH like a previous hernia, increasing age, BMI, bladder neck contracture,intraoperative profuse bleeding > 1000 ml., diabetes or infection of the surgical wound, were evaluated. Results 15 pts. (17,4%) developed a postoperative IH from 6 months to two years after RRP. 27 pts.(31,4%) underwent IH repair before RRP and of these,7 pts.(8,1%)developed a contralateral postoperative IH. Important risk factors for the development of post-RRP IH were a low BMI <25KG/m2 (40%)and diabetes (27%)in pts. with increasing age (mean 64,2 yrs.) while the other risk factors considered were not significantly associated with the postoperative IH risk. Conclusions A higher incidence of IH is noted in the post radical prostatectomy population compared with the general adult male population, suggesting that the procedure has an increased risk of IH formation. The incision of the transversalis fascia, a component of the internal inguinal ring, is the surgical step that rise the risk for an hernia formation. Old pts. with a low BMI and diabetes are particularly prone to increased morbidity from IH. Urologists should consider this finding when counseling pts. for complications, and a prophylactic surgery for high risk subjects should be considered at the time of radical prostatectomy to decrease the risk of postoperative IH formation. Funding none
Authors
Giacomo Perugia
Pier Paolo Prontera Emanuele Corongiu Giuseppe Borgoni Milena Polese Antonio Rossi Piergiorgio Tuzzolo Marcello Liberti |
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MP97-07 |
Impact of reverse stage migration on the outcome of node positive prostate cancer patients treated with radical prostatectomy: results of a large, two-center experience |
Prostate Cancer: Localized: Surgical Therapy VIII | 17BOS |
Abstract: MP97-07 Sources of Funding: none Introduction The aim of this study was to evaluate the impact of the year of surgery on clinical, pathological and oncological outcomes in N+ prostate cancer (PCa) patients who underwent radical prostatectomy (RP) and extended pelvic lymph node dissection (ePLND) Methods 1,653 patients with N+ PCa treated with RP and ePLND at two tertiary care referral centres between 1998 and 2013. Lowess functions were used for graphical representation of the year-by-year trends in clinical, pathological characteristics and use of adjuvant treatments. Linear regression was used to test statistical significance of those temporal trends. Multivariable Cox regression analyses (MVA) were used to assess the relationship between year of surgery and oncological outcomes, namely biochemical recurrence-BCR and clinical recurrence-CR. Covariates consisted of patient age, preoperative PSA, pathological stage (pT2 vs. pT3a vs. ≥pT3b), positive surgical margins-PSM, pathological Gleason score (6 vs. 3+4 vs. 4+3 vs. ≥8) and year of surgery Results Overall, 50.6 and 20.1% had BCR and CR, respectively. A significant decrease in the median PSA was observed over time (p=0.02). A similar trend was seen for clinical stage T3 (from 24.8% in 1998 to 6.7% in 2013; p<0.001). Conversely, biopsy Gleason ≥8 dramatically increased from 23% in 1998 to 53.1% in 2013 (p<0.001). We observed a considerable increase in the median number of lymph nodes removed (from 13.4 in 1998 to 20.5 in 2013; p=0.003), associated with an increased rate of patients with ≥3 positive lymph nodes (from 5.6% in 1998 to 30.9% in 2013; p=0.002). Pathological stage remained stable over time (all p?0.8). Conversely, the rate of pathological Gleason 4+3 and ≥8 increased significantly (from 17.6 to 43.1% and from 13.6 to 45.2% in 1998 and 2013, respectively; all p<0.001). The rate of PSM increased between 1998 and 2007, and remained stable thereafter. There was a trend towards lower use of adjuvant therapies (hormonal therapy-HT and radiotherapy with or without HT from 2004 to 2013; p<0.001), with increasing rates of men conservatively managed after RP (p<0.001). At MVA, year of surgery was associated with higher risk of BCR (HR: 1.08; p<0.001) and CR (HR: 1.09; p<0.001) Conclusions A trend towards more aggressive disease and worse cancer control was observed in more contemporary N+ PCa patients treated with RP which paralleled a lower rate of utilization of adjuvant therapies. These data should be taken into account when selecting the proper post-operative management of N+ PCa patients Funding none
Authors
Paolo Dell'Oglio
Derya Tilki Emanuele Zaffuto Raisa S. Pompe Giorgio Gandaglia Nicola Fossati Armando Stabile Thomas Steuber Nazareno Suardi Francesco Montorsi Markus Graefen Alberto Briganti |
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MP97-08 |
Prediction of extreme upgrade from biopsy grade 1 to grade 4 or 5 at radical prostatectomy: the importance of the extent of biopsy sampling |
Prostate Cancer: Localized: Surgical Therapy VIII | 17BOS |
Abstract: MP97-08 Sources of Funding: none Introduction Gleason grading is an important predictor of oncologic outcomes in prostate cancer (PCa) patients. However, some patients with biopsy grade 1 disease might experience extreme upgrading to grade group 4-5 at radical prostatectomy (RP). We identified predictors of extreme upgrading in men treated at a single referral center Methods We identified 1,718 patients diagnosed with biopsy grade group 1 PCa, clinical stage T1/T2, at a single center between 1991 and 2015 and treated with RP. Extreme upgrading was defined as switching to grade 4 or 5 at final pathology. Patients were stratified according to presence of extreme upgrading. Uni- and multivariable logistic regression analyses (MVA) assessed the relationship between clinical and preoperative characteristics and the risk of extreme upgrading. Finally, 146 individuals diagnosed with biopsy grade 4-5 PCa and clinical T1 or T2 disease were abstracted from the database and compared with patients who experienced extreme upgrading at RP. Cox regression analyses evaluated differences in biochemical recurrence (BCR) rates according to grade group 1 vs. grade 4-5 PCa at biopsy after adjusting for confounders Results 46 individuals (2.7%) were diagnosed with grade 4-5 PCa after RP. These patients were older compared to those who did not experience extreme upgrading (p<0.01) and had a significantly higher PSA at diagnosis (7.6 vs. 6.2 mg/dL; p=0.03). A lower number of cores were taken during biopsy for patients who experienced extreme upgrading at RP (12 vs 14; p<0.01). At MVA, age (OR: 1.05; p=0.03), PSA (OR: 1.04; p<0.001) and the number of cores taken (OR: 0.92; p=0.01) were independent predictors of extreme upgrading. The MVA model was used to plot predicted probability of extreme upgrading at RP according to the number of cores taken (Fig. 1). When comparing patients who experienced extreme upgrading with 146 individuals diagnosed with biopsy grade 4-5 PCa, those diagnosed with biopsy grade 1 were at lower risk of BCR (HR: 0.52; p=0.02) Conclusions An adequate biopsy sampling reduces the risk of underestimation of high-risk PCa. Patients with grade 1 PCa experience better outcomes compared to those diagnosed with more aggressive disease at biopsy. These considerations are of pivotal importance for more accurate risk stratification Funding none
Authors
Emanuele Zaffuto
Giorgio Gandaglia Marco Bandini Paolo Dell'Oglio Nicola Fossati Francesco Pellegrino Vincenzo Mirone Vito Cucchiara Marco Bianchi Federico Dehó Emanuele Montanari Nazareno Suardi Rodolfo Montironi Francesco Montorsi Alberto Briganti |
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MP97-09 |
Venous thromboembolic events in patients undergoing open and minimally invasive radical prostatectomy: population-based time trend analysis |
Prostate Cancer: Localized: Surgical Therapy VIII | 17BOS |
Abstract: MP97-09 Sources of Funding: none Introduction The rate of venous thromboembolic events (VTE) after open (ORP) or minimally invasive radical prostatectomy (MIRP) for prostate cancer (PCa) might be decreasing over the last decade. The aim of the present study was to assess the 30- and 90-day VTE rates and mortality over time. Methods Using the Surveillance Epidemiology and End results (SEER)- Medicare database, we identified 35104 nonmetastatic PCa patients who underwent RP between 1994 and 2009. The annual incidence rates of VTE and mortality were analyzed over the observation period. The estimated annual percentage change (EAPC) was calculated using the least squares log linear regression method. Based on stepwise selection, risk factors for VTE were identified. Multivariable logistic regression models were performed to test the effect of these variables on VTE rates. Results At 30 days after RP, 931 (2.7%) VTE and 87 (0.25%) deaths were recorded. Additionally, at 90-days, 1112 (3.2%) VTE and 121 (0.3%) deaths were registered. Over a period of 15 years, annual 30-day VTE and mortality rates decreased from 3.5% to 2.2% and from 0.4% to 0.2%, respectively. Similarly, 90-day VTE and mortality rates decreased from 4.2% to 2.7% and from 0.6% to 0.3%. Independent VTE-risk factors consisted of older age, longer hospital stay, pelvic lymph node dissection (PLND) and blood transfusions. In multivariable analysis, prostatectomy type (ORP or MIRP) did not affect VTE or mortality rates. Conclusions Although, VTE are rare complications, they may result in patient demise. In consequence, patients with one or multiple risk factors should be targeted with preventive strategies. Funding none
Authors
Raisa Sinaida Pompe
Emanuele Zaffuto Helen Davis Bondarenko Zhe Tian Jonas Schiffmann Sami-Ramzi Leyh-Bannurah Hartwig Huland Markus Graefen Derya Tilki Pierre I. Karakiewicz |
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MP97-10 |
Can We Modulate the Extent of Nodal Dissection according to the Preoperative Risk of Lymph Node Invasion in Prostate Cancer Patients Undergoing Radical Prostatectomy? |
Prostate Cancer: Localized: Surgical Therapy VIII | 17BOS |
Abstract: MP97-10 Sources of Funding: none Introduction An extended pelvic lymph node dissection (ePLND) should be considered in prostate cancer (PCa) patients undergoing radical prostatectomy (RP) at increased risk of lymph node invasion (LNI). However, whether the removal of presacral and common iliac nodes should be included is still a matter of debate. Methods 4,790 PCa patients treated with RP and an anatomically defined ePLND between 2003 and 2016 at a single center were identified. The risk of LNI was calculated according to the Briganti nomogram. The number of positive nodes and the proportion of patients with positive nodes in the common iliac and presacral stations was plotted over the calculated risk of LNI according to the Briganti nomogram using lowess-smoothed fit curve. Patients were stratified according to the risk of LNI in 3 categories: <10%, 10-30%, and >30%. The number of positive nodes and the proportion of patients with positive nodes in the common iliac and presacral stations were compared. Multivariable analyses tested the association between the calculated risk of LNI and involvement of common iliac and presacral nodes after adjusting for the number of nodes removed and pathologic Gleason score. Results The risk of LNI according to the Briganti nomogram was <10, 10-30, and >30% in 4,569 (95.4%), 115 (2.4%), and 106 (2.2%) patients. The median number of nodes removed was 16 and 487 (10.2%) patients had LNI. A total of 483 (99.2%) patients had LNI located to the internal iliac, external iliac, or obturator nodes, while 40 (8.2%) and 22 (4.5%) patients had positive nodes in the common iliac and presacral stations. None of the patients with positive common iliac nodes had negative pelvic nodes. The number of positive nodes increased according to the risk of LNI (P<0.001). The median number of positive nodes was 1 vs. 3 vs. 5 in patients with a risk <10, 10-30, and >30% (P<0.001). The proportion of involvement of the presacral and common iliac nodes increased according to the risk of LNI and was 0.1 vs. 5.2 vs. 10.4 and 0.3 vs. 5.0 vs. 18.9 for individuals with a risk of LNI <10, 10-30, and >30% (all P<0.001). The risk of LNI was an independent predictor of the number of positive nodes and of involvement of the presacral and common iliac nodes (all P<0.001). Conclusions The presacral and common iliac lymph nodes are involved by nodal metastases in more than 10% of patients with a calculated risk of LNI >30%. An ePLND that includes the dissection of the presacral and common iliac nodes should then be considered in men with a risk of LNI >30%. Funding none
Authors
Giorgio Gandaglia
Emanuele Zaffuto Paolo Dell'Oglio Nicola Fossati Vincenzo Scattoni Marco Bianchi Andrea Gallina Umberto Capitanio Franco Gaboardi Francesco Montorsi Alberto Briganti |
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MP97-11 |
Impact of Previous Experience with Open Surgery and Initial Annual Robotic Caseload on Positive Surgical Margin Rates after Robot-assisted Radical Prostatectomy |
Prostate Cancer: Localized: Surgical Therapy VIII | 17BOS |
Abstract: MP97-11 Sources of Funding: none Introduction Although previous studies assessed the learning curve phenomenon associated with the introduction of robot-assisted radical prostatectomy (RARP), evidence is scarce regarding the impact of previous experience with open radical prostatectomy (ORP) as well as annual robotic caseload on outcomes. Methods We evaluated the first ≤200 patients with localized prostate cancer treated with RARP by 6 surgeons between 2006 and 2016 (n=1,010). Patients were stratified according to previous experience with ORP of the surgeon (no experience vs. at ≥500 open cases). The rates of positive surgical margins (PSM) were compared using the chi-square test. Multivariable logistic regression analyses assessed the impact of previous experience with ORP on the risk of PSM. Surgeons without experience with ORP were stratified according to their annual caseload during the first 200 cases in two groups: ≤40 vs. >40 cases per year. Multivariable logistic regression analyses tested the impact of annual caseload on the risk of PSM. Results Overall, 4 (n=610) vs. 2 surgeons (n=400) had no vs. high experience with ORP. Differences were observed with regards to clinical stage, preoperative PSA, and biopsy Gleason score (all P≤0.02). The rate of PSM was lower among surgeons with previous experience with ORP (13.8 vs. 22.3%; P<0.001). Surgeons with no experience had 2.7-fold higher odds of PSM compared to those with experience with ORP (P=0.01). Overall, 2 surgeons with no experience with ORP had a caseload of ≤40 RARP per year while 2 surgeons performed >40 procedures per year during their first 200 cases. Among surgeons with no experience with ORP, the PSM rates were different according to annual caseload (33.7 vs. 17.4% for ≤40 vs. >40 cases per year). In multivariable analyses, surgeons with a lower caseload had a 2-fold higher probability of PSM (P=0.001). No differences were observed in the rate of PSM between surgeons without previous experience with ORP performing >40 procedures per year and their counterparts with experience with open surgery (17.4 vs. 13.8%; P=0.1). This was confirmed at multivariable analyses (P=0.1). Conclusions Surgical experience with previous ORP reduces the risk of PSM in the first robotic cases. A higher annual caseload of initial robotic cases allowed non-open surgeons to reach PSM rates comparable to what achieved by robotic surgeons with previous significant ORP experience. A sufficient annual surgical caseload in the initial learning curve should be guaranteed to optimize perioperative surgical outcomes. Funding none
Authors
Giorgio Gandaglia
Nazareno Suardi Paolo Dell'Oglio Nicola Fossati Emanuele Zaffuto Giuseppe Saitta Marco Bandini Giorgio Guazzoni Franco Gaboardi Vincenzo Mirone Rocco Damiano Andrea Gallina Francesco Montorsi Alberto Briganti |
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MP97-12 |
Changes Over Time in Node Positive Prostate Cancer Rates and Features Among Men Treated with Radical Prostatectomy and Extented Pelvic Lymph Node Dissection at a Single Referral Center |
Prostate Cancer: Localized: Surgical Therapy VIII | 17BOS |
Abstract: MP97-12 Sources of Funding: none Introduction The stage migration phenomenon and the introduction of robot-assisted radical prostatectomy (RARP) might have changed the characteristics of prostate cancer (PCa) patients in terms of risk and features of lymph node invasion (LNI). Methods 5,328 PCa patients treated with open radical prostatectomy or RARP and an extended pelvic lymph node dissection (ePLND) between 2005 and 2016 were identified. All nodal specimens were retrieved in multiple packages according to the anatomical location and evaluated by high-volume uro-pathologists. The year-per-year trend of pathologic characteristics was reported. Multivariable (MVA) logistic regression analyses tested the impact of year of surgery and RARP on the risk of LNI and on the site of nodal invasion after adjusting for confounders. Results Overall, 3,159 (59.3%) and 2,169 (40.7%) patients were treated with ORP and RARP. Median number of nodes removed increased over time both for ORP and RARP (from 15 to 18 and from 9 to 21; all P<0.001). The proportion of patients with LNI was 11.2% and increased from 10.8 to 16.3% between 2005 and 2015 (P<0.001). Patients treated in more recent years were at higher risk of LNI (P=0.001). In 585 individuals with LNI, median number of positive nodes and maximum diameter of metastases were 2 and 5 mm and did not change over time (P≥0.5). Overall, 44.8, 73.3, and 15.4% patients with LNI had involvement of the external iliac, obturator, and internal iliac nodes. While the proportion of positive internal iliac nodes increased (from 10 to 37.5%; P<0.001), the rate of obturator nodes involvement decreased (from 80.7 to 42.5%; P<0.001). The proportion of positive internal iliac nodes was higher among those treated with RARP (20.3 vs. 14.1%; P=0.05). At MVA, year of surgery and RARP were associated with a higher probability of positivity in the internal iliac nodes and a lower probability of LNI in the obturator nodes (all P<0.001). No differences were recorded over time and according to the technique in the proportion of positive external iliac nodes (from 43.9 to 52.5%; P=0.6). Overall, 5.5 and 8.9% patients had LNI in the presacral and common stations. The proportion of men with positive presacral and common iliac nodes did not change over time and according to the technique (P≥0.1). Conclusions We observed an increased proportion of patients with positive internal iliac lymph nodes over time. This was likely related to the introduction of RARP, which may allow for more precise dissection in this area and a more accurate nodal staging. Funding none
Authors
Emanuele Zaffuto
Giorgio Gandaglia Paolo Dell'Oglio Nicola Fossati Renzo Colombo Vincenzo Mirone Andrea Gallina Vito Cucchiara Umberto Capitanio Nazareno Suardi Emanuele Montanari Shahrokh F. Shariat Francesco Montorsi Alberto Briganti |
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MP97-13 |
Association of Extended Pelvic Lymph Node Dissection with Thromboembolic Events and Lymphocele Formation Among Men Undergoing Robotic Assisted Laparoscopic Prostatectomy with Pelvic Lymph Node Dissection |
Prostate Cancer: Localized: Surgical Therapy VIII | 17BOS |
Abstract: MP97-13 Sources of Funding: none Introduction Lymphadenectomy (LND) has become increasingly important in the surgical treatment of prostate cancer amidst an inverse stage migration in patients undergoing robotic assisted laparoscopic prostatectomy (RALP). As such, utilization of extended LND (eLND) during RALP has increased. However, eLND may be associated with increased perioperative morbidity, especially thromboembolic events (VTE) and lymphocele formation. We examined the association of eLND with VTE and lymphocele formation in a contemporary institutional cohort. Methods We identified 134 patients in a prospectively maintained institutional database who underwent robotic assisted laparoscopic prostatectomy (RALP) with lymph node dissection (LND) from 1/2014 through 7/2016. Standard (sLND) and extended (eLND) LND were defined as removal of <13 and ?13 lymph nodes, respectively, based on prior literature. Primary endpoints included incidence of VTE and lymphocele within 90 days postoperatively. Logistic regression was used to evaluate the association of clinicopathologic features with VTE._x000D_ Results A total of 134 patients underwent RALP, including 81 (60.5%) with standard LND (sLND) and 51 (39.6%) with eLND. Median age at surgery was 62 (IQR 57,67), and median follow-up was 283.5 (IQR 103, 496) days. There were no statistically significant differences in baseline clinicopathologic features across eLND and sLND groups. Overall, median lymph node yield was 12 (IQR 8, 16). The overall rate of TEE was 7.5% with a median time to occurrence of 20.5 (IQR 10, 44) days. The rate of TEE was not significantly different between patients who underwent sLND or eLND (6.2% versus 9.4%, p=0.52). On univariable analysis, only longer operative time (OR 1.02, p=0.01) was associated with VTE. The overall rate of lymphocele was 5.3%, with a median time to occurrence of 44 (IQR 10, 63) days. The rate of lymphocele did not differ between patients who underwent sLND or eLND (7.7% versus 3.8%, p=0.44). _x000D_ Conclusions In this contemporary population of patients undergoing RALP with LND, eLND was not associated with a statistically significant difference in the rate of symptomatic VTE or lymphocele formation when compared to sLND. _x000D_ Funding none
Authors
Jorge Pereira
Holly Shillan Christopher Tucci Gyan Pareek Dragan Golijanin Boris Gershman Joseph Renzulli |
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MP97-14 |
Functional outcome of radical prostatectomy after repeat biopsy |
Prostate Cancer: Localized: Surgical Therapy VIII | 17BOS |
Abstract: MP97-14 Sources of Funding: None Introduction To analyse functional outcome of radical prostatectomy (RP) in patients with repeat prostate biopsies (Bx). We investigated whether there is an association between the number of prior Bx and erectile dysfunction (ED) and incontinence after RP. Methods In all, 12,218 patients who underwent RP between January 2007 and March 2015 after a known number of prior Bx were included in the analysis. Number of Bx sessions (range 1 to ≥3) was examined as categorical (1, 2 and ≥3) variable. The association between number of prior Bx sessions and erectile function, measured by IIEF-score as well as the association between number of prior Bx sessions and continence, measured as use of no or only one security pad was analyzed using multivariable logistic regression model. Results Of the 12,218 men 10,771 (88.2%) had only 1 Bx, 1,004 (8.2%) had 2 Bx and 443 (3.6%) had ≥3 Bx. More Bx sessions were associated with higher age at surgery (median 65, 65 and 67 yrs, p<0.001). PSA preoperatively was significantly higher in patients with multiple Bx (median 6.6, 7.6 and 10.2 ng/ml, p<0.001) and patients were significantly more often classified as high-risk according to D&[prime]Amico (18.2, 16.7, 28.2%, p<0.001). Prostate volume was significantly higher (median 38, 42 and 45ccm, p<0.001) in patients with multiple Bx._x000D_ IIEF-5 score prior surgery did not differ among Bx groups. Robotic assisted RP was performed more often in patients with multiple Bxs (p<0.001). More Bx sessions were associated with more often performed bilateral nerve sparring (67, 73.5 and 77.6%, p<0.001). In multivariable logistic regression predicting incontinence at 1 year after surgery, patients with 2 vs 1 Bx had a significantly higher likelihood of incontinence (OR 1.26, p=0.08). No difference was seen between patients with ≥3 vs 1 Bx session. No difference among groups occurred 2 and 3 yrs after surgery. _x000D_ In multivariable logistic regression predicting ED using IIEF-5 score at 1, 2 and 3 yrs after surgery, no differences occurred among Bx groups._x000D_ Conclusions Multiple biopsy sessions are not associated with worse erectile function in men undergoing radical prostatectomy. Recovery to continence is slightly prolonged in patients with multiple Biopsies. 3 years after surgery, almost no differences occur among biopsy groups. Funding None
Authors
Clemens Rosenbaum
Philipp Mandel Pierre Tennstedt Markus Graefen Derya Tilki Georg Salomon |
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MP97-15 |
New Approach: from laparoendoscopic single-site radical prostatectomy (LESS-RP) to transurethral-assisted LESS-RP (TU-LESS-RP) |
Prostate Cancer: Localized: Surgical Therapy VIII | 17BOS |
Abstract: MP97-15 Sources of Funding: none Introduction Conventional laparoendoscopic radical prostatectomy (LRP) is widely accepted as a standard procedure to treat localized prostate cancer (PCa). Recently, the use of transumbilical laparoendoscopic single-site radical prostatectomy ( LESS-RP) has grown, as it is less invasive for patients, and we have adopted this procedure for prostatectomy cases. The advantages of LESS-RP, such as lower postoperative pain and its cosmetic excellence, have been pointed out. However, LESS-RP is recognized to be a technically challenging procedure even for experts, especially in suturing and dissection. To overcome these challenges, we introduce transurethral-assisted transumbilical laparoendoscopic single-site radical prostatectomy (TU-LESS-RP) . With the technology, many operational equipments can be used through natural orifice to lower the operation difficulty and shorten the operation time. This study is to evaluate the feasibility and advantages of transurethral-assisted technology in LESS-RP for PCa patients. _x000D_ Methods From Jan. 2014 to Dec.2015, 118 patients underwent RP in our center, including 11 patients were performed by LESS-RP (a single-port with four channels was inserted into the 2.5 cm periumbilical incision), and 107 were performed by TU-LESS-RP (home-made transurethral port were used, Suction and dissociation devices were inserted into transurethral port to assist the surgical operator). All data referring to patient demographics, pathology, and perioperative outcomes were recorded and analyzed. Results All the operations were successfully accomplished. No conversion into conventional laparoscopic or open surgery was performed. Compared with LESS-RP, TU-LESS-RP is easier to identify the neck of bladder, avoid the injury of rectum, make anastomosis quickly, expose the anatomic structures clearly , and so on. Consequently, with this technology we make the LESS-RP easy to master and shorten the operation and anastomosis time significantly. Meanwhile, we got satisfied cosmetic and continent results for patients. According to our data, TU-LESS-RP has more significant advantage than LESS-RP in following aspects: the mean operating time (135 min vs 215 min), the median estimated blood loss (108 ml vs 466 ml) , the length of stay (9 d vs 16.5 d), and indwelling catheter time (7.5 d vs 14.5 d). All these patients had satisfied continent and cosmetic effects. For patients experienced lymph nodes dissection, the operating time was 36 min, the average lymph nodes was 10.6, and two patients with positive results (3/9 and 2/12). Conclusions LESS-RP is technically challenging although with advantage of less invasive and more cosmetic effects even for experts. To solve these problems, TU-LESS-RP has been developed in our institution, and it has been proved more feasible and safer for localized PCa patients. The technology could minimize the interference between the laparoscopic equipments, shorten the operating time, decrease the risk and complications. TU-LESS-RP for localized PCa patients has just begun, and the number of cases experienced is still small. Being cosmetically highly favorable, this procedure will likely be further developed as a less invasive surgery in the future. Funding none
Authors
Qingyi Zhu
Yunfei Wei Jian Su Lin Yuan Yang Zhang Qingling Zhang Chen Zhu Luming Shen Zijie Lu Zijie Lu Zijie Lu |
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MP97-16 |
Robotic salvage-lymphadenectomy for nodal-only recurrences after radical prostatectomy: perioperative and early oncological outcomes |
Prostate Cancer: Localized: Surgical Therapy VIII | 17BOS |
Abstract: MP97-16 Sources of Funding: none Introduction Salvage-lymphadenectomy (sLAD) is offered to patients with nodal-only recurrences after radical prostatectomy (RP). However, there is still controversy regarding appropriate patient selection for and oncological benefits from sLAD. Especially with the advent of 68Ga-PSMA-PET/CT as a highly sensitive targeted imaging tool, the concept of sLAD seems to be a promising approach and evaluation of efficacy is needed. Methods We evaluated perioperative and oncological outcomes of patients with nodal-only recurrences after RP who underwent robotic sLAD at our institution. Recurrence was detected by targeted imaging (18F-Choline- or 68Ga-PSMA-PET/CT). Results Data from 26 patients with a median age of 66.5 years [IQR 62;72] were analyzed with a median time from RP to sLAD of 40.1 months [IQR 14;61.5], median preoperative PSA 2.31 ng/ml [IQR 0.83;5.68]. Imaging of recurrence sites was performed with 18F-Choline-PET/CT in 11 and 68Ga-PSMA-PET/CT in 15 patients, the majority of suspicious nodes were located around the iliac vessels (67%). Median operation time was 130.5min [IQR 118;170], median blood loss 35ml [IQR 10;100], median hospitalization time 3 days [IQR 3;4]. The median number of removed nodes was 7 [IQR 4;14] with a median of 1 [IQR 0;3,5] positive node. While in the first patients only suspicious lymph nodes were removed, an extended bilateral LAD was done in all patients from 2016 on (n=12). No major complications occurred. Postoperative PSA values were available for 21 patients (10 choline, 11 PSMA), relative PSA-changes from preoperative values are shown in the figure. Complete biochemical response (cBCR, postoperative PSA-nadir <0.2ng/ml) was observed in 6 patients. Median time from sLAD to initiation of systemic treatment was 5 months [IQR 3.3;13.2]._x000D_ _x000D_ Conclusions Robotic sLAD is a viable treatment option with low morbidity that can be offered to patients with nodal-only recurrences after RP. Yet, cBCR is only observed in a minority of patients and virtually all patients will eventually have to undergo systemic treatment. Nonetheless, sLAD may at least delay the start of systemic therapy especially with the use of 68Ga-PSMA-PET/CT, which showed very promising results in our series. Funding none
Authors
Johannes Linxweiler
Matthias Saar Zaid Al-Kailani Michael Stöckle Stefan Siemer Carsten H. Ohlmann |
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MP97-17 |
A Comparison of Intraperitoneal Onlay Mesh Repair vs. Minimally Invasive Suture Repair of Inguinal Hernias during Robotic-Assisted Laparoscopic Radical Prostatectomy |
Prostate Cancer: Localized: Surgical Therapy VIII | 17BOS |
Abstract: MP97-17 Sources of Funding: This study was supported the Sidney Kimmel Center for Prostate and Urologic Cancers, the National Institutes of Health/National Cancer Institute Cancer Center Support Grant P30 CA008748, and by David H. Koch through the Prostate Cancer Foundation. Introduction We sought to compare the safety and effectiveness of two techniques for minimally invasive inguinal hernia (IH) repair, intraperitoneal onlay mesh (IPOM) repair vs. suture repair, in patients undergoing concurrent robotic-assisted laparoscopic radical prostatectomy (RALP). Methods In a single tertiary-care institution study, we retrospectively identified patients who underwent RALP and minimally-invasive IH repair concurrently from 2010 to 2015. IH were repaired using either an IPOM or a running suture. We assessed the impact of the IH repair technique on perioperative outcomes, 90-day complications, and IH recurrence. Results Of 2,239 patients undergoing RALP during the study period, 51 patients (2.3%) underwent concurrent minimally invasive IH repair; 28 underwent IPOM repair, and 23 underwent suture repair. The proportion of patients with previous ipsilateral IH repair was higher in the IPOM group. We found no evidence of a significant difference in age, body mass index (BMI), preoperative physical exam findings, postoperative pain, or overall 90-day complication rates between the two groups. Operative time and length of hospitalization were significantly shorter in the IPOM group. Postoperative complications requiring intervention (Clavien-Dindo ≥ III) were more frequent in the suture group (p=0.03) The IH recurrence rate was lower in the IPOM group by a clinically relevant but not statistically significant difference (4% vs. 9%; p=0.58) Conclusions In patients undergoing RALP and IH repair, IPOM repair is feasible, and may be associated with better perioperative outcomes and safety profile than suture repair. The effectiveness of IPOM repair was superior but not significantly. A prospective comparison against the gold-standard technique is warranted. Funding This study was supported the Sidney Kimmel Center for Prostate and Urologic Cancers, the National Institutes of Health/National Cancer Institute Cancer Center Support Grant P30 CA008748, and by David H. Koch through the Prostate Cancer Foundation.
Authors
Pedro Recabal
Ricardo G. Alvim Toshikazu Takeda Behfar Ehdaie Jonathan Coleman Vincent P. Laudone |
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MP97-18 |
Longitudinal health-related quality of life after robot-assisted radical prostatectomy |
Prostate Cancer: Localized: Surgical Therapy VIII | 17BOS |
Abstract: MP97-18 Sources of Funding: none Introduction Robot-assisted radical prostatectomy (RARP) has been reported to be associated with less incontinence than a retropubic radical prostatectomy (RRP) and laparoscopic radical prostatectomy (LRP); however, urinary continence continues to occur at a constant rate. There are few reports of urinary incontinence following a RARP to perform a detailed examination of the impact on the patients’ postoperative quality of life (QOL). Therefore, in this study, we examined the association between health-related QOL and urinary continence following RARP. Methods From October 2010 to August 2016, 319 patients underwent RARP at our hospital. An SF-8 evaluation was performed for 154 retrospectively selected patients with observable data for 24 months (preoperative, and postoperative 1, 3, 6, 9, 12, and 24-month evaluations) for our analysis. Evaluation items: physical function (PF), role physical (RP), bodily pain (BP), general health (GH), vitality (VT), social functioning (SF), role emotional (RE), mental health (MH), physical component summary (PCS), and mental component summary (MCS) were compared before and after surgery. In addition, “pad free” was defined as no incontinence, and we examined the relationship between the postoperative urinary continence and SF-8 data. Results The average age at surgery was 65 (range: 48–76) years, the average preoperative PSA was 9.16 ng/mL (range: 1.17–35.4), and the average prostate volume was 31.6 mL (range: 11–131). We observed a significant reduction at one month post-surgery compared with the preoperative values for all of the scores (all p < 0.0001), and the values recovered to the preoperative status between 3 and 12 months after surgery. The BP, GH, RE, MH and MCS were significantly increased compared with the preoperative values (BP: after nine months; GH: after nine months; RE: after 18 months; MH: after three months; and, MCS: at 12 months). For the group that achieved a pad-free status, the GH, VT, SF, and MH were significantly higher compared to those in the non-achievement group one month after surgery. Moreover, the RF, RP, RE, and MCS were significantly higher in the pad-free achieving group after three months after surgery. Significant differences in BP were not recognized after surgery between the two groups. Conclusions Although all of the scores significantly decreased within one month post-surgery, the values recovered to the preoperative score within 12 months. No urinary continence after surgery appears to be associated with a favorable recovery of patient QOL following RARP. Funding none
Authors
Yusuke Kimura
Masashi Honda Yetsuya Yumioka Noriya Yamaguchi Hideto Iwamoto Bunya Kawamoto Toshihiko Masago Shuichi Morizane Katsuya Hikita Atsushi Takenaka |
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MP97-19 |
Surgical Outcomes in the Management of High Risk Prostate Cancer using the Surgical Outcomes for Advanced Prostate Cancer Score |
Prostate Cancer: Localized: Surgical Therapy VIII | 17BOS |
Abstract: MP97-19 Sources of Funding: None Introduction Principles of high quality oncologic surgery suggest that complete excision be achieved with negative surgical margins and adequate staging. Obtaining quality outcomes in Radical prostatectomy (RP) for high risk prostate cancer can be difficult given the increased risk of extra-prostatic extension and inability to directly visualize the disease intra-operatively. Little is known about the clinical predictors of a quality surgical outcome in patients with high risk prostate cancer. We hypothesize that higher volume providers have improved surgical outcomes. Methods Patients diagnosed with prostate cancer were selected from the National Cancer Database between 2010-2013. Patients with biopsy Gleason sum ≥ 8 or PSA > 20 and no clinical evidence of metastasis were included for analysis. A Surgical Outcomes for Advanced Prostate cancer (SOAP) score was generated for each patient. Patients received 2 points each for negative surgical margins and sampling of ≥ 5 pelvic lymph nodes and 1 point each for no readmission with in 30 days, no mortality within 30 days, and hospital length of stay ≤ 2 days. Patients were considered to have a good surgical outcome with a SOAP score ≥ 6. Provider volume was calculated by number of RPs reported from the treatment facility with high volume centers considered to be ones in the top third of reported RPs. Multivariable logistic regression was conducted to determine factors independently associated with quality surgical outcomes using the SOAP score. Results We identified 72,864 patients with high risk disease, of whom 42.5% (n=31,008) were treated with RP. Overall, 34.1% of patients had a quality surgical outcome with a SOAP score ≥ 6. On multivariable logistical regression, factors associated with a quality surgical outcome included surgery at a high volume center (OR 1.8: CI 1.6-1.9; p= <0.01), surgery at an academic hospital (OR 1.8: CI 1.7-1.9: p= <0.01), cN1 stage (OR 1.6: CI 1.2-2.0; p= <0.01), and omission of neoadjuvent hormonal therapy (OR 1.4: CI 1.3-1.5; p= <0.01). Factors associated with a poor surgical outcome include robotic approach (OR 0.81: CI 0.76-0.87; p= <0.01), PSA > 30 (OR 0.59: CI 0.55-0.64; p= <0.01), and African American ethnicity (OR 0.89: CI 0.82-0.96; p= <0.01). Conclusions For patients with high risk prostate cancer, treatment at high volume centers and at academic centers appear to be associated with a high quality surgical outcomes. Given the increased use of this management strategy, optimizing surgical quality is needed in order to achieve the best outcomes for this aggressive malignancy. Funding None
Authors
John Francis
Simon Kim Hui Zhu Robert Abouassaly |
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MP97-20 |
Prediction of non-biochemical recurrence rate after robot assisted radical prostatectomy (RARP) in a Japanese cohort: Development of a postoperative nomogram |
Prostate Cancer: Localized: Surgical Therapy VIII | 17BOS |
Abstract: MP97-20 Sources of Funding: none Introduction Previously, we developed the postoperative nomogram to predict the non-biochemical recurrence in patients with open and RARP (IJU 21:479, 2014). However, we found the significant differences of pathological and prognostic outcomes between open and RARP (AUA2016 Hirasawa). Therefore, we up-dated and developed the postoperative nomogram to predict the non-biochemical recurrence rate using the Japanese patients treated with RARP. Methods A total of 1000 Japanese patients with T1-3N0M0 prostate cancer who underwent RARP and pelvic lymph node dissection at Tokyo Medical University hospital from 2009 to 2015 were studied. Patients with neoadjuvant therapy were excluded. A nomogram was constructed based on Cox hazard regression analysis evaluating the prognostic significance of serum PSA and pathological factors in the RARP specimens. The discriminating ability of the nomogram was assessed by the concordance index (C-index), and the predicted and actual outcomes were compared with a bootstrapped calibration plot_x000D_ . Results With a mean follow up of 32.0 months, a total of 145 patients (14.5%) experienced_x000D_ biochemical recurrence with a 5-year non-biochemical recurrence rate of 80.0%. A Cox hazard regression analysis showed that preoperative PSA (p<0.0005), prostatectomy Gleason score (p<0.0005), pathological stage (p=0.001), surgical margins (p<0.0005), and lymphovascular invasion (p=0.0024) were significant factor to predict biochemical recurrence. Based on this analysis, a nomogram was constructed to predict non-biochemical recurrence using PSA level and pathological features in RARP specimens. The concordance index was 0.80, and the calibration plots appeared to be accurate._x000D_ Conclusions Since RARP became most popular procedure in Japan, our postoperative nomogram can provide valuable information to many patients regarding the need for adjuvant/salvage radiation or hormonal therapy after RARP. To our knowledge, our nomogram may be the first nomogram for the non-Caucasian Asian population who were treated with RARP Funding none
Authors
Kazuki Hasama
Makoto Ohori Yosuke Hirasawa Tatsuo Gondo Go Nagao Takashi Mima Takeshi Kashima Yoshihiro Nakagami Yoshio Ono Kazunori Namiki Rie Inoue Takashi Nagao |
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MP98-01 |
Programmed cell death-1 expression in BCG relapsing tumors is significantly associated with stage progression in non-muscle invasive bladder cancer patients |
Bladder Cancer: Basic Research & Pathophysiology V | 17BOS |
Abstract: MP98-01 Sources of Funding: none Introduction The programmed cell death-1 (PD-1) pathway has been suggested to play an important role in tumor immune escape. We evaluated the change of PD-1 expression before and after BCG therapy and its prognostic significance in non-muscle invasive bladder cancer (NMIBC) patients. Methods We evaluated 78 matched tissue samples of NMIBC in both previous tumors before BCG therapy and BCG-relapsing tumors, which was defined as recurrence after achieving a disease-free status by initial BCG instillations for 6 months. We counted PD-1 positive tumors infiltrating lymphocytes under x200 magnification immunohistochemically and when the number of PD-1 positive cells was more than 18, PD-1 expression was defined as high. Results The median follow-up interval after BCG relapse was 81 months. The median number of PD-1 positive cells in previous tumors just before BCG therapy was 3.5, which was significantly lower than that in BCG-relapsing tumors (17.0, p<0.001). High PD-1 expression was observed in 20 previous tumors just before BCG therapy (25.6%) and 36 BCG-relapsing tumors (46.2%). An increase in PD-1 expression after BCG therapy was observed in 52 cases (66.6%, Figure A). After excluding 10 muscle invasive bladder cancers at the time of BCG-relapsing, subsequent stage progression was noted in 8 (11.8%). Kaplan-Meier curves showed that the 5-year progression-free survival rate was 74.1% in patients with PD-1 high expression in BCG-relapsing tumors, which was significantly lower than that in patients with PD-1 low expression (94.1%, p=0.042, Figure B). Multivariate Cox regression analysis showed that PD-1 high expression (HR=8.27, p=0.033) was an independent risk factor for stage progression. Conclusions PD-1 was induced by BCG therapy and PD-1 expression in BCG-relapsing tumor might be an important indicator for predicting stage progression in NMIBC. Funding none
Authors
Keishiro Fukumoto
Eiji Kikuchi Shuji Mikami Nozomi Hayakawa Akira Miyajima Mototsugu Oya |
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MP98-02 |
A potential role of aberrant DNA methylation in the chemoresistance in bladder cancer cells. DNA methylation inhibitors could re-sensitize drug-resistance bladder cancer cells. |
Bladder Cancer: Basic Research & Pathophysiology V | 17BOS |
Abstract: MP98-02 Sources of Funding: none Introduction Aberrant DNA methylation is one of the well-known epigenetic changes in cancer, although its involvement in the chemoresistance remains to be elucidated. In this study, we aimed to unravel the roles played by DNA methylation in chemoresistance in bladder cancer (BCa). Methods We established gemcitabine (GEM)-resistant (T24-RG and UMUC3-RG) or cisplatin (CDDP)-resistant (T24-RC and UNUC3-RC) BCa cell lines by continuously treating their parental cells. Genome-wide DNA methylation was assessed by Infinium HumanMethylation450 BeadChip (HM450). To assess the chromatin accessibilities, cells were treated with a CpG methyltransferase M.SssI, after which DNA methylation was analyzed by HM450. To evaluate whether treatment with epigenetic drugs could overcome the chemoresistance in BCa, cells were treated with a DNA methyltransferase (DNMT) inhibitor 5-aza-2’-deoxycytidine (5-Aza-CdR) and/or a histone deacetylase (HDAC) inhibitor suberoylanilide hydroxamic acid (SAHA), after which they were treated with or without GEM or CDDP. Results HM450 assays revealed increased levels of methylation at a number of CpG sites in the resistant cells as compared the parental cells (730 sites in T24-RC and 3856 sites in UMUC3-RC, respectively), however, a number of CpG sites remained unmethylated but loss chromatin accessibility in the resistant cells (1391 sites in T24-RG and 1322 sites in UMUC3-RG, respectively. In CDDP-resistant BCa cells, a combination treatment with 5-Aza-CdR and CDDP synergistically suppressed cell proliferation, suggesting that 5-Aza-CdR restored CDDP-sensitivity (Figure A, B). In contrast, 5-Aza-CdR didn’t show any growth inhibitory effects in GEM-resistant cells (Figure C, D). Moreover, a treatment with SAHA with or without 5-Aza-CdR also failed to restore GEM-resistance in BCa cells (Figure E, F). Conclusions Our results suggest that epigenetic alteration may be one of key factors for drug resistance, drug resistance cells could be desensitized by DNA methylation inhibitors especially in the CDDP-resistance in BCa cells. Funding none
Authors
Nobuo Shinkai
Naotaka Nishiyama Stephanie Yi Christopher E. Duymich Tetsuya Shindo Peter A. Jones Hiromu Suzuki Naoya Masumori Gangning Liang |
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MP98-03 |
T-DM1, a novel HER2 antibody-cytotoxic drug conjugate, has anti-metastatic potential and is effective in bladder cancer with HER2 IHC score 2+/3+ |
Bladder Cancer: Basic Research & Pathophysiology V | 17BOS |
Abstract: MP98-03 Sources of Funding: none Introduction Although prior clinical trials testing trastuzumab in urothelial carcinoma of the bladder (UCB) have failed, recent genomic studies suggest that UCB could potentially respond to HER2-targeted therapy if patients are selected optimally. T-DM1 is an antibody-drug conjugate consisting of trastuzumab linked to the cytotoxic agent DM1. It showed a significant survival advantage in breast cancer patients refractory to trastuzumab. Our previous study demonstrated that T-DM1 has significant anti-tumor effects in pre-clinical models of HER2-overexpressing UCB. These effects were superior to trastuzumab and depended on level of HER2 expression. Here, we studied the potential anti-metastatic function and optimal patients of T-DM1 in UCB. Methods HER2 expression in bladder cancer treated by radical cystectomy was examined by the same immunohistochemistry (IHC) criteria as for breast cancer. HER2 expression level in UCB cell lines was examined by western blotting (WB), qRT-PCR, FISH and FACS in adherent (AD) and anchorage independent (AI) culture conditions. Results HER2 over-expression (score 2+ or 3+) in IHC was detected in 59 of 159 (37%) bladder cancer patients. HER2 expression was higher in lymph node metastases than in primary tumors. Higher HER2 expression was detected in all cell lines cultured in AI conditions, compared to those in AD conditions. Furthermore, T-DM1 significantly inhibited colony formation in soft agar compared to control IgG or trastuzumab. Since anoikis is a pre-requisite for metastasis, these results suggest that HER2 expression contributes to the establishment of metastasis and T-DM1 could have anti-metastatic potential. The bladder cancer cell line with the highest HER2 expression (BOY) was equivocal HER2 amplification by FISH (HER2/CEP17 ratio: 1.8, HER2 copy number: 4.7), which is known to correspond to HER2 IHC score 2+ in patient tissue. BOY responded most sensitively to T-DM1, and low concentration (10nM) T-DM1 induced apoptosis only in BOY. This suggests T-DM1 could be effective in patients with HER2 over-expression (IHC score 2+/3+). Conclusions Our pre-clinical results suggest that T-DM1 could have anti-metastatic potential and be a promising targeted therapy for patients with HER2 score 2+/3+ UCB. T-DM1 warrants clinical evaluation in these patients. Funding none
Authors
Tetsutaro Hayashi
Htoo Zarni Oo Wolfgang Jäger Kohei Kobatake Akihiro Goriki Roland Seiler Tilman Todenhöfer Na Li Ladan Fazli Akio Matsubara Peter Black |
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MP98-04 |
Defective ERCC2 confers increased cisplatin and ionizing radiation sensitivity in bladder cancer cells |
Bladder Cancer: Basic Research & Pathophysiology V | 17BOS |
Abstract: MP98-04 Sources of Funding: Supported in part by funds from T32 CA082088 Introduction Background: Genetic alterations within ERCC2 correlate with extraordinary responses to neoadjuvant cisplatin-based chemotherapy and bladder-sparing ionizing radiation (IR) in muscle-invasive bladder cancer (MIBC). Two studies correlated ERCC2 mutations with pathologic response to chemotherapy and improved disease-free and bladder intact survival following trimodality therapy. We sought to characterize the biological significance of these mutations in bladder cancer cells using CRISPR/Cas9-mediated ablation of ERCC2 function. Methods Methods: The ERCC2 T484A/M point mutation was the most common alteration (4 of 36 patients) within a prospectively collected cohort of 299 bladder cancer patients sequenced at our institution. We infected the ERCC2 wild-type KU19-19 bladder cancer cell line with a CRISPR/Cas9 lentivirus targeting residues 481-487 of ERCC2 and identified a cell clone harboring an ERCC2 in-frame deletion (M483_T484del). Following exposure to cisplatin and IR, cell viability was examined using Cell-titer Glo and clonogenic assays. Apoptosis was gauged by subG1 cell fraction measurement by flow cytometry. Results Results: ERCC2 mutant cells exhibited significantly increased cisplatin sensitivity compared to parental cells (IC50 0.3uM vs 2.0uM, p<0.0001). Cisplatin treatment after 48 hours resulted in increased apoptosis in ERCC2 mutant vs parental cells (sub-G1 fraction 52% vs 16%, p=0.01). ERCC2 mutant cells were more sensitive to combined IR (2 Gy) and cisplatin (1uM) compared to parental cells (SF2Gy (surviving fraction 17 % vs 60%). Conclusions Conclusions: ERCC2 mutations enhance cisplatin and IR sensitivity in a bladder cancer cell line model. ERCC2 alterations are likely the genetic basis for extraordinary response to cisplatin chemotherapy and IR in MIBC patients. Prospective genetic sequencing may help select ERCC2 mutant MIBC patients who are most likely to respond to chemotherapy or trimodality bladder-sparing therapy. Funding Supported in part by funds from T32 CA082088
Authors
Qiang Li
Andrew Bell Emmet Jordan Sizhi Gao Jennifer Ma Eugene Pietzak Guido Dalbagni Bernard Bochner Jonathan Rosenberg Dean Bajorin David Solit Nadeem Riaz Gopa Iyer |
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MP98-05 |
Checkpoint inhibition with Systemic Anti-Programmed Cell Death Ligand-1 and Intravesical TMX-101 Decrease Tumor Burden in a Mouse Model of Urothelial Carcinoma |
Bladder Cancer: Basic Research & Pathophysiology V | 17BOS |
Abstract: MP98-05 Sources of Funding: UroGen Pharma, Ra'anana, Israel Introduction Urothelial carcinoma (UC) of the bladder is susceptible to immunotherapy with checkpoint inhibitors, including anti-programmed cell death ligand-1 (anti-PD-L1). However, checkpoint inhibitor treatment has not yet extended to patients with localized UC. We hypothesize that intravesical TMX-101, a bladder formulation of a toll-like receptor-7 agonist that demonstrates efficacy against carcinoma in situ, will enhance the anti-tumor effects of systemic anti-PD-L1 in an orthotopic mouse model of UC. Methods We used 32 female C57Bl/6 mice aged 6-8 weeks with MB49 murine UC tumors implanted into the bladder. Treatments (intravesical TMX-101 or vehicle and intraperitoneal anti-PD-L1 or isotype) were given on days 3, 6, and 9 following tumor implantation. Mice were treated with one of four regimens: 1) vehicle + isotype, 2) TMX-101 + isotype, 3) Vehicle + anti-PD-L1, or 4) combination therapy (TMX-101 + anti-PD-L1). Mice were euthanized on day 11. Bladder weight was used as a measure of tumor burden and compared using the Kruskal-Wallis test. Fluorescence activated cell sorting (FACS) analysis of blood, spleen, and regional lymph nodes was performed for T-cell populations._x000D_ Results Mean bladder weight in mice treated with TMX-101 (34.8±4.7mg), anti-PD-L1 (34.8±3.8mg), and combination TMX-101 and anti-PD-L1 (26.4±3.5mg) was less than in control treated mice (84.8±29.1mg). However, only the combination therapy was statistically significant (p<0.05; Figure 1). As controls, no differences in kidney or spleen weights were found between groups. Histologic analysis confirmed immune cell infiltration in tumors. FACS analysis of blood, spleen, and lymph nodes showed no differences in relative T-cell populations._x000D_ Conclusions Intravesical TMX-101 and anti-PD-L1 combination therapy significantly reduced tumor burden as demonstrated by bladder weights and histology in an orthotopic mouse model of non-muscle invasive bladder UC. Funding UroGen Pharma, Ra'anana, Israel
Authors
Andrew Lenis
Karim Chamie Shiyin Yao Dennis Carson Tomoko Hayashi |
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MP98-06 |
Efficacy of recombinant bacille Calmette-Guérin secreting interleukin-15 against bladder cancer |
Bladder Cancer: Basic Research & Pathophysiology V | 17BOS |
Abstract: MP98-06 Sources of Funding: none Introduction Mycobacterium bovis bacillus Calmette-Guerin (BCG) has been used for the treatment of bladder cancer for almost 40 years, although the antitumor effector mechanisms remain elusive. Recent our study demonstrated interleukin (IL)-17 produced by γδT cells plays a key role in the recruitment of neutrophlis to the bladder after BCG instillation, which is important for the antitumor activity against bladder tumor. And, other studies reported that IL-15 plays an important role in neutrophil migration during inflammation. In the present study, we constructed a recombinant BCG expressing the fusion protein of IL-15 (BCG-IL-15) and examined the efficacy of BCG-IL-15 in providing protection against bladder cancer. Methods Six-week-old female C57BL/6 (B6) mice or CδKO mice (B6 background) were intravesically inoculated with 2 x 105 bladder tumor cells (MB49 cells) on day 0. On day 1, 8, 15, and 22 after tumor implantation, mice were inoculated intravesically with either 2 x 106 BCG-IL-15, BCG or PBS weekly. Results BCG-IL-15 treatment prolonged the survival of mice inoculated with bladder cancer cells, compared with BCG treatmnet. We analyzed the effector cells (neutrophils and γδ T cells), which were reported to play key roles in the anti-tumor response. We found infiltration of neutrophil and γδ T cells were significantly elevated in BCG-IL-15 treated mice. Moreover, we confirmed the importance of neutrophils and γδT cells in antitumor effect of BCG-IL-15 therapy by depleting neutrophils with anti Gr-1 antibody and using γδ T cells KO mice (Cδ KO mice). To examine whether IL-17 production was induced by intravesical instillations of BCG-IL-15, we measured vesical IL-17 production by ELISA. IL-17 production after BCG-IL-15 treatment was significantly increased. Moreover, although we previously reported TCRγδand CD25-positive population were IL-17 producing γδT cells, the percentage and the absolute number of TCRγδ and CD25-positive cells of BCG-IL-15-treated mice significantly increased. Conclusions These results suggested that IL-17 produced by γδT cells and chemokines (MIP-2 and MIP-1) induced by BCG-IL-15 played a key role in the recruitment of neutrophlis to the bladder wall. And we believe BCG-IL-15 can become one of the promising drugs for the non muscle invasive bladder cancer. Funding none
Authors
Ario Takeuchi
Masaki Shiota Katsunori Tatsugami Masatoshi Eto |
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MP98-07 |
LimD2 expression is upregulated in bladder cancer lymph node metastases, correlates with the aggressive basal molecular phenotype, and is implicated in bladder cancer metastasis. |
Bladder Cancer: Basic Research & Pathophysiology V | 17BOS |
Abstract: MP98-07 Sources of Funding: McIntyre Introduction The mechanisms of bladder cancer metastasis are incompletely understood. To this end, we performed gene expression profiling comparing matched primary tumors to lymph node metastases. LimD2, a gene previously implicated in papillary thyroid cancer metastasis through modulation of integrin signaling, was found to be upregulated in bladder cancer lymph node (LN) metastases. We sought to further characterize the relationship of LimD2 and bladder cancer metastasis. Methods RNA from both primary tumor and lymph node metastases from 29 patients with pN+ disease at cystectomy was collected and used for gene expression profiling. Immunohistochemistry was performed to confirm the results at the cellular and protein level. LimD2 expression in primary tumors was evaluated in silico in several cohorts including the TCGA. LimD2 expression in urothelial cancer cell lines of both basal and luminal molecular phenotypes was evaluated by western blot. Constructs resulting in LimD2 overexpression and knockdown were stably transfected in urothelial cancer cell lines which will then be used for in vitro and in vivo metastatic assays. Results In patient-matched cystectomy/lymphadenectomy samples, LimD2 RNA expression was 4.7 fold higher in lymph node metastases compared to primary tumors (paired t-test p< 0.0001). These results were confirmed at the cellular and protein level by immunohistochemistry in a subset of the same patient samples. In silico analysis in several cohorts showed that LimD2 expression in the primary tumor was higher in basal and TCGA cluster IV molecular phenotypes, compared with luminal phenotypes (p=0.039, p=0.002 respectively). This pattern was confirmed in urothelial cancer cell lines, as cells with a basal phenotype (T24, J82, TCCSUP) showed much higher expression of LimD2 protein compared with luminal phenotype cells (UC14, RT112, UC6). Conclusions LimD2 expression is upregulated during bladder cancer metastasis and is correlated with aggressive basal molecular phenotypes. Given its ability to modulate integrin signaling, LimD2 is mechanistically heavily implicated in bladder cancer metastasis. Funding McIntyre
Authors
James Ferguson
Roger Li Michael Metcalfe Hongzhuang Peng Frank Rauscher David McConkey Colin Dinney |
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MP98-08 |
Long non-coding RNA, MEG3, suppresses bladder cancer invasion by competitively binding miR-27a and promoting protein translation of PHLPP2 tumor suppressor |
Bladder Cancer: Basic Research & Pathophysiology V | 17BOS |
Abstract: MP98-08 Sources of Funding: NIH/NCI CA165980, CA177665, CA112557, and NIH/NIEHS ES000260 Introduction MEG3 is a long non-coding RNA (lncRNA) transcribed from putative tumor suppressor locus 14q32 that is frequently silenced epigenetically in human bladder cancer. The biological consequences of MEG3 silencing in bladder cancer cells remain poorly defined. This study was designed to understand the effects and the underlying mechanisms of MEG3 down-regulation in bladder cancer biology. Methods Full-length lncRNA MEG3 and its controls were stably transfected into human bladder cancer cell lines, T24T and UMUC3, that were originally derived from high-grade, muscle-invasive bladder cancers. The effects of MEG3 expression on bladder cancer cells including proliferation and invasion were accessed. RNA immunoprecipitation was used to identify the binding between MEG3 and miR-27a. RNA binding-site point-mutation experiments and luciferase reporter assay were used to study 3’-UTR activity of PHLPP2 and the promoter activity of c-Myc, respectively. Results We found that stable expression of MEG3, but not its controls, in T24T and UMUC3 cells strongly inhibited human bladder cancer cell proliferation and invasion. MEG3 exerted these anti-tumor effects by binding specifically to microRNA, miR-27a, and competing its binding for the mRNA of PHLPP2, a tumor suppressor that inhibits the AKT pathway. By so doing, MEG3 markedly reduced the activity of miR-27a and in turn increased the protein translation of PHLPP2. As a consequence, the upregulated PHLPP2 decreased c-Jun phosphorylation at Ser63/73, and inhibited c-Myc transcription, thus reducing the invasiveness of bladder cancer cells. Conclusions We demonstrate for the first time that MEG3, transcribed from a gene locus with recurrent epigenetic silencing in human bladder cancer, is a putative tumor suppressor. MEG3 acts as a competing endogenous RNA (ceRNA) that binds miR27a releasing its inhibition on tumor suppressor PHLPP2, the latter of which inhibits oncogenes/invasion-promoters c-Jun and c-Myc. Silencing of MEG3 reverses all these tumor-suppressive effects and leads to bladder cancer cell proliferation and invasion. Funding NIH/NCI CA165980, CA177665, CA112557, and NIH/NIEHS ES000260
Authors
Chao Huang
Xin Liao Jingxia Li Xue-Ru Wu Chuanshu Huang |
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MP98-09 |
SYNERGISTIC IMMUNO-PHOTOTHERMAL NANOTHERAPY (SYMPHONY): A NOVEL TREATMENT FOR LOCALIZED AND METASTATIC BLADDER CANCER |
Bladder Cancer: Basic Research & Pathophysiology V | 17BOS |
Abstract: MP98-09 Sources of Funding: Duke University Introduction We developed a novel treatment for localized and metastatic bladder cancer comprised of gold nanoparticle-based photothermal therapy and immunotherapy (SYMPHONY). We demonstrate that it effectively ablates primary tumors, destroys metastases abscopally, and induces potent anti-tumor immunity. Methods MB49 murine bladder cancer cells were injected into the bilateral flanks of C57BL/6 mice and grown until 100 mm3 in size. PEG-functionalized gold nanostars, developed and manufactured by our team, were administered intravenously. A 808-nm laser (0.6 W/cm2) was used to trigger plasmonic heat production from the gold nanostars in the left flank 24 hours after injection, while the contralateral flank was left untreated. Anti-PD-L1 antibody immunotherapy was co-administered intraperitoneally and repeated q3days. Mice were assessed for ipsilateral and contralateral tumor response and survival. Flow cytometry, multiplex cytokine profiling, and T cell receptor sequencing were used to characterize the immune response. Mice achieving a complete response were rechallenged with an additional injection of MB49 tumor cells 90 days later. Results Gold nanostar-mediated phototherapy alone completely ablated ipsilateral tumors in 4/5 of mice (pT0 at necropsy) but contralateral tumors grew and all 5 mice required sacrifice within 14 days. Anti-PD-L1 therapy alone slowed tumor growth in 3/5 mice, but tumors rapidly began growing again and 5/5 mice required sacrifice by 45 days. Combined treatment (i.e. SYMPHONY) ablated 5/5 ipsilateral tumors and resulted in partial (3/5) and complete responses (2/5) of untreated contralateral tumors, demonstrating a strong abscopal effect. After 90 days of follow-up, the two mice achieving a complete response with SYMPHONY were rechallenged with MB49 and neither developed a tumor over the ensuing 4 weeks indicating strong and effective immune memory. Flow cytometry showed CD4 and CD8 T cell proliferation, decreased myeloid derived suppressor cells, and increased IL2 with SYMPHONY. Conclusions SYMPHONY treatment resulted not only in effective ablation of primary tumors but also in immune-mediated abscopal destruction of untreated distant tumors. Strong and permanent anti-tumor immunity developed in some mice, indicating that with further optimization, SYMPHONY may be able to cure more advanced bladder cancers. Funding Duke University
Authors
Steven C. Brousell
Yang Liu Paolo F. Maccarini Gregory M. Palmer Wiguins Etienne Yulin Zhao Chen-Ting Lee Tuan Vo-Dinh Brant A. Inman |
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MP98-10 |
Utility of High Throughput Screening in Identifying and Repurposing Small Molecule Inhibitors for Urothelial Carcinoma |
Bladder Cancer: Basic Research & Pathophysiology V | 17BOS |
Abstract: MP98-10 Sources of Funding: This research was supported by the Intramural Research Program of the U.S. National Institutes of Health, National Cancer Institute, Center for Cancer Research. Introduction In this study we performed the first identified quantitative high throughput screening to identify potential targets in urothelial cancer cell lines. We noted a potential new therapy (bardoxolone methyl) and validated this compound with further in vitro studies in cell lines not included in the screen. Methods We screened 8 bladder cancer cell lines against 1,912 oncology-focused drugs using a 48 hr cell proliferation assay with an ATP-based readout (CellTiterGlo), for activity and potency of the compounds in a dose response manner. We identified candidate drugs based on two parameters: 1) more than 70% inhibition at 48 hours 2) a curve class of -1.1/-1.2 indicating curve class with good fit (r2>0.9). Follow up assays in additional cell lines, including viability, spheroid culture, nuclear localization assay, invasion, cell cycle and murine xenograft models were used as confirmation of efficacy and mechanism of the bardoxolone methyl. Results Ward clustering analysis of the initial cell lines (figure 1a) along with curve class demonstration (1b) and medication grouping efficacy (1c) is presented here. Among the candidate drugs which were most active in all compounds, bardoxolone methyl was the most attractive based on IC 50 and previous human safety studies. Invasion assays (Figure 2a) 3-dimensional culture (2b) cell cycle arrest (2c) demonstrated excellent in vitro efficacy. Murine models were then created which highlighted strong inhibition of tumor growth in murine xenograft. (Figure 2d) Conclusions Quantitative high throughput screening was successful in identifying bardoxolone methyl as a novel treatment of urothelial carcinoma in vitro. Repurposing of this molecule may allow for future patient trials in urothelial malignancies. Funding This research was supported by the Intramural Research Program of the U.S. National Institutes of Health, National Cancer Institute, Center for Cancer Research.
Authors
Louis Krane
Reema Railkar Tom Sanford Benjamin Gibbs Carole Sourbier Christopher Ricketts Darmood Wei Kai Hammerich Abhinav Sidana Brad Scroggins Rajarshi Guha Kelli Wilson Craig Thomas Piyush K Agarwal |
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MP98-11 |
GPX2 is a prognostic marker and has a therapeutic potential via regulation of oxidative stress in bladder cancer |
Bladder Cancer: Basic Research & Pathophysiology V | 17BOS |
Abstract: MP98-11 Sources of Funding: none Introduction Reactive oxygen species (ROS) have been identified as important chemical mediators in cell growth and differentiation. The glutathione redox system is the main mechanism protecting against damage caused by ROS in the human body. In this study, we investigated the role and therapeutic potential of the glutathione redox system in bladder cancer. Methods The expression levels of glutathione peroxidase 2 (GPX2) and Ki-67 proteins were analyzed in human transurethral resection (TUR) specimens by immunohistochemistry; correlations between the GPX2 expression and prognosis were also analyzed. In addition, male F344 rats were given 0.05% BBN in drinking water and 0.1% Phenyl isothiocyanate in their diet for 36 weeks. Bladder tissue samples were collected from each animal for analyses. Furthermore, the rat cell line, BC31, and human cell lines, T24, RT4, TCC-SUP, and 5637, were transfected with GPX2 siRNA and negative control siRNA (NC).Subsequently, cell proliferation rates and ROS levels were investigated by cell counting, DCFH assay, western blotting, and flow cytometry. siRNA- or NC- transfected BC31 cells were subcutaneously implanted into nude mice. Results GPX2 was strongly expressed in low grade and low MIB-1 index cancers. PFS and CSS rates were significantly better in patients with higher GPX2 than in those with lower GPX2. Furthermore, GPX2 expression was significantly lower in the normal epithelium of the control group of animals with bladder cancer when compared with those in the treated group, and GPX2 expression was significantly higher in urothelial cancer than in the normal epithelium. BC31 and RT4 cells strongly expressed GPX2 when compared with the other cell lines. Silencing of GPX2 caused significant growth inhibition, and the DCFH assay revealed significant reductions in ROS levels in the siRNA- treated cells. Caspase-dependent apoptosis was fund to be the cause for the decrease in proliferation rates in the siRNA group. Interestingly, tumor growth was significantly inhibited in the BC31-implanted nude mice using the siRNA strategy for Gpx2. Conclusions Our findings demonstrated that GPX2 plays several important roles in carcinogenesis through the regulation of apoptosis against intracellular ROS, and may be considered as a novel marker or therapeutic target in bladder cancer. Funding none
Authors
Taku Naiki
Aya Naiki-Ito Toshiki Etani Keitaro Iida Ryosuke Ando Takashi Nagai Noriyasu Kawai Satoru Takahashi Takahiro Yasui |
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MP98-12 |
Foxa1 Knockout is Associated with Increased Carcinogenic Susceptibility and Androgen Receptor Expression in Murine Bladder Cancer |
Bladder Cancer: Basic Research & Pathophysiology V | 17BOS |
Abstract: MP98-12 Sources of Funding: R00CA17212 Introduction In the US, men are 3 to 4 times more likely to be diagnosed with bladder cancer (BC), however, women frequently present with more advanced disease and have inferior clinical outcomes. Recent data indicates androgen (AR) and estrogen receptors (ERα and ERβ) play an important role in BC tumorigenesis and progression. These hormone receptors physically interact with transcription factor Forkhead box A1 (FOXA1), playing an important role in transcriptional activity of AR and ER. While the role for FOXA1/AR/ER complexes in BC is unknown, Foxa1 knockout (KO) results in sex-specific changes in murine urothelial differentiation. Interestingly, BC development in mice exposed to the carcinogen N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) also occurs in a sex-dependent manner. Therefore, we initiated a study to determine the impact of Foxa1 KO on sex-dependent development of BC in mice. Methods To determine the effect of Foxa1 KO on BC development in males and females, Foxa1 ablation was achieved using a tamoxifen-inducible ubiquitin Cre (UBC-CreERT2) system. Control and KO mice were then exposed to BBN for 16 weeks and bladders were harvested for H&E, immunohistochemistry (IHC), and qPCR. Results Following 16 weeks of BBN treatment, female control mice appeared relatively resistant to carcinogenesis compared to males, which exhibited pre-neoplastic changes including keratinizing squamous metaplasia. However, Foxa1 KO followed by BBN treatment resulted in development of keratinizing squamous metaplasia in females and progression to muscle invasive BC in males. IHC for Krt14 and Ki67 confirmed the presence of squamous differentiation and increased proliferative index in both male and female Foxa1 KO mice treated with BBN. Interestingly, our analysis also shows that nuclear AR expression is increased in male control bladder tissue compared to female control bladder tissue. However, Foxa1 KO increases AR expression independent of sex. Conclusions Overall, our data indicates that Foxa1 KO in adult male and female mice renders them more susceptible to carcinogen exposure. Interestingly, Foxa1 KO resulted in development of keratinizing squamous metaplasia in female mice. Additionally, AR was slightly increased in Foxa1 KO mice, independent of sex. These data indicate loss of FOXA1 in human BC may be associated with increased AR expression and activity, and subsequent disease progression. Future work includes determining ERα and ERβ expression following Foxa1 KO, as well as the mechanism by which Foxa1 KO alters AR expression and activity in BC. Funding R00CA17212
Authors
Lauren Shuman
Zongyu Zheng Hironobu Yamashita Joshua Warrick Klaus Kaestner David DeGraff |
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MP98-13 |
HOTAIR affects bladder cancer epithelial-to-mesenchyme transition through both the Canonical WNT-pathway and extracellular vesicles |
Bladder Cancer: Basic Research & Pathophysiology V | 17BOS |
Abstract: MP98-13 Sources of Funding: Wilmot Foundation Cancer Research Fellowship Introduction _x000D_ Previously we identified the long non-coding RNA Hox antisense intergenic transcript (HOTAIR) enriched in urothelial bladder cancer (UBC) cell lines, extracellular vesicles (ECVs), patient tumors and urinary ECVs. Importantly, HOTAIR affects the expression of genes involved in epithelial-to-mesenchyme transition (EMT). Critically, we found reduced HOTAIR expression correlates with decreased in vitro migration and invasion. Many of the genes affected by HOTAIR expression are in the canonical Wnt-pathway. HOTAIR is a known to facilitate EMT through the canonical Wnt-pathway in other tumors. Determining the importance of the Wnt-pathway in UBC may open up new treatment options. Here we show that HOTAIR is necessary for Wnt-responsiveness and its expression increases during Wnt-pathway activation. EMT is also regulated through intercellular communication mediated by ECVs. Given HOTAIR regulates thousands of genes, we hypothesized that ECVs from HOTAIR knockdown cells would have limited ability to facilitate EMT. In fact, HOTAIR knockdown cells produce fewer exosomes with altered protein cargo and do not facilitate migration or invasion, suggesting that targeting of HOTAIR therapeutically would affect EMT through both the Wnt-pathway and ECVs functionality. _x000D_ _x000D_ Objective: _x000D_ To evaluate the role of HOTAIR in WNT-mediated and EVC-mediated EMT_x000D_ Methods _x000D_ UBCs treated with LiCl or rWNT and gene expression was analyzed by qRTPCR, western blot and immunohistochemistry. We used scratch and 3D spheroid invasion assays to measure in vitro EMT in rWNT treated or untreated UBC cells. shRNA or siRNA against HOTAIR were used and WNT target and antagonist gene expression was measured by qRT-PCR. Migration and invasion were measured using scratch wound assay and 3D spheroid assay. TCF7L2 binding sites were identified in the promoter region of HOTAIR by sequencing. siRNA against TCF7L2 or beta-catenin reduced HOTAIR expression. ECVs isolatedd by ultracentrifugation and sucrose gradient were analyzed using the Nanosight. ECVs protein analysis was performed with LC MS/MS mass spectrometry and western blot. EVC-mediated migration and invasion was evaluated by wound and 3D invasion assay. _x000D_ Results _x000D_ TCGA data reveals WNT pathway genes are affected in human UBC. LiCl or rWNT treated UBCs have increased EMT related gene expression. rWnt facilitates UBC in vitro migration and invasion in a HOTAIR-dependent fashion. Reduced HOTAIR expression correlates with decreased WNT-target and increased WNT-antagonist gene expression. Importantly, HOTAIR is a target of canonical WNT signaling. Reduced HOTAIR expression affects UBC EVC number, content and in vitro migration and invasion._x000D_ Conclusions _x000D_ These data support a role for the canonical WNT-pathway in UBC in a manner dependent on HOTAIR expression. Therefore, therapeutic targeting of the WNT-pathway may affect UBC tumor progression through reduced HOTAIR expression. Importantly, loss of HOTAIR affects the expression of hundreds of genes that results in reduced ECVs number, content, and ability to affect in vitro migration and invasion. _x000D_ Funding Wilmot Foundation Cancer Research Fellowship
Authors
Thomas Osinski
Claudia Berrondo Jonathan Flax Samuel Richheimer Victor Kucherov Carla Beckham |
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MP98-14 |
Cathepsin S inhibition changes regulatory T-cell activity in regulating bladder cancer and immune cell proliferation and apoptosis |
Bladder Cancer: Basic Research & Pathophysiology V | 17BOS |
Abstract: MP98-14 Sources of Funding: none Introduction Regulatory T cells (Tregs) are immune suppressive cells, but their roles in tumor growth have been elusive, depending on tumor type or site. Our prior study demonstrated a role of cathepsin S (CatS) in reducing Treg immunosuppressive activity. We want to explore that should CatS inhibition in Tregs may exacerbate tumor growth. Methods Using mouse bladder carcinoma MB49 cell subcutaneous implant tumor model, we detected the difference in tumor growth, whether mice were given saline- or CatS inhibitor-treated Tregs. Results mice that received inhibitor-treated Tregs had fewer splenic (1.16±0.09 vs. 2.05±0.20 CD25+Foxp3+ percentage in total CD4+ T cells, P=0.003) and tumor (8.96±0.84 vs. 13.06±0.68 CD25+Foxp3+ percentage in total CD4+ T cells, P<0.005) Tregs, and lower levels of tumor (13.16±0.90% vs. 19.58±1.46% Ki67+ area, P<0.002) and splenic cell (14.31±1.18 vs. 18.82±1.00% Ki67+ area, P=0.008) proliferation than mice that received saline-treated Tregs. In vitro, inhibitor-treated Tregs showed lower proliferation and higher apoptosis than saline-treated Tregs when cells were exposed to MB49. In contrast, both types of Tregs showed no difference in proliferation when they were co-cultured with normal splenocytes. Inhibitor-treated Tregs had less apoptosis in splenocytes, but more apoptosis in splenocytes with MB49 conditioned media than saline-treated Tregs. In turn, we detected less proliferation and more apoptosis of MB94 cells after co-culture with inhibitor-treated Tregs, compared with saline-treated Tregs. B220+ B-cell proliferation and apoptosis, CD4+ T-cell proliferation and apoptosis, and CD8+ T-cell proliferation and apoptosis were also lower in splenocytes co-cultured with inhibitor-treated Tregs than with saline-treated Tregs. Under the same conditions, the addition of cancer cell-conditioned media greatly increased CD8+ T-cell proliferation (25.80±0.65 vs. 16.60±0.46% CD45.1–CD8+Ki67+ cells, P<0.001) and reduced CD8+ T-cell apoptosis (17.60±0.26 vs. 20.40±0.55% CD45.1–CD8+Annexin V+ cells, P=0.021). Conclusions CatS inhibition of Tregs may reduce overall T-cell immunity under normal conditions, but enhance CD8+ T-cell immunity in the presence of cancer cells. Funding none
Authors
Xiang Yan*
Chun Wu Tao Chen Marcela M. Santos Conglin Liu Chongzhe Yang Lijun Zhang Jingyuan Ren Hongqian Guo Galina K. Sukhova Guoping Shi |
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MP98-15 |
Nuclear prothymosin-α can enhance PTEN expression transcriptionally and Nrf2 expression through inhibiting TRIM-21-mediated ubiquitination in human bladder cancer |
Bladder Cancer: Basic Research & Pathophysiology V | 17BOS |
Abstract: MP98-15 Sources of Funding: none Introduction Prothymosin-α(PTMA) is a nuclear protein that is usually transported into the nucleus and involves many biologic functions. We previously reported loss of nuclear PTMA protein or cytoplasmic accumulation is significantly associated with poor patients' survival in human urothelial carcinoma. The underlying molecular mechanisms were explored. Methods Paraffin-embedded tumors were collected from 151 bladder cancer patients for PTMA immunostaining. The correlates with clinicopathologic characteristics and patients' survival were explored. Either ectopic nuclear, or cytoplasmic PTMA expression in human bladder cancer J82 cells were used for in vivo tumorigenesis assays and analysis of mRNA differential array. PTMA immunoblot from BFTC905 bladder cancer cells was investigated with proteomics and Tripartite motif-containing protein 21(TRIM21) was further explored the biological significance of the interaction with PTMA. Results Loss of nuclear PTMA expression was significantly associated with tumor grade (p=0.01), stage (p=0.01), and was an independent prognostic indicator for short disease-free survival (HR, 1.54; 95% CI 1.12-2.12; p=0.009). In vivo tumorigenesis study showed cytoplasmic PTMA-expressing J82 xenografts exhibit significantly more rapid tumor growth and shorted survival than those with nuclear PTMA-expressing ones (p<0.05). Chromatin immunoprecipitation study showed nuclear PTMA protein rather than cytoplasmic one can bind with and enhance PTEN promoter expression. Nuclear PTMA expression in bladder tumors exhibited higher PTEN mRNA levels. Immunoprepicitation studies confirmed nuclear PTMA can bind with TRIM21 and PTMA can enhance TRIM21 and NRF2 expression in dose-dependent manner though inhibiting TRIM-21-mediated ubiquitination. The metaanalysis from 2 published datasets showed PTMA expression correlates with NRF2-targeted NAD(P)H quinone dehydrogenase 1(NQO1) expression (p=0.009). Conclusions In this study we demonstrated that loss of nuclear PTMA expression decreased disease-free survival in bladder cancer. Nuclear PTMA can enhance PTEN expression transcriptionally and Nrf2-targeted antioxidative response through inhibiting TRIM-21-mediated ubiquitination in human bladder cancer. Funding none
Authors
Yuh-Shyan Tsai
Shih-Kai Lan Hsin-Tzu Tsai Tzong-Shin Tzai |
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MP98-16 |
Down-regulation of pyruvate kinase 2 by RNAi and small molecule inhibitor overcomes cisplatin resistance of bladder cancer cells in vitro and in vivo |
Bladder Cancer: Basic Research & Pathophysiology V | 17BOS |
Abstract: MP98-16 Sources of Funding: VA Introduction Chemoresistance to cisplatin is a principal cause of treatment failure and disease progression of advanced bladder cancer. In the present study we explore the novel relationship between cisplatin resistance and pyruvate kinase 2 (PKM2) – a rate-limiting enzyme responsible for Warburg effect in cancer cells, and whether down-regulating PKM2 by RNAi or small molecules reduces chemoresistance and enhances chemosensitivity of bladder cancer cells to cisplatin. Methods Cell lines from mouse and human bladder cancer and their derivatives expressing RNAi of PKM2 were assessed for their chemosensitivity to cisplatin or shikonin - a chemical inhibitor of PKM2, or both. The effects and mechanisms of PKM2 inhibition on cisplatin-resistance were examined. Cisplatin and shikonin as single or dual agents for inhibiting bladder cancer proliferation and metastasis were further tested in syngeneic mice. Results Shikonin binds PKM2 and inhibits bladder cancer cell proliferation in a dose-dependent but pyruvate kinase activity-independent manner. Down-regulation of PKM2 by shRNA blunts cellular responses to shikonin but enhances the responses to cisplatin. Shikonin and cisplatin together exhibit significantly greater growth inhibition and apoptosis than when used alone. Experimentally induced cisplatin-resistance is strongly associated with PKM2 overexpression, and cisplatin-resistant cells respond sensitively to shikonin. In syngeneic mice, shikonin and cisplatin together, but not as single-agents, markedly reduces bladder cancer growth and lung metastases. Conclusions PKM2 overexpression is a key mechanism of natural and acquired chemoresistance of bladder cancer to cisplatin. Inhibition of PKM2 via RNAi or chemical inhibitors may be a highly effective approach to overcome chemoresistance and improve the outcome of advanced bladder cancer. Funding VA
Authors
Xing Wang
Fenglin Zhang Herbert Lepor Moon-shong Tang Chuanshu Huang Xue-Ru Wu |
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MP98-17 |
Targeting Protein Kinase D2 May Represent a Therapeutic Strategy for Bladder Cancer |
Bladder Cancer: Basic Research & Pathophysiology V | 17BOS |
Abstract: MP98-17 Sources of Funding: This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. This research was also made possible through the NIH Medical Research Scholars Program, a public-private partnership supported jointly by the NIH and generous contributions to the Foundation for the NIH from the Doris Duke Charitable Foundation, the American Association for Dental Research, the Colgate-Palmolive Company, Genentech, and other private donors. For a complete list, visit the foundation website at http://www.fnih.org. Introduction Protein Kinase D (PKD) is downstream of protein kinase C and it can regulate cell survival, proliferation, invasion, and migration. It has been implicated in several cancers and exists in three major isoforms. We sought to investigate the role of PKD2 in bladder cancer. Methods PKD2 protein expression was assessed using Oncomine data for normal urothelium and bladder tumors. Several bladder cancer cell lines (T24, T24T, UMUC1, and TCCSUP) were assessed for cell proliferation, growth in low attachment agar (GILA), invasion, and migration with and without stable knock-down of PKD2. The UMUC1 cell line was evaluated in xenografts for tumor growth with and without stable knock-down of PKD2. A flank xenograft experiment was performed with oral gavage in mice using CRT0066101, a pan-PKD inhibitor. Western blot analysis was used to confirm silencing and evaluate downstream targets of PKD2. Results Oncomine data confirmed increased mRNA expression of PKD2 in bladder tumors compared with normal urothelium. Selective knock-down of PKD2 in the cell lines inhibited cell proliferation, GILA colony formation, invasion, and migration. UMUC1 cells with silenced PKD2 failed to grow tumors in xenografts. Tumor xenografts treated with CRT0066101 had significant tumor growth inhibition compared to tumor controls (p<0.0001). Loss of phosphorylated c-Jun, a key mediator of cell proliferation and apoptosis, is noted with PKD2 silencing and PKD pharmacologic inhibition. Conclusions PKD2 is overexpressed in bladder tumors and inhibition of PKD2 either through selective silencing of PKD2 or the use of a pan-PKD inhibitor results in tumor growth inhibition in cell lines and xenografts. Targeting PKD2 results in loss of active c-Jun and may represent a therapeutic strategy in urothelial cancer. Funding This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. This research was also made possible through the NIH Medical Research Scholars Program, a public-private partnership supported jointly by the NIH and generous contributions to the Foundation for the NIH from the Doris Duke Charitable Foundation, the American Association for Dental Research, the Colgate-Palmolive Company, Genentech, and other private donors. For a complete list, visit the foundation website at http://www.fnih.org.
Authors
Mohammad siddiqui
Iawen Hsu Quentin Li Thomas Sanford Reema Railkar Piyush Agarwal |
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MP98-18 |
Inhibition of HSP90 synergistically potentiates antitumor effect of NVP-BEZ235 and satraplatin combination therapy in cisplatin-resistant human bladder cancer cells through the down-regulation of AKT and ERK signaling |
Bladder Cancer: Basic Research & Pathophysiology V | 17BOS |
Abstract: MP98-18 Sources of Funding: This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2012R1A1A2043965). Introduction Here we report the role of HSP90 in platinum resistance in human bladder cancer cells and synergistic antitumor effect of HSP90 inhibition on the combination therapy of NVP-BEZ245 and platinum in cisplatin-resistant human bladder cancer cells. Methods To evaluate differential gene expression according to different platinum sensitivity in human bladder cancer cells, we conducted microarray analysis-based gene expression profiling with cisplatin sensitive (T24) and resistant (T24R2) human bladder cancer cells and the results were validated by Western blot analysis. To test synergism between drugs combination index based on CCK-8 assay and also colony forming assay were used. To determine mechanisms underlying synergistic interaction between drugs, flow cytometry and Western blot analysis were performed. Results Gene expression profiling showed that the expression of 5,021 and 1,727 genes had more than two-fold and four-fold changes between T24 and T24R2 cells after platinum treatment. Especially Hsp90 (HSP90AA1, HSP90AA2) and RAS-MEK-MAPK and PI3K-AKT-mTOR signaling pathways showed significantly different expressions in the two cell lines. The combination of NVP-BEZ235 and satraplatin showed strong synergistic antitumor effect in cisplatin-resistant T24R2 cells. However, we found that both NVP-BEZ235 monotherapy and combination treatment with satraplatin caused increased phosphorylation of MEK1/2 and ERK1/2 despite of the suppression of PI3K/AKT signaling in T24R2 cells. The addition of 17-DMAG, HSP90 inhibitor to NVP-BEZ235 and satraplatin combination therapy down regulated both AKT and ERK signaling and synergistically enhanced antitumor effect in T24R2 cells through the caspase-dependent apoptosis and phase-specific cell cycle arrest. Conclusions The present study demonstrated that HSP90 plays important role for the platinum resistance in human bladder cancer cells. Also our findings suggest that through the inhibition of HSP90 activity, antitumor effect of PI3K/mTOR inhibitor and platinum combination therapy can be synergistically potentiated. Funding This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2012R1A1A2043965).
Authors
Cheol Yong Yoon
Mi Kyung Gong Dong Heok Kang Myung Soo Kim Won Sik Jung Young Sik Kim In Rae Cho Young Deuk Choi |
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MP98-19 |
Tumor-suppressive microRNA-26a-5p/-26b-5p inhibit cancer cell migration and invasion through targeting PLOD2 that is a potential prognostic marker in bladder cancer |
Bladder Cancer: Basic Research & Pathophysiology V | 17BOS |
Abstract: MP98-19 Sources of Funding: none Introduction The molecular mechanisms of muscle invasion and distant metastasis in bladder cancer (BC) are not well understood. MicroRNA (miRNA) expression signature of various human cancers have reported that miR-26a-5p/-26b-5p were frequently downregulated in cancer tissues, suggesting these miRNAs act as tumor-suppressors. However, their functions in BC remains unknown. The aim of this study was to investigate the functional role of /-26b-5p and to identify molecular targets that contribute to metastasis in BC. Methods Expression of miR-26a-5p/-26b-5p and their target genes were evaluated in 69 BC clinical BC specimens and 23 normal bladder epithelia (NBE) by real-time PCR. We performed gain-of-function studies (cell proliferation, migration and invasion) by using miR-26a/b transfectants in BC cell lines (T24 and BOY). Putative target genes were listed by in-silico study using the gene expression omnibus (GEO) and TargetScan. We performed loss-of-function studies by using si-RNA transfectants to evaluate the functional role of the target gene. Luciferase reporter analyses were employed to validate direct binding between the target gene and miR-26a/b in BC cells. Overall survival (OS) of the BC patients was evaluated by the Kaplan-Meier analysis. Results The expression levels of miR-26a-5p/-26b-5p in clinical BCs were significantly downregulated compared to that in NBE (p < 0.0001 and p = 0.0006, respectively). miR-26a-5p/-26b-5p transfectants significantly suppressed cell migration and invasion, suggesting these miRNAs act as tumor-suppressors. Procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2) was identified as a direct regulation of miR-26a-5p/-26b-5p by luciferase reporter assay. Kaplan-Meier analysis revealed that the patients with higher PLOD2 expression showed lower overall survival probabilities than those with lower expression (p = 0.0153). Loss-of-function study showed that cell migration and invasion were significantly inhibited in si-PLOD2 transfectans. Conclusions PLOD2 was directly regulated by tumor-suppressive miR-26a-5p/-26b-5p, and might be good prognostic markers for survival of BC patients. Recent studies showed that PLOD2 function as a collagen cross-linking enzyme associate with extracellular matrix (ECM) stiffness. Aberrant expression of PLOD2 by regulation of these miRNAs might cause extracellular matrix (ECM) disruption and promoting metastasis. Funding none
Authors
Kazutaka Miyamoto
Naohiko Seki Ryosuke Matsushita Masaya Yonemori Hirofumi Yoshino Takashi Sakaguchi Satoshi Sugita Hideki Enokida Masayuki Nakagawa |
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MP98-20 |
The role of Toll-like receptor 4 in bladder cancer progression. |
Bladder Cancer: Basic Research & Pathophysiology V | 17BOS |
Abstract: MP98-20 Sources of Funding: none Introduction Toll-like receptors (TLRs) play important roles in immune response and have been reported that expression levels of these molecules were related to prognoses of several kinds of cancer. It has been reported that the expression level of TLR4 is reduced in bladder cancer. However, the role of TLR4 in bladder cancer is still unclear. The aim of this study is to clarify the effects of TLR4 expression on prognosis of bladder cancer patients and to elucidate its underlying mechanisms. Methods To evaluate the effects of TLR4 expression on prognosis, we analyzed the clinical outcomes of 95 patients with bladder cancer and also conducted immunohistochemistry for TLR4 in bladder cancer specimens. The cancer-specific survival was determined by Kaplan-Meier method and the statistical significance was examined by Log-rank test. We also performed multivariate analysis to evaluate the relationship between TLR4 expression and clinical outcomes. We checked the effects of TLR4 depletion on cell growth and invasive abilities of bladder cancer cells. To clarify the underlying mechanisms, we also analyzed the gene expression profiles in TLR4-depleted cells. These results were validated by quantitative RT-PCR. We also confirmed our finding by using data from public database. Results The expression levels of TLR4 were inversely correlated with local invasion and worse prognosis (log-rank test, p=0.007). Although the effect of TLR4 depletion on cell growth was small, it could dramatically enhance invasion ability of cancer cells. We also observed morphologic changes in these cells. Both gene ontology analysis and gene set enrichment analysis of microarray data revealed that most of upregulated genes in TLR4-depleated cells were related to differentiation of epithelium cells. Among these genes, small proline-rich protein (SPRR) family genes which are related to poor prognosis of squamous cell carcinoma were upregulated in TLR4-depleated cells. By analyzing data from public database, we confirmed that expression levels of SPRRs family genes were inversely correlated with TLR4 expression and positively correlated with poor prognosis of bladder cancer patients. Furthermore, we found that expression of TLR4 diminished in the areas with squamous differentiation in bladder cancer. Conclusions Our finding suggested that TLR4 is related to bladder cancer aggressiveness through regulation of squamous differentiation. Funding none
Authors
Tomoya Fukawa
Terumichi Shintani Kei Daizumoto Tomoharu Fukumori Masayuki Takahashi Hiro-omi Kanayama |
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MP99-01 |
Proteomic analysis of urinary extracellular vesicles from high Gleason score prostate cancer |
Prostate Cancer: Basic Research & Pathophysiology IV | 17BOS |
Abstract: MP99-01 Sources of Funding: This study was supported by grants from the Princess Takamatsu Cancer Research Fund, JSPS KAKENHI Grant Number JP15K10588, and Osaka University project MEET. Introduction Extracellular vesicles (EVs) are microvesicles secreted from various cell types. EVs contain microRNAs, proteins, and mRNAs and play a role in intercellular communications via the mechanisms of exocytosis and endocytosis. We aimed to discover a new biomarker for high Gleason score (GS) prostate cancer (PCa) in urinary EVs via quantitative proteomics. Methods EVs were isolated from urine after massage from 18 men (negative biopsy [n = 6], GS 6 PCa [n = 6], or GS 8-9 PCa [n = 6]). EV proteins were labeled with iTRAQ and analyzed by LC-MS/MS. Candidate proteins were further analyzed by selected reaction monitoring/multiple reaction monitoring (SRM/MRM). Results Proteins extracted from EVs were enriched with CD9 protein, which is a marker of EVs, compared with unprocessed urinary proteins. EVs labeled with anti-CD9 antibody conjugated with Au colloids were also confirmed by electron microscopy. We identified and quantified 3530 proteins in the urinary EVs by LC-MS/MS. Thirty-six proteins increased in patients with PCa compared to those with negative biopsy (ratio > 2.0, p < 0.1). Four proteins increased in patients with GS 8-9 PCa compared to those with negative biopsy or GS 6 PCa (ratio > 2.0, p < 0.1). Twenty-seven proteins were chosen for further analysis and verified in 29 independent urine samples (negative [n = 11], PCa [n = 18]) using SRM/MRM. Among these candidate markers, fatty acid binding protein 5 (FABP5) was higher in the cancer group than in the negative group (p = 0.009) and was significantly associated with GS (p for trend = 0.011). Univariate logistic analysis showed that FABP5 was significantly associated with prostate cancers with GS 7 or more (p < 0.001). Even after adjusting for age, PSA, and PSA density, FABP5 was significantly associated with prostate cancer with GS 7 or more (p = 0.003). The receiver-operator characteristics curve analysis showed that the area under the curve (AUC) for the prediction of GS ? 7 by FABP5 was 0.856 (95% CI 0.708–1.00, p = 0.002), whereas the AUC value for prediction by serum PSA was 0.511 (95% CI 0.280–0.757, p = 0.87). Conclusions We applied the proteomic analysis to discover biomarkers in EVs in urine collected after prostate massage. FABP5 in urinary EVs could be a potential biomarker of high GS prostate cancer. Additional large-scale studies are warranted to confirm this finding. Funding This study was supported by grants from the Princess Takamatsu Cancer Research Fund, JSPS KAKENHI Grant Number JP15K10588, and Osaka University project MEET.
Authors
Kazutoshi Fujita
Hideaki Kume Kyosuke Matsuzaki Atsunari Kawashima Takeshi Ujike Akira Nagahara Motohide Uemura Yasushi Miyagawa Takeshi Tomonaga Norio Nonomura |
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MP99-02 |
Overexpression of HSD3B1 Confers Resistance to Enzalutamide in Prostate Cancer |
Prostate Cancer: Basic Research & Pathophysiology IV | 17BOS |
Abstract: MP99-02 Sources of Funding: This work is supported in part by grants NIH/NCI CA140468, CA168601, CA179970, DOD PC130062, and US Department of Veterans Affairs, ORD VA Merits I01BX0002653. Introduction Most prostate cancer (PCa) patients receiving enzalutamide (Enza) develop drug resistance within 24 months of exposure. This creates a need to better understand the underlying causes of Enza resistance so that improved treatment methods can be developed. Previous studies demonstrate that uncontrolled intraprostatic androgen synthesis promotes Enza resistance. HSD3B1 is a key enzyme contributing to androgen synthesis and its expression is associated with PCa progression. The aim of this study is to determine the contribution of HSD3B1 to Enza resistance in PCa. Methods Enza resistant C4-2B PCa cells (C4-2B MDVR) were generated by chronically exposing parental C4-2B cells to increasing Enza concentrations (5-40 ?M) for >12 months and maintained in 20 µM Enza. Differences in gene expression between C4-2B MDVR and parental cells was determined by microarray and RNA-seq. HSD3B1 expression was knocked down in C4-2B MDVR cells using shRNA and cell number was determined in media containing FBS, charcoal dextran stripped FBS (CD-FBS), or CD-FBS supplemented with 100 nM pregnenolone (P5), 100 nM DHEA, or 10 nM DHT in the presence and absence of 20 µM Enza. PSA secretion was determined by ELISA and PSA-luciferase activity was measured by reporter assay. C4-2B MDVR cells were also treated with apigenin, which has been shown to reduce HSD3B1 expression, and cell number and PSA outcomes were determined under the previously mentioned treatment conditions. Results HSD3B1 expression is higher in C4-2B MDVR cells compared to parental C4-2B cells as measured by Microarray and RNA-seq. This correlates to increased intracrine androgens in C4-2B MDVR cells compared to C4-2B cells as examined by LC-MS. Knockdown of HSD3B1 in C4-2B MDVR resensitized cells to Enza in FBS, CD-FBS+DHT and CD-FBS+P5 conditions as determined by a reduction in cell number and PSA secretion and/or luciferase activity in response to Enza. No response was seen in CD-FBS or CD-FBS+DHEA. Supplementation of parental C4-2B cells with 100 nM P5, but not DHEA, improved resistivity to Enza. Apigenin, a potential inhibitor of HSD3B1 expression, resensitized C4-2B MDVR cells to Enza. Conclusions HSD3B1 overexpression in C4-2B MDVR cells contributes to Enza resistance and modulation of this enzyme could be a viable strategy to improve Enza treatment response in PCa cells. HSD3B1 activity appears to be reliant on select androgen precursors, such as pregnenolone, indicating preference towards a specific androgen synthesis pathway by HSD3B1 in mediating Enza resistance. Funding This work is supported in part by grants NIH/NCI CA140468, CA168601, CA179970, DOD PC130062, and US Department of Veterans Affairs, ORD VA Merits I01BX0002653.
Authors
Cameron Armstrong
Chengfei Liu Wei Lou Christopher Evans Allen Gao |
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MP99-03 |
RIOK2 is a mediator of obesity enhanced prostate cancer growth |
Prostate Cancer: Basic Research & Pathophysiology IV | 17BOS |
Abstract: MP99-03 Sources of Funding: The Stewart Rahr – Prostate Cancer Foundation Young Investigator Award and NIH Research Supplement to Promote Diversity in Health-Related Research from the NCI 3R01-CA125618-08S1 (EM) as well as NCI awards CA131235 and 5K24CA160653-03 (SF) Introduction Obesity is a growing global and U.S. health problem. For 2012, an estimated 117,000 cancer cases in the U.S. were deemed preventable by achieving and maintaining a healthy weight, including 11% of all advanced prostate cancers (PC). Obesity is associated with greater risk of high-grade PC, recurrence after therapy, metastases, and PC specific death. We exploited this link to identify actionable targets by performing a shRNA genomic screen in obese and lean mice targeting the entire kinome. Our functional screen identified multiple kinases, which appear to be essential for obesity-driven PC growth including kinases previously implicated in PC and others not previously studied such as Right Open Reading Frame Kinase 2 (RIOK2). Methods LAPC-4 cells were inoculated with an shRNA library of ~5000 lentivirus targeting 513 kinases. 5x106 cells (~1,000 cells per shRNA) were grafted to chronically obese mice. Tumors were established to ~200 mm3 and a portion collected for reference. Remaining mice were randomized to continue on ad lib WD or 25% CR diet. Genome-integrated shRNA inserts were amplified using nested barcoded primers and sequenced using Illumina Hi-Seq 2000 and quantified. A virtual screen based on a RIOK2 homology model generated using MODELLER based on two RIOK2 crystal structures. Global gene expression analysis of RNA from scramble control and RIOK2 knockdown with two shRNAs in 22RV1 cells was conducted with Affymetrix U133A Plus Array. Results RIOK2 expression correlates with Gleason grade in radical prostatectomy tissue and RIOK2 kinase activity is elevated in metastatic vs localized PCs. ENCODE ChIP-seq data shows Androgen Receptor and Myc bind to the RIOK2 promoter and regulate expression. Targeting RIOK2, via newly identified small molecule inhibitors reduces cell viability and soft agar colony growth. Gene set enrichment analysis of RIOK2 depleted PC cells showed reduction of cell cycle, adipogenesis, EMT and cancer stem cell genes. RIOK2 also regulates Neuropeptide Y2 Receptor (NYP2R), which is part of the NPY obesogenic signaling axis that correlates with obesity and worse PC outcomes. Conclusions Our in vivo screen highlighted RIOK2 as an actionable PC target in obese hosts. Targeting RIOK2, pharmacologically with our lead compounds or genetically, drastically reduces PC cell viability. RIOK2 may regulate NPY2R expression, which when coupled with elevated NPY in both obese hosts and PCs can amplify NPY pro-tumorigenic signaling. Funding The Stewart Rahr – Prostate Cancer Foundation Young Investigator Award and NIH Research Supplement to Promote Diversity in Health-Related Research from the NCI 3R01-CA125618-08S1 (EM) as well as NCI awards CA131235 and 5K24CA160653-03 (SF)
Authors
Everardo Macias
David Corcoran Jen-Tsan Chi Stephen Freedland |
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MP99-04 |
Truncated-CRMP4 by calpain-2 suppresses CRMP4 to promote metastasis of prostate cancer via promoter methylation through E2F1/NF-?B/DNMT1 signaling |
Prostate Cancer: Basic Research & Pathophysiology IV | 17BOS |
Abstract: MP99-04 Sources of Funding: This work was supported by National Natural Science Foundation of China (81372728, 81572503). Introduction Metastasis is the primary cause of cancer-specific death in patients with prostate cancer (PCa). Previous studies identified promoter methylation is responsible for the repression of the tumor metastasis-suppressor gene collapsing response mediator protein-4 (CRMP4) in metastatic PCa. However, the underlying mechanisms for promoter methylation remain unknown. Methods In this study, calpain-2 expression in prostatic benign and cancer tissues was determined using immunohistochemistry (IHC). The effects of truncated-CRMP4 by calpain-2 in migration and invasion of PCa cells and the underlying mechanisms were explored. The role of nuclear factor-kappaB (NF-kB) in CRMP4 promoter methylation was evaluated. In addition, the downstream signaling regulated by CRMP4 were determined. Results Calpain-2 was differentially upregulated in metastatic PCa Calpain-2 was differentially upregulated in metastatic PCa tissues. N-terminally truncated-CRMP4 by calpain-2 enhanced the ability of migration and invasion via nuclear translocation and subsequently activation of E2F1-mediated DNA methyltransferase 1 (DNMT1) expression. In addition, NF-kB RelA/p65 recruited DNMT1 to directly bind to and methylate the CRMP4 promoter in which Serine276 phosphorylation of p65 was essential. Furthermore, CRMP4 CRMP4 exhibited anti-metastatic function by inhibiting the expression of vascular endothelial growth factor C (VEGFC) via Sema3B- Neuropilin2 signaling. Conclusions Calpain-mediated cleavage of CRMP4 promotes PCa metastasis by suppression of CRMP4 transcription via nuclear translocation of N-terminally truncated fragment and subsequent activation of E2F1/NF-kB/DNMT1 signaling which in turn enhanced CRMP4 promoter hypermethylation. Targeting re-expression of CRMP4 may be of great significance in the treatment of patients with metastatic PCa. Funding This work was supported by National Natural Science Foundation of China (81372728, 81572503).
Authors
Xin Gao
Yunhua Mao Zheng Chen Jun Pang Ke Li |
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MP99-05 |
ELL2 regulates DNA double-strand break repair in prostate cancer cells |
Prostate Cancer: Basic Research & Pathophysiology IV | 17BOS |
Abstract: MP99-05 Sources of Funding: 9R01CA186780 and 1P50CA180995 Introduction Androgens are known to protect prostate cancer cells from DNA damage. Recent studies showed regulation of DNA repair genes by androgen receptor (AR) signaling in prostate cancers. We recently reported that androgen-regulated protein and potential tumor suppressor ELL2-associated factor 2 (EAF2) can enhance DNA repair through Ku70/Ku80 in the prostate. ELL2 (elongation factor, RNA polymerase II, 2), a component of the super elongation complex (SEC), is an important factor for RNA Pol II transiting from promoter-proximal paused state into elongation state. ELL2 is also regulated by androgens and frequently down-regulated in prostate cancer. These observations led to our hypothesis that ELL2 can regulate DNA repair through Ku70/Ku80 in prostate cancer cells. Methods Prostate cancer cells, in the presence or absence of siRNA of ELL2, were treated with ?-irradiation or doxorubicin and then collected for detecting the level of DNA damage marker ?H2ax or neutral comet assay. Nonhomologous end-joining (NHEJ) and homologous recombination (HR) assays were used to test the role of ELL2 in these two double-strand break (DSB) repair pathways. Co-immunoprecipitation was used to determine the interaction between ELL2 and NHEJ pathway proteins Ku70 and Ku80. We examined the effect of ELL2 knockdown on Ku70 and Ku80 recruitment in response to laser microirradiation. Results Knockdown of ELL2 sensitized prostate cancer cells to DNA damage and overexpression of ELL2 protected prostate cancer cells from DNA damage. Knockdown of ELL2 impaired NHEJ repair but not HR. Transfected ELL2 co-immunoprecipitated with both Ku70 and Ku80 proteins. ELL2 could binds to and co-accumulated with Ku70/Ku80 proteins at sites of DNA damage. Knockdown of ELL2 dramatically/significantl inhibited Ku70 and Ku80 accumulation and retention at DSB sites in prostate cancer cells, and also impaired recruitment of Ku70/Ku80 to DSB sites. The impaired recruitment of Ku70 and Ku80 proteins to DNA damage sites upon ELL2 knockdown was rescued by re-expression of an ELL2 transgene insensitive to siELL2. Conclusions This study suggests that ELL2 is an important factor mediating androgen protection of DNA damage via Ku70/Ku80 in prostate cancer cells. Funding 9R01CA186780 and 1P50CA180995
Authors
Yachen zang
Yibin Zhou Leizhen Wei Joel B. Nelson Lan LI Boxin xue Yuxi Shan Zhou Wang |
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MP99-06 |
High fat diet-induced inflammation accelerates tumor progression in mice model for prostate cancer |
Prostate Cancer: Basic Research & Pathophysiology IV | 17BOS |
Abstract: MP99-06 Sources of Funding: none Introduction Inflammation could be associated with progression of prostate cancer. High fat diet (HFD) causes obesity and systemic inflammation, and might be associated with progression of prostate cancer. The aim of this study is to elucidate how HFD affects tumor progression and local immune cells using model mice for prostate cancer. Methods HFD or control diet (CD) had been administered to normal mice and model mice <Pb-Cre+;Ptenfl/fl)> until 22 weeks old. Tumor progression was evaluated by prostate weights, H&E staining, and Ki67 staining. The fractions of immune cells in the prostatic tissues were assessed by flow cytometry. We compared these factors of HFD-fed mice to CD-fed mice, and evaluated the changes of tumor progression and immune cells after administration of celecoxib (8mg/kg/day) to HFD-fed and CD-fed model mice. Results Prostate weights were significantly increased in HFD-fed model mice compared to CD-fed model mice (0.72 ± 0.57g vs 0.30 ± 0.14g, p =0.029), while there were no significant changes in between HFD-fed and CD-fed normal mice. Prostate cancer was pathologically more invasive, and the ratio of Ki67-positive cells to tumor cells of these areas was significantly increased in HFD-fed model mice compared to CD-fed model mice (30.0 ± 13.8% vs 7.8 ± 2.9%, p =0.002). The fraction of Myeloid-Derived Suppressor Cells (MDSCs) was significantly increased in HFD-fed model mice compared to CD-fed model mice (p =0.044). The M2/M1 macrophage ratio was significantly increased in HFD-fed compared to CD-fed model mice (p =0.011), while the ratio was significantly decreased in HFD-fed compared to CD-fed normal mice (p =0.037). Administration of celecoxib to HFD-fed model mice significantly decreased the prostate weights (0.28 ± 0.10g, p =0.040) and the ratio of Ki67-positive cells (8.3 ± 5.6%, p =0.005), and also decreased the fraction of MDSCs significantly (p =0.035) and the M2/M1 ratio (p =0.114). Administration of celecoxib to CD-fed model mice did not decrease the prostate weights. Conclusions HFD-induced pro-tumor changes of immune cells could accelerate tumor progression of prostate cancer, which was suppressed by celecoxib. Inflammation could be one of the key regulators for progression of prostate cancer. Funding none
Authors
Takuji Hayashi
Kazutoshi Fujita Yu Ishizuya Cong Wang Yoshiyuki Yamamoto Toshiro Kinouchi Kyosuke Matsuzaki Norihiko Kawamura Atsunari Kawashima Akira Nagahara Takeshi Ujike Motohide Uemura Satoshi Nojima Eiichi Morii Norio Nonomura |
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MP99-07 |
AP4 Promotes Proliferation and Metastasis of Castration-Resistant Prostate Cancer through binding and up-regulation of L-plastin |
Prostate Cancer: Basic Research & Pathophysiology IV | 17BOS |
Abstract: MP99-07 Sources of Funding: None Introduction The transition from androgen-dependent to castration-resistant prostate cancer (CRPC) is a lethal event of uncertain molecular etiology. The aim of this study was to identify the mechanism that AP4 promotes the proliferation and metastasis of CRPC by upreguating of L-plastin. Methods A total of 136 paired PCa and adjacent normal tissues were collected from patients who underwent prostatectomy between 2005 and 2015. The univariate and multivariate Cox regression analyses showed that AP4 expression was independent prognostic factor in patients with prostate cancer (PCa). The EMSA, supershift assays and CHIP-qPCR experiments noted that AP4 directly binds to L-plastin promoter. The in vitro and in vivo experiments were performed. Results Previously, we reported that L-plastin is involved in the metastasis of PCa and up-regulated by androgen. Recently, we found that L-plastin is activated even after androgen deprivation, suggesting that androgen-independent factors might regulate its expression. Here, we noted that an androgen-independent factor, which locates in the area close to the transcription initiation site (-216 to +118) of L-plastin promoter, might facilitate the up-regulation of L-plastin. AP4 was then identified as a key transcription activator, which directly binds to L-plastin promoter. The microarray analysis noted that L-plastin is the differentially expressed downstream target gene of AP4. Furthermore, we demonstrated that AP4 upregulated L-plastin expression, which promotes the proliferation and metastatic of CRPC in vitro and in vivo. Importantly, AP4 level was increased in CRPC tissues compared with ASPC. Overexpression of AP4 was significantly correlated with poor survival, Gleason score over 7 and lymph node metastasis in a large cohort of PCa tissues (n=136). Conclusions Our study characterizes a new mechanism in CRPC, in which AP4 increases the progression of CRPC through binding L-plastin promoter. Strategies designed to target AP4 may provide novel therapeutic agents for the management of CRPC. Funding None
Authors
Changhao Chen
TIanxin Lin Thomas B Lam Yue Zhao Jian Huang |
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MP99-08 |
SPOP mutant prostate cancer is not driven by ERG stabilization |
Prostate Cancer: Basic Research & Pathophysiology IV | 17BOS |
Abstract: MP99-08 Sources of Funding: Prostate Cancer Foundation, National Cancer Institute, Urology Care Foundation Introduction Prostate cancer with ERG rearrangements constitute nearly 50% of cancers, while 10% of prostate cancers have recurrent mutations in SPOP. SPOP mutations and ERG rearrangements are mutually exclusive in prostate cancer, and are both thought to be early events in oncogenesis. Recent largely biochemical work has suggested that the predominant downstream regulator of SPOP mutation is stabilization of the ERG oncoprotein. However the oncologic relevance of this finding in murine and human cancers is unclear. Methods We utilized a mouse model in which the SPOP F133V mutation in combination with loss of PTEN results in the accelerated development of high grade prostate intraepithelial neoplasia (HgPIN) and invasive adenocarcinoma. SPOP mutation is a clear driver of carcinogenesis in these models, and the phenotype of these cancers phenocopies human SPOP mutant prostate cancer. We generated prostate organoids from these genetically altered mice and studied these organoids and mice using immunohistochemistry (IHC), immunoblotting, immunofluorescence (IF), and RNA sequencing. We also examined the evidence for SPOP stabilization of ERG being a major driver of prostate cancer in human tumors using multiple institutional and publicly available RNA and DNA sequencing data sources. Results We found that murine SPOP driven prostate adenocarcinoma and HgPIN did not express ERG by immunohistochemistry or western blotting. ERG expression was also not present in the presence of SPOP mutation in prostate organoids derived from these mice by IHC, IF, or western blot. Furthermore, mice engineered to coexpress F133V and ERG did not demonstrate evidence of ERG protein upregulation relative to those expressing ERG only. _x000D_ _x000D_ In our institutional human data, we found that none of 8 SPOP mutant cancers expressed ERG. We also found that ERG mRNA is expressed below levels that are generally considered adequate for expression in SPOP mutant cancers. Additionally, ERG rearrangement and SPOP mutation result in vastly distinct gene expression signatures. Organoids derived from SPOP mutant mice do not express ERG mutant gene signatures. Furthermore human SPOP mutant tumors cluster distinctly from ERG rearranged tumors relative to normal prostate tissue, and non-ERG rearranged non-SPOP mutant prostate cancers. Similarly, ERG and SPOP mutant cancers have discrepant methylation signatures, and develop different patterns of genomic rearrangements._x000D_ Conclusions While SPOP may affect ERG stabilization in certain models, we find no evidence that SPOP stabilization of ERG is driver of mouse or human prostate cancer. Funding Prostate Cancer Foundation, National Cancer Institute, Urology Care Foundation
Authors
Jonathan Shoag
Deli Liu Mirjam Blattner Andrea Sboner Juan Miguel Mosquera Brian Robinson Yu Chen Christopher Barbieri |
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MP99-09 |
Prostate cancer genomics – identification of prognostic markers from the bone marrow |
Prostate Cancer: Basic Research & Pathophysiology IV | 17BOS |
Abstract: MP99-09 Sources of Funding: none Introduction Disseminated tumor cells (DTC) can be detected in the bone marrow of a high proportion of patients with prostate cancer. The prognostic value of these DTCs, however, remains a matter of debate. Moreover, robust DTC-specific biomarker are not yet identified. The aim of this study was to evaluate gene expression differences in bone marrow derived from patients with early tumor recurrence after radical prostatectomy (RP) and patients without recurrence, respectively. Methods The initial discovery cohort of patients was subdivided into two groups: one with early recurrence after RP and one without recurrence. All patients underwent intraoperative bone marrow (BM) aspiration biopsy. RNA was isolated from nine BM biopsies of each cohort using the PAXgene RNA isolation kit. To identify differently expressed genes the TaqMan® OpenArray® Human cancer panel was used. Identified genes were further validated in a validation cohort encompassing 30 BM biopsies for each group. Quantitative PCR was performed to evaluate the significance of previously identified differentially expressed genes. Results Of 245 patients with intraoperative BM biopsy nine patients showed an early recurrence within two years after RP. We correlated the results with nine patients with high risk PC (Gleason ? 8) and no recurrence within five years after RP. Altogether, 13 overexpressed and two downregulated genes in the recurrence group were identified. The validation with 58 patients resulted in a significant overexpression of CHPT1 (p=.0029), MYC (p<.0001), MCM6 (p<.0001) and CTNNB1 (p<.0001). Conclusions For the first time, gene expression profiling of BM biopsies from patients with recurrence after RP was performed. In this single-center cohort of patients with recurrence after radical prostatectomy CHPT1, MYC, MCM6 and CTNNB1 were significantly overexpressed compared to a cohort without recurrence after RP. Thus, our data implicate a predictive valence of target genes MYC, CTNNB1, MCM6 and CHPT1 with regard to prostate cancer recurrence after RP. Funding none
Authors
Simone Bier
Jörg Hennenlotter Ursula Haerle Eleni Karpatsi Arnulf Stenzl Tilman Todenhöfer Christian Schmees |
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MP99-10 |
SYNERGISTIC CONTRIBUTIONS OF ABL1 AND ABL2 TO AN ?3?1 INTEGRIN – ABL KINASE – HIPPO SUPPRESSOR PATHWAY IN PROSTATE CANCER |
Prostate Cancer: Basic Research & Pathophysiology IV | 17BOS |
Abstract: MP99-10 Sources of Funding: NIH R01 CA136664 (C.S.S.), NIH R01 CA130916 (M.D.H.), NIH P30 CA086862 (University of Iowa Holden Comprehensive Cancer Center), Andersen-Hebbeln Prostate Cancer Research Fund Introduction Integrin α3β1, a major receptor for laminin isoforms in the prostate epithelial basal lamina, is frequently downregulated in prostate cancer. We have uncovered an α3β1-Abl kinase-Hippo signaling axis that functions to suppress prostate cancer progression and metastasis. Disrupting this pathway by depleting α3 integrin or treating with the Abl kinase inhibitor, imatinib, unleash an aggressive, metastatic phenotype in a pre-clinical model of castrate-resistant prostate cancer (CRPC). Here, our objective was to elucidate the specific contributions of the two Abl kinases, Abl1 and Arg/Abl2 to suppressing a metastatic phenotype, and investigate an Abl-targeted therapeutic, GNF-5, which does not also cross-inhibit the PDGF receptor or c-Kit._x000D_ Methods We used a combination of genetic and pharmacological approaches to interfere with α3 integrin and Abl kinase activity in CRPC cells and examined the effects on metastasis in vivo and in vitro assays of malignant behavior. Results Loss of α3 integrin promoted progression and metastasis in vivo and low anchorage 3D growth, migration and invasion in vitro. These phenotypes were linked to disruptions in a signaling pathway leading from α3 integrin through Abl kinases to limit the activity of YAP and WWTR1/TAZ, the transcriptional coactivators that are the targets of the Hippo suppressor pathway. The highly specific, allosteric Abl kinase inhibitor, GNF-5, and imatinib, produced essentially identical increases in 3D growth, phenocopying the loss of α3 integrin. Depleting either Abl1 or Abl2 by RNAi promoted 3D growth and migration, and depleting both kinases simultaneously produced synergistic effects, dramatically increasing both growth in 3D and cell migration. Conclusions The presence of a novel α3β1-Abl kinase-Hippo suppressor pathway in prostate cancer suggests new potential strategies for targeting integrin signaling pathways in prostate cancer and may help to explain the failure of imatinib in prostate cancer clinical trials. Funding NIH R01 CA136664 (C.S.S.), NIH R01 CA130916 (M.D.H.), NIH P30 CA086862 (University of Iowa Holden Comprehensive Cancer Center), Andersen-Hebbeln Prostate Cancer Research Fund
Authors
Afshin Varzavand
William Hacker Deqin Ma Katherin Gibson-Corley Maria Hawayek James Brown Michael Henry Christopher Stipp |
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MP99-11 |
Angiomotin regulates prostate cancer cell proliferation by signaling through Hippo-YAP pathway |
Prostate Cancer: Basic Research & Pathophysiology IV | 17BOS |
Abstract: MP99-11 Sources of Funding: This work was supported by grants from National Science Foundation of China (NSFC 81172439 and 81402110), NIH RO1CA174798, prostate cancer SPORE P50 CA140388, Cancer Prevention and Research Institute of Texas (CPRIT RP110327, RP150179), the Prostate Cancer Foundation, and cancer center core grant CA16672. Introduction Angiomotin (AMOT) is a family of proteins found to be a component of the apical junctional complex of vertebrate epithelial cells and is recently found to play important roles in neurofibromatosis type 2 (NF-2). Whether AMOT plays a role in prostate cancer (PCa) is unknown. Methods Purified GST-AMOTp80 was used as immunogen for antibody generation. Real-time PCR, western blot and immunohistochemistry were used to identify the expression of AMOT. To study the function of AMOT, retroviral vector were constructed, also shRNA was used to knockdown AMOT in cells. Cell migration and invasion assays were performed by using transwell chambers. Nuclear and cytoplasmic protein fractions were prepared by using NE-PER reagents (Pierce). The SPSS 19.0 software was used for statistical analysis. Chi-square test and t test were used for the comparisons between groups. Results AMOT is expressed as two isoforms, AMOTp80 and AMOTp130, which has a 409 aa N-terminal domain that is absent in AMOTp80. Both AMOTp80 and AMOTp130 are expressed in LNCaP and C4-2B4, but at a low to undetectable level in PC3 cells. Further study showed that AMOTp130 and AMOTp80 have distinct functions in PCa cells. We found that AMOTp80 functioned as a tumor promoter by enhancing PCa cell proliferation while AMOTp130 did not. Mechanistic studies showed that AMOTp80 signaled through the Hippo pathway by promoting the nuclear translocation of YAP, resulting in an increased expression of YAP target protein BMP4. Moreover, inhibition of BMP receptor activity by LDN-193189 abrogates AMOTp80-mediated cell proliferation. Conclusions Together, this study reveals a novel mechanism whereby the AMOTp80-Merlin-MST1-LATS-YAP-BMP4 pathway leads to AMOTp80-induced tumor cell proliferation. Funding This work was supported by grants from National Science Foundation of China (NSFC 81172439 and 81402110), NIH RO1CA174798, prostate cancer SPORE P50 CA140388, Cancer Prevention and Research Institute of Texas (CPRIT RP110327, RP150179), the Prostate Cancer Foundation, and cancer center core grant CA16672.
Authors
Pengfei Shen
Hao Zeng Angelica Ortiz Chien-Jui Cheng Yu-Chen Lee Guoyu Yu Song-Chang Lin Li-Yuan Yu-Lee Sue-Hwa Lin |
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MP99-12 |
Impact of Hippo pathway protein expression in residual cancer after neoadjuvant chemohormonal therapy with docetaxel for high-risk localized prostate cancer |
Prostate Cancer: Basic Research & Pathophysiology IV | 17BOS |
Abstract: MP99-12 Sources of Funding: None Introduction Hippo pathway regulates tissue homeostasis, organ size, and tumorigenesis. Here we investigated the expression of Hippo pathway proteins in docetaxel- and castration-resistant prostate cancer (PCa) cell line and human PCa tissues in patients who underwent radical prostatectomy (RP) with and without neoadjuvant chemohormonal therapy. Methods Docetaxel-resistant subline (22Rv-1-DR) was generated and confirmed the expression of Hippo pathway-related proteins including YAP, p-YAP, TAZ, and MOB4A. A tissue microarray with 210 cores from 70 high-risk localized PCa patients who underwent RP without neoadjuvant therapy (NNA), with neoadjuvant hormonal therapy (NHT), or with neoadjuvant chemohormonal therapy with docetaxel (CHT) was used to assess the nuclear and cytoplasmic expression of YAP and MOB4A in cancer cells. Expression levels among the three groups were statistically analyzed. Multivariate analyses were performed to investigate the prognostic factors of biochemical recurrence (BCR) in patients who underwent surgery with CHT. Results The expressions of nuclear YAP (nYAP) and nuclear p-YAP were markedly higher in 22Rv-1-DR cells than those in parental 22Rv-1.Cytoplasmic MOB-4A was down-regulated in 22Rv-1-DR cells. In human PCa tissues, YAP was expressed both in the nucleus and the cytoplasm, whereas MOB4A was mainly expressed in the cytoplasm. There was no difference in the mean nYAP intensity score in cancer cells between the NNA and NHT groups, whereas the mean nYAP intensity score was significantly higher in the CHT group than in the NHT groups (p = 0.034). The patients with a high nYAP intensity score in residual cancer cells after CHT had a significantly higher BCR rate than those with a low nuclear immunoreactivity score (p = 0.033). On multivariate analysis, preoperative PSA level and high nYAP intensity score were independent prognostic factors for BCR in patients with PCa treated with CHT. Conclusions nYAP expression in residual cancer cells is a potential prognostic marker for BCR in high-risk PCa patients who underwent RP after neoadjuvant chemohormonal therapy. The Hippo pathway may play an important role in chemohormonal resistance in patients with PCa. Funding None
Authors
Shintaro Narita
Taketoshi Nara Huang Mingguo Kazuyuki Numakura Hiroshi Tsuruta Atsushi Maeno Mitsuru Saito Takamitsu Inoue Shigeru Satoh Hiroshi Nanjo Tomonori Habuchi |
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MP99-13 |
Impact of antitumor microRNA-145-3p regulated RNA networks in castration-resistant prostate cancer |
Prostate Cancer: Basic Research & Pathophysiology IV | 17BOS |
Abstract: MP99-13 Sources of Funding: none Introduction Due to its metastatic nature, patients with castration-resistant prostate cancer (CRPC) are difficult to cure and very poor prognosis. To date, there is no effective therapeutic resume for this disease. Therefore, understanding molecular mechanisms of promoting metastasis in CRPC would help to improve therapies for the disease. _x000D_ Currently, numerous studies have indicated that microRNAs (miRNAs) are aberrantly expressed in several cancers, including CRPC. In this study, we constructed a miRNA expression signature to identify miRNA regulated RNA networks in CRPC using autopsy specimens from patients with androgen deprivation therapy (ADT) failure. Based on the signature, dual-strands of pre-miR-145 (miR-145-5p and miR-145-3p) were significantly reduced in CRPC specimens. We focused on the passenger strand miR-145-3p that was significantly reduced in CRPC tissues. The aim of this study was to investigate the functional significance of miR-145-3p and its regulated RNA networks in CRPC._x000D_ Methods Expression levels of miR-145-3p were evaluated in prostate needle biopsy specimens and autopsy CRPC specimens. Gain-of-function studies were performed by miR-145-3p transfection into PCa cells. Genome-wide gene expression analysis and in silico analysis were applied to investigate molecular targets regulated by miR-145-3p in PCa cells. TCGA database was applied to analyze cohort of CRPC patients. Results Downregulation of miR-145-3p was validated in hormone naive PCa and CRPC specimens (P < 0.0001). Patients with lower expression of miR-145-3p tend to have shorter BCR-free interval (P = 0.0739). Restoration of miR-145-3p significantly inhibited cancer cell migration and invasion in PCa cell lines (P < 0.0001). We identified 4 responsible genes (MELK, NCAPG, BUB1 and CDK1) by miR-145-3p regulation. The expressions of MELK, NCAPG, BUB1 and CDK1 were significantly elevated as tumour stage and lymph node stage advanced and all four genes significantly predicted disease-free survival of PCa patients (P < 0.0001, P = 0.0002, P < 0.0001 and P < 0.0001, respectively). Moreover, these four genes were overexpressed in metastatic lesions of CRPC specimens by immunohistochemistry. Conclusions Dual-strand of tumor-suppressors, miR-145-5p and miR-145-3p, were identified based on miRNA signature. miR-145-3p regulated RNA networks were deeply involved in CRPC pathogenesis. Small RNA sequencing for lethal CRPC specimens and current in silico approaches provide us with novel therapeutic strategies for CRPC. Funding none
Authors
Akira Kurozumi
Yusuke Goto Nijiro Nohata Satoko Kojima Takayuki Arai Atsushi Okato Mayuko Kato Yukio Naya Tomohiko Ichikawa Naohiko Seki |
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MP99-14 |
PDCD4 is a check point of miR-21 induced castration resistance in human prostate cancer |
Prostate Cancer: Basic Research & Pathophysiology IV | 17BOS |
Abstract: MP99-14 Sources of Funding: 5R01 CA143299 Introduction Elevated expression of miR-21, and androgen receptor (AR) regulated microRNA, is sufficient to induce castration resistant prostate cancer growth. However, the mechanism of miR-21-mediated castration resistance remains unclear. PDCD4 (programmed cell death 4) has been known as a tumor suppressor gene and also known as a potent target of miR-21. In this study, we identify PDCD4 as a check point of miR-21 induced castration resistant growth in human prostate cancer. Methods Hormone-sensitive prostate cancer cell lines (LNCaP, LAPC4) were used for this study. These cells were transiently transfected with miR-21 mimics, anti-PDCD4 siRNAs, or PDCD4 expression vectors (pCMV-PDCD4) and plated into three different media conditions (complete media, with Bicalutamide, androgen depleted) in order to evaluate PDCD4 function on androgen-dependent, castration resistant growth, and protein expression. In rescue experiments, cells were co-transfected with miR-21 and control or pCMV-PDCD4 vectors. Cell viability was evaluated by MTS assay. Protein expression levels were measured by western blotting. Results Androgen stimulation elevates miR-21 expression and reduces PDCD4 protein expression (Fig 1A). Transfection with miR-21 inhibits PDCD4 protein expression in LNCaP and LAPC4 cells (25-40%), as well as luciferase reporters that contain the predicted miR-21 targeting regions from the PDCD4 3&[prime]UTR (Fig 1B). In addition, androgen deprivation reduces miR-21 expression and increases PDCD4 protein level (Fig 1C). miR-21 inhibitor blocked miR-21-induced PDCD4 protein suppression (Fig 1B). In cell viability assay, both miR-21 or anti-PDCD4 siRNA transfected cells induced cell growth and castration resistant cell growth (Fig 2A). Moreover, miR-21 induced cell growth was inhibited by PDCD4 overexpression (Fig 2B). Conclusions Our results demonstrate that miR-21 regulates PDCD4 protein expression, and that PDCD4 contributes to miR-21 induced cell growth and castration resistance. Therefore, PDCD4 could be a check point of miR-21 induced castration resistance. Funding 5R01 CA143299
Authors
Kenji Zennami
Koji Hatano Ross Liao Fatima Rafiqi Su Mi Choi Shawn Lupold |
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MP99-15 |
Taxane resistance in prostate cancer: a role for miRNA 181a |
Prostate Cancer: Basic Research & Pathophysiology IV | 17BOS |
Abstract: MP99-15 Sources of Funding: This work is supported in part by grants NIH/NCI This work was supported in part by grants NIH/NCI CA140468, CA168601, CA179970, and DOD PCRP PC150040. Introduction Docetaxel (DTX) is one of the primary drugs used for treating castration resistant prostate cancer (CRPC). Unfortunately, over time patients invariably develop resistance to DTX therapy and their disease will continue to progress. The mechanisms by which resistance develops is still incompletely understood. This study seeks to determine the involvement of miRNAs, specifically miR-181a, in DTX resistance in CRPC. Methods Total RNA from parental C4-2B prostate cancer cells and DTX resistant C4-2B cells (C4-2B TaxR) was submitted for small RNA deep sequencing. Data was analyzed to ascertain which miRNAs expressions were most altered in C4-2B TaxR cells compared to parental cells. Having identified an increase in miR-181a in resistant cells, its expression was modulated in C4-2B and C4-2B TaxR cells by transfecting them with miR-181a mimics or antisense, respectively. Following transfection, cell number was determined after 48 h with or without DTX. Cross resistance to cabazitaxel induced by miR-181a was also determined. Western blots were used to determine ABCB1 protein expression and rhodamine assays used to assess activity. Phospho-p53 expression was assessed by western blot and apoptosis was measured by ELISA in C4-2B TaxR cells with inhibited miR-181a expression with or without DTX. Results miR-181a is significantly upregulated in C4-2B TaxR cells compared to parental C4-2B cells as analyzed by small RNA sequencing. Overexpression of miR-181a in C4-2B cells confers DTX and cabazitaxel resistance. Knockdown of miR-181a in C4-2B TaxR cells re-sensitizes them to treatment with both DTX and cabazitaxel. miR-181a knockdown alone induced apoptosis in C4-2B TaxR cells which is further enhanced by DTX. We next assessed if miR-181a altered expression or activity of ABCB1, which is overexpressed/active in C4-2B TaxR cells and promotes resistance to DTX by pumping the drug out of cells. We found that miR-181a does not impact ABCB1 expression or activity. Since we previously demonstrated that phospho-p53 can modulate DTX sensitivity, we determined if miR-181a can alter p53 expression in C4-2B TaxR cells. Knockdown of miR-181a in C4-2B TaxR cells induced phospho-p53 expression, suggesting that miR-181a induced resistance to DTX is mediated by inhibition of phospho-p53 expression. Conclusions Overexpression of mir-181a in C4-2B TaxR cells contributes to their resistance to DTX and inhibition of mir-181a expression can restore treatment response. This is due, in part, to modulation of p53 phosphorylation and induction of apoptosis. Funding This work is supported in part by grants NIH/NCI This work was supported in part by grants NIH/NCI CA140468, CA168601, CA179970, and DOD PCRP PC150040.
Authors
Cameron Armstrong
Chengfei Liu Wei Lou Christopher Evans Allen Gao |
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MP99-16 |
miR-221 modulates tumor growth in vivo and is a regulator of TGF-? signaling in human prostate cancer |
Prostate Cancer: Basic Research & Pathophysiology IV | 17BOS |
Abstract: MP99-16 Sources of Funding: SNF Grant 310030L_156905 Introduction Prostate Cancer (PCa) is the most common cancer diagnosed in males and the second leading cause of death from cancer in men. Despite the advances in cancer therapy, when PCa progress to castration resistant phase, patients develop incurable bone metastases. Therefore, understanding of the processes that regulate homing and survival of metastatic cancer cells in the bone is crucial for the identification of new therapies. TGF-β signaling plays a major role in bone remodeling and according to the &[Prime]vicious cycle hypothesis&[Prime] is a master regulator of maintenance of prostate cancer cells in lytic bone lesions. microRNAs (miRs) are a class of small non-coding RNAs that regulates many biological process. miR-221 expression has been previously associated with prostate cancer progression. Here we studied the effect of miR-221 on TGF-β signaling and the impact of miR-221 on tumor growth in vivo. Methods miR-221 was overexpressed in PC3 and RWPE-1 cells and PMEPA was monitored by RT-qPCR and western blot. Expression of miR-221 in PC3 and RWPE-1 cells was assessed by RT-qPCR. Predicted targets were identified in silico (Targetscan and microRNA.org). Luciferase assay was used to investigate the interaction between miR-221 and PMEPA1. For zebrafish experiment, fluorescently labelled PC-3M-Pro4 cells overexpressing miR-221 were injected in the duct of cuvier of zebrafish embryos. Results We found that miR-221 overexpression resulted in decreased PMEPA1 mRNA and protein in PC-3 human prostate cancer cells. PMEPA1 is a master regulator of TGF-β signaling and luciferase reporter assay revealed that miR-221 can directly interact with PMEPA1 3&[prime] UTR. Our experiments showed an enhancement of the proliferative effect of TGF-β in PC-3 cells, following enforced miR-221 expression. In conclusion, we observed increased Smad2 activation upon TGF-β treatment in miR-221 overexpressing PC-3 cells. Inoculation of fluorescently labelled highly metastatic PC-3M-Pro4 cells overexpressing miR-221 in the Duct of Cuvier (DC) of zebrafish embryos resulted reduced tumor burden compared to control. Finally, we found an inverse correlation between miR-221 and PMEPA1 expression in normal vs. tumor tissue collected from PCa patients. Conclusions Our results indicate that miR-221 is a regulator of TGF-β signaling via modulation of PMEPA1 and miR-221 overexpression can reduce tumor growth in vivo. Therefore, miR-221 represents an interesting molecule to target PCa and to interfere with the maintenance of PCa cells in the bone microenvironment. Funding SNF Grant 310030L_156905
Authors
Eugenio Zoni
Markus Krebs Philip Herreiner Charis Kalogiro Lanpeng Chen Ewa Snaar-Jagalska George N. Thalmann Marianna Kruithof-de Julio Hubertus Riedmiller Burkhard Kneitz Martin Spahn |
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MP99-17 |
CircularRNA-C17 alters the anti androgen-enzalutamide resistance in castration-resistant prostate cancer via regulating androgen receptor variant ARv7 expression |
Prostate Cancer: Basic Research & Pathophysiology IV | 17BOS |
Abstract: MP99-17 Sources of Funding: This work was supported by NIH grant CA156700 and George Whipple Professorship Endowment, and Taiwan Ministry of Health and Welfare Clinical Trial and Research Center of Excellence (DOH102-TD-B-111-004), and National Natural Science Foundation of China ?81672526?; Introduction Circular RNAs (circRNAs) as a form of non-coding RNA could affect the formation and development of tumors. The expression of the androgen receptor splicing variant ARv7 has been demonstrated to play a key role for the development enzalutamide (Enz) resistance in castration-resistant prostate cancer (CRPC). Methods Western blot?invasion assay and chip assay were used. Results circRNA17 (hsa_circ_001305) has a lower expression in C4-2 Enz-resistant cells compared to that in C4-2 parental cells. Knocking down circRNA17 in C4-2 parental cells increased the expression of ARv7 that resulted in decreased sensitivity to Enz and increased cell invasion. Conclusions circRNA17 can alter the Enz sensitivity and cell invasion in CRPC cells via modulating the miR-181c-5p-ARv7 signaling and targeting this newly identified signaling may help us to develop a better therapy to further suppress the CRPC. Funding This work was supported by NIH grant CA156700 and George Whipple Professorship Endowment, and Taiwan Ministry of Health and Welfare Clinical Trial and Research Center of Excellence (DOH102-TD-B-111-004), and National Natural Science Foundation of China ?81672526?;
Authors
Gang Wu
Yin Sun Chawnshang Chang Denglong Wu |
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MP99-18 |
Role of long non-coding RNA PVT1 in regulating MYC in human cancer |
Prostate Cancer: Basic Research & Pathophysiology IV | 17BOS |
Abstract: MP99-18 Sources of Funding: American Cancer Society 125627-RSG-14-074-01-TBG _x000D_ NIH/NCI 1R01CA200643-01A1 _x000D_ Institute of Prostate and Urological Cancer_x000D_ Masonic Cancer Center, University of Minnesota_x000D_ Introduction Though gain of 8q24.21 is a common mutation in human cancers, its functional annotation is limited to studying myelocytomatosis (MYC), the prominent oncogene in the amplicon. However, MYC is co-gained with an adjacent long non-coding RNA gene plasmacytoma variant translocation 1 (PVT1), CCDC26 and gasdermin C (Gsdmc). Whether copy number gain of one or more of these genes drives neoplasia is unknown. Methods We developed chromosome engineered mouse strains with an extra copy of 1) Myc, 2) Pvt1, Ccdc26, Gsdmc, and 3) Myc, Pvt1, Ccdc26, Gsdmc. These mice were crossed with transgenic mice harboring rat Neu was introduced to test the change in the latency in mammary tumor development. We also used genetically engineered human cancer cell lines to identify the molecular basis of co-operation between MYC and PVT1 in human cancer. Results Only the mice with an extra copy of Myc, Pvt1, Ccdc26, Gsdmc developed adenocarcinomas, suggesting that may co-operate with Pvt1, Ccdc26 or Gsdmc to promote cancer. Si-RNA mediated knockdown of Pvt1/PVT1 reduced the proliferation rates in the tumors. Ablation of PVT1 decreased MYC protein levels, suggesting a PVT1-dependence of MYC protein in MYC amplified cancer cells. These data suggests that PVT1 can potentiate MYC in human cancers. CRISPR-cas9 mediated deletion of PVT1 in HCT116 impaired tumor formation in xenografts, and significantly reduced MYC levels. Additionally, we have identified the putative functional domain of PVT1 which confers its oncogenic potential. We have recently discovered that the exon 2 of PVT1 can undergo ‘backsplicing’ and form circular RNA of 410 bases (CircPVT1). This CircPVT1 is more abundant in MYC-driven cancer cell lines. Though PVT1 is known as a long non-coding RNA, we found that CircPVT1 can form an open reading frame (ORF) of 104 amino acids, which we have annotated as PVT1 encoded protein upon circularization (PEPc). While CRISPR-Cas9 mediated deletion of PVT1 exon 2 results into decreased MYC levels and reduced transformation potential in MYC-driven cancer cells, PEPc can independently augment MYC when added exogenously to LNCaP cells, and increase their transformation potential. Conclusions These results suggest that PEPc may play a key role in boosting MYC levels in metastatic prostate cancers. We propose that the dependence of high levels of MYC on PVT1 provides a much-needed therapeutic window against MYC protein, known to be refractory to small molecule inhibition. Funding American Cancer Society 125627-RSG-14-074-01-TBG _x000D_ NIH/NCI 1R01CA200643-01A1 _x000D_ Institute of Prostate and Urological Cancer_x000D_ Masonic Cancer Center, University of Minnesota_x000D_
Authors
Kojiro Tashiro
Yuen-Yi Tseng Badrinath Konety Anindya Bagchi |
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MP99-19 |
Targeting lncRNA-GAS5 suppresses castration resistant prostate cancer cell growth via interaction and suppression androgen receptor (AR) transactivation |
Prostate Cancer: Basic Research & Pathophysiology IV | 17BOS |
Abstract: MP99-19 Sources of Funding: none Introduction The androgen receptor (AR) plays an important role in the progression of prostate cancer (PCa) before and after the castration-resistant stages. Androgen-deprivation therapy (ADT) has become a key treatment for advanced PCa. Although ADT initially achieves significant clinical response, PCa eventually relapses and progresses into castration-resistant prostate cancer (CRPC), a more aggressive form of PCa characterized by the resistance to ADT manipulation. Recent studies have demonstrated that remaining AR remains critical to the development of CRPC. Therefore, better dissecting the mechanism(s) underlying the targeting AR in CRPC would hold promise for overcoming the challenge of CRPC treatment. Methods LNCaP, DU145 and C4-2 were employed in this study. A series of cell and tumor, biochemical, molecular biologic assays such as UV Cross-Linking and Immunoprecipitation (CLIP) assay?RNA Immunoprecipitation, TUNEL assay?RNA-pull down assay, Proliferation assay, Luciferase assay were carried out. Results We found that GAS5, a long non-coding RNA (lncRNA), could interact and suppress AR transactivation in castration resistant PCa C4-2 cells. Targeting lncRNA-GAS5 by siRNA enhanced the expression of AR target gene PSA via alteration of AR recruitment to the PSA promoter. The consequences of suppression of AR transactivation led to suppress cell proliferation and enhance cell apoptosis in C4-2 cells in the castration resistant condition. In return, the suppressed AR could also modulate the lncRNA-GAS5 expression in a feedback regulation mechanism._x000D_ the figure shows GAS5 was downregulated in clinical CRPC specimen compared to primary PCa samples. A gene expression microarray dataset (GSE22606) deposited in public database was analyzed, where n denotes the mumble of total samples and p stands for the adjusted R statistical p value. Conclusions These results revealed that LncRNA-GAS5 might play important roles to target the remaining AR signals in PCa at the castration resistant stage and targeting LncRNA-GAS5 to alter these remaining AR signals in CRPC. Funding none
Authors
qiang dang
kun du peng wu huijian zhang yi zuo shaobin zheng |
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MP99-20 |
Allyl isothiocyanate up-regulates miR-30a-5p expression through a ROS responsive transcription factor, activator protein 1 (AP-1) |
Prostate Cancer: Basic Research & Pathophysiology IV | 17BOS |
Abstract: MP99-20 Sources of Funding: none Introduction Allyl isothiocyanate (AITC) is one of the most widely studied isothiocyanates that inhibits the survival of human prostate cancer (PCa) cells while not affecting normal prostate epithelial cells. microRNA 30a-5p (miR-30a-5p) was reported as a tumor suppressor and regulates epithelial to mesenchymal transition (EMT) in bone metastasis and castration-resistant PCa. In this study, we investigated whether AITC affects the expression of miR-30a-5p and the mechanism underlying this regulation. Methods Human PCa cell lines (Rv1 and PC3) were used in this study. The expression level of miR-30a-5p in AITC-treated cells was detected using stem-loop RT and QPCR. The expression of a validated miR-30a-5p target Ets Related Gene (ERG) by QPCR and Western blot in cells treated with AITC or transfected with miR-30a-5p. The expression level of phosphor-c-jun was detected by immunofluorescent and Western blot. Reporter vector bearing antisense sequence of miR-30a-5p was served as inhibitor of AITC-induced miR-30a-5p. Results The expression of miR-30a-5p was increased in AITC-treated cells. The expression of ERG was down-regulated in AITC-treated or miR-30a-5p transfected cells. The expression of ERG was attenuated in AITC-treated cells transfected with miR-30a-5p antisense inhibitor, suggesting AITC regulates ERG expression through miR-30a-5p. Furthermore, we found the AP-1 is a potential regulator of miR-30a-5p expression by analyzing 10 kb nucleotides sequence up-stream of miR-30a-5. Accumulation of c-Jun was detected in AITC-treated cells, and treatment of ROS inhibitor or catalase inhibitor attenuated AITC-induced c-Jun activation, suggesting AITC activates c-Jun translocation was mediated by AITC-induced ROS. In addition, the up-regulated miR-30a-5p was also attenuated in AITC-treated cells pretreated with catalase-inhibitor further provide evidence that miR-30a-5p is an important effector of AITC. Conclusions Herein, we show for the first time that AITC regulates the expression of miR-30a-5p through ROS generation and AP-1 activation. These results could potentially contribute to a therapeutic application of AITC in prostate cancer patients. Funding none
Authors
Hung-En Chen
J-Fan Lin Yi-Chia Lin Te-Fu Tsai Kuang-Yu Chou Thomas I.S. Hwang |
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PD01-01 |
Results from a randomized, double blind, placebo-controlled trial to evaluate efficacy and safety of intra-trigonal injection of Onabotulinum toxin A in patients with Bladder Pain Syndrome/Interstitial Cystitis. |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Interstitial Cystitis I | 17BOS |
Abstract: PD01-01 Sources of Funding: Allergan Introduction Pain relief is the key corner of Bladder Pain Syndrome/Interstitial cystitis (BPS/IC) management. The present prospective, randomized, double-blind, placebo-controlled (saline) clinical trial aims to evaluate the analgesic efficacy and safety of intra-trigonal injection of OnaBotA in patients with BPS/IC refractory to common treatment. _x000D_ _x000D_ Methods Nineteen women with a pain score more than 4 in a 0-10 visual analogue scale (VAS) were enrolled. Patients were randomized to receive 100 Units (U) in 10 ml of saline (n=10) of OnaBotA (Botox) or the equivalent volume of saline (n=9) in 10 points of the bladder trigone under cystoscopic guidance and general anaesthesia. The primary outcome was VAS at 12 weeks (w). Secondary outcomes included VAS at 4 and 8w, day and night time frequency in a 3-day bladder diary, O’Leary-Sant score (OSS) and QoL 4, 8 and 12w after treatment. Treatment Benefit Scale (TBS) was evaluated at 12w. Side effects were registered, in particular post-void residual volumes (PVR) and urinary tract infections (UTIs)._x000D_ Results are presented as mean values ± standard deviation. T-test was used to compare the 2 arms at each time point._x000D_ Results Mean age was identical (OnaBotA: 44±10y vs Saline: 48±11y). According to ESSIC classification each arm had 3 cases with Hunner lesions. At baseline the two groups were balanced for all clinical variables (table 1). _x000D_ At 12w VAS for pain was significantly lower in OnaBotA arm (3.1±2.8 versus 5±2.2, p<0.05). VAS was numerically lower in OnaBotA arm also at 4 and 8w (table 1). OSS, and QoL were significantly better in the OnabotA arm at 8 and 12w (table 1). Urinary frequency was numerically lower in OnaBotA arm (table 1). Treatment Benefit Scale was 1.9±0.9 in the OnabotA group versus 3.1±0.8 in the Saline group (p<0.05). _x000D_ Five UTIs occurred, 2 in Saline and 3 in the OnaBotA arms. No cases of voiding dysfunction were observed. _x000D_ Conclusions This RCT demonstrates that intra-trigonal injection of 100U of OnaBotA is significantly better than placebo to reduce pain and to improve QoL in patients with refractory BPS/IC. Adverse events associated with intra-trigonal injection of 100U of OnaBotA were mild. No cases of urinary retention occurred._x000D_ Funding Allergan
Authors
Rui Pinto
Daniel Costa Afonso Morgado Pedro Pereira João Silva Francisco Cruz |
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PD01-02 |
Gene Therapy with Replication-Deficient Herpes Simplex Virus (HSV) Vectors Encoding Poreless TRPV1 (PL) or Protein Phosphatase 1α (PP1α) in a Rat Model of Hydrogen Peroxide-induced Cystitis |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Interstitial Cystitis I | 17BOS |
Abstract: PD01-02 Sources of Funding: DOD W81XWH-12-1-0565; NIH DK088836 Introduction Increased afferent excitability is considered to be an important pathophysiological basis of interstitial cystitis/bladder pain syndrome (IC/BPS) and overactive bladder (OAB). Also, transient receptor potential vanilloid 1 (TRPV1) receptors are known to be involved in afferent sensitization. Therefore, we investigated the effect of gene therapy with HSV vectors encoding PL or PP1α, a negative regulator of TRPV1, using a rat model of long-lasting cystitis induced by hydrogen peroxide (HP). Methods HSV vectors encoding green fluorescent protein (GFP), PL or PP1α were injected into the bladder wall of female SD rats. One week later, 1% HP or normal saline (NS) was administered into the bladder. Awake cystometry (CMG), resiniferatoxin (RTX)-induced nociceptive behaviors such as licking and freezing, NGF mRNA expression in the bladder, bladder weight and histology were evaluated 2 weeks after viral injection. Results In CMG, the GFP/HP group showed a significant decrease in intercontraction intervals compared to the GFP/NS group, which were significantly prolonged by 57.8% and 68.0% in PL/HP and PP1α/HP groups (p<0.01), respectively. The number of freezing behavior was significantly lower in PL/HP and PP1α/HP groups by 86.1% and 93.5%, respectively, compared to the GFP/HP group. Compared with the GFP/NS group, the GFP/HP group had significantly heavier bladder weight, whereas the PL/HP group and PP1α/HP group showed significantly lighter bladder weight than the GFP/HP group. Hematoxylin and eosin staining of bladder sections showed substantial inflammation characterized by inflammatory cell infiltration, and detrusor hypertrophy in the bladder in the GFP/HP group compared with GFP/NS group, which were alleviated in PL/HP and PP1α/HP groups. In RT-PCR, the GFP/HP group showed higher significantly (p<0.05) expression of NGF mRNA in the bladder mucosa than the GFP/NS group, which was significantly decreased in the PL/HP and PP1α/HP groups (p < 0.05). Conclusions HSV vectors-mediated gene delivery of PL or PP1α significantly reduced bladder overactivity and enhanced bladder pain sensitivity in HP cystitis rats. Also, both treatments can reduce bladder inflammatory changes and increased bladder weight at least in part through amelioration of NGF overexpression in the bladder mucosa. Thus, HSV-mediated TRPV1-targeting gene therapy could be effective for the treatment of IC/BPS including Hunner-type IC that is often associated with bladder inflammation. Funding DOD W81XWH-12-1-0565; NIH DK088836
Authors
Shun Takai
Tsuyoshi Majima Takahiro Shimizu Naoki Wada Nobutaka Shimizu Takahisa Suzuki Eiichiro Takaoka Momokazu Gotoh William Goins Joseph Glorioso Naoki Yoshimura |
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PD01-03 |
Stress-induced adrenergic dysregulation alters neural-glial distribution and phenotype |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Interstitial Cystitis I | 17BOS |
Abstract: PD01-03 Sources of Funding: AUA Urology Care Foundation Research Scholar Award. R37 DK54824. NIH RO1 DK57284 Introduction There is evidence (in patients and preclinical models) that stress can enhance painful sensations in patients with functional pain syndromes such as interstitial cystitis/bladder pain syndrome (IC/BPS). Though the underlying mechanisms have yet to be fully explored, findings reveal increased autonomic (sympathetic) dysregulation as well as a role for central augmentation. In this regard, activation of spinal cord (SC) glial cells can increase excitability of neurons leading to the initiation and maintenance of bladder hyperalgesia and impaired bladder storage function (urgency, frequency). Our goal was to examine whether chronic stress (using the water avoidance stress or WAS model) can alter neural-glial distribution and chemistry, which may play a role in micturition and pain behavior. Methods Adult female Wistar-Kyoto rats were exposed to WAS by placement on a pedestal in a water-filled container (1hr/day x10 consecutive days) versus handled controls. Previous published findings have revealed WAS rats exhibit long-lasting urinary frequency and hyperalgesia. SC (L6) were harvested from anesthetized animals, and either cryosectioned (for immunocytochemistry) or homogenized (for RT-PCR). The following were investigated: calcitonin gene-related peptide (CGRP; sensory fibers), microglia (IBA-1), Toll-like receptor (TLR-4), purinergic receptor subtypes (P2X4, P2X7). Separate groups of both WAS and control animals were treated 2 days prior then every other day with the adrenergic antagonist phenoxybenzamine (PB; 2 mg/kg i.p.) or saline, respectively. Results WAS increased neural CGRP (40%) and IBA-1 (2 fold) expression in the L6 SC dorsal horn and central canal (regions receiving input from nociceptive fibers). We find PB reduced CGRP expression (92% decrease) as well as IBA-1 in WAS SC. Further, both TLR-4 as well as P2X4 and P2X7 purinergic receptor are increased (50%) in WAS, suggesting microglia activation with chronic stress. Conclusions Taken together, our findings suggest increased communication between the sympathetic nervous system and bladder sensory neurons that may play an important role in chronic pain conditions. This includes abnormal neural sprouting and altered morphology and chemistry of SC glial cells, which are likely to play an important role in modifying neural activity resulting in changes in bladder function and sensory mechanisms. Funding AUA Urology Care Foundation Research Scholar Award. R37 DK54824. NIH RO1 DK57284
Authors
Bronagh McDonnell
Aura Kullmann Amanda Wolf-Johnston Anthony Kanai Peter Grace Linda Watkins Larissa Rodriguez Lori Birder |
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PD01-04 |
Stress induced visceral pain is mediated by alpha 1A adrenoceptors |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Interstitial Cystitis I | 17BOS |
Abstract: PD01-04 Sources of Funding: Ana Charrua is supported by Fundacao para a Ciencia e Tecnologia (FCT) fellowship SFRH/BPD/68716/2010. _x000D_ This work was supported by the PFD Research Foundation and ICA IC/PBS Research Grant. Introduction Chronic water avoidance stress (WAS) result in long-standing bladder pain and exhibits many of the findings observed in BPS/IC patients. However, the exact mechanism by which WAS induces visceral pain is unknown._x000D_ Since chronic stimulation of alpha1A adrenoceptors increases the activity of bladder nociceptors, we investigate if changes induced by WAS are mediated by a similar adrenergic mechanism._x000D_ Methods WAS was induced in adult female Wistar rats by placing the animals on a pedestal in the centre of a cage filled with water at room temperature, for 1h/day, for 10 consecutive days. Lower abdomen pain threshold was measured using von Frey filaments, at baseline (day 0) and after WAS (day 11). Colonic activity was also measured at day 0 and day 11. At day 12, WAS were anaesthetised, urine collected and noradrenaline levels by determined HPLC, and bladder frequency determined by cystometry. Bladders were harvested, sectioned and stained with HE to analyse urothelium integrity and with Toluidine blue to quantify mast cells. These experiments were repeated in WAS animals treated with the alpha1A AR Silodosin (0.2 mg/kg.day). Non-stressed rats were used as controls. Comparisons were done using T-test and Kruskal-Wallis followed from Dunn's Multiple Comparisons Test. Results The results are summarized in table 1._x000D_ _x000D_ Conclusions WAS result in an increase in noradrenaline urinary levels, suggesting the involvement of the adrenergic system. As silodosin treatment prevented the development of bladder pain, bladder hyperactivity and mast cells accumulation, alpha 1A AR is likely to play a role in chronic adrenergic stimulation associated with WAS. These findings may be relevant for the treatment of BPS/IC. Funding Ana Charrua is supported by Fundacao para a Ciencia e Tecnologia (FCT) fellowship SFRH/BPD/68716/2010. _x000D_ This work was supported by the PFD Research Foundation and ICA IC/PBS Research Grant.
Authors
Rita Matos
Paula Serrão Larissa Rodriguez Lori Birder Francisco Cruz Ana Charrua |
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PD01-05 |
Significant Linkage Evidence for Interstitial Cystitis/Painful Bladder Syndrome on Chromosome 3 |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Interstitial Cystitis I | 17BOS |
Abstract: PD01-05 Sources of Funding: Interstitial Cystitis Association Introduction Interstitial cystitis/painful bladder syndrome (IC/PBS) is a chronic pain condition with unknown etiology. Family history is one of the strongest known risk factors, suggesting a genetic contribution. We hypothesized that related IC/PBS cases were more likely to have a genetic etiology. The purpose of this study was to perform a genetic linkage analysis for IC/PBS. Methods Using the Utah Population Database (a population-based genealogy resource linked to medical records at the largest Utah healthcare provider), 13 high-risk pedigrees (defined as having a statistical excess (p<0.05) of IC/PBS cases among relatives who were hospital patients compared to expected number of cases using age- and sex-matched hospital rates for IC/PBS) were used for this analysis. Each pedigree had at least two sampled cases; case status was confirmed in the medical record using natural language processing. DNA was obtained from stored, non-cancerous, formalin-fixed, paraffin-embedded (FFPE) tissue blocks (e.g., appendix). Pedigrees ranged in size from 2 to 12 genotyped cases (n=48). Genotype data were obtained from Illumina OmniExpress BeadChip array (~710, 0000 SNPs); all SNPs passed quality control filters prior to linkage analysis. We eliminated highly correlated SNP markers (i.e., high linkage disequilibrium). Parametric linkage analysis using general dominant and recessive models was performed using the Markov Chain, Monte Carlo linkage analysis method, MCLINK. Results are reported as heterogeneity logarithm of odds scores (HLODs), defined as suggestive (HLOD ≥ 1.86) and significant (HLOD ≥ 3.3) linkage evidence. We also reported the number of individual pedigrees considered &[Prime]linked&[Prime] to a significant genomic peak (i.e., pedigree LOD score ≥ 0.588). Results Significant genome-wide linkage evidence was found on chromosome 3p21-3q13 with a maximum HLOD score of 3.56 under a dominant model. There were 4 pedigrees (30.8%) that had at least nominal linkage evidence (LOD ≥ 0.588) in this region. The most informative pedigree for linkage included 12 IC/PBS cases and had an individual LOD score of 2.1 in this region. Other regions with suggestive evidence for linkage included 1p21-1q25, 4q12-13, 9p24-22, and 14q24, all under a dominant model. Conclusions While the etiology of IC/PBS is unknown, this study provides evidence that a genetic variant(s) on chromosome 3 likely contributes to IC/PBS predisposition. Further study of the pedigrees underlying this significant linkage evidence and sequence analysis of the affected cases may provide insight into genes contributing to IC/PBS. Funding Interstitial Cystitis Association
Authors
Kristina Allen-Brady
Kerry Rowe Melissa Cessna Peggy Norton |
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PD01-06 |
Low anesthetic bladder capacity is associated with a unique mucosal gene expression profile in IC/BPS patients |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Interstitial Cystitis I | 17BOS |
Abstract: PD01-06 Sources of Funding: _x000D_ Interstitial Cystitis Association Pilot Research Program Grant _x000D_ R21DK106554-01 (NIDDK) Introduction The goal of this study was to test the hypothesis that the low capacity (≤ 400 ml) bladder mucosal gene expression profile represents a bladder-centric IC/BPS sub-phenotype. This hypothesis is based on data from our previously reported pilot study showing that a subset of IC/BPS patients (those with a severely diminished bladder capacity {BC; ≤ 400 ml}) displayed a unique gene expression profile. Methods Selection of female IC/BPS patient biopsy samples from our tissue bank (IRB00018552) for gene expression profiling was made on the basis of anesthetic bladder capacity. All patients had undergone therapeutic bladder hydrodistention per the AUA guideline algorithm. There were 3 groups: (1) low capacity group (BC ≤ 400 ml; N=13), (2) BC between 450-1500 ml (N=28) and, (3) control group (non-IC/BPS patients undergoing a pelvic reconstruction procedure; N=7). Total RNA was isolated from mucosal biopsies (per standard protocols) and assayed on whole genome microarrays (Illumina HT v4 BeadArray). Results Mucosal gene expression profiles differ significantly between controls and IC/BPS patients (Figure 1A). Key differences in the Epithelial Adherens Junction Signaling pathway were apparent (p = 5.14E-05) between these two groups. Among only IC/BPS patients, gene expression profiles were also significantly different between those with a low capacity compared to those with BC > 400 (Figure 1B). One striking pathway impacted in this comparison was the EIF2 Signaling (eukaryotic translation initiation factor) pathway (p = 8.2E-26). Finally, gene expression profiles in the low BC group with Hunner&[prime]s lesions were significantly different from those without lesions (Figure 1C). Not surprisingly, differential expression analysis produced inflammatory disease (p = 1.46E-9) as a top classifier in this group comparison. Conclusions Mucosal gene expression in low anesthetized bladder capacity patients is distinct from gene expression profiles in higher capacity samples and from controls. These findings suggest low BC patients, with or without Hunner&[prime]s lesions, represent a sub-phenotype of IC/BPS and these gene expression differences, if confirmed, may yield additional therapeutic targets for this bladder-centric phenotype. Funding _x000D_ Interstitial Cystitis Association Pilot Research Program Grant _x000D_ R21DK106554-01 (NIDDK)
Authors
Stephen Walker
Gopal Badlani Catherine Mathews Joao Zambon Robert Evans |
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PD01-07 |
Expression of the programmed death ligand 1 in interstitial cystitis is correlated with the bladder pain degree and hydrodistension outcome |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Interstitial Cystitis I | 17BOS |
Abstract: PD01-07 Sources of Funding: This work was supported by Grants from the National Natural Science Foundation of China to (Granted No. 81200548). Introduction To explore the function of inflammatory regulation by PD-L1 on the onset and progression of interstitial cystitis (IC). Methods The clinical data of IC patients underwent hydrodistension (HD) plus bladder biopsy from 2009 to 2016 at our center were reviewed. The IC was diagnosed as: 1.pressure or pain at bladder accompanied by frequency and nocturia ≥ six weeks; 2. glomerulation or Hunner's ulcer on cystoscopy; 3. exclusion of other disease by pathology. The UPOINT scoring (Urinary symptom, Psychosocial symptom, Organ-specific symptom, Infection, Neurologic symptom and Tenderness) was assessed. HD outcomes were evaluated according to global response assessment (GRA) and UPOINT at postoperative 3 mo. The inflammation degree was semi-quantitatively assessed on Haematoxylin and eosin (H&E) staining. The immunohistochemistry (IHC) for PD-L1 expression dection and immunofluorescence for T cell and B cell counting were performed. Results The present study includes 8 males and 32 females with median age of 57 years. The inflammation degree of the bladder wall on H&E is negatively correlated with disease course (P=0.026) and positively correlated with the bladder pain degree (P<0.001). HD is effective at postoperative 3 mo in 19 subjects (GRA≥2), whose UPOINT scores indicate a highest relief rate of the bladder pain (89.5%, 17/19) followed by urinary symptoms (52.6%, 10/19). There are 17, 15, 7 and 1 subjects having none, mild, moderate and high degree of PD-L1 expression (fig. A). And PD-L1 expression degree is correlated with H&E inflammation degree and T cell count (fig. B). Further, PD-L1 expression degree and T cell count are positively correlated with the bladder pain degree (fig. B). Among the 12 subjects with severe inflammation on H&E, HD is more effective for subjects with moderate or high PD-L1 expression (83.3% vs. 16.7%, P=0.04) (fig. C).And subjects with moderate or high PD-L1 expression tended to have more effective hydrodistension outcome than subjects without PD-L1 expression (7/8 vs. 7/17, P=0.038). Conclusions PD-L1 expression is more common in IC patients with serious bladder pain and severe bladder inflammation. IC patients with higher degree of PD-L1 expression tend to have more effective HD outcome. Funding This work was supported by Grants from the National Natural Science Foundation of China to (Granted No. 81200548).
Authors
Yuke Chen
Wei Yu Yang Yang Shiliang Wu Jie Jin |
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PD01-08 |
Novel Contrast Mixture Improves Bladder Wall Contrast For Visualizing Interstitial Cystitis |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Interstitial Cystitis I | 17BOS |
Abstract: PD01-08 Sources of Funding: 1R41DK108397;P30CA047904 Introduction Past attempts at contrast enhanced MRI (CE-MRI) of the bladder have been unable to enhance the image contrast between bladder wall and lumen in order to effectively resolve the bladder wall changes associated with cystitis or malignancy. Here we tested whether combined contrast-enhanced magnetic resonance imaging (CCE-MRI), using a mixture of Gadolinium and iron-oxide based contrast agent (ferumoxytol) is superior to CE-MRI in enhancing the image contrast of bladder wall. Each FDA approved agent in the contrast mixture is constituted of different particle size and have different contrast effects on the spin-echo imaging protocol. Methods Under isoflurane anesthesia, T1-weighted imaging of adult female Sprague-Dawley rat bladder was performed using standard turbo spin echo sequences at 7 Tesla, before and after transurethral instillation of 0.3 mL of single contrast (CE-MRI) or combined contrast mixture (CCE-MRI) composed of 0.4-64 mM of gadolinium chelate (Gadavist/Gd-DTPA) and 5 mM ferumoxytol. Bladder wall contrast was assessed in control group exposed to saline and in cystitis group exposed to 0.5 mL of protamine sulfate (10 mg/mL) for 30min Results CCE-MRI following instillation of 0.4-4 mM gadavist (gadolinium ) and 5 mM ferumoxytol mixture was superior to CE-MRI (instillation of either Gadavist or ferumoxytol) in achieving the maximum contrast between the lumen and bladder wall. T1-relaxation enhancement in bladder lumen by gadavist is masked by the T2 effect from localization of the larger ferumoxytol nanoparticles in the lumen, but the diffusion of gadavist into the lesions caused by protamine is marked by the hyperintense signal in bladder wall. The normalized hyperintensity in the bladder wall increased from 0.46 ±0.07 in control group to 0.73± 0.14 in the protamine group (p < 0.0001). Conclusions CCE-MRI following instillation of the contrast mixture is superior to CE-MRI using individual contrast agents in the visualization of bladder wall changes likely associated with cystitis or malignancy. CCE-MRI relies on differences in particle size and contrast mechanisms of gadolinium chelates and ferumoxytol. This novel approach has the potential to distinguish diffuse versus a focal disruption in the bladder wall integrity of interstitial cystitis patients, facilitating accurate diagnosis and improved patient care. Funding 1R41DK108397;P30CA047904
Authors
Pradeep Tyagi
Joseph Janicki T. Kevin Hitchens Lesley Foley Mahendra Kashyap Naoki Yoshimura Jonathan Kaufman |
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PD01-09 |
Impact of cystectomy and urinary diversion upon long-term narcotic usage among patients with interstitial cystitis/bladder Pain Syndrome: Institutional Data Cross-Referenced with a Statewide Tracking System. |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Interstitial Cystitis I | 17BOS |
Abstract: PD01-09 Sources of Funding: None Introduction Narcotic prescribing patterns among physicians are receiving increased scrutiny, especially in states with high rates of drug abuse, such as North Carolina (NC). Patients with interstitial cystitis (IC)/bladder pain syndrome (BPS) are often provided narcotic therapy as part of a multimodal approach. Some of these patients may progress to cystectomy with urinary diversion (CWUD), but the impact upon long-term narcotic usage is unknown. We sought to determine the rate of persistent narcotic usage among IC/BPS patients undergoing CWUD. Methods An IRB-approved, prospectively collected single-surgeon database of IC/BPS patients who underwent CWUD from April 2010 to April 2016 was reviewed. Patients residing outside of NC were excluded. The remainder was queried via the North Carolina Controlled Substance Reporting System, which tracks all statewide dispensing of Schedule II-V substances. Cases were evaluated for the total amount of dispensed substances for the year prior to surgery and up to one year postoperatively, and converted to oral morphine equivalents. The difference in usage was compared by a Student’s 2-tailed t-test. Prescriptions filled within the first 30 days after surgery were excluded. Results 32 patients met inclusion criteria, 84.3% of which had additional chronic pain disorders. Mean age was 55 years and mean preoperative anesthetic bladder capacity was 433 cc. Mean follow-up was 744 days. All patients were narcotic users preoperatively. Following CWUD, 25/32 (78%) patients filled database-registered prescriptions after the 30-day postoperative window. The most commonly dispensed oral narcotics were oxycodone and hydrocodone. Compared to preoperative totals, mean postoperative morphine equivalents decreased by 52.6% (NS; p = 0.254). Two patients initiated therapy with fentanyl patches in the year after surgery. Conclusions Following CWUD for IC/BPS, 78% of patients can be expected to continue narcotic therapy. Although mean usage appears to decrease postoperatively, the difference was not significant, and may be related to the prevalence of coexisting pain disorders in this population. This information is critical to setting patient expectations and for educating state medical boards. Future work is necessary to determine whether postoperative substance usage is potentially related to withdrawal and if alternative regimens are feasible. Funding None
Authors
David Koslov
Dino Vilson Alison Rasper Marc Colaco Robert Evans Ryan Terlecki |
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PD01-10 |
Effects of Repeat Hydrodistention for Interstitial Cystitis |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Interstitial Cystitis I | 17BOS |
Abstract: PD01-10 Sources of Funding: Ruth L. Kirschstein National Research Service Award 4TL1TR000435 10 (PK) Introduction Cystoscopy and hydrodistention is a therapeutic procedure for interstitial cystitis (IC) which achieves symptomatic relief in many patients, though its use varies widely between providers. The long term effects of repeated hydrodistention are not well understood and it is not known if patients suffer a reduction in bladder capacity due to these multiple procedures or develop ulcerating disease over time. We sought to investigate the effects of multiple hydrodistentions in patients with IC. Methods We retrospectively queried our institutional records for patients without ulcerative disease who underwent 2 or more hydrodistentions for IC over a ten year period. Patient charts were reviewed for demographic and clinical factors at the time of diagnosis and treatment. Results There were 97 patients who underwent multiple cystoscopy and hydrodistention procedures for non ulcerative IC during the ten year study period. The cohort was 98% female and 92% Caucasian. Mean age at diagnosis was 35.7 years, and mean BMI was 27.1. Average number of procedures performed was 3.7 (range 2 to 18), and mean time between procedures was 430.6 days. Within this cohort 63.3% of patients had at least 1 comorbid pain disorder. Mean initial and final anesthetic bladder capacity were 723.9cc and 753.1cc, respectively, which were not significantly different (p=0.15). One patient in this cohort later developed ulcerative disease which was not present at initial cystoscopy. Among patients who completed AUA symptom questionnaires before and after hydrodistention, both symptom and quality of life scores were significantly improved following treatment (17.1 vs 14.3, 4.3 vs 3.6, p <0.001 for both). The complication rate during the study period was 0.83% and comprised an extraperitoneal bladder perforation managed conservatively, anaphylaxis to DMSO instillation, and transient tachycardia with hypotension. Conclusions Repeated hydrodistention did not decrease bladder capacity over time and development of ulceration was rare. In this cohort of patients it had significant positive effects on symptom control and quality of life. Hydrodistention is a safe procedure with low complication rates. Funding Ruth L. Kirschstein National Research Service Award 4TL1TR000435 10 (PK)
Authors
Peter Kirk
Yahir Santiago-Lastra John Stoffel J Quentin Clemens Anne Pelletier Cameron |
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PD01-11 |
Electron microscopic study of the urothelium in patients with interstitial cystitis and ketamine related cystitis – A association with clinical characteristics. |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Interstitial Cystitis I | 17BOS |
Abstract: PD01-11 Sources of Funding: self-founding Introduction The aim of this study is to investigate the association between the electron microscopic (EM) urothelium characteristics and clinical symptoms severity in patients with interstitial cystitis (IC) and ketamine cystitis (KC). Methods IC and KC patients who were admission for hydrodistention were enrolled. The cold-cup biopsy bladder specimens were taken during hydrodistention for transmission EM (TEM) and scanning EM (SEM). In TEM, the urothelium cell layers number, integrity of umbrella cells and tight junction complexes were investigated. In the SEM, the umbrella cell intact, uniform and deep folding were evaluated. All of these EM findings were grading with a 4 point scale (0: normal, 1: mild defect, 2: moderate defect, 3: severe defect). Visual Analogue Scale (VAS) pain score, cystometric bladder capacity (CBC) and maximal bladder capacity under general anesthesia (MBC) in these patients were recorded. Chi-square test was used to evaluate the association between symptoms severity and EM findings. Bladder biopsies were also taken from the patients with stress urinary incontinence and were considered as normal control. Results A total of 9 KC and 9 IC patients were enrolled. In the IC patients, the EM revealed inconsistence of umbrella cells size, decreased urothelium cell layers, decreased umbrella cell folding and tight junctional complexes. In the patients with severe KC, the EM showed almost totally denuded urothelium and exposure collagen. (Figure 1 A and B ). In TEM, the KC patients with more VAS pain score have more severe defect of urothelium cell layers and integrity of umbrella cells (p=0.018). The IC patients with more severe VAS pain score have more severe defect of tight junctional complexes in TEM (Table 1.) The CBC and MBC in KC and IC patients were not significantly associated with EM findings. Conclusions In EM, the urothelium defects were more severe in KC than IC. Urothelium defect in TEM may be associated with bladder pain severity in KC and IC patients. Funding self-founding
Authors
Jia-Fong Jhang
Hann-Chorng Kuo |
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PD01-12 |
Bladder Hyperpermeability Induces Persistent Visceral Pain: A Novel Mechanism for Visceral Organ Crosstalk |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Interstitial Cystitis I | 17BOS |
Abstract: PD01-12 Sources of Funding: None Introduction The comorbidity between interstitial cystitis (IC) and irritable bowel syndrome (IBS) involves visceral organ cross sensitization. Previously we showed that infusion of protamine sulfate (PS) into the bladder increased bladder and colonic permeability and heightened colonic sensitivity within 24 hrs. Here we investigate the hypothesis that PS into the bladder causes persistent visceral organ hypersensitivity via activation of specific neuronal populations in the spinal cord. Methods Bladder hyperpermeability was induced in ovariectomized (OVX) female Sprague Dawley rats (n=44) through the transurethral infusion of PS (1 mg/ml); control rats received a sham infusion (n=13). Bladder and colonic permeability were assessed in vitro 1, 3, or 5 days post PS infusion via transepithelial electrical resistance (TEER). Bladder and colonic sensitivity were assessed in vivo 1, 3, or 5 days post PS infusion. Referred bladder hyperalgesia was measured using von Frey filaments (0.16-15g) applied to the suprapubic region and quantified via the frequency of withdrawal responses. Colonic sensitivity was assessed as the visceromotor behavioral response (VMR) to graded pressures (0-60mmHg) of isobaric colorectal distension (CRD) and quantified as the number of abdominal contractions. Neuronal activity in the spinal cord was assessed ex-vivo via immunofluorescence of phosphorylated extracellular signal-regulated kinase (pERK). Results PS infusion into the bladder caused no overt changes in bladder or colonic histology. However, PS significantly decreased bladder TEER (Day 5: 1628±39 vs. 2579±21 Ω/cm2, P<0.001, n=5) and colonic TEER (Day 5: 135±8 vs. 224±17 Ω/cm2, P<0.001, n=7) as compared to controls. Five days post bladder PS, rats exhibited bladder hyperalgesia (65±8 vs. 24±5 % withdrawal response at 15g, P<0.001, n=11) and colonic hypersensitivity (31±1.4 vs. 15±0.8 abdominal contractions at 60 mmHg, P<0.0001, n=11). PS treatment enhanced pERK expression within the dorsal horn of the spinal cord for up to 5 days (13±0.5 vs. 5±0.7 neurons/section, P<0.0001, n=12). Conclusions In response to a single infusion of PS into the bladder, our data highlights a persistent increase in i) permeability and pain sensitivity of the bladder and colon and ii) neuronal activity in the spinal cord. These findings advance our understanding of the mechanisms of visceral organ crosstalk and highlight the comorbidity between IC and IBS. Funding None
Authors
Quinn Baker
Ehsan Mohammadi Casey Ligon Beverley Greenwood-Van Meerveld |
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PD02-01 |
Types of pelvic floor defects in women with pelvic organ prolapse |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Pelvic Prolapse I | 17BOS |
Abstract: PD02-01 Sources of Funding: none Introduction This study presents a new potentially useful three-dimensional (3D) non-invasive tool to determine the basic 3D models of the pelvic floor, static and dynamic, in patients with pelvic organ prolapse (POP) which help to identify the main types of pelvic floor defects and to create an individual approach to their reconstruction. Methods We scanned 42 patients who were suffering from POP (no less than Grade 2 by Pelvic Organ Prolapse Quantification (POP-Q)) at rest and during Valsalva maneuver by using an Artec® 3D optic portable scanner. Pelvic floor 3D models were generated. We calculated the volume of the prolapsed vaginal wall using Dynamic prolapse increment (DPI). It was defined as an increase in the prolapse volume from the rest to its maximal Valsalva probe (DPI = (Vval – Vrest) / Vrest %). Results The average value of the DPI in women with POP was 648% (95% CI 194-1102%). It indicated the presence of an advanced mobility of the pelvic floor and the need to use mesh surgical correction of POP in some cases. According to generated pelvic floor 3D models, six basic types of pelvic defects were allocated. The central defects of an anterior vaginal wall along with mixed one (cystocele combined with uterine prolapse or rectocele) were the most common defects of the pelvic floor (in 24 and 26%, respectively). The lateral defect occurred in 7%, the asymmetric one - in 10%, urethra cystocele - in 19%, the isolated uterine defect - 10% and enterocele - 5% (Figure 1). Conclusions The detection of types of pelvic floor defects in women with POP by 3D modeling may allow creating of synthetic implants for an individual pelvic floor reconstruction, taking into account patients' reserves of pelvic floor mobility. It will contribute reducing the risk of possible functional complications of surgical correction of POP. The further investigations of the pelvic floor dynamic features in women are necessary. Funding none
Authors
George Kasyan
Nataliya Tupikina Dmitry Pushkar |
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PD02-02 |
The study of overactive bladder associated with pelvic organ prolapse. |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Pelvic Prolapse I | 17BOS |
Abstract: PD02-02 Sources of Funding: none Introduction The aim of this study was to elucidate the impact of pelvic organ prolapse (POP) repair on overactive bladder (OAB) symptoms in women with POP and the mechanism of de novo OAB. And we also tried to identify preoperative factors for persistent postoperative OAB symptoms. Methods A total of 106 patients with POP who underwent POP repair in our hospital were included and retrospectively analyzed. Each women had a urinalysis, pelvic examination, urodunamic study, MRI and answered a urinary questionnaire. OAB was defined by OAB symptom score (OABSS) , and POP severity was classified by POP Quantification. They were divided into clinically preoperative OAB group (n=47) and non-preoperative OAB group (n=59). Results In 47 preoerative OAB patients, OAB symptoms were improved after surgical treatment in 31 cases (65.9%). There were correlation between OAB improvement after POP repair and preoperative POP-Q stage (p=0.034?c.c 0.348 ), presence of para-vaginal defect (p<0.01?c.c 0.538). In 59 non-preoperative OAB patients, de novo OAB were observed in 5 cases (8.4%). There were correlation between de novo OAB appearance and hypertension (p<0.01?c.c 0.674 ). Conclusions Women with severe POP or para-vaginal defect who undergo surgical repair experience significant improvement in OAB symptoms after surgery, hyperextension of the bladder wall was considered to be the cause of OAB by stimulating the stretch receptors. Severe POP or para-vaginal defect are considered a predictor of improvement of OAB symptoms after POP surgery. In addition, bladder blood flow disturbance due to hypertension was possibly one of the causes of de novo OAB in POP patients. Funding none
Authors
masao kataoka
Kanako Matsuoka Junya Hata Hidenori Akaihata Souichirou Ogawa Nobuhiro Kushida Ken Aikawa Yoshiyuki Kojima |
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PD02-03 |
Frailty And The Role Of Obliterative Versus Reconstructive Surgery For Pelvic Organ Prolapse; A National Study |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Pelvic Prolapse I | 17BOS |
Abstract: PD02-03 Sources of Funding: NIDDK K12 DK83021-07; K12 Urologic Research (KURe) Career Development Program, Pepper Center Research Career Development Core (RCDC) Advanced Scholar Award Introduction There are many surgical options for pelvic organ prolapse (POP) repairs spanning from obliterative procedures, such as colpocleisis, to reconstructive options including open abdominal, vaginal, and laparoscopic/robotic colpopexy. In theory, obliterative POP repairs would be ideally suited for frail older individuals due to their reported shorter operative time, lower blood loss, and faster recovery, however, this has yet to be demonstrated on a large national sample of women. The objective of this study was to determine whether frailty predicts the type of POP surgery performed (i.e., obliterative versus reconstructive) and the odds of postoperative complications among all types of POP procedures. Methods This is a retrospective cohort study of women undergoing obliterative and reconstructive surgery for POP in the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) from 2005 to 2013. We quantified frailty using the NSQIP Frailty Index (NSQIP-FI) and used logistic regression models predicting type of procedure (colpocleisis) and odds of post-operative complications. Results We identified a total of 12,731 women undergoing POP repairs, 5.3% of which were colpocleisis procedures, from 2005-2013. Among women undergoing colpocleisis, the average age was 79.2 years and 28.7% had a NSQIP-FI of 0.18 or higher, indicating frailty. Women undergoing colpocleisis procedures had higher odds of being frail (OR 1.9 95% CI 1.4-2.6 for NSQIP-FI 0.18 compared to NSQIP-FI 0) and were older aged (OR 486.2 95% CI 274.5-861.3 for age 85+ compared to <65). For all types of POP procedures, frailty increased the odds of complications (OR 1.5 95% CI 1.2-1.9 for NSQIP-FI 0.18 compared to NSQIP-FI 0), after adjusting for age and type of POP procedure. Conclusions For POP surgery, age is more strongly associated with the selection of a colpocleisis procedure than frailty, however, frailty is more strongly associated with postoperative complications than age for all types of POP procedures. Furthermore, surgeons may be basing their selection of type of POP procedure on age, whereas frailty may be a better predictor of outcomes. Furthermore, incorporating frailty into preoperative decision-making is important for improving expectations and outcomes among older women considering all types of POP surgery. Funding NIDDK K12 DK83021-07; K12 Urologic Research (KURe) Career Development Program, Pepper Center Research Career Development Core (RCDC) Advanced Scholar Award
Authors
Anne M Suskind
Chengshi Jin Louise C Walter Emily Finlayson |
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PD02-04 |
Practice Patterns in the Diagnosis and Treatment of Fecal Incontinence with Sacral Neuromodulation: Can Urologists Impact this Gap in Care? |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Pelvic Prolapse I | 17BOS |
Abstract: PD02-04 Sources of Funding: None Introduction An analysis of the National Health and Nutrition Evaluation Survey revealed the prevalence of fecal incontinence (FI) at 8% of non-institutionalized adults from 2005-2010. Many patients will not seek treatment due to embarrassment, and the condition is underdiagnosed. Sacral neuromodulation (SNM) has been shown to be successful for FI patients who have failed conservative management, and with our expertise in SNM and pelvic medicine, urologists and female pelvic medicine and reconstructive surgery (FPMRS) urologists can play a key role in treating FI. We examine the practice patterns and use of SNM for FI in a tertiary care institution with a urology FPMRS team. Methods The electronic medical record (EMR) for our institution was queried for all unique patients seen from October 1, 2015 to September 30, 2016. The number of patients seen for a diagnosis of FI (ICD-10 R15.9 and R32) was then determined for the institution as a whole, the urology department, and the FPMRS urology providers. The patients who underwent first stage SNM for FI were then analyzed to determine the number of patients who progressed to a second stage SNM procedure. Results The EMR query revealed a patient population of 217,664, with 10,747 seen in the urology department. 1,799 (0.8%) were seen with a diagnosis of FI in the institution as a whole. 20.7% of FI patients were seen in urology, with the majority (65.9%) seen by FPMRS providers. Fourteen patients underwent first stage SNM, and all of them progressed to a second stage procedure. Conclusions In our medical center, the number of patients seen for FI (0.8%), was significantly lower than the prevalence of the condition in the general population. A large number of these patients are seen by urologists, and specifically by FPMRS providers. Despite a published success rate of >80%, only a fraction of these (5.7%) underwent a SNM procedure. Because patients with urinary incontinence are more likely to have FI, urologists are in a unique position to identify these patients and offer them treatment that can potentially improve their quality of life. We acknowledge a gap in diagnosis and care of patients with FI and an opportunity for urologists to help patients with this devastating yet treatable condition. Funding None
Authors
Dena Moskowitz
Sarah Adelstein Alvaro Lucioni Kathleen Kobashi Una Lee |
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PD02-05 |
Defining the prevalence of asymptomatic microscopic hematuria among women with pelvic organ prolapse: implications for recommending subsequent diagnostic evaluation |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Pelvic Prolapse I | 17BOS |
Abstract: PD02-05 Sources of Funding: None Introduction Conflicting reports exist regarding the prevalence of asymptomatic microscopic hematuria (AMH) in women with prolapse, with rates as high as 20% having been reported. Thus, we sought to evaluate the prevalence of AMH in women presenting with pelvic floor disorders and the relationship of prolapse stage with AMH. Methods The charts of women evaluated in a Female Pelvic Medicine and Reconstructive Surgery clinic between January 2015 and July 2016 were retrospectively reviewed. The prevalence of AMH (defined as ≥3 red blood cells per high power field on microscopy on one urinalysis) for women presenting with symptomatic pelvic organ prolapse was recorded. As a comparison cohort, the rate of AMH was determined as well for women evaluated for urinary incontinence (UI) without symptomatic pelvic organ prolapse. Prolapse stage was evaluated by Pelvic Organ Prolapse Quantification system. Patient features were evaluated for association with the presence of AMH using Pearson chi-square and Wilcoxon rank-sum tests. Results Overall, 455 of the 498 patients evaluated (91%) had a urinalysis with microscopy. The prevalence of AMH was 3.3% (15/455), and was not significantly different between women presenting for prolapse (9/264, 3.4%) versus UI (6/191, 3.1%; p=0.87). Likewise, the presence of stage ≥2 anterior prolapse was not associated with an increased rate of AMH (p=0.91). Increased rates of AMH were associated with voided versus catheterized specimens (15.2% vs 2.4%; p=0.003). Hematuria evaluation identified two cases of urothelial bladder cancer (one low-grade non-invasive, one muscle-invasive), one urethral mesh erosion, and one asymptomatic kidney stone, while the remaining evaluations were negative. Conclusions We found a prevalence of AMH in women with pelvic organ prolapse lower than previously reported and consistent with prior population screening studies, as well as with patients presenting for UI. As such, AMH noted among women with pelvic organ prolapse should not be ascribed solely to the presence of prolapse. Funding None
Authors
Brian Linder
Stephen Boorjian Emanuel Trabuco John Gebhart John Occhino |
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PD02-06 |
DYNAMIC PELVIC MRI IN THE EVALUATION OF PELVIC ORGAN PROLAPSE AND CORRELATION WITH PHYSICAL EXAM FINDINGS |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Pelvic Prolapse I | 17BOS |
Abstract: PD02-06 Sources of Funding: None. Introduction Dynamic Pelvic Floor Magnetic Resonance Imaging (dMRI) provides objective evaluation of pelvic organ prolapse (POP), and few studies have compared physical examination (PE) to dMRI. We present the largest series comparing dMRI with PE findings._x000D_ Methods A total of 274 consecutive patients underwent dMRI with defecography, and charts were retrospectively reviewed for Baden-Walker grading of POP (Grade 0-4), absolute dMRI values, and grading by dMRI (Grade 0-3). Exclusion criteria included incomplete PE or dMRI, and males. Clinically significant POP was defined as Baden-Walker (B-W) Grade ≥3 and dMRI Grade ≥2 with clinically insignificant POP defined as B-W Grade 0-1 and dMRI Grade 0. Spearman correlation was performed between absolute dMRI values and POP grade._x000D_ Results In total, 178 female patients had both PE and dMRI as part of their POP assessment. In the anterior compartment, there was a moderate positive correlation (r=0.652) between dMRI values and PE. PE and dMRI had 90.7% agreement in patients without clinically significant cystocele. Clinically significant cystoceles on PE were read as Grade ≥2 on dMRI in 84.6% of subjects. _x000D_ _x000D_ Correlation between PE and dMRI for apical prolapse was poor (r=0.195). For patients without significant apical prolapse, PE and dMRI had 59.2% agreement. Clinically significant apical prolapse on PE was read as dMRI Grade ≥2 in 62.9% of subjects. However, dMRI detected 30 patients with enterocele with PE agreeing in only 9 patients. Three of these 30 patients (10%) with pure enterocele were misdiagnosed as rectocele on PE. Conversely, PE detected 20 patients with enteroceles with dMRI confirmation in 9 cases. _x000D_ _x000D_ Correlation between PE and dMRI was also poor in the posterior compartment (r=0.277). PE and dMRI had 55.4% agreement in patients without significant posterior prolapse, whereas clinically significant rectoceles were read as dMRI Grade ≥2 in 77.7% of subjects. _x000D_ Conclusions This is the largest study to date comparing dMRI to PE for the evaluation of POP. dMRI correlated well with PE in the anterior compartment but yielded little additional diagnostic value. Correlation in the posterior compartment was poor, but dMRI tended to agree with PE in higher grades of POP. dMRI was superior to PE in the detection of enterocele and was better able to distinguish enterocele from rectocele. dMRI may add the most diagnostic value in cases where the presence of enterocele is unclear. _x000D_ Funding None.
Authors
Frank C. Lin
Hina A. Tiwari Bobby T. Kalb Joel T. Funk Christian O. Twiss |
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PD02-07 |
The Use of Google Trends© to Detect Public Awareness of the FDA Communications on the Use of Morcellation of Uterine Specimens |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Pelvic Prolapse I | 17BOS |
Abstract: PD02-07 Sources of Funding: None Introduction Complications related to power morcellation of uterine specimens in women undergoing minimally invasive surgery, specifically an increase in undetected cancer, led to the FDA communications in April and November 2014. The former discouraged and the latter recommended against the use of power morcellation for women undergoing hysterectomy or myomectomy. Subsequently, practitioners drastically decreased the use of power morcellation (Wright 2016). Our aim was to determine the effect of increased patient awareness of complications on the decrease in use of the morcellator. We tested this using Google Trends&[copy], a public tool that provides data on temporal patterns of search terms and correlated this data with the timing of the FDA communication. Methods Weekly relative search volume (RSV), representing normalized and scaled reference points, was obtained from Google Trends&[copy] using the search term &[Prime]morcellation.&[Prime] Higher RSV correspond to increases in weekly search volume. The search volumes were divided into three groups: April 2012 to March 2014 (the 2 years prior to the FDA communication), a one-year period following the update, and thereafter with the distribution of the weekly RSV over the three periods tested using one-way analysis of variance. Results The mean RSV prior to the FDA communication was 12.0 (standard deviation (SD)=15.8), compared to 60.3 (SD=24.7) in the one year after the update and 19.3 (SD=5.2) thereafter (p<0.001). Conclusions Google search activity about morcellation of uterine specimens increased significantly after the FDA communications regarding power morcellation. This trend indicates an increased public awareness regarding morcellation and its complications, and therefore more extensive pre-operative counseling and alteration of surgical technique and clinician practice may be necessary. Funding None
Authors
Lauren N. Wood
Juzar Jamnagerwalla D. Joseph Thum Andrew R. Medendorp Shlomo Raz Ja-Hong Kim |
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PD02-08 |
Preventative Concomitant Sling for De-Novo Stress Urinary Incontinence After Robotic Sacral Colpopexy Does Not Improve Long Term Continence or Satisfaction |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Pelvic Prolapse I | 17BOS |
Abstract: PD02-08 Sources of Funding: none Introduction There is a 44% risk of stress urinary incontinence (SUI) following sacral colpopexy and some advocate a concomitant sling to prevent this. Robotic Sacral Colpopexy (RSC) may carry a different risk of de-novo SUI and women may be just as satisfied with a delayed mid-urethral sling (MUS). This would reduce unnecessary MUS. We sought to determine this risk and evaluate the hypothesis that delayed MUS following RSC will have similar long term pad use, Quality of Life (QoL), Distress (UDI-6), and Impact scores (IIQ-7) compared to concomitant MUS. Methods Retrospective review was undertaken and subjects were grouped based on continence status at the time of RSC. Incontinence was defined by self-report at any follow up visit, SUI on the supine stress test, or decision for MUS. Results A retrospective review of the Indiana University RSC database between 2009 and 2015 identified 135 women who underwent RSC. 79 had no preoperative SUI and 29/79 (36.7%) of patients had at least one episode of de-novo SUI following RSC over a follow up of 17.9 months. 98 patients were evaluable post-operatively. 47/57 (82%) initially dry patients elected no concomitant MUS, and ultimately 5/47 (11%) of those chose a delayed sling at an average follow up time of 23.9 months. 10/57 (18%) preoperatively dry women elected to undergo a concomitant MUS at the time of RSC. Those undergoing delayed sling reported similar post-operative pad use, UDI-6, QoL, and IIQ-7 scores (Table 1) compared with those not undergoing a sling, suggesting that a delayed sling did not have a negative impact on QoL. Those choosing to undergo concomitant MUS reported more pads per day preoperatively (2.6 vs. 0.4) including pad use from urge incontinence. With regard to satisfaction the patients who were dry pre-operatively and chose no sling scored better (2.25 vs. 6.2, p<0.01) on the IIQ-7 compared with those choosing a concomitant sling. Conclusions Patients undergoing RSC without concomitant MUS have similar de-novo SUI rates to those undergoing open colpopexy. There appears to be no advantage to concomitant MUS at the time of RSC for women exhibiting no preoperative SUI. Funding none
Authors
Charles Powell
Bridget Eckrich Jeffrey Rothenberg Thomas Gardner |
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PD02-09 |
Adjustable midurethral tape for surgical treatment of stress urinary incontinence: short-term outcomes. |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Pelvic Prolapse I | 17BOS |
Abstract: PD02-09 Sources of Funding: None Introduction Suburethral sling procedure is common and the most effective technique in treating female stress urinary incontinence (SUI). Obstructive voiding is one of the most common problems of sling surgery, its frequency is on average 7,3% (0-33,9). In 2,3% cases surgical intervention is required. The aim of the study was to evaluate the efficacy and safety of adjustable midurethral tape for surgical treatment of SUI. Methods Our prospective study included 212 women, suffering from SUI. All patiens underwent transobturator adjustable midurethral tape (UroSling, Lintex) placement. This tape can be adjusted during 2 days after surgery by tighting (pulling up the ends of the tape left uncut) or loosing (pulling down the central part of the tape by special ligatures). The pre- and postoperative evaluation included history taking, validated questionnaires (UDI-6, UIQ-6, PFIQ-7, I-QOL, ICIQ-SF, VAS), vaginal examination, cough stress test, uroflowmetry, bladder ultrasound and measurement of post-void residual urine volume, 24-hours Pad-test. Results Mean operation time was 14,6 minutes. No patients had intraoperative bladder injury or clinically significant bleeding. One day after surgery 30,18% (n=64) women required tape tension adjustment, 25% (n=16) of them had obstructive flow pattern, Qmax<12 ml/s and post-void residual urine volume was more than 100 ml. After tension adjustment none of the patients had any signs of obstructive voiding. _x000D_ After 12-month follow-up there were no significant decrease of Qmax and average flowrate (p<0,05). No cases of obstructive voiding, urinary retention, vaginal mesh extrusion or wound infection were detected. De novo urgency and urgent urinary incontinence appeared in 9 (4,24%) and 2 (0,94%) patients respectively. The objective cure rate was 92,45% (n=196) and 3,77% (n=8) of women noted a significant improvement, although in 8 (3,77%) patients operation was ineffective. The subjective cure rate according to questionnaires was 93,86% (n=207). _x000D_ _x000D_ Conclusions Transobturator adjustable midurethral tape proved to be high effective and safe method of treating women with SUI. It demonstrated low rate of intra- and postoperative complications and significantly decreased the risk of infravesical obstruction development compared with traditional methods. Funding None
Authors
Dmitry Shkarupa
Alexey Pisarev Nikita Kubin Anastasia Zaytseva Olga Staroseltseva |
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PD02-10 |
Transvaginal Mesh does not cause Carcinogenesis |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Pelvic Prolapse I | 17BOS |
Abstract: PD02-10 Sources of Funding: AUA Data Grant Introduction Synthetic mesh for vaginal prolapse surgery has been placed under scrutiny, with concerns about a causal association between mesh and causation of carcinogenesis. There are a lack of data regarding the systemic response to polypropylene mesh implantation. We sought to investigate a potential link between the carcinogenesis and synthetic polypropylene mesh repairs using statewide administrative data._x000D_ Methods Adult women undergoing surgery for pelvic organ prolapse (POP) with vaginal mesh between January 2008 and December 2009 in New York State were identified using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) procedure codes and Current Procedural Terminology Coding System, Fourth Edition (CPT-4) codes. This two-year time period was chosen because it occurred after the mesh insertion code came into use, yet allowed for long-term follow-up with respect to the outcomes of interest. The cancers were chosen based on the most common cancers occurring in women based upon data collected from the CDC and NCI.. Patients in the mesh cohort were 1:3 individually matched to a control cholecystectomy cohort based on comorbidities and procedure date. The development of carcinogensis was determined before and after matching for 1-year, 2-year and entire follow-up (up to 5 years until December 2014). Differences between groups, defined by frequency of new diagnoses of malignancy were assessed using chi-squared (?2) tests in the entire cohort and using stratified Mantel–Haenszel ?2 tests for paired data in the matched cohort. _x000D_ Results A total of 2,301 patients underwent mesh based POP surgery between January 2008 and December 2009. 1,699 patients undergoing mesh based POP surgery were matched to 5097 patients undergoing cholecystectomy based on demographics, comorbidities and procedure date. Mesh-based surgery was not associated with an increased risk of developing a cancer diagnosis at 1-year (Risk ratio (RR) 0.41, 95% CI 0.23-0.75), 2-year (RR 0.57, 95% CI 0.39-0.84) and during entire follow up of up to 5 years (RR 0.67, 95% CI 0.53-0.84)._x000D_ Conclusions Mesh-based vaginal surgery was not associated with the development of cancers. This data refutes claims against mesh as a cause of carcinogenesis._x000D_ Funding AUA Data Grant
Authors
Bilal Chughtai
Art Sedrakyan Jialin Mao Dominique Thomas Karyn Eilber Jennifer Anger J. Quentin Clemens |
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PD02-11 |
ADDITIONAL TREATMENTS, SATISFACTION, AND QUALITY OF LIFE IN WOMEN AFTER TRANSVAGINAL AND ABDOMINAL PELVIC ORGAN PROLAPSE REPAIR |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Pelvic Prolapse I | 17BOS |
Abstract: PD02-11 Sources of Funding: None Introduction We evaluated satisfaction, quality of life, and additional treatments after transvaginal (TV) and abdominal (ABD) pelvic organ prolapse (POP) repair. Methods Adult women enrolled in a prospective POP database were reviewed. Baseline and outcomes data one year after surgery were collected from medical records, validated Pelvic Floor Distress Inventory (PFDI), and mailed surveys, and analyzed with descriptive statistics, Fishers Exact, and two sample t tests. Results Two hundred twenty-two patients were identified from the database, of whom 147 (66%) had TV and 75 (34%) had ABD repair. TV patients were older (mean 64.1 vs. 59.7 years; p=0.003) but no differences in BMI, race, marital status or other demographics were identified. Preoperative mean anterior (TV 2.7 vs. ABD 3.1; p=0.003) and apical (TV 2.1 vs. ABD 3.1; p<0.001) POP grades were more severe in the ABD patients compared to the TV patients. Baseline PFDI scores however were similar between groups (TV 115.8 vs. ABD 111.6, p=0.605). At one year PFDI scores were improved in both groups, though were significantly higher in the TV group (45.6 vs. 32.6; p=0.032). Absolute score improvement from baseline to 1-year did not differ (TV -67.6 vs. ABD -76.1, p=0.353). The majority of patients in both groups reported moderately or markedly improved overall symptoms (TV 79/101; 78% and ABD 51/59; 86% p=0.199) and quality of life (80/101; 79% and 51/59; 87% p=0.252). Similar proportions of patients in both groups (TV 52/109; 48% vs. ABD 21/62; 34%, p=0.108) had additional POP treatments including pelvic floor physical therapy, medications, coping strategies, and surgical procedures. Specifically, there was no difference in rates of additional surgical treatments for prolapse between groups (TV 32/109; 29% vs. ABD 10/62; 11%, p=0.053). Most TV and ABD patients were satisfied (68/101; 68% and 48/59; 81%, p=0.055, respectively) and would recommend to a friend (85/99; 86% and 55/57; 96%, p=0.052). Conclusions This study suggests that although symptoms, satisfaction and quality of life improve after both TV and ABD prolapse repair, women seek additional treatments as early as the first year after POP repair. Funding None
Authors
Laura Nguyen
Natalie Gaines Larry Sirls Kim Killinger Morgan Gruner Michelle Jankowski Kenneth Peters |
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PD02-12 |
THE EFFECT OF RESIDENT INVOLVEMENT IN PELVIC PROLAPSE SURGERY: A RETROSPECTIVE STUDY FROM A NATIONWIDE INPATIENT SAMPLE |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Pelvic Prolapse I | 17BOS |
Abstract: PD02-12 Sources of Funding: None. Introduction Conflicting evidence exists regarding the impact of resident involvement on surgical outcomes. The primary aim of this study is to assess the impact of resident involvement on perioperative complications in pelvic organ prolapse surgery using the National Surgical Quality Improvement Database (NSQIP). Methods The NSQIP database was queried from 2009 through the end of 2013 to identify all cases of pelvic organ prolapse repair using relevant Current Procedural Terminology (CPT) codes. This analysis included both urologic and gynecologic surgeons. We first stratified and analyzed this data by resident participation. To control for the effect of pre-operative comorbidity, propensity scores of resident involvement were calculated. The probability that any given case would be assigned to the “Resident Involvement� arm is represented on a scale of 0 to 1. To analyze cases according to similar probabilities, all cases were then divided into quartiles. Because the 25th and 50th quartiles were the same value (probability of 0.407), three groups were created (Q1/2, Q3, Q4). Stratification by resident involvement and comparision of perioperative outcomes were performed within each group. As a control, complications of transurethral resection of prostate (TURP) and nephrectomy (both total and partial) were stratified by resident involvement. Results We identified 2,644 cases that included resident participation. Across all groups, resident involvement was associated with increased post-operative urinary tract infections, overall perioperative complications and procedure length. Resident involvement in cases was without significant change with 481/1159 (41.5%) in 2009 to 685/1624 (42.2%) in 2010 to 598/1356 (44.1%) in 2011 and finally 595/1399 (42.5%) in 2012. In the first group, resident involvement was associated with increased readmissions, pulmonary embolism, and sepsis. In the second and third groups, resident involvement was associated with increased rates of superficial surgical site infection. Nephrectomy cases demonstrated similar outcomes. Resident involvement in TURP was associated only with increased procedure lengths and decreased post-operative length of stay. Conclusions Resident involvement in pelvic organ prolapse surgery was associated with an increased risk of adverse outcomes. A similar effect was seen with nephrectomy but not with a more simple endoscopic urologic procedure Funding None.
Authors
Maxx Caveney
Catherine Matthews Majid Mirzazadeh |
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PD03-01 |
Metastases and death after 15 year of follow-up in men with screen-detected low-risk prostate cancer treated with protocol based active surveillance, radical prostatectomy or radiotherapy |
Prostate Cancer: Epidemiology & Natural History I | 17BOS |
Abstract: PD03-01 Sources of Funding: none Introduction The recently published outcomes of the ProtecT trial showed no difference in PCa-specific survival after a median of 10 yr follow-up between surgery (RP), radiotherapy (RT) and active monitoring (AM) in men with screen detected localized prostate cancer (PCa) [1]. However, data also showed a higher rate of metastatic (M+) PCa in the AM arm. Caveat of ProtecT are the randomization of PCa cases into the AM arm that are considered high risk and the AM protocol which is substantially different from current Active Surveillance (AS) protocols. Methods From men diagnosed with PCa at the 1st and 2nd screening round of ERSPC Rotterdam (1993-2003) considered suitable for AS (i.e Gleason score ≤3+3, ≤T2a PCa cases), we calculated PCa-specific survival and rate of M+ PCa and compared these outcomes between men treated with AS predominantly according to the PRIAS protocol (n=223), having had a RP (N=365) or treated with RT (n=312)._x000D_ Results Baseline characteristics are listed in Table 1 and reflect the non-randomized setting. However, statistically significant differences do not automatically translate to clinically relevant differences. After a median follow-up of 15-yr (IQR 12-17 yr), 18 men died from PCa. Similar to ProtecT, no significant difference in PC specific survival was found between AS (97.2%; 95% CI: 94.7-99.7), RP (98.5%; 95% CI: 97.2-99.8), and RT (97.5%; 95% CI: 95.5-99.5), log-rank p=0.36. However, contrary to ProtecT, M+-free survival was also similar with rates of 96.9% (95% CI: 94.4-99.4) for AS, 97.9% (95% CI: 96.3-99.5) for RP and 96.6% (95% CI: 94.4-99.0) for RT, log-rank p=0.42 (Table 2). Conclusions The current data support a comparable long-term risk of disease progression of low-risk PCa in men initially treated with AS according to a protocol including regular monitoring with PSA, DRE and prostate biopsy and men opting for immediate active treatment. Personal preferences including considerations on quality of life will become more and more important in the treatment decision of low-risk PCa._x000D_ _x000D_ 1. Hamdy et al. NEJM. PMID: 27626136 Funding none
Authors
Jan Verbeek
Chris Bangma Frank-Jan Drost Monique Roobol |
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PD03-02 |
Frequency of DNA Repair Gene Mutations in Localized and Metastatic Prostate Cancer |
Prostate Cancer: Epidemiology & Natural History I | 17BOS |
Abstract: PD03-02 Sources of Funding: None Introduction DNA repair gene mutations are important molecular alterations in prostate cancer pathogenesis. Germline mutations in DNA repair genes, particularly BRCA2, were recently recognized as associated with metastatic prostate cancer. Prostate tumors with DNA repair defects may also be particularly sensitive to platinum based chemotherapy and PARP inhibitor therapy. We sought to characterize alterations in DNA repair pathway genes in both primary and metastatic prostate tumors. Methods We studied the distribution of DNA repair gene mutations in 936 prostate cancers harvested from localized and metastatic tumors. Tumor DNA underwent hybrid capture for all coding exons of 395 cancer-related genes plus select introns from 19 or 31 genes frequently rearranged in cancer. Captured libraries were sequenced to a median exon coverage depth of >500x using Illumina sequencing and were analyzed for base substitutions/insertions, copy number alterations and rearrangements. We utilized two described lists of genes involved in DNA repair : our own in-house list of 74 (UCD) and a list of 20 DNA repair genes associated with cancer predisposition syndromes utilized in a recent publication by Pritchard et al. Nine genes were in common between the two lists yielding a total of 85 unique DNA repair genes. We further stratified the frequency of mutations by tissue site (prostate versus metastases). Only tissues represented by at least 10 samples in the set were included (868). Frequencies of DNA repair defects were compared across metastatic sites by Pearson’s Chi-squared test. Results We identified 228/936 unique samples with at least one likely functional mutation in a DNA repair gene (24.4%). Mutations were identified in 20.1% of prostate tumors (13% UCD, 18.4% Pritchard et al.) and in 18.8% of bone metastases. The highest rates of DNA repair mutations were found in visceral metastases including brain, pelvis and liver, which were significantly higher than either prostate tissue or bone sites (p=<0.01). The most commonly (?1% of samples) mutated genes in the DNA repair pathways are: BRCA2 (11.43%), ATM (5.77%), MSH6 (2.46%), MSH2 (2.14%), ATR (1.60%), MLH1 (1.28%), and BRCA1 (1.18%). Conclusions DNA repair gene mutations are more common in metastatic than localized prostate tumors. Visceral metastases appear enriched for these mutations compared with localized tumors or bone and lymph node metastases. Genomic profiling may identify prostate cancers potentially sensitive to platinum-based chemotherapy or PARP inhibition. Funding None
Authors
Allison Glass
Primo Lara Ryan Hartmaier Ralph deVere White John McPherson Marc Dall'Era |
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PD03-03 |
Does prostate cancer represent the main cause of death in all node positive prostate cancer patients? The impact of competing causes of mortality according to tumor characteristics and recurrence status |
Prostate Cancer: Epidemiology & Natural History I | 17BOS |
Abstract: PD03-03 Sources of Funding: none Introduction A risk stratification of N+ prostate cancer (PCa) patients according to tumor characteristics was recently proposed (Abdollah et al. JCO 2014). The aim of this study was to assess whether the rate of other cause mortality (OCM) differs in N+ PCa patients according to these 5 risk-groups, after accounting for the risk of cancer specific mortality (CSM). This would allow to improve patient stratification and to identify candidates for additional therapies Methods We evaluated 1,312 N+ PCa patients treated with radical prostatectomy and pelvic lymph node dissection at two tertiary referral centers between 1988 and 2014. Patients were stratified into the 5 established risk-groups: very low-risk (≤2 N+, and Gleason score ≤6); low-risk (≤2 N+, Gleason score 7-10, pT2/pT3a and negative surgical margins); intermediate-risk (≤2 N+, Gleason score 7-10 and pT3b/pT4 or SM+); high-risk (3-4 N+); very high-risk (>4 N+). Poisson smoothed cumulative incidence methods were used to assess 8-year OCM according to risk groups, after accounting for the risk of CSM. The same analyses were performed among men who experienced BCR after RP (n= 633, 48.2%) Results The median follow-up after RP was 82 months (IQR 37.1-147). During the study period, 18.1% of men died from other causes and 14.6% died from PCa. The leading cause of death at 8-year was OCM in the very low and low risk groups (12.6 and 8.3% vs. 2.5 and 7.6% for CSM, respectively). Conversely, CSM was the main cause of death in the remaining groups (Fig 1a). When the same analyses were repeated in men who had BCR after RP, CSM was the leading cause of death in all risk-groups except in very low-risk patients, where the 8-year OCM and CSM were similar (5.9 and 5.8%, respectively; Fig. 1b). Conclusions PCa is not invariably the main cause of death in all N+ patients treated with curative intent. Patients with less aggressive disease are more likely to die from other causes. Conversely, when N+ patients recur, they will likely succumb from PCa rather than from other causes, regardless of tumor aggressiveness. These results could help physicians sparing unnecessary treatments in N+ men with lower likelihood of dying from PCa and to plan timely salvage treatments in virtually all N+ men who recur Funding none
Authors
Paolo Dell'Oglio
Emanuele Zaffuto Armando Stabile Giorgio Gandaglia Michele Colicchia Nicola Fossati Umberto Capitanio Federico Dehó Renzo Colombo Roberto Bertini Francesco Montorsi R. Jeffrey Karnes Alberto Briganti |
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PD03-04 |
Long-Term Rates of Prostate Cancer Diagnosis and All-Cause Mortality in a Population-Based Cohort of Men with an Initially Negative Prostate Biopsy |
Prostate Cancer: Epidemiology & Natural History I | 17BOS |
Abstract: PD03-04 Sources of Funding: None Introduction Transrectal ultrasound-guided prostate biopsies (TRUS-Bx) have a high false-negative rate, and thus men with a negative TRUS-Bx frequently undergo repeat biopsies leading to subsequent diagnoses of prostate cancer (PCa). Long-term outcome data on such patients is lacking, as previous studies have only reported the short-term rates of PCa diagnosis in small cohorts of men with a negative TRUS-Bx. Our objective was to determine both the long-term rates of PCa diagnosis and all-cause mortality in a large, population-based cohort of men with a single negative TRUS-Bx. Methods This was a retrospective, population-based study of 124,067 men who had an initially negative TRUS-Bx in Ontario, Canada between April 1994 and March 2015. All included men were older than 40 years and had no prior history of PCa. Using data from the Ontario Health Insurance Plan, Ontario Cancer Care Registry, and Registered Persons Database, housed at the Institute of Clinical and Evaluative Sciences, we were able to determine the 5, 10, 15, and 20 year rates of PCa diagnosis and all-cause mortality in such men. Results Mean age at date of first negative TRUS-Bx was 63.55 years (SD=8.75). Total follow-up time was 974986.07 person-years, with mean follow-up per patient at 7.86 years (SD=5.37). The total number of subsequent PCa diagnoses was 21,869, accounting for an incidence rate of 22.25 per 1000 person-years. The 5, 10, 15, and 20-year rates of PCa diagnosis were 0.130, 0.187, 0.220, and 0.239, respectively. The total number of deaths in our cohort was 21,375, accounting for a death incidence rate of 21.92 per 1000 person-years. The 5, 10, 15, and 20-year all-cause mortality rates were 0.068, 0.155, 0.260, and 0.380, respectively. Conclusions Based upon these long-term population-based data, a significant proportion of men with an initially negative TRUS-Bx subsequently receive a diagnosis of PCa, with risk of diagnosis continuously rising. These data suggest that long term follow up of at risk men is warranted. Funding None
Authors
Rashid Sayyid
Shabbir Alibhai Rinku Sutradhar Maria Eberg Kinwah Fung David Urbach Neil Fleshner |
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PD03-05 |
External Validation of the Age-Adjusted Prostate Cancer-Specific Comorbidity Index (PCCI), a Claims-Based Tool for Prediction of Life Expectancy in Men with Prostate Cancer |
Prostate Cancer: Epidemiology & Natural History I | 17BOS |
Abstract: PD03-05 Sources of Funding: None Introduction Accurate assessment of life expectancy (LE) is critical to appropriate case selection for men with prostate cancer. We previously reported the age-adjusted Prostate Cancer Comorbidity Index (PCCI), a LE prediction tool that uses a weighted score incorporating age and comorbidities to estimate 2, 5, and 10-year mortality in men with prostate cancer. We sought to operationalize the PCCI for clinical application using claims data and externally validate it across a nationally representative sample. We then compared its ability to identify patients at risk for overtreatment with the age-adjusted Charlson comorbidity index. Methods We sampled 181,209 men with prostate cancer diagnosed from 2000 to 2011 in the Veterans Affairs healthcare system. We used claims data within 12 months of biopsy to determine comorbidities at diagnosis. We used Kaplan-Meier analysis to plot overall survival and multivariable Cox proportional hazards analysis to assess risk discrimination between PCCI and Charlson score subgroups. We then compared the number of men with <10-year LE who were treated with surgery or radiation between the two indices. Results Kaplan-Meier analysis showed a stepwise increase in risk of overall mortality with increasing PCCI score (Figure). Ten-year mortality among men with PCCI scores of 1-2, 3-4, 5-6, 7-9, and 10+ was 26%, 36%, 41%, 52%, and 69%, respectively. Multivariable models showed excellent risk discrimination with hazard ratios of 1.22 (95%CI 1.18-1.27), 1.69 (95%CI 1.61-1.76), 2.08 (95%CI 2.00-2.17), 2.88 (95%CI 2.76-3.00), 4.50 (95%CI 4.32-4.69) for PCCI scores of 1-2, 3-4, 5-6, 7-9, and 10+, respectively. The PCCI identified 30,610 men with LE <10 years (<50% median survival at 10 years) vs. 25,455 men in the Charlson index. Furthermore, the PCCI identified significantly more men with <10-year LE who were overtreated with surgery or radiation compared with the Charlson index: 12,531 (41%) vs. 7,098 (28%) (p<0.0001). Conclusions The age-adjusted Prostate Cancer Specific Comorbidity Index (PCCI) showed excellent prognostic utility across a nationally representative sample of men with prostate cancer. It was superior to the Charlson index in identifying men at risk for overtreatment due to limited LE. _x000D_ _x000D_ Funding None
Authors
Timothy Daskivich
I-Chun Thomas Ted Skolarus John Leppert |
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PD03-06 |
Contemporary trends in incidence of metastatic prostate cancer among US men: Results from nationwide analyses |
Prostate Cancer: Epidemiology & Natural History I | 17BOS |
Abstract: PD03-06 Sources of Funding: none Introduction Studies have noted contrasting findings with regards to the contemporary incidence of metastatic prostate cancer (PCa) in the US. We sought to assess the trends in the incidence of metastatic PCa using nationally representative data._x000D_ Methods We used data from the 18 population- based tumor registries of Surveillance, Epidemiology and End Results (SEER) 2004-2013 database. We focused on 23,003 men aged 45 and above diagnosed with clinically metastatic PCa (ICD-O-3 code C61.9) between the years 2004-2013, using the American Joint Committee on Cancer 6th (2004-09) and 7th (2010+) clinical M staging. We assessed the temporal trends in the delay- and age-adjusted incidence (per 100,000 US men) of metastatic PCa, using annual percentage change (APC; weighted least squares method). Analyses were stratified by year groups (2004-2008 vs. 2009-2013) and age categories (45-74 vs 75 and above). We also performed sensitivity analyses using JoinPoint regression to identify the time points associated with a change in the incidence of metastatic PCa, overall and stratified by aforementioned age groups. Results Overall, there was a non-significant change in incidence between 2004-2008, but a significant increase between 2009-2013 (APC 2.9%, p=0.01). For men aged 45-74, metastatic PCa incidence increased by 2.6% per year between 2009-2013 (p=0.008, Figure 1b). Men aged ≥75 showed a significant decline in the incidence of metastatic PCa for 2004-2008 (APC -2.5%, p=0.02), and a non-significant increase for 2009-2013 (APC 3.2%, p=0.1; Figure 1b). JoinPoint regression analyses showed similar findings, with a significant increase in metastatic PCa incidence starting in 2009 overall and for men aged 45-74 (Figures 1c-e). Conclusions Our results suggest an increase in the incidence of metastatic PCa in the US, beginning in the more contemporary time period (2009-13) for men aged 45 and above. Future large scale studies are warranted to validate our findings, identify the causes and understand its implications on health care policy for US men. Funding none
Authors
Deepansh Dalela
Maxine Sun Patrick Karabon Thomas Seisen Sriram Eleswarapu Quoc-Dien Trinh Mani Menon Firas Abdollah |
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PD03-07 |
The impact of socioeconomic status, race, and insurance type on the risk of newly diagnosed metastatic prostate cancer in the United States |
Prostate Cancer: Epidemiology & Natural History I | 17BOS |
Abstract: PD03-07 Sources of Funding: NIH 5U01CA196390 and the Prostate Cancer Foundation – Hagen Special Challenge. Introduction We hypothesize lower socioeconomic status (SES) may lead to higher risk of mPCa regardless of race and insurance status and partly explain existing disparities in PCa outcomes. We therefore used a large national cancer registry to compare socioeconomic, demographic, and clinical characteristics of men presenting with and without mPCa. Methods All men diagnosed with adenocarcinoma of the prostate in the National Cancer Data Base from 2004 to 2013 were identified. A four-level composite metric of SES was created using census-based income and education data. Multivariable logistic regression analysis was used to evaluate the association of various factors such as race/ethnicity and insurance status with the likelihood of presenting with mPCa while controlling for SES. Results Of the 1,034,754 patients with PCa, 4% presented with mPCa. Metastatic PCa was diagnosed in 3% of patients in the highest SES group and 5% in the lowest SES group (lowest vs highest SES: adjusted OR 1.39, 95% CI 1.35-1.44, p<0.001). Likewise, having Medicaid or no insurance (12.5%; OR 3.91, 95% CI 3.78-4.05, p<0.001) was associated with greater odds of mPCa compared to having private insurance or Medicare (3.6%). Compared to White men (3.6%), Black (5.9%; adjusted OR 1.47, 95% CI 1.43-1.51, p<0.001) and Hispanic men (6.2%; OR 1.22, 95% CI 1.17-1.28; p<0.001) had higher odd of metastatic diagnoses. SES disparities in the diagnosis of mPCa were seen within race/ethnicity and insurance groups (Figure). Decreasing SES lead to larger increases in the absolute risk of mPCa among Black and Hispanic men and men with Medicaid or no insurance compared to White men and men with private insurance or Medicare, respectively. Conclusions There is an inverse relationship between SES and odds of presenting with mPCa. Having no insurance or Medicaid and being of Black or Hispanic race/ethnicity increased odd of mPCa even when controlling for SES. Decreasing SES lead to increased risk of mPCa even within each race/ethnicity and insurance groups, especially for non-White men and men with Medicaid or no insurance. The effect of SES on mPCa presentation may partly explain existing disparities in PCa outcomes.? Funding NIH 5U01CA196390 and the Prostate Cancer Foundation – Hagen Special Challenge.
Authors
Adam Weiner
Richard Matulewicz Jeffrey Tosoian Joseph Feinglass Edward Schaeffer |
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PD03-08 |
Impact of Age, Comorbidity, and PSA Doubling Time on Long-Term Competing Risks for Mortality Among Men with Non-Metastatic Castration-Resistant Prostate Cancer |
Prostate Cancer: Epidemiology & Natural History I | 17BOS |
Abstract: PD03-08 Sources of Funding: None Introduction Given the protracted course of prostate cancer (PC) progression, competing risks of mortality is a key consideration in determining prognosis and treatment in all stages of the disease. We sought to examine the impact of age, Charlson Comorbidity Index (CCI), and PSA doubling time (PSADT) on all-cause mortality (ACM), prostate cancer-specific mortality (PCSM), and other-cause mortality (OCM) in a nationally representative sample of men with non-metastatic castration-resistant PC (M0/Mx CRPC)._x000D_ Methods We analyzed 1,238 men diagnosed with M0/Mx CRPC in 2000 or later from 8 Veterans Affairs hospitals in the SEARCH database. CCI and PSADT were calculated at the time of M0/MX CRPC diagnosis, and cause of death was defined as PCSM or OCM. Men were divided into subgroups based on age (<70, 70-79, and ≥80), CCI (0, 1, 2, and 3+), and PSADT (<9 months, ≥9 months). Multivariable Cox proportional hazards analysis and competing risks regression analysis were used to determine the relative impact of age, CCI, and PSADT on ACM, PCSM, and OCM. Models were adjusted for race, year of diagnosis, site, biopsy Gleason score, PSA at CRPC, primary treatment, months from androgen deprivation to CRPC, and PSA velocity. Results Men in our sample were generally older (<70, n=344; 70-79, n=418; ≥80, n=476), and the majority had CCI ≥2 (n=701). Competing risk regression analysis revealed that the risk of PCSM was appreciable for all subgroups, particularly among those with PSADT<9mos. However, the hazard of OCM was substantially higher for older, sicker men with high PSADT (Figure 1). For example, among men aged ≥80, those with CCI ≥3 and PSADT≥9 mos, cumulative incidence of PCSM/OCM at 5 years was 20%/50% compared with 30%/19% for CCI 0 and PSADT<9mos. Multivariable analysis showed that higher comorbidity burden predicted higher hazard of OCM across all ages; among those with CCI ≥3 (vs. 0), hazard ratios for OCM were 2.7 (95%CI 1.1-6.3), 2.0 (95%CI 1.1-3.6), and 2.5 (95%CI 1.5-4.0) for those aged <70, 70-79, and ≥80, respectively. Conclusions Among men with M0/Mx CRPC, age, comorbidity, and PSADT are predictive of cause of death. Understanding the competing risks of PCSM and OCM is a critical consideration when counseling patients regarding prognosis and treatment of advanced PC. Funding None
Authors
Colette Whitney
Lauren Howard Stephen Freedland Christopher Amling William Aronson Matthew Cooperberg Christopher Kane Martha Terris Timothy Daskivich |
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PD03-09 |
Rising Incidence of Metastatic Prostate Cancer in California, 1988-2014 |
Prostate Cancer: Epidemiology & Natural History I | 17BOS |
Abstract: PD03-09 Sources of Funding: This work was supported by the NCI Comprehensive Cancer Center Support Grant, (P30CA93373) Introduction Early detection of prostate cancer with PSA based screening can reduce the risk of prostate cancer mortality by 21%. Screening for prostate cancer has dramatically declined in the United States since the United States Preventive Services Task Force (USPSTF) recommended against routine PSA based prostate cancer screening for all men in 2012. This led to dramatic reductions in the diagnosis of localized disease across all clinical risk groups. We sought to study trends in newly diagnosed metastatic prostate cancer incidence, specifically the impact of patient age and race. Methods We analyzed new prostate cancer incidence by stage at diagnosis between 1988-2014 using data from the California Cancer Registry. We further stratified cases by age and four major race/ethnicity groups (non-Hispanic white (NHW), non-Hispanic black (NHB), Hispanic and non-Hispanic Asian/PI (API)). Incidence rates per 100,000 were age-adjusted to the 2000 US Standard Population. Joinpoint regression was used to detect changes in incidence and to calculate the average percent change (APC) over time. Joinpoint finds the best fit model with the smallest number of joinpoints and will not add an additional joinpoint if it does not make significant improvement on the model. Results Adjusted rates of remote prostate cancer incidence for men of all races aged 65-74 and NHW men of all ages significantly increased over the most recent time period by 2.4% and 1%, respectively, p<0.05 (Figure 1 and 2). In contrast, incidence of remote prostate cancer continued to decline for NHB (-2.42%), Hispanic (-1.94%), and API (-1.66%) men. Localized disease incidence continues to decline significantly for all age and racial groups. Conclusions Incidence rates of newly metastatic prostate cancer have significantly increased for the first time in California for men aged 65-74 and white men. Although not possible to determine the etiology of these findings, decreased PSA screening and early detection of aggressive as well as indolent tumors is likely to contribute. _x000D_ Funding This work was supported by the NCI Comprehensive Cancer Center Support Grant, (P30CA93373)
Authors
Marc Dall'Era
Ralph Devere White Danielle Rodriguez Rosemary Cress |
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PD03-10 |
Validation of the 2015 Prostate Cancer Prognostic Grade Groups for Predicting Long-Term Oncologic Outcomes in a Shared Equal Access Health System. |
Prostate Cancer: Epidemiology & Natural History I | 17BOS |
Abstract: PD03-10 Sources of Funding: none Introduction The 2015 prostate cancer grading system was introduced to simplify pathologic stratification. We examine the performance of the Prognostic Grade Groups (PGG) in the Shared Equal Access Regional Cancer Hospital (SEARCH) database with respect to long term prostate cancer outcomes and whether associations vary by race within an equal access healthcare system. Methods We performed a retrospective review of men undergoing radical prostatectomy at one of six Veterans Affairs hospitals between 1988 and 2015. We identified 4,325 men with available data. The prognostic ability of PGG for multiple long term clinical endpoints was examined using Cox models. Interactions between PGG and race were tested. Results The cohort consisted of PGG 1 through 5, respectively: 2,077(48%), 1,171(27%), 521(12%), 409(10%), 147(3%). 1,596(38%) were African American. Median follow up was 86(IQR: 45 to 135) months. Higher PGG was associated with higher stage, older age, more recent year of surgery and surgical center (p<0.02). African American men had a lower PGG distribution (p=0.028). Higher PGG was associated with increased risk of all clinical endpoints on univariable and multivariable regression including biochemical recurrence(BCR), adjuvant therapy, castrate resistant prostate cancer(CRPC)[Figure 1, left], metastases, prostate cancer specific mortality(PCSM) and overall survival(OS)[Figure 1, right](all p<0.001). _x000D_ We found no significant interactions with race in predicting any of the measured outcomes. (BCR: p=0.78, adjuvant therapy: p=0.60, CRPC: p=0.91, metastases: p=0.61, PCSM: p=0.83, OS: p=0.21). Conclusions The 2015 Prognostic Grade Groups predicted multiple long term clinical endpoints after prostatectomy in a large, multiracial cohort of men. The predictive value for survival endpoints was similar in Caucasian and African American men. _x000D_ Funding none
Authors
Ariel Schulman
Lauren Howard Kae Jack Tay Rajan Gupta Efrat Tsivian Christopher Amling William Aronson Matthew Cooperberg Christopher Kane Martha Terris Stephen Freedland Thomas Polascik |
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PD03-11 |
Comorbidity and prostate-cancer specific mortality |
Prostate Cancer: Epidemiology & Natural History I | 17BOS |
Abstract: PD03-11 Sources of Funding: None; PcBaSe Sweden is funded by the Swedish Research Council (25-2012-5047). Introduction Comorbidities are medical disorders co-existing in patients with prostate cancer (PCa). Comorbidity, like PCa, is age-related and prevalent, influencing treatment choices. Although comorbidity may adversely affect competing-cause mortality in PCa patients, the impact on PCa-specific mortality is not known. Methods Using the PcBaSe Sweden composite population-based dataset, 118543 men diagnosed with PCa between 1998 and 2012, and followed up for survival until 2014 were identified. Median follow-up was 8.3 (IQR=5.2-11.5) years to death from PCa or other causes. Patients were categorised by patient (marital status, educational level) and tumour (serum Prostate-specific Antigen [PSA], tumour grade and clinical stage) characteristics, and treatment type (Radical Prostatectomy [RP], Radical Radiotherapy [RT], Androgen Deprivation Therapy [ADT] or Watchful Waiting [WW]). Data were stratified by Charlson Comorbidity Index (CCI) (0, 1, 2, >/=3) and treatment type. Mortality from PCa and other causes were calculated following stabilized inverse probability weighting (SIPW) adjustments for patient and tumour characteristics, and treatment type. Kaplan-Meier estimates and Cox regression were used to calculate hazard ratios. Ethical approval (EPN DnR 2012/499-31/4). Results In the complete unadjusted dataset, an effect of increasing comorbidity was observed on PCa-specific and other-cause mortality. Following adjustments for patient and tumour characteristics, the effect of comorbidity on PCa-specific mortality was lost, while maintained for other-cause mortality. Following additional adjustment for treatment type, an effect of comorbidity on PCa-specific mortality was not observed, while present for other-cause mortality. Conclusions During the study period in Sweden, comorbidity appeared to affect other-cause, but not PCa-specific, mortality after accounting for patient and tumour characteristics, and treatment type. Increasing comorbidity did not impact on PCa-specific mortality irrespective of radical treatment (RP or RT). Consequently, in population-based comparative PCa treatment effectiveness studies, the differences in oncological outcomes may not be due to the varying distribution of comorbidity among treatment groups, hence comorbidity is unlikely to be a confounder. Funding None; PcBaSe Sweden is funded by the Swedish Research Council (25-2012-5047).
Authors
Prabhakar Rajan
Prasanna Sooriakumaran Tommy Nyberg Olof Akre Stefan Carlsson Lars Egevad Gunnar Steineck Peter Wiklund |
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PD03-12 |
Prostate Cancer Incidence Stratified by Race and Gleason Score: A SEER Database Analysis of the USPSTF Guideline Era |
Prostate Cancer: Epidemiology & Natural History I | 17BOS |
Abstract: PD03-12 Sources of Funding: None Introduction In 2008 and extended in 2012, the US Preventive Services Task Force (USPSTF) issued guidelines stating there was insufficient evidence to support prostate cancer screening. Using the Surveillance Epidemiology and End Result (SEER) database, we sought to determine the effect of recent USPSTF recommendations on prostate cancer incidence based on Gleason score (GS), and to identify differences in GS based on race. Methods SEER database was analyzed from 2008-2013. Patients were divided based on recorded race. GS were stratified as low (2-6), intermediate (7) or high (8-10). Incidence was compared between 2008 and 2013 by determining incidence rate ratio (IRR) and annual percentage change (APC). Statistical analysis was performed with SEERSTAT and excel, confidence interval was set at 95%, with p< 0.05 as significant. Results 337,504 patients diagnosed with prostate cancer within SEER 18 between 2008 and 2013 were included in the analysis. The mean age range was between 65-74 years. Majority (68.1%) of patients were White, followed by 14.6% Black. GS 2-6 was recorded for 41.8%, followed by GS 7 in 36.2% of patients, and GS 8-10 in 15.9% of patients. Cumulative six year GS 2-6 incidence was noted to be 76.2, 52.9, 44.7 and 25.0 per 100,000 for Black (B), White (W), Hispanic (H), and Asian/Pacific Islanders (API), respectively. GS 7 incidences were 81.3, 46.4, 36.2 and 23.4 per 100,000 for B, W, H, and API, respectively. GS 8-10 was reported in 37.5, 21.0, 21.7 and 18.0 per 100,000 for B, W, H, and API, respectively. The IRR demonstrated a decline in incidence across races and Gleason scores. Between 2008 and 2013 GS 7 IRRs were 0.74 B, 0.65 W, 0.61 H, 0.60 API and GS 8-10 IRRs were 0.85 B, 0.89 W, 0.83 H, 0.78 API. APC significantly declined among all races for GS 2-6 (-8.56 B, -8.87 W, -8.63 H and -8.68 API) and GS 7 (-6.54 B, -8.56 W, -9.23 H and -9.91 API). Additionally, APC significantly declined for B and H GS 8-10 (-3.51 B, -4.39 H). APC of GS 8-10 incidence showed no statistically significant increase or decline for W and API (-2.28 W, -5.05 API). Conclusions Analysis of SEER demonstrates a decline in incidence of prostate cancer among all races. Notably, there was a decline in GS 8-10 prostate cancer incidence for B, W, H, and API groups, suggesting reduced diagnosis of aggressive prostate cancer in the USPSTF guideline era. Funding None
Authors
Daniel Au
Johar Syed Sameer Siddiqui |
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PD04-01 |
Determinants of All-cause Mortality in patients with metastatic Papillary Renal Cell Cancer |
Kidney Cancer: Advanced (including Drug Therapy) I | 17BOS |
Abstract: PD04-01 Sources of Funding: Intramural research program at National Institutes of Health Introduction While prognostic factors determining survival in metastatic clear cell renal cell cancer patients are well established, little is known about predictors of outcome in metastatic papillary renal cell cancer (pRCC) patients. We aim to determine the predictors of all-cause mortality (ACM) in pRCC patients. Methods Retrospective evaluation of the medical records of patients with metastatic pRCC seen at National Cancer Institute (2000-2014) was undertaken. Patient demographics, tumor characteristics and outcomes were studied. Kaplan-Meier Survival analysis was done to estimate overall survival (OS). Multivariate Cox proportional-hazards regression analysis was done to identify predictors of ACM. Results 106 consecutive patients with metastatic pRCC were identified. The median age and follow up time after the diagnosis of metastases was 50 years (11-80) and 33.8 mon (2.3-246.7) respectively. Twenty-one (19.8%) and 42 (39.6%) patients had papillary type 1 and papillary type 2 renal cancers respectively; in 43 (40.5%) patients, tumors were classified as papillary, not otherwise specified. Half (53) of patients had hereditary origin of pRCC. Median estimated OS of the entire cohort was 37.5 mon. There was no difference in survival between patients with hereditary or sporadic pRCC (p=0.80) or among patients with different subtypes of pRCC (p=0.79). On univariate analysis, elevated serum corrected calcium, elevated lactate dehydrogenase, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio and presence of malignant ascites significantly affected the patients&[prime] prognosis. Corrected Calcium (p=0.03) and NLR (p=0.004) were found to be independent predictors of ACM on multivariate analysis. Conclusions To our knowledge, this is the largest single center series evaluating survival and predictors of ACM within patients with metastatic pRCC. OS was comparable between different subtypes of metastatic pRCC. Elevated NLR and serum corrected calcium are significantly associated with worse OS. Future validation in larger multi-institutional cohorts could justify incorporating corrected calcium and NLR in nomograms predicting ACM in metastatic pRCC. Funding Intramural research program at National Institutes of Health
Authors
Abhinav Sidana
Amit Jain Meet Kadakia Akhil Muthigi Louis Krane Martha Ninos Julia Friend Johanna Shih Ramaprasad Srinivasan |
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PD04-02 |
Adjuvant sunitinib in patients with high risk renal cell carcinoma: Subgroup analyses from S-TRAC trial |
Kidney Cancer: Advanced (including Drug Therapy) I | 17BOS |
Abstract: PD04-02 Sources of Funding: The study was funded by Pfizer Inc. Introduction Adjuvant sunitinib (SU; 50 mg daily, schedule 4/2) significantly improved disease-free survival (DFS) vs. placebo (PBO) in patients with locoregional renal cell carcinoma (RCC) at high risk of tumor recurrence after nephrectomy (hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.59-0.98; P=0.03, median: 6.8 vs. 5.6 years, respectively). We report new details on study population, treatment, pattern of recurrence, and the relationship between baseline factors and DFS. Methods Treatment exposure was assessed by treatment group during cycles. Disease recurrence was based on centrally confirmed imaging and/or histological findings. Subgroup analyses of DFS were conducted to explore the potential influence of baseline factors including, modified UISS criteria (T3 low, T3 high, T4-Any T, N+, and T3 high+T4-Any T, N+), age (<45, 45-65, ≥65 years), gender (male, female), Eastern Cooperative Oncology Group performance status (ECOG PS; 0, ≥1), weight (18.5≤BMI<25, 25≤BMI<30, BMI≥25, BMI≥30), and neutrophil-to-lymphocyte ratio (≤3, >3). Other baseline risk factors explored in the subgroup analyses included UISS criteria and Fuhrman grade. Results Overall, 615 patients were enrolled from 97 sites. >70% of patients received SU treatment for ≥6 cycles (~8 months) and 56% completed the full 1-year treatment. A total of 97 patients (31.4%) in the SU arm and 122 (39.9%) in the PBO arm developed metastatic disease recurrence. Most common sites of distant recurrence (SU:PBO) were lung (13%:16%), lymph node (7%:9%), and liver (4%:5%). The benefit of adjuvant sunitinib over placebo (HR<1) was observed across several subgroups of patients (Table 1). Additional subgroups analyses, including detailed Fuhrman grades and UISS criteria, will be presented._x000D_ _x000D_ _x000D_ _x000D_ _x000D_ _x000D_ Conclusions The subgroup analyses showed improved DFS with adjuvant SU vs. placebo in several subgroups. These results support the primary analysis showing benefit for adjuvant SU in patients with RCC at high risk for recurrent disease after nephrectomy. Funding The study was funded by Pfizer Inc.
Authors
Allan Pantuck
Jean-Jacques Patard Anup Patel Alain Ravaud Robert J Motzer Hardev S Pandha Daniel J George Yen-Hwa Chang Bernard Escudier Frede Donskov Ahmed Magheli Giacomo Carteni Brigitte Laguerre Piotr Tomczak Jan Breza Paola Gerletti Mariajose Lechuga Xun Lin Michelle Casey Michael Staehler |
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PD04-03 |
Survival following neoadjuvant targeted therapy and cytoreductive nephrectomy in mRCC patients with tumor thrombus; a contemporary multi-institutional series |
Kidney Cancer: Advanced (including Drug Therapy) I | 17BOS |
Abstract: PD04-03 Sources of Funding: none Introduction Cytoreductive nephrectomy (CN) for metastatic renal cell cancer (mRCC) with tumor thrombus is complex and pre-surgical targeted therapy may be used in selected patients who have a very limited life expectancy. The purpose of this study was to evaluate overall survival (OS) for mRCC patients with thrombus treated with pre-surgical therapy prior to CN compared to upfront cytoreductive surgery. . Methods Comprehensive data was reviewed for 486 mRCC patients with tumor thrombus treated surgically between 2000 to 2015 at six centers. Patients were divided into two groups: PSCN, (pre-surgical therapy +CN; N=39); upfront CN (n=447).Patients were stratified using IMDC criteria into risk groups (61 patients excluded for missing data) and OS compared using the Kaplan Meier method. Results Thrombus level (Neves) was 0,1,2,3, and 4 in 131(29.3%), 59(13.1%),154(34.4%), 61(13.6%) and 42 (9.4%) in upfront CN patients and 13 (13.3%),10 (25.6%), 9 (23.1%), 5(12.8%) and 2 (5.1%) in PSCN patients. _x000D_ _x000D_ After risk stratification, 26/39 (66.6%) PSCN and 209/387 (54.0%) upfront CN patients were IMDC intermediate risk. Median OS (IQR) month was not different for PSCN 26.2(13.1-na) vs. upfront CN 24.6(9.9-50.1) IMDC intermediate risk patients, (p=0.36). _x000D_ _x000D_ A total of 13/39 (33.3%) PSCN and 178/398 (47.5%) upfront CN patients were IMDC poor risk. Median OS (IQR) was not different for PSCN 38.1 months (10.1-49.4) vs. UCN 13.4 months (5.1-33.8) IMDC poor risk patients, (p=0.28)._x000D_ _x000D_ Conclusions No difference was identified in OS for patients who received neoadjuvant targeted therapy prior to CN compared to upfront CN. Future studies should evaluate the optimal use of neoadjuvant therapy in poor risk mRCC patients with thrombus. _x000D_ _x000D_ Funding none
Authors
Shivashankar Damodaran
Philippe E. Spiess Jose A. Karam Vitaly Margulis Viraj A. Master Jay D. Raman Wade J. Sexton Datta Patil Leonardo D. Borregales Haley Robyak Surena F. Matin Christopher G. Wood E. Jason Abel |
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PD04-04 |
The effect of anatomical location of retroperitoneal lymph node metastases on cancer specific survival in patients with clear cell renal cell carcinoma |
Kidney Cancer: Advanced (including Drug Therapy) I | 17BOS |
Abstract: PD04-04 Sources of Funding: None Introduction Positive nodal status and the number of positive nodes are well known independent predictors of survival in renal clear cell carcinoma (ccRCC) patients. However, no study has ever tested whether the location of nodal metastases does affect cancer specific survival (CSS) in ccRCC patients. Methods Among 2,884 patients treated with nephrectomy at two European Tertiary Care Centers, 419 (14.4%) underwent open extended retroperitoneal lymph node dissection (LND) defined as the removal of hilar, side-specific (paraaortic or pre-retrocaval) and interaortocaval nodes. Cox regression analyses were used to assess the effect of the area involved (hilar vs. side-specific vs. interaortocaval) and the number of anatomical areas affected by nodal disease (1 vs. 2 vs. 3 areas) on CSS. Multivariable analyses were adjusted for age, pathologic T stage, metastases at diagnosis and Fuhrman grade. Results ccRCC patients who were selected for nephrectomy and extended LND (n=419) showed pT1-pT2 in 37.4%, pT3 in 56.1% and pT4 in 6.4% of patients. Mean tumor size was 9 cm (median 8.3, range 1-23). Overall, 95 patients (22.9%) showed nodal disease at final pathology. Mean number of nodes removed was 15 (range 3-58). Hilar nodes vs. paraaortic/precaval vs. interaortocaval were found positive in 11% vs. 18% vs. 12% of the cases, respectively. In 46 (11%), 26 (6.2%) and 23 (5.5%) cases 1, 2 or all retroperitoneal nodal areas were affected, respectively. Among patients with 1 positive nodal site, 26% of patients were positive only in the interaortocaval area and 54.3% only in side-specific station. Among patients with 2 positive nodal areas, 3.8% had hilar and interaortocaval areas involved but not side-specific one, and 53.8% had side-specific and interaortocaval areas involved but not hilar one. Mean follow up period of 75.1 months. CSS at 1 and 2 years resulted 58% and 40% vs. 56% and 28% vs. 37% and 30% for patients with 1, 2 or 3 areas affected by nodal disease (p=0.5), respectively. At MVA, the number of nodal stations involved by disease did not affect CSS (all p>0.5). Conversely, the presence of nodal disease in the interaortocaval area resulted an independent predictor of CSS (Hazard Ratio 1.8, p=0.05). Conclusions When ccRCC patients harbour nodal disease, its spreading is not systematic and can occur at any nodal station without involving the others. However, the number of anatomical areas involved by nodal invasion does not affect CSS. Conversely, presence of interaortocaval positive lymph nodes is an independent predictor of CSS in RCC patients. Funding None
Authors
Alessandro Nini
Alessandro Larcher Carlo Terrone Alessandro Volpe Fabio Muttin Francesco Ripa Federica Regis Roberta Lucianò Alberto Briganti Roberto Bertini Francesco Montorsi Umberto Capitanio |
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PD04-05 |
RADICAL NEPHRECTOMY AND CAVO-ATRIAL THROMBECTOMY ON NORMOTHERMIC CARDIOPULMONARY BY-PASS AND BEATING HEART: OUR EXPERIENCE |
Kidney Cancer: Advanced (including Drug Therapy) I | 17BOS |
Abstract: PD04-05 Sources of Funding: NONE Introduction Usually, kidney cancer with cavoatrial extension is managed with cardiopulmonary by-pass (CBP) and deep hypothermia circulatory arrest (DHCA). _x000D_ In this study, we aim to report the feasibility, safety and effectiveness of radical nephrectomy with cavoatrial thrombectomy on normothermic CPB and beating heart._x000D_ Methods Through a laparotomic median incision, the urological equipe mobilised the colon and exposed the kidney. The renal vascular pedicle was exposed and the radical nephrectomy with adrenalectomy was performed. The right or left renal veins, that were obstructed by neoplastic thrombus (NT), were isolated. The liver was mobilized to allow the exposition of the intra and supra hepatic inferior vena cava (IVC), completely occupied by the NT. Sternotomy and pericardiothomy were performed by the heart surgery equipe. Aortic arch, superior VC and the IVC just above iliac veins were cannulated. On normothermic CBP and beating heart, right atriotomy and a “J� incision on IVC were simultaneously performed. At the same time, the heart surgeons and urologists removed the NT from the right atrium (RA) and pulmonary artery (PA), the left or right renal vein (RV) and the IVC. The IVC wall was resected only if infiltrated by the thrombus. RA and IVC were closed and the patient was weaned from CBP. Results We treated 8 patients (pts; range 51-74 yrs) affected by renal tumor with a NT extended from the right (3 pts) or the left (4 pts) RV to all IVC and to the RA. The diagnosis was incidental in 3 pts. One pt had a previously cardio-pulmunar by-pass. In one case the thrombus partially involved the right supra hepatic veins and the left renal vein; in other patient the thrombus jutted out a right branch of PA. Distant metastasis were detected in 3 pts. A significant coronary disease was diagnosed in 1 patient and was contemporarily resolved with CABG._x000D_ Median CPB time: 113 min (range 40-240); Surgical time: 380 min (range 360-440). Estimated blood loss 800 ml (range 300-2000). Autologous blood transfusion: 700 ml (range 500-1000)_x000D_ Intensive care stay: 4 days (range 1-7). Post operative in-hospital stay: 9,5 days (range 7-20). Post operative complications: atrial fibrillation in 1 case; anaemia in 1 case treated with blood transfusion; intestinal ischemia in 1 pt with nodal involvement of mesenteric artery and who died one day after surgery._x000D_ A post-surgical transthoracal echocadiography demonstrated regular parameters without any residual thrombus in RA and normal cardiac function in all pts. The 1-month post operative total body CT showed a regular IVC with no signs of persistent disease._x000D_ The median CSS was 23 months (range 7-38)._x000D_ Conclusions In our experience, management of T3c kidney cancer with a beating heart normothermic CBP appears a feasible, safe and effective technique. As neither hypothermia nor heart arrest are needed, our technique improves patient recovery and reduces risks for complications. Furthermore, with cannulation of lower IVC, other vascular access for lower venous return are not necessary. Funding NONE
Authors
ELENA STRADA
ANTONIO GALFANO silvia secco GIOVANNI PETRALIA dario di trapani CLAUDIO FRANCESCO RUSSO ALDO MASSIMO BOCCIARDI |
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PD04-06 |
Robot assisted radical nephrectomy and inferior vena cava thrombectomy: surgical technique, perioperative and oncologic outcomes |
Kidney Cancer: Advanced (including Drug Therapy) I | 17BOS |
Abstract: PD04-06 Sources of Funding: none Introduction Radical nephrectomy with Inferior vena cava (IVC) thrombectomy for renal cancer is one of the most challenging urologic surgical procedures. We describe surgical technique and present perioperative and oncologic outcomes of 35 consecutive cases of completely intracorporeal robot-assisted radical nephrectomy with IVC level I (5.7%) II (65.7%) and III (28.6%) tumor thrombectomy treated at two tertiary referral centers. Methods Thirty-five consecutive patients with renal tumor and IVC thrombus were treated between July 2011 and September 2016. Baseline, perioperative and follow-up data were collected into prospectively maintained IRB approved databases. Key steps of surgery include: a meticulous isolation of IVC; the isolation and sealing of all lumbar and collateral vessels, a full monolateral retroperitoneal dissection for staging purpose and to have a complete control of IVC; isolation of left renal vein, Tourniquet placement and infrarenal IVC control. IVC incision and thrombectomy; cava suture with 3/0 visi-black monocryl or 5/0 goretex; restoration of IVC flow; nephrectomy. We report perioperative and oncologic outcomes of 35 consecutive patients treated in two tertiary referral centers. Results All procedures were successfully completed; open conversion was necessary in one case (2.8%). Median operative time was 300 minutes. Twenty-one patients (68.6%) did not experience any complication. Ten patients (28.6%) required blood transfusion (Clavien grade 2); one patient (2.8%) had a Clavien grade 3a complication (gastroscopy); two patients (5.7%) had Clavien grade 3b complications (reintervention due to bleeding from adrenal gland and subphrenic ascess requiring drainage, respectively); one patient (2.8%) experienced a PRESS syndrome requiring ICU admission (Clavien 4a). _x000D_ Out of 13 patients who underwent cytoreductive nephrectomy and IVC thrombectomy, only one patient died of disease progression 14 months postoperatively. Both 2-yr cancer specific and overall survival rates in this subpopulation were 88.9%._x000D_ Twenty-two patients received surgery with curative intent and 5 of these experienced disease recurrence: 2-yr metastasis free, cancer specific and overall survival rates were 56%, 100% and 94.4%, respectively._x000D_ Conclusions Robotic IVC thrombectomy is a challenging surgical procedure. In tertiary referral centers this procedure is feasible, safe and associated with favorable perioperative outcomes and encouraging short term oncologic outcomes. Funding none
Authors
Giuseppe Simone
David Hatcher Mariaconsiglia Ferriero Francesco Minisola Leonardo Misuraca Gabriele Tuderti Salvatore Guaglianone Andre Luis De Castro Abreu Monish Aron Mihir Desai Inderbir Singh Gill Michele Gallucci |
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PD04-07 |
Higher PD-L1 mRNA level in clear cell renal cell carcinomas is associated with a favorable outcome |
Kidney Cancer: Advanced (including Drug Therapy) I | 17BOS |
Abstract: PD04-07 Sources of Funding: Supported by National Natural Science Foundation of China(Grand number 81572506) Introduction Renal cell carcinoma (RCC) is one of the most common urological tumors. The role of programmed cell death 1 ligand 1 (PD-L1) in RCCs in predicting outcome of the patients is yet unclear. Methods We analyzed the clinical and RNA-seq data of 522 kidney clear cell cancer (KIRC), 259 kidney papillary cell carcinoma (KIRP) and 66 kidney chromophobe (KICH) patients from The Cancer Genome Atlas (TCGA) database. Results In KIRC patients with high PD-L1 mRNA level and low PD-L1 mRNA level in tumors, the median overall survival periods were 45.0 and 37.1 months respectively (p=0.002). Multivariate Cox regression tests found that PD-L1 mRNA level in tumor was an independent predictor for overall survival status in KIRC patients (HR=0.7, 95% CI 0.5-0.9, p=0.007). However, no significant difference in overall survival status was found between high and low PD-L1 groups in KIRP and KICH cohorts.Gene-set enrichment analysis on the data from databases of TCGA and GSE53757 dataset in GEO showed that several pathways relating to immunological functions were activated in KIRCs with high PD-L1 mRNA expression, and glycolysis and epithelial-mesenchymal transition pathways relating to tumor progression and metastasis were up-regulated in KIRCs with low PD-L1 mRNA level. Conclusions In conclusion, higher PD-L1 mRNA level in KIRC tissues was associated with a favorable outcome due to the higher immunological responses in tumor tissues. Funding Supported by National Natural Science Foundation of China(Grand number 81572506)
Authors
Xianghui Ning
Yanqing Gong Shiming He Teng Li Jiangyi Wang Shuanghe Peng Jinchao Chen Jiayuan Liu Nienie Qi Yinglu Guo Kan Gong |
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PD04-08 |
Metastasectomy is Associated with Improved Survival in the Targeted Therapy Era for Metastatic Renal Cell Carcinoma |
Kidney Cancer: Advanced (including Drug Therapy) I | 17BOS |
Abstract: PD04-08 Sources of Funding: none Introduction In the targeted therapy era, many questions remain unanswered regarding the surgical management of metastatic renal cell carcinoma (mRCC). While currently there appears to be evidence to suggest a survival benefit from cytoreductive nephrectomy (CN), little is known about the survival benefit of CN combined with metastasectomy in the targeted therapy era. Methods From an institutional database of 2,906 patients surgically treated for renal masses between 2005 and 2016, we identified 80 patients with mRCC who underwent CN, 44 of whom also underwent a metastasectomy. Cox regression analysis was used to evaluate the survival benefit of metastasectomy combined with CN compared to CN alone. Additionally, we identified patients who achieved an R0 resection with metastasectomy. Results 44 patients underwent a total of 54 metastasectomies. 25.9% of removed metastases were bone lesions, 20.3% were adrenal, 12.9% were lung, and 12.9% were brain. Examining the temporal relationship of metastasectomy and CN, we found that 22.2% of metastasectomies occurred prior to CN, while 42.5% and 35.1% had resections during and after CN, respectively. Having a metastasectomy was associated with improved overall survival (HR=0.53, p=0.02, 95% CI 0.31-0.92). Additionally, achieving an R0 status after metastasectomy achieved and even greater survival benefit compared to non-R0 metastasectomy and CN alone (HR=0.26, p=0.006, 95% CI (0.1-0.69) (Figure 1). Conclusions Metastasectomy in the setting of CN was associated with improved overall survival in the targeted therapy era. Furthermore, the principle of achieving even greater cancer control, and thus improved overall survival, with an R0 resection holds firm. Funding none
Authors
Zeyad Schwen
Gregory Joice Hiten Patel Michael Gorin Mohamad Allaf Phillip Pierorazio |
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PD04-09 |
Should Patients with Metastatic Non-Clear Cell Renal Cell Carcinoma Undergo Cytoreductive Nephrectomy? |
Kidney Cancer: Advanced (including Drug Therapy) I | 17BOS |
Abstract: PD04-09 Sources of Funding: none Introduction Cytoreductive nephrectomy (CN) for patients with metastatic clear cell RCC (ccRCC) has been shown to be beneficial in 2 prospective clinical trials as well as several retrospective studies. However, studies on CN in patients with non-clear cell RCC(nccRCC) are scarce and conflicting. Our aim was to evaluate if CN was associated with a survival advantage for patients with metastatic nccRCC. Methods We retrospectively reviewed the clinical characteristics and outcomes of patients with metastatic nccRCC who either underwent CN followed by systemic therapy or were treated with systemic therapy alone (no CN), and were followed at our institution prior to January 2016. Fisher’s exact test, chi-square and Kruskal-Wallis tests were used to compare demographic and clinical characteristics of the patients. Overall Survival (OS) was estimated using Kaplan-Meier product-limit estimator and modeled with Cox proportional hazards regression. Results 129 patients with metastatic nccRCC underwent CN and 306 patients did not. Median overall survival for the CN and no CN groups were 1.49 and 0.59 years, respectively (p<0.001). Patient demographic characteristics are summarized in Table 1. 3-year survival probabilities were 0.04 and 0.23 for the no CN group and CN group, respectively (p<0.001, Figure 1). CN group had lower rates of death compared to the no CN group (HR:0.40; 95% CI:0.28 – 0.56; p<0.001). Larger tumor size, lower ECOG performance status and higher T stage were found to be independent risk factors for worse overall survival. Conclusions CN in the setting of nccRCC was associated with an apparent survival advantage, and should be performed in well-selected patients with metastatic nccRCC. Funding none
Authors
Sarp Keskin
Firas Petros Kai-jie Yu Yara Aboshady Leonardo Borregales Patrick Kenney Surena Matin Jose Karam Christopher Wood |
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PD04-10 |
External Validation of the Mayo Clinic Stage, Size, Grade, and Necrosis score in patients with renal cell carcinoma and venous tumor thrombus |
Kidney Cancer: Advanced (including Drug Therapy) I | 17BOS |
Abstract: PD04-10 Sources of Funding: none Introduction Several prognostic tools have been developed for patients with renal cell carcinoma (RCC). However, those calculators usually consider T3 tumors a single entity and little is known of their performance in patients with tumor thrombus. We assess the value of the Mayo Clinic Stage, Size, Grade, and Necrosis (SSIGN) score for prognosis of cancer-specific survival (CSS) in a large multicenter patient cohort with RCC and venous tumor thrombus. Methods The records of 846 patients collected by 17 international centers within the International Renal Cell Carcinoma-Venous Thrombus Consortium were retrospectively analyzed. Patients were treated with radical nephrectomy and tumor thrombectomy from 1971 to 2014. SSIGN scores were assigned (Table 1) and grouped in the analysis as in prior validation studies. Kaplan-Meier and Cox regression analyses examined CSS. Harrell&[prime]s concordance index was calculated. Results Median follow-up was 35 months (interquartile range [IQR], 11-68 months) in the 390 patients alive at last follow-up; 456 (53.9%) died of any cause and 351 (41.5%) died of RCC. The median primary tumor diameter was 9 cm (IQR, 7.0-11.4). Tumor stage, grade, and necrosis distributions are shown in Table 1. The median SSIGN score was 7 (IQR, 5-9). All SSIGN features were significantly associated with CSS in univariate analysis. All but tumor size remained significant after controlling for other factors (Table 1). Harrell's concordance index was 0.72 for prediction of CSS compared to 0.81-0.88 in prior studies, this study notably including pT3-T4 patients only. Five- and ten-year survival was significantly worse in patients with scores 7-9 and 10+. Figure 1 shows survival curves. Conclusions This analysis of the largest reported patient cohort with RCC and tumor thrombus demonstrates prognostic utility of the SSIGN score though pT3 subclassification was not considered in the original tool development. This may serve as a useful clinical tool in patients with tumor thrombus for follow-up counseling and clinical trial design. Funding none
Authors
Adam Lorentz
Caroline Tai Umberto Capitanio Joaquin Carballido Gaetano Ciancio Siamak Daneshmand Christopher Evans Paolo Gontero Axel Haferkamp Markus Hohenfellner William Huang EstefanÃa Linares Espinós Juan MartÃnez-Salamanca James McKiernan Francesco Montorsi Sascha Pahernik Juan Palou Raj Pruthi Paul Russo Douglas Scherr Martin Spahn Carlo Terrone Derya Tilki Cesar Vera-Donoso Daniel Vergho Eric Wallen Richard Zigeuner John Libertino Viraj Master |
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PD04-11 |
Delay of the Initiation of Systemic Therapy after Cytoreductive Nephrectomy is Not Associated with Worse Overall Survival |
Kidney Cancer: Advanced (including Drug Therapy) I | 17BOS |
Abstract: PD04-11 Sources of Funding: none Introduction Cytoreductive nephrectomy (CN) remains a mainstay in the treatment of metastatic renal cell carcinoma (mRCC). Prior literature has shown around 2/3rds of patients do not receive timely systemic therapy (ST) after CN, however there is limited understanding of how a delay affects progression and survival. Our aim was to identify whether a delay of the initiation of ST was associated with worse overall survival as well as to further characterize the reasons for a delay. Methods From an institutional database of 2,906 patients surgically treated for renal masses between 2005 and 2016, we identified 70 patients who underwent CN for mRCC and who were initiated on ST in the adjuvant setting. Cox regression analysis was used to evaluate whether delays in systemic therapy > 3 months and > 6 months were predictive of worse overall survival. Results Of the 70 patients, the majority had a favorable ECOG performance status (90% ECOG 0-1, 10% ECOG 2-3) while only 3 patients had brain metastasis at time of CN. Median age at diagnosis was 60 years. Our cohort had a 2-year overall survival of 60.8% from diagnosis and 49.4% after initiation of ST with a median follow-up of 27.1 months. Median time to ST after CN was 3 months (IQR 1.53-6.77). 94.2% of patients received targeted therapy while the remainder were treated with IL-2. Delays in initiating ST after CN were not associated with worse overall survival > 3 months after CN (HR = 0.64, p= 0.387, 95% CI 0.24-1.75) and from 3 to <6 months (HR = 0.5, p = 0.208, 95% CI 0.17-1.47). Interestingly, delays in ST > 6 months were associated with improved survival (HR = 0.19, p=0.017, 95% CI 0.74-0.017). Of the patients who experienced unintended delays, 42.3% were awaiting a clinical trial, 30.8% experienced delayed ST due to patient preference or poor follow-up, and 19.2% had a complication from surgical therapy. Conclusions A delay in the initiation of ST in patients with mRCC after CN did not appear to be associated with worse overall survival. The improved survival in patients who initiated ST > 6 months and trend towards improved survival at > 3 months after CN is likely related to an immortal time bias. Ongoing randomized controlled trials may provide more evidence regarding the optimal timing of ST after CN and the clinical implications of a delay in ST. Funding none
Authors
Zeyad Schwen
Hiten Patel Michael Gorin Gregory Joice Mohamad Allaf Phillip Pierorazio |
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PD04-12 |
Clinical correlation of patient-derived xenograft model using the ex-ovo avian embryo to predict targeted therapy tumor resistance in renal cell carcinoma |
Kidney Cancer: Advanced (including Drug Therapy) I | 17BOS |
Abstract: PD04-12 Sources of Funding: none Introduction Tyrosine kinase inhibitors (TKIs) are the mainstay of treatment for metastatic renal cell carcinoma (mRCC), with up to 20% of tumours exhibiting de novo resistance to TKIs. At present, there is no method of predicting response to systemic targeted therapy. We present a descriptive study of a prospective cohort of mRCC patients & the correlation of clinical outcomes to the responses predicted by patient-derived xenograft (PDX) models using the ex-ovo avian embryo. Methods We prospectively collected demographic, pathologic, & clinical data on 26 patients with mRCC undergoing cytoreductive nephrectomy. PDX models were tested in 5 patients. Six core biopsies were taken from each primary tumor. Cores were sectioned & engrafted directly onto embryonic day 9 chorioallantoic membranes (CAMs) of avian embryos & treated with topical sunitinib or a DMSO control. On day 6 post-engraftment, Doppler & contrast-enhanced ultrasound were performed to assess vascularity & perfusion of tumours grown on the CAM models. A composite vascularity & perfusion score was obtained and used to determine the presence or absence of a response to TKIs compared to the control. Tumours were considered TKI-sensitive if there was a response in ≥4 cores. Tumours with responses in ≤3 cores were considered TKI-resistant. Clinical progression on CT scan was based on RECIST criteria. Results Results are summarized in Table 1. All tumours demonstrated heterogeneous responses to TKIs in the PDX model. Using the criteria of ≥4 cores responding to TKI therapy, we would expect a good response in patient 3, who does not have evidence of clinical progression after 5 months of maintenance on sunitinib. Moreover, patient 3 had 3 cores engrafted from a metastatic deposit, which all responded well to sunitinib in the PDX model. Patients 1 & 2 continued to show signs of progression despite switching to alternative agents, and both have discontinued systemic therapy due to intolerable side effects or enrolment in another clinical trial respectively. Patients 4 & 5 have not started on systemic targeted therapy. Conclusions Further studies in a larger population are warranted to explore the potential of the PDX model to serve as a novel phenotypic biomarker in the prediction of targeted therapy tumor resistance in RCC. Funding none
Authors
Melissa Huynh
Matthew Lowerison Victor McPherson Hon Leong Nicholas Power |
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PD05-01 |
The Evolving Clinical Picture of Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS): A Look at 1310 Patients over 16 Years. |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Prostate & Genitalia I | 17BOS |
Abstract: PD05-01 Sources of Funding: Canadian Institute for Health Research Introduction Advancements in clinical phenotyping and treatment modalities seems to be changing the clinical face of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). We sought to retrospectively analyze trends in CP/CPPS patients presenting to our chronic prostatitis (CP) clinic for evaluation and treatment over a 16-year period. Methods CP/CPPS patients were evaluated between 1998 and 2014 with chronic prostatitis symptom index (CPSI) and comprehensive assessment allowing retrospective (1998-2009) and prospective (2010-2014) UPOINT categorization. Patients were then stratified in four cohorts, based on year of presentation: 1998-2001, 2002-2005, 2006-2009 and 2010-2014 and variations in symptom scores and patterns, UPOINT categorization and treatment modalities amongst cohorts were analyzed. Continuous variables were analyzed using ANOVA while categorical variables were analyzed using chi-squared test for trend in proportions. Results A total of 1349 patients with CP were evaluated in a single tertiary referral clinic. Bacterial prostatitis patients (n=39) were excluded. Mean age of the 1310 CP/CPPS patients was 44.7, while mean CPSI pain, urination, quality of life (QOL) and total scores were 10.6, 4.8, 7.9 and 23.3 respectively. Overall, the most prevalent UPOINT domain, urinary (U) (71.8%) predicted for a higher CPSI urination score (6.3), more frequent penile tip pain (37%), dysuria (48%) and more treatment with alpha-blockers (70%). Increase in UPOINT domains predicted higher CPSI pain, QOL and total scores. Pain location did not predict UPOINT domain or treatment modality. Trends over time included increased prevalence of psychosocial (P), organ (O) and tenderness (T) domains as well as increased use of alpha-blockers, neuromodulation and phytotherapy as treatment modalities. There was little variation in age, CPSI scores and pain locations over time. Conclusions The changing clinical face of CP/CPPS reflects the increased recognition of psychosocial and pelvic floor pathology along with the concomitant use of associated therapies. There was little variation of pain/urinary symptom patterns and QOL. The more things &[Prime]appear&[Prime] to change, the more they stay the same. Funding Canadian Institute for Health Research
Authors
R. Christopher Doiron
Victoria Tolls J. Curtis Nickel |
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PD05-02 |
Feasibility Testing of a Male Chronic Genital Pain Clinic to Identify Men with Chronic Unexplained Orchialgia |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Prostate & Genitalia I | 17BOS |
Abstract: PD05-02 Sources of Funding: none Introduction Chronic pain is an important public health issue across the world. Men with chronic unexplained orchialgia (CUO) are an understudied population, for whom there are significant knowledge gaps related to prevalence, demographics, etiology, and reliable treatment. This research begins to address these knowledge gaps. Methods This was a one-year feasibility study consisting of a convenience sample of men with chronic genital pain (non-pelvic pain) seen in an adult urology specialty clinic focused on men with CUO, and staffed by a nurse practitioner. Results A total of 228 men were evaluated in this half-day clinic (Figure 1): 107 were new referrals; 15 were scheduled for a second opinion; and 106 were previously evaluated for pain issues. In 125 men a diagnosis other than pain or pain at non-scrotal/testicular sites was identified, meaning that in 84% of men referred for “unexplained� orchialgia an actual cause was established. The algorithm for evaluation is shown in Figure 2. This is the first project to report the range of diagnoses associated with CUO in a given timeframe. After identifying etiologies, 20 men had true unexplained pain. This busy academic department sees over 38,000 visits a year, suggesting a prevalence for true CUO at < 1%. Conclusions Far fewer men than anticipated had truly unexplained chronic orchialgia. Offering a dedicated clinic for men with chronic genital pain provided rapid access to specialized expertise and accelerated diagnosis of etiologies for chronic genital pain. Conservative symptom management was the first course of treatment pursued during the timeframe of data collection. This specialized clinic decreases costs to the healthcare system, utilizing a staged screening strategy that maximized the value of tests and treatments offered, and by scheduling men with a specialized, but non-surgical, clinician. Future research will include ongoing data collection to achieve a larger sample size. Funding none
Authors
Susanne Quallich
Janis Miller Cynthia Arslanian-Engoren Anne Pelletier Cameron |
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PD05-03 |
Utility of Trigger Point Injection as an Adjunct to Physical Therapy in Men With Chronic Prostatitis/Chronic Pelvic Pain Syndrome |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Prostate & Genitalia I | 17BOS |
Abstract: PD05-03 Sources of Funding: None Introduction Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) is often associated with pelvic floor muscle spasm. While pelvic floor physical therapy (PT) is often effective, some men are unable to resolve their symptoms and have residual trigger points (TP). TP injection has been used for treatment in several neuromuscular pain syndromes. The objective of this study was to examine the efficacy and side effects of TP injection in men with CP/CPPS and pelvic floor spasm refractory to PT Methods Using an IRB approved Men's Health Registry we reviewed the records of all men with a diagnosis of CP/CPPS who received at least 1 TP injection. Patients were phenotyped with UPOINT (all had the T domain for tenderness of muscle) and symptoms measured with the NIH Chronic Prostatitis Symptom Index (CPSI). Response was measured by a 5 point Global Response Assessment (GRA) and change in CPSI (paired t test). For pelvic TPs, a pudendal block was done in lithotomy position and then each TP was identified transrectally by palpation. A nerve block needle was passed through the perineum into the TP confirmed by palpation. Between 0.5-1 cc was injected into each TP of a local anesthetic mixture (30:70 of 2% lidocaine and 0.25% bupivacaine). For anterior TPs, an ultrasound guided ilioinguinal block was done first and then each TP injected by direct palpation through the abdominal skin. Men were offered up to 3 sets of injections separated by 6 weeks each. Results We identified 37 patients who had a total of 68 procedures. 3 men had no followup after their first injection and were included for side effects but not for outcome. Indication was failure to progress on PT in 33, recurrent symptoms in 1 and refusal to do PT in 3. Mean age was 43.7 years (range 21-70) and median UPOINT domains was 3 (range 1-5). Initial total CPSI was 28.8+/-6.0. 16 men had 1 injection, 11 had 2 and 10 had 3. All had pelvic TPs injected and 9 also had anterior TPs. By GRA, 12 had significant improvement (35.3%), 10 had some improvement (29.4%), 11 had no change (32.3%) and 1 was worse (2.9%). Mean CPSI dropped from 28.7+/-6.1 to 21.8+/-7.2 (p<0.0001). 18 men had a drop of 6 or more points in CPSI (53%). Of note, none of 3 men who were noncompliant with PT had benefit. 3 men had temporary numbness in the lateral thigh after the injection (4.4%) and 1 had difficulty weight bearing on 1 leg for about 30 minutes. Conclusions TP injection in CP/CPPS patients as an adjunct to PT is well tolerated and leads to symptom improvement in about half, but is not a standalone cure. Durability and long term results are yet to be determined. Funding None
Authors
Anup Shah
Daniel Shoskes |
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PD05-04 |
Early Experience with Microsurgical Spermatic Cord Denervation in a Canadian Centre |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Prostate & Genitalia I | 17BOS |
Abstract: PD05-04 Sources of Funding: None. Introduction Microsurgical spermatic cord denervation (MSCD) is an effective surgical technique to manage chronic medically refractory orchalgia, but has not been widely accepted by Canadian Urologists. This paper reviews the early experience of a single Urologist in Canada Methods 18 consecutive testicular units underwent MSCD over a 48 months by a single surgeon in a Canadian centre. All patient's had reversible causes of pain ruled out and had a successful diagnostic spermatic cord block._x000D_ Results A total of 18 patients underwent microsurgical spermatic cord denervation by a single surgeon over 4 years. The average patient age was 45 years. The average pre-procedural pain score was 8.5/10. The average post procedural pain score in respond was 0.4/10. The overall success rates was 83% (15/18), with a complete response seen in 61% (11/18) and a partial but acceptable response in 22% (4/18). The failure rate was 17% (3/18) with these patients demonstrating no significant change in their postoperative pain scores. The complication rate was 11% (2/18) with 1 postoperative testicular loss and 1 postoperative hydrocele. The recurrence rates was also 11% (2/18) with these patients having a recurrence in their pain after 6 months of follow-up. Conclusions Chronic orchialaia is a challenging entity to treat with poor reported success rates in the literature for both medical and surgical treatments._x000D_ _x000D_ Our results are consistent with the medical literature._x000D_ _x000D_ Microsurgical spermatic cord denervation does offer a favourable success rate and acceptable complication rate and should be considered part of the armamentarium for the treatment of chronic medically refractory orchialgia. Funding None.
Authors
Darby Cassidy
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PD05-05 |
Microdenervation of the Spermatic Cord for Post Vasectomy Pain Syndrome- A Single Surgeon’s Experience |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Prostate & Genitalia I | 17BOS |
Abstract: PD05-05 Sources of Funding: none Introduction Post Vasectomy Pain Syndrome (PVPS) is an uncommon urological problem that remains a challenge to manage. We aim to evaluate the outcomes of patients who underwent microdenervation of the spermatic cord (MDSC) for PVPS at our institution. Methods A retrospective study of 161 patients who underwent MDSC by a single surgeon from March 2002 to October 2016. Pain was documented using the visual analogue scale (VAS). Spermatic cord block (SCB) was performed on all patients and success was defined as VAS ?1 for >4 hours. Patients who responded to a SBC were candidates for MDSC. All patients failed medical therapy prior to MDSC. All prior procedures for PVPS were performed elsewhere. Surgical success was defined as postoperative VAS of ?1. Results 29 patients underwent MDSC for PVPS. Median follow up was 37 months (1st quartile 20 months, 3rd quartile 100 months). Median duration of pain prior to surgery was 57 months (1st quartile 36months, 3rd quartile 112 months). Pain was bilateral in 14 (48%), left in 11 (38%) and right in 4 (14%) patients. 9 patients (31%) had worsening pain on ejaculation. Data on SCB was available on 23 patients with success rate of 96%. Median preoperative pain on VAS score was 7 (range 2-10). Median pain following SCB on VAS score was 0 (range 0-5). Median postoperative pain on VAS score was 0 (range 0-9). Success was obtained in 71% of patients and patients with involvement of multiple structures in the scrotum (ie: testis, epididymis, spermatic cord) are more likely to have a successful surgery, p=0.016. 5 patients failed a prior epididymectomy and 3 patients failed a vaso-vasostomy for PVPS and this had no correlation with the success of MDSC, p=0.89 Conclusions MDSC is successful and durable in 71% of our patients and is a valuable approach for PVPS especially when pain involves multiple structures in the scrotum (ie: testis, epididymis, spermatic cord). MDSC is equally as effective on patients who had previously failed a prior procedure for PVPS. All but three patients with PVPS had improvement in VAS following MDSC. No patient had a worsening VAS following MDSC. This is the largest study to date evaluating MDSC for the treatment of PVPS. Funding none
Authors
Wei Phin Tan
Peter Tsambarlis John Richgels Laurence Levine |
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PD05-06 |
PHYSICAL THERAPY FOR ORCHALGIA |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Prostate & Genitalia I | 17BOS |
Abstract: PD05-06 Sources of Funding: none Introduction Chronic pelvic pain and orchalgia are challenging conditions to treat in urologic practice. Recent research and treatment have begun to focus on musculoskeletal dysfunction as a major contributor to pelvic pain and orchalgia. The objective of this study is to assess the clinically reported outcomes of patients in our center that presented with orchalgia who underwent physical therapy._x000D_ Methods A retrospective chart review was conducted on men who initially presented to our practice with orchalgia from January 2009 to June 2016 and referred for pelvic floor physical therapy. Each patient had a urologic assessment prior to physical therapy referral. Patients were evaluated and treated by our physical therapy team according to any presenting musculoskeletal impairments/complaints. Treatments included pelvic alignment exercises, therapeutic stretching/strengthening, manual therapy, dry needling and biofeedback. Following treatment, a subjective global response measure was assessed based on patients&[prime] self-reports of improvement. Additionally, if available, NIH Chronic Prostatitis Symptom Index (NIH-CPSI) data was collected. Statistical analysis was performed in SAS 9.4 (SAS Institute, Cary, NC) where all P-values less than 0.05 were considered statistically significant. Results A total of 392 patient charts met inclusion criteria for this retrospective study. Average age was 42.8 years with mean longevity of symptoms of 32.8 months. 49.1% had co-existing urinary complaints. Pre-treatment average day pain was 4.5 (analog scale 1-10); worst day pain was 7.6. 83.2% of patients indicated their testicular pain was better, 16.1% reported no change and 0.7% reported worsening of their pain at average follow up of 6.4 months. 150 patients (38%) completed a NIH-CPSI questionnaire both pre and post treatment. Of these patients, those who reported improvement in their pain (n=138) had decrease in pain scores from average of 16.7 to 11.3, decrease in urinary score from 2.6 to 2.0, and improvement in quality of life score from 8.1 to 4.2; each was statistically significant (p<0.01). Patients who did not improve or had worsening of symptoms with physical therapy (n=12) did not have statistically significant improvement in pain, urinary or quality of life scores (p=0.36, p=0.78, p=0.17; respectively). Conclusions Physical therapy serves as a valid and effective treatment option for patients with orchalgia, following a comprehensive urologic examination. The significant subjective and objective improvement reported by this group of patients with no adverse side effects points towards early referral to a pelvic physical therapy practice. Funding none
Authors
Matthew Nielsen
Charles Gresham Erin Glace Courtney Anderson Hadiza Galadima Jessica Delong Jeremy Tonkin Ramon Virasoro Kurt McCammon |
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PD05-07 |
Role of PDE -5 inhibitor in the treatment of Chronic pelvic pain syndrome: A randomized control trial |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Prostate & Genitalia I | 17BOS |
Abstract: PD05-07 Sources of Funding: NONE Introduction Chronic prostatitis/Chronic pelvic pain syndrome (CP/CPPS) is a common urological problem of young males. Alpha blockers, antibiotics and analgesics are commonly used drugs for CP/CPPS but there are no treatment guidelines available. We evaluated the effectiveness of PDE5-inhibitors in CP/CPPS. Methods Total of 68 patients were randomized into two groups. Group A (n=32) received alfuzosin and levofloxacin (standard treatment) whereas group B (n= 36 ) received tadalafil 5mg (PDE 5 inhibitor) in addition to alfuzosin and levofloxacin for 6weeks.The groups were analyzed pre and post treatment with National Health Institute Chronic Prostatitis Symptom Index (NIH-CPSI), International Index of Erectile Function ( IIEF-5), International Prostate Symptom Score(IPSS), scores and uroflowmetry. Results Changes observed in the NIH-CPSI of group B at six weeks were greater than those at baseline (group A, ?8.4 vs. group B, ?18.0; p<0.05). The mean change in total IPSS from baseline was higher in group B than that in group A (group A, ?3.4 vs. group B, ?8.8; p <0.05). Change in IPSS-QOL index from baseline was significant in Group B (group A, -0.63 vs. group B,-2.03 ; p<0.05). Group B showed a significantly greater increase in the IIEF-EF score than group A (group A -0.7 vs. group B +6.4; p<0.05). Qmax pre and post therapy showed significant improvement in group B when adjusted for age (group A, -2.9 vs group B, +2.56; p<0.05). Conclusions PDE-5 inhibitor results in significant improvement in CP/CPPS symptoms and quality of life and is well tolerated. Funding NONE
Authors
Prabhjot Singh
Abhishek Shukla Prem Nath Dogra |
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PD05-08 |
Transcutaneous electrical nerve stimulation for treatment of refractory chronic pelvic pain syndrome in men: a prospective study. |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Prostate & Genitalia I | 17BOS |
Abstract: PD05-08 Sources of Funding: none Introduction Chronic pelvic pain syndrome (CPPS) presents a therapeutic challenge since 20–65% of all CPPS patients are refractory to conventional therapies. Transcutaneous electrical nerve stimulation (TENS) is an established treatment for chronic musculoskeletal pain and may also be a valuable option in pelvic pain. The aim of this study is to evaluate the effect of TENS for treating men with refractory CPPS Methods A consecutive series of 42 men treated with TENS for refractory CPPS was evaluated prospectively at 2 academic tertiary referral centers._x000D_ The effects of treatment were evaluated using the National Institutes of Health Chronic Prostatitis Symptom Index (0-43) at baseline and after 12 weeks of TENS treatment. _x000D_ Subjective (need to continue treatment to sustain the effect) and objective (improvement of NIH-CPSI Index > 50%) responses were assessed after 12 weeks of treatment. Adverse events related to TENS were also assessed._x000D_ Results After 12 weeks of treatment, a subjective response was obtained in 27 (62%) patients and an objective one in 14 (33%) patients. 08 patients showed a final score < 10. Quality of life (QoL) and urinary symptoms also improved significantly in those patients (p<0.001; 95%, CI). No adverse events related to TENS were noted. Conclusions TENS may be an effective and safe treatment for refractory CPPS in men, warranting randomized, placebo-controlled trials. Funding none
Authors
Yassine EL Abiad
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PD05-09 |
Pollen extract in association with vitamins (DEPROX 500 ®) versus Serenoa Repens in chronic prostatitis/chronic pelvic pain syndrome; a single center experience. |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Prostate & Genitalia I | 17BOS |
Abstract: PD05-09 Sources of Funding: none Introduction Chronic prostatitis/chronic pelvic pain syndrome are reported in literature ranging from 1 to 14,2%. Category III prostatitis is called chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), and by definition it is characterized by pelvic pain for more than 3 of the previous 6 months, urinary symptoms and painful ejaculation, without documented urinary tract infections from uropathogens. The focus of therapy is pain relief and in the last years the research is addressed to find some phitotherapic solutions. The aim of the present study was to assess the impact on the patient’s quality of life and symptoms of Deprox 500 ® in comparison with Serenoa Repens 320 mg. Methods This is a single-center randomized controlled trial, comparing the efficacy and the IPSS/NIH-CPSI score variation in patients with CP/CPPS. All consecutive patients with a diagnosis of CP/CPPS referred to our center from January 2016 to August 2016 were screened to be enrolled in this study. The first outcome was the evaluation of IPSS/NIH-CPSI score variation and the assessment of the quality of life and symptoms at the end of the therapy. The second outcome was to evaluate the role of comorbidity in the CP/CPPS therapy. Patients with medical treatment for LUTS such as alfa-blocker or 5-ARI, major concomitant diseases and with residual urine volume >50 ml were not included in this study. All patients were randomized in two groups; one was treated with Deprox 500 ® mg 2 tabs/day for 6 weeks and the other with Serenoa Repens 320 mg, 1 tab/day for 6 weeks. Results A total of 63 patients concluded the therapy and were included in the data analysis. Of those patients 29 were treated with Deprox 500 ® and 34 with Serenoa Repens. The mean score variation was IPSS -12,7 + 4.3 for Deprox and IPSS – 7.8 + 4.7 for Serenoa Repens (p-value = 0.0005) and NIH-CPSI -17.3 + 3.1 for Deprox and NIH-CPSI – 13.6 + 4.8 for Serenoa Repens (p-value = 0.0016). By accounting only the symptoms part of NIH-CPSI questionnaire, the mean score variation reported was – 11.5 + 2.5 for Deprox group and – 9.02 + 4.0 for Serenoa Repens group (p value = 0.009321). Furthermore, by analysing the comorbidity subgroups, in patients with hypertension the mean IPSS score variation was -14.3 + 3.2 for Deprox and – 9.02 + 4.0 for Serenoa Repens. Conclusions Deprox 500 ® appears to be more effective in patients with CP/CPSI; improving IPSS and NIH-CPSI scores up to 74.5% and 84.5% respectively. Furthermore, in patients with hypertension the antioxidant effect of Deprox 500 ® reduces the mean IPSS score of 82.7%. Funding none
Authors
Nicola Macchione
Michele Catalani |
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PD05-10 |
Antibiotic prophylaxis prior to urinary catheter removal after radical prostatectomy does not prevent urinary tract infections: A randomized controlled clinical trial |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Prostate & Genitalia I | 17BOS |
Abstract: PD05-10 Sources of Funding: University of Rochester Department of Urology Introduction In an effort to reduce the incidence of symptomatic urinary tract infections (UTI) after urinary catheter removal after radical prostatectomy, many urologists administer prophylactic antibiotics. Currently, there are no consensus recommendations on this subject. Our objective was to determine whether antibiotic prophylaxis at urinary catheter removal after radical prostatectomy reduces the incidence of clinical UTIs. A secondary objective was to determine if prophylactic antibiotics increase in the incidence of Clostridium difficile (C. diff) infection. Methods Patients undergoing radical prostatectomy were enrolled (n=175) in an IRB approved prospective randomized controlled clinical trial. 4 patients were excluded for postoperative complications and 4 withdrew. The treatment group (n=83) was given ciprofloxacin the evening prior to and morning of catheter removal. The control group (n=84) received no antibiotics. All patients received up to 24 hours of routine peri-operative antibiotics. Catheters were removed at 7-10 days after surgery. Urine cultures (UC) were obtained preoperatively, at catheter removal, 3-12 months postoperatively and with development of any UTI symptoms. Clinical UTI was defined as positive UC with at least one organism >100,000 cfu/ml with at least 1 UTI symptom/sign. Statistical analyses were performed with two-sample T test for continuous variables, and Pearson&[prime]s chi-square or Fisher&[prime]s exact test for categorical values. The Jennison and Rurnbull method was used to determine futility. Results There was no significant difference in patient characteristics, perioperative data, post-operative readmissions or complications. There was no significant difference in the incidence of UTI: 5 (6.02%) in the antibiotic group and 5 (5.95%) in the control group (p=1). There was no significant difference in the incidence of C. diff infections between the two groups: 0 (0%) in the antibiotic group and 3 (3.57%) in the control group (p=0.24). There were no significant differences in postoperative complications or readmissions. Enrollment was discontinued after Interim analysis revealed a futility index of 98.22%. Conclusions This prospective randomized controlled trial provides evidence that antibiotic prophylaxis at the time of urinary catheter removal after radical prostatectomy does not reduce the incidence of clinical UTIs. We also did not find any association between the incidence of C. diff infection and administration prophylactic antibiotics. Funding University of Rochester Department of Urology
Authors
Claudia Berrondo
Changyong Feng Janet Kukreja Edward Messing Jean Joseph |
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PD05-11 |
Contemporary perceptions of human papillomavirus and penile cancer – perspectives from a national survey |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Prostate & Genitalia I | 17BOS |
Abstract: PD05-11 Sources of Funding: none Introduction To assess the contemporary knowledge of Human Papillomavirus (HPV) and its association with penile cancer in a nationwide cohort from the US. Methods We utilized the Health Information National Trends Survey (HINTS), a cross-sectional telephone survey performed in the US initiated by the National Cancer Institute. The most recent iteration, HINTS 4 Cycle 4, was conducted in mail format between August 19 and November 17, 2014. Primary endpoints included knowledge of HPV and its causal relationship to penile cancer. Baseline characteristics included sex, age, education, race & ethnicity, income, residency, personal or family history of cancer, health insurance status, and internet use. Multivariable logistic regression assessed predictors of HPV and penile cancer knowledge. Results An unweighted sample of 3,376 respondents was extracted from the HINTS 4, Cycle 4. Whereas 64.4% of respondents had heard of HPV, only 29.5% of these were aware that it could cause penile cancer. Men were significantly less likely to have heard of HPV than women (OR 0.32 95% CI 0.24-0.43). Older age; African-American, Asian, and "other race"; being married; from a lower education bracket; having a personal cancer history; and those without internet access were significantly less likely to have heard of HPV. None of our examined variables were independent predictors for the knowledge of the association of penile cancer and HPV. Conclusions Our analysis of a large, nationally representative survey demonstrates that the majority of the American public is familiar with HPV but lack a meaningful understanding between this virus and penile cancer. Primary care providers and specialists should be encouraged to intensify counseling about this significant association as a primary preventive measure of this potentially fatal disease. Funding none
Authors
Michael E. Zavaski
Christian P. Meyer Julian Hanske Björn Löppenberg Nicolas von Landenberg Philipp Gild Alexander P. Cole Mani Menon Felix K.H. Chun Margit Fisch Jairam R. Eswara Mark Preston Adam S. Kibel Maxine Sun Quoc-Dien Trinh |
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PD06-01 |
CLOVIZ: Clinical Outcomes Visualization of IMDC Criteria in Metastatic Renal Cell Carcinoma for Patient-Centered Decision Making |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making I | 17BOS |
Abstract: PD06-01 Sources of Funding: Urology Care Foundation Research Scholar Fund and the Society for Urologic Oncology Introduction The International Metastatic Renal Cell Carcinoma Database (IMDC) Criteria (Heng Criteria) is a validated risk prediction tool for patients with metastatic renal cell carcinoma (mRCC). It provides valuable prognostic data but clinical application can be challenging due to limited available tools. We created an interactive visualization to facilitate clinical application of IMDC Criteria. Methods A multi-institutional cohort of 436 patients with mRCC was used to create an interactive visualization depicting IMDC Criteria at the patient level. Usability testing was performed with non-medical lay-users and medical oncology fellows. Subjects used the tool to calculate median survival times based on IMDC Criteria in six increasingly complex clinical scenarios. Confidence using the tool was surveyed and measured along a 5-point Likert scale. Results The interactive visualization is available at http://www.cloviz.org. 400 lay-users and 15 medical oncology fellows completed clinical scenarios and surveys. Overall, lay-users were able to obtain the exact correct answer in 48% of scenarios, compared to 60% of medical oncology fellows. The proportion of exact correct answers decreased with increasing task complexity, but the proportion of answers within 25% of the expected answer remained stable at 68-78% for lay-users and 73-93% for medical oncology fellows. When surveying usability, 65% of lay-users felt it was easy to use, compared to 80% of fellows, and 83%-87% felt it became intuitive with increasing use, respectively. Among lay-users, 69-77% were confident selecting lab values and drug names, compared to 87-93% of medical oncology fellows. 75% of lay-users felt it helped them better understand survival in mRCC. 68% of lay-users wanted to use a similar tool with their doctor, while 87% of medical oncologists wanted to use this with patients and 93% wanted to incorporate it into their clinical practice in some way. Conclusions A graphical method of interacting with a validated nomogram for mRCC outcomes provides real-time individual level data that can be used by untrained nonmedical users and medical oncologists, with potential for use in the clinic setting. Funding Urology Care Foundation Research Scholar Fund and the Society for Urologic Oncology
Authors
Anobel Odisho
Sumanta Pal Michael Shapiro Ashley Dixon J. Connor Wells Jose Manuel Ruiz-Morales Toni Choueiri Daniel Heng John Gore |
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PD06-02 |
Decisional quality and the impact of shared decision making among patients with urologic stone disease |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making I | 17BOS |
Abstract: PD06-02 Sources of Funding: Supported in part by the H. H. Lee Research Program. Introduction Various practice guidelines advocate shared decision making (SDM) for preference-sensitive decisions. Decisional quality is a multidimensional construct that can be used to measure the impact of the decision making process. Decisional quality has been defined to include decisional conflict, disease specific knowledge, patient satisfaction, and sense that SDM has occurred in the visit. For patients that have urologic stone disease, little is known about decisional quality and shared decision making. Methods We identified new patients scheduled for evaluation of kidney stones within a large academic clinical setting. After the initial consultation, we conducted a patient feedback telephone survey. The survey instrument included the 4-item SURE instrument to evaluate decisional quality, 3 related items which measured specific concepts related to decisional conflict, 10 items measuring disease-specific knowledge, 1 item addressing patient satisfaction, the Net Promoter Score survey to measure patient loyalty, three items from the Shared Decision Making Questionnaire (SDM-Q), and a single question querying health literacy. We also evaluated their treatment preferences before and after the consultation. Results A total of 29 out of 30 patients we contacted participated in the survey. Fourteen patients had perfect SURE scores (SURE=4), indicating no decisional conflict, while 15 patients had scores indicating high decisional conflict after seeing the counseling urologist. Patients with perfect SURE scores reported improved perceived interactions with their urologist, feeling more included in the treatment decision (p = 0.0063), and were more likely to discuss treatment options (p = 0.0052). The total SDM scores indicated that patients without evidence of decisional conflict reported more perceived shared decision making (p = 0.0009). These patients also had higher Net Promoter Scores (higher intended physician loyalty) (p = 0.0086). There was no significant difference between the two groups in health literacy scores or disease specific knowledge scores. Conclusions This cross-sectional analysis of patients with nephrolithiasis suggests that lower decisional conflict after a urologic consultation for nephrolithiasis is associated with more shared decision-making and with higher levels of patient loyalty after consultation. Our data identifies specific areas that can be targeted with pre-consultation interventions aimed at building a solid foundation of shared decision making with the intent of improving decisional quality. Funding Supported in part by the H. H. Lee Research Program.
Authors
Matthew Pollard
Joseph Shirk Casey Pagan Sylvia Lambrechts Lorna Kwan Nazih Khater Christopher Saigal |
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PD06-03 |
Personalized Decision Support for Localized Prostate Cancer: Results of a Multi-site Randomized Trial |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making I | 17BOS |
Abstract: PD06-03 Sources of Funding: NIH 5R01NR009692 Introduction Men with new localized prostate cancer (LPC) face a confusing set of care options. The purpose of our trial was to evaluate decisional conflict (DC) after access to decision support, the Personal Patient Profile-Prostate (P3P), or usual care (UC). Methods Men were randomized to P3P+UC or UC alone after responding to a baseline query of influential personal factors. The P3P, a tailored educational/coaching tool, was provided prior to the options review consult at 7 practices across the US. The low literacy DC scale (DCS) was administered at baseline and 1 month. One-month DCS (total score (TS) and 4 subscales) was compared by group using ANCOVA. Factors previously identified as influencing DC (age, education, partner status, working status, income, race, D&[prime]Amico risk levels, information resources, baseline/one-month decisional status, baseline DCS and study site) were assessed univariately and then adjusted in multivariable analysis. Backwards model selection was used and two-way interactions checked. Results 392 (198 P3P, 194 UC) men were randomized. 309 (155 P3P, 154 UC) men returned 1 month DCS. No significant study group effect was indicated for the TS or subscales univariately. In multivariable analyses, P3P marginally reduced TS conflict (LSmean=3.19, P=0.06) and significantly reduced conflict related to being informed (LSmean =6.99, P=0.0004). There were significant group interactions with partner status for the TS and income for the informed subscale. Unpartnered P3P users had significantly lower total conflict compared to partnered men in both groups (P=0.0005) and UC unpartnered men (p=0.03). Among low income men, UC had significantly higher conflict on the informed subscale compared to P3P users (P<0.0001) and higher income men in both groups (P<0.0001). Overall, partnered and/or low income men had higher conflict in TS, as well as in 3 subscales. Men undecided at 1-mo had significantly higher conflict in TS and all subscales. Study site significantly impacted the TS, informed and value clarity subscales. Men who were working or used the Internet for information had significantly lower conflict in the value clarity subscale. Low D&[prime]Amico risk level was significantly associated with higher uncertainty. Conclusions The P3P is superior to UC with regard to informing men about LPC options. Our results have implications for who is at risk for greater DC. Men with lowest risk disease, and likely more options, are more uncertain. Men with partners/spouses and low income men are more likely to be conflicted. Decision support for partners is an important next step. Funding NIH 5R01NR009692
Authors
Donna Berry
Fangxin Hong Traci Blonquist Barbara Halpenny Martin Sanda Viraj Master Christopher Filson Peter Rossi Peter Chang Gary Chien Randy Jones Tracey Krupski Mitchell Sokoloff Leslie Wilson Seth Wolpin |
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PD06-04 |
Feasibility and initial report of incorporating a shared decision making metric at point of service in men with localized prostate cancer |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making I | 17BOS |
Abstract: PD06-04 Sources of Funding: None Introduction Multiple treatment options exist for men with localized prostate cancer. Shared decision making (SDM), a process in which clinicians and patients collaborate to make decisions that are well informed and consistent with patients&[prime] preferences and values, helps guide patients through this decision making process and improves patient satisfaction. The objective of this study was to evaluate the feasibility and initial outcomes of measuring SDM among men with newly diagnosed localized prostate cancer, and to assess patients&[prime] perceptions of the value of existing decision support resources. Methods Over a one year period, all men with newly diagnosed localized prostate cancer were enrolled prospectively in this pilot study at an academic tertiary care center. All men were referred for nurse navigation, were offered referral to urology and radiation oncology, and were provided access to a prostate cancer educational website. At the time of informed consent for their chosen managment option (surveillance, surgery, radiation), men were invited to complete CollaboRATE, a validated 3-question survey measuring perceptions of SDM, along with measures assessing the perceived value of available decision support resources. Descriptive and correlational analyses were conducted to examine the prevalence of SDM and its associations with the perceived value of decision support resources. Results Annualized volume of prostate cancer diagnosis within our medical center was 249 per year, and 132 patients (53%) completed CollaboRATE. Descriptive frequencies of perceived value and CollaboRATE scores are reported in Table 1. Correlations between CollaboRATE and perceived value scores were non-significant. Conclusions Routine measurement of SDM and patient perceptions of the value of decision support resources is feasible but challenging, and though the prevalence of SDM was high it was not optimal. Physicians represent the most highly valued decision support resource. Measuring SDM and the value of decision support services from the patient perspective provides useful information to improve the quality of care for patients with newly diagnosed localized prostate cancer. Funding None
Authors
Patrick Murray
Paul Han Gregory Mills Stephen Prato Caitlin Gutheil Leo Waterston Jesse Sammon Moritz Hansen |
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PD06-05 |
A randomised controlled trial evaluating the utility of a patient decision aid to improve a prostate cancer clinical trial related decision-making and recruitment |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making I | 17BOS |
Abstract: PD06-05 Sources of Funding: Prostate Cancer Foundation of Australia and Royal Australian and New Zealand College of Radiologists Research Grant. Introduction Randomised controlled clinical trials are considered the ‘gold-standard’ for evaluating medical treatments. However, recruitment to clinical trials is low overall, with both patients and clinicians reporting difficulties with the consent process. Decision Aids DAs)may improve this process by ensuring patients weigh up the pros and cons of all their options and make informed value-sensitive decisions. We aimed to evaluate the utility of a DA for potential participants of a prostate cancer clinical trial (Trans-Tasman Radiation Oncology Group’s RAVES 08.03), in reducing decisional conflict, improving knowledge and potentially improving informed trial recruitment. Methods Potential participants for RAVES were identified by their urologist or radiation oncologist (RO) and invited to participate in the DA study. Participants received a pre-randomised package containing the standard RAVES participant information sheet and either the custom developed DA or a blank notebook. The packages were identical in appearance and both participant and recruiting clinician were blinded to the intervention. Questionnaire measures of decisional conflict and knowledge (including RAVES knowledge) were administered at baseline, one and six months. The primary outcome measure was decisional conflict. Secondary outcomes measured included knowledge about clinical trials and RAVES as well as recruitment to RAVES. Results 127 men (median age = 63 years) were recruited through urologists (n = 91) and radiation oncologists (n = 36). 61 men were randomised to the DA arm and 66 to the control arm. Decisional conflict was significantly lower (p = 0.0476) and knowledge regarding RAVES was significantly higher (p = 0.033) in the DA arm. 18% of the DA arm (11 of 61) and 9% of the control arm (6 of 66) were recruited to RAVES. This difference did not reach statistical significance. Of the 5 men from the urologist sample who subsequently entered RAVES (5.5%), all 5 were from the DA arm (p=0.017). Of the 11 men from the RO sample who subsequently entered RAVES (30.5%), there was no significant difference in recruitment by the DA intervention. Conclusions This study is the first to demonstrate the utility of a DA in reducing decisional conflict and improving trial knowledge in men making decisions regarding a prostate cancer clinical trial participation. The DA also improved trial recruitment in a sub-group of patients. Funding Prostate Cancer Foundation of Australia and Royal Australian and New Zealand College of Radiologists Research Grant.
Authors
Puma Sundaresan
Brittany Ager Phyllis Butow Stephanie Tesson Daniel Costa Andrew Kneebone Maria Pearse Henry Woo Ilona Juraskova Sandra Turner |
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PD06-06 |
The Burden of Cystoscopic Bladder Cancer Surveillance – Anxiety, Discomfort, and Patient Preferences for Decision Making |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making I | 17BOS |
Abstract: PD06-06 Sources of Funding: Department of Veterans Affairs VISN 1 Career Development Award; Conquer Cancer Foundation Career Development Award; Dartmouth-Hitchcock Medical Center Department of Surgery internal Career Development Award Introduction Periodic cystoscopic surveillance involves a trade-off for patients with non-muscle-invasive bladder cancer (NMIBC), who must balance their discomfort and anxiety related to cystoscopy against the risk for cancer recurrence. The 2016 AUA NMIBC guideline recommends shared decision making for these patients, although evidence on the topic is scarce. We examined patient discomfort, anxiety, and preferences for decision making in NMIBC to inform future work on implementing shared decision making. Methods Veterans with a prior diagnosis of NMIBC were invited to complete a validated survey instrument assessing procedural discomfort and worry and to participate in focus groups about their experience and desire to be involved in surveillance decision making. Focus group transcripts were analyzed qualitatively, using (1) systematic iterative coding, (2) triangulation involving multiple perspectives from urologists and an implementation scientist, and (3) searching and accounting for disconfirming evidence. Results 12 patients participated in 3 focus groups. Median number of lifetime cystoscopy procedures was 6.5 (interquartile range (IQR) 4-10). Based on survey responses, participants experienced a high degree of procedural discomfort (mean 62 of maximum possible (max) 70, IQR 46-64,) and worry (mean 36 of max 42, IQR 31-42). Qualitative findings are summarized in the Table. Participants expressed substantial pre-procedural anxiety and worry about disease. Most did not perceive themselves as having a defined role in decision making surrounding their surveillance care. Their preferences to be involved in decision making, however, varied widely, ranging from acceptance of the physician's recommendation to uncertainty to dissatisfaction with not being involved more in determining the frequency and intensity of surveillance. Conclusions Bladder cancer patients experience substantial discomfort, anxiety, and worry related to surveillance cystoscopy and potential progression of disease. While some patients may be content to defer surveillance decisions to their physicians, others would prefer to be more involved. Future work should focus on defining patient-centered approaches to surveillance decision making and developing effective shared decision support tools. Funding Department of Veterans Affairs VISN 1 Career Development Award; Conquer Cancer Foundation Career Development Award; Dartmouth-Hitchcock Medical Center Department of Surgery internal Career Development Award
Authors
Kevin Koo
Lisa Zubkoff Brenda Sirovich John Seigne Philip Goodney Florian Schroeck |
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PD06-07 |
The transition from a statewide prostate cancer treatment program to comprehensive insurance under the Affordable Care Act in low-income men |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making I | 17BOS |
Abstract: PD06-07 Sources of Funding: Supported by a Research Scholar Grant RSGI-15-017-01 CPHPS from the American Cancer Society Introduction The Affordable Care Act (ACA) has increased insurance coverage most significantly among the working poor and childless adults previously ineligible for Medicaid. We report on a prospective cohort of low-income, uninsured men with prostate cancer (CaP) in their transition from a statewide CaP treatment and navigation program (IMPACT) to comprehensive health insurance under the ACA. Methods We engaged 25 men in semi-structured telephone interviews focusing on their initial experience transitioning from IMPACT to ACA-based insurance coverage. Interviews were recorded and transcribed for review. Transcripts were coded for themes around patient experience with IMPACT, the insurance enrollment process, and initial experience with comprehensive health insurance. Results Demographic and quality of life are summarized in Table 1. Four thematic domains were identified: 1) insurance enrollment process, 2) attributes and challenges of care in IMPACT, 3) attributes and challenges of care with ACA-based insurance, and 4) overall changes in care after insurance enrollment. Major findings are presented in Table 2. Twenty-three men enrolled in Medicaid. Fifteen men reported completing a paper application with 24% of patients receiving help from social workers and 20% from family members. Insurance coverage began more than 3 months after completing the application 40% of the time. Ten men reported that navigating CaP treatment was easier with IMPACT. Twelve patients reported improved access to care with insurance, while 6 patients reported increased health care costs and 5 reporting decreased health care costs after insurance enrollment. 24% of patients were able to keep the same primary doctor and urologist after enrollment. Conclusions Low-income men gaining insurance coverage under the ACA are predominantly enrolling in Medicaid. They face delays in coverage and interruptions in continuity of care, but report improved access. The relative burden of healthcare costs after gaining insurance is mixed. Funding Supported by a Research Scholar Grant RSGI-15-017-01 CPHPS from the American Cancer Society
Authors
Jamal Nabhani
Grecia Vargas Lorna Kwan Sarah Connor Arlene Fink Sally Maliski Mark Litwin |
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PD06-08 |
Disparity in Minority Representation within Medicare Accountable Care Organizations |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making I | 17BOS |
Abstract: PD06-08 Sources of Funding: American Cancer Society (MSRG-15-103-01-CHPHS to MJR), AUA/Urology Care Foundation Rising Stars in Urology Research Program Introduction Minority health care is frequently concentrated among relatively few providers that tend to have incrementally fewer financial resources. The development of accountable care organizations (ACOs) serves to improve the value of care delivered to populations with emphasis on care coordination. However, it is not known if minority patients have equal representation or access to ACOs._x000D_ _x000D_ Methods The distribution of race within 220 Medicare Shared Savings Program ACOs was ascertained from the 2013 MSSP Public Use File. The ZIP Code Tabulation Areas (ZCTA) in each ACO were weighted according to its representation within the ACO. The distribution of race was then calculated for the ZCTAs that an ACO covered according to the 2010 U.S. Census and compared to the distribution in the ACO. The degree of disparity was calculated as: (% minority in community – % minority in ACO) / % minority in community. Results Overall, the median disparity between the representation of all minorities in the community compared to the ACO was 41.6% [interquartile range (IQR) 25-51%, see Fig.]. Among black beneficiaries, the median disparity was 27.1% (IQR 11-48%). There was a median 65.6% disparity (IQR 52-79%) among Hispanics and 57.5% disparity (IQR 43-67%) among Asians. The vast majority of ACOs exhibited large degrees of disparity, with 77.7% and 64.6% of the ACOs having a disparity of more than 50% among Hispanic and Asian communities, respectively. Thirteen ACOs (5.9%) had a large negative disparity, where the proportion of minorities within the ACOs was larger than in the community. Federally qualified health centers (FQHC) were largely represented in these ACOs with a negative disparity; on average there were 11 FQHC represented in ACOs with a negative disparity compared to 0.9 FQHC in ACOs with a positive disparity (p<0.01). Conclusions Our findings show that all minority patients are consistently under-represented in early MSSP ACOs. This raises concerns that minority patients in the community have less access to physicians and provider groups who participate in ACOs and the potential benefits conferred by this delivery system innovation. The development of ACOs may ultimately exacerbate known racial disparities germane to urologic practice unless incentives are aligned to promote inclusion of minority populations in alternative payment models. Funding American Cancer Society (MSRG-15-103-01-CHPHS to MJR), AUA/Urology Care Foundation Rising Stars in Urology Research Program
Authors
Daniel Lee
Robert Gambrel Amy Graves Melinda Buntin David Penson Matthew Resnick |
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PD06-09 |
Healthcare Disparities: Do Medicaid patients have longer wait times for outpatient urological evaluation? |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making I | 17BOS |
Abstract: PD06-09 Sources of Funding: none Introduction Insurance status has been demonstrated to be a barrier to prompt urological care. Telephone surveys reveal that substantially fewer urologists accept Medicaid compared to Medicare or private insurance. There is a paucity of urologic literature evaluating discrepancies in wait times for Medicaid patients versus other forms of insurance. We sought to evaluate wait time disparities in academic urology programs for Medicaid compared to Medicare patients. Methods The cohort was identified from the online listing of all ACGME accredited urology residency programs. An IRB-approved standardized script was used to contact each institution to determine if they accepted Medicaid patients. For institutions that accepted Medicaid, separate calls were made to establish the earliest appointment time available for a fictional patient with Medicaid and then Medicare insurance. Discrepancies in wait times between insurance type were compared. All statistical analysis was performed using SPSS v24.0. Results All 131 ACGME accredited academic urology programs were surveyed. Of these, 10 (7.6%) did not accept new patients with Medicaid insurance. 13 institutions (9.92%) declined to participate in our study. There were 108 academic urology clinics in our final analysis. Of these, 59% (n=64) had longer wait times for Medicaid patients. Overall, there was a significant difference (p<0.001) between the mean wait times for a new patient visit with Medicare (23 days, STD 20.8) versus Medicaid (35 days, STD 27.5). For Medicaid appointments, 73.1% (n=79) were scheduled in resident run clinics only. When stratified by AUA section, academic urology programs had longer average wait times for Medicaid patients when compared to Medicare patients. However, only the New York (n=16, 26.8 vs 10.1 days, p=0.022) and Southeastern (n=23, 41.8 vs 26.8 days, p=0.050) sections had significantly longer wait times (Table 1). Conclusions Our data suggests that patients with Medicaid experience longer wait times for their initial urological evaluation. Barriers to timely clinical evaluation have been cited as a reason for emergency room visitation. Awareness of such disparities in urologic care is an early step toward improving the quality of healthcare for all individuals. Funding none
Authors
Wai Lee
Andrew Chen Ramsey Al-Khalil Tal Cohen William T. Berg Wayne C. Waltzer Jason Kim Howard L. Adler |
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PD06-10 |
Patient refusal of neo?adjuvant chemotherapy for muscle invasive bladder cancer |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making I | 17BOS |
Abstract: PD06-10 Sources of Funding: none Introduction While use of neo?adjuvant chemotherapy (NAC) prior to radical cystectomy (RC) for muscle?invasive bladder cancer (MIBC) has been steadily increasing over the last decade, the majority of patients are not receiving NAC. Little is known about the reasons as to why these patients do not receive NAC. Our objective was to evaluate the rate of patient refusal of NAC, and examine descriptive characteristics associated with patient refusal of NAC. Methods Using the National Cancer Data Base, patients who underwent RC between 2004?2013 for a diagnosis of cT2 MIBC were included. Among patients who did not receive NAC, patients were categorized as (i) having been recommended NAC and refused, or (ii) not recommended NAC due to patient risk factors. Bivariable analysis was used to determine associations for not receiving NAC between age, gender, race, income level, insurance status, education level, type of facility, distance to oncology provider, and trend over time. Results Of 8298 patients who underwent cystectomy, 524 did not receive NAC and had complete data regarding reasons for declining treatment. 58% of those included were recommended NAC but refused (n = 305), while 42% of patients were not recommended NAC due to risk factors (n = 219). Over the defined timeframe, an increasing trend toward patient refusal of NAC was seen (49% over 2004?2007, 59% over 2008?2010, 63% over 2011?2013, p = 0.06). Many patients (58%) seen at academic or comprehensive community cancer programs did not receive NAC due to patient refusal (58% vs. 42%, p=0.06). Patients with lower levels of education were less likely to refuse NAC, however these findings were not statistically significant. Travel distance to provider was also not associated with likelihood of patient refusal of NAC (p = 0.45). No statistically significant association was found between age, gender, race, income or insurance status and the reason why NAC was not administered. Conclusions Patient refusal of NAC prior to RC for MIBC is becoming more common. A higher education level and care received at an academic or comprehensive cancer facility was more likely to be associated with refusal of NAC, suggesting that patient counseling affects patient treatment choice prior to RC. Funding none
Authors
Pauline Filippou
Allison Deal Benjamin McCormick Gopal Narang Matthew Nielsen Raj Pruthi Eric Wallen Hung-Jui (Ray) Tan Michael Woods Angela Smith |
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PD06-11 |
Factors Affecting Delays in Neoadjuvant Chemotherapy and Radical Cystectomy: An Analysis of the National Cancer Database Cohort |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making I | 17BOS |
Abstract: PD06-11 Sources of Funding: none Introduction Delay in radical cystectomy (RC) for urothelial bladder cancer has been associated with decreased overall survival (OS). However, this association was observed before the increased adoption of neoadjuvant chemotherapy (NAC). We sought to analyze the effect of delays in the NAC setting and the factors associated with delays using a large registry based cohort. Methods Using the National Cancer Database, we identified patients who underwent NAC and RC for muscle-invasive urothelial bladder cancer from 2006-2013. Patients with metastatic disease and prior treatment with immunotherapy were excluded. Time points for delays from diagnosis to initiation of NAC and from diagnosis to RC were tested for association with survival. Logistic regression was used to identify factors associated with delays in treatment. Cox-proportional hazards models were used to examine the relationship of delays to OS. Results Based on inclusion criteria, 2,034 patients were identified. Median time from diagnosis to initiation of NAC and diagnosis to RC were 39 and 155 days, respectively. Delays were defined as >10 weeks for diagnosis to NAC and >6 months for diagnosis to RC. On multivariate analysis, significant factors associated with delay to NAC included, black race (OR 2.20, 95% CI (1.17,3.48)), no insurance (OR 2.10, 95% CI (1.17, 3.78)), Medicaid insurance (OR 2.25, 95% CI (1.34, 3.80)), Medicare insurance (OR 1.51, 95% CI (1.16, 1.97)), reporting at academic hospital (OR 1.42, 95% CI (1.06, 1.91)), and diagnosis elsewhere than treatment hospital (OR 1.74, 95% CI (1.29, 2.34)). For delay to RC, significant independent factors were male gender (OR 1.36, 95% CI (1.06, 1.74)), black race (OR 1.64, 95% CI (1.06, 2.55)), no insurance (OR 1.89, 95% CI (1.14, 3.16)), Medicaid insurance (OR 1.84, 95% CI (1.16, 2.91)), Medicare insurance (OR 1.33, 95% CI (1.07, 1.65)), and diagnosis elsewhere than treatment hospital (OR 1.87, 95% CI (1.50, 2.33)). Delays in NAC or RC did not have a significant effect on OS, complete response (P0), or downstaging. Conclusions There are several factors associated with delays in treatment of muscle invasive bladder cancer, including race, insurance, and care transitions. In the setting of NAC, delays do not seem to have a significant effect on OS or pathological response. More studies are needed to determine the reasons for these socioeconomic differences in treatment times and if improvements can be made to improve access to care for invasive bladder cancer. Funding none
Authors
Greg Gin
Nora Ruel John Sfakianos Steven Kardos Matthew Galsky Clayton Lau Kevin Chan Sumanta Pal Bertram Yuh |
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PD06-12 |
Trends in Utilization and Approach to Lymph Node Dissection During Radical Nephrourerectomy for High Grade Upper Tract Urothelial Carcinoma |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making I | 17BOS |
Abstract: PD06-12 Sources of Funding: Data grant from National Cancer Database, a collaboration between the Commission on Cancer, the American Cancer Society and the American College of Surgeons. Introduction There is an inferred benefit to regional lymph node dissection (LND) during radical nephroureterectomy (RNU) for high grade upper tract urothelial carcinoma (HG UTUC). We evaluated trends in utilization of regional LND using the National Cancer Database. We hypothesized that increased use of minimally invasive surgical approaches as well as lower volume RNU centers would be associated with LND utilization. Methods We included adults undergoing RNU for pathologically confirmed HG UTUC from 2004-2012. We examined patient demographic, clinical, disease severity (i.e. clinical stage/nodal status), surgical, and hospital-level factors associated receipt of LND using multivariable logistic regression. Sensitivity analyses assessed for consistency of trends in LND use across clinical stage/nodal status as well across center volume of RNU experience (lowest quartile RNU performed over the study period, interquartile, and top quartile). Results Of 11,258 patients undergoing RNU for HG UTUC, 2,028/11,258 (18%) were minimally invasive, and 1,009/11,258 (9%) utilized LND. LND was more common in recent years (5.8% in 2004, 12.5% in 2012 [OR 4.7, 95%CI 3.6-6.1 for surgery in 2010-2012 versus 2004-2006]). LND rate for open RNU was 11.6% versus 6.3% for minimally invasive RNU (OR 0.50, 95%CI 0.39-0.67). By 2012, open LND rate rose to 15.8%; minimally invasive LND remained stable at 6.4% (p<0.001). For RNU case volume 79 unique centers were represented, 18 centers were low (<2 cases/year), 40 were intermediate (2 to 4 cases/year) and 21 were high (≥5 cases/year). Center volume was associated with LND (16.9% in top quartile volume centers, compared with 5.5% in lowest quartile volume centers [OR 3.9, 95%CI 3.3-4.6]). Conclusions Utilization of regional LND during RNU for HG UTUC increased over time, driven mainly by increased utilization during open RNU. LND was performed at a greater rate in higher volume centers, even after adjustment for disease severity, and may be a quality metric for oncologic management of HG UTUC. Funding Data grant from National Cancer Database, a collaboration between the Commission on Cancer, the American Cancer Society and the American College of Surgeons.
Authors
Liam C. Macleod
James Kearns Wayne Brisbane Jonathan L. Wright George R. Schade Daniel W. Lin John L. Gore Atreya Dash |
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PD07-01 |
The 4Kscore Test Accurately Predicts Aggressive Prostate Cancer in Men of all Ages and Race. |
Prostate Cancer: Detection & Screening II | 17BOS |
Abstract: PD07-01 Sources of Funding: none Introduction A recent study confirmed the 4Kscore accurately predict aggressive prostate cancer. We assessed whether the performance of the 4Kscore Test differed by age or race. _x000D_ _x000D_ Methods 1312 men referred for prostate biopsy made up the cohort for these analyses. Differential calibration by age was assessed using logistic regression with an interaction between age and the 4Kscore Test for the outcome of a Gleason 3+4 cancer. We further categorized patients by age into subgroups of less than 55, 56-69, and 70 or older. The AUC for the 4Kscore Test was calculated in each age subgroup and confidence intervals for the difference in AUCs between groups were estimated. Similar analyses were performed to assess differential calibration and discrimination of the 4Kscore Test in African Americans versus the rest of the cohort. Finally, Decision curve analysis was used to assess the clinical utility of the 4Kscore Test for predicting aggressive prostate cancer within these sub groups of age and race. Results Among the cohort, 291 (22%) men were found to have high-grade cancer on prostate biopsy. There was no evidence to suggest a difference in discrimination of high-grade prostate cancer by either age or race, with the difference in confidence intervals surrounding the AUC’s overlapping zero. We found evidence of a difference in calibration by age when age was modeled as a continuous score (p=0.045). However, on sensitivity analysis looking at age categorized, we found no evidence of differential miscalibration (p=0.15). We found evidence of a difference in calibration by race (p=0.02), with scores slightly under predicting Gleason 7 cancer among African American men. Decision curve analysis found a higher net benefit for using the 4Kscore Test to decide on the need for biopsy in all of age and race subgroups. Conclusions We found no evidence of differential discrimination of Gleason 7 prostate cancer by age or race. There is some evidence to suggest miscalibration by age and race but this requires further assessment. Decision curve analysis suggests there is a clinical benefit to using the 4Kscore Test to decide on the need for a prostate biopsy in men of all ages and race. Funding none
Authors
Bruno Nahar
Daniel Sjoberg Stephen Zappala Vivek Venkatramani Dipen Parekh Sanoj Punnen |
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PD07-02 |
PCA3 in prostate cancer risk assessment: How does it help in real life? Result of a 5–year prospective study |
Prostate Cancer: Detection & Screening II | 17BOS |
Abstract: PD07-02 Sources of Funding: none Introduction To assess interest of Prostate Cancer Antigen 3 (PCA3) screening in prostate cancer (PCa) diagnostic management after an individual risk assessment. Methods From 2011 to 2016, patients with elevated PSA and negative prostate biopsies (PB) were included in an open monocentric prospective study after approval of Institutional review board. Each patient had an urinary PCA3 test to assess the risk of PCa with three different nomograms (Prostate Cancer Prevention Trial Risk Calculator (PCPT), PCPT + PCA3, PCPT 2.0). After consultation, decision to perform biopsy was at urologist discretion. A logistic regression analysis was performed to determine predictive factors (PF) for PCa diagnostic at 12 months and 5 years. Success of screening was defined as positive PB in the first year after consultation or no PCa diagnosed at the end of the follow up. While, failure was defined as negative PB in the first year after consultation or PCa diagnosed more than 12 months after consultation._x000D_ Results In our study, 516 patients were included with mean age 64.7 (IQR47_85), mean PSA 8.1ng/mL (0.27_119.8), mean PCA3 score 22 (1_533) and 18.9% had suspicious digital rectal examination. At 12 months, 6 PF of success were found: low PSA ratio (p=0.08), low prostatic volume (p<0.01), high PSA density (p<0.01), high PCA3 (p<0.01), high PCPT risk (p=0.04) and high PCPT + PCA3 risk (p<0.01). At 5 years, after primary screening, PCA3 score isolated or integrate in PCPT risk calculator was the only one biological PF of consultation success (PCPT + PCA3 (p<0.01) and PCA3 rates (p<0.01). The rate of success was 46.5% and 94% at 12 months and 5 years respectively after primary screening (figure 1). Conclusions In our study, PCA3 was able to reach a high rate of positive biopsy at 12 months and allowed to avoid 94% of prostate biopsy at 5 years. Funding none
Authors
Marine Lesourd
Jean Baptiste Beauval Benjamin Pradere Daniel Portalez Xavier Gamé Eric Huygue Michel Soulié Pascal Rischmann Bernard Malavaud Mathieu Roumiguié |
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PD07-03 |
MICHIGAN PROSTATE SCORE (MiPS): AN ANALYSIS OF A NOVEL URINARY BIOMARKER PANEL FOR THE PREDICTION OF PROSTATE CANCER AND ITS IMPACT ON BIOPSY RATES |
Prostate Cancer: Detection & Screening II | 17BOS |
Abstract: PD07-03 Sources of Funding: None Introduction The Michigan Prostate Score (MiPS) is a validated and commercially available early detection test for prostate cancer combining serum PSA with urinary PCA3 and T2:ERG expression. This novel biomarker reports individual patient risk estimates for biopsy detection of any MiPS and of high-grade (Gleason score >6) prostate cancer HG MiPS. We investigated the impact of MiPS on clinical decision-making and prostate biopsy frequency rates and correlated MiPS and HG MiPS with final biopsy pathology results._x000D_ _x000D_ _x000D_ _x000D_ _x000D_ _x000D_ Methods MiPS testing was offered to men referred for initial or repeat prostate biopsy at a single, tertiary institution as an alternative to proceeding directly to a biopsy between October 2013 and January 2015. Patient characteristics, PSA, PCA3, T2:ERG, and biopsy pathology were analyzed to see how MiPS and HG MiPS risk prediction models affected the decision for prostate biopsy as well as biopsy pathology. One-way ANOVA was used to correlate MiPS scores with biopsy rates and clinical outcomes. Results 149 men underwent MiPS testing, of whom 67.8% had not undergone a prior prostate biopsy. Median age was 65.2, and median PSA was 9.5 ng/ml. The mean predicted risks for detection of any and high-grade cancer were 41.5% and 26.0%, respectively. The 73 men (49%) who proceeded to prostate needle biopsy had higher MiPS (52.7% vs. 30.7%, p<0.001) and HG MiPS scores (35.2% vs. 18.2%, p<0.001) than those who did not undergo biopsy. Among those biopsied, MiPS, HG MiPS, PCA3, and T2:ERG were significantly higher in those with cancer (all p<0.05) found on biopsy. PSA alone was not associated with cancer diagnosis (p=0.82). Conclusions The combination of urinary PCA3 and T2:ERG in a test panel for prostate cancer reduced the use of prostate biopsy by 51% among men referred for prostate biopsy. MiPS and MiPS HG were closely correlated with the presence of any cancer and high-grade cancer, respectively. These findings support the clinical utility and validity of MiPS for stratifying prostate cancer risk and guiding high-yield biopsy utilization. Funding None
Authors
Amir H. Lebastchi
Christopher M. Russell Alexander M. Helfand Takahiro Osawa Javed Siddiqui Rabia Siddiqui Arul M. Chinnaiyan Priya Kunju Rohit Mehra Debbie Snyder Scott A. Tomlins Jont T. Wei Todd M. Morgan |
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PD07-04 |
CLINICAL PERFORMANCE OF AN EPIGENETIC ASSAY TO IDENTIFY OCCULT HIGH-GRADE PROSTATE CANCER IN AFRICAN AMERICAN MEN |
Prostate Cancer: Detection & Screening II | 17BOS |
Abstract: PD07-04 Sources of Funding: MDxHealth Introduction Men with persistent clinical risk factors for prostate cancer (PCa) often undergo repeat prostate biopsy for fear of occult disease missed by the first biopsy procedure. Cancer-specific DNA methylation occurs early on during the oncogenic process, and these epigenetic changes can be detected in prostate biopsy tissue at a distance from the actual tumor through a field effect. Several previously reported studies on the epigenetic assay demonstrated a negative predictive value (NPV) of 90% for all PCa and 96% for high-grade disease (Gleason Score (GS) >/=7) in men undergoing repeat prostate biopsy. We evaluated the clinical performance of this assay in a population of African American (AA) men. Methods The study population consisted of 237 AA men from seven urology centers across the U.S., all of whom were undergoing standard 12-core trans-rectal ultrasound guided repeat biopsy within 30 months from a negative index biopsy. Men with atypical small acinar proliferation at index biopsy were excluded. All biopsy cores were profiled for the epigenetic biomarkers GSTP1, APC and RASSF1 using a multiplexed quantitative DNA methylation-specific PCR assay. Results For each patient, a median of 12 cancer-negative cores from the index biopsy were analyzed. Upon repeat biopsy, 130 (55%) subjects had no PCa detected and 107 (45%) were diagnosed with PCa. Of the 107 subjects with PCa, 72 (67%) were diagnosed with GS =6 PCa and 35 (33%) with GS >7 disease. Based on the expected PCa prevalence of 18% in the repeat biopsy setting, the epigenetic assay yielded an NPV of 91% and PPV of 28% for detection of all PCa. For men diagnosed with high-grade PCa, the test yielded a NPV of 96%. The epigenetic assay interrogates the DNA methylation intensity of the three cancer-related biomarkers, and higher intensities were observed for men diagnosed with high-grade PCa relative to those men with no PCa detected upon biopsy (p=0.001). _x000D_ Conclusions In this group of AA men, we successfully validated an epigenetic assay to assess the need for repeat biopsy by profiling PCa-negative index biopsies. Results were consistent with previous studies performed on cohorts that were predominantly Caucasian. The epigenetic assay improved the identification of AA men at risk for occult high-grade disease upon repeat biopsy. Funding MDxHealth
Authors
Leander Van Neste
Carlton Barnswell Mark Jalkut Ronald Tutrone James Sylora Ronald Anglade Myron Murdock Kelvin A. Moses Zvi Shiffman Todd Vandenberg Nikhil Shah Jonathon Silberstein Jack Groskopf Wim Van Criekinge Robert Waterhouse |
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PD07-05 |
Utility of Digital Rectal Examination (DRE) in Detection of Clinically Significant Prostate Cancer: Age and Prostate-specific Antigen (PSA)-Based Analysis |
Prostate Cancer: Detection & Screening II | 17BOS |
Abstract: PD07-05 Sources of Funding: None Introduction Updated guidelines from the National Cancer Care Network (NCCN) advocate for DRE screening only in those men with elevated PSA. We sought to investigate the effect of serum PSA levels on the association between DRE and subsequent detection of high-grade prostate cancer (Gleason ≥ 7) in a large, nationally representative cohort. Methods We analyzed all men who underwent DRE (n=35,350) within the screening arm of the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening trial for high-grade prostate cancer. With a follow up of 314,033 person-years and 1,612 high-grade cancers detected, we performed age-adjusted competing-risks regression analysis to evaluate the interaction between time varying suspicious DRE and serum PSA. Results 10-yr cumulative incidence of high-grade cancer was 5.8% (95% C.I. 5.5-6.1). Higher risk was seen among those with suspicious vs. non-suspicious DRE. There was a statistically significant interaction between PSA and DRE, with a smaller increase in relative risk for DRE with higher PSA (p=0.01). However, increases in absolute risk were small and clinically irrelevant for PSA < 2 (2.2% vs 1.1% risk of high grade cancer at 10 years), but of clinical importance for PSA 3-10 (37.5% vs 19.5%). Increases in risk were of equivocal clinical relevance for PSA 2-3 (9.0% vs 6.0%). Conclusions DRE demonstrated increasingly prognostic utility when PSA >3, limited utility when PSA <2, and some benefit in the setting of equivocal PSA 2-3. These findings provide support for the NCCN guideline recommendation to restrict DRE to men with higher PSA, as a follow-up test to improve specificity rather than as a primary screening modality to improve sensitivity. Further research is warranted on the value of DRE in men with PSA 2-3. Funding None
Authors
Joshua Halpern
Clara Oromendia Michael Cosiano Jonathan Shoag Sameer Mittal Karla Ballman Andrew Vickers Jim Hu |
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PD07-06 |
Regional variation in the screening, biopsy, and diagnosis of prostate cancer in a Medicare population |
Prostate Cancer: Detection & Screening II | 17BOS |
Abstract: PD07-06 Sources of Funding: The Hitchcock Foundation Introduction The Dartmouth Atlas has reported wide regional variation in PSA screening and diagnosis of prostate cancer. However, the relationships between screening, diagnosis, and intervening biopsy have not been explored. In this study, we evaluated regional relationships between these events. Methods We performed a cross-sectional analysis of a 100% Medicare fee-for-service sample from 2012, including men aged 68 years or older. The unit of analysis was hospital referral region (HRR) (n=306). Regional rates of PSA screening, prostate biopsy, prostate cancer diagnosis were calculated, adjusting for age and race. Correlation coefficients were calculated between these events. Regions were stratified by quartile for each practice, and those with concordant or discordant practices were identified (e.g. for screening and biopsy: high/high, high /low, low/high, low/low). Results There was wide regional variation in all events. PSA screening rates ranged from 13-30% (mean 21.7%), biopsy 0.03-0.8% (0.18%),diagnosis 0.4-2.2% (1.0%). Overall, PSA screening did not correlate with biopsy (r=-0.04; p=0.40) or treatment (r=-0.06; p=0.29), but did weakly correlate withdiagnosis (r=0.17; p=0.003). Biopsy correlated moderately with diagnosis (r=0.33; p<0.0001). There was a wide range of concordant and discordant practices among regions. Conclusions Practice patterns in the screening, biopsy, and diagnosis of prostate cancer vary throughout the United States (>2-fold, >20-fold, and >5-fold from lowest to highest region, respectively). Overall, PSA screening rates were independent of biopsy or treatment, implying that screening does not necessarily lead to a cascade of procedures. While biopsy and diagnosis correlated overall, there were multiple regions with discordant practice patterns. Further study of factors underpinning variation, and outcomes associated with different practice patterns, is needed to improve care quality and increase standardization of practice._x000D_ _x000D_ _x000D_ _x000D_ Funding The Hitchcock Foundation
Authors
Rachel A. Moses
Andrea M. Austin Donald Carmichael Elias S. Hyams |
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PD07-07 |
Personal PSA screening and treatment choices for localized prostate cancer among expert physicians |
Prostate Cancer: Detection & Screening II | 17BOS |
Abstract: PD07-07 Sources of Funding: None Introduction Prostate-specific antigen (PSA) based prostate cancer (PCa) screening and treatment choice for localized PCa remain highly controversial. The physician surrogate method seeks to identify acceptable healthcare interventions by ascertaining the interventions physicians select for themselves. We surveyed urologists, radiation oncologists, and medical oncologists with respect to their personal practices and recommendations to immediate family members regarding PSA screening and the treatment of localized PCa. Methods A hierarchical, contingent survey was developed by consensus among a team of urologists, radiation oncologists, and medical oncologists. After piloting, it was electronically circulated to eligible members of the Canadian Urological Association, Genitourinary Radiation Oncologists of Canada, Urologist, Medical Oncologist and Radiation Oncologist Members of the American Medical Association, Urological Society of Australia and New Zealand and Confederacion Americana de Urologia. We characterized physicians’ choices regarding PSA screening and PCa treatment. Among urologists and radiation oncologists, we assessed for correlation between specialty and treatment selection. Results Of 893 respondents, 869 provided consent and completed the survey. Their median age was 50 years (IQR 41-60 years) and most were male (n=807; 93%) and lived in Canada (n=413; 47%) or the United States (n=143; 16%). 719 (83%) were urologists, 89 (10%) radiation oncologists, 9 (1%) medical oncologists, 8 (1%) other specialties (e.g. internist) and 45 did not provide specialty information. Of 807 male respondents, 494 (61%) had personally undergone PSA screening and 662 (82%) planned to in the future. Of 62 female respondents, 43 (69%) had recommended PSA testing to immediate family members. In total, 784 of 869 respondents (90%) endorsed past or future screening for themselves or for relatives. 30 (4%) of men had been diagnosed with PCa personally and 16 (26%) of women had recommended PCa treatment to an immediate family member. After restricting to responses from urologists and radiation oncologists, there was a significant correlation between physician specialty and the treatment selected (Phi coefficient=0.61; p=0.001). Conclusions Physicians who routinely treat PCa are very likely to undertake PCa screening themselves or recommend it for their immediate family members. Among those diagnosed with prostate cancer, there is a significant correlation between specialty and treatment selection. Funding None
Authors
Christopher Wallis
Douglas Cheung Laurence Klotz Venu Chalasani Ricardo Leao Juan Garisto Gerard Morton Robert Nam Ian Tannock Raj Satkunasivam |
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PD07-08 |
A Novel Nomogram to Predict Postoperative Biochemical Recurrence in Patients with Localized High-Risk Prostate Cancer |
Prostate Cancer: Detection & Screening II | 17BOS |
Abstract: PD07-08 Sources of Funding: None Introduction Currently utilized nomograms for prostate cancer were developed using populations primarily composed of men with low- and intermediate-risk disease. However, there is a need to elucidate accurate, patient-specific point estimates for oncologic outcomes in men with high-risk (HR) and very high-risk (VHR) disease to enable patients and providers to make superior clinical decisions. We therefore sought to construct a novel nomogram that predicts biochemical recurrence (BCR) from a contemporary cohort of men with HR and VHR prostate cancer. Methods A total of 1,241 men with HR or VHR prostate cancer who underwent radical prostatectomy from 2005 to 2015 were identified from Johns Hopkins (n = 620, training cohort) and the Cleveland Clinic (n = 621, validation cohort). The primary endpoint was BCR after radical prostatectomy. Cox multivariable regression was performed to model characteristics and outcomes in the training cohort. The AUC of the model in the training cohort was adjusted for optimism by subjecting the model to bootstrapping with 100 resamples. Model accuracy was assessed using the time-dependent area under the receiver operator characteristic curve (AUC) in the validation cohort. Results A total of 494 men developed BCR, with 245 arising from the training cohort and 249 from the validation cohort. The overall BCR-free probability was 49.0% (95% CI: 45.4%-52.9%) at 5 years. The nomogram for postoperative BCR probability was developed using age, race, PSA, Gleason grade group, clinical stage, and number of cores with Gleason score 8-10 disease [Figure 1]. Model AUC was 0.730 after optimism-adjustment, as compared to 0.700 and 0.654 in the existing Stephenson and Cancer of the Prostate Risk Assessment (CAPRA) nomograms, respectively [Figure 2]. The nomogram demonstrated similar accuracy in the external validation cohort (AUC = 0.734). Conclusions Accurate and individualized risk assessment for the outcome of BCR is imperative for optimizing clinical decisions and designing clinical trials. We have herein described a novel predictive tool created exclusively from men with HR and VHR prostate cancer demonstrating better discriminative ability than existing nomograms for the prediction of postoperative BCR in this important patient population. Funding None
Authors
Ridwan Alam
Jeffrey J. Tosoian Yaw A. Nyame Lamont Wilkins Kasra Yousefi Meera R. Chappidi Chandana A. Reddy Elizabeth B. Humphreys Debasish Sundi Brian F. Chapin Andrew J. Stephenson Eric A. Klein Ashley E. Ross |
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PD07-09 |
Prostate specific antigen testing after radical prostatectomy: can we stop at 20 years? |
Prostate Cancer: Detection & Screening II | 17BOS |
Abstract: PD07-09 Sources of Funding: None Introduction While our understanding of early and intermediate biochemical recurrence is robust, the time-course and clinical features of delayed biochemical recurrence are less well defined. We examined the clinical features and outcomes associated with delayed biochemical recurrence after radical prostatectomy, specifically amongst men with over 20 years of follow-up. Methods 16,720 men underwent radical prostatectomy and 2,699 experienced biochemical recurrence. We determined predictors of delayed biochemical recurrence as well as metastasis-free survival and cancer specific survival rates for recurrence at various time points after radical prostatectomy. We performed a subset analysis of the 732 men with 20 or more years of recurrence free follow-up. Actuarial metastasis-free and cancer specific survival was calculated to determine the actuarial probability of biochemical recurrence at 30 years after radical prostatectomy. Results The majority of biochemical recurrence occurred within five years of radical prostatectomy, and decreased with each five-year period. Delayed biochemical recurrence was associated with favorable metastasis-free survival and cancer specific survival compared to early biochemical recurrence (Figure). Amongst the 732 men with an undetectable prostate specific antigen at 20 years, 17 (2.3%) developed a biochemical recurrence, a single patient developed metastatic disease, and none died due to prostate cancer. The actuarial probability of biochemical recurrence amongst men with an undetectable prostate specific antigen at 20 years increased with adverse pathologic features. Conclusions Men with delayed biochemical recurrence have favorable clinical features and improved survival. Men with an undetectable prostate specific antigen 20 years after radical prostatectomy had a very low rate of recurrence and no deaths due to prostate cancer. This suggests that 20 years is a reasonable time point to discontinue PSA testing. _x000D_ _x000D_ Figure. Kaplan-Meier curves for actuarial (a) metastasis-free survival and (b) cancer-specific survival, stratified by the timing of biochemical recurrence (4 groups)._x000D_ Funding None
Authors
Wesley Ludwig
Zhaoyong Feng Bruce Trock Elizabeth Humphreys Patrick Walsh |
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PD07-10 |
Malignancies in Male BRCA Mutation Carriers – Results from a Prospectively Screened Cohort of Patients Enrolled to a Dedicated Male BRCA Clinic |
Prostate Cancer: Detection & Screening II | 17BOS |
Abstract: PD07-10 Sources of Funding: The study was funded by the ASCO career development award, Israel Cancer Association, and German Israeli Foundation. Introduction There is an increased risk of various cancers, and especially prostate cancer, among men with germline mutations in BRCA genes. However, thus far there are no cancer screening guidelines for this population. _x000D_ We report cancer rate and type in a prospectively screened cohort of patients enrolled to a dedicated male BRCA clinic. _x000D_ Methods Between February 2014 and July 2016 we evaluated 207 men at our male BRCA clinic: 146 known BRCA mutation carriers and 61 men who underwent genetic counselling, 8 of whom were found to be BRCA carriers._x000D_ Patients ≥ 40 years of age were screened for prostate, breast, colorectal, pancreatic and skin malignancies using a standard protocol. _x000D_ We report patient characteristics, type and prevalence of tumors identified upon enrollment to the clinic and during the initial screening._x000D_ Results A total of 154 BRCA mutation carriers comprised the study cohort; 92 men (60%) had a BRCA1 mutation and 61 (40%) a BRCA2 mutation. One patient had a mutation in both BRCA types. Common mutations were 185delAG in BRCA1 (69/93, 74%) and 6174delIT in BRCA2 (51/62, 82%). Median age at enrollment was 50 years (IQR 42, 63). All patients had a family history of cancer (1-10 cases per family)._x000D_ A total of 24 patients (16%) were diagnosed with cancer upon enrollment or during initial screening. Median age at cancer diagnosis was 55 years (IQR 44, 64). Four patients had multiple malignancies (2-4 cases per patient). Figure 1 summarizes cancer type and rate stratified by mutation type. The most common malignancy was prostatic adenocarcinoma identified in 7/93 patients with BRCA1 mutation (8%), and 3/62 patients with BRCA2 (5%). Overall,16/24 patients (67%) were surgically treated for their cancer. Conclusions Malignancy rates in male BRCA mutation carriers are substantially higher than those reported for the general population in corresponding age groups. Prostate cancer is the most prevalent cancer apparent in up to 8% of patients at a median age of 50 years. Unlike other reports, prostate cancer was prevalent among BRCA1 carriers and not restricted to BRCA2. Funding The study was funded by the ASCO career development award, Israel Cancer Association, and German Israeli Foundation.
Authors
Roy Mano
Ofer Benjaminov Inbal Kedar Yaara Bar Sivan Sela Rachel Ozalvo Jack Baniel David Margel |
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PD07-11 |
Prostate cancer screening in high risk families. A Eight-year prospective program in young first degree relatives aged 40-49. |
Prostate Cancer: Detection & Screening II | 17BOS |
Abstract: PD07-11 Sources of Funding: Programme Hospitalier de Recherche Clinique, Ligue Nationale contre le Cancer (Comité du Finistère) Introduction Targeted screening in high risk families due to familial aggregation, is recommended as early as 40-45 years in first degree relatives (FDR) of prostate cancer (PCa) patients according to high risk and early onset of the disease. We aimed to assess this concept in FDR 40-49 years old (yo). Methods We obtained a serum PSA testing, yearly, in a 8-year PCa screening program, in 345 FDR (brothers or sons), 40-49 yo, of PCa patients treated, between 1994-1997. A systematic genealogical analysis previously performed, allowed to define the familial PCa status: at least 1 PCa in the family (range: 1-7), so the screened men were classified into: hereditary status (3+ PCa:11.3%), familial without obvious hereditary pattern (2 PCa:19.2%) or sporadic (1 PCa:69.5%). Prostatic biopsies (PBx) were performed when PSA >4ng/mL, until 2002, while when PSA >2.5ng/mL therafter. Results Mean age at screening was 45.5y. A total of 1344 screening tests were performed during this program (Table)._x000D_ Of the 345 screened men, 21 (6%) had at least one PSA level > 4 ng/ml of the 8 assessments (Table). PBx: diagnosed 7 PCa (2%) in 41, 43, 44, 45, 46 and 48 (2 cases) yo men, were negative in 5 relatives, were not done in 9 cases (1 refusal, 2 due to other medical problem, 6 due to control PSA <4ng/ml including 3 cases <2.5ng.ml). The positive predictive value of PSA >4ng/mL was 7/12 (58%). The proportion of men with PSA >4ng/mL in 2+ PCa families was significantly higher than in sporadic families: 2.9% vs 0.9% (p=0.013). In addition, 37 relatives (10.7%) had at least one PSA level >2.5ng/mL and <4ng/mL, and PBx diagnosed 2 more PCa (43 and 47 yo.) and most frequently were not done due to not indicated at that time (before 2003). Of the 208 relatives with PSA <1ng/mL at baseline: none had PSA >2.5ng/mL during the 4 consecutive years, while 7 had PSA >2.5ng/mL at 6th round (n=2), 7th round (n=4) and 8th round (n=1), the latter being diagnosed with PCa at 50 yo._x000D_ Conclusions Those results suggest that PCa is not frequent in 40-49 yo. FDR, however diagnosed in 9/345 (2.6%) of cases of whom 4 times before 45 y. Therefore we recommend to start screening as soon as 40 yo. in high risk families with annual PSA testing, except when baseline PSA is <1ng/mL case in which next PSA testing may be performed 5 years later. Funding Programme Hospitalier de Recherche Clinique, Ligue Nationale contre le Cancer (Comité du Finistère)
Authors
PIERRE CALLEROT
MARIE-PIERRE MOINEAU ISABELLE CUSSENOT FRANCOISE BASCHET JOEL L'HER LAURENT DOUCET LUC CORMIER PHILIPPE MANGIN OLIVIER CUSSENOT GEORGES FOURNIER ANTOINE VALERI |
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PD07-12 |
Molecular profiling of multi-focal prostate cancer and concomitant lymph node metastasis: implications for tissue-based prognostic biomarkers |
Prostate Cancer: Detection & Screening II | 17BOS |
Abstract: PD07-12 Sources of Funding: Prostate Cancer Foundation Introduction Current tissue-based prognostic biomarker assays claim that genetic assessment of a single focus is sufficient to predict disease behavior. We analyzed and compared the genetic profiles of multifocal prostate cancer (PCa) with concordant lymph node metastasis (LNM) to determine if expression based prognostic tests are robust to multifocality. Methods This IRB-approved study comprised patients who underwent radical prostatectomy and lymph node dissection that revealed N1 disease or discordant multifocal disease (low- and high-grade foci). DNA and RNA were co-isolated from each tumor focus pre-identified on formalin fixed paraffin embedded specimens. High depth, targeted DNA and RNA next generation sequencing was performed to characterize the genetic and transcriptional signature of each sample, using the Oncomine Comprehensive (11 patients) or Comprehensive Cancer (DNA, 3 patients) Panels and a custom targeted RNAseq panel comprising genes for deriving prognostic signatures. Results A total of 67 primary tumor and 17 LMN foci (with control tissue when available) from 14 patients were analyzed. We observed significant intra- and inter-patient molecular heterogeneity. For example, in patient #1, while all four regions of high-grade primary tumor showed TP53 somatic mutations and some broad copy number alterations (CNAs) with two samples from the LNM, tumor areas near the positive margin showed more complete concordance than intraprostatic regions. Critically, a low-grade primary tumor focus in this case showed no somatic mutation or CNA overlap with the high-grade or LNM samples. In patient #4, all tumor and LNM foci shared a large number of somatic mutations, including a frameshift mutation in PTEN, with no high level CNA identified, consistent with a hypermutated genotype. By targeted RNAseq, low-grade and high-grade tumors from the same patient showed distinct expression profiles using genes included in available prognostic signatures (Figure 1)._x000D_ Conclusions Our results challenge the claim that expression based prognostic tests are robust to multifocality. Additional molecular studies are needed to better characterize the biologically dominant lesion in multi-focal PCa and hold promise for the development of improved prognostic biomarkers. Funding Prostate Cancer Foundation
Authors
Simpa Salami
Daniel Hovelson Romain Mathieu Jeremy Kaplan Martin Susani Christopher Russell Nathalie Rioux-Leclercq Shahrokh Shariat Scott Tomlins Ganesh Palapattu |
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PD08-01 |
The role of glycoconjugates in formation of the human sperm reservoir |
Infertility: Basic Research & Pathophysiology II | 17BOS |
Abstract: PD08-01 Sources of Funding: none Introduction Despite to many animal models, the human sperm reservoir has not been described or characterized yet. The formation of the sperm reservoir is pivotal for maintaining sperm fertilizing capacity and for successful fertilization and pregnancy. In this study, the binding mechanism of human sperm to oviduct epithelium was investigated regarding glycoproteins on the surface of sperm plasma membrane and the surface of the oviduct epithelium. It was recently shown that several parts of sperm glycocalix might play an important role in the interaction with the female reproductive tract (Tecle and Gagneux, 2015) and potentially in formation of a sperm reservoir in the oviduct Methods Oviducts from 16 women that undergo hysterectomy treatment and 100 semen samples from healthy and infertile patients were analysed. For sperm-oviduct interaction, oviducts with naturally occurring spermatozoa and manually inseminated sperm were sampled. For this reason samples were prepared and analysed by Scanning Electron Microscopy (SEM). Fixed tissue sections from oviducts (ampulla region) were stained with Hoechst3342 and Fluorescein isothiocyanate (FITC) conjugated WGA, ConA, MPA and MAA lectins that recognize specific sugar residues on surface of tissues. Fresh sperm specimen were washed, fixed and stained with a FITC-conjugate of sialic acid, fucose, mannose and galactose. Fluorescence was analysed with a confocal scanning microscope. Results With SEM experiments showed that sperm can be found bound to the oviduct after three days of sexual intercourse; secretory cells play an important role in sperm binding. We found that N-acetylglucosaminyl residues are only situated on top of secretory cells in the oviduct; galactose and sialic acids residues were rare. Mannose can be found in cytoplasm of cells. It can be seen that molecules on plasma membrane bind different sugar motifs and that these molecules are mainly located in head region. Conclusions Our experiments give indication that glycoconjugates on surface of oviduct epithelium and sperm plasma membrane might take part in this important interaction. With this knowledge investigation on idiopathic infertility for men regarding surface binding molecules might be possible in future. Funding none
Authors
Susanne Bour
Rick Paschold Irene Alba-Alejandre Armin Becker Christian G Stief Sabine Koelle Matthias Trottmann |
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PD08-02 |
Loss of IFT140 Function May Disrupt Spermatogenesis by Regulating Germ Cell Apoptosis |
Infertility: Basic Research & Pathophysiology II | 17BOS |
Abstract: PD08-02 Sources of Funding: ASH is a K12 scholar supported by a Male Reproductive Health Research (MRHR) Career Development Physician-Scientist Award (Grant # HD073917-01 to DJL) from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Program Introduction We previously identified a homozygous, 6 nucleotide deletion in exon 22 of the intraflagellar transport 140 (IFT140) gene in a consanguineous family of non-obstructive azoospermic brothers using whole-exome sequencing. Data in Drosophila and mice implicate IFT family proteins in the modulation of cell signaling pathways, which are involved in the differentiation and proliferation of germ cells. The objective of this study is to determine the mechanism by which loss of IFT140 function may disrupt spermatogenesis. Methods Ift140 function was silenced in C18-4, a mouse type A spermatogonial cell line. Ift140 mRNA levels were evaluated using quantitative real-time PCR (qPCR). Gene expression studies were performed in triplicate on an oligonucleotide array (Qiagen) of 84 cell signaling genes of various known signaling pathways using Ift140 siRNA and a scrambled control (GE Dharmacon). Genes whose expression was more than 1.5x up or down relative to control were considered dysregulated and were validated and analyzed for statistical significance using REST software (Qiagen). The down-regulation of one target, Fas, was validated at the protein level by immunofluorescent staining. Knockdown and control cultures were treated with Sunitinib (2μM, 8 hours) to induce apoptosis, and a cell survival assay was performed. _x000D_ Results Ift140 knockdown was 75% efficient in C18-4 cells at 72 hours. Forty-one genes were down-regulated and 25 genes up-regulated. Eighteen genes&[prime] expression changes were indeterminate due to low expression in both groups. The expression of seven genes (Fas, Slc27a4, Serpine1, Bcl2l1, Cebpd, Sqstm1, Socs3) was more than 2x down-regulated while 5 genes (Slc2a1, Stat1, Hes1, Bmp4, Wnt6) were 1.5x to 2x down-regulated. Expression of five genes (Jag1, Csf1, Wisp1, Gata3, Bcl2) was more than 1.5x up-regulated. Fas, Bcl2, Bcl2l1, Slc2a1, Csf1, andBmp4 were significantly dysregulated (p<0.05). Co-immunofluorescent staining showed concordant down-regulation of Fas protein in Ift140-silenced cells. Upon Sunitinib treatment to induce apoptosis, 63.4% of Ift140-silenced cells survived 8 hours compared to 25.7% of scramble-control cells (p<0.05)._x000D_ Conclusions We observed statistically significant changes in the expression of key genes in the NFkB and TGFβ/BMP/Hedgehog pathways as well as major dysregulation in additional genes of the Notch, Wnt, Jak/Stat, TGFβ, PPAR, p53, and oxidative stress signaling pathways upon Ift140 knockdown in mouse male germ cells. The data suggests that silencing of Ift140 inhibits apoptosis, which may in turn cause spermatogenic failure._x000D_ Funding ASH is a K12 scholar supported by a Male Reproductive Health Research (MRHR) Career Development Physician-Scientist Award (Grant # HD073917-01 to DJL) from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Program
Authors
Amin Herati
Peter Bulter Dolores Lamb |
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PD08-03 |
Profiling of Human Adult Spermatogonial Stem Cells Reveals Transcription and Signaling Programs for Self Renewal and Differentiation |
Infertility: Basic Research & Pathophysiology II | 17BOS |
Abstract: PD08-03 Sources of Funding: This work was supported by HHMI. Introduction Male fertility relies on the proper regulation of human adult spermatogonial stem cells (SSCs), which either self-renew or commit to unipotent differentiation (spermatogenesis). The future of male fertility lies in culturing human SSCs, and is currently the core limitation of the field. Mouse SSCs can be cultured, manipulated, and transplanted back into the testis. However, the conditions used to culture mouse SSCs fail to support the growth and germline identity of human SSCs. To better understand human SSC self-renewal and differentiation, and to enable long-term culturing, we aimed to conduct molecular/genomic profiling of human SSCs. Methods First, we derived methods to purify the self-renewing human SSC (which bear the surface marker SSEA4), and differentiating human spermatogonia (which bear KIT). We profiled RNA/transcription (via bulk and single-cell RNA sequencing), DNA methylation (via whole-genome bisulfite sequencing) and determined the promoters and enhancers that have open chromatin (via ATAC-seq) in SSEA4-enriched SSCs. We also conducted RNA/transcription profiling of differentiating KIT+ spermatogonia to provide comparisons to SSEA4+ SSCs. Results Here, we successfully profiled RNA, chromatin and DNA methylation in human SSEA4+ SSCs, and RNA in KIT+ spermatogonia. We identified transcription factors and signaling pathway components that are unique to either SSEA4+ SSCs or KIT+ spermatogonia. Importantly, several factors including receptor/ligand systems and transcription factors appear unique to humans (not utilized in the mouse), results of which inform the biology of human SSC self-renewal and differentiation, and should inform and guide human SSC cell culturing. Remarkably, we find the core pluripotentcy genes (e.g. OCT4, SOX2, NANOG) repressed in SSCs, with portion apparently poised for activation in SSCs by open chromatin, creating a condition of ‘latent’ pluripotency likely to impact their developmental potential. Conclusions Human SSCs have been extensively profiled, revealing signaling and transcription factor pathways of likely importance. Latent pluripotency in SSCs may enable rapid activation of pluripotency following fertilization, but may also create susceptibiliy to forming germ cell tumors – enabling their plasticity to form tumors with all three germ layers. Overall, our findings provide insights into understanding unipotency and pluripotency in human SSCs, possible mechanisms for germ cell tumor formation, and guidance for in vitro culturing of human SSCs. Funding This work was supported by HHMI.
Authors
Jingtao Guo
Edward J. Grow Chongil Yi Douglas T. Carrell James M. Hotaling Bradley R. Cairns |
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PD08-04 |
WHOLE EXOME SEQUENCING OF A CONSANGUINEOUS TURKISH FAMILY IDENTIFIES A MUTATION IN X?LINKED FHL1 IN BROTHERS WITH MALE FACTOR INFERTILITY |
Infertility: Basic Research & Pathophysiology II | 17BOS |
Abstract: PD08-04 Sources of Funding: Hussman Institute for Human Genomics_x000D_ _x000D_ _x000D_ Introduction Up to 80% of patients with a diagnosis of nonobstructive azoospermia (NOA) have a negative result on genetic testing. We sequenced the exomes of a consanguineous Turkish family comprised of the mother and father, who are cousins, and their four sons. Two sons had NOA and two had chest wall deformities and oligospermia. Standard genetic testing revealed no karyotype abnormalities or Y microdeletions. Using whole exome sequencing (WES) data and homozygosity mapping we sought to investigate the genetic cause of abnormal semen parameters in the sons._x000D_ _x000D_ Methods Extraction of DNA was performed from blood samples followed by whole exome sequencing. Variants were annotated using the ANNOVAR software tool. The filter based annotation feature was used to assess variants for rarity, deleterious nature, conservation, and confirmed familial segregation as well as absence in the control population. _x000D_ _x000D_ Results A non?synonymous mutation in “four?and?a?half lim domains 1� (FHL1) was identified in this consanguineous family from Turkey. This mutation in exon 6 (Xchr:135292164 G>A) of FHL1 is a nonsynonymous SNP and likely a disease?causing mutation as it is predicted to be damaging (SIFT 0.026, mutation taster score 1/D, and Polyphen2 0.846), is a rare variant (ExAC allele frequency of 1.11%), segregates with the disease, and is highly conserved (GERP 5.57). Family segregation of the variants showed the presence of the homozygous mutation in the brothers with NOA and low sperm counts, heterozygous mutation in the mother, and homozygous wild type in the father indicating an X?linked inheritance pattern. Conclusions Using WES, we identified an X linked mutation in FHL1 as a likely disease?causing variant in a Turkish family with two sons diagnosed with NOA. Our data reinforce the clinical role of WES in the molecular diagnosis of highly heterogeneous genetic diseases, where conventional genetic approaches have previously failed to define a genetic diagnosis. Funding Hussman Institute for Human Genomics_x000D_ _x000D_ _x000D_
Authors
Raul Clavijo
Samuel Cohen anthony griswold Emre Bakircioglu Ranjith Ramasamy |
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PD08-05 |
Identifying differential mRNA and miRNA expression patterns in dilated and collapsed seminiferous tubules reveals unique “niche” for spermatogenesis in men with severe forms of infertility |
Infertility: Basic Research & Pathophysiology II | 17BOS |
Abstract: PD08-05 Sources of Funding: None Introduction Non-obstructive azoospermia (NOA) is a cause of male infertility secondary to genetically driven defects in spermatogenesis. Testicular sperm extraction (TESE) is successful in identifying small number of sperm in 50% of men with NOA. During TESE, predominantly collapsed seminiferous tubules (ST) are identified with rare areas of dilated STs that are more likely to harbor viable sperm. Hence we hypothesize that miRNA regulated control of mRNA expression along STs leads to optimal environments for spermatogenesis within the human testis. Methods STs were obtained from 7 patients, including 3 with NOA, and 2 patients with Sertoli-cell only (SCO). In the three NOA patients, single STs were cut based on the differences in diameter along the same ST into: full/dilated or empty/collapsed tubules. Quantitative PCR was performed on all tubules for GFR?1 and values expressed per vimentin and clusterin. ACTB was used as a housekeeping gene. Expression of GFR?1 was corrected for number of Sertoli cells (vimentin/clusterin). MiRNA expression profiles were determined for each segment of STs and normalized to let-7a. GenEx software was used to identify differentially expressed miRNAs using adjusted p<0.0007 and minimum of 2-fold difference. _x000D_ Results Quantitative PCR showed a statistically significant decrease in the relative expression of GFR?1 between dilated and collapsed STs (p<0.001) indicating an abnormal number of spermatogonial stem cells (SSC) or spermatogonia. A set of 12 miRNA were identified to be differentially expressed and linked to known signaling pathways in Sertoli cells and SSCs Conclusions Our data supports the hypothesis that unique miRNA profiles support normal SSC division that correlate into islands of spermatogenesis, especially in men with NOA. This data in conjunction with previous observations that SSCs are likely present in patients with SCO offers new targets for further research and possible therapeutic intervention Funding None
Authors
Sameer Mittal
Anna Mielnik Alexander Bolyakov Peter Schlegel Darius Paduch |
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PD08-06 |
RNA Sequencing. Exploring Histologic Phenotypes of Non-Obstructive Azoospermia |
Infertility: Basic Research & Pathophysiology II | 17BOS |
Abstract: PD08-06 Sources of Funding: P50 HD076210, U1 1U01HD074542-01, Frederick J. and Theresa Dow Wallace Fund of the New York Community Trust, the Mr. Robert S. Dow Foundation, Irena and Howard Laks Foundation_x000D_ _x000D_ This work was supported in part by the Urology Care Foundation Research Scholar Award Program and AUA New York Section Research Scholar Fund Introduction Non-obstructive azoospermia due to testicular failure can be histologically classified into 3 phenotypes: sertoli cell only (SCO), early maturation arrest (eMA), and late maturation arrest (lMA). Genetics of NOA is largely unknown and identification of genetic mutations leading to NOA has been inconclusive. In our study, we focused on large scale exome sequencing in testicular tissue from men with NOA to determine candidate genes for mechanistic, diagnostic and therapeutic evaluation._x000D_ Methods Total RNA was extracted from tissue harvested from testicular biopsy. 37 patients with non-obstructive azoospermia (NOA) and 3 histologic phenotypes: SCO, eMA, lMA as well as normal controls (NL). RNA libraries were sequenced on an Illumina HiSeq 2000 platform. Results were mapped to the genome and transcriptome using TopHat (v2.0.8). Cufflinks was then used to quantify the number of reads. RNA Seq data was expressed as FPKMs and normalized using TMM. JMP genomics was used to identify differentially expressed (DE) transcripts at FDR = 0.001. Due expected loss of specific germ cells populations in lMA, eMA, and SCO syndrome, we focused our analysis on overexpressed transcripts in each histological category as compared to NL control. _x000D_ _x000D_ Results Among 21,879 mapped transcripts 10,777 were DE between SCO and NLs. Using a contingency analysis, 6,169 genes were DE between eMA and normal when compared to SCO and normal DE (p<0.0001), and are likely involved in entry into meiosis and function of primary spermatocytes. Most overexpressed and DE genes include: JUN, BTG2, and RASAL1, which are expressed in the testis and previously described to regulate cell cycle and proliferation. 30 genes were DE between lMA and NL but not DE between NL and eMA, suggesting a mechanistic role in lMA as they are not due to loss of spermatids or spermatozoa. Here, most DE genes include SMIM8, SNF280C and OTUD6A and are exclusively expressed in testis based on GEO human tissues expression profile. To validate our analytical approach, we demonstrated a loss of SYCP3 (marker of primary spermatocytes) in SCO and down regulation of PRM1 (spermatids) in SCO, eMA, and lMA compared to NL. Expression of SOX9 (Sertoli marker) and INSL3 (Leydig marker) were similar across all groups._x000D_ Conclusions Using whole exome sequencing to directly compare DE of genes among the differing phenotypes of SCO, eMA, and lMA have allowed us to identify active gene transcripts localized to specific stages of arrested spermatogenesis. Additionally, we identified a small subset of genes which are over expressed, potentially contributing to the pathology of NOA._x000D_ _x000D_ Funding P50 HD076210, U1 1U01HD074542-01, Frederick J. and Theresa Dow Wallace Fund of the New York Community Trust, the Mr. Robert S. Dow Foundation, Irena and Howard Laks Foundation_x000D_ _x000D_ This work was supported in part by the Urology Care Foundation Research Scholar Award Program and AUA New York Section Research Scholar Fund
Authors
Ryan Flannigan
Anna Mielnik Alex Bolyakov Jen Grenier Brian Robinson Phil V. Bach Darius Paduch |
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PD08-07 |
Loss of germ cells does not affect levels of miRNA202-5p expression in an LRAT knockout model indicating that loss of miR202-5p in SCO is the primary defect in men with azoospermia |
Infertility: Basic Research & Pathophysiology II | 17BOS |
Abstract: PD08-07 Sources of Funding: This work was supported by: P50 HD076210, U1 1U01HD074542-01, Frederick J. and Theresa Dow Wallace Fund of the New York Community Trust, the Mr. Robert S. Dow Foundation, Irena and Howard Laks Foundation; Urology Care Foundation Research Scholar Award Program and AUA New York Section Research Scholar Fund Introduction Sertoli cell only (SCO) syndrome is the most severe form of male factor infertility. We have previously demonstrated loss of expression of miRNA202-5p in Sertoli cells in men with SCO; however, it is unknown if such loss of miRNA-202-5p in Sertoli cells is due to the loss of germ cells or is a primary event. Our objective was to evaluate if loss of germ cells will lead to secondary loss of miRNA202-5p expression. An inducible SCO animal model, Lecithin: Retinol Acyltransferase (LRAT) knockout (KO) mouse was used to answer our question. Methods 9 LRAT KO animals were fed either Vitamin A sufficient (ASuf) or Vitamin A deficient (ADef) diets for 8wks, with the latter known to produce SCO. H&E of testicular slides was used to assess histology. Immunofluorescence (IF) with antibodies against SYCP3 (marker of spermatocytes) was used to confirm loss of meiotic cells in LRAT KO Adef mice. RNAseq and smallRNA sequencing was performed using total RNA extracted from testes. Sequencing results were processed using JMP Genomics. Expression levels of GFRa1, PLZF, SCYP3, PRM1, TNP, CLU, and VIM were used to evaluate loss of different germ cell populations in the Adef group, and to normalize the data to the number of Sertoli cells. MicroRNA202-5p expression (Sertoli specific), miR-34c (germ cell specific) and let-7 (ubiquitous) were measured from sequencing data and further confirmed using QRT-PCR. Results were statistically significant at FRD=0.01 Results 3 mice were evaluated in each respective group, LRAT Asuf and ADef conditions, at both 6 and 8wk time points. Histology, IF, and sequencing data demonstrated that spermatogenesis was present in all groups except for LRAT ADef mice at 8 weeks. Histology revealed heterogeneity, with most tubules resembling SCO in LRAT ADef testes. Normal spermatogenesis was observed in LRAT KO Asuf mice, and hypo spermatogenesis was observed inLRAT KO ADef mice at 6wks. There was no significant change in expression levels of miR202-5p between LRAT ASuf an ADef groups at 8wks. However, expression of miR34c was significantly decreased in the LRAT Adef group. Let-7 expression remained same. Conclusions Loss of meiotic germ cells in LRAT KO ADef mice did not result in loss of miRNA-202-5p expression when compared to controls despite development of predominantly SCO histology. Our results provide strong evidence that the observed loss of expression of miRNA202-5p in men with SCO is not due to the primary loss of germ cells but is a result of primary miRNA-202-5p dysfunction in Sertoli cells. _x000D_ Funding This work was supported by: P50 HD076210, U1 1U01HD074542-01, Frederick J. and Theresa Dow Wallace Fund of the New York Community Trust, the Mr. Robert S. Dow Foundation, Irena and Howard Laks Foundation; Urology Care Foundation Research Scholar Award Program and AUA New York Section Research Scholar Fund
Authors
Ryan Flannigan
Anna Mielnik Alex Bolyakov Phil Bach Jen Grenier Lorraine Gudas Peter Schlegel Darius Paduch |
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PD08-08 |
S-NITROSOGLUTATHIONE REDUCTASE (GSNOR) KNOCKOUT MICE: A NOVEL MODEL OF MALE INFERTILITY |
Infertility: Basic Research & Pathophysiology II | 17BOS |
Abstract: PD08-08 Sources of Funding: This work was supported in part by the Urology Care Foundation Research Scholar Award Program to RR_x000D_ Introduction Nitrosative stress is regulated by S-nitrosylation of cysteine thiols. Mice lacking S-nitrosoglutathione reductase (GSNOR KO mice), a denitrosylase that regulates S-nitrosylation, show increased levels of S-nitroslyated proteins and exhibit nitrosative stress. Nitrosative stress, similar to oxidative stress, can affect spermatogenesis. We hypothesized that GSNOR KO male mice will exhibit impaired fertility and spermatogenesis. Methods Male wild-type (WT) and GSNOR KO mice (N=6 each) were studied after postnatal day 42, at a stage where they have completed the first wave of spermatogenesis. Testes were either fixed and/or frozen for further analysis. Histology of testes was quantified using Johnsen score, epididymal sperm counts was determined using an automated counter, serum testosterone levels was determined using ELISA and GSNOR protein within the testis was evaluated using immunofluorescence and Western blot analysis. Results GSNOR KO males exhibited significantly smaller testes as compared to WT (0.1± 0.0 grams vs. 0.07± 0.0 grams, p<0.05). Furthermore, serum testosterone levels was significantly lower in the GSNOR KO as compared to WT mice (370.18 ± 0.0ng/mL vs. 42.55 ± 21.7 ng/mL, p<0.05). Histological analyses using Johnsen score of GSNOR KO testes showed evidence of degeneration of seminiferous tubules, overall reduction in post-meiotic cells and disrupted spermatogenesis (9.5 vs. 6.5, p<0.05). We observed a ~2-fold reduction in epididymal sperm count in GSNOR KO males compared to WT males, indicating that spermatogenesis was impaired, but not globally arrested (2054 ± 35.35 sperms vs. 1236 ± 86.26 sperms, p<0.05). Wild type testis showed extremely high levels of GSNOR protein expressed in the germ cells as well as Leydig cells. Conclusions This is the first study demonstrating the association between GSNOR and male fertility. GSNOR KO males exhibit small testes with impaired spermatogenesis and reduced fertility. Attempts to decrease nitrosative stress can reverse impaired spermatogenesis. Funding This work was supported in part by the Urology Care Foundation Research Scholar Award Program to RR_x000D_
Authors
Shathiyah Kulandavelu
Marilia Sanches Santos Rizzo Zutti HIMANSHU ARORA Oleksandr Kryvenko Emad Ibrahim Nancy L Brackett Joshua M. Hare Ranjith Ramasamy Thomas Masterson |
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PD08-09 |
How does advanced paternal age affect the next generation? |
Infertility: Basic Research & Pathophysiology II | 17BOS |
Abstract: PD08-09 Sources of Funding: none Introduction Older fathers have a significantly higher chance of generating offspring with a high prevalence of genetic abnormalities, childhood cancers, and neuropsychiatric disorders, including schizophrenia, autism, and bipolar disorder (1). We know very little about how paternal aging affects future generations or why certain syndromes are particularly susceptible to the paternal-age effect. A recent trend toward delayed paternity (in the US, births to fathers over 40 years has risen from 7.5% in 1992 to 10.1% in 2000 (2)) and a widespread use of assisted reproductive technologies (which resulted in 61,610 US infants in 2011 (3)) makes it imperative for our species to understand how aging effects germ cells and how paternal factors affect the next generation. The current studies on paternal aging are mostly descriptive and we lack animal models to address the mechanisms. Methods While a diverse pool of RNAs exists in sperm, it was the dogma that only sperm contribute DNA to the next generation. However, recent studies have shown that the effects of an animal’s environment, such as traumatic stress and high fat diet, during adolescence can be passed down to the next generation through sperm RNAs(4–6). In this study, we sequenced both small RNAs (miRNAs and piRNAs) and long RNAs (mRNAs, transposable elements, and non-coding RNAs) from sperm of C57/B6 wild-type mice of the ages 8 weeks, 15 months and 21 months. Results We detected a distinct miRNA profile during paternal aging and an age-dependent decrease in RNA surveillance for transposable elements in male germ cells. Conclusions In conclusion, the sperm RNA changes can be used as biomarkers to evaluate the aging process in old males. We envision that this work will pave the way for further studies on sperm RNA transgenerational effects. _x000D_ Reference_x000D_ 1. D. Malaspina, C. Gilman, T. M. Kranz, Fertil Steril 103, 1392 (2015)._x000D_ 2. M. King, P. Bearman, Int J Epidemiol 38, 1224 (2009)._x000D_ 3. S. Sunderam et al., MMWR Surveill Summ 63, 1 (2014)._x000D_ 4. K. Gapp et al., Nat Neurosci 17, 667 (2014)._x000D_ 5. U. Sharma et al., Science 351, 391 (2016)._x000D_ 6. Q. Chen et al., Science 351, 397 (2016)._x000D_ Funding none
Authors
Jiang Zhu
Xin Li |
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PD08-10 |
Does detection of DDX4 mRNA in cell free seminal plasma represents a reliable non-invasive germ cell marker in patients with non-obstructive azoospermia? |
Infertility: Basic Research & Pathophysiology II | 17BOS |
Abstract: PD08-10 Sources of Funding: none Introduction Sensitivity of application of molecular transcripts as non-invasive biomarkers for assessment of spermatogenesis in cases with non-obstructive azoospermia is hindered; mostly by the restricted number of gametocytes in seminal fluid. In addition, histopathological examination of testicular biopsies of those cases is sometimes impeded by the focal distribution of spermatogenesis._x000D_ The aim of the present work was to investigate the potential application of DDX4 gene expression in cell free seminal mRNA as a non-invasive biomarker for the identification of the presence of germ cells in men with non-obstructive azoospermia and to correlate this factor with other predictors of spermatogenesis in non-obstructive azoospermia, namely: testicular biopsy._x000D_ Methods Thirty-nine infertile males diagnosed as non-obstructive azoospermia (NOA) by means of testicular biopsy, were enrolled in this study. A group of twenty-eight normospermic fertile males served as a control group. The study was approved by the Ethics Committee. All patients provided informed consent to participate in this study. _x000D_ Thorough history taking and physical examination were carried out. Semen was collected by masturbation after 3-5 days of abstinence and was analyzed according to World Health Organization guidelines, 2010. Serum follicle stimulating hormone (FSH), luteinizing hormone (LH) and testosterone level were all assayed on AdviaTM Centaur Immunoassay System._x000D_ Two male reproductive organs-specific genes were chosen; DDX4 which is a germ cell-specific gene,and TGM4 (transglutaminase 4) which is a prostate specific gene which was included as a control gene. Gene expression for both DDX4 and TGM4 genes were performed using TaqMan® Gene Expression Assays. Gene expression was assessed using the 2-??Ct method._x000D_ Results Thirty-nine azoospermic males participated in the present study. A group of 28 normospermic fertile males served as a control group. Both groups were matched for age. Level of both serum FSH and LH was statistically higher, while serum testosterone showed statistically lower values in azoospermic males (p?0.001). Histopathological examination of testicular biopsies categorized azoospermic males into 20.5% (n= 8) with maturation arrest (MA), 17.9 % (n= 7) with incomplete Sertoli Cell Only Syndrome (icSCOS) and 61.5 % (n=24) with complete Sertoli Cell Only Syndrome (cSCOS)._x000D_ In patients with azoospermia, TGM4 gene was detected in 100% of semen samples. Positivity for DDX4 gene was detected in 17 out of 39 males with NOA which was attributed to MA in 35.3% (n=6/17), icSCOS in 23.5% (n=4/17) and cSCOS in 41.2% (n=7/17). Both DDX4 and TGM4 genes were consistently detected in semen samples of all control subjects._x000D_ Conclusions Detection of germ cell non stage specific gene mRNA in cell free seminal plasma is a non-invasive screening tool of non-obstructive azoospermia. It is a good positive diagnostic tool but not a good negative one, as some DDX4 negative cases were proved by testicular biopsy to be cases of maturation arrest and not cases of complete Sertoli Cell Only Syndrome. Moreover, it could detect foci of spermatogenesis in casesb histopathologically diagnosed as complete Sertoli Cell Only Syndrome. Funding none
Authors
Wafaa Abdallah
Doaa Hashad Rania Abdelmaksoud Mohamed Mohieeldin Hashad |
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PD08-11 |
Leydig Stem Cell Autograft in Mice: A Novel Approach to Increase Serum Testosterone while Preserving Fertility |
Infertility: Basic Research & Pathophysiology II | 17BOS |
Abstract: PD08-11 Sources of Funding: This work was supported in part by the Urology Care Foundation Research Scholar Award to RR. Introduction Leydig cell loss or dysfunction is associated with impaired testosterone production. Exogenous testosterone supplementation can be used to treat low testosterone, however it has several adverse effects including infertility due to negative feedback on the hypothalamic-pituitary-gonadal axis. We studied testosterone production in mouse models following autograft in skin with Leydig stem cells isolated from testes. Methods A total of 10 wild-type adult C57/BL6 mice were included in the study. Orchiectomy was conducted in seven mice (4 experimental and 3 negative controls) and the remaining three were used as positive controls. Leydig stem cells were harvested from testis by collagenase/trypsin digestion. Cells from each mouse were allowed to grow separately in the media containing DMEM, FBS (10%), P/S, ITS, Dexamethasone, EGF, PDGF-AA. After 10 days following orchiectomy, 1 X 106 cells from four animals were autografted in the subcutaneous tissue. After four weeks, grafts and blood were harvested. We evaluated testosterone production, graft morphology, and expression of Leydig cell markers. Results We successfully isolated and cultured up to 1 million Leydig stem cells / testis from all 7 animals. These cells were differentiated and converted into functional adult Leydig cells in vitro. Stem cell property of cultured cells was confirmed by IF and qPCR in which the expression of PDGFR-? was high in regular media vs differentiation induction media and expression of 3BHSD was low in regular media vs differentiation induction media. The autografts were able to survive in animals for at least one month. H&E staining showed the presence of Leydig stem cells subcutaneously. Testosterone levels were almost doubled in autograft mice as compared to negative controls. Conclusions Our results indicate that Leydig stem cells can be isolated and cultured from wild-type mice. Leydig stem cell autograft can a novel therapeutic approach to increasing serum testosterone while simultaneously preserving fertility. Funding This work was supported in part by the Urology Care Foundation Research Scholar Award to RR.
Authors
HIMANSHU ARORA
Marilia Sanches Santos Rizzo Zutti Bruno Nahar Joshua M. Hare Ranjith Ramasamy |
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PD08-12 |
In Vitro Expansion and Manipulation of Human Spermatogonial Stem Cells |
Infertility: Basic Research & Pathophysiology II | 17BOS |
Abstract: PD08-12 Sources of Funding: California Institute for Regenerative Medicine (RB5-07210)_x000D_ Introduction Spermatogonial stem cells (SSCs) are essential for the generation of sperm, an event that occurs throughout adult life. Moreover, SSCs have therapeutic potential. A prime application for SSC transplantation is cancer survivors who went through gonadotoxic therapy during their prepubertal period, and thus no mature sperm could be cryopreserved prior to treatment. Despite the importance of human SSCs, remarkably little is known about them, including the mechanisms driving their self-renewal and expansion. Here, we demonstrate effective ways to culture, expand, and manipulate gene expression in human SSCs. _x000D_ Methods Human testicular biopsies were obtained from fertile donors and cultured either as slices (organ culture) or as dispersed cells. RHOXF2 was depleted using a RHOXF2 small hairpin (sh) RNA that we cloned into a lentiviral vector. Immunostaining, FACS, and quantitative (q) RT-PCR were used to assess gene expression. _x000D_ Results Human testicular organ cultures exhibited a modest increase in SSC and spermatogonia markers and a dramatic decline in advanced germ cell markers (Fig. 1A). This suggests a proliferative expansion of spermatogonia, including SSCs, and loss of more differentiated germ cells. Cultured dissociated germ cells exhibited a similar pattern of marker expression except that advanced germ cell markers did not decline in level (Fig. 1B). Clusters of germ cells were observed in these cultures, possibly indicative of proliferative expansion (Fig. 1C). FACS analysis with the human SSC marker, SSEA4, revealed that both culture conditions increased the number of SSEA4+ cells, confirming expansion of SSCs/undifferentiated spermatogonia. Lentivirus infection with a RHOXF2 shRNA successfully depleted RHOXF2 expression (Fig. 1D), demonstrating the ability to manipulate gene expression in human spermatogonial cell cultures. Conclusions We show that human spermatogonia expressing SSC markers can be cultured and modestly expanded in vitro, either as tissue slices or dissociated cells. Our methods to culture and manipulate gene expression in human spermatogonia can be used to decipher mechanisms underlying human SSC self-renewal as a means to expand SSCs in vitro for clinical application. Funding California Institute for Regenerative Medicine (RB5-07210)_x000D_
Authors
Hye-Won Song
Tung-Chin Hsieh Miles Wilkinson |
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PD09-01 |
Patient Satisfaction with the Use of Telemedicine in the Management of Prostate Cancer |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making II | 17BOS |
Abstract: PD09-01 Sources of Funding: none Introduction Telemedicine is gaining in popularity and has demonstrable efficacy in carrying out patient interviews over a video-conference system. The amenability of telemedicine to evaluate prostate cancer at various stages of disease has not yet been studied. Our primary objective was to evaluate patient satisfaction in the evaluation of patients with prostate cancer at various stages using telemedicine encounters (TME). Methods We performed a retrospective review of 424 consecutive TME at an urban academic urology practice carried out from its inception in October 2015 to August 2016; 219 patients (52%) completed our satisfaction survey. After each encounter, patients were asked to rate their satisfaction with their provider and of their use of a HIPAA-compliant video-conference system separately on a Likert scale of 1 to 5, with 5 being the most favorable and 1 being the least favorable. Of patients who completed the survey, 30 individual TME had prostate cancer as the primary diagnosis. These TME were separated according to the reason for each TME, and the mean (μ) satisfaction scores were calculated for each reason. ANOVA testing was used to determine significant difference in patient satisfaction based on reason for TME. Results The breakdown of the 30 encounters is as depicted in Table 1. There was no significant difference in satisfaction between the reasons for each visit [patient-provider satisfaction (PPS) p= 0.27; patient-system satisfaction (PSS) p= 0.94]. Of note, 10 prostate biopsy discussion encounters and 2 PSA follow-up encounters were carried out as part of the patients' active surveillance protocol. 8 prostate biopsy visits were carried out for discussion of a newly positive prostate biopsy result or an increase in the patient's Gleason Score with μ PPS = 4.88 and μ PSS = 4.88. For the remaining visits with no change in biopsy results, μ PPS = 5.0 and μ PSS = 4.5. Conclusions Our results suggest that video visits can satisfactorily be carried out in the management of prostate cancer; particularly with patients undergoing active surveillance. Discussion of newly positive biopsies or an advanced Gleason score may also satisfactorily be carried out. Funding none
Authors
Deborah Glassman
Ajay Puri Sarah Weingarten Judd Hollander Anna Stepchin Edouard Trabulsi |
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PD09-02 |
Racial Variation in the Refusal of Initial Treatment Plan Among Men Diagnosed with Localized Prostate Cancer |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making II | 17BOS |
Abstract: PD09-02 Sources of Funding: none Introduction Racial disparities in prostate cancer treatment and outcomes are a persistent public health problem. Communication between physician and patient about the clinical implications of prostate cancer and the trade-offs between different primary treatment options remains critical to prostate cancer management. To evaluate the communication about treatment options for prostate cancer, we assessed variation in the refusal of primary therapy among men diagnosed with prostate cancer from a national database. Methods Using the National Cancer Database (NCDB), we identified all men diagnosed with localized prostate cancer from 2004 to 2013. The primary outcome was patient refusal of surgical or radiation therapy, annotated in the NCDB when recommended treatment was not performed with documentation of patient refusal. Multivariable logistic regression analysis was performed to determine clinical factors associated with patient refusal of primary therapy after meeting with a radiation oncologist or urologist. We also examined the association of all-cause mortality with refusal of therapy using Cox proportional hazards regression. Results During the study interval, we identified 1,153,871 men diagnosed with localized prostate cancer. The median age was 65 years old. The most common primary therapies were surgery (55%) and radiation therapy (37%). Overall, 21,893 men refused any primary therapy (2.1%), which occurred in 2.0% of patients offered surgery and 2.5% of patients offered radiation. On multivariable analysis, African American (AA) men were more likely to refuse primary therapy compared to white men diagnosed with localized prostate cancer (OR:1.3; 95% CI 1.2-1.3). Similar findings were seen among patients with low income compared to high income (OR: 1.2; 95% CI 1.16-1.23). Refusal of primary therapy was also associated with higher all-cause mortality (HR: 1.2; 95% CI: 1.2-1.3) after adjusting for clinical stage, Gleason score, and treatment. Conclusions Although this occurs infrequently, AA men diagnosed with localized prostate cancer are more likely to refuse primary therapy, which is also associated with worse survival. Increased attention to improving patient communication about the severity of prostate cancer and risks and benefits of treatment is needed. Funding none
Authors
Kelly Scarberry
Kyle Scarberry Robert Abouassaly Christopher Gonzalez Cary Gross Nilay Shah Neal Meropol Sarah Psutka Sandip Prasad Laura Bukavina Simon Kim |
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PD09-03 |
Three-year functional outcomes after radiation, surgery or observation for localized prostate cancer in the CEASAR study |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making II | 17BOS |
Abstract: PD09-03 Sources of Funding: Funding for the study was provided by Agency for Healthcare Research and Quality (1R01HS019356, 1R01HS022640); Patient-Centered Outcomes Research Institute (CE-12-11-4667); Vanderbilt Institute of Clinical and Translational Research (UL1TR000011 from NCATS/NIH); NIH/NCI Grant 5T32CA106183 (MDT). Each of these provided financial support through grants, but none was involved in the conduct of the study. Introduction Prostate cancer (PCa) treatments are associated with urinary, sexual, and bowel side effects. Previous comparative effectiveness studies are limited by narrow inclusion criteria and outmoded treatments. Herein, we present 3-year functional outcomes in a diverse population of patients receiving contemporary treatment for localized PCa. _x000D_ _x000D_ Methods The Comparative Effectiveness Analysis of Surgery and Radiation (CEASAR) study is a prospective, population-based, cohort study of men diagnosed with localized PCa in 2011-2012. Men 80 years old or younger, with newly diagnosed cT1 or cT2 PCa, prostate specific antigen less than 50 ng/dL, were accrued from five Surveillance Epidemiology, and End Results (SEER) registry sites and from the Cancer of the Prostate Strategic Urologic Research Endeavor. Patient-reported urinary, sexual and bowel function, using the 26-item Expanded Prostate Index Composite (EPIC) at baseline, 6, 12, and 36 months after enrollment (range 0-100, higher score indicates better function). _x000D_ _x000D_ Results The analytic cohort contained 2,543 men: 26% non-white; 45% low-risk, 39% intermediate risk, 16% high risk. 1,523 (59.9%) men underwent radical prostatectomy (RP), 599 (23.6%) external beam radiotherapy (EBRT), and 421 (16.6%) active surveillance (AS). At 3 years, sexual function after RP was significantly worse than EBRT (-17.1 points; 95% CI: -21.7 to -12.6; p<0.001), Figure. Differences in sexual function between EBRT and AS at 3 years, while statistically significant, were not clinically significant (-5.9 points; 95% CI -11.0 to -0.8; p=0.023). RP was associated worse urinary continence scores than EBRT (-18 points; 95%CI: -20.6, -15.5; p<0.001) or AS (-13.4 points; 95% CI: -16.8, -10.1; p<0.001). At 3 years, 14% of RP men reported moderate or big problem with urinary leakage compared to 5% for EBRT and 6% for AS (p<0.001). Functional outcomes were driven largely by baseline function and treatment (Figure). There were no clinically significant differences in bowel or hormone function and no difference in survival. _x000D_ _x000D_ Conclusions The effects of modern treatments are similar to the effects of older modalities noted in prior studies. This information will provide a foundation for shared decision making, rooted in contemporary population-based data._x000D_ _x000D_ Funding Funding for the study was provided by Agency for Healthcare Research and Quality (1R01HS019356, 1R01HS022640); Patient-Centered Outcomes Research Institute (CE-12-11-4667); Vanderbilt Institute of Clinical and Translational Research (UL1TR000011 from NCATS/NIH); NIH/NCI Grant 5T32CA106183 (MDT). Each of these provided financial support through grants, but none was involved in the conduct of the study.
Authors
Daniel Barocas
JoAnn Alvarez Matthew Resnick Tatsuki Koyama Mark Tyson Karen Hoffman David Penson |
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PD09-04 |
A randomised controlled feasibility study: A multimodal supportive care intervention in men and their partners/carers affected by metastatic prostate cancer |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making II | 17BOS |
Abstract: PD09-04 Sources of Funding: The Urology Foundation Introduction A metastatic prostate cancer diagnosis and its treatments carry significant morbidity and related unmet supportive care needs. Such unmet needs have a profound decrement on patients and their families. We aimed to deliver at multimodal intervention based approach that targeted unmet needs for men and their partner/carers and compared this to current standard care. Methods A two arm randomised controlled feasibility trial compared standard care to a multimodal supportive care intervention that combined an educational seminar on prostate cancer thrivership and individualized care from a designated prostate cancer specialist nurse. This involved in-depth assessment using patient reported outcome measures (PROMs) in routine clinical practice, followed up with a tailored plan of ongoing support to address informational, emotional, social and practical needs. 38 participants and 10 carers/partners completed validated and reliable self-reported measures at baseline and at 3 months. 32 Semi-structured interviews were conducted with men, carers/partners and members of the multidisciplinary team. Self-efficacy was included as the potential moderator/mediator of intervention effect. Primary outcomes are unmet supportive care needs and quality of life. An economic evaluation was conducted alongside the randomised trial. Results 29 participants in standard care arm (age 77.5, SD 6.2 years) identified a range of unmet supportive care needs related to physical, psychological/emotional, intimacy/sexual, practical, health system/informational, existential and patient/clinician communication needs. 19 participants (age 74.9, SD 8.2, years) in the interventions group, reported overall high satisfaction with the intervention and acceptance of PROMs in routine clinical practice, with less prevalence of unmet needs compared to standard care over time. Men and carers/partners perceived that they had derived benefit from this model of care. Certain themes clearly emerged as important for participants, including being listened to by someone who could facilitate emotional expression, being provided with individually tailored information and receiving practical help and evidence-based advice for managing the consequences of cancer and its associated treatments. Significant cost-savings emerged in favour of the intervention. Conclusions This study has demonstrated that a multimodality supportive care intervention for men and their carer/partners affected by metastatic prostate cancer can achieve optimal supportive care. The active components of the intervention have been distinguished and provide the basis for the development of a larger sufficiently powered trial. Funding The Urology Foundation
Authors
Catherine Paterson
Charlotte Primeau Ghulam Nabi |
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PD09-05 |
Participation of Black Men with Prostate Cancer: A Longitudinal Assessment of 25 Years (1991-2015) of Randomized Controlled Trials |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making II | 17BOS |
Abstract: PD09-05 Sources of Funding: Departmental, NIH (U54MD008620) Introduction Black men experience the highest prostate cancer burden in the United States and globally. One of the factors that may contribute to the slow progress in eliminating prostate cancer disparities among Black men is their underrepresentation in randomized controlled trials (RCTs) of new treatment modalities. We conducted this study to assess the current status of Black men's participation in RCTs for prostate cancer. Methods We performed a protocol-driven systematic review for all published prostate cancer RCTs over a 25-year time period (1991-2015) searching PUBMED. We only included RCTs of patients with an established diagnosis of prostate cancer and excluded studies of screening and diagnosis. For studies that resulted in multiple publications, only the initial study was included. We excluded secondary and subgroup analyses. Results We found 584 unique trials that met the inclusion criteria, which we analyzed by type of intervention, sample size, disease stage, number of sites, origin, type of funding, publication year, the year enrollment began, and whether the study reported the inclusion of Black men. The median sample size of all trials was 125.5 (IQR = 60-286.5) and the median number of sites was 5 (IQR = 1-22). One hundred and eleven of the 584 (19.0%) trials worldwide and 81 of 189 (42.9%) of trials conducted exclusively within the US reported the enrollment of Black men. Of those trials that reported the inclusion of Black men, the median percentage of the study population was 10.55% overall (IQR = 6.6%-19.8%) and 12.27% (IQR = 7.0%-21.2%) for studies based exclusively in the United States. Among the 111 trials that reported the racial composition of participants, the median number of Black patients was 20 (IQR = 8-37.5). In studies conducted exclusively within the US, the median number of black patients was 17 (IQR = 8-31). Conclusions Less than 1 in 5 studies globally and half of studies from the US reported the participation of Black men. We found no study that enrolled Black men exclusively or that prospectively stratified analysis based on race. There is a critical need for greater involvement and better reporting of Black men's participation in prostate cancer trials. Funding Departmental, NIH (U54MD008620)
Authors
Laurel Nightingale
Michael Dumas Raymond Ogagarue Folakemi Odedina Christopher Warlick Philipp Dahm |
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PD09-06 |
CAN A SIMPLE COUNT OF SEVERAL COMMON COMORBIDITIES ACCURATELY PREDICT LONG-TERM, OTHER CAUSE MORTALITY IN MEN WITH PROSTATE CANCER? |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making II | 17BOS |
Abstract: PD09-06 Sources of Funding: None Introduction Physicians need practical methods to accurately estimate life expectancy when counseling older men with comorbidities regarding treatment of prostate cancer. Although numerous nomograms exist for prediction of life expectancy (LE), few are used in practice due to the difficulty of integration into busy clinical workflows. We sought to determine if survival could be accurately predicted if reduced to a count of several common comorbidities that pose a high risk to mortality. In selecting these comorbidities, we aimed to balance frequency and risk in order to maximize identification of men at risk for overtreatment based on <10-year LE. Methods We sampled 1,598 men with newly diagnosed prostate cancer at two Southern California Veterans Affairs Medical Centers from 1998 to 2004. We created rank-ordered lists of comorbidities organized by frequency and highest risk of mortality. Separate ranked lists were then created by differentially weighting comorbidities by frequency to risk ratios: 1:6, 1:4, 1:2, 1:1, 2:1, 4:1, and 6:1. By successively adding comorbidities from highest- to tenth highest-ranked, a set of 10 candidate comorbidity indices was constructed for each list. Using competing risks regression analysis, we determined c-index, the number of men with <10-year LE, and the number of men with <10-year LE treated with surgery or radiation for each index. Results Candidate comorbidity indices heavily weighted by frequency were poor at identifying men with <10-year LE, while indices heavily weighted by risk of mortality failed to identify men who were overtreated. Six candidate indices each found more than 300 men with <10-year LE (range 303-392); all six were weighted either 2:1, 1:1, or 1:2 by frequency to risk ratio and included highly similar comorbidities. Two of the six indices identified more than 200 men with <10-year LE overtreated with surgery or radiation (range 173-203). The candidate index with the highest number overtreated was weighted 1:1 by frequency to risk and included six comorbidities: 1) chronic obstructive pulmonary disease 2) congestive heart failure 3) peripheral vascular disease 4) stroke 5) myocardial infarction 6) exertional angina. C-index for this index was 0.66. Conclusions A simple count of six comorbidities predicts the risk of 10-year other-cause mortality and robustly identifies men who are overtreated for early stage prostate cancer. Simplifying estimation of life expectancy may be key to operationalizing this critical variable for prostate cancer decision-making. Funding None
Authors
Kian Asanad
Douglas Skarecky Thomas Ahlering Stephen Freedland Timothy Daskivich |
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PD09-07 |
The impact of shared decision making software on decisional quality of men undergoing treatment for BPH: An interim analysis |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making II | 17BOS |
Abstract: PD09-07 Sources of Funding: Supported in part by the H. H. Lee Research Program. Introduction Shared decision making (SDM) allows patients and physicians to develop a treatment plan together by thoroughly exploring clinical risks and benefits in the setting of patient-specific values and concerns. This method of counseling can help to reduce decisional conflict, which has been identified as an indicator of decisional quality. Using novel SDM software, we aimed to examine the impact of shared decision making interventions on decisional conflict in patients seeking treatment for benign prostatic hyperplasia (BPH). Methods All new patients evaluated for BPH were offered SDM software before their initial urologic visit either in person or by phone. Willing participants utilized the software at home or in the waiting area prior to their visit. The software provides education, preference assessment for relevant outcomes, and personalized decision analysis for the patient. A report from the software is sent to the counseling urologist and the patient. Following consultation with a urologist, patients completed a follow up questionnaire measuring disease-specific knowledge, satisfaction with care, and decisional conflict using the validated SURE scale (SURE=4, high decisional quality; SURE= 0-3, low decisional quality). Questionnaire results were compared to baseline data collected from patients who did not receive the SDM module. Results Data was available for 35 men in the SDM pilot group and 103 men from the control group. They were well matched in demographics and health literacy. Among all participants, significantly fewer men in the SDM group felt unsure regarding treatment options (12% vs 37%, p = 0.0059) and were more likely to have made a shared decision (SDM score 1.87 vs 2.19, p=0.0503). There was no significant difference in overall SURE score between control and pilot study participants (3.0 vs 2.7, p=0.3). Among participants who reported some decisional conflict (n=76), SDM pilot study participants were more likely to report adequate support to make a treatment choice than the control participants (82% vs 57%, p = 0.0564). Conclusions Our interim analysis of a novel SDM intervention for men with BPH shows an improvement in understanding treatment options and shared decision making. The SDM software provided additional support among those patients who felt some decision conflict after their initial consultation. These differences may become more significant as we accrue more pilot-study patients. Funding Supported in part by the H. H. Lee Research Program.
Authors
Matthew Pollard
Joseph Shirk Casey Pagan Sylvia Lambrechts Lorna Kwan Christopher Saigal |
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PD09-08 |
Sacral Neuromodulation in California from 2005 to 2011: What Are the Real-World Success Rates? |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making II | 17BOS |
Abstract: PD09-08 Sources of Funding: Valley Medical Care Foundation Introduction Sacral neuromodulation (SNS) is approved by the Food and Drug Administration for the treatment of refractory urge urinary incontinence, frequency/urgency, idiopathic urinary retention and fecal incontinence. Prior to placement of an implantable pulse generator, all patients must undergo a trial stimulation to ensure improvement in their condition. The success rate for staged SNS implantation of a pulse generator (defined as > 50% improvement) varies greatly in the literature (ranging from 40 to 90%). We sought to determine success rates in California using a statewide registry. Methods We accessed non-public records from the California Office of Statewide Health Planning and Development (OSHPD) Ambulatory Surgery Database for the years 2005 to 2011. This dataset captures all non-federal ambulatory surgical visits within the state. Appropriate Current Procedural Terminology, 4th edition (CPT) procedure codes and International Classification of Disease, 9th edition (ICD-9) diagnosis codes were used to analyze all SNS procedures and their indication. Patients were followed longitudinally using unique patient record linkage numbers. Staged success was defined as the proportion of patients who received a stage 2 SNS generator implantation after their stage 1 tined lead trial. Results We identified 4,098 patients with SNS procedure codes. After excluding patients who only underwent generator exchange, lead revision or lead explantation, our final cohort included 2,765 patients. The majority of patients were female (77%), over 60 years of age (68%), Caucasian (74%) and had Medicare (60%). A total of 1,396 patients underwent a stage 1 trial of tined-lead implantation, of which 962 subsequently underwent stage 2 pulse generator placement (staged success rate of 69%). Staged success rates were 72% for urge urinary incontinence, 69% for urgency/frequency, 57% for urinary retention, 68% for interstitial cystitis and 67% for neurogenic bladder. Success rates were similar after stratification by race/ethnicity and insurance coverage. Conclusions While the success rates for staged SNS implantation in the state of California were less than that observed in many single center academic series; they are better than previously reported for Medicare patients, and suggestive of a success rate of greater than two thirds. Funding Valley Medical Care Foundation
Authors
Amy D. Dobberfuhl
Amandeep Mahal Craig V. Comiter Christopher S. Elliott |
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PD09-09 |
Nationwide Disparities in Testicular Cancer Care Delivery: Racial, Ethnic and Economic Markers of Patient Vulnerability |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making II | 17BOS |
Abstract: PD09-09 Sources of Funding: This work was supported by a data grant from the National Cancer Database, a collaboration between the Commission on Cancer, the American Cancer Society and the American College of Surgeons. Introduction Testis cancer is often curable, yet early presentation is a key determinant of survival and treatment morbidity. Testis cancer affects the young, who may have less consistent health care access. This may result in delay in diagnosis and impede timely mobilization of complex healthcare resources needed for cancer care. In this context, we analyze men with testis cancer in the National Cancer Database (NCDB). Methods The NCDB identified adult males with testicular germ cell tumors (2004-2013). Markers of care delays included: higher stage presentation (stage III+), large primary lesion (>6cm), delayed orchiectomy (>10 days post-diagnosis), and overall mortality. Key risk factors we hypothesized to be associated with care delays included race/ethnicity, socioeconomic factors and insurance status. Outcomes were assessed with multivariable hazards regression (survival) or logistic regression (others). Results Among 31,964 men, 17% had higher stage presentation, 29% had a large primary, and 9.9% had delayed orchiectomy and 4.8% died during follow up. All outcomes were significantly associated with multiple risk factors for care delays on multivariable analysis. Between 2004 and 2013, Medicaid coverage increased from 6.6% to 11.2%, and uninsured status increased from 10.4% to 13.1% (Pearson p for linear trend <0.001). The most consistent and greatest magnitude association with poor disease specific outcomes was insurance status (e.g. for mortality HR for Medicaid 1.9, 95% CI 1.6-2.3, and for uninsured HR 1.7, 95% CI 1.5-2.1, for large primary Medicaid OR 1.8, 95% CI 1.7-2.0, uninsured OR 2.1, 95% CI 2.0-2.3 [referent private payer]). Conclusions We find association between severity of disease and markers of poor access to care. Medicaid expansion is a strategy employed to increase coverage by the Affordable Care Act. As such, it will be important to monitor whether gains in coverage translate to improvements in cancer outcomes._x000D_ Funding This work was supported by a data grant from the National Cancer Database, a collaboration between the Commission on Cancer, the American Cancer Society and the American College of Surgeons.
Authors
Liam Macleod
Shannon Cannon Oliver Ko Jonathan Wright George Schade Daniel Lin John Gore Atreya Dash |
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PD09-10 |
Temporal Trends in Management and Outcomes of Testicular Cancer: A Population-Based Study |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making II | 17BOS |
Abstract: PD09-10 Sources of Funding: none Introduction Treatment guidelines for early-stage testicular cancer have increasingly recommended de-escalation of therapy. We sought to describe changes in routine clinical practice and whether this has compromised survival in the general population. Methods The Ontario Cancer Registry was linked to electronic records of treatment to identify all patients diagnosed with testicular cancer and treated with orchiectomy in Ontario during 2000-2010. Treatment after orchiectomy was classified as radiotherapy (RT), retroperitoneal lymph node dissection (RPLND), chemotherapy, or none. Stage of disease at diagnosis was not available. Cancer-specific (CSS) and overall survival (OS) were measured from date of orchiectomy. The chi-squared test was used to evaluate temporal trends in practice patterns; the log-rank trend test was used to evaluate whether outcomes changed over time. Results Orchiectomy pathology reports were available for 86% (2821/3281) of all cases in Ontario; the study population included 1580 and 1105 cases of seminoma and non-seminoma (NSGCT); other histologies were excluded. Median age was 34 years. _x000D_ _x000D_ Among patients with seminoma there was a significant increase in the proportion of patients with no active treatment after orchiectomy (from 33% to 66%, p<0.001). Use of RT decreased over time (57% to 18%, p<0.001) and use of chemotherapy remained stable (from 16% to 17%, p=0.344). Post-orchiectomy practice patterns remained relatively stable among patients with NSGCT: no treatment 29% to 41% (p=0.221); chemotherapy 69% to 55% (p=0.203); RPLND 27% to 26% (p=0.308). Among the 296 patients undergoing RPLND, 61% were performed in the post-chemotherapy setting; this proportion remained stable over time (p=0.423). _x000D_ _x000D_ OS for the entire cohort at 5 and 10 years was 96% and 94%. CSS at 5 and 10 years was 97% and 97%. There was no significant change in OS or CSS for seminoma (98% and 99% respectively) or NSGCT (96% and 96%) over the study period. Conclusions Since 2000 there has been de-escalation of treatment among men with seminoma, with surveillance alone predominating in recent years. Practice patterns for NSGCT have remained stable since 2000. Outcomes achieved in the general population are very good and have not decreased over time with de-escalation of therapy. Funding none
Authors
Michael Leveridge
D Robert Siemens Kelly Brennan Jason Izard Safiya Karim Christopher Booth |
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PD09-11 |
Management of the post-pubertal undescended testis: an updated risk analysis |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making II | 17BOS |
Abstract: PD09-11 Sources of Funding: None Introduction The undescended testicle (UDT) presents a problem in post-pubertal (PP) men as it carries an increased risk of developing a testicular germ cell tumor (GCT). Management of the PP patient with an UDT must weigh the relative risk of peri-operative mortality (POM) to remove the UDT against the lifetime risk of death from developing a GCT. _x000D_ The most recent analysis of this management dilemma is 15 years old and utilizes now outdated data. In their paper, investigators found that men who are healthy (ASA 1 or 2) should be advised to undergo orchiectomy, while those older than 50 should be advised to remain under close observation. _x000D_ However, newer studies on the prevalence of UDT, GCT mortality rates and POM risk may change this recommendation. We undertook an update to this previous report as these more contemporary data may establish new criteria in the management of the PP UDT._x000D_ Methods The most recent data on GCT mortality in the U.S. were obtained from the National Center for Health Statistics. The lifetime risk of death from GCT in the male population was calculated for each 5-year interval. Standard life tables were used to calculate the cumulative risk over a man’s lifetime based on the age at presentation. _x000D_ The prevalence of UDT in PP males and the percentage of men with GCT who have a history of UDT were identified through literature search. The relative risk of GCT in men with UDT was expressed as the ratio of observed to expected prevalence of UDT among patients with GCT. The prevalence of UDT in GCT men was calculated as a weighted value based on the number of patients in each individual study. _x000D_ As there is no orchiectomy specific POM data, we utilized data from patients undergoing similar (“low risk�) surgical procedures stratified by ASA class. Orchiectomy was considered a low risk procedure based on the Cleveland Clinic cardiac risk stratification for non-cardiac surgery._x000D_ Mortality rates were plotted to determine the age when ASA class specific POM exceeds the risk of mortality from GCT. _x000D_ Results Lifetime risk of dying from GCT decreases with increasing age. POM exceeded risks of death from GCT for men after age 46 for ASA class 1 and age 25 for ASA class 2. Men with an ASA class higher than 2 have a higher risk of POM compared to GCT for all ages. Conclusions Previous evaluations in the management of men with PP UDT required updating. We found a lower age at which observation is advised compared to the previous report. Thus, we advocate for prophylactic orchiectomy only in men who are under 46 years if ASA class 1 and under 25 years if ASA class 2. Men with an ASA class higher than 2 should always undergo observation. Funding None
Authors
Ankur Shah
Blake Wynia Paul Feustel Jennifer Knuth Charles Welliver |
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PD09-12 |
The Impact of Surgeon and Hospital Experience on the Perioperative Outcomes of Patients Receiving Robotic Partial Nephrectomy |
General & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making II | 17BOS |
Abstract: PD09-12 Sources of Funding: None. Introduction Robot use for assistance with partial nephrectomies (PN) has increased drastically over the past decade with adoption rates by robot-naive surgeons continuing to rise steadily. Despite this, little is known about the impact of surgeon experience and hospital volume on peri-operative outcomes and the cost of management for patients undergoing robotic PN. Thus, we sought to compare peri-operative success and in-hospital cost between surgeons and hospitals with low, medium and high robotic PN volumes. Methods Utilizing an all-payer hospital clinical and economic database, we identified a nationally representative sample of 50,282 patients undergoing robotic PN within the United States between 2003 and 2015 after survey weighting. Annual surgeon and hospital robotic PN volumes were calculated and surgeons and hospitals were subsequently divided into tertiles corresponding to low, medium and high volumes. Results High volume surgeons and hospitals had a significantly higher rate of older patients compared to their peers and were more likely to practice at a hospital that was academic, larger than 500 beds and in an urban setting (all p<0.001). Patients treated by high volume surgeons also had fewer overall complications compared to low volume surgeons (24.4% vs. 31.3%, p =0.002) as well as a 35% lower odds of having a major complication after adjusting for relevant patient and hospital characteristics (OR: .65, 95% CI: 0.47 to 0.90, p = 0.009). Hospitals performing a high volume of robotic PN also had fewer overall complications compared to low volume hospitals (24% vs. 27%, p=0.01) and 43% lower multivariate odds of having a major complication (OR: .57, 95% CI: 0.41 to 0.79, p=0.001). The patient's length of stay was significantly shorter for both high volume surgeons and hospitals, respectively, compared to low and medium volume surgeons (p<0.001). Total cost of stay after adjusting for inflation was not significantly different regardless of surgeon and hospital experience in robotic PN surgery. The mean decrease in cost for high volume surgeons and hospitals compared to their low volume peers was $28.6 (p=0.933) and $186.5 (p=0.56), respectively. Conclusions Increased experience in robotic PN by both surgeons and hospitals is associated with lower complication rates and shorter length of stays, but in-hospital cost is not significantly affected by provider experience. Funding None.
Authors
Yash Khandwala
In Gab Jeong Ye Wang Deok Hyun Han Jae Heon Kim Shufeng Li Steven L. Chang Benjamin I. Chung |
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PD10-01 |
Outcomes of fluorescence supported lymph node dissection in robot-assisted radical prostatectomy – a prospective randomized clinical trial |
Prostate Cancer: Localized: Surgical Therapy I | 17BOS |
Abstract: PD10-01 Sources of Funding: None Introduction The detection of lymph node metastases has a major impact on patients with prostate cancer. However, there is still a debate on the extent of pelvic lymphadenectomy, the usage of near-infrared fluorescence (NIRF) and sentinel node dissection in radical prostatectomy. This study aims to demonstrate the outcomes of NIRF lymph node dissection in robot-assisted radical prostatectomy._x000D_ Methods 120 patients with intermediate (72%) or high risk (28%) prostate cancer were prospectively randomized (1:1): in the intervention group indocyanine green (ICG) was injected transrectally into the prostate before docking of the robot. In both groups an extended pelvic lymph node dissection (ePLND) was performed including eventual dissection of fluorescent lymph nodes (LN) in the ICG group. _x000D_ Results After exclusion of two drop-outs, 59 patients were allocated in the control (A) and intervention group (B) with a median PSA of 8,6 ng/ml. Median console time was 159 (A) vs. 168 (B) minutes (p=0,20) with a longer time for NIRF ePLND: 43 (A) vs. 55 minutes (B) (p=0,001). Overall, 2609 LN (median 22 LN) were found. In the ICG group 582 fluorescent LN were identified, while 899 were non-fluorescent. Significantly more LN could be harvested in B with median 25 LN vs. 17 in A (p<0,001). In 6 of the 59 patients in the intervention group, 19 additional fluorescent LN were found outside of the routine ePLND field. 15 out of 118 patients presented 87 nodal metastases. These metastases were detected in 6 patients in A (25 cancerous LN) vs. 9 patients in B (62 positive LN) (p=0,40). In 7 of 9 patients, NIRF ePLND identified at least one cancer-positive LN (sensitivity 78%), although 35 of 62 cancerous LN were non-fluorescent. No adverse reactions to ICG, no significant differences in complication rates (p=0,15); lymphocele occurred in one patient in A and in three patients in B (p=0,62). After six months, 5,8% vs. 3,7% showed a PSA>0,2 ng/ml (p=0,37) with a median PSA of 0,01 ng/ml in both groups (p=0,96). There was no difference in adjuvant therapy with 10 patients undergoing radiation therapy, 7 patients with androgen deprivation therapy (ADT) and 3 patients with combined radiation and ADT (p=0,78)._x000D_ Conclusions Without increased risk for the patient, NIRF ePLND leads to a significantly higher yield of lymph nodes. While it therefore seems to be beneficial with regard to a better understanding of the lymphatic drainage and a more meticulous diagnostic approach, the sensitivity seems not to be sufficient to recommend stand-alone NIRF sentinel lymph node dissection._x000D_ Funding None
Authors
Nina Harke
Christian Wagner Katarina Urbanova Michael Godes Mustapha Addali Bernhard Fangmeyer Andreas Schuette Jorn H. Witt |
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PD10-02 |
Time to biochemical recurrence (BCR) in patients with localized high-risk prostate cancer (PC) treated with neoadjuvant androgen blockade (NAB) prior to radical prostatectomy (RP): Results of a pooled analysis of three phase 2 trials |
Prostate Cancer: Localized: Surgical Therapy I | 17BOS |
Abstract: PD10-02 Sources of Funding: None Introduction Despite local therapy, a significant portion of men with high-risk PC develop progressive disease. NAB prior to RP is an approach that can potentially maximize survival outcomes in a subset of patients with localized disease. The objective of this pooled analysis was to evaluate the time to BCR in patients treated with NHT pre-RP. Methods This analysis included patients enrolled on three neoadjuvant trials at three institutions: Dana-Farber/Brigham and Women's Cancer Center, University of Washington, and Beth Israel Deaconess Medical Center. Study 08295 evaluated 3 months of either 1) a luteinizing hormone-releasing hormone agonist (LHRHa) + dutasteride, 2) LHRHa + dutasteride + bicalutamide, or 3) LHRHa + dutasteride + bicalutamide + ketoconazole. Study 09107 evaluated either 1) 12 weeks of abiraterone acetate (AA) and 24 weeks of a LHRHa or 2) 24 weeks of AA and 24 weeks of a LHRHa. Study 12089 evaluated 6 months of 1) enzalutamide or 2) enzalutamide + LHRHa + dutasteride. BCR is defined as a prostate specific antigen (PSA) >=0.2 ng/mL, which is confirmed, or need for salvage radiation therapy or androgen deprivation therapy. The distributions of time to BCR are estimated using the Kaplan Meier method. Results This analysis included 72 patients (total patient cohort 133): 57% (n=41) enrolled on 09107, 38% (n=27) enrolled on 12089, and 6% (n=4) enrolled on 08295. Overall, median follow-up was 3.4 years from RP. Prior to initiation of NAB, 12 patients (17%) had clinical T3 disease and median PSA was 8.3 ng/mL. The majority of patients had Gleason 8-10 disease (n=46, 64%). Median age at RP was 59. Eleven patients (16%) had tumor measuring <= 0.5 cm at largest diameter at RP. Four patients (6%) had a pathologic complete response (pCR). Positive margins, extraprostatic, seminal vesicle or lymph node involvement was present in 9 (13%), 39 (56%), 43 (61%), and 8 (11%) patients, respectively. Twenty-three patients (32%) experienced a BCR and the 3-year BCR free rate was 70% (57%-80%). No patient with a pCR or tumor measuring <= 0.5 cm experienced a BCR. Five patients (7%) developed metastatic disease and there was one death related to PC. Conclusions NAB results in cases with little or no residual tumor. Metrics of efficacy other than survival are needed; in this subset analysis of patients with available PSA data, we demonstrate that patients with minimal residual tumor and pCR have not experienced BCR. Funding None
Authors
Rana McKay
Bruce Montogomery Wanling Xie Zhenwei Zhang Glenn Bubley Daniel Lin Mark Preston Quoc-Dien Trinh Andrew Wagner Elahe Mostaghel Philip Kantoff Peter Nelson Mary-Ellen Taplin Adam Kibel |
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PD10-03 |
EXTENDED RADICAL PROSTATECTOMY FOLLOWING NEOADJUVANT CHEMOHORMONONAL THERAPY (LOW DOSE ESTRMUSTINE + LHRH AGONIST/ANTAGONIST) CONTRIBUTES TO GOOD CANCER CONTROL FOR PATIENTS WITH HIGH RISK LOCALIZED PROSTATE CANCER |
Prostate Cancer: Localized: Surgical Therapy I | 17BOS |
Abstract: PD10-03 Sources of Funding: none Introduction Patients with high-risk prostate cancer (PCa) according to D&[prime]Amico risk categories are prone to a pathological diagnosis of positive margins or lymph node invasion and biochemical recurrence, despite having undergone radical prostatectomy (RP). Methods 84 high-risk PCa patients prospectively underwent &[prime]extended&[prime] RP following neoadjuvant chemohormonal therapy (NCH); primarily 6 months of estramustine phosphate 280 mg bid, along with a LH-RH agonist/antagonist. Our surgical technique was developed to reduce the rates of positive surgical margins. The goal is to approach the muscle layer of the rectum by dissecting the mesorectal fascia and continuing the dissection through the mesorectum until the muscle layer of the rectum is exposed. The procedure was safely performed as a result of good recognition of the structure between the perineal body and the rectal surface. We also performed extended lymphadenectomy if the patients meet two or more of D&[prime]Amico risk categories Results Pathological analysis revealed that positive surgical margins were found in only two patients. More than 1 year had elapsed after surgery in 64 of the 84 patients with the median follow-up period of 36.1 months. Among those 64 patients, 12 (18.8%) experienced PSA recurrence (Table 1). Kaplan-Meier analyses revealed that significant poorer PSA progression-free survival were observed in patients with younger age, higher positive biopsy core ratio, positive extra-prostate extension (EPE), lymph node metastasis, and higher pathological stage (pT3a/b). Multivariate Cox-regression analysis revealed that higher pathological stage (pT3a/b) was the only independent valuable for predicting PSA progression failure (Table 2). These 12 cases received salvage androgen deprivation therapy followed-by external beam radiotherapy and showed no progression after the salvage therapies (median follow-up period, 22.9 months after PSA progression). Conclusions NCH concordant with extended RP is feasible and contributes to negative surgical margins that might provide good cancer control for patients with high-risk PCa. Funding none
Authors
Hideki Enokida
Shuichi Tatarano Hiroaki Nishimura Akihiko Mitsuke Hirofumi Yoshino Ryosuke Matsushita Masayuki Nakagawa |
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PD10-04 |
Functional outcomes and Quality of life after radical prostatectomy: Patient reported outcomes of a tertiary high-volume center |
Prostate Cancer: Localized: Surgical Therapy I | 17BOS |
Abstract: PD10-04 Sources of Funding: none Introduction First results from the ProtecT trial reported on worse functional outcomes for radical prostatectomy (RP) patients compared to their radiation or active surveillance counter partners. We investigated this question for patients undergoing RP in a tertiary high-volume center. Methods A total of 14016 men underwent RP between 2005 and 2013 at a tertiary high-volume center. Standardized questionnaires assessing urinary continence (UC), lower urinary tract symptoms (LUTS), erectile (EF) and bowel (BF) function as well as overall health and quality of life (QoL) were completed annually after RP. Additional data for UC and EF were available at three months after RP. UC was defined as the use of zero or 1-safety pad per 24 hours. General EF was assessed using the IIEF-5 (International Index of erectile function) score. EF was defined as a score of ≥3 points in the second question of the IIEF-5 questionnaire: &[Prime]When you had erections with sexual stimulation, how often were your erections stiff enough for penetration?&[Prime] LUTS were analyzed according to the ICSmaleSF (International Continence Society Male Short-Form) instrument. For evaluation of BF, occurrence of bloody stools was documented. Overall health and QoL was investigated using the last two questions of the EORTC-30 questionnaire. Results Post-RP UC rates at 3-months, 1-year UC and 3-years were 74.4%, 86.9% and 86.8% for all patients and considerably higher compared to the results of the ProtecT trial. Similar, recovery of erectile function was better at all three time points with a 3-months EF recovery rate of 26.6% and a 3-year rate of 45.4%. In patients who were potent prior to RP and had bilateral nerve sparing, EF rates were 60.4% three years after RP. LUTS and occurrence of bloody stools was comparable to the ProtecT trial with a mean voiding score of 1.83% and occurrence of bloody stools in less than 1%. Both, overall health and QoL reached a mean of 5.7 out of a total of 7.0 points. Conclusions Compared to the results of the ProtecT trial, functional outcomes were considerably better for patients undergoing RP in a high-volume center. Although RP is associated with UI and erectile dysfunction, most patients reported very good overall health and QoL one year after RP. Funding none
Authors
Raisa Sinaida Pompe
Philipp Mandel Sami-Ramzi Leyh-Bannurah Pierre I. Karakiewicz Felix K. Chun Georg Salomon Hartwig Huland Markus Graefen Derya Tilki |
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PD10-05 |
Underestimation of Prostate Cancer Risk at Diagnosis Among African American Men |
Prostate Cancer: Localized: Surgical Therapy I | 17BOS |
Abstract: PD10-05 Sources of Funding: none Introduction African American (AA) men suffer from a disproportionately high burden of clinically significant prostate cancer, with an increased risk of aggressive or advanced stage disease. Even among men thought to have low risk disease at diagnosis, data suggests that AA men are at an increased risk of adverse pathology after radical prostatectomy (RP) compared to men of other races. These data suggest an underestimation of disease risk at diagnosis among AA men. In the current study, we compared pre- and post-treatment estimates of prostate cancer risk, to determine whether inaccurate assessment of disease risk at diagnosis differs by race. Methods We identified Caucasian and AA men who underwent radical prostatectomy (RP) at our institution between 2012 to 2016. CAPRA and CAPRA-S scores were determined as estimates of pre- and post-operative disease risk, and differences between each patient's CAPRA and CAPRA-S scores were calculated. Underestimation of disease risk at diagnosis was defined as a CAPRA score less than CAPRA-S score. Rates of risk under and over-estimation were compared among racial groups, and multivariable logistic regression was used to determine factors associated with risk underestimation. Results 391 men met inclusion criteria, including 284 Caucasian (72.6%) and 107 AA (27.4%) men. As shown in table 1, the distribution of CAPRA and CAPRA-S scores did not differ significantly by race (CAPRA p=0.81, CAPRA-S p=0.69). Differences between each individual patient's CAPRA and CAPRA-S score are shown in table 2. Risk underestimation occurred in 37% of AA men, compared to 26% of Caucasian men (p = 0.09). Multivariable logistic regression showed that AA race (p = 0.05) and higher serum PSA at diagnosis (p = 0.01) were associated with risk underestimation, whereas age at biopsy, Gleason score, and clinical stage were not. Conclusions Underestimation of prostate cancer risk at diagnosis appears to be more common in AA compared to Caucasian men. These findings suggest a need for improved risk assessment at diagnosis, and argue for more aggressive treatment of prostate cancer in AA men. Funding none
Authors
Nathan Peffer
Daniel Parker Laura Giusto Joshua Jones Anastasia Kamenko Daniel Eun Michel Pontari Jack Mydlo Adam Reese |
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PD10-06 |
Intra-operative Optical Imaging Utilizing Anti-PSMA (Prostate Specific Membrane Antigen) Fluorescent Antibody during Robot Assisted Radical Prostatectomy (RARP) |
Prostate Cancer: Localized: Surgical Therapy I | 17BOS |
Abstract: PD10-06 Sources of Funding: None Introduction Identification of prostatic tissue from non-prostatic tissue can help preserve potency, continence, as well as decrease positive margins. PSMA, a transmembrane glycoprotein expressed by neoplastic prostate epithelium, is a possible target for identification of prostate tissue. MDX1201, an investigational new drug (IND) composed of fully human IgG with conjugated fluorescent marker (AlexaTM488) with specificity against PSMA was safely administered in mice models. The antibody-fluorescent dye complex was shown to bind to cells expressing PSMA demonstrating significant staining of prostatic adenocarcinoma. We performed the first in-human FDA-approved phase I 3+3 dose finding study of intravenously (IV) administered MDX1201 in intermediate- to high-risk patients undergoing RARP and extended lymph node (LN) dissection. Methods Patients received a single intravenous infusion of MDX1201 four days prior to RARP to allow for safety evaluation. A 488 nanometer laser was attached to the da Vinci Si surgical robot camera at the time of RARP to allow for visualization of fluorescent dye marking presence of prostatic cancerous tissue. 5 mg dose was given to the first 3 patients, and then the dose was escalated to 15 mg provided safety considerations permit. Patients with prior prostate cancer treatment were excluded. Results MDX1201 was successfully administered to 5 patients, with no adverse events observed. Initial 5 mg dose failed to show visualization of fluorescent dye in first 3 patients. Of the 15 mg dose patients, patient #4 demonstrated fluorescence ex vivo within the sectioned prostate that correlated with pathological findings, while patient #5 demonstrated fluorescence in-vivo with mild prostatic fluorescence at the right apex, left apex, left mid, and also moderate fluorescence demonstrated at the right external iliac LNs. For patient #5, histopathologic examination confirmed tumor to the mid right lobe (dominant nodule), with a minor focus in anterior left lobe near the base. There was no LN metastasis in this patient (pT2cN0). In the five patients (median PSA 9.5, 80% intermediate-risk, 100% > pT2c), the median LN yield was 18 with no LN involvement in any patient. No positive margins were detected. Conclusions We demonstrate the first in human study using an anti PSMA antibody demonstrating fluorescence in the prostate. Identification of prostatic tissue using a conjugated fluorescent marker with specificity against PSMA may help guide preservation of critical structures. Funding None
Authors
Avinash Chennamsetty
William Chu Justin Emtage Paul Gellhaus Jonathan Yamzon Clayton Lau Bertram Yuh Tommy Tong David Colcher Timothy Wilson Ali Zhumkhawala |
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PD10-07 |
RELIABILITY OF PROSTATE HISTOSCANNING IN THE LOCALIZATION AND VOLUME ESTIMATION OF CARCINOMA PROSTATE |
Prostate Cancer: Localized: Surgical Therapy I | 17BOS |
Abstract: PD10-07 Sources of Funding: none_x000D_ Introduction Prostate HistoScanning TM (PHS) is a novel ultrasound-based technology that uses computer-aided analysis to quantify tissue disorganization induced by malignant processes to visualize the position and extent of tumor. Objective of this study was to determine extent to which PHS can identify tumor foci that correspond to a volume of ? 0.50 mL. Methods Between November 2014 and May 2015,34 men underwent PHS before scheduled radical prostatectomy (RP). 3D-data required for PHS analysis were acquired by transrectal ultrasonography and analyzed using organ-speci?c tissue-characterization algorithms.PHS analysis results were compared with histology of the whole mounted prostate. Results A total of 204 sextants were studied in 34 patients. Prostate volume and PHS identified lesion volume were 13.49±13.85 mL and 3.10±2.06 mL respectively. PHS correlated well with step sectioned RP specimen tumor volume (Spearman’s coefficient of rank correlation=0.55, p = 0.007). Using the clinically accepted volume threshold of 0.50 mL- sensitivity, speci?city, positive and negative predictive values of PHS were 88.4%, 50%, 78.2% and 68%, respectively. Conclusions PHS has the ability to reliably detect cancer foci more than 0.5 mL within the prostate. Further exploratory studies are required to assess its role in the management of prostate carcinoma. Funding none_x000D_
Authors
Abhishek Singh
Ankush Jairath Jaimin Shah Arvind Ganpule Ravindra Sabnis Mahesh Desai |
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PD10-08 |
Light-reflectance spectroscopy to detect positive surgical margins at radical prostatectomy: exploration of new algorithms to refine detection rate |
Prostate Cancer: Localized: Surgical Therapy I | 17BOS |
Abstract: PD10-08 Sources of Funding: none Introduction Light-reflectance spectroscopy (LRS) is a novel technology which can reliably detect positive surgical margins (PSMs) for Gleason score ≥7 prostate cancer in ex vivo radical prostatectomy (RP) specimens. Furthermore, LRS can provide near-immediate feedback to the surgeon and potentially influence surgical decision making. Our objective was to refine our technique using a new algorithm to increase the efficacy and performance of this technology. Methods A prospective evaluation of ex vivo RP specimens using LRS was performed at a single institution from March 2016 to October 2016. LRS measurements were performed on selected sites on the prostate capsule, marked with ink, and correlated with pathological analysis. The previous 5 feature algorithm, which has been validated using both a training and testing set, was further optimized with an additional 4 features. This new 9 feature algorithm included additional shifts in slope at specific points along the 690 nm - 770 nm wavelength range to better differentiate malignant from benign tissue. The sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and area under the receiver operating characteristic curve (AUC) for LRS predicting PSMs using the 5 and 9 point algorithms were calculated._x000D_ Results 197 sites in 34 RP specimens were evaluated by LRS and histopathology. The 5 and 9 point algorithms behaved similarly for Gleason groups 1-2 showing poor sensitivity (33%,33%), PPV (18%,27%), and AUC (0.54,0.59). Specificity was better in the 9 compared to the 5 point algorithm (85.3 vs. 74.4%, respectively). Both algorithms performed much better for Gleason groups 3-4. Specificity was improved for the 9 point algorithm compared to the 5 (90.6 vs. 84.4%, respectively). Sensitivity was improved for the 5 point algorithm compared to the 9, (100 vs. 77.8%, respectively). Both algorithms had great NPV for low grade and high grade cancer. Conclusions Incorporating features of both LRS algorithms improves performance to reliably detect PSMs of higher grade prostate cancer. This is likely secondary to increased cellular density in these cancers causing more differential light scattering. Further refinements and additional prospective evaluations may allow incorporation into clinical practice. Funding none
Authors
Igor Sorokin
Noah Canvasser Xinlong Wang Henry Chan Hanli Liu Payal Kapur Claus Roehrborn Jeffrey Cadeddu |
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PD10-09 |
Effect of Dehydrated Human Amnion/Chorion Membrane Allograft on Urinary Continence Following Robot-assisted Radical Prostatectomy |
Prostate Cancer: Localized: Surgical Therapy I | 17BOS |
Abstract: PD10-09 Sources of Funding: none Introduction Urinary incontinence following radical prostatectomy is one of the major concerns for both patients and surgeons. Efforts are being made to shorten the duration and degree of post-operative urinary incontinence, hence decreasing postoperative morbidity. Dehydrated Human Amnion/Chorion Membrane Allograft (AmnioFix®) is a biodegradable material that may decrease postoperative nerve inflammation and improve postoperative outcomes (i.e. potency and continence). We aim to determine the effect of adding the dehydrated human amnion/chorion membrane allograft (Amniofix®) on the neurovascular bundles on post-operative urinary incontinence in patients who underwent nerve sparing (complete bilateral, unilateral or partial)Robot-assisted Radical Prostatectomy (RARP). Methods Retrospective review of 362 consented patients who underwent nerve sparing RARP between 2015-2016. AmnioFix® usage, times to one and zero pads after catheter removal and type of nerve sparing were recorded. Cox proportional hazard modeling was used to evaluate the association between the use of AmnioFix® and postoperative times to one and zero pads. Results Of the 362 patients analyzed, AmnioFix® was used in 138 patients (38%). Mean age of the cohort was 63. Patients with AmnioFix® allograft used reached the use of 1 (even occasional) and 0 pads at a mean of 1.28 months and 2.84 respectively, whereas those with no allograft had means of 1.61months and 3.20 months. In the allograft group, 64% of patients reached < 1 pads within 6 months of the RARP, compared to 48% in the no allograft group. In the model adjusted for PSA density, prostate weight, nerve sparing, age, race, and CAPRA risk, allograft use increased the likelihood of using < 1 pads within 12 months of RARP by 50% compared to those without the allograft (HR: 1.52, 95%CI: 1.10 to 2.10, p= 0.011). Men with complete nerve sparing were 44% more likely to report < 1 pads within 12 months of RARP compared to partial/unilateral nerve sparing (HR: 1.44, 59%CI: 0.996 to 2.09, p =0.052). Younger age was also an independent predictor of better continence following RARP. Study limitations include limited sample size and retrospective nature. Conclusions The use of dehydrated human amnion/chorion membrane allograft at the time of RARP appears to improve time to complete continence and increase likelihood of using 1 and 0 pads within 12 months of surgery. Age and complete nerve sparing remain important determinant factors for continence. Our data warrant a prospective trial to evaluate the benefit of the anionic allograft. Funding none
Authors
Khaled Refaai
Hao Nguyen Ameli Niloufar Wang Huiqing Matthew Cooperberg Peter Carroll |
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PD10-10 |
Racial disparities in delivering definitive therapy for intermediate-high risk localized prostate cancer: the impact of facility features and socioeconomic characteristics |
Prostate Cancer: Localized: Surgical Therapy I | 17BOS |
Abstract: PD10-10 Sources of Funding: none Introduction The gap in prostate cancer (PCa) survival between Blacks and Whites has widened over the past decade. Investigators hypothesize that this disparity may be partially attributable to differences in rates of definitive therapy between races. We therefore sought to examine the variation in use of definitive therapy among Black and White men for localized PCa. Methods Using data from the National Cancer Data Base, we identified 283,135 White and Black men >=40years of age with biopsy confirmed localized intermediate-high risk PCa diagnosed between January 2004 and December 2013. Multilevel logistic regression was fitted to predict the odds of receiving definitive therapy for PCa. Sensitivity and subgroup analyses were performed to adjust for inherent patient and facility-level differences. Results 82.9% (n=185,647) of White men received definitive therapy compared to 73.7% (n=43,662) of Black men over a 10-year period. Overall rates of definitive therapy during that time increased for both White (81.3% vs. 83.3%, p<0.001) and Black (72.8% vs. 75.4%, p=0.001) men. However, 38.5% of treating facilities demonstrated significantly higher rates of definitive therapy in White men, compared to just 0.8% of facilities favoring Black men. Conclusions After adjusting for sociodemographic and clinical factors, we found significant facility-level variation in rates of definitive therapy for intermediate-high risk localized PCa among White and Black men, with most facilities favoring therapy in Whites. Our study is limited by the retrospective nature of the cohort. Funding none
Authors
David F. Friedlander
Nicolas von Landenberg Philipp Gild Quoc-Dien Trinh Patrick Karabon Maxine Sun Paul L. Nguyen Adam S. Kibel Toni K. Choueiri Joel S. Weissman Mani Menon Firas Abdollah |
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PD10-11 |
Analysis of the predictive utility of Prognostic Grade Groups (PGG) for predicting perioperative oncologic outcomes of radical prostatectomy in the Shared Equal Access Regional Cancer Hospital (SEARCH) database. |
Prostate Cancer: Localized: Surgical Therapy I | 17BOS |
Abstract: PD10-11 Sources of Funding: none Introduction In 2015, Prognostic Grade Groups (PGG) 1 through 5 were introduced to reclassify Gleason pathology reporting. We studied the performance of the Prognostic Grade Groups (PGG) in the Shared Equal Access Regional Cancer Hospital (SEARCH) database for predicting perioperative oncologic outcomes within a multiracial equal access healthcare system. Methods We reviewed records of men who underwent radical prostatectomy at one of six Veterans Affairs hospitals between 1988 and 2015. 4,200 men with available data were included. The predictive utility of biopsy PGG for multiple perioperative clinical endpoints was examined using logistic regression models. Interactions between PGG and race were tested. Results The cohort consisted of PGG 1 through 5, respectively: 1,989(47%), 1,142(27%), 515(12%), 402(10%), 152(4%). 1,569(38%) were African American(AA). Higher biopsy PGG was associated with higher stage, older age, higher preoperative PSA and more positive biopsy cores (p≤0.012). Higher PGG was associated with higher risk of extracapsular extension(ECE), seminal vesicle invasion(SVI), positive surgical margins(PSM) and lymph node involvement(LNI) and lower likelihood of achieving PSA nadir <0.01 after surgery (all p<0.001). Lower PGG was more likely to be upgraded at surgery (p=<0.001). [Table 1 outlines risks associated with each PGG group.] AA men had decreased risk of upgrading (p=0.001). None of the other endpoints varied by race(p>0.1). Conclusions Prostate Prognostic Grade Groups predicted multiple perioperative oncologic endpoints after prostatectomy in a large, multiracial cohort of men. In this cohort, African American men had lower rates of pathologic upgrading at surgery. Funding none
Authors
Ariel Schulman
Lauren Howard Kae Jack Tay Rajan Gupta Efrat Tsivian Christopher Amling William Aronson Matthew Cooperberg Christopher Kane Martha Terris Stephen Freedland Thomas Polascik |
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PD10-12 |
Prognostic significance of the proportion of ductal component in ductal adenocarcinoma of the prostate |
Prostate Cancer: Localized: Surgical Therapy I | 17BOS |
Abstract: PD10-12 Sources of Funding: none Introduction In prostate cancer, ductal adenocarcinoma is mixed with usual acinar adenocarcinoma. However, whether the proportion of ductal component affects oncologic outcomes is currently unknown. Here, we investigated whether the proportion of the ductal component predicts oncologic outcomes in ductal adenocarcinoma. Methods We retrospectively reviewed clinical data from 3,038 patients with prostate cancer who underwent radical prostatectomy at our institution between 2005 and 2014. We excluded patients who received neoadjuvant or adjuvant treatment. Patients were stratified based on the proportion of the ductal component. We compared the probability of biochemical recurrence between groups and investigated how the proportion of the ductal component influences biochemical recurrence using Kaplan-Meier estimates and Cox regression models, respectively. Results Of 2,648 patients, 101 (3.8%) had ductal adenocarcinoma and 2,547 (96.2%) had acinar adenocarcinoma. Biochemical recurrence-free survival for patients with ductal adenocarcinoma was significantly lower compared with those with acinar adenocarcinoma (p<0.001). When ductal cases were stratified by the proportion of the ductal component, biochemical recurrence-free survival for the high ductal component (≥ 30%) group was significantly lower compared that of the low ductal component (< 30%) group (p = 0.023). In univariate and multivariate Cox regression analyses, a high ductal component was a significant predictor of biochemical recurrence (hazard ratio 2.508, 95% confidence interval 1.133-5.552, p = 0.023). Conclusions The prognosis for ductal adenocarcinoma can be stratified by the proportion of the ductal component. This marker could potentially be used as a surrogate for poor prognosis or as a determinant for adjuvant therapy. Funding none
Authors
Won Sik Jang
Myung Soo Kim Jae Won Park Jong Soo Lee Jong Won Kim Jae Yong Jeong Sung Ku Kang Young Sig Kim In Rae Cho Young Deuk Choi |
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PD11-01 |
Comparison between the diagnostic accuracies of 18F-fluorodeoxyglucose (FDG) Positron Emission Tomography (PET)/Computed Tomography (CT) and morphological imaging in recurrent urothelial carcinomas: a retrospective, multi-center study |
Imaging/Radiology: Uroradiology II | 17BOS |
Abstract: PD11-01 Sources of Funding: None Introduction To evaluate the diagnostic accuracies of FDG PET/CT and morphological imaging(CT and MRI) in recurrent urothelial cancer (UC) after primary treatment. Methods Data of patients with recurrent UC after primary treatment were collected in a retrospective multicenter (San Raffaele Hospital, Milan; IOV–IRCCS, Padua; Hospital of Ferrara, Ferrara; Mayo Clinic, Rochester; University of Bologna) study. Inclusion criteria were: 1)patients with a known history of UC in the bladder and/or in the upper urinary tract (UTUC); 2)FDG PET/CT images after curative treatment of the primary tumor; 3)morphological imaging modalities (CT and MRI) performed before at least 3 months from PET/CT and 4)available standard of reference (e.g. histological data or imaging modalities) for the assessment of PET/CT findings. Exclusion criteria were other abdominal tumours and chemotherapy administration concomitant to imaging and non-urothelial cancer variants. Sensitivities, specificities, positive and negative predictive values were evaluated for all patients and separately for bladder and UTUC. Results Overall, 287 patients were included in the study. Two-hundred thirteen patients underwent cystectomy (74.2%), 35 nephoureterectomy (12.2%), 32 both cystectomy and nephoureterectomy (11.1%) and 7 other type of treatment for UTUC (endo-urology or segmental ureterectomy). Neoadjuvant and adjuvant treatments were performed in 36 (12,5%) and 111 (38,7%) patients, respectively. Sensitivity and specificity of PET/CT for the detection of recurrent UC were 94% (91%-96%) and 79% (68%-88%), respectively (Table 1). However, sensitivity was higher for bladder than UTUC cancer (95% vs. 85%) while specificity was lower in bladder cancer (78% vs. 85% for bladder and UTUC, respectively). The distribution of pathological FDG uptake was: 58 at local site, 126 at lymph nodes, 58 at skeletal site, 53 at lung, 28 at liver and 26 in other sites. PET/CT and morphological imaging modalities findings were available in 198 patients. The results were positively concordant in 137 patients, negatively concordant in 23 patients and discordant in 38 patients (20 negative at ceCT/MRI vs positive at PET/CT and 18 positive at ceCT/MRI and negative at PET/CT) (K Cohen= 0.426; p<0.001). Sensitivities, specificities and accuracies of FDG PET/CT and morphological imaging for the detection of recurrent bladder and UTUC cancer were 94% (90%-97%) vs. 86% (81%-92%), 79% (67%-92%) vs. 59% (44%-74%) and 91% (87%-95%) vs. 81% (75%-86%), respectively. Conclusions FDG PET/CT has a high diagnostic accuracy for the identification of recurrent UC, particularly in patients with bladder cancer. Moreover, its performance seems higher than conventional imaging for both bladder and UTUC cancer. Funding None
Authors
Fabio Zattoni
Vincenzo Ficarra Alberto Briganti Michele Colicchia Stefano Fanti R. Jeffrey Karnes Elena Incerti Val Lowe Marco Moschini Stefano Panareo Maria Picchio Ilaria Rambaldi Riccardo Schiavina Filiberto Zattoni Laura Evangelista |
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PD11-02 |
Non-Contrast Imaging Characteristics of Papillary Renal Cell Carcinoma (pRCC): Implications for Diagnosis and Subtyping |
Imaging/Radiology: Uroradiology II | 17BOS |
Abstract: PD11-02 Sources of Funding: none Introduction Non-contrast CT imaging may be helpful in distinguishing cystic from solid lesions with a proposed cutoff of <20 HU. Current guidelines suggest that renal lesions <20HU on pre-contrast study require no further evaluation as they are most commonly benign cysts. We evaluated the frequency of pRCC presenting with low pre-contrast attenuation that might otherwise be considered radiographically benign, as well as the relationship of this metric to histologic subtype of pathologically proven pRCC. Methods The prospectively maintained Fox Chase Cancer Center kidney cancer database was reviewed for pT1 or T2 pRCC between 2003-2015. Patients were categorized by papillary subtype. Preoperative non-contrast CT images were analyzed. Maximum tumor diameter was measured in centimeters. Attenuation was calculated as the average Hounsfield Units (HU) from 6 distinct axial regions. Low attenuation was defined as ? 20 HU and high attenuation as >20 HU. We assessed the relationship between pre-operative renal mass attenuation and pRCC subtype using logistic regression controlling for stage, age, gender and laterality. Results 58 patients were identified with pT1 or pT2 pRCC in whom preoperative non-contrast CT images were evaluable. 24 (41%) had type 1 and 34 (59%) had type 2 pRCC. No significant differences were noted in age (median 66.75 vs. 63.41 years, p = 0.23) or tumor diameter (median 5.27 vs. 6.32 cm, p = 0.18). 27 patients (47%) exhibited an average preoperative non-contrast ROI ? 20 HU, of which 6 patients (22%) were type 1 pRCC and 21 patients (78%) were type 2 pRCC. Type 1 pRCC demonstrated a higher attenuation than type 2 tumors using both average and max attenuation (29.6 vs. 20.6 HU, p <0.01; and 37.3 vs 26.3 HU, p = <0.01, respectively). After adjustment, HU was an independent predictor of pRCC subtype. Relative to low-density tumors, high-density tumors were 80% less likely to be type 2 pRCC (OR = 0.20, 95% CI 0.06-0.70, p=0.01). Conclusions Nearly half of our evaluated pRCC presented with low attenuation lesions (<20HU) on unenhanced CT and would have been dismissed as benign lesions under current guidelines. Importantly, we demonstrate that not only were these low attenuation lesions not benign, but they were associated with the more aggressive type 2 subtype. These data contradict the opinion that low attenuation renal lesions require no further evaluation, and suggest that attenuation on non-contrast CT imaging is insufficient as a single parameter to rule out malignancy. Funding none
Authors
Anand Badri
Nikhil Waingankar Kristin Edwards Alexander Kutikov Rosaleen Parsons David Chen Marc Smaldone Rosalia Viterbo Richard Greenberg Robert Uzzo |
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PD11-03 |
Impact of magnetic resonance spectroscopic imaging on differential diagnosis of renal tumors. |
Imaging/Radiology: Uroradiology II | 17BOS |
Abstract: PD11-03 Sources of Funding: none Introduction The utility of magnetic resonance imaging (MRI) for diagnosis of a renal tumor is controversial. MR spectroscopy (MRS), a noninvasive method utilized for assessment of biochemical tissue characteristics in vivo, has value for differentiation of tumors in the brain, breast, and prostate. However, there are few reports of MRS examinations of kidneys. Here, we evaluated the diagnostic potential of MRS for renal tumors._x000D_ Methods We analyzed 45 renal tumors in 45 patients (age 60-82 years, median 62 years; clinical stage: T1a, n=25; T1b, n=9; T2a, n=1; T2b, n=1; T3a, n=6; T4, n=1). All patients underwent pre-operative MRS examinations with a 1.5 T MR device equipped with a phased array type external surface coil, in which respiratory-triggered single voxel MRS was performed with a point-resolved spectroscopy sequence (TR, 2000 ms; TE, 135 ms). The obtained spectra were analyzed for choline resonances at 3.2 ppm, after normalization for noise outside the diagnostic range. Choline/noise ratio (CNR) values were automatically calculated using the “R� software package, then the CNRs in spectra obtained from both cancerous and benign tumors were compared. Histological results were defined as the standard for reference._x000D_ Results Of the 45 tumors examined, 41 including 3 cystic tumors were malignant in histological findings, while 2 were histologically diagnosed as angiomyolipoma (AML), 1 as oncocytoma and 1 as tuberculous granuloma (TG). In all cases, the obtained spectra were of sufficient quality for diagnosis. The mean choline CNR value for malignant lesions was 3.4, while that was 1.01 for AML, 1.05 for oncocytoma, and 1.12 for TG. Malignant renal tumors tended to show higher CNR values than benign tumors as well as in tumors with higher grade. _x000D_ _x000D_ Conclusions Although further studies are necessary, our findings indicate that MRS has potential to differentiate malignant from benign renal tumors. Furthermore, it may be an effective diagnostic tool for cystic renal tumor cases. Funding none
Authors
Masahiro Sumura
Haruki Ajiki Chiaki Koike Keita Inoue Keisuke Nakanishi Hiroaki Yasumoto Tsuyoshi Yoshizako Hajime Kitagaki Hiroaki Shiina |
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PD11-04 |
Conventional Versus Computer Assisted Stereoscopic Ultrasound Needle Guidance for Renal Access: A Randomized bench-top crossover trial |
Imaging/Radiology: Uroradiology II | 17BOS |
Abstract: PD11-04 Sources of Funding: None Introduction During urologic surgery, ultrasound (US) is an established method for needle guidance, but difficulty in visualizing the needle trajectory may add technical complexity to the procedure. Needle guidance systems may simplify these procedures. The purpose of this randomized bench-top crossover trial was to compare conventional ultrasound and a computer assisted stereoscopic needle guidance system for obtaining renal access and mass biopsy. Methods Subjects were randomly assigned to target one structure in either a renal access or mass biopsy phantom using conventional or computer assisted US guidance (figure 1)in two crossover trials. Recorded outcomes included time to hit the designated target, number of successful trials, number of punctures, and number of course corrections. Participant demographics and opinions of the two ultrasound modalities were also obtained. Statistical analysis was performed using student t-test for numerical variables and the chi-square test for categorical variables. P value 0.05 was considered significant. Results Of the 71 subjects enrolled in this study, 11 were attending physicians, 27 were residents, and 32 were medical students. The computer assisted system significantly shortened the access time between skin puncture and target contact compared to conventional US(79.4 vs. 51.1 s; p=0.009) respectively. Number of needle course corrections during computer assisted trials was significantly decreased compared to conventional US (0.48 vs. 2.53; p<0.001). There was no significant difference in the number of successful punctures between conventional US and computer assisted trials (1.90 vs. 1.71; p=0.236) respectively. Novice subjects were significantly faster with computer assisted US needle guidance (70 sec vs. 107 sec; p<0.001), while experienced ultra-sonographers trended towards faster overall performance with conventional US needle guidance (91 sec vs. 126 sec; p=0.052). Seventy-three percent of subjects preferred the computer assisted system over conventional ultrasound. Conclusions A computer assisted system has potential for improving patient safety during renal access and mass biopsy by reducing needle access time and course corrections, as well as making ultrasound guidance more available to a wider urologic audience. Funding None
Authors
Alexander Thomas
Jerry Thomas Mohamed Keheila Braden Mattison Benjamin West David Ruckle Samuel Abourbih Reed Krause Vi Dinh D. Daniel Baldwin D. Duane Baldwin |
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PD11-05 |
Contrast-enhanced ultrasound as a replacement for fluoroscopic nephrostogram following percutaneous nephrolithotomy |
Imaging/Radiology: Uroradiology II | 17BOS |
Abstract: PD11-05 Sources of Funding: NIH R21-DK-10943 Introduction Fluoroscopic nephrostogram is commonly used to evaluate ureteral patency after percutaneous nephrolithotomy. However, it can incur a significant exposure to ionizing radiation. We have reported feasibility and safety for contrast-enhanced ultrasound nephrostogram with collecting system microbubble contrast injection to obviate the need for radiation exposure. In this study, we compared contrast-enhanced ultrasound to fluoroscopic nephrostogram in evaluating ureteral patency after percutaneous nephrolithotomy. _x000D_ Methods After obtaining institutional review board approval for off-label use of an ultrasound contrast agent, consecutive patients with kidney stones who underwent percutaneous nephrolithotomy at our medical center were eligible for enrollment in this prospective cohort non-inferiority study. Postoperative day 1 after surgery, contrast-enhanced ultrasound and fluoroscopic nephrostogram were performed within 2 hours of one other for each patient to identify ureteral patency, the primary outcome for this study. Results from both imaging studies were reviewed in a blinded fashion by two experienced radiologists and compared. _x000D_ Results Eighty-six imaging studies were performed in 76 patients during the study period from September 2015 to September 2016. Females (58.3%) predominated males (41.7%) with a mean age of 51.2±16.1 years and a mean body mass index of 29.6±8.4 kg/m2. Four studies were excluded due to technical factors preventing imaging interpretation. For the remaining 82 studies, 66 (80.5%) demonstrated concordance for detecting ureteral patency between the two imaging techniques. Within the 16 (19.5%) discordant studies,15 showed antegrade urine flow on contrast-enhanced ultrasound but not on fluoroscopic nephrostogram, and one antegrade flow on fluoroscopic nephrostogram but not on ultrasound. For discordant studies, 97.5% of tubes were managed according to ultrasound results. No adverse events were noted related to any contrast-enhanced ultrasound studies. While contrast-enhanced ultrasound utilized no ionizing radiation, fluoroscopic nephrostograms provided a mean radiation exposure dose of 13.1±17.5 mGycm2 for patients. _x000D_ Conclusions Contrast-enhanced ultrasound can be used to perform a nephrostogram with ultrasound contrast administered via a nephrostomy tube. This novel imaging technique is non-inferior to fluoroscopic nephrostogram, safe for patients, and devoid of radiation exposure in evaluating ureteral patency following percutaneous nephrolithotomy. Funding NIH R21-DK-10943
Authors
Thomas Chi
Manint Usawachintachit David Tzou Helena Chang Benjamin Sherer Marshall Stoller Stefanie Weinstein John Mongan |
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PD11-06 |
Cystic Renal Masses: Is the Bosniak classification system an adequate predictor of survival? |
Imaging/Radiology: Uroradiology II | 17BOS |
Abstract: PD11-06 Sources of Funding: None Introduction We evaluate intervention rates and survival outcomes of complex renal cysts in a single center experience. Outcomes stratified by initial classification according to the Bosniak classification system. Methods We used a radiology data-mining system (Montage; Montage Healthcare Systems, Philadelphia, PA, USA) to retrospectively review the radiology database in an academic health center between 2001 and 2013 to identify all cases of "complex cyst." Primary end points were overall (OS) and cancer specific survival (CSS). Results 248 patients were identified using the Montage system to have radiographic reports of complex renal cysts. Of these, 141 (56.9%), 86 (34.7%), and 21 (8.4%) had Bosniak 2F, 3 and 4 cysts, respectively. Median follow-up was 66.05±54.24 months with an average of 3.61 scans (all modalities) per year. Of the 244 patients for whom we had follow-up, there were no cancer-specific deaths and overall mortality was 7.4%. Only 1 patient (4.7%) with a Bosniak 4 lesion at diagnosis developed metastases during follow-up. 20 patients underwent percutaneous biopsy of a solid nodule within the cyst; 7 (35%) were found to have renal cell carcinoma, and all of these patients received treatment. With regards to intervention, 6 (4.3%), 31 (36.0%) and 13 (61.9%) of the Bosniak 2F, 3 and 4 patients underwent either surgical or ablative intervention, respectively. Indication for intervention was predominantly age (median age: intervention 50.3±14.6, no intervention 63.4±13.3). Median time to intervention from initial identification was 6.45 months. Extirpative surgery with radical (17 patients, 34%) or partial nephrectomy (30 patients, 60%) was the predominant intervention, while 3 patients (6%) underwent ablation. While 4 patients (8.5%) had benign final pathology, the remainder had RCC: 23 (48.9%) clear cell RCC, 10 (21.2%) multilocular cystic RCC, 7 (14.9%) papillary type 1 RCC, 3 (6.4%) papillary type II RCC and 1 (2.1%) tubulocystic RCC. The majority (95.1%) were Fuhrman grade 1 or 2; 2 patients (4.9%) were Fuhrman grade 3. None of the patients undergoing intervention had evidence of recurrence during follow-up. Even when excluding patients undergoing intervention, CSS remained 100%. Conclusions Cancer-specific survival and overall survival for patients diagnosed with Bosniak 2F-4 complex renal cysts remains quite high; there were no cancer-specific deaths, even in the group that received no intervention. Reconsideration of management guidelines for complex renal cysts based on Bosniak classification system is warranted, particularly for Bosniak 3 cysts. Funding None
Authors
Thenappan Chandrasekar
Ardalan E. Ahmad Kamel Fadaak Michael A.S. Jewett Antonio Finelli |
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PD11-07 |
Chemoprophylaxis during Transrectal Prostate Needle Biopsy: Interim analysis of randomized clinical trial(NCT02423759) |
Imaging/Radiology: Uroradiology II | 17BOS |
Abstract: PD11-07 Sources of Funding: none Introduction Post Transrectal biopsy infectious complications (PTBICs) are increasing due to rising fluoroquinolone resistance (FQ-R). Targeted prophylaxis based on prebiopsy rectal swabs has reduced PTBICs. However, rectal swab prior to every biopsy would create a burden for laboratories and extra costs. A randomized trial testing 3 chemoprophylaxis Methods Men presented for prostate biopsy were randomized to receive ciprofloxacin 500mg B.I.D for 3days from the night of biopsy(group A), augmented prophylaxis using ciprofloxacin and single prebiopsy shot of 160mg gentamycin IM(group B) and rectal swab culture based prophylaxis(group C). _x000D_ Primary end point is occurrence of postprocedure sepsis[ge]2 of SIRS (systemic inflammatory response syndrome) criteria. Inflammatory markers were used for postprocedure screening; CRP(C reactive protein), ESR(Erythrocyte sedimentation rate) and TLC(total leucocyte count). Secondary endpoint is occurrence of FQ-R in the screened men. Men were assessed 2 weeks prior to biopsy, at time of biopsy and 2 weeks after._x000D_ Results Since November 2015, 258patients were randomized 89, 94 and 80 patients in groups A, B and C respectively. Baseline data was comparable among the 3 groups including prebiopsy urine culture with significant growth in 8 (8.9%), 8 (8.5%) and 10 (12%) in groups A, B and C respectively (P 0.6) and were treated before biopsy. _x000D_ Postprocedure fever occurred in 19 (21.3%), 9 (9.5%) and 8 (10%) in groups A, B and C respectively (P 0.03). Sepsis was reported in 5 (5.6%), 5 (5.3%) and 4 (5%) in groups A, B and C respectively (P 0.9) and 2 (2.2%) patients in group A required hospitalization. Figure 1 shows that the degree of change in TLC and ESR-1stH group was significantly more in group A than other groups (P 0.04 and 0.02 respectively). Urine culture 2 weeks after biopsy showed significant growth in 23 (25.8%), 5 (5.3%) and 11 (13.7%) in groups A, B and C respectively (P 0.002)_x000D_ Significant bacterial growth was noted in 62 (77.5%) out of 80 rectal swabs, FQ-R was reported in 55/62 (88.2%) Conclusions With increasing FQ-R, ciprofloxacin alone is not an optimal prophylactic approach. Augmented prophylaxis with single dose gentamycin is an effective approach. Targeted prophylaxis might be used when gentamycin is contraindicated. Funding none
Authors
Ahmed M. Atwa
Ahmed M. Elshal Ahmed R. El-Nahas Mohamed A. El-Ghar Hashim Farg Ali Elsorougy Essam Elsawy Asaad Gaber Yasser Farag Abdelwahab Hashem Hossam Nabeeh Ahmed Mosbah |
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PD11-08 |
Computer-aided diagnosis of prostate cancer using a deep neural networks algorithm in pre-biopsy multiparametric magnetic resonance imaging |
Imaging/Radiology: Uroradiology II | 17BOS |
Abstract: PD11-08 Sources of Funding: none Introduction Magnetic resonance imaging (MRI) provides a noninvasive assessment of the prostate that improves the detection of prostate cancer and can reduce unnecessary biopsies. The excessive variation in the performance and interpretation of MRI is, however, a major barrier to its widespread acceptance and use. In this study, we employed computer-aided diagnosis with a deep neural networks algorithm for prostate cancer detection using multiparametric MRI (mpMRI). Methods Between 2010 and 2015, 354 patients underwent extended systematic prostate biopsy with MRI-targeted biopsy (MTB), and 209 patients with negative mpMRI underwent systematic prostate biopsy (SB). All patients with PSA levels of less than 20 ng/ml and negative findings of digital rectal examination were included as subjects. mpMRI was interpreted by an experienced radiologist. For the supervised training using deep neural network architecture, we selected 163 mpMRI-positive patients who were diagnosed with prostate cancer by MTB and 135 mpMRI-negative patients who were not diagnosed with prostate cancer by SB. We chose representative T2-weighted and diffusion-weighted (DW) MRI images from both mpMRI-positive and mpMRI-negative patients. The 298 pairs of T2-weighted and DW images labeled as &[Prime]cancer&[Prime] or &[Prime]no cancer&[Prime] were randomly divided into 248 training and 50 test datasets, and the measure of diagnostic accuracy was calculated. The structure of the deep neural network model we used contains an input layer, three fully connected hidden layers, and an output layer (figure 1). The layers in the networks have ReLu non-linear activation units, and their learning rate was 0.01 for 10 epochs with a dropout ratio of 0.5. Results In the 50 hold-out validation test datasets, the mean area under the curve and the accuracy were 0.84 (0.72-0.99) and 0.81 (0.72-0.96). The mean positive predictive value, negative predictive value, sensitivity, and specificity of the algorithm were 0.89 (0.74-1.00), 0.75 (0.50-1.00), 0.76 (0.50-1.00), and 0.88 (0.18-1.00), respectively. Conclusions Computer-aided diagnosis with a deep neural networks algorithm for prostate cancer with mpMRI can provide reproducible interpretation and a greater level of standardization and consistency. Funding none
Authors
Junichiro Ishioka
Yoh Matsuoka Masaya Itoh Masaharu Inoue Toshiki Kijima Soichiro Yoshida Minato Yokoyama Kazutaka Saito Kazunori Kihara Yasuhisa Fujii Hiroshi Tanaka Tomo Kimura |
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PD11-09 |
The accuracy of real-time MRI-TRUS fusion image-guided transperineal target biopsy with needle tracking of mechanical position-encoded stepper in the detection of the significant prostate cancer for the biopsy naïve men |
Imaging/Radiology: Uroradiology II | 17BOS |
Abstract: PD11-09 Sources of Funding: none Introduction To evaluate the accuracy of real-time elastic fusion image-guided transperineal prostate biopsy with needle tracking of mechanical position-encoded stepper in the detection of the significant prostate cancer for the biopsy naive men. Methods The patients with PSA level less than 20 ng/ml who were suspected as having prostate cancer from mpMRI scans were recruited prospectively. Target biopsies for each cancer-suspicious lesion real-time elastic fusion image-guided transperineal prostate biopsy with needle tracking of mechanical position-encoded stepper (Figure) and 12-cores systematic biopsies using the BioJet® system (D&K Technologies GmbH, Barum, Germany). Pathological findings of biopsy cores and whole mount specimen were analyzed. Results Two hundred fifty patients were included in the present study. Biopsy-proven significant cancer detection rate in the patients was 59% (148 of 250 patients). There was significantly different of the cancer detection rates in the patients between the target (58%, 145 of 250 patients) and systematic biopsy (34%, 86 of 250 patients) (p<0.0001). In targeted biopsy cores (n=527), biopsy-proven significant cancer detection rates (36% vs. 2.1%, p<0.0001), median positive core length (median 8mm vs. median 2mm, p<0.0001), median positive core percent (50% vs. 10%, p<0.0001), and median Gleason score (p<0.0001) were significantly higher compared with the results in systematic biopsy cores (n=3000). Biopsy-proven significant cancer detection rates of the targeted lesions with the Prostate Imaging and Reporting and Data System classification 3, 4, and 5 were 6.8%, 49%, and 80%, respectively. In whole mount specimen, the geographic locations in 96% of significant cancers were diagnosed before radical prostatectomy by both of targeted biopsy and mpMRI findings. Conclusions The biopsy-proven significant cancer detection rate using the present biopsy was significant higher, and the targeted biopsy cores had a significantly higher grade and larger length compared with systematic biopsies. The accuracy of geographic diagnosis of the significant cancer in the results shows the present biopsy method as a promising method. Funding none
Authors
Sunao Shoji
Shinichiro Hiraiwa Takahiro Ogawa Masanori Kawakami Mayura Nakano Hidenori Zakoji Toyoaki Uchida Takuma Tajiri |
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PD11-10 |
Impact of Gleason Pattern 4 Cribriform Architecture on Prostate Cancer Detection Using Multiparametric MRI |
Imaging/Radiology: Uroradiology II | 17BOS |
Abstract: PD11-10 Sources of Funding: none Introduction The ability to accurately identify prostate cancer on multiparametric MRI (mpMRI) has been shown to be directly related to the size and grade of the tumor. No studies to date have evaluated how different architectural patterns affect the performance of mpMRI. Our objective was to determine whether Gleason pattern 4 architecture impacts tumor visibility on mpMRI and correlate with final histopathology. Methods A total of 83 tumors were identified within 22 radical prostatectomy specimens from patients who underwent MR/US fusion biopsy followed by radical prostatectomy at our institution from January 2015-July 2016. Each tumor focus was characterized by: % Gleason pattern 4, overall Gleason score, predominant architectural pattern (poorly formed, cribriform, fused), tumor size, axis (anterior/posterior), region (apex/mid/base), laterality (left/right), and presence of extraprostatic extension. Each region of interest (ROI) on mpMRI, ranging from PIRADS 3-, was re-reviewed and paired with its corresponding pathological tumor focus. Tumors not paired with an ROI were classified as "not visible." Multiple logistic regression was performed to determine predictors of tumor visibility._x000D_ Results Out of 83 tumors identified, 33/83 (40%) were Gleason 3+3 (36%) and 50/83 (36%) were Gleason 3+4 or above. Among Gleason pattern 4 tumors, 14/50 (28%), 18/50 (36%), and 18/50 (36%) had predominantly poorly formed, cribriform, and fused gland architecture, respectively. MpMRI detected 17/30 (57%) of Gleason 3+4, 6/14 (43%) of Gleason 4+3, and 2/5 (40%) of Gleason 4+4 and above. Among tumors containing Gleason pattern 4, increasing tumor size and non-cribriform architecture predicted individual tumor detection on multivariate analysis (p = 0.002 and p = 0.011, respectively). Cribriform predominant tumors were detected by MRI in 5/17 (21%) compared to 20/33 (61%) when poorly formed or fused glands were the predominant architecture (p = 0.01). The size threshold for detection of cribriform tumors was higher than that of other architectural patterns (Figure)._x000D_ Conclusions Independent of lesion size, cribriform predominant tumors are less visible on mpMRI. Clinically this could limit the utility of mpMRI in men with known cribriform tumors, since these tumors behave more aggressively than other Gleason pattern 4 tumors._x000D_ Funding none
Authors
Matthew Truong
Hiroshi Miyamoto Eric Weinberg Gary Hollenberg Edward Messing Thomas Frye |
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PD11-11 |
Do patients who undergo multiparametric MRI for prostate cancer need any other imaging? Results from a statewide collaborative |
Imaging/Radiology: Uroradiology II | 17BOS |
Abstract: PD11-11 Sources of Funding: Blue Cross Blue Shield of Michigan Introduction Multiparametric MRI (mpMRI) has an increasing role in prostatic disease management. For prostate cancer (PCa), guidelines typically recommend CT abdomen/pelvis (CT) and bone scan for high-risk patients, but MRI may provide similar information about lymph node (LN) and bony metastases. We investigated the use of mpMRI, CT, and bone scan in PCa patients within the Michigan Urological Surgery Improvement Collaborative (MUSIC) registry. Methods Imaging outcomes entered into the MUSIC registry between June and October 2016 were reviewed. Of 402 patients receiving mpMRI, 46 and 94 also had CT and bone scan, respectively, within 90 days of MRI. mpMRI detection rates of LN and bone metastases were compared to CT and bone scan. Positive LNs were defined as greater than 8mm in the short axis. Clinical correlation of PCa metastases was reviewed for all patients and pathologic confirmation was available for select patients. Results Of the 402 patients undergoing mpMRI after PCa diagnosis, 11.4% received CT. Bone scan was performed for staging in 23.4% of patients undergoing mpMRI, including 4.2%, 14.4%, and 81.0% of patients with low, intermediate, and high-risk PCa, respectively. LN suspicious for metastases were identified on 2.7% of MRI and 4.3% of CT. No patients had LN identified on both CT and MRI; 2 and 1 patients had LN identified only on CT or MRI, respectively. Bone metastases were identified on 2.7% of MRI and 7.4% of patients undergoing bone scan. For patients having both MRI and bone scan, 2 of 6 patients with suspicious bone lesions (33%) and 1 of 4 (25%) with indeterminate lesions on mpMRI were confirmed on bone scan. Of 7 patients with positive bone scans, 4 had mpMRI without suspicious bone lesions. Conclusions mpMRI performs similar to CT for the detection of LN metastases, and can detect bone metastases. Literature suggests that only 5% of patients with bone metastases have lesions only outside of the area studied with MRI (Woo et al. J AJR 2016; 206:1156-63). MRI&[prime]s ability to stage prostate cancer patients in place of CT and possibly bone scan shows promise. Our study, though limited by a small number of subjects, suggests that MRI performed by diverse practices and reviewed by multiple radiologists may not have the same results. A comparison of MRI versus CT on a larger scale may confirm our findings. Funding Blue Cross Blue Shield of Michigan
Authors
Justin Drobish
Ji Qi Tae Kim James Montie Sabrina Noyes Dinesh Telang Brian Lane Michigan Urological Surgery Improvement Collaborative |
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PD11-12 |
Feasibility of Automating the Measurement of Kidney Stone Diameter, Volume, and Density on CT |
Imaging/Radiology: Uroradiology II | 17BOS |
Abstract: PD11-12 Sources of Funding: None Introduction Several options exist for estimating renal and ureteral stone burden on CT, including volume, surface area, and maximum diameter. To date, no specific measure is accepted as the gold standard for use in research or clinical care. This is because calculating all these individual parameters is difficult and time consuming. Therefore, we developed an automated tool for calculating clinically relevant urinary stone parameters on CT. Methods An algorithm was developed that identifies stones on CT based on an attenuation threshold within a region of interest (ROI). A threshold of 250 Hounsfield units (HU) was selected to ensure that the stone remains a single object, while eliminating adjacent soft-tissue. For each CT, the images were exported, an ROI was identified by a board-certified radiologist, and the algorithm was applied to this ROI (MATLAB 9.1; Natick, MA) (Figure 1). Stone parameters analyzed included volume, maximum diameter, largest diameter in x, y and z dimensions, cumulative diameter, and HU. Volume was measured by summing all voxels within the stone and this value was correlated (Pearson correlation) to the calculated volume using the formula for a sphere (4/3πr3, where r is the maximum radius). Results As a pilot validation study of the algorithm, a total of 10 consecutive patients (11 stones) with a history of nephrolithiasis who underwent a CT from 1/2016-4/2016 were included in this analysis. Table 1 outlines the calculated parameters for each stone. The correlation between measured (voxel sum) and calculated (sphere formula) stone volume was 0.577. Conclusions Automated calculation of clinically relevant urinary stone parameters, such as maximum diameter, measured volume, and stone density can easily be obtained and visualized at the point-of-care. Measured and calculated stone volume have a weak correlation, likely due to the variability in stone shape. Future investigations will determine how automated stone measurements can help us to identify which patients will have treatment success. Funding None
Authors
Justin Ziemba
George Fung Rishab Gurnani Elliot Fishman Brian Matlaga Satomi Kawamoto |
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PD12-01 |
A novel family of natural products that targets uropathogenic Escherischia coli iron acquisition |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Kidney & Bladder I | 17BOS |
Abstract: PD12-01 Sources of Funding: National Institutes of Health: R01DK097362 and T32AI007528_x000D_ Urology Care Foundation Fellow_x000D_ American Society of Microbiology Career Development Grant_x000D_ MTRAC Mi-Kickstart Award_x000D_ Introduction Both the physical and financial burdens of urinary tract infections (UTIs) are staggering. In the U.S. alone, UTIs result in an estimated societal cost of $5.1 billion. UTIs are primarily caused by uropathogenic Escherichia coli (UPEC) and 1 in 40 women experience chronic UTIs during their lifetime. Women experiencing at least two UTIs per year are often given antibiotics prophylactically. As anticipated, the rates of resistance to these antibiotics in UPEC strains have steadily risen over the past few decades, highlighting the need for new antibiotic scaffolds and therapeutic strategies to treat UTIs. Iron, an essential nutrient used as a co-factor in many biological processes, is restricted in the host environment. Notably, the primary site of UPEC infection, the bladder, has dramatically lower iron levels than the sera. It is not surprising then that UPEC strains deficient in iron acquisition are attenuated. Based on the requirement of iron for full virulence of UPEC and the need for new antibiotic drug scaffolds, the objective of this study was to identify novel natural products that inhibit wildtype UPEC growth in low iron conditions. Methods To identify novel scaffolds and validate bacterial iron acquisition as a viable therapeutic target, we screened 33,000 marine microbial-derived natural product extracts (NPEs) against an unmodified UPEC clinical isolate. This ensured that active hits are not susceptible to Gram-negative efflux pumps. The NPEs were collected from the supernatants of marine bacteria as complex mixtures. To identify the structures of the active molecules, marine bacteria were cultured on a large scale and pure molecules were isolated from the NPEs using column chromatography and HPLC. The structures were elucidated using high-resolution mass spectrometry and 2-D NMR. Results We identified 204 NPEs that reduce wildtype UPEC growth in low iron by over 90% without chelating iron or impacting bacterial viability in iron-replete medium. From these hits, we have purified a novel family of cyclic natural products that inhibit bacterial growth at nanomolar concentrations. Preliminary data suggest that these small molecules are interfering with iron acquisition machinery. Conclusions These exciting data provide the foundation for exploring the structure-activity relationships of these compounds with their bacterial targets, which will inform the development of antimicrobial therapies that target iron homeostasis in UPEC and other Gram-negative bacteria. Funding National Institutes of Health: R01DK097362 and T32AI007528_x000D_ Urology Care Foundation Fellow_x000D_ American Society of Microbiology Career Development Grant_x000D_ MTRAC Mi-Kickstart Award_x000D_
Authors
Laura Mike
Ashootosh Tripathi David Sherman Harry Mobley |
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PD12-02 |
Antimicrobial gene expression and UTI susceptibility is dependent on IL-6/Stat3 signaling |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Kidney & Bladder I | 17BOS |
Abstract: PD12-02 Sources of Funding: SPU 2016 research grant; K08 grant DK102594 from NIDDK Introduction Urinary tract infections (UTI) are a significant source of morbidity. Due to rising antibiotic resistance patterns, alternate treatments are needed. Prior work has demonstrated induction of urine and serum IL-6 in pyelonephritis and renal scarring. IL-6 has been linked to antimicrobial peptide (AMP) production in other organs via Stat3 phosphorylation on Tyr705. As a result, we sought to evaluate the potential role of IL-6/Stat3 induced signaling on urothelial AMP expression and UTI susceptibility. Methods We infected 6 week old female C57BL/6J or C3H/HeOuJ mice transurethrally with UPEC and measured IL-6, phosphorylated (p-)Stat3, and AMP expression by ELISA, qRT-PCR, Western blotting, and immunofluorescence microscopy. The requirement for Lipopolysaccharide (Lps) / Toll-like receptor 4 (Tlr4) signaling was established using Lps-hyporesponsive C3H/HeJ mice, compared to C3H/HeOuJ Lps-sensitive controls. We evaluated the roles of IL-6 in p-Stat3, AMP production, and UPEC clearance using IL-6 neutralizing antibody and IL-6 knock out (KO) mice. We determined the contribution of Stat3 to AMP production via tamoxifen-inducible Stat3 conditional KO mice. We measured bacterial burden by serial plating on LB agar. Results were evaluated by Mann-Whitney U test with p <0.05 being significant. Results Upon UPEC infection, we observed a time dependent induction of urinary IL-6 secretion and bladder p-Stat3. Sustained expression of IL-6 and p-Stat3 required intact Tlr4 signaling. P-Stat3 localized to the nuclei of infected bladder urothelium. Bladder AMP mRNA levels increased following peak IL-6 secretion and p-Stat3. IL-6 KO mice exhibited absent urothelial p-Stat3 and severely blunted AMP mRNA induction following experimental UTI, leading to impaired UPEC clearance. Conversely, intraperitoneal administration of recombinant IL-6 induced bladder p-Stat3 and AMP expression in the absence of infection. Conditional Stat3 deletion reduced bladder AMP mRNA levels at baseline and following experimental UTI. IL-6 neutralizing antibody reduced p-Stat3 levels in C3H/HeOuJ mice, with increased renal UPEC colonization and pyelonephritis severity. Conclusions IL-6 is both necessary and sufficient for urothelial p-Stat3 and AMP transcription, and genetic or acquired IL-6 deficiency leads to increased UTI susceptibility. This implicates IL-6 and Stat3 as master regulators of urothelial AMP transcription in states of sterility and infection. Therapeutic manipulation of the IL-6/Stat3 axis provides a mechanism to alter AMP expression to treat and even prevent UTI. Funding SPU 2016 research grant; K08 grant DK102594 from NIDDK
Authors
Christina Ching
Sudipti Gupta Birong Li Brian Becknell |
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PD12-03 |
Normal perineal microbiome in prepubertal females with dysbiosis if recurrent urinary tract infections |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Kidney & Bladder I | 17BOS |
Abstract: PD12-03 Sources of Funding: Research Institute at Nationwide Children's Hospital Clinical and Translation Research Intramural Funding Program Introduction Specific microbial signatures exist in the body to regulate external pathogens. While prior work has focused on the role of the adult genitourinary microbiome in urinary tract health, little research investigates the normal pediatric perineal microbiome and aberrations related to urinary tract infections (UTIs). We strove to define the genitourinary microbiome in the normal developing prepubertal female child and compared this to a small cohort of children with recurrent UTIs. Methods After IRB approval, we consented healthy females at pediatric well-child visits to participate. Children were divided into 4 groups of significant developmental milestones: 1) 0-3 week old newborns; 2) 5-9 month old infants transitioning to solid foods; 3) 3-5 year old toddlers undergoing toilet training; and 4) 9-12 year old premenstrual girls. We also enrolled girls from the urology clinic with a history of UTIs (>50,000 colony forming units) who have been off antibiotics >1 month. Four swabs were taken on each patient: 1) genitourinary (urethral/vaginal introitus); 2) perirectal; 3) periauricular; 4) oral. Next generation 16S rRNA sequencing was performed to identify age and location of specific microbial signatures as well as a signature associated with recurrent UTIs. Results A total of 40 patients were recruited: a) 13 newborns; b) 6 infants; c) 13 toddlers; d) 6 premenstrual girls; and e) 2 recurrent UTIs. Children with recurrent UTI were 15 months and 2 years old. There was a clear evolution of the perirectal and genitourinary microbiomes with age, showing divergence at 5-9 months of age. The newborn group had the tightest clustering of bacteria between perirectal and genitourinary microbiomes. Those with recurrent UTI fall outside of any age group clustering let alone their specific age group (Figure 1). Conclusions We are the first to describe the normal prepubertal microbiome. There is a clear divergence and personalization of perirectal and genitourinary microbiomes as early as 5-9 months of age. Likely the tight clustering of newborn perirectal and genitourinary microbiome is a result of the maternal genitourinary microbiome. Children with recurrent UTIs have a dysbiosis of their perineal microbiome compared to children without. This could represent a target of UTI prevention and/or treatment. Funding Research Institute at Nationwide Children's Hospital Clinical and Translation Research Intramural Funding Program
Authors
Christina Ching
Elizabeth Lucas Shareef Dabdoub Purnima Kumar Sheryl Justice |
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PD12-04 |
Leukotriene B4 signaling activates innate urothelial defenses and protects the bladder and kidneys against uropathogenic E. coli (UPEC) |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Kidney & Bladder I | 17BOS |
Abstract: PD12-04 Sources of Funding: NIH Introduction Leukotriene B4 (LTB4), a dihydroxy fatty acid derived from arachidonic acid, acts as a chemoattractant in non-urothelial tissues and plays a role in innate host defenses. However, virtually nothing is known about the role or, the lack thereof, of LTB4 in the urinary tract, which is the focus of the present study. Methods Adult wild-type female mice (7-9 weeks) were inoculated via the transurethral route with type 1 piliated cystitis strain UTI89 or pyelonephritis strain CFT073 (107 cfu in 20 μl PBS). Urothelial production and urinary secretion of LTB4 was measured by ELISA, and its localization determined by confocal immunofluorescence microscopy. The effects of LTB4 deficiency on UPEC infections were examined by administering the wild-type mice with zileuton, an inhibitor of LTB4 production and by using knockout mice lacking arachidonate 5-lipoxygenase (ALOX5), a key enzyme in LTB4 biosynthesis. The resultant neutrophil infiltration, intracellular bacterial community (IBC) formation and clearance, neutrophil myeloperoxidase (MPO) activity, bacterial colony forming units were assessed under specific conditions and controls. Results In the wild-type mice, both UPEC strains UTI89 and CFT073 triggered an 8-fold increase of LTB4 in urothelium over PBS controls 2 hours after inoculation. The urothelial level of LTB4 continued to rise, peaking at 12 hours and subsiding considerably at 24 hours, the two time points coinciding with the accumulation and clearance of IBC, respectively. Urine levels of LTB4 lagged slightly behind that of urothelium, probably reflecting time required for protein secretion. Inhibition of LTB4 by zileuton included in the UPEC inocula significantly reduced MPO activity and neutrophil infiltration in the urothelium. In ALOX5 knockout mice, UTI89 and CFT073 inoculation caused four times more IBC than in wild-type mice. Consistent with this, neutrophils were extremely sparse in ALOX5 mice in comparison to the wild-type controls. Additionally, CFT073 were recovered in large numbers from the kidneys of ALOX5 knockout mice, but not from those of wild-type mice. Conclusions Our study provides the first experimental evidence indicating that LTB4 signaling initially in the urothelium and later through the neutrophils plays a crucial role in eliciting innate urothelial defenses and in clearing UPECs from the lower and upper urinary tract. Deficiency in LTB4 signaling may contribute significantly to the increased susceptibility of the urinary system to uropathogenic E. coli-caused infections. Funding NIH
Authors
Yan Liu
Ellen Shapiro Herbert Lepor Xue-Ru Wu |
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PD12-05 |
Big potassium channel (BK) activity in female mouse bladder umbrella cells is enhanced by bacterial lipopolysaccharide: an acute host response in urinary tract infection (UTI) pathogenesis |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Kidney & Bladder I | 17BOS |
Abstract: PD12-05 Sources of Funding: Naratil Pioneer Award from Women's Health Research at Yale Introduction Urothelial cells grown as a monolayer cannot recapitulate the differential function of urothelial cells (e.g. apical, intermediate, basal urothelial cells). Lipopolysaccharide (LPS) has been used as a surrogate for E. coli in study of host response to urinary tract infections. We isolated basal membrane of apical urothelial cells from urothelial tissue for patch clamp studies. We measured potassium channel activities in the apical cell and how the large conductance potassium channel activity changed when the urothelium was exposed to LPS. Methods Female C57BL/6 mice 8 to 12 weeks of age were used. Pure urothelium was dissected out using our published technique. Urothelium was placed luminal side down and umbrella cells were exposed after removing basal and intermediate cells with a glass micropipette (Fig. 1). Both inside-out and cell attached configurations were used. Urothelium was exposed to 40 µg/ml of LPS for 30 minutes. Blockers of BK (paxilline, iberiotoxin), LPS (polymyxin B), protein kinase A (H89) were also used. RT-PCR was performed to assess expression of BK and LPS-receptors (TLR4, CD14, and MD-2). Results Two K conductances were found, 28.3±1pS and 200.6±4pS. The 200pS channel was sensitive to intracellular calcium, voltage and blocked with iberiotoxin and paxilline. RT-PCR confirmed presence of BK in urothelium. This suggested that the 200pS channel was the BK channel. LPS significantly increased BK channel activity of NPo from 0.50±0.13 to 1.62±0.31 (p<0.001) (Fig. 2); this effect was abrogated by polymyxin B (Fig. 2) and H89. TLR4, CD14 and MD-2 mRNAs were expressed only in the urothelium and not lamina propria or detrusor smooth muscle. Conclusions To our knowledge, this is the first time basal membranes of umbrella cells have been patch clamped. LPS significantly increased BK channel activity. This change in apical membrane activity represents an early host urothelial cell response to UTI. While we did not study the downstream results of increased BK activity, it is likely that this would have shown increased urothelial cytokine release. This BK-dependent cytokine release mechanism has been described in macrophages. Funding Naratil Pioneer Award from Women's Health Research at Yale
Authors
Ming Lu
Jian-ri Li Yan Li Shan Yu Toby Chai |
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PD12-06 |
Inflammasome Activation Early in the Development of Diabetic Bladder Dysfunction |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Kidney & Bladder I | 17BOS |
Abstract: PD12-06 Sources of Funding: 2017 Urology Care Foundation Residency Research Award sponsored by the Russell Scott, Jr, MD Research Fund; Intramural Funds provided by the Division of Urology, Department of Surgery of the Duke University School of Medicine Introduction The NLRP3 inflammasome has gained recognition for its role in mediating inflammation through its activation of pro-inflammatory cytokines like IL-1β. It has been implicated in diabetic sequelae such as nephropathy, retinopathy, neuropathy, and vasculopathy, and in sterile cystopathy such as hemorrhagic cystitis and bladder outlet obstruction. We hypothesize that the NLRP3 inflammasome is activated in the inflammatory response in diabetic bladder dysfunction (DBD), the most common of all diabetic complications. Methods Ins2 (Akita) diabetic mice and age-matched controls underwent 4hr voiding assays to determine development of early DBD, defined as increased frequency and smaller voided volumes. Inflammation and fibrosis were compared through bladder weights, Evans Blue assay, Masson&[prime]s trichrome stain, and H&E stain. Active caspase-1, a functional moiety of activated inflammasome, was targeted intracellularly by a fluorescent caspase inhibitor and measured through flow cytometry. Paired geometric mean fluorescence intensity was compared via paired T-test, and all other univariate analysis was performed with ANOVA. Significance was defined as p<.05. Results Diabetic mice demonstrated DBD as early as week 11 with increased frequency of voids (p<.01), increased total voided volume (p<.05), and decreased volume per void (p<.05), compared to wild type mice. Inflammasome activation was evident as witnessed by increased active caspase-1 in diabetic mice (Figure 1). Diabetic mice also had increased Evans blue extravasation, indicating increased capillary permeability, an early sign of inflammation. Furthermore, diabetic bladders demonstrated hypertrophy compared to wild type bladders (20.6 vs 18.9mg; p=0.2); however, there was no increase in collagen deposition or histological changes on H&E staining. Conclusions Inflammasomes are activated early in the development of diabetic bladder dysfunction and may contribute to the onset of voiding dysfunction. Funding 2017 Urology Care Foundation Residency Research Award sponsored by the Russell Scott, Jr, MD Research Fund; Intramural Funds provided by the Division of Urology, Department of Surgery of the Duke University School of Medicine
Authors
Brian Inouye
Francis M Hughes Robin Lütolf Clay Rouse Wen-Chi Foo J Todd Purves |
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PD12-07 |
Histone deacetylase inhibitor suberoylanilide hydroxamic acid ameliorates hemorrhagic cystitis via DNA damage repair gene pathways |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Kidney & Bladder I | 17BOS |
Abstract: PD12-07 Sources of Funding: National Institutes of Health Grant R01CA108646 (NCI) Introduction Hemorrhagic cystitis is a highly-morbid inflammatory bladder disease associated with nitrogen mustard alkylating agents, most notably cyclophosphamide. Acrolein, a reactive oxygen species metabolite of cyclophosphamide, has been shown to silence DNA damage repair genes via global methylation pathways. 8-oxoguanine DNA glycosylase (Ogg1) is one such silenced base excision repair enzyme that can restore DNA integrity. Subsequent inflammation from the accumulation of DNA damage results in bladder smooth muscle pyroptotic cell death. We hypothesized that reversing inflammasome-induced imprinting and gene silencing in the bladder smooth muscle could prevent hemorrhagic cystitis. Methods Experiments were carried out using cultured detrusor fibroblasts, B6 wild-type mice, and Ogg1 knockout mice. Hemorrhagic cystitis was induced with either cyclophosphamide or acrolein. Mesna, the current standard of care treatment to prevent hemorrhagic cystitis; Nicotinamide, a vitamin B-3 analog shown to ameliroate bladder inflammation; and suberoylanilide hydroxamic acid, a histone deacetylase (HDAC) inhibitor with anti-inflamatory properties, were added to treatment groups. Harvested tissues and cells were subjected to bisulfite sequencing and chromatin immunoprecipitation analysis to evaluate DNA methylation patterns and epigenetic imprinting. Results There was enhanced recruitment of Dnmt1 and Dnmt3b to the Ogg1 promoter in acrolein treated bladder fibroblasts as demonstrated by the pattern of CpG-island methylation and resultant bisulfite sequencing. Accumulation of reactive oxygen species with spontaneous pyroptotic signaling was found in Ogg1 knockout detrusor cells. Suberoylanilide hydroxamic acid restored Ogg1 expression to physiologic levels moreso than either nicotinamide or Mesna in all hemorrhagic cystitis models. Additionally, suberoylanilide hydroxamic acid restored histologically-visible cyclophosphamide-induced bladder damage to that of normal untreated control mice. Conclusions The pattern of epigenetic imprinting induced by inflammation suggests a novel therapeutic target for the treatment of hemorrhagic cystitis. HDAC inhibitors can reactivate Ogg1 expression by altering DNA methylation through Dnmt3B regulation. More broadly, the data suggest that re-programming epigenetic imprinting could limit the inflammatory process induced by not only cyclophosphamide but by a multitude of other toxic insults as well. Funding National Institutes of Health Grant R01CA108646 (NCI)
Authors
Subhash Haldar
Christopher Dru Rajeev Mishra Manisha Tripathi Frank Duong Bryan Angara Neil Bhowmick |
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PD12-08 |
The Role of IL-10 in Unilateral Ureteral Obstruction: Regulation of Angiogenesis and Fibrosis |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Kidney & Bladder I | 17BOS |
Abstract: PD12-08 Sources of Funding: NIGMS R01 GM111808 Introduction Clinical unilateral ureteral obstruction (UUO) results from pathologies like ureteral calculi, malignancy, trauma, and periureteral fibrosis. UUO requires prompt surgical intervention to prevent progressive inflammation, fibrosis, and kidney function impairment. Novel therapies are needed to recover renal function and architecture after obstruction. Previous reports show the anti-inflammatory cytokine interleukin-10 (IL-10) attenuates fibrosis in a murine model. We and others have shown IL-10 regulates angiogenesis and endothelial progenitor recruitment during dermal and ischemic cardiac tissue repair. We hypothesize that IL-10 can promote angiogenesis and prevent microvascular rarefaction in a murine UUO model. Methods 8 week-old C57BL/6J (WT) mice and IL-10 null male mice were injected with lenti-IL-10/lenti-GFP (1x1010 IU) under the renal capsule. Three days after injection, UUO was performed. 14 days after UUO, UUO/sham kidneys and serum were collected for RNA, ELISA and immunohistochemical analysis of VEGF and TGFβ isoforms. Primary fibroblasts were isolated from 8-10 week-old male WT mice. IL-10 (50 ng/ml or 200 ng/ml) was added to cultures. VEGF and TGFβ-1 gene expressions were assessed by qPCR at 1, 2, 3 and 6h. Levels of TGFβ-1 and TGFβ-3 were determined at 48h by ELISA. Data presented as mean±SD, n=3/treatment group. P value by ANOVA. Results IL-10 treatment, in vitro, increased VEGF expression (related to physiologic angiogenesis) and altered the expression of TGFβ isoforms (related to pathologic fibrosis). Lenti-Il10 treatment in mice with UUO reduced fibrotic changes between tubules (45±7%, p<0.05) and attenuated tubular dilatation (p<0.05, n=30/group). CD31, an endothelium marker essential to preserving tubular integrity, was normally expressed in healthy kidney parenchyma and decreased after UUO. IL-10 null mice showed a lower basal level of CD31 than WT mice. In both WT and IL-10 null mice, IL-10 treatment preserved CD31, suggesting a role in rescuing integral peritubular capillaries. Conclusions Ureteral obstruction can cause remodeled renal architecture and decrease in renal function. Our results in a murine UUO model show that IL-10 can effectively promote angiogenesis in vitro and prevent microvascular rarefaction in vivo. Mice treated with IL-10 show decreased fibrotic change and increased markers for tubular integrity. These results from the in vivo studies of UUO, and the in vitro studies of IL-10&[prime]s influence in angiogenesis and fibrosis of the kidney, may lead to novel treatments for the sequelae of urinary tract obstruction. Funding NIGMS R01 GM111808
Authors
Bethany Desroches
Xinyi Wang Pu Duann Meredith Rae Swathi Balaji Sundeep Keswani |
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PD12-09 |
Connective Tissue Growth Factor Induction Promotes Epithelial Maladaptive Repair in Renal Fibrosis |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Kidney & Bladder I | 17BOS |
Abstract: PD12-09 Sources of Funding: NIH RO1 GM 057242; Department of Veterans Affairs Introduction Chronic kidney disease (CKD) is a widely prevalent and often silent condition. Effective treatment to halt renal fibrosis progression to CKD is largely lacking. Connective tissue growth factor (CTGF) renal upregulation is evident in various nephropathies including obstructive uropathy and is linked to fibrosis progression. Precise mechanisms of CTGF contribution to the maladaptive phenotype (e.g., epithelial dedifferentiation, growth arrest, fibrotic factor induction) however, are largely unknown. Methods Human kidney tubular epithelial cells (HK-2) were stably transduced with either control or CTGF expression via lentiviral transduction to mimic CTGF induction in kidney injury. Western analysis was used to confirm CTGF overexpression and to investigate the effects of CTGF overexpression on various fibrotic markers. Epithelial cell-cell communication studies involved transfer of conditioned media from control or CTGF stably expressing epithelial cells to similarly seeded normal HK-2 cultures. Microscopy was used to evaluate cell morphologic changes. Cell death is confirmed by Annexin staining. Results Prolonged epithelial CTGF overexpression resulted in upregulation of pro-fibrotic factors including fibronectin and plasminogen activator inhibitor 1 (PAI-1), induction of plasticity maker, vimentin, and downregulation of expression of epithelial cell adhesion molecule (E-cadherin), compared to vector transduced HK-2 controls. Epithelial cells with CTGF overexpression assume a mesenchymal morphology and undergo growth inhibition. Cell-cell communication experiments reveal that paracrine factors secreted by CTGF expressing HK-2 cells trigger growth inhibition and a fibrotic response in normal HK-2 cells. CTGF expression in older epithelial cultures also induces markers of DNA damage and cell death compared to similarly aged control vector transduced cultures. Conclusions Epithelial CTGF induction promotes upregulation of fibrotic factors, induction of epithelial dedifferentiation, suppression of cell growth and orchestrates (via paracrine mechanisms) dysfunction in normal renal epithelia. CTGF, therefore, could be an attractive drug target against renal fibrosis and CKD progression. Funding NIH RO1 GM 057242; Department of Veterans Affairs
Authors
Alex Arnouk
Roel Goldschmeding Paul Higgins Rohan Samarakoon |
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PD12-10 |
Kidney Injury Molecule-1 as a potential urinary biomarker of hydroneprosis may not be affected by inflammatory causes in the urinary tract |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Kidney & Bladder I | 17BOS |
Abstract: PD12-10 Sources of Funding: The study was partially funded by an unrestricted Internal Research Fund award granted to the investigation team by the Department of Surgery, Schulich School of Medicine & Dentistry._x000D_ Introduction Newly discovered biomarkers have been used to assess renal function in several clinical situations, and diverse studies have suggested a relationship between urinary tract obstruction and increased levels of these biomarkers. It has been postulated that some inflammatory conditions may affect the expression of these markers precluding its use in our population. We planned to evaluate the urinary levels of Kidney Injury Molecule-1 in a set of urological patients to determine which factors may be associated with its expression._x000D_ Methods From a prospective observational cohort study, we included patients with hydronephrosis caused by renal stone disease or ureteric stricture, and patients with non-obstructive nephrolithiasis. Demographical, clinical and radiological characteristics were evaluated before and after surgical treatment. Urinary normalized KIM-1 concentration was measured using ELISA analyses in three different occasions, one preoperative and in two postoperative assessments. Non-parametric tests were used to compare KIM-1 levels during follow-up. The presence of stone disease, double J stent and hydronephrosis were noted and dichotomized. Correlations between biomarkers' levels and clinical or radiological characteristics were assessed using Spearman's correlation coefficient. Results Forty-eight patients and eleven controls were included in the final analysis. First and second postoperative assessment were performed with a median of 17 days (IQR 9.5) and 59 days (IQR 34) after the surgical procedure. Patients with hydronephrosis showed a higher KIM-1 concentration than no-hydro patients and controls (1.19 vs 0.60 ng/mg creatinine, p=0.002). After analyzing KIM-1 expression in hydronephrosis patients exclusively, we found significantly higher levels at baseline, compared to both postoperative evaluations (p<0.001). KIM-1 showed a weak correlation with age, female gender, BMI, Charlson Comorbidity Index and presence of hydronephrosis (p<0.0001). Although, its expression was not correlated with the estimated glomerular filtration rate, leukocyturia, or presence of stone disease. The distribution of KIM-1 levels amongst patients with non-obstructive stone disease did not significantly change despite the surgical management. Conclusions This exploratory study found that urinary KIM-1 expression could potentially be affected by some patients' baseline characteristics. However, our results corroborate that urinary KIM-1 may be a reliable marker of hydronephrosis. Funding The study was partially funded by an unrestricted Internal Research Fund award granted to the investigation team by the Department of Surgery, Schulich School of Medicine & Dentistry._x000D_
Authors
Daniel Olvera-Posada
Stephen Pautler Alp Sener John Denstedt Hassan Razvi |
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PD12-11 |
Decreased Vascular Endothelial Growth Factor in Radiation Cystitis |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Kidney & Bladder I | 17BOS |
Abstract: PD12-11 Sources of Funding: This research was supported by the Aikens Center for Neurology Research and the Urology Care Foundation Research Scholars Program (Bernadette M.M. Zwaans). Introduction Radiation cystitis (RC) is a severely debilitating and inflammatory condition of the bladder resulting from radiation therapy to the pelvic area for which there is no curative therapy. 5-10% of cancer patients who have received pelvic radiation will develop RC, though little is known about the histological and molecular changes that drive the disease progression. A major histological hallmark of RC is vascular damage and hemorrhaging. Therefore, our study focuses on identifying early molecular changes that drive the vascular defect observed in RC using a mouse model of RC. In addition, we aim to identify potential urine biomarkers that could identify RC development prior to the appearance of symptoms. Methods Female C57BL/6 mice received a single dose of 40 Gy radiation delivered specifically to the bladder using a Small Animal Radiation Research Platform, a technique that simulates radiation treatment in human patients. Bladder tissues were harvested at 2 and 12 weeks post irradiation and processed for histology or molecular analysis. In addition, changes in vascular endothelial growth factor (VEGF) and cytokine/chemokine expression were analyzed in human urine samples from cancer survivors that received pelvic radiation. Results Bladder irradiation was well tolerated by mice. By 12 weeks, decreased bladder vascularization was detected in irradiated animals as was an increase in inflammatory cells clustered around blood vessels. This vascularization defect coincided with a loss of VEGF levels. Decreased VEGF expression was also identified in urine from symptomatic RC patients, in comparison to age-matched controls. Conclusions Radiation therapy for the treatment of pelvic tumors can cause severe damage to the bladder that can develop into radiation (hemorrhagic) cystitis. Blood loss through the urine is a major hallmark of RC and is caused by vascular defects that are currently not well understood. In this study irradiated mouse bladders developed reduced vascularization which coincided with a loss of VEGF expression. In addition, low levels of VEGF were also identified in the urine of symptomatic RC patients. Our findings suggest VEGF as a potential therapeutic target to treat the vascular defect in RC. Funding This research was supported by the Aikens Center for Neurology Research and the Urology Care Foundation Research Scholars Program (Bernadette M.M. Zwaans).
Authors
Bernadette Zwaans
Sarah Bartolone Heinz Nicholai Michael Chancellor Laura Lamb |
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PD12-12 |
Evaluation of Surface Micropattern (Sharklet) on Foleys Silicon Catheter in reducing Urinary Tract Infections |
Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Kidney & Bladder I | 17BOS |
Abstract: PD12-12 Sources of Funding: None Introduction Catheter-associated urinary tract infection (CAUTI) is a major preventable cause of harm in hospitalized patients. Previous in vitro studies have shon wthat a unique surface micropattern on catheter surface reduces bacterial biofilm formation. This single center, open labelled, randomized interventional study evaluated if the Sharklet micropatterned catheter (SC) reduces UTI in catheterized patients, when compared to a standard silicone Foley catheter. (NCT02835456) Methods Fifty eligible adult men requiring temporary urethral catheterization for a period between 3 and 30 days were randomized into two groups with standard silicone Foley catheter insertion in one and SC in other. On removal, parts of the catheters (tip, middle part and base) were examined for bacterial colonization/biofilm using scanning electron microscopy. The patients were also assessed for incidence of symptomatic UTI, significant asymptomatic bacteriuria, pain and discomfort. Results The mean age and duration of catheterization were similar among both groups. None of the patients developed symptomatic CAUTI. The outer surface of the SC had significantly lower biofilm formation when compared to the standard silicone catheter in all parts of the catheter (Tip: P= 0.003, Middle part: P=0.013 and Base: P=0.013). However, this difference was not noted in the inner surface of the catheters (P= 0.511, P=0.245, P=0.810 respectively); which may be attributed to the absence of micropattern in the inner surface of SC. There was significantly lower pain and discomfort in patients using SC when compared to the standard catheter (p=0.018). Conclusions Catheters that can reduce CAUTI have the advantage of improving the care of millions of disabled and elderly patients and reducing the enormous costs of managing complications associated with indwelling Foley catheter. However, none of the numerous strategies tested until now, like antibiotic or silver impregnation on catheter surface have proved to be useful in this regard. This is the first trial to test the efficacy of Sharklet micropattern on urinary catheter surface in a clinical setting. The promising results of this study opens the arena for novel mechanical modifications on catheter surface which may be both cost effective and clinically beneficial. Funding None
Authors
Vinodh Kumar Adithyaa Arthanareeswaran
Andras Magyar Lila Soos Bela Koves Abinaya Ravichandran Chandra Nora Justh Imre Miklos Szilagyi Tenke Peter |
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PD13-01 |
Pregnancy Outcomes in Men Evaluated for Sperm Aneuploidy – A Graded-Model of Risk |
Infertility: Epidemiology & Evaluation I | 17BOS |
Abstract: PD13-01 Sources of Funding: AWP is a K12 scholar supported by a Male Reproductive Health Research (MRHR) Career Development Physician-Scientist Award (Grant # HD073917-01 to DJL) from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Program. This work is also supported in part by the Burnett Research Fund. Introduction Embryos conceived by men with sperm aneuploidy are at increased risk for implantation failure (IF) or spontaneous abortion (SAB) and can be assessed using fluorescent in situ hybridization (FISH). The relationship between sperm FISH findings and risk of SAB or IF is unclear. Here we investigate the reproductive outcomes of couples with abnormal sperm FISH results._x000D_ _x000D_ Methods Telephone survey and chart review of men with sperm FISH testing and semen analysis was performed. Male age, female age, and female reproductive factors were recorded for each live birth, SAB, and IF. Sperm aneuploidy was defined using FISH, which examines autosomes 13, 18, 21, and the sex chromosomes. We performed linear regression to assess the impact of sperm aneuploidy FISH results on pregnancy outcomes. _x000D_ Results Data were collected from 99 men with 434 reproductive outcomes. Of 99 sperm FISH tests, 94 were abnormal. Mean±SD male age was 37.1±7.3 years, female age was 33.4±5.0 years, and length of infertility was 47.4±33.9 months. Total number of abnormal FISH components (range 0-4, with each chromosomal abnormality considered an abnormal FISH component) was found to best model SAB risk. Controlling for female age and semen parameters, the total number of abnormal FISH components significantly predicted SABs (p=0.001). Each additional abnormal FISH component increased the risk of SAB by 9.33% (p=0.001) for all reproductive outcomes. When only pregnancies achieved through natural conception were considered, the risk of SAB increased by 10.4% with each abnormal FISH component (p=0.003). Female age approached significance in both models; each year increased the risk of SAB by 1.2% (p=0.081). Sperm disomy, male age, female reproductive factors, semen volume, sperm density, and sperm motility did not predict SABs (p>0.05) (Figure 1). Abnormal FISH testing did not predict IF (p=0.259). The overall pregnancy rate in men with abnormal sperm FISH was 0.95% using IUI, 10.2% using IVF, 14.8% using IVF/ICSI, and 50% when preimplantation genetic screening (PGS) was added to IVF. _x000D_ Conclusions The incidence of aneuploid abnormalities of chromosomes 13, 18, 21, and the sex chromosomes on sperm FISH testing predicts SABs. Couples with abnormal sperm FISH results should be counseled regarding the potential negative pregnancy outcomes, and IVF with PGS discussed._x000D_ _x000D_ Funding AWP is a K12 scholar supported by a Male Reproductive Health Research (MRHR) Career Development Physician-Scientist Award (Grant # HD073917-01 to DJL) from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Program. This work is also supported in part by the Burnett Research Fund.
Authors
Taylor P. Kohn
Alexander W. Pastuszak Matthew F. Cherches Stephen M. Pickett Dolores J. Lamb Larry I. Lipshultz |
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PD13-02 |
Impact of Abstinence Time on Semen Parameters in a Large Population Based Cohort of Subfertile Men |
Infertility: Epidemiology & Evaluation I | 17BOS |
Abstract: PD13-02 Sources of Funding: This investigation was supported by the University of Utah Study Design and Biostatistics Center, with funding in part from the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant 8UL1TR000105 (formerly UL1RR025764). Introduction Traditionally, most fertility clinics recommend 2-5 days of abstinence before semen collection. However, the impact of abstinence time on semen quality in subfertile patients is not known. We hypothesized that shorter abstinence times were associated with reduced sperm quality for subfertile couples. We used a large population of subfertile men to test this hypothesis. _x000D_ Methods From 2002-2013, we retrospectively reviewed 19255 semen analyses from 15623 subfertile patients visited at our fertility clinic. For each encounter, data on patient age and semen parameters were extracted along with abstinence time. Abstinence time was categorized into 4 groups (≤2 days; >2 & ≤5 days; >5 & ≤7 days; >7 days). Sperm concentration, count, and total motile sperm count (TMSC) were log-transformed for analyses due to distribution skew and reported as ratios. Linear mixed effect regression models adjusted for age were used to test the effect of abstinence categories on semen parameters. Estimates and their 95% confidence intervals (CIs) were reported, and significance was assessed at the 0.05 level._x000D_ Results A total of 11782 encounters (10095 patients) remained for the final analysis after exclusion of patients <18 years old, azoospermic samples, and those with missing values. Mean age was 32.4 (standard deviation: 6.5) and median abstinence time was 4.0 days. Table 1 summarizes encounter data stratified by abstinence days. On average a consecutive increase in abstinence category was associated with increases in: concentration (0.32 ml, 95% CI: 0.28, 0.37), ejaculate volume (12%, CI: 7, 17), total sperm count (23%, CI: 19, 29) and TMSC (20%, CI: 15, 26). However, an increase in abstinence time was associated with decreases in: sperm viability (-1.67%, CI: -2.14, -1.20), total motility (-1.81%, CI: -2.36, -1.26), progressive motile sperm (-1.35%, CI: -1.94, -0.76), and normal tail morphology (-1.05%, CI: -1.41, -0.68). All p-values were <0.001. Conclusions Although shorter abstinence time was associated with slightly better sperm viability, motility and morphology, changes in TMSC might be more clinically relevant for infertility purposes. Lengthening the abstinence period may increase the total count and TMSC, which could be beneficial for subfertile patients with lower TMSC at baseline. Funding This investigation was supported by the University of Utah Study Design and Biostatistics Center, with funding in part from the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant 8UL1TR000105 (formerly UL1RR025764).
Authors
James R. Craig
Sorena Keihani Chong Zhang Angela P. Presson Jeremy B. Myers William O. Brant Kenneth I. Aston Benjamin R. Emery Timothy G. Jenkins Douglas T. Carrell James M. Hotaling |
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PD13-03 |
The Age of Fathers is on the Rise in the US: Data from 1973 to 2015 |
Infertility: Epidemiology & Evaluation I | 17BOS |
Abstract: PD13-03 Sources of Funding: None. Introduction The influence of parental demographics on fertility and birth outcomes is a topic of great interest to both epidemiologists and the lay public. Given logistics and certainty of exposures, data on all births in the US is often reported at the maternal level. While paternal characteristics are also known to influence birth outcomes, generational trends of paternal characteristics of child births within the United States have been poorly characterized. We sought to summarize the demographics of fathers in the US over the past 4 decades as well as describe the patterns of missing paternal data on birth certificates. _x000D_ Methods We evaluated 158,621,397 U.S. births spanning from 1973 to 2015 using data from the National Vital Statistics System of the Centers for Disease Control. Paternal, maternal and infant characteristics were analyzed and paternal ages of all births and first births were presented over time along with the mean difference in age between parents. Characteristics of births with known and unknown paternity were also compared. Results There has been a significant increase in mean paternal age among whites, blacks and asians over the past 40 years. In 1973, the mean paternal age for all births was 27.6, and 24.6 for first births, rising to 31.4 and 29.1, respectively, in 2015. Paternal age increased for all races combined and each race individually. However, interracial differences in mean age were apparent with asians > whites > blacks. The mean age difference between parents was similar over the past 40 years. In 1973, the mean parental age difference was 2.8 years—2.7 years for whites, 3.2 years for blacks and 4.2 years for asians. In 2015, the mean overall difference was 2.5 years with the difference between asian fathers and their partners decreasing the most to 3.2 years. Of all the recorded births in 1973, 91.3% had knowledge of paternal identity. This fell to 85.5% of fathers identified in 1991 and resides at 88.4% in 2015. Over the past decade, mothers younger than 20 years had the lowest proportion of reported paternal identity at 67.7% with black mothers under 20 at 50.4%. Overall, births without paternal identity were more likely associated with young, black mothers who reported less weight gain during pregnancy, and lower birth weight children. Conclusions Overall, paternal age is rising in the US in parallel with maternal age, a trend encompassing all races. The proportion of missing paternal data is also increasing in recent years. Given the association between paternal factors and birth characteristics, further understanding of these trends is necessary. Funding None.
Authors
Yash Khandwala
Chiyuan Zhang Michael L. Eisenberg |
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PD13-04 |
Results of a North American survey on the characteristics of men being assessed in male infertility clinics: the Andrology Research Consortium |
Infertility: Epidemiology & Evaluation I | 17BOS |
Abstract: PD13-04 Sources of Funding: Society for the Study of Male Reproduction Introduction The Andrology Research Consortium was established by the Society for the Study of Male Reproduction, a specialty section of the American Urological Association, to characterize men presenting for infertility investigation. Methods A standardized questionnaire capturing information about the infertile couples' demographics, reproductive history, previous fertility investigations, lifestyle factors and use of medications was completed by patients in 19 different clinics treating men with infertility across North America. Results A total of 2506 men completed the questionnaires. The mean age of the men and their female partners was 38 +/- 7 (SD) and 34 +/- 5 years old, respectively. 1505/2421 (62%) were referred by a reproductive endocrinologist and 524/2421 (22%) by their PCP. Of the 812 who answered this question, 688 (85%) reported that they were told that they had an abnormal sperm test. _x000D_ Prior to the consultation with the male infertility clinic, 274/2023 (14%) reported having used Intra-uterine insemination (IUI) with another 168/2168 (7.7%) reported the use of in-vitro fertilization (IVF) or intracytoplasmic sperm insertion (ICSI) therapy to treat the infertility. Only 31/274 (11%) of the couples who had undergone IUIs and 17/168 (10%) of those using IVF/ICSI reported a previous male fertility investigation. _x000D_ Potentially reversible causes of male infertility like use of medications and smoking were relatively common. Overall, 35/2384 (1.5%) men reporting using propecia and 74/2218 (3.3%) using testosterone. This data was skewed by the results from the University of Toronto where patients reported far lower use of propecia (1/1274) or testosterone (7/1274). Excluding the University of Toronto results, 34/1110 (3.1%) and 67/944 (7.1%) of the men reported using propecia and/or testosterone, respectively. While uncommon, 2 men reported that they had used IUI or IVF while remaining on propecia or testosterone. The testosterone was prescribed principally by PCPs, but many of the men reported that they obtained testosterone from non-physicians. In total, 352/2034 (17.3%) reported smoking. Conclusions Most men presenting to our male infertility clinics are referred from reproductive endocrinologists with abnormal sperm test results. Among couples who had previously been treated with advanced reproductive technologies like IUI, IVF or ICSI, only 11% had been referred to a urologist prior to the therapies. We identified a number of potentially reversible causes for the male sub-fertility in this group supporting the idea that more urology is needed, not less. Funding Society for the Study of Male Reproduction
Authors
Keith Jarvi
Susan Lau Kirk Lo Ethan Grober J Trussell James Hotaling Thomas Walsh Peter Kolettis Victor Chow Arma Zin Marc Goldstein Aaron Spitz Marc Fischer Scott Zeitlin Eugene Fuchs Mary Samplaski Jay Sandlow Robert Brannigan Ed Ko Tung-Chin Hsieh James Smith |
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PD13-05 |
Testicular Cancer Among Infertile Men: A Cost Based Rationale for Promoting Testicular Self Examinations |
Infertility: Epidemiology & Evaluation I | 17BOS |
Abstract: PD13-05 Sources of Funding: AWP is a K12 scholar supported by a Male Reproductive Health Research (MRHR) Career Development Physician-Scientist Award (Grant # HD073917-01) from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Program Introduction Testicular cancer (TC) is the most common malignancy among men 15-34 years old, and infertile men are at increased risk for TC. Here, we investigate the costs of screening infertile men for TC, and the cost savings associated with early detection and treatment of TC among infertile men. _x000D_ Methods Incidence, prevalence and hazard ratios for TC and infertility were extracted from the literature and used to calculate the annual number of TC cases among infertile men. Costs associated with TC screening and treatment were compiled using existing Medicare reimbursement databases and published data. These costs were used to model the costs of screening and treatment of infertile men at risk for TC._x000D_ Results Using incidence, prevalence and census data, the number of infertile men in the U.S. was calculated to be 2,350,000. Using co-prevalence data, 375 new cases of TC per year were estimated in the infertile male population. Screening using testicular self-examination (TSE) resulted in no cost burden. Prior to treatment, confirmation of the diagnosis of TC in men with testicular masses included tumor markers and scrotal ultrasound; these costs are folded into treatment costs. Early treatment was defined as radical orchiectomy followed by low-dose chemotherapy. Late TC treatment was defined as radical orchiectomy followed by chemotherapy and retroperitoneal lymph node dissection (RPLND), as well as salvage chemotherapy. The total cost associated with early treatment of infertile men diagnosed with TC using TSE was $7,035,394, in contrast with a total cost of $19,350,096 for late treatment of this population. Thus, the cost savings resulting from early detection of TC in infertile men using TSE is approximately $12,314,701 per year._x000D_ _x000D_ Conclusions Infertile men are at increased risk for TC. We find that early screening for TC among infertile men via TSE can result in early TC detection and significant cost savings resulting from early treatment. Despite U.S. Preventive Services Task Force (USPSTF) recommendations against TSE, TSE among infertile men represents a cost effective means of early TC detection in this at risk population. _x000D_ Funding AWP is a K12 scholar supported by a Male Reproductive Health Research (MRHR) Career Development Physician-Scientist Award (Grant # HD073917-01) from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Program
Authors
Adithya Balasubramanian
Naveen Yadav Edgar W. Kirby Alexander W. Pastuszak Larry I. Lipshultz |
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PD13-06 |
Sex-specific thyroid cancer and melanoma risk in relatives of men with poor semen quality |
Infertility: Epidemiology & Evaluation I | 17BOS |
Abstract: PD13-06 Sources of Funding: This work was supported by the National Institutes of Health - National Institute of Aging [Grant numbers 1R21AG036938-01, 2R01 AG022095 and 1K12HD085852-01]. Introduction Male infertility is an indicator of somatic health and has been linked to increased risk of cancer. Previous studies have shown increased thyroid cancer and melanoma risk in first (FDR) and second-degree relatives (SDR) of infertile men. In this study, investigate sex differences in cancer risk amongst FDRs and SDRs of men who underwent semen analysis (SA) as part of an infertility work-up relative to fertile population controls, in order to better understand the broader health implications of male infertility. Methods 12,889 men with SA and complete FDR data and 8,032 men with SA and complete SDR data were matched by age and birth year to an equal number of fertile population controls with complete familial data from the Utah Population Database (UPDB). We performed a retrospective cohort analysis of thyroid cancer and melanoma risk by gender for FDRs (n = 130,689) and SDRs (n = 247,204) of these men using the Utah Cancer Registry (UCR). Cox proportional hazard regression models were used to test the association between semen quality and adult onset cancer. Models were stratified by sex and run separately for the following semen parameters: sperm count, sperm concentration, sperm motility, total motile count, sperm head morphology, and vitality. Results The FDRs and SDRs of azoospermic men had significantly increased overall risk of thyroid cancer relative to fertile controls (HR 2.12, 95% CI 1.26 - 3.57). By sex, female FDRs of azoospermic men had increased risk of thyroid cancer compared with male FDRs (HR 2.31, 95% CI 1.33 - 3.99 and HR 1.54, 95% CI 0.48 - 4.97, respectively), while no significant difference was seen amongst male and female SDRs (HR 1.57, 95% CI 1.03 - 2.39, and HR 1.54, 95% CI .95 - 2.52). There were no significant differences in thyroid cancer risk amongst male and female SDRs based on any of the semen parameters. No overall or sex specific difference in the risk of melanoma for FDRs or SDRs of men who underwent SA compared with relatives of fertile control subjects was observed. Conclusions Our results suggest that male infertility may be associated with increased overall and sex-specific risk thyroid cancer in relatives. Further study is needed to understand potential environmental exposures or shared biologic mechanisms of infertility and cancer that may account for these observations. Funding This work was supported by the National Institutes of Health - National Institute of Aging [Grant numbers 1R21AG036938-01, 2R01 AG022095 and 1K12HD085852-01].
Authors
Piyush Pathak
Heidi Hanson Ross Anderson William Lowrance Ken Smith Kenneth Aston Douglas Carrell James Hotaling |
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PD13-07 |
MEN WITH INSULIN RESISTANCE ARE AT INCREASED RISK OF AZOOSPERMIA: RESULTS FROM A CROSS-SECTIONAL STUDY |
Infertility: Epidemiology & Evaluation I | 17BOS |
Abstract: PD13-07 Sources of Funding: none Introduction Insulin resistance (IR) is patho-physiologically linked to metabolic syndrome (MetS). Previous study showed a correlation between MetS and a reduced male fertility potential. We aimed to investigate whether men with IR are at higher risk of decreased reproductive health Methods Complete demographic, clinical and laboratory data from 272 consecutive infertile men (infertility defined according to the WHO definition) were considered for this analysis. Azoospermia was defined as the absence of sperm in 2 consecutive semen analyses. Health-significant comorbidities were scored with the Charlson Comorbidity Index (CCI). Glucose and insulin levels were measured for every man after a 12-h overnight fast, and homeostasis model assessment-estimated insulin resistance (HOMA-IR) index was then calculated. HOMA-IR was classified using the 2.6 cut-off, previously shown to be an accurate predictor of IR (Ascaso et al. Diabetes Care 2003). Logistic regression models tested the odds (OR, 95%CI) of non-obstructive azoospermia (NOA) after adjusting for age, BMI, comorbidities (CCI>0), FSH, testicular volume, and HOMA-IR >2.6. Results Mean (interquartile range) patient age was 38 (IQR 35-42) years. Median BMI 25 (IQR 23-27) kg/m2. Of 272, 16 (6%) men had a CCI≥1. A HOMA-IR suggestive for IR was found in 47 (17%) men. Overall, NOA was found in 64 (24%) men. Compared to men without IR, men with IR were older [median age 41 (IQR 37-44) vs. 38 (IQR 35-42) years], had higher median BMI [27 (IQR 25-29) vs. 25 (IQR 23-26) kg/m2]; and, a higher rate of NOA [14/47 (30%) vs. 50/225 (22%)]. At multivariable logistic regression analysis, men with IR were at higher risk of NOA [OR 2.46 (CI: 1.06-5.72)], after accounting for patient age, BMI, CCI, FSH values, and testicular volume. Conclusions A consistent proportion of infertile men (17%) showed a HOMA-IR suggestive for IR. This finding is worrying not only in terms of general health, but also considering male fertility potential, since men with IR have a more than doubled risk of NOA. Funding none
Authors
Walter Cazzaniga
Eugenio Ventimiglia Paolo Capogrosso Filippo Pederzoli Nicola Frego Luca Boeri Massimo Alfano Federico Dehò Franco Gaboardi Vincenzo Mirone Lorenzo Piemonti Francesco Montorsi Andrea Salonia |
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PD13-08 |
Shift Work is Associated with Altered Semen Parameters in Infertile Men |
Infertility: Epidemiology & Evaluation I | 17BOS |
Abstract: PD13-08 Sources of Funding: AWP is a K12 scholar supported by a Male Reproductive Health Research (MRHR) Career Development Physician-Scientist Award (Grant # HD073917-01) from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Program. Introduction Shift work negatively impacts circadian rhythms and the hypothalamic-pituitary-gonadal (HPG) axis, an integral regulator of spermatogenesis. Here we examine the impact of shift work on semen parameters and reproductive hormones in infertile men._x000D_ _x000D_ Methods Men presenting with infertility to an academic andrology clinic between January 2014 and October 2016 completed shift work and sleep quality surveys and underwent semen analysis and hormone testing. Men were included in this analysis if unable to achieve a pregnancy within 12 months, and had no known genetic or obstructive causes of infertility. Fertile control men, all having fathered a child within the past 5 years, underwent semen analysis and hormone testing, and also completed the above surveys. Controls prior to starting testosterone therapy (TTh) underwent semen analysis, hormone testing, and completed the same surveys as infertile men. No men in either group had prior TTh use._x000D_ _x000D_ Results The analysis comprised 198 men: 75 infertile shift workers, 96 infertile non-shift workers, and 27 fertile controls. When comparing shift to non-shift workers, male age, female age, and duration of infertility were not different (Table 1). Sperm density, total motile count (TMC), and testosterone levels were lower in shift workers (p=0.012, 0.019, 0.026, respectively). No differences in semen volume, sperm motility, LH or FSH levels were observed. When comparing infertile shift workers to fertile controls, lower sperm density and TMC, and higher LH and FSH, were observed among shift workers. Semen parameters among infertile men were regressed against sleep quality, sleep quantity, and difficulty sleeping, and an inverse U-shaped trend observed, as previously published [Jensen et al.]. The TMC of men with moderate sleep difficulty was 15.4 M sperm/mL greater than men with no difficulty sleeping, and 4.72 M sperm/mL greater than men with severe sleep difficulty (p=0.018). This inverse U-shaped trend was also observed for sleep quality, but only approached significance._x000D_ Conclusions Infertile shift workers have worse semen parameters than non-shift workers, consistent with alterations in the HPG axis observed in shift workers. Sleep quality influences TMC, but this relationship follows a U-shaped, rather than linear, trend. _x000D_ _x000D_ Funding AWP is a K12 scholar supported by a Male Reproductive Health Research (MRHR) Career Development Physician-Scientist Award (Grant # HD073917-01) from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Program.
Authors
Taylor P. Kohn
Alexander W. Pastuszak Stephen M. Pickett Jaden R. Kohn Larry I. Lipshultz |
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PD13-09 |
Medication Patterns and Fertility Rates in a Cohort of Anabolic Steroid Users |
Infertility: Epidemiology & Evaluation I | 17BOS |
Abstract: PD13-09 Sources of Funding: none Introduction Anabolic steroid (AS) use is increasing, with a 6.4% lifetime abuse rate for males. Use of high doses of AS can manifest with a variety of adverse effects on multiple different organ systems. Specifically, AS impact the male reproductive system via central suppression of gonadotropins leading to decreased endogenous testosterone production, testicular atrophy, and impaired spermatogenesis. Despite the known contraceptive effect of androgens, spontaneous pregnancies while using AS are often reported within online communities of users. Therefore, our objective is to describe self-reported medication patterns and fertility rates in a population of anabolic steroid users. Methods Nine bodybuilding forums were identified using Google search terms. After receiving permission from the websites, a link to an anonymous 49 item questionnaire was posted. Data was collected using Survey Monkey. Information collected included demographics, anabolic steroid use, ancillary medications, and fertility outcomes. Only men attempting to achieve a pregnancy while using testosterone and other AS constituted the cohort of the current study. Results A total of 323 participants initiated the survey, of whom 97 (30%) met inclusion criteria. The majority of men were 25-44 years old (63.9%), married (75.5%) and Caucasian (88.7%). Ancillary drug use was common with only 5.2% denying drug use other than anabolic steroids. The most commonly reported ancillary drugs were antiestrogens (selective estrogen receptor modulators and/or aromatase inhibitors - 89.7%) and sexual enhancement medications (68%). The overall fertility rate was 92.8% with 82.5% achieving pregnancy within one year. Only 13.5% sought fertility evaluation with treatment required in 8.3%. Age at initiation of anabolic steroid use, maximum dosage utilized, yearly duration of supplementation, and number of years using steroids were not associated with a prolonged duration to pregnancy or decreased rate of pregnancy Conclusions Fertility rates are maintained in a population of AS users and are relatively equivalent to age-matched historical controls. This surprising finding may be related to the common use of washout periods, adjunctive medications (SERMs, AIs), and incomplete suppression of the hypothalamic pituitary testicular axis despite large doses of AS. Funding none
Authors
Mary E. Westerman
Cameron M. Charchenko Manaf Alom Francisco Maldonado Tanner Miest Landon Trost |
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PD13-10 |
Barriers in Access to Male Oncofertility Care among Men Receiving Targeted Cancer Therapy |
Infertility: Epidemiology & Evaluation I | 17BOS |
Abstract: PD13-10 Sources of Funding: None Introduction The use of Tyrosine Kinase Inhibitors (TKI) in men with certain malignancies has in many cases improved the course of illness from rapidly fatal to a chronic disease requiring long-term treatment. However, very little has been published on TKI effects on male fertility despite the potential for significant risk to fertility. Many major organizations have guidelines advocating fertility preservation (FP) for all patients at risk of impaired fertility from cancer treatment, yet it is unclear how often men receiving TKI are counseled on the fertility risks of their oncologic treatments and the need for FP. We sought to identify potential barriers to accessing oncofertility care, assess baseline understanding of treatment-related infertility, and characterize reproductive expectations of men receiving TKI treatment. Methods A retrospective cohort of men receiving TKI at UCSF completed a single detailed questionnaire. Cancer history, consultation with treating physician about the possible effects on fertility, obstacles to fertility preservation methods and satisfaction with treatment decisions were addressed. Results Fifty-one patients receiving TKI participated in the study. The mean age was 46 years (range 21-72). Thirty-one (61%) had chronic myelogenous leukemia and 26 (51%) had received prior treatment for cancer (11 surgery, 12 chemotherapy, 3 radiation). While 18 (36%) said they would like to have children in the future and 24 (46%) had some degree of concern that their cancer treatment might affect their fertility, 26 (51%) were not given any information about the fertility risks of TKI by their medical team, 30 (59%) were not able to discuss possible ways to protect their fertility, and 39 (76%) did not have the opportunity to discuss protecting their testicles from cancer treatments. Furthermore, 32 (63%) felt they had encountered some barrier to fertility care prior to receiving their cancer treatment, including 11 (22%) who were not provided a referral to a fertility specialist, and 14 (27%) who did not understand that the cancer treatment might affect their fertility. Conclusions Nearly half of the patients surveyed worried about the reproductive risks of TKI, and most felt they had not received enough information about these risks. Furthermore, the majority of men experienced barriers to oncofertility care. These findings highlight the need for medical providers to take a proactive approach to discuss potential fertility risks in men on TKI. Funding None
Authors
Joris Ramstein
Puneet Kamal Katy Tsai James Smith |
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PD13-11 |
COST?EFFECTIVENESS OF FERTILITY PRESERVATION IN TESTIS CANCER PATIENTS |
Infertility: Epidemiology & Evaluation I | 17BOS |
Abstract: PD13-11 Sources of Funding: Urology Care Foundation Research Scholars Award Introduction Paternity is an important concern among young testicular cancer survivors. Despite this, some affected men elect not to cryopreserve sperm prior to undergoing cancer treatment, because of the perceived costs of cryopreservation and the perceived successes of assisted reproductive technology (ART). The goal of this study investigated the cost-effectiveness of sperm cryopreservation compared to fertility management after undergoing cancer therapy among men with testicular cancer. _x000D_ Methods We performed a systematic search of the Pubmed database for the following variables: risk of azoospermia after orchiectomy, 2 year surveillance, chemotherapy, RPLND, and radiation therapy (RT); rate of natural conception after cancer therapy, rate of conception with the use of IUI, and IVF/ICSI. Costs of cryopreservation were based on costs published commercial sperm cryobank companies. A decision tree was constructed using the TreePlan add-in for Microsoft Excel (TreePlan Software, San Francisco, California). The cost-effectiveness outcome was determined by the overall weighted cost of a given management branch divided by that branch’s likelihood of pregnancy. A sensitivity analysis was performed for the price of microTESE between $3,000 to $11,000 and banking for a range of 2 to 10 years._x000D_ Results Of the total 1,113 articles identified, 55 papers were pertinent to the study question, and included. Patients undergoing chemotherapy or active surveillance had the highest chance of azoospermia over a year after treatment, at 18%. The average cost of banking was $402 one time fee with an additional $343/year. In patients undergoing active surveillance, banking had a lower cost-per-pregnancy when storing for less than 4 years and microTESE was $9,000 or greater. Banking prior to chemotherapy is more cost-effective when banking for 6 or fewer years regardless of microTESE price. Patients receiving RPLND, banking was more cost-effective when banking for 4 or fewer years and the cost of microTESE was $7,000 or greater. Banking was more cost-effective when done for 8 or fewer years regardless of price in patients undergoing RT._x000D_ Conclusions A large proportion of men have recovery of spermatogenesis following chemotherapy or RT for testicular cancer (82% and 94%, respectively). Nevertheless, sperm cryopreservation prior to chemotherapy or RT remains the most cost-effective strategy for fertility preservation, across a range of possible costs associated with surgical sperm retrieval and ART. Funding Urology Care Foundation Research Scholars Award
Authors
Kirven Gilbert
Ajay Nangia Akanksha Mehta |
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PD13-12 |
“The Back-up Vasectomy Reversal.” Testicular sperm extraction at the time of vasectomy reversal in the couple with advanced maternal age: A cost-effectiveness analysis |
Infertility: Epidemiology & Evaluation I | 17BOS |
Abstract: PD13-12 Sources of Funding: none Introduction Vasectomy is an effective family planning method; however 6% will request vasectomy reversal (VR). Average time to VR is 6-10 years after vasectomy with a female partner age of 31-37. VR alone is a cost effective method of regaining fertility; however, the presence and degree of advanced maternal age (AMA) in this population has not been well studied. We evaluated different management options to resume family building in a couple with prior vasectomy using a cost effectiveness analysis model. Methods A model-based cost-utility analysis was performed estimating the mean cost and quality adjusted life years (QALYs) in couples with infertility due to a male history of vasectomy and a female history of AMA over a 1 year time period. The model was constructed evaluating fertility outcomes on 3 surgical options for the male partner: VR, testicular sperm extraction (TESE), or combination VR with TESE. Separate models were then built stratifying for female partner age: <35, 35-37, 38-40, and >40 years. Model QALY estimates obtained from the literature were: 0.56 for an infertile couple and 0.63 for an infertile couple who becomes pregnant. Average patient charges for VR, TESE, and in vitro fertilization (IVF) were calculated from data supplied by high volume academic centers. TreeAge was utilized as the modeling software. Results The surgical options for the male resulted in 4 fertility strategies: natural conception, IVF, failed natural conception followed by IVF, and failed IVF followed by natural conception. The table below lists the cost/QALY for the 4 different fertility strategies stratified by female age. Conclusions VR with natural conception is the most cost effective means of fertility in all age groups evaluated. The back-up VR (combination VR and TESE) was more cost-effective and had a better monetary benefit profile than IVF alone in the maternal age groups of <35, 35-37, and 38-40. In couples with maternal age >40 years, the relatively low per cycle success rate of either approach (VR and natural conception, TESE and IVF) shows that the opportunity to conceive naturally post VR in any non-IVF ovulatory cycle added greatly to the potential success without significantly increasing cost. The back-up VR approach allows for this unique opportunity. Funding none
Authors
James Craig
Jeremy Myers William Brant Sara Lenherr Thomas Walsh Joseph Alukal Jim Hotaling |
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PD14-01 |
Variation in 90-day episode payments for urological cancer surgery: implications for bundled payment programs |
General & Epidemiological Trends & Socioeconomics: Value of Care: Cost and Outcomes Measures I | 17BOS |
Abstract: PD14-01 Sources of Funding: National Cancer Institute (1-R01-CA-174768-01-A1) to Dr. David Miller Introduction Aiming to reduce variation in spending for common surgical procedures, Medicare and other payers have moved toward alternative reimbursement models such as episode-based bundled payments. However, little is known about the variation in 90-day episode spending for urological cancer surgery. Methods Using linked SEER-Medicare data, we identified a study cohort that included all Medicare beneficiaries who underwent cystectomy, prostatectomy, or nephrectomy for cancer from 2008 through 2011. We then calculated total episode payments by aggregating hospital, physician, and post-acute care claims from the index surgical hospitalization through 90 days post-discharge. Total payments were then compared to examine hospital level-variation within each procedure type. Next, we evaluated differences in hospital, physician, and post-acute care payments between the highest and lowest spending quartiles based on mean total episode payments. Finally, we assessed the &[Prime]payment signatures&[Prime] among the most expensive hospitals for each condition. Results From 2008 through 2011, we identified 90-day episodes of care for 1,768 cystectomies, 8,755 prostatectomies, and 4,305 nephrectomies. We observed wide variation in mean episode payments for all three conditions (cystectomy mean $31,836: range $22,322 to $41,706, prostatectomy mean $9,580: range $7,535 to $15,694, nephrectomy mean $16,554: range $10,857 to $25,675). For cystectomy, payments for the index hospitalization represented 50.1% of the total cost variation, whereas for prostatectomy the primary driver was physician fees (34.6%), and for nephrectomy post-acute care costs varied the greatest (37.7%). Each of the most expensive hospitals demonstrated a unique signature for the payment component that was driving high total episode payments (Figure). Conclusions Ninety-day episode payments for urological cancer surgery vary widely across hospitals in the United States. The key drivers of payment variation differ for individual procedures and hospitals. Accordingly, hospitals will need individualized data and clinical re-design strategies to succeed with implementation of episode-based payment models for urological cancer care. Funding National Cancer Institute (1-R01-CA-174768-01-A1) to Dr. David Miller
Authors
Jonathan Li
Zaojun Ye Hye Sung Min Deborah Kaye Lindsey Herrel James Dupree David Miller Chad Ellimoottil |
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PD14-02 |
Centers for Medicare and Medicaid Services’ (CMS) Hospital Compare Star Rankings and short-term outcomes after major urological cancer surgery |
General & Epidemiological Trends & Socioeconomics: Value of Care: Cost and Outcomes Measures I | 17BOS |
Abstract: PD14-02 Sources of Funding: This project was supported by the National Cancer Institute (T32-CA-180984-03 to Deborah R. Kaye and 1-R01-CA-174768-01-A1 to David C. Miller). Introduction In an effort to help patients identify high-quality hospitals, CMS recently released Hospital Compare, a 5-star hospital ranking system. We evaluated the relationship between CMS hospital star rankings and short-term outcomes after major urological cancer surgery. Methods Using national Medicare claims and public-use files from the Hospital Compare program, we identified patients aged 66 to 99 who underwent a major prostate, bladder or kidney cancer surgery from January 1, 2011 through November 30, 2013. For each patient, we determined the CMS star rating (i.e., 1-5-star) for the hospital performing the surgery, as well as the occurrence of 30- day complications, mortality, readmissions, and/or prolonged length of stay. Hospital Compare excludes cancer specific quality measures in its methodology. We then performed univariable and multivariable analyses to examine the overall and procedure-specific associations between hospital star ratings and each surgical outcome. Results We identified 122,321 patients undergoing prostate, bladder, or kidney cancer surgery at 2,147 hospitals rated in the Hospital Compare file. Five percent of hospitals were graded 1 star, 24% 2 stars, 44% 3 stars, 25% 4 stars and 3% 5 stars. For all three procedures combined, we identified a significant, inverse association between CMS star ranking and the occurrence of each adverse outcome (Figure 1). For instance, adjusted rates of readmission for 1- vs 5-star hospitals, were 11.3% and 8.1%, respectively (p=<0.001); likewise, rates of mortality at 1 and 5 star hospitals were 1.7% and 0.6%, respectively (p=<0.001). We identified similar relationships in separate procedure-specific analyses (Table 1). Conclusions Short-term outcomes after major urological cancer surgery are better for Medicare beneficiaries treated at hospitals with higher CMS Hospital Compare star ratings, suggesting a potential role for these rankings in guiding choice of hospitals. Additional research is needed, however, to determine if the star rankings accurately reflect other measures of quality in urological cancer care. Funding This project was supported by the National Cancer Institute (T32-CA-180984-03 to Deborah R. Kaye and 1-R01-CA-174768-01-A1 to David C. Miller).
Authors
Deborah R. Kaye
Chad Ellimootil James M. Dupree Zaojun Ye Lindsey A. Herrel Hye Sung Min Edward C. Norton David C. Miller |
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PD14-03 |
POST-ACUTE CARE AS A DRIVER OF EPISODE COST VARIATION FOR AMBULATORY STONE SURGERY |
General & Epidemiological Trends & Socioeconomics: Value of Care: Cost and Outcomes Measures I | 17BOS |
Abstract: PD14-03 Sources of Funding: Blue Cross Blue Shield of Michigan Introduction Because many post-acute care (PAC) services, including emergency department (ED) visits, after ambulatory stone surgery are potentially avoidable, they are coming under payer scrutiny. In this context, we analyzed claims data to describe variation in total episode costs for ambulatory stone surgery across a diverse set of hospitals, examining PAC as a driver of this variation. Methods We used Medicare and private insurer claims to identify patients who underwent ambulatory stone surgery (ureteroscopy or shockwave lithotripsy) at hospitals in Michigan (2012-2015) from the Michigan Value Collaborative. We defined surgical episodes that extended from the surgery date through 30 days post-discharge and totaled costs for all relevant services during this window. We then categorized component payments to the hospital for the index surgery, as well as those for professional services, subsequent hospitalizations, and PAC. Finally, after aggregating across episodes within a year by hospital, we placed hospitals into quartiles based on their mean total costs and compared component payments at high- versus low-cost hospitals. Results In total, we identified 7,807 patients who underwent ambulatory stone surgery at 69 hospitals in Michigan. The mean total cost for hospitals was $9,538 ($13,044 and $9,037 for episodes associated with and without an ED visit after surgery, respectively) and ranged from $7,317 to $11,914 across hospital quartiles (62.8% difference, P < .001). Payments were higher for hospitals in the highest cost quartile across all payment components (Figure). The index surgery payments contributed the most (64%) to the variation in total costs between high- and low-cost hospitals (Figure), followed by those for subsequent hospitalizations (13%), professional payments (12%), and PAC payments (11%). Conclusions We observed significant variation in total episode costs for ambulatory stone surgery, driven, in part, by payments for PAC. As such, efforts to reduce the use of PAC services, including ED visits, after ambulatory stone surgery is likely to improve cost-efficiency. Funding Blue Cross Blue Shield of Michigan
Authors
John M. Hollingsworth
Hechuan Hou Jim Dupree Brian Seifman Adam Kadlec Anita Tekchandani David Leavitt Khurshid Ghani |
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PD14-04 |
Routine home health after prostatectomy does not reduce ED visits or catheter complications |
General & Epidemiological Trends & Socioeconomics: Value of Care: Cost and Outcomes Measures I | 17BOS |
Abstract: PD14-04 Sources of Funding: Blue Cross and Blue Shield of Michigan. Introduction Routine use of home health care after prostatectomy is a potential source of practice pattern variation and adds costs with unclear benefits. We evaluated the relationship between home health care use after prostatectomy and deviations from the usual care pathway and costs. Methods We identified all men who underwent a laparoscopic radical prostatectomy from 04/01/2014 through 10/31/2015 in the Michigan Urological Surgery Improvement Collaborative (MUSIC) with insurance from Medicare or a large commercial payer. We determined variation in home care use after prostatectomy by urology practice. We then compared the rates of ED visits and readmissions within 16 days of discharge, prolonged catheter use, catheter reinsertion rates, and price-standardized 90 day episode costs for those who did and did not receive home care. Routine home care was defined as home care initiated within 4 days of discharge among patient discharged without a drain. Results We identified 647 patients meeting our inclusion criteria, of whom 13% received home health care. Patient and cancer characteristics were similar between cohorts (Table 1). Use of routine home care after prostatectomy varied from 0 to 53% across 33 practices in MUSIC (p=0.05). Unadjusted, patients with home care had increased rates of ED visits within 16 days (15.5% vs 6.9%, p<0.01), similar rates of catheter duration > 16 days (3.6% vs 3.0%, p=0.79) and need for catheter replacement (1.2% vs 2.5%, p=0.46), and a trend toward decreased readmissions rates (0 vs 4.1%, p=0.06). After controlling for patient and cancer characteristics, only the increased rate of ED visits remained significant (p<0.01). . Home health care cost an average of $1,000 per episode. Average total episode cost were $15,556 with home care and $13,788 without it. There were no differences in index hospitalization costs. Conclusions Routine home health care does not decrease ED visits or catheter complication rates. Its use is associated with increased 90-day episode costs. These data suggest that careful patient selection for home health care is necessary to improve the value of the service, as measured by cost, quality, and appropriateness. Funding Blue Cross and Blue Shield of Michigan.
Authors
Deborah R. Kaye
John Syrjamaki Chad Ellimootil M Hugh Solomon Thomas J. Maatman Susan Linsell Khurshid R. Ghani David C. Miller James E. Montie James M. Dupree for the Michigan Urological Surgery Improvement Collaborative |
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PD14-05 |
Economic implications of urologist prescription practices among Medicare Part D beneficiaries |
General & Epidemiological Trends & Socioeconomics: Value of Care: Cost and Outcomes Measures I | 17BOS |
Abstract: PD14-05 Sources of Funding: Ruth L. Kirschstein National Research Service Award 4TL1TR000435 10 (PK) Introduction Millions of patients take prescription medications each year for common urologic conditions. Generic and brand name drugs often have widely divergent pricing despite similar therapeutic benefit and side effect profiles. Because prescriptions will only increase as the US population ages, we examined urologist prescription patterns for generic and brand name drugs used to treat three common urologic conditions, and consequent economic implications for Medicare Part D spending. Methods We extracted all 2014 urologist prescription claims and payments from the Medicare Part D Prescriber Public Use File. We categorized oral medications used to treat three urological conditions: benign prostate enlargement, erectile dysfunction, and overactive bladder. We then examined total claims, payments, and 30 day cost for each medication with at least 1,000 prescription claims. Last, we estimated the excess annual Medicare Part D payments associated with use of non generic and higher cost medications. We selected a low cost and/or generic drug as a cost comparator for each drug class, then calculated the difference between the actual cost of non comparator drugs and the cost of equivalent length prescriptions of the comparator. Results The total claims, total payments, and 30 day cost for medications by urologic condition are shown (Table). Within drugs for benign prostate enlargement, the excess Medicare Part D payment for drugs other than generic tamsulosin or finasteride was $158,935,926. Among erectile dysfunction medications, the excess payment for drugs other than Levitra was $3,105,023. Within drugs for overactive bladder, the excess payment for drugs other than generic oxybutynin extended-release was $248,430,484. The total excess Medicare Part D prescription payment for higher cost and non generic drugs prescribed by urologists in 2014 was $410,471,433. Conclusions Among Medicare Part D beneficiaries, we found excess payments for higher cost and non generic drugs prescribed by urologists for three common conditions approached a half billion US dollars. Increasing low cost and generic drug use where available evidence is equivocal represents a promising policy target to reduce Part D medication spending. Funding Ruth L. Kirschstein National Research Service Award 4TL1TR000435 10 (PK)
Authors
Peter Kirk
Tudor Borza James Dupree John Wei Chad Ellimoottil Megan Caram Brent Hollenbeck Ted Skolarus |
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PD14-06 |
The Incidence and Financial Impact of Scrotal Pain and its Management on the US Healthcare System in the United States between 2007 and 2014 |
General & Epidemiological Trends & Socioeconomics: Value of Care: Cost and Outcomes Measures I | 17BOS |
Abstract: PD14-06 Sources of Funding: None. Introduction Scrotal pain is a common complaint in urologic practice. To date, there is little data on the prevalence and treatment patterns of the disease. Moreover, little is known about the financial burden on the medical system. Thus, we sought to characterize scrotal pain and its impact among men in a large US insurance claims database. Methods We analyzed subjects from the Truven Health MarketScan claims database from 2007 to 2014. This US database provides information of insurance claims filed for the care of privately-insured individuals with employment-based insurance through a participating employer. Clinical encounters for scrotal pain were identified using ICD-9 codes. The total number of visits and patient demographics were enumerated. Codes for the pharmaceuticals prescribed for scrotal pain were also extracted and analyzed. Results In 2007, 0.83% of all men older than 18 years of age (87,333 men) in our cohort were seen for scrotal pain increasing to 0.98% (154,840 men) in 2014. The mean number of visits per year for each patient who was evaluated at least once for their scrotal pain remained relatively constant, 1.38 visits per person in 2007 (62,943 total visits) and 1.40 in 2014 (117,419 total visits) with a mean patient age around 41 years. The mean cost of medications prescribed per year for each man with scrotal pain was $185.23 and the mean overall cost for these patients was $754.06 per year, which equates to roughly $116M in 2014. In 2007, the majority of pain medications prescribed for scrotal pain were opiates and NSAIDS at 14.5% and 11.0% of all men with scrotal pain, respectively. Opiate prescription increased to 43.4% and NSAIDS increased to 35.9% in 2014. Muscle relaxant and anticonvulsant prescription also increased substantially from 3.2% to 15.79% and 0.7% to 3.9%, respectively over the same time interval. Conclusions The incidence of scrotal pain has risen over the past 8 years affecting nearly 1% of all men and contributing to the high economic burden of this disease. The utilization of prescription medication is increasing with more men being prescribed opiates over the period of observation. Given the rising prevalence of scrotal pain and changing treatment patterns, greater epidemiologic understanding of this disease is necessary to ensure optimal management of these patients. Funding None.
Authors
Yash Khandwala
Chiyuan Zhang Michael L. Eisenberg |
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PD14-07 |
Health System Structure and Readmissions after Urologic Cancer Surgery |
General & Epidemiological Trends & Socioeconomics: Value of Care: Cost and Outcomes Measures I | 17BOS |
Abstract: PD14-07 Sources of Funding: Urology Care Foundation Research Scholars Award, Society of Urologic Oncology Introduction Readmissions have become a focus of quality improvement as policy makers emphasize the delivery of value-based care. Vertically integrated health systems have the greatest ability and incentive to minimize unplanned readmissions. We compare 30-day readmission rates for patients undergoing urologic oncology surgery between three types of health systems in California: an integrated health system (IHS), safety-net hospitals (SNH), and traditional hospital systems (non-SNH). Methods We used California Office of Statewide Health Planning and Development data from 2007-2011, including all patients in California undergoing radical prostatectomy (RP) for prostate cancer, radical cystectomy (RC) for bladder cancer, and partial nephrectomy (PN) or radical nephrectomy (RN) for kidney cancer. We compared risk adjusted readmission rates using Medicare Hospital Readmissions Reduction Program models with the addition of patient socioeconomic status (SES). A separate model was used for each cohort. Comorbidity was assigned using the Elixhauser Index. Patient SES was derived from a Census based neighborhood score at the ZIP code level. Results Overall, 19-21% of RP, RC, PN, and RN were performed at an IHS hospital; 5-9% at a SNH. There were 1,185 readmissions in RP, 999 in RC, 537 in PN, and 1,107 in RN. Unadjusted 30-day readmissions at IHS hospitals were 3.6% in compared to 3.1% in SNH and 3.3% in non-SNH, 26.7% for RC compared with 25.3% for non-SNH and 25.2% for SNH, 8.4% for PN compared with 9.6% for non-SNH and 10.7% for SNH, and 8.0% for RN compared with 8.3% for non-SNH and 9.5% for SNH (all non-significant). In multivariate models (Table), higher patient comorbidity was associated with increased readmission rates across all 4 cohorts. Additional factors associated with readmissions included female sex and open surgical approach in PN, and age, open approach, distance from hospital, and urban status in RN, and age in RP. Across all 4 surgical cohorts, hospital system type was not associated with readmissions. Conclusions Irrespective of health system structure, readmissions among urologic oncology patients are driven by patient characteristics, such as comorbidity, and not hospital type or health system structure. This has important implications for the delivery of value-based care as hospitals become more vertically integrated to improve outcomes. Funding Urology Care Foundation Research Scholars Award, Society of Urologic Oncology
Authors
Anobel Odisho
Ruth Etzioni David Penson John Gore |
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PD14-08 |
A Population-Based Analysis of the Incidence, Cost, and Outcomes of Post-operative Delirium Following Major Urologic Cancer Surgeries |
General & Epidemiological Trends & Socioeconomics: Value of Care: Cost and Outcomes Measures I | 17BOS |
Abstract: PD14-08 Sources of Funding: None Introduction Post-operative delirium is associated with poor outcomes and increased healthcare costs in the elderly. A population-based analysis of incidence, outcomes, and cost of delirium has not been characterized in major urologic cancer surgeries. Methods Using the Premier Hospital Database, we retrospectively identified patients who had undergone radical prostatectomy (RP), radical nephrectomy (RN), partial nephrectomy (PN), and radical cystectomy (RC) from 2003 to 2013. Delirium was defined using International Classification of Disease, Ninth-Revision (ICD-9) codes, as well as post-operative use of antipsychotics, sitters, and restraints. We constructed regression models to assess for mortality, discharge disposition, length of stay (LOS), and direct hospital costs. Survey-weighted adjustment for hospital clustering was used to achieve estimates generalizable to the US population. Results We identified 165,387 patients representing a weighted total of 1,097,355 patients from 490 hospitals. 30,063 (2.7%) experienced post-operative delirium. The greatest incidence occurred after RC, with 6,268 cases (11%). After adjusting for patient, hospital, and peri-operative characteristics, patients with post-operative delirium had greater odds of in-hospital mortality (OR 3.65; 95% CI 2.56-5.22; p <0.001), 90-day mortality (OR 1.47; 95% CI 1.08-1.99; p = 0.013), discharge with home healthcare (OR 2.25; 95% CI 1.94-2.61; p <0.001), discharge to skilled nursing facilities (OR 4.64; 95% CI, 3.93-5.48; p <0.001), and an increase in median LOS by 0.9 days (95% CI 0.84-0.96; p <0.001). Patients with post-operative delirium also had an increase in direct hospital costs by $2,697 (95% CI, $2,250-$3,144; p <0.001). When stratified by type of surgery, the greatest difference in cost was seen in patients following RC ($30,859 vs. $26,607; p<0.001). The largest driver of costs was in room and board across all surgeries (p<0.001). Conclusions Patients with post-operative delirium experience worse outcomes, prolonged LOS, and increased admission costs following major urologic cancer surgeries. In particular, the largest incidence and costs occurred in delirious patients after RC. Further research is warranted in order to identify high-risk patients and devise preventive strategies. Funding None
Authors
Albert Ha
Ross Krasnow Tammy Hsieh Adam Kibel James Rudolph Benjamin Chung Steven Chang |
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PD14-09 |
Identifying patients with microhematuria at risk for a missed or delayed diagnosis: who is not being evaluated in a timely fashion? |
General & Epidemiological Trends & Socioeconomics: Value of Care: Cost and Outcomes Measures I | 17BOS |
Abstract: PD14-09 Sources of Funding: Research reported in this abstract was supported, in part, by the National Institutes of Health's National Center for Advancing Translational Sciences, Grant Number UL1TR001422. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Introduction Many patients with microhematuria (MH) do not complete the recommended evaluation: cystoscopy and genitourinary imaging. These patients are therefore at risk of a missed or delayed diagnosis. We sought to determine factors associated with a lower likelihood of completing a MH evaluation in a large health system as a step toward targeted quality improvement efforts. Methods Patients 35 and older with a new diagnosis of MH (>3 RBC/hpf) in the absence of a benign cause were included. Data was source from our multi-center enterprise data warehouse during the years 2012-2015. Demographic and urinalysis (UA) data as well as details about the timing and completion of cystoscopy and appropriate imaging were collected. Regression modeling was used to determine factors associated with completing the MH evaluation within 1 year. Results In total, 7,888 patients were included: 1,191 (15.1%) had a partial evaluation and 470 (6.0%) underwent a complete evaluation. Median days to complete evaluation was 77 [IQR 35-235]. Of those who had a partial evaluation, 37.1% had a cystoscopy and 62.9% had an imaging study. Younger patients, male patients, those with more severe MH on index UA, and those with a positive follow up UA all had higher unadjusted rates of evaluation. After adjusting for all covariates, male sex (OR 1.27, 95% CI 1.01-1.58), increasing MH severity on index UA (more RBC/hpf), and positive follow up UA (OR 3.21, 95% CI 2.49-5.14) but not age were significantly associated with receiving a complete evaluation within 1 year (Table 1). Of patients who had a documented complete evaluation 5.7% (n=27), 2.3% (n=11), and 14.3% (n=67) were diagnosed with bladder cancer, kidney cancer, and urolithiasis, respectively. Conclusions Few patients complete a timely evaluation for their MH. Hematuria severity and male sex are significantly associated with a higher likelihood of receiving a complete MH evaluation. Funding Research reported in this abstract was supported, in part, by the National Institutes of Health's National Center for Advancing Translational Sciences, Grant Number UL1TR001422. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Authors
Richard Matulewicz
Jason Cohen John Oliver DeLancey Joshua Meeks |
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PD14-10 |
Cost-Effectiveness of Common Diagnostic Approaches for Evaluation of Asymptomatic Microscopic Hematuria |
General & Epidemiological Trends & Socioeconomics: Value of Care: Cost and Outcomes Measures I | 17BOS |
Abstract: PD14-10 Sources of Funding: None Introduction Asymptomatic microscopic hematuria (AMH) is highly prevalent and may signal occult genitourinary (GU) malignancy. Common diagnostic approaches differ in their costs and effectiveness in detecting cancer. Given the low prevalence of GU malignancy among patients with AMH, it is important to quantify the cost implications of detecting cancer for each approach. We sought to estimate the effectiveness, costs, and incremental cost-effectiveness ratio (ICER) for common diagnostic approaches evaluating AMH. Methods We performed cost-effectiveness analysis using a decision-analytic model with inputs from the medical literature. Four diagnostic approaches were evaluated relative to the reference case of no evaluation: computed tomography (CT) alone; cystoscopy alone; CT and cystoscopy combined; and renal ultrasound (US) and cystoscopy combined. The index patient was an adult with AMH on urinalysis. Primary outcomes were cancers detected and costs per 10,000 patients evaluated, and ICERs. Results CT alone was dominated by all other strategies, detecting 221 cancers at a cost of $9,300,000. US and cystoscopy detected 245 cancers and was most cost-effective with an ICER of $53,810 per cancer detected. Replacing US with CT detected just 1 additional cancer at an ICER of $6,380,484 per cancer detected. US and cystoscopy remained the most cost-effective approach in subgroup analysis._x000D_ _x000D_ The model was not sensitive to any inputs within the proposed ranges. Using probabilistic sensitivity analysis, US and cystoscopy was the dominant strategy in 100% of simulations._x000D_ Conclusions The combination of renal US and cystoscopy is most cost-effective among four approaches for the initial evaluation of AMH. The use of US in lieu of CT as first-line will reduce the morbidity and costs associated with evaluation of AMH. Given these findings, urologists must critically evaluate the appropriateness of our current clinical guidelines to reflect the most effective screening strategies for patients with AMH. Funding None
Authors
Joshua Halpern
Bilal Chughtai Hassan Ghomrawi |
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PD14-11 |
Evaluating the Cost Effectiveness of the Asymptomatic Microhematuria Guidelines |
General & Epidemiological Trends & Socioeconomics: Value of Care: Cost and Outcomes Measures I | 17BOS |
Abstract: PD14-11 Sources of Funding: none Introduction In 2012, the American Urological Association released updated guidelines for asymptomatic microhematuria management that required only a single positive microscopic urinalysis, as opposed to requiring a confirmatory urinalysis. This change was motivated by questions regarding the validity of a confirmatory urinalysis and literature supporting only a single urinalysis. The cost effectiveness of this new guideline was not considered. Methods We used a decision tree model to compare an immediate microhematuria evaluation based on a single positive urinalysis (Upfront) versus a delayed evaluation requiring a confirmatory positive urinalysis (Confirmed). Cancer detection rates were estimated from studies on asymptomatic microhematuria. Costs were based on national Medicare reimbursement. One-way and two-way sensitivity analyses were performed on critical estimated inputs. Results The Upfront workup was 66% more costly than Confirmed ($776 vs. $466/patient), while gaining 0.03 life-years, for an incremental cost effectiveness ratio of $10,719/life-year gained. However, the analysis was sensitive to variation of 2 uncertain parameters: the probability of a delayed cancer diagnosis with the Confirmed strategy (base case value 1.67%) and loss of life expectancy with a delayed diagnosis (base case 1.11 year). When simultaneously varying them in a 2-way sensitivity analysis (Figure) with a $100,000/life-year threshold, Upfront is favored unless the probability of delayed diagnosis with in Confirmed was < 0.15% or if loss in life expectancy with delay was < 0.15 years. Conclusions From a cost effectiveness standpoint, a confirmed positive urinalysis is favored if there is a low likelihood of delayed cancer detection or if there is a minimal loss in life expectancy from a delayed diagnosis. More definitive evaluation of the cost effectiveness of asymptomatic microhematuria guidelines will require a better estimation of these unknown parameters. Funding none
Authors
Jathin Bandari
Bruce Jacobs Kenneth Smith |
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PD14-12 |
Comparison of Initial and Follow-Up Hospital Costs for Minimally Invasive vs. Open Radical Cystectomy in a Nationally Representative Sample |
General & Epidemiological Trends & Socioeconomics: Value of Care: Cost and Outcomes Measures I | 17BOS |
Abstract: PD14-12 Sources of Funding: none Introduction Previous studies demonstrated higher initial hospitalization and 90-day hospital costs for minimally-invasive (MIRC) vs. open radical cystectomy (ORC). These studies were limited in that they were conducted with Medicare databases (>65 years-old) or private payer databases (<65 years-old). Therefore, our objective was to compare initial, 30-day, and 90-day follow-up hospital costs for patients undergoing MIRC vs. ORC in a nationally representative sample containing both Medicare and non-Medicare beneficiaries. Methods We queried the 2013 Nationwide Readmissions Database for bladder cancer patients undergoing RC. ICD-9 codes were used to determine surgical approach. Initial, 30-day, and 90-day hospital costs, length of stay (LOS), and complication rates were compared between MIRC and ORC patients. Multivariable linear regression was performed to determine if surgical approach was a significant predictor of 30-day and 90-day hospital costs after controlling for patient and hospital characteristics. Multivariable logistic regression was performed to compare the odds of 30-day and 90-day readmission between MIRC vs. ORC. Results In the cohort, 4918 ORCs and 1608 MIRCs were performed. The initial hospital costs were significantly higher for MIRC vs. ORC ($36970 vs. $32111, p=0.005). However, MIRC patients had a shorter LOS (8.9 vs. 10.6 days, p<0.001) and lower perioperative complication rate (37.3% vs. 43.2%, p=0.01) than ORC patients, respectively. Both 30-day ($4403 vs. $4571, p=0.8) and 90-day ($8013 vs. $8432, p=0.7) follow-up hospital costs were comparable for MIRC vs. ORC, respectively. After adjustment, there was still no significant difference in 30-day (βmirc=$-45 [95%CI: -1377,1287]) and 90-day (βmirc=$-222 [95%CI: -2441, 1997]) follow-up hospital costs between surgical approaches. In multivariable models, when comparing MIRC vs. ORC the odds of 30-day (OR=0.93 95%CI [0.63, 1.18]) and 90-day readmission (OR=1.01 95%CI [0.79, 1.29]) were comparable. Conclusions In this nationally representative study that includes both Medicare and non-Medicare patients, higher perioperative hospital costs for MIRC vs. ORC were driven by higher initial hospital costs as 30 and 90-day follow-up hospital costs were comparable. This higher initial cost of MIRC cannot be explained by LOS or complication rates, which are significantly lower for MIRC. As use of MIRC continues to expand, future studies are needed to identify potential areas to decrease costs associated with MIRC during the initial hospitalization. Funding none
Authors
Meera Chappidi
Max Kates Trinity Bivalacqua Phillip Pierorazio |
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PD15-01 |
Retzius Space Reconstruction Following Transperitoneal Laparoscopic Robot-Assisted Radical Prostatectomy: Does It Have Any Added Value ? |
Prostate Cancer: Localized: Surgical Therapy II | 17BOS |
Abstract: PD15-01 Sources of Funding: none Introduction Retzius space sparing (RSS) during laparoscopic robot-assisted radical prostatectomy (RALP) has been offered as an act that reduces perioperative complications and enables faster gaining of full urinary continence due to bladder anatomy preservation. Retro and trans-peritoneal techniques have been proposed, whereby RSS has been implemented. We sought to explore whether Retzius space reconstruction (RSR) following transperitoneal RALP will be an advantageous step as well. Methods One hundred consecutive transperitoneal RALP cases performed by a single surgeon were retrospectively reviewed. The Retzius space has been opened by dissecting the bladder away from the anterior abdominal wall to the level of both internal rings. In the last 50 cases (Group 2) the peritoneal layer has been sutured back thus repositioning the bladder back to the anterior abdominal wall and reconstructing the Retzius space. _x000D_ Peri-operative factors were analyzed and compared between the two groups. Data are given as either number (%) or median (Inter-Quartile Range). _x000D_ Results Demographic and peri-operative data did not differ between the two groups (Table 1). Intra and post operative complications are detailed in Table 2. As seen, Group 2 demonstrated shorter length of stay (LOS) compared with the control group (Group 1) (p=0.001), as well as faster urinary continence recovery (i.e: 0 pads) (p=0.005). Moreover, lower numbers of Clavien-Dindo grade 3 complications, post-operative ventral hernias and urinary leak were seen in Group 2 compared with Group 1. Conclusions RSR following transperitoneal RALP is a simple and efficient step that potentially reduces early and late post operative complications, shortens LOS and accelerates full urinary continence. Funding none
Authors
Yasmin Abu-Ghanem
Zohar Dotan Jacob Ramon Dorit Zilberman |
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PD15-02 |
Hypothermic nerve-sparing radical prostatectomy facilitates earlier recovery of potency at one year |
Prostate Cancer: Localized: Surgical Therapy II | 17BOS |
Abstract: PD15-02 Sources of Funding: None Introduction Regional hypothermia (RH) had been suggested based on pilot trial as an attempt to accelerate the return of potency after radical prostatectomy by reducing the consequences of acute trauma and the inflammatory cascade. We investigated its substantial advantage in large number of patients, in comparison with normothermia (NT) counterparts. Methods Among 930 nerve-sparing robotic assisted radical prostatectomies (RARPs) for non-high risk patients with minimal follow-up of 12 months after initial 100 cases, RARP cases were divided into 2 groups, half (n=464) in NT followed serially by half, n=466 under RH. RH was achieved by devising an endorectal cooling balloon system using cold saline (4°C.). Postoperatively, potency was defined as recovery with an IIEF-5 score over 17. Results The mean (±SD) age (61.4±7.4 vs. 60.7±7.4 yrs), prostate volume (54.1±18.2 vs. 51.8±19.3 g), preoperative PSA (5.8±0.8 vs. 5.6±2.8 ng/ml), and body mass index (BMI; 27.1 ±3.4 vs. 26.7 ±3.4 kg/m2) were similar between RH and NT group. IIEF-5 scores were higher in RH groups both at 3M (6.9 ±7.7 vs. 4.9±6.4 p<.001) and 12M (13.2 ±8.3 vs. 9.8 ±8.7 p=.001), despite of their similarity on preoperative score (20.0 ±6.5 vs. 19.6 ±6.9, p=.422). In RH group return of potency was 17.35% at 3 months vs 9.7% in NT, p=.002 and 44.4% at 12 months vs 29.0% in NT, p=.008._x000D_ For 421 men (44.3%) with relatively young (<65 yrs) and normal preoperative IIEF-5 (> 21), potency rate at 3 and 12 months was 27.0 % and 75.0% in RH group versus (17.1% and 47.1% in NT, p=.024 and .003, respectively). In this particular subgroup, multiple logistic regression models on potency at 12 months using covariates of age, GS, PSA, pathologic stage, prostate volume, BMI, preoperative IIEF-5, and learning curve demonstrated RH as a significant predictor (Odds ratio; OR=5.44, p=.013, R2=.198) along with prostate volume (over 50g: OR=.352, p=.010) and pathologic stage (over T3: OR=.382, p=.027). However in a multiple linear regressions identical covariates, RH was the sole predictor on return of potency at 12 months (Table 1)._x000D_ Conclusions Applying regional hypothermia during RARP significantly improves the recovery of sexual function after surgery in patients with minimum a year follow-up Funding None
Authors
Young-Hwii Ko
Douglas Skarecky Linda Huynh Thomas Ahlering |
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PD15-03 |
Does intraoperative evaluation of retrograde leak point pressure (RLPP) during robotic assisted radical prostatectomy (RALP) for proper autologous sling tensioning improves early urinary continence (EUC) recovery compared to autologous sling alone? |
Prostate Cancer: Localized: Surgical Therapy II | 17BOS |
Abstract: PD15-03 Sources of Funding: none Introduction Urinary continence recovery remains one of the most bothersome side effect of modern radical prostate surgery and several technical modifications, especially in RALP procedures, have been reported in order to improve EUC recovery, such as the use of suburethral slings. Proper sling tensioning is of pivotal importance to restore the proper sphinteric capacity._x000D_ With the aim to improve the EUC recovery after RALP, we evaluate the impact of the use of intraoperative evaluation of the RLPP for proper sling tensioning of a 6-branch retropubic suburethral autologous sling, created and placed during (RARP), compared to the use of the 6-branch sling alone with subjective evaluation of its tensioning._x000D_ Methods In 44 continent and neurologically healthy patients (mean age 66.7 years – range 53-75; mean BMI 26.8 – range 20.3 – 36) – Group 1, affected by localized prostate cancer and submitted to RARP at our Institution, RLPP was evaluated: a)before pneumoperitoneum induction, b)after pneumoperitoneum induction, c)after urethrovescical anastomosis and d)during suburethral autologous sling tensioning._x000D_ Proper sling tensioning had the goal to restore RLPP as close as possible to its value at stage b (after pneumoperitoneum induction)._x000D_ EUC recovery was assessed at time of catheter removal, 10 and 30 days post catheter removal through a structured interview including the record of the daily number of pads used. Urinary continence was defined as the use of no pad. The results were compared to a similar cohort of 60 patients (mean age 64.2 years – range 51-79; mean BMI 25.6 – range 21.1 – 33.1) submitted to RALP at our Institution – Group 2, where the 6-branch sling were subjectively tensioned by the surgeon._x000D_ Results Complete data collection was available for all (100%) patients. Mean surgical time was 218 min (range 150-320) vs 200 (range 145-315), mean postoperative stay was 4.9 days (range 3-11) vs 3.5 (range 2-9) and mean catheterization time was 9.93 days (range 7-13) vs 5.4 (range 5-7) in Group 1 and Group 2 respectively . Postoperative complications occurred in 3 patients (6%), including 1 case of acute urinary retention after catheter removal in Group 1 and in 7 patients (11%) including 1 case of acute urinary retention in Group 2. Table 2 lists the EUC recovery results in both groups. The 2 patients that experienced acute urinary retention at the time of catheter removal was treated uneventfully with a further 7-days catheterization._x000D_ _x000D_ Table 1_x000D_ EUC recovery – 0 pads_x000D_ (n of patients - %) 6-branch autologous sling and tensioning following RLPP 6-branch autologous sling and subjective tensioning P value_x000D_ Catheter removal 36 (81.8) 36 (60) 0.02_x000D_ 10 days 38 (86.4) 42 (70) 0.03_x000D_ 30 days 38 (86.4) 52 (87) ns_x000D_ Conclusions Our initial experience indicates that the use of a six-branches suburethral autologous sling in association of intraoperative RLPP evaluation for its proper tensioning is safe, effective and reproducible and offers superior EUC recovery in patients submitted to RALP procedures compared to the use of the autologous sling alone with its subjective tensioning related to the surgeon’s experience and feeling. Funding none
Authors
Andrea Cestari
Carolina Lolli Mattia Sangalli Matteo Zanoni Massimo Ghezzi Patrizio Rigatti |
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PD15-04 |
A randomized controlled trial examining the impact of the Retzius- sparing approach on early urinary continence recovery after robot-assisted radical prostatectomy |
Prostate Cancer: Localized: Surgical Therapy II | 17BOS |
Abstract: PD15-04 Sources of Funding: none Introduction Retzius-sparing (posterior) robot-assisted radical prostatectomy (RARP) may expedite urinary continence (UC) recovery. We compared the short-term (≤3 months) UC, urinary function (UF) and UF-related bother outcomes of posterior RARP compared to standard approach (anterior) RARP in a randomized controlled trial (RCT). Methods 120 patients aged 40-75 with low-intermediate risk prostate cancer (PCa) undergoing primary RARP by a single surgeon were randomized 1:1 to posterior (n=60) or anterior RARP (n=60). Primary outcome was UC (defined as 0 pad/one security liner per day and verified using 24-hour pad weights) 1 week after catheter removal. Secondary outcomes were time to UC recovery, UF and UF-related bother scores (measured by the International Prostatic Symptom Score (IPSS) and IPSS-Quality-of-Life scores respectively) assessed at 1 week, 2 weeks, 1 and 3 months following catheter removal. UC recovery was analyzed using Kaplan-Meier method and Cox proportional hazards regression. Linear generalized estimating equations (GEE) were used to compare UF and UF-related bother scores. Results Median age of the cohort was 61 years. 75.8% harbored intermediate-risk PCa. 71.2% in the posterior vs. 48.3% in the anterior arm were continent 1-week post-catheter removal (p=0.01); corresponding median 24-hour pad weights were 5 and 25 gm respectively (p=0.001). Posterior RARP showed faster UC recovery (figure 1); 94.9% in posterior vs. 85.8% in anterior RARP arms were continent at 3 months (p=0.018), and findings were confirmed on multivariable regression analyses. Urinary bother scores were significantly lower in the posterior vs. anterior RARP group at 1,2 and 4 weeks on GEE analyses (figure 2). _x000D_ Conclusions This single-center RCT shows that in the hands of an experienced surgeon, Retzius-sparing approach of RARP resulted in earlier recovery of UC and lower UF-related bother than standard RARP in patients with low-intermediate risk PCa Funding none
Authors
Deepansh Dalela
Wooju Jeong Madhu Ashni-Prasad Akshay Sood Firas Abdollah Patrick Karabon Mireya Diaz Sriram Eleswarapu Jesse Sammon Brad Baize Andrea Simone Mani Menon |
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PD15-05 |
Real-world outcomes of open versus robot-assisted radical prostatectomy |
Prostate Cancer: Localized: Surgical Therapy II | 17BOS |
Abstract: PD15-05 Sources of Funding: U.S. Department of Defense Prostate Cancer Research Program DOD TIA grant W81XWH-13-2-0074 Introduction Identifying the optimal surgical approach for patients with localized prostate cancer (PCa) remains controversial due to the lack of robust, long-term, prospective data. We assessed surgical outcomes and changes in patient-reported urinary and sexual quality of life (QOL) over time in patients undergoing open radical prostatectomy (ORP) vs. robot-assisted radical prostatectomy (RARP) in a large, prospective, mostly community-based, nationwide PCa registry. Methods Within the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry, we identified patients who underwent radical prostatectomy (RP) between 2004 and 2016 for localized PCa. Demographic and clinicopathologic data and surgical outcomes were compared between ORP vs. RARP groups. Self-reported, validated questionnaires were used to evaluate urinary and sexual QOL at different time points. Repeated measures mixed-models assessed changes in function and bother over time in each domain. Scores were adjusted for surgical approach, time, surgical approach-time interaction, patient age and year at diagnosis, number of comorbidities, clinical Cancer of the Prostate Risk Assessment (CAPRA) score, prostate volume, body mass index at diagnosis, degree of nerve-sparing, and type of clinical site. Results In total, we included 1,892 men (n=1,137 ORP; n=755 RARP) in our analysis. The RARP cases reflected the first such cases performed at each CaPSURE site. Men undergoing RARP had more lymph nodes dissected at RP (median 7 vs. 4; p≤0.01 ). CAPRA score, Gleason grade at biopsy and RP, and pathologic T-stage were lower in ORP patients (all p<0.01). In a subset analysis with 1,451 men reporting baseline and follow-up QOL data, ORP patients had higher urinary incontinence (ORP 69±26 vs. RARP 62±27) and bother scores (ORP 75±29 vs. RARP 68±28; both p<0.01) <1 year after RP. Differences in sexual outcomes did not differ between groups, nor did any QOL scores beyond one year. Conclusions Most patients experienced changes in urinary and sexual QOL in the first three years following RP. The patterns of change over time were similar between ORP and RARP patients in a community-based cohort, reflecting the initial learning curve with RARP in this population. Funding U.S. Department of Defense Prostate Cancer Research Program DOD TIA grant W81XWH-13-2-0074
Authors
Annika Herlemann
Janet E. Cowan Peter R. Carroll Matthew R. Cooperberg |
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PD15-06 |
Impact of tumor location on biochemical recurrence of pT3 prostate cancer. |
Prostate Cancer: Localized: Surgical Therapy II | 17BOS |
Abstract: PD15-06 Sources of Funding: none Introduction The impact of the zonal origin of cancer on the prognosis after radical prostatectomy has been controversial. We investigated the influence of tumor location (anterior vs. posterior) on biochemical recurrence (BCR) after laparoscopic radical prostatectomy (LRP). Methods We reviewed 1082 patients undergoing LRP between 2005 and 2015, among whom there were 544 patients with pathological data on the location of the index tumor who did not receive neoadjuvant/adjuvant therapy. We defined the largest lesion as the index tumor if there were several masses. BCR was defined as PSA > 0.2 ng/mL. Differences of the BCR rate between groups were examined by Kaplan-Meier analysis and the Cox proportional hazards model. Results There were 234 patients (43%) with an anterior tumor and 310 patients (57%) with a posterior tumor. The anterior group had less T3 disease (61 patients, 26%) than the posterior group (111 patients, 36%) and a Gleason score of 4+4 or more was less frequent in the anterior group (24 patients, 10%) than in the posterior group (60 patients, 19%), although the differences were not significant. During a median follow-up period of 5.0 years, 75 patients (14%) experienced BCR. As shown in Figure 1, there was no significant difference of the BCR rate between patients with T2 disease and those with anterior T3 disease (hazard ratio: 1.29, 95% CI: 0.58-2.92, p=0.528), while their 5-year BCR-free survival rates were 91% and 89 %, respectively. Patients with posterior T3 disease had a higher BCR rate than those with anterior T3 disease (hazard ratio: 1.88, 95% CI: 0.85-4.13, p=0.118). Their 5-year BCR-free survival rates were 90% and 79%, respectively. Conclusions These results indicate that anterior index tumors are more likely to have favorable pathological characteristics. Especially in patients with T3 disease, anterior tumors are associated with a lower BCR rate after LRP. Funding none
Authors
KIMIHARU TAKAMATSU
Kazuhiro Matsumoto Kazunori Shojo Shinya Morita Kazunobu Shinoda Takeo Kosaka Ryuichi Mizuno Toshiaki Shinojima Eiji Kikuchi Akira Miyajima Mototsugu Oya |
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PD15-07 |
Erectile-function and oncologic outcomes after open retropubic and robot-assisted radical prostatectomy: results from a large, prospective Swedish trial |
Prostate Cancer: Localized: Surgical Therapy II | 17BOS |
Abstract: PD15-07 Sources of Funding: None Introduction Whether surgeons perform better utilizing a robot-assisted laparoscopic technique compared to an open approach during prostate-cancer surgery, is hotly debated. To understand pros and cons of respective techniques, we need more data separating results for high and low-risk tumors. Methods In a prospective trial we recruited men with prostate cancer from seven open and seven robot-assisted surgery study centers (2008-2011). Information on patient-reported erectile-function was collected before, three, 12 and 24 months after surgery. Urologists reported the degree of neurovascular-bundle preservation. Pathologists assessed rates of positive surgical margins. Biochemical recurrence rate was measured at three, 12 and 24 months. Results We have information from 2545 men (1792 robot-assisted and 743 open surgery). Among 1702 preoperatively potent men, we found enhanced erectile-function recovery in the robot-assisted group at three months with smaller differences at 12 and 24 months. For patients with high-risk tumors, point estimates for erectile-function recovery were higher in the open-surgery group. Correlations between the degree of neurovascular bundle preservation and erectile-function recovery were greater for robot-assisted surgery. In prostate-confined tumors, 10.2 versus 17.0 percent positive surgical margin rates were observed for open and robot-assisted surgery, respectively (adjusted RR 0.59; 95%CI 0.45-0.79); corresponding figures for non-prostate-confined tumors were 48.1 percent and 33.3 percent (adjusted RR 1.42; 95%CI 1.17-1.74). Differences in two-year biochemical recurrence between open and robot cohorts were seen in the non-prostate-confined tumors (adjusted RR 1.66; 95%CI 1.17-2.36) but not in prostate-confined tumors. Conclusions When comparing robot-assisted laparoscopic surgery with open surgery, tumor characteristics distinguish the results for erectile-function recovery and oncologic outcome in opposite directions. This observation highlights possibilities to improve the plane of surgery irrespective of technique used. Funding None
Authors
Prasanna Sooriakumaran
Gio Pini Tommy Nyberg Maryam Derogar Stefan Carlsson Johan Stranne Anders Bjartell Jonas Hugosson Gunnar Steineck Peter Wiklund |
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PD15-08 |
Association Between Early Urinary Continence and Erectile Function Recovery after Robot-Assisted Radical Prostatectomy: Development of a Novel Postoperative Risk Score To Optimize Patient Counseling and Follow-up |
Prostate Cancer: Localized: Surgical Therapy II | 17BOS |
Abstract: PD15-08 Sources of Funding: none Introduction The identification of patients less likely to recover erectile function (EF) after surgery is crucial for counseling and for the early administration of proerectile treatments. We aimed at developing a model to predict EF recovery in prostate cancer (PCa) patients treated with robot-assisted radical prostatectomy (RARP). Methods We included 833 PCa patients treated with RARP between 2006 and 2016. Postoperative UC recovery was defined as being pad-free over a 24-hour period. Early continence was defined as UC within 60 days from surgery. Postoperative EF was defined as an Erectile Function-Erectile Function (IIEF-EF) domain score ≥22. Kaplan-Meier and Cox regression analyses assessed the impact of early UC on EF recovery. Covariates were age, preoperative IIEF-EF, Charlson comorbidity index (CCI), nerve-sparing, adjuvant radiotherapy (aRT), and early UC recovery. Predictors of EF were used to develop a novel risk score based on the cumulative number of risk factors. Kaplan-Meier analyses assessed the impact of the risk score on EF rates. A decision-curve analysis (DCA) assessed the net benefit associated with the use of our model. Results Median preoperative IIEF-EF was 25. Overall, 746 (90%) patients were treated with nerve-sparing surgery and 54 (6.3%) patients received aRT. Median follow-up was 36 months. The proportion of patients who experienced early UC recovery was 337 (40.5%). At 3-year follow-up, the UC and EF recovery rates were 85.9% and 45.8%. The 3-year EF rates were higher in patients who were continent within 2 months compared to those incontinent at this time point (53.8 vs. 40.4%; P<0.001). In multivariable analyses, age <65 years, a preoperative IIEF-EF ≥22, the receipt of nerve-sparing surgery, no aRT, and early UC recovery were associated with an increased probability of EF recovery (all P≤0.01). Based on these factors, a risk score predicting EF was calculated. When patients were stratified according to the risk score (≤2 vs. 3 vs. ≥4), the 3-year were 10.9 vs. 32.0 vs. 60.6%, respectively (P<0.001). At the DCA, clinical risk prediction improved for men with a probability of EF recovery between 15 and 60%. Conclusions Early UC recovery is associated with the probability of subsequent EF recovery. A risk score based on pre- and postoperative characteristics to predict EF recovery should be used for patient counseling in the early postoperative setting and for the identification of candidates for more aggressive proerectile therapies. Funding none
Authors
Giorgio Gandaglia
Nazareno Suardi Andrea Gallina Paolo Dell'Oglio Nicola Fossati Vito Cucchiara Marco Moschini Marco Bandini Emanuele Zaffuto Andrea Salonia Franco Gaboardi Rocco Damiano Vincenzo Mirone Francesco Montorsi Alberto Briganti |
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PD15-09 |
Identifying the optimal candidate for salvage lymph node dissection for nodal recurrence of prostate cancer: results from a large, multi-institutional analysis |
Prostate Cancer: Localized: Surgical Therapy II | 17BOS |
Abstract: PD15-09 Sources of Funding: none Introduction Salvage lymph node dissection (SLND) represents a possible treatment for prostate cancer (PCa) patients experiencing nodal recurrence after local treatment. We aimed at identifying the optimal candidates for SLND based on pre-operative characteristics. Methods The study included 538 patients who experienced PSA rise and nodal recurrence after RP who underwent SLND at eight tertiary referral centres. Lymph node recurrence was documented by positron emission tomography / computed tomography (PET/CT) scan using either 11C-choline or 68Ga-prostate-specific-membrane-antigen (PSMA) ligand. The study outcome was systemic progression (skeletal and / or visceral metastasis). Multivariable Cox regression analysis was used to develop a predictive model for the study outcome. Predictors consisted of patient age, PSA level at SLND, PSA doubling time (PSADT), diagnostic tracer (11C-choline vs. PSMA), site of nodal positive imaging (pelvic vs. retroperitoneal vs. both), and number of positive spots at PET/CT. Multivariable-derived coefficients were used to develop a novel risk-calculator. Results imaging was positive in pelvic, retroperitoneal, and pelvic + retroperitoneal regions in 400 (15%), 58 (11%), and 80 (15%) patients. The number of positive spots was 1, 2, and ≥3 in 277 (52%), 120 (22%), and 141 (26%) patients. At a median follow-up of 44 months, 88 (16%) patients experienced systemic progression. At multivariable analysis, age (HR: 0.96; p=0.046), PSA at SLND (HR: 1.02; p=0.006), PSADT (HR: 0.99; p=0.001), PSMA tracer (HR: 0.11; p=0.003), positive imaging in both pelvic and retroperitoneal regions (HR: 1.69; p=0.02), and ≥3 positive spots (HR: 1.71; p=0.01) were significantly associated with M1b-c stage. The multivariable model had a predictive accuracy of 75%. Three pre-operative groups were defined based on the risk calculator: low- (<33%), intermediate- (33-66%), and high-risk (>66%). Distant metastasis-free survival at 3 years was significantly different among the three groups (3% vs. 10% vs. 39%, p<0.0001). Conclusions We reported the largest series available of patients treated with SLND. At mid-term follow-up, roughly 15% of men developed systemic progression after surgery. We developed a risk calculator based on pre-operative characteristics to discern patients who would benefit the most from SLND from other patients who should be spared from the side effects of SLND. Funding none
Authors
Nicola Fossati
Nazareno Suardi Giorgio Gandaglia Armando Stabile Michele Colicchia R. Jeffrey Karnes Friederike Haidl David Pfister Daniel Porres Axel Heidenreich Christian Gratzke Annika Herlemann Christian Stief Antonino Battaglia Wouter Everaerts Steven Joniau Hein Van Poppel Alexey V. Aksenov Daniar K. Osmonov Klaus-Peter Juenemann ADL Abreu Fabio Almeida C. Fay Inderbir Gill Alexandre Mottrie Francesco Montorsi Alberto Briganti |
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PD15-10 |
Surgical expertise is the major determinant of decreased complication rates in contemporary patients treated with robot-assisted radical prostatectomy |
Prostate Cancer: Localized: Surgical Therapy II | 17BOS |
Abstract: PD15-10 Sources of Funding: none Introduction The aim of this study was to identify factors associated with post-operative complications after robotic-assisted radical prostatectomy (RARP) in contemporary patients and to assess the probability of freedom from relevant complications according to surgical expertise Methods 1,214 patients treated with RARP by 4 high-volume surgeons at a single referral centre between 2006 and 2015. All surgeons had a previous high-volume experience with open RP (at least 200 cases). Surgical expertise was coded as the progressive number of procedure done by each surgeon, starting from the first robotic case. Multivariable logistic regression analyses (MVA) were used to predict 90-day relevant complications (Clavien Dindo system 2-5) which were prospectively recorded for all men. Covariates consisted of age at surgery, Charlson comorbidity index, D'Amico risk groups, number of nodes removed, intra-operative time and log-transformed surgical expertise. A locally weighted, scatterplot smoothing method was used to graphically assess the multivariable effect of surgical expertise on the probability of complications Results Overall, 245 (20.2%) patients experienced post-op complications, of which 13.8 and 8.1% were graded 2-5 and 3-5, respectively. The most common complications were lymphoceles (8.5%), blood transfusions (4.4%), fever requiring antibiotics (4.2%), anastomosis leakage (3.5%), pelvic hematoma (2.8%), post-surgical hernia (2.1%) and urinary retention (1.2%). Overall, 4.7% of patients with lymphoceles required percutaneous drainage, 1.1% with pelvic hematoma and 1.2% with post-surgical hernia required reoperation. There were 4 (0.2%) admissions to intensive care units for cardiac events (Clavien IVa). At MVA, surgical expertise (OR: 0.8; p=0.01) and number of nodes removed (OR: 1.03; p=0.005) were independent predictors of 90-day complications. Figure 1 a-b represents the inverse association between surgical expertise and complications after RARP which was maintained across all risk groups Conclusions Among contemporary patients, the rate of complications related to RARP is not negligible. Surgical expertise is the major determinant of decreased risk of postoperative complications, regardless of disease characteristics Funding none
Authors
Paolo Dell'Oglio
Armando Stabile Emanuele Zaffuto Giorgio Gandaglia Nicola Fossati Marco Bandini Giulio Patruno Aldo Brassetti Federico Dehó Giorgio Guazzoni Gianluca D'Elia Nazareno Suardi Franco Gaboardi Francesco Montorsi Alberto Briganti |
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PD15-11 |
More extensive lymph node dissection at radical prostatectomy is associated with improved outcomes after salvage radiotherapy for rising PSA after surgery: a long-term, multi-institutional analysis |
Prostate Cancer: Localized: Surgical Therapy II | 17BOS |
Abstract: PD15-11 Sources of Funding: none Introduction Salvage radiation therapy (SRT) is a therapeutic option for men with PSA rising after radical prostatectomy (RP). While several studies have addressed potential predictors of outcome after SRT, none have investigated the role of the extent of pelvic lymph node dissection (PLND) on SRT outcomes. We hypothesised that cancer control of SRT are improved in men who underwent more extensive PLND at the time of RP. Methods The study included 728 patients who received SRT for either PSA rising after RP or PSA persistence after surgery that was defined as PSA level ≥0.1 ng/ml 1 month after RP. All patients received local radiation to the prostate and seminal vesicle bed at one of six tertiary referral centres; irradiation of the pelvic lymph node region (whole pelvic RT) was left to the discretion of the treating physician. The study outcome consisted of clinical recurrence after SRT as identified by radiologic imaging. Clinical recurrence included pelvic nodal, retroperitoneal nodal, skeletal, and visceral metastasis. Multivariable analysis tested the association between clinical recurrence and the number of lymph nodes removed, which was considered as a continuous variable. Covariates consisted of: pT stage (≤pT3a vs. ≥pT3b), pathologic Gleason score (≤7 vs. ≥8), surgical margin (negative vs. positive), PSA level at SRT, and radiation field (prostatic bed vs. whole pelvis). Results Median patient age was 66 years, while the median number of nodes removed at RP was 7 (IQR 0, 13). Overall, 500 (69%) patients received SRT for PSA rising after RP and 228 (31%) were irradiated for PSA persistence. Median PSA at SRT was 0.30 ng/ml. Whole pelvic SRT was delivered to 187 (27%) patients. Median follow-up was 94 months (IQR 48, 128), during which time. 27 (3.7%), 13 (2.1%), 61 (7.7%), and 11 (1.3%) patients developed pelvic, retroperitoneal, skeletal, and visceral metastasis, respectively. On multivariable analysis, the number of lymph nodes removed at RP was significantly inversely associated with the risk of clinical recurrence following SRT (hazard ratio: 0.97; 95% CI 0.95, 0.99; p=0.039). Conclusions This is the first study demonstrating a significant inverse correlation between the number of lymph nodes removed and the risk of clinical recurrence after SRT. These data suggest the need for consideration of alternative approaches to management for patients with PSA elevation after RP in whom a lower number of nodes were removed at surgery, including multimodal salvage therapy. Funding none
Authors
Nicola Fossati
R. Jeffrey Karnes Stephen Boorjian Michele Colicchia Alberto Bossi Cesare Cozzarini Claudio Fiorino Barbara Noris Chiorda Giorgio Gandaglia Thomas Wiegel Shahrokh F. Shariat Gregor Goldner Steven Joniau Antonino Battaglia Karin Haustermans Gert De Meerleer Valérie Fonteyne Piet Ost Hein Van Poppel Francesco Montorsi Alberto Briganti |
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PD15-12 |
The impact of nerve sparing radical prostatectomy on oncological and functional outcomes in patients with high risk prostate cancer: A retrospective long-term single center study. |
Prostate Cancer: Localized: Surgical Therapy II | 17BOS |
Abstract: PD15-12 Sources of Funding: none Introduction Whether patients (pts) with high risk prostate cancer (HR PCa) should undergo radical prostatectomy (RP) remains a matter of debate. The aim of the present study was to assess functional and oncological outcomes following RP in pts with HR PCa. Methods We evaluated 316 consecutive pts with HR PCa (according to the NCCN guidelines: pT3a tumor, a PSA level greater than 20 ng/mL, or a Gleason score between 8 and 10) who underwent RP and pelvic lymph node dissection from 1996 to 2015. Continence (CO) and potency (PO) were assessed at 3, 6, 12 and 24 months (mts). Pts who reported absence of erection sufficient for penetration prior to RP were excluded for evaluation of potency. Multivariable logistic regression models tested whether uni- and bilateral nerve sparing (NS) were a predictor of CO or PO at different time points after RP. Occurrence of local recurrence was prospectively entered into our database. For evaluation of positive surgical margins (PSM), pathology reports were retrospectively analyzed together with an uropathologist. Results At 3, 6, 12, 24 mts, overall continence rates were 87%, 93%, 96% and 98%, respectively. Attempted NS RP was associated with higher continence rates at all time points compared to no NS RP (Fig). In multivariable analysis, NS was associated with a more than 2.5-fold higher probability of CO at 3 mts (OR 2.74, 95% CI 1.18-6.36, p=0.02)._x000D_ Overall potency rates were 15%, 31%, 47%, and 50% at 3, 6, 12, and 24 mts, respectively. Attempted nerve sparing RP was associated with higher potency rates at all time points compared to no NS RP (Fig). In multivariable analysis, NS was associated with a more than 6 to10-fold higher probability of PO at 6, 12 and 24 mts (p<0.0001, p=0.01 and p=0.001). The Clavien 30- and 90-day complication rate (p=0,3 and 0,2) as well as the percentage of major complications (p=0,2 and 0,1) were not higher in pts with attempted NS compared to pts without attempted NS. Likewise occurrence of PSM and local recurrence were not observed more frequently in pts with attempted NS._x000D_ Conclusions Attempted NS in pts with HR PCa is associated with higher CO and PO rates after RP without compromising oncological outcome and occurrence of complications. Funding none
Authors
Marc Alain Furrer
Tobias Gross Daniel P. Nguyen Silvan Boxler Vera Genitsch Fiona C. Burkhard George N. Thalmann |
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PD16-01 |
Endoscopic description of renal papillary abnormalities in stone disease by flexible ureteroscopy - a proposed classification of severity and type. |
Stone Disease: Surgical Therapy I | 17BOS |
Abstract: PD16-01 Sources of Funding: none Introduction The goal of this original work was to describe papillary abnormalities using flexible ureteroscopy into a new classification and to assess their relation with stone composition. Methods We performed a prospective monocentric single operator study aiming to describe various aspects of renal papillae. Data have been prospectively collected during consecutive 164 sequential flexible ureterorenoscopies required for the treatment of renal stones from May 2011 to March 2015. The collected stones have been examined by microscopy and infrared spectrometry. Serum and urine biochemical samples have been systematically analysed. Results 74 patients (45.1%) had renal papillary abnormalities on at least one papilla, excluding typical Randall’s deposits alone. Various abnormalities were reported, some of them being present in the same patient: tip papillary erosions (51.3%), anchored papillae calculi (47.3%), subepithelial stones (18.9%), cryptic papillae (10.8%), extrophic papillae (9.46%) and intraductal deposits (2.7%). Associations between papillary abnormalities and stone types were found. Intraductal deposits were systematicaly associated with carbonate apatite IVa2 stones and hypocitraturia. A “first step” classification has been established to standardize the description of these papillary abnormalities for future reports and studies. Conclusions This study highlights the necessity of papillary abnormalities description in further multicentric studies and ureteroscopy’s reports. The established classification needs multicentric evaluation and validation. The endoscopic observation and knowledge of pathological aspects of the papillae should help to better understand pathogenesis of nephrolithiasis. Medical or surgical treatments of some abnormalities should be also discussed and evaluated to improve the prevention of stone recurrence. Funding none
Authors
Christophe Almeras
Michel Daudon Guillaume Ploussard Jean Romain Gautier Olivier Traxer Paul Meria |
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PD16-02 |
Modified Ergonomic Lithotripsy (MEL): A prospective single centre study demonstrating a Novel method for Retrograde Intrarenal Surgery (RIRS) to achieve high stone free rates without surgeon fatigue |
Stone Disease: Surgical Therapy I | 17BOS |
Abstract: PD16-02 Sources of Funding: none Introduction RIRS in larger stones and complex renal anatomy when done conventionally challenges a surgeon, causing fatigue leading to poor outcomes and stone free rates._x000D_ The Avicenna Robot addresses precision and surgeon fatigue. However, cost is a limiting factor._x000D_ _x000D_ We used the MEL position with definitive maneuvers intra-operatively allowing focused lithotripsy to improve higher stone free rates with the hypothesis of being more cost efficient._x000D_ -To describe,assess and review outcomes of our institute at Singapore doing RIRS in a modified lithotomy position to improve ergonomics for the endourologist especially in large calculi and complex anatomy._x000D_ - To assess surgeon fatigue and stone free rates(SFR) and the need for ancillary equipment and procedures._x000D_ Methods 100 Renal units had MEL from July 2015 to November 2016. A diagnostic retrograde pyelogram and semi rigid ureteroscopy was followed by a 11-13fr or 12/14fr 42-45 cm access sheath insertion in men and 35-36 cm in women._x000D_ Position: Lithotomy with head up and table incline at 35 degrees, respiratory rate controlled at 7-8 per minute. 20 minutes prior to completion of procedure 10 mg furosemide was given to induce diuresis_x000D_ _x000D_ Surgeon stool was raised such that hands were at the level of access sheath to relax shoulders and allow normal maneuvering without stress on flexible scope. _x000D_ SFR defined as residual fragments less than 3 mm was determined by CT scan 1 month or 3 months after surgery._x000D_ Results All 100 cases involving 3 primary surgeons had successful RIRS by MEL technique with minimal fatigue._x000D_ Mean operative time for large stones 90.8 min _x000D_ Mean laser time 53.6 min._x000D_ 18% cases needed a basket to re-position stones._x000D_ Rate of sepsis 3%_x000D_ Average hospital stay was 2 days_x000D_ Scopes serviced: 2 _x000D_ No loss in scope functionality. Good visibility maintained. Conclusions _x000D_ Having reproduced the MEL technique for 100 cases with no added morbidity and good outcomes, we believe that our aims were successful._x000D_ We propose this technique as an alternative to standard RIRS ._x000D_ It definitely minimizes need for accessories is cost and surgeon effective,unless Avicenna becomes the cheapest alternative way forward in future._x000D_ Funding none
Authors
VINEET GAUHAR
SARVAJIT BILIGERE GIRIDER SWAMINATHAN RUO XUAN GOH CHIN TIONG HENG |
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PD16-03 |
A decision analysis model of observation vs. immediate re-Intervention for asymptomatic residual fragments < 4mm following Ureteroscopic lithotripsy: a study from the EDGE Consortium |
Stone Disease: Surgical Therapy I | 17BOS |
Abstract: PD16-03 Sources of Funding: none Introduction To assess the cost-effectiveness of observation vs. intervention on asymptomatic residual fragments less than 4mm in diameter following ureteroscopic laser lithotripsy using a decision analysis model. Methods :Outcomes data from a previously published analysis of residual fragments after ureteroscopic lithotripsy were utilized. A decision analysis model was constructed to compare the cost-effectiveness of initial observation of residual fragments compared to immediate intervention. Cost for the observation arm consisted of ED visits, hospitalizations, and re-interventions. The cost-analysis model extended for 3 years to account for delayed re-intervention rates on fragments of this size. Expected value calculations and sensitivity analyses were performed to determine the optimal treatment pathway based on overall cost-effectiveness. Results Two hundred thirty-two patients were found to have asymptomatic residual fragments < 4mm on follow-up imaging following ureteroscopic lithotripsy. There were 191 patients in the observation group and 41 in the immediate-intervention group. Decision analysis modeling demonstrated that when comparing initial observation to immediate re-intervention, the cost was $2965 vs. $4504, respectively. The difference in cost was largely driven by the fact that over 3 years, approximately 56% of patients remain asymptomatic without ED visit, readmission or re-intervention wherease 44% of patients incurred at least one of those 3 complications. This represents an approximate annual per-patient savings of $513, and $1539 over three years when observation is selected over immediate re-intervention. Conclusions Our decision analysis model demonstrates superior cost-effectiveness for observation over immediate re-intervention for asymptomatic residual stones < 4mm following ureteroscopic lithotripsy. The cost-savings are primarily due to a plurality of patients not requiring intervention if observed. Based on these findings, careful stratification and selection of patients may enable surgeons to improve cost-effectiveness of managing small, asymptomatic residual fragments following ureteroscopic lithotripsy. Funding none
Authors
Michal Ursiny
Alan Yaghoubian Mitchell Humphreys Hillary Brotherhood Benjamin Chew Manoj Monga Amy Krambeck Amy Krambeck Cameron Charchenko An Qi Wang Roger Sur Nicole Miller Tracy Marien Yui-Hui Chang Bodo Knudsen Courtney Yong Brian Matlaga Vernon Pais Ojas Shah Brian Eisner |
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PD16-04 |
Infection Prevention Bundle for Upper Tract Endoscopy for Urolithiasis |
Stone Disease: Surgical Therapy I | 17BOS |
Abstract: PD16-04 Sources of Funding: none Introduction Retrograde endoscopic surgery has become a powerful tool in the treatment of ureteral and renal calculi. Infectious complications from these procedures however are a major concern, with rates ranging from 7 -25%. Mortality from septic complications has been reported as high as 25%. The purpose of this study is to share our easily implementable infection reduction bundle. Methods All retrograde endoscopic cases for ureteral and kidney stones undertaken from 2012- 2014 were reviewed retrospectively. All patients were subject to the same protocol as follows. _x000D_ _x000D_ 1) Once a safety wire was in place, IV furosemide (20mg) was administered to induce a brisk diuresis and to provide an increased pressure gradient against pyelovenous backflow._x000D_ 2) Low-pressure environment is maintained by gravity irrigation only (40-60cmH2O). Pressure irrigation is never utilized. _x000D_ 3) 2-way intermittent suction device is used to allow improved visibility and periodic reduction in renal pelvic pressure._x000D_ 4) Complex cases which require longer operative time (>2 hours) are staged._x000D_ _x000D_ Patients&[prime] charts were queried for post-operative infectious complications._x000D_ _x000D_ Results 194 patients were included in the study with 266 treatment episodes. 205 stone burdens underwent single session treatments while 29 stone burdens required two sessions and one stone burden required a third. 23% of patients had a history of UTIs and 32% of patients grew bacteria from their stones. No patients returned to the emergency department or required readmission to the hospital due to an infectious complication. No cases of fever or sepsis were noted.(Table 1) Conclusions We present a protocol for reduction of infection risk that has yielded excellent outcomes in a tertiary care population without sacrificing stone-free rates. Each step of our protocol is done to minimize the amount of bacteria and endotoxins that can reach the systemic circulation. This is done by increasing the pressure gradient against pyelovenous backflow via the use of furosemide, and minimizing renal pelvic pressure through low pressure gravity irrigation using an intermittent 2-way suction pump. Staging procedures further reduces risk by minimizing time infectious material can be absorbed. Lastly, our protocol is easily implementable into any stone practice. Funding none
Authors
Dennis Joseph Thum
Ali Afshar Justin Houman Devin Patel Alex Hannemann Gerhard Fuchs |
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PD16-05 |
Factors Associated with Post-Operative Infection after Percutaneous Nephrolithotomy: a Systematic Review and Meta-Analysis |
Stone Disease: Surgical Therapy I | 17BOS |
Abstract: PD16-05 Sources of Funding: None Introduction Despite antibiotics, sepsis remains the most common cause of perioperative mortality after percutaneous nephrolithotomy (PCNL). There have been numerous studies investigating risk factors for the development of post-operative infection in PCNL patients. Herein, we describe our meta-analysis of the risk factors for the prediction of post-PCNL infectious complications. Methods The electronic databases were searched using a combination of the terms "percutaneous nephrolithotomy", "risk factors", "infection", and "sepsis." The primary outcome was post-PCNL infection as defined by fever >38°C or sepsis as defined by the Sepsis Consensus Definition Committee. Risk factors for infection in each study were identified and included for analysis if present in at least 2 studies. We used quantitative effect sizes in odds ratio to assess each endpoint. Outcomes were pooled using the inverse variance technique with random-effects models. Results After application of criteria, 24 studies were found, of which 12 were prospective and 12 were retrospective. Of the 12 prospective studies, pre-operative urine culture, renal pelvis culture, stone culture, number of access points, hydronephrosis, perioperative blood transfusion and struvite stone composition were found to be significantly associated with post-operative infection. Of the 12 retrospective studies pre-operative urine culture, stone cultures, number of access points, blood transfusion, stone size and staghorn formation were significantly associated with infection. _x000D_ _x000D_ Conclusions In both prospective and retrospective studies, pre-operative urine culture, stone culture, number of access points and need for blood transfusion were found to be significant factors. This indicates that the presence of bacteria in the urine/stone pre-operatively as well as the amount of trauma the kidney sustains during the procedure are predictors of post-operative infection. We believe that this is the first meta analysis to identify these risk factors. Funding None
Authors
Win Shun Lai
Dean Assimos |
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PD16-06 |
Increasing the Size of Ureteral Access Sheath During Retrograde Intrarenal Surgery Improves Surgical Efficiency Without Increasing Complications |
Stone Disease: Surgical Therapy I | 17BOS |
Abstract: PD16-06 Sources of Funding: Watts Family Fellowship in Urologic Research Introduction Prior studies have suggested that larger ureteral access sheaths (UAS) may improve stone free rates (SFR) for larger calculi. The purpose of this study was to directly compare intraoperative and postoperative outcomes and complications between standard (12/14 Fr) and larger (14/16 Fr) ureteral access sheath (UAS). Methods We retrospectively reviewed demographic, preoperative, intraoperative, and postoperative data of 257 consecutive patients who underwent ureteroscopy for nephrolithiasis by a single surgeon from January 2013 through July 2015. Patients were separated into 3 groups: no UAS, a 12/14 Fr UAS, or 14/16 Fr UAS. Outcomes included differences in stone-free rate, post-procedure related events (PRE), ureteral injuries and postoperative complications. Results A UAS was used in 65.4% (168/257) patients, with 73.8% (124/168) utilizing a 12/14 Fr UAS and 26.2% (44/168) utilizing a 14/16 Fr UAS. Those patients in whom a 14/16 Fr UAS was employed had greater stone burden compared to the 12/14 Fr UAS group (180.8±18.0 vs. 104±9.1 mm2, p<0.001). When comparing 12/14 Fr and 14/16 Fr ureteral access sheaths, there was no significant difference in ureteral injury rate (7.3% vs 4.6%, respectively; p=0.63), complications (10.5% vs 11.4%, respectively; p=0.87), or overall stone-free rate (78.1% vs. 81.3%, p=0.70). The mean amount of stone burden treated per minute of operative time was more than 30% higher in the 14/16 Fr UAS group compared to 12/14 Fr UAS group (2.11 vs 1.62 mm2/min; p=0.01). Conclusions The use of a 14/16 Fr UAS allows for similar stone-free rate and improved operative efficiency with no increased risk of ureteral injury or postoperative complications when compared to the 12/14 Fr UAS. Funding Watts Family Fellowship in Urologic Research
Authors
Chad Tracy
George Ghareeb Charles Paul Nathan Brooks |
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PD16-07 |
Determining optimal stent duration following ureteroscopy: 3 vs 7 days |
Stone Disease: Surgical Therapy I | 17BOS |
Abstract: PD16-07 Sources of Funding: Watts Family Fellowship in Urology within the Department of Urology at the University of Iowa Introduction Many urologists elect to place a stent following ureteroscopy for nephrolithiasis, but little data exists on the optimal duration to leave a stent. Indwelling stents are associated a number of undesirable symptoms. We sought to determine whether there are any differences in postoperative outcomes for patients with a 3-day versus 7-day stent following ureteroscopy for nephrolithiasis. Methods Following Institutional Review Board approval, we retrospectively reviewed 247 patients who underwent unilateral ureteroscopy with lithotripsy from 2010-2016. 79 of these patients removed a stent with an extraction string at either 3 or 7 days post-operatively. The transition from 7-day to 3-day stenting occurred in May 2014. These two groups were compared with regard to demographic information, pre-operative variables, and post-operative outcomes. Results 33% of all patients experienced a post-procedure related event (phone call, extra clinic visit, emergency department visit) within 30 days of their procedure, 39% of 3-day stent patients compared to 21% of 7-day patients (p=0.11). Within the 3 days following stent removal, 3-day stent patients were significantly more likely to have a post-procedure related event than 7-day patients (23% vs 3%, p=0.026). There was a trend towards more frequently reported flank pain in 3-day patients (33% vs 14%, p=0.075). There was no difference between the groups in clinically insignificant stone fragments, post-operative hydronephrosis, or hospital readmissions. _x000D_ Conclusions One third of patients with a post-operative ureteral stent will seek additional medical care in the 30 days following ureteroscopy. It does not appear that leaving a stent for 3-days versus 7-days results in improved outcomes and may, in fact, lead to worse outcomes with regard to post-operative events and flank pain, particularly in the 3 days following stent removal. This pilot study provides a framework for future prospective analyses of appropriate stent duration in this population of patients. Funding Watts Family Fellowship in Urology within the Department of Urology at the University of Iowa
Authors
Charles Paul
Nathan Brooks George Ghareeb Chad Tracy |
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PD16-08 |
Impact of prior ureteral stent on future treatment decisions: EDGE multi-institutional survey. |
Stone Disease: Surgical Therapy I | 17BOS |
Abstract: PD16-08 Sources of Funding: None Introduction While well recognized that ureteral stents cause significant postoperative discomfort, implications of their impact on quality of life have not been fully evaluated. In particular, it is unknown whether prior stent experience affects subsequent treatment decisions. We previously developed and validated a survey to assess the effect of prior experience on willingness to undergo future stone therapy in general, and willingness to accept higher postoperative risks in order to forgo stent placement in particular. Methods The survey assessing the impact of decreased quality of life on subsequent treatment decisions was distributed to patients with a history of ureteral stent at three geographically disparate academic centers between July and October 2016. Responses were encoded in duplicate to ensure accuracy. Statistical analysis was performed using Chi square analyses. Results A total of 131 surveys were completed. Assessing prior stent experience, those reporting more pain with the stent were less likely to accept surgery for an asymptomatic stone (p=0.001). See Figure 1. When informed that ureteroscopy with stent omission would have a small increased risk of unplanned return visit compared with ureteroscopy with a stent, 24% chose surgery without a stent. However, of those reporting worse pain with the stent than the stone, 40% of respondents were willing to forgo stent. Conversely, of those that reported worse pain with the stone, only 11% chose surgery without a stent (p=0.004). When assessing impact of quality of life changes, only decreased interest in socializing (p=0.019) and decreased appetite (p=0.010) were associated with a higher likelihood to choose stent omission. Other consequences of stent placement (e.g. missed work, inability to care for family, exercising less, and decrease sexual activity) were not associated with a higher likelihood of choosing surgery without a stent. Conclusions Patients experiencing more pain with their stent than the inciting stone are less willing to treat asymptomatic renal stones and are more willing to accept greater postoperative risk in order to forgo future ureteral stents. With increased emphasis on shared medical decision making, an enhanced understanding of factors affecting these decisions is important in order to appropriately counsel patients. Funding None
Authors
Annah Vollstedt
Rajiv Raghavan Manoj Monga Anna Zampini Ojas Shah Rafael Yanes Stephanie Thompson Vernon Pais Jr |
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PD16-09 |
Externalized ureteral catheter versus Double J stenting in tubeless percutaneous nephrolithotomy: A prospective, randomized study. |
Stone Disease: Surgical Therapy I | 17BOS |
Abstract: PD16-09 Sources of Funding: None Introduction Since introduction, tubeless PCNL has undergone various technical modifications to further improve the outcome. Several published literature report that use of an externalized ureteral catheter during tubeless PCNL can obviate the stent related discomfort and the need for a second procedure (i.e. cystoscopic removal of stent). We conducted a prospective, randomized study to compare the outcomes using 2 different techniques (externalized ureteric catheter and double J stent) of internal drainage following tubeless PCNL. Methods From June 2011 to March 2016, a total of 492 patients underwent tubeless PCNL at our institution. A double J stent was placed in all cases of bilateral simultaneous PCNL, residual stone fragments, PCNL in solitary kidney and in patients with renal failure, so were excluded from study (n=55). Rest 437 patients were randomized into 2 groups: Group A (Tubeless PCNL with externalized ureteral catheter n= 225) and Group B (Tubeless PCNL with double J stent n=212). Study parameters include baseline (age, sex, stone burden, stone location/laterality, anomalous kidneys, past history of stone surgery), intraoperative (operating time, number of punctures, supracostal access, blood loss) and postoperative (analgesia requirement, hospital stay, stent related symptoms, complications, cost of treatment) and appropriate statistical methods were used for analysis. Results Baseline characteristics were comparable in both the groups. No statistical significant difference was observed between the groups with regards to operating time, number of punctures, site of puncture (supracostal or infracostal) and blood loss. Analgesia requirement (P= 0.04), hospital stay (P= 0.02), stent related symptoms (P=0.001) and treatment cost (P=0. 005) were significantly less in group A. Conclusions Our study demonstrated that tubeless PCNL using a ureteric catheter is a safe, reliable and relatively cost effective technique. It can reduce the complications associated with double J stent without affecting the efficacy of the procedure. However, the surgeon must ensure complete stone clearance in order to avoid ureteric colic. Further prospective, randomized trials are required to substantiate our results. Funding None
Authors
Gyanprakash Singh
Datteswar Hota Sabyasachi Panda Samir Swain Pramod Kumar Mohanty |
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PD16-10 |
Is PCNL a safe and effective option for Octogenarian patient?. Analysis of over 4000 cases from a national database. |
Stone Disease: Surgical Therapy I | 17BOS |
Abstract: PD16-10 Sources of Funding: None Introduction It is commonly believed that elderly octogenarian (>80 yrs) patients may not be offered PCNL because of the possible additional risks of major surgery associated with advanced age. We analyzed 4166 cases performed over a 2 year period and compared the stone complexity, complication rate and outcomes of the octogenarian patient (OP) compared to the younger patient (YP) aged under 80 years._x000D_ Methods The British Association of Urological Surgeons (BAUS) PCNL database has invited data submission for PCNL since 2011. We extracted data from the database for a 2 year period 2014-15. _x000D_ _x000D_ Comparisons were made using Chi Squared testing Results 4166 PCNL procedures performed between 01/01/2014 and 31/12/2015 were abstracted from the BAUS (British Association of Urological Surgeons) PCNL database. _x000D_ 172 procedures (4.1 %) were performed in OP who make up 4.9% of the UK population. M:F 84:88 , L:R:bilat = 88:83:1. BMI analysis revealed that fewer octogenarian patients were categorised as overweight or obese than the younger population (p< 0.05)_x000D_ _x000D_ There was no difference in the size or complexity of stone between the 2 group (p=0.68)) or stone dimension differences (<2cms vs >2cms) between the 2 populations._x000D_ _x000D_ Complications both intraoperative (OP:YP, 22:314 p<0.05) and postoperative (OP:YP 21:285 p<0.05) were more common in the older patient group. However there was no difference comparing the incidence of Clavien Dindo (CD) 2 or less (OP:YP 14:188) to CD3b and above (OP:YP 7:92)between the 2 groups. Transfusion rates were commoner in the older age group (OP:YP 8:49 p<0.05) relating to more complex stones (GSS 3-4). Sepsis was not significantly more common in the older patient group by either stone size or complexity. _x000D_ _x000D_ Older patients length of stay (LOS) was significantly longer (5.06 vs 3.24 days 95%CI) for stones of lower complexity (GSS 1-2). There was no difference in LOS for more complex stones (GSS 3-4)._x000D_ _x000D_ There were no significant differences in stone clearance rates by stone complexity between the 2 groups either prior to discharge or at follow up._x000D_ There were no differences in follow up rates between the 2 populations._x000D_ Conclusions PCNL is a safe option for elderly patients. The outcomes were equivalent to younger patients. There were increased complications amongst the older patient group especially relating to transfusion associated with more complex stones. There was no difference in the serious complication rates between the 2 groups. Length of stay was significantly longer for older patients with less complex stones._x000D_ There is no difference in stone free rates at follow up between the older and younger patient groups Funding None
Authors
Stuart Irving
Oliver Wiseman William Finch James Armitage Sarah Fowler John Withington Jonathan Glass Neil Burgess |
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PD16-11 |
Percutaneous Management of Calyceal Diverticula: Associated Factors and Outcomes |
Stone Disease: Surgical Therapy I | 17BOS |
Abstract: PD16-11 Sources of Funding: None. Introduction The choice of treatment for symptomatic calyceal diverticula (CD) depends on size, location, and degree of stone burden. Percutaneous treatment is preferred for large CD, lower pole CD, and CD with a large stone burden, but its safety for anterior CD has not been evaluated. In addition, the necessity to treat the diverticular neck and the need for metabolic evaluation remains controversial. We sought to shed some light on these issues based on our significant experience. Methods We identified 51 patients in our IRB approved Endourology database with stone bearing CD that were treated percutaneously by a single experienced surgeon. We separated patients into those with stones only in their CD (CD only) and those who also had renal calculi outside of their diverticulum (CD plus). Demographic data, size and location of the CD, treatment of the diverticular neck, intra-operative and post-operative outcomes, stone analysis, and 24-hr urine parameters were recorded. Urine parameters were also compared to stone formers without CD (non-CD). Results CD only patients are younger (44 vs. 54 y, p=0.024), have lower BMI (23.2 vs. 27, p=0.032), and are more often female (71% vs. 44%, p = 0.046) compared to non-CD patients. Anterior CD (66%) were more common than posterior, and 52% of the CD were found in the upper pole. Average CD size was 2.5cm with a stone burden of 1.47 cm. PCNL was performed safely and completely in 98% of the patients, with a complication rate of 4%. The diverticular neck was dilated in 44% of the cases. In follow-up there was 1 symptomatic recurrence managed by ureteroscopy. Calcium phosphate was contained in 82% of stones. All CD patients had at least one metabolic derangement, similar to regular stone formers, but with unusually high levels of urinary calcium and pH (Table 1). Conclusions Percutaneous treatment of CD is safe and effective regardless of size or location (including anterior CD). Infundibular neck dilation does not appear to be necessary. A significant proportion of CD patients have metabolic abnormalities. Stone formation is likely a result of stasis and metabolic factors, and CD patients are at risk for future renal calculi. Funding None.
Authors
Egor Parkhomenko
Timothy Tran Kyle Blum Julie Thai Mantu Gupta |
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PD16-12 |
A comparison among pcnl, miniperc and ultraminiperc for lower calyceal stones between 1 and 2 cm: a multicenter experience |
Stone Disease: Surgical Therapy I | 17BOS |
Abstract: PD16-12 Sources of Funding: none Introduction We performed a prospective randomized comparison among PerCutaNeous Lithotripsy (PCNL), MiniPerc (MP) and UltraMiniPerc (UMP) for lower calyceal stones between 1 and 2 cm to evaluate the efficacy and the safety of these procedures Methods Methods: Patients with a single lower calyceal stone with an evidence of a CT diameter between 1 and 2 cm were_x000D_ _x000D_ enrolled in this multicentric study. Exclusion criteria were the presence of coagulation impairments, age less than 18 or more_x000D_ _x000D_ then 75, presence of acute infection, presence of cardiovascular or pulmonary comorbidities. Patients were randomized into three groups: Group A: patients treated with PCNL; Group B: patients treated with MP; Group C: patients treated with UMP. Patients were controlled with abdomen X ray and CT scan after 3 months. A negative X ray or an asymptomatic patients with stone fragments less than 3 mm big. and a negative urinary colture were the criteria to assess the stone-free status. A statistical analysis was carried out to asses patients data, success and complications rates, re-treatment rate and need for auxiliary treatment. Results Results: Between January 2014 and June 2016, 132 consecutive patients were enrolled in this study. 44 pts for the group A, 47 for group B and 41 for group C. The mean stone size was 16.38 mm. in g roup A, 17.82 mm. in Group B and 15.23 mm. in Group C (p=0.34). The overall stone free rate was 86.3% for group A, 82.9% for group B and 78.0 % for group C. The retreatment rate was significantly higher in group C compared to the other two groups, 12.1% (p<0.05). The auxiliary procedure rate was comparable for group A and B and C (p>0.05). The complication rate was 13.6%, 4.2% and 2.4% respectively for group A, B and C. Conclusions Conclusions: PCNL and MP were more effective than UMP to obtain a better stone free rate. Auxiliary and re-treatment rate were similar. On the other hand for such this kind of stones PCNL had more complications. MP and UMP find a better indication in stones less than 1.5 cm in size. Funding none
Authors
Serena Maruccia
Stefano Casellato Gianluigi Taverna Javier Romero Otero Francesco Sanguedolce orietta dal piaz emanuele montanari paolo verze vincenzo mirone Giorgio Bozzini |
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PD17-01 |
A subanalysis of a randomized controlled trial:Abdominal vs laparoscopic sacrocolpopexy |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Pelvic Prolapse II | 17BOS |
Abstract: PD17-01 Sources of Funding: NONE Introduction This is a sub analysis of our previous RCT that compared abdominal (AS) versus laparoscopic Sacrocolpopexy (LS). In present study enrolled patients were divided in 3 subgroups: Sacrocolpopexy (SC), Hysterectomy (HY)and SC and Hysterosacropexy (HS).The aim of this study is to compare AS vs LS in each of the subgroups Methods Patients with symptomatic pelvic organ prolapse (POP)> stage II were assigned to one of the two groups (LS or AS). Surgery was performed by 2 senior surgeons skilled in both procedures. The analysis was performed in the 3 different surgical subgroups: SC for vaginal vault prolapse (group 1), HY and SC for advanced utero-vaginal prolapse (group 2) and HS when uterus was preserved (group 3).The primary outcome included the anatomic results (POP-Q system). Cure was defined as POP stage? I, for the apex or point C/D ? -5, for total vaginal length at least 7 cm. Secondary outcomes included complication rate, operating time, intra-operative blood loss, hospital-stay length, functional results and satisfaction (PGI-I scores). Statistical analysis : The Mann-Whitney, McNemar, X2 test. Results 121 consecutive women were included in the RCT (60 AS, 61 LS). In this sub-analysis we compared 3 surgical subgroups: Group 1 (28): 14 AS, 14 LS; Group 2 (45): 24 AS, 21 LS; Group 3 (47): 22 AS, 25 LS. The groups were comparable for demographic and clinical characteristics. Mean follow-up was of 45.4 months. There was a statistical functional and anatomical improvement in all subgroups in both groups.The recurrences (stage I or II) in anterior compartment were significantly more common in the LS group (in particular in group3) (p=0.015), while in posterior compartment was more frequently but not significantly present in the AS group (p=0.736). Intra-operative median blood loss(p<0.001), hospital stay (p<0.0001) and median operating time (group 3 p<0.0001 and group 2 p?0.022) were lower in LS in all the 3 subgroups. There were no significant differences in the grade of complications among surgical subgroups in both groups (AS p=0.845, LS p=0.250). The majority of complications were observed in group 2 (16/24 in AS and 9/21 in LS, p=0.193). There were 3 mesh exposure in LS ( 2 group 2 and 1 group 1) and 1 in AS (group 2). Conclusions LS can be considered an excellent option in patients with severe urogenital prolapse,with functional and anatomical outcomes and patient's satisfaction as good as AS in all the subgroups. The recurrence rate of anterior compartment is higher in LS especially when uterus is preserved. LS had best intraoperative and peri operative results compared to AS group. Funding NONE
Authors
Ester Illiano
Luigi Mearini Alessandro Zucchi Manuel Di Biase Elisabetta Costantini |
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PD17-02 |
THE IMPACT OF CONCURRENT PROCEDURES ON PERIOPERATIVE OUTCOMES AMONG WOMEN UNDERGOING ABDOMINAL SACROCOLPOPEXY: MIDURETHRAL SLING PLACEMENT IS ASSOCIATED WITH INCREASED RISK OF COMPLICATION |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Pelvic Prolapse II | 17BOS |
Abstract: PD17-02 Sources of Funding: None Introduction Abdominal sacrocolpopexy (ASC) is the gold standard surgical correction for apical prolapse, but there is variability in concurrent procedures. Given the paucity of data on the impact of concurrent procedures on perioperative outcomes, we assessed if hysterectomy or midurethral sling (MUS) placement incur an increased risk of 30-day complications. Methods We queried the American College of Surgeons National Surgical Quality Improvement Project database using current procedure terminology codes to identify women who underwent ASC between 2006 and 2013 and any concurrent procedure. Statistical analysis of outcomes was performed using chi-square test and multivariate regression. Results A total of 4,944 women underwent ASC, with open approach used in 1,302 (26.3%) and laparoscopy in 3,642 (73.7%). The majority were performed by gynecologists (92.3%) and surgical approach did not differ by specialty (p>0.05). Hysterectomy was performed in 2,963 cases (59.9%) and MUS was placed in 1,699 cases (34.3%). Gynecologists were more likely than urologists to perform a concurrent hysterectomy (64.0% vs 11.4%, p<0.01) and/or place MUS (34.8% vs 29.6%, p=0.04). There was no difference in overall complications or 30-day readmission based on surgeon specialty, resident involvement, or concurrent hysterectomy (p>0.05). Overall rate of reoperation was low (1.5%) and did not differ if concurrent procedure was performed (p>0.05). Relative to patients undergoing ASC without MUS, patients who had MUS placed had a higher incidence of urinary tract infection (UTI, 4.94% vs 2.31%, p<0.01) and overall complications (7.71% vs 6.07%, p=0.03), but no difference in 30-day readmissions (1.9% vs 2.6%, p=0.1). On multivariate regression analysis, MUS was associated with increased odds of UTI (OR 2.6, p<0.01) and overall complication (OR 2.09, p<0.01), and laparoscopic approach was associated with decreased odds of overall complication (OR 0.49, p<0.01; Table 1). Conclusions At time of ASC, MUS placement is associated with increased risk of UTI and overall complications. Resident involvement, performing hysterectomy, and surgeon specialty are not associated with differences in complications or readmission. Funding None
Authors
William R Boysen
Andrew Cohen Melanie Adamsky Joseph Rodriguez Sarah Faris Gregory Bales |
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PD17-03 |
Matched pair analysis comparing heavy weight versus lighter weight wide pore polypropylene mesh for robotic sacrocolpopexy |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Pelvic Prolapse II | 17BOS |
Abstract: PD17-03 Sources of Funding: none Introduction All FDA approved wide pore polypropylene Y-mesh grafts available for robotic sacrocolpopexy have variance in the mesh weight, pore size, thickness, surface area ratio and suture pull out strengths. In this study we evaluated results observed for robotic sacrocolpopexy performed with two separate wide pore polypropylene Y meshes that differ markedly in their physical properties. Methods Data is collected from an IRB approved prospectively maintained retrospective database of robotic sacrocolpopexy cases performed at an 836 bed tertiary care hospital by a single surgeon. Using analysis matched for covariates of BMI, POP-Q stage, surgeon, and previous attempts at repair, we evaluated whether the weight of the Y-mesh influenced the anatomic outcome and rate of de novo SUI at two year follow-up. Results Between 2011 and 2016, a total of 175 patients underwent robotic sacrocolpopexy for POP-Q Stage IV VVP. 50 patients undergoing repair with a heavy mesh weight (52 g/m2, 527 microns thick, and a suture pull out strength of 18.3 N) were matched to 50 patients undergoing repair with a lighter weight mesh ( 25 g/m2, 200 microns thick, and suture pull out strength of 23.3 N). At two year follow-up, anatomic success for apical prolapse was 100% and 2 patients (4%) in each group were found to have residual Grade 2 anterior prolapse and 2 patients (4%) in each group found to have Grade 2 posterior prolapse. De novo SUI was found in 5 patients (10%) in the heavy mesh group and 4 patients (8%) in the lighter mesh group. All de novo SUI patients did not have a mid urethral sling, MUS, placed at the time of the procedure. There was one mesh erosion in the light weight mesh group in a salvage patient that underwent concomitant pre-existing mesh removal at the time of surgery. Conclusions Although the two Y-meshes are markedly different in their weight, surface area, thickness and suture pullout strength, there was no observed significant difference in the anatomic success of repair, the rate of de novo stress urinary incontinence or mesh erosion. The rates of de novo SUI seen in this study, have led us to perform a MUS procedure at the time of sacrocolpopexy for all Grade IV prolapse patients. Funding none
Authors
Robert Carey
Ali Harris Maximilian Carey Karim Ghazli |
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PD17-04 |
Polyvinyldenfluorid (PVDF) versus Polypropylene (PP) mesh for sacrocolpopexy |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Pelvic Prolapse II | 17BOS |
Abstract: PD17-04 Sources of Funding: none Introduction The aim of this study was to compare a polymer mesh made of Polyvinyldenfluorid to polypropylene, the mesh material most commonly used in pelvic organ prolapse (POP) surgical repair, in terms of anatomical and functional results as well as safety, in patients who underwent sacrocolpopexy (SC) Methods This series included women who underwent SC for stages III or IV POP, according to the POP- Quantification (POP-Q) system, from 2005 to 2015, using either PP (Cousin Biotech Sacromesh®) or PVDF (DynaMesh®-PRS) mesh._x000D_ All women were preoperatively evaluated with history, physical examination and urodynamics. Urinary and sexual symptoms were assessed with the Urogenital Distress Inventory (UDI), the Incontinence Impact Questionnaire (IIQ-7) and the Female Sexual Function Index (FSFI) questionnaire. At the follow-up all patients were recalled and re-assessed with physical examination and the same questionnaires also used at baseline._x000D_ Patients’ satisfaction was recorded with the VAS score and the Patient Global Impression–Improvement (PGI-I) questionnaire._x000D_ Results Between January and May 2016, 136 patients with at least 1 year follow-up were re-assessed: 73 who had polypropylene mesh POP repair (PP group) and 63 who had PVDF mesh repair (PVDF group). The only significant difference between the two groups was duration of follow-up: 94.9±21.7 months for the PP and 29.8±13.8 months for the PVDF group because the last one was marketed later. _x000D_ Postoperative anatomical correction rates (success: POP stages 0 or I), voiding and storage symptoms, urgency and stress incontinence, questionnaire scores and mesh erosion rates are reported in Table 1. Most outcomes were not significantly different between the two groups with the exception of storage symptoms, sexual symptoms and UDI-6 scores that were better in the PVDF group._x000D_ Subjective patient satisfaction was high in both groups with no significant differences between them_x000D_ Conclusions Our results suggest that PVDF is at least as safe as polypropylene when used in POP repair. PVDF filaments have an excellent biocompatibility reducing adverse foreign body reactions such as granuloma formation, are associated with reduced bacterial colonization and maintain their tensile strength longer than polypropylene, that may explain the better results of PVDF in storage and sexual symptoms Funding none
Authors
Manuel Di Biase
Illiano Ester Elena Sarti Alessandro Zucchi Raffaele Balsamo Antonio Pastore Elisabetta Costantini |
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PD17-05 |
Laparoscopic versus Robotic assisted Sacrocolpopexy: a randomized, controlled trial |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Pelvic Prolapse II | 17BOS |
Abstract: PD17-05 Sources of Funding: none Introduction The present randomized study compares Laparoscopic sacropexy (LSC) and Robotic assisted sacropexy (RASC) in women with advanced pelvic organ prolapse (POP) to demonstrate the equivalence between the two techniques Methods Consecutive patients affected by symptomatic POP stage>II according to the POP-Q classification were prospectively randomized to test the clinical equivalence of RASC and LS. All women were preoperatively evaluated with history and physical examination. Urinary and sexual symptoms were assessed with the Urogenital Distress Inventory (UDI), the Incontinence Impact Questionnaire (IIQ-7) and the Female Sexual Function Index (FSFI) questionnaire. As primary outcome we evaluated the anatomical results considering as failure a POP>2 stage. Then we evaluated the difference between the two groups in terms of hospital stay length, blood loss, operating time, presence of voiding or storage symptoms and sexual function through the aforementioned questionnaires_x000D_ Results To date 21 patients have been randomized to RASC and 19 to LSC. The mean follow-up was 23,36 months. No significant inter-group differences emerged in the pre-operative evaluations of age (mean 63.5 vs 58.82 yrs for RASC and LSC, p=0.06) and BMI (mean 24.59 vs 25.41 kg/m2 for RASC and LSC, p=0.55)._x000D_ The objective success rate was 81% for RASC vs 78,9% for LSC (p=0.6), 85% for RASC vs 63,2% for LSC (p=0.8) and 100% for RASC vs 94,7% for LSC (p=0.57) for cystocele, rectocele and point c/D repair respectively._x000D_ Although not significant, operating time was longer for LSC (mean 213 min for LSC vs 184 min for RASC, p=0.11) and intra-operative blood loss was higher in RASC (mean 32 ml for RASC vs 47 ml for LSC, p=0.46). No difference emerged in hospital stays (mean 3.8 days for LSC vs 3.9 days for RASC, p= 0.8). Functional results are reported in table 1. No major complications were detected, only 2 grade III complication according to Clavien-Dindo classification has been reported in the LSC group (1 bladder injury and 1 mesh exposure). The subjective success rate was very high, 100% of patients of both groups reported to be “much” and “very much” improved at the PGI-I questionnaire Conclusions RASC aims at providing a similar excellent outcome as LSC in terms of anatomical results, satisfaction rate, complications, sexual function and voiding and storage symptoms relief Funding none
Authors
Ester Illiano
Manuel Di Biase Pasquale Di Tonno Gaetano De Rienzo Alessandro Zucchi Luigi Mearini Daniele Maglia Elisabetta Costantini |
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PD17-06 |
Direct to Consumer Advertising for Robotic Assisted Sacrocolpopexy: Are Patients Getting the Right Information? |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Pelvic Prolapse II | 17BOS |
Abstract: PD17-06 Sources of Funding: None Introduction Direct to consumer advertising targeting the patient has an increasingly pervasive effect on patient care. To date, however, we have little information addressing how this information is portrayed to patients on consumer websites. To analyze whether centers made unsubstantiated claims regarding outcomes of sacrocolpopexy, we examined whether web sites provided clinical data or referenced peer-reviewed publications as part of their advertising Methods We compiled an electronic database for the clinical direct-to-consumer advantages and/or disadvantages of robotic sacrocolpopexy using the first three Google pages with the search term “robotic sacrocolpopexy�. Advertising was then classified based on presentation of benefits/ advantages only, risks only, and both risks and benefits to determine the balance of information provided to consumers. We further classified the information based on whether or not peer-reviewed references were present on the webpages. Results A total of 25 of 29 websites were found to have information on advantages/disadvantages of sacrocolopexy. 4 were excluded because they had no discussion of advantages/disadvantages. Of the 25, 8 were research articles all containing references, 0 were insurance websites, 14 were hospital specific websites, 13 of which had no supporting references. Of the hospital websites, 5 were academic medical centers, 4 of which had no references. 3 were non-academic medical centers containing no references, and 6 were individual practices, all of which had no references. 7 were gynecology practices, all with no references, 6 were urology practices, 5 of which had no references. The most common advantages presented for the robotic approach included shorter hospital stays/recovery time (15) and decreased blood loss (13), with the most common disadvantage being high cost (5, see Table1). Conclusions Direct to consumer advertising in robotic sacrocolpopexy had many websites reporting benefits without describing risks or referencing the material on the websites. We need to ensure our advertising messages to consumers offer a balanced view of surgical interventions in accordance with the American Medical Association Code of Ethics Opinion on Advertising and Publicity. Funding None
Authors
Brent Medoff
Juzar Jamnagerwalla Dominique Dana Marie Thomas Bilal Chughtai Jennifer T. Anger |
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PD17-07 |
Autologous Fascia Sacrocolpopexy After Complete Removal of Sacrocolpopexy Mesh |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Pelvic Prolapse II | 17BOS |
Abstract: PD17-07 Sources of Funding: none Introduction Sacrocolpopexy (SC) using synthetic mesh is considered by many to be the gold standard for apical pelvic organ prolapse repair. Although uncommon, this procedure is not without risk of mesh-related complications. We sought to review our experience with patients suffering from complications of SC mesh placement including pain and mesh exposure necessitating complete mesh removal. We also describe our technique for simultaneous reconstruction with autologous rectus fascia. Methods Patients undergoing complete SC mesh removal for mesh-related complications at our institution from March 2013 to September 2016 were identified. Complete mesh removal was defined as excision of SC mesh in its entirety from the sacral promontory to the vaginal cuff or cervix if present, including partial vaginectomy and/or trachelectomy when necessary to completely remove the mesh. After complete mesh removal all patients underwent concomitant SC using autologous rectus fascia to mitigate against recurrent prolapse. A strip of rectus fascia 10cm in length was harvested at the margin of the incision and fashioned into an L shape. The horizontal segment of the L was fixed to the reconstructed vaginal apex and the vertical segment was fixed to the sacral promontory. The electronic medical record was retrospectively reviewed to identify patient demographics, perioperative characteristics, complications within 60 days, and short term surgical outcomes. Complications were graded using the Clavien system and those with a grade ? 3 were classified as major complications. Results Nineteen patients were identified. Median patient age was 56 years old (range 35-78). Median time from mesh placement to removal was 4.5 years (range 0-13 years). Indications include pelvic pain which was present in all patients in this series and mesh exposure in 8 patients (42%). Median operative time was 228 minutes (range 133-362). Median estimated blood loss was 200ml (range 50-1000ml). Median length of stay was 5 days (range 2-9). The rate of minor and major complications within 60 days was 36.8% and 5.3% respectively. One patient had a delayed presentation of ureteral obstruction managed with ureterolysis. There were no cases of bladder or bowel injury. At a median follow up of 296 days no patients required secondary surgery for vault prolapse. Conclusions Autologous rectus fascia SC at the time of complete removal of synthetic SC mesh can be accomplished safely with a low rate of major complications. These are short term findings and longer term follow up is needed to assess anatomic and functional outcomes. Funding none
Authors
Andrew Medendorp
Zaid Chaudhry Janine Oliver Lauren Wood Ja-Hong Kim Zachery Baxter Shlomo Raz |
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PD17-08 |
Is Vaginal Mesh a stimulus of autoimmune disease? |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Pelvic Prolapse II | 17BOS |
Abstract: PD17-08 Sources of Funding: Funded from American Urological Association Data Grant Program Introduction To investigate a potential link between the development of systemic/ autoimmune disorders and synthetic polypropylene mesh repairs. Methods New York State Department of Health Statewide Planning and Research Cooperative System data was utilized to conduct this retrospective cohort study. Adult women undergoing surgery for pelvic organ prolapse (POP) with vaginally implanted mesh between January 2008 and December 2009 in inpatient and ambulatory surgery settings in New York State were identified. Two separate control cohorts were created with whom to compare outcomes, including a colonoscopy cohort and a vaginal hysterectomy cohort (without POP repair or sling). Patients in the mesh cohort were individually matched to the control cohorts based on demographics, comorbidities and procedure date. The development of systemic/ autoimmune disease was determined before and after matching for 6-month, 1-year, 2-year and entire follow-up (up to 5 years until December 2014) and differences between groups were evaluated. Results A total of 2,257 patients underwent mesh based POP surgery between January 2008 and December 2009. In the control cohorts, 114,399 patients underwent colonoscopy and 9,395 underwent vaginal hysterectomy. When patients were matched based on demographics, comorbidities and procedure time, mesh-based surgery was not associated with an increased risk of developing autoimmune disease at any of the evaluated time periods. Conclusions Mesh-based vaginal surgery was not associated with the development of systemic/ autoimmune diseases. This data refutes claims against mesh as a cause of systemic disease. Funding Funded from American Urological Association Data Grant Program
Authors
Bilal Chughtai
Art Sedrakyan Jialin Mao Karyn S Eilber Jennifer T Anger J. Quentin Clemens |
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PD17-09 |
Five-year experience with pelvic floor mesh explant surgery: Patient characteristics and patient reported outcomes |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Pelvic Prolapse II | 17BOS |
Abstract: PD17-09 Sources of Funding: None Introduction Complications related to mesh implants for pelvic organ prolapse or incontinence are an important and controversial issue. However, there is limited literature on preoperative factors and outcomes of patients undergoing mesh removal. We present our experience with pelvic floor mesh explant surgery at a tertiary referral center. We aim to evaluate patient characteristics in an effort to identify factors that could predispose patients to mesh complications and assess patient reported outcomes to determine if preexisting symptoms successfully abate following mesh removal. Methods This is a retrospective case series of consecutive patients undergoing removal of mesh graft for treatment of symptomatic mesh related complications from 2011-16. Cases were identified by CPT codes 57287, 57295 and 57296. Patient demographics, comorbidities, symptoms and mesh factors were evaluated. Patient reported outcomes were determined by validated self-assessment instruments: patient global impression of improvement (PGI-I) and Likert satisfaction scale (0-10). Results 147 symptomatic patients underwent complete or partial pelvic floor mesh removal by 3 subspecialized urologists. Results and presenting symptoms are summarized in Table 1. Associated comorbidities include prior or current tobacco use, psychiatric disease, chronic pain, irritable bowel syndrome and fibromyalgia. 80% of patients reported pain. Mesh exposure or erosion was identified in 83% of patients. Mid urethral sling comprised 86% of explanted mesh grafts. At mean follow up of 14 months, 68% reported improvement after surgery (PGI-I mean 2.9, SD ± 1.68) and were satisfied (Likert score mean 7.4, SD ± 3). Conclusions Excision of symptomatic mesh implants can successfully improve presenting symptoms and bother based on intermediate follow-up. Most patients undergoing mesh removal presented with pain in the presence of mesh erosion or exposure, but 28% reported pain in the absence of mesh exposure or erosion. This cohort also demonstrates coexisting psychiatric, immunosuppressive, and other chronic pain conditions that should be further investigated for impact on the development of mesh complications. Patients who do develop symptomatic pelvic floor mesh complications should be counseled on the option of surgical removal. Funding None
Authors
Elliot Blau
Sarah Adelstein Alvaro Lucioni Kathleen Kobashi Una Lee |
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PD17-10 |
VAGINAL MESH REMOVAL OUTCOMES: EIGHT YEARS OF EXPERIENCE AT AN ACADEMIC HOSPITAL |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Pelvic Prolapse II | 17BOS |
Abstract: PD17-10 Sources of Funding: None Introduction There is much data in the literature about the complications of vaginal mesh; however, there is much less addressing the clinical outcomes for patients who undergo vaginal mesh removal due to complications from their mesh. The objective of this study is to describe the clinical history leading up to as well as the outcomes after vaginal mesh removal surgery at an academic, tertiary care hospital. Methods A retrospective study of patients who underwent vaginal mesh removal from 2008 to 2015. Demographics, clinical history, physical exam, pre- and post-operative symptoms, and number of re-operations were abstracted. Fisher&[prime]s exact test with significance at p<0.05 was used for comparative statistics. Results Between February 2008 and November 2015, 84 patients underwent vaginal mesh removal at our hospital. The median time interval from initial mesh placement to removal was 58 months (range 0.4 to 154 months). Most patients (n=61, 73%) had no prior history of mesh removal surgery. The most common pre-operative symptoms were vaginal pain (n=52, 62%), dyspareunia (n= 46, 55%), and pelvic pain (n=42, 50%). Intraoperative complications were infrequent with injury to the urethra, bladder, and bowel occurring in 1 patient each (n=3, 4%). Of patients presenting for follow up within 4-6 weeks post-operatively, 45 (83%) were deemed better than before surgery. Pre-operative symptoms that improved by six weeks or greater following mesh removal surgery were mesh erosion (p<.0001), vaginal pain (p<.0001), vaginal bleeding (p=0.0028), vaginal discharge (p=0.0127), dyspareunia (p=0.0024), and pelvic pain (p=0.0005). There were no identifiable risk factors to predict which patients would have persistent post-operative symptoms or who would require more than one mesh removal surgery. After vaginal mesh removal, 29 patients (35%) required one or more re-operations with 3 being the highest number of reoperations. Conclusions Vaginal mesh removal surgery is safe and can alleviate many pre-operative symptoms. Some patients require more than one procedure and the risk factors for reoperations are unclear. Funding None
Authors
Olivia O. Cardenas-Trowers
Pouran Malekzadeh David E. Nix Kenneth D. Hatch |
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PD17-11 |
LONG-TERM FOLLOW-UP OF ANTERIOR VAGINAL REPAIR: A COMPARISON AMONG COLPORRAPHY, COLPORRAPHY WITH REINFORCEMENT BY XENOGRAFT, AND MESH. |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Pelvic Prolapse II | 17BOS |
Abstract: PD17-11 Sources of Funding: none Introduction The aim of our study was to assess the long-term efficacy, the outcomes, and the complications in patients treated for pelvic organ prolapse (POP) with transvaginal anterior colporrhaphy alone (AC), AC and reinforcement by porcine Xenograft (Pelvisoft®) (AC-P), and AC and reinforcement by polypropylene mesh (AC-M). Methods A retrospective analisis of a prospectively maintained database of women undergoing cystocele repair between 2000 and 2015 was performed. In a cohort of 123 women, the follow-up was completed in 109: 42 patients underwent AC, 19 AC-P, and 48 AC-M. Mean follow-up was 94.80 ± 51.72 months. Subjectives outcomes have been evaluated by validated questionnaires. The personal patient satisfaction rate was also measured by the questions “are you satisfied with the surgical procedure?” and “would you confirm the same surgical choice at the time of the counseling before surgery?”. Objective outcomes have been evaluated considering a failure an anterior vaginal wall recurrence ? II° POP-Q and 2° Baden-Walker Halfway System. Results In all the surgical techniques used the results of PGI-I questionnaire showed a general perceived benefit of treatment as well as the results of PPBC questionnaire indicated an improvement from the previous bladder condition. The personal patient’s satisfaction rate was higher in the AC-P group. In all groups most of the interviewed women would confirm the same surgical choice. _x000D_ We find anatomical success rate > 80% in all groups with no statistically significant difference. Data showed a higher rate of complications in the AC-M group (p<0.05). _x000D_ Table 1 summarizes the characteristics of the patients, outcomes and complications. The larger number of complications in AC-M group (p<0.05) could explain the lower subjective satisfaction of patients. Conclusions Considering the recent FDA order to reclassify surgical mesh to class III, and the recent SCENHIR document on “Safety of surgical meshes used in urogynecological surgery” our data show in the AC group good results in a very long follow-up. The additional support given by a mesh, or a xenograft, does not increase with statistically significance the anatomic cure rate. Rather, the use of prosthetic devices leads more complications rate. Funding none
Authors
Matteo Balzarro
Emanuele Rubilotta Antonio Benito Porcaro Nicolò Trabacchin Sarti Alessandra Maria Angela Cerruto Salvatore Siracusano Walter Artibani |
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PD17-12 |
TWENTY?YEAR EXPERIENCE WITH THE ANTERIOR VAGINAL WALL SUSPENSION PROCEDURE: A NATIVE TISSUE VAGINAL REPAIR FOR STRESS URINARY INCONTINENCE WITH EARLY STAGE ANTERIOR COMPARTMENT PROLAPSE |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Pelvic Prolapse II | 17BOS |
Abstract: PD17-12 Sources of Funding: None Introduction To report on the mid and long term outcomes for the anterior vaginal wall suspension (AVWS) procedure for stress urinary incontinence (SUI) with early stage anterior compartment prolapse. Methods Following IRB approval, the long term prospective Access database of non neurogenic women who underwent AVWS for SUI and early stage anterior compartment prolapse was reviewed in women with complete pre and postoperative records and minimum 6 month follow up. Preoperative evaluation included detailed history, validated questionnaires (UDI 6, QoL), physical examination, and standing lateral voiding cystourethrogram (VCUG). Follow up included physical examination, questionnaires, and one VCUG at 6 to 12 months postoperatively. Failure was measured by Kaplan Meier curves using time to reoperation for incontinence as documented in the most recent patient encounter. Mixed effects model least square means were used for baseline versus post AVWS mean score comparison and for follow up period mean score comparison. Results Between 1996 and 2016, 235 patients met inclusion criteria. Median follow up was 5.3 years, with 47 (20%) patients having over 10 year follow up. Mean SD were: age 62.0 (11.0), BMI 26.0 (6.4), and parity 2.4 (1.3). 104 (44%) patients underwent AVWS alone. Among concomitant procedures, hysterectomy (LAVH) was the most common. Aa and Ba points, questionnaire results, and QoL consistently improved postoperatively and remained improved over time (Table 1). VCUG findings also improved for urethral support and cystocele reduction. Additional therapy was required in 12 (5%) patients, with sling placement (4) or injectable agents (8). Conclusions The AVWS procedure can durably correct SUI secondary to urethral hypermobility by restoration of anatomical support to the bladder neck and bladder base. Funding None
Authors
Alexander Rozanski
Philippe Zimmern Alana Christie Feras Alhalabi |
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PD18-01 |
Randomized study evaluating short-term functional outcomes of robot-assisted radical prostatectomy in low-risk prostate cancer patients |
Prostate Cancer: Localized: Surgical Therapy III | 17BOS |
Abstract: PD18-01 Sources of Funding: None Introduction Many techniques have been described to optimize functional outcomes of robot-assisted radical prostatectomy (RARP). Our objective was to test the impact of surgical technique on post-operative urinary continence recovery (UCR), urinary bother symptoms and erectile function (EF) recovery in a randomized study in high-volume center. Methods From July to December 2015 89 low-risk PCa patients signed the IC and were randomized in Group 1 (n=45, RARP with full bilateral nerve sparing (NS) and lateral prostatic fascia preservation with amniotic membrane allograft nerve wrap) and Group 2 (n=44, conventional RARP with bilateral NS). Posterior rhabdosphincter reconstruction (PRR) was performed in all cases. Patients started tadalafil 5 mg OAD from Day of catheter removal. Groups were comparable for clinical and pathological variables. We evaluated: 1) UCR rate, defined as the use of 0 pad/day; 2) post-op urinary bother symptoms measured using the QoL question in the IPSS questionnaire (no bother, score 0-2; bother, score 3 and more); 3) EF recovery rate, defined as IIEF-5>17. Results Patients with full NS, preservation of lateral prostatic fascia and amniotic membrane use had significantly higher rates of UCR at 1 week, 1 and 3 months and EF recovery rates at 3 and 6 months. Urinary bother scores were lower in these men at 1, 3 and 6 months post-RARP (table 1). There was no difference in positive surgical margins and intra- / post-RARP complication rate. Results were confirmed on multivariable analyses (odds ratio for Group 1 vs. Group 2 - 2.2 for UCR [p=0.006], 1.8 for EF recovery [p=0.004] and 3.6 for urinary bother [p=0.01])._x000D_ Conclusions Lateral prostatic fascia preservation with amniotic membrane allograft nerve wrap significantly improved the rate of post-RARP urinary continence, urinary bother and EF recovery in a group of low-risk PCa patients with bilateral NS and PRR in a randomized study. This in turn can translate into a higher post-operative QoL and/or patient satisfaction. _x000D_ The definition of surgical Pentafecta describing intraoperative technical manoeuvers optimizing functional outcomes may include 1) bilateral nerve sparing, 2) preservation of lateral prostatic fascia, 3) PRR, 4) amniotic membrane allograft use and 5) watertight anastomosis._x000D_ Funding None
Authors
Alexander Govorov
Dmitry Pushkar Konstantin Kolontarev Pavel Rasner Vladimir Dyakov |
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PD18-02 |
Measuring to improve: patient reported outcomes during the first year after prostatectomy in a statewide collaborative |
Prostate Cancer: Localized: Surgical Therapy III | 17BOS |
Abstract: PD18-02 Sources of Funding: Blue Cross and Blue Shield of Michigan and grant 1T32-CA180984 from the National Cancer Institute. Introduction The Michigan Urological Surgery Improvement Collaborative established its patient reported outcomes program (MUSIC PRO) with the dual objectives of systematically measuring and improving population-level urinary and sexual function outcomes after radical prostatectomy (RP). Herein, we report statewide outcomes from the first-year after RP and examine differences in patient-reported urinary function (UF) across surgeons to identify initial improvement opportunities. Methods Initiated in 2014, MUSIC PRO involves electronic collection of validated questionnaire data from men treated in 23 diverse academic and community urology practices. Men are surveyed at baseline, 3, 6, 12, and 24 months after RP. For all MUSIC PRO patients, we determined the proportion reporting good overall UF (score range 0-21, good function ≥ 17) and good overall erectile function (EF) (score range 0-30, good function ≥22) at baseline and during the first year after RP. After limiting the cohort to include only men treated by surgeons with ≥10 patients having good baseline UF, we evaluated surgeon-specific differences in the proportion of patients returning to good UF by 3 months post-operatively. Results From 4/2014 through 10/2016, 1,593 and 1,447 men completed baseline UF and EF surveys, respectively. Throughout the first year, response rates varied from 83-97%. At baseline, 77.6% of men reported good UF. While only 38.9% of men report similar good UF at 3 months post-RP, this proportion is much closer to baseline one year from surgery (65.3%) (Figure 1a). For EF, 58.6% of patients reported good function at baseline; this proportion decreased to 10.6% at 3 months, and then improved progressively to 21.8% after one year (Figure 1a). Across 21 MUSIC surgeons, there was broad variation in the proportion of patients reporting a return to good UF by 3 months (range 0-63.9% p<0.001) (Figure 1b). Conclusions Across the state of Michigan, most men recover baseline levels of good urinary function, but not sexual function, during the first 12 months after radical prostatectomy. Surgeon-specific differences in short-term urinary control outcomes highlight a quality improvement opportunity being addressed through continued measurement, technical assessments and refinements, and survivorship interventions. Funding Blue Cross and Blue Shield of Michigan and grant 1T32-CA180984 from the National Cancer Institute.
Authors
Gregory Auffenberg
Rodney Dunn Tae Kim James Peabody Mani Menon David Miller for the Michigan Urological Surgery Improvement Collaborative |
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PD18-03 |
Long-Term Health Related Quality of Life in Prostate Cancer Patients Requiring Radiotherapy After Radical Prostatectomy |
Prostate Cancer: Localized: Surgical Therapy III | 17BOS |
Abstract: PD18-03 Sources of Funding: NIH (MGS, CC), Urology Care Foundation Scholar grant (AM, PC), and Movember True North (AM, DP, MGS)._x000D_ Introduction While the effects of radical prostatectomy (RP) on urinary and sexual health related quality of life (HRQOL) have been well-studied, how long-term HRQOL may be further modified by adjuvant or salvage radiotherapy (XRT) after RP has not been fully characterized. Methods We evaluated RP subjects from the PROSTQA (2003-2006) and RP2 (2010-2013) Consortiums, two separate multicenter prospective cohorts of men who underwent treatment for localized prostate cancer in US academic medical centers (Sanda et al. NEJM 2008). Subjects completed EPIC-26 at pre-treatment baseline and annually thereafter by third party telephone interview. We used the unpaired t-test to compared long-term changes in the sexual, urinary incontinence, and urinary irritation domains between men who 1) did not undergo adjuvant or salvage XRT (RP-only), 2) received adjuvant XRT: within 1 year of RP, and 3) received salvage XRT: >1 year post-RP. Results Of the 1131 men who underwent RP, 1097 had RP-only, 57 had adjuvant XRT, and 50 had salvage XRT. Mean follow up was 49.7 months (range 0-122.9). Subjects who underwent post-RP XRT were significantly more likely to have a higher baseline PSA, Gleason 8-10 disease, T2 disease (vs T1) than those who underwent RP only. Patients receiving post-RP XRT had worse outcomes in sexual, urinary incontinence and urinary irritation domains (p<0.05 during longitudinal follow up, fig 1). However, further stratification of men receiving post-RP XRT into those receiving salvage XRT contrasted to adjuvant XRT showed that adjuvant XRT had worse sexual HRQOL than RP-only in the first 2 years, whereas salvage XRT had worse sexual HRQOL than RP-only throughout 9 years of follow up (p<0.05) . Other HRQOL domains did not show this differential. Conclusions Adjuvant and salvage XRT negatively affect HRQOL in patients treated with RP. These deleterious effects are more clearly observed in subjects undergoing salvage XRT. As follow-up for the RP2 consortium continues to mature, further study is needed to determine whether these findings are related to treatment effects or baseline differences between subjects. Funding NIH (MGS, CC), Urology Care Foundation Scholar grant (AM, PC), and Movember True North (AM, DP, MGS)._x000D_
Authors
Louis Aliperti
Dattatraya Patil Akanksha Mehta Christopher Filson Catrina Crociani Martin Sanda Peter Chang PROSTQA-RP2 Consortium PROSTQA Consortium |
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PD18-04 |
Prostate cancer-related anxiety in long-term survivors after radical prostatectomy |
Prostate Cancer: Localized: Surgical Therapy III | 17BOS |
Abstract: PD18-04 Sources of Funding: none Introduction During the first postoperative years prostate cancer (PC)-specific anxiety is correlated with clinicopathological characteristics and psychosocial distress. However, little is known about the following years. The objective of this study is to examine parameters influencing on prostate specific antigen (PSA) - and PC-Anxiety of long-term survivors after radical prostatectomy (RP). Methods 4,719 survivors were identified from the multi-center German prospective database Familial prostate cancer. We evaluated the association of the Memorial Anxiety Scale for Prostate Cancer (MAX-PC) with sociodemographic characteristics, family history of PC, global health score/quality of life (EORTC quality of life questionnaire-C30 subscale), depression/anxiety (Patient Health Questionnaire - 4), latest PSA-level >= 0.2 ng/ml, time since RP and current therapy using hierarchical multiple regression analysis. Results Mean age at survey was 75.2 years with a median follow-up of 11.5 years. The final regression model showed younger age, lower global health status/quality of life, higher depression/anxiety scores, higher latest PSA-level and shorter time since RP predicting a higher level of PSA- and PC Anxiety, respectively. Familial PC predicted only for PSA-Anxiety (all p < 0.05). The final regression model explained 12% of the variance for PSA-Anxiety and 24% for PC-Anxiety. Conclusions PC-specific anxiety is still relevant even many years after surgery. Besides depression and anxiety, younger age, shorter time since RP and a rising PSA-level play an important role during follow-up. Survivors who fulfill these characteristics are at higher risk to develop PC-specific anxiety which have need to be kept in mind by the treating physician regarding to a successful follow-up. Funding none
Authors
Kathleen Herkommer
Valentin H. Meissner Andreas Dinkel Birgitt Marten-Mittag Jürgen E. Gschwend |
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PD18-05 |
Effect of perioperative patient education on long-term satisfaction rates of low-risk prostate cancer patients after radical prostatectomy |
Prostate Cancer: Localized: Surgical Therapy III | 17BOS |
Abstract: PD18-05 Sources of Funding: none Introduction Amongst patients diagnosed with localised prostate cancer, the subsets of patients with low-risk disease are of particular interest since several evidence based therapeutic options are available to them, including radical prostatectomy (RP), radiotherapy, and active surveillance. To date, little is known about health-related quality of life with regard to patient satisfaction in general and the effect of perioperative patient counselling in particular. In the current study, we evaluate patient-reported functional outcomes after RP and analyze the effect of perioperative patient education on satisfaction rates among low-risk prostate cancer patients. Methods Inclusion criteria encompassed low-risk prostate cancer patients as defined by the D&[prime]Amico criteria, undergoing nerve-sparing RP excluding pelvic lymphadenectomy. Patient-centred functional outcomes, subjective evaluation of perioperative counselling, and patient satisfaction rates were documented. Stress urinary incontinence (SUI) was assessed by daily pad usage. Erectile dysfunction (ED) was assessed using IIEF5 score. Patients histories were attained from the electronic medical records. The effect of pre-defined predictive features for satisfaction rates was analysed in low-risk patients. Statistical analyses included Fisher exact test, Mann-Whitney-U test, and binary logistic regression models (p<0.05). Results 266 patients met the inclusion criteria. Median follow-up was 94 months (68-118). The global satisfaction rate was 75.1%. Regarding SUI, 69.5% of patients required no pads, 67.1% felt very well informed, while 11.7 % felt poorly educated. Regarding ED, an IIEF score of ≥18 was reached by 33.7%. 59.6% felt very well educated, while 13.0% felt poorly informed. Poor patient counselling regarding SUI and ED led to significantly decreased long-term satisfaction rates [40.7%, 33.3% (p<0.001)]. In multivariate analysis, poor ED patient counselling [OR 0.190, 95%CI 0.055-0.652 (p=0.008)], and postoperative IIEF5 score [OR 3.061, 95%CI 1.013-3.111 (p=0.013)] could be confirmed as independent predictors for patient satisfaction. Conclusions In the current study, we provide a detailed patient-centred analysis of multiple functional outcome parameters in a long-term follow-up after RP. Firstly, our findings highlight the effect of perioperative patient education on long-term patient satisfaction rates. In addition, our results advocate a structured patient counselling process to increase the postoperative quality of life in low-risk prostate cancer patients that have undergone RP (instead of active surveillance). Funding none
Authors
Alexander Kretschmer
Alexander Buchner Markus Grabbert Anne Sommer Christian G. Stief Ricarda M. Bauer |
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PD18-06 |
5 years follow-up of a prospective randomised controlled trial comparing laparoscopic versus robot-assisted radical prostatectomy: oncological and functional outcomes |
Prostate Cancer: Localized: Surgical Therapy III | 17BOS |
Abstract: PD18-06 Sources of Funding: none Introduction The aim of this study was to report the 5-year functional and oncologic outcomes of our previously published prospective randomized study comparing RARP vs LRP. Methods From 1/2010 to 1/2011, 120 patients with organ-confined prostate cancer were enrolled and randomly assigned to RARP or LRP. All patients were treated by a single surgeon with a trans-peritoneal anterograde approach. Continence, potency and serum PSA were reported at 1,3,6,12 months and then every 6 months until the 60th month postoperatively. Complications _x000D_ For the survival analysis biochemical Recurrence (BCR) was defined as any postoperative cancer treatment (radiation, hormonal/chemotherapy) or PSA above 0.2 ng/ml._x000D_ A Generalized Estimating Equations model was used to compare the time series of functional results, Kaplan-Meier and Cox model were used to analyse the oncologic outcomes. Results The probability to be continent and potent over time was more than doubled in the RARP group (OR 2.47, p<0.021 and OR 2.35, p<0.028, respectively)._x000D_ Five years BCRFS was 81.6% for both the RARP and LRP groups. At Cox proportional hazards models Pathological GS, Positive surgical margins (PSMs) and pT (pT3a vs pT2; pT3b vs pT2) stage were associated with a significant increase of BCR risk (HR 3.74, 4.61, 2.80 and 12.69, respectively) _x000D_ None of the patients died due to oncological causes; conversely, three patients in the RARP group and two patients in the LRP group died due to cardiovascular events. _x000D_ Conclusions All along the 5-yr follow-up, the robotic approach allows for better functional results if compared to pure laparoscopic, without compromising oncological outcomes. Funding none
Authors
Francesco Porpiglia
Cristian Fiori Riccardo Bertolo Matteo Manfredi Fabrizio Mele Diletta Garrou Daniele Amparore Giovanni Cattaneo Enrico Checcucci Stefano De Luca Roberto Passera Roberto Mario Scarpa |
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PD18-07 |
The impact of travel distance to the treatment facility on overall mortality in prostate cancer patients: evidence from the National Cancer Data Base |
Prostate Cancer: Localized: Surgical Therapy III | 17BOS |
Abstract: PD18-07 Sources of Funding: None Introduction To investigate the impact of travel distance to the treating facility on the overall mortality (OM)-risk of patients with prostate cancer (PCa) in the United States. Methods We identified 775,999 PCa patients within the National Cancer Data Base 2004-2012. Independent predictors of travel distance (intermediate [12.5-49.9miles] and long [49.9-249.9miles] vs. short [<12.5miles]) and the effect of distance on OM were calculated using multivariate regression analyses. Additional analyses evaluated the distance effect on OM in all patients and in selected subgroups. Results Overall, 54.5%, 33.4%, and 12.1% traveled short, intermediate, and long distances, respectively. Residency in rural area, and receiving treatment at academic/high-volume centers independently predicted long travel distance. Non-Hispanic blacks and Medicaid- insured were less likely to travel long distances (all P<0.001). At multivariate analysis, traveling intermediate distance (hazard ratio [HR]=0.97; 95% confidence interval (CI)=0.95-0.99; P<0.001) and long distance (HR=0.87; 95% CI=0.83-0.92; P<0.001) were associated with lower OM risk, as compared to short distance (Figure 1). In subgroup analyses, long travel distance was associated with decreased OM in non-Hispanic whites, privately-insured, Medicare-insured, and patients treated at academic or high-volume centers (P<0.001), but not in non-Hispanic blacks (P=0.3). Long travel distance was associated with an increased OM in Medicaid- insured patients (P<0.001; Figure 2). Conclusions Our results suggest that interestingly not only patients traveling longer distances live longer, but that even if they are going the extra mile, their OM outcomes are likely to be influenced by baseline socioeconomic and facility specific factors. Specifically, we observed concerning socioeconomic disparities in the access to care regarding a higher travel burden, which translated into less favorable OM outcomes for non-Hispanic blacks and non-privately insured patients. Funding None
Authors
Malte W. Vetterlein
Björn Löppenberg Patrick Karabon Deepansh Dalela Tarun Jindal Akshay Sood Quoc-Dien Trinh Mani Menon Firas Abdollah |
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PD18-08 |
Prospective Multicenter Comparison of Open and Robotic Radical Prostatectomy: The PROST-QA/RP2 Consortium |
Prostate Cancer: Localized: Surgical Therapy III | 17BOS |
Abstract: PD18-08 Sources of Funding: PROST-QA Consortium Funded by National Institutes of Health Grants R01 CA95662, RC1 CA146596, and RC1 EB011001. The Multicentric Spanish Group of Clinically Localized Prostate Cancer was supported by a grant from Instituto de Salud Carlos III FEDER: Fondo Europeo de Desarrollo Regional (PI13/00412). Dr. Chang is supported by a Urology Care Foundation Research Scholar Award and the Martin and Diane Trust Career Development Chair in Surgery. Introduction Comparisons of robot-assisted laparoscopic (RALP) and open radical prostatectomy (ORP) are often limited by retrospective approaches, non-patient-reported health-related quality of life (HRQOL) evaluations, or single center/surgeon analyses. Herein we present a prospective, multicenter comparison of RALP and ORP. Methods We evaluated men from two prospective, multicenter, longitudinal studies treated from 2003-2012 with a pre-specified analytic goal of comparing RALP (n=549) and ORP (n=545). Subjects completed EPIC-26 HRQOL questionnaires at pre-treatment, 2, 6, 12, and 24 months post-operatively, with follow-up compliance >85%. We used univariate mixed models with cohort as a random effect to assess differences in baseline demographic and cancer characteristics, and the chi-square test to evaluate differences in surgical and peri-operative outcomes between surgical approaches. We evaluated for predictors of HRQOL domain score changes over time using semi-parametric generalized estimated equation modeling with compound symmetrical correlation structure, controlling for nesting within cohort. Results We found no significant differences in demographics, cancer characteristics, pathologic T stage, or margin status between surgical approaches. ORP subjects were more likely than RALP subjects to undergo lymphadenectomy (89% vs 47%; p<0.01) and nerve sparing (94% vs 89%; p<0.01). RALP subjects had less mean intraoperative blood loss (192 vs 805 mL; p<0.01), shorter mean hospital stay (1.6 vs 2.1 days; p<0.01), and fewer blood transfusions (1% vs 4%; p<0.01), wound infections (2% vs 4%; p=0.02), other infections (1% vs 4%; p<0.01), deep vein thrombosis (DVT; 0.5% vs 2%; p=0.04), and unplanned catheterizations (3% vs 7%; p<0.01) than ORP subjects. RALP subjects reported less surgical pain (p=0.04), less pain interference with activity (p<0.01) and higher incision satisfaction (p<0.01). Surgical approach was not a significant predictor of HRQOL change over time in any of the five EPIC-26 HRQOL domains. Conclusions In this multicenter, prospective evaluation of ORP and RALP, surgical approach was not a significant predictor of post-surgical HRQOL change. RALP subjects had superior incisional/pain outcomes, shorter hospital stays, and fewer post-surgical complications such as blood transfusions, infections, DVTs, and unplanned catheterizations. These results should help guide treatment counseling and be integrated into future cost analyses. Funding PROST-QA Consortium Funded by National Institutes of Health Grants R01 CA95662, RC1 CA146596, and RC1 EB011001. The Multicentric Spanish Group of Clinically Localized Prostate Cancer was supported by a grant from Instituto de Salud Carlos III FEDER: Fondo Europeo de Desarrollo Regional (PI13/00412). Dr. Chang is supported by a Urology Care Foundation Research Scholar Award and the Martin and Diane Trust Career Development Chair in Surgery.
Authors
Peter Chang
Andrew Wagner Meredith Regan Dattatraya Patil Catrina Crociani Larry Hembroff Linda Stork Kyle Davis John Wei David Wood Christopher Saigal Mark Litwin Jim Hu Eric Klein Adam Kibel Gerald Andriole Matthew Cooperberg Peter Carroll Joseph Smith Misop Han Alan Partin Martin Sanda PROST-QA and PROST-QA/RP2 Consortiums |
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PD18-09 |
Long-term functional outcome in a large cohort of patients undergoing radical prostatectomy |
Prostate Cancer: Localized: Surgical Therapy III | 17BOS |
Abstract: PD18-09 Sources of Funding: None. Introduction Goal of the study was a prospective patient-centered analysis of functional outcomes after radical prostatectomy (RP) in large cohort of 870 patients. Methods Patient-centered functional outcomes were assessed with the validated ICIQ-SF questionnaire and daily pad usage for the evaluation of stress urinary incontinence (SUI). Erectile dysfunction (ED) was assessed using IIEF5 score. In addition quality of life (QOL) in these patients was evaluated with the EORTC QLQ-C30 questionnaire. Statistical analyses included log-rank test, Mann-Whitney-Test and Kruskal-Wallis-ANOVA test (p<0.05). Results 870 patients were included in the study. Median follow-up was 76 months. Regarding SUI, 63% stated that they needed no pads, 17% of patients needed one pad per day. 38% of patients reported of no incontinence (0 p. in ICIQ), 26% of included patients reported of a mild incontinence (1-5 p. in ICIQ). ICIQ score was significantly higher in older patients (= 75 y. vs. >75 y.; p<0.001) and improved statistically significant over time (3 mo. vs. 1, 2 and 3 years; all p<0.001). Regarding ED, an IIEF score of ?20 was reached by 39% of patients. The patients´ global impressions of their overall health (q. 29 EORTC QLQ-C30) resp. the subjective QOL (q. 30 EORTC QLQ-C30) were both high with median of 6 points. Younger patients (= 75 y. vs. >75 y.; p=0.011) showed a higher QOL score and the QOL score improved statistically significant over time (3 mo. vs. 1, 2 and 3 years; p=0.002, p=0.040 and p<0.001). In multivariate analysis time and tumor stage could be identified as independent risk factors on QOL score, IIEF-5 score, ICIQ score and pads per day for SUI with improving score over time (each p<0.001). Conclusions We provide a prospective patient-centered functional outcome analysis in a large cohort of patients after radical prostatectomy and highlight the importance of an appropriate counselling regarding the postoperative functional outcomes and their impact on QOL. Funding None.
Authors
Markus Grabbert
Alexander Buchner Christopher Butler Ransohoff Maria Apfelbeck Christian Stief Ricarda Bauer |
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PD18-10 |
THE EFFECT OF NERVE SPARING STATUS ON SEXUAL FUNCTION: 3?YEAR RESULTS FROM THE CEASAR STUDY |
Prostate Cancer: Localized: Surgical Therapy III | 17BOS |
Abstract: PD18-10 Sources of Funding: U.S. Agency for Healthcare Research and Quality (Grants 1R01HS019356 and 1R01HS022640-01); the National Cancer Institute, National Institutes of Health (Grant R01-CA114524), and the following contracts to each of the participating institutions: N01-PC-67007, N01-PC-67009, N01-PC-67010, N01-PC-67006, N01-PC-67005 and N01-PC-67000, and through a contract from the Patient-Centered Outcomes Research Institute Introduction Nerve sparing (NS) contributes to recovery of sexual function after prostatectomy, but may not be necessary in men with low baseline function. We evaluated the effect of NS in men with low and high baseline function over 3 years after prostatectomy. Methods The Comparative Effectiveness Analysis of Surgery and Radiation (CEASAR) study is a prospective, population-based, observational study of men with localized prostate. Patient-reported sexual function was measured using the 26-item Expanded Prostate Index Composite (EPIC) at baseline, 6, 12, and 36 months after treatment. To identify the effect of NS on post-treatment sexual function for both high and low baseline sexual function, we fit unadjusted and adjusted models with interactions between nerve sparing status, time since treatment and baseline sexual function, controlling for comorbidity, race, use of erectile aids, disease risk, depression, and anxiety scores in the adjusted model. R2 plot was used to show the contribution of each factor to sexual function outcome. NS status was defined as none (NNS), unilateral (UNS) or bilateral (BNS), according to the operative report. We grouped NNS with UNS, as there was negligible difference in EPIC domain scores. We dichotomized baseline sexual function into low (EPIC domain score <80) and high (>80). Results Among 1373 participants, 415 men with high baseline sexual function underwent BNS and 84 underwent NNS/UNS. In 648 men with low baseline function, 365 men underwent BNS and 86 men underwent NNS/UNS. From the unadjusted model, men with high baseline function had a 7.8 point difference (CI -0.4, 16) in EPIC domain scores between NNS/UNS and BNS at 3 years and in men with low baseline function, there was an 8.9 point difference (CI 2.5, 15.4). In the adjusted model, there was also no statistically significant difference between NNS/UNS and BNS. Baseline sexual function and time since treatment accounted for most of the variation in sexual function scores. Conclusions These data suggest that BNS has a small impact on function, the same magnitude of effect regardless of baseline function, raising concern that operative reports inadequately reflect actual degree of NS. We confirm that baseline function is the main driver of post-prostatectomy sexual function. Funding U.S. Agency for Healthcare Research and Quality (Grants 1R01HS019356 and 1R01HS022640-01); the National Cancer Institute, National Institutes of Health (Grant R01-CA114524), and the following contracts to each of the participating institutions: N01-PC-67007, N01-PC-67009, N01-PC-67010, N01-PC-67006, N01-PC-67005 and N01-PC-67000, and through a contract from the Patient-Centered Outcomes Research Institute
Authors
Svetlana Avulova MD
JoAnn Rudd Alvarez MA Tatsuki Koyama PhD Matthew J. Resnick MD, MPH David Penson MD, MPH Daniel A. Barocas MD, MPH |
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PD18-11 |
Prospective Randomized Trial of Pelvic Drain Placement Versus No Pelvic Drain Placement after Robot-Assisted Radical Prostatectomy (RARP) |
Prostate Cancer: Localized: Surgical Therapy III | 17BOS |
Abstract: PD18-11 Sources of Funding: None Introduction The prophylactic placement of a pelvic drain (PD) after prostatectomy has long been an empiric practice despite lack of high-level evidence of clinical benefit. However, with RARP and improvements to surgical technique, routine pelvic drainage may not be necessary in the contemporary setting. We sought to determine if eliminating the prophylactic placement of a PD after RARP affects incidence of early postoperative adverse events. Methods Prostate cancer patients scheduled to undergo RARP were randomized prospectively at the end of surgery in a double-blinded study to undergo PD placement or no PD placement. Patient with prior radiotherapy, prior extensive pelvic surgery and demonstrable intra-operative leakage upon bladder irrigation at the end of the procedure were excluded. Demographic data, preoperative and postoperative results for the two groups were compared. The primary endpoint was overall (Clavien I-V) incidence of complications, specifically to assess that 90-day complication rate in the no PD group was within 10% of the 90-day complication rate in the PD group, in a non-inferiority setting. Results From September 2012 to April 2016, 179 RARP patients were randomized into two groups: Group 1 did not receive a PD (n=85) while Group 2 did receive a PD (n=94). Between the two groups, no difference was observed in baseline characteristics such as age, body mass index, race, and ethnicity. Patients in group 1 and 2 were comparable in median PSA (6.3 vs 5.8 respectively, p=0.5), clinical stage (p=0.4), D’Amico risk classification (p=0.4), median lymph nodes dissected (18 vs 18, p=0.4) and proportion of patients receiving an extended pelvic lymph node dissection (71.8% vs 78.7% respectively, p=0.5). The incidence of 90-day overall (Clavien I-V) complications in the no PD group (22.4%) was not inferior to the incidence of 90-day overall complications in the PD group (26.6%, p=0.015 for difference of proportions <10%). Similarly, the incidence of 90-day major (Clavien > III) complications in the no PD group (7.1%) was not inferior to the incidence of 90-day major complications in the PD group (4.3%, p=0.037 for difference of proportions <10%). The symptomatic lymphocele rates (1.2% in Group 1, 3.2% in Group 2) were comparable between the two arms (p=0.6). Conclusions The incidence of early postoperative overall and major adverse events in the no PD group was not inferior to the group who received a PD. In properly selected patients, the use of a PD after RARP can be safely withheld without significant additional morbidity. _x000D_ _x000D_ Funding None
Authors
Avinash Chennamsetty
Ali Zhumkhawala Bertram Yuh Clayton Lau William Chu Justin Emtage Paul Gellhaus Nora Ruel Kevin Chan Jonathan Yamzon |
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PD18-12 |
De novo overactive bladder after robot-assisted laparoscopic radical prostatectomy |
Prostate Cancer: Localized: Surgical Therapy III | 17BOS |
Abstract: PD18-12 Sources of Funding: none Introduction Robot-assisted laparoscopic radical prostatectomy (RALP) is becoming a popular treatment option for localized prostate cancer. Although the potency and stress urinary incontinence after RALP have been assessed in detail, few studies have described the storage dysfunctions such as overactive bladder (OAB) that occur after RALP. In the present study, we investigated the storage function following RALP, with a focus on de novo OAB, and evaluated the factors related to the occurrence of de novo OAB after RALP._x000D_ Methods We prospectively examined 150 patients without OAB who underwent RALP for localized prostate cancer, and the pre- and postoperative (3 months) urodynamic studies.The evaluated urodynamic parameters were maximum urethral closing pressure (MUCP) and functional profile length (FPL). At the evaluation after 3 months of RALP, we divided the patients into two groups: patients with de novo OAB (de novo OAB group) and patients without OAB after surgery (OAB-free group). We compared the operative and urodynamic parameters between the groups and evaluated the factors related to the occurrence of de novo OAB. In the present study, OAB was defined as a score of 2 or more on the urgency component of the overactive bladder symptom score (OABSS), and a total OABSS of 3 or more. _x000D_ Results De novo OAB after RALP was observed in 43 patients (28.7%). The International Prostate Symptom Score (IPSS) and OABSS in the de novo OAB group deteriorated significantly from 8.4 to 17 and from 2.1 to 9.3, respectively, whereas those in the OAB-free group improved significantly from 8.2 to 7.4, and from 2.8 to 2.7, respectively. Additionally, there was a significant difference in the incontinence rate, preoperative MUCP, postoperative MUCP, and postoperative FPL, as observed from the univariate comparison of operative and urodynamic parameters between the groups (Table). Multivariable logistic regression analysis performed using factors related to de novo OAB showed that postoperative MUCP was the only significant factor for predicting de novo OAB._x000D_ Conclusions The incidence rate of de novo OAB after RALP was about 30%, which was thought to be unexpectedly high. The decrease in urethral function was related to de novo OAB after surgery, and it was attributed to the increased reflex response of the urethral afferent pathway. Funding none
Authors
Yoshihisa Matsukawa
Yasuhi Yoshino Yasuhito Funahashi Tsuyoshi Majima Tokunori Yamamoto Momokazu Gotoh |
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PD19-01 |
Active surveillance for non-muscle invasive bladder cancer (NMIBC): result from Bladder Cancer Italian Active Surveillance (BIAS) project. |
Bladder Cancer: Non-invasive II | 17BOS |
Abstract: PD19-01 Sources of Funding: None Introduction Active surveillance (AS) is an accepted policy for some urological low risk malignancies, such as prostate cancer and small renal tumors in elderly patients. Low-risk non-muscle invasive bladder cancer (NMIBC) has a low probability of progression (0.8 % at five years for pTa G1 and pTa G2 tumors) and preliminary data showed that, in selected cases, AS could be a safe and valid alternative to standard transurethral resection of bladder tumor (TURBT). We report our single centre experience of a prospective cohort study in patients with low-risk NMIBC selected for a monitoring program (Bladder Cancer Italian Active Surveillance - BIAS project). Methods This is an observational prospective longitudinal study (EC approval: ICH/1390/C780) enrolling patients, aged ≥ 18 yrs, with a history of low-grade pTa-pT1a tumours with recurrence. Inclusion criteria were: negative cytology (three consecutive negative samples), ≤ 5 endoscopic lesions, diameter ≤ 10 mm and no carcinoma in situ (CIS) or persistent gross haematuria. Cases were followed-up by urine cytology and in-office flexible cystoscopy at intervals of four months in the first year, and then every six months annually. The primary outcome was to test the adherence to monitoring (AS) defining a failure as any progression in number/dimension/positive cytology/signs (gross haematuria persistent) or any further intervention (resection or electro-fulguration). Secondary end-point consisted in the assessment of pathological progression defined as up-grading and up-staging at failure. A descriptive statistical analysis with qualitative variables presented by frequency distribution and the quantitative variables by the mean or median with ± SD/IQR was applied. Results Overall, 99 patients (mean age 72.1 ± 14.7 years) underwent 120 AS events from June 2008 to September 2016. The median follow-up was 44 months (IQR:51). The median time between first TURBT and recruitment to AS was 22.5 mo (IQR:12.5). The median number of TURBT before AS entry was 2 (r. 1-4). The pathological characteristics at entry showed pTa and pT1a in 80 and 19 patients respectively; 69 had G1 (69.7%) and 30 G2 (30.3%). Patients remained under AS for a median time of 21.3 months (IQR:21.5); 5 patients were lost to FU due to deaths, which were not related to bladder cancer. A failure was observed in 40 (40.4%) patients, corresponding to 45 events (37.5%). Within failure events, 17 (37.8%) were due to dimensions, 10 (22.2%) to number and 3 to contemporary dimension and number increase. Gross haematuria was the cause of failure in 10 events and positive cytology in 5. No patient experienced stage and grade progression. Eleven failures presented as pT1a and 31 as pTa; 6 failures were classified as G3, 9 G2 and 27 G1. In three patients the TURBT did not reveal neoplasia in pathological samples. One (1%) patient showed CIS. The overall adherence to controls was 95%. Conclusions Current findings seem to support AS for NMIBC as a reasonable option in patients with small, low stage, low-grade recurrent papillary bladder cancer after TURBT. Although the current population is one of the largest with a long-term follow-up, further multicentre studies under randomisation criteria are mandatory in order to include AS in our daily practice. Funding None
Authors
Rodolfo Hurle
Massimo Lazzeri Giovanni Lughezzani NicolòMaria Buffi Alberto Saita Luisa Pasini Silvia Zandegiacomo Alessio Benetti Giovanni Forni Piergiuseppe Colombo Roberto Peschechera Paolo Casale Giuliana Lista Pasquale Cardone Giorgio Guazzoni |
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PD19-02 |
Is there a role for upper urinary tract imaging surveillance in the follow-up of non-muscle invasive bladder cancer? |
Bladder Cancer: Non-invasive II | 17BOS |
Abstract: PD19-02 Sources of Funding: none Introduction Patients with non-muscle invasive (NMI) bladder cancer (BC) are at increased risk for metachronous upper tract urinary cancer (UTUC). Thus, routine upper tract imaging surveillance is recommended for early detection of UTUC during BC follow-up of patients with high-grade BC. However, evidence for the utility of this investigation is scarce. We aimed to assess the effectiveness of routine upper tract imaging surveillance during NMIBC follow-up. Methods A retrospective analysis of all patients treated and followed for NMIBC in a tertiary care academic center between 2003 and 2013 was performed. Results of all routine upper tract computerized tomography (CT) scans were assessed for UTUC detection. Kaplan-Meier curves were calculated to assess 5- and 10-year UTUC-free survival. Results 315 patients were followed in our center after NMIBC treatment (pTa: 206 patients (66%), pT1: 99 patients (31%), CIS: 10 patients (3%)). 159 patients (50%) presented with LG and 156 (50%) with HG disease. Mean follow-up was 56 months. Overall, 396 abdominal CT scans were performed of which 230 were classified as routine upper tract imaging surveillance. The overall 5- and 10-year UTUC-free survival was 98.5% (standard error (SE) 0.9) and 97.6% (SE 1.3), respectively. Four patients (1.2%) were diagnosed with UTUC in the follow-up. All patients presented with pTa LG disease. Two of these patients (50%) were diagnosed by routine upper tract imaging, whereas the other two patients (50%) were diagnosed after detection of hydronephrosis on ultrasound (n=1) or hematuria (n=1). Overall 115 routine upper tract CT scans had to be performed to detect one UTUC. Conclusions In our cohort the prevalence of UTUC was only 1.2%. Interestingly, all UTUCs were diagnosed in LG NMIBC patients, questioning the recommendation to perform upper tract surveillance exclusively in high-risk BC. Of the patients diagnosed with UTUC only half was detected by routine upper tract imaging. A large-scale prospective study is warranted to assess the role of upper tract surveillance in general and to define the optimal modalities for UTUC detection. Funding none
Authors
Benedikt Kranzbühler
Uwe Bieri Cédric Poyet Burkhardt Seifert Tullio Sulser Thomas Hermanns |
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PD19-03 |
The value of immediate post-operative intravesical epirubicin instillation in intermediate and high risk non muscle invasive bladder cancer (NMIBC): a randomized controlled trial |
Bladder Cancer: Non-invasive II | 17BOS |
Abstract: PD19-03 Sources of Funding: None Introduction There are insufficient data supporting the general recommendation of the European Association of Urology (EAU) that “all” patients with NMIBC should receive immediate instillation of chemotherapy after transurethral resection of bladder tumor (TURBT). The study objective is to test the value of immediate post-operative intravesical instillation of epirubicin in patients with intermediate and high risk NMIBC. Methods After approval of the institutional review board, 260 patients were randomly allocated into two groups, including TURBT alone in arm A and TURBT plus epirubicin 50 mg in 50 ml saline in arm B. All patients were monitored for post-operative complications. Adjuvant instillation therapy was administered to all patients according to risk categorization. Patients were followed every three months by cystourethroscopy and urine cytology. The primary end points were recurrence, progression and/or death from cancer. Results Of the 260 patients, 236 were eligible and followed for a mean of 19.6 months. The two study arms were comparable regarding perioperative baseline demographic criteria. Intermediate and high risk groups were defined in 24 and 94 patients in arm A, compared to 28 and 90 in arm B (p=0.64). There was no statistically significant difference between the two arms regarding recurrence rate (27.1% vs. 26.2%), interval to first recurrence (16.3±6.6 vs. 16.4±6.4 months) or progression rate to muscle invasion (8.5% vs. 5.9%). Number of recurrences, size, site and associated CIS in the first recurrence were also comparable between the two arms. Using the 1973 WHO grading system, the number of patients with grade 3 recurrence was higher in arm A (18 patients) than arm B (7 patients). However, using the 2004 WHO/ISUP system, there was no significant difference in the recurrence grade. Recurrence and progression-free survival were comparable between the two arms (Log-rank test; p=0.88 and 0.47, respectively). According to modified Dindo-Clavian system, post-operative complications were all low grade. There was no significant difference between the two arms, regarding the rate and the grade of the reported complications. Conclusions These data indicate that immediate post-TURBT instillation of epirubicin is ineffective in intermediate and high risk NMIBC. It neither prolongs time to recurrence, time to progression nor reduces the number of recurrences. We advocate strict specification of patient and tumor criteria in which immediate instillation is indicated. Funding None
Authors
Amr A El-Sawy
Ahmed M El-Assmy Mahmoud A Bazeed Bedeir Ali-El-Dein |
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PD19-04 |
Immediate intravesical chemotherapy for low grade bladder tumors in California: An underutilized practice and its impact on recurrence |
Bladder Cancer: Non-invasive II | 17BOS |
Abstract: PD19-04 Sources of Funding: University of California, Davis Academic Senate Introduction The use of intravesical chemotherapy (IC) immediately following transurethral resection of bladder tumor (TURBT) for low grade (LG) non muscle invasive bladder cancer (NMIBC) has been well demonstrated to reduce local recurrence and is supported by current guidelines. We sought to demonstrate patterns of uptake for this practice as well as its impact on outcomes at a population level as an initial step in developing quality improvement initiates in NMIBC. Methods Incident cases of LG Ta or T1 NMIBC diagnosed between 2005 and 2012 were identified from the California Cancer Registry and linked to hospital records of the Office of Statewide Health Planning and Development. Tumor, patient, and hospital characteristics were included in the analysis. We determined rates of IC utilization following TURBT in patients with LG Ta or T1 NMIBC. Multivariable logistic regression models were utilized to determine predictors of IC utilization. Cumulative incidence functions and Cox Proportional Hazards (PH) models were used to determine predictors of recurrence-free survival (RFS), bladder cancer-specific survival (CSS), and overall survival (OS) with utilization of IC as the primary effector variable. Results The final cohort consisted of 10,031 patients with LG NMIBC diagnosed in California between 2005 and 2012, with initial TURBT ≤ 45 days from diagnosis. The overall rate of IC utilization was 5.1%, but demonstrated an increase from 1.7% (2005-2006) to 9.6% (2011-2012). On multivariable logistic regression analysis, variables associated with increased odds of immediate IC instillation included more recent year of diagnosis (OR 1.74, CI 1.60-1.90 for 2 year increments). Factors associated with lower odds of receiving IC included Hispanic race (OR 0.62, CI 0.43-0.88) and Asian/Pacific Islander race (OR 0.58, CI 0.37-0.91). The cumulative incidence of recurrence at 24 months for patients who received IC was 25.2% compared to 30.2% among those that did not receive IC. On multivariable Cox PH analysis, use of IC was significantly associated with an 18% improvement in RFS (HR 0.82, CI 0.70-0.97). Conclusions Utilization of IC for LG NMIBC remains dismally low in routine practice, with less than 10% of patients receiving this standard of care even in more recent years. Poor utilization of this practice is associated with increased rates of recurrence. Strategies utilizing robust implementation of scientific methods should be studied as a means to overcome a major shortcoming in the quality of care provided to patients with LG NMIBC. Funding University of California, Davis Academic Senate
Authors
Stanley Yap
Ann Brunson Neil Pugashetti Rosemary Cress Theresa Keegan Ralph DeVere White Ted Wun |
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PD19-05 |
The benefit of continuous saline bladder irrigation after transurethral resection in high grade non-muscular invasive bladder cancer - a single center randomized prospective study |
Bladder Cancer: Non-invasive II | 17BOS |
Abstract: PD19-05 Sources of Funding: None Introduction We have reported the efficacy and safety of continuous saline bladder irrigation (CSBI) after transurethral resection of bladder tumor (TURBT) in low grade non-muscle invasive bladder cancer (NMIBC) (Onishi T et al. AUA 2016 Annual Meeting, BJU Int, 2016). The aim of this study was to evaluate the efficacy and safety of CSBI after TURBT in patients with high grade NMIBC. Methods In this prospective randomized study, 226 patients with presumed primary NMIBC eligible for TURBT were enrolled. Patients were randomly allocated to receive CSBI (2,000 ml/h for first 1 hour, then 1,000 ml/h for 2 hours, and then 500 ml/h for 15 hours) or a single immediate instillation of mitomycin C (MMC) after TURBT. The patients with high grade NMIBC were subjected to analyses. Primary end point is recurrence-free survival, and secondary end points were progression-free survival and adverse events. Results A total of 147 patients (75 in CSBI group and 72 in MMC group) remained for analysis after exclusion criteria had been applied. The median follow-up period was 36 months. No significant differences in patients’ characteristics were observed between the groups. The 5-year recurrence-free rates for CSBI and MMC were 60.5% (95% confidence interval [CI]: 0.48-0.70) and 67.2% (95% CI: 0.54-0.77), respectively. Kaplan-Meire analysis of recurrence-free survival did not show any significant differences between the groups (log rank test: P=0.56). Furthermore, there were no significant differences between the groups in terms of tumor progression rate and the median time to first recurrence. The incidence of adverse events was significantly lower in CSBI group (8.0% vs 34.7%, P<0.001). Conclusions The results show that CSBI after TURBT may be a treatment option even for patients with high grade NMIBC in terms of its prophylactic effect and safety. Funding None
Authors
Takehisa Onishi
Takuji Shibahara Masahiko Nishii Masaki Yoshikawa Tadashi Yabana Katunori Utida |
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PD19-06 |
High-risk non-muscle invasive bladder cancer (HR-NMIBC) treated with sequential BCG / Electromotive Drug Administration Mitomycin-C (EMDA-MMC): 2% disease-specific mortality at 4 years’ follow-up |
Bladder Cancer: Non-invasive II | 17BOS |
Abstract: PD19-06 Sources of Funding: None Introduction Sequential BCG/EMDA-MMC was previously reported to be superior to BCG alone, and since 2009, has been the standard induction regimen in our institution for the treatment of HR-NMIBC. We now present medium-term outcomes from this study. Methods From June 2009 to June 2013, all patients undergoing bladder conservation for HR-NMIBC were offered sequential BCG/EMDA-MMC. BCG (Immucyst until June 2012, Oncotice since Sept 2012) was given in weeks 1 and 2, and EMDA-MMC (40mg, intravesical current 20mA for 30 mins) in week 3, and this cycle was repeated 3 times for a total of 9 weeks. Maintenance treatment was with 3 doses of BCG every 6 months, commencing 3 months after induction. Response was assessed by GA cystoscopy 8 weeks post induction, followed by 6-monthly flexible cystoscopy. Results 151 patients with HR-NMIBC were treated, of whom 44 (29%) received primary cystectomy, leaving 107 patients (71%) treated with sequential BCG/EMDA-MMC. 86/107 (80%) had high grade Ta/T1 disease, of whom 34 (32%) also had carcinoma in situ (CIS). 19/107 (18%) had primary CIS. 2 (2%) had recurrent, large volume, low grade disease. Median length of follow-up was 47 months (range 4-87 months). 1 patient was lost to follow-up immediately after induction and was excluded from analysis. _x000D_ _x000D_ Overall, 37/106 (35%) patients had disease recurrence. 7/106 (7%) had disease progression, of whom 2/106 (2%) progressed to higher stage NMIBC, 3/106 (3%) progressed to muscle invasive bladder cancer (MIBC), and 2/106 (2%) developed distant metastases. 11/106 (10%) eventually underwent cystectomy for the following reasons: progression to MIBC (3/11), disease recurrence (7/11) and severe bladder storage symptoms (1/11). 17/106 patients (16%) have died, of which 2/106 (2%) died from bladder cancer. _x000D_ _x000D_ As previously reported, 30/107 patients were unable to complete the full 9-dose induction schedule, 16/30 directly due to side effects. There was no significant difference in recurrence rates between patients who received a full (36%) versus a reduced (30%) induction schedule (X2=0.39, p=0.53)._x000D_ Conclusions Despite the challenge of a 4-year recurrence rate of 35%, a low progression rate to muscle-invasive and metastatic disease of 5% and disease-specific mortality of 2% continue to attest to the oncological efficacy of sequential BCG/EMDA-MMC. Funding None
Authors
Christine Gan
Suzanne Amery Kathryn Chatterton Muhammad Shamim Khan Kay Thomas Tim O' Brien |
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PD19-07 |
One-year follow-up results after sequential intravesical bacillus Calmette-Guérin and device-assisted chemo-hyperthermia (Mitomycin C delivered by the Combat BRS system) for high risk non-muscle invasive bladder cancer patients...a bacillus Calmette-Guérin-sparing strategy |
Bladder Cancer: Non-invasive II | 17BOS |
Abstract: PD19-07 Sources of Funding: None Introduction Until October 2014, our standard bladder-sparing treatment for high risk (HR) non-muscle invasive bladder cancer (NMIBC) was a full-dose intravesical bacillus Calmette-Guerin (BCG) 6-week induction course and maintenance BCG for 1-3 years. In response to the BCG shortage, we modified our regimen to sequential full-dose BCG and device-assisted chemo-hyperthermia (Mitomycin C [MMC] delivered by the Combat BRS system). Here we present our 1-year results after start of treatment. Methods The 6-week induction regimen became BCG (weeks 1,2), Combat BRS (weeks 3,4,5) and BCG (week 6). Nine further Combat BRS maintenance treatments were given by 1 year comprising 3 sets of weekly instillations for 3 weeks. We reviewed the 1-year follow-up results of 50 HR-NMIBC (high grade [grade 3] and/or carcinoma in situ [CIS]) patients who commenced treatment between October 2014 and September 2015. T1 tumours represented 62% of cases and were routinely re-resected. CIS was detected in 40% of cases. We excluded 11 patients from this series who had concurrent upper urinary tract or prostatic urothelial tumours, previous radiotherapy or BCG or a course of MMC. Results Of 50 patients, 44 (88%) were disease-free by 1 year; 3 (6%) had refractory HR-NMIBC at 6 months, 2 (4%) progressed to MIBC by 6 months and 1 (2%) presented with metastatic disease at 1 year. All 6 had CIS and/or T1 at diagnosis. Forty-three patients (86%) tolerated Combat BRS treatment; 2 reacted with rashes during maintenance and 5 had bladder-related tolerability issues. Conclusions Our oncological results with sequential BCG/Combat BRS at 1 year are at least comparative at this time-point with those expected for HR-NMIBC patients on maintenance BCG. Tolerability and compliance shows great promise. Funding None
Authors
TR Leyshon Griffiths
William JF Green Peter T Grice Jonathan C Goddard Roger C Kockelbergh |
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PD19-08 |
Radiofrequency-induced thermo-chemotherapy effect (RITE) plus mitomycin versus a second course of bacillus Calmette-Guérin (BCG) or institutional standard in patients with recurrence of non-muscle invasive bladder cancer following induction or maintenance BCG therapy (HYMN): A open-label, multicentre, phase III randomised controlled trial |
Bladder Cancer: Non-invasive II | 17BOS |
Abstract: PD19-08 Sources of Funding: Cancer Research UK funded the trial administration (trial number CRUK/09/012). Kyowa Hakko UK Ltd kindly gave the trial a total of GBP75,000 which helped to fund the procurement and maintenance costs of the Synergo system. Medical Enterprises Europe B.V. supplied the Synergo system at a discounted rate and its associated disposables to the participating sites. All funders had no role in the study design, data collection, data analysis, data interpretation, writing of the report and in the decision to submit the paper for publication. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication. Introduction Despite maintenance BCG, ≥50% of patients will develop bladder cancer recurrence and 10-20% will progress within 52 months. There is no effective second-line therapy for NMIBC following BCG failure. The combination of intravesical mitomycin-C (MMC) with RITE has shown efficacy when compared to BCG. This study aims to determine whether RITE improves disease-free survival (DFS) compared to standard of care in patients with recurrence of NMIBC following BCG. Methods This multicentre, open-label, phase III randomised controlled trial was performed in 14 UK centres (ClinicalTrials.gov: NCT01094964). Patients with NMIBC who developed recurrence following BCG induction/ maintenance therapy were randomly assigned (1:1) to either RITE (60 min, 40 mg mitomycin-C at 42°C) using the Synergo® SB-TS 101 System or a second course of BCG/ institutional standard. All patients had complete resection of papillary visible tumours and must be either unfit or unwilling to have radical cystectomy. Randomisation was stratified by centre, CIS and prior BCG response. Primary outcomes were DFS and complete response (CR) at three months in patients with CIS at randomisation. A log-rank test was performed to compare arms on an intention-to-treat basis. Results Between May 2010 and July 2013, 104 patients were randomised. 48 (46%) assigned to RITE and 56 (54%) control. Median DFS was 35.1 months (IQR: 23.1-445.3 months) with no difference between treatment arms (HR 1.32, [0.83-2.1], p=0.23). Three-month CR in CIS patients for both treatment arms were similar (RITE: 75% vs control: 80%, p=0.62). DFS in patients with papillary-only disease was higher in RITE patients (HR 0.42, [0.19-1.03], p=0.0531) but not significantly different in CIS-only patients (HR 1.61, [0.8-3.2], p=0.17). Papillary disease and concurrent CIS patients had significantly better DFS in the control arm (HR 6.9, [2.06-23.25], p<0.001). No difference in adverse events between treatment arms were observed. Conclusions The HYMN trial did not show an overall difference between RITE and the control arm. However, there was a benefit for RITE in participants with papillary-only disease. RITE was well tolerated with comparable adverse events compared with BCG. Further trials are needed to investigate the efficacy of RITE in CIS patients. Funding Cancer Research UK funded the trial administration (trial number CRUK/09/012). Kyowa Hakko UK Ltd kindly gave the trial a total of GBP75,000 which helped to fund the procurement and maintenance costs of the Synergo system. Medical Enterprises Europe B.V. supplied the Synergo system at a discounted rate and its associated disposables to the participating sites. All funders had no role in the study design, data collection, data analysis, data interpretation, writing of the report and in the decision to submit the paper for publication. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.
Authors
Wei Shen Tan
Laura Buckley Adam Devall Laurence Loubière Ann Pope Mark Feneley Jo Cresswell Rami Issa Hugh Mostafid Sanjeev Madaan Rupesh Bhatt John McGrath Vijay Sangar Leyshon Griffiths Toby Page Dominic Hodgson Shibs Datta Lucinda Billingham John Kelly |
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PD19-09 |
Performance of a novel urine-based biomarker for the monitoring of bladder cancer recurrence |
Bladder Cancer: Non-invasive II | 17BOS |
Abstract: PD19-09 Sources of Funding: Zetiq Technologies Ltd. Introduction The accurate detection of low-grade (LG) urothelial cell carcinoma (UCC) may be challenging, particularly in cases where cytomorphologic features overlap with those of non-neoplastic changes. _x000D_ CellDetect is a unique histochemical stain which enables color discrimination, in addition to morphological examination, for the differentiation between benign and malignant cells in urine specimens. A multi-institutional blinded study has recently shown that this color feature significantly improves the sensitivity for LG tumors when compared to standard urine cytology. The objective of the present study was to confirm this performance in an independent cytology laboratory. Methods Voided urine samples were collected from a first cohort of patients undergoing routine cystoscopic surveillance. To enrich the study with positive cases, a second cohort of patients scheduled for transurethral resection (TURBT) was also enrolled. The patients from both cohorts had a documented history of bladder cancer. _x000D_ Urine samples were processed into two cytocentrifuge smears and each slide was stained with either CellDetect or standard cytology stain. Both specimens were observed by a cytopathologist blinded to the final diagnosis. The results were then compared to the gold standard (biopsy for positive cases and biopsy or cystoscopy for negative cases). Results 73 patients were enrolled in this study, among which 51 were UCC-negative and 22 UCC-positive. The sensitivity of CellDetect was 82% compared to 59% for standard cytology (p<0.05) while the specificity was not significantly different (86% versus 94%). Moreover, the urine-based biomarker was able to detect 73% of the LG tumors compared to 45% by standard cytology. In addition, it correctly diagnosed 91% of the HG tumors compared to 73% for standard stain._x000D_ _x000D_ Conclusions This study validates the usability of CellDetect in clinical settings. Particularly, it confirms its ability to accurately identify UCC recurrence throughout all cancer grades. This could be particularly useful in LG cases where cytomorphologic criteria overlap with benign reactive conditions. Funding Zetiq Technologies Ltd.
Authors
Ofer Nativ
Sarel Halachmi Kohava Biton Marina Zlotnik Chen Yoffe Noa Davis Yael Glickman Jacob Bejar |
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PD19-10 |
The Chemoablative Effect of VesiGel Instillation in Patients with NMIBC – Response Rate and 1-Year Durability |
Bladder Cancer: Non-invasive II | 17BOS |
Abstract: PD19-10 Sources of Funding: UroGen Pharma, Ra'anana, Israel Introduction Endoscopic resection of low-grade (LG) tumors in patients with non-muscle invasive bladder cancer (NMIBC) is limited by incomplete imaging of all lesions, deep resections that preclude use of immediate intravesical therapy, and significant pain that hastens drainage of any intravesical agent. VesiGel, a novel sustained release thermosensitive hydrogel formulation of Mitomycin C (MMC), was developed to overcome these limitations. This study evaluated the primary chemoablative properties of VesiGel in the treatment of patients with LG NMIBC as an alternative to transurethral resection of bladder tumor (TURBT). Methods 64 patients with LG NMIBC who were all eligible for TURBT were enrolled in the study after informed consent was obtained. The study consisted of 3 groups: Group A- VesiGel 0.06% (40mg at 64mL gel; n=20); Group B- VesiGel 0.12% (80mg at 64mL gel; n=22), and Group C- MMC 0.1% (40mg in 40mL water; n=23). All patients underwent 6 weekly instillations. Response was evaluated 2-4 weeks after the last instillation via cystoscopy and biopsy. Patients who demonstrated a CR were followed without any additional treatment. Recurrence and follow up were calculated based on the first cystoscopy documenting a CR. Kaplan Meier survival analysis was used to compare recurrence free survival (RFS). Results CR rate was 45.0%, 86.4% and 69.6% in groups A, B and C, respectively. For patients with smaller tumors (size ≤1cm2), the CR rate was 50.0%, 87.5% and 77.8%, respectively. For larger tumors (>1cm2), the CR was 40%, 83.3% and 40.0%, respectively. For patients with ≤3 tumors, the CR rate was 50.0%, 81.3% and 80.0%, while for patients with >3 tumors, the CR rate was 0%, 100% and 50%, respectively. Of the 44 patients with a CR, 36 had follow up data available. Kaplan-Meier survival analysis showed no difference in RFS between groups (log rank test: p=0.46). Conclusions These preliminary results provide an initial indication of the ablative effect of VesiGel and its potential use as an alternative to TURBT. Compared with aqueous MMC 0.1%, VesiGel 0.12% was superior in the treatment of larger and multifocal tumors. Durability data has yet to mature but is promising given the higher predicted 1-year recurrence scores for patients in the VesiGel 0.12% group. Funding UroGen Pharma, Ra'anana, Israel
Authors
Andrew Lenis
Karim Chamie Boris Friedman Andrea Tubaro Ami Sidi Daniel Kedar Lorenzo Colombo Dov Engelstein Joan Palau Gregory Wirth Ilan Leibovitch Eddy Fridman Ifat Klein Michal Jeshurun Fred Witjes |
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PD19-11 |
What false-negative rates are bladder cancer patients and uro-oncologists willing to accept in order to avoid surveillance cystoscopy? |
Bladder Cancer: Non-invasive II | 17BOS |
Abstract: PD19-11 Sources of Funding: None Introduction Surveillance cystoscopy in patients with non-muscle invasive bladder cancer is associated with pain, anxiety, and often necessitates antibiotic prophylaxis. Novel imaging and blood/urine based non-invasive alternatives are being developed to detect bladder cancer recurrence/progression in this patient population. We conducted a questionnaire-based hypothetical study to determine what test performance characteristics and cost would a non-invasive test(s) need in order for patients and their physicians to avoid cystoscopy. Methods A questionnaire was administered to two populations (patients with previous history of non-muscle invasive bladder cancer and uro-oncologists) to establish an acceptable false negative (FN) rate and cost for such test(s). Patients were surveyed at time of follow up in the cystoscopy clinic at Toronto General Hospital. Physician members of the Society of Urologic Oncology were surveyed via an online questionnaire. Participants were questioned regarding demographics and other characteristics that might influence chosen error rate and cost. A chi-square test was used to determine if such relationships exist. Statistical significance was set at p <0.05. Results 137 patient and 51 physician responses were obtained. 102 (75%) of the patients were male and 35 (25%) were female. 77% of patients were not comfortable with a non-invasive test(s) in place of repeat cystoscopy, with a further 14% requesting a false-negative (FN) rate of 0.5% or better. 75% of uro-oncologists were comfortable with an alternative non-invasive test, with 31% of responders requesting a FN rate of 5% or better and 33% a FN rate of 1% or better. A cost of $100-500 was deemed appropriate by 61% of physician responders. Demographics and other participant characteristics did not influence FN rate or cost choices. Conclusions Majority of bladder cancer patients are not comfortable with a non-invasive test(s) in place of surveillance cystoscopy, as opposed to most uro-oncologists who are. Given the importance of patient input in clinical decision-making, it appears that non-invasive tests will not replace surveillance cystoscopies in the near future, unless they achieve equivalent accuracy. Funding None
Authors
Rashid Sayyid
Abdallah Sayyid Ricardo Leao Ardalanejaz Ahmad Hanan Goldberg Robert Hamilton Girish Kulkarni Antonio Finelli Alexandre Zlotta Neil Fleshner |
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PD19-12 |
The RevoLix(TM) 2??m continuous wave laser en bloc enucleation for nonmuscle-invasive bladder cancer |
Bladder Cancer: Non-invasive II | 17BOS |
Abstract: PD19-12 Sources of Funding: None Introduction The purpose of this study was to evaluate the safety and short-term outcome of laser en bloc enucleation using the The RevoLix(TM) 2??m continuous wave (CW) laser in the treatment of nonmuscle-invasive bladder cancer (NMIBC). Methods From October 2015 to March 2016, 28 patients (19 males and 9 females) with a single papillary NMIBC were selected for 2 ?m CW laser en bloc enucleation. The mean tumor diameter was 1.8 cm (range 0.5-4.0 cm). We used glass rinsing bottle to obtain the en bloc tumor. Peri-operative data and oncological results were retrospectively collected. Results All surgeries were successfully completed. There was no major complication such as bladder hemorrhage, vesicle perforation, or obturator nerve reflex occurrence during the operation. Mean operative time was 26.7 minutes (range 16-37 minutes). No significant intraoperative or postoperative bleeding occurred in all cases. The stages of bladder cancer included 15 Ta and 13 T1. With the 6 to 12 months follow-up, no tumor recurrence was observed. Conclusions The 2??m CW laser en bloc enucleation is a safe and effective option for the treatment of NMIBC. All the different intravesical sites of the NMIBC can be enucleated with 2??m CW laser. Moreover, it may improve the accurate valuation of tumor stage. Although the long-term outcomes are still unknown, the short-term oncological outcomes are satisfactory. Funding None
Authors
Hai Bi
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PD20-01 |
Outcomes of radical nephrectomy with level IV tumor thrombus using cardiopulmonary bypass |
Kidney Cancer: Localized: Surgical Therapy I | 17BOS |
Abstract: PD20-01 Sources of Funding: None Introduction Upwards of 15% of cases of renal cell carcinoma (RCC) have vascular involvement at diagnosis. While tumor thrombus is often limited to the ipsilateral renal vein, about 1% extend though the IVC into the right atrium. Complete surgical resection is the mainstay of treatment, but few centers have experience with such advanced disease. We examine our experience with resection of level IV tumor thrombus using cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA). Methods Twenty two consecutive patients who underwent resection of RCC with cavoatrial thrombectomy using DHCA at a single tertiary center from 2000-2016 were analyzed. Complications within 30 and 90 days were captured and classified using the Clavien-Dindo system. Overall survival (OS), cancer-specific survival (CSS), and recurrence free survival (RFS) estimates were generated using Kaplan-Meier analysis. Results Median age was 63 years (IQR 54.5-66.5) and 13 (59%) patients were male. Median tumor size was 8.75 cm (6.25-11.75) and 14 (64%) were right sided. Surgical pathology revealed 4 tumors (18%) were pT4, while the remainder were pT3c. 77% of tumors were clear cell, while the remainder were papillary. Of the 12 patients who underwent regional lymphadenectomy, 33% had LN+ disease. Five patients (23%) had ipsilateral adrenal involvement, while 4 (18%) had non adrenal metastatic involvement, most commonly the liver (50%). Positive surgical margin was present in 77% of cases, most commonly involving the renal vein. Patients received a median 6 units of PRBC intra-op, with a CPB time of 136 (120.5-148.75) minutes. Median length of stay was 13 days (8-14). Two patients (9%) experienced peri-operative mortality, while 31.8% and 36.4% of patients experienced major complications, respectively. Most commonly encountered major complications were pulmonary (9%), re-exploration for bleeding (9%) and renal failure requiring dialysis 3 (13.6%). Kaplan-Meier analysis revealed OS, CSS, and RFS estimates at 22 mo (95% CI 0.79.7), 41 mo (95% CI 0-92), and 16 mo (95% CI 0.1-31.9) respectively. Conclusions Surgical resection for patients with level IV tumor thrombus using CPB and DHCA can be accomplished with acceptable morbidity and mortality. Overall prognosis remains poor, but improvement in surgical morbidity by experienced multi-disciplinary teams paves the way for the possibility of multi-modal treatments combining surgery with newer targeted and/or immunotherapy agents. Funding None
Authors
David Golombos
Christopher Lau Padraic O'Malley Abimbola Ayangbesan Patrick Lewicki LaMont Barlow Leonard Girardi Douglas Scherr |
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PD20-02 |
Laparoscopic inferior vena cava thrombus surgery by pure retroperitoneal approach |
Kidney Cancer: Localized: Surgical Therapy I | 17BOS |
Abstract: PD20-02 Sources of Funding: None Introduction Management of renal cell carcinoma (RCC) with tumor thrombus extending to the renal vein and inferior vena cava (IVC) is very challenging. The aim of this study was to evaluate the benefit of pure retroperitoneal laparoscopic radical nephrectomy with inferior vena cava thrombectomy in such patients. Methods From Jan 2014 to Sep 2016, 18 patients underwent laparoscopic radical nephrectomy for renal cell cancer combined with tumor thrombus of the inferior vena cava. Thrombus extension classified by the Mayo Clinic and the 2009 TNM classifications, complications, postoperative management, and survival results were analyzed. The surgeries were preformed by retroperitoneal approach totally. For substantial level I-II involvement, complete caval isolation, including laparoscopic control of infra-renal and supra-renal IVC, contra-lateral renal vein and lumbar veins was performed. ? Following thrombus extraction, the cavotomy was repaired with 4-0 prolene suture on RB-1 needle. Results Of these patients, 8 patients had level I, 10 had level II thrombi according to the Mayo Clinic staging. Totally retroperitoneal laparoscopic approach was performed in patients with stage I to II thrombi. There was no intraoperative mortality and open conversion. The median follow-up interval was 13.6 months. Metastatic diseases did not develop in any patient. Conclusions The tumor thrombus level with IVC determines the surgical approach and method. Our results show that Mayo level I-II caval vein tumor thrombus can be safely surgically treated by pure retroperitoneal laparotomy. Funding None
Authors
Shudong Zhang
Lulin Ma Lei Liu Yu Tian |
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PD20-03 |
Robotic Inferior Vena Cava Thrombectomy in 64 Patients: Predictors of Intra-operative Efficiency |
Kidney Cancer: Localized: Surgical Therapy I | 17BOS |
Abstract: PD20-03 Sources of Funding: none Introduction Inferior vena cava (IVC) tumor thrombectomy for kidney cancer is one of the most challenging urologic oncologic operations, routinely performed open. After reporting the initial series of level III robotic IVC thrombectomy (J Urol. 2015; 194, 929), we have standardized our technique across 3 institutions. Herein, we report the largest series to date (n=64) and identify clinical parameters that predict intraoperative efficiency and success._x000D_ _x000D_ Methods This is an IRB-approved, 3-center, retrospective analysis of prospectively-collected data. 64 consecutive patients with level I-III IVC tumor thrombus underwent robotic IVC thrombectomy (01/2011 to 10/2016): Level I (2, 3.1%), Level II (52, 81.2%), Level III (10, 15.6%). Patient demographics, imaging data, intraoperative parameters, pathology data, complications, and oncologic outcomes were collected. Results Robotic IVC thrombectomy was successful in 63 patients (98%); 1 patient was electively converted to open surgery for failure to progress. Median BMI was 25 kg/m2 (21-42) and ASA score was 2 (1-4). Primary kidney tumor was left-sided in 14 patients (21%). Median IVC thrombus length was 4 cm (1.5-12). Median operative time was 4 hrs (1-8), estimated blood loss (EBL) 260cc (20-7,000), peri-operative transfusion rate 21.5% (median/mean units transfused/patient = 0/1.2) and hospital stay 6 days (1-32). Complications occurred in 8 patients (12%): Clavien 3a (2), Clavien 3b (2), Clavien 4 (4). Pathology revealed renal cell carcinoma (n=63) and adult Wilms&[prime] tumor (n=1). One-year cancer-specific and overall survival rates were 100% and 97.9%._x000D_ _x000D_ &[prime]Trifecta&[prime] of operative efficiency was defined as realization of the following 3 parameters: OR time < 4 hrs, no transfusions and no complications. Trifecta outcome was achieved in 24 patients (38%). Characteristics of patients in whom trifecta was achieved were: thrombus level II (100%), thrombus characteristics: no arterialization, no caval wall involvement, no projection into contralateral renal vein (92-96%), right-sided primary renal tumor (92%), no bland tumor thrombus (88%) and complete occlusion of IVC (0%). In the trifecta group, median thrombus length and diameter were 4 cm and 2.4 cm, respectively, median EBL was 165cc. With increasing experience, there were no discernible trends regarding operative time, EBL, or complications._x000D_ Conclusions This is the largest series to date of robotic IVC thrombectomy surgery. This is a safe and feasible procedure when performed by experienced surgeons. Additional follow up is needed to determine long-term oncologic outcomes._x000D_ Funding none
Authors
David Hatcher
Xin Ma Giuseppe Simone Salvatore Guaglianone Mariaconsiglia Ferriero Baojun Wang Michele Gallucci Xu Zhang Inderbir Gill |
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PD20-04 |
Perioperative outcomes of robotic and open partial nephrectomy for moderately and highly complex T1b renal tumors |
Kidney Cancer: Localized: Surgical Therapy I | 17BOS |
Abstract: PD20-04 Sources of Funding: None Introduction Robotic approach is well-accepted standard for cT1a, however some urologists may question it for more complex cT1b lesions. We aimed to compare outcomes between robotic partial nephrectomy (RPN) and open partial nephrectomy (OPN) for moderately or highly complex (RENAL Score ≥7) T1b tumors. Methods We retrospectively reviewed 1230 consecutive cases, consisting of 823 RPN and 407 OPN, performed for renal mass at a single academic tertiary center between 2011 and 2016. Of these, data on 143 RPN and 78 OPN cases for moderately or highly complex T1b tumors. Baseline patient factors, and tumor characteristics, operative, postoperative, functional and oncologic outcomes were compared between groups. Results Apart from a higher age among OPN cases (59.7 vs. 64.2 yrs. p=0.01), demographic characteristics were similar between groups. No statistically significant differences were seen in tumor size (p=0.54) or margin status (p=0.83) between groups. The patients in the RPN group had less estimated blood loss (150 vs. 300 cc, p<0.01), lower intraoperative transfusion rates (2.1% vs. 12.8%, p<0.01), and shorter length of stay (3 vs. 5 days, p<0.01). Patients who underwent RPN were found to have lower overall (Clavien grade 1-5; 18.9 vs. 39.7 %, p<0.01), and lower major (Clavien grade 3-5; 4.2 vs. 15.4 %, p<0.01) complication rates. Multivariable logistic regression analysis demonstrated open approach (OR 2.8, CI 1.4-5.4, p=0.002) and high BMI (OR 1.05, CI 1.01-1.1, p=0.01) to be independent factors for overall complications. There was no difference in estimated glomerular filtration rate preservation rates between groups for early (p=0.2) and latest (p=0.1) functional follow-up. Oncological outcomes were similar between the two groups. Conclusions For moderately or highly complex T1b tumors RPN appears to be a safe and effective alternative to OPN with the advantages of shorter length of stay and less blood loss. Funding None
Authors
Önder Kara
Matthew J. Maurice Pascal Mouracade Ercan Malkoç Julien Dagenais Ryan J. Nelson Jaya Sai Chavali Khaled Fareed Robert J. Stein Amr Fergany Jihad H. Kaouk |
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PD20-05 |
Comparison between Partial Nephrectomy and Radical Nephrectomy for T2N0M0 Tumors, a Study Based on the National Cancer Database |
Kidney Cancer: Localized: Surgical Therapy I | 17BOS |
Abstract: PD20-05 Sources of Funding: none Introduction The role of partial nephrectomy (PN) for T2 renal tumors is less established. We reviewed the National Cancer Database (NCDB) to compare the complications and overall survivals of PN and RN for T2N0M0 tumors. Methods We reviewed the NCDB from 2004 to 2014 to identify all T2N0M0 renal cancers treated with partial or radical nephrectomies. Variables of interest included patient demographics, tumor characteristics, margin status, conversion from minimally invasive (MIS) to open approach, length of stay, 30-day unplanned readmissions and overall survival. The hazard ratios (HR) of variables on survivals were determined by Cox regression analysis. Survival curves were plotted. p-value <0.05 defined statistical significance in all analyses. Results A total of 22586 patients had T2N0M0 renal cancer treated with PN or RN._x000D_ _x000D_ Table 1 shows patient demographics and tumor characteristics between the groups._x000D_ _x000D_ Table 2 shows margins status, conversion from MIS to open approach, length of stay and 30-day unplanned readmissions between the groups._x000D_ _x000D_ Mean duration of follow-up was 44.4 months and 48.4 months for PN and RN respectively. Diagram 1 shows overall survival curves in the 2 groups (p < 0.0005 by Log rank, Breslow & Tarone-Ware tests)._x000D_ _x000D_ Table 3 shows HR of variables on overall survival by Cox regression analysis. Age, Charlson score, tumor size, histology and grade exert significant effects on survival. A clear survival trend is also seen with socioeconomic status based on income and education, but may not achieve statistical significance. Conclusions While associated with a slightly higher positive margin rate and longer mean duration of stay, PN results in better overall survival than RN for T2N0M0 renal tumors. Funding none
Authors
Cheuk Fan Shum
Clinton D Bahler Chandru P Sundaram |
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PD20-06 |
THE ONCOLOGIC OUTCOMES OF PARTIAL NEPHRECTOMY FOR pT3 RENAL CELL CARCINOMA |
Kidney Cancer: Localized: Surgical Therapy I | 17BOS |
Abstract: PD20-06 Sources of Funding: none Introduction Partial Nephrectomy (PN) is a well established treatment for small localized disease – pT1a tumors. Better renal function compared to radical nephrectomy (RN), with similar oncologic control, expanded the PN indication for larger and more complex tumors in some reference institution, including pT3a. The role of PN in this type of tumor still unknown and the potential risk of positive margins and negative outcomes are uncertain. We performed this study to assess the impact of PN on outcomes among patients with pT3a tumors Methods 692 patients underwent PN or RN from 2005 to 2016 at MSKCC and expressed a pathological stage of pT3a. 18 patients with metastasis at diagnosis, 1 patient with a single kidney, 1 patient with hereditary cancer syndrome and 68 patients with histology other than Clear Cell, Chromophobe, or Papillary were excluded. Group comparisons were made using Wilcoxon rank-sum and Fisher’s exact test for continuous and categorical variables, respectively. Outcomes of interest included estimated blood loss, warm ischemia time, estimated glomerular filtration rate at 6 months, length of stay, margin status, Fuhrman grade, tumor size, pathological histology, and symptoms index at presentation Results Among our cohort, 376 (62%) and 228 (38%) patients with were scheduled for RN and PN, respectively. Of the 228 patients originally scheduled for PN, 12% were converted to RN intraoperatively. A smaller proportion of patients scheduled to undergo PN had clear cell/conventional histology (77% vs 88%; p=0.001) on pathology compared to patients scheduled for RN. Among patients with clear cell or papillary histology, a larger proportion of patients scheduled for PN had lower Fuhrman grade (24% vs 10.3% had FG 1 or 2; p<0.0001) on pathology than patients scheduled for RN. Of our 604 patients, 111 patients died, 33 from kidney disease. The median follow up time for survivors was 2.0 years from surgery. On multivariable analysis, scheduled PN was non-significantly associated with better OS (HR 0.62; 95% C.I. 0.37, 1.03; p = 0.064), better CSS (HR 0.51; 95% C.I. 0.18, 1.49; p = 0.2), and better RFS (HR 0.56; 95% C.I. 0.29, 1.07; p=0.081). From the estimates of the hazard ratio, we suspect that the bias related to surgeons choosing PN or RN based on low or high risk disease is not appropriately adjusted for in our model Conclusions We found no evidence to suggest that PN has poorer outcomes than RN in patients with pT3a tumors. The inherent benefits of PN on renal function preservation make this approach very attractive even in larger and complex tumors Funding none
Authors
Ricardo Alvim
Shawn Mendonca Toshikazu Takeda Souhil Lebdai Amy Tin Melissa Assel Paul Russo Jonathan Coleman |
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PD20-07 |
Oncologic and survival outcomes for pathologic T3a upstaging in clinically localized renal masses: Does partial nephrectomy increase oncological risk? |
Kidney Cancer: Localized: Surgical Therapy I | 17BOS |
Abstract: PD20-07 Sources of Funding: Stephen Weissman Kidney Cancer Research Fund Introduction Pathological upstaging (PU) may be noted after surgical management of clinically localized renal cell carcinoma (RCC). We investigated rates and risk factors for PU in the setting of different clinical stages, as well as impact on PU recurrence and survival, and the effect of nephron sparing surgery in setting of PU. Methods Multicenter, retrospective analysis of patients with clinically localized RCC (cT1-2). Patients were stratified by presence of T3a PU and by surgical approach. Primary outcome was recurrence. Secondary outcome was overall survival (OS). Multivariable analysis (MVA) was used for recurrence, and Kaplan?Meier analysis (KMA) was utilized for recurrence free survival (RFS) and OS. Results We analyzed 2443 patients (1093 RN/1350 PN, mean follow up 69.4 months). Rate of T3a PU was 13.3% (cT1a 6.3%, cT1b 15.3%, cT2 31.6%, p<0.001). Compared to pT1-2 tumors, T3aPU had similar positive margin rates (3.0% vs. 4.3%, p=0.235) but higher rate of recurrence (7.4% vs. 31.0%, p<0.001) and all-cause mortality (16.1% vs. 27.7%, p<0.001). MVA for recurrence demonstrated T3aPU (OR 2.6, p<0.001), tumor size (OR 1.18, p<0.001), high nuclear grade (OR 1.87, p<0.001), and RN (OR 2.23, p<0.001) to be associated factors. Cumulative risk of recurrence for T3aPU plus high nuclear grade was OR 3.92 (p<0.001). KMA for RFS stratifying T3aPU by cT stage and treatment modality revealed 5 year RFS for PN vs. RN in cT1a (91.1% vs. 74.4%, p=0.063), cT1b (100.0% vs. 70.8%, p=0.031) and cT2 (44.7% vs. 43.2%, p=0.557, figure). KMA for OS stratifying T3a PU for different cT stage and treatment modality revealed 5 year OS for PN vs. RN in cT1a (95.0% vs. 83.4%, p=0.074), cT1b (100.0% vs. 74.1%, p=0.088) and cT2 (83.3% vs. 60.6%, p=0.207; figure). Conclusions Patients with T3a PU have worsened RFS and OS compared to patients with similar clinical T stage not upstaged. Recurrence and OS are not adversely affected by PN. Increasing tumor size correlates with increased risk of recurrence, and combination of high nuclear grade and PU places patients at greater risk for recurrence. Funding Stephen Weissman Kidney Cancer Research Fund
Authors
Zachary Hamilton
Deepak Pruthi Alessandro Larcher Aaron Bloch Charles Field Katherine Fero Sean Berquist Abd?elrahma Hassan Daniel Han Michael Liss Thomas McGregor Umberto Capitanio Francesco Montorsi Ithaar Derweesh |
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PD20-08 |
Oncologic Outcomes of Patients with Positive Surgical Margins after Partial Nephrectomy: A 25-Year Single Institution Experience |
Kidney Cancer: Localized: Surgical Therapy I | 17BOS |
Abstract: PD20-08 Sources of Funding: None Introduction Partial nephrectomy (PN) has become the standard treatment for small renal masses. However; it carries a risk of incomplete tumor excision and potential tumor recurrence. As such, positive surgical margins (PSMs) remain a concerning issue. We evaluated outcomes of PSMs and risk of disease recurrence in patients with clinically localized renal neoplasms undergoing PN. Methods We reviewed our database to identify patients who underwent PN between 1990 and 2015 with PSMs on final pathology. Tumors with malignant pathology were isolated and statistically analyzed for demographics and oncologic follow-up. Cancer-specific survival, overall survival and recurrence-free survival were estimated using the Kaplan-Meier method. Results A total of 2297 patients underwent PN at our institution. Of these, 50 (2.2%) patients had PSMs on final pathology. There were 30 (1.3%) patients with renal cell carcinoma (RCC) and 20 (0.9%) patients with benign tumors who had PSMs. Patient demographics for those who had PSMs with malignant pathology reported as median for age of 59 years, BMI of 31 kg/m2 and Charlson Comorbidity Index of 2. The primary tumor size was 3.2 cm (range, 2.0-10.0), nephrometry score was 8.0 (range, 5-10), and median number of resected tumors was 1.0 (range, 1-10). There were 17 (57%) patients with bilateral renal masses at presentation, of these 11 (64%) patients have had prior surgical treatment for RCC including 2 of 3 patients with hereditary RCC. Histology was most commonly clear-cell RCC in 20 (67%), stage was primarily pT1a in 21 (70%), and Fuhrman was grade 2 in 17 (57%) of these tumors. _x000D_ There were 7 (23%), and 5 (17%) patients with PSMs that developed recurrence and metastasis; respectively during a median follow-up of 57 months. Recurrence at the surgical bed was found in 3 patients whereas contralateral and bilateral kidney recurrences were found in 2 patients each. Metastases to bone and lung were found 1 and 4 patients; respectively. As projected by the Kaplan-Meier method in the population with RCC, the 5-year cancer-specific survival, overall survival and recurrence-free survival was 95.8%, 92% and 78.2%; respectively. _x000D_ Conclusions There was a low rate of PSMs in our large cohort of patients undergoing PN despite complexity of these renal masses and disease multifocality at presentation. However; efforts should be made intraoperatively to achieve complete surgical excision with negative margins since patients with PSMs have an increased risk for disease recurrence. Funding None
Authors
Firas Petros
Kai-Jie Yu Michael Metcalfe Sarp Keskin Courtney Chang Cindy Gu Surena Matin Jose Karam Christopher Wood |
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PD20-09 |
Surgical approach does not impact positive margin rate in partial nephrectomy for large renal masses |
Kidney Cancer: Localized: Surgical Therapy I | 17BOS |
Abstract: PD20-09 Sources of Funding: None Introduction Utilization of partial nephrectomy (PNx) has expanded to include treatment of an increasing number of renal masses ≥4cm by various surgical approaches. Recent evidence has suggested risk of recurrence with positive surgical margin (PSM) is increased in the presence of high-risk features, including stage ≥T2. While surgical approach has been associated with PSM in PNx for small renal masses (<4 cm), its impact on margin status for large renal masses is unclear. Methods Using the National Cancer Data Base (NCDB), we identified patients undergoing PNx for clinical T1b and T2a renal cell carcinoma (RCC) from 2011 to 2013. Primary outcome was surgical margin status. Multivariable regression modeling was performed to identify patient, facility, and surgical factors, including surgical approach (open, laparoscopic, or robotic) on PSM in patients undergoing PNx. Results Of 7495 undergoing PNx for cT1b and T2a renal masses from 2011 to 2013, 504 (6.72%) had PSM. On multivariable analysis, age > 60 years (OR 1.57 [95% CI 1.01-2.44] p=0.048), African American race (OR 1.52 [95% CI 1.06-2.17] p=0.023), education level (OR 1.48 [95% CI 1.03-2.14] p=0.034), rural setting (OR 4.82 [95% CI 2.45-9.46] p<0.01), mixed histology (OR 1.84 [95% CI 1.04-3.24] p=0.035), undifferentiated tumor grade (OR 2.42 [95% CI 1.26-4.65] p<0.01), as well as having surgery performed at a non-academic facility (OR 1.57 [95% CI 1.15-2.15] p<0.01) were associated with PSM. Surgical approach (laparoscopic and robotic vs. open) (p=0.119 and p=0.437, respectively) and stage (T2a vs. T1b) (p=0.182) were not associated with PSM. Conclusions Surgical approach is not independently associated with increased risk of PSM for large renal masses, which is contrary to previous reports pertaining to cT1a lesions. Surgery at an academic facility was protective against having a positive margin. These data are important given the unclear oncologic significance of margin status in these tumors. Funding None
Authors
Abimbola Ayangbesan
David Golombos Padraic O'Malley Patrick Lewicki LaMont Barlow Xian Wu Paul Christos Douglas Scherr |
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PD20-10 |
Does tumor complexity have an impact on MIC and Trifecta outcome in robot-assisted partial nephrectomy? A multi-center study of over 500 cases |
Kidney Cancer: Localized: Surgical Therapy I | 17BOS |
Abstract: PD20-10 Sources of Funding: None Introduction Partial nephrectomy is standard of care for renal tumors up to 7 cm and there is a widespread use of the minimal invasive approach since the introduction of robot-assisted surgery. However, there might still be some reservations in complex tumor constellations. Our study aims to demonstrate that robot-assisted partial nephrectomy (RAPN) provides good results for high risk tumors in comparison with less complex renal masses._x000D_ Methods Since 2008, 538 robot-assisted partial nephrectomies were performed at Missionsaerztliche Klinik, Wuerzburg (n=361), St. Antonius Hospital, Gronau (n=60), and Augusta-Kranken-Anstalt Bochum (n=117). To assess functional and oncological outcome, both MIC criteria (negative margins, ischemia time < 20 minutes, no major complications) as well as the Trifecta (negative surgical margins, WIT < 25 minutes, no complications) were applied. _x000D_ Results 60,6% of the tumors were of low and intermediate complexity (PADUA score 6-7, n=123, score 8-9, n=203, group A) while 39,4% were highly complex (score 10-12, B). There were no significant differences in ASA score or BMI. Median clinical tumor size was 28 in the low vs. 37 mm in in the high complexity group (p<0,001). While there was no significantly prolonged skin-skin time (160 vs. 163 minutes, p=0,17), ischemia time was shorter for tumors of low and intermediate complexity (11 vs. 12 minutes, p<0,001). More intraoperative transfusions were necessary in the high risk group (0 vs. 3, p=0,06). Neither intra- (3,4 vs. 6,6%) nor postoperative (Clavien-Dindo, 21% vs. 25%, p=0,3) complication rates showed significant differences between both groups. On postoperative day 1, a median decrease of hemoglobin of -2,4 g/dl was found in B vs. -2,2 g/dl (p=0,042) in group A. There was a median creatinine increase of 0,10 vs. 0,17 mg/dl (p<0,001) and loss of eGFR of 9,4 vs. 15,1 ml/min (p<0,001) on demission. Benign tumors were found in 26% of the patients with low/intermediate-risk lesions vs. 21% in the high complexity group. In 3% of high complexity tumors a positive surgical margin (R1) with 3% Rx vs. 2% and 2% for A was found (p=0,29). MIC criteria could be achieved in 82% (A) vs. 76% (B, p=0,80) and Trifecta criteria in 74% (A) vs. 69% (B, p=0,20). Conclusions Significant differences between high and low complexity groups could only be identified in ischemia time and renal function. However, complication rates as well as quality criteria as indicated by MIC and Trifecta were similar in both groups. Therefore, RAPN is a very good therapeutic option also in highly complex tumors. Funding None
Authors
Nina Harke
Christian Wagner Alexander Roosen Frank Schiefelbein Burkhard Ubrig Georg Schoen Jorn H. Witt |
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PD20-11 |
Acute Kidney Injury after Partial Nephrectomy: Impact on Long-term Stability of Renal Function |
Kidney Cancer: Localized: Surgical Therapy I | 17BOS |
Abstract: PD20-11 Sources of Funding: None Introduction Acute kidney injury (AKI) is associated with increased risk of developing chronic kidney disease (CKD) in the general population. AKI is frequently observed after partial nephrectomy (PN), however the long-term functional impact of AKI in this setting has not been adequately studied. Methods From 2004-2014, 90 solitary kidneys managed with PN had necessary studies for analysis of percent function and renal parenchyma preserved before and after surgery. Functional data including serum creatinine (SCr) and glomerular filtration rate (GFR) was required at all of the following time points: pre-operative (<3 months prior to PN), peak post-operative, new baseline (3-12 months post-operative), and long-term (>12 months post-operative). AKI was classified by RIFLE (Risk/Injury/Failure/Loss/End?stage) defined by either standard criteria (comparison of peak SCr to preoperative SCr) or proposed criteria (comparison to projected postoperative SCr based on parenchymal mass reduction). Long-term functional deterioration was defined as decline in GFR >20% between new baseline and long-term follow-up, or need for dialysis >12 months post-operatively. Relationship between AKI grade and long-term functional outcomes was assessed by multivariable logistic regression, controlling for pertinent patient, tumor, and perioperative characteristics. Results Median age was 64 years. Median duration of follow-up was 45 (IQR=29-90) months. Warm ischemia was used in 47% of patients, and overall median ischemia time was 29 minutes. Median parenchymal mass preservation was 80% and median GFR preserved was 79%. Based on standard criteria, AKI grade 1/2/3 occurred in 31%, 19%, and 18%, respectively, and analogous findings for the proposed criteria were 22%, 13%, and 7%. Fourteen (16%) patients experienced long-term functional decline. On multivariable analysis, presence of AKI and degree of AKI did not associated with long-term functional decline after PN, whether defined by standard or proposed criteria (all p>0.5). Limitations include retrospective design. Conclusions AKI related to surgery (AKI-S) may not have the same adverse functional implications as AKI due to medical causes (AKI-M). AKI-M is typically due to longstanding medical comorbidities, such as CHF, while AKI-S is primarily due to a transient ischemia insult that will not be repeated. Additional study, with larger sample sizes and longer follow-up will be required to further elucidate the relationship between AKI and CKD after PN. Funding None
Authors
Joseph Zabell
Wen Dong Diego Aguilar Palacios Joseph Abraham Sudhir Isharwal Erick Remer Steven C. Campbell |
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PD20-12 |
RISK OF URINE LEAK IN HIGH?RISK PATIENTS AFTER MINIMALLY INVASIVE PARTIAL NEPHRECTOMY WITHOUT COLLECTING SYSTEM CLOSURE |
Kidney Cancer: Localized: Surgical Therapy I | 17BOS |
Abstract: PD20-12 Sources of Funding: None Introduction Minimally invasive partial nephrectomy (MIPN) has become the gold standard for surgical treatment of small renal masses, and techniques have proliferated to decrease ischemia time, prevent complications, and improve outcomes. Dogma mandates that collecting system be closed after tumor excision to prevent postoperative urine leak, but our experience suggests that this step is not necessary, and may actually increase the risk of compromising underlying structures. We report our experience with MIPN without collecting system closure for patients at high risk of urine leak, as determined by parameters described in the urologic literature. Methods We reviewed the data for patients over a 10 year period that underwent MIPN, including clinical and radiographic features. We also performed a literature review to identify predictors of postoperative urine leak-defined as persistent drain output or elevated fluid creatinine requiring any intervention. Our surgical technique has been described previously and involves a fibrin glue bolster secured with parenchymal sutures. Results We identified 210 patients who underwent MIPN between May 2006 and October 2016 and met all inclusion criteria. Urine leak occurred in 3/210 (1.4%) patients overall. No patients deemed high risk by RENAL nephrometry score developed urine leak after surgery (0/13). Patients deemed high risk by Renal Pelvis Score had a urine leak rate of 2.0% (3/150), compared to published rate of 23.6%. Additionally, patients at low risk by RENAL score (<7) had leak rate of 1.3% (1/76), while moderate risk patients (7-8) had leak rate of 1.9% (2/103), compared to the published rates of 7.4 and 13.6%, respectively. Only one patient with a tumor size greater than 7cm (n=9) and one with tumor size less than 4cm (n=121) experienced a postoperative urine leak. Conclusions Our technique for MIPN shows superior outcomes with respect to urine leak in high-risk patients compared to traditional techniques that include formal collecting system closure. We have successfully applied our approach to pure lap, hand-assisted, and robot-assisted laparoscopic procedures. These results challenge accepted dogma that formal collecting system closure is necessary for the prevention of urine leak formation. Omitting this step decreases the complexity of the closure, shortens warm ischemia time, and may actually reduce the risk of urine leak. Funding None
Authors
Amul Bhalodi
Adam Berneking Stephen Strup Jason Bylund |
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PD21-01 |
Determinants of health-related quality of life after surgery: Ureteroscopic versus shock wave lithotripsy |
Stone Disease: Surgical Therapy II | 17BOS |
Abstract: PD21-01 Sources of Funding: none Introduction The aim of this study was to compare the longitudinal health-related quality of life (HRQoL) at 4 time points between patients undergoing ureteroscopic lithotripsy (URSL) and patients undergoing shock wave lithotripsy (SWL). We also aimed to evaluate the factors that significantly affect the HRQoL in patients with urolithiasis. Methods We evaluated a total of 262 patients who underwent lithotripsy (SWL, n = 61; URSL, n = 201) for upper urinary tract calculi treatment between June 2012 and January 2015. All patients were administered the Short-Form 36-item survey (SF-36) to assess HRQoL at 4 time points: prior to surgery, on the day of discharge, and 1 and 6 months after lithotripsy. We evaluated stone-free rates, the occurrence of complications, and analgesic requirements in order to compare the effects of SWL versus URSL on HRQoL. Results On the day of discharge, patients in the URSL group had significantly lower average scores on the SF-36 survey in 5 different domains (physical function, role physical, social functioning, role emotional, and mental health) and in 1 summary scale (role component score [RCS]) than the SWL group. The stone-free rate at 3 months after lithotripsy was significantly lower in the SWL group than in the URSL group (72.1% vs. 93.0%; p < 0.001). Moreover, the analgesic requirements were lower in the SWL group than in the URSL group (0.3 ± 0.08 vs. 0.9 ± 0.20; p < 0.001). Multivariate analysis identified age and analgesic requirements as predictors of lower HRQoL on the RCS summary scale (p=0.029 and p=0.002, respectively). Conclusions Patients who underwent SWL had a higher post-lithotripsy HRQoL, but lower stone-free rates, compared to those who underwent URSL. Higher postoperative pain appeared to be the primary cause of the lower HRQoL in the URSL group. In order to determine the appropriate treatment approach, it is essential to understand not only the surgical outcomes and recurrence rates but also the HRQoL associated with each treatment strategy. Funding none
Authors
Shuzo Hamamoto
Teruaki Sugino Rei Unno Kazumi Taguchi Ryosuke Ando Shinsuke Okada Takaaki Inoue Atsushi Okada Keiichi Tozawa Takahiro Yasui |
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PD21-02 |
Minimizing the Cost of Treating Asymptomatic Ureterolithiasis |
Stone Disease: Surgical Therapy II | 17BOS |
Abstract: PD21-02 Sources of Funding: none Introduction The management of patients with ureterolithiasis who report resolution of their symptoms but do not recall passing the stone presents a clinical challenge. We sought to analyze the cost of differing management strategies for these patients. Methods We performed a cost minimization analysis using published efficacy data and Medicare reimbursement costs. We constructed a decision analysis tree (Fig 1) which we used to compare: a) ureteroscopy with planned lithotripsy; b) follow-up imaging to determine presence or absence of stone using computed tomography (CT), abdominal plain film (KUB), or ultrasound (US); or c) continued observation. We performed sensitivity analyses, varying threshold values, to determine the factors driving costs. Results Observation was associated with the lowest costs for patients when the probability of spontaneous stone passage was higher than 62% (Fig 2). Initial imaging with CT was the least costly approach for patients with an intermediate probability of stone passage, 21-62%. Proceeding directly with ureteroscopy was associated with the lowest costs when the probability of spontaneous stone passage was less than 21% (Stones about >8mm in size). When the sensitivity of US is modeled to be high (>79%), it surpasses CT scan as the least costly approach across a wide range of spontaneous passage rates Conclusions The probability of spontaneous passage of a ureteral stone can be used to optimize treatment strategies for patients. Observation minimizes costs for patients with stones likely to pass spontaneously, whereas ureteroscopy minimizes costs for stones unlikely to pass. For ureteral stones with an intermediate probability of spontaneous passage, CT imaging to guide treatment is associated with the lowest estimated costs. Funding none
Authors
Remy Lamberts
Simon conti John Leppert Christopher Elliott |
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PD21-03 |
Percutaneous Access Obtained By Urologist Is Associated With Decreased Complications, Shorter Length of Stay, and Lower Hospital Costs in PCNL |
Stone Disease: Surgical Therapy II | 17BOS |
Abstract: PD21-03 Sources of Funding: none Introduction Percutaneous nephrolithotomy (PCNL) is an effective minimally invasive technique for removal of large upper tract urinary stones. Renal access (RA) can be obtained by interventional radiologist or urologist prior to PCNL. The aim of the study was to evaluate the impact of the specialty of the physician obtaining access on perioperative outcomes, complications, and costs of PCNL. Methods We used data from the Premier Hospital Database, a nationally representative hospital discharge database, which collects data from over 600 non-federal hospitals throughout the US. We identified patients undergoing PCNL using ICD9-CM codes with a corresponding diagnosis code for nephrolithiasis. Procedure codes related to RA were linked to physician specialty. We examined patient demographics, Charleson comorbidity index (CCI), postoperative complications, length of stay, and direct hospital costs as well as surgeon volume, hospital size, type and location stratified by specialty of the physician obtaining RA. A multivariable regression model was created adjusting for potential confounders. Results We identified 19,985 patients undergoing PCNL between 2003-2015. Urologists obtained access in 18.5% of cases. RA by urologist was more commonly performed by high-volume surgeons (37.0% vs 9.8% p<0.001) and hospitals with <400 beds (19.1% vs 17.9% p=0.04). RA by urologist was associated with lower 90-day complication rate (16.9% vs 18.8% p=0.008) and lower rates of prolonged hospitalization >2 days (31.6% vs 68.4%, p<0.001). _x000D_ There was no association between patient&[prime]s CCI, age, race, insurance, hospital location (urban vs non-urban, and hospital type (teaching vs non-teaching) with regard to physician specialty obtaining RA. On multivariable analysis, RA by urologist was associated with lower rates of any complication (Clavien 1-5), shorter hospitalization (<2 days) and lower direct admission costs (<$12,515) Figure 1._x000D_ Conclusions PCNL is performed with urologists obtaining percutaneous access the minority of the time in the United States. High-volume urologists are more likely to obtain their own access. Access by urologist is associated with lower overall complications, shorter hospitalizations, and lower direct hospital costs. Funding none
Authors
Ruslan Korets
Jacqueline M Speed Ye Wang Steven L Chang |
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PD21-04 |
Comparison of Ultrasound-Guided, Conventional Fluoroscopic, and a Novel Laser Direct Alignment Radiation Reduction Technique for Percutaneous Nephrolithotomy |
Stone Disease: Surgical Therapy II | 17BOS |
Abstract: PD21-04 Sources of Funding: None Introduction Currently, urologists routinely use either ultrasound or conventional fluoroscopic guidance during percutaneous nephrolithotomy (PCNL).In an attempt to reduce the radiation exposure during PCNL, a novel laser Direct Alignment Radiation Reduction Technique (DARRT) was developed where the renal access is guided by a laser sight placed upon the C-arm. The purpose of this study is to compare the outcomes of these 3 techniques in patients undergoing percutaneous stone surgery. Methods In this chart review, the first 25 consecutive patients undergoing PCNL using laser DARRT were compared to 25 US-guided and 25 conventional access patients. These 3 cohorts were matched in terms of age, body mass index, stone burden and location. Primary outcomes were total fluoroscopy time and access fluoroscopy time. Secondary outcomes included stone burden, operative time, estimated blood loss, stone free status and major complications ( ≥Clavien III). Patients with residual fragments ≤4 mm were considered to be stone free. Statistical analysis was done using ANOVA for continuous variables and the chi-square test for categorical variables. A p value <0.05 was considered significant. Results There were no differences between the 3 cohorts in baseline demographics and mean stone burden (Table 1). The stone free rates between the US (68%), conventional PCNL (76%) and laser DARRT (84%) were similar (p=0.27). Major complications and EBL were not significantly different between the groups. Operative time for the laser DARRT was 20 minutes shorter than the conventional PCNL and 24 minutes shorter than the US, however, this difference did not reach significance (p=0.58). Mean access fluoroscopy time was 3, 844 and 8.9 seconds, and total fluoroscopy time was 8.5, 944.6 and 17.4 seconds for US, conventional, and laser DARRT PCNL respectively. Both US and laser DARRT had significantly lower total and access fluoroscopy times than conventional PCNL (p<0.01 for all comparisons). Conclusions The use of the novel laser DARRT and US-guided technique both resulted in a >98% reduction in the fluoroscopy time compared to the conventional technique. The operative time and stone free rates of the laser DARRT compared favorably with the US-guided and conventional techniques. Funding None
Authors
Samuel Abourbih
Mohamed Keheila Patrick Yang Muhannad Alsyouf Jason Smith Braden Mattison Nazih Khater Jim Shen Salim Cheriyan D. Duane Baldwin |
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PD21-05 |
A new navigation system of renal puncture for endoscopic combined intrarenal surgery: real-time virtual sonography-guided renal access |
Stone Disease: Surgical Therapy II | 17BOS |
Abstract: PD21-05 Sources of Funding: none Introduction Real-time virtual sonography (RVS) is a diagnostic imaging support system that synchronizes real-time ultrasonography and computed tomography images to provide volume and position data, side-by-side, in real-time. The aim of our study was to evaluate the clinical utility of RVS to guide percutaneous renal puncture for endoscopic combined intrarenal surgery (ECIRS) for large renal calculi. Methods We retrospectively evaluated surgical outcomes in 15 patients with renal calculi (36.3 ± 4.2 mm) who underwent RVS-guided ECIRS at our center between April 2014 and July 2015. Preoperative computed tomography images, obtained with patients in the prone position, were used as input into the RVS system. Renal puncture was performed using the RVS system, with patients in the prone split-leg position, under direct endoscopic vision. Renal puncture was repeated until a papilla was successfully pierced. After inserting the miniature percutaneous tract, two urologists worked simultaneously to fragment the renal calculi. We evaluated the number of puncture attempts required to gain papilla access through the calyx, the surgical time, the stone-free rate, and the occurrence of complications. Results All renal punctures were successfully performed, with an average of 1.6 ± 0.3 attempts required to gain papilla access through the calyx. In 86.7% of cases, renal punctures were performed through the lower pole of the calyx. The mean surgical time was 118.3 ± 15.3 min, with no requirement for nephrostomy tube insertion in 60.0% of cases (9 cases). The mean decrease in hemoglobin level was 0.9 ± 0.3 g/dL. Complete stone clearance after a single treatment session was achieved in 80.0% of cases(12 patients). Three patients experienced complications, including two cases of transient fever. None of the patients required a blood transfusion, and there was no incidence of complications with a Clavien grade ≥ 2. Conclusions We successfully applied RVS guidance to targeted renal puncture, providing evidence of the clinical utility of RVS for improving the precision of the calyceal puncture while decreasing the incidence of bleeding-related complications during ECIRS. RVS-guided renal access may have great potential to improve treatment for renal calculi and as a learning tool for novice operators. Funding none
Authors
Shuzo Hamamoto
Teruaki Sugino Rei Unno Kazumi Taguchi Ryosuke Ando Shinsuke Okada Takaaki Inoue Atsushi Okada Keiichi Tozawa Takahiro Yasui |
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PD21-06 |
“Does Size of Sheath Matter ?” for Minimally Invasive Percutaneous Nephrolithotomy : Our Prospective and Randomized Trial for small size ( 10-20 mm ) Renal Calculi |
Stone Disease: Surgical Therapy II | 17BOS |
Abstract: PD21-06 Sources of Funding: None. Introduction Minimally Invasive PCNL (MIP) is a promising modality in the treatment of small size renal calculi. There is no consensus regarding ideal size of Nephrostomy Tract/Sheath for minimally invasive treatment modality. We prospectively compared outcomes in use of three different sizes of Sheaths ( 7.5, 12, 15.5 F ) during MIP for 10-20 mm size Renal Calculi. Methods : A total of 153 patients having Renal Calculi of 10-20 mm size were treated at our center between July 2015 and April 2016. Computer generated randomization Schedule was used to assign the use of Outer sheath size during MIP. 7.5 F sheath(n=42), 12F (n=66), and 15.5 F( n=45) was used in our study, where mean stone size was 13.4, 14.6, and 14.1 mm respectively. Rest of the patient demographics were comparable in each group. Hardness of all calculi were evaluated by the use of House Field Units on CT Scan. Pressure Irrigation pump was used for irrigation and Holmium Laser(20-40W) Lithotripsy with quartz fiber was used for stone fragmentation. OR time, Stone free rates, Post-operative Analgesic Use, Clavien Complication rate, Hospital Stay and Ancillary procedure requirement was noted in each group. X-ray KUB, Sonography and non-contrast CT Scan was used on post-operative day 3 to confirm stone free status. Use of DJ stent or Nephrostomy tube was decided as per merits of the case. Results Primary Stone free rate was defined as complete clearance on Non contrast CT scan on postoperative day 3. There was no significant difference (p=.124) in Primary stone free rate in 7.5 F (83.4%) and 12 F(84.9%) sheath group. 15.5F(96.5%) sheath group stone free rate was significantly higher(p>0.05) and OR Time(38±5) was lower (p=0.004) compared to other two groups. There was no significant difference in postoperative complications (Clavien Grade I &II) in either groups. Analgesic use in all groups was similar. 2 patients in 7.5 F sheath group and 4 in 12 F Sheath group needed ancillary procedure for complete stone clearance. Mean hospital stay was not significantly different in either groups. Primary stone free rate was 99% in Calculi with Housfield Unit <790±32 compared to those (81.5%) with Housefield Unit of >1150±89 in all groups. Conclusions Efficacy of miniaturized equipment with 7.5 F, 12 F and 15.5 F outer Sheath in treatment of 10-20 mm renal calculi is similar and has lower morbidity. Higher Primary Stone free rate with lower OR Time in 15.5 F Sheath group, irrespective of hardness of calculus, makes it more preferred size of equipment in Minimally Invasive PCNL. Funding None.
Authors
Ajay Bhandarkar
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PD21-07 |
Prospective Randomized Study of Flexible Ureteroscopic Holmium Laser Lithotripsy Using High-Frequency Stone Dusting Versus a Low-Frequency Stone Breaking Protocol for the Treatment of Renal Stones Larger than 2 cm |
Stone Disease: Surgical Therapy II | 17BOS |
Abstract: PD21-07 Sources of Funding: logistic support for the trail provided by lumenis. Introduction Flexible Uretero-Renoscopy (FRUS) is used in cases with large (>2 cm) renal stones, but the duration of surgery gets unduly prolonged and there is increase incidence of staged procedure. Methods A single-center prospective randomized double-arm study was performed to compare the high-frequency stone dusting and low-frequency stone breaking laser settings in FURS for the treatment of high-burden stone disease. Patients with stone size of >2 cm and <5 cm in the case of a single stone or the cumulative size of the largest stone diameters for stones ?5 cm in case of multiple stones were included. The primary end point was the procedure time. Results The planned enrollment included 15 patients in each arm of the study. After 6 patients were enrolled in each arm, an interim analysis was performed, and the results were reported to the human research ethics committee (HREC). The average number of stones in each renal unit was 1.53±0.7 and 2.01±0.8 in Groups 1 and 2, respectively. The average stone bulk was 4734±2387 cc and 5666.67±1032.796 cc in Groups 1 and 2, respectively. In Group 1, eleven patients (11/15) could be completely cleared of stones at the end of one month after a single-stage FURS using high frequency dusting protocols. In Group 2, (50%) the stones could be cleared after a single session of FURS using the low frequency stone breaking protocol at the end of one month in three patients. Conclusions A high-frequency stone dusting protocol was significantly more effective than a low-frequency stone breaking protocol for FURS in the treatment of high bulk renal calculus disease. Funding logistic support for the trail provided by lumenis.
Authors
Abhishek Singh
Abhinav Jain Arvind Ganpule Ravindra Sabnis Mahesh Desai |
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PD21-08 |
Is endoscopic evaluation at the end of retrograde intra-renal surgery a reliable predictor of post-operative significant residual fragments? |
Stone Disease: Surgical Therapy II | 17BOS |
Abstract: PD21-08 Sources of Funding: None Introduction Post-operative imaging used to assess retrograde intra-renal surgery (RIRS) results affects stone-free rates (SFR). Imaging after RIRS may be unnecessary if surgeon&[prime]s endoscopic evaluation (EE) at the end of RIRS proved to be reliable._x000D_ The objective of our study was to assess the reliability of surgeon&[prime]s EE at the end of RIRS. Methods We made a retrospective analysis on all consecutive RIRS performed for renal stones from January 2009 to August 2016 and included in a prospectively maintained database. RIRS were performed with fiber optics instruments in one-day surgery under spinal anesthesia. A ureteral access sheath was used, laser lithotripsy was performed and significant fragments extracted. Multiple stones, stones > 2 cm and staged procedures were included. Surgeons recorded their EE particularly about the presence of significant residual fragments (SRF). Residual fragments were considered clinically insignificant (CIRF) if ≤ 4 mm. Primary endpoint of our study was the ability of EE made by an expert surgeon to exclude the presence of SRF at US at 2-3 weeks. Chi-square and Fisher tests were used for statistical analysis. Results 294 RIRS were included. EE was available in 281 cases and US in 211. Mean stone size was 12.31 mm ± 4.87 mm (SD). In 68 cases (23.13%) stones were multiple. Post-operative US outcomes significantly differed from urologist&[prime]s EE in term of SRF, CIRF and SFR (p < 0.0001), independently from the number of RIRS performed per year by the surgeon (p < 0.001). 14% more patients were found stone-free (SFR 0U) at US compared to EE, 28% less were found to have CIRF and 14% more to have SRF. Table 1 shows how the concordance of EE and US outcomes varied in relation with surgeon&[prime]s expertise. In particular the difference in terms of SRF and CIRF decreased when EE was made by a surgeon performing ≥ 20 RIRS/year. The absence of SRF assessed at EE by a surgeon performing ≥ 20 RIRS/year was confirmed at US in 92% of cases. The probability to diagnose at US SRF not assessed at EE increased to 36% when EE was made by surgeons performing < 20 RIRS/year (OR = 6.4). Conclusions Post-operative US outcomes significantly differed from urologist&[prime]s EE. EE underestimated SFR and overestimated CIRF. SRF were underestimated at EE, but an expert surgeon reliably predicted the absence of SRF. Funding None
Authors
Andrea Bosio
Eugenio Alessandria Ettore Dalmasso Dario Peretti Federico Vitiello Alessandro Bisconti Paolo Destefanis Paolo Gontero |
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PD21-09 |
TRUE STONE FREE RATES OF FLEXIBLE URETEROSCOPY FOR RENAL CALCULI UTILIZING STRICT CT CRITERIA |
Stone Disease: Surgical Therapy II | 17BOS |
Abstract: PD21-09 Sources of Funding: None Introduction Stone free rate (SFR) determines ureteroscopy (URS) success rates. Inconsistent reporting using X-ray, ultrasound or CT scan contributes to data heterogeneity. A CT scan provides the most accurate assessment of SFR. Low dose CT scan (LDCT) is an attractive follow up imaging option, offering reduced radiation dose while preserving superior stone fragment visualization of a CT scan. We sought to assess SFR at our high volume institution using low dose CT scan (LDCT) to provide the most accurate assessment of contemporary ureterosopy success rates. Methods A retrospective review of all patients undergoing flexible URS for renal stones with subsequent LDCT scan within 6 months of operation date. The operation note, CT report and images of every patient were reviewed to determine a "true", zero fragment SFR. A ureteral access sheath was placed and meticulous basketing of all stone fragments rather than dusting were utilized wherever possible. Patients with ureteral calculi alone, without co-existing renal calculi were not included in this study. Patients with true nephrocalcinosis (as determined by visual inspection of papilla at the time of URS) were assigned the "stone free" category. Results Flexible URS was performed in 202 renal units of 150 patients with intrarenal calculi from September 2003 to July 2016. 71 out of 150 patients (47%) were male. 140 renal units were completely stone free by LDCT assessment representing a 69% "true" SFR. 62 renal units had residual fragments. The largest fragment size was 1mm in 3% (6/202 renal units), 2-4 mm in 19% (39/202 renal units) and > 4 mm in 8% (17/202 renal units). Conclusions True stone free rate in patients undergoing flexible ureteroscopy for renal calculi utilizing active basketing of fragments, as determined by strict low dose CT assessment, is 69%. In patients with residual fragments, the majority are 2-4 mm in size. Funding None
Authors
Nadya E. York
Hazem M. Elmansy Marcelino E. Rivera Amy E. Krambeck James E. Lingeman |
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PD21-10 |
Active stone removal can prevent urolithiasis-related deaths in patients with poor performance status. |
Stone Disease: Surgical Therapy II | 17BOS |
Abstract: PD21-10 Sources of Funding: None. Introduction Controversies exist as to whether active stone removal should be performed in patients with poor performance status (PS) because of their short life expectancy and perioperative risks. The purpose of the present study was to clarify whether stone removal for patients with poor PS improves their prognosis. Methods We retrospectively reviewed the charts of 81 patients with poor PS (Eastern Cooperative Oncology Group PS 3 or 4) treated for upper urinary tract stones from January 2009 to March 2016. Seven patients who experienced spontaneous stone expulsion were excluded and 74 patients were enrolled in this study. Patients were classified into operation group and non-operation group based on the presence of active stone removal. We defined stone-specific survival (SSS), and compared overall survival (OS) and SSS between two groups by Kaplan-Meier method/log-rank test. In addition, univariate and multivariate analyses of OS and SSS were performed using Cox proportional hazards model. Results A total of 52 patients (70.3%) received active stone removal (operation group) by either ESWL (n=6), ureteroscopy (n=39), percutaneous nephrolithotomy (n=6) or nephrectomy (n=1). Overall stone free-rate was 78.8% and perioperative complication was observed in 9 patients (17.3%). While, 22 patients (29.7%) underwent conservative treatment (non-operation group). Operation and non-operation groups showed two-year OS rates of 88.0% and 38.4%, respectively (p<0.01), and two-year SSS rates of 100% and 61.3%, respectively (p<0.01) (Figure). On multivariate analysis, stone removal was not significant, but was considered possible favorable predictor for OS (HR 0.43, 95% CI 0.16 – 1.09) after adjustment for factors including age and Charlson comorbidity index. Moreover, stone removal was only independent predictor for SSS (HR 0.06, 95% CI 0.00 – 0.43) (Table). Conclusions Active stone removal could prevent stone-related deaths, possibly leading to prolonged overall survival in patients with poor PS. Funding None.
Authors
Shimpei Yamashita
Yasuo Kohjimoto Takashi Iguchi Akinori Iba Isao Hara |
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PD21-11 |
PCNL in geriatric patients: an evaluation of outcomes, complications and discharge needs |
Stone Disease: Surgical Therapy II | 17BOS |
Abstract: PD21-11 Sources of Funding: None Introduction Growing numbers of geriatric patients present for definitive management of kidney stones. Geriatric patients with large stones may be candidates for percutaneous nephrostolithotomy (PCNL), however their care-related needs may differ from younger patients. We reviewed our PCNL experience in geriatric patients to better define surgical outcomes, complications, and discharge needs. Methods We retrospectively analyzed patients undergoing PCNL from 2012-2015 in our institution. Preoperative characteristics, surgical outcomes, complications, and discharge needs were compared between two groups: geriatric patients (aged ≥65 years) and non-geriatric patients (<65years). Statistical analysis was performed with students t-test and chi-squared test. Results We analyzed 287 consecutive patients: 89(31%) patients ≥65 years; 198(69%) patients <65 years (mean age 72 vs 48 years, p<0.001). The results can be seen in Table 1. Geriatric patients were more likely Caucasian (91% vs 73.7%, p=0.001), had fewer positive preoperative urine cultures (27% vs 41.6%, p=0.017), and had higher American Society of Anesthesiologist scores (mean 2.83 vs 2.55, p<0.001). OR time (mean 159 vs 185 minutes, p=0.003) and estimated blood loss (41 vs 56 mL, p=0.014) were less in the geriatric group. The residual stone fragment size was less after one procedure (0-2 mm: 72.9% vs 58.5%; 3-4 mm: 15.6% vs 17.5%; >4 mm: 11.5% vs 24%, p=0.024) in the geriatric group. There were no differences in 30 day readmissions (12.4% vs 12.6%, p=0.95), total complications (30.3% vs 27.3%, p=0.594) or major complications (9.0% vs 5.6% ≥ Clavien III p=0.279) between the geriatric and non-geriatric groups respectively. Length of stay (3.1 vs 3.2 days, p=0.852) was similar between the groups, however the geriatric group was more often discharged with services to assist with nephrostomy tubes or wound dressings (21.3% vs 9.1%, p=0.016)._x000D_ Conclusions PCNL is an acceptable surgical option in appropriately selected geriatric patients. These patients require more home nursing care, but otherwise do well compared to younger patients. This information may be helpful for both patient counseling and discharge planning in the geriatric stone population. Funding None
Authors
Brandon Otto
Russell Terry John Shields Forat Lufti Mohit Gupta Vincent Bird |
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PD21-12 |
ECIRS (Endoscopic Combined IntraRenal Surgery) in the Galdakao-modified supine Valdivia position |
Stone Disease: Surgical Therapy II | 17BOS |
Abstract: PD21-12 Sources of Funding: None Introduction ECIRS (Endoscopic Combined IntraRenal Surgery) in the Galdakao-modified supine Valdivia position is an evolution of the traditional prone percutaneous nephrolithotomy (PNL) for the treatment of large/complex urolithiasis, combining an antegrade rigid and flexible approach with retrograde flexible ureteroscopy. The aim of the present work is to report our 12-years experience, highlighting ECIRS safety and efficacy. Methods We performed 310 consecutive ECIRS (11/2010-11/20169 standardized step-by-step pre-, intra- and post-operatively. The semirigid 6.5F Wolf ureteroscope and the flexible Storz FlexX2/C ureteroscopes were used for retrograde access. Percutaneous access was gained under ultrasound-assisted biplanar fluoroscopy guidance +/- Endovision contribution (24 Ch in 65% of the cases, 30 Ch in 31%, smaller accesses in 4%), using in 78% one-step balloon dilation. Results Mean age of the 310 patients (210 males, 100 females) was 55 years +/- 20 s.d. (range 19 months-82 years). The ASA score was 1-3, mean BMI 30 kg/m2 +/- 5 s.d., 10% urinary malformations, 7% skeletal deformities, 74% symptomatic for UTI/colics. Urolithiasis (206 left, 104 right renal stones, 15% bilateral, all compositions) had a mean stone size 51 mm +/- 22 s.d. (range 13-72 mm). Stones were single in 55%, multiple/staghorn in 45% of cases, with 24% coexistent ureteral stones. Mean operative time was 88 minutes +/- 35 s.d., including patient positioning. Preliminary semirigid ureteroscopy was performed in 81% of cases, additional flexible ureteroscopy in 53%. Endovision aid to fluoroscopy/ultrasound renal access (90% inferior calyx, 94% single access) was possible in 39% of cases. Retrograde ureteroscopy (ureteral stone treatment, in situ lithotripsy, stone fragments retrieval in calyces parallel to the access tract,…) had an active role in 54% of cases. The stone-free rate was 89.8%, 94.3% after an early second percutaneous look during the same hospital stay. The overall complication rate was 7.4% (1.6% of cases Clavien 3 and never more, no ureteral lesions). Mean fluoroscopy time of the “really-endoscopic� cases was 3.3 minutes +/- 1.2 s.d., versus 5.5 +/- 3 s.d. of the other ECIRS. Conclusions ECIRS represents a comprehensive approach to PNL, personalizing stone management and tailoring all intraoperative choices on the patient. Retrograde flexible ureteroscopy, after preliminary evaluation of the dynamic anatomy of collecting system and stones, actively contributes to safety and efficacy of ECIRS, optimizing stone-free rates and reducing complications and radiation exposure. Funding None
Authors
Cesare Marco Scoffone
Cecilia Cracco |
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PD22-01 |
Glans Necrosis Following Penile Implant: What Can Be Learned? |
Sexual Function/Dysfunction: Surgical Therapy II | 17BOS |
Abstract: PD22-01 Sources of Funding: none Introduction Glans necrosis following penile implant is a very rare complication. The literature has a paucity of information with only 5 single case reports. Glans necrosis is devastating to both patient and physician. The blood supply of the glans penis is twofold: dorsal penile arteries and corpus spongiosum muscle. Glans necrosis initially presents with a dusky, sometimes blistered glans on first post op day. The dilemma of immediate implant removal or continued observation perplexed each surgeon. Methods The patients were collected from the experience of large volume implanters in 7 countries. We report 19 cases following prosthesis implantation (8 rods, 11 inflatable) examining etiology and treatment outcomes with the hope of both prevention & optimum treatment suggestion. From this patient population we compiled risk factors and adjunctive surgical maneuvers that might compromise vascularity of the Glans Penis. 7 of the patients had pre-operative Doppler showing arterial patency of the dorsal arteries. Risk factors detected were:_x000D_ Severe arteriosclerotic cardiovascular disease (ASCVD) (84%) _x000D_ Diabetes (84%)_x000D_ Smoking (72%)_x000D_ Previous removal of implant usually for infection (68%)_x000D_ Radiation Therapy (56%)_x000D_ 79% of patients had 60% of these comorbidities. 53% of patients had 80% risk factors_x000D_ Surgical maneuvers found in the population during prosthesis placement were_x000D_ Subcoronal incision for coincident circumcision or penile degloving (89%)_x000D_ Penile wrap with elastic bandage (74%)_x000D_ Coincident distal urethral injury &/or repair (28%)_x000D_ Sliding procedure for penile lengthening (28%) Results 15 (79%) patients had expectant management i.e., implant preservation & observation. All sustained significant loss of glans; most required relocation of urethral meatus. 4 (21%) patients were managed with immediate prosthesis removal and hyperbaric oxygen. All healed without sequelae._x000D_ Conclusions Prospective implant patients with many of the risk factors -- diabetes, smoking, radiation therapy, previous implant removal, & severe ASCVD -- should not undergo coincident subcoronal incision for circumcision, distal urethral repair, or penile lengthening. Occlusive elastic penile bandage should be avoided. Upon development of signs of glans ischemia, immediate implant removal is mandatory for prevention of glans necrosis. Funding none
Authors
Steven Wilson
Cesar Mora-Estaves Paulo Egydio David Ralph |
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PD22-02 |
Long Acting Preoperative Local Anesthetic Block to Limit Opioid Administration After Inflatable Penile Prosthesis Insertion |
Sexual Function/Dysfunction: Surgical Therapy II | 17BOS |
Abstract: PD22-02 Sources of Funding: None Introduction With the growing epidemic of opioid abuse there is a increased focus on prescribing narcotic analgesics. Surgeons must consider ways to limit these prescriptions. Placement of an inflatable penile prosthesis (IPP) for refractory erectile dysfunction (ED) has high satisfaction rates (92-100% ), but is associated with significant postoperative pain usually requiring opioid analgesics for 7-10 days. Use of bupivacaine liposome injectable suspension has been shown to provide a reduction in postoperative pain and opioid use, although nearly 100 times more expensive than bupivacaine HCl. Our objective was to evaluate the feasibility of a long acting preoperative local anesthetic block in discharging patients on postoperative day (POD) 0 after IPP placement without an opioid prescription and to demonstrate ease of administration. Methods 85 men underwent IPP placement for refractory ED with a local penoscrotal block. A mixture of 0.5% ropivacaine 20cc, 1% lidocaine 20cc, sodium bicarbonate 1cc, and dexamethasone 4mg was prepared prior to administration. The local anesthetic block was given using a 22-gauge needle into the pudendal space bilaterally, subcutaneous penile ring, and the external inguinal ring. The IPP was placed using a modified no touch technique through a subcoronal (88%), infrapubic (11%), or penoscrotal (1%) approach._x000D_ Results In addition to local penoscrotal block, 27 (32%) and 58 (68%) patients received general anesthesia and monitored anesthesia care respectively. The Wong-Baker FACES Visual Analog Scale was used to evaluate pain in the recovery room with an average score of 4.4 (range 0-6). All patients were discharged home on POD 0 with a prescription for Acetaminophen or NSAIDs; none were prescribed opioids. Patients were evaluated on POD 2 and, 9 (11%) patients required a prescription for opioid analgesics. However, at POD 7-10 days, no patients were taking opioids. To reinforce the ease of administration, we are currently analyzing resident administration of the local anesthetic block. Conclusions Use of preoperative local penoscrotal block allows for discharge home on POD 0 without opioid analgesics after IPP placement. This local anesthetic mixture is more cost effective than bupivacaine liposome injectable suspensions. With proven efficacy in IPP placemen this local penoscrotal block could be adopted for other penoscrotal surgeries. As opioid addiction and overdose continues to be a public health concern, innovative techniques such as we describe to limit postoperative narcotic requirements are paramount. Funding None
Authors
John Griffith
Robert Valenzuela |
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PD22-03 |
OXIDIZED REGENERATED CELLULOSE (FIBRILLAR™) REDUCES RISK OF POSTOPERATIVE HEMATOMA FOLLOWING INFLATABLE PENILE PROSTHESIS |
Sexual Function/Dysfunction: Surgical Therapy II | 17BOS |
Abstract: PD22-03 Sources of Funding: none Introduction Oxidized regenerated cellulose (ORC) (Fibrillar®) is a topical absorbable hemostatic agent widely used in various urologic surgical procedures. Little is known regarding the impact of hemostatic agents in reducing risk of hematoma formation among men undergoing urologic prosthetic surgery. This study reports our initial experience with ORC as a hemostatic adjunct during inflatable penile prosthesis (IPP) surgery to determine the effect on postoperative drain output and subsequent complications. Methods Beginning in March 2016 ORC was placed as a pledget within the corporotomy closure of all men undergoing IPP insertion. Demographic, intraoperative, and postoperative parameters including cumulative overnight postoperative drain output were evaluated among cases with (March 2016 to present) and without ORC (December 2015 to March 2016) using an identical surgical technique by a single surgeon. Continuous variables were compared with the Mann-Whitney U test. Categorical variables were compared with Fisher's exact test. Results During the study period 61 men underwent IPP procedures. ORC was used in 27/61 cases (44%) causing a 38% reduction in median drainage output compared to the control group (40 mL vs. 65 mL; p=0.01). There was no difference in demographic, perioperative, or device-related characteristics. There were 2 IPP explantations secondary to infection, both of which occurred in the control group; one of which was directly related to hematoma formation. After controlling for other clinical features, the use of ORC (β -31, 95% CI: -61 to -1.3; p=0.04) was the only factor independently associated with a reduction in drain output. Conclusions This study suggests that the use of ORC pledgets during corporotomy closure of IPP reduces risk of hematoma formation. Funding none
Authors
Alexander Rozanski
Alexander Liu Nabeel Shakir Boyd Viers Travis Pagliara Billy Cordon Maia VanDyke Jeremy Scott Allen Morey |
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PD22-04 |
"Distal Corporal Anchoring Stitch" a technique to address distal corporal crossovers and impending lateral extrusions of a penile prosthesis |
Sexual Function/Dysfunction: Surgical Therapy II | 17BOS |
Abstract: PD22-04 Sources of Funding: none Introduction Distal corporal crossover and impending lateral extrusion of a penile prosthesis may cause pain and place the patient at risk for erosion. Distal fixation of penile prosthesis is a useful surgical adjunct to treating patients with previously unidentified distal crossovers, delayed distal crossovers and impending lateral extrusion. We provide another method for its management, the "Distal Corporal Anchoring Stitch". Methods A lateral, subcoronal incision is utilized on the side where the crossed over or laterally extruding cylinder should be positioned. Dissection is carried through Bucks fascia, followed by a transverse incision of the Tunica Albuginea where the distal aspect of the affected cylinder is delivered. A 4-0 PDS suture is threaded through the distal cylinder ring of the implant. A new, properly positioned intracorporal channel is created and the suture is passed through the distal end of this channel. Once the suture is through the glans and the cylinder is in the correct position, a small cruciate incision is made on the glans, at the location of the anchor stitch. The suture is tied with the knot buried in the glans tissue. Results A total of 53 patients have undergone treatment of their distal penile implant crossover with a distal corporoplasty utilizing this method. This technique ensures that the cylinder remains in the newly created, appropriately positioned channel. No patients experienced infections, wound healing defect, glandular hypoesthesia, anesthesia, altered sensation or pain in the glans related to the suture and only two reported recurrence of a lateral herniation not requiring further treatment. Conclusions The "Distal Corporal Anchoring Stitch" is a safe and efficacious technique in securing distal fixation of the inflatable penile. Funding none
Authors
Gian Maria Busetto
Gabriele Antonini Francesco Del Giudice Ettore De Berardinis Paul E. Perito |
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PD22-05 |
HIGH SUBMUSCULAR PLACEMENT OF UROLOGIC PROSTHETIC BALLOONS AND RESERVOIRS: REVIEW OF 500 CASE EXPERIENCE AND REFINED TECHNIQUE FOR OPTIMAL OUTCOMES |
Sexual Function/Dysfunction: Surgical Therapy II | 17BOS |
Abstract: PD22-05 Sources of Funding: none Introduction Since 2011, we have routinely placed urologic prosthetic balloons and reservoirs (UPBRs) in a high submuscular (HSM) location during inflatable penile prosthesis (IPP) and artificial urinary sphincter (AUS) surgery. The HSM technique involves blunt dissection through the external inguinal ring to position the device in a pocket between the transversalis fascia and rectus abdominis muscle. Here we review our experience of over 500 HSM cases to compare complication rates to a prior series of Space of Retzius (SOR) cases and to describe our refined HSM technique to prevent reoperation. Methods A retrospective review was performed of patients who underwent inflatable penile prosthesis and/or artificial urinary sphincter placement between January 2009 and April 2016. Complications, intraoperative consults, and need for revision were recorded and compared between both placement modalities (HSM vs RP). Results During the study period, 815 prosthetic implants and revisions were performed, including 527 HSM cases (IPP reservoirs, n= 292; AUS balloons, n= 235). Total implant revisions across the HSM time period occurred in 64 patients (12.3%), of which only 1.5% (N=8) were attributable to the UPBR. Most common reasons for reoperation were "pain or bother" (n=4) or herniation (n=4). UPBRs placed in the SOR had a similar rate of herniation at 1% (n=3) from 2009-2011 but higher rate of deep pelvic complications compared to HSM cases (Table 1); however, no deep pelvic complications have occurred in the past 390 HSM cases since deploying our refined technique. Conclusions Further experience with HSM placement of UPBR confirms that it is well tolerated, with rare complications that are usually minor in nature. Compared to the SOR approach, the complication rates for UPBRs appear similar in frequency but potentially less catastrophic, with a lower risk to bladder or vascular structures. Our refined technique appears to further reduce risk of complications seen early in our experience. Funding none
Authors
Travis Pagliara
Boyd Viers Jeremy Scott Allen Morey |
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PD22-06 |
Rear Tip Extenders During Inflatable Penile Prosthesis Placement: Impact on need for revision |
Sexual Function/Dysfunction: Surgical Therapy II | 17BOS |
Abstract: PD22-06 Sources of Funding: None Introduction Inflatable penile prosthesis (IPP) placement is a commonly performed procedure in the treatment of erectile dysfunction (ED). Although many patients do not experience postoperative complications, some require revision surgery. Anecdotally, some have challenged the use of rear tip extenders (RTE) during surgery under the assumption that their presence decreases axial rigidity. The objective of this study is to measure the utilization patterns of RTEs over time, and determine if their use is associated with the need for IPP surgical revision. Methods A retrospective review was conducted involving 65,448 cases of IPP placement between 2000 and 2015. Cases were stratified into 2 groups based on the presence (Group A) or absence (Group B) of rear-tip extender use during IPP replacement. Collected variables include the need for revision surgery, whether or not RTEs were used, and the date of revision surgery. Primary endpoints included prevalence of RTE usage from 2000 to 2015, as well as comparison of revision rates between Group A and Group B. Results There were 35,046 (53.5%) patients in Group A and 30,402 (46.5%) patients in Group B. Between 2000 and 2015 there was a statistically significant increase in the percentage of IPP placements utilizing RTEs from 6-8% of IPP procedures in 2000 to 82% and 93% of IPP placements in 2014 and 2015, respectively (P < 0.0001, see figure 1). Revision rates for both Group A and Group B changed in a parabolic fashion between 2000 and 2015. Group A revision rates increased from less than 1% in 2000 to a peak of 3.7% in 2011, followed by a decrease to 2.4% in 2015. Similarly, Group B revision rates increased from less than 1% in 2000 to a peak of 3% in 2012, followed by a decrease to 0.5% in 2015 (see figure 2). Comparing the revision rate of the two groups over the 15-year period demonstrated a two-fold increase in the rate of revision with the use of RTE (Group A 1.34%, Group B 2.65, P < 0.0001) Conclusions The use of RTEs has increased over the last 15 years, however there appears to be a higher rate of revision surgery if the implant utilizes RTE. Given the frequent use of RTE in IPP surgery, further studies to understand this association are needed. Funding None
Authors
Kenneth DeLay
Andrew Gabrielson Faysal Yafi Wayne Hellstrom |
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PD22-07 |
Subtunical Versus Conventional Penile Prosthesis Implantation A Prospective Randomized Study |
Sexual Function/Dysfunction: Surgical Therapy II | 17BOS |
Abstract: PD22-07 Sources of Funding: none Introduction One of the most common causes of patient dissatisfaction after penile implant (PI) surgery is subjective decrease in penile volume during sexual arousal. It has been suggested that this may be explained by decreased volume of cavernosal smooth muscle, which occurs during corporal dilation. This study compared the penile length and volume as well as patient satisfaction in men after PI who were randomized to either standard corporal dilation or dilation performed purely in the sub-tunical space. Methods 110 patients were randomly assigned into two groups for malleable penile prosthesis implantation. Group A (n= 48) patients undergoing sub-tunical dilation; this technique used a Metzenbaum scissor placed through a standard corporotomy and passed ventrally sub-tunically in both proximal and distal directions. Group B (n=62) patients underwent classic corporal dilation, where dilation was conducted with Hegar dilators, with dilation up to 13mm. Patients with Peyronie’s disease (PD) were excluded. Postoperative assessment included completion of the sexual health inventory for men (IIEF-5) and a proprietary satisfaction questionnaire . We asked questions on shaft and glans engorgement . How close is your shaft /glans engorgement after surgery to befor surgery? Are you satisfied with your shaft/glans engorgement after surgery (1-5 SCALE).Patients were followed at 6 and 12 weeks and 6 months after PI surgery. Penile length ( from pubic bone to tip)and mid –shaft penile girth were measured at baseline and at each postoperative visit, and also recorded by the patient during sexual excitation . Results Both groups were matched at baseline for mean age (53.41±12.36 and 54.95±11.63 years group A and B respectively), comorbidity profile and IIEF-5 score. There were significant differences in length gain (baseline vs 6 months) and postoperative girth between groups A and B (Table 1). Patient satisfaction was higher in group A. according to patient satisfaction Q and IIEF-5 scores which were matched at baseline (7.2 versus 7.3) but different after surgery: 22.5 vs 18.2, 23 vs 17.9, 22.1 vs 19.1 (both p>0.01). Conclusions Sub-tunical dilation at the time of PI surgery appears to translate into greater penile volume gain after surgery and higher patient satisfaction. Funding none
Authors
Osama Abdelwahab
Tarek Soliman Hammoda Sherif Mohamed Habous John Mulhall |
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PD22-08 |
Times are a changing: Defining the spectrum of bacteria causing inflatable penile prosthesis infections in the era of infection-retardant coated devices. |
Sexual Function/Dysfunction: Surgical Therapy II | 17BOS |
Abstract: PD22-08 Sources of Funding: None Introduction Infection-retardant coatings on penile implants have significantly reduced the incidence of device infections. The coatings primarily target coagulase- negative Staphylococcus species. Traditionally, these organisms have been implicated in the majority of implant infections. We desired to ascertain the spectrum of bacterial species responsible for implant infections in the era following the widespread adoption of infection-retardant coated devices Methods The study cohort was derived from two prospective databases of patients undergoing penile implant surgery from two high- volume centers between February, 2004 and July, 2016. Included were those patients undergoing primary implant placement, revision surgery, and external referrals for management of an infected implant. Descriptive data included: patient age, comorbidities, first-time or revision surgery, and the organisms causing infection. Over the last 10 years, both centers have pursued an aggressive policy of performing salvage surgery. Patients who are not candidates for salvage surgery include those with systemic toxicity, purulence, cellulitis, a systemic inflammatory response, and significant soft tissue or urethral destruction. Results The cohort consisted of 39 patients, including 12 (2.8%) infections following 430 primary implant surgeries, 20 (5.5%) infections following 365 revision surgeries and 6 patients with infected implants referred from external sources (3 primary and 3 revision). Average patient age was 64.2 +/- 6.7 years. Table 1 depicts the spectrum of organisms encountered. . There were no differences between the groups in terms of comorbidities. Based upon the criteria above, only 18 (46%) patients were candidates for salvage surgery, of which 12 (67%) were successful. Conclusions The spectrum of bacterial species causing penile implant infections has changed in the era of infection-retardant coated devices. Contemporary infections are much more likely to be caused by Staph. aureus, and nearly 50% of infections are caused by gram negative bacteria. The aggressive nature of these bacteria limits the number of patients who are candidates for salvage surgery, and reduces the likelihood of an infected patient undergoing successful salvage surgery. Funding None
Authors
Bruce Kava
Steven Wilson |
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PD22-09 |
New Data Regarding HIV Status as a Predictor of Postoperative IPP Infection |
Sexual Function/Dysfunction: Surgical Therapy II | 17BOS |
Abstract: PD22-09 Sources of Funding: None Introduction Penile prosthesis infections remain challenging despite advancements in surgical technique, device improvements and adoption of antibiotic prophylaxis guidelines. Previous studies have shown that inherent patient health factors can significantly influence inflatable penile prosthesis (IPP) infection. Among these studies are data that indicate that immunocompromised patients are at higher risk for infectious complications. This study compares IPP infection rates in our HIV positive and HIV negative patients. Methods This study is a retrospective analysis of 952 patients who underwent IPP implantation by ten surgeons at three institutions. HIV status was preoperatively reviewed and no patient had viral loads, CD4 counts, or defining illnesses consistent with AIDS. Patient data were compiled after extensive review of operative reports, inpatient notes, consult notes, and follow-up visits. Age, comorbidities, overall health status, IPP manufacturer, and antibiotic prophylaxis were similar between all patients. We performed univariate statistical analysis to determine if HIV status was a significant predictor of infectious complications. Results Of 952 total patients, 25 patients were HIV positive. Twenty-eight patients (3%) in the HIV negative group had postoperative IPP infection. Two of the 25 HIV (4%) positive patients had a post-operative infection. Statistical analysis via Fisher's exact test confirmed the absence of a significant difference in infection rates between HIV positive and negative men (p=0.19). Conclusions HIV status is a not a significant predictor of infectious complications in our series of patients undergoing IPP implantation. To our knowledge this is the largest series of HIV positive patients undergoing IPP implantation in the literature. Our overall infection rate is consistent with previously published large series of implant patients. Further investigation is needed into the role of immune compromise on infection in primary implant and revision implant cases. Funding None
Authors
Martin Gross
Jared Wallen SriGita Madiraju Kevin Tayon Natan Davoudzadeh Harris Nagler Paul Perito Ricardo Munarriz Doron Stember |
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PD22-10 |
Penile Prosthesis in Solid Organ Transplant Recipients – A Matched Cohort Study |
Sexual Function/Dysfunction: Surgical Therapy II | 17BOS |
Abstract: PD22-10 Sources of Funding: none Introduction Solid organ transplantation, with its associated immunosuppression, has generally been considered a relative contraindication to penile prosthesis (PP) placement due to a perceived increased risk of complications. However, there are limited data to support this belief. We compared re-operation rates after PP in solid organ transplant patients to age-matched controls. Methods A retrospective analysis of all patients with a history of solid organ transplant that also underwent PP placement by one of three surgeons at a large, tertiary, academic center was performed. Data extracted from the medical record included age and comorbidities at implantation, device type, organ transplanted, and need for any PP reoperation (due to infection, malfunction, etc). A cohort of age-matched controls was identified for comparison. Descriptive statistics are presented as mean ± standard deviation and comparative statistics include student t-test and chi-squared test or Fisher exact test, as appropriate. Results We identified 26 patients who had undergone both solid organ transplant and PP between 1999-2015, along with an age matched group of patients who underwent PP alone. Transplants consisted of heart (N=3), liver (N=2), and kidney (N=21), with 4 kidney patients simultaneously receiving a pancreas. Mean follow up time was 29.5 months in the transplant group and 13.5 months in the PP alone group. Age at PP did not significantly differ between patients with versus without transplant (53.7±8.1 v 56.4±9.0, p 0.26), nor did BMI (30.3±5.5 v 30.2±4.7, p 0.92), history of prostate surgery (7.7% v 15.4%, p 0.39), rectal surgery (3.9% v 3.9%, p 1.00), hyperlipidemia (69.2% v 69.2%, p 1.00), hypertension (92.3% v 76.9%, p 0.25), or heart disease (57.7% v 30.8%, p 0.093). Peripheral vascular disease was more common in patients with versus without transplant (26.9% v 3.9%, p 0.021), as was stroke (19.2% v 0.0%, p 0.05) and diabetes (84.6% v 53.6%, p 0.016). No significant differences in reoperation rates existed between patients with versus without transplant (7.7% v 11.5%, p 1.00), nor between the type of organ transplanted (p 1.00). No differences in reoperation rate by implant model (2-piece versus 3-piece) were noted (p 0.47). Conclusions This study shows that outcomes of penile prosthesis placement in solid organ transplantation patients do not differ from those in non-transplant patients. Additionally both 2-piece and 3-piece implants had similar outcomes. Penile prostheses appear to be a safe option for treating erectile dysfunction in solid organ transplant recipients. Funding none
Authors
Andrew Sun
Paurush Babbar Nitin Yerram Hans Arora Drogo Montague Bradley Gill |
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PD22-11 |
A Cut-off Hba1c Value Of 8.5% Predicts Increased Risk Of Penile Implant Infection |
Sexual Function/Dysfunction: Surgical Therapy II | 17BOS |
Abstract: PD22-11 Sources of Funding: none Introduction Uncontrolled diabetes mellitus (DM) marked by elevated glycosylated hemoglobin A1c (HBA1c) values, has been correlated in some studies with an increased rate of infection after penile implant surgery. This study aimed to explore the association between HbA1C level and penile implant infection and to define if a cut-off value existed Methods Between 2009-15 HbA1c levels were obtained on all patients undergoing penile implant surgery. Preoperative, perioperative and postoperative management was identical for the entire cohort. Univariate analysis was performed to define predictors of implant infection. HbA1c levels were analyzed as a continuous variable and sequential analysis was conducted utilizing 0.5% increments to define a cut-off level predicting implant infection. Multivariable analysis was performed with the following factors entered into the model: Diabetes yes/no; HbA1C level; patient age; implant type; vascular risk factor number; presence of PD; BMI and surgeon volume. A ROC curve was generated to define the optimal HbA1C cut-off for infection prediction Results 902 implant procedures have been performed over this period of time. The mean HbA1c level = 8 ± XX%, with 81% of men having HbA1c >6%. Mean age = 56.6 years. 685 (76%) implants were malleable, and 217 (24%) were inflatable. 302 (33.5%) patients had also a diagnosis of PD. Overall infection rate was 8.9% (80/902 subjects). Patients who had implant infection had significantly higher mean HbA1c levels, 9.5% vs 7.8% (p<0.001). Grouping the cases by HbA1c level we found infection rates were: 1.3% with HBA1c <6.5%, 1.5% @ 6.5-7.5%, 6.5% @ 7.6-8.5%, 14.7% @ 8.6-9.5%, 22.4% @ >9.5%. (p<0.001). Patient age, implant type, and vascular risk factor number were not predictive. Predictors defined on MVA were: PD, increased BMI, high HbA1C while a high-volume surgeon had a protective effect and was associated with a reduced infection risk. Using ROC analysis, we found that a serum HBA1C cut-off level of 8.5% predicted infection with a sensitivity of 80% and a specificity of 65% Conclusions Uncontrolled DM is associated with increased risk of infection after penile implant surgery. The risk is directly related to HbA1C level. A threshold value of 8.5% is suggested for clinical use to identify patients at increase infection risk Funding none
Authors
Mohamad Habous
Raanan Tal Osama Abdelwahab Osama Laban Saad Mahmoud Alaa Tealab Saleh Binsaleh John Mulhall |
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PD22-12 |
A Retrospective Analysis of the Influence of High Dose Gentamicin on IPP Infection Rates |
Sexual Function/Dysfunction: Surgical Therapy II | 17BOS |
Abstract: PD22-12 Sources of Funding: None Introduction Penile prosthesis infections remain challenging despite advancements in surgical technique, device improvements and adoption of antibiotic prophylaxis guidelines. This study compares inflatable penile prosthesis (IPP) infections in patients who received standard dose, non-weight-based (NWB) intravenous gentamicin preoperatively versus high dose, weight-based (HD) intravenous gentamicin as antibiotic prophylaxis. Methods This study is a retrospective cohort comparison of 139 consecutive IPP patients who underwent implantation by a single surgeon between November 2014 and April 2015 using 1gram of IV vancomycin and 80 mg NWB IV gentamicin. These patients were matched with 184 consecutive IPP patients who underwent implantation between May 2015 and December 2015 using 1 gram of IV vancomycin and HD IV gentamicin dosed for 5 mg/kg of actual body weight. Patient data were compiled after extensive review of operative reports, inpatient notes, consult notes, and follow-up visits. Age, comorbidities, overall health status, IPP manufacturer, and oral antibiotics received 2 days prior to surgery were similar between the two cohort groups. Surgical technique and antibiotic irrigation were also indistinguishable between the cohorts. We performed univariate statistical analysis to determine significant predictors of infectious complications. Results The NWB patients suffered four postoperative IPP infections (2.8%). Three of four implants were in patients who had undergone primary implantation. One implant patient in the NWB gentamicin cohort had an infection after device removal and replacement. Two of these four patients underwent successful salvage with malleable implants, the rest underwent device explant. In contrast, none of the patients (0.0%) in the HD gentamicin cohort had a postoperative infection. The HD gentamicin cohort included 17 removal and replacement patients. Conclusions An antibiotic prophylaxis regimen consisting of high dose, weight-based gentamicin along with vancomycin reduced the rate of infectious complications in our series of patients undergoing IPP implantation. Further prospective studies are needed to compare NWB and HD gentamicin dosing to determine the utility of this regimen in primary implant and revision implant cases. Funding None
Authors
Martin Gross
Jared Wallen SriGita Madiraju Kevin Tayon Ricardo Munarriz Paul Perito |
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PD23-01 |
Comparative study between monopolar and bipolar TURP regarding the effect on the sexual function in male patients with LUTS by the use of IIEF (self-questionnaire scoring system) |
Benign Prostatic Hyperplasia: Surgical Therapy & New Technology III | 17BOS |
Abstract: PD23-01 Sources of Funding: None Introduction Compare the different impact of monopolar and bipolar TURP (Trans-urethral resection of the prostate) on the sexual function of male patients with LUTS (Lower urinary tract symptoms) by the use of IIEF ( International index of erectile function ) and to identify statistical risk factors associated with development of post-operative ED (Erectile dysfunction). Methods This study was a comparative prospective study between monopolar and bipolar TURP regarding their effect on the sexual function of male patients with LUTS by the use of IIEF. It was taken into consideration age, associated comorbidities, preoperative medications, smoking, assisted methods to obtain erection, duration of the operation, weight of the specimen and intraoperative complications (e.g. perforation (.The IIEF scores were compared one day before the surgery and 3 and 6 months after the surgery in the two limbs of the study monopolar vs. bipolar. The study design is a nonrandomized clinical trial that was carried out on a total number of 98 consecutive Egyptian patients who underwent TURP, 58 patients by the monopolar technique, 40 patients by the bipolar technique for the treatment of symptomatic benign prostatic hyperplasia. The study was done at the Department of Urology, Cairo University, between April 2014 and April 2015. An informed consent was obtained from all patients prior to enrollment in the study. Patients had to have stable sexual partners for 6 months before surgery and for 6 months postoperatively until follow-up. Results Patients were classified into two groups: patients experienced change in the EF score by less than 4 and patients experienced change in the EF score by ? 4. Change in the EF score by ? 4 was defined as the minimal clinically importance difference that is clinically perceived by the patient as a change in his erection. The incidence of ED after monopolar TURP was 22.4%, the incidence of ED after bipolar TURP was 30% and the overall incidence of post-operative ED was 25.5%. There was no statistically reported difference between monopolar and bipolar TURP on developing post-operative ED (p value 0.33 at the 3rd month and 0.397 at the 6th month). The risk factors that have been statistically associated with high incidence of post-operative ED in the whole population of study were DM (P value0.001), intraoperative capsular perforation (P value 0.0001) and preoperative use of PDE5I (P value0.004). In the monopolar group DM (P value0.002) and Intra-operative capsular perforation (P value0.00001) were the statistically significant factors associated with high incidence of post-operative ED. In the bipolar group there were no significant risk factors associated with high incidence of post-operative ED, and that were explained by the smaller sample size in the bipolar arm of the study. Other factors which were the age, the operative time, the weight of the specimen, preoperative EF score, preoperative IIEF score, smoking, COPD, cardiovascular disorders, preoperative use of alpha blocker and intraoperative or postoperative bleeding which were studied in our study showed no statistically significant impact on developing postoperative ED either in the monopolar or the bipolar arm. Conclusions TURP carries a risk of post-operative ED around 25.5% and the patient should be aware of this degree of ED. The most commonly affected domain of the 5 IIEF domains by TURP is the orgasmic domain (retrograde ejaculation) and the patient should be consented on this before the operation. Generally there is no difference between the monopolar TURP and the bipolar TURP in developing post-operative ED. DM, intraoperative capsular perforation and pre-operative use of PDE5I are important risk factors for developing post-operative ED. Larger number of patients should be included in future studies to validate these results. Funding None
Authors
G. El Shorbagy
M. El Ghoneimy A. El Feel M. Abdel Rassoul H. Hussein A. Kassem M. El Gammal |
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PD23-02 |
Transurethral enucleation with bipolar for benign prostatic hyperplasia: 2-year outcome and learning curve based on a single surgeon’s experience with 584 consecutive patients |
Benign Prostatic Hyperplasia: Surgical Therapy & New Technology III | 17BOS |
Abstract: PD23-02 Sources of Funding: none Introduction Recently, transurethral enucleation with bipolar (TUEB) was developed to enable adenoma enucleation in hospitals that do not have laser systems. The TUEB loop consists of a spatula attached to the standard tungsten wire loop, which allows urologists to perform endoscopic blunt adenoma enucleation with arrest of bleeding. This would be the first and largest study to assess 2-year outcomes and the learning curve from a single surgeon&[prime]s experience with 584 consecutive patients who underwent TUEB for benign prostatic hyperplasia (BPH). Methods We retrospectively assessed the perioperative outcomes and 2-year follow-up data of patients with BPH treated with TUEB. Between December 2011 and August 2016, 584 consecutive patients underwent TUEB for BPH, performed by a single surgeon. The patients were preoperatively assessed in terms of the International Prostate Symptom Score (IPSS), quality of life score (QOLs), serum prostate-specific antigen (PSA) level, and uroflowmetry parameters. Intraoperative and postoperative outcomes were also evaluated. Early and late postoperative complications were recorded. The patients were evaluated at the 3-, 12-, and 24-month follow-up by using IPSS, QOLs, and uroflowmetry. Results The mean (± standard error) age was 69.6 ± 0.26 years; estimated prostate volume, 54.7 ± 0.90 cm3 (range, 23-160 cm3); operative time, 58.0 ± 1.1 min; and prostatic specimen weight, 30.6 ± 0.68 g. The overall efficiency of the TUEB procedure (prostatic specimen weight [grams] / operative time [minutes]) was 0.54 ± 0.01 g/min. The efficiency increased proportionally with the weight of the prostatic specimen. TUEB appears to have a steep learning curve, and the efficiency of the procedure increased markedly and remained stable when the experience level exceeded 50 cases. The PSA reduction before and after the operation was 80.2% ± 0.78%. The maximum flow rate (26.7 ± 1.3 mL/s, p < 0.001), mean flow rate (15.5 ± 0.45 mL/s, p < 0.001), IPSS (3.8 ± 0.19, p < 0.001), and QOLs (1.0 ± 0.06, p < 0.001) significantly improved at the 2-year follow-up compared with the baseline values. None of the patients experienced persistent stress incontinence or needed autologous and homologous blood transfusion after TUEB. Conclusions TUEB represents an effective and safe alternative enucleation technique for the complete removal of adenomatous prostate tissue in patients with BPH, regardless of gland size. The relief from bladder outlet obstruction also proved to be durable after the 2-year follow-up. Funding none
Authors
Yosuke Hirasawa
Yuji Kato Kiichiro Fujita |
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PD23-03 |
Prospective Randomized Study Comparing Monopolar with Bipolar Transurethral Resection Of Prostate On A Large Cohort Of Patients With Benign Prostatic Obstruction: Long Term Outcomes |
Benign Prostatic Hyperplasia: Surgical Therapy & New Technology III | 17BOS |
Abstract: PD23-03 Sources of Funding: None Introduction Monopolar transurethral resection of the prostate (TURP) is the gold standard surgical treatment for bothersome moderate to severe lower urinary tract symptoms (LUTS) secondary to benign prostate obstruction with enlarged prostates. The aim of the study is to compare monopolar vs. bipolar TURP focusing on operative and functional outcomes with a long term follow-up. Methods From January 2007 to July 2013 a total of 379 patients were randomized and prospectively scheduled to undergo bipolar (202) or monopolar (177) TURP. International prostate symptom score (IPSS), IPSS-Quality of life (QoL), post-void residual and maximum flow rate were assessed preoperatively and postoperatively at 3, 12, 24 and 36 months. Operative time, length of catheterization and length of hospitalization were all recorded. Rates of urethral strictures and bladder neck contractures were also reported. Results Perioperative results showed no statistical significance between the two groups in terms of catheterization days, post-void residual, IPSS, IPSS-QoL score, blood transfusion and TUR syndrome. The operative time was proved to be statistically significant in the monopolar group while the hospitalization days was found statistically significant in the bipolar group. The 3, 12, 24 and 36 months follow up showed significant and equal improvements in LUTS related to BPO in the 2 treatment groups. Conclusions Monopolar and bipolar TURP are safe and effective techniques for BPH. The 2 significant differences between them were operative time in favour of the monopolar group and hospitalization days in favour of the bipolar group. Bipolar TURP has the principle advantage in preventing TUR syndrome that was reported in 2 monopolar TURP patients. Funding None
Authors
Giovanni Palleschi
Antonio Luigi Pastore Yazan Al Salhi Andrea Fuschi Gennaro Velotti Antonino Leto Antonio Carbone |
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PD23-04 |
Thulium laser enucleation (thulep) versus transurethral resection of the prostate in saline (turis): a randomized prospective trial to compare costs per procedure |
Benign Prostatic Hyperplasia: Surgical Therapy & New Technology III | 17BOS |
Abstract: PD23-04 Sources of Funding: none Introduction To compare the costs per procedure between thulium laser transurethral enucleation of the prostate (ThuLEP) and transurethral bipolar resection of the prostate (TURIS) for treating benign prostatic hyperplasia (BPH) in a prospective randomized trial. Methods The study randomized 208 consecutive patients with BPH to ThuLEP (n = 102) or TURIS (n =106). For all patients were evaluated preoperatively with regards to blood loss, catheterization time, irrigation volume, hospital stay and operative time. At 3 months after surgery they were also evaluated by International Prostate Symptom Score (IPSS), maximum flow rate (Qmax), and postvoid residual urine volume (PVR) to see if a cost reduction could be correlated with a worst outcome_x000D_ Results The patients in each study arm each showed no significant difference in preoperative parameters. Compared with TURIS, ThuLEP had same operative time (53.69±31.44 vs 61.66±18.70 minutes, P = .123) but resulted in less hemoglobin decrease (0.45 vs 2.83 g/dL, P = .005). ThuLEP also needed less catheterization time (1.3 vs 4.8 days, P = .011), irrigation volume (29.4 vs 69.2 L, P = .002), and hospital stay (1.7 vs 5.2 days, P = .016). Average cost for a ThuLEP was 1181 euros while was 1761,16 for a TURIS (p< .005). During the 3 months of follow-up, the procedures did not demonstrate a significant difference in Qmax, IPSS, PVR, and QOLS._x000D_ Conclusions ThuLEP and TURIS both relieve lower urinary tract symptoms equally, with high efficacy and safety. ThuLEP was statistically superior to TURIS as a cheaper procedure. However, procedures did not differ significantly in Qmax, IPSS, PVR, and QOLS through 3 months of follow-up_x000D_ Funding none
Authors
Giorgio Bozzini
Stefano Casellato Serena Maruccia giovanni saredi paolo parma Gianluigi Taverna |
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PD23-05 |
Inferior tissue ablation after 120W greenlight laser vaporization does not translate into inferior clinical outcome compared conventional TURP: 3-year results of a prospective 3D ultrasound volumetry study |
Benign Prostatic Hyperplasia: Surgical Therapy & New Technology III | 17BOS |
Abstract: PD23-05 Sources of Funding: none Introduction Functional short-term outcome following 120W greenlight laser vaporization (LV) has been shown to be comparable to conventional transurethral resection of the prostate (TURP). However, mid-term results following 80W greenlight LV revealed that high retreatment rates are common after the procedure most likely due to insufficient tissue ablation. Short-term outcome of our 3D ultrasound volumetry study revealed a significantly lower volume reduction one year after 120W LV compared to TURP. Additional follow-up was now performed to investigate further changes in volume reduction and associated clinical outcome 3 years after LV and TURP. Methods A total of 174 patients (120W LV; n=98, 56% vs. TURP; n=76, 44%) were included in this prospective study and were followed for 3 years. Transrectal 3D ultrasound and planimetric volumetry of the prostate was performed preoperatively, after catheter removal, 6W, 6M, 12M and 3Y. Clinical outcome parameters (PSA, IPSS, Qmax, residual volume) were recorded preoperatively and at each follow-up visit. Results Median initial prostate volume was not significantly different between the groups (LV: 44.1ml, TURP: 44.8ml; p=0.47). After catheter removal, the relative prostate volume reduction (RVR) was significantly lower following LV (table). Six weeks and six months after LV RVR increased significantly (both p<0.001). However, RVR remained significantly lower after LV throughout the entire 3-year observation period (table). All clinical outcome parameters improved significantly and remained so for 3 years without relevant differences between the groups. No significant differences in overall re-treatment rates were observed (LV: 5 (5.1%), TURP: 5 (6.5%), p=0.75) Conclusions After 3 years, prostate volume reduction remained inferior after 120W greenlight LV compared to TURP. However, as yet the lower volume reduction did not translate into inferior functional outcome or higher retreatment rates. Further follow-up of our cohort will reveal if the extent of tissue ablation impacts the long-term outcome of the procedures. Funding none
Authors
Benedikt Kranzbühler
Oliver Gross Christian D. Fankhauser Marian S. Wettstein Nico C. Grossmann Etienne X. Keller Daniel Eberli Tullio Sulser Cédric Poyet Thomas Hermanns |
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PD23-06 |
Thulium vapoenucleation of the prostate versus holmium laser enucleation of the prostate: 6-month safety and efficacy results of a prospective randomized trial |
Benign Prostatic Hyperplasia: Surgical Therapy & New Technology III | 17BOS |
Abstract: PD23-06 Sources of Funding: Boston Scientific (#ISRURO400001) Introduction To compare the 6-month outcomes of thulium vapoenucleation of the prostate (ThuVEP) with holmium laser enucleation of the prostate (HoLEP) for patients with symptomatic benign prostatic obstruction (BPO). Methods A prospective randomized trial comparing ThuVEP with HoLEP was conducted from February 2015 to February 2016 at the Asklepios Klinik Barmbek. A total of 94 patients with symptomatic BPO were prospectively randomized to ThuVEP (n=48) or HoLEP (n=46). All patients were assessed preoperatively by International Prostate Symptom Score (IPSS), Quality of Life (QoL), maximum urinary flow rate (Qmax), post-void residual urine (PVR), PSA, and prostate volume measurement by transrectal ultrasound. The patients were reassessed with the same tests at 1-month and 6-month follow-up. The complications were noted and classified according to the modified Clavien classification system. Patient data were expressed as median (interquartile range) or numbers (%). Results There were no statistically significant differences in any baseline characteristics between the groups. Median age at surgery was 73 (67-76) yrs. and median prostate volume was 80 (46.75-100) cc. 43 (45.7%) patients presented in urinary retention with an indwelling catheter. The median operative time was 60 (41-79) minutes without significant differences between the groups. There were no significant differences between the groups regarding catheter time (2 (2-2) days) and postoperative stay (2 (2-3) days). Clavien 1 (13.8%), 2 (3.2%), 3a (2.1%), and Clavien 3b (4.3%) complications occurred without significant differences between the groups. However, the occurrence of acute postoperative urinary retention was significantly higher after HoLEP compared to ThuVEP (15.2% vs. 2.1%, p≤0.022) at 4-week follow-up. At 6-month follow-up, median Qmax (10.7 vs. 25.9 ml/s), PVR (100 vs. 6.5 ml), IPSS (20 vs. 5), QoL (4 vs. 1), PSA (4.14 vs. 0.71 μg/l), and prostate volume (80 vs. 16 ml) had improved significantly (p<0.001) compared to baseline without differences between the groups. The median PSA decrease was 79.7% (58.8-90.6%) and the median prostate volume reduction was 74.5% (68.57-87.63%) without differences between the groups. The reoperation rate was zero at 6-month follow-up. Conclusions ThuVEP and HoLEP are both safe and effective procedures for the treatment of symptomatic BPO. Both procedures give equivalent and satisfactory micturition improvement with low morbidity and sufficient prostate volume reduction at 6-month follow-up. Funding Boston Scientific (#ISRURO400001)
Authors
Christopher Netsch
Benedikt Becker Christian Tiburtius Christina Moritz Arcangelo Venneri Becci Thomas Herrmann Andreas Gross |
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PD23-07 |
Effect of Holmium Laser Enucleation of the Prostate (HoLEP) on the Sexual Function |
Benign Prostatic Hyperplasia: Surgical Therapy & New Technology III | 17BOS |
Abstract: PD23-07 Sources of Funding: none Introduction The surgical intervention in patients with the lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia (BPH) may affect the sexual function; however modern approaches to treatment (enucleation techniques) may preserve sexual function. Holmium laser enucleation of the prostate (HoLEP) is one of them. _x000D_ The aim of the study was to evaluate the sexual and erectile function in patients with benign prostatic hyperplasia who were subjected to HoLEP. Methods Four hundred and fifty-nine patients with benign prostatic hyperplasia (mean age 68.7 years) who experienced holmium laser enucleation of the prostate participated in the study. All the patients were tested according to the International Index of Erectile Function (IIEF) to assess their sexual function, and the IPSS ? QoL scores were also determined for all the patients to evaluate the results of the operation. Results The patient's erectile function, ejaculation, sexual desire, and the general satisfaction with sexual intercourse were evaluated according to the IIEF. All the patients were examined both before surgery and 6 and 12 months after the operation. It is important to note that most parameter values remained virtually unchanged, although the ejaculation quality score decreased due to retrograde ejaculation in 297 patients (64.7%). _x000D_ Note that all the patients reported better satisfaction with sexual intercourse (from 22.1 to 23.3) that correlated with an improvement in the QoL and IPSS scores. The number of patients with complaints of erectile disorders was not increased. The effect of this surgical intervention was more pronounced in the group of patients with more severe pre-existing erectile dysfunction. _x000D_ _x000D_ _x000D_ Conclusions HoLEP results in a significant improvement in the IPSS, QoL and does not influence the values pertaining to the erectile function (IIEF). Despite the occurrence of postoperative retrograde ejaculation in a large percentage of patients, most of them did not regard this complication as significant, which was evidenced by higher QoL and IIEF scores in the postoperative period compared with the preoperative findings. These facts allow us to characterize HoLEP as a technique that helps to preserve and, in certain cases, to improve the erectile and sexual function in patients with benign prostatic hyperplasia. Funding none
Authors
Petr Glybochko
Yuriy Alyaev Leonid Rapoport Mikhail Enikeev Dmitry Enikeev Nikolay Sorokin Roman Sukhanov Alim Dymov Otabek Khamraev Denis Davydov Mark Taratkin |
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PD23-08 |
True Cost of Morcellation: Comparison of the Lumenis® VersaCut™ and Wolf Piranha Morcellators |
Benign Prostatic Hyperplasia: Surgical Therapy & New Technology III | 17BOS |
Abstract: PD23-08 Sources of Funding: None Introduction Holmium laser enucleation of the prostate (HoLEP) for the management of benign prostatic hyperplasia has two procedural steps: Enucleation of the adenoma and tissue morcellation. While a recent randomized trial evaluating the two currently available morcellators found no significant difference in morcellation efficiency an analysis of cost was not performed factoring in the expense of operating room (OR) time. Therefore, we aim to evaluate the true cost associated with each device in a matched cohort analysis. Methods An institutional review board approved prospectively maintained database of HoLEP patients was utilized for this study. We evaluated all patients from 2013, the last year our institution exclusively used the VersaCutâ„¢ morcellator a reusable blade device, and matched them 1:1 with the most recent patient cohort utilizing the Piranha morcellator, a disposable blade device. Statistical analysis utilizing student t-Test was performed evaluating differences in means regarding morcellation efficiency, cost of morcellation including the expense of OR time and disposable instrument costs. Results We identified 142 patients within our institutional database who underwent HoLEP in 2013 with the VersaCut device and matched them 1:1 to our most recent group of patients undergoing the same procedure with the Piranha. There were no statistically significant differences between the previous and most recent group with regards to patient age (69.8 versus 69.9 yrs, p=0.9) and total enucleated tissue weight (72.8 versus 77.7g, p=0.46), respectively. However, when compared with the Versacut group, morcellation efficiency (4.4 versus 7.0 g/min, p<0.01) and expense of OR time ($1420.80 versus $992.21, p<0.005) both favored the Pirahna morcellator system. When the costs of disposable instruments were factored into the analysis with OR time costs, total cost still favored the Pirahna morcellator ($1338.81versus $1637.50, p<0.05). Conclusions In a matched cohort comparing morcellation cost utilizing both the VersaCutâ„¢ and Piranha morcellation devices, we identified a significant improved efficiency and improved cost savings utilizing the Piranha morcellator even when controlling for disposable costs. Funding None
Authors
Marcelino Rivera
James Lingeman Nadya York Hazem Elmansy Amy Krambeck |
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PD23-09 |
Factors associated with early recovery of stress urinary incontinence following Holmium laser enucleation of prostate in patients with benign prostatic hyperplasia |
Benign Prostatic Hyperplasia: Surgical Therapy & New Technology III | 17BOS |
Abstract: PD23-09 Sources of Funding: none Introduction We investigated factors associated with early recovery of stress urinary incontinence (SUI) following holmium laser enucleation of prostate (HoLEP) in patients with BPH. Methods We retrospectively reviewed the medical records of 393 patients who had undergone HoLEP for BPH. Those with prostate cancer diagnosed before or after HoLEP, a history of other prostatic and/or urethral surgery, moderate to severe postoperative complications, and neurogenic causes were excluded. Patients with SUI following HoLEP were included, and we divided the patients into two groups: the early recovery of SUI group and the persistent SUI group. Early recovery of SUI was defined as recovery of SUI within one month after HoLEP, and persistent SUI was defined as SUI is still present after one month. Preoperative clinical and urodynamic factors, as well as perioperative factors, were compared between groups. Results SUI following HoLEP was found in 86 patients (86/393, 21.9%). Thirty-three patients (33/86, 38.4%) showed recovery of SUI within one month, and SUI was still present in 53 patients (53/86, 61.6%) after one month. The preoperative clinical characteristics and urodynamic parameters are shown in Table 1. The transitional zone volume of prostate in the early recovery of SUI group was higher than that in the persistent SUI group. In a comparison of perioperative factors, enucleation ratio (enucleation weight/transitional zone volume) in the early recovery of SUI group was lower than that in the persistent SUI group. (0.65 ± 0.32 vs 0.9 ± 0.69, P = 0.010) A multivariate analysis showed that the enucleation ratio (OR 4.252, 95%CI 1.112-16.261, P = 0.034) was significantly associated with the early recovery of SUI. Conclusions Persistent SUI for more than one month following HoLEP occurred in some patients, and the high enucleation ratio could be associated with it. These patients would need early management for SUI following HoLEP. Funding none
Authors
Kang Jun Cho
Jun Sung Koh Hyun Woo Kim Dong Hwan Lee Hyo Sin Kim Joon Chul Kim |
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PD23-10 |
Convective radiofrequency thermal therapy: durable two-year outcomes of a randomized controlled and prospective crossover study to relieve lower urinary tract symptoms due to benign prostatic hyperplasia |
Benign Prostatic Hyperplasia: Surgical Therapy & New Technology III | 17BOS |
Abstract: PD23-10 Sources of Funding: NxThera, Inc. Introduction We report 2-year outcomes of a randomized controlled trial (RCT) plus 1-year results of a crossover trial after treatment with convective radiofrequency (RF) water vapor thermal therapy (Rezum System) for lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH). RF energy generates wet thermal energy in the form of water vapor that convectively disperses through tissue interstices, remaining confined within prostate zones to achieve rapid ablation of obstructive tissue. Methods Men ≥ 50 years old with International Prostate Symptom Score (IPSS) ≥13, maximum flow rate (Qmax) ≤ 15 ml/s and prostate volume 30-80 cc were randomized 2:1 to RF thermal therapy with the Rezum System and control. Rigid cystoscopy with simulated active treatment sounds served as the control procedure. After unblinding at 3 months, control subjects were requalified for the crossover study. The primary endpoint compared IPSS reduction at 3 months and evaluations continued to 24 months Results Mean IPSS was reduced by 50% after RF thermal therapy (-11.2) vs. 20% (-4.3) for control at 3 months (p<0.0001); relief of LUTS remained durable with 51% improvements at 2 years (p<0.0001). The ≥5 (moderate) or ≥8 point (marked) IPSS decreases occurred in 84% and 74% of men through 24 months, respectively; 75% of these had severe LUTS (IPSS ≥19). Qmax increased 68% (6.2 ml/s) at 3 months vs. no change in controls (p <0.0001) and remained significantly improved at 2 years. Crossover subjects (n=53) had IPSS, Qmax and quality of life markedly improved after RF thermal therapy vs. prior control procedure (p <0.024 - <0.0001). Median lobe treatments were performed in 58 of 188 (31%) subjects in both studies; those with and without median lobe ablation achieved similarly reduced IPSS and improved Qmax. Sexual function assessments with the International Index of Erectile Function and Male Sexual Health Questionnaire remained stable. No de novo erectile dysfunction was reported. Conclusions Convective RF thermal therapy is a minimally invasive office or outpatient procedure requiring minimal anesthesia to achieve early, clinically meaningful LUTS relief and improved flow rate that remain durable for at least 2 years. Therapy is applicable to all obstructed prostate zones including median lobe. Patients experience minimal side effects. Rezum therapy conserves sexual function and presents an attractive alternative for men exploring a nonsurgical option for moderate to severe LUTS/BPH. Funding NxThera, Inc.
Authors
Claus Roehrborn
Steven Gange Marc Gittelman Kenneth Goldberg Kalpesh Patel Neal Shore Richard Levin Michael Rousseau J. Randolf Beahrs Jed Kaminetsky Barrett Cowen Christopher Cantrill Lance Mynderse James Ulchaker Thayne Larson Christopher Dixon Kevin McVary |
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PD23-11 |
Aquablation of the Prostate for Symptomatic Benign Prostatic Hyperplasia: Two-Year Results |
Benign Prostatic Hyperplasia: Surgical Therapy & New Technology III | 17BOS |
Abstract: PD23-11 Sources of Funding: Procept Biorobotics Introduction Early data concerning Aquablation (water jet-based prostate ablation) for lower urinary tract symptoms due to benign prostatic hyperplasia has suggest efficacy similar to that of Transurethral Resection of the Prostate (TURP) in the short term. This study sought to examine the medium-term results with this technique. Methods A prospective single-arm multicenter trial was conducted at 3 centers in Australia and New Zealand with 2-year follow-up. Participants were men aged 50-80 years with moderate-to-severe lower urinary tract symptoms, prostates <80g and obstruction as determined by pressure-flow urodynamic studies. All patients underwent Aquablation with image guidance. Follow-up was performed at 1 and 2 years. Results Twenty-one men underwent Aquablation with a mean age of 69.7 (range 62-78) years and prostate volume of 57.2 (30-102) mL. Two-year follow-up was available in 16 subjects. Mean IPSS score improved from 22.8 at baseline to 6.8 at 12 months and 6.7 at 24 months. Qmax improved from 8.6 cc/sec at baseline to 14.8 sec at 24 months. PVR decreased from 116 cc at baseline to 38 cc at follow-up. There were no adverse events (> Clavien 3) between year 1 and year 2. Conclusions This phase II study provides evidence to support the medium-term safety and effectiveness of Aquablation for symptomatic BPH. Funding Procept Biorobotics
Authors
Peter Gilling
Paul Anderson Andrew Tan |
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PD23-12 |
COMPARISON OF PERIOPERATIVE OUTCOMES BETWEEN HOLMIUM LASER ENUCLEATION OF THE PROSTATE AND ROBOTIC ASSISTED SIMPLE PROSTATECTOMY |
Benign Prostatic Hyperplasia: Surgical Therapy & New Technology III | 17BOS |
Abstract: PD23-12 Sources of Funding: None Introduction Simple prostatectomy is the standard surgical treatment for benign prostatic hypertrophy (BPH) in men with large prostates. There are increasing efforts to treat BPH with minimally invasive techniques including holmium laser enucleation of the prostate (HoLEP) and robotic assisted simple prostatectomy (RSP). Herein we compare perioperative outcomes for patients undergoing one of these two procedures. Methods Patient demographics and perioperative outcomes were compared between 600 patients undergoing HoLEP and 32 patients undergoing RSP at two separate academic institutions between 2008 and 2015. Results Patients undergoing HoLEP and RSP had comparable ages (71 vs. 71, p=0.96) and baseline AUA symptom scores (20 vs. 24, p= 0.21). There was no difference in mean specimen weight (96 vs. 110 g, p=0.15). Mean operative time was reduced in the HoLEP cohort (103 vs. 274 minutes, p<0.001). Patients undergoing HoLEP had lesser decreases in hemoglobin, decreased transfusions rates, shorter hospital stays, and decreased mean duration of catheterization. There was no difference in the rate of complications Clavien grade 3 or greater (p=0.33). Conclusions HoLEP and RSP are both efficacious treatments for large gland BPH. In expert hands HoLEP appears to have a favorable perioperative profile. Further studies are necessary to compare long-term efficacy, cost, and learning curve influences, especially as minimally invasive approaches become more widespread. Funding None
Authors
Mimi W. Zhang
Marawan M. El Tayeb Michael S. Borofsky Casey A. Dauw Kristofer R. Wagner Patrick S. Lowry Erin T. Bird Tillman C. Hudson James E. Lingeman |
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PD24-01 |
Comparative assessment of efficacies between two alternative therapeutic sequences with novel androgen receptor-axis-targeted agents in patients with chemotherapy-naive metastatic castration-resistant prostate cancer |
Prostate Cancer: Advanced (including Drug Therapy) I | 17BOS |
Abstract: PD24-01 Sources of Funding: None Introduction Accumulating findings suggest that sequential treatment with androgen receptor-axis-targeted (ARAT) agents, abiraterone acetate (AA) and enzalutamide (Enz), in either order has limited efficacy for metastatic castration-resistant prostate cancer (mCRPC). Furthermore, there has been a strong trend toward the movement of novel ARAT therapies into the front-line for mCRPC treatment prior to the introduction of docetaxel within the last few years, due to the favorable tolerability of ARAT agents compared with taxanes. Considering these findings, it is still important to determine the optimal sequencing order of novel ARAT agents for mCRPC patients. The objective of this study was to compare the efficacies of sequential therapies with novel ARAT agents in patients with docetaxel-naive mCRPC. Methods This study included 108 consecutive mCRPC patients who sequentially received AA and Enz, in either order, without prior treatment with docetaxel. The combined prostate-specific antigen (PSA) progression-free survival (PFS) was defined as the sum of PFS1 and PFS2, representing PSA PFSs on the first and second ARAT agents, respectively. Results Of the 108 patients, 49 and 59 received ARAT therapy with the AA-to-Enz sequence (AA-to-Enz group) and that with the reverse sequence (Enz-to-AA group), respectively. No significant differences in the baseline characteristics were noted between the two groups. In the overall patient population, the PSA response rate to the second-line ARAT agent (56.5%) was significantly lower than that to the first-line ARAT agent (21.3%). The combined PSA PFS in the AA-to-Enz group (median, 18.4 months) was significantly superior to that in the Enz-to-AA group (median, 12.8 months). Furthermore, multivariate analysis identified the treatment sequence (i.e., AA-to-Enz versus Enz-to-AA group) in addition to performance status as an independent predictor of combined PSA PFS in these patients. Conclusions Although cross-resistance between ARAT agents is a common phenomenon in docetaxel-naive mCRPC patients, different efficacies were observed favoring the AA-to-Enz rather than Enz-to-AA sequence in this series. Thus, when ARAT agents are to be introduced sequentially, it may be advisable to provide ARAT therapy according to the AA-to-Enz sequence. Funding None
Authors
Yuto Matsushita
Hideaki Miyake Seiichiro Ozono |
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PD24-02 |
68Ga-PSMA PET/CT improves biochemical response after salvage lymph node dissection for nodal recurrence in prostate cancer patients |
Prostate Cancer: Advanced (including Drug Therapy) I | 17BOS |
Abstract: PD24-02 Sources of Funding: None. Introduction The management of patients with biochemical recurrence (BCR) after curative treatment for prostate cancer (PCa) remains controversial. Our aim was to investigate if preoperative 68Ga-PSMA-HBED-CC (68Ga-PSMA) positron emission tomography / computed tomography (PET/CT) improves biochemical response (BR) in patients undergoing salvage lymph node dissection (sLND) for recurrent PCa while evaluating complications, predictors and overall survival rates. Methods Between 2005 and 2016 we performed sLND in 104 PCa patients diagnosed with nodal recurrence on either 18F-fluoroethylcholine (18F-FEC) or 68Ga-PSMA PET/CT after radical prostatectomy (RP). Surgical complications according to Clavien-Dindo classification, and BR, BCR after BR, clinical recurrence (CR), and cancer-specific survival (CSS) were evaluated. Survival rates were assessed and logistic regression was used to determine predictors of BR and CR after sLND. Results Mean follow-up after sLND was 45.7 ± 30.4 months. Mean patient age and prostate-specific antigen (PSA) at sLND were 64.7 ± 7.0 years and 8.2 ± 14.8 ng/mL. 12.7%, 17.6% and 53.9% of patients underwent radiotherapy (RT), androgen deprivation therapy (ADT) and both RT + ADT after RP. Mean number of lymph nodes (LNs) removed was 17.1 ± 15.0 per patient at sLND; mean number of positive LNs was 5.2 ± 7.4 per patient. 29.8% of patients developed complete BR (cBR) (PSA <0.2 ng/mL), and 56.7% of partial BR (PSA postoperative < PSA preoperative). Patients diagnosed with preoperative 68Ga-PSMA PET/CT showed a significantly higher rate of cBR after sLND compared to 18F-FEC PET/CT (45.7 vs. 21.7%, p=0.040). BCR after cBR was detected in 71.0% of patients, and CR on PET/CT occurred in 70.2% of patients during follow-up. The 5-year BCR-free, CR-free and CSS rates were 6.2%, 26.0%, and 82.8%, respectively. At multivariate logistic regression, continuous PSA (p=0.031) and choice of PET tracer (p=0.048) were independent predictors of cBR. Overall rate of Clavien-Dindo Grade III complications was low (4.8%). Conclusions sLND may be safely performed with low complication rates. While preoperative staging with 68Ga-PSMA seems superior to 18F-FEC PET/CT, only a limited number of patients developed cBR after surgery. The majority of patients progressed to BCR and CR after cBR. The real clinical benefit of sLND for nodal recurrence after RP with regard to improved survival needs to be assessed in future prospective randomized trials. Funding None.
Authors
Annika Herlemann
Alexander Kretschmer Alexander Buchner Alexander Karl Stefan Tritschler Lina El-Malazi Vera Wenter Harun Ilhan Peter Bartenstein Christian Georg Stief Christian Gratzke |
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PD24-03 |
Oncological outcomes of patients treated with salvage lymphnode dissection (sLND) for positron-emission tomography (PET) positive prostate cancer (PCa) relapse |
Prostate Cancer: Advanced (including Drug Therapy) I | 17BOS |
Abstract: PD24-03 Sources of Funding: none Introduction The role of salvage lymphnode dissection (sLND) in patients (pts) with PET positive PCa relapse to delay the administration of systemic therapy is still under debate. The aim of our study was to describe the oncological outcomes of pts undergoing sLND after positive PET signals for suspicious nodal recurrence. Methods Between 2009 and 2016, 43 consecutive patients with nodal uptake at PET/CT scan (Cholin, Acetate, PSMA, Bombesin) suggesting presence of nodal recurrence after curative treatment underwent 49 sLNDs at a single institution. After surgery, PSA values were measured systematically. When post-sLND PSA nadir was <0.01 ng/ml, salvage treatment failure (sTF) was defined by biochemical recurrence (BCR, PSA >0.2 ng/ml, Group A). When post-sLND PSA Nadir was >0.01 ng/ml, sTF was recorded when post-sLND PSA value reached the pre-sLND value (Group B) or when an additional salvage PCa treatment was given (Group C). Student't T test was used to compare means. Results Overall, 42 and 1 out of 43 patients underwent radical prostatectomy and brachytherapy, respectively. Mean and median PSA value at PET/CT scan were 6.7 and 2.9 ng/ml (IQR 1.2-6.1), respectively. Open and laparoscopic sLNDs were performed in 37/49 (76%) and 12/49 (34%), respectively. Histological report was positive for PCa in 36/49 sLND (73%). Five of 36 patients were lost at follow up. Group A consisted of 4 patients and 2 had sTF. Group B and C consisted of 14 and 13 patients and all had sTF. Mean and median PSA value before sLND in Group A, B, C were 1.4 and 1.3 ng/ml (IQR 0.6-2.2), 9 and 3.5 ng/ml (IQR 1.6-12.9), 9.4 and and 3.5 ng/ml (IQR 2.3-16.9), respectively. Median PSA nadir in group B and C was 0.67 ng/ml (IQR 0.36-2.6) and 3.14 ng/ml (IQR 0.7-4.4), respectively (p=0.3). Median time to sTF was 11 months (IQR 8-55 months), 5 months (IQR 1.7-13.2) and 4 months (IQR 2.0-10) for group A, B and C. Mean time to sTF in Group A was significantly superior to mean time in Group B and C together (p=0.01). Only 2 of 43 patients were long-term free of recurrence. Limitations of this study are missing PET controls after sLND and PSA persistence, low patient numbers and the retrospective design. Conclusions Only pts with positive histological report with a PSA nadir <0.01 ng/ml after sLND seem to have a long-term benefit. Pts with a PSA nadir >0.01ng/ml have a delay of systemic treatment of up to 5 months. Pts without PSA response do not benefit from sLND. Funding none
Authors
Andreas Hiester
Alessandro Nini Günter Niegisch Peter Albers Volker Mueller-Mattheis Robert Rabenalt |
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PD24-04 |
The importance of imaging studies to monitor treatment with novel AR-targeted agents in metastatic castration resistant prostate cancer (mCRPC). |
Prostate Cancer: Advanced (including Drug Therapy) I | 17BOS |
Abstract: PD24-04 Sources of Funding: None Introduction Abiraterone acetate (AA/P) and enzalutamide (ENZ) represent the treatment of choice in men with asymptomatic or mildly symptomatic mCRPC. Altough serial PSA measurements are required to monitor response and progression, the role of serial imaging studies is unclear in daily routine. It was the purpose of our study to evaluate the potential additional benefit of imaging to monitor the disease. Methods A total of 56 patients with mCRPC underwent systemic first line treatment with ENZ or AA/P after failing primary LHRH-therapy. Mean serum testosterone was 34.4 (18 – 48) ng/dl. Patients underwent analysis of the serum markers PSA, alk. Phosphatase, CRP, hemoglobine, and LDH at 3-months intervals. In addition imaging studies were repeated at 3-months intervals or in case of PSA or symptomatic progression. Results Mean duration of AA/P treatment is 12.7 (2-19) months and mean duration of ENZ therapy is 17.2 (3- 29) months. A PSA-response was achieved in 76% and 81% in the AA/P and the ENZ group, respectively. Beside PSA, responding patients in the AA/P group demonstrated a significant decrease in serum concentrations of LDH (367,96 225,4U/l) and alk. Phosphatase (249,59 117U/l) whereas responding pts in the ENZ group demonstrated a decrease in LDH only (339,5 228,33U/l). Median duration of PSA response is 10.8 and 11.5 months in the AA/P and the ENZ group, respectively. Despite stable serum levels of 0.6 (0.2-0.9) ng/ml and an asymptomatic status, 8 patients exhibited a significant radiographic progression in number and size of lymph node metastases (n=5) or skeletal metastases (n=3). 4 pts underwent local therapy of the progressing site by stereotactic radiation and in 4 pts treatment was switched to docetaxel. Conclusions Despite considerable and stable PSA-response 15% of our patients exhibited significant metastatic progression which would not have been detected without serial imaging studies. Therefore, we strongly advocate imaging studies even in the presence of stable PSA serum levels. _x000D_ Funding None
Authors
Isabel Heidegger
David Pfister Daniel Porres Pia Paffenholz Axel Heidenreich |
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PD24-05 |
Impact of abiraterone acetate in the post-docetaxel setting on the survival of metastatic castration-resistant prostate cancer patients: a population-based study in Quebec |
Prostate Cancer: Advanced (including Drug Therapy) I | 17BOS |
Abstract: PD24-05 Sources of Funding: Prostate Cancer Canada Discovery Grant 2013_x000D_ Cote-Sharp Family Foundation Introduction Abiraterone was introduced in Quebec in 2012 for metastatic castration-resistant prostate cancer (mCRPC) in the post-docetaxel setting. This study described abiraterone utilization in the early post-approval period and its clinical effectiveness in Quebec, for both post-chemotherapy patients and patients unfit for chemotherapy. Methods A retrospective cohort study was conducted using Quebec public healthcare administrative databases. The study population consisted of men 40 years and older with a diagnosis of prostate cancer (PCa), and who received androgen-deprivation therapy (ADT) (orchiectomy or luteinizing hormone-releasing hormone analogs or antagonists (LHRHa)) between January 2001 and July 2013. In addition, patients should have received a first treatment of abiraterone between 2012 and 2013. Treatment groups were defined as: 1) Abiraterone post chemotherapy and 2) Abiraterone “exception patient”, for chemotherapy-ineligible patients treated with abiraterone authorized by the “exception patient” measure category. Study outcomes included overall survival since abiraterone initiation, abiraterone duration, and hospitalization days. Cox proportional hazard regression was used to estimate the effectiveness of abiraterone in the post-docetaxel setting adjusted for several covariates. Results Our cohort consisted of 303 mCRPC patients treated with abiraterone (abiraterone post-chemotherapy: 99 and abiraterone “exception patient”: 204). The median age was 75.0 for the abiraterone post-chemotherapy group and 80.0 for the abiraterone “exception patient” group. The corresponding median survivals were 12 and 14 months, respectively (log-rank test p-value=0.815). Risk of death was similar in the abiraterone post-chemotherapy and abiraterone “exception patient” groups (hazard ratio (HR): 0.89; 95%CI 0.57-1.38). Conclusions Effectiveness of abiraterone in older patients who were chemotherapy ineligible was similar to that of patients with prior docetaxel exposure. Overall, real-world survival benefits of abiraterone were similar to the results of the COU-AA-301 trial. Funding Prostate Cancer Canada Discovery Grant 2013_x000D_ Cote-Sharp Family Foundation
Authors
Alice Dragomir
Joice Rocha Marie Vanhuyse Fabio Cury Jason Hu Noémie Prévost Armen Aprikian |
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PD24-06 |
TRENDS IN MANAGEMENT OF BONE HEALTH IN MEN WITH METASTATIC PROSTATE CANCER: ANALYSIS FROM THE SURVEILLANCE, EPIDEMIOLOGY, AND END RESULTS MEDICARE DATABASE |
Prostate Cancer: Advanced (including Drug Therapy) I | 17BOS |
Abstract: PD24-06 Sources of Funding: Northshore University Health System Introduction Bone loss and fracture are known risks of androgen-deprivation therapy (ADT), particularly among patients with bone metastases. According to National Comprehensive Cancer Network (NCCN) guidelines, bisphosphonate or denosumab therapy (bone therapy, BT) is indicated for men with metastatic castrate resistant prostate cancer (mCRCP), and should be considered for men with metastatic prostate cancer (mCP) who are at high risk of fracture. We analyzed rates of adherence to these recommendations and factors associated with receiving BT in the Surveillance, Epidemiology, and End Results (SEER) Medicare database. Methods Using the 2004-2011 SEER Medicare database, we identified all men older than 65 with mCP, with bone metastases and receiving ADT. We collected their clinical and demographic data, and whether BT was administered. Because our study period preceded the approval of novel agents for mCP and the shift to upfront chemotherapy, we defined castrate resistance as the initiation of chemotherapy. Statistical analysis was performed using SAS v9.3 (Cary, NC). Results A total of 2563 men were treated with ADT for mCP, and BT was administered to 431 (16.8%). Utilization of BT increased significantly during the study period, from 5.9% in 2004 to 35.2% in 2011 (p<0.01). On multivariate analysis, men had increased odds of receiving BT if year of diagnosis was later than 2008 or an oncologist was involved in their care, and decreased odds of BT if receiving care in a less urban area (p<0.05, Table 1). Among the subset of men with mCRCP (433, 16.9%), BT was administered to 136 (31.4%). On multivariate analysis, age 80-85 and diagnosis year later than 2010 were associated with increased odds of BT (OR 2.57 and 1.57, respectively; p=0.01). Adverse events related to BT were rare, with osteonecrosis of the jaw occurring in 7 (1.6%) and hypocalcemia in 34 (8.0%). Conclusions Utilization of BT among men with mCP is increasing, though the overall usage of these medications remains low. Among men with mCRCP, only 31.4% received bone health treatments in accordance with NCCN guidelines. As novel anti-androgens expand the role of urologists in management of mCRCP, careful consideration of appropriate management of bone health must not be overlooked. Funding Northshore University Health System
Authors
William R. Boysen
Joseph Rodriguez Kristine Kuchta Melanie A. Adamsky Brian T. Helfand Sangtae Park |
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PD24-07 |
Efficacy and safety of radium-223 by radical local therapy at initial diagnosis: a retrospective subgroup analysis of ALSYMPCA trial |
Prostate Cancer: Advanced (including Drug Therapy) I | 17BOS |
Abstract: PD24-07 Sources of Funding: Bayer Pharmaceuticals Introduction Radium-223 (Ra-223), a targeted alpha therapy, significantly improved overall survival (OS) versus (vs) placebo (pbo) for patients (pts) with metastatic castration resistant prostate cancer (mCRPC) in ALSYMPCA trial (HR = 0.70; 95% CI, 0.58-0.83; P < 0.001) and was well tolerated. We hypothesized that outcome with Ra-223 in ALSYMPCA is similar whether or not pts underwent radical local therapy (RLT) for prostate cancer (PC) at initial diagnosis. Methods ALSYMPCA eligible pts had progressive mCRPC with ≥2 bone lesions and no known visceral metastases. Pts were randomized 2:1 to 6 injections of Ra-223 (55 kBq/kg IV; q4 wk) plus best standard of care (BSoC) or matching pbo plus BSoC. Exploratory subgroup analyses were performed to evaluate outcome of Ra-223 vs pbo by RLT (defined as radical prostatectomy or radiation to prostate) and according to metastatic status at initial diagnosis. Results 921 pts were treated (Ra-223, n = 614; pbo, n = 307). 392 (43%) received RLT at initial diagnosis and 529 (57%) did not. Median OS was longer with Ra-223 vs pbo regardless of whether pts received RLT or not [(with RLT: 15.3 vs 11.8 mo, HR: 0.704 (0.523-0.948); without RLT: 14.7 vs 10.8 mo; HR: 0.684 (0.543-0.862)] (table). _x000D_ _x000D_ Metastatic status at diagnosis was documented for 576 pts (63%); 306 were documented as non-metastatic (M0) and 270 as metastatic (M1). Median OS was longer with Ra-223 vs pbo regardless of metastatic status at diagnosis [M0: 14.1 vs 9.6 mo, HR: 0.674 (0.491-0.925); M1: 15.6 vs 11.5 mo, HR: 0.638 (0.454-0.895)] (table)._x000D_ _x000D_ Therapies received prior to ALSYMPCA trial initiation were mainly RLT (mostly M0), bilateral orchiectomy, LHRH agonist, anti-androgens, chemotherapy and external radiotherapy to bone. These prior therapies were generally balanced between Ra-223 and pbo groups. _x000D_ _x000D_ Safety and pts demographics for the subgroups will be presented. _x000D_ _x000D_ _x000D_ Conclusions Compared with pbo, Ra-223 improved OS in mCRPC patients. A subgroup analysis indicates that OS is consistent regardless of whether pts had received RLT or not at initial diagnosis. Similarly, OS is consistent regardless of metastatic status at initial diagnosis. Funding Bayer Pharmaceuticals
Authors
Laurence Klotz
Christopher Sweeney Adam Dicker Nicholas Vogelzang Michael Morris Frank Verholen Volker Wagner Cindy Lu Christopher Parker Oliver Sartor |
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PD24-08 |
Testosterone Responders to Continuous Androgen Deprivation Therapy Exhibit Considerable Variation in Testosterone Levels on Follow up |
Prostate Cancer: Advanced (including Drug Therapy) I | 17BOS |
Abstract: PD24-08 Sources of Funding: None Introduction Lower nadir serum testosterone (T) levels in prostate cancer (PCa) patients receiving continuous androgen deprivation therapy (ADT) has been shown to be associated with improved cancer-specific survival and time to hormone resistance. In light of recommendations for measuring T level and acting on its result, we set out to determine whether variations in serum T levels exist among patients with ideal testosterone castration response. Methods Serum T levels were obtained retrospectively from a random sample of 551 PCa patients receiving continuous ADT between 2007 and 2016, accounting for a total of 4,815 measurements. All patients achieved T levels ≤0.7 ng/mL during course of treatment (i.e. ideal T responders), and all T levels recorded were obtained subsequent to achieving a T level ≤0.7 ng/mL. Serum T levels were measured using a chemiluminescent microparticle immunoassay (Abbott Diagnostics® ARCHITECT i2000). Statistical significance was set at p=0.05. Analysis was performed using SPSS v23.0. Results Mean patient age was 73.7 years. Mean T level was 0.52 ng/mL (std dev=0.34 ng/mL). There was no significant association between patient age and T levels (p= .07). Serum T levels did not demonstrate any diurnal variation, as there was no association between time of day that blood samples were drawn and T levels (p= .14). After attaining T levels ≤0.7 ng/mL, 237 (43.0%), 127 (23.0%), and 25 (4.5%) patients subsequently achieved T levels >0.7, >1.1 and >1.7 ng/mL, respectively, with 85% of patients who had a T level >0.7 ng/mL having at least one additional T level measurement >0.7 ng/ml within 5 years. Ideal T levels of ≤0.7 ng/mL were re-achieved in 185 (78.1%), 84 (66.1%) and 15 (60.0%) of patients who had T levels measurements of >0.7, >1.1, and 1.7 ng/ml, respectively. Conclusions Ideal T responders to continuous ADT demonstrate considerable variation in serum T levels on follow up. Elevated T level measurements among patients on continuous ADT must be interpreted in light of these findings. Repeat T level measurements are recommended prior to implementing a change in clinical management. Funding None
Authors
Rashid Sayyid
Abdallah Sayyid Nathan Perlis Hanan Goldberg Karen Chadwick Antonio Finelli Alexandre Zlotta Robert Hamilton Girish Kulkarni Neil Fleshner |
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PD24-09 |
In Men with Castration-Resistant Prostate Cancer Visceral Metastases Predicts Shorter Overall Survival: What Predicts Visceral Metastases? Results from the SEARCH Database |
Prostate Cancer: Advanced (including Drug Therapy) I | 17BOS |
Abstract: PD24-09 Sources of Funding: None Introduction Although visceral metastases (VM) are widely recognized to portend worse prognoses compared to bone and lymph metastases in prostate cancer, currently little is known about what predicts VM and the extent to which men with VM do worse, particularly at the time of initial diagnosis of metastatic castration-resistant prostate cancer (mCRPC). Our study aimed to determine whether men with VM at initial mCRPC diagnosis have worse overall survival and identify predictors of VM. Methods We analyzed 494 men diagnosed with CRPC post-1999 and no known metastases from five Veterans Affairs hospitals of the SEARCH database who later developed metastases. Radiology scans (bone scan, MRI, CT scan, X-ray) within 30 days of initial metastasis diagnosis were reviewed to collect information on bone, visceral, and lymph node metastases. We analyzed the 236 men who had a CT scan performed. Predictors of VM and overall survival were evaluated using logistic regression and Cox models, respectively. Variables included age, year, race, treatment center, biopsy Gleason, primary localized treatment, metastases in lymph nodes, PSA, PSA doubling time, time from androgen deprivation therapy to CRPC, and time from CRPC to metastases. Results Of the 236 mCRPC patients, 38 (16%) had VM. Regarding VM, 19 (50%), 8 (21%), and 16 (42%) patients had metastases in the liver, lungs, and other locations, respectively. VM was a predictor of overall survival on crude analysis (HR=1.88, 95% CI 1.30-2.72, p=0.001) and after risk adjustment (HR=1.84; 95% CI 1.24-2.72, p=0.002). Age, year, treatment center, PSA, and time from CRPC to metastases were significant in predicting overall survival (all p<0.05). None of the variables tested were associated with having VM (all p>0.09). Conclusions Neither demographic, tumor, nor PSA-kinetic characteristics were predictive of having VM, but VM predicted worse overall survival. There are currently no known clinical predictors of VM; however, since patients with VM have worse overall survival, there remains a need for further research to determine what predicts VM. Efforts targeted at identifying novel biomarkers for VM have the potential to have the greatest impact for those suffering from this particular disease state. Funding None
Authors
Colette Whitney
Lauren Howard Edwin Posadas Christopher Amling William Aronson Matthew Cooperberg Christopher Kane Martha Terris Stephen Freedland |
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PD24-10 |
Interim Analysis of NCT02458716: Feasibility of Cytoreductive Prostatectomy in Men Newly Diagnosed with Metastatic Prostate Cancer |
Prostate Cancer: Advanced (including Drug Therapy) I | 17BOS |
Abstract: PD24-10 Sources of Funding: none Introduction Emerging evidence has suggested that local tumor control may enhance the effect of subsequent therapies in patients with metastatic prostate cancer. However, little is known about surgical safety of cytoreductive prostatectomy (CRP). In this study, we report the first interim analysis of a phase I study evaluating the safety and feasibility of CRP. Methods The study was approved by the IRB and activated in June, 2015. Individuals with newly diagnosed clinical metastatic prostate cancer to lymph node and bones (cT1-3N1M0 or cT1-3N0M1a-b) were recruited. Men with visceral metastasis (M1c) or ECOG PS ≥ 2 were not eligible. Following surgery, all patients received androgen deprivation therapy. The primary endpoint is the major complication rate. The secondary outcome measures are the time to PSA nadir and rate of incontinence (pad-free). Results A total of 21 patients from two institutions have been enrolled and undergone CRP. Of the 20 patients with complete data, the median (range) age at surgery was 62 (53-73). Overall, six (35.3%) perioperative complications were observed, including one major complication (Clavien III or higher). There were five minor complications, including deep venous thrombus (Clavien II), postoperative ileus (Clavien II), and three cases of urethral anastomotic leaks (Clavien I). In men with minimum of 6 month follow-up, 63.6% of men had PSA < 0.2 ng/ml, and 50% of men were pad free (Table 1). Conclusions CRP is surgically feasible in carefully selected patients. However, early incontinence rate is high. Further studies are warranted to further define long-term complications and verify the oncologic benefits of the surgery. Funding none
Authors
Bertram Yuh
Young Suk Kwon Brian Shinder Sinae Kim Nara Lee Nora Ruel Shigeo Horie Seok-Soo Byun Dong Hyeon Lee Robert Dipaola Isaac Yi Kim |
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PD24-11 |
Evaluation of a Multimodal Strategy to Accelerate Drug Evaluations in Early Stage Metastatic Prostate Cancer |
Prostate Cancer: Advanced (including Drug Therapy) I | 17BOS |
Abstract: PD24-11 Sources of Funding: The Sidney Kimmel Center for Prostate and Urologic Cancers, NIH/NCI P30 CA008748, NIH/NCI P50 CA092629, and David H. Koch Fund for Prostate Cancer Research Introduction The paradigm of first testing systemic treatments in advanced disease followed by development in earlier disease states and finally large-scale trials evaluating whether the approach, in combination with local therapy, can prevent or delay the time-to-event measures of disease progression or death in patients with &[Prime]high-risk&[Prime] tumors is no longer practical now that 6 life-prolonging systemic therapies in metastatic castration-resistant prostate cancer are available. Our objective was to evaluate a multimodal treatment platform and a short term endpoint of treatment efficacy as a new strategy to rapidly evaluate and prioritize regimens for large-scale phase 3 testing. Methods We conducted a pilot study of twenty men with oligometastatic M1a (extrapelvic nodal disease) or M1b (bone disease) at diagnosis. All sites of disease were treated using a multimodal approach that included androgen deprivation (ADT), radical prostatectomy plus pelvic lymphadenectomy (retroperitoneal lymphadenectomy in the presence of clinically positive retroperitoneal nodes), and stereotactic body radiotherapy to osseous disease and/or the primary site. ADT was discontinued in responding patients. Outcomes of each treatment were assessed sequentially. The primary endpoint of &[Prime]no evidence of disease&[Prime] (NED) was defined by an undetectable PSA (<0.05 ng/mL) with noncastrate levels of testosterone at 20 months (>150 ng/dL). Results Each treatment modality contributed to the outcome: 95% of the cohort achieved an undetectable PSA with multimodal treatment, including 25% of patients after ADT alone and an additional 50% and 20% after surgery and radiotherapy, respectively. Overall, 20% of patients (95% confidence interval 3-38%) achieved the primary endpoint, which persisted for 5, 6, 27+, and 46+ months. All patients meeting the primary endpoint had been classified with M1b disease at presentation Conclusions Treatment directed at all sites can eliminate detectable disease in selected patients with newly diagnosed metastatic prostate cancer. A multimodal treatment strategy inclusive of the NED endpoint for patients who present with disease that is beyond the limits of curability by any single modality should be considered to enable the evaluation of new approaches in order to prioritize large-scale testing in early stages of advanced disease. Funding The Sidney Kimmel Center for Prostate and Urologic Cancers, NIH/NCI P30 CA008748, NIH/NCI P50 CA092629, and David H. Koch Fund for Prostate Cancer Research
Authors
Matthew O'Shaughnessy
Sean McBride Hebert Alberto Vargas Karim Touijer Michael Morris Daniel Danila Vincent Laudone Bernard Bochner Joel Sheinfeld MinYuen Teo Erica Dayan Lawrence Bellomo Glenn Heller Michael Zelefsky James Eastham Peter Scardino Howard Scher |
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PD24-12 |
Overall Survival Analysis of African American and Caucasian Patients Receiving Sipuleucel-T: Preliminary Data From the PROCEED Registry |
Prostate Cancer: Advanced (including Drug Therapy) I | 17BOS |
Abstract: PD24-12 Sources of Funding: This study was sponsored by Dendreon Pharmaceuticals, Inc Introduction Sipuleucel-T (sip-T) is an FDA-approved autologous cellular immunotherapy targeting prostatic acid phosphatase in select men with metastatic castration-resistant prostate cancer (mCRPC). Previous retrospective analyses of three sip-T phase 3 trials showed a 30.7-mo overall survival (OS) advantage for African American (AA) patients (pts) vs control pts while in the IMPACT trial, sip-T extended median OS by 4.1 mo vs control (McLeod AUA 2012 #P953). The PROCEED registry provides a prospective opportunity to confirm these observations in a larger group of AA pts. Methods PROCEED (NCT01306890) enrolled men with mCRPC. In this analysis, two Caucasian (CAU) pts were matched to each AA pt by baseline prostate-specific antigen (PSA), as PSA correlates with OS in pts receiving sip-T (Schellhammer 2013). OS and time to first anticancer intervention (tACI) post-sip-T were examined; univariate and multivariate analyses evaluated independent factors associated with OS. Results 420 CAU pts were matched to 210 AA pts; all received ≥1 sip-T infusion. CAU pts had significantly higher baseline median hemoglobin levels (p<0.001; 13.0 g/dL vs 12.1 g/dL for AA pts) and were more likely to receive prior local therapy (p=0.02) or prior chemotherapy (p<0.001). CAU pts had a longer tACI of 9.3 mo vs 7.6 mo for AA pts. However, AA pts had a significantly longer median OS of 39.5 mo vs 28.1 mo for CAU pts (p<0.001; HR 0.665, 95% CI 0.530-0.835). After univariate and multivariate analyses, six baseline characteristics were significantly associated with OS (Table). Younger age, lower PSA or alkaline phosphatase, and higher hemoglobin levels were independently associated with longer OS. No prior chemotherapy and the AA race were also independent predictors of extended OS. Conclusions Post-sip-T, median OS for AA pts was significantly extended by nearly 1 year compared with matched CAU pts. In this large prospective analysis, AA race emerged as an independent predictor of longer OS in multivariate analyses, confirming observations of prior retrospective analysis of phase 3 trial data. These results should stimulate additional studies on the biologic basis for AA men's enhanced response to sip-T and potentially other immunotherapies. Funding This study was sponsored by Dendreon Pharmaceuticals, Inc
Authors
A. Oliver Sartor
Andrew Armstrong Chiledum Ahaghotu David McLeod Matthew Cooperberg David Penson Philip Kantoff Nicholas Vogelzang Arif Hussain Christopher Pieczonka Nancy Chang Celestia Higano |
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PD25-01 |
ENGINEERING BUCKLING FORCE STUDY FOR SUPPORTING THAT CYLINDER CONSTRICTION AND REAR TIP EXTENDER ARE ASSOCIATED WITH REDUCED AXIAL RIGIDITY – THE IMPLICATIONS ON CLINICAL PRACTICE |
Sexual Function/Dysfunction: Surgical Therapy III | 17BOS |
Abstract: PD25-01 Sources of Funding: None Introduction Inadequate axial penile rigidity may occur in some patients solely on the basis _x000D_ of unusual tissue mechanical and/or geometric factors, despite adequate _x000D_ intracavernosal (intraluminal) pressure values and sufficient hemodynamic _x000D_ integrity. The objectives were to study influence on cylinder distensibility and _x000D_ the rear tip extender (RTE) on axial rigidity. Methods A penile model fixture and bucking test using Instron equipment was _x000D_ performed to evaluate bucking force vs cylinder constriction with 4 cm sleeve _x000D_ lengths with diameters of 11 and 12 mm and the effects of adding RTE _x000D_ (figures 1 & 2). _x000D_ Results When the cylinder diameter is constricted with a sleeve the buckling force _x000D_ decreases (figure 1). Any cylinder with a 2 cm RTE performs worse than _x000D_ another cylinder of the same length without RTE’s. The 16 cm + 2 cm RTE _x000D_ buckles at a lower force (4 lb) than a 18 cm cylinder with no RTE’s (7.3 lb). _x000D_ With the 3 cm RTE’s the cylinders all perform nearly the same due to the fact _x000D_ that the cylinder base is out of the fixture and the taper leading into the base _x000D_ promotes buckling (figure 2). Conclusions A restriction at a localized area along the cylinder length decreases the _x000D_ buckling resistance. Using a longer cylinder without RTE’s is better than using _x000D_ a shorter one with RTE’s. Keeping the cylinder base deep in the crus _x000D_ improves buckling resistance. _x000D_ Funding None
Authors
Paulo Egydio
Jeffrey Taylor Grant Taylor Irwin Goldstein |
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PD25-02 |
Taking Responsibility for Female Prepucial Disorders: Urologic Management of Phimosis-Based Clitorodynia |
Sexual Function/Dysfunction: Surgical Therapy III | 17BOS |
Abstract: PD25-02 Sources of Funding: none Introduction Clitorodynia, which occurs in 5% of women with dyspareunia, is a distressing, often disabling sexual pain syndrome associated with burning, stinging, and/or sharp pain. Clitorodynia is considered a localized form of vulvodynia confined to the glans clitoris, common clitoral shaft and/or prepucial area. Like men with penile pain secondary to phimosis with underlying balanitis, a subgroup of women have clitorodynia secondary to adhesions of prepucial skin to the glans clitoris with clitoral pain secondary to underlying balanitis and keratin pearls. This pain is like a grain of sand in the eye. Since urologists are well-trained in surgical management of male prepucial disorders, they are in the best position to surgically manage phimosis/adhesion-associated clitorodynia. In-office lysis of adhesion under local anesthesia is a feasible treatment for the majority of patients. For those unable to tolerate the local procedure, or adhesions recur, we perform a dorsal slit procedure under anesthesia. Methods 15 patients (mean age 35 years, range 18-62) with adhesions from clitoral hood to glans obscuring the corona of the glans clitoris were managed by a urologist. Results All 15 underwent in-office management of clitoral adhesions. A dorsal nerve block was performed with 5 mL of mixture lidocaine/bupivacaine. A Jacobson hemostat forceps was used to bluntly lyse epithelial adhesions and remove underlying keratin pearls until the corona was visualized completely around the circumference of the glans clitoris. Additional local anesthetic was injected for post-operative pain control. The patient was told to tub soak twice daily and carefully retract the clitoral hood sufficiently to see the corona to prevent re-adherence of the adjacent clitoral hood to the glans. Even after initial healing the corona should be seen by retracting the hood daily to prevent adhesions. No patient had recurrence of adhesions 6 months post procedure. 13/15 women had significant reduction of clitoral pain._x000D_ Conclusions Urologists familiar with surgical management of the prepuce are uniquely positioned to treat phimosis/adhesion-based clitorodynia. Release of adhesions can be achieved in-office under local anesthesia with preservation of the prepuce or as a dorsal slit procedure. Closed compartment balanitis clitorodynia is a treatable and should be in the scope of a urologist&[prime]s care. Funding none
Authors
Rachel Rubin
Julea Minton Catherine Gagnon Ashley Winter Irwin Goldstein |
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PD25-03 |
Fear of postoperative infection following placement of inflatable penile prosthesis at an academic training center is unwarranted: Data from a single surgeon series |
Sexual Function/Dysfunction: Surgical Therapy III | 17BOS |
Abstract: PD25-03 Sources of Funding: None Introduction Primary care providers (PCPs) harbor misconceptions regarding penile prosthetic surgery, largely overestimating the rate of infection. Additionally, men in the community may fear operations involving surgeons-in-training. Rates of infection following surgery for primary placement and revision of inflatable penile prostheses (IPP) is estimated as 1-3% and 10-18%, respectively. Our objective was to determine the contemporary incidence of infection following IPP surgery at an academic training center. Methods Review of a prospectively collected single-surgeon database was performed. All cases of IPP placement from January 2011 to November 2016 were reviewed. Information regarding training level of assistant surgeon(s) was collected, and follow-up data was compiled regarding postoperative infections and need for revision surgery. Cases involving total synthetic corporal reconstruction were excluded. Results 246 cases meeting inclusion criteria were identified. Mean patient age was 64.5 years, and mean follow-up was 28 months. Distribution involved 205 (83%) for primary placement, 37 (15%) for removal/replacement, and 4 (2%) in setting of prior device removal. Diabetes was noted in 29% of men. Trainee involvement was noted in 100% of cases. Rates of involvement by postgraduate year (PGY) were 81 (PGY2 or lower), 23 (PGY3), 12 (PGY4), 113 (PGY5), 112 (PGY6). Two operations were performed for suspected infection, one based on pain and one based on fever of unknown origin. Both were without intraoperative evidence of infection and all operative cultures were negative. One received simple removal/replacement and the other received removal with subsequent finding of pulmonary source for fever. Thus, the postoperative infection rate in this series was 0%. Conclusions In this contemporary series from an academic training center, infection following IPP surgery is uncommon, even with 100% involvement of surgeons-in-training. This data should be used to better inform PCPs and members of the general public potentially interested in restoration of sexual function. Fear of involving residents in IPP surgery appears to be unwarranted. Funding None
Authors
Kara E. McAbee
Alison M. Rasper Ryan P. Terlecki |
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PD25-04 |
Molecular Analysis Using PCR to Amplify Extracted 16S Ribosomal DNA Appears to Identify Biofilm and Antimicrobial Sensitivities/Resistances on Penile Prostheses In-Vivo |
Sexual Function/Dysfunction: Surgical Therapy III | 17BOS |
Abstract: PD25-04 Sources of Funding: Coloplast Corp. Introduction Previous studies have used traditional culture methods to identify microbial biofilm composition present at removal and replacement of penile prostheses. Molecular analysis (PathoGenius Laboratories, Lubbock, TX) PCR amplifies extracted 16S ribosomal DNA, which is then sequenced and compared to known bacterial and fungal taxonomies to identify isolates and microbial susceptibilities. The purpose of this study was to identify biofilm compositions and antimicrobial sensitivities/resistances at penile prosthesis removal/replacement using 16S ribosomal DNA testing. Methods Level 1 testing rapidly analyzed samples for most commonly found microbes in wound or ear, nose, and throat samples. Each sample composition was identified by quantitative PCR analysis with a specified panel of pathogens. Level 2 testing universally assessed for relative quantities of bacteria and fungi. DNA sequencing methods were used to identify the pathogens’ genetic signatures and the estimated percentages of organisms present in each specimen. Biofilm pathogens were evaluated against 34 unique antimicrobial agents. Results Intraoperative penile prosthesis capsule specimens were submitted for analysis at the time of revision surgery. Quantitative PCR analysis of common pathogens resulted in 14 specimens with low bacterial loads and 4 specimens with medium bacterial loads. 16S ribosomal DNA testing produced positive results in 5 of 18 specimens. One of these specimens had 2 separate fungi, while the other four positive specimens had 9, 13, 14, and 8 separate bacteria species respectively. Some of the bacteria identified during 16S ribosomal DNA testing were known prosthetic infectious pathogens. All isolates had sensitivities/resistances to 34 unique antimicrobial agents, enabling the physician to accurately tailor treatments for each patient. Conclusions 16S ribosomal DNA molecular testing has proven to be beneficial in its thorough analysis of biofilm composition and antimicrobial sensitivities/resistances on inflatable penile prostheses at the time of revision surgery. Future identification of biofilm and antimicrobial sensitivities/resistances may be improved with 16S ribosomal DNA molecular testing. Funding Coloplast Corp.
Authors
Gary Tan
Lauren Dawn Christopher Smith Gerard Henry |
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PD25-05 |
&[Prime]Andrianne mini-jupette&[Prime] graft at the time of inflatable penile prosthesis placement for the management of post-prostatectomy climacturia and minimal urinary incontinence |
Sexual Function/Dysfunction: Surgical Therapy III | 17BOS |
Abstract: PD25-05 Sources of Funding: none Introduction Following radical prostatectomy (RP), erectile dysfunction may ensue, often necessitating the need for inflatable penile prosthesis (IPP) insertion. Other consequences of RP include urinary incontinence and climacturia. The &[Prime]mini-jupette&[Prime] is a mesh that is used to approximate the medial aspects of the bilateral corporotomies at the time of IPP insertion. We hypothesize that, as the cylinders expand on inflation, this may help limit climacturia, as well as leakage in patients with minimal incontinence. Methods We conducted a pilot multi-center study of patients with post-RP ED and climacturia and/or mild urinary incontinence (≤2pads/day) undergoing IPP insertion with concomitant placement of a &[Prime]mini-jupette&[Prime] graft. Results Seven patients underwent the &[Prime]mini-jupette&[Prime] procedure. The median age of the population was 61 years (53-70). Four patients had post-RP climacturia and 7 patients had post-RP incontinence (mean 1.9 pads/day [SD 0.4]). Four patients received a Coloplast Titan, 2 an AMS 700 LGX, and 1 an AMS 700 CX IPP. Mean corporotomy size was 3.2cm (1.3). Types of grafts used were Tutoplast pericardium in 4 patients, biomesh/polypropylene in 2, and Vypro-mesh in 1.Mean graft measurements were as follows: length 3.1cm (1.4), width 3.0cm (0.9), and surface area 9.6cm2 (7.6). No intra-operative or post-operative complications were reported at a mean follow-up of 2.7 months (1.5). Climacturia and incontinence were subjectively improved in 3 (75%) and 7 patients (100%), respectively. All patients were satisfied with the use of their IPP. Conclusions The &[Prime]mini-jupette&[Prime] procedure is an excellent, safe and easy technique that can be used for subsets of patients with post-RP climacturia and/or minimal incontinence. Longer follow-up and larger patient cohorts are needed to confirm the long term safety and benefits of this intervention. Funding none
Authors
Faysal A Yafi
Robert Andrianne Georgios Hatzichristodoulou Jeffrey D Brady Murray D. Schwalb Steven K Wilson |
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PD25-06 |
Pre-vaginoplasty bilateral orchiectomy for transgender women: an efficient surgical technique that preserves collateral tissues and sensation |
Sexual Function/Dysfunction: Surgical Therapy III | 17BOS |
Abstract: PD25-06 Sources of Funding: None Introduction For M to F transgender women, bilateral orchiectomy provides significant medical benefit: if allows many patients to use a lower dose of estrogen (used for feminization). Estrogen at the high doses that transgender women require has significant cardiovascular risks. Bilateral orchiectomy also allows immediate and complete discontinuation of Spironolactone, a potent diuretic also commonly used for feminization. _x000D_ In general, patients not ready for vaginoplasty benefit from early bilateral orchiectomy._x000D_ A technique specific for transgender patients which anticipates future vaginoplasty surgery by preserving collateral tissues to be used later with vaginoplasty, and which can be done via a minimally invasive approach, has not been described. Methods We describe a trans-scrotal technique for bilateral orchiectomy via a single midline scrotal incision that excises the cord at the level of the external inguinal ring. In our experience, is fast/efficient, and is associated with very low post-operative pain and morbidity. Furthermore, this technique spares a little described adipose tissue pedicle that is superficial to the spermatic cord, and which we use to support the neo-labia majora at time of subsequent MtoF vaginoplasty surgery. _x000D_ Outcomes for a consecutive series (single surgeon) of 40 MtoF transgender women are described, including specific post-operative wound care instructions and complications. Results All patients were discharged home on same day of surgery. Mean operative time was 27 minutes. No significant complications occurred in this series. A total of 3 small (<2 cm) hematomas occurred. No wound infections or wound dehiscence occurred. Post op pain was minimal, and over half of the patients in this series managed post-op pain with NSAIDS only within the first 5 days, and thereafter required no analgesics. Conclusions Bilateral orchiectomy for transgender women has significant medical benefit and can be done with minimal morbidity, on an outpatient basis. Given the latter, bilateral orchiectomy should be offered to transgender patients that meet WPATH Standards of Care Guidelines criteria. The technique we describe anticipates future vaginoplasty surgery, spared adipose tissue needed for vaginoplasty, and minimizes risk to scrotal skin that will be later used for vaginoplasty. Funding None
Authors
Maurice Garcia
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PD25-07 |
Durasphere as New Agent for the Treatment of Hypermobile glans |
Sexual Function/Dysfunction: Surgical Therapy III | 17BOS |
Abstract: PD25-07 Sources of Funding: none Introduction Despite proper sizing and placement of a penile implant, a subset of patients present postoperatively with glanular hypermobility. This is characterized by sensation of a soft glans penis, pain during intercourse associated with cylinder tip pressure, or the appearance of droopy glans with maximal inflation. Previous studies have discussed the use of PDE5 inhibitors and/or intraurethral alprostadil to treat the hypermobile glans. In this study we present our results of subcoronal Coloplast (Minneapolis, MN) Durasphere® injections as a surgical treatment for the hypermobile glans._x000D_ Methods Durasphere is a safe, sterile bulking agent composed of carbon-coated zirconium beads suspended in a water based beta-glucan gel. It has long been used as a bulking agent in the treatment of urinary incontinence caused by intrinsic sphincter deficiency (ISD). This is a retrospective review of 16 patients who underwent glanular bulking with Durasphere by a single surgeon from 2014-16. Patient data were compiled after extensive review of operative reports, inpatient notes, consult notes, and follow-up visits. Results Sixteen patients underwent a total of 61 subcoronal Durasphere injections (mean 3.6, range 2-8). Fifteen of these patients have been seen in follow-up on average 50.5 weeks since their injections. 86.6% reported satisfaction with their treatment regimen quoting reduced or absent pain during intercourse and subjectively improved stability of their glans penis as reasons for satisfaction. 3 adverse events have been noted but all have healed with conservative management and no patients have lost their implant. Conclusions Durasphere has a safe and effective history in ISD treatment and our initial data suggests that similarly successful results are obtainable for glanular hypermobility treatment in experienced hands. We believe subcoronal Durasphere injections should be a viable option in the armamentarium of treatments for true glanular hypermobility due to high patient satisfaction, ease of intervention, and low adverse events. Proper diagnosis requires expert evaluation to ensure that the penile implant is appropriately sized and positioned in order to rule out floppy glans syndrome and SST deformity. As opposed to true glanular hypermobility, these conditions are caused by an undersized implant and require surgical revision. Funding none
Authors
Jared J Wallen
SK Madiraju KG Tayon MS Gross RE Carrion PE Perito |
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PD25-08 |
High Flow Priapism is associated with high risk of Erectile Dysfunction and corporal fibrosis |
Sexual Function/Dysfunction: Surgical Therapy III | 17BOS |
Abstract: PD25-08 Sources of Funding: none Introduction High-flow priapism is characterised by a prolonged non-painful erection secondary to the formation of an arterial-lacunar fistula usually following perineal blunt trauma. This leads to high arterial blood flow into the lacunar spaces, as the high-resistance helicine arteries are bypassed. The condition is therefore not considered an emergency as blood remains oxygenated and cellular damage is not expected. Current management includes conservative measures or angioembolisation of the cavernosal artery. The aim of this study is to review the real life outcomes of a large group of men referred to a tertiary specialist centre following a diagnosis of HFP. Methods Twenty-three patients were identified from a prospective database between 2008 and 2016. Diagnosis was based on blood-gas analysis, clinical and radiological findings. Patients were managed either conservatively (n=3) or with super selective angioembolisation of the cavernosal artery (n=20). Outcome measures studied were resolution of priapism, number of embolisations and development of long-term erectile dysfunction. Results All patients had high flow priapism confirmed on colour penile Doppler studies. Trauma was the causative factor in 83% of cases. In 15 patients (88%) 2 or less embolisations were necessary to achieve persistent detumescence. Erectile dysfunction was reported in 89% of patients at last follow-up. Recovery of erectile function over time occurred in 11%. An MRI scan of the penis was performed in 8 patients and showed the presence of corporal fibrosis in all cases; a further 2 had corporal fibrosis demonstrated on ultrasonographic imaging. 50% managed conservatively developed corporal fibrosis on imaging (vs. 40% embolised). Conclusions Our data suggests that angioembolisation has a high success rate in producing detumescence but also that, if not promptly treated, high flow priapism leads to corporal fibrosis and ultimately erectile dysfunction. Therefore a conservative approach should be discouraged and patients should proceed to early angioembolisation._x000D_ _x000D_ Funding none
Authors
Odunayo Kalejaiye
Christina Fontaine Amr Moubasher Giovanni Chiriaco Marco Capece Pippa Sangstar Evangelos Zacharacis Amr Raheem Asif Muneer Nim Christopher Miles Walkden Giulio Garaffa David Ralph |
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PD25-09 |
Emerging Mechanical Failures and Complications of Ectopically Placed Conceal Reservoirs |
Sexual Function/Dysfunction: Surgical Therapy III | 17BOS |
Abstract: PD25-09 Sources of Funding: None Introduction The AMS Conceal inflatable penile prosthesis (IPP) reservoir was introduced to the US market in February 2011. Unlike prior spherical models, the Conceal reservoir is known for its low profile and flat shape, which has rendered the Conceal the most common choice for ectopic placement. Consistent with its innovative shape, the reservoir allows for flexibility in filling volume, which ranges from 60 mL to 100 mL. This study seeks to identify any emerging mechanical failures and complications related to ectopic placement of the Conceal reservoir. Methods Our single surgeon database of IPP implantation from February 2011 to December 2015 was reviewed and all reservoir-related mechanical failures and complications were identified. Only AMS inflatable penile prostheses with Conceal reservoirs were included in this study. Coloplast penile prostheses and malleable implants were excluded. The location of the reservoir, as well as the volume of saline used to fill the reservoir, were part of the data analyzed. Results A total of 210 AMS IPP with Conceal reservoirs were included in this study. From this data set, there were four cases (1.9%) with reservoir-related mechanical failure or complication requiring revision surgeries. Of those four, two cases (0.95%) were mechanical failures resulting from the reservoir leaking. In both cases, the cause of leak was identified as an intrinsic point of weakness at the apex of the reservoir caused by inward folding of an unfilled segment. The inward folding of the reservoir was observed at volumes of 60 to 80 mL. In the remaining two cases (0.95%), the reservoir complication observed was refractory abdominal muscle pain related to ectopic location and intra-fascial placement. In both cases, revision surgery with reservoir repositioning resolved the pain. Conclusions While ectopic placement of the Conceal reservoir is mechanically reliable, it must be filled in excess of 80 mL to prevent inward reservoir folding and resultant reservoir leakage. Additionally, with surgical consent, it is prudent for the patient to be counseled on the possibility of abdominal muscle pain when the reservoir is placed ectopically, though they should be informed that such pain is a rare side effect. Funding None
Authors
Yasmeen Jaber
Run Wang |
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PD25-10 |
Surgical Management of Priapism: Complications data from the NSQIP database |
Sexual Function/Dysfunction: Surgical Therapy III | 17BOS |
Abstract: PD25-10 Sources of Funding: none Introduction Ischemic priapism unresolved by medical therapy typically progresses to surgical management with a distal or proximal penile shunt. Due to the infrequent nature of these cases, little has been reported regarding complications. As other treatment options arise, such as immediate penile prosthesis placement for long standing ischemic priapism, it is important to consider the hospital stay and complication rates of the current standard of care. Methods A retrospective cross sectional analysis was performed using the National Surgical Quality Improvement Project (NSQIP) database. Cases of penile shunts were identified from 2006-2014 using the ICD-9 procedure codes 54435 for distal corporoglanular shunt, 54430 for corporospongiosal shunt, and 54420 for corporosaphenous shunt. Univariate analysis was performed to compare 30-day complication rates for the different types of shunts. Results A total of 104 patients underwent operative management for ischemic priapism, 58.7% of which were listed as emergent cases. Mean age was 44.6 ± 13 years. Of the entire sample, 31.7% underwent a corporoglanular shunt, 54.8% underwent a corporospongiosal shunt, and 13.4% underwent a corporosaphenous shunt. Length of stay was longer for corporospongiosal shunts (2.19±1.98) than corporoglanular (1.88±2) or corporosaphenous shunts (1.5±1.23). Post-operative complications occurred in 4.81% of the sample. The more common complications were urinary tract infection (1.9%) and blood transfusion (1.9%). Corporospongiosal shunts exhibited higher overall complications (7.02%), followed by corporoglanular (3.03%) and corporosaphenous shunts (0%). Reoperation occurred in 8.45% of proximal shunts, versus 3.03% of corporoglanular shunts. Reoperation was more common if the case was listed as emergent (9.84%). Conclusions Ischemic priapism unresponsive to medical therapy continues to be a challenging problem. It appears that though complication rates overall are low for both proximal and distal penile shunts, the reoperation rate is substantial for proximal penile shunts. This should be considered when determining whether to perform a proximal shunt versus placement of an immediate penile prosthesis. Funding none
Authors
David Qi
Erik Lehman Susan MacDonald |
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PD25-11 |
A Biomechanical Comparison Between the AMS LGX 700 and the Coloplast Titan |
Sexual Function/Dysfunction: Surgical Therapy III | 17BOS |
Abstract: PD25-11 Sources of Funding: None Introduction The development of the inflatable penile prosthesis (IPP) ushered in a new era in the management of erectile dysfunction. Despite multiple innovations to improve the function and reliability, there is no current data comparing the biomechanical properties of these devices. We aim to compare the resistance of the Coloplast Titan to the AMS LGX penile prosthesis cylinders to longitudinal (penetration) and horizontal (gravity) forces. Methods We compared two cylinder sizes from each company: Coloplast Titan (18cm and 20cm) and the AMS LGX (18cm and 21cm). To evaluate axial rigidity, which simulates forces during penetration, we performed a longitudinal load compression test to determine the load required to cause the cylinder to kink. To test horizontal rigidity, which stimulates the horizontal forces exerted by gravity, we performed a modified cantilever test and measured the degrees of bend for each device. All devices were tested at 10, 15, and 20 PSI to simulate in-vivo pressures. Results The main outcome measurement for the longitudinal load test (penetration) was the force required for the inflated cylinder to bend, thereby impacting its rigidity. The main outcome for the horizontal rigidity test (gravity) was the angle of displacement, in which a lower angle represents a more horizontally rigid device. Longitudinal column testing (penetration) demonstrated that less force was required for the AMS device to kink compared to the Coloplast implant across all three-fill pressures tested. The Coloplast Titan also had a lower angle of displacement on the modified cantilever test (gravity) when compared to the AMS implant across all fill pressures. Conclusions The Coloplast Titan demonstrated greater resistance to both longitudinal (penetration) and horizontal (gravity) forces in this study. The AMS device was more sensitive to fill pressures. In contrast, the Coloplast Titan&[prime]s ability to resist both types of forces was less dependent on the device fill pressure. Funding None
Authors
Jonathan Beilan
Enrique Barrera Ge Leihui Paul Perito Steven Wilson Rafael Carrion Tariq Hakky |
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PD25-12 |
Evaluation of Inflatable Penile Prostheses: How they perform in the lab? |
Sexual Function/Dysfunction: Surgical Therapy III | 17BOS |
Abstract: PD25-12 Sources of Funding: Prostheses were donated by the manufacturing companies Introduction We sought out to describe and evaluate the existing inflatable penile prostheses (IPP) in an independent lab setting Methods New IPPs were obtained from the two manufacturers: American Medical Systems (Minnetonka, MN) and Coloplast (Minneapolis, MN). The AMS700 LGX (18 cm), CX (18 cm), CXR (15 cm), Coloplast Titan-Touch (18 cm) and Titan-Narrow (14 cm) were interrogated. We measured internal pressure, length and girth of the cylinders at 2ml increments. A urodynamic individual transducer connected to an analog amplifier and recording system was utilized to measure pressure. Rigidity and axial loading of the different IPPs were evaluated with a compression system. Results Regular-sized prostheses were inflated to 22 ml and narrow prostheses to 16 ml. Coloplast Titan Touch showed a girth of 17.8 mm at 22 ml compared to 15.6 mm for AMS700 LGX, and 16.5 mm for CX. AMS700 LGX increased a length of 13 mm from baseline, a feature that was unique to that prosthesis among all those tested (Figure 1). Rigidity curves as assessed by compression showed significant variability with both Titan prostheses and AMS CX-R exhibiting similar curve pattern and requiring a higher load to reach 50% compression. The buckling experiment showed different patterns of deformity (Figure 2). Conclusions Data suggests that these prostheses exhibit significant physical differences. The clinical impact of these differences is poorly elucidated. These variations in the prostheses behaviors could be considered by the physician and the patient while objectively assessing the choice of the prosthesis. These findings could aid in objective patient counseling. Funding Prostheses were donated by the manufacturing companies
Authors
Paholo Barboglio Romo
Harshitha P. Chikkatur Sahana Beldona Yooni Yi Tim M. Bruns Bahaa S. Malaeb |
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PD26-01 |
The Association of PTSD and Chronic Prostatitis/Chronic Pelvic Pain Syndrome in Young Male Veterans |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Non-neurogenic Voiding Dysfunction II | 17BOS |
Abstract: PD26-01 Sources of Funding: None Introduction Men with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) are two times more likely to report mental health diagnoses such as anxiety and depression. Additionally, men reporting a history of sexual abuse are at increased risk for symptoms of CP/CPPS. Male veterans with mental health diagnoses are also at increased risk of lower urinary tract symptoms. We hypothesize that an association exists between CP/CPPS and post-traumatic stress disorder (PTSD) in young male veterans, and that these veterans may be more likely to report a history of sexual trauma or be subject to invasive urologic procedures. Methods We reviewed VA administrative data from October 1, 2010 to September 30, 2015 for male veterans, ages 18-45 diagnosed with PTSD (ICD-9 code 309.81). Medical records were then examined for pelvic pain diagnoses including chronic pelvic pain (789.09; 338.29, 608.9, 625.5, 788.99, 788.99, 596.9, 599/599.8, 625.5), chronic prostatitis (601.0, 601.1, 601.9, 600.90-1, 600.0-1; 601.8, 602.8) and pain associated with voiding (788.1, 788.6). Veterans with diagnoses of spinal cord injury and neurogenic bladder were excluded. Records were examined for ICD-9 diagnoses of history of sexual trauma (general, military or any) and CPT codes for cystoscopic, urodynamic, bladder outlet and prostatic ultrasound procedures. Data were obtained for a preparatory-to-research pull. Results Our initial database query yielded approximately 392,000 veterans with a diagnosis of PTSD and 1.3 million veterans without documented PTSD. Veterans with PTSD were more likely to have a diagnosis of CP/CPPS than their non-PTSD counterparts (18.5% vs. 8.7%, p<0.001). Veterans with PTSD were more likely to have a history of military sexual trauma (2.8% vs. 0.5%, p<0.001) or non-military sexual trauma (0.4% vs. <0.1%, p<0.001) compared to veterans without PTSD. Young veterans with PTSD were also more likely to have a cystoscopy (0.8% vs. 0.5%, p<0.001) and/or undergo urodynamics (1.0% vs. 0.5%, p<0.001) versus those without PTSD. Rates of transrectal ultrasound-guided prostate procedures and bladder outlet procedure were not significantly different between the two groups. Conclusions Young male veterans with PTSD are twice as likely to carry a diagnosis of CP/CPPS. Those with PTSD and CP/CPPS are six times more likely to report a history of sexual trauma and are twice as likely to undergo a certain urologic procedures. We recommend improved assessment for sexual trauma and consideration of referral to mental health providers by uroIogists treating young male veterans with CP/CPPS. Funding None
Authors
Marah Hehemann
Michelle Van Kuiken Bella Etingen Frances M. Weaver Jeffrey Branch |
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PD26-02 |
THE EFFECT OF SACRAL NEUROMODULATION ON COMPLETE CONTINENCE AT 5 YEARS FOR SUBJECTS WITH URINARY INCONTINENCE |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Non-neurogenic Voiding Dysfunction II | 17BOS |
Abstract: PD26-02 Sources of Funding: This study was sponsored by Medtronic Introduction This abstract describes the rate of complete urinary continence at 5 years in this prospective, multicenter post-approval study of sacral neuromodulation (SNM) with the InterStim® System. Subjects with bothersome symptoms of overactive bladder (OAB) including urinary urge incontinence (UI) and/or urgency-frequency (UF), who had not exhausted all medication options (failed at least 1 anticholinergic medication and had at least 1 medication not tried) were included in the InSite study. Methods Subjects with successful test stimulation received an InterStim implant. Implanted subjects were followed at 3 months, 6 months, and annually to 5 years post-implant. Therapeutic success for UI subjects was defined as a ≥50% improvement in average leaks/day from baseline. Complete continence was defined as 100% improvement in leaks/day compared to the baseline. Therapeutic success and complete urinary continence through 5 years were evaluated for all implanted UI subjects with diary data at baseline and follow-up visits (completers analysis). Results Of 272 OAB subjects that were implanted, 91% were female and the mean age was 57 years. Of these, 202 subjects qualified as having UI based on the baseline voiding diary and they had an average of 3.1±2.7 leaks/day. As shown in the figure, over time the UI therapeutic responder rate was consistently high, ranging from 76% through 83% through different follow-up visits. The UI therapeutic responder rate at 5 years was 76% (95% CI: 69-84%). From 3 months through 5 year follow-up, a range of 33% through 46% of UI subjects achieved complete urinary continence at different follow-up visits. At 5 years, 45% of UI subjects achieved complete urinary continence. For all implanted subjects the most common device-related AEs were undesirable change in stimulation (60/272, 22%), implant site pain (40/272, 15%), and therapeutic product ineffective (36/272, 13%). Conclusions This multicenter study shows that SNM is an effective and sustainable therapy for UI subjects through 5 years of follow-up. A large portion of subjects were able to achieve complete continence at 5 years. Funding This study was sponsored by Medtronic
Authors
Steven Siegel
Jeffrey Mangel Craig Comiter Samuel Zylstra Erin T. Bird Tomas L. Griebling Daniel Culkin Suzette E. Sutherland Kellie Berg Fangyu Kan Karen Noblett |
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PD26-03 |
SER120 Nasal Spray is Effective in Patients with Nocturia Irrespective of Etiology: A Pooled Analysis of Two Randomized, Placebo-Controlled Phase 3 Trials |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Non-neurogenic Voiding Dysfunction II | 17BOS |
Abstract: PD26-03 Sources of Funding: Allergan plc, Serenity Pharma LLC. Introduction Nocturia (waking at night to void) is a bothersome condition associated with many underlying etiologies. Two randomized, placebo-controlled phase 3 trials demonstrated the efficacy/safety of SER120, a very low-dose desmopressin nasal spray formulation in patients (pts) with nocturia. A pooled analysis of the two trials compared the efficacy of SER120 in nocturia pts with contributing etiologies of nocturnal polyuria (NP), overactive bladder (OAB), and benign prostatic hyperplasia (BPH). Methods Two phase 3 trials enrolled pts ≥50 y of age with ≥2 nocturic episodes/night (irrespective of etiology) for at least 6 months. Pts (N=1333) were randomized 1:1:1 to SER120 0.75 mcg, 1.5 mcg or placebo for a 12-week treatment period after a 2-week double-blind, placebo lead-in phase. Data from the two phase 3 trials were pooled for analysis by the contributing etiologies of NP (n=1045); OAB (n=366); and BPH (n=518). The co-primary efficacy endpoints were mean change from baseline in nocturic episodes/night and percentages of pts with ≥50% reduction in mean nocturic episodes/night. Results Overall, the baseline mean nocturic episodes/night were 3.3, 3.4 and 3.3 in the SER120 0.75 mcg, 1.5 mcg, and placebo groups, respectively. SER120 at both doses resulted in significantly greater reductions in nocturic episodes/night vs placebo, regardless of etiology. The mean reductions in nocturic episodes with SER120 0.75 and 1.5 mcg vs placebo were -1.4 and -1.5 vs -1.2 in pts with NP (P<.0001 for both doses); -1.4 and -1.5 vs -1.0 in OAB pts (P=.0015; P<.0001 ); and -1.3 and -1.4 vs -1.1 in BPH pts (P=.0236; P=.0063). A significantly higher percentage of pts achieved ≥50% reduction in nocturic episodes/night in groups with NP (37.3% and 48.0% vs 27.5%; P=.0055; P<.0001), OAB (40.2% and 48.9% vs 28.3%; P=.0452; P=.0005) and BPH (31.4% and 38.3% vs 22.5%; P=.0012 for 1.5 mcg). Conclusions SER120 at doses of 0.75 mcg and 1.5 mcg is effective for the treatment of nocturia in pts with any etiology or a combination of etiologies, including those diagnosed with NP, OAB and BPH. Pts experienced significantly greater reductions in mean nocturic episodes with SER120 at both doses, regardless of etiology. Significantly higher responder rates were achieved with SER120 at both doses in pts with NP and OAB, and with SER120 1.5 mcg dose in pts with BPH. SER120 had an adequate safety profile and was well tolerated. Funding Allergan plc, Serenity Pharma LLC.
Authors
David Sussman
Jed Kaminetsky Mitchell Efros Scott MacDiarmid Steven Abrams Emily Weng Maria Cheng Seymour Fein Roger Dmochowski |
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PD26-04 |
Medium Term Outcomes of Ventral -Onlay Buccal Mucosa Graft Substitution Urethroplasty for Urethral Stricture in Females |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Non-neurogenic Voiding Dysfunction II | 17BOS |
Abstract: PD26-04 Sources of Funding: None Introduction Female urethral stricture causes significant morbidity. There is a high rate of recurrence following endoscopic management. Urethroplasty for female urethral stricture (FUS) is a rare but increasingly common procedure. We report our medium term outcomes for ventral-onlay buccal mucosa graft substitution urethroplasty (VOBMGSU) in treating FUS. Methods From our prospectively acquired database we reviewed the outcomes of 22 consecutive women (median age 50 years, range 34-72) with FUS having VOBMGSU from June 2012 and with a minimum follow up of 6 months (median 21.5, range 6-51). Data was analysed for complications, stricture recurrence, change in median peak free flow rate (Qmax) and median post-void residuals (PVR). Statistical analysis was performed using the Wilcoxon signed rank test, Students TTest and Mann-Whitney U Test . Results At last follow-up 21/22 (95%) of women were stricture free. Median Qmax was significantly improved from 7 ml/s (range 3.5-11.2) to 18 ml/s (range 5- 37) (p < 0.05). Median PVR was significantly reduced from 100mls (range 0-300) to 15 mls (range 0-150) (p < 0.05). Short and longer-term complication rates were low. 1 patient developed mild de novo stress urinary incontinence, which settled with conservative measures by 6 months. Conclusions Early and medium term results indicate that VOBMGSU is an excellent treatment for female urethral stricture that can avoid the need for the repeat procedures regularly required after traditional endoscopic management. Funding None
Authors
Bashir Mukhtar
Marco Spilotros Mahreen Pakzad Rizwan Hamid Jeremy Ockrim Tamsin Greenwell |
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PD26-05 |
The impact of atherosclerosis-induced pelvic ischemia on LUTS in elderly men |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Non-neurogenic Voiding Dysfunction II | 17BOS |
Abstract: PD26-05 Sources of Funding: Portuguese Association of Urology Introduction Several studies demonstrated the association between LUTS and atherosclerosis risk factors and metabolic syndrome. However, a direct impact of chronic pelvic ischemia on LUTS in elderly men was never fully determined. The only evidence is coming from animal models of iliac obstruction which show significant bladder dysfunction after ischemia. Herewith, we investigated LUTS and urinary levels of nerve growth factor (NGF) in elderly men with chronic pelvic ischemia caused by documented aorta, unilateral or bilateral common/internal iliac obstruction._x000D_ Methods Thirteen men >60y, with aorta, unilateral or bilateral common/internal iliac artery occlusion documented by angio-CT scan or angiography, were enrolled from the vascular surgery department. Twelve men >60y without significant aorto-iliac disease, as confirmed by image studies, were used as controls. Exclusion criteria included neurogenic bladder dysfunction, bladder or prostate cancer, prostate surgery, pelvic radiotherapy or chronic treatment for LUTS. _x000D_ Participants underwent urological examination, including IPSS score to assess LUTS, uroflowmetry, postvoid residual (PVR) and prostate volume determination._x000D_ Urine samples were collected from all participants and urinary NGF was measured by ELISA to explore the presence of chronic neurogenic inflammation._x000D_ Results Data are summarized in the table. Both groups were identical for age and prostate volume. BMI was slightly higher in the control group. IPSS score was statistically significant higher in the pelvic ischemia group than in controls. The IPSS difference between the two groups was 3 points. Urinary NGF/creatinine was significantly higher in the ischemic patients. _x000D_ Conclusions Severe pelvic ischemia in elderly men is associated with a significant increase in LUTS and chronic bladder neurogenic inflammation, as suggested by the increase of NGF release, a neurotrophin that may sensitize bladder primary afferents. These findings confirm the relevance of pelvic ischemia in bladder function and validate animal models of bilateral iliac artery occlusion currently under use to investigate the pathophysiologic mechanisms at stake._x000D_ Funding Portuguese Association of Urology
Authors
Daniel Costa
Alice Porto Ana Coelho João Neves LuÃs Vale Carlos Silva Tiago Antunes-Lopes Francisco Cruz |
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PD26-06 |
Efficacy and Safety of Mirabegron Add-On Therapy to Solifenacin in Older Patient Populations With Overactive Bladder |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Non-neurogenic Voiding Dysfunction II | 17BOS |
Abstract: PD26-06 Sources of Funding: Astellas Pharma Europe Ltd. Introduction Older overactive bladder (OAB) patients usually have more symptom severity, comorbidity, and poorer quality of life vs younger patients. We report efficacy/safety/tolerability of solifenacin (SOLI) + mirabegron (MIRA) vs SOLI alone in older incontinent OAB patients refractory to SOLI monotherapy from BESIDE, a randomized, double-blind, parallel group multicenter Phase 3B study (NCT01908829). Methods Adults with ≥3 months of OAB and an average of ≥2 incontinence episodes/24h entered a 2-week screening/washout period before a 4-week run-in of single-blind daily SOLI 5mg. Patients remaining incontinent at baseline (BL; ≥1 episode during a 3-day diary) were randomized 1:1:1 to daily double-blind combination (COMBN; SOLI 5mg+MIRA 25mg, increased to 50mg at Week 4), SOLI 5mg or 10mg for 12 weeks. Primary endpoint was change from BL to end of treatment (EOT) in mean number of incontinence episodes/24h. Safety assessment included frequency of treatment-emergent adverse events (TEAEs). Pre-defined age subgroup data are reported for patients aged <65y, ≥65y, <75y, and ≥75y. Results Reductions in mean number of incontinence episodes/24h and micturitions/24h from BL to EOT were greater with COMBN vs SOLI monotherapy across subgroups. Incontinence treatment differences between COMBN and SOLI 5mg, and micturition frequency differences between COMBN and SOLI monotherapy were consistent across subgroups, however the difference in incontinence between COMBN and SOLI 10mg was more pronounced in patients aged ≥65y and ≥75y (Table). Overall the frequency of TEAEs was higher in older subgroups. Overall the frequency of TEAEs was lower with COMBN and SOLI 5mg vs SOLI 10mg, respectively, in each subgroup (<65y [34.4 and 30.3 vs 35.2%], ≥65y [39.0 and 39.4 vs 48.7%], <75y [35.4 and 32.3 vs 38.6%] and ≥75y [39.7 and 40.9 vs 49.1%]). The most common group of TEAEs with COMBN, SOLI 5mg and 10mg, respectively, was gastrointestinal disorders which occurred more often in the older subgroups (<65y [13.4 vs 12.0 and 15.2%], ≥65y [15.2 vs 13.3 and 20.5%], <75y [14.0 vs 12.2 and 16.6%] and ≥75y [13.7 vs 13.6 and 20.0%]). Conclusions Combination therapy with SOLI 5mg+MIRA 50mg provides additional treatment benefit vs SOLI monotherapy in incontinent older OAB patients with an insufficient response to SOLI 5mg. Funding Astellas Pharma Europe Ltd.
Authors
William Gibson
Scott MacDiarmid Moses Huang Emad Siddiqui Matthias Stölzel Nurul Choudhury Marcus Drake |
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PD26-07 |
Urethral Diverticula in Women are Associated with Increased Urethra-Sphincter Complex Volumes . |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Non-neurogenic Voiding Dysfunction II | 17BOS |
Abstract: PD26-07 Sources of Funding: None Introduction The aetiology of urethral diverticula in women is unknown. Blockage of drainage and subsequent infection of paraurethral glands have been suggested but the primary initiating pathology remains to be elucidated. We have postulated that functional obstruction secondary to a high-tone non-relaxing sphincter may be the primary initiating pathology leading to the formation of a proximal to mid-urethral diverticulum (UD). As urethral pressure profilometry is unreliable in a urethra with a diverticulum, the urethra-sphincter complex volume may be used as a proxy for the maximal urethral closure pressure. _x000D_ We assessed whether urethra-sphincter complex volumes in female patients with proximal to mid-UD are higher than those without. Methods The clinical and MRI data of 17 women with a mean age (± SD) of 49.4 years (±13.2 ) with the ostium of the diverticulum at or proximal to 2/3 the length of the urethra were reviewed. A consultant uro-radiologist outlined the urethra-sphincter complex using pelvic axial small field of view T2-weighted MRI sequences with 3 mm slices. OsiriX&[copy] was used to determine the urethra-sphincter complex volume. The findings were compared with a control group consisting of 24 age matched women of mean age 50.8 years (± 11.2 years) having MRI for unrelated conditions._x000D_ Results The mean urethra-sphincter complex volume for the UD group was 10.01 cm3 (±6.97 cm3). The mean urethra-sphincter volume of the control group was 3.92 cm3 (± 1.60 cm3). This difference was statistically significantly (p = 0.01). Conclusions Women with proximal-urethral diverticulum have significantly higher urethra-sphincter complex volumes than those who do not. This finding suggests that high pressure in the proximal urethra during a void secondary to a high-tone non-relaxing sphincter may contribute to the formation of a urethral diverticulum. Funding None
Authors
Eskinder Solomon
Sahar Naseeri Sachin Malde Mahreen Pakzad Rizwan Hamid Jeremy Ockrim Tamsin Greenwell |
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PD26-08 |
A long term comparison of adherence of drug therapy in 1,917 patients with overactive bladder |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Non-neurogenic Voiding Dysfunction II | 17BOS |
Abstract: PD26-08 Sources of Funding: none Introduction Antimuscarinic are the current pharmacological mainstay for overactive bladder (OAB). However, adverse events resulting from antimuscarinics are inevitable in some patients. Discontinuation rates of 70% to 90% within the first year of therapy have been reported for various OAB medications, because the therapy did not produce the treatment bene?t expected. Mirabegron, which acts as a subtype of relaxation of detrusor, appeared on the Japanese market in 2011, and it provides a new treatment option for OAB. Currently, there are few published studies on the long-term persistence with drug therapy among OAB patients. The purposes of this study were to evaluate OAB pharmacotherapy adherence. Methods Patients 18 years of age or older who received an OAB diagnosis and OAB medication prescription for one ?3-adrenoceptor and six antimuscarinics were identified from April 2013 to August 2016. The study cohort consisted of 1,917 OAB patients in Aichi Medical University Hospital. Medication status such as persistence, switching, adherence and the reasons for discontinuation were examined. Persistence was measured by the length of continuous medication with OAB drugs. Time to discontinuation was defined as the number of days between the first dispense date and the expected end date of the last refill. The cumulative incidence of medication persistence was estimated using Kaplan-Meier method. Patients who remained on treatment until the end of the follow-up were regarded as censored data, and the length of follow-up period was assigned as the time of persistence. The proportion of persistence was compared according to each drug using the log-rank test. Results The mean patient age and time of persistence were 72.0 years and 323.9 days, and the following drugs were prescribed to OAB patients for 245 of imidafenacin, 24 of oxybutynin, 747 of solifenacin, 17 of tolterodine, 67 of fesoterodine, 100 of propiverine hydrochloride, and 723 of mirabegron. The 1-year persistence rate of each drug were 31.6%, 17.4%, 35.9%, 12.5%, 21.9%, 36.5% and 41.7%, respectively. The median of time to discontinuation were 184 days, 112 days, 196 days, 182 days, 77 days, 189 days and 231 days, respectively. Patients taking mirabegron demonstrated statistically significantly greater adherence than those taking antimuscarinics in both sexes. Conclusions Mirabegron was associated with higher levels of persistence and adherence than antimuscarinics in our large and long term cohort. Funding none
Authors
Keishi Kajikawa
Kent Kanao Shingo Morinaga Hiroyuki Muramatsu Hiroshi Saiki Ikuo Kobayashi Yoshiharu Kato Masahito Watanabe Kogenta Nakamura Makoto Sumitomo |
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PD26-09 |
STAGED APPROACH TO SLING REMOVAL IN WOMEN PRESENTING WITH PAIN ONLY |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Non-neurogenic Voiding Dysfunction II | 17BOS |
Abstract: PD26-09 Sources of Funding: None Introduction There is a debate on the need for complete or partial removal of midurethral slings (MUS) in women presenting with pain only after sling placement. We reviewed our staged approach to determine the rates of success after each procedure. Methods Following IRB approval, a prospectively maintained database of women requiring suburethral sling removal (SSR) for pain only between 2005 and 2015 was queried. Data reviewed by a third party investigator not involved in patient care from an electronic medical record included: demographics, type of MUS, onset and location of pain, evaluation (including imaging), surgical findings, and short and long term outcomes, including additional procedures for additional mesh sling arm removal (retropubically for TVT/SPARC and groin dissection for TOT). Pain was ranked by self-report as no pain, improved, same or worse. SSR was performed vaginally with the goal of excising just the suburethral portion of the MUS. Results Of 47 patients, 21 (44.6%) were rendered pain-free after SSR alone (Table 1. Flow chart). Among those with residual pain (26), 12 elected conservative management while 7 opted for a secondary retropubic arms removal and another 7 for a secondary translabial obturator arm dissection. None were found to have infected slings. Among the 14 who underwent a secondary procedure for residual pain after SSR, 5 (36%) were rendered pain-free, 3 (21%) improved, 5 (36%) reported the same amount of pain and 1 (7%) had worse pain..After this secondary procedure, 6 women opted for PMR management. Ultimately, despite staged approach and PMR management, 1 (7%) remained with invalidating pain. Conclusions Nearly half of women operated for pain only after MUS placement find durable relief after an SSR procedure alone, whereas another 30% elected additional removal of residual mesh arms either suprapubically or in the obturator area. Funding None
Authors
Carlos Finsterbusch
Feras Alhalabi Philippe Zimmern |
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PD26-10 |
OnabotulinumtoxinA Provides Early and Consistent Improvements in Overactive Bladder Symptoms and Quality of Life Outcomes in Patients with Overactive Bladder |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Non-neurogenic Voiding Dysfunction II | 17BOS |
Abstract: PD26-10 Sources of Funding: Allergan plc Introduction OnabotulinumtoxinA (onabotA) 100U was shown to significantly reduce urinary incontinence (UI) and improve quality of life (QOL) at week (wk) 12 after treatment (tx) in overactive bladder (OAB) patients (pts) in 2 large, placebo (pbo)-controlled phase 3 trials. The earliest time for tx response was not assessed in the phase 3 trials. Here we present an interim analysis of an ongoing post-marketing study of onabotA tx response and QOL outcomes as early as wk 1 postinjection in OAB pts with UI. Methods OAB pts were randomized 1:1 to receive their 1st tx with onabotA 100U (n=129) or pbo (n=125). Pts could receive an additional tx with open-label onabotA 100U after fulfilling prespecified criteria. This interim analysis presents data up to wk 12 after tx 1. Assessments at wks 1, 2, 6 and 12 (primary timepoint) postinjection included the proportions of pts who achieved 100% UI reduction (ie, &[Prime]dry&[Prime]; co-primary endpoint) and ≥75% and ≥50% UI reduction, mean change from baseline in daily episodes of urgency UI, micturition, nocturia, and in the Incontinence-QOL (I-QOL) total score. Adverse events (AEs) were also assessed. Results Baseline mean UI episodes/day were 5.4 (onabotA) and 6.0 (pbo). As early as wk 1 after onabotA, significantly higher proportion of pts achieved 100% UI reduction vs pbo (24.0% vs 4.8%) and continued through wk 2 (25.6% vs 5.6%), wk 6 (32.6% vs 8.0%) and wk 12 (31.8% vs 7.2%) (P<.001 for all timepoints). Similarly, a significantly higher proportion of onabotA-treated vs pbo pts achieved ≥75% and ≥50% UI reduction as early as wk 1 (45.0% vs 20.8%, and 58.9% vs 36.0%, respectively; P<.001 for both) which continued through wk 12. Decreases were noted with onabotA vs pbo in other urinary symptoms as early as wk 1 and continued through wk 12. The early onset of onabotA response was also evidenced by the significantly greater improvements in I-QOL score at wk 1 (14.3 vs 5.6; P<.001) that were ~1.5x the minimally important difference (MID; +10 points). At wks 2-12 after onabotA, improvements in I-QOL score were consistently ~2-3x the MID and significantly greater than pbo (P<.001 for all timepoints). OnabotA was well tolerated; urinary tract infection was the most common AE (21.1% vs 6.4%). Conclusions This interim analysis showed a significant and consistent tx response with onabotA vs pbo in OAB pts as early as wk 1 postinjection, with significant reductions in UI episodes and improvements in OAB symptoms and QOL outcomes which continued through wk 12. OnabotA was well tolerated. Funding Allergan plc
Authors
Kurt McCammon
Alfred Kohan Jed Kaminetsky Angelo Gousse Jennifer Gruenenfelder Amelia Orejudos Tamer Aboushwareb Scott MacDiarmid |
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PD26-11 |
Symptoms and noninvasive parameters that predict detrusor underactivity in men with lower urinary tract symptoms: an analysis using a large group of patients undergoing pressure flow study |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Non-neurogenic Voiding Dysfunction II | 17BOS |
Abstract: PD26-11 Sources of Funding: none Introduction Underactive bladder (UAB) is a symptom complex suggestive of detrusor underactivity (DU). However, DU can be diagnosed at present only on the basis of an invasive pressure flow study (PFS), which has hampered the development of clinical research and effective treatment for UAB. Noninvasive diagnostic approaches for DU could potentially facilitate the diagnosis and research of this field. We therefore investigated to identify the noninvasive predictive factors for DU using a large group of patients undergoing PFS. Methods We reviewed 2838 male patients who underwent PFS for lower urinary tract symptoms (LUTS). Age, International Prostate Symptom Score (IPSS), post-void residual volume (PVR), prostate volume (PV), and PFS parameters were obtained and analyzed. DU was defined as bladder contractility index <100. A multivariate logistic regression model was used to identify the factors associated with DU. Results Of the patients, 1355 patients (46%) were classified as having DU. In univariate analysis, the prevalence of DU was significantly increased with increasing age (P<0.001) and PVR elevation (P<0.001), but decreased with increasing PV (P<0.001). The assessment of subjective symptoms using IPSS questionnaire revealed that patients with DU had a statistically significant higher occurrence of frequency (P=0.01), intermittency (P=0.001) and weak stream (P=0.01) compared with non-DU patients. On the other hand, the occurrence of urgency symptom (P<0.001) was significantly lower in DU patients. In multivariate analysis, increasing age, PVR elevation, small PV, and several symptoms including frequency, intermittency, weak stream and urgency were selected as predictive factors for DU. Conclusions Several symptoms (frequency, intermittency, urgency and weak stream), increasing age, PVR elevation and small PV could be predictive factors of male DU. Combined evaluation of these factors might be useful for the diagnosis and better understanding of the clinical presentation of male DU. Funding none
Authors
Ryo Namitome
Mineo Takei Ryosuke Takahashi Tomoko Maki Ken Lee Shunichi Kajioka Akito Yamaguchi Masatoshi Eto |
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PD26-12 |
Does Stress Incontinence Decrease the Rate of Catheterize After Intradetrusor OnabotulinumtoxinA in the Mixed Incontinence Patient? |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Non-neurogenic Voiding Dysfunction II | 17BOS |
Abstract: PD26-12 Sources of Funding: None Introduction Intradetrusor OnabotulinumtoxinA (ONA) is frequently used to treat urgency urinary incontinence. One possible side effect is incomplete bladder emptying requiring the temporary use of clean intermittent catheterization (CIC). The goal of this study is to examine if patient reported stress urinary incontinence (SUI) had an effect on the rate of CIC. Methods A retrospective chart review of patients receiving ONA in the New York University Urology faculty practice between 5/2010 and 9/2016 were reviewed. Unique subjects were identified by CPT and/or J codes for intradetrusor injection of ONA. Charts were reviewed for demographic information, past medical and surgical history, symptoms of SUI (patients with SUI had urgency predominate mixed incontinence), post void residual (PVR) before and after first ONA infection and if catheterization was required after their first ONA injection. Subjects with a diagnosis of neurogenic bladder or a history Multiple Sclerosis, Parkinson’s disease, Cerebral Vascular Accident with residual deficits, Spinal Cord injury, spinal surgery, urethral stricture, baseline catheterization requirement, or prior anti-incontinence surgery were excluded from the analysis. In general, CIC was recommended for patients with a PVR 200-349 ml with symptoms or for a PVR ? 350 ml with or without symptoms. The association between SUI and the need CIC after ONA was examined using a Fischer’s Exact Test. Results 265 charts were identified as having undergone intradetrusor ONA injection. A total of 115 subjects were are included in the analysis. Subject age at the time of injection ranged from 20-95 years with a mean age of 67.0 +/- 17.2 years. Subjects with SUI had a mean age of 72.6 +/- 10.1 years. 61.7% of subjects were female. Subjects with and without SUI had similar pre injection PVRs, 28.3 ml +/- 47.2 ml and 37.7 ml +/- 46.4 ml, respectively. The overall total rate of CIC was 14.7%. There were 85 patients without SUI and the CIC rate was 18.8% compared to a CIC rate of 3.3% for the 30 subjects reporting symptoms of SUI (P=0.041). Conclusions In this retrospective chart review, subjects with SUI demonstrated a significantly lower rate of incomplete bladder emptying requiring CIC. This may be due to a decrease in outlet resistance associated with SUI. As we gain more experience with the use of ONA in varied clinical settings and patient populations we can look for populations with extremely low rates of CIC. Funding None
Authors
Dianne Glass MD, PhD
Daniel Hoffman MD Ekene Enemchukwu MD, MPH Nirit Rosenblum MD Benjamin Brucker MD Victor Nitti MD |
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PD27-01 |
5 Year Prospective, Randomized, Controlled Study Results on the Minimally Invasive Prostatic Urethral Lift (PUL) |
Benign Prostatic Hyperplasia: Surgical Therapy & New Technology IV | 17BOS |
Abstract: PD27-01 Sources of Funding: NeoTract, Inc. Introduction The Prostatic Urethral Lift (PUL) has been previously shown to rapidly and durably address lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia with minimal side effects. The 5 year concluding data from the largest multi-center, randomized, controlled, study on PUL is herein presented. Methods PUL procedure involves placing permanent UroLift® implants into the lateral lobes of the prostate to enlarge the urethral lumen. Enrollment criteria included age ? 50 years, IPSS (International Prostate Symptom Score) ? 13, peak flow rate ? 12 ml/s, and prostate volume 30 - 80 cc. At 19 centers in North America and Australia, 206 men with symptomatic LUTS were randomized to PUL (N = 140) or sham control (N = 66). Patients and assessors were kept blinded to treatment arm for 3 months. Assessments for PUL subjects continued through 5 years. Results PUL patients experienced symptom relief by 1 month (IPSS: 44% and QoL: 42%, p < 0.001) and remained improved through 5 years (IPSS: 38% and QoL: 54%, p < 0.001). Peak urinary flow rate remained improved 41% at 5 years. Sexual function was preserved in the PUL cohort, as assessments show stable erectile function average score and improved ejaculatory function and ejaculatory bother average scores (p<0.001). Further, no patient was found to experience de novo, sustained erectile or ejaculatory dysfunction. Adverse events were typically mild and transient. Conclusions The final long term data from the largest study on the PUL procedure demonstrates that this minimally invasive approach improves symptoms durably. Quality of life, BPH impact index and peak flow rate improvements are also sustained. As assessed by questionnaires and adverse event reporting, erectile and ejaculatory function are preserved. The final 5 year analysis indicates stable symptom relief and facilitates the understanding of the long term effects of the PUL procedure. Funding NeoTract, Inc.
Authors
Claus Roehrborn
Steven Gange Neal Shore Jonathan Giddens Damien Bolton Barrett Cowan Anthony Cantwell Kevin McVary Peter Chin Alexis Te Shahram Gholami Prem Rashid William Moselely Ronald Tutrone Sheldon Freedman Peter Incze K. Scott Coffield Fernando Borges Daniel Rukstalis |
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PD27-02 |
Comparison of Convective Radiofrequency Water Vapor Energy Ablation of Prostate (Rez?m®) to MTOPS Trial cohort |
Benign Prostatic Hyperplasia: Surgical Therapy & New Technology IV | 17BOS |
Abstract: PD27-02 Sources of Funding: None Introduction First-line therapy for lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (LUTS/BPH) is medical therapy. Convective radiofrequency water vapor energy ablation of prostate has shown promising intermediate-term results for LUTS/BPH. This study compared results of WaVE ablation of prostate with a historical cohort receiving combination medical therapy from the NIDDK sponsored Medical Therapy of Prostatic Symptoms (MTOPS) study. Methods Results from the treatment arm of a double-blinded, randomized, controlled trial investigating WaVE ablation of prostate were compared to the results of the MTOPS combination therapy arm, receiving both doxazosin and finasteride, restricted only to those subjects with prostate volume 30cc or lager and IPSS 13 or worse. IPSS, BPH Impact Index (BPHII), Qmax, and PVR were compared at 3 months, 6 months, 1 year, and 2 years. Propensity score weighting was also performed to eliminate differences in IPSS, QOL and prostate volume between the groups at baseline and outcomes were again assessed at 3 months, 6 months, 1 year, and 2 years. Results 129 and 386 subjects were in the WaVE and MTOPS cohorts, respectively. Baseline characteristics show similar age (63.3, 63.1, p = 0.73), BMI (28.7, 28.1, p = 0.17), IPSS (21.5, 19.4, p < 0.001), Qmax (9.9, 10.3, p = 0.17), and PVR (82, 73.2, p = 0.16). The WaVE cohort had lower PSA (2.1, 2.6, p = 0.0033), larger prostate volume (46, 37.8, p < 0.0001), and worse QOL (4.4, 3.3, p < 0.0001). Following treatment the WaVE cohort was significantly better than the MTOPS cohort at all time points in improvement in IPSS and BPHII. Change in Qmax was not significantly different between the two groups. Propensity score weighted analysis showed no difference in IPSS or BPH Impact Index at all time points. Qmax was greater in the WaVE cohort in the first year but was similar at 2 years. PVR was significantly improved in the MTOPS cohort from 6 months through 2 years. Conclusions WaVE prostate ablation has similar early and intermediate-term outcomes as combined medical therapy does for treatment of LUTS/BPH when adjusted for propensity score. Primary treatment decision may depend on discussion of adverse events and medication burden. Longer-term follow-up is necessary to assess the durability of WaVE prostate ablation. Funding None
Authors
Nikhil Gupta
Bradley Holland Danuta Dynda Tobias Köhler Kevin McVary |
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PD27-03 |
The new MediTate® temporary implantable nitinol device (i-TIND) in the treatment of bladder outlet obstruction due to BPH: results of one arm, multi-center prospective, study |
Benign Prostatic Hyperplasia: Surgical Therapy & New Technology IV | 17BOS |
Abstract: PD27-03 Sources of Funding: none Introduction Temporary Implantable Nitinol Device (TIND - MediTate®) is a new device for the treatment of lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH). We already published the feasibility and safety of TIND implantation, herein we report the results of a one-arm, multi-center, international prospective study to assess the efficacy of second generation of MediTate i-TIND in subjects with BPH. Methods The i-TIND is comprised of three nitinol elongated struts and an anchoring leaflet and it is preloaded by crimping it into the delivery system. In expanded configuration, the struts of the i-TIND exert radial force that causes ischemic necrosis and subsequent incisions of bladder neck and prostatic urethra. i-TIND was implanted under light sedation, using a rigid 22F cystoscope. The device was removed 5 days later in an outpatient setting, with no need of anesthesia. Forty patients with LUTS were enrolled in this multi-center study from Oct 2014. Inclusion criteria were: IPSS score ? 10, peak urinary flow (Qmax) < 12 ml/sec and prostate volume < 75 cc. All patients discontinued medical therapy for BPH before the implantation._x000D_ Demographics, perioperative, functional results and quality of life (QoL) were evaluated. For the purpose of this study we reported the results of 3 and 6 months follow-up._x000D_ Results Patients' age (mean+ SD) was 65.7 y (9.1) and BMI (mean+ SD) was 26.5 (4.1). Prostate volume (mean+ SD), IPSS score (median, range), QoL (median, range) and Qmax (mean+ SD), were 35.3 (+12.5) cc, 25(13-35), 4 (2-5), and 7.5 (2.87) ml/sec respectively. All the implantations and the removals of device were successfully concluded with no intraoperative complications. Three months after implantation IPSS score, QoL and Qmax were 7 (1-29), 1 (0-5) and 12.4ml/sec (4.9); after six months were 7 (0-29), 2 (0-4) and 14 ml/sec (+6.01) respectively. No patients reported ejaculatory dysfunction during follow-up. Differences in terms of IPSS score, QoL and Qmax when comparing preoperative and 6 months postoperative results were statistically significant (p<0.05); specifically the mean change from baseline to month 6 in IPSS score was -15.33 and the mean change of Qmax was 6.2 ml/sec. During the follow up no patients required pharmacologic treatment or surgery for BPH. Conclusions Second generation i-TIND implantation is a safe and effective minimally-invasive option for the treatment of BPH related LUTS at least at short term follow up. Further studies are required to assess durability of these results. _x000D_ _x000D_ Funding none
Authors
Francesco Porpiglia
Cristian Fiori Daniele Amparore Arya Manit Gregor Kadner Massimo Valerio Claude Shulman |
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PD27-04 |
Endoscopic enucleation of the prostate using 532nm Green laser (GreenLEP) compared to Holmium laser system (HoLEP) : multicenter evaluation of the learning curve in the surgical treatment of Benign Prostate Obstruction |
Benign Prostatic Hyperplasia: Surgical Therapy & New Technology IV | 17BOS |
Abstract: PD27-04 Sources of Funding: None Introduction Assessment of the learning curve, perioperative morbidity and functional outcome of endoscopic enucleation of the prostate with 532nm Green laser (GreenLEP) compared to Holmium laser system (HoLEP) in the surgical treatment of Lower Urinary Tract Symptoms (LUTS) related to Benign Prostate Obstruction (BPO)._x000D_ Methods From December 2013 to January 2016, 123 patients with LUTS due to BPO underwent endoscopic enucleation of the prostate (67 GreenLEP and 56 HoLEP) in two centers by two surgeons with no previous enucleation experience. Perioperative data (prostate volume, operative times, Clavien-Dindo complications and functional outcomes (IPSS score, Qmax)) were prospectively collected. Statistical analysis retrospectively compared the two surgical techniques. To assess the impact of the learning curve, patients were divided in two groups: group1, the first half of experience and group2, the second half, in each technique (Chi2 test and ANOVA)._x000D_ Results Mean prostate volumes were 124.2 and 72.3 g in GreenLEP and HoLEP groups, respectively (p<0.001). Mean enucleation and morcellation times were shorter in GreenLEP group (63.5 vs 80.4 min and 0.15 vs 0.24 min/g, p<0.001 and p=0.005, respectively) (Table 1). Operative times were lower in GreenLEP group (0.87 vs 1.6min/g, p<0.001). Ten patients experienced TURP conversion for hemostasis in GreenLEP group (90% in the sub group1), no in HoLEP group (p=0.003). Hospital stay was longer in HoLEP group (4.2 vs 2.5 days, p>0.001). Operative parameters (operative time and hospital stay) were improved in the group1 (p<0.001). Mean IPSS scores were lower in GreenLEP group while post-operative PSA levels were similar (Fig1). Conclusions In the learning curve, GreenLEP provides promising results and comparable functional outcomes to HoLEP technique with a possible shorter operative time and hospital stay._x000D_ Funding None
Authors
Romain Huet
Maximilien Baron Francois-Xavier Nouhaud Jean-Nicolas Cornu Karim Bensalah Benoit Peyronnet Gregory Verhoest Louis Sibert Sebastien Vincendeau Romain Matieu |
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PD27-05 |
Complications of Holmium Laser Enucleation of the Prostate: A Single Centre Case Series with 13 years of follow-up |
Benign Prostatic Hyperplasia: Surgical Therapy & New Technology IV | 17BOS |
Abstract: PD27-05 Sources of Funding: None Introduction Holmium laser enucleation of the prostate (HoLEP) is an established effective alternative treatment option to the traditional transurethral resection of the prostate for bladder outflow obstruction secondary to benign prostatic hyperplasia. As a relatively new procedure long-term outcomes for patients undergoing HoLEP are still being studied. We describe the complications of a large single centre case series with up to 13 years of post-operative follow-up. Methods A retrospective review of a prospective database of all HoLEP procedures performed by or under supervision of a single consultant urological surgeon was undertaken. All case notes were reviewed for complications up to October 2016 and recorded in accordance with the Clavien-Dindo classification system. Statistical analysis was performed using a Mann-Whitney U test. Results 969 cases of HoLEP were performed at our centre between December 2003 and October 2016. There was a statistically significant improvement in both urinary flow rate and post-void residual volumes (p<0.0001). Median pre-operative flow rate was 8.4ml/s (range 1-26.3) (n=536) and post-operative flow rate was 19.5ml/s (range 1.8-68.4) (n=649). Median pre-operative post-void residual volumes were 263mls (range 0-5000) (n=718) and post-operative residual volumes were 71mls (0-1000)._x000D_ 188 patients (23.6%) were discharged from hospital on the day of surgery; 479 (60.1%) on day 1; 85 (10.7%) on day 2; 45 (5.6%) stayed 3 days or more (n=797)._x000D_ Post-operative early and late complications are recorded within the table._x000D_ Conclusions HoLEP is an effective and safe treatment for bladder outflow obstruction associated with few early and late complications. Funding None
Authors
Danielle Whiting
Thomas Smith Branimir Penev Mark Cynk |
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PD27-06 |
THULIUM LASER VAPORESECTION OF THE PROSTATE AND BIPOLAR TRANSURETHRAL RESECTION OF THE PROSTATE IN PATIENTS WITH BENIGN PROSTATIC HYPERPLASIA – SINGLE CENTER PROSPECTIVE RANDOMIZED STUDY |
Benign Prostatic Hyperplasia: Surgical Therapy & New Technology IV | 17BOS |
Abstract: PD27-06 Sources of Funding: None Introduction In recent years, laser surgery has been widely used to treat benign prostatic hyperplasia (BPH). A thulium laser was recently introduced for BPH surgery. We compared the effectiveness and safety of thulium laser vaporesection of the prostate (ThuVaRP) with that of bipolar transurethral resection of the prostate (TURP). Methods From January 2014 to March 2016, 186 patients who were advised TURP for symptomatic BPH were randomized into two groups. We analyzed and compared outcomes of 93 patients who underwent ThuVaRP and 93 patients who underwent bipolar TURP. All patients were assessed by using the International Prostate Symptom Score, transrectal ultrasonography, the serum prostate-specific antigen (PSA) level, uroflowmetry, and postvoid residual volume before and 1 month after surgery. These patients were followed up for six months. All complications and short term outcomes were compared between the two groups. Results ThuVaRP was superior to TURP in catheterization time and length of hospital stay. However, operation time was longer with ThuVaRP than with TURP. In patients with a large prostate more then 100 grams, operation time was much longer with ThuVaRP. One month after surgery, the decrease in PSA was greater with ThuVaRP than with TURP, and the increase in maximal urine flow rate was greater with ThuVaRP than with TURP. The postoperative complication transient urinary incontinence was significantly different between the ThuVaRP group (17.6%) and the TURP group (4.2%). Other complications and short term followup results were comparable between both groups._x000D_ Conclusions The effectiveness and safety of ThuVaRP and TURP were comparable. _x000D_ ThuVaRP is a promising alternative surgical technique to TURP for BPH_x000D_ Funding None
Authors
Prarthan Joshi
Puvvada Sandeep Prasad Mylarappa Ramesh Desigowda Arvind Nayak Kuldeep Aggarwal |
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PD27-07 |
Preoperative transrectal ultrasonographic findings can predict the improvement of the peak urinary flow rate after surgical treatment of benign prostatic enlargement in patients with lower urinary tract symptoms |
Benign Prostatic Hyperplasia: Surgical Therapy & New Technology IV | 17BOS |
Abstract: PD27-07 Sources of Funding: none Introduction We investigated whether preoperative prostatic urethral angle (PUA) and intravesical prostatic protrusion (IPP) on transrectal ultrasonography (TRUS) were associated with the improvement of peak urinary flow rate after surgical treatment of benign prostatic enlargement (BPE) in patients with lower urinary tract symptoms. Methods A total of 173 men who underwent photoselective vaporization of prostate (PVP) for symptomatic BPE from August 2012 to March 2016 were retrospectively reviewed. Preoperative TRUS was performed and total prostatic volume, transitional zone volume were measured. According to the PUA, the patients were divided into two groups and comparatively analyzed. Surgical outcomes were assessed by the ratio of the international prostate symptom score (IPSS) / quality of life (QoL), the difference in the peak urinary flow rate (Qmax) / post-voided residual urine (PVR) before and at 1, 3, 6, 12, 24, 36 months postoperatively. Sucessful surgical outcome was defined to achievement of increase by ? 30% of Qmax after surgery compared to baseline. Results The 90 patients were in Group A (PUA < 48°) and 83 patients were in Group B (PUA (≥ 48°). The age, body mass index, prostatic specific antigen, total prostate volume, PVR, IPSS voiding symptom scores, storage symptom scores and QoL scores were comparable between two groups. However, the rate of IPP and Qmax showed significantly difference (P < 0.05). The successful improvement of Qmax was observed in 107 (61.8%) patients. Multivariate analysis revealed that preoperative IPP (OR 3.921(1.244-12.353), P = 0.020) and higher PUA (≥ 48°, OR 2.353(1.177-4.703), P = 0.015) were independent predictors of successful surgical outcome after PVP. Conclusions Preoperative higher PUA and IPP were the independent risk factors to the improvement of the peak urinary flow rate after surgical treatment of patients with symptomatic BPE. Larger scale prospective study is needed. Funding none
Authors
Juhyun Park
Chu Hong Park Inyoung Sun Sung Yong Cho Min Chul Cho Hyeon Jeong Hwancheol Son |
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PD27-08 |
Endoscopic enucleation of the prostate in the learning curve versus open simple prostatectomy: Morbidity and early functional outcomes |
Benign Prostatic Hyperplasia: Surgical Therapy & New Technology IV | 17BOS |
Abstract: PD27-08 Sources of Funding: none Introduction Endoscopic enucleation of the prostate (EEP) is considered as a less invasive treatment than open simple prostatectomy (OP) for prostate adenoma >80 ml. Nevertheless, the learning curve of EEP is still challenging. Our objective was to assess perioperative outcomes and functional results between EEP (GreenLEP and HoLEP) within the learning curve and OP done by experimented surgeons. Methods We prospectively enrolled the first 30 cases of GreenLEP and the first 32 cases of HoLEP which have been grouped together (EEP group) and retrospectively compared them with the 46 consecutives OP performed by seasoned senior surgeons (OP group). Greenlight® enucleation was performed with the &[laquo]en bloc&[raquo] technic (GreenLEP) using the HPS® fibre, HoLEP was performed with three lobes technic using the Lumenis® laser 100W Holmium. We collected patient&[prime]s characteristics, perioperative outcomes, functional results and complications after a 6-months follow-up. Comparisons between groups were performed using χ2 test and Fisher exact test for discrete variables and Mann-Whitney test for continuous variables. Results Patients characteristics were similar except for prostate volume (OP: 139 ±6.2g, EEP: 102 ±7,5; P<0.001). Operative time was longer in the EEP group (108 ±4min vs 76 ±5min; P<0.001). Time before catheter removal was shorter in the EEP group (P<0.001) and hospital length of stay which was higher in the OP group (9.5 ±0.4 days vs 4.3 ±0.3 days , P<0.001). Complications rate was lower in the EEP: 24% (n=15) vs 46% (n=21); P=0.02 (Table 1). Decrease of prostate volume, IPSS and quality of life score were similar between both groups. Postoperative stress urinary incontinence was comparable between groups at 1 month (40% vs 26.8%, p=0.15) and 3 months (22.4% vs 12.5%, P= 0.19) of follow-up._x000D_ Conclusions Whatever the laser technic (Greenlight or holmium), we suggest that endoscopic enucleation remains less morbid and provides similar functional outcomes than OP even in the learning curve._x000D_ Funding none
Authors
Benjamin PRADERE
Benoit PEYRONNET Jérome Gas Benoit Bordier Pascal Rischmann Julien Guillotreau Mathieu Thoulouzan Michel Soulié Kevin Zorn Xavier Gamé Vincent Misraï |
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PD27-09 |
Photoselective vaporization of the prostate with Greenlight laser XPS 180W, Green laser enucleation of the prostate and open prostatectomy for benign prostatic obstruction: a comparative analysis of perioperative and short term results |
Benign Prostatic Hyperplasia: Surgical Therapy & New Technology IV | 17BOS |
Abstract: PD27-09 Sources of Funding: none Introduction To assess perioperative outcomes and short term results after Photoselective vaporization of the prostate (PVP), laser enucleation of the prostate (GreenLEP) with Greenlight and standard open prostatectomy (OP) in patients with enlarged prostate glands and LUTS related to benign prostatic obstruction. Methods From January 2012 to September 2015, data from 1034 patients treated with PVP, GreenLEP and OP at two institutions were collected. Perioperative data and short term results including uroflowmetry measures and International Prostate Symptom Score (IPSS) were collected. Patients with prostate glands ≥ 80ml and LUTS related to BPH were retrospectively included in the analysis. Patients were matched and three groups of 50 patients treated with PVP, GreenLEP or OP were compared._x000D_ Results Mean prostate volume was comparable in the three groups (120 vs 120.5 vs 122.2 mL, p=0.952, respectively) . A longer operative time, a lower rate of postoperative bleeding complications (p=0.018) and a shorter length of bladder irrigation (p<0.001), catheterization (p<0.001) and hospital stay (p<0.001) were observed in PVP and GreenLEP groups(Table 1 & 2). At 3 and 12 months, PVP was associated with a lower maximal urinary flow and a higher IPSS than OP and GreenLEP (p<0.001, p=0.025 and p=0.020, respectively) (Figure 1). Patients treated with PVP had a higher risk of re-treatment than those treated with GreenLEP or OP (log rank test: p=0.059). Conclusions PVP and GreenLEP are associated with longer operative time but better post-operative outcomes than OP. However, regarding functional outcomes, PVP might be less effective than OP and GreenLEP in prostate glands over 80mL. Funding none
Authors
Romain Huet
Sébastien Vincendeau Philippe Sebe Alexandre Colau Bertrand Guillonneau Benoit Peyronnet Gregory Verhoest Karim Bensalah Romain Mathieu |
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PD27-10 |
Robotic Simple Prostatectomy: The USC Experience |
Benign Prostatic Hyperplasia: Surgical Therapy & New Technology IV | 17BOS |
Abstract: PD27-10 Sources of Funding: none Introduction Open simple prostatectomy has been a traditional approach for the treatment of prostates larger than 100 grams, however is associated with a significant risk for complications. In the past years, the role of robotic simple prostatectomy (RSP) in the surgical treatment of BPH has been increasing. RSP is associated with reduced blood loss and fewer blood transfusions, lower reoperation rates and a shorter hospital stay in comparison to open approach. Herein, we report the results of our series of RSP. Methods From May 2011 to September 2016, 129 consecutive men underwent transvesical RSP at the University of Southern California. Baseline demographics, pathology data, perioperative complications, 90-d complications, and functional outcomes were assessed. Results Median age was 70 yr (range: 52-89), BMI was 28.2 kg/m2(range:16.4-48), baseline International Prostate Symptom Score (IPSS) was 27 (range: 3-35), prostate volume was 137.5ml (range: 53.8-300), postvoid residual (PVR) was 247.5ml (range: 27-645), maximum flow rate (Qmax) was 8ml/s (range:0-24), and preoperative PSA was 6.15 ng/ml (1.9-56.3). Forty-eight patients were catheter dependent before surgery. Median operative time was 225min (135-400), estimated blood loss was 100ml (range: 10-1000), and hospital stay was 3 d (range: 1-21). There were no intraoperative complications, no conversions to open surgery and only 1 patient (0.8%) required blood transfusion. Six patients had a concomitant robotic diverticulectomy and 5 patients had concomitant cystolithotomy. Final pathology revealed prostate cancer in 7 patients (5.4%). Six patients experienced Clavien 3 complications (clot retention, n=3; bladder neck contracture, n=1; pulmonary embolism, n=2) . Median postoperative IPSS was 7.5 (P < 0.001), PVR was 6 (p < 0.001) and Qmax was 19.5 (p<0.001). Median follow-up was 7 months (2-61). Conclusions RSP is a safe and effective for treatment of BPH. Functional outcomes are excellent, with statistically significant improvement of IPSS, Qmax and PVR. _x000D_ _x000D_ Funding none
Authors
Carlos Fay
Daniel Melecchi Freitas Andre Abreu Sameer Chopra Nariman Ahmadi Toshitaka Shin Michael Qiu Giovanni Cacciamani Oishi Masakatsu Mihir Desai Inderbir Gill Andre Berger Monish Aron |
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PD27-11 |
Comparative effectiveness of transurethral resection techniques for benign prostatic hyperplasia – analysis of an all payer inpatient discharge database |
Benign Prostatic Hyperplasia: Surgical Therapy & New Technology IV | 17BOS |
Abstract: PD27-11 Sources of Funding: none Introduction Monopolar transurethral resection (mTURP) is the conventional surgical standard of care for bladder outlet obstruction (BOO) secondary to benign prostatic enlargement (BPH). Alternatively, holmium laser techniques, bipolar TURP (bTURP) and Greenlight photovaporization of the prostate (GL-PVP) constitute modern options with favorable safety profiles. However, current literature comparing various BOO treatment modalities is limited by sample size, study design, and the absence of cost data. We sought to compare costs and complication patterns of mTURP, bTURP and GL-PVP in a large, US all-payer discharge database. Methods Using the Premier Research Database, we identified 20,323 men 40-80 years with a diagnosis of BPH who underwent a BOO procedure between 2003-2013. Using propensity weighted logistical regression, we assessed trends and perioperative outcomes of mTURP, bTURP, and GL-PVP._x000D_ Results mTURP remained the most frequently performed procedure during the study period, but its utilization decreased by 20% during that time (p<0.001) (Figure 1). Whereas there were no significant differences between bTURP and mTURP with regards to OR time (p>0.99), LOS (p=0.82), and 90-day complication rates (p=0.34), GL-PVP was associated with longer OR times (+12 minutes, 95% CI: 10.25 to 13.75, p<0.001) but demonstrated a shorter LOS (OR: 0.51, 95% CI: 0.37 to 0.7, p<0.001) relative to mTURP. Both bTURP ($982, 95% CI: $509-1456, p<0.001) and GL-PVP ($1536, 95% CI: $1296-1775, p<0.001) were associated with higher 90-day direct hospital costs compared to mTURP._x000D_ Conclusions We show that the volume of inpatient endoscopic management of BPH has decreased significantly over the past decade. We found only a modest perioperative safety and outcome benefit with bTURP and GL-PVP over mTURP, while both procedures were associated with higher costs. Funding none
Authors
Christian P. Meyer
Philipp Gild Nicolas von Landenberg David F. Friedlander Jairam R. Eswara Mani Menon Felix K.H. Chun Margit Fisch Maxine Sun Benjamin L Chung Chung Steven L Chang Quoc-Dien Trinh |
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PD27-12 |
Multicenter International Experience of 180W LBO Laser Photo-vaporization in Men with very Large Prostates (prostate volume>200cc) |
Benign Prostatic Hyperplasia: Surgical Therapy & New Technology IV | 17BOS |
Abstract: PD27-12 Sources of Funding: none Introduction According to EAU and AUA guidelines on management of male non-neurogenic lower urinary tract symptoms (LUTS), PVP XPS is superior to TURP with regard to intra-operative safety and postoperative complication rates such as bleeding. The experience of the GL system with very large glands (>200mL) is very limited. In the present study, we aimed to describe perioperative results as well as functional outcomes and complications of photo-vaporization of prostate glands bigger than 200 cc using the GL system. Methods Retrospective analysis of prospectively maintained multi center database was performed to select subgroup of men having very large prostates (>200mL) treated with the Greenlight-XPS laser using PVP for the treatment of symptomatic BPH. IPSS, Qmax, PVR and PSA were measured at 6, 12, 24, 36 and 48 months. Durability was evaluated using BPH re-treatment rate at 12, 24 and 36 months. Additionally complications were recorded using the Clavien-Dindo classification. Results A total of 38 (9%) men had prostates larger than 200mL. Men with very large prostates were older (76 vs 72 years, p=0.05), had higher PSA levels (9.9 vs 6.2 ng/dL, p=0.005) and had more indwelling catheters (55.6 vs 41.3, p=0.001). Patients with very large prostates had longer OR lasing times (94 vs 52 min), less energy density delivered (2.8 vs 3.4 kJ/mL) and longer time to removal of catheter (48 vs 24 hours). In terms of complications men with very large prostates had more LUTS at 6 months and the re-treatment rate were the same at 2 years (4.9 vs 5%). Finally, functional outcomes were similar however very large prostates had a smaller PSA drop in comparison (28 vs 50%). Conclusions PVP Greenlight XPS-180W is an acceptable technique for very large prostates (>200mL). However, OR times, energy density delivery, PSA drop at two years of follow up, catheterization time and LUTS are a concern in this particular subgroup. This should be used for patient counseling and surgery planning. Funding none
Authors
Roger Valdivieso
Pierre-Alain Hueber Malek Meskawi Vincent Misrai Kevin Zorn |
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PD28-01 |
Association between germline genetic variation and progression in men with low-risk prostate cancer on active surveillance |
Prostate Cancer: Localized: Active Surveillance I | 17BOS |
Abstract: PD28-01 Sources of Funding: Prostate Cancer Canada_x000D_ Introduction Active surveillance (AS) is the preferred initial treatment for men with localized, low-risk prostate cancer (PC). Challenges in AS include: determining optimal candidates, modifying follow-up by risk strata, and defining clinically significant progression. Although the association between germline genetic variation and PC risk and PC-specific outcomes has been investigated, their influence on AS is unclear. Methods DNA from peripheral blood samples was available in 490 men followed for AS at Princess Margaret Cancer Center. All men satisfied low-risk criteria: Gleason score <7, <4 positive cores, <50% involvement of any core, and prostate-specific antigen (PSA) level <10.0ng/dL, and had ?1 postdiagnostic biopsy. We genotyped 360,345 SNPs using a custom array (OncoArray); all SNPs had a call rate ?95% and a minor allelic frequency ?1%. Univariate Cox proportional hazards assessed genetic variants and time to pathological (failing to meet low-risk criteria at biopsy) and therapeutic progression (first of pathological progression or initiation of active therapy for any reason). Secondary analyses evaluated the same outcomes for 11 candidate SNPs previously studied for PC grade progression. Results Over a median 44-months of follow-up, 206 (42%) and 227 (46%) men progressed pathologically and therapeutically. Men who progressed had worse pathological characteristics at diagnosis (PSA, prostate volume, number of positive cores, and max percent of core involvement; p<0.05). Results of the 5 most highly correlated SNPs are presented in Table 1. After correcting for multiple analyses, one SNP (rs4464333) remained associated with pathological progression (HR 5.51, 95%CI 3.01-10.1, p=3x10 -8) and one SNP (rs6583016) remained borderline-associated with therapeutic progression (HR 2.30, 95%CI 1.67-3.17, p=3x10 -7). Of the 11 SNPs previously studied for grade progression, rs7141529 associated with therapeutic progression (HR 1.32 95%CI 1.02-1.73, p=0.03). Conclusions We identified 2 novel germline genotypic variants that significantly associated with an increased risk of progression in men undergoing AS. These findings may improve patient selection for, and follow-up on AS, and need validation in other cohorts. Funding Prostate Cancer Canada_x000D_
Authors
Viranda Jayalath
Antonio Finelli Maria Komisarenko Narhari Timilshina Qihuang Zhang Wei Xu Neil Fleshner Robert Hamilton |
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PD28-02 |
The Impact of Clinical CCP Testing in Men with Localized Prostate Cancer for Expanding the Population of Men Eligible for Active Surveillance |
Prostate Cancer: Localized: Active Surveillance I | 17BOS |
Abstract: PD28-02 Sources of Funding: none Introduction Active surveillance (AS) is an established treatment modality for select men with prostate cancer (PC). Eligibility criteria are based on clinicopathologic features including PSA and Gleason grade. Prior studies have validated a combined cell-cycle progression risk (CCR) score, which combines cell-cycle progression (CCP) gene expression data with the Cancer of the Prostate Risk Assessment (CAPRA) score to add significant prognostic discrimination to newly diagnosed PCs. Our objective was to assess the value of the CCR score for identifying men with higher risk clinicopathologic characteristics who qualify for AS. Methods Prostate biopsy samples from 17,017 men were submitted by their physicians for CCP testing (Myriad Genetic Laboratories). The CCP score was calculated from RNA expression of 46 genes (31 CCP and 15 housekeeping genes), and combined with CAPRA to generate the CCR score. Clinicopathological data was obtained from physician-completed test request forms. A threshold CCR score of 0.8 was previously developed and validated in a cohort of conservatively managed men (survival data censored at 10 yrs). We evaluated the proportion of men eligible for AS based on their CCR score whose clinicopathologic criteria would traditionally disqualify them from AS: PSA>10ng/mL, Gleason grade group≥2 (Gleason Score ≥3+4), higher AUA risk. Results Overall, 66.6% of clinically tested men qualified for AS based on their CCR score. Table 1 shows that a proportion of tested men with higher risk clinicopatholic features qualified for AS based on their CCR score, including AUA intermediate (42.9%) and high (14.1%) risk as well as Gleason grade group 2 (48.8%) and Gleason grade group >2 (1-3%). In addition, 48% of men with Gleason score 6 and PSA >10 ng/mL qualified for AS. Conclusions Clinical characteristics and Gleason grade are often used as stand-alone indicators to offer men with localized PC immediate definitive treatment rather than AS. However, our study demonstrates that a significant proportion of men who qualify for AS based on their CCR score have a range of PSA and Gleason grade prostate cancer that may not traditionally be considered for AS. This supports using CCR score to improve risk stratification in PC and identify men for AS. Funding none
Authors
Behfar Ehdaie
Steve Stone Ryan Bernhisel James Eastham Thomas Keane John Davis E David Crawford Michael Brawer Daniel Lin Peter Scardino |
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PD28-03 |
Correlation between a genomics test and adverse pathology after radical prostatectomy among Active Surveillance candidates |
Prostate Cancer: Localized: Active Surveillance I | 17BOS |
Abstract: PD28-03 Sources of Funding: Blue Cross and Blue Shield of Michigan and grant 1T32-CA180984 from the National Cancer Institute Introduction There is growing interest among urologists in the community about the extent to which prostate cancer (CaP) genomic tests can further risk stratify men who are candidates for active surveillance (AS). In this context, we evaluated the relationship between results from the Prolaris cell cycle progression genomics test and the frequency of adverse pathological outcomes among men treated with radical prostatectomy (RP) in a large, community-based practice. Methods For all patients undergoing Prolaris testing in a large urology practice from 7/2013 through 4/2016, we linked test results with clinical data from the Michigan Urological Surgery Improvement Collaborative (MUSIC) clinical registry. We then identified all men that met the published MUSIC appropriateness criteria for AS (i.e., any Gleason Score (GS) ?6 or GS 3+4 with ?3 positive cores and no more than 50% of any core involved), and also underwent RP as primary therapy. Genomic test results with an estimated 10-year CaP-specific mortality >3% were classified as high-risk. We then compared the frequency of adverse pathological outcomes with RP – defined as the presence of primary Gleason pattern 4 or 5 cancer and/or pathological stage T3 or T4 disease – among men with high- versus low-risk genomics results. Results We identified 118 patients who were candidates for AS based on MUSIC criteria, had a Prolaris test, and primary treatment with RP. Among the entire group, 49 (42%) and 69 patients (58%) had low and high-risk genomics results, respectively. When limited to patients with only GS 6 cancer on diagnostic biopsy (n=26), only 4 men (15%) had high-risk Prolaris results. For the entire cohort (Figure 1a), patients with high-risk genomic results were more likely to have pathological stage T3 or T4 tumors (36.2% vs 12.2%, p =0.004). Among the men with only GS 6 cancer on biopsy, none of the 22 patients with a low-risk genomics result had primary pattern 4 or 5 cancer (Figure 1b). Conclusions Among patients seen in a large, community practice who are candidates for AS, high-risk results from a cell cycle progression genomics test are more frequently associated with the presence of T3 or T4 disease at RP. Our findings suggest a potentially useful role for these tests in further risk-stratifying men considering AS for early-stage CaP. Funding Blue Cross and Blue Shield of Michigan and grant 1T32-CA180984 from the National Cancer Institute
Authors
Patrick Hurley
Greg Auffenberg Ji Qi Chris Maurino Samantha Farida Ivi Latifi Donald Moylan Bincy Johnson David Miller Kirk Wojno for the Michigan Urological Surgery Improvement Collaborative |
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PD28-04 |
The Influence of Psychosocial Constructs on the Adherence to Active Surveillance for Localized Prostate Cancer in a Prospective, Population-Based Cohort |
Prostate Cancer: Localized: Active Surveillance I | 17BOS |
Abstract: PD28-04 Sources of Funding: This work was supported by NIH/NCI Grant 1R03CA173812 (DAB). It was also supported by NIH/NCI Grant 5T32CA106183 (MDT); American Cancer Society MSRG-15-103-01-CPHPS (MJR); the US Agency for Healthcare Research and Quality (grants 1R01HS019356 and 1R01HS022640-01); the National Cancer Institute, National Institutes of Health (grant R01-CA114524), and the following contracts to each of the participating institutions: N01-PC-67007, N01-PC-67009, N01-PC-67010, N01-PC-67006, N01-PC-67005, and N01-PC-67000, and through a contract from the Patient-Centered Outcomes Research Institute Introduction Disease-related factors influence men on active surveillance (AS) for localized prostate cancer (PCa) to discontinue AS and seek treatment, but so too may psychosocial factors. This study sought to evaluate the influence of psychosocial factors such as PCa anxiety, social support, participation in medical decision-making (PDM), and education level on patient decisions to discontinue PCa AS in the absence of disease progression. Methods The Comparative Effectiveness Analysis of Surgery and Radiation (CEASAR) study is a prospective, population-based cohort study of men with localized PCa diagnosed in 2011-2012. PCa anxiety, social support, PDM, education level, and patient reasons for discontinuing AS were assessed through patient surveys. A Cox proportional hazards model examined the relationship between psychosocial variables and time to discontinuing AS. Results Of 531 AS patients, 165 (30.9%) underwent treatment after median follow-up of 37 months. Whereas 69% of patients cited only medical reasons for discontinuing AS, 31% cited at least one personal reason, and 8% cited personal reasons only. Patients with some college education discontinued AS significantly earlier (HR: 2.0, 95% CI: 1.2, 3.2) than patients with less education. PCa anxiety, social support, and PDM were not associated with seeking treatment. Conclusions We found that 31 percent of men who choose AS for PCa discontinue AS within 3 years. Eight percent of men who sought treatment did so in the absence of disease progression. Education, but not psychosocial factors, seems to influence seeking definitive treatment. Future research is needed to understand how factors unrelated to disease severity influence treatment decisions among AS patients in order to identify opportunities to improve adherence to AS. Funding This work was supported by NIH/NCI Grant 1R03CA173812 (DAB). It was also supported by NIH/NCI Grant 5T32CA106183 (MDT); American Cancer Society MSRG-15-103-01-CPHPS (MJR); the US Agency for Healthcare Research and Quality (grants 1R01HS019356 and 1R01HS022640-01); the National Cancer Institute, National Institutes of Health (grant R01-CA114524), and the following contracts to each of the participating institutions: N01-PC-67007, N01-PC-67009, N01-PC-67010, N01-PC-67006, N01-PC-67005, and N01-PC-67000, and through a contract from the Patient-Centered Outcomes Research Institute
Authors
Maximilian Lang
Mark Tyson JoAnn Alvarez Tatsuki Koyama Karen Hoffman Matthew Resnick Matthew Cooperberg Xiao-Cheng Wu Vivien Chen Lisa Paddock Ann Hamilton Mia Hashibe Michael Goodman David Penson Daniel Barocas |
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PD28-05 |
Worldwide variation in determinants for inclusion and follow-up in active surveillance for low-risk prostate cancer: results of the Movember Foundation’s Global Action Plan Prostate Cancer Active Surveillance (GAP3) Initiative |
Prostate Cancer: Localized: Active Surveillance I | 17BOS |
Abstract: PD28-05 Sources of Funding: The Movember Foundation Introduction In August 2014, the Movember Foundation launched the GAP3 initiative, which covers the largest centralized prostate cancer (PCa) active surveillance (AS) database to date. Its primary goal is to create a global consensus on the selection and monitoring of men with low risk PCa. Ultimately, worldwide uniform guidelines will be developed. Methods The global database was created by combining patient data from established AS cohorts worldwide. The database contains information on clinical and demographic characteristics at time of PCa diagnosis for all men included in the GAP3 cohort, their clinical follow-up, including information on discontinuation of AS and potential following treatments. Descriptive analyses were performed by a team of statisticians from the five Movember regions around the world (the USA, Canada, Australasia, the UK and Europe). Results The GAP3 database illustrates variability in inclusion criteria and follow-up on 14,024 patients from 25 centers (Figure 1). At time of diagnosis, median age was 65 yr (IQR 60-70); median PSA was 5.4 ng/ml (IQR 4.0-7.3); median PSA density was 0.12 ng/ml (IQR 0.09-0.17); and median prostate volume was 44 cc (IQR 33-59). Most men had a clinical stage T1 (71%), a biopsy Gleason score of 6 (87%), one tumor-positive biopsy core (61%) and no comorbidity (64%). Men on AS had a median follow-up time of 2.4 years (IQR 1.1-4.7 years). Maximum follow-up time was 21.3 years. After 5, 10 and 15 years of follow-up, respectively, 57%, 37% and 22% of men were still on AS; 23%, 30% and 35% discontinued due to protocol-based progression (Figure 2). Conclusions GAP3 is the largest worldwide data effort to date integrating patient data from men with PCa on AS protocols. The results of GAP3 will allow individual patients and clinicians to have greater confidence in the personalized decision to either delay or proceed with active treatment. Funding The Movember Foundation
Authors
Sophie Bruinsma
Liying Zhang Chris Bangma Monique Roobol Ewout Steyerberg Daan Nieboer Mieke Van Hemelrijck |
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PD28-06 |
Variation in the use of active surveillance for low-risk prostate cancer |
Prostate Cancer: Localized: Active Surveillance I | 17BOS |
Abstract: PD28-06 Sources of Funding: none Introduction To assess utilization of active surveillance in men with low-risk prostate cancer at Commission on Cancer designated facilities and to evaluate the influence of institutional factors associated with receipt of active surveillance. Methods Retrospective cohort of 40,215 men within the National Cancer Data Base, with low-risk prostate cancer, as defined by National Comprehensive Cancer Network guidelines, diagnosed between 2012 and 2013. Multivariable and mixed-effects models were used to examine variation and factors associated with active surveillance. Results Between 2012 and 2013 the overall rate of active surveillance was 14%. Unadjusted proportion of patients eligible for active surveillance ranged from 0% to 100%. The adjusted probability of active surveillance receipt by institution varied from 0% to 53%. Mean adjusted probability of receiving active surveillance was 0.033 (95% confidence interval [CI] 0.023-0.256). Relative to patients treated at Comprehensive Community Cancer Centers patients treated at Community Cancer Programs and academic institutions had higher odds of receiving active surveillance (odds ratio [OR] 2.74, 95% CI 1.94-3.88; p<0.001 and OR 2.50 95%, CI 1.77-3.54; p<0.001, respectively). Relative to patients treated at very low volume facilities, patients treated at very-high volume facilities had higher odds of receiving active surveillance (OR 3.50, 95%CI 1.84-6.68; p<0.001). Patient and hospital-level variables accounted for 41% of the overall variation, whereas the treating institution accounted for 35% of the unexplained variability. Conclusions The overall use of active surveillance at Commission on Cancer designated facilities remains low at 14%. Significant variation in the use of active surveillance was seen across facilities with patients treated at academic and very high volume centers being more likely to receive active surveillance. A non-negligible proportion of the variation is explained by the treating institution. Given the current concerns for overdiagnosis and overtreatment of indolent prostate cancer, policies need to be implemented to achieve higher rates of active surveillance in prostate cancer patients when appropriate. Funding none
Authors
Björn Löppenberg
David F. Friedlander Andrew Tam Jeffrey J. Leow Anna Krasnova Paul Nguyen Adam S. Kibel Stuart R. Lipsitz Mani Menon Maxine Sun Toni K. Choueiri Quoc-Dien Trinh |
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PD28-07 |
Tracking of Prior Positive Sites by MRI/US Fusion Improves Detection of Gleason Score Upgrading |
Prostate Cancer: Localized: Active Surveillance I | 17BOS |
Abstract: PD28-07 Sources of Funding: The project described was supported in part by Award Number R01CA158627 from the National Cancer Institute. Introduction Gleason Score (GS) upgrading is seen during subsequent biopsy in up to one-third of men in active surveillance (A.S.) programs. Most A.S. biopsies have been performed in a blind fashion. Using MRI/US fusion biopsy, follow-up targeting of MRI lesions can now be performed. We sought to compare such MRI-targeted follow-up biopsies with biopsy of tumor spots outside of MRI-visible lesions. The latter biopsy method, called tracking biopsy, is another feature of MRI/US fusion but has been rarely reported. Methods Subjects were 138 consecutive men (mean age 63.4 years) enrolled in A.S. (2009-2016), who had 2 subsequent MRI/US fusion (Artemis) biopsies: confirmatory (6-12 months after initial diagnosis) and surveillance (12 months after that). At confirmatory biopsy, MRI targets and a 12-core template were sampled. At surveillance biopsy, MRI lesions were sampled again and tumor spots detected previously by systematic biopsy were also re-sampled, using the 3D tracking function of the Artemis device (accurate within 3 mm) (Figure). At surveillance biopsy, approximately 5 cores were taken by targeting and 5 by tracking. All men had GS6 lesions at confirmatory biopsy. Upgrading to GS≥3+4 at surveillance biopsy was the endpoint._x000D_ Results At surveillance biopsy, mean PSA was 4.5 ng/ml (IQR 2.6-5.9) and prostate volume was 46.3 cc (IQR 34.5-59.0). Overall rate of upgrading was 19% (26/138). When MRI-visible lesions were resampled without any tracking biopsies being taken (N=59), upgrading was found in 8 (13%). When prior tumor was sampled by tracking an MRI-invisible lesion (N=23), upgrading was found in 6 (24%). When both targeted and tracking biopsies were performed (N=56), upgrading was found in 12 (21%). Of 56 men having both biopsy methods, upgrading in 12 was detected by targeting in 8 and by tracking in 8; however, 4 of the upgrades (50%) were not detected by each method. Upgrading beyond GS7 was only seen in one patient. _x000D_ Conclusions At surveillance biopsy for men on A.S., tracking biopsy detects GS upgrading as often as biopsies targeting MRI lesions. However, 50% of upgrading detected by one method were missed by the other. Combining methods increased detection of GS upgrading. Tracking of prior positive sites, even when outside of MRI-visible lesions, is a valuable addition to A.S._x000D_ Funding The project described was supported in part by Award Number R01CA158627 from the National Cancer Institute.
Authors
Edward Chang
Tonye Jones Daniel Margolis Jiaoti Huang Shyam Natarajan Devi Sharma Merdie Delfin Frederick Dorey Leonard Marks |
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PD28-08 |
Concordance between Physician-Documented versus Patient-Reported Comorbidities in Prostate Cancer: validation of a novel informatics tool |
Prostate Cancer: Localized: Active Surveillance I | 17BOS |
Abstract: PD28-08 Sources of Funding: Supported in part by a Cancer Center Support Grant from the National Institutes of Health/National Cancer Institute (NIH/NCI) made to Memorial Sloan Kettering Cancer Center (P30-CA008748). Introduction An appropriately documented medical history is critical in the decision-making process regarding prostate cancer treatment. This is traditionally performed through the standard anamnesis at the clinic visit. We implemented a novel Web tool allowing patients to report their own medical history from home before their visit. The physician then reviews the information with the patient during the clinic visit and modifies if needed, after which it is entered into the electronic medical record. We sought to examine the concordance between physician-documented versus patient-reported collection of comorbidities. Methods Comorbidities were collected for a sample of 213 new prostate cancer visits to our Urology clinic through an online survey ("Baseline Medical History") before the clinical encounter. The frequency distributions of comorbidities as reported by patients before physician review was compared to those documented by physicians for a sample of 298 consecutive patients presenting to the same Urology clinic before the survey went live. Results Patient satisfaction with the survey was excellent. Comorbidities were highly comparable between the two groups. Life expectancy estimates were similar between groups. A few comorbidity categories were reported in higher frequency in the patient-reported group compared to the physician-documented group: cardiovascular (25% vs. 20%), vascular-related (8.5% vs. 4.4%), neurologic (7.5% vs. 1.7%), gastrointestinal (30% vs. 25%), musculoskeletal comorbidities (30% vs. 21%), as well as other cancers (30% vs. 12%). Genitourinary comorbidities, including problems with urination and erectile dysfunction, were higher in the physician group (68% vs. 53%). Conclusions Patients completing a medical history, at their own pace and in the comfort of their own home, provide relatively accurate and complete information, even before physician review. Electronic capturing of patient-reported comorbidities thus allows for an efficient method of obtaining a patient's medical history and likely a more complete medical record. Funding Supported in part by a Cancer Center Support Grant from the National Institutes of Health/National Cancer Institute (NIH/NCI) made to Memorial Sloan Kettering Cancer Center (P30-CA008748).
Authors
Katherine Fleshner
Amy Tin Nicole Benfante Sigrid Carlsson Andrew Vickers |
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PD28-09 |
Does MRI-Fusion Prostate Biopsy Improve Risk Reclassification for Patients with Prostate Cancer on Active Surveillance Compared to Transrectal Ultrasound-Guided Saturation Biopsy |
Prostate Cancer: Localized: Active Surveillance I | 17BOS |
Abstract: PD28-09 Sources of Funding: none Introduction It has been shown that transrectal ultrasound (TRUS)-guided saturation prostate biopsy (SB) improves detection of prostate cancer (PCa) progression or risk reclassification compared to extended prostate biopsy (EB) in patients who elect for active surveillance (AS). This study aims to compare the accuracy of MRI-fusion biopsy to SB in detecting PCa reclassification in patients on AS. Methods We reviewed 228 prostate biopsies from 177 patients diagnosed with PCa who elected AS. Only patients who fit the low risk NCCN criteria were included: Gleason score (GS) ≤ 6, PSA ≤ 10 ng/ml, clinical stage T1 or T2a, and percentage of positive cores ≤ 33% of total cores sampled at the time of diagnostic biopsy. Pathological progression or reclassification on surveillance biopsies was defined as no longer meeting the standard definition of low risk by Gleason score and/or disease volume. Results The mean age of men at diagnosis was 66.7 (SD ±8.3) years. Among 228 prostate biopsies, 53 were MRI fusion biopsies and 175 were SB (≥ 20 cores). Disease reclassification was seen in 77/175 (44%) of SB and 19/53 (36%) in MRI fusion biopsies. 13 of 19 patients underwent disease reclassification detected by a combination protocol of both MRI targeted and standard biopsy, while 6/19 were reclassified by MRI targeted biopsy alone. A greater degree of disease re-classification was seen with the SB technique as compared to both targeted-only MRI-fusion targeted biopsy (44% vs. 11.3%, P<0.0001) and combined systematic and targeted MRI fusion biopsy (44% vs. 24.5%, P=0.01). We further compared the rate of cancer progression (reclassification) at the time of each subsequent surveillance biopsy (Table 1, 2). Conclusions In patients with low risk PCa who elect for AS, we demonstrated that SB might confer a better rate of detection for reclassification than protocols involving MRI fusion techniques for confirmatory or surveillance biopsies at our institution. Funding none
Authors
Ahmed El Shafei
Yaw Nyame Hans Arora Mohamed Eltemamy Onder Kara Ercan Malkoc Khaled Fareed J Stephen Jones |
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PD28-10 |
Multiparametric-MRI prior to repeat biopsy for active surveillance can identify men with high-risk prostate cancer |
Prostate Cancer: Localized: Active Surveillance I | 17BOS |
Abstract: PD28-10 Sources of Funding: none Introduction Active surveillance (AS) is a viable treatment option for men with low risk prostate cancer. To date no biomarker, including PSA is able to substitute for repeat prostate biopsies to reliably monitor men for disease progression. Multi-parametric MRI has emerged as the imaging modality of choice for localized prostate cancer. We studied the ability of mp-MRI to predict the outcome of repeat biopsy for men with low risk prostate cancer undergoing AS. Methods We queried our IRB approved institutional database for men with prostate cancer undergoing mp-MRI. We identified all men with low or low-intermediate risk disease managed initially with AS. All men underwent mp-MRI prior to repeat prostate biopsy. Mp-MRI was analyzed for number and character of lesions by selected radiologists according to prostate imaging reporting and data system (PIRADS) version 2. Trans-rectal US guided prostate biopsies were performed with and without fusion technology depending on presence and size of visible lesions. Men with no or PIRADS 1,2 MRI lesions underwent standard template biopsies with a minimum of 12 cores including anterior zone sampling. Men with visible PIRADS 3-5 lesions underwent lesion directed, targeted biopsies along with template biopsies. Disease re-classification was defined as higher Gleason score on repeat prostate biopsy. Results Eighty-six men diagnosed with low risk prostate cancer elected for AS and underwent mp-MRI prior to repeat prostate biopsy. The median interval between MRI and repeat biopsy was 2.6 months. Sixty-seven percent of men (57 of 86) showed at least one PIRADS 4 or 5 lesion. Twenty-seven (31%) of men had disease reclassification on confirmatory biopsy including seven men with Gleason 8 or 9 disease. 18.5% of men with no identifiable or PIRADS 1-3 lesions had grade reclassification compared with 42% of men with PIRADS 4 or 5 lesions. (p=0.03). All grade reclassification in patients with lesions characterized as PIRADS 3 or less was from 3+3 to 3+4. Of the 42% of men with PIRADS 4 or 5 lesions who reclassified on confirmatory biopsy, 7/57 (12%) reclassified to Gleason 8 or 9 on confirmatory biopsy. Conclusions Men on active surveillance with no identified or PIRADS ?3 lesions on mp-MRI are still at risk for disease reclassification on repeat biopsy, although no high-risk cancers are missed by MRI. Men with PIRADS 4 or 5 lesions are at higher risk for reclassification including to Gleason 8-10 disease after repeat biopsy. Funding none
Authors
Nicolai Hübner
Christopher Evans Stanley Yap Michael Corwin John Mcgahan Thomas Loehfelm Marc Dall'Era |
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PD28-11 |
Prospective study of biopsy Decipher scores in potential candidates for active surveillance |
Prostate Cancer: Localized: Active Surveillance I | 17BOS |
Abstract: PD28-11 Sources of Funding: GenomeDx Biosciences Introduction The Decipher test was extensively validated for the prediction of metastasis after radical prostatectomy, and has recently become available for use in biopsy specimens to aid in treatment selection for newly diagnosed patients. A recent study reported that patients with high-risk biopsy Decipher score (>0.60) had a 25% cumulative incidence of metastasis at 5 years post-biopsy. The objective of the current study was to examine the distribution of Decipher scores in a prospective biopsy population, including the proportion of low- and intermediate-risk patients who fall into the Decipher high-risk category. Methods From February to August 2016, de-identified Decipher test results were recorded for 1,558 consecutive biopsy specimens. Pathological re-review was performed centrally for 77% of these cases. Decipher scores were classified as low (<0.45), intermediate (0.45-0.60) and high (>0.6). Fisher’s exact test was used to examine the association between biopsy Decipher and clinical variables. Results Of 315 patients classified as NCCN low-risk, 57% also had low Decipher scores, while 26% and 17% were classified as Decipher intermediate and high-risk, respectively. Among NCCN low risk patients with high Decipher scores, 45% harbored Gleason pattern 4 on pathology re-review. After excluding patients regraded as Gleason pattern 4 disease, 62%, 25% and 13% had low, intermediate and high-risk Decipher scores. Among NCCN intermediate risk patients, 36% had high Decipher scores. Decipher showed a significant risk differential between favorable and unfavorable sub-groups with 43% and 34% classified as Decipher low-risk (p=0.014). Conversely, high Decipher scores were recorded for 33% of NCCN favorable intermediate-risk and 44% of NCCN unfavorable intermediate-risk patients. Conclusions In this prospective analysis, high biopsy Decipher scores were found in close to 1/5 of patients with low and favorable intermediate-risk disease who might be considered candidates for active surveillance. Due to heterogeneity in pathologic assessment, Decipher provides an additional objective metric for proper risk stratification prior to treatment decisions. Future studies are needed to examine the long-term outcomes in these patients, and potential changes in decision-making based on Decipher results discordant with clinical risk strata. Funding GenomeDx Biosciences
Authors
Stacy Loeb
Eric A. Klein Zaid Haddad MarÃa Santiago-Jiménez Lucia L.C. Lam Fabiola M.R. Pinhero Tyler Kolisnik Adam Cole Seong Ra Kasra Yousefi Elai Davicioni Robert B. Den Daniel E. Spratt Ashley E. Ross |
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PD28-12 |
Effects of Initial Gleason Grade on Outcomes During Active Surveillance for Prostate Cancer |
Prostate Cancer: Localized: Active Surveillance I | 17BOS |
Abstract: PD28-12 Sources of Funding: None Introduction Active surveillance (AS) for low-risk prostate cancer is increasingly utilized, however, whether men with GS 3+4 disease are appropriate candidates remains a matter of debate. We evaluated the effects of the initial Gleason grade on biopsy progression, treatment and outcomes after radical prostatectomy (RP). Methods We prospectively followed men on AS at our institution between 1990 and 2016. Those diagnosed with Gleason 3+3 or 3+4 were included. Life tables were used to estimate progression-free survival (progression defined as increase in Gleason grade ?3+4 or volume >33% positive cores or >50% single core), treatment-free survival, and PSA recurrence-free survival after delayed RP. Multivariate Cox proportional hazards regression was used to determine risk factors for progression, treatment and recurrence after RP. Multivariate logistic regression was used to determine risk factors for adverse pathology (defined as Gleason ?4+3 or stage ?pT3b or pN1) at RP. Models were adjusted for age, race, PSA density (PSAD), total number of biopsies and percentage of cores positive at diagnosis. Results We included 1,171 men with Gleason 3+3 or 3+4 on initial biopsy and ?1 follow-up biopsy. A total of 1,056 (91%) had Gleason 3+3 and 106 (9%) 3+4. Patients with Gleason 3+4 had lower progression-free survival (20% vs 40%, p<0.01) by any biopsy criteria and treatment-free survival (52% vs 64%, p<0.01) at 5 years. Patients diagnosed with Gleason 3+3 who upgraded were at higher risk for treatment at 5 years than those with 3+4 and no upgrade (57% vs 37%, p<0.01). Risk factors for biopsy progression were initial Gleason 3+4 pathology (HR 1.4 95% CI 1.0-1.8) and PSAD (HR 1.7 95% CI 1.5-2.0), while total number of biopsies was associated with a lower risk (HR 0.7 95% CI 0.7-0.8). PSAD was a risk factor for treatment (HR 1.9 95% CI 1.6-2.3) while total biopsies (HR 0.6 95% CI 0.6-0.7) was associated with a lower risk. Among 333 men who underwent delayed RP, there was no significant difference between diagnostic 3+4 versus 3+3 in recurrence-free survival at 3 years (80% vs 90%, p=0.23). Gleason 3+4 at diagnosis and/or subsequent biopsy upgrade was associated with adverse pathology at RP, when controlling for age, race, PSAD, total number of biopsies and number of cores positive. Conclusions While Gleason 3+4 at initial biopsy is a risk factor for progression and treatment on AS and adverse pathology at RP, it is not associated with PSA relapse after RP suggesting that such patients are suitable candidates for AS. However, longer – term follow up is ongoing. Funding None
Authors
Selma Masic
Samuel Washington Janet Cowan Hao Nguyen Katsuto Shinohara Matthew Cooperberg Peter Carroll |
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PD29-01 |
Complications and interventions in patients with artificial urinary sphincters. |
Trauma/Reconstruction/Diversion: Urethral Reconstruction (including Stricture, Diverticulum) II | 17BOS |
Abstract: PD29-01 Sources of Funding: University of Toronto Research Program in Functional Urology. Introduction The artificial urinary sphincter (AUS) is the most widely known treatment for male stress urinary incontinence. However, there are a lack of population-based data regarding rates of long-term AUS-related complications, including the need for revision/removal and reimplantation. We sought to characterize long-term rates of AUS revision/removal and reimplantation among all patients undergoing initial AUS insertion in the province of Ontario. Further, we sought to identify risk factors for these outcomes. Methods We conducted a population-based, retrospective cohort study of all male patients who underwent AUS implantation from 1994-2013 in Ontario, Canada, a single payer government-funded health system. Hospital procedure codes and physician billing codes were used to identify patients who had initial AUS treatment and a subsequent revision/removal, or reimplantation. The Kaplan-Meier method and multivariable Cox proportional hazards models were used to examine the cumulative incidence of AUS reimplantation and revision/removal and to identify risk factors, respectively. Results A total of 1632 male patients underwent implantation of AUS between 1994 and 2013. Overall, 10-year AUS reimplantation and revision/removal-free survival rates were 73.3% and 65.7%, respectively. Pre-implantation radiotherapy was not significantly associated with the risk of AUS reimplantation (p=0.17) or revision/removal (p=0.95). The risk of AUS reimplantation was significantly lower for patients who underwent AUS insertion at a hospital in the highest volume quartile of AUS surgeries (what is the quartile/yr) (Hazard Ratio (HR)=0.55, 95% CI 0.37-0.82), compared to those in the lowest quartile. Increasing comorbidity was associated with an increasing risk of AUS removal/revision (p=0.0008). Patient age at the time of implantation, region of residence, income quintile, and hospital type (academic vs. community) were not significantly associated with AUS reimplantation or revision/removal. Conclusions Most men who undergo AUS placement will still have a device in situ, without repeat surgeries, at 10 years following insertion. Radiotherapy does not appear to increase the risk of repeat surgeries. High volume centres have the lowest rates of reimplantation and patients with increasing morbidity have the highest risk of removal /revision. Standard clinical and epidemiologic data do not appear to predict the risk of these outcomes. Funding University of Toronto Research Program in Functional Urology.
Authors
Vladimir A Ruzhynsky
Christopher JD Wallis Sidney B Radomski Refik Saskin Lesley Carr Robert K Nam Armando Lorenzo Sender Herschorn |
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PD29-02 |
Outcomes of Urethroplasty to Treat Strictures Arising From Artificial Urinary Sphincter (AUS) Erosions and Rates of Subsequent AUS Reimplantation |
Trauma/Reconstruction/Diversion: Urethral Reconstruction (including Stricture, Diverticulum) II | 17BOS |
Abstract: PD29-02 Sources of Funding: This project was supported in part by a generous reconstructive urology educational grant from American Medical Systems Inc., Minnetonka, MN. Introduction Urethral stricture can result after AUS cuff erosion. There is limited data describing the success of urethroplasty and the rate of AUS reimplantation in these patients. We hypothesized that urethroplasty and AUS reimplantation was feasible in most men. Methods From 2009-2016, we identified patients from Trauma and Urologic Reconstruction Network of Surgeons (TURNS) database, as well as the Cleveland Clinic, Duke University, and University of Alberta. We included patients with a history of urethral stricture arising from AUS erosion who underwent urethroplasty ± subsequent AUS reimplantation. Information was gathered on demographics, initial AUS placement, stricture and urethroplasty specifics, AUS reimplantation, and outcomes. In results analysis we included men with follow up of > 3 months. Results 31 men were identified. Mean age was 73.2 y (SD: 7.0). Radical prostatectomy was the etiology of incontinence in 87%, with 33% having radiation therapy. Prior to urethroplasty, patients had a median of 3 (range: 2-9) urethral operations. Mean duration of initial AUS was 43.4 months (SD: 39.9, range: 1-144) prior to erosion. Mean stricture length was 1.7 cm (SD: 0.8, range 0.5-4.5) found within the bulbar urethra in all cases (9 proximal, 16 middle, 6 distal). Anastomotic (28) and buccal graft substitution (3) urethroplasty were performed. 3/28 patients who had a urethrogram post-operatively had contrast extravasation; all resolved with observation. Post-operative complications included: wound infection (3), and myocardial infarction (1). 29 men had follow up > 3 months. Follow up cystoscopy was performed in 28 patients at a median of 4.5 months (range 2-42) and showed no recurrences. Overall mean follow up was 28.2 months (SD: 16.2, range 6.5-71). Two men had stricture recurrence, but these occurred after AUS reimplantation and repeat erosion. _x000D_ _x000D_ In 27 men (87%), AUS was replaced at mean of 6.2 months (SD: 2.6, range 3-13) after urethroplasty, with either transcorporal placement (18) or standard technique (9). 25 men had follow-up > 3 months after AUS (mean 23.1 months, SD: 15.1, range 4-57); operative complications occurred in 11/25 patients (44%) and included: pump migration (2), sub-cuff atrophy (3), and erosion (6). The 19 men with AUS remaining reported ≤1 pad per day leakage. _x000D_ Conclusions In patients with urethral stricture after AUS erosion, urethroplasty is very successful and AUS reimplantation rates are high. However, AUS reimplantation after urethroplasty has a high erosion rate even in the short-term. Funding This project was supported in part by a generous reconstructive urology educational grant from American Medical Systems Inc., Minnetonka, MN.
Authors
Sorena Keihani
Jason C. Chandrapal Andrew C. Peterson Joshua A. Broghammer Nathan Chertack Sean P. Elliott Keith F. Rourke Nejd F. Alsikafi Jill C. Buckley Thomas G. Smith Bryan B. Voelzke Lee C. Zhao William O. Brant Jeremy B. Myers |
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PD29-03 |
Modified Transcorporal Cuff Placement in Complex Artificial Urinary Sphincter Implants |
Trauma/Reconstruction/Diversion: Urethral Reconstruction (including Stricture, Diverticulum) II | 17BOS |
Abstract: PD29-03 Sources of Funding: none Introduction _x000D_ The transcorporal (TC) artificial urinary sphincter (AUS) cuff placement was first described in 2002 for cases requiring revision for erosion and urethral atrophy. A distal cuff location is often required in patients undergoing artificial urinary sphincter re-implantation after previous erosion or in those requiring revision because of urethral atrophy at the original cuff site. Dissecting the urethra at a more distal site increases the risk of urethral injury and erosion, and often the urethral circumference is so small. A distal cuff placement using TC dissection that leaves corporal tunica albuginea on the dorsal surface of the urethra, allowing for its safer mobilization and adding to its bulk. We present a technical modification on the TC AUS cuff placement based on the use of local tunica albuginea flaps._x000D_ Methods _x000D_ The charts of 11 patients submitted to a modified TC cuff placement during a period of 7 years were analysed. The age of the patients ranged from 53 to 81 years (mean of 69 years). The initial approach to the distal urethral and corporal bodies is similar to the classic TC approach. The two bilateral vertical incisions, on each side of the urethra, was modified for a creation of two bilateral tunica albuginea flaps with a rectangular shape. Those flaps are mobilized medially to cover the lateral and ventral portions of the urethra . As on the classic TC approach the corporal septum was opened to create a space to the cuff placement. The tunica albuginea gap created by the flaps mobilization was closed with grafts or treated with glues. A 5.0 cuff was used in 2 cases, a 5.5 cuff in 6 cases and a 6.0 cuff in 3 cases. The modified TC cuff placement was used in 5/11 patients with a history of urethroplasty (4/5 irradiated patients), in 2/11 patients with a history of radiotherapy to treat prostate cancer, in 4/11 patients with a history of previous erosion/infection AUS implants ( 1 or 2 surgeries)._x000D_ Results After a mean follow up of 27,3 months, the rate of implant explantation was 27% (2 associated to cuff erosion and 1 to infection without erosion). 7/11 (63,6%) were using 1 pad or less. A temporary retention was observed in 5/11 patients (45,5%). In 5/11 patients (45,5%) a staged implant was performed . In 3 patients, the cuff was placed on the first procedure and the PRB balloon/cuff on the second procedure. In 2 patients we used a silicone tape was implanted on the first procedure and the AUS implanted on a second procedure. Conclusions The modified TC AUS cuff placement is an safe and viable technique and could be used as part of the technical armamentarium to deal with complex AUS implants. Funding none
Authors
André Cavalcanti
Carlos Felipe Restreppo Henrique Florindo Roberto Medeiros Túlio Rojas Neildo Chaves |
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PD29-04 |
Incidence of Stress Incontinence Following Posterior Urethroplasty Among Radiation-Induced Posterior Urethral Stenoses |
Trauma/Reconstruction/Diversion: Urethral Reconstruction (including Stricture, Diverticulum) II | 17BOS |
Abstract: PD29-04 Sources of Funding: None Introduction No data exists regarding the frequency of de novo stress urinary incontinence (SUI) in patients with an intact bladder neck who undergo excision and primary anastomotic (EPA) urethroplasty for radiation-induced urethral stenoses (RIUS). We identified the risk for SUI in RIUS patients with urethral stenoses between the membranous and mid-prostatic urethra. A secondary aim was to compare the incidence of SIU to patients with pelvic fracture urethral injuries (PFUI) following EPA urethroplasty. Methods Patients who underwent successful EPA urethroplasty between 2008-2016 were reviewed. Only patients with a history of RIUS from prostate cancer or PFUI from blunt trauma were included. Patients at risk for developing SUI were excluded: open bladder neck on pre-operative fluoroscopy, bladder neck dissection during urethroplasty, prior bladder neck surgery (robotic, open, or endoscopic prostate surgery), urinary tract fistula, failed prior posterior urethroplasty, or SUI at baseline. SUI was defined by patient reported outcome measures and subjective complaints. Cystoscopy was performed to assess for anatomic success of urethroplasty._x000D_ Results Of the total 135 patients, 47% (36/77) of RIUS and 57% (33/58) of PFUI met the inclusion criteria. Among the RIUS cohort, mean follow up was 18 months and mean stricture length was 2.5 cm. Radiated urethral strictures involved the prostatic urethra in 67% (24/36), and surgical scar excision beyond the prostate apex was necessary in 56% (20/36). The overall incidence of de novo SUI among RIUS patients was 33% (12/36). Among those with de novo SUI, 75% (9/12) had prostatic urethral involvement and 50% (6/12) required dissection beyond the prostate apex. For RIUS patients, 2/12 (17%) underwent artificial urinary sphincter (AUS) placement while the remaining 10 patients reported a mean use of 2.3 pads per day (range 1-4). SUI following urethroplasty in PFUI patients was less common (12%, 4/33). One PFUI patient underwent AUS placement while the remaining 3 patients did not report use of pads. Conclusions Among RIUS patients with an intact bladder neck, SUI is common following excision of scar in the prostatic urethra, affecting a third of the patients. SUI is less common among PFUI patients, likely related to more a reliable stricture location at the bulbomembranous urethra. Funding None
Authors
Paul H Chung
Paige Esposito Hunter Wessells Bryan B Voelzke |
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PD29-05 |
The Scope and Management of Urethral Complications after Radiotherapy for Prostate Cancer |
Trauma/Reconstruction/Diversion: Urethral Reconstruction (including Stricture, Diverticulum) II | 17BOS |
Abstract: PD29-05 Sources of Funding: None Introduction Radiotherapy is one of the most commonly employed treatments for localized prostate cancer. Complications arising from these treatments are not well defined. Our objective is to better define the scope and management of lower urinary tract complications after prostate radiotherapy. Methods A retrospective review was performed of patients with severe urethral complications related to prostate radiotherapy referred to a single urologist over a 11-year period (Dec 2004 to Dec 2015). Records were reviewed to describe patient signs, symptoms, complications and treatments. Complications included urethral stricture/stenosis/contracture, incontinence, erectile dysfunction, prostate necrosis/abscess, pubic osteomyelitis/fistula, UTI, hematuria, acute urinary retention, genitourinary pain, radiation proctitis, radiation cystitis, rectourethral fistula and de novo (secondary) malignancy. Descriptive statistics, Fishers exact test and unpaired t-test were employed where appropriate to summarize clinical findings. Results 120 patients were identified at a mean age of 67.8 years and a mean RTOG morbidity score of 3.9. The mean time to first complication after radiotherapy was 57.7 months (1-219) and number of complications per patient was 5.1(±2.2). 55.8% of patients had external beam radiotherapy, 38.3% had brachytherapy and 5.8% had combined radiation modalities. The most common complications were urethral stricture/stenosis (88.3%), refractory storage LUTS (88.3%), incontinence (45.8%), erectile dysfunction (60.0%), radiation cystitis (50.8%), acute urinary retention (50.0%) and hematuria (42.5%). Other notable complications included prostate necrosis/abscess (14.2%), pubic osteomyelitis/prostatosymphyseal fistula (3.3%), de novo cancer (5.8%), and rectourethral fistula (0.8%). Patients required a mean of 7.4±4.4 (1-30) treatments for radiation related complications over the study period and 49.2% of patients required major urologic surgery. Required procedures included urethral dilation/urethrotomy (77.5%), urethral reconstruction (44.2%), incontinence surgery (6.7%), transurethral resection (prostate, bladder, contracture)(43.3%), cystolithopaxy (11.7%) and urinary diversion (6.7%). 13.3% of patients were treated with an indwelling suprapubic catheter. Patients with complications related to combined radiotherapy had more complications (7.0 vs. 5.0; p=0.016) including incontinence (85.7% vs. 44.2%; p=0.04), de novo malignancy (28.6% vs. 4.4%; p=0.05), pubic osteomyelitis (28.6% vs. 1.8%; p=0.02), and tended to require a higher number of procedures (10.1 vs. 7.2; p=0.08)._x000D_ Conclusions Lower urinary tract complications related to radiotherapy are very seldom an isolated problem and require a tremendous amount of resources and urologic intervention. Patients with combined radiotherapy complications have a higher number of complications and typically require more interventions. Funding None
Authors
Jon Witten
Keith Rourke |
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PD29-06 |
Predicting Endoscopic Treatment Success for Post-Prostatectomy Bladder Neck Contracture: Long-term time-to-recurrence analysis |
Trauma/Reconstruction/Diversion: Urethral Reconstruction (including Stricture, Diverticulum) II | 17BOS |
Abstract: PD29-06 Sources of Funding: None Introduction The natural history of endoscopic treatment for recurrent bladder neck contracture (BNC) after radical prostatectomy (RP) and predictors of treatment failure have been poorly studied. Using the largest known series of post-RP BNC series to date, we sought to assess long-term success of the initial endoscopic treatments for BNC and to identify factors that predict endoscopic treatment failure. Methods Between January 2005 and December 2014, we retrospectively reviewed 6,179 RP cases, and identified 302 incidents of BNC. BNC was defined as a symptomatic, cystoscopically confirmed narrowing of the bladder neck that occurred after prostatectomy. After exclusion criteria, 237 were available for analysis. Patient characteristics, prostatectomy technique, post-prostatectomy complications, and endoscopic treatment type were assessed for their association with endoscopic treatment failure. Endoscopic treatment success was defined as BNC resolution after ≤2 endoscopic treatments. The Kaplan-Meier method and log rank test were used to evaluate 5-year endoscopic treatment success over time. Multivariable Cox regression was performed to identify independent predictors of treatment failure. Results 5-year endoscopic treatment success was 76.7% after two procedures and 40.7% after one procedure. Median follow up was 54.5 months. The median time to BNC diagnosis was 2.9 months. Endoscopic treatment type (dilation vs. hot incision vs. cold incision) was not associated with treatment success after the first (p=0.86) or second (p=.27) treatment. On multivariable analysis, independent predictors of endoscopic treatment failure were non-nerve-sparing prostatectomy technique (HR 2.22, 95% CI 1.21-4.07, p=0.01) and post-prostatectomy urine leak (HR 2.74, 95% CI 1.42-5.29, p<0.01). Interestingly, prior radiation, surgical approach, bladder neck reconstruction and transfusion did not predict BNC treatment failure. [Table 1] Conclusions Endoscopic treatment is an effective management option for most post-prostatectomy BNC with promising 5-year outcomes. Non-nerve-sparing prostatectomy technique and post-prostatectomy urine leak predict endoscopic treatment failure. Patients with these factors are at greatest risk for requiring multiple treatments. Funding None
Authors
Daniel Ramirez
Matthew Maurice Ryan Nelson Jeremy Reese Ercan Malkoc Onder Kara Oktay Akca Kenneth Angermeier Hadley Wood Eric Klein Jihad Kaouk |
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PD29-07 |
Open Repair of Bladder Neck Contractures (BNC) with or without Adjuvant Radiotherapy – our experience in 42 patients |
Trauma/Reconstruction/Diversion: Urethral Reconstruction (including Stricture, Diverticulum) II | 17BOS |
Abstract: PD29-07 Sources of Funding: none Introduction BNC are thought to occur in approximately 0.4-32% of patients after radical prostatectomy (RP). The majority are managed endoscopically but a small number are refractory to all forms of treatment. This study describes our experience in this group of patients. Methods 42 patients, aged 49 - 76 (mean 63.5 years) presented with refractory BNC between March 07 and March 15. 32 had a RP alone. 10 had RP and adjuvant or salvage radiotherapy. Because of our previous experience in treating patients with urorectal fistulae, patients having revision of their vesico-urethral anastomosis with a history of radiotherapy were very carefully selected and only those with a bladder capacity of at least 200ml and with relatively normal urodynamic parameters were selected for reconstruction. All surgery was performed through a transperineal approach as for a pelvic fracture-related urethral injury. All patients required full mobilisation of the bulbar urethra, opening of the inter crural plane and an inferior wedge pubectomy. An artificial sphincter (AUS) was implanted 3 to 6 months later to restore continence. Results Of the 32 post-surgical patients 31 (97%) had a successful outcome. 3 of these had a simultaneous repair of a urorectal fistula (9%). Of the 10 patients who had had radiotherapy, 7 had a patent anastomosis and 6 (60%) of these were dry following implantation of an AUS. 1 other patient had 4 consecutive sphincter implants all of which eroded. 1 patient developed a re-stenosis and was managed thereafter by suprapubic catheterisation. Two had incomplete healing of their anastomosis and developed a urosymphyseal fistula and unfortunately were subsequently worse off as a result of their surgery. Conclusions Patients with a recalcitrant BNC after RP with no history of radiotherapy can be treated as with any other traumatic urethral stenosis – in this instance iatrogenic trauma by revision of the vesico-urethral anastomosis. The results are very satisfactory. With careful selection some patients who have had radiotherapy can be treated in the same way but there should be careful evaluation of the state of the pubis and pubic symphysis preoperatively as well as careful urodynamic evaluation of the bladder function, to avoid the very poor outcome in patients who fail such surgery. _x000D_ _x000D_ All patients must be counseled that this will almost certainly be a two-stage reconstruction - the first to dis-obstruct them by revision of the VUA and then secondly to implant an AUS for the almost (but not necessarily) inevitable sphincter weakness incontinence following dis-obstruction. _x000D_ Funding none
Authors
Stella Ivaz
Simon Bugeja Stacey Frost Mariya Dragova Daniela E Andrich Anthony R Mundy |
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PD29-08 |
When to remove the Foley catheter after endoscopic realignment of traumatic disruption of the posterior urethra? |
Trauma/Reconstruction/Diversion: Urethral Reconstruction (including Stricture, Diverticulum) II | 17BOS |
Abstract: PD29-08 Sources of Funding: none Introduction To verify a correlation between the period of urethral stenting after endoscopic urethral realignment and the incidence of post-operative urethral stricture. This study was designed to evaluate the outcome of continuing urethral stenting till the gap between the 2 realigned urethral segments has been completely epithelialized. Methods Eighteen patients underwent endoscopic urethral realignment after traumatic disruption of the posterior urethra. Post-operative urethroscopy was done using the flexible cystoscope to assess the progress of urethral healing. The urethral Foley catheter that acted as a stent and also for urine drainage was removed when complete mucosal healing was observed by urethroscopy. Post-operative development of urethral stricture was noted and uroflowmetry was done at 12–36 months. Results Endoscopy 6 weeks after realignment showed 50%-75% epithelialization in all patients(figure 1). At 9 weeks, epithelialization was 100% in 15/18 patients (83%) and complete epithelialization at 12 weeks in all patients (figure 2). After stent removal, 1 patient (5.6%) developed a mild symptomatic stricture that was successfully treated by a single session of visual urethrotomy. All 18 patients had normal uroflowmetry readings at 12-36 months after realignment. Conclusions Following endoscopic urethral realignment, urethral stenting till mucosal healing was complete reduced the incidence of subsequent urethral stricture. Urethroscopy showed complete mucosal healing in 9–12 weeks after realignment. During a follow-up period of 12-36 month, 94.4% of the patients were symptom-free. Presence of asymptomatic large-caliber strictures or possibility of development of symptomatic strictures during longer follow-up periods can’t be ruled out. Funding none
Authors
Hamed El Darawani
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PD29-09 |
Prediction of intraoperative difficulty and outcome of anastomotic urethroplasty for pelvic fracture urethral injuries: Revisiting retrograde urethrography |
Trauma/Reconstruction/Diversion: Urethral Reconstruction (including Stricture, Diverticulum) II | 17BOS |
Abstract: PD29-09 Sources of Funding: none Introduction Anastomotic urethroplasty (AU) for pelvic fracture urethral injury (PFUI) is a challenging procedure, notably, if corporeal splitting and/or inferior pubectomy (CS/IP) are required. Consequently, a long learning curve is surely needed. Herein, we used retrograde urethrogram (RGU) to envisage the intraoperative difficulty during AU for PFUI. We hypothesized that as deep as the urethra goes into the pelvis, the more complexity is anticipated. Methods A retrospective review for patients underwent AU for PFUI at a tertiary referral center was conducted between January 2010 and March 2016. The standard position for RGU is semi-lateral with only one obturator foramen is visualized. To address how deep the urethra goes into the pelvis, an imaginary line is drawn from the pubis symphysis down to a point midway between the tips of pubic rami, representing theoretically the midsagittal plane of the perineal membrane. Zones where the proximal end of the anterior urethra is present, are (A) anterior to the line, (B) on the line, and (C) across the line posteriorly (Fig.). The complexity of the procedure was defined as the need of any auxiliary maneuver beyond distal urethral mobilization (CS/IP) to achieve adequate anastomosis. Predictors were tested only in patients with successful AU. Further analysis was performed to detect the association between this hypothesis and the outcome defined by the need for instrumentation after AU. Results 129 patients were analyzed. 39 (30%) patients required auxiliary procedures beyond mobilization of the distal urethra and 36 (27.9%) reported failure. Among patients with successful AU, zone C was the only factor significantly associated with complex AU [13 (44.8%) vs 12 (18.8%)]. Furthermore, zone C [Odds ratio (OR): 4.9, p=0.006], as well as combined pelvic fracture (OR: 4.6, p=0.009), were the only independent predictors of treatment failure. Conclusions We defined a simple method to predict intraoperative complexity and treatment failure after AU for PFUI. This is might be of help for_x000D_ preoperative counseling and intraoperative planning by selecting cases for training and reserving particular ones for high volume_x000D_ surgeons. Funding none
Authors
Ahmed Harraz
Amr Elbakry Mohamed Tharwat Mohamed Fadallah Islam Fakhreldin Ahmed El-Assmy Ahmed Mosbah Adel Nabeeh |
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PD29-10 |
Prediction of the type of urethroplasty for pelvic fracture urethral injury by pubo-urethral stump angle measured on preoperative MRI |
Trauma/Reconstruction/Diversion: Urethral Reconstruction (including Stricture, Diverticulum) II | 17BOS |
Abstract: PD29-10 Sources of Funding: none Introduction Delayed urethroplasty for pelvic fracture urethral injury (PFUI) remains a clinical challenge in part because it may not be possible to predict from urethrography or urethroscopy findings the type of repair required. We therefore examined whether the type of reconstruction needed for PFUI repair can be predicted from preoperative magnetic resonance imaging (MRI) findings. Methods The records of 74 male patients with PFUI who underwent MRI of the pelvis at least 3 months after injury and, subsequently, anastomotic urethroplasty by a single surgeon (AH) during 2008 and 2015 were analyzed retrospectively. Pubo-urethral stump angle (PUA) was defined as the angle, measured in sagittal T2-weighted MRI, between the long axis of the pubis and the line between the lower border of the inferior pubic ramus and the proximal urethral stump. MRI findings including PUA were reviewed by two expert radiologists (HE and SS) without any knowledge of the patients&[prime] clinical information. The association of MRI findings and the procedures required during delayed urethroplasty was analyzed. Results Delayed urethroplasty was performed by the simple perineal approach in the 28 patients (38%) who required only bulbar urethral mobilization with/without crural separation and by an elaborate approach in the 46 patients (62%) who additionally required inferior pubectomy or an abdominoperineal approach. The overall success (defined as no recurrent stricture on urethroscopy) rate was 94.6%. MRI findings that in univariate analysis were significantly associated with a need for the elaborate approach were disruption at the prostate apex (p = 0.001), greater urethral defect length (p < 0.0001), lower ratio of bulbar urethral length to urethral defect length (p = 0.0005), presence of a paraurethral false passage (p = 0.0257), longer distance between the lower border of the inferior pubic ramus and the proximal urethral stump (< 0.0001), and lower PUA (p < 0.0001). MRI findings not significantly associated with a need for the elaborate approach were the bulbar urethral length (p = 0.69), lateral displacement of prostatic urethra (p = 0.19), and bulging of the rectum into the urethral gap (p = 0.15). In multivariate analysis, only low PUA was an independent predictor of a need for the elaborate perineal approach (p=0.045, OR=4.8, 95% CI 1.0-25.5). Conclusions PUA measured on MRI could provide information useful for predicting the type of reconstruction needed for PFUI repair. Funding none
Authors
AKIO HORIGUCHI
HIROMI EDO SHIGEYOSHI SOGA MASAYUKI SHINCHI KEIICHI ITO HIROSHI SHINMOTO RYUICHI AZUMA TOMOHIKO ASANO |
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PD29-11 |
Magnetic Resonance Imaging (MRI) in pelvic fracture urethral injuries to evaluate urethral gap: A new point of technique |
Trauma/Reconstruction/Diversion: Urethral Reconstruction (including Stricture, Diverticulum) II | 17BOS |
Abstract: PD29-11 Sources of Funding: None Introduction MRI is a helpful especially in complex cases of PFUI, which includes long gaps, floating bone chips, rectourethral fistula and bladder neck injury. Conventionally radiologists perform MRI on an empty bladder. Urologists and radiologist assess urethral gap using voiding cystourethrogram (VCUG) and retrograde urethrogram (RGU) studies. The aim of this study was to evaluate the urethral gap via MRI using a new point of technique. Methods From 1996 to 2016 1032 cases of PFUI have been seen at our institution with 10%being complex. MRI was routinely acquired for complex PFUI by radiologists using traditional protocol . We formulated a recent new technique where the images were obtained using urine as a natural MRI contrast. Ten consecutive cases of complex PFUI were prospectively evaluated with the new MRI protocol. First, a T2 image acquisition was performed. Urethral gap measurements by 4 radiologists were recorded for each case._x000D_ _x000D_ A second T2 image acquisition was performed with patient lying on the table with a full bladder, SPC clamped, straining to pass urine post administration of Tamsulosin while at the same time a premixed solution of sterile saline and lubricating jelly is instilled in the urethra. The bladder was filled physiologically with patient drinking water prior to the study. Urethral gap assessments were repeated using the same 4 radiologists ._x000D_ _x000D_ Additionally, 4 urologists were shown images from each phase of the study and their visual score was recorded – very satisfactory (4), satisfactory (3), disappointed (2) and extremely disappointed (1)._x000D_ Results Table 1_x000D_ Figure 1 Conclusions The described novel technique of MR assessment of urethral gap in pelvic fracture urethral injuries shows promising results and is a true reflection of the actual urethral gap which helps in planning surgical approach. The simple modification of having a full bladder, use of Tamsulosin and straining (dynamic images) helps to mimic a conventional VCUG and RGU along with advantages of MRI. Funding None
Authors
Pankaj Joshi
Devang Desai Sandesh Surana Hazem Orabi Sanjay Kulkarni |
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PD29-12 |
Female Urethral Distraction Injuries: A Systematic Review of the Literature |
Trauma/Reconstruction/Diversion: Urethral Reconstruction (including Stricture, Diverticulum) II | 17BOS |
Abstract: PD29-12 Sources of Funding: none Introduction Female urethral distraction injuries are rare and most commonly associated with pelvic fracture. We sought to systematically review the literature to determine the optimal management of this rare injury. Methods Using Meta-analysis Of Observational Studies in Epidemiology (M.O.O.S.E) criteria, we searched Cochrane, Pubmed and OVID databases for all articles available before June 30, 2016 using the terms “female pelvic fracture urethroplasty,” “female urethral distraction,” “female pelvic fracture urethral injury,” “female pelvic fracture urethra girls.” Three reviewers (CF, JA, DP) independently reviewed the titles, abstracts, and articles. We excluded articles based on animal models, transgender surgery, obstetric trauma, cancer or if they did not pertain to the treatment of female urethral injuries. Results We identified 162 individual articles from the databases. 51 articles met our criteria for full review. There were 158 female patients with urethral trauma, with almost twice as many children (? 18 years) as compared to adults (>18years), 99 vs 59. Of these injuries, 83 were managed with immediate repair via primary alignment (17) or anastomotic repair (66) and 75 were managed with delayed repair. Rates of urethral stenosis and fistula were highest after primary alignment. Urethral integrity appears to be similar following both primary anastomosis and delayed repair; however, patients experienced significantly more incontinence and vaginal stenosis following delayed repair. Those patients who underwent delayed urethral repair were more likely to undergo more extensive reconstructive surgery than those who underwent primary repair. _x000D_ Conclusions There is a paucity of data in the literature on the optimal management of female urethral distraction defects. Based on our review of the available literature, primary anastomotic repair of a female urethral distraction defect via a vaginal approach appears optimal. This contrasts with the management of male pelvic fracture-related urethral distraction defects, in which primary anastomotic repair is considered injurious, and primary alignment is considered optimal. Funding none
Authors
Devin Patel
James Weinberger Cynthia Fok Jennifer Anger |
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PD30-01 |
URETEROSCOPY IN PREGNANT WOMEN WITH COMPLICATED COLIC PAIN: A TWO CENTER-MATCHED RETROSPECTIVE STUDY |
Stone Disease: Surgical Therapy III | 17BOS |
Abstract: PD30-01 Sources of Funding: None Introduction Clinical presentation of ureteral stones during pregnancy is generally with renal colic pain. The aim of this study is to present our experience in the management of renal colic during pregnancy in emergency settings. Methods 208 pregnant patients who presented to emergency department with renal colic pain and underwent ureteroscopy (URS) due to failed conservative therapy were enrolled in the study. Urinary tract stones were diagnosed either with ultrasound (US) examination or during URS. Laser lithotripsy and double J (DJ) stent placement were routinely done in all patients with ureteral stones. The incidence of infective complications and premature uterine contractions (PUC) due to URS were compared. Results No stone was identified in 36.1% (n=75) of patients with using US and diagnostic URS. Of the remaining 133 patients, 30 (22.6%) had no stone in US but rather diagnosed during diagnostic URS. The type of anesthesia had no significant effect on PUC. An increased risk of sepsis and PUC was found in patients with fever at the initial presentation. Interestingly, PUC was more frequent in patients with lower serum magnesium levels. There was a significant correlation with time delay until the intervention and the risk of urosepsis and PUC, individually. Conclusions Ureteroscopy is a safe option in evaluation of pregnant patients with unresolved renal colic. According to the current findings, timing of the operation is the most important factor affecting the septic risks and abortion threat. Surgical intervention with URS must be planned as soon as possible. Funding None
Authors
Salvatore Butticè
Tarik Emre Sener Antonio Simone Laganà Salvatore Giovanni Vitale Christopher Netsch Yiloren Tanidir Rosa Pappalardo Carlo Magno |
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PD30-02 |
FURS vs Shockwave lithotripsy for treatment of (1-2) cm renal stones in children with a solitary kidney: A prospective randomized study |
Stone Disease: Surgical Therapy III | 17BOS |
Abstract: PD30-02 Sources of Funding: none Introduction To compare the safety and outcome of FURS and shock wave lithotripsy (SWL) for treatment of (1-2) cm renal stones in children with a solitary kidney. Methods Between April 2011 and April 2016, all children (< 15 years) with a renal stones (1-2) cm in a solitary kidney were randomized into two groups – group 1, FURS ; group 2 SWL. In FURS group , A 7.5 Fr flexible ureteroscope (FURS) was introduced into the ureter over a hydrophilic guidewire under visual and fluoroscopic guidance without access sheath . Complete stone dusting using 200 ?m laser fiber (0.2– 1.0 joules power and15–30 Hz frequency) was done in all cases ended with a 5 Fr JJ stent insertion. The children were discharged home 4 hours postoperative in absence of the complications. Both groups were compared as regard the stone hardness, size, the complications (intraoperative and postoperative), the number of anaesthesia sessions and the need for auxiliary procedure. Results 11 cases with median age (9.3 years vs 9.6 years, P = 0.55) were enrolled in each group. The stone size was (11+_ 4 mm vs 13 _+ 3 mm, P = 0.30), the stone hardness (785 +_ 85 HU vs 800 _+ 75 HU, P= 0.36) were comparable between the two groups. All cases of SWL group need preoperative DJ stent (3 for their obstructive anuria while the remaining to avoid post SWL obstructive anuria) while DJ stent were inserted in 2 cases of FURS group because of their presentation as an obstructive anuria and one case intraoperative for passive ureteral dilation of a tight ureter that not allow introduction of the FURS. 6 cases in SWL group need a second session of SWL vs one in FURS group with passive ureteral dilation (P = 0.001). The stone free rate after 1 month was 95 % in SWL group including the second sessions vs 96% in FURS group (P = 0.04). 4 cases of SWL group needs URS and another DJ stent after its removal because of obstructive anuria by stone fragments vs only one case in FURS group (P = 0.001). Intraoperative complication in the form mucosal perforation was reported in one case of FURS group while no intraoperative complication was recorded in SWL group. The hospital stay was comparable in both groups (4+_ 1 hours in SWL group vs 4 h+_ 1.5 hours in FURS group )(P = 0.30). The anaesthetic sessions (including stent removal) were 47 sessions in SWL group vs 24 sessions in FURS group (P = 0.001). Conclusions FURS and SWL are comparable as regard the stone free rate in paediatric renal stone (1-2) cm with a solitary kidney. FUR carries the advantage of single session procedure, less need to postoperative auxiliary procedure with resultant less anaesthetic sessions. SWL carries the advantages of low intraoperative complications. Funding none
Authors
wael gamal
ahmed mmdouh |
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PD30-03 |
Same session bilateral ureteroscopy for multiple stones: results from the Clinical Research Office of Endourological Society (CROES) Ureteroscopy (URS) Global Study |
Stone Disease: Surgical Therapy III | 17BOS |
Abstract: PD30-03 Sources of Funding: none Introduction We present an international experience with ipsilateral ureteroscopy (I-URS) for multiple ureteric and renal stones and bilateral URS (B-URS) for multiple, bilaterial ureteric and renal stones, using data collected from the Clinical Research Office of the Endourological Society (CROES) Ureteroscopy Global Study. Our objective was to compare I-URS and B-URS treatment characteristics and outcomes as well as the outcomes of multiple single-session stone treatments (I-URS and B-URS) with single stone URS treatments. Methods The CROES Ureteroscopy Global Study includes 114 centers in 32 countries. Patients undergoing B-URS, I-URS, and URS for a single stone were identified from January, 2010 to October, 2012. Intra-operative characteristics and post-operative outcomes were identified for each patient. Univariate regression analysis and inverse-probability weighted regression adjustment (IPWRA) analyses were used to compare outcomes and adjust for difference between centres. Results The CROES URS Global Study consists of 11885 patients. A total of 2153 (18.7%) patients were treated for multiple stones with 1880 (87.3%) and 273 (12.7%) patients undergoing I-URS and B-URS respectively. The univariate and IPWRA models for B-URS versus I-URS and multiple versus single stone treatments show that patients with B-URS and multiple stone treatments have lower stone free rates, higher re-treatment rates, and longer operating times compared to patients whom underwent I-URS and single stone treatment. There was no difference in complication rates between B-URS, I-URS, and single stone ureteroscopy. Conclusions This study represents the largest series of patients undergoing URS for bilateral and multiple ipsilateral stones. Our findings suggest a decrease in stone free rates, increased re-treatment rates, increased operating time and a longer hospital admission in patients treated for multiple stones. The treatment of multiple stones and B-URS is safe when compared to single stone and I-URS. Funding none
Authors
Kenneth Pace
Tad Kroczak Nienke Wijnstok Guido Kamphuis Tarik Esen Chrysovalantis Toutziaris Benjamin Silva Jean de la Rosette |
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PD30-04 |
Perioperative management of low-dose aspirin in surgical kidney stone management: a survey of current endourologic practice patterns. |
Stone Disease: Surgical Therapy III | 17BOS |
Abstract: PD30-04 Sources of Funding: None Introduction The recently published American Urological Association guidelines on the surgical management of kidney stones state that ureteroscopy (URS) is the preferred treatment for patients on continuous antiplatelet regimens, however multiple recent case series questioned whether continuing low-dose aspirin at the time of percutaneous nephrolithotomy (PCNL) or extracorporeal shockwave lithotripsy (ESWL) could be safe in certain settings. We conducted a survey study to further define current practice trends and guide future research into the topic. Methods An electronic survey was sent to approximately 2000 members of the Endourology Society in September of 2016. 184 substantive responses (9.2%) were received from members in six continents. The resulting data was analyzed and associations were measured by Pearson's chi-squared test. Results 63% of respondents were fellowship trained, 67% practiced in academic centers, and 70% practiced in North America or Europe. 79% of respondents stated that they routinely performed URS on patients taking 81 mg of Aspirin (ASA) daily as opposed to only 29% when asked the same question with regard to PCNL (Odds Ratio (OR): 17.4, p < 0.001) and 18% with regard to ESWL (OR: 9.2, p < 0.001). Those in academic practice were more likely to perform PCNL (OR: 2.4, p = 0.02) but not ESWL (p = 0.51) on patients while taking ASA. Respondents from outside North America or Europe rarely reported performing PCNL or ESWL on patients taking ASA (40% vs. 5%, p <0.001 and 22% vs 7%, p = 0.01). Neither fellowship training nor high case volumes were associated with an increased likelihood of performing PCNL or ESWL in patients taking ASA; however if a surgeon performed fellowship training in North America or Europe, they were significantly more likely to routinely perform PCNL on patients taking ASA (p <.0001). Those who performed PCNL or ESWL on ASA were significantly less likely to consult cardiology regarding cessation of ASA pre-operatively (p <.001). There was a trend toward younger physicians performing PCNL and ESWL on ASA (p = 0.06, 0.05, respectively). Conclusions Urologists commonly perform URS in patients taking aspirin, but only a minority perform ESWL and PCNL in patients on ASA. There was a wide regional variation in aspirin usage in ESWL. Surgeons in academic centers and with fellowship training from North America or Europe were more likely to perform PCNL on ASA. The next step is to evaluate the safety and outcomes of remaining on ASA for surgery. Funding None
Authors
Joshua Ebel
Brian Eisner Michael Lipkin Ben Chew Bodo Knudsen |
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PD30-05 |
Risk factors predicting post-percutaneous nephrolithotomy transfusion |
Stone Disease: Surgical Therapy III | 17BOS |
Abstract: PD30-05 Sources of Funding: None Introduction Percutaneous nephrolithotomy (PCNL) is the standard of care for treatment of large renal stones. While complications associated with PCNL are uncommon, post-PCNL hemorrhage requiring blood transfusion is a common concern. We investigate risk factors for transfusion following PCNL using a prospectively collected database. Methods An institutional review board approved, prospectively maintained database of patients undergoing percutaneous nephrolithotomy was utilized for this investigation. All patients undergoing PCNL who received a blood transfusion in the post-operative period were included in this study. These patients were matched 1:1 for BMI and stone composition. A statistical analysis was performed utilizing student t-test and Fischer’s exact test for continuous and categorical variables, as well as stepwise multivariate logistic regression analysis to identify risk factors for blood transfusion. Results A total of 1448 patients were identified, of those, 49 (3.3%) received a blood transfusion in the post-operative period. Patients who received a blood transfusion were older (mean (SD) 60.7 (16) versus 53.5 (17) years, p=0.03), more likely to have: a bilateral procedure (67.7 versus 40.6%, p=0.02), a diagnosis of diabetes (73% versus 44%, p=0.03), paralysis/contractures (12.2% vs 0%, p<0.01) a lower pre-operative hemoglobin (12.6 (2.0) versus 13.6 (2.1) gm, p=0.01) and a longer primary procedure length (163.8 (57.0) versus 131.9 (48.5) min, p=0.01). On forward stepwise multivariate logistic regression analysis the presence of diabetes (OR 4.7, 95% CI 1.5 - 14.7, p=0.008) and bilateral procedure (OR 7.1, 95% CI 1.9-26.4, p=0.003) was significantly associated with receipt of a transfusion. Conclusions The overall transfusion rate within our patient population was low at 3.3%. However, patients with a pre-operative diagnosis of diabetes and those undergoing a bilateral procedure had an increased risk for a transfusion. Patients with diabetes and those undergoing a bilateral procedure should be counseled appropriately regarding the increased risk for bleeding related complications. Funding None
Authors
Marcelino Rivera
James Lingeman Matthew Mellon Nadya York Hazem Elmansy Amy Krambeck |
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PD30-06 |
Transparenchymal Renal Surgery Decreases Kidney Function in Patients with Stones Larger than 4 cm and Stones in Multiple Locations |
Stone Disease: Surgical Therapy III | 17BOS |
Abstract: PD30-06 Sources of Funding: none Introduction Percutaneous nephrolithotomy (PCNL) is a transparenchymal procedure that leads to nephron loss during tract access, dilation and instrumentation. Previous studies have demonstrated no significant difference in renal function during uncomplicated PNL. These studies used the Modification of Diet in Renal Disease (MDRD) equation to estimate GFR. This equation is limited in its accuracy for patients with glomerular filtration rates (GFR) > 60 ml/min/1.73 m2. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation provides an accurate estimation of renal function for patients with GFR both above and below 60.Here, we sought to examine factors that may influence changes in GFR as estimated by CKD-EPI. _x000D_ Methods The last 100 patients that underwent PNL at our institution were reviewed (2014-2015). Pre- and post-operative GFR was calculated based upon both the MDRD and CKD-EPI formulas. Clinical and radiographic parameters were assessed. Statistical difference was determined using Student?s t-test. _x000D_ Results 100 patients were included in the study. All patients had one access tract. Dilation of a 30-French access tract was achieved with a balloon dilator. When using MDRD, 76 of 100 patients were unable to have GFR difference detected due as their GFR exceeded 60 ml/min/1.73 m2. In contrast, pre- and postoperative GFR was able to be compared with all patients using CKD-EPI. The average change in GFR for the entire cohort was +3.39 ml/min/1.73 m2. Patients with stones in three or more locations had a significant decrease in GFR compared with those in one or two locations (-5.7 versus +5.5 ml/min/1.73 m2, p < 0.001). Similarly, patients with stones larger than 4 cm had an average decrease in GFR, while GFR was noted to increase in patients with stones smaller than 4 cm (-4.1 versus +5.5 ml/min/1.73 m2, p = 0.009). In addition, patients with CKD Stage 1 or normal renal function, as well as patients with staghorn stones had a significant comparative decrease in GFR._x000D_ Conclusions Overall, there was no significant change in GFR among patients that underwent PNL. However, treatment of stones in multiple locations, staghorn stones and treatment of larger stones resulted in a significant decrease in GFR. Funding none
Authors
Timothy Tran
Gyan Pareek |
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PD30-07 |
OUTPATIENT TUBELESS MINI-PCNL FOR MODERATE TO LARGE RENAL STONES: OUR ONGOING EXPERIENCE |
Stone Disease: Surgical Therapy III | 17BOS |
Abstract: PD30-07 Sources of Funding: none Introduction Percutaneous nephrolithotomy (PCNL) for the treatment of renal calculi has traditionally been an inpatient procedure often requiring a multi-day hospitalization. Large-bore nephrostomy tubes and ureteral stents have also been traditionally placed for control of bleeding and urinary drainage. Currently, more advanced technology as well as smaller operating nephroscopes and lithotripters have made PCNL a less morbid procedure with the possibility of being done on an outpatient basis. Our aim is to show that mini-PCNL can be safely performed in a tubeless fashion on an outpatient basis. Methods We performed a retrospective chart review of patients that underwent mini-PCNL at our institution by a single fellowship-trained endourologist. Only those patients who were discharged home the same day without nephrostomy tubes or ureteral stents were included. Cases were performed using mini-nephroscopes with an outer diameter of 15 to 17.5-Fr. Results There were 15 patients included for analysis. Average age was 51.3 years. The group was 53% female and 47% male. Mean BMI and ASA score were 29.31 and 2.4, respectively. Total operative time averaged 55.6 minutes [range 27 - 106]. Mean estimated blood loss was 12.87-mL [range 3-30-mL]. Stone size ranged from 1.3-cm to 3-cm. Left and right sided stones were split evenly. There were multiple stones in 47% of patients. Primary stone location varied, but the majority were in the renal pelvis or the lower pole. Renal access was obtained in a middle or interpolar calyx 53% of the time, and 47% in the lower pole. Laser or ultrasonic lithotripsy was utilized. FLOSEAL was administered in the tract, and no stents or nephrostomy tubes were left. All patients were discharged home. No patients were readmitted or had unplanned ER visits so far. All patients with follow-up were stone free on KUB and RUS imaging. Conclusions Mini-PCNL using operating nephroscopes up to 17.5-Fr can be safely performed on an outpatient basis in a tubeless fashion without nephrostomy tubes or ureteral stents. Some of our patients went home with Foley catheters that were removed the following morning. With the advent of improved optics and smaller ultrasonic lithotripters, mini-PCNL is a worthwhile option for patients with renal calculi that can be accomplished safely in a cost-saving outpatient basis, all while rendering patients stone free with one procedure. With changes in reimbursement for hospitals and physicians in the future, outpatient mini-PCNL could serve as a sound option for those with moderate to large renal stones who wish to be rendered stone free in one operation and avoid ureteral stents. Funding none
Authors
Kyle Basham
John Fisher Jeremy Archer Ryan Pickens |
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PD30-08 |
Device-Related Deviation During Percutaneous Nephrolithotomy: Review of the Manufacturer and User Facility Device Experience (MAUDE) Database. |
Stone Disease: Surgical Therapy III | 17BOS |
Abstract: PD30-08 Sources of Funding: none Introduction Percutaneous nephrolithotomy (PCNL) is a standard approach for the access to and treatment of large stones from the upper urinary tract. PCNL is a complex, multistep surgery requiring multiple classes of devices. Malfunctions of devices are important to best address issues of patient safety and surgical quality which has not yet been standardized. Herein we describe the first reports of device-related malfunctions during PCNL reported in the Manufacturer and User facility Device Experience (MAUDE) database. _x000D_ Methods The publicly available MAUDE database was examined for device-related deviation, impediment for use, or frank malfunction during PCNL. The database was queried for &[Prime]percutaneous nephrolithotomy&[Prime] for reports from 2005 to 2016. Duplicate cases, cases with incomplete data, or non-verifiable reporter cases were excluded. _x000D_ _x000D_ Results A total of 218 reports were identified with the most common reported device classes including the lithotripter 53 (24.3%), wires 43 (19.7%), balloon dilators 30 (13.8%) and occlusion balloons 28 (12.8%). The most common deviation included broken off device fragments with use of wires and lithotripters while a bursting balloon was the most common balloon-reported malfunction. Resultant complications to the patient included need for a second procedure 12 (24.4%), bleeding 8 (16.3%), retained stone fragments 7 (14.2%), prolonged procedure 4 (8.2%), ureteral injury 2 (4.1%) and conversion to an open procedure 2 (4.1%). Reporters included the physician 143 (65.5%), nursing staff 18 (8.3%) and risk manager 10 (4.6%) and the device was evaluated by the manufacturer in 93 (42.7%) of cases. _x000D_ Conclusions A wide range of device-related deviation from diverse product classes is reported during PCNL that in select cases resulted in patient morbidity. A working knowledge of the scope of potential malfunctions is critical during performance of this multistep procedure. _x000D_ Funding none
Authors
Neel Patel
Ariel Schulman Nikil Uppaluri John Phillips Muhammad Choudhury Sensuke Konno Majid Eshghi |
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PD30-09 |
Which flexible ureteroscopes (digital vs optical) can easily reach the difficult lower pole calyces and have better end-tip deflection? |
Stone Disease: Surgical Therapy III | 17BOS |
Abstract: PD30-09 Sources of Funding: none Introduction All modern flexible ureteroscopes have a deflection of at least 270°, but approaching a difficult lower pole acute angled calyx can still be very difficult. The aim of our study was to find which ureteroscopes are better when dealing with a sharp angled calyx and to compare the deflection of the last few centimetres (cm) of the ureteroscope tip. Methods Using a training model for flexible ureteroscopy (K-Box®, Porges-Coloplast), we identified an acute angle calyx and we tried to access it with 9 different ureteroscopes (BOA vision and COBRA vision, Richard Wolf®; FLEX X2 and FLEX Xc, Karl Storz®; LithoVue, Boston Scientific®; URF-P5, URF-P6, URF-V and URF-V2, Olympus®). _x000D_ Passing the scope through a 10/12 Fr ureteral access sheath respectively (using ReTrace, Coloplast sheath) (except 12/14 Fr sheath for COBRA vision), with the tip out at 1 cm, 2 cm, 3 cm and 4 cm, we measured the maximum tip deflection for every ureteroscope. Results All optical ureteroscopes (URF-P5, FLEX X2) except the URF-P6 were able to access the sharp angled calyx. Except FLEX Xc, none of the digital ureteroscopes reached the difficult calyx._x000D_ _x000D_ All optical ureteroscopes had better end-tip deflection compared to the digital scopes with the exception of FLEX Xc, which was as deflectable as the optical ureteroscopes. Conclusions Digital ureteroscopes tend to be more rigid and the last centimeters of their tip seems to be less flexible, possibly due to the size of the camera capsule. When approaching a difficult, acute angled lower pole calyx, it might be better to use a fibre-optic ureteroscope. Funding none
Authors
Laurian Dragos
Salvatore Buttice Tarik Emre Sener Silvia Proietti Achilles Ploumidis Catalin Iacoboaie Steeve Doizi Jeremie Berg Bhaskar Somani Olivier Traxer |
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PD30-10 |
Tipless Nitinol Stone Baskets: Comparison of Penetration Force, Radial Dilation Force, Opening Dynamics, and Deflection |
Stone Disease: Surgical Therapy III | 17BOS |
Abstract: PD30-10 Sources of Funding: none Introduction Tipless nitinol baskets are commonly used during ureteroscopic procedures for urinary calculi manipulation and retrieval. We aimed to evaluate and compare 5 commercially available tipless nitinol stone baskets(2.2F): 2.2F Coloplast Dormia No-Tip®, 1.5F Sacred Heart Medical Halo®, 2.2F Cook NCircle Nitinol Tipless Stone Extractor®, 1.9F Bard SkyLite Tipless Nitinol Basket® and the 1.9F Boston Scientific Zero Tip® Nitinol Stone Retrieval Basket for penetration force, radial dilation force, opening dynamics and resistance towards deflection. Methods Each of the 5 baskets were tested for penetration force (safety metric) - 5 repetitions with 2 baskets tips of each model) with a motorized sliding stage model and digital force gauge to assess perforation of a piece of aluminum foil with the basket tip. Radial force (functional metric for ureteric calculi) was tested by measuring maximal force of an opened basket between two blocks on a digital scale (10 repetitions for each basket). Opening/closing dynamics for each basket were measured by determining the width of the basket at 0.5 mm increments of basket length with digital calipers and light microscopic visualization. Limitation of deflection (functional metric) was tested by measuring the difference in maximal upward and downward angle of deflection of a ureteroscope with and without a basket in place. Results The Sacred Heart Halo 1.5F basket had the highest mean force required to perforate the foil at 0.676N +/- 0.117 (p<0.0001). The Coloplast No-Tip Dormia 2.2F basket required the lowest mean force required to perforate at 0.105N +/- 0.043 (p<0.0001). The Sacred Heart Halo 1.5F basket had the highest mean radial dilation force at 3.04 g +/- 0.15 (p<0.0001). The Cook NCircle 2.2F basket had the lowest mean radiation dilation force at 1.24 g +/- 0.084 (p<0.0001). The Cook NCircle 2.2F had the most linear pattern of opening, while the Coloplast No-Tip Dormia 2.2F and the Sacred Heart Halo 1.5F exhibited exponential opening dynamics. The Cook NCircle 2.2F limited scope deflection the most with a decrease in 4° downward and 10° upward (net 14° of lost deflection). The Sacred Heart Halo 1.5F had the least influence on deflection with a decrease in 3° downward and 5° upward (net 8° of lost deflection) Conclusions The penetration force, radial dilation force, opening dynamics and resistance to deflection varied between 5 commonly available tipless nitinol stone baskets. A small diameter 1.5F basket is capable of providing optimal performance, while sacrificing linear opening. Funding none
Authors
Nishant Patel MD
Arash Akhavein MD Bryan Hinck MD Rajat Jain MD Manoj Monga MD |
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PD30-11 |
Use of Moses Pulse Modulation Technology to Improve Holmium Laser Lithotripsy Outcomes: A preclinical study |
Stone Disease: Surgical Therapy III | 17BOS |
Abstract: PD30-11 Sources of Funding: None Introduction Efficient Holmium laser lithotripsy is limited by two main factors: retropulsion and energy transmission in water, which depends on fiber-stone distance. Recently, Lumenis developed the Moses technology, including the Moses D/F/L fibers, using pulse modulation resulting in improved energy transmission through water and reduced retropulsion. The Moses technology modulates the energy pulse that enables emission of a controlled portion of energy to create a bubble, known as the &[Prime] Moses effect &[Prime], while leaving a portion that travels through the bubble to the stone. The aim was to conduct a preclinical study investigating the effect of the Moses technology on Holmium laser lithotripsy comparing the Moses mode to the Regular mode in terms of lithotripsy efficiency and laser-tissue interaction Methods Several experiments were performed to explore the advantages of the Moses technology using the Lumenis P120H system and Moses D/F/L fibers. Experiments included: stone fragmentation efficiency at 1 mm distance; effect on retropulsion (reaction to a single pulse) measured by high-speed camera; efficiency of in vitro laser lithotripsy measured by procedural time, and lasing-pause ratios. In addition, a porcine ureteroscopy model was used to assess stone fragmentation and dusting as well as laser-tissue interaction when the laser fiber touched the ureteral wall. Results Stone fragmentation tests showed that the Moses mode resulted in significantly higher ablation volume when compared with Regular mode (160% higher; p=0.001). Stone displacement experiments following a single pulse showed significant reduction in retropulsion when using the Moses mode. The stone movement was reduced by 50 times at 0.8J and 10Hz (p=0.01). The pronounced reduction of retropulsion in the Moses mode was clearly observed during in vitro fragmentation settings (higher energy) and during dusting for smaller stones (low energy, high Hz). There was also significant reduction in procedure time (average 35% reduction for fragmentation and 23% for dusting, p=0.01) and longer lasing duration with shorter pauses indicating reduced need to reposition the fiber due to lack of retropulsion. Histological analysis of the porcine ureter after direct lasing in the Moses mode showed less damage than in the Regular mode. Conclusions The Moses technology resulted in more efficient laser lithotripsy in addition to significantly reduced stone retropulsion resulting in significantly shorter procedural time and greater margin of safety. Funding None
Authors
Mostafa Elhilali
Shadie Badaan Ahmed Ibrahim Sero Andonian |
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PD30-12 |
How to perform the dusting technique for calcium oxalate stones during Ho:YAG lithotripsy |
Stone Disease: Surgical Therapy III | 17BOS |
Abstract: PD30-12 Sources of Funding: This study was supported by grant no. 04-2012-0260 from the SNUH Research Fund. Introduction To determine the most efficacious setting of Ho:YAG laser with a maximum power output of 120 W with in vitro phantom-stone dusting technique. Methods A laser was used to treat two 4 x 3 x 3 mm3 sized phantom stones in 5 mL syringes with 1 mm-sized holes at the bottom. According to the pulse width (short 500, middle 750, long pulse 1,000 ?sec), maximal pulse repetition rates from 50 to 80 Hz were tested with pulse energy of 0.2, 0.4, 0.5, and 0.8 J. Six times of the mean dusting times were measured at each setting. Dusting was performed at continuous firing of the laser until the stones become dusts < 1 mm. Results The mean Hounsfield unit of phantom stones was 1,309.0 ± 60.8. The laser with long pulse generally showed shorter dusting times than short or middle pulse width. With increasing the pulse energy to 0.5 J, the dusting time decreased. However, the pulse energy of 0.8 J showed longer dusting times than those of 0.5 J. On the post-hoc analysis, the pulse energy of 0.5 J, long pulse width, and the repetition rates of 70 Hz demonstrated significantly shorter dusting times than other settings. Conclusions The results suggest that the pulse energy of 0.5 J, long pulse width, and the repetition rates of 70 Hz provided the most efficacious dusting with the high-power output 120 W Ho:YAG laser among all settings by in vitro reproducible experiments with phantom stones which mimicked calcium oxalate monohydrate calculi. Funding This study was supported by grant no. 04-2012-0260 from the SNUH Research Fund.
Authors
Jeong Woo Lee
Juhyun Park Min Chul Cho Hyeon Jeong Hwancheol Son Sung Yong Cho |
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PD31-01 |
The Natural History of Untreated Peyronie’s Disease: Curvature, Length, and Pain |
Sexual Function/Dysfunction: Peyronie's Disease I | 17BOS |
Abstract: PD31-01 Sources of Funding: None Introduction Relatively limited data exist on the natural history of untreated Peyronie’s Disease (PD). Here, we sought to evaluate and report on the natural history of patient-reported changes in penile curvature, pain, and shortening in men with untreated PD. Methods We identified all patients who underwent evaluation for PD at our institution between 1990 and 2012. 719 patients were randomly selected to receive a mail-in questionnaire with questions relating to the natural history of PD, including topics of change in curvature, pain, and shortening over time. Results were subsequently summarized as a descriptive report, and statistical comparisons were performed where appropriate. Results A total of 162 patients (23% response rate) completed the mail-in survey. Of these, 125 had no history of prior intralesional or surgical therapy for PD, and these patients comprised our study cohort. Median (IQR) patient age at diagnosis was 65 (62;68), and PD duration was 8.4 (5;12) years. Eighty-six percent of patients presented with penile curvature including 46% dorsal/ventral and 54% lateral, per patient report. Twelve percent of patients reported multi-planar curvature and 84% estimated their curvature as < 45 degrees. Penile curvature resolved in 16%, improved in 27%, worsened in 20%, and remained stable in 37% of patients. Interestingly, 12% of patients developed a new penile curvature at a median (IQR) of 17 (11;39) months after initial presentation, and these patients were significantly more likely to report worsening of their initial penile curvature (p=0.01). Fifty-four percent of patients reported penile indentation or narrowing. Penile pain was reported in 60% of patients, of whom the pain improved (18%) or resolved (64%) at a median (IQR) of 12 (6;24) months. Sixty-five percent of patients reported penile shortening, with 30% noting progressive shortening over time. Conclusions The current report provides additional understanding on the natural history of untreated PD. Contrary to some reports, the majority of men note curvature stability or improvement, resolution of pain, and progressive penile shortening over time. Only 20% reported worsening of curvature after disease stability, with 12% developing de novo curvature. This information significantly enhances our understanding and provides data for counseling patients with newly diagnosed PD. Funding None
Authors
Matthew Ziegelmann
Raevti Bole Ross Avant Brian Montgomery Manaf Alom Landon Trost |
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PD31-02 |
Factors Predicting Clinical Presentation in Men with Peyronie&[prime]s Disease |
Sexual Function/Dysfunction: Peyronie's Disease I | 17BOS |
Abstract: PD31-02 Sources of Funding: AWP is a K12 scholar supported by a Male Reproductive Health Research (MRHR) Career Development Physician-Scientist Award (Grant # HD073917-01) from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Program. This work is also supported in part by the Burnett Research Fund. _x000D_ Introduction Peyronie&[prime]s disease (PD) can cause penile plaque development, resulting in penile deformity and limiting sexual function, and can have a negative psychological impact. Here, we identify predictors of PD risk and progression. Methods A retrospective analysis of 212 men with PD presenting to a single academic andrology clinic was performed. Age, date of disease onset, body mass index (BMI), smoking history, erectile dysfunction (ED), hyperlipidemia (HLD), diabetes mellitus (DM), hypertension (HTN) and past and current medications were evaluated. All cases were confirmed with penile ultrasound to quantify plaque size, as well as degree and direction of penile curvature. Linear and logistic regression analysis was used to examine relationships between variables. Results Men with PD and ED (ED+PD group) and those with PD alone (PD group) were examined for variables that impact PD development and progression. Of the 212 men with PD, 149 (70.3%) self-reported ED. Furthermore, smoking and HLD were significantly associated with the development of ED in men with PD. Nineteen men were current and 41 were former smokers. The prevalence of ED was 64% in men without HLD but 79% in men with HLD (p=0.018). Logistic regression demonstrated that both HLD and smoking history increased the risk of ED (OR 2.3 and 2.2, 95% CI 1.16-4.47 and 1.14-7.59, respectively). Penile curvature and plaque characteristics did not correlate with the presence of ED, suggesting a vascular etiology for the ED in men in our cohort, rather than one related to fibrosis. In non-smokers, the presence of HLD was associated with a plaque volume that was 151.27 mm3 greater than in men without HLD, adjusting for age, BMI, and duration of PD (p=0.018). History of trauma, age of onset, duration of symptoms and overall plaque volume were not correlated with angle of curvature. When assessing angle of curvature, a 1 cm increase in plaque length correlated with an 8.8 degree increase in curvature. Conclusions Hyperlipidemia contributes to increased PD plaque volume and risk of ED, independent of penile curvature or plaque characteristics, suggesting a vascular etiology for ED in some men with PD. These data provide a basis for cardiovascular risk factor modification in affected men. Furthermore, longer penile plaques correlate with more significant penile curvature. These results further facilitate risk stratification and counseling of men with PD. _x000D_ Funding AWP is a K12 scholar supported by a Male Reproductive Health Research (MRHR) Career Development Physician-Scientist Award (Grant # HD073917-01) from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Program. This work is also supported in part by the Burnett Research Fund. _x000D_
Authors
Katherine M. Rodriguez
Jaden R. Kohn Taylor P. Kohn Larry I. Lipshultz Alexander W. Pastuszak |
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PD31-03 |
Contemporary Trends in the Surgical Management of Peyronie&[prime]s Disease in New York State |
Sexual Function/Dysfunction: Peyronie's Disease I | 17BOS |
Abstract: PD31-03 Sources of Funding: None Introduction In 2015 the American Urological Association (AUA) released guidelines on the management of Peyronie&[prime]s Disease (PD). We sought to characterize the surgical therapies being utilized for the management of PD in New York State prior to the release of the AUA guidelines. Methods The New York Statewide Planning and Research Cooperative System (SPARCS) database was queried for men undergoing surgery for Peyronie&[prime]s Disease from 2003 to 2014. Patients were identified using ICD-9-CM diagnosis codes for PD (60785). Surgical intervention was determined using ICD-9-CM and CPT codes. Patient demographics and comorbidities were recorded and treatment strategy was stratified by erectile dysfunction status. Results A total of 1,655 men underwent surgery for Peyronie&[prime]s Disease, corresponding to a rate of 1.9 cases per 100,000 person-years. Of the 1,655 men treated surgically for PD, 69.7% had concomitant ED. 97% (1124/1154) of these men underwent inflatable penile prosthesis (IPP) placement. Amongst men with PD who underwent IPP, 56.7% (637/1124) were treated with a concomitant straightening procedure. The use of plaque excision or incision and grafting (PEG/PIG) at the time of IPP was rare (45/1124, 4.0%), indicating that 96% of adjunctive maneuvers used to achieve straightening were either penile modeling or tunical plications. In men with PD without ED, 7% (35/501) underwent IPP placement with the remainder of procedures split almost evenly between tunical plication (235/501, 46.9%) and PEG/PIG (231/501, 46.1%). Only 2.8% (13/466) of men with PD treated with non-implant surgery went on to have an IPP. Conclusions This is the first published description of PD surgical practice patterns derived from a large, population-based dataset. 70% of men that underwent surgery for PD in New York had concomitant ED and received an IPP. In the vast majority of these cases, complex reconstructive procedures using grafting was not required. Patients with PD without ED were usually treated with non-implant procedures, and these men only rarely went on to receive an IPP. Funding None
Authors
Michael J Lipsky
Wilson Sui Alexander C Small Ricardo Munarriz James A Kashanian Doron S Stember Peter J Stahl |
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PD31-04 |
Onset Of Peyronie’s Disease After Diagnosis And Management Of Prostate Cancer: A Population Analysis |
Sexual Function/Dysfunction: Peyronie's Disease I | 17BOS |
Abstract: PD31-04 Sources of Funding: PB was supported by The Frederick J. and Theresa Dow Wallace Fund of the New York Community Trust. Introduction The incidence of Peyronie&[prime]s disease (PD) after treatment of prostate cancer (PCa) has been estimated to be as high as 16% in the three years after radical prostatectomy (RP). Despite its high prevalence in the post-RP, PD-screened population, the prevalence amongst all PCa patients is unknown. We hypothesized that PD incidence is generally under-diagnosed in men with PCa and that incidence rates vary based on PCa treatment. Methods We analyzed subjects contained within the Truven Health MarketScan claims database from 2007-2014. This US database provides information of insurance claims filed for the care of privately-insured individuals with employment-based insurance through a participating employer. Men with PCa were identified and stratified based on their treatment modality: RP, radiation (XRT), chemotherapy and RP (C-RP), chemotherapy alone (C) or no treatment (N). Men were followed both from entry in the cohort as well as from diagnosis of PCa after prostate biopsy. The cohort of men was followed longitudinally and assessed for subsequent new diagnoses of PD occurring at least one day after PCa treatment. Both PD incidence and timing of PD onset were analyzed and compared between the five PCa treatment modalities. Results 140,595 men with PCa were identified, of which 60,749 (43%) underwent RP, 31,499 (22%) XRT, 7,216 (5%) C-RP, 18,083 (13%) C, and 37,658 (27%) N. Average age and follow-up were 58 years and 3.5 years, respectively. Overall, new-onset PD was identified in 912 men (0.65%). The incidence of PD was highest in the RP and C-RP groups when compared to the XRT, C and N groups (Table). The onset of PD appeared to be quicker in RP patients compared to XRT, though the difference was not statistically significant. Among younger men (<60y) who may have better erectile function, be more sexually active, and therefore be more sensitive to detecting penile deformities, PD occurred quicker in RP vs XRT patients (1.4 vs 2.0 years) Conclusions These PD incidence figures are dramatically lower than other published data, suggesting there is an under-appreciation of PD as a sequela of PCa treatment amongst patients and practitioners. PD appears to occur more commonly and rapidly after RP compared to XRT. Given that early treatment may alter the course of PD, additional research is warranted to understand these findings. Funding PB was supported by The Frederick J. and Theresa Dow Wallace Fund of the New York Community Trust.
Authors
Phil V. Bach
Shufeng Li John P. Mulhall Michael L. Eisenberg |
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PD31-05 |
The Depression and Relationship impact in Peyronie's Disease Study (DRIPD): Baseline Population Characteristics and Predictors |
Sexual Function/Dysfunction: Peyronie's Disease I | 17BOS |
Abstract: PD31-05 Sources of Funding: none Introduction There is a growing body of literature focusing on the impact PD on men's mental health and relationships. Aim: to assess the impact of PD on men's psychological and relationship health. Methods Patients were administered 3 validated questionnaires at presentation: the Self-Esteem and Relationship (SEAR) questionnaire includes 5 components, scores standardized by transforming onto a scale of 0-100, higher scores being more favorable; the Center for Epidemiologic Studies Depression Scale (CES-D), with moderate and severe depressive symptoms were defined as >14 and >21, respectively; the Peyronie's Disease Questionnaire (PDQ) 3 domains, psychological & physical symptoms, pain, symptom bother. Multivariable analysis (MVA) was used to explore predictors of baseline scores. Factors entered into the model included: age, sexual orientation, degree of curvature; duration of PD at presentation, the presence of non-curvature deformity, patient reported loss of length, stretched flaccid penile length, pain, penile instability, and ability to penetrate._x000D_ _x000D_ Results Data from 204 men have been analyzed. Mean age = 56±12 years. Median PD duration = 9 months, mean curvature = 39±21 degrees, ED in 39%. 82% of patients were partnered with mean relationship duration=20 years. The mean penile length was 11 cms. 25% of the sample met the CES-D cut-off for depression: 13% moderate, 12% severe. Mean SEAR scores: total 54±24; sexual relationship 44±28 ; confidence 68±24; self esteem 68±25; overall relationship 70±30. These scores are similar to SEAR scores reported by men with moderate to severe ED. Mean PDQ scores: psychological & physical 11±6; pain 5±6; bother 7±4. Theses trends are similar to PDQ scores reported in the phase 3 Xiaflex studies (IMPRESS I & II). On MVA, higher CES-D scores were related to the inability to penetrate (β=0.18, p=0.04). Lower SEAR total scores were related to inability to penetrate (β=-0.30 p=0.01) and greater curvature (β=-0.25, p=0.04). Higher PDQ Bother scores were related to greater curvature (β=0.33, p=0.02), and marginally related to perceived loss of penile length (β=0.24, p=0.06) and inability to penetrate (β=0.22 p=0.09). Conclusions The data reinforce the significant prevalence of depression as well as psychosexual and relationship health in degree to men with ED. Common predictors of psychological and relationship variables were inability to penetrate, greater curvature, and perceived loss of penile length. Quality of life questionnaires into clinical practice might benefit some patients. Funding none
Authors
Jean-Etienne Terrier
Lawrence C Jenkins Christian J Nelson John P Mulhall |
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PD31-06 |
The Safety and Efficacy of Collagenase Clostridium Histolyticum in Combination With Vacuum Therapy for the Treatment of Peyronie’s Disease |
Sexual Function/Dysfunction: Peyronie's Disease I | 17BOS |
Abstract: PD31-06 Sources of Funding: Funding support provided by Endo Pharmaceuticals Inc. Introduction To evaluate collagenase clostridium histolyticum (CCH) injection with vacuum therapy for treatment of Peyronie's disease (PD). Methods In this open-label study, patients with PD were stratified by penile curvature degree and randomized 1:1 to CCH plus vacuum therapy with or without modeling. Each treatment cycle consisted of 2 CCH injections (0.58 mg, separated by 24-72 hours) and twice-daily vacuum therapy (initiated ~2 weeks after second CCH injection in a given cycle). Modeling was performed 24-72 hours after last CCH injection of each treatment cycle. Patients who did not achieve penile curvature less than 15 degrees by ~6 weeks after previous cycle received up to 4 cycles. Penile curvature and the Peyronie's Disease Questionnaire (PDQ) were assessed. Results Each group included 15 patients. Penile contusion (86.7% and 100.0% in the CCH plus vacuum plus modeling and the CCH plus vacuum group, respectively), penile swelling (73.3% and 100.0%), and penile pain (53.3% and 33.3%) were the most frequent adverse events. All were mild, local, and transient. No incidences of corporal rupture or penile fracture were reported. Penile curvature at baseline was similar between treatment groups (mean [SD], 59.0 degrees [15.0] and 58.3 degrees [12.2] for the CCH plus vacuum plus modeling and CCH plus vacuum only group, respectively). At week 36, mean improvement in penile curvature was similar in both groups (mean change [SD]; CCH plus vacuum plus modeling, 23.7 degrees [10.9] or 39.3% [13.2%]; CCH plus vacuum only, 23.3 degrees [7.2] or 41.1% [11.5%]; difference, 0.3 degrees [95% CI: -7.3, 6.6] and 1.8% [95% CI: -7.5%, 11.0%]). Mean (SD) improvement in the PDQ bother score at week 36 was similar in the CCH plus vacuum plus modeling (2.4 [2.5]) and the CCH plus vacuum only (3.8 [3.0]) groups (difference, 1.4 [95% CI: -0.9, 3.8]). Results were similar for other secondary efficacy endpoints. Conclusions CCH plus vacuum therapy with and without modeling improved penile curvature in patients with PD with report of mild local adverse events. Funding Funding support provided by Endo Pharmaceuticals Inc.
Authors
David Ralph
Amr Abdel Raheem Genzhou Liu |
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PD31-07 |
Concurrent Penile Traction Therapy In Men Undergoing Collagenase Clostridium Histolyticum for Peyronie’s Disease |
Sexual Function/Dysfunction: Peyronie's Disease I | 17BOS |
Abstract: PD31-07 Sources of Funding: None Introduction The impact of penile traction therapy (PTT) in conjunction with Collagenase clostridium histolyticum (CCH) has not been reported. Here we sought to evaluate outcomes in patients performing PTT concurrently with CCH. Methods A prospective database was maintained for all patients treated with CCH between March 2014 and July 2016. All patients were instructed to perform PTT with the Andropenis® (Andromedical America-Asia; New York) for a minimum of three hours daily. Patient-reported PTT use was collected with each injection series. Final curve assessments were performed after completing the therapy. We retrospectively reviewed data on all patients who completed CCH, and statistical analysis was performed to evaluate outcomes based on use, frequency, and duration of PTT. Results 51 patients who completed CCH had complete data available. Mean (SD) baseline curve was 660 (25.0), and mean (SD) improvement post-CCH was 210 (17) degrees (p<0.0001). 35 (69%) men reported PTT use for a mean (SD) 10 (6) hours per week. No significant difference in curve improvement was identified based on utilization of PTT (200 with PTT versus 240 without, p=0.30). Similarly, there was no difference based on frequency or duration of PTT (Figure 1, p=0.60). No associations were identified between PTT and functional outcomes including intercourse restoration and surgery prevention were identified. SPL increased non-significantly by a mean (SD) of +0.4 (2) cm in the PTT group, compared with -0.3 (2) in the non-PTT group (p=0.21). Importantly, PTT use declined in both frequency and duration with subsequent injection series. Conclusions PTT utilization with the Andropenis® declined in both frequency and duration with subsequent injection series. There was no significant difference in curve improvement with a mean 10 hours of weekly concurrent PTT. While not statistically significant, there was a trend towards increased SPL with PTT. The current series represents a “true to life” experience, wherein utilization patterns, attrition, and compliance issues are relevant factors impacting efficacy. Funding None
Authors
Matthew Ziegelmann
Boyd Viers Brian Montgomery Joshua Savage Landon Trost |
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PD31-08 |
Successful Treatment of Residual Curvature in Peyronie’s Disease in Men Previously Treated with Intralesional Clostridium Collagenase Histolyticum |
Sexual Function/Dysfunction: Peyronie's Disease I | 17BOS |
Abstract: PD31-08 Sources of Funding: None Introduction Intralesional clostridium collagenase histolyticum (CCH) injection into the Peyronie&[prime]s plaque is a treatment option for men with dorsal and dorsolateral curve with no hourglass deformity. The success and feasibility of surgically correcting residual curvature after intralesional CCH remains poorly characterized. Methods We performed a retrospective analysis of patients who had intralesional CCH treatment for Peyronie&[prime]s disease (PD) who subsequently underwent penile plication (PP), plaque incision and grafting (PIG), or inflatable penile prosthesis (IPP) placement as part of their treatment for residual curvature. Results Nine men who underwent PP, PIG, or IPP for the treatment of residual curvature after intralesional CCH were identified (Table). Six patients underwent PP, one patient underwent PIG and two patients underwent IPP with ancillary straightening maneuvers. The mean time (in days) from the last CCH injection to surgical correction was 128.9. The mean pre-CCH curvature was 69.4 degrees and the mean post-CCH curvature was 52.78 degrees. Seven out of nine patients had no residual curvature after surgical treatment. Increased fibrosis with increased surgical difficulty was noted in three out of nine patients. No post-operative complications were noted. Conclusions The surgical treatment of PD after intralesional CCH is safe and effective in men who desire correction of residual curvature. There may be increased technical difficulty in some patients. Funding None
Authors
Kenneth DeLay
Javier Ramirez Hoang MT Nyguyen Faysal Yafi Wayne Hellstrom |
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PD31-09 |
Penile prosthesis implantation (PPI) plus corporeal reconstruction with collagen-fleece grafting in the treatment of Peyronie's disease (PD) with or without ED |
Sexual Function/Dysfunction: Peyronie's Disease I | 17BOS |
Abstract: PD31-09 Sources of Funding: None Introduction The most successful treatment option of Peyronie's disease remains surgical, despite also being the most invasive. There are described several techniques for the correction of penile curvature, being technically demanding those in which grafts are used. We present our initial experience and preliminary results of partial plaque incision and grafting with self-adhesive film containing collagen combined with PPI (inflatable or malleable) in the treatment of Peyronie's disease. Methods Between January 2015 and August 2016 we operated 14 patients using this technique, six by implantation of a malleable prosthesis and the other eight with inflatable. Five of them kept proper erectile function and three had significant shortening of the penis without curvature. Four of them had been previously operated: one inflatable prosthesis + modeling; and other with sequelae after simple plication. The mean presurgical PDQ PD bother score was 9.7(8-12). Surgery was performed in the case of malleable through a single incision (with penile degloving) while IPP was performed either by 2 incisions (scrotal + penile degloving) or through a single incision (Kulkarni approach). Curvature correction was made by partial plaque incision with an H modified technique in the area of maximum curvature (or corporeal relaxing incisions) and placing a patch without suturing, covering prosthethic material. Results The mean operative time was 69 (55-85) min. The mean postsurgical penile lengthening was 4.5 (3-6) cm. There was an improvement in PDQ PD bother score of 4.5(2-5) points. No patients had hematoma, glans isquemia or any infectious complications. All patients showed good capability of penetration and correction of the penile curvature (<10 grades of residual curvature in the seven patients) 3 months after surgery. Six patients had glans hypoestesia at this time, while after the first three months, only 3 of them remains symptomatic. The overall satisfaction rate was of 90%. Conclusions In our experience, plaque incision and collagen fleece grafting during penile prosthesis implantation seems to be a safe and reproducible technique that yelds higher satisfaction rates and greater penile lengthening than prosthesis implantation alone. Also this technique could be consider in the management of sequalae after PD surgery. Funding None
Authors
Claudio Martínez Ballesteros
Juan Ignacio Martínez-Salamanca Eugenio Cerezo Agustín Fraile Esaú Fernández Pascual Luis Del Portillo Joaquín Carballido |
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PD31-10 |
Hydroxyapatite in Peyronie’s Plaques |
Sexual Function/Dysfunction: Peyronie's Disease I | 17BOS |
Abstract: PD31-10 Sources of Funding: None Introduction About a third of Peyronie&[prime]s Disease (PD) patients have evidence of tunica albuginea mineralization at presentation on B-mode ultrasound. The nature of both small and large mineral deposits in PD plaques was characterized by Energy Dispersive X-ray Spectroscopy (EDS) and micro CT. Methods Tissue specimens were collected from PD patients after surgery with patients&[prime] consent and institutional approval and stored frozen. X-rays were used to identify post-surgical specimens with mineralization. The soft tissues in PD plaques with mineral foci were digested with 0.2% pronase for 2h followed by 0.025% bacterial collagenase P overnight at 37 oC. Mineral foci resistant to enzyme digestion were gold coated and analysed by EDS using a JEOL JSM electron microscope. Other PD plaques were fixed with ethanol and phosphotungstic acid (PTA) and imaged by micro CT. Results Mineral foci in PD plaques were resistant to enzyme digestions by the general protease pronase and subsequent digestion by bacterial collagenase. When the mineral content of the enzyme resistant foci were analysed by EDS they showed a Ca/P ratio of 1.80 +/- 0.09. The Ca/P ratios were very similar for both large and small foci. For comparison rabbit tibial bone treated in a similar manner had Ca/P ratio of 1.76 +/- 0.09. The location of the mineral within the collagenous plaques was imaged using micro CT with PTA as a contrast agent to stain the collagen fibers. Micro CT images of the mineralized plaques showed mineral deposition at the interface between collagenous layers with different degrees of PTA stain contrast. Conclusions Mineral foci in PD plaques were enzyme resistant. The high Ca/P ratio (1.80) of mineral deposits in PD plaques were indicative of mature hydroxyapatite (Ca/P 1.67) found in bone. This high ratio was similar in both small and large mineral foci in the PD enzyme resistant tissues. The location of the mineral deposits and adjacent unmineralized collagenous matrix could readily be visualized by micro CT when PTA was used to stain the collagen fibers. Funding None
Authors
Thomas Schmid
Robin Pourzal Joseph Temple Laurence Levine |
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PD31-11 |
The Origins of Calcified Peyronie's Plaque |
Sexual Function/Dysfunction: Peyronie's Disease I | 17BOS |
Abstract: PD31-11 Sources of Funding: R01 DK10509701 (TL); R21 DK109912 (SPH, MLS); R01 DE022032 (SPH) Introduction Calcified Peyronie's plaque (CPP) is thought to be mineralized type I collagen of the tunica albuginea (TA) and within the corpus cavernosum (CC). The mechanistic link transforming a fibrous and vascularized to a mineralized tissue and subsequently impairing function at an organ-level is poorly understood. It is hypothesized that origins of CPP lay at the interface between the circumferential TA and CC, in that the residing pericytes around small diameter vessels produce osteogenic markers, prompting calcification at the CC-TA interface. _x000D_ Methods Twelve human CPPs were surgically excised, fixed, dehydrated and scanned using a high resolution X-ray computed tomography (micro-CT) at 4X and 10X magnifications (4.5µm and 1.8µm voxel size respectively) and further analyzed with AVIZO for mineral density, porosity and structure. Tissues were processed and stained histologically, and imaged using an Olympus BX51 microscope. _x000D_ Results CPP contained pores (A) with a diameter range of 10-18µm (A, C), see figure. Micro-CT data demonstrated an interface with a lower mineral density of 765 ±172mg/cc between layers 1 and 2 (A in figure) compared to the average mineral density of 1049 ±142mg/cc. Interfacial zone between TA and CC contained tubules of diameter 18±3.5µm with mineralized lumen walls (A). Histological analyses of seemingly non-calcified regions adjacent to CPP, contained similar diameter tubules patent with erythrocytes (region 1 in B in figure), and were within a disorganized extracellular matrix (ECM) positive for increased expression of elastin (bottom row, elastin) within regions positive for alizarin red (bottom row, AR: mineral). These patterns were consistently observed at the interface between TA and CC regions. _x000D_ Conclusions The branch-like structure of 10-18µm pores is similar to that of the venous structure at the interface between the TA and CC, suggesting that cells within and around the small diameter vessel could play a role in biomineralization, likely following an insult on the outer layers of the TA. Increased expression of elastin alters ECM stiffness within the outer TA prompting a change in smooth muscle stiffness of the CC, and collectively over time can receive signals from the interface to accelerate biomineralization along the length of the penis._x000D_ Funding R01 DK10509701 (TL); R21 DK109912 (SPH, MLS); R01 DE022032 (SPH)
Authors
Matthew Hennefarth
Ling Chen Misun Kang Ryan Hsi Amanda Reed-Maldonado Guiting Lin Marshall Stoller Tom Lue Sunita Ho |
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PD31-12 |
Whole Exome Sequencing Identifies Genes and Pathways with Potential Involvement in Peyronie&[prime]s and Dupuytren&[prime]s Diseases |
Sexual Function/Dysfunction: Peyronie's Disease I | 17BOS |
Abstract: PD31-12 Sources of Funding: AWP is a K12 scholar supported by a Male Reproductive Health Research (MRHR) Career Development Physician-Scientist Award (Grant # HD073917-01) from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Program. This work is also supported in part by the Burnett Research Fund. Introduction Peyronie&[prime]s disease (PD) is inherited in a subset of men and has a co-prevalence of ≈20% in men with Dupuytren&[prime]s disease (DD), a related fibrotic diathesis. Recent forward-genetic screening for genetic factors with potential involvement in PD and DD identified several candidate genes involved in fibrosis and inflammation. Here, we examine nucleotide-level genetic alterations with potential involvement in pathogenesis of PD and DD in a father-son duo using whole-exome sequencing. Methods Whole-exome genomic data was generated at the RNA and Genomic Profiling Sequencing Core (https://www.bcm.edu/garp/), and mapped using BOWTIE2 to the human genome build UCSC hg19; single nucleotide variants (SNVs) were inferred using the GATK platform and annotated using the annovar software, and then filtered for novel, non-synonymous SNVs. Enriched pathways were determined using the Gene Set Enrichment (GSEA) method, and the gene set collection from the Molecular Signature Database (MSigDB). Results Whole-exome sequencing identified 95/117 unique SNVs in each sample, with 150 SNVs shared between the two samples. Further analysis identified 150 nonsynonymous SNVs shared between the samples. Pathway analysis revealed enrichment of genes in known PD and DD pathogenic pathways including collagen formation / extracellular matrix organization (COL1A2, CRTAP), regulation of cell proliferation (SPEG, QSOX1, FGR1OP, LRP5), and the inflammatory response (HLA-DRB5, KDM6B). Several pathways not previously implicated in PD and DD were identified, including chromosomal rearrangement (FGFR1OP, COL1A2, AUTS2, AFF1, SHANK3), EGF-like domain-containing genes (MUC3A, SNED1, CD93, FAT2, SSPO, LRP5, MUC4), and maintenance of gastrointestinal epithelium (MUC2, MUC6, MUC4). SNVs in disease-associated genes, including osteoporosis and Parkinson&[prime]s disease, as well as SNVs in genes involved in head and neck, genitourinary, gastrointestinal, neurologic, and lung malignancies, were also identified. Neither of the two family members have reported any of the listed conditions to date. Conclusions In addition to pathways that can affect fibrosis, men with a genetic predisposition to PD and DD exhibit genetic alterations in cellular functions and disease-related pathways, including malignancies. This is the first study to genetically link fibrotic diatheses to other health conditions, and future work should focus on confirming these relationships. Moreover, men with PD or DD may warrant additional follow-up after diagnosis and treatment of these conditions. Funding AWP is a K12 scholar supported by a Male Reproductive Health Research (MRHR) Career Development Physician-Scientist Award (Grant # HD073917-01) from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Program. This work is also supported in part by the Burnett Research Fund.
Authors
Alexander W. Pastuszak
Yofre Cabeza-Arvelaiz Suman Maity Larry I. Lipshultz Dolores J. Lamb Cristian Coarfa |
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PD32-01 |
IMPACT OF ACCOUNTABLE CARE ORGANIZATIONS ON PROSTATE SPECIFIC ANTIGEN (PSA) TESTING AND PROSTATE BIOPSY |
General & Epidemiological Trends & Socioeconomics: Value of Care: Cost and Outcomes Measures III | 17BOS |
Abstract: PD32-01 Sources of Funding: This work was supported by the American Cancer Society (RSG_x000D_ 12-323-01-CPHPS), the National Cancer Institute (R01 CA168691, R01_x000D_ CA174768, T32 CA180984) and the National Institute on Aging (R01_x000D_ AG048071). Introduction The USPSTF recommendations against PSA screening for prostate cancer have reduced screening and result in fewer diagnoses. Accountable Care Organizations (ACOs), which aim to improve population health and enhance financial stewardship, have the potential to accelerate the impact of such national recommendations. The extent to which ACOs translate such evidence into practice inevitably will determine their ability to improve value. In this context, we examined the effect of Medicare Shared Savings Program (MSSP) ACO participation on screening PSA tests and prostate biopsy. Methods We performed a retrospective cohort study using a 20% national Medicare sample to evaluate rates of PSA testing and prostate biopsy among men without prostate cancer between 2010 and 2014. Patients were aligned to ACOs based on MSSP alignment criteria. We measured secular trends over time and performed a difference-in-differences analysis to determine the causal effects of ACOs on rates of PSA testing and prostate biopsy by comparing outcomes in the post-implementation period to the pre-implementation period. Results Among 1.1 million eligible men without prostate cancer, 144,109 (13.7%) were aligned to an ACO. In the non-ACO group we noted a 14% decrease in the annual rate of PSA testing and a 10% decrease in the annual rate of prostate biopsy (both p < 0.001). As shown in the Figure, ACOs had no effect beyond the secular trend on the rate of PSA testing (difference-in-differences estimator p=0.11). However, ACOs accounted a slower decline in the rate of biopsies performed (difference-in-differences estimator p=0.043). Conclusions Screening PSA testing and prostate biopsy rates decreased significantly over our study period. The rate of PSA testing, the decision for which is largely under the control of primary care physicians, was not affected by ACO participation. Conversely, the rate of prostate biopsy, the decision for which is under the control of urologists, resulted in a slower decrease in biopsy performance among ACO aligned men. Better engagement of ACOs with specialists is necessary for these organizations to achieve their objective. Funding This work was supported by the American Cancer Society (RSG_x000D_ 12-323-01-CPHPS), the National Cancer Institute (R01 CA168691, R01_x000D_ CA174768, T32 CA180984) and the National Institute on Aging (R01_x000D_ AG048071).
Authors
Amy N. Luckenbaugh
Tudor Borza Samuel R. Kaufman Phyllis Yan Lindsey A. Herrel Ted A. Skolarus Edward Norton Florian R. Schroeck Bruce L. Jacobs David C. Miller Vahakn B. Shahinian Brent K. Hollenbeck |
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PD32-02 |
Understanding pre-enrollment first year costs of urological cancer care for hospitals that went on to participate in Medicare Accountable Care Organizations |
General & Epidemiological Trends & Socioeconomics: Value of Care: Cost and Outcomes Measures III | 17BOS |
Abstract: PD32-02 Sources of Funding: This project was supported by the National Cancer Institute (5-T32-CA-180984-03 to Deborah R. Kaye and 1-R01-CA-174768-01-A1 to David C. Miller) Introduction Accountable care organizations (ACOs) are a new delivery model that many believe will enhance care coordination and quality, while lowering costs, in patients with complex diagnoses like cancer. However, understanding the degree to which ACO participation improves outcomes depends on the performance of participants before they became ACOs. In this context, we measured and compared the total first year costs (i.e, initial phase) of urological cancer care among hospitals that did or did not enroll in the Medicare Shared Savings Program (MSSP) ACO. Methods Using linked SEER-Medicare claims, we identified patients >65 years who were diagnosed with prostate, bladder, or kidney cancer from 2008 through 2012. The initial phase of cancer care was defined by the 12 months after diagnosis for patients living > 12 months. Costs of cancer care were calculated by aggregating hospital, physician and post-acute care claims. We first attributed patients to the hospital at which they received the majority of their initial cancer care. Hospitals were then flagged as ACO or non-ACO hospitals (based on current hospital participation) using the MSSP ACO Provider File. Finally, we compared total and component costs during the initial phase of cancer care according to ACO participation status. Results We identified 64,879 patients with prostate cancer, 19,554 patients with bladder and 9,484 patients with kidney cancer. The proportion of patients receiving care at a hospital that subsequently enrolled in the ACO program was 4%, 5%, and 5% for prostate, bladder, and kidney cancer, respectively. Prior to the initiation of the ACO program, patients attributed to current ACO hospitals had lower aggregate first year costs for prostate (p<0.001) and kidney cancer (p<0.001), but not bladder cancer (p=0.938). Differences in inpatient spending were +$305, +$1,245, and -$1,535 for prostate, bladder and kidney cancer, respectively (Figure). Conclusions Prior to formal participation, patients treated at hospitals now enrolled in the MSSP ACO program had lower costs for the first 12 months after diagnosis for prostate and kidney cancer, but not bladder cancer. Evaluations of the impact of ACO participation on costs of urologic cancer care may therefore be most fruitful among patients with bladder cancer. Funding This project was supported by the National Cancer Institute (5-T32-CA-180984-03 to Deborah R. Kaye and 1-R01-CA-174768-01-A1 to David C. Miller)
Authors
Deborah R. Kaye
Hye Sung Min Chad Ellimootil Zaojun Ye Jonathan Li Lindsey A. Herrel James M. Dupree David C. Miller |
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PD32-03 |
Impact of Medicare Shared Savings Program Accountable Care Organizations on Prostate Cancer Treatment |
General & Epidemiological Trends & Socioeconomics: Value of Care: Cost and Outcomes Measures III | 17BOS |
Abstract: PD32-03 Sources of Funding: This work was supported by the American Cancer Society (RSG 12-323-01-CPHPS), the National Cancer Institute (R01 CA168691, R01 CA174768, T32 CA180984) and the National Institute on Aging (R01 AG048071). Introduction Prostate cancer is the most common and among the most costly cancer in US men. Uncertainties regarding optimal management lead to treatment variations and increase cost. Accountable care organizations (ACO) can potentially improve care by decreasing variation (i.e. avoidance of treatment in low value settings) and constraining costs. Our objective was to determine the effect of Medicare Shared Savings Program (MSSP) ACOs on prostate cancer care. Methods Using a 20% Medicare sample we perform a retrospective cohort study of men with newly diagnosed prostate cancer from 2010-2013. We assigned patients to ACOs based on their primary care provider's MSSP ACO participation. We then performed a difference-in-differences analysis comparing the impact of ACO participation on initial prostate cancer curative treatment, treatment of men with a very high 10-year non-cancer mortality risk (i.e. those least likely to benefit) and per beneficiary payments. Outcomes in the post-implementation period were compared to outcomes in the pre-implementation. Results We identified 33,461 men with incident prostate cancer of which 5,015 (15%) were assigned to an ACO. Overall, 58% of men were diagnosed in the pre-ACO implementation period. We noted secular trends in the non-ACO group from pre- to post-implementation in overall curative treatment (4.2% decline, p<0.001), treatment of men with the highest non-cancer mortality risk (6.2% increase, p=0.11) and annual per beneficiary payments 4.0% decrease (p<0.001). ACO participation had no significant effect beyond the secular trend (Figure) on overall treatment or annual payments (difference-in-differences estimator p=0.8, p=0.09, respectively). There was a significant relative decrease in treatment among men with the highest mortality risk of 17% (p=0.03), however did this not lead to differences in cost. Conclusions Curative treatment of prostate cancer and annual per beneficiary payments decreased significantly between 2010 and 2013. For men diagnosed with prostate cancer, ACO participation did not impact trends in treatment or cost. However, among men least likely to benefit, ACOs resulted in a decline in treatment of prostate cancer. Funding This work was supported by the American Cancer Society (RSG 12-323-01-CPHPS), the National Cancer Institute (R01 CA168691, R01 CA174768, T32 CA180984) and the National Institute on Aging (R01 AG048071).
Authors
Tudor Borza
Samuel R. Kaufman Phyllis Yan Lindsey Herrel Amy N. Luckebaugh David C. Miller Ted A. Skolarus Bruce L. Jacobs Edward Norton Vahakn B. Shahinian Brent K. Hollenbeck |
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PD32-04 |
Surgeon Engagement in Early Accountable Care Organizations |
General & Epidemiological Trends & Socioeconomics: Value of Care: Cost and Outcomes Measures III | 17BOS |
Abstract: PD32-04 Sources of Funding: American Cancer Society (MSRG-15-103-01-CHPHS to MJR), AUA/Urology Care Foundation Rising Stars in Urology Research Program Introduction Despite marked growth in Accountable Care Organizations (ACOs), little is known about either the magnitude of surgeon engagement or key drivers of surgeon engagement in early ACO programs. We aimed to characterize the landscape of surgeon engagement in early ACOs and identify specialty-, organization-, and market-factors associated with early ACO participation. Methods Using data from SK&A, a commercial research firm, we evaluated independent, group, and integrated U.S. surgical practices, performing a cross-sectional analysis of 2015 ACO enrollment among 125,425 U.S. surgeons. We fit a multivariable logistic regression model to evaluate associations between ACO affiliation, surgical specialty, and organizational structure while adjusting for surgeon characteristics. Results Of 125,425 U.S. surgeons, 27,956 (22.3%) reported enrollment in at least 1 ACO program in 2015. We identified significant heterogeneity in the proportion of ACO-enrolled surgeons by surgical specialty, with trauma and transplant reporting the highest magnitude of ACO enrollment, (36% for both) and plastic surgeons reported the lowest magnitude of ACO enrollment (12.9%) followed by ophthalmology (16.0%) and hand (18.6%). 22.8% of urologists reported at least 1 ACO contract. Practice organization was strongly associated with ACO enrollment, with surgeons in group practices and integrated health systems had higher odds of ACO affiliation relative to those practicing independently (aOR 1.57, 95% CI 1.50, 1.64; aOR 4.87, 95% CI 4.68, 5.07, respectively). We observed a statistically significant interaction (p<0.001) between surgical specialty and practice organization. Model-derived predicted probabilities revealed that, within each specialty, surgeons in an integrated health system had the highest predicted probabilities of ACO affiliation while those practicing in groups had smaller predicted probabilities and those practicing independently generally had the lowest. This pattern was largely consistent across surgical specialties. Conclusions We observed considerable variation in ACO enrollment among U.S. surgeons. Observed variation appears to be largely mediated by differences in practice organization, with surgeons practicing in integrated health systems more likely to engage in ACO contracts than those in independent practice. Funding American Cancer Society (MSRG-15-103-01-CHPHS to MJR), AUA/Urology Care Foundation Rising Stars in Urology Research Program
Authors
Matthew Resnick
Amy Graves Melinda Buntin Michael Richards David Penson |
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PD32-05 |
Prostate Cancer Screening: Effect of Early Medicaid Expansion |
General & Epidemiological Trends & Socioeconomics: Value of Care: Cost and Outcomes Measures III | 17BOS |
Abstract: PD32-05 Sources of Funding: None Introduction The Affordable Care Act of 2010 transformed medical insurance and healthcare access for Americans. A significant component of the ACA, was expansion of Medicaid eligibility for low income individuals. Five states (CA, CT, MN, NJ, WA) & DC expanded Medicaid eligibility prior to the ACA mandate. The effect that improved coverage had on the prevalence of prostate specific antigen (PSA) screening is unknown. Methods We compared the rate of self-reported PSA as a function of state Medicaid early expansion (MEE) vs. non-expansion (NE). Data from the 2012 and 2014 Behavioral Risk Factor Surveillance System was used to identify asymptomatic men (aged 40-64) without prostate cancer who reported PSA testing in the past 12 months. Age, race, income, education, insurance, marital status, smoking, access to healthcare provider (HCP), and HCP&[prime]s recommendation to have PSA test were extracted. Income categories were stratified by relationship to federal poverty level (FPL): <138% FPL; 138-400% FPL; >400% FPL. Multivariate logistic regression models were used to evaluate the odds of and rate of change in PSA screening among MEE and NE states. Results Among 158,103 survey respondents, the prevalence of PSA screening decreased between 2012 and 2014 (OR 0.87, p<0.001), rates were similar in MEE and NE states (OR 1.02, p=0.8). The decrease was smallest in low-income populations <138% FPL than in higher income populations (OR 0.92, p=0.27; OR 0.88, p=0.002; and OR 0.85, p<0.001 respectively). Men <138% FPL were more likely to undergo PSA screening if living in a MEE than NE state (OR 1.6, p=0.04). In this population of men <138% FPL in MEE states, there was an increase in PSA screening (Figure 1), especially if they were Hispanic or Non-Hispanic black (NHB) males (OR 1.53 and 1.62 respectively, both p<0.001). Though access to HCP and insurance status were lowest among those <138% FPL, these variables did not significantly affect the prevalence of PSA screening. Conclusions Regardless of income or expansion of access, self-reported PSA screening declined between 2011 and 2013. This may be in part due to the 2012 United States Preventive Services Task Force recommendation against PSA-based screening. However, Medicaid expansion decreased the disparity between PSA baseline screening rates for low-income populations, particularly among Hispanic and NHB males. Funding None
Authors
Jesse Sammon
Emily Serrel Patrick Karabon Gregory Mills Mani Menon Firas Abdollah Quoc-Dien Trinh |
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PD32-06 |
The State of Urologic Malpractice: An Analysis of Recent Claims Data and Trends |
General & Epidemiological Trends & Socioeconomics: Value of Care: Cost and Outcomes Measures III | 17BOS |
Abstract: PD32-06 Sources of Funding: None Introduction The climate of medical professional liability continues to evolve. Given the resulting impact on practicing urologists, we provide data on urologic malpractice claims, associated costs, and recent trends. Methods We analyzed urological provider level medical malpractice claim data from the Physician Insurers Association of America (PIAA). Available data from 2010-2014 were compared to 2005-2009 to investigate recent trends. Monetary data has been adjusted for inflation and is reported in 2014 dollars. Results From 2010-2014, 1216 total claims were filed with 27% resulting in an indemnity payment. In comparison to data from 2005-2009, number of total claims increased by 5.5% (1153 claims from 2005-2009), average indemnity payment increased by 1.8% to $360,606, and the average defense expenses increased by 13.3% to $44,339. From 2010-2014, the average indemnity paid for closed urologic claims was 4.1% higher than the combined average for all other 28 medical specialties in the analysis; however, the average defense expenses for closed urologic claims were 13.6% lower. The majority of urological claims were dropped, withdrawn, or dismissed (65.4%), while other common outcomes included settlement (24.3%), a defendant verdict (6.6%), claim settlement via dispute resolution process or contract agreement (2.0%), and plaintiff verdict (0.7%). The most frequent occurrence resulting in a claim was improper performance of a procedure (42%). Calculus of the kidney and ureter (127/1216 claims) was the most prevalent presenting medical condition resulting in a claim followed by malignant neoplasms of the prostate (120 claims) and hyperplasia of the prostate (59 claims). The most common procedures leading to closed claims were operative procedures on the prostate and seminal vesicles (132/1216 claims), operative procedures on the kidney (118 claims), and diagnostic procedures of the bladder (100 claims). Temporary injury was the most frequently claimed patient outcome (308 claims, average indemnity $274,790), while the highest average indemnity paid was for major permanent injury ($676,870). Conclusions Urologic claims, indemnity payments and defense expenses continue to increase; however, the majority of claims do not result in indemnity payments. An understanding of claim trends and errors may assist urologists when evaluating risk management strategies and may contribute to improving patient outcomes. Funding None
Authors
M. Ryan Farrell
Christopher Coogan |
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PD32-07 |
Evidence in Support of Using a Singular Score to Characterize a Surgeon&[prime]s Operative Spending Behavior |
General & Epidemiological Trends & Socioeconomics: Value of Care: Cost and Outcomes Measures III | 17BOS |
Abstract: PD32-07 Sources of Funding: UCSF Teaching to Choose Wisely Grant, 2015-2016 Introduction Cost-control initiatives targeting physicians are currently underway to improve cost-efficient clinical care. Little is known regarding surgeon-specific cost choices. We sought to characterize surgeon periorperative spending to evaluate the accuracy of a singular score summarizing surgeon cost-efficiency. Methods All surgeons operating at UCSF Medical Center from July 2012-October 2015 across all specialties were included. Mean OR cost was calculated combining surgical supplies and time in the OR ($/minute). Cases were included if ≥ 4 surgeons performed said operation and all included surgeons completed ≥ 20 operations. Z-scores, defined as [(cost of surgeon&[prime]s case) - (median cost for said case across all surgeons)] / [standard deviation (SD) of all surgeons&[prime] costs for said case], were calculated for each surgeon and surgical case performed. Estimated mean z-scores were then calculated using mixed effects modeling. Surgeons&[prime] z-score variability was evaluated using calculated SDs. Results 257 surgeons across 17 surgical subspecialties were included in the analysis. The mean raw z-score was -0.12 ranging from -1.85 to 3.4 with SD of 0.78. The estimated z-score variability across the surgeons ranged from -0.5 to 0.5 SDs from the average estimated z-score (Figure 1). When comparing surgical subspecialties, the variability of z-scores ranged from 0.06 to -0.07. In individual subspecialties, the variability (SD) ranged from 0.25 to 0.02. Conclusions The z-score variability across all surgeons was small, supporting consistent surgeon-spending behavior across diverse cases. This supports using a surgeon&[prime]s estimated mean z-score as a singular and accurate metric characterizing surgeons&[prime] cost behavior. Funding UCSF Teaching to Choose Wisely Grant, 2015-2016
Authors
Matthew Truesdale
Christy Boscardin Thomas Chi |
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PD32-08 |
CAUSES, TIMING, AND HOSPITAL COSTS OF INDEX VS. NON-INDEX HOSPITAL READMISSIONS FOLLOWING RADICAL PROSTATECTOMY: IMPLICATIONS FOR COST CONTAINMENT STRATEGIES |
General & Epidemiological Trends & Socioeconomics: Value of Care: Cost and Outcomes Measures III | 17BOS |
Abstract: PD32-08 Sources of Funding: none Introduction Recent policy efforts have focused on bundling payments across multiple providers for acute inpatient hospitalization and 90 days after hospital discharge. Given the volume and financial impact, radical prostatectomy (RP) will likely be targeted as episode-based payment policies expand. To date, there are no studies investigating non-index readmissions (hospital that did not perform the surgery) during 90-day RP episodes. Our objective was to compare the causes, outcomes, and hospital costs of patients with index vs. non-index readmissions following RP to better understand the impact of non-index readmissions in the 90-day RP episode. Methods The 2013 Nationwide Readmissions Database was queried for prostate cancer patients undergoing RP. Sociodemographic characteristics, hospital costs, and causes of readmission were compared among index and non-index readmitted patients. Multivariable logistic regression models used to identify predictors of index, non-index, and subsequent readmission, prolonged length of stay (pLOS) upon readmission, and high-cost readmission. Results While 5.4%(2154/39892) of patients were readmitted, their care accounted for 10.4% of perioperative (90 day) hospital costs. Compared to index readmissions (n=1505), non-index readmissions (n=649) were more likely from high-volume RP centers (OR=2.18, 95%CI[1.06-4.50]). Non-index readmissions had higher average readmission costs ($11,903 vs. $9,447, p=0.02) and increased odds of high-cost readmission (OR=1.78, 95%CI[1.22-2.60]), but comparable odds of pLOS (OR=1.39, 95%CI[0.94-2.01]), subsequent readmission (OR=1.56, 95%CI[0.92-2.63]) and in-hospital mortality rates (0% vs. 0.2%, p=0.4). Among gastrointestinal complication patients, non-index readmissions had higher rates of laparotomy/laparoscopy (17% vs. 2.9%, p=0.01). Conclusions This nationally representative study of RP patients demonstrates non-index readmissions are associated with comparable outcomes but higher hospital costs than index readmissions likely associated with differences in the rate and/or type of operative management. The benefits of undergoing RP at high-volume centers should be carefully balanced with the increased odds of non-index readmissions and higher costs associated with them. As payers, providers, and patients continue to look for cost containment strategies and bundle the 90-day post hospitalization period, non-index readmissions are a potential target to decrease healthcare costs for RP patients. Funding none
Authors
Meera Chappidi
Max Kates C.J. Stimson Heather Chalfin Jeffrey Tosoian Misop Han Mohamad Allaf Ashley Ross H. Ballentine Carter Phillip Pierorazio Alan Partin Trinity Bivalacqua |
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PD32-09 |
Downstream Procedures following the Use of Bone Scan in the Staging of Muscle-invasive Bladder Cancer |
General & Epidemiological Trends & Socioeconomics: Value of Care: Cost and Outcomes Measures III | 17BOS |
Abstract: PD32-09 Sources of Funding: Robert M. Turner II, MD was supported in part by the National Institutes of Health Institutional TL1 award (5TL1TR000145-10)._x000D_ _x000D_ Bruce L. Jacobs, MD is supported in part by the National Institutes of Health Institutional KL2 award (KL2TR000146-08), the GEMSTAR award (R03AG048091), the Jahnigen Career Development Award, and the Tippins Foundation Scholar Award._x000D_ Introduction A bone scan may be considered prior to radical cystectomy to exclude bone metastases in high-risk patients. However, false positive bone scans can occur due to tracer uptake in benign bone lesions with reactive osteoblastic change, resulting in the need for additional procedures such as x-ray, computed tomography (CT), magnetic resonance imaging (MRI), and bone biopsy to further evaluate bone scan findings. The current burden of these downstream procedures is unknown. We aim to quantify the use of downstream procedures following staging bone scans in patients with muscle-invasive bladder cancer. Methods Using Surveillance, Epidemiology, and End Results (SEER)- Medicare data, we identified 4404 patients diagnosed with muscle-invasive bladder cancer from 2004-2011. We further identified those who underwent a bone scan prior to treatment within 6 months of diagnosis. Using outpatient and carrier claims files, we determined the proportion of patients who underwent a subsequent x-ray, CT, MRI, and/or bone biopsy within 3 months of the bone scan and prior to treatment. Results Among patients diagnosed with muscle-invasive bladder cancer during the study period, 1373 (31%) were identified as having completed a staging bone scan. Overall, 231 patients (17%) received downstream bone-specific x-rays, 340 patients (25%) received bone-specific CTs, and 103 patients (8%) received bone-specific MRIs. The use of bone biopsy was rare (n = 17; 1%). Conclusions Use of bone scan in the staging of muscle-invasive bladder cancer often results in the need for additional downstream imaging. The cost burden of this downstream imaging highlights a potential disadvantage of the routine use of this staging modality. Funding Robert M. Turner II, MD was supported in part by the National Institutes of Health Institutional TL1 award (5TL1TR000145-10)._x000D_ _x000D_ Bruce L. Jacobs, MD is supported in part by the National Institutes of Health Institutional KL2 award (KL2TR000146-08), the GEMSTAR award (R03AG048091), the Jahnigen Career Development Award, and the Tippins Foundation Scholar Award._x000D_
Authors
Robert Turner II
Jonathan Yabes Benjamin Davies Dwight Heron Bruce Jacobs |
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PD32-10 |
Data feedback affords modest effect in driving physician behavior toward value-based care for BPH surgery |
General & Epidemiological Trends & Socioeconomics: Value of Care: Cost and Outcomes Measures III | 17BOS |
Abstract: PD32-10 Sources of Funding: AUA Data Grant and Urology Care Foundation Research Scholar Award Program Introduction For provider organizations transitioning to value-based care models, physician engagement and support in testing new models is critical. Little is known about how to optimally engage physicians in these activities, which simultaneously target cost and quality of care. To test whether individualized physician feedback would improve adherence to a value-based care pathway, we gave quarterly surgeon-specific feedback on outcomes, practice patterns, and cost data. We hypothesized that value-based care pathway (VBCP) adherence would modestly increase. Methods We studied men undergoing surgery for uncomplicated BPH at our institution between March 1, 2013 and December 17, 2015. In April 2014, we defined and introduced a value-based care pathway (VBCP) for BPH to surgeons in our department. Physicians confidentially received their outcomes, cost, and practice pattern data compared to de-identified colleague data in a quarterly email from the Department leadership. Rates of pathway adherence were measured pre- and post-intervention. We used t-tests for physician-level evaluation using the physician as the unit of analysis. A multilevel logistic regression model was fit for patient-level analyses using random intercepts for the physician. Results There were 225 patients with complete data available representing 18 treating urologists. Two value-based pathways were used for analysis. The AUA recommended pathway requires PSA testing when indicated, urinalysis, and post-void residual (PVR) measurement, but is silent on surgery type or preoperative invasive testing. The VBCP requires in addition that cystoscopy or urodynamics are not performed preoperatively and bipolar transurethral resection/vaporization is the operation of choice. In the physician-level analysis, AUA recommended compliance increased from 1.8% to 9.2% (p=0.02) while increasing from 3.5% to 11.8% (p=0.03) in the patient-level analysis. VBCP compliance increased from 0% to 5% in physician-level (p=0.002) and patient-level (p=0.03) analyses. Conclusions Surgeon-specific data feedback, in isolation, very modestly drove physician behavior toward value-based care models for BPH surgery. VBCP adherence remained low throughout the study period. Further studies are needed to better understand whether physician-identified reporting of data or financial incentives might facilitate the transition to value-based care in urologic surgery. Funding AUA Data Grant and Urology Care Foundation Research Scholar Award Program
Authors
Alan L Kaplan
Vishnukamal Golla Catherine M. Crespi Jamal Nabhani Mark S. Litwin Christopher Saigal |
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PD32-11 |
Impact of pretreatment small renal mass biopsy on costs for patients considering surgery |
General & Epidemiological Trends & Socioeconomics: Value of Care: Cost and Outcomes Measures III | 17BOS |
Abstract: PD32-11 Sources of Funding: NIH T35DK062709-11 Introduction Approximately 15-20% of incidental renal masses ≤4cm are benign including oncocytomas and lipid poor angiomyolipomas (AML), which can be managed non-surgically. Increasing utilization of small renal mass biopsy (SRMB) may decrease upfront costs and preserving renal function in untreated patients. The objective of this study is to evaluate if increasing biopsy utilization reduces surgical treatment and upfront (30 day) costs for patients with small renal masses (SRM). Methods Clinical and pathologic data were reviewed from patients with incidental SRM who were treated surgically and/or received SRMB from 2003-2015. Patients not considering surgery were excluded. Patients were divided into 2 cohorts (2003-2009 and 2010-2015) for analysis based on increased SRMB utilization at our institution. 2015 Medicare costs were used to calculate comprehensive costs of surgery and biopsy for 30 days following surgery. Results Of 437 patients with renal masses ≤4cm, SRMB was performed in 6% of 199 patients treated from 2003-2009 and 54% of 238 patients from 2010-2015. The rate of surgery for benign tumors from 2003-2009 was higher than 2010-2015, 19.7% vs. 12.3%, p=0.04. _x000D_ _x000D_ In patients treated without biopsy from 2010-2015, benign surgery rate was 21.8%. From 2010-2015, 42 patients with benign tumors were identified using SRMB and avoided surgery (10 AML, 32 oncocytoma). _x000D_ _x000D_ Given the upfront cost of $2,020.44 USD for ultrasound guided biopsy and $12,153.01 USD for partial nephrectomy, cost of care per patient were calculated each two cohorts. _x000D_ _x000D_ The cost per patient in the 2003-2009 vs. 2010-2015 cohort was $12,274.85 USD vs. $11,094.98 USD. Increased biopsy utilization was associated with $1,179.86 (9.6%) cost savings per patient. For 2010-2015, increased use of biopsy saved $280,840 USD in estimated upfront treatment costs. _x000D_ Conclusions Pretreatment biopsy for renal masses ≤ 4cm reduces surgery for benign tumors and subsequently decreases the upfront cost of care per SRM patient by $1,179.86 USD. Funding NIH T35DK062709-11
Authors
Amy H. Lim
Maria Rozo Sara L Best Shane A Wells Meghan G Lubner Timothy J Ziemlewicz Fred T Lee Louis J Hinshaw Stephen Y. Nakada E. Jason Abel |
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PD32-12 |
Understanding the Effect of the Hospital Readmission Reduction Program on Surgical Readmissions |
General & Epidemiological Trends & Socioeconomics: Value of Care: Cost and Outcomes Measures III | 17BOS |
Abstract: PD32-12 Sources of Funding: This work was supported by the American Cancer Society (RSG 12-323-01-CPHPS), the National Cancer Institute (R01 CA168691, R01 CA174768, T32 CA180984) and the National Institute on Aging (R01 AG048071). Introduction Readmissions after surgery lead to poorer patient outcomes and increased costs. The Hospital Readmission Reduction Program (HRRP) was developed with the goal of reducing preventable readmission through penalties for hospitals with excess readmission rates for certain targeted conditions. We aim to evaluate the effect of this program on targeted and non-targeted surgical conditions. Methods We used a 20% Medicare sample to identify readmissions following targeted (total hip arthroplasty, total knee arthroplasty) and non-targeted (cystectomy, abdominal aortic aneurysm repair, colectomy, lung resection) procedures from 2006 to 2014. Multivariable logistic regression was used to calculate adjusted readmission rates. Changes in hospital level readmission rates were analyzed for three distinct time periods (Pre, Measurement, Penalty) corresponding to the HRRP implementation timeline, using an interrupted time series approach. Results We identified 538,293 targeted and 165,432 non-targeted procedures performed at 2,779 hospitals. There was a significant decrease in the odds of readmission for all procedures, except cystectomy (Table) which also had the highest readmission rate at 27%. Prior to the policy, the readmission rate for non-targeted procedures was decreasing faster than that of targeted procedures (Figure). However, this trend reversed during the Measurement period (difference in slope for targeted to non-targeted -0.10 [95% Confidence Interval -0.16 to -0.044]). Neither group had a significant change during the Penalty period. Conclusions While the HRRP effectively decreased readmissions for targeted surgery, there was no spillover benefit for non-targeted procedures. To decrease the burden of readmission after cystectomy, future efforts should focus on identifying the interventions that resulted in readmission reduction for targeted procedures and evaluating their effectiveness in this population. Funding This work was supported by the American Cancer Society (RSG 12-323-01-CPHPS), the National Cancer Institute (R01 CA168691, R01 CA174768, T32 CA180984) and the National Institute on Aging (R01 AG048071).
Authors
Tudor Borza
Mary K. Oerline Ted A. Skolarus Bruce L. Jacobs Amy N. Luckebaugh Matthew Lee Rita Jen Vahakn B. Shahinian Brent K. Hollenbeck |
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PD33-01 |
Non-canonical activation of Hedgehog signaling in prostate cancer cells mediated by the binding of transcriptionally active androgen receptors to Gli transcription factors |
Prostate Cancer: Basic Research & Pathophysiology I | 17BOS |
Abstract: PD33-01 Sources of Funding: Canadian Institutes of Health Research and the Terry Fox Research Institute Introduction Canonical (smoothened-driven) Hedgehog signaling regulates the activities of Gli transcription factors and their ability to induce cell proliferation, motility and invasion. While there are numerous reports of constitutive Hedgehog/Gli activity in prostate cancer (PCa) cells, there is little evidence for a role of smoothened in this activity. Previously we showed that Gli proteins bind to full length- (FL-) and truncated- (t-) androgen receptors (ARs) at the N-terminal tau5 transactivation domain and that this binding co-activates AR transcriptional activity in PCa cells. Here we show, conversely, that transcriptionally active AR binds to a critical protein processing domain on Gli2/Gli3, alters their post-translational proteolytic processing and drives non-canonical Hedgehog signaling that facilitates androgen-independent growth of PCa cells. Methods Site-specific mutations were introduced into the Gli2 C-terminal domain to identify the peptides involved in AR recognition. GST-pulldown was used to test binding of the mutated peptide to AR-tau5 peptide. Western blotting was used to quantify AR expression and the proteolytic states of Gli2 and 3 in LNCaP, LNCaP-AI, LN95 and VCaP cells. AR or Gli3 protein was knocked down with siRNAs. A Gli-luciferase reporter was used to measure functional Gli activity in cells and qPCR was used to determine how AR or Gli expression manipulation affected expressions of endogenous Gli-responsive genes. Proximity ligation assays with antibodies against AR and Gli3 was used to quantify the relative binding of these proteins in androgen-dependent and androgen-independent cell lines. Results Mutations in a repeat serine/arginine-rich peptide in the C-terminal domain of Gli2 (aa820-836) blocked Gli2 binding to AR. This peptide encompasses the Gli protein processing domain that regulates a site-specific proteolysis that renders transcriptionally active Gli proteins into transcriptional repressors. Binding of liganded AR to this site blocked Gli proteolysis and maintained Gli in transcriptionally active states. Knockdown of AR in androgen growth-independent cell lines induced proteolytic inactivation of Gli in PCa cells. Knockdown of Gli3 in these cells induced a loss of AR protein. Proximity ligation assays showed that binding between Gli3 and AR was higher in androgen-independent cell lines. Conclusions Transcriptionally active AR protein binding to Gli proteins protects both from a natural degradation process and provides a non-canonical means to activate Hedgehog signaling in PCa cells. Since Gli proteins regulate the expressions of growth-promoting genes, our findings suggest that the growth effects of androgens on PCa cells are the results of a non-canonical Hedgehog activation process. Funding Canadian Institutes of Health Research and the Terry Fox Research Institute
Authors
Na Li
Sarah Truong Mannan Nouri Amy Anne Lubik Ralph Buttyan |
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PD33-02 |
Prostate Cancer Aggressiveness is Mediated by Akt and NF-&[kappa]B Signaling Pathways: A Systems Biology Approach |
Prostate Cancer: Basic Research & Pathophysiology I | 17BOS |
Abstract: PD33-02 Sources of Funding: Department of Defense grant W81XWH-15-1-0558, USPHS R21CA193080, R03CA186179 and VA Merit Review 1I01BX002494 to SG. Introduction Prostate cancer remains the second leading cause of cancer-related deaths in American men. Often an indolent disease, patients remain asymptomatic for years. Easily treatable tumors and other, often fatal, highly aggressive forms are difficult to distinguish. Current prognosis and treatment stratification do not accurately predict clinical outcome. Hence there is an urgent need for improved markers to determine prognosis and appropriate treatments. We identified two key signaling pathways (PI3K-Akt and NF-&[kappa]B) whose constitutive activation correlates with prostate cancer progression. Using an integrated approach of quantitative experimentation and mathematical modeling, we seek to develop a multi-level, hierarchical, quantitative systems biology model - where the lower level captures the dynamic molecular processes of the signaling pathways and the higher level models the cancer phenotype. Methods p-Akt (Ser473) and NF-&[kappa]B/p65 protein expression was analyzed in benign and cancer specimens of various Gleason grades and their co-localization by immunohistochemistry. We also utilized androgen-responsive LNCaP cells (possessing increased Akt activity due to mutation in PTEN gene) and androgen-refractory PC-3 cells with constitutive activation of Akt and NF-&[kappa]B and their treatment with specific inhibitors. Western blotting was performed to determine the expression of native/active forms of Akt and NF-&[kappa]B and their effector proteins. Subsequent work include connecting the model of cell signaling to the physiologically &[Prime]higher&[Prime] levels using mechanistic details or statistical models. Results Compared to benign tissue, cancer specimens exhibited constitutive activation of p-Akt (Ser473) and NF-&[kappa]B/p65 which was more pronounced in high-grade cancer (Gleason grade 7-10). Immunohistochemical analyses further demonstrated co-localization of these proteins in a subset of aggressive cancer tissues. Individual treatment of cell lines with Akt Inhibitor VIII (0.075-1.8μM) and NF-&[kappa]B inhibitor Parthenolide (0.32-60μM) for 24-72 h demonstrated partial suppressive effect in cancer cell growth; whereas concurrent blocking of Akt and NF-&[kappa]B/p65 at 1:10μM ratio resulted in potentiated toxicity and inhibition of downstream effector proteins in both cell lines. The categorical behaviors were explored by extensive simulations conducted to explore possible parameterizations of the model and to define the range of potential responses. A differential equation based (mass action and Michaelis-Menten) mathematical model was constructed and structurally calibrated/validated using experimental data. The resulting behaviors were identified and categorized according to the severity of pathway activity. Model parameterization (numerical values of reaction rates and basal protein levels) was accomplished by adopting portions of the models estimating the remaining unknowns from available experimental data. Conclusions Our results suggest that Akt activation provides long-term cell survival by activating pathways that influence NF-&[kappa]B-dependent gene transcription, and hence plays a role in prostate cancer aggression. Funding Department of Defense grant W81XWH-15-1-0558, USPHS R21CA193080, R03CA186179 and VA Merit Review 1I01BX002494 to SG.
Authors
Eswar Shankar
Rajnee Kanwal Aditi Goel Xiaoping Yang Sanjeev Shukla Gregory MacLennan Pingfu Fu Jing Li Anant Madabhushi Sanjay Gupta |
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PD33-03 |
Pharmacologic Targeting of TGF-β mediated EMT in Prostate Cancer |
Prostate Cancer: Basic Research & Pathophysiology I | 17BOS |
Abstract: PD33-03 Sources of Funding: Urology Care Foundation Postdoctoral Research Scholarship (ZC), and the James F. Hardymon Endowment in Urologic Research. Introduction Dysregulation of transforming growth factor-β (TGF-β) and insulin-like growth factor (IGF) axis has been linked to reactive stroma dynamics in tumor microenvironment during prostate cancer progression. IGFBP3 induction is initiated by stroma remodeling and could represent a potential therapeutic target for prostate cancer treatment. A lead quinazoline-based Doxazosin® derivative, DZ-50, generated in our laboratory, inhibits prostate tumor growth and vascularity via inducing anoikis and disrupting focal adhesions. Molecular profiling revealed that process of epithelial-mesenchymal-transition (EMT) is also targeted by DZ-50. In this study, we investigated the effect of DZ-50 on EMT landscape, EMT to mesenchymal-epithelial-transition (MET) conversion, and migratory ability of prostate cancer cells within prostate tumor microenvironment. Methods Human prostate cancer cells LNCaP, LNCaP overexpressing TGF-β type II receptor (TβRII), and cancer associated fibroblasts (CAFs) derived from human prostate cancer specimens, were used. Antitumor effect of DZ-50 against prostate cancer epithelial cells and CAFs was evaluated using cell viability assays. Effect of the drug on EMT key regulators (including IGFBP3) was determined using RT-PCR and Western blot analysis. Drug-induced phenotypic conversions of EMT were evaluated by confocal microscopy. Impact of TGF-β from the stroma microenvironment or exogenous addition of the cytokine, on migration of prostate tumor cells, was assessed using Matrigel assays. Results DZ-50 induced cell death in prostate cancer epithelial cells and CAFs, in a concentration-dependent manner. DZ-50 downregulated IGFBP3 mRNA and protein expression and contributed to MET in LNCaP cells. DZ-50 decreased nuclear IGFBP3 expression with no effect on total protein and promoted MET in LNCaPTβRII cells. In addition, TGF-β reversed DZ-50-induced MET by upregulating IGFBP3 expression in LNCaPTβRII cells. Co-cultures of LNCaPTβRII with CAFs promoted prostate cancer cell migration via TGF-β, an effect that was inhibited by DZ-50. Conclusions Our results demonstrate that DZ-50 inhibits prostate cancer cell migration and invasion. DZ-50 caused reversal of EMT to MET by regulating IGFBP3 and potentially targeting the prostate stroma in tumor microenvironment. This evidence integrates new signaling mechanisms underlying the antitumor effect of DZ-50 and calls for pre-clinical studies to establish the therapeutic value of this compound in advanced metastatic prostate cancer. Funding Urology Care Foundation Postdoctoral Research Scholarship (ZC), and the James F. Hardymon Endowment in Urologic Research.
Authors
Zheng Cao
Shahriar Koochekpour Stephen Strup Natasha Kyprianou |
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PD33-04 |
Targeted next-generation sequencing analysis of primary prostate cancer identifies potential therapeutic targets |
Prostate Cancer: Basic Research & Pathophysiology I | 17BOS |
Abstract: PD33-04 Sources of Funding: The Urology Foundation Introduction Personalised medicine strategies are increasingly reliant on DNA sequencing to stratify patients. Here we demonstrate the feasibility of using a cancer hot spot panel using targeted next-generation sequencing (NGS). In particular we concentrated on recurrent somatic mutations in cell signalling pathways or processes that can be clinically actionable or targeted by emerging therapies. Methods Formalin-fixed paraffin embedded (FFPE) primary prostate cancer samples were obtained from the Welsh Cancer Bank. Targeted-NGS was performed using the Life Technologies Ion Torrent: Ion AmpliSeq Cancer Hotspot Panel v2 and the Ion Personal Genome Machine sequencer. The hotspot panel covers ~2800 COSMIC mutations of 50 oncogenes and tumour suppressor genes. Standard IHC techniques were also used concentrating on markers of the Wnt, PI3-Kinase (PI3K) and MAP-Kinase (MAPK) oncogenic signalling pathways. Results 61 primary prostate cancer samples were sequenced, 58 from radical retropubic prostatectomy (RRP) specimens and 3 from transurethral resection of prostate (TURP) sections, with a range of Gleason Scores (GS). _x000D_ _x000D_ 21/61 (34.4%) samples harboured a mutation in a cell cycle pathway gene such as TP53 or RB1 and 3/61 (4.9%) in a DNA repair gene such as ATM. 10/61 (16.5%) of samples harboured a mutation in a gene associated with the Wnt pathway such as APC or CTNNB1. 14/61 (23.0%) of samples analysed had a mutation in a gene commonly associated with the PI3K pathway such as PTEN or AKT1. 5/61 (8.2%) had a mutation in a gene associated with the MAPK pathway such as KRAS. _x000D_ _x000D_ IHC profiles were analysed on 317 prostate samples: 73 normal and 244 cancers. There was greater expression of markers associated with Wnt, PI3K and MAPK signalling pathways in prostate cancer samples when compared to normal samples. There was greater expression in high-risk GSs with some markers associated with biochemical recurrence following RRP. Furthermore, we were able to separate low- and high-risk GS samples based on molecular profiles using markers of the Wnt, PI3K and MAPK and principle components analysis._x000D_ Conclusions Targeted NGS and IHC can identify recurrent mutations and signalling pathway aberrations within primary prostate cancer samples, which have potential to be targeted and used in routine clinical practice. In addition, the molecular signatures of low- and high-risk are different and can be separated using a combination of markers and IHC. This finding could explain the marked difference in the behaviours of these tumours types. Funding The Urology Foundation
Authors
Matthew Jefferies
Adam Cox Alan Clarke Howard Kynaston |
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PD33-05 |
Targeted next generation sequencing to characterize magnetic resonance imaging visible and invisible prostate cancer: biological insights and therapeutic implications |
Prostate Cancer: Basic Research & Pathophysiology I | 17BOS |
Abstract: PD33-05 Sources of Funding: None Introduction While multiparametric magnetic resonance imaging (mpMRI) of the prostate has improved disease detection, up to 20% of patients with negative mpMRI harbor high grade prostate cancer (PCa). In this study, we sought to characterize and compare the molecular profiles of mpMRI visible and invisible PCa. Methods Patients who underwent mpMRI prior to radical prostatectomy were identified for this IRB-approved study. mpMRI for each patient was reviewed by a radiologist with expertise in prostate mpMRI and histopathology reviewed by a genitourinary pathologist. Whole-mount histopathology was co-registered with axial mpMRI images. DNA and RNA were co-isolated from all tumor foci pre-identified on formalin-fixed paraffin-embedded specimens. High depth, targeted DNA and RNA next generation sequencing was performed to characterize the molecular profile of each tumor focus using the Oncomine Comprehensive Panel (DNA sequencing) and a custom targeted RNAseq panel assessing PCa relevant genes. _x000D_ _x000D_ _x000D_ _x000D_ Results A total of 26 primary tumor foci from 10 patients were analyzed. The median number of PCa foci was 3. Of the 14 (54%) invisible lesions on mpMRI, 5 (36%) were Gleason 3+4=7 (Table 1). We detected high-confidence prioritized genetic mutations in 54% (14/26) of tumor foci, 43% (6/14) of which were in mpMRI-invisible lesions. Additionally, 64% (9/14) of lesions exhibiting prioritized mutations were Gleason 7. Notable point mutations were in APC, AR, ARID1B, ATM, ATRX, BRCA2, FAT1, MAP3K1, NF1, SPEN, SPOP, TP53, and a frameshift mutation was detected in SOX2. The expression profile of mpMRI visible and invisible lesions were similar (Figure 1)._x000D_ Conclusions We found no significant difference in the molecular profile of visible and invisible cancer foci on mpMRI. However, 36% of mpMRI invisible lesions exhibited biologically significant mutations. More work is needed to further characterize the molecular basis for mpMRI prostate cancer visibility. Funding None
Authors
Simpa Salami
Daniel Hovelson Aaron Udager Matthew Lee Nicole Curci Jeremy Kaplan Arvin George Matthew Davenport Scott Tomlins Ganesh Palapattu |
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PD33-06 |
MCAM supports the aggressive phenotype in human prostate cancer |
Prostate Cancer: Basic Research & Pathophysiology I | 17BOS |
Abstract: PD33-06 Sources of Funding: SNF Grant 310030_156933 Introduction Prostate Cancer (PCa) is the most common cancer in males and the second leading cause of death from cancer in men. When PCa progress from localized disease to castration resistance, the formation of incurable metastases, primarily in the bone, is almost inevitable. Therefore, understanding the factors that regulate homing and survival of metastatic cancer cells in the bone is important for the identification of new therapeutic targets. High MCAM expression has been detected in the stroma of lytic and blastic lesions in preclinical models of PCa bone metastasis. The objective of this study is to characterize the role of MCAM in the maintenance of the aggressive phenotype in human PCa. Methods We used shRNAs to knockdown the expression of MCAM in the lytic PC-3M-Pro4Luc2_dTomato and in the blastic C4-2B_dTomato PCa cell lines. We validated the knockdown at protein level and tested the effect with functional assays such as migration, proliferation. RT-qPCR was used to test MCAM knockdown on EMT markers. The effect of the knockdown on the maintenance of cancer stem/progenitor-like cells was measured by ALDEFLUOR. Results MCAM knockdown reduced proliferation in PC-3M-Pro4Luc2_dTomato PCa cells and resulted in increased E-Cadherin expression. Conversely, no effect on proliferation was measured on C4-2B_dTomato cells. It has been described that metastatic human PCa cells target the hematopoietic stem cell (HSC) niche in the bone marrow at the level of an &[raquo]endosteal/osteoblast&[laquo] niche and a &[raquo]vascular/perivascular&[laquo] niche. We set-up an in vitro model of &[raquo]osteoblast niche&[laquo] to study the behavior of prostate cancer cells upon co-culture with osteoblasts and to measure the resulting effects on cancer stem/progenitor-like markers. We found that MCAM is required for the osteoblast-mediated induction of ALDH activity on PCa cells and MCAM knockdown prevented the increase in the size of the ALDHhigh subpopulation in PC-3M-Pro4Luc2_dTomato, mediated by human osteoblasts. Additionally, MCAM knockdown in PCa cells co-culture with osteoblast, prevented the induction of MCAM expression by osteoblasts compared to non-targeted control. Finally, we showed that MCAM is significantly increased in the highly metastatic ALDHhigh cells and identified a new subset of ALDHhigh / MCAMhigh cells which could be depleted upon MCAM knockdown. Conclusions We detected a new subset of ALDHhigh/MCAMhigh cells and demonstrated that MCAM influences the maintenance of an aggressive-mesenchymal phenotype in human PCa. Therefore, MCAM represent an interesting target molecule to modulate the behavior of aggressive PCa cells. Funding SNF Grant 310030_156933
Authors
Eugenio Zoni
Letizia Astrologo Janine Melsen Irena Klima Joel Grosjean Gabri van der Pluijm Marco G. Cecchini Marianna Kruithof-de Julio George N. Thalmann |
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PD33-07 |
CCRL2 regulates prostate cancer organ specific metastasis through the interaction with CCR5 |
Prostate Cancer: Basic Research & Pathophysiology I | 17BOS |
Abstract: PD33-07 Sources of Funding: MOST103-2320-B-038-039-MY3, MOHW105-TDU-B-212-134001 Introduction To evaluate the expression level of chemokine receptors in response to chemokines released by reactive stroma, quantitative PCR to evaluate the mRNA level of chemokine receptors was performed. Methods To check the expression level of CCRL2, we performed qRT-PCR and western blot analysis. Cell tracking assays were performed to analyze its role in chemoattraction. Proximity ligation assays were conducted to analyze the co-localization of CCRL2 and CCR5. To analyze the role of CCRL2 in regulation of cancer cell metastasis, we conducted in vivo analysis. Stromal cell overexpressed CCL5 were inoculated in renal capsule, followed by intra-peritoneal injection of prostate cancer cell overexpressed CCRL2 to determine the organ specific metastasis. To analyze the population of cells expression CCRL2, cell sorting assays was conducted. Results We noticed the significant increasing of CCRL2 (86-fold) in androgen insensitive prostate cancer cells. Knockdown of CCRL2 declined 75% of migration activities induced by CCL5, suggests CCRL2 involve in CCL5 induce cancer migratory activities. IHC analysis of CCRL2 in paired prostate cancer patients was performed and revealed increasing of CCRL2 expression in malignant prostate cancer locus, whereas no CCRL2 can be detected in the benign region of same patient. Proximity ligation assays (PLAs) of benign, high grade tumor and tissues collected from patients less than 5-year survive demonstrated the PLA signals only in the lethal progression on patients. In vivo xenograft mice model studies demonstrated the organ specific cancer metastasis can be enhanced after overexpressed CCRL2 in cancer cells. Cell sorting assays indicated that CCRL2 only expressed in less than 10% population of prostate cancer cells. Molecular analysis of CCRL2 demonstrated that CCRL2 regulated EZH2 expression in prostate cancer cells. Conclusions Our studies indicated the increased expression of CCRL2 play a central role in cancer cell migration induced by chemokine CCL5. CCL5, secreted by bone stromal cells after interaction with dormancy cancer cell, may induce directional migration and invasion of circulating cancer cells. Clinical analyses demonstrated increased of CCRL2 in malignant prostate cancer. Inhibition of these homing mechanisms might significantly decreased cancer cell metastatic activities of AIPC patients. Funding MOST103-2320-B-038-039-MY3, MOHW105-TDU-B-212-134001
Authors
Chia-Ling Hsieh
Kuan-Chou Chen Shian-Ying Sung |
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PD33-08 |
Expression Profiles of ERG and SPINK1 in Latent, Incidental, and Metastatic Prostate Cancer |
Prostate Cancer: Basic Research & Pathophysiology I | 17BOS |
Abstract: PD33-08 Sources of Funding: none Introduction TMPRSS2:ERG fusion is the most frequent genetic event in prostate cancer (PC), resulting in ERG overexpression. In Western populations, approximately 50% of PCs express fusion products; however, our previous study showed that ERG expression was less frequent in a cohort of Japanese patients with localized PC (15/92, 16.3%). The association between ERG overexpression and the clinical behavior of PC is controversial. SPINK1 overexpression is noted in approximately 10% of patients with localized PC, mutually exclusive of ERG overexpression. Although the association of SPINK1 overexpression with an aggressive PC phenotype has been reported, its prognostic significance is unclear. PC is occasionally diagnosed at autopsy and during cystoprostatectomy for bladder cancer; most of these cases are thought to represent the latent phase of the tumor. Thus, assessment of ERG and SPINK1 expression in latent, incidental, and metastatic PC (the most aggressive form) may be useful in evaluating the association between ERG and SPINK1 expression and the biological aggressiveness of the tumor. Methods In total, 151 autopsies among institutional autopsy records from 2009 to 2015 and 84 cystoprostatectomy specimens were included. Each prostate gland was fixed and sliced into step sections. Ninety-eight prostate biopsy specimens from a cohort of patients who received an initial diagnosis of metastatic PC between 2003 and 2012 were investigated. ERG and SPINK1 expression was assessed by immunohistochemistry and the expression patterns were compared to clinicopathological parameters. Results PC was identified in 53/151 autopsies and 20/84 cystoprostatectomy specimens. ERG and SPINK1 expression patterns were not significantly different [4/73 (5.5%) and 5/73 (8.3%) in the latent/incidental PC cohort and 14/98 (14.3%) and 12/98 (12.2%) in the metastatic PC cohort, respectively]. SPINK1 was almost exclusively expressed in ERG-negative tumors, except in one case. In the metastatic PC cohort, ERG and SPINK1 expression patterns were not associated with age, prostate-specific antigen level, and the Gleason score. SPINK1 expression was significantly associated with a shorter time to castration-resistant PC (P=0.0151), although ERG expression was not associated with clinical outcomes. Conclusions ERG and SPINK1 expression was not significantly different between latent/incidental PC and metastatic PC. SPINK1 expression may be a predictor of a shorter response to androgen deprivation therapy in metastatic PC. Funding none
Authors
Takahiro Kimura
Hiroyuki Inaba Haruhisa koide Shun Sato Yasutoshi Yoshiyama Toshihiro Yamamoto Jun Miki Hiroyuki Takahashi Shin Egawa |
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PD33-09 |
Expression of Neuropilin 2 as prognostic factor in patients with prostate cancer |
Prostate Cancer: Basic Research & Pathophysiology I | 17BOS |
Abstract: PD33-09 Sources of Funding: none Introduction Neuropilin 2 (NRP2) as co-receptor for the VEGF-C-receptor has to been shown highly expressed and seems to be associated with worse outcome for survival in several tumour entities._x000D_ Here, we investigated the expression of NRP2 in prostate cancer and correlated it with the overall survival (OS) and cancer-specific survival (CSS) in patients with prostate cancer (PCa)._x000D_ Methods For the generation of a tissue microarray (TMA), prostate tissue specimens were used from 400 patients with localized PCa undergoing radical prostatectomy (RP) between 1996 and 2005. Follow-up data regarding OS and CSS were obtained. Patients were stratified according to prognostic high-risk factors in PCa: pT≥3, GS≥8, pN1. Diagnostic hematoxylin and eosin stained tissue sections from the RP specimen were reviewed and representative tumor areas were assigned. From these areas each six tumor cores and two tumor-free cores were selected per patient and mounted into a total of 14 paraffin blocks. The protein expression of VEGF-C and NRP2 was analyzed by immunohistochemistry. The intensity of membranous staining of VEGF-C and NRP2 was assessed in four categories (0-3). For statistics, the mean of the intensity values in all PCa tissues cores per patient was calculated and correlated with clinicopathological and survival parameters. The prognostic impact of expression of VEGF-C (≤ median vs. > median) and of NRP2 (signal vs. no signal) was assessed by Kaplan-Meier analyses for CSS and OS and by log-rank test. Uni- and multivariate Cox&[prime]s proportional hazard regression analyses were performed to assess the independent prognostic impact of NRP2 and VEGF-C. Results The median follow-up was 10a (0.34-17.6a). In patients with evidence of NRP2 expression, the mean CSS was 15.5a whereas in patients without expression of NRP2 the mean CSS was 16.1a (p=0.007). Especially patients with high-risk PCa and without evidence of NRP2 expression showed a significantly longer CSS than patients with NRP2 expression (pT2 vs. pT≥3: 15.5a vs. 12.3a; p=0.05; GS≤7 vs. GS≥8: 15.6a vs. 14.4a; p=0.024; pN0 vs. pN1: 15.4a vs. 13.3, p=0.018). In multivariate analysis, the NRP2 expression emerged as an independent predictor for the CSS in all patients (HR 2.36; 95%-CI 1.17-4.71; p=0.016) as well as in the subgroups. However, there was no significant association between the NRP2 expression and the OS. Furthermore, the VEGF-C expression was associated neither with OS nor with CSS. Conclusions The expression of NRP2 in PCa is significantly associated with a shorter CSS and might be an independent prognostic factor for the CSS especially in patients with high-risk PCa. Funding none
Authors
Angelika Borkowetz
Marieta Toma Michael Froehner Pia Hoenscheid Susanne Fuessel Kati Erdmann Kaustubh Datta Michael Muders Manfred Wirth |
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PD33-10 |
Preoperative Sex Hormones Profiles and Pathological Features of Localized Prostate Cancer are related to both Total and Bioavailable Testosterone |
Prostate Cancer: Basic Research & Pathophysiology I | 17BOS |
Abstract: PD33-10 Sources of Funding: the Foch Foundation Introduction In localized prostate cancer (PCa), impact of biochemical hypogonadism on cancer emergence and progression is still controversial. We aim to compare preoperative sex hormones plasma profiles and pathological features in localized PCa patients according to gonadal status assessed by total (TT) and bioavailable (BT). Methods A new large prospective cohort study of 1125 (age 63.9, height 175 cm, weight 82,2 kg, BMI 26.8 30 kg/m2, waist circumference 101cm) localized PCa patients were recruited in 4 urological centre in France, from 6/2013-6/2016. Metabolic syndrome (MetS) parameters were collected. Assay of TT, BT, DHT, E1, and E2 were performed by GC-MS. A centralized cross- checked review of pathological data (Predominant Gleason pattern 4 (PrdGP4), stage) was done. Results The cohort has been divided in 4 groups; the 1st group consists of patients with T and BT in the normal range (? 3 ng/ml and BT ? 0,8 ng/ml), a low T in the 2nd, a low BT in the 3rd and both low T and BT in the 4th._x000D_ The percentages of PrdGP4 and pT?3a were one-third in the normal gonadal patients going statistically up to one half in the hypogonadal. A 10% weight increase, due to fat, occurred in the low T patients, while no change occurred in the low BT, indicating a dichotomy in the action of T and BT. _x000D_ A dramatic difference in SHBG concentration between low BT and low T concentrations was observed, conferring to SHBG a key role in selecting patients at a high risk of an aggressive PCa. In fact, when considering hypogonadal patients by a threshold of TT? 3 ng/ml only, we miss 90 patients (8%) that had low BT, because of a high SHBG, no Mets but, a high %PrdG4._x000D_ Conclusions Thus, a serum low BT delineate a population of aggressive PCa risk more than obesity. Consequently, for treatment decision-making, in addition to TT and obesity, BT should be assessed in the arsenal for the management of localized PCa. Funding the Foch Foundation
Authors
Henry Botto
Yann Neuzillet Marc Schneider Morgan Rouprêt Sarah Drouin Marc Galiano Xavier Cathelineau Vincent Molinié Camelia Radulescu Eva Comperat Frank Giton Jean Fiet Thierry Lebret Jean-Pierre Raynaud |
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PD33-11 |
Real-time monitoring of tumor progression and drug responses in a preclinical mouse model of prostate cancer |
Prostate Cancer: Basic Research & Pathophysiology I | 17BOS |
Abstract: PD33-11 Sources of Funding: This study was supported by scientific research grants from the Pearl River Nova Program of Guangzhou (No. 2013J2200044), the Project Supported by Guangdong Natural Science Foundation (No. 2015A030313291), and the Ministry of Education, Culture, Sports, Science and Technology of Japan (No. KAKENHI 25861425, 15K20093). Introduction Prostate cancer is a major cause of death in men around the world. Despite a variety of treatments, disease progression and metastases still occur in most cases. Given the promising effect of combination with immunotherapy for prostate cancer, the construction of an immunocompetent mouse model for simultaneous monitoring of tumor volume, tumor biomarker and immune cell functions, would be useful for further understanding the mechanism of tumor progression and immune regulation. Methods Through genetic engineering techniques, a new cell line, RM9-Luc-pIRES-KLK3 was constructed. The cells were inoculated into immunocompetent mice of strain C57BL/6 via dorsal flank, dorsolateral prostate and tail vein to obtained subcutaneous model, orthotopic model and metastasis model, respectively. Tumor volumes, non-invasive imaging and prostate-specific antigen (PSA) were evaluated. In the metastasis models, either anti-CTLA-4 antibody or PBS was administered to the tumor bearing mice, and the status of circulating immune cells was assessed by flow cytometry. Results The new cell line, RM9-Luc-pIRES-KLK3 was successfully constructed and steadily expressed PSA and Luc, which were confirmed by Western blotting and bioluminescence detection in vitro. The level of expression was positively correlated with cell counts. Three days after injection, RM9-Luc-pIRES-KLK3 cells grew readily in the mice and the tumors could be detected by IVIS imaging system from then on. Four days later, PET scan was conducted to confirm the lesions. The intensity of bioluminescence imaging in coronal section and FDG uptake in sagittal slices of PET imaging were totally overlay. Comparing with PBS treated mice; MDSCs and T regs in peripheral blood were significantly decreased in the tumor bearing mice treated with anti-CTLA-4. Meanwhile, the proportion of CD44+CD62? effector and memory T cells on CD3+CD8+ cells were significantly increased by >2–3 times after CTLA-4 blockade compared with the control treatment, as well as IFN? and TNF?. Conclusions The presented models were ideally suited for real-time tracking of drug response and imaging of tumor progression and immune function. In comparison with traditional methodologies, this biomarker/imaging-based approach could lead to improved, early, and sensitive assessment of tumor status. Funding This study was supported by scientific research grants from the Pearl River Nova Program of Guangzhou (No. 2013J2200044), the Project Supported by Guangdong Natural Science Foundation (No. 2015A030313291), and the Ministry of Education, Culture, Sports, Science and Technology of Japan (No. KAKENHI 25861425, 15K20093).
Authors
Peng Huang
Peng Xu xiezhao Li Naijin Xu Abai Xu Masami Watanabe Hiromi Kumon Chunxiao Liu Yasutomo Nasu |
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PD33-12 |
The role of fatty acid binding protein 4 in prostate stromal tumor microenvironment and prostate cancer progression |
Prostate Cancer: Basic Research & Pathophysiology I | 17BOS |
Abstract: PD33-12 Sources of Funding: none Introduction Fatty acid binding protein 4 (FABP4) is a small FA chaperone molecule. FABP4 is highly expressed in adipocytes and macrophages affect the metabolic process, but the function of FABP4 in cancer including prostate cancer (PCa) is unclear. In the present study, we investigated the expression pattern and role of FABP4 in PCa and prostate stromal cells (PrSC). Methods The expression of FABP4 in PCa, PrSC and the conditioned medium were determined by the Western blotting, Immunohistochemistry and ELISA. Cytokine levels in the conditioned medium and serum was measured by the Human cytokines array kit. The metastatic and invasive PCa model was established by intraperitoneum injection of PC-3 M Luc-C6 cells into male 6-week-old Balb/c nu/nu mice, and the functional role of FABP4 was investigated. Results FABP4 was highly expressed and secreted in the PCa PC-3 cells, and stimulated the PrSC to secretion of proinflammatory cytokine IL-8 and IL-6. PrSC augmented PCa cell?invasiveness by the secretion of IL-6 and IL-8 in response to secreted FABP4 by PCa cells. In addition, FABP4 directly stimulated the PCa cell invasiveness by the upregulation of MMPs by activation of AKT and ERK signal pathways. PrSC and HFD condition increased the PCa cell invasiveness by the upregulation FABP4, IL-8 and MMPs in vivo. FABP4 was highly expressed in human PCa. The serum FABP4 levels was significantly higher in the PCa patients than normal individual (p = 0.001), and the levels of FABP4 was associated with the Gleason Score (GS, p = 0.018), and advanced PCa pathological T stage (pT, p = 0.022). Conclusions FABP4 was overexpressed and secreted in the PCa, and directly stimulated the PCa progression. PrSC was activated, and augmented the PCa invasiveness by the secretion of IL-6 and IL-8 in response to secreted FABP4 by PCa cells in the prostate stromal tumor microenvironment. FABP4 may be a useful therapeutic target for prostate cancer. Funding none
Authors
Mingguo Huang
Atsushi Koizumi Takamitsu Inoue Shintaro Narita Tomonori Habuchi |
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PD34-01 |
Anastomotic Bulbar Urethroplasty: To Transect or Not To Transect? |
Trauma/Reconstruction/Diversion: Urethral Reconstruction (including Stricture, Diverticulum) III | 17BOS |
Abstract: PD34-01 Sources of Funding: None Introduction Anastomotic urethroplasty is an effective but occasionally controversial treatment for short bulbar urethral strictures. Non-transecting variations of anastomotic urethroplasty were created in part to address this controversy. The objective of this study is to assess current outcomes of anastomotic urethroplasty and compare outcomes of transecting and non-transecting techniques. Methods 171 patients with complete follow-up underwent anastomotic bulbar urethroplasty from September 2003 to May 2016. Patient age, stricture length, location, etiology, 90-day complications and semi-quantitative assessment of sexual dysfunction were recorded. The primary (objective) outcome was success defined as urethral patency >16Fr on routine follow-up cystoscopy. Secondary outcome measures included 90-day complications (Clavien ≥2) and de novo sexual dysfunction assessed at 6 months. Statistical comparison between transecting and non-transecting cohorts was made using Cox Regression Analysis and Chi-square when appropriate. Results One hundred and thirty patients underwent transecting anastomotic urethroplasty while 41 had a non-transecting anastomotic urethroplasty. Mean stricture length was 1.5±0.5cm (range 1-3) with a mean patient age of 43.0±18.0 years. 78.9% of patients failed prior endoscopic treatment (135/171) and 2.4% failed prior urethroplasty (4). Overall there was a 98.2% (168/171) success rate with a mean follow-up of 74.9(±46.7) months. 7.0% (12/171) of patients experienced a 90-day postoperative complication of Clavien ≥2 including 2.9% wound-related complications (5), 1.8% scrotal hematomas (3), 1.8% UTI (3), and 0.6% urethral bleeding (1). 9.9% reported an adverse change in sexual function including 6.4% erectile dysfunction (11), 1.8% ejaculatory dysfunction (3), 1.2% painful erection (2), and 0.6% chordee (1). When comparing transecting and non-transecting technique success using Cox Regression analysis there was no difference in urethroplasty success (97.7% vs. 100%; p=0.63) and no difference in postoperative complications (7.7% vs. 4.9%; p=0.73) but patients undergoing transecting anastomotic urethroplasty were more likely to report an adverse change in sexual function (13.1%; vs. 0%; p=0.013). Conclusions Anastomotic urethroplasty remains a highly effective treatment for short-segment bulbar urethral strictures with relatively minimal associated morbidity. Newer non-transecting anastomotic urethroplasty techniques appear to compare favorably in the short-term and may reduce the risk of associated sexual dysfunction. Funding None
Authors
Dave Chapman
Adam Kinnaird Jon Witten Keith Rourke |
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PD34-02 |
he long-term results of non-transecting bulbar urethroplasty |
Trauma/Reconstruction/Diversion: Urethral Reconstruction (including Stricture, Diverticulum) III | 17BOS |
Abstract: PD34-02 Sources of Funding: none Introduction The non-transecting approach to bulbar urethroplasty was popularised by Jordan et al and Andrich et al and is being used by an increasing number of surgeons. We reviewed our experience with this procedure. Methods Between January 2009 and December 2015, 125 men with a mean age of 42 (range 16-77) years have undergone a "non-transecting approach" to their bulbar urethral stricture. 112 patients had idiopathic strictures, 5 had iatrogenic strictures, 5 had urethral trauma, 5 were post-radical prostatectomy strictures and 3 were post-TURP strictures. In the same timeframe, 36 transecting anastomotic urethroplasties were performed for straddle injuries and 201 dorsal patch bulbar urethroplasty were performed for long urethral strictures. _x000D_ _x000D_ 58 patients had a non-transecting mucosal anastomotic repair, 48 patients had a non-transecting augmented urethroplasty using buccal graft and 19 underwent a Heineke-Mikulicz-type stricturoplasty alone. _x000D_ _x000D_ All patients underwent clinical assessment and flow rate studies and urethrograms prospectively. _x000D_ Results Clinically, 116 patients (92.8%) were happy with the result of their surgery, 2 were unhappy (but had normal flow rates) and there were 4 failures, who all underwent revisional surgery. 3 patients were lost to follow-up. The mean post-operative peak flow rate was 34.9mls per second, in 102 patients. 7 patients had flow rates of less than 15mls per second, including the 4 failures, 3 patients voided less than 100mls and where therefore not assessable and 13 patients refused a flow rate study or were lost to follow-up (n=3). On antegrade/retrograde urethrogram, 120 were normal, 1 had a slightly reduced calibre but had a normal flow rate, there were 4 recurrent strictures and 9 refused or were lost to follow-up (n=3). _x000D_ _x000D_ Overall 118 of 122 patients (96%) were a success clinically by radiology and flow rate study as well as subjectively. _x000D_ Conclusions The non-transecting approach to bulbar urethroplasty gives results that are at least as good as previously reported for excision and primary anastomosis or augmented anastomotic urethroplasty or dorsal patch urethroplasty. The increasingly widespread use of this procedure is therefore entirely justified. Funding none
Authors
Stacey Frost
Stella Ivaz Simon Bugeja Mariya Dragova Daniela E Andrich Anthony R Mundy |
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PD34-03 |
Post-TURP urethral strictures can be managed successfully with urethroplasty |
Trauma/Reconstruction/Diversion: Urethral Reconstruction (including Stricture, Diverticulum) III | 17BOS |
Abstract: PD34-03 Sources of Funding: None Introduction Urethral stricture disease is seen in 2-9% of patients after transurethral resection of the prostate (TURP) but data is limited as to treatment outcomes. Our purpose is to establish patterns of disease severity and treatment for post-TURP stricture among 7 high volume centers. Methods A retrospective database was created for patients who underwent management of post-TURP strictures at 7 reconstructive urology centers. Data consisted of demographics, TURP method, location/length of urethral strictures, interventions prior to urethroplasty, surgical technique used for urethroplasty, and outcomes. Exclusion criteria included age <18 and follow-up period <1 year. Success was defined as no need for intervention within the observation period. Data analysis was done from 7 institutions for a total of 130 patients. Results Mean age was 68 years (range 41-86). 77% of patients underwent monopolar TURP (n=100). Other modalities reported were: 10% bipolar TURP (n=13), 3% GreenLightTM laser (n=4), 3% holmium laser (n=4), 2% other lasers (n= 3) and 5% unknown modality (n=6). Urethral stricture locations were: 29% bulbar urethra (n=38), 17% membranous urethra (n=22), 11% penile urethra (n=15), 5% fossa navicularis urethra (n=6), and 38% multiple locations (n=49). The average intraoperative length of strictures was 4.4cm (range 1-23cm). Average number of endoscopic interventions prior to urethroplasty is 3.6 (range 0-36)._x000D_ _x000D_ Urethroplasty techniques were: anastomotic (33%, n=43), dorsal graft (39%, n=51), ventral graft (15%, n=19), flap (6%, n=8), perineal urethrostomy (2%, n=3). 5% of patients underwent advanced reconstructive techniques such as: double graft, augmented dorsal anastomotic, Duckett, or first stage Johanson (n=6). Overall success rate was 85% with an average time-to-failure of 23 months (range 2-151 months). Success rates for patients who had prior endoscopic intervention (urethrotomy or dilation) was 83% versus those with no prior endoscopic intervention who had a success rate of 100%, p> 0.05. Complications were reported in 17% of patients, including recurrent UTI, erectile dysfunction, urinary incontinence, and penile shortening. Conclusions Our study represents the first multi-institutional report on the severity and management of post-TURP urethral strictures. Our data shows that the majority of post-TURP strictures are successfully managed with urethroplasty, with 85% success. Better success rates are seen in patients with no prior endoscopic intervention, suggesting early urethroplasty or referral to a reconstructive urology center is warranted. Funding None
Authors
Omar E. Soto-Aviles
Mashrin L. Chowdhury Esther K. Liu Ibraheem Malkawi Maha Husainat William Du Comb Jonathan Warner Francisco Martins Christopher Gonzalez Justin Han Reynaldo Gomez Javier Angulo Nicolaas Lumen Dmitriy Nikolavsky Richard Santucci |
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PD34-04 |
One-Stage Urethroplasty Using Dorsal and Ventral Buccal Mucosal Graft: Long-Term Validated Outcomes |
Trauma/Reconstruction/Diversion: Urethral Reconstruction (including Stricture, Diverticulum) III | 17BOS |
Abstract: PD34-04 Sources of Funding: none Introduction We report the short and long term results and sexual side effects of dorsal-ventral buccal graft urethroplasty (dorsal approach) for the 1 stage repair of long obliterative/near-obliterative anterior urethral strictures. Methods We reviewed our prospectively maintained database. Only patients who underwent cystoscopy (4 months after surgery) and completed validated questionnaires in 2016 were included. Technical success was defined by a minimum urethral caliber of >16 French 4 months after surgery. Questionnaires included International Prostate Symptom Score (IPSS), Sexual Health Inventory for Men (SHIM), Male Sexual Health Questionnaire Ejaculatory Dysfunction Short Form (MSHQ-EjD-SF), and urethroplasty specific patient reported outcome measures (PROMs). A Wilcoxon signed-rank test was used to evaluate change in mean IPSS. Results We identified 26 patients, and 3 were excluded for lacking cystoscopy or questionnaire. Mean age at time of surgery was 54 years (19-77). Mean follow-up was 60 months (4-210). All patients had a history of prior urethral surgery or self-catheterization, 70% with multiple procedures. Ten patients (43%) had prior open urethral reconstruction, including 7 with tissue transfer. Single buccal mucosal graft was used in 30%, bilateral in 70%, and a third lower lip graft in 9%. The 4-month technical success rate was 87%. The success rates for those with and without prior open reconstruction were 90% and 85%, respectively. Two of the 3 failures (defined by urethral caliber slightly < 16 French) would be considered successfully repaired by less stringent criteria (providing a 95.6% success rate) as they required no additional procedures and were &[Prime]very satisfied&[Prime] with IPSS of 2 and 3. There was no significant change in mean IPSS from postoperative cystoscopy to last follow up (5.2 to 5.9, p=0.46). In 2016, the mean SHIM and MSHQ-EjD-SF scores were 14 and 8, respectively. Regarding patient satisfaction, 74% are very satisfied, 17% are satisfied, and 9% are unsatisfied. Conclusions The dorsal and ventral buccal graft repair via dorsal approach, a 1-stage non-transecting technique of circumferential substitution urethroplasty, is associated with a high patient satisfaction, and validated questionnaires demonstrate lasting results. Funding none
Authors
Kristi Hebert
Martin Hofmann Joel Gelman |
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PD34-05 |
Effect of Patient and Surgical Characteristics on Treatment Failure in 491 One-Stage Ventral Onlay Buccal Mucosal Graft Urethroplasties |
Trauma/Reconstruction/Diversion: Urethral Reconstruction (including Stricture, Diverticulum) III | 17BOS |
Abstract: PD34-05 Sources of Funding: None Introduction Multivariable assessment of independent predictors of treatment failure after ventral onlay buccal mucosal graft urethroplasty (VO-BMGU) is commonly limited by small samples sizes. Our aim was to generate a prediction model for treatment failure in a large and homogeneous contemporary population using easily available patient and surgical characteristics. Methods 491 men underwent one-stage VO-BMGU at our institution between 01/2009 and 12/2015. Treatment failure was defined as any postoperative instrumentation needed. First, we compared the distribution of patient (age, BMI) and surgical characteristics (previous treatments, site of stenosis, surgical volume, length of graft, and success of voiding trial 21 days post-surgery) between patients with treatment success und treatment failure. Secondly, we performed Cox regression analyses to identify independent predictors of treatment failure. In subgroup analyses, we identified predictors of treatment failure in 406 men undergoing VO-BMGU who had never received a urethroplasty before. Results At a median follow-up of 34.3 months (IQR 22.3-54.2 months), treatment success rates were 96.1% at three months, 92.3% at six months, 87.7% at 12 months, and 79.8% at 36 months. Overall, 98 (20%) patients suffered from treatment failure. In multivariable Cox regression analyses, age (HR=1.01; 95% CI=1.00-1.03; P=0.047), second (HR=1.02; 95% CI=1.02-2.82; P=0.043) and third tertile of length of graft (HR=1.74; 95% CI=1.03-2.94; P=0.038), as well as failure at voiding trial 21 days after surgery (HR=2.32; 95% CI=1.51-3.56; P<0.001) held true as significant independent predictors of treatment failure. In multivariable subgroup analyses, failure at voiding trial 21 days after surgery (HR=2.49; 95% CI=1.54-4.02), length of graft above the median (>4cm; HR=1.78; 95% CI=1.08-2.89), and penile stenosis (HR=2.00; 95% CI=1.17-3.43; all P≤0.022) were independent predictors of treatment failure. Previous treatment or surgical volume did not influence treatment failure significantly neither in main, nor in subgroup analyses (all P≥0.3)._x000D_ Conclusions In a large contemporary cohort of 491 patients undergoing VO-BMGU we found age, length of buccal mucosal graft, and delayed suprapubic catheter removal due to failure at voiding trial 21 days after surgery highly predictive of treatment failure. Our model may help in patient counseling during the postoperative setting regarding the stricture recurrence risk and function as basis for future clinically practicable risk calculators. Funding None
Authors
Malte W. Vetterlein
Clemens M. Rosenbaum Philipp Gild Christian P. Meyer Carla Loewe Tim A. Ludwig Felix K.-H. Chun Oliver Engel Roland Dahlem Margit Fisch Luis A. Kluth |
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PD34-06 |
Calculating the Risk of Urethral Stricture Recurrence After Anterior Urethroplasty |
Trauma/Reconstruction/Diversion: Urethral Reconstruction (including Stricture, Diverticulum) III | 17BOS |
Abstract: PD34-06 Sources of Funding: none Introduction A prediction model that accurately predicts risk of stricture recurrence after anterior urethroplasty is lacking. We hypothesized that such a model would be dependent on both patient and stricture characteristics and could predict recurrence with high sensitivity and specificity. Methods We created models based on clinical outcomes of consecutive men undergoing anterior urethroplasty by one of 6 surgeons in the Trauma and Urologic Reconstruction Network of Surgeons (TURNS) from 2010 to 2015. The outcome variable of interest was stricture recurrence, defined as the need for a secondary procedure. All available pre-operative and operative variables, including interaction variables when deemed appropriate, were initial candidates and the final model was chosen by stepwise selection. Receiver operating characteristic (ROC) curves were created and the area under the curve (AUC) was reviewed. Colinearity with stricture length and location variables dictated that separate models for standard excisional (EPA) and substitutional (flap and/or graft; SUB) repairs be created. Surgeon effects were accounted for through an exchangeable structure of the working correlation matrix. Results There were 547 EPA and 706 SUB repairs used for model creation, of which recurrence was noted in 20 (3.7%) and 67 (9.5%) respectively. AUC was marginally higher for the SUB model (0.7777) versus the EPA model (0.7601). Significant variables in the SUB model included number of prior DVIUs (OR 1.14; 95% CI 1.07-1.21), stricture etiologies of prior TURP (OR 3.77; 2.07-6.89), ureteroscopy (OR 4.07; 1.66-10.02), infection (OR 5.77; 2.57-12.05) and/or lichen sclerosus (OR 3.33; 1.06-10.42) and ventral (OR 3.53; 1.55-8.03) or sandwich (OR 3.70; 2.23-6.11) graft placement. Stricture length was not an independent predictor (OR 1.03; 0.99-1.07) and smoking was protective (OR 0.58; 0.36-0.95). In the EPA model, only stricture length (OR 1.31; 1.12-1.53) and pre-operative urine residual (OR 1.00; 1.00-1.00) were significant variables. Conclusions Traditional pre- and intraoperative variables used to create these prediction models led to AUCs well below 0.8, indicating only moderate clinical usefulness. The low recurrence rate affected robust EPA model creation, though longer EPA repairs were more likely to fail as predicted. The SUB model was heavily dependent on stricture etiology and location of graft placement. Improved collection of pathologic, morphologic and surgical characteristics appears necessary if improvement in the prediction capabilities of these models is desired. Funding none
Authors
Christopher Tam
Amy Hahn Jacob Oleson Sean Elliott Bryan Voelzke Benjamin Breyer Jeremy Myers Alex Vanni Bradley Erickson |
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PD34-07 |
COMPLICATIONS OF URETHRAL RECONSTRUCTION ARE MINIMAL COMPARED TO OTHER UROLOGICAL PROCEDURES |
Trauma/Reconstruction/Diversion: Urethral Reconstruction (including Stricture, Diverticulum) III | 17BOS |
Abstract: PD34-07 Sources of Funding: none Introduction Although urethroplasty for the treatment of urethral stricture disease provides excellent functional outcomes, the associated postoperative morbidity remains underreported. The purpose of this study was to report and classify postoperative complications utilizing the Clavien-Dindo classification system in comparison to those reported from a variety of other common urological surgical procedures. Methods A retrospective review of over 1000 urethroplasty cases by a single surgeon from 2007-2014 was performed. Complications <90 days after surgery were identified and grouped by Clavien-Dindo classification (minor Clavien 1-2, and major Clavien 3-5). Clinical characteristics and outcomes were compared between men with and without complications. Mutivariable logistic regression models assessed risk factors associated with postoperative complications. Results Of the 573 procedures reviewed, 121 complications occurred in 107 (18%) procedures within 90 days of urethroplasty. Complications included 70 (12%) minor (Clavien 1-2) and 37 (6%) major (Clavien 3-5) (Table 1). In comparison to other urologic procedures, the complication rate of urethroplasty was similar to other reconstructive procedures such as pyeloplasty. Treatment failure was more common in men who experienced a <90 day complication (39% vs 15%, p<0.0001). Per procedure, the most common complications included: urinary tract infection (N=21, 4%), wound complication (N=16 , 3%), acute urinary retention (N=13, 2%), refractory bladder spasms (N=13, 2%), and urine leak (N=11, 2%). Median time to complication was 26 days (IQR 17-40). Men experiencing a any <90 day complication were more likely to have a history of radiation (28% vs 18%, p=0.04), benign prostatic hyperplasia (BPH) (28% vs 18%, p=0.04), and undergo substitution urethroplasty relative to excision primary anastomosis and urethrostomy (23% vs 18% vs 6%, p=0.03). There was no difference in stricture length, location, prior endoscopic procedures, age, or other comorbidities. On multivariable analysis, substitution urethroplasty (OR 1.68, 95%CI 1.04-2.68; p=0.03) and BPH (OR 1.90, 95%CI 1.02-3.43; p=0.04) were associated with risk of any postoperative complication. Meanwhile, history of radiation therapy (OR 3.12, 95%CI 1.29-8.63; p=0.03) and BPH (OR 4.50, 95%CI 1.89-10.55; p=0.0009) were independently associated with risk of major complications. Conclusions Relative to other surgical procedures, urethroplasty has acceptable complication rates with a low incidence of major complications similar to that reported after pyeloplasty. Risk factors for complications include substitution urethroplasty and radiation. Funding none
Authors
Boyd Viers
Travis Pagliara Charles Rew Lauren Folgosa-Cooley Alexander Rozanski Christine Shiang Jeremy Scott Allen Morey |
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PD34-08 |
Real-world effectiveness outcomes for urethroplasty |
Trauma/Reconstruction/Diversion: Urethral Reconstruction (including Stricture, Diverticulum) III | 17BOS |
Abstract: PD34-08 Sources of Funding: None Introduction Urethral stricture disease is common condition with significant quality of life and economic implications. While endoscopic treatment with incision or dilation is the most common treatment approach, guidelines increasingly recommend urethroplasty based on its high success rates. Whether real world, community practice outcomes mirror those of large volume single center institutional series is unknown. For these reasons, we conducted a population-based study of patients treated with urethroplasty and their outcomes. Methods We identified male patients who underwent urethroplasty between 2001 and June 2015 based on ICD-9 codes and administrative claims from a large, national US health insurer (ClinformaticsTM Data Mart Database, OptumInsight, Eden Prairie, MN). We assessed utilization of endoscopic treatments (urethrotomy and dilation) prior to and after urethroplasty. We defined urethroplasty failure by any subsequent urethral dilation, urethrotomy, or urethroplasty after initial urethroplasty. We examined factors associated with failure using multivariable logistic regression and Cox proportional hazards models. Results We identified 1345 patients treated with urethroplasty. Urethroplasty failure occurred in 344 (26%) of patients. Repeat urethroplasty was performed in 139 (40%) of failures (range 2-8). Increased number of endoscopic treatments prior to first urethroplasty was associated with urethroplasty failure. The mean (±SD) time to failure was 270 ± 42 days. Conclusions Our population-based study demonstrated significantly lower success rates for urethroplasty than previously published reports. Strategies to achieve better outcomes for patients with urethral stricture disease include increasing referrals to reconstructive urologic surgeons, and knowledge and technique transfer to community urologists interested in providing this service rather than repeated, low-value endoscopic treatment. Funding None
Authors
Robert Goldfarb
Steven Brandes Peter Kirk Tudor Borza Yongmei Qin Ted Skolarus |
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PD34-09 |
The Utility of Uroflowmetry Parameters in Urethroplasty Surveillance is Limited |
Trauma/Reconstruction/Diversion: Urethral Reconstruction (including Stricture, Diverticulum) III | 17BOS |
Abstract: PD34-09 Sources of Funding: None Introduction Limited data supports the use of uroflowmetry parameters (Qmax:max flow; Qave: average flow; VV: voided volume) to assess for urethral patency and rule out stricture recurrence in post-urethroplasty surveillance._x000D_ Methods From years 2012-2015, data were collected on 125 patients who underwent anterior and posterior urethroplasties and had follow-up at 3 and 12 months with cystoscopy, International Prostate Symptom Score (I-PSS) and uroflowmetry parameters. The ability to pass a 17 French flexible cystoscope was defined as a successful repair. Analyzing the receiver operating characteristics we calculated the area under the curve (AUC) to compare uroflowmetry parameters and I-PSS against cystoscopy. Results There were 208 encounter visits within the first 12 months, of which there were 164 cystoscopy procedures. Success was determined in 147/164 (90%). Uroflowmetry parameters were provided in 105 patients and 103 subjects were not able to void or had a VV < 100 mL. I-PSS data was available for 136 patients. Qmax of ≥10 ml/sec has a high positive predictive (92%) value and our study confirmed a significant AUC of 0.75 (p=0.002). However, the NPV is limited and cystoscopy showed that half of these subjects with a low flow (<10 ml/sec) won't have a stricture. The AUC for Qmax ≥15 mL was 0.705 (p = 0.002) with a sensitivity of 92% and specificity of 34%. When comparing (Qmax-Qave) > 8 to cystoscopy, the AUC was 0.691 (p = 0.018) with a 93% sensitivity and 29% specificity. When assessing the AUC of I-PSS Weakness score of <3, the AUC was found to not be significant. No significance was found when completing a univariate analysis of I-PSS total score and quality of life score to cystoscopy. Conclusions Uroflowmetry parameters of Qmax >10 mL, Qmax >15 mL, Qmax-Qave > 8 mL are not specific enough to determine recurrences of urethral stricture. The I-PSS total score, weakness score or QOL are neither sensitive nor specific enough to detect recurrences._x000D_ Funding None
Authors
Yooni Yi
Paholo Barboglio Romo Bahaa Malaeb |
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PD34-10 |
Value of Early Surveillance Cystourethroscopy after Bulbar Urethroplasty on Recurrence Risk: A TURNS Study |
Trauma/Reconstruction/Diversion: Urethral Reconstruction (including Stricture, Diverticulum) III | 17BOS |
Abstract: PD34-10 Sources of Funding: None Introduction Surveillance protocols after bulbar urethroplasty vary. Flexible cystourethroscopy allows for direct visualization of the repair and is often used for surveillance. However, repeated cystourethroscopy following urethroplasty is costly and has significant patient burden. We evaluate the use of single cystourethroscopy performed in the early post-operative period and its ability to predict clinical success in men who underwent bulbar urethroplasty. Methods We identified patients from TURNS database from 1/1/2010-3/31/2016, who underwent urethroplasty for isolated bulbar strictures and received surveillance cystourethroscopy within 6 months of their procedure. We excluded patients with history of previous urethroplasty, lichen sclerosus, radiation, failed hypospadias repair, and any patients with clinical recurrence prior to surveillance cystourethroscopy. Our primary outcome was utility of cystourethroscopy findings (normal caliber, >17 French strictured rings, or inability to pass scope [<17 French strictured rings]) in predicting risk of clinical recurrence._x000D_ Results 844 patients were identified. Mean age and BMI was 43 years (SD:15.5) and 30.0 kg/m2 (SD:6.6), respectively. 41 (5%) patients had a history of diabetes. 42 (5%) patients were current smokers and 72 (9%) were former smokers. 648 (77%) had excision and primary anastomosis and 196 (23%) had substitution urethroplasty with buccal graft. Mean operative stricture length was 3.0 cm (SD:1.8). Median time to first post-operative cystourethroscopy was 3.6 months (IQR: 3.1, 4.0). On cystourethroscopy, 608 (72%) had normal findings, 134 (16%) had >17 French strictured rings, and 102 (12%) had <17 French strictured rings. A total of 32 (4%) patients required a secondary procedure at a median time of 2.05 (IQR: 0.1-10.8) months. Cumulative 1-year rate for secondary procedures for recurrence were 0.01 (95% CI: 0-0.03) for normal urethra on first cystourethroscopy, 0.06 (95% CI: 0-0.13) for >17 French strictured rings, and 0.27 (95% CI: 0.13-0.39) for <17 French strictured rings (Figure). Conclusions Repeated cystourethroscopy has limited use after bulbar urethroplasty in predicting clinical failure in patients with normal caliber urethra on single early surveillance cystourethroscopy. Funding None
Authors
Darshan Patel
Ragheed Al-Dulaimi Sean Elliott Alexander Vanni Bradley Erickson Bryan Voelzke Benjamin Breyer Christopher McClung Thomas Smith, III Angela Presson Jeremy Myers |
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PD34-11 |
Multi-institutional Outcomes of Endoscopic Management of Stricture Recurrence after Urethroplasty |
Trauma/Reconstruction/Diversion: Urethral Reconstruction (including Stricture, Diverticulum) III | 17BOS |
Abstract: PD34-11 Sources of Funding: None Introduction Approximately 10-20% of patients will have a recurrence after urethroplasty. Initial management of these recurrences is often with urethral dilation (UD) and direct vision internal urethrotomy (DVIU) but the success rates of these procedures are not well known. Methods We retrospectively reviewed bulbar urethroplasty data from 5 surgeons from the Trauma and Urologic Reconstruction Network of Surgeons (TURNS). Men who underwent UD or DVIU for a <17F lumen plus symptoms of recurrence were identified. Analyses compared success rates of recurrence management (UD vs. DVIU) and initial urethroplasty type (substitution vs. excisional repair, EPA) using time to event statistics: Kaplan Meier curves and Cox regression models. Failure of UD or DVIU was defined as the inability to pass a 17Fr cystoscope through the urethra into the bladder. Results There were 53 men with recurrence that were initially managed endoscopically, 10 with UD and 43 with DVIU. Mean time to recurrence after urethroplasty was 7.6 months. At a mean follow-up of 16.3 months after UD or DVIU, success was 41.5% in the overall cohort: 48.8% for DVIU vs. 10% for UD. Kaplan Meier curves are shown in Figure 1. On Cox modeling, UD had a higher rate of subsequent failure compared to DVIU (hazard ratio, HR: 3.15, p=0.03). Patients undergoing EPA had a trend towards higher rates of recurrence after secondary endoscopic procedures vs. those undergoing substitution urethroplasty (HR: 2.41, p=0.05) Conclusions DVIU is more successful than UD in the management of stricture recurrence after bulbar urethroplasty. DVIU appears to be more successful for patients with a recurrence after a substitution urethroplasty compared to after an EPA, perhaps indicating a different mechanism of recurrence for EPA (ischemic) versus substitution urethroplasty (technical) Funding None
Authors
Shyam Sukumar
Sean Elliott Jeremy Myers Bryan Voelzke Thomas Smith Alexandra Carolan Michael Maidaa Bradley Erickson |
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PD34-12 |
TERTIARY URETHROPLASTY: IS THE THIRD TIME A CHARM? |
Trauma/Reconstruction/Diversion: Urethral Reconstruction (including Stricture, Diverticulum) III | 17BOS |
Abstract: PD34-12 Sources of Funding: none Introduction While repeat urethroplasty following primary treatment failure is often successful, limited data exist describing outcomes among men requiring additional urethral surgeries. We aim to describe the characteristics and outcomes among men undergoing tertiary urethroplasty compared to primary and secondary repairs. Methods A retrospective review of over 1000 urethroplasty cases by a single surgeon from 2007-2014 was performed to identify men undergoing primary, secondary, and tertiary urethroplasty procedures. Tertiary urethroplasty was defined as urethral reconstruction following two or more previous urethroplasty failures. Clinical characteristics and outcomes were compared between groups. Mutivariable logistic regression models evaluated the association between number of previous urethral surgeries and treatment success. Results Among 573 urethroplasty cases having complete data available, 46 (8%) tertiary procedures were compared with 87 (15%) secondary and 440 (77%) primary procedures. Tertiary strictures were more often located in the penile urethra (50% vs 29% vs 17%, p<0.0001), and underwent substitution urethroplasty (61% vs 41% vs 23%, p<0.0001). Failure rates were higher for tertiary cases (37%) vs 20% and 13 % for secondary and primary procedures (p=0.0001) during follow up (mean 17 months). The estimated 24-month stricture recurrence-free survival was lower for tertiary cases (44% vs 75% vs 75%, p=0.07), but success rates of perineal urethrostomy (100%) and excision primary anastomosis (90%) were far greater than substitution urethroplasty (50%). Tertiary repairs were more likely to have a history of hypospadias (58% vs 20% vs 2%, p<0.001) and chronic kidney disease (17% vs 5% vs 9%, p=0.003). No difference was noted in age, medical comorbidities, nor frequency of <90 day complications. On multivariable analysis controlling for history of hypospadias, stricture location, and type of surgery, tertiary urethroplasty was associated with an increased risk of treatment failure relative to primary (OR 2.88, 95%CI 1.29-6.65; p=0.02) and secondary (OR 2.11, 95%CI 0.87-5.14; p=0.09) urethroplasty. Conclusions While tertiary urethroplasty is associated with an increased risk of treatment failure relative to primary and secondary urethroplasty, many patients can expect to experience durable resolution of obstructive voiding symptoms. Funding none
Authors
Travis Pagliara
Boyd Viers Charles Rew Lauren Folgosa-Cooley Alexander Rozanski Christine Shiang Jeremy Scott Allen Morey |
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PD35-01 |
A Randomized Double-Blind Controlled Study Assessing Electro-Acupuncture for the Management of Post-operative Pain after Percutaneous Nephrolithotomy |
Stone Disease: Surgical Therapy IV | 17BOS |
Abstract: PD35-01 Sources of Funding: None. Introduction Percutaneous nephrolithotomy (PCNL) is the gold standard procedure for large renal calculi, but post-operative pain remains a major concern. Modifications of the PCNL technique have been developed in part to decrease pain. More recently, acupuncture has been described as an adjunct to reduce pain following abdominal, spinal, and orthopedic surgeries. Among the benefits of acupuncture are its ease of performance, non-invasiveness, and lack of significant side effects. In comparison to traditional acupuncture, electro-acupuncture has shown enhanced efficacy, possibly due to central endorphin release. We sought to investigate the effects of electro-acupuncture on patients undergoing PCNL. Methods A double blind, randomized, sham controlled study design was used. Fifty patients undergoing PCNL by a single surgeon were randomized to one of three groups: true electro-acupuncture (EA, n = 17), sham electro-acupuncture (Sham, n = 20), and no acupuncture (Control, n = 13). Acupuncture was performed by a licensed acupuncturist 1 hr prior to surgery. All study personnel, except the acupuncturist were blinded to the intervention. PCNL was performed according to standard protocol and without intra-operative nerve block or local anesthetic. Pain scores (visual analog scale (VAS)), narcotic use (morphine equivalents (ME)), and side effects were recorded at set intervals post-operatively. Results Mean VAS scores for flank and abdomen in the EA group were lower at all time periods compared to sham and control groups. In fact, 2 patients in the EA group did not require any post-operative narcotics. Mean cumulative opioid usage was lower in the EA group immediately post-operatively compared to both sham and control groups (Table 1). No differences between groups were found for nausea and vomiting. No adverse effects of EA were noted. Conclusions Electro-acupuncture significantly reduces acute post-operative pain and narcotic usage without any adverse effects. This promising adjunct for post-operative pain control warrants further validation. Funding None.
Authors
Egor Parkhomenko
Rohit Chugh Jillian Capodice Timothy Tran Julie Thai Kyle Blum Mantu Gupta |
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PD35-02 |
Costs Variations For Percutaneous Nephrolithotomy In The United States From 2003 To 2013: A Contemporary Analysis Of An All-Payer Discharge Database |
Stone Disease: Surgical Therapy IV | 17BOS |
Abstract: PD35-02 Sources of Funding: None Introduction We aim to investigate costs variations for percutaneous nephrolithotomy (PCNL) in the United States using a population-based cohort. Methods Using the Premier Healthcare Database (Premier Inc, Charlotte, NC), we identified all patients diagnosed with kidney/ureter calculus (ICD-9: 592) who underwent PCNL (ICD-9: 55.04 or 55.03 combined with 55.21) from 2003 to 2013. We evaluated 90-day direct hospital costs (2015 USD); high costs were those above the 90th percentile and low costs were those below the 10th. We constructed a multilevel hierarchical regression model and calculated the pseudo-R2 of each variable, which translates to a percentage representing the variability contributed by that variable on 90-day direct hospital costs. Results Our final cohort consisted of 73,392 patients who underwent PCNL during the 11-year study period. Mean costs overall were $14374 (95% CI: $14150 - $14596). Mean cost in the low-cost group was $5,787 (95% CI: $5716 - $5856) versus $38,590 (95% CI: $37,357 - $39,923) in the high-cost group. Figure 1 shows mean costs (a) per surgeon and (b) per hospital ranked in ascending order and plotted along with 95% CI. Patient, hospital and surgical characteristics had a modest contribution toward costs variations (4.83%, 2.43%, 0.16%). Significant predictors of high costs include poorer comorbidity status (Charlson score ≥2 vs. 0: OR 2.98, p<0.001), region of hospital (West vs. Midwest: OR 1.96, p<0.01, Northeast OR 1.77, p=0.02), and hospital bedsize (>600 vs. <400 beds: OR 1.95, p<0.01. Factors less likely to be associated with high costs include age (OR: 0.99, p=0.04) and private insurance (vs. Medicare, OR 0.54, p<0.001). Conclusions Our contemporary analysis showed that patient, hospital and surgical characteristics had only a modest effect on costs variations for PCNL. Poor comorbidity status contributes to high costs highlighting the importance of patient selection. Larger hospitals in the West and Northeast are associated with higher costs; this may due to referral of complex stone cases to these centers. Funding None
Authors
Jeffrey Leow
Christian Meyer Benjamin Chung Steven Chang Quoc Dien Trinh Naeem Bhojani |
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PD35-03 |
A Randomized Control Trial of Preoperative Prophylactic Antibiotics Prior to Percutaneous Nephrolithotomy in the Low Risk Population: A Report from the EDGE Consortium |
Stone Disease: Surgical Therapy IV | 17BOS |
Abstract: PD35-03 Sources of Funding: None. Registered under ClinicalTrials.gov ID NCT02384200 Introduction Single institution studies have suggested possible benefit of a week of preoperative antibiotics prior to percutaneous nephrolithotomy (PNL). Yet prior studies are limited by lower methodology (Level IIa)1, including heterogeneous populations2, or utilizing quasi-sepsis definitions2. Other than the recommended peri-operative dose of IV antibiotics <24 hours per AUA Best Practice Statement, the duration/benefit of preoperative antibiotics remains unclear. We sought to perform a rigorous (adhering to CONSORT guidelines) multi-institutional trial assessing utility of preoperative PNL antibiotics for patients at low risk of infectious complications. Methods We performed a randomized controlled trial (RCT) coordinated across 7 academic stone centers for low risk PNL patients. Low risk patients were defined as those with negative urine cultures and under no antibiotic treatment course within 14 days of procedure, and without any urinary drains (catheters, stents, nephrostomy tubes). Patients randomized to the intervention arm received nitrofurantoin 100 mg twice daily for 7 days preceding surgery. All enrolled patients received standard preoperative dose of ampicillin (vancomycin if allergic) and gentamicin (ceftriaxone if eGFR<60 or allergic). PNL was performed per the usual practice of each treating surgeon. Baseline patient and stone characteristics were recorded. Perioperative infection related adverse events within the first 30 days were compared in both groups. Results Thirty-four patients were randomized to each arm. Adverse events occurring within the first 30 days of procedure are reported in Table 1. The infection rate after PNL in the intervention arm was 17.6% (6/34) versus 11.8% (4/34), p=0.49. Two of the patients in the intervention arm with infectious complications needed readmission and two others required admission to the intensive care unit. Total length of hospital stay demonstrated no difference between the two groups (1.09 versus 1.47, p=0.2). There was no mortality reported during this study period. Conclusions There appears to be no advantage to providing one week of preoperative oral antibiotics in patients at low risk for infectious complications. Less than 24 hours peri-operative antibiotics as per AUA Best Practice Statement appears sufficient. We continue to analyze this low risk group with a more robust data set, as well as analyze preoperative antibiotic benefit in other stratified risk groups. _x000D_ _x000D_ 1. Mariappan et al. BJU Int 2006_x000D_ 2. Kumar et al. Urol Res 2012_x000D_ Funding None. Registered under ClinicalTrials.gov ID NCT02384200
Authors
Seth Bechis
Joel Abbott Ben Chew Nicole Miller Amy Krambeck Mitchell Humphreys Vernon Pais, Jr Manoj Monga Roger Sur |
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PD35-04 |
Prospective Randomized Trial of Antibiotic Prophylaxis Duration for Percutaneous Nephrolithotomy: Preliminary Results |
Stone Disease: Surgical Therapy IV | 17BOS |
Abstract: PD35-04 Sources of Funding: None Introduction The American Urologic Association (AUA) recommends 24 hours or less of perioperative antibiotics for percutaneous renal surgery; however, these are not based on randomized trials. Only recently have small, randomized studies been published to support the use of 24 hours of antibiotics in low risk patients undergoing percutaneous nephrolithotomy (PCNL). We aimed to compare the efficacy of a single-day versus short-course protocol of antibiotic prophylaxis for PCNL. Methods Low risk patients with a sterile pre-operative urine culture undergoing PCNL were randomized to either antibiotics for 24 hours (24H) or until external urinary catheters were removed (CR). Per AUA recommendations, patients were given a 1st generation cephalosporin, or ciprofloxacin in cases of penicillin allergy. Exclusion criteria included age <18 years, receiving antibiotics immediately prior to the procedure, history of sepsis from stone manipulation, presence of indwelling catheter >1 week, plan for multi-stage procedure, immunosuppression, pregnancy, multiple antibiotic allergies, and patients who are breastfeeding. Descriptive statistics and Fisher’s exact test were used to compare infection-related events and complication rates within 30 days of the procedure between groups. Results Since 2014, 41 patients have been randomized to either 24H (20) or CR (21). Mean duration of antibiotic administration was 25 hours and 45 hours in the 24H and CR groups, respectively. Demographics, comorbidities, and surgical parameters (including operative time) were similar between groups. Mean stone size was larger in the CR group (20 mm ± 5.86) compared to the 24H group (16 mm ± 5.23), p = 0.035. There have been no differences in febrile episodes or rates of systemic inflammatory response syndrome (SIRS). Only one patient (24H group) had evidence of bacteremia, while one patient in each arm had a urinary tract infection post-operatively. Overall complication rates were similar between the two groups (Table 1). Conclusions In the preliminary stages of our study, a 24-hour protocol for antibiotic prophylaxis does not increase the risk of infection-related events or overall complications compared to giving antibiotics until external catheters are removed in patients undergoing PCNL. Funding None
Authors
Patrick Samson
Samir Derisavifard Bradley Morganstern Vinay Patel David Leavitt Geoffrey Gaunay Piruz Motamedinia Sammy Elsamra Jaspreet Toor Arthur Smith David Hoenig Zeph Okeke |
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PD35-05 |
How Do You Like Your Popcorn? An Evaluation of Laser Settings and Location in the Efficiency of the Popcorn Effect |
Stone Disease: Surgical Therapy IV | 17BOS |
Abstract: PD35-05 Sources of Funding: None Introduction There are many techniques for laser lithotripsy of urinary stones. The "popcorn" method involves placing a laser fiber in the center of a collection of stones and firing continuously, allowing fragments to further dust into smaller particles. Our aim was to examine different locations and laser settings on the efficiency of this lithotripsy method. Methods Pre-fragmented BegoStone phantoms were created between 2-4mm in size to mimic typical popcorning conditions. A 0.5g collection of fragments was placed into two 3D-printed models (a 2 cm spherical calyx model and 4x2 cm ellipsoid pelvis model, Figure 1) and a 200µm laser fiber was positioned at the top of the stones. The laser was fired for 2 minutes with constant irrigation, with 5 trials performed at each setting: 0.2J/50Hz, 0.5J/20Hz, 0.5J/40Hz, 1J/20Hz. The fragmentation efficiency was determined by calculating the mass of stones reduced to sub-2mm particles after 48h of drying. Statistical analysis was performed with ANOVA and Student's T-test. Additionally, high-speed photography was used to examine the mechanism of the popcorn effect. Results The trials within the calyx model were significantly more efficient compared to the pelvis model (0.18g vs 0.13g, p<0.05). When comparing laser settings, there was a difference between groups by one-way ANOVA (F[3,36] = 7.92, p = 0.0003). Post hoc tests showed that 20W settings were significantly more efficient than 0.2J/50Hz (p<0.05) although 0.5J/20Hz was not significantly less efficient than the 20W settings (Figure 2). High-speed imaging shows the majority of fragmentation is due to intermittent stone contact with the laser as opposed to stone-stone interaction. Conclusions The popcorn effect is most efficient in a smaller space as in the calyx model and as such we recommend displacement of stones into a calyx for popcorning. The 0.5J/20Hz setting produces efficient popcorning at a lower power of 10W, reducing fiber burnback and potential for injury, and is our recommended setting. Funding None
Authors
Daniel Wollin
Ruiyang Jiang Westin Tom Daniela Radvak W Neal Simmons Glenn Preminger Michael Lipkin |
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PD35-06 |
Can CT Imaging Predict Stone Impaction? |
Stone Disease: Surgical Therapy IV | 17BOS |
Abstract: PD35-06 Sources of Funding: None. Introduction A stone is considered impacted if it is not passable with a guide wire or contrast. These stones are more difficult to treat and have a higher morbidity with ureteral stricture rates as high as 24%. Factors predicting stone impaction have not been clearly identified. We sought to evaluate if pre-operative Computed tomography (CT) findings can predict the presence of an impacted stone. Methods From our prospectively maintained database of 1049 kidney stone formers between 01/2014 - 06/2016, we identified 47 patients with impacted stones (IS) and compared them to 34 who had non-impacted stones (NIS). All patients were treated with ureteroscopic laser lithotripsy by a single surgeon. We excluded patients who had prior stents or surgery for their stone. CT was reviewed to calculate stone size, stone volume, degree of hydronephrosis (0-3) and Hounsfield units (HU) of the stone as well as distal and proximal to the stone. Demographic data, CT imaging, labs, and intraoperative factors were used for comparison between groups. Results There were no differences in age, gender or BMI between IS and NIS. IS patients had a greater stone size, volume, HU under the stone, HU under/above ratio and degree of hydronephrosis compared to NIS patients. No differences in pre- or post-operative creatinine, stone density or HU above the stone was noted between the two groups. Patients above the cut-off value of 27 HU for the ureter distal to the stone were noted to have impacted stones with a sensitivity of 85%, specificity of 85%, positive predictive value of 89% and negative predictive value of 81%. Conclusions Impacted stones are associated with greater ureteral density distal to the stone, higher stone volumes and greater degrees of hydronephrosis on pre-operative CT. These criteria may help predict which patients are more likely to have impacted stones. Funding None.
Authors
Egor Parkhomenko
Timothy Tran Sumit De Julie Thai Kyle Blum Mantu Gupta |
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PD35-07 |
Preliminary results of a prospective randomized trial of safety guidewire use in ureteroscopic stone surgery: to use or not to use |
Stone Disease: Surgical Therapy IV | 17BOS |
Abstract: PD35-07 Sources of Funding: None Introduction Up-to-date, urology guidelines introduce safety guidewire (SGW) as an integral tool in ureteroscopy and recommended its routine use. However, the necessity of SGW placement in endourological procedures lack evidence and is being suggested as an expert opinion. Present study aimed to evaluate the use of SGW placement and its necessity in treatment of ureteral stones with semi-rigid ureteroscopy (s-URS). Methods A total of 160 patients with ureteral stones were stratified according to ureteral stone location and prospectively randomized into two groups' according to SGW usage or not in s-URS between July 2014 and August 2016. Ureteroscopy and litotripsy were done with a semi-rigid ureteroscope of 6.4/7.8 Fr (Olympus) and laser. Chi-square and student t-test were used for comparing data._x000D_ Results Of all patients, in 79 interventions were done under the guidance of SGW (SGW group) and in 81 without the guidance of SGW (No- SGW group). In No-SGW group 10 patients needed SGW introduction as it was difficult to access or advance the ureteroscope into the ureteral orifice or throughout the ureter and in SGW group SGW could not be introduced in 8 patients. These patients were excluded from the study. There were no significant differences in patient demographics and findings between the two groups, except female/male patient ratio and mean BMI which was higher in the SGW group (Table 1-2). Among all patients only 1 patient (1.3%) in SGW group experienced a complication of Clavien 3 and/or higher, which was ureteral perforation. Conclusions The preliminary results of our study reveal that, routine use of SGW placement does not help to decrease complication and/or treatment failure rates. Safety guidewire concept has to be re-evaluated with further prospective randomized trials. Funding None
Authors
Yiloren Tanidir
Bahadir Sahin Tarik Emre Sener Muhammed Sulukaya Cagri Akin Sekerci Ilker Tinay Ferruh Simsek |
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PD35-08 |
Utilization of pressurized vs non-pressurized irrigation during ureteroscopy in the absence of ureteral access sheath: Comparative retrospective study |
Stone Disease: Surgical Therapy IV | 17BOS |
Abstract: PD35-08 Sources of Funding: None Introduction Ureteroscopy (URS) is a common urologic procedure for removing upper urinary tract stones and evaluating other abnormalities of the urinary tract. Pressurized irrigation is frequently used to aid visualization by increasing the flow through the working channel. However, this can lead to postoperative renal colic, intrarenal reflux, rupture of the fornix, and, more seriously, sepsis, especially in the absence of ureteral access sheath (UAS). Here within, we evaluate the safety of pressurized irrigation during ureteroscopy in the absence of UAS. Methods After IRB approval, a retrospective chart review was performed comparing patients in whom pressurized irrigation was used during URS in the absence of UAS to those in whom pressure was not used from February 2014 to September 2016. Pressurized irrigation was performed utilizing automated external compression to the irrigation bag with maximum pressure set at 150 mm Hg; in the other cohort, hand irrigation was performed using 60 ml syringe and IV extension tubing. Statistics were performed in Prism (Graph Pad) and included means, standard deviations, chi squared tests, and student&[prime]s t-tests. Results Group (A) consisted of 206 patients in which pressurized irrigation was used. Group (B) consisted of 25 patients in which hand irrigation was used during their URS. In group (A), 52.9% were male vs in group (B), 36%. Group (B) were younger on average, with a mean age of 43±18.5, compared with group (A) whose mean age was 53±19.2 (p<0.05). In Group (A), 110/206 patients were stented preoperatively compared with 15/25 in Group (B) (p=0.67). Procedure times were 59±44 minutes in Group (A) and 67±35 minutes in Group (B) (p=0.38) Complication rates were 13.1% vs 24% in groups (A) and (B), respectively (P=0.14). Emergency Department (ED) return rate was 27 (13.1%) vs 6 (24%) in groups (A) and (B), respectively (P=0.14). Most complications in both cohorts were Urinary tract infection (UTI) and pain-associated complications. UTI was encountered in 5 vs 3 patients in groups (A) and (B), respectively (p<0.05). No occurrences of sepsis in either group. There was no calyceal rupture or intraoperative extravasation in either cohort. Conclusions Pressurized irrigation in the absence of UAS during URS appears to be safe. There was no significant difference in procedure times and, although there were more complications and ED visits in the hand irrigation group, many of these were experienced by a single patient who experienced a significant number of complications. Funding None
Authors
Karen Doersch
Amr Elmekresh Preston A. Milburn Graham Machen Kyle Hart Marawan El Tayeb |
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PD35-09 |
Comparison of A Novel Single-Use Flexible Ureteroscope to Currently Existing Reusable and Single-Use Flexible Ureteroscopes |
Stone Disease: Surgical Therapy IV | 17BOS |
Abstract: PD35-09 Sources of Funding: None Introduction Due to the high cost and limited durability associated with reusable ureteroscopes, single-use ureteroscopes have been gaining popularity in recent years. We aimed to directly compare the YouCare Single-Use fiberoptic flexible ureteroscope (YC-FR-A) to contemporary reusable/single-use flexible ureteroscopes in regards to optics, resolution, deflection, and irrigation flow. Methods Four flexible ureteroscopes, YC-FR-A (YouCare Tech, China), LithoVue (Boston Scientific, USA), Flex-Xc (Karl Storz, Germany), and Cobra (Richard Wolf, Germany), were assessed in vitro for image resolution, distortion, color representation, and grayscale imaging. Ureteroscope deflection was tested with an empty channel followed by placement of a 200µm laser fiber and a 1.9F wire basket. Irrigation flow was measured using normal saline at a height of 100cm through an empty channel, channel with 200µm laser fiber, and channel with 1.9F basket. Results The optical and functional characteristics of the four ureteroscopes are shown in Table 1. The YC-FR-A showed a resolution of 5.04 lines/mm and 4.3% image distortion. No substantial difference was demonstrated in color reproducibility or in the discernment of gray-scales between ureteroscopes. The YC-FR-A had an impressive one-way deflection of 349 degrees at baseline but lacks two-way deflection capability. In addition, there was a loss of deflection ability with any instrument in the working channel, with a loss of deflection ranging from 17.7 degrees to 30.3 degrees. With an empty channel, the YC-FR-A showed a maximum flow rate of 59 mL/min, which is the highest flow rate among the tested ureteroscopes. However, the flow rate decreased to 28.7 and 16.7 mL/min with laser fiber and basket in the working channel, respectively. Conclusions The YouCare Single-Use fiber-optic ureteroscope has comparable resolution to the Cobra fiberoptic ureteroscope but cannot match the two digital ureteroscopes tested. Although the one-way deflection and ergonomics of the YC-FR-A are not intuitive, this scope can be a viable alternative to the current reusable/single-use flexible ureteroscopes on the market; additionally, newer digital models in production may be more competitive. Funding None
Authors
Daniel Wollin
Ruiyang Jiang Daniela Radvak Charles Scales Michael Ferrandino W Neal Simmons Glenn Preminger Michael Lipkin |
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PD35-10 |
A Prospective Case Cohort Study Demonstrates that LithoVueTM, a Single-Use Flexible Disposable Ureteroscope, Reduces Operative Time |
Stone Disease: Surgical Therapy IV | 17BOS |
Abstract: PD35-10 Sources of Funding: NIH P20-DK-100863 (MLS, TC), NIH R21-DK-109433 (TC), and NIH K12-DK-07-006: Multidisciplinary K12 Urologic Research Career Development Program (TC)_x000D_ Introduction LithoVueTM (Boston Scientific), a novel single-use digital flexible ureteroscope, was released in January 2016. There are currently scant data regarding its performance in humans. Our center has been utilizing Lithovue as a primary ureteroscope for all cases since March 2016. Here we present procedural outcomes comparing LithoVue to reusable ureteroscopes in patients undergoing ureteroscopy for upper urinary tract pathology. Methods Data from upper urinary tract ureteroscopy were prospectively collected for this case cohort study with 30 days of clinical follow up. Flexible reusable ureteroscope (URF-P6, Olympus) cases performed August 2014-April 2015 were compared to consecutive LithoVue cases performed March 2016-September 2016. Differences in procedural outcomes, operative times and time spent in hospital were analyzed using t-test, chi-square and Fisher's exact tests._x000D_ Results One hundred and fifteen cases utilizing LithoVue and 65 cases utilizing reusable ureteroscopes met criteria. For all patients, mean age at surgery was 53.8±14.4 years, males (51.1%) slightly predominated females, and mean BMI was 29.6±9.0 kg/m2. Most cases were conducted for removal of kidney or ureteral stones (78.9%), followed by diagnostic purposes (17.2%) and treatment of urothelial carcinoma (3.9%). Demographics, surgical indications, laterality, procedural outcomes, complications, as well as stone size, location, total burden, and composition were comparable between the LithoVue and reusable ureteroscope groups. _x000D_ _x000D_ For all cases, reusable scope procedures lasted 64.5±37.0 minutes compared to 54.1±25.7 minutes for LithoVue procedures (p <0.05) and for stone removal cases, 70.3±36.9 versus 57.3±25.1 minutes respectively (p <0.05). Scope failure occurred in 4.4% of LithoVue cases and 7.7% of reusable cases (p = 0.27)._x000D_ _x000D_ Using multivariate regression analysis, controlling for stone size, patient age, and BMI, the use of LithoVue was associated with a 14 and 15.5-minute reduction in procedure (p <0.05) and operating room durations (p <0.05) respectively. Conclusions We present a case-cohort study of the largest single-center experience with LithoVue to date. Our data suggest that LithoVue represents a feasible, safe alternative to reusable flexible ureteroscopes with a low rate of scope failure comparable to that of reusable scopes. Its use was associated with a significant, potentially cost-saving finding of shorter procedure and overall operating room duration. This finding warrants further investigation._x000D_ Funding NIH P20-DK-100863 (MLS, TC), NIH R21-DK-109433 (TC), and NIH K12-DK-07-006: Multidisciplinary K12 Urologic Research Career Development Program (TC)_x000D_
Authors
Manint Usawachintachit
Dylan Isaacson Kazumi Taguchi David Tzou Ryan Hsi Benjamin Sherer Marshall Stoller Thomas Chi |
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PD35-11 |
New digital single-use flexible ureteroscope (PUSEN TM): first clinical experience |
Stone Disease: Surgical Therapy IV | 17BOS |
Abstract: PD35-11 Sources of Funding: None Introduction We report the clinical results of flexible ureteroscopy using the new digital single-use flexible ureteroscope from PUSEN TM(New South Wales, Australia). This device has an outer diameter of 9 Fr, with a working channel of 3,6 Fr. The deflection system has both options of standart and reverse modes with maximum deflection of 270°in both directions. Methods Between August and October 2016 we performed flexible ureteroscopy (FUR) using the new device. The primary outcome was stone free rates , secondary outcomes were total time of the procedure, total time of fluoroscopy and perioperative complications. The tertiary outcome was the behavior of the instrument during and at the end of the procedure_x000D_ Results A total of eleven FUR were performed. The present study included eight male patients and three female patients, with an average age of 39 years (range 23-65 years). All the patient were treated using a 12 Fr access sheath and holmium laser lithotripsy(260 µm fiber). The average stone size was 6 mm (range 4-10 mm), and stones were located as follow: 3 in proximal ureter, 6 in renal pelvis and 2 in lower calix. Total time taken to complete the surgery was 45 minutes (range 25-85 min). The number of stones treated per patient varied between 1 and 4. Mean fluoroscopy time was 50 seconds. We achieved 100% stone free rate in eight cases and 80% in the remaining three. One patient present an ureteral wall injury, with mucosal erosion at time of ureteral access sheath placement. A double J stent was placed in all patients. The device behaves properly during and at the end of the procedure, there was no loss in image quality or deflection capacity, being able to safely finish all the cases carried out. Conclusions With respect to outcomes evaluated in this study with the PUSENTM digital single use flexible ureteroscope seems to be similar in comparison to reusable flexible ureteroscope. The clinical results achieved in the present study suggest that this device could be considered a valid method to treat endoscopically renal and proximal ureteral stones reducing maintenance costs._x000D_ Funding None
Authors
José A. Salvadó
Alfredo Velasco Rubén Olivares José M. Cabello Manuel Díaz Sergio Moreno |
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PD35-12 |
Unplanned Emergency Department Visits and Hospital Admissions Following Ureteroscopy: Do Ureteral Stents Make a Difference? |
Stone Disease: Surgical Therapy IV | 17BOS |
Abstract: PD35-12 Sources of Funding: none Introduction The comparative effectiveness of ureteral stents placed during ureteroscopy for urinary stone disease is widely debated. We sought to evaluate unplanned medical visits within the early post-operative period after ureteroscopy in patients with and without ureteral stent placement. Methods We identified all ureteroscopic procedures for urinary stone disease in the California Office of Statewide Health Planning and Development (OSHPD) database from 2010-2012. The primary outcome was any emergency department visit or inpatient hospital admission in the first 7 days following ureteroscopy. Patients were sub-categorized by type of ureteroscopy (i.e. laser lithotripsy, basket retrieval, diagnostic) and analyzed for significant differences between stented and unstented patients. Multivariable logistic regression was performed to determine if ureteral stent placement was independently associated with unplanned visits. Results Our analytic cohort included 17,129 patients undergoing 18,860 ureteroscopy procedures. A ureteral stent was placed in 86.2% of patients undergoing laser lithotripsy, 70.5% of patients receiving basket retrieval, and 54.0% of patients undergoing diagnostic ureteroscopy. In the 7 days following ureteroscopy, 6.6% of patients were seen in the emergency department and 2.2% of patients were admitted. In a fully adjusted model, the utilization of a ureteral stent was not associated with emergency department visits or inpatient admissions. Conclusions Ureteral stent placement during ureteroscopy does not increase the odds of emergency department visits and inpatient admissions in the early post-operative period. Funding none
Authors
Harsha R. Mittakanti
Simon Conti Alan C. Pao Joseph Liao John T. Leppert Christopher S. Elliott |
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PD36-01 |
The Validated LACE Score Identifies Patients at Increased Risk of 90-day Readmission and Mortality Following Radical Cystectomy |
Bladder Cancer: Invasive III | 17BOS |
Abstract: PD36-01 Sources of Funding: None Introduction Radical cystectomy for bladder cancer is performed in an aged, highly comorbid population, and associated with high rates of readmission. We investigated the LACE score, a validated prediction tool for readmission and mortality, in the radical cystectomy population._x000D_ Methods Patients who underwent radical cystectomy for bladder cancer were identified by ICD-9 codes from the Healthcare Cost and Utilization Project State Inpatient Database for California between years 2007-2010. The LACE score was calculated as previously described, with components of L: length of stay, A: acuity of admission, C: comorbidity, and E: number of emergency department visits within 6 months preceding surgery (Figure). Descriptive statistics were performed, and multivariable logistic regression models were fit in a non-parsimonious fashion, including all patient demographic and clinical variables, in order to isolate the effect of the LACE score on outcomes (90-day readmission and mortality). Results Of 3,470 radical cystectomy patients, 638 (18.4%) experienced 90-day readmission, and 160 (4.6%) 90-day mortality. At a previously validated 'high-risk' LACE score ≥ 10, patients experienced an increased risk of 90-day readmission (22.8% vs 17.7%, p=0.002) and mortality (9.1% vs 3.5%, p<0.001). On adjusted multivariable analysis, 'high risk' patients by LACE score had increased 90-day odds of readmission (aOR=1.24, 95% CI: 0.99-1.54, p=0.050) and mortality (aOR=2.09, 95% CI: 1.47-2.99, p<0.001). Separate multivariate models demonstrated a one point increase in LACE score had a 7.3% increased adjusted odds of readmission, and a 33.2% increased odds of mortality. Conclusions The LACE score reasonably predicts patients at risk for 90-day readmission and mortality following radical cystectomy. Providers may use the LACE score to target high-risk patients for closer follow-up or intervention. Funding None
Authors
Jennifer L Saluk
Robert H Blackwell William S Gange Matthew AC Zapf Anai N Kothari Marcus L Quek Paul C Kuo Gopal N Gupta Robert C Flanigan |
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PD36-02 |
Impact of Non-modifiable Patient Factors on Perioperative Outcome Following Radical Cystectomy with Enhanced Recovery Protocol |
Bladder Cancer: Invasive III | 17BOS |
Abstract: PD36-02 Sources of Funding: none Introduction Enhanced recovery after surgery (ERAS) protocols in the setting of radical cystectomy have consistently improved perioperative outcomes. Though known to impact individual surgical and post-operative course, the influence of non-modifiable patient factors on perioperative outcomes has not been well-quantified. We sought to determine how various non-modifiable patient factors impact perioperative outcomes following radical cystectomy with ERAS. Methods We retrospectively reviewed our IRB approved prospectively-maintained bladder cancer database. Patients who underwent open radical cystectomy for urothelial carcinoma with ERAS protocol were identified. Non-modifiable patient factors including age, race, BMI, charlson comorbidity index (CCI), and ASA score were examined. Univariate and multivariate analysis was completed to determine impact of these factors on length of hospital stay, 30 and 90 day complications and readmission. Results A total of 289 patients were identified who underwent open radical cystectomy with ERAS by three urologic oncologists between 5/2012 and 3/2016. Patient characteristics are described in Table 1. On multivariable analysis, age, race, CCI, and perioperative transfusion significantly impacted length of stay (Table 2). 30-day complication and readmission occurrences were impacted similarly by both preoperative hemoglobin level and perioperative transfusion though only perioperative transfusion remained significant on multivariable analysis (p=0.008 and p=0.005). No significant impact was found on 90 day complication or readmission. Conclusions Patient age, race, and CCI significantly impact length of hospital stay following radical cystectomy with enhanced recovery protocol. Perioperative transfusion is significantly associated with 30-day complication and readmission. Fixed patient factors should be accounted for in risk-adjustment and reimbursement models. Funding none
Authors
Daniel Zainfeld
Jie Cai Gus Miranda Anne Schuckman Siamak Daneshmand Hooman Djaladat |
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PD36-03 |
Perioperative outcomes of open radical cystectomy in octogenarians: results from two high-volume centres |
Bladder Cancer: Invasive III | 17BOS |
Abstract: PD36-03 Sources of Funding: None Introduction Following the global trend of population aging, researchers and clinicians are increasingly facing the challenges of surgical management of malignancies in elderly patients. Although RC is a long-established treatment of muscle-invasive bladder cancer, little data are available on the postoperative outcomes of this intervention in the octogenarians. Contemporary representative open RC series report an overall complication rate ranging between 30% and 70% for any age category. Complication rate for our octogenarians lie within this range. The aim of our study was to evaluate the safety of open radical cystectomy (RC) in octogenarians, considering the potentially higher risk for postoperative complications due to the generally unfavourable comorbidity profile in this patient category. Methods We retrospectively evaluated a cohort of 44 patients aged ≥80 years treated with open RC and urinary diversion at two high-volume urology units between July 2013 and December 2015. Median age was 83 years. Charlson score was ≥3 in 41 (93%) patients, and ASA score was ≥ 3 in 34 (77%) patients. RC was performed in 42 (95%) patients for muscle-invasive bladder cancer and in 2 (5%) patients for benign disease._x000D_ Orthotopic ileal neobladder (V.I.P. technique), ileal conduit and cutaneous ureterostomies were performed in 1 (2%), 20(45%) and 20 (45%) patients, respectively. In 3 (8%) patients no urinary diversion was performed since they were already on dialysis for chronic kidney disease. Primary outcome was rate of 90-day complications graded according to Dindo-Clavien classification. Secondary outcomes were: operative time,estimated blood loss, recovery of bowel activity measured as timing of stool passage, and length of hospital stay. Results Overall 90-day complications were recorded in 23(52%) pts. Complications were grade II in 11 (25%) patients (blood transfusions), grade IIIa in 5 (11%) (1 wound dehiscence,1uretero-ileal leakage, 1 uretero-ileal stricture, 1 urinary fistula and 1 unilateral hydroureteronephrosis treat with nephrostomy), grade IIIb in 5 (11%) (3 wound dehiscence, 1 bowel obstruction, 1 pelvic bleeding), grade IV in 1 (2%) (myocardial infarction) and grade V in 1 (2%).Median operative time was 258 min (interquartile range [IQR]190-305). Median estimated blood losswas 700 ml (IQR 550-840). Stool passage was observed in 2 (5%) patients on POD 1, in 2 (5%) on POD 2, in 4 (9%) on POD 3, in 6 (14%) on POD 4 and in 30 (68%) on POD ≥5. Median length of hospital stay was 13 days (IQR 8-17). Conclusions Open RC in octogenarians appears feasible with an acceptable complication rate. Thus, ages hould not be considered as an absolute exclusion criterion for RC, particularly when this operationis performed in high-volume referral centres. Funding None
Authors
Vito Palumbo
Fabio Zattoni Afrovita Kungulli Sabrina La Falce Mattia Calandriello Alessandro Crestani Gianluca Giannarini Giacomo Novara Filiberto Zattoni Vincenzo Ficarra |
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PD36-04 |
Does Sarcopenia Impact Oncologic Outcomes in Patients Undergoing Adjuvant Chemotherapy Following Radical Cystectomy? |
Bladder Cancer: Invasive III | 17BOS |
Abstract: PD36-04 Sources of Funding: None Introduction Sarcopenia, defined as decreased muscle mass, has proven to be an easily accessible and accurate indication of frailty in the elderly population. It has been shown to predict cancer-specific and overall survival in patients undergoing radical cystectomy for urothelial carcinoma of the bladder. However, no studies have reported the impact of sarcopenia on the toxicity of chemotherapy and prognosis of patients treated with adjuvant chemotherapy. The aim of our study was to compare survival outcomes of sarcopenic and non-sarcopenic patients who are undergoing adjuvant chemotherapy after having undergone radical cystectomy. Methods We performed a retrospective cohort analysis of all patients who underwent radical cystectomy between 2005 and 2012 for high-risk superficial or muscle-invasive urothelial or undifferentiated bladder cancer who also underwent adjuvant chemotherapy for disease found to be metastatic or locally advanced at the time of surgery. Cohorts were separated on the basis of sarcopenia, defined as a normalized Total Psoas Area (TPA) of less than 8 cm2/m2 on CT. Overall survival was estimated using the Kaplan-Meier method and compared with the log-rank test. Results A total of 56 patients were identified for this study. 14 of the 56 patients (25%) who underwent adjuvant cisplatin-based chemotherapy were determined to be sarcopenic. Overall survival after the start of adjuvant therapy for sarcopenic patients was 25.12 months, as compared to non-sarcopenic patients who demonstrated an overall survival of 44.30 months (p<0.05). The 5-year survival rates were 21% and 36% for the two groups, respectively. While the time to local and distant recurrences was greater in the non-sarcopenic patients, as compared to those with sarcopenia, there was no statistically significant difference. Conclusions Our analysis has indicated that patients with sarcopenia have a worse overall survival when treated with adjuvant chemotherapy after radical cystectomy. In order to conclude whether sarcopenic patients should be receiving adjuvant therapy, future studies must match these patients with sarcopenic patients who met criteria to receive adjuvant chemotherapy after radical cystectomy, yet decided to forego treatment._x000D_ _x000D_ Funding None
Authors
Taylor Peak
Marc Colaco Ashok Hemal |
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PD36-05 |
The prognostic value of postoperative clinical and laboratory parameters regarding the oncological outcome of patients undergoing radical cystectomy for urothelial cell carcinoma of the bladder |
Bladder Cancer: Invasive III | 17BOS |
Abstract: PD36-05 Sources of Funding: none Introduction Radical cystectomy (RC) represents the current standard for the curative treatment of localized muscle-invasive and high-risk BCG-refractory non-muscle invasive bladder cancer (BC). Besides its curative intention RC can be associated with a substantial postoperative morbidity compromising the oncological outcome. So far there is only limited data suggesting postoperative clinical and laboratory parameters that could predict the oncological outcome and the cancer specific survival (CSS), respectively. The aim of this study was to evaluate potential postoperative clinical and laboratory parameters to predict the oncological outcome of patients undergoing RC for BC. _x000D_ _x000D_ Methods A single-centred retrospective data analysis of patients undergoing RC between 2004 and 2015 for BC was performed. Besides routine blood parameters (leucocytes, creatinine, Hb, CRP and thrombocytes), Clavien-classification, wound healing disorders (WD) and length of stay at the intensive care unit (ICU) were recorded. For all parameters a hazard ratio (HR) concerning the CSS was calculated on a univariate basis. Secondly a HR was calculated respecting the given postoperative parameters while including also postoperative staging (TNM-classification) parameters on a multivariate basis. Results In total 751 patients (n=751) with a complete dataset were identified. The HR concerning CSS was significant in univariate analysis for following parameters: creatinine-level (HR=1.34; p <0.001), CRP-level (HR=1.03; p0.031), thrombocyte count (HR=1.0002; p=0.037), post-operative WD (HR=1.85; p<0.001), Clavien-Score (1-3 vs. 3+) (HR=1.47;p= =0.027) and postoperative length of stay at the ICU (HR=2.84;p0.001). With the inclusion of the post-interventional TNM-classification the HR concerning CSS turned out to be significant on a multivariate analysis for TNM-values only. (pT<3 vs. pT3-4 HR=3.48, p =0.001; pN0 vs. pN+ HR=1.60, p =0.037 and M0 vs. M1 HR=2.44, p= 0.005). _x000D_ _x000D_ Conclusions In univariate analysis routine postoperative blood parameters, such as creatinine, CRP and thrombocyte count seem to be associated with a decrease in CSS. A closer monitoring and potentially intervention in a postoperative setting might be beneficial for these patients. ICU inhabitancy and WD after RC also show a degrading tendency regarding CSS in our cohort. However, multivariate analysis respecting TNM information shows that the studied parameters are no independent predictive markers for CSS. Funding none
Authors
Jan-Friedrich Jokisch
Tobias Grimm Alexander Buchner Alexander Kretschmar Gerald Schulz Birte Schneevoigt Christian Stief Alexander Karl |
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PD36-06 |
Is four days hospital stay after robotic assisted radical cystectomy feasible? A multidisciplinary enhanced recovery program challenge |
Bladder Cancer: Invasive III | 17BOS |
Abstract: PD36-06 Sources of Funding: None Introduction Radical cystectomy is the standard surgical treatment for muscle-invasive bladder cancer associated with substantial morbidity, prolonged hospital stay and mortality. We report a case series from an institution with a de novo cystectomy service. Our aim was to evaluate enhanced recovery after surgery protocol (ERP), focusing on length of stay (LOS), early complication and readmission rates, as key performance indicators that attest to quality of care after robotic assisted radical cystectomy (RARC). Methods Between April 2013 and October 2015, 150 (124 male and 26 female) patients underwent RARC with newly devised multimodal ERP in a new regional referral centre. On discharge patients were expected to return to their homes, support by family and friends is encouraged, however special nursing services were not provided. Results The median age was 70 years old, 74% of cases had a Body Mass Index (BMI) <30kg/m2, 53% a CardioPulmonary Exercise Test anaerobic threshold <11 and 86% American Anaesthesiology Score (ASA) score ≤2. The median LOS was 5 days (1st IQR 4 3rd IQR 7). 61% of the patients left hospital between day 3 and 5. Post-operative day 4 was the most frequent day of discharge from hospital. Age (p=0.003) and complications (p<0.001) were the only factors that showed a statistically significant association with the 4-day LOS cut-off. The incidences of post-treatment complications were 42% (63 of 150) for minor (Clavien-Dindo grade <3) and 8% (12 of 150) for major (≥ 3). There was only one death within 30 days of surgery. The incidence of readmission to hospital 30 days after operation was 14% (24 of 150). We found complications (p=0.005) and intra/ extra corporeal diversion (p=0.028) to be significantly associated with readmission. Conclusions Our multimodal stepwise approach to RARC and ERAS with the holistic care of the patient and involvement of the patient&[prime]s family and social surroundings leads to an unprecedented and reproducibly low LOS. Elderly patients should receive preoperative counselling about their increased risk of longer hospital stay, optimisation through prehabilitation programs and closer perioperative monitoring Funding None
Authors
Dimitrios Moschonas
Ricardo Soares Murthy Kusuma Alison Roodhouse Chris Jones Hugh Mostafid Michael Swinn Simon Woodhams Matthew Perry Krishnaji Patil |
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PD36-07 |
Restrictive Transfusion in Radical Cystectomy is Safe |
Bladder Cancer: Invasive III | 17BOS |
Abstract: PD36-07 Sources of Funding: none Introduction To determine the safety of a restrictive transfusion protocol (RTP) in patients radical cystectomy (RC) patients that are typically elderly with significant co-morbidity, given that perioperative blood transfusion (PBT) has been linked to poorer oncologic outcomes in this setting. Methods _x000D_ Outcomes for 173 consecutive patients meeting inclusion criteria undergoing RC for urothelial carcinoma (UC) from April 2010 to June 2014 by a single surgeon employing RTP were analyzed from an IRB approved, prospectively collected database. Results Outcomes for 173 consecutive patients meeting inclusion criteria undergoing RC for urothelial carcinoma (UC) from April 2010 to June 2014 by a single surgeon employing RTP were analyzed from an IRB approved, prospectively collected database. _x000D_ Results: Median follow-up was 3.1 years (range=0-5.1 years). Median age was 70 years (38-93). 46 patients (26.6%) received PBT. PBT patients had higher EBL (500 vs. 350, p=0.001), lower baseline hematocrit (28.9 vs. 33.3, p=0.005), and similar operative time (5.8 vs. 5.3 hours, p=0.01) and LOS (5.5 vs. 5, p=0.07). At discharge and 3 week follow-up there was no difference in hematocrit (p>0.05). In the no PBT group 90-day (65.6 vs. 86.7%, p=0.007) and high grade (15.6 vs. 34.8%, p=0.003) complication rates were lower. There were no differences in cardiac complication rates. On multivariable analysis predictors of PBT were age (OR=1.06, 95% CI [1.01, 1.11]), CCMI ?2 (OR=2.68, CI [1.09-7.04]), neoadjuvant chemotherapy (OR=3.74, CI [1.46, 10.19]), ?pT3 (OR=5.5, CI [2.33, 13.73]), baseline hematocrit (OR=0.95, CI [0.87, 1.00]) and EBL, although marginally (OR=1.001, CI [1, 1.003]). PBT was associated with lower RFS (HR=2.16, CI [1.13, 41.12], p=0.02) (Figure 1) and OS (HR=2.25, CI [1.25, 4.88], p=0.01)(Figure 2). Conclusions The use of RTP in RC is safe. PBT was associated with poorer RFS and OS independent of clinicopathologic characteristics. Funding none
Authors
Sumeet Syan-Bhanvadia
Swar Shah Jie Cai Gus Miranda Siamak Daneshmand |
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PD36-08 |
Perioperative allogeneic blood transfusion does not adversely impact survival after radical cystectomy for urinary bladder cancer - a competing-risks analysis from a multi-institutional european series |
Bladder Cancer: Invasive III | 17BOS |
Abstract: PD36-08 Sources of Funding: none Introduction Previous studies have been inconclusive whether the receipt of perioperative allogeneic blood transfusion (PBT) independently confers an impaired oncological outcome in patients treated with radical cystectomy (RC) for high-grade recurrent or muscle-invasive bladder cancer. Aim of this study was to evaluate the effect of perioperative PBT at RC on recurrence-free (RFS) and overall survival (OS) and cancer-specific (CSM) and other-cause mortality (OM) in a contemporary European multicenter cohort. Methods We relied on the Prospective Multicenter Radical Cystectomy Series (PROMETRICS), which includes data of 679 patients undergoing RC at 18 European tertiary care centers in 2011. Patients with missing information on PBT, American Society of Anesthesiologists (ASA) physical status, follow-up, survival data, or disease recurrence, as well as clinically metastatic patients were excluded from further analyses._x000D_ The association between PBT and oncological outcomes, as well as OCM was assessed using Cox and logistic regression analyses. Imbalances in clinicopathological features of patients receiving PBT vs. patients not receiving PBT were mitigated using conventional adjusting as well as inverse probability of treatment weighting (IPTW). Results The final population consisted of 525 patients with a median follow-up of 26 months (IQR: 21-30 months) of whom 275 patients (52.4%) received PBT. The two groups (PBT vs. no PBT) differed significantly with respect to most clinicopathological features including perioperative blood loss (median: 1000ml; IQR: 650-1600ml vs. median: 570ml; IQR: 400-800ml)._x000D_ Independent predictors of receipt of PBT in multivariate logistic regression analysis were sex (odds ratio (OR)=4.66; 95% confidence interval (CI)=[2.34-9.29]; p<0.001), body mass index (OR=0.92; 95% CI=[0.87-0.97]; p=0.003), type of urinary diversion (OR=0.40; 95% CI=[0.22-0.75]; p=0.004), estimated blood loss (OR=1.29; 95% CI=[1.21-1.39]; p<0.001), and any complication within 30 days (OR=3.00; 95% CI=[1.75-5.15]; p<0.001)._x000D_ Unweighted and unadjusted survival analyses revealed a significant increase in cumulative incidences of CSM and OCM in the two groups (p=0.017 and p<0.001, respectively)._x000D_ After IPTW-adjustment, those differences no longer held true. PBT was not associated with RFS (HR=0.92; 95% CI=[0.53-1.59]; p=0.76), OS (HR=1.07; 95% CI=[0.56-2.04]; p=0.84), CSM (sub-HR=1.09; 95% CI=[0.62-1.93]; p=0.76) and OCM (sub-HR=1.02; 95% CI=[0.27-3.84]; p=0.95) in IPTW-adjusted Cox regression and competing-risks regression analyses. The same held true in conventional multivariate Cox and competing-risks regression analyses, where pathological tumor stage and lymphovascular invasion were the only independent predictors of CSM (HR=3.71, 95% CI=[2.06-6.68], p<0.001 and HR=2.49, 95% CI=[1.43-4.33], p<0.001) as well as disease recurrence (HR=4.48, 95% CI=[2.45-8.16], p<0.001 and HR=2.76, 95% CI=[1.56-4.87], p<0.001)._x000D_ Conclusions This study could not determine an adverse impact of PBT on oncological outcome and overall survival after adjusting for differences in patient characteristics._x000D_ Funding none
Authors
Malte W. Vetterlein
Philipp Gild Luis A. Kluth Michael Gierth Hans-Martin Fritsche Maximilian Burger Chris Protzel Oliver Hakenberg Nicolas von Landenberg Florian Roghmann Joachim Noldus Philipp Nuhn Michael Rink Felix K.H. Chun Matthias May Margit Fisch Atiqullah Aziz |
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PD36-09 |
Institutional Volume is Associated with Reduced 90 Day Mortality Rates for both Open and Robotic Radical Cystectomy |
Bladder Cancer: Invasive III | 17BOS |
Abstract: PD36-09 Sources of Funding: Department of Urology and Department of Biostatistics, Winthrop University Hospital Introduction Perioperative mortality and readmission rates are evolving metrics of care being monitored in radical cystectomies (RC). We aim to evaluate these outcomes in open radical cystectomies (ORC) and robotic assisted radical cystectomies (RARC) reported in the National Cancer Data Base adjusted by surgery type. Methods Using the National Cancer Data Base, patients treated with RC from 2003 to 2010 were identified. We evaluated the association between 90-day conditional mortality and readmission with respect to surgery type, adjusted by patient (age, gender, race/ethnicity, Charlson-Deyo score, tumor type, clinical stage, margin status and receipt of neoadjuvant chemo-or radiotherapy) and facility characteristics (overall cystectomy volume and facility type [Academic/Research, Comprehensive Community, or other]). Results 16,923 RC cases (13,236 ORC, 3,687 RARC) were identified with 480 deaths (3.6%) after ORC and 99 deaths (2.7%) after RARC within 90 days, conditional upon surviving 30 days post-surgery. Comparing <3 cystectomies/year to >20 cystectomies/year, 90-day overall conditional mortality rates decreased from 4.0% to 2.5%. In stratified analyses, 90-day conditional mortality rates decreased from 4.2% to 2.7% for ORC and 2.7% to 2.0% for RARC. Center volume was strongly associated with 90-day conditional survival (p=0.002), independent of surgery type. In multivariable analysis of 90-day conditional mortality, age (OR=1.03, 95% CI: 1.02-1.04, p<0.0001), comorbidites (OR=1.4, 95% CI: 1.12-1.6, p=0.0005), margin rates (OR=3.5,95% CI: 2.9-4.3, p<0.0001) as well as facility volume (OR=0.99, 95% CI: 0.98-1.00, p=0.001), were predictive of 90-day conditional mortality. Cystectomy volume did not predict 30 day readmission, however, Charlson-Deyo score 1-2 (OR=1.274, 1.112-1.461 95% CI, p=0.0005) and receipt of neoadjuvant chemo- or radiotherapy (OR=1.161, 1.032-1.307 95% CI, p=0.0134) were significantly associated with 30-day readmission. Conclusions Patients were less likely to incur death following robotic or open cystectomy within 90 days as institutional cystectomy volume increased. 30 day readmission rates were not influenced by institutional cystectomy volume. Funding Department of Urology and Department of Biostatistics, Winthrop University Hospital
Authors
Kaitlin Kosinski
Melissa Fazzari Michael Kongnyuy Daniel Halpern Marc Smaldone Jeffrey Schiff Aaron Katz Anthony Corcoran |
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PD36-10 |
Venous Thromboembolism Rates Following Radical Cystectomy Stratified by Method of Prophylaxis. |
Bladder Cancer: Invasive III | 17BOS |
Abstract: PD36-10 Sources of Funding: None Introduction Venous thromboembolism (VTE), comprised of deep venous thrombosis (DVT) and pulmonary embolus (PE), remains a significant complication following radical cystectomy. Recently, utilization of prophylactic dosed post-discharge subcutaneous enoxaparin has been reported to decrease VTE rates following radical cystectomy. We compared the rates of VTE following radical cystectomy at post-operative day 90 during three separate eras where patients received either prophylaxis with warfarin (1985-2007), subcutaneous heparin (2009-2012) while hospitalized, or subcutaneous heparin followed by 30-days of subcutaneous enoxaparin (2013-2015) following discharge. Methods We used a prospectively maintained database to identify all patients who underwent radical cystectomy for primary bladder cancer with intent to cure at our institution from 1985-2015. Rates of VTE during the three different eras of VTE prophylaxis were calculated and compared. Multivariable logistic regression modeling was used to identify independent risk factors for VTE following radical cystectomy. Results 2694 patients were identified during this time period and 168 patients were excluded for missing data. A total of 4.43% (n=112, 57 DVT only) patients developed VTE. Rates of VTE were not significantly different between methods of VTE prophylaxis, (p=0.8673). Multivariable logistic regression analysis identified age (OR 1.027, 95%CI 1.003-1.051), BMI (OR 1.073, 95%CI 1.034-1.113), non-orthotopic diversion (OR 0.456, 95%CI 0.261-0.794), and hospital length-of-stay (OR 1.038, 95%CI 1.011-1.064) to be independent predictors of VTE. Conclusions VTE rates in patients treated with extended post-discharge prophylactic dosed subcutaneous enoxaparin were not significantly different than VTE rates in patients treated with warfarin or subcutaneous heparin while hospitalized at 90 days post-operatively. Age, BMI, non-orthotopic urinary diversion, and hospital length-of-stay were independent predictors for VTE in patients following radical cystectomy. These results conflict with recently published reports and highlight the need for a randomized controlled trial for VTE prophylaxis following radical cystectomy. _x000D_ Funding None
Authors
Cory Hugen
Alexander Stern Jie Cai Gus Miranda Anne Schuckman Hooman Djaladat Siamak Daneshmand |
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PD36-11 |
Comparison of Total 90 Day Costs for Open Versus Robotic Cystectomy |
Bladder Cancer: Invasive III | 17BOS |
Abstract: PD36-11 Sources of Funding: None Introduction _x000D_ Gold standard therapy for muscle invasive bladder cancer (BC) and high risk recurrent non-muscle invasive BC is radical cystectomy (RC) with pelvic node dissection. Traditionally this has been an open approach, however recent data demonstrates that robotic RC is a safe and viable option with good oncologic outcomes. A concern is the cost differential between open RC (ORC) and robotic RC (RRC). We perform a single center matched study comparing the total 90 day cost between open and radical cystectomy. Methods _x000D_ With IRB approval, we assessed a single center prospectively collected RRC database for patients between 2007 and 2015. We matched RRC cases 1:1 by age and year of surgery with a retrospective ORC database. All patients who underwent adjunct procedures and procedures with two or more surgeons were excluded from the study. We then performed a comparison of clinical and pathological variables as well as 90 day technical, professional and total costs, including hospital readmissions and complication related costs. Costs are represented as a fraction of RRC over the ORC. Student&[prime]s unpaired t-test and Fisher&[prime]s exact tests were used to analyze data between the two cohorts. Results _x000D_ We identified 126 RRC patients and matched the with 106 ORC patients. 83% of the RRC was male (104/126) vs. 78% (83/126) of the ORC group (P=0.501). Median age of RRC was 66.50 (61-73 IQR), and for ORC was 67 (61-74 IQR) (p=0.501). 33% of RRC vs. 37% of ORC were clinical stage < T2, 49% of RRC vs. 45% of ORC were cT2, and 18% RRC vs. 18% of ORC were > cT2 (p=0.491). Mean Charleston Comorbidity score was 1.3 (1.05 std. dev.) for RRC and 1.99 (1.89 std. dev) for ORC (p=0.006). 21% (26/126) of RRC and 13% (14/104) of ORC had a continent diversion. Of the RRC cases, 52% (65/126) of the diversions were done robotically. Median length of hospital stay was 6.5 days (5-9 IQR) for RRC and 7 days (5-9 IQR) for ORC (p=0.385)._x000D_ _x000D_ The 90 day total cost for RRC was 1.15 times greater than for the ORC cohort (p=0.084). Professional Fees for the RRC were 1.05 times greater than the ORC (p=0.3454) and the technical fees of RRC were 1.18 times that of the ORC (p=0.074). 82% of the cost for the RRC, and 81% of the ORC costs were technical. _x000D_ Conclusions _x000D_ In a matched cohort, the total 90 day post-operative costs for robotic approach was not statistically significantly more than the open. This was primarily related to technical costs, and the initial capital required for either approach was not included. Funding None
Authors
Michael Metcalfe
Zachary Compton Roger Li James Ferguson Debashish Sundi Justin Nguyen Ashish Kamat Jay Shah Colin Dinney Neema Navai |
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PD36-12 |
Comparing complications and survival of primary cystectomy vs. salavage cystectomy after Trimodal Therapy |
Bladder Cancer: Invasive III | 17BOS |
Abstract: PD36-12 Sources of Funding: none Introduction Patients with advanced bladder cancer may receive radical cystectomy (RC) or Trimodal therapy (TMT) as treatment. After TMT, failure to respond to induction therapy or recurrence may be followed by salvage RC. We compare the timing and nature of complications, and overall survival between these two procedures at our institution. Methods We retrospectively identified patients from our contemporary cohort spanning from 2002 to 2013 that underwent primary RC and 22 patients that underwent TMT followed by salvage RC for disease progression. Patients were limited to those with a diagnosis of bladder cancer without radiographic evidence of lymph node or distant metastasis. Early (≤90 day) complication rates were compared using Fisher&[prime]s exact test. Overall survival and late (>90 day) complications were compared using Kaplan Meier curves, and the log-rank test. Results From 2003 to 2013 we identified 239 patients who underwent primary RC and 22 patients who underwent salvage RC. The median age of the cohort was 68, 76% were male and the median follow-up was 5 years. The groups had similar baseline characteristics, except that those that underwent salvage RC had higher rates of tobacco use (95% vs 68%, p=0.006), and were less likely have a neobladder (4.6% vs 8.8%, p=0.03). 43 patients (17%) that underwent primary cystectomy received neoadjuvant chemotherapy. _x000D_ _x000D_ There were no significant differences between salvage RC and primary RC in terms of overall survival (log-rank P=0.8) or disease specific survival (P=0.7). _x000D_ _x000D_ The overall early complication rate was 77% after salvage RC compared to 57% after primary RC (p=0.07). Early infectious complications were significantly higher after salvage (36% vs 11%, p=0.002). _x000D_ _x000D_ The 1-, 3-, and 5-yr overall late complications rate after salvage RC was 8.3%, 36%, and 68% compared to 5.8%, 14%, and 16% after primary RC (log-rank p=0.033, Figure 1), respectively. _x000D_ After salvage, there was an increased rate of late infectious (23% vs 7.5, p=0.03) and late gastrointestinal (27% vs 4.0%, p=<0.001) complications. _x000D_ Conclusions The overall survival, disease specific survival, and overall early complication rates are comparable between primary cystectomy and salvage cystectomy after TMT. _x000D_ Funding none
Authors
Matthew Mossanen
Ross E. Krasnow Alberto C. Pieretti Adam S. Feldman Jason A. Efstathiou Michael L. Blute Niall M. Heney Matthew F. Wszolek |
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PD37-01 |
Four vs ten months of induction ADT for intermittent therapy: A prospective CURC randomized trial. |
Prostate Cancer: Advanced (including Drug Therapy) II | 17BOS |
Abstract: PD37-01 Sources of Funding: This study was funded by an unrestricted grant from Ferring Labs to the CURC. Introduction Intermittent androgen deprivation therapy (IADT) is widely used for the treatment of men with prostate cancer. However, the optimal duration of ADT induction is unknown. Duration of IADT induction varies from 3 to 12 months in phase 2 and 3 studies, but different periods of induction have never been compared prospectively. This is the first report of a randomized CURC trial comparing the effect of 4 months vs 10 months of degarelix induction on the length of the off treatment interval in men with biochemical failure. _x000D_ Purpose: To assess the effect of 4 months vs. 10 months of degarelix therapy on the length of the off treatment interval in men receiving IADT for biochemical recurrence after definitive local therapy_x000D_ Methods This was a prospective, open label, multicentre randomized trial. 101 patients were enrolled, and 91 were randomized. Eligible patients had biochemical recurrence after definitive local therapy with surgery or radiation, a rising PSA > 5.0, and no evidence of bone metastases. Patients were stratified for PSA < or > 10, and Gleason score <= or > 7. Patients were randomly allocated to 4 or 10 months of degarelix (240 mg loading dose, then 80 mg/mo). The primary end point was the time until PSA reached 5.0 during the off treatment interval. Secondary endpoints included the effect of 4 vs 10 months of induction ADT on PSA nadir, time to CRPC, testosterone recovery, BMD loss, and side effects. Results The median age was 75, and median PSA was 12. There was no difference between the 2 groups in median age, PSA, BMI, racial distribution, Gleason score, T stage, ECOG, smoking history, or baseline testosterone. _x000D_ The median time off treatment was 22.8 months. There was no difference between 4 and 10 months of ADT induction in the median off treatment interval (p=0.38) (Fig 1). PSA nadir < 0.1, but not baseline PSA predicted for a more prolonged off treatment duration. There was no difference in time to testosterone recovery between the groups (median 7.2 months). _x000D_ Conclusions There was no difference in the duration of the off treatment interval between the 4 and 10 month degarelix groups. This study suggests that a shorter course of ADT induction offers comparable benefit with respect to the duration of the off treatment interval in men with PSA failure and may reduce the side effects and costs of ADT. _x000D_ _x000D_ Funding This study was funded by an unrestricted grant from Ferring Labs to the CURC.
Authors
Laurence Klotz
Andrew Loblaw Rob Siemens Paul Ouellette Anil Kapoor Fred Saad |
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PD37-02 |
PHASE III STUDY OF INTERMITTENT MONOTHERAPY VERSUS CONTINUOUS COMBINED ANDROGEN DEPRIVATION |
Prostate Cancer: Advanced (including Drug Therapy) II | 17BOS |
Abstract: PD37-02 Sources of Funding: none Introduction Intermittent androgen deprivation therapy can only be appropriately evaluated in a randomized fashion. We present updated follow up results, to Sept 2016, from the SEUG 9901 Phase III study comparing the intermittent monotherapy with continuous combined androgen deprivation using an LHRH analogue and ciproterone acetate and associated components of quality of life. Methods Patients with advanced prostatic cancer and M1 received cyproterone acetate (200 mg/day), administered for two weeks, and LhRh agonists (1 monthly depot injection)started after two weeks of Lead-in-therapy, and given every four weeks thereafter. After 3 months when the PSA is bellow 4 ng/ml, patients where randomised between continuous therapy LhRh plus CPA (200 mg/day) and intermittent therapy CPA (300 mg/day). Results 1045 men with a median PSA of 15.9ng/ml were registered between October 1999 and September 2007. 24.5% of registered patients have a PSA less than 10ng/ml; 39.5% of registered patients have a PSA greater than 20ng/ml. 90.3% have a T3 tumour and 5.6% T4; only 14% have metastatic prostate cancer, 63% have Gleason Score 6-7 and 21% Gleason 8+. 918 patients (aged 44-81, mean 72) have been randomized 462 to Intermittent therapy and 456 to Continuous. The median PSA at randomisation is 1.0 ng/ml ranging from 0.1 to 9. 49.2% of patients have a PSA less than 1 ng/ml at randomisation._x000D_ _x000D_ The maximum follow up is 15.6 years with a median of 5.8 years. 630 (310 Intermittent, 320 Continuous) patients have died; 200 from prostate cancer (100 Intermittent and 100 Continuous), 267 from CVD (125 Intermittent and 142Continuous), 43 from other metastatic disease (27 Intermittent and 16 Continuous) 120 from Other Causes, including unknown cause (58 Intermittent and 62 Continuous). _x000D_ _x000D_ Median survival is 6.5 years (95% CI 6.0, 6.9) and 535 patients have been followed up for at least five years, with 361 for at least 7 years and 195 for at least 10 years (22% of those randomized to intermittent therapy and 21% of those on continuous). Metastatic status, PSA at randomisation and age at randomization are all prognostic factors for survival. M1 patients have an increased risk of dying (HR=1.67, 95% CI 1.30, 2.13) and there is a trend for an increasing hazard of death with increasing age so that men aged 75+ have a hazard ratio of 1.73 (95% CI 1.16, 2.57) compared to men aged under 60. Men whose PSA falls to between 2 and 4 have an increased hazard of dying relative to those whose PSA falls below 0.5 (HR=1.88, 95% CI 1.53, 2.30). There was no evidence that T Stage (p=0.76) or Gleason score (p=0.09) are associated with an increased risk of death. _x000D_ _x000D_ Adjusting for Age, PSA and metastatic status, patients on continuous therapy had an elevated hazard of death, HR= 1.13 (95% CI 0.97, 1.32), p = 0.13. The hazard of a CVD death is HR=1.22 (95% CI 0.96, 1.55, p = 0.11), while for other metastatic disease it is HR = 0.64(95% CI 0.35, 1.19, p = 0.16). For Prostate cancer HR = 1.08 (95% CI 0.82, 1.43 , p = 0.57), and for other causes of death it is HR = 1.18 (95% CI 0.82, 1.70 , p = 0.36)._x000D_ Conclusions Follow up has been extended to a maximum of 15 years and 20% of patients are still in active follow up. We are much closer to the 658 deaths specified in the protocol and there is no evidence that an initial treatment with intermittent therapy is harmful to patients in that overall survival is poorer. If anything, survival is poorer on continuous therapy driven largely by elevated cardio vascular deaths. There is no difference in prostate cancer deaths, though those randomized to intermittent therapy have a greater hazard of a death due to a non-prostate cancer Funding none
Authors
Fernando Calais da Silva Junior
Fernando Calais da Silva Senior Frederico Gonçalves Jan Kliment Américo Santos Spiros Pastidis Antonio Queimadelos Chris Robertson |
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PD37-03 |
ANDROGEN DEPRIVATION THERAPY AND THE INCIDENCE OF AUTOIMMUNE DISEASES IN 17,168 PATIENTS WITH PROSTATE CANCER |
Prostate Cancer: Advanced (including Drug Therapy) II | 17BOS |
Abstract: PD37-03 Sources of Funding: This research was supported by the Ministry of Science and Technology Taiwan (MOST 104-2320-B-016-012-MY3)_x000D_ Introduction Androgen deprivation therapy (ADT) has been the mainstay treatment for advanced prostate cancer for more than seven decades. However, the relationship between ADT and the incidence of autoimmune diseases remains unclear. Methods A population-based nationwide cohort study of 17,168 patients diagnosed with prostate cancer between 1996 and 2013 was identified from the Taiwan National Health Insurance Research Database (NHIRD).Incident autoimmune diseases were ascertained at least 180 days after prostate cancer diagnosis. We used 1:1 propensity score–matched analysis ,multivariable-adjusted Cox proportional hazards models to investigate the association between ADT use and the risk of autoimmune diseases Results Of the 17,168 selected prostate cancer patients, 16,379 patients were met our inclusion and exclusion criteria, with 7,025 receiving ADT and 9,354 were no-ADT users. After 1:1 propensity score matching, there were 5,590 ADT users and 5,590 non-ADT users in the study cohort. During a mean follow-up period of 5.1 years, 457 patients were newly diagnosed with autoimmune diseases with 155 among ADT users and 302 among non-ADT users. Kaplan-Meier curves demonstrated a higher cumulative probability of remaining autoimmune diseases-free among ADT users (Figure 1). Compared to non-ADT users, ADT group was statistically associated with a decreased risk of autoimmune diseases (adjusted hazard ratio (HR) 0.63, 95%CI 0.52-0.76) after Cox proportional hazards models. More specially, ADT users had a decreased risk of Graves' disease (aHR 0.46, 95%CI 0.23-0.91), psoriasis (aHR 0.53, 95%CI 0.29-0.97), type 1 diabetes (aHR 0.33, 95%CI 0.17-0.63), and uveitis (aHR 0.51, 95%CI 0.26-0.97) (Table 1)._x000D_ Conclusions The result of this study indicated that ADT use in patients with prostate cancer may decrease the risk of autoimmune diseases, especially in Graves’ disease, psoriasis, type 1 diabetes, and uveitis. Further studies are warranted to further investigation to obtain a better understanding between ADT and autoimmune diseases._x000D_ Funding This research was supported by the Ministry of Science and Technology Taiwan (MOST 104-2320-B-016-012-MY3)_x000D_
Authors
Jui-Ming Liu
Heng-Chang Chuang Chun-Te Wu Ren-Jun Hsu |
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PD37-04 |
Statins and oral treatments in patients with metastatic castration resistant prostate cancer (mCRPC): Real-world outcomes |
Prostate Cancer: Advanced (including Drug Therapy) II | 17BOS |
Abstract: PD37-04 Sources of Funding: Janssen Scientific Affairs, LLC Introduction The literature suggests that statin treatment may influence outcomes for patients across cancers such as pancreatic and breast cancer. Although 30% of men ≥age 40 use statins, little is known about the impact of statins on outcomes for patients treated for mCRPC, particularly the potential for variation in the effect of mCRPC oral treatments. This study examined the association between statin use, mCRPC oral treatments, and patient outcomes in a real-world setting. Methods A national health claims database was used to conduct a retrospective study of patients initiated on oral treatments for mCRPC (abiraterone acetate plus prednisone (ABI) or enzalutamide (ENZ)) from 2012-2015. Treatment cohorts and index date were defined based on first medication initiated (ABI/ENZ). Included patients had: ≥1 prostate cancer claim (ICD-9-CM 185.xx) from 6 months pre- to 30 days post-index date; ≥6 month pre-index and ≥3 months post-index health plan enrollment (retaining patients who died). Outcomes assessed included new central-nervous system conditions, bone, brain and visceral metastases, duration of treatment, and mortality. Descriptive analyses and Cox proportional hazards assessed the impact of statins and of ABI/ENZ; models adjusted for age, region, pre-index comorbidities, bone/brain/visceral metastases and docetaxel use. Results Follow-up statin use was similar for the cohorts, with 40.82% of 1,095 ABI vs. 38.24% of 421 ENZ treated (P=0.36) patients using statins. The proportion of days covered by statins were 63% (ABI) and 60% ENZ (P=0.16). Follow-up statin use was associated with lower hazards of entering hospice (HR: 0.51, P=0.005), discontinuing oral mCRPC treatments (HR: 0.62, P=0.001), and mortality (HR: 0.54, P <0.001). ABI patients with statins had a lower hazard of CNS events (HR: 0.79; P=0.031), while ENZ patient with statins had a higher hazard of CNS events (HR: 1.09; P=0.026). ENZ patients with follow-up statins had a higher hazard of bone/brain metastases (HR: 1.24, P=0.006). Conclusions For a population of real-world patients with mCRPC, statins were associated with improved outcomes and may lead to variability in the effect of oral treatments. Funding Janssen Scientific Affairs, LLC
Authors
Nicole Engel-Nitz
Ajay Behl Cori Blauer-Peterson Nancy Dawson |
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PD37-05 |
Impact of stage migration on metastatic prostate cancer: evidence of more favourable disease characteristics over time |
Prostate Cancer: Advanced (including Drug Therapy) II | 17BOS |
Abstract: PD37-05 Sources of Funding: none Introduction Recent studies suggested an inverse stage migration towards more aggressive pathological characteristics in high-risk prostate cancer. We evaluated whether patients with metastatic prostate cancer (mPCa) experienced changes in clinical patterns and oncological outcomes in the most recent years. Methods Within the Surveillance, Epidemiology and End Results (SEER) database, we identified 12,681 patients diagnosed with mPCa between 2004 and 2013. Only patients with complete clinical data were considered. After stratification according to the year of diagnosis, lowess smoother weighted functions were used to plot the prevalence of each metastatic stage, according to the sixth edition of American Joint Committee on Cancer [AJCC] Cancer Staging Manual (M1a, M1b, M1c), according to local T stage (T1, T2, T3+) and according to biopsy Gleason score (≤6, 7, ≥8). Similarly, overall mortality rates at 2-year were evaluated for patients diagnosed between 2004 and 2011. Temporal trends were quantified using the annual percentage change (APC) with the least squares linear regression. Results Overall, 700 (5.7%) M1a, 9,192 (74.8%) M1b and 2,399 (19.5%) M1c patients were identified. The prevalence of M1c stage significantly decreased from 21.7% in 2004 to 15.6% in 2013 (APC: 5.46%: 95% CI: 3.21-7.82; p<0.01). Local T staging significantly changed over the study period. Specifically, an increasing rate has been observed of individuals with local T1 disease, ranging from 22.8% in 2004 to 36.1% in 2013 (APC: 4.72%; 95% CI: 3.41-6.07; p<0.001). The proportion of patients with T2 disease decreased from 48.7% in 2004 to 36.1% in 2013 (APC: -3.09%; 95% CI: 2.25-3.94; p<0.001). No statistically significant variation has been observed for T3+ stage (p=0.1). Similarly, a decrease in the proportion of patients with gleason score of ≤6 or 7 was observed (both p<0.001). This was accompanied by a significant increase in the proportion of patients with gleason score of 8 or higher, which increased from 67.2% in 2004 to 84.4% in 2013 (APC: 2.54%; 95% CI: 2.14-2.94; p<0.001). The 2-year mortality rates after diagnosis decreased from 43.7% in 2004 to 39.0% in 2011 (APC: 1.89%; 95% CI: 1.33-2.45; p<0.001). Conclusions The stage migration phenomenon that has been described in surgically-treated PCa holds valid also in the metastatic setting. This results in a higher proportion of high-grade cancer when diagnosed at metastatic stage. However, early detection efforts resulted in a decreasing rate of patients with visceral metastases (stage M1c) and decreasing 2-year mortality rates. Funding none
Authors
Emanuele Zaffuto
Helen Davis Bondarenko Raisa S. Pompe Paolo Dell'Oglio Giorgio Gandaglia Nicola Fossati Armando Stabile Marco Bandini Francesco Montorsi Alberto Briganti Pierre I. Karakiewicz |
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PD37-06 |
A new era: Automated extraction of detailed prostate cancer information from narratively written health records. Pioneer work from a European tertiary care center |
Prostate Cancer: Advanced (including Drug Therapy) II | 17BOS |
Abstract: PD37-06 Sources of Funding: none Introduction Detailed pathological information are necessary for follow-up analyses and new prediction tool development. Most institutional databases harbour a lack of either quantity or quality of such data. Expensive manpower needs to be manually invested for this purpose in daily clinical practice. _x000D_ Natural language (NLP) processing presents immense potential to automate the information-gathering process in the field of urology. To propose and validate a novel tool to extract specific detailed pathological information from written health records that contain continuous, narrative text in an automated and precise way. Methods Overall, 1500 postoperative narrative pathology reports of patients undergoing radical prostatectomy in 2015 were analyzed. Of these, 750 reports were randomly selected as training data and the remaining 750 reports were used as validation data. Using domain knowledge from clinical experts and Stanford treebank parser for German, rule based extraction algorithms were created for pathological staging, Gleason percentages, prostate dimension and laterality of the tumor by iterative review of misclassified reports until there are no longer any misclassified reports in the training data. Each number found in the reports was also verified by clinical experts. Results By applying the developed NLP system on the validation data, we assed the accuracy of each information extracted. The NLP derived accuracy for pT-stage, pN-stage, Gleason percentage, prostate weight, prostate volume and laterality of the tumour were 100%, 100%, 100%,100% and 97%, respectively. Conclusions We developed a novel NLP method that could extract detailed pathological information from a narrative, written pathological report with very high accuracy. This automated method can be implemented with the aim to greatly increase the efficiency and accessibility of research data in academic centers. Funding none
Authors
Sami-Ramzi Leyh-Bannurah
Zhe Tian Pierre Karakiewicz Dirk Pehrke Hartwig Huland Markus Graefen Lars Budäus |
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PD37-07 |
Treatment Trends for Metastatic Prostate Cancer Over the Last Decade: Insights from the National Cancer Database |
Prostate Cancer: Advanced (including Drug Therapy) II | 17BOS |
Abstract: PD37-07 Sources of Funding: None Introduction The incidence of metastatic prostate cancer has been increasing over the past decade. The landscape of treatment options has changed over this time period with the addition of new approaches to treatment, including the immunologic Sipuleucel-T (approved in 2010), and the chemotherapeutic agent Docetaxel, for which level 1 evidence for its first line use in hormone-sensitive disease became available in 2015. To our knowledge, there is no previous large scale study investigating the trends in management over the last 10 years, nor baseline utilization of newer agents. Methods The National Cancer Database (NCDB) was used to identify cases of metastatic prostate cancer, defined as cM1, between 2004-2014. No changes to diagnostic criteria of metastatic disease were made during this time period. To minimize reporting bias, only hospitals contributing at least one case per year for the entire decade were included. Treatments codes were categorized and compared between years of diagnosis. Descriptive statistics were performed in Stata. Results A total of 49,586 cases were included. The percentage of patients opting for surgical intervention as a care component (mostly palliative TURP) decreased over time, 12.7% in 2004 vs. 11% in 2014. Likewise, there has been a slight decrease in utilization of all forms of radiation therapy with 26.9% receiving radiotherapy in 2004 compared to 24.6% in 2014. The use of hormone therapy has increased 10% over the last decade (70.5% vs. 80.8%). Use of chemotherapy rose sharply over recent years but remains low. Single agent chemotherapy has increased from 3% in 2013 to 14% in 2014. Sipuleucel-T immunotherapy has seen modest use since its FDA approval in 2010, comprising <1% of patients in 2010, to 6.4% in 2014. Conclusions The treatment landscape for prostate cancer has changed dramatically over the last 10 years. Primary treatment plans are less likely to include radiation or surgical intervention, as one would expect given that local control is uncommonly recommended in the context of metastatic disease. The usage of hormone therapy continues to rise. Use of immunotherapy with Sipuleucel-T remained low at CoC accredited hospitals four years after its introduction. Possibly as a reflection of CHAARTED demonstrating benefit in high volume M1 disease, docetaxel use increased in 2014. Based on recent evidence supporting its first-line use for castrate sensitive M1 disease, we expect to see increased utilization going forward, with our study serving as a baseline for future comparison._x000D_ Funding None
Authors
Jared P. Schober
Kristian D. Stensland Karim Hamawy Alireza Moinzadeh David Canes |
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PD37-08 |
Enhancing the efficacy of Valproic Acid in prostate cancer cells with nutritional supplements |
Prostate Cancer: Advanced (including Drug Therapy) II | 17BOS |
Abstract: PD37-08 Sources of Funding: None Introduction The use of histone deacetylase inhibitors (HDACIs) in treating Castrate Resistant Prostate Cancer is well studied. We have previously published the beneficial effects of treating Bladder as well as Prostate cancer (CaP) in animal models with Valproic acid (VPA), a type I HDACI. Docosahexaenoic acid (DHA), an Ω-3 fatty acid, is a primary structural component of the human brain, skin, sperm, testicles and retina. Fish oil, a popular nutritional supplement, is a major source of DHA. Over two decades of research show favorable effects of DHA on bone health, as well as a chemo-sensitizing agent in treating cancer. Here we report an interim analysis of a randomized, controlled phase II study of VPA in patients with non-metastatic biochemical progression of (BCR) CaP, and the utility of combining DHA with VPA in potentially reducing side effects. Methods Patients with non-metastatic BCR CaP were screened for eligibility and randomized into either observation or VPA (oral, twice daily) arms. Serum VPA and PSA levels were monitored bi-weekly and monthly. We also investigated methods of minimizing the side effects of VPA while maintaining efficacy. Results Treatment with VPA resulted in an increased PSA doubling time (PSADT) in patients from 4.02 to 40.67 months, while the PSADT in the control group stayed relatively unchanged at 6.34 to 6.95 months. However, the treatment group suffered from debilitating fatigue and lethargy at the dose required for effective treatment. As such we investigated options of reducing the VPA dose while maintaining efficacy. Both in vitro and in a mouse model we demonstrate that combining VPA with DHA has a greater efficacy. In the in vitro model we show that in the combination we can reduce the dose of VPA by half and still maintain similar efficacy. Also chronic treatment with the combination had a much greater effect on cell kill as opposed to acute treatment. Moreover, folic acid, another common supplement, enhances cell kill by the combination. Conclusions Based on our studies VPA could be used in combination with DHA, a supplement, to delay or even prevent the use of hormone therapy in prostate cancer patients with BCR. In addition, both clinicians and patients should be made aware of the effects of dietary supplements, as they can positively or potentially negatively affect the efficacy of certain drugs. Funding None
Authors
Wasim H. Chowdhury
Anna-Barbara O'James Abhinav Sidana Jatindar Goyal Daniel Oh Grace I. Todd Mizanur Rahman Ronald Rodriguez |
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PD37-09 |
Identification of Epithelial to Mesenchymal Transition (EMT) Selective Cytotoxic Compounds in Prostate Cancer Cells |
Prostate Cancer: Advanced (including Drug Therapy) II | 17BOS |
Abstract: PD37-09 Sources of Funding: Andersen-Hebbeln Prostate Cancer Research Fund Introduction Metastasis, the major driver of mortality in advanced prostate cancer, starts in the prostate when cancer cells start to invade the surrounding stromal tissue. This first step may involve EMT characterized by the loss of epithelial characteristics and the gain of mesenchymal features. Thus, developing therapeutic compounds specifically targeting this process may provide a therapeutic opportunity. Methods In this study, we have developed a cell-based high-throughput screening protocol using the high content Operetta imaging platform to identify EMT cytotoxic compounds. A library of 2,640 compounds (Microsource) was screened on a co-culture of epithelial-like prostate cancer cells (PC3E GFP cells) and EMT-like prostate cancer cells (TEM 4-18 mCherry cells), both derived from the PC-3 cell line. After 72h exposure to compounds, relative numbers of GFP- and mCherry-positive cells were quantitated using the Operetta system. Dose-response curves were established for each compound exhibiting a greater toxicity against EMT-like cells. _x000D_ Results Among the compounds tested, monensin and salinomycin, both monovalent cation ionophores, exhibited a relatively greater toxicity against EMT-like cells. The highest potency and selectivity for the EMT-like cells was obtained with nigericin, another monovalent cation ionophore, followed by monensin and salinomycin. In addition to inducing apoptosis and a cell cycle arrest, monensin rapidly induced a swelling of golgi apparatus most likely resulting in a blockage of intracellular protein trafficking leading to cell death. In addition, we evaluated the toxicity of monensin in 24 cancer cell lines from different origins and classified them as resistant or sensitive. We analyzed publically available gene expression data and performed a Gene Set Enrichment Analysis to identify the gene sets differentially represented in the two groups. Supporting our hypothesis, the gene set involving EMT was enriched in the sensitive group. Conclusions In this study we identified monensin, salinomycin and nigericin as potent EMT-selective cytotoxic compounds. Understanding the mechanism-of-action of these compounds may lead to insight about the metastatic process and point to new therapeutic directions. Funding Andersen-Hebbeln Prostate Cancer Research Fund
Authors
Marion Vanneste
Qin Huang Meng Wu James Brown MIchael Henry |
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PD37-10 |
Biochemical Validation of Piperlongumine as a Potent Therapeutic Against Neuroendocrine Prostate Cancer |
Prostate Cancer: Advanced (including Drug Therapy) II | 17BOS |
Abstract: PD37-10 Sources of Funding: Deane Prostate Health, Icahn School of Medicine at Mount Sinai. Both Shalini S Yadav and Kamlesh K Yadav are supported by the Prostate Cancer Foundation Young Investigator Awards. Research in Dudley's lab is supported by grants from National Institutes of Health R01 DK098242 and U54 CA189201. Introduction Recent studies have highlighted the existence of a highly lethal and drug-resistant variant of prostate cancer (PCa) termed neuroendocrine prostate cancer (NEPC). We have used a genomics-based drug-repositioning approach to identify piperlongumine, a natural product constituent of the fruit of the Long pepper (Piper longum), as a potential therapeutic against NEPC. The efficacy of this drug was tested in the NEPC cell line model NCI-H660 and compared to several other PCa cell lines in a modified WST-1 assay. Pre-clinical testing in mouse xenograft models of NEPC was also undertaken. Finally, the ability of piperlongumine to inhibit p-STAT3 signaling and promote apoptosis in cell lines and extracted tumors were measured by western blot analyses. Methods PCa cell lines (LNCaP, 22Rv1, Du145, PC3, H660 and RWPE) were grown in complete media (RPM1 10%FBS, Advanced DMEM 5%FBS or Keratinocyte-SFM) and treated with piperlongumine for 3 or 7 days. IC50 values were generated from WST assay data using Prism6. Nude mice (n=5) were injected with 1.5x106 H660 cells on each flank, and intraperitoneally administered with either 2.5mg/kg piperlongumine (n=3) or DMSO (n=2) daily for 3 weeks after tumors formed 200mm3 in volume. Tumor volume was measured daily with calipers. Western blot analyses were performed on protein lysates extracted from tumors and PCa cells treated with 0-10 ?M of drug. Results Piperlongumine was highly effective in inhibiting the growth of H660 cells _x000D_ (IC50 = 0.4 ?M) compared to LNCaP, 22Rv1, Du145, PC3, and RWPE cells. On average, the growth rate of untreated tumors was 2.7 times greater than those treated was piperlongumine. Treated H660 cells exhibited significant inhibition of p-STAT3 and increases in cPARP1 levels while other cell lines displayed little to no fluctuation. _x000D_ Conclusions Using drug-repositioning approaches we have identified a lead compound that inhibits the growth of the highly drug-resistant NEPC cell line NCI-H660. Remarkably, piperlongumine happens to be a water-soluble plant product with no known side effects. Funding Deane Prostate Health, Icahn School of Medicine at Mount Sinai. Both Shalini S Yadav and Kamlesh K Yadav are supported by the Prostate Cancer Foundation Young Investigator Awards. Research in Dudley's lab is supported by grants from National Institutes of Health R01 DK098242 and U54 CA189201.
Authors
Kamlesh K Yadav
Khader Shameer Jennifer Stockert Cordelia Elaiho Benjamin Readhead Shalini S Yadav Joel Dudley Ashutosh Tewari |
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PD37-11 |
CHEK2 mutations increase risk for prostate cancer but do not differentiate risk of lethal from indolent disease |
Prostate Cancer: Advanced (including Drug Therapy) II | 17BOS |
Abstract: PD37-11 Sources of Funding: The study is partially supported by the National Key Basic Research Program Grant 973 of China (2012CB518301), the Key Project of the National Natural Science Foundation of China (81130047), PCW Fund, and the Rob Brooks Fund for Personalized Cancer Care at NorthShore University HealthSystem. Introduction A recent study published in the New England Journal of Medicine found that CHEK2 germline pathogenic mutations are associated with metastatic prostate cancer (PCa) risk. The objective of this study is to assess whether CHEK2 germline mutations differentiate risk of lethal from indolent PCa. Methods A retrospective case-case study of 261 patients who died of PCa and 352 patients with localized PCa of European American descent was conducted. Germline DNA from each of the 613 subjects was sequenced for DNA repair genes and cancer-related genes through whole exome sequencing (WES) or targeted sequencing. Mutations were annotated according to the American College of Medical Genetics guidelines. Results Among the 613 PCa patients in the study, 11 (1.79%) carried CHEK2 germline pathogenic mutations, which was significantly higher than the estimate from the general population (ExAC database: 0.61%, P<0.0001). However, the mutation carrier rate in lethal PCa patients (5/261=1.92%) was not significantly higher than either the localized cases in our study (6/352=1.70%, P=1.00) or in The Cancer Genome Atlas (2/406=0.49%, P=0.12). Among lethal cases, CHEK2 mutation carriers and non-carriers had similar mean age of death (77.0 and 73.0 years, respectively, P=0.72) and mean time to death (10.0 and 8.0 years, respectively, P=0.96). In the survival analysis of the entire study, CHEK2 mutations did not predict PCa-specific survival (Figure, log-rank P=0.86, comparing with non-carriers). In contrast, germline mutations of BRCA1/2 and ATM predicted worse PCa specific survival (all log-rank P<0.05, comparing with CHEK2 carriers and non-carriers). Conclusions CHEK2 germline mutations increase risk for PCa, but do not differentiate risk of lethal from indolent disease or PCa-specific survival. Funding The study is partially supported by the National Key Basic Research Program Grant 973 of China (2012CB518301), the Key Project of the National Natural Science Foundation of China (81130047), PCW Fund, and the Rob Brooks Fund for Personalized Cancer Care at NorthShore University HealthSystem.
Authors
S. Lilly Zheng
Rong Na Misop Han Kristian Novakovic Kathleen Wiley Sarah Isaacs Alan Partin Michael McGuire Patrick Walsh Charles Brendler Brian Helfand William Isaacs Jianfeng Xu |
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PD37-12 |
Evaluation of niclosamide as a potent inhibitor of androgen receptor variants to overcome resistance to abiraterone and enzalutamide in advanced prostate cancer |
Prostate Cancer: Advanced (including Drug Therapy) II | 17BOS |
Abstract: PD37-12 Sources of Funding: This work is supported in part by grants NIH/NCI CA140468, CA168601, CA179970, DOD PC130062, and US Department of Veterans Affairs, ORD VA Merits I01BX0002653, and by a Stand Up To Cancer—Prostate Cancer Foundation-Prostate Dream Team Translational Cancer Research Grant SU2C-AACR-PCF DT0812, made possible by the generous support of the Movember Foundation. Introduction Use of enzalutamide and abiraterone has improved treatment of advanced prostate cancer. However, development of resistance to these agents frequently occurs. Androgen receptor variants, particularly AR-V7, have been shown to drive resistance to abiraterone and enzalutamide. This study aimed to test whether niclosamide can overcome resistance and improve therapies by targeting androgen receptor variants. Methods Resistant prostate cancer cells to enzalutamide and abiraterone were generated by continuous culturing the cells in media containing increasing doses of either enzalutamide or abiraterone. Drug screening was conducted using luciferase activity assay to determine the activity of AR-V7 after treatment with the compounds in the Prestwick Chemical Library, which contains about 1120 FDA-approved drugs. The effects of the identified inhibitors on AR-V7 activity and abiraterone/enzalutamide sensitivity were characterized in CRPC and enzalutamide/abiraterone resistant prostate cancer cells in vitro and in vivo. Results Resistant prostate cancer cells to enzalutamide and abiraterone were generated, respectively. Both resistance cells express high levels of androgen receptor variants including AR-V7. Drug screening identified niclosamide, an anthelmintic agent approved by FDA for the treatment of tapeworm infections, as a potent AR-V7 inhibitor in prostate cancer cells. Niclosamide significantly decreased AR-V7 protein expression by protein degradation through a proteasome dependent pathway. Niclosamide also inhibited AR-V7 transcription activity and reduced the recruitment of AR-V7 to the PSA promoter. Niclosamide inhibited resistant prostate cancer cell growth in vitro and tumor growth in vivo. Furthermore, combination of niclosamide with either enzalutamide or abiraterone resulted in significantly inhibition of enzalutamide/abiraterone-resistant tumor growth. These results suggest that niclosamide enhances abiraterone/enzalutamide therapy and overcomes resistance to abiraterone/enzalutamide in castration resistant prostate cancer cells. Based on these preclinical studies, combination of niclosamide with abiraterone/enzalutamide trials are currently underway. Conclusions Niclosamide is a promising inhibitor of androgen receptor variants to treat advanced prostate cancer patients, especially those resistant to abiraterone or enzalutamide. Clinical trials with combination of niclosamide and abiraterone/enzalutamide are currently underway. Funding This work is supported in part by grants NIH/NCI CA140468, CA168601, CA179970, DOD PC130062, and US Department of Veterans Affairs, ORD VA Merits I01BX0002653, and by a Stand Up To Cancer—Prostate Cancer Foundation-Prostate Dream Team Translational Cancer Research Grant SU2C-AACR-PCF DT0812, made possible by the generous support of the Movember Foundation.
Authors
Chengfei Liu
Wei Lou Joy Yang Chong-Xian Pan Primo Lara Christopher Evans Allen Gao |
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PD38-01 |
Natural History and Predictors of Uretero-Enteric Strictures after Robot-Assisted Radical Cystectomy |
Trauma/Reconstruction/Diversion: Ureter (including Pyeloplasty) and Bladder Reconstruction (including fistula), Augmentation, Substitution, Diversion II | 17BOS |
Abstract: PD38-01 Sources of Funding: Roswell Park Alliance Foundation Introduction Uretero-enteric strictures of the (UES) represent the most common complication requiring reoperation after radical cystectomy. We sought to investigate the prevalence and predictors of developing UES after robot-assisted radical cystectomy (RARC). Methods We retrospectively reviewed our RARC database and identified patients who developed UES. Data was reviewed for demographics and perioperative outcomes. UES were further described in terms of their presentation, time to diagnosis, laterality, and management. Kaplan Meier method was used to compute time to UES and a logistic regression model was fit to evaluate and assess predictors of stricture development. Results Our database included 418 patients. Uretero-ileal complications were identified in 70 (17%): strictures 51 (12%); malignant obstruction 9 (2%); and leakage 10 (2%). Median time to UES following RARC was 5 months (IQR 2-12). UES occurred at a rate of 12%, 16% and 19% at 1, 3 and 5 years after RARC (Figure 1). Thirteen (25%) had bilateral strictures, 23 (45%) had right and 15 (29%) had left. Patients had an average of 2 interventions prior to successful management. Patients with UES had higher BMI (31 vs 28, p=0.02), received neoadjuvant chemotherapy (NAC) more frequently (36% vs 23%, p=0.05), received intra-corporeal diversion (ICUD) more often (84% vs 63%, p=0.004) and had shorter lengths of resected ureters (15 vs 20 mm, p=0.02; 15 vs 22 mm p<0.001, on the left and right sides respectively). They developed more urinary tract infections (UTI) (37% vs 12%, p<0.001) and postoperative urine leakage (10% vs 2%, p=0.02). Multivariable logistic regression revealed that BMI (OR=1.07, CI 95% 1.02-1.13, p=0.008), ICUD (OR=3.07, CI 95% 1.40-6.72, p=0.005), longer length of the right resected ureter (OR=0.69, CI 95% 0.53-0.89, p=0.004), year of RARC (2009-2012 OR 4.03, 95% CI 1.49-10.96, p=0.006; 2012-2016 OR 3.31, 95% CI 1.18-8.77, p=0.02), postoperative UTI (OR=4.27, CI 95% 2.23-8.18, p<0.001) and leakage (OR=4.64, CI 95% 1.46-14.81, p=0.009) were significantly associated with UES. Conclusions Multiple factors which can be modified were associated with higher incidence of UES following RARC. Funding Roswell Park Alliance Foundation
Authors
Youssef Ahmed
Ahmed Hussein Paul May Basim Ahmad Taimoor Ali Prasanna Kumar Khurshid Guru |
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PD38-02 |
Utilization of Indocyanine Green Fluorescence Angiography Prior to Intracorporeal Ureteroileal Anastomosis Following Robotic Radical Cystectomy |
Trauma/Reconstruction/Diversion: Ureter (including Pyeloplasty) and Bladder Reconstruction (including fistula), Augmentation, Substitution, Diversion II | 17BOS |
Abstract: PD38-02 Sources of Funding: none Introduction Ureteroileal strictures are diagnosed in 2-10% of patients following radical cystectomy and urinary diversion. Poor vascularity of the distal ureteric stumps is a well-known cause factor. Indocyanine-green (ICG) is an exogenous tracer that helps in assessing the vascularity of tissues. Herein, we report a proof-of-concept and our initial experience in using ICG prior performing intracorporeal ureteroileal anastomosis following robotic radical cystectomy (RRC). Methods From April to November 2016, the use of ICG was analyzed in 10 patients who underwent RRC with intracorporeal urinary diversion (IUD). Intravenous ICG (25mg) was administered prior to ureteroileal anastomosis and the non-enhanced distal ureters were excised prior to ureteric spatulation. Anastomosis was performed in routine manner with 4-0 vicryl sutures over ureteric stents. Results Among 10 patients who underwent to RRC-IUD (5 neobladders and 5 ileal conduits), ICG revealed poor distal ureteric enhancement in 7 patients (70%). Three (30%) patients required bilateral distal ureteral resection, three (20%) patients required left distal ureteral resection and one (10%) patient required right distal ureteral resection. Median resected ureteral length was 2 cm (1-4). Median operative time was 480 minutes (410-620), median EBL was 200 ml (100-650) and median hospital of stay was 5.5 days (3-9). Three patients experienced Clavien 2 complications (fever, n=2 and ileus, n=1). At a median follow-up of 81 days (7-198), no anastomotic strictures were identified. Conclusions Intravenous injection of ICG prior to ureteroileal anastomosis is a useful tool to evaluate distal ureter vascularity and to identify and excise the transition point of the non-vascularized ureteral segment. Longer follow-up is required to evaluate rates of anastomotic strictures. Funding none
Authors
Daniel MO Freitas
Toshitaka Shin Nariman Ahmadi Carlos Fay Andre Luis Abreu Masakatsu Oishi Giovanni Cacciamani Mihir Desai Inderbir Gill Andre Berger Monish Aron |
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PD38-03 |
Ureteroenteric anastomosis in orthotopic neobladder creation: Does perioperative UTI impact stricture rate? |
Trauma/Reconstruction/Diversion: Ureter (including Pyeloplasty) and Bladder Reconstruction (including fistula), Augmentation, Substitution, Diversion II | 17BOS |
Abstract: PD38-03 Sources of Funding: None Introduction Radical cystectomy and urinary diversion is the primary treatment of patients with muscle invasive bladder cancer, which is associated with peri-operative complication rates as high as 60%. Ureteroenteric anastomotic stricture (UEAS) is a potential source significant morbidity. The etiology of UEAS is thought be either due to ischemia or inflammation. We sought to evaluate our experience with benign UEAS in our orthotopic neobladder (ON) population. _x000D_ Methods We retrospectively reviewed the charts of patients who underwent radical cystectomy and ON between 2000-2015 at MD Anderson Cancer Center and had at least 6 months of follow up. We reviewed operative reports regarding the type of anastomosis (interrupted versus running), suture type (absorbable braided versus monofilament). In those patients with UEAS, we also evaluated for history of radiation therapy and urinary tract infection (UTI). _x000D_ Results A total of 418 patients underwent creation of ON. The average age was 59 (SD 9.4 years) and 90% were males. The mean follow up was 57 months (6-183 months). There were 37 patients (8.9%) that developed UEAS, 42 renal units. Figure 1 demonstrates the number of strictures diagnosed per year. The mean time to diagnosis was 15.8 months (0.85-90 months). Management included placement of a nephrostomy tube or stent in 47% of patients and 32% underwent revision of anastomosis; while one patient underwent nephrectomy and the remainder were not treated at our institution. UEAS occurred in 30 patients with an interrupted anastomosis and 4 had running anastomoses and 3 were unknown. We found that anastomosis type and suture type were not predictive of UEAS (p=0.594, p=0.586), but that perioperative UTI within 30 days of surgery and recurrent UTI were predictive of UEAS (OR 3.27 p=0.002, OR 7.06 p<0.001), while radiation was not significant (p=0.128). _x000D_ Conclusions UEAS are associated with potentially significant morbidity following ON creation. UEAS may occur early following urinary diversion, but may also occur as late as 7 years following surgery, owing to the importance for continued observation of these patients even into survivorship. Certainly, technical factors and surgeon experience may indeed contribute to the rate of UEAS, but it appears that perioperative UTI heralds future stricture development._x000D_ Funding None
Authors
Cooper Benson
Brittani Barrett-Harlow Kathryn Cunningham Yasmin Bootwala Clay Pendleton William Graber O. Lenaine Westney |
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PD38-04 |
Objectively defined urinary continence after radical cystectomy and ileal orthotopic neobladder: Effects on health-related quality of life |
Trauma/Reconstruction/Diversion: Ureter (including Pyeloplasty) and Bladder Reconstruction (including fistula), Augmentation, Substitution, Diversion II | 17BOS |
Abstract: PD38-04 Sources of Funding: none Introduction Comparability of current literature regarding the impact of stress urinary incontinence (SUI) outcomes after radical cystectomy (RC) and orthotopic ileal neoblader (ONB) on health-related quality of life (HRQOL) is impaired since definitions of continence vary and are usually based on subjective patient reports on pad usage. In addition, previous studies analysed women only, focused on particular subdivisions of HRQOL, or did not analyse the impact of assistive devices such as condom catheters and clean intermittent self-catheterization. In the current study, we correlate objectified and detailed continence outcomes with HRQOL after ONB. Methods Questionnaires were sent to 244 patients who underwent RC with ONB diversion between 2004 and 2015, and information about the current continence status was retrieved. To objectify postoperative urine loss, daytime and nocturnal pad tests were performed. Continence was also assessed using the validated ICIQ-SF score. Continence was defined as need of up to one safety pad and urine loss of <10g per pad test. HRQOL was assessed using the validated EORTC QLQ-C30 score. Statistical analysis included Fisher test, Mann-Whitney-U test, Spearman rank correlation, and binary regression models (p<0.05). Results 178 patients (73.0%) answered the QLQ-C30 questionnaires and were included in the study. Median follow-up was 61 months. Median daytime pad use was 1 and median daily urine loss based on pad testing was 4.0g, leading to a daytime continence rate of 48.5%. The mean daily urine loss based on 24hrs pad testing correlated significantly with decreased physical functioning (R=-0.355, p<0.001), and global health status (R=-0.282, p<0.001). Continence success had a significant impact on postoperative global health status (p=0.017). In addition, we found a significantly decreased global health status for patients using a condom catheter (p=0.049) and patients suffering from pollacisuria (p=0.001). Patients who had performed pelvic floor muscle training had a significantly better global health status (p=0.035). In multivariate analysis, only ICIQ-SF score (p=0.001, OR=0.805) and need for condom catheters (p=0.015, OR=0.123) were independent predictors for worse HRQOL outcomes based on global health status. A history of pelvic floor muscle training was an independent predictor of increased HRQOL (p=0.009, OR=10.459). Conclusions This is the first study to correlate objective continence outcomes with HRQOL after RC and ONB. Need of condom catheters and increased ICIQ-SF scores are independent predictors for worse HRQOL outcomes. Furthermore, we show significant beneficial effects of pelvic floor muscle training on patients HRQOL. Funding none
Authors
Alexander Kretschmer
Tobias Grimm Alexander Buchner Markus Grabbert Maria Apfelbeck Birte-Swantje Schneevoigt Friedrich Jokisch Gerald Schulz Ricarda M. Bauer Christian G. Stief Alexander Karl |
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PD38-05 |
Predictors of Urinary Retention after Radical Cystectomy and Orthotopic Neobladder |
Trauma/Reconstruction/Diversion: Ureter (including Pyeloplasty) and Bladder Reconstruction (including fistula), Augmentation, Substitution, Diversion II | 17BOS |
Abstract: PD38-05 Sources of Funding: None Introduction To investigate the prevalence of urinary retention in male bladder cancer patients who underwent radical cystectomy and orthotopic neobladder (NB) and to identify potential predictors of retention, if any. Methods Using an IRB approved, prospectively maintained database, we identified 265 males who underwent radical cystectomy with NB at our institution from 3/2000 to 6/2015 and completed post operative questionnaires regarding catheterization. The mean age at surgery was 65.7 years and mean BMI was 27.42. Univariate logistic analysis was performed for potential predictors of catheterization and urinary retention. Retention was defined as 3 or more catheterizations per day or self-reported inability to void without catheterizing. Results The need to catheterize at all was noted in 33 of 265 (12.4%) patients. Of these, 11 (4.2% of the total) were determined to be in retention or required catheterization to void. Data regarding the number of catheterizations per day was available in 32 of these patients (Table 1). Univariate analysis showed that increasing BMI significantly predicted the need for catheterization (p = 0.009, coefficient = 0.097). Diabetes and moderate-to-severe renal disease approached significance (p-value = 0.075 and 0.09, respectively), but there were otherwise no significant predictors of the need to catheterize. Additionally, no significant predictors of urinary retention were found (Table 2). Conclusions In males undergoing radical cystectomy with NB, retention requiring catheterization to void is uncommon. In this large cohort, the rate of any catheterization at all was 12.4%, of which a small fraction (4.2%) had complete urinary retention. BMI was found to significantly correlate with the need to catheterize, but age, medical comorbidities, pathologic stage, and receiving neoadjuvant chemotherapy did not have significant correlations with urinary retention. Larger power studies are required to further evaluate these predictors. Funding None
Authors
Saum Ghodoussipour
Jacob Lifton Gus Miranda Sumeet Syan-Bhanvadia Siamak Daneshmand |
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PD38-06 |
Cystectomy and Urinary Diversion for Benign Disease: Patient Characteristics and Predictors of Post-Operative Outcomes from a Contemporary National Cohort |
Trauma/Reconstruction/Diversion: Ureter (including Pyeloplasty) and Bladder Reconstruction (including fistula), Augmentation, Substitution, Diversion II | 17BOS |
Abstract: PD38-06 Sources of Funding: none Introduction We expand our knowledge on the risks of cystectomy and urinary diversion for benign disease by analyzing 30-day morbidity, readmission, mortality, and predictors of adverse outcomes in a multi-center, prospectively maintained, outcomes based clinical cohort. Methods This is an analysis of data obtained from academic and community medical centers during the years of 2007 to 2015 through the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP). The study population consists of patients who underwent cystectomy with urinary diversion for benign disease. Patients were identified based upon their primary CPT code as well as documented ICD-9 codes. The primary outcome was a composite 30-day morbidity measure which includes mortality, readmission, return to the operating room, sepsis, transfusion, wound compilations, deep vein thrombosis, pulmonary embolism, renal failure and prolonged mechanical ventilation. Results We identified 405 patients who underwent cystectomy for benign disease. 246 (60.7%) patients experienced morbidity within 30 days following surgery. Overall mortality was 1.5%. 20.8% were readmitted within 30 days after surgery. Furthermore, 31.1% required transfusion, 14.3 % had sepsis or septic shock and 4.4% required a return to the operating room. Bivariate analysis demonstrated that operative time was a significant predictor of major morbidity (p 0.0009), as well as post-operative length of stay (p 0.0051). Other predictors of morbidity included smoking (p 0.0113), and hematocrit <30 (p 0.0210). Predictors for post-operative length of stay included functional dependence (p 0.0091), albumin <3 (p 0.0184), and pre-op weight loss >10% (p 0.0307). Conclusions Patients undergoing cystectomy and urinary diversion for benign disease experienced post-operative morbidity at a high rate with over 60% of patients encountering some form of complication. Smoking, anemia, and longer operative times were associated with increased morbidity. Poor nutrition, poor functional status, weight loss and longer operative times were associated with longer length of stay after surgery. These results illuminate potential modifiable risk factors for improving outcomes and decreasing cost. Funding none
Authors
Scott Erpelding
Adam Dugan Andrew James Stephen Strup Shubham Gupta |
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PD38-07 |
Robot-assisted intracorporeal right colon continent cutaneous urinary diversion and augmentation cystoplasty: A single institution experience |
Trauma/Reconstruction/Diversion: Ureter (including Pyeloplasty) and Bladder Reconstruction (including fistula), Augmentation, Substitution, Diversion II | 17BOS |
Abstract: PD38-07 Sources of Funding: None Introduction Continent cutaneous diversion (CCD) is a less commonly utilized diversion choice following open or robotic cystectomy. We have previously described a novel technique for robotic intracorporeal CCD. Meanwhile, continent cutaneous augmentation cystoplasty (CCAC) is a viable option for patients with neurogenic bladder. There is limited worldwide experience performing intracorporeal CCD and no studies describing intracorporeal CCAC. Principles developed in robotic CCD can be readily applied to robotic CCAC. We share our experience with these novel robotic procedures. Methods Robotic cystectomy was performed in patients undergoing CCD using a standard 6-port technique. The patient and robot were then repositioned for intracorporeal bowel mobilization and segmentation, ileocolonic anastomosis, uretero-colonic anastomoses, pouch construction, tapering of catheterization channel, reinforcement of ileocecal valve, and stoma creation. All patients were placed on an evidence-based Enhanced Recovery after Surgery protocol postoperatively. Operative times, intraoperative blood loss (EBL), length of stay (LOS), and complications occurring within 90 days of surgery were reviewed. Results Ten robotic intracorporeal right colon urinary diversions, including four robotic intracorporeal CCAC and six robotic intracorporeal CCD, were performed. Mean total operative times for cystectomy and intracorporeal urinary diversion were 7.8 and 10 hours for CCAC or CCD respectively (5.4-9.5; 7.9-12.9). Mean EBL was 181ml (75-300) for CCAC and 250ml (100-500) for CCD. Mean LOS for CCAC and CCD groups was 10 and 8.8 days respectively (5-18, 4-18). A single CCAC patient required transfusion postoperatively. Two high grade complications (Clavien III or greater) were reported in the CCAC group (50%). One high grade complication was reported in the CCD group (17%). Within 30 days of surgery, no CCAC and two CCD patients required readmission (0%, 33%). With a median follow up of 17 months, no incontinence was reported and all patients were able to catheterize without difficulty. Conclusions We demonstrate that robotic intracorporeal CCD and CCAC are technically feasible and safe with good functional outcomes. Further evaluation of these novel surgical techniques along with comparative studies are needed. Funding None
Authors
Spencer Craven
John Sigalos Rose Khavari Alvin Goh |
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PD38-08 |
Does the use of recreational Ketamine pose a challenge on bladder reconstructive surgery? |
Trauma/Reconstruction/Diversion: Ureter (including Pyeloplasty) and Bladder Reconstruction (including fistula), Augmentation, Substitution, Diversion II | 17BOS |
Abstract: PD38-08 Sources of Funding: none Introduction Regular use of recreational ketamine causes severe damage to the urinary tract. Patients present with a spectrum of debilitating symptoms including pain, urinary frequency, haematuria and renal failure. _x000D_ _x000D_ The aim of this study was to evaluate management strategies and outcomes in patients undergoing surgical intervention following damage to their urinary tract associated with ketamine use. _x000D_ Methods A retrospective review of prospectively collected data between 2007 and 2015 was performed. Evaluation included CT urogram, cystoscopic evaluation of bladder capacity +/- biopsy. Indications and outcomes for surgical intervention were assessed. Results 42 patients were identified. 63% were male and mean age at presentation was 28.7 (range 23-55). All bladder biopsies confirmed an eosinophilic inflammatory infiltrate. A significant proportion of patients (83.3%) were found to have reduced cystoscopic and functional bladder capacity of <300 ml (mean 190 mls, range 70-550). _x000D_ _x000D_ 29 patients were treated conservatively with a view to symptom resolution. 2 patients underwent dilatation for urethral strictures. 4 patients underwent repeated intra-detrusor onabotulinum toxin injection with minimal subjective symptom relief. 2 of these patients proceeded to have major reconstruction._x000D_ 13 patients underwent reconstruction which included simple cystectomy (5/13), substitution cystoplasty (6/13), augmentation cystoplasty (6/13), ileal conduit diversion (1/13), ureteric interposition using ileum (2/13) and appendix Mitrofanoff formation (6/13). Of these patients 53.8% (7/13) had one or more complications requiring additional intervention _x000D_ _x000D_ Complications included urine leak (1/7), anastomotic leak (2/7), adhesional small bowel obstruction (1/7), wound necrosis (1/7), ureteric stricture (3/7) and Mitrofanoff stenosis (1/7). One patient was lost to follow up and there was 1 death from pneumonia 5 years following and unrelated to surgery. _x000D_ Conclusions In a tertiary, high volume reconstructive unit we found ketamine patients seemed to be at particular risk of significant peri-operative complications. There did not appear to be any other common factor apart from their use of ketamine and the significant inflammatory change associated with its misuse. _x000D_ _x000D_ We therefore recommend meticulous pre-operative evaluation and multidisciplinary consultation for all patients to determine optimal treatment strategies prior to undertaking major bladder reconstructive surgery. _x000D_ Funding none
Authors
Neha Sihra
Simon Rajendran Jeremy Ockrim Dan Wood |
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PD38-09 |
PROSPECTIVE EVALUATION OF CONTINENCE FOLLOWING OPEN RADICAL CYSTECTOMY AND ORTHOTOPIC URINARY DIVERSION AND THE EFFECT OF PELVIC FLOOR PHYSICAL THERAPY |
Trauma/Reconstruction/Diversion: Ureter (including Pyeloplasty) and Bladder Reconstruction (including fistula), Augmentation, Substitution, Diversion II | 17BOS |
Abstract: PD38-09 Sources of Funding: None Introduction We evaluated the continence outcomes in patients undergoing orthotopic neobladder (ONB) diversion following radical cystectomy (RC) using validated pad usage questionnaires and in a subgroup who underwent pelvic floor physical therapy (PFPT). Methods Under IRB approval, we identified 1269 patients that underwent open RC from 2002 to 2015 (ONB 74%, 85% male). From 2012, patients were prospectively followed with a validated, pictorial pad usage questionnaire. A subgroup of patients received PFPT as an intervention to assist their continence. Interventions focused on improving pelvic floor muscle strength and coordination. Manual, visual and surface EMG biofeedback training were incorporated to improve neuromuscular re-education of the pelvic floor as well as behavioral modifications for bladder re-training, timed voiding and general bladder and bowel health. Frequency of visits started from 1x/week over 4-6 sessions, and longer thereafter._x000D_ Results A total of 153 male patients with available pad usage questionnaires were followed from September 2012 to August 2015. Daytime continence rates increase from 59% at <3 months to 92% by 12-18 months postoperatively. Nighttime continence rates increased to 51% by 18-36 months postoperatively. Overall catheterization rate was 13.1%. 17 patients underwent PFPT during this period, with a median age of 70 yrs. There was no significant difference between groups for age, BMI, or Charlson comorbidity index. Univariate analysis showed there is a shorter median time to first daytime continence in PFPT group compared to non-intervention group (89 days vs 182 days respectively; p=0.06), while this was not significant for the nighttime continence (median 134 vs 311; p=0.12). Kaplan Meier curves also showed higher continence rates in PFPT group at 1 year (0.710.13) compared to non-PFPT ones (0.60.04), although the difference was not significant (p=0.25) (figure 1)._x000D_ Conclusions Following ONB, continence improves significantly by 6 months, and plateaus with 92% of patients achieving daytime continence by 12-18 months. Those who received PFPT tend to have faster return to daytime continence in the first year. Further research with bigger sample size is needed to support the value of PFPT in continence after RC and ONB. Funding None
Authors
Soroush Bazargani
Thomas Clifford eileen Johnson Kevin Wayne Gus Miranda Jie Cai Hooman Djaladat Anne Schuckman siamak Daneshmand |
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PD38-10 |
Factors Influencing Intraoperative Conversion from Planned Orthotopic to Non-Orthotopic Urinary Diversion During Radical Cystectomy |
Trauma/Reconstruction/Diversion: Ureter (including Pyeloplasty) and Bladder Reconstruction (including fistula), Augmentation, Substitution, Diversion II | 17BOS |
Abstract: PD38-10 Sources of Funding: None Introduction The decision to perform continent orthotopic neobladder (NB) versus non-continent ileal conduit (IC) or continent cutaneous diversion (CCD) at the time of radical cystectomy requires thorough preoperative planning and counseling. Still, preconceived plans may change due to unforeseen intraoperative challenges. Herein, we investigate factors that contribute to this change in plan. Methods Using an IRB approved, prospectively maintained database, we identified 711 patients with bladder cancer who underwent radical cystectomy from 2002 to 2015. Of these, 392 were consented on the day of surgery to NB as their first choice of urinary diversion. 348 patients ultimately received NB while 38 received IC and 6 CCD. We compared those who received NB after being offered such on initial consultation with those who received either IC or CCD to determine factors that may have been involved in the decision. Results Factors for intraoperative change in plan are listed in Table 1. On statistical analysis, patients who ultimately received NB were significantly more likely to have organ confined disease (p=0.005), lower ASA score (p=0.006) and to undergo an open surgical approach (p=0.011) (Table 2). Conclusions The factors influencing the choice of urinary diversion in patients undergoing radical cystectomy are complex. Oncologic, metabolic, and technical factors must be weighed along with patient preference on initial consultation. We found that amongst those consented for NB, those with organ confined disease, lower ASA score and those undergoing an open approach, were more likely to ultimately receive a NB. As plans may require change intraoperatively, a more clear understanding of the factors involved will improve shared decision making in the future. Funding None
Authors
Natalie Hartman
Nariman Ahmadi Saum Ghodoussipour Giovanni Caccamani Daniel Melecchi Freitas Carlos Fay Toshitaka Shin Andre Berger Mihir Desai Siamak Daneshmand |
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PD38-11 |
Kidney transplantation in patients with bladder augmentation : long term outcomes |
Trauma/Reconstruction/Diversion: Ureter (including Pyeloplasty) and Bladder Reconstruction (including fistula), Augmentation, Substitution, Diversion II | 17BOS |
Abstract: PD38-11 Sources of Funding: None Introduction The aim of this study was to assess the results of kidney transplant (KT) in patients with bladder augmentation (BA). Methods Between 1988 and 2015, 64 patients with BA (3 after KT) underwent kidney transplantation, due to significant lower urinary tract dysfunction. There were 40 males and 24 females. Ten second and 1 third KT were performed, comprising 75 KT in 64 patients. 44 were from living donor and 31 from deceased donor. Mean age at first KT was 22.54±15.09 (3-64) years and mean age at first bladder augmentation was 18.31 ± 13.83 (2-64) years. The etiology of bladder dysfunction was neurogenic bladder due to spina bifida (23 patients), posterior urethral valve (12 patients), vesico-urethral reflux (6 patients), tuberculosis (8 patients) and other causes (14 patients).The bowel segments used in the augmentation included ileum in 45(70.3%) patients, ileocecal in 3(4.7%) patients and sigmoid in 4(6.3%) patients. The ureter was used in 12 (18.8%) patients. Redo BA was performed in 4 patients (1 ureterocistoplasty and 3 ileocistoplasty), all after ureterocistoplasty. In 2 patients, it was performed before the first kidney transplant. Results Mean follow-up after first BA was 172.47 ±112,07 (11-522) months. Overall patient survival was 77.6% and actuarial graft survival at 1,2,5,7,9 and 10 years was 92%, 87.6%, 81.2%, 67.8%, 65.7% and 53.9%, respectively. Surgical complications included 1 vesicocutaneous fistula and 1 stenosis of ureteral reimplant. 51(79.7%) patients were in clean intermittent catheterization. Symptomatic or febrile urinary tract infections (UTI) occurred at least 1 episode in 79.3% of patients. Ten (62.5%) patients died of unrelated cause and 6 (37.5%) patients died due to related causes. The main cause of graft loss was chronic allograft nephropaty in 21 (77.7%) patients. Conclusions Augmentation cystoplasty is a safe and effective treatment for lower urinary dysfunction. Patients must be followed up closely with special attention to UTIs. Survival graft after 10 years seems to similar to regular KT recipients. Funding None
Authors
Kleiton Yamaçake
Affonso Piovesan Renato Falci Gustavo Messi Ioannis Antonopoulos Flavio Jota de Paula Rafael Locali Elias David-Neto William Nahas |
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PD38-12 |
The Effect of Radiotherapy on the Outcome of the Repair of Urorectal Fistulae |
Trauma/Reconstruction/Diversion: Ureter (including Pyeloplasty) and Bladder Reconstruction (including fistula), Augmentation, Substitution, Diversion II | 17BOS |
Abstract: PD38-12 Sources of Funding: none Introduction Urorectal fistulation is an uncommon consequence of a number of problems but particularly after the treatment of prostate or rectal cancer. Where there is little doubt that post-surgical fistulae can be repaired with satisfactory results, the impact of radiotherapy on the outcome of fistula repair is controversial. Herein we review our experience. Methods We have repaired 127 urorectal fistulae in the last 10 years with a minimum of one year of follow-up. 24 patients have died or have been lost to follow-up leaving 41 patients who had an abdomino-perineal repair and 62 patients who had a transperineal repair - 103 patients in all. _x000D_ _x000D_ Of the 41 patients having an abdomino-perineal repair, 37 (90%) had had radiotherapy, or the combination of radiotherapy and surgery. Only 4 (10%) patients had a surgical cause of their fistula (NB these patients do not include patients with vesico-colic fistulae or other intra-abdominal fistulae). In the transperineal group 18 had had previous radiotherapy (29%) and the remaining 44 were purely post-surgical fistulae (71%). The principle implication for an abdomino-perineal repair is to deal with sepsis in the pre-sacral space or to deal with radiotherapy problems affecting the bladder or otherwise for omental wrapping of any repair._x000D_ Results After a tansperineal repair there were 5 failures in each of the two groups. All 10 failures underwent an abdomino-perineal repair subsequently with a satisfactory outcome in 4 out of 5 in each group. The overall success rate of transperineal repair, therefore, is in excess of 95%. _x000D_ After abdomino-perineal repair the success rate in both groups was in excess of 90% in both the surgical and the irradiation group. _x000D_ Conclusions 91% of patients with post-surgical fistulae can be treated by transperineal surgery with a 98% success rate. Only 31% of post-irradiation patients can be treated transperineally. The other 69% will require an abdomino-perineal repair and both approaches are only suitable in carefully selected patients, although the results are satisfactory in 95%. Although the overall success rate is satisfactory, the postoperative morbidity of post-irradiation patients undergoing abdomino-perineal surgery is high (62%), the recovery is protracted and the return to functional normality prolonged. Funding none
Authors
Stella Ivaz
Simon Bugeja Stacey Frost Mariya Dragova Daniela E Andrich Anthony R Mundy |
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PD39-01 |
Low incidence of clean intermittent catheterization with onabotulinumtoxinA in diverse age groups of overactive bladder patients with substantial improvements in treatment response |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Non-neurogenic Voiding Dysfunction III | 17BOS |
Abstract: PD39-01 Sources of Funding: Allergan plc Introduction The potential need for clean intermittent catheterization (CIC) is known to increase in overactive bladder (OAB) patients (pts) after onabotulinumtoxinA (onabotA) treatment. We determined the risk of CIC, and efficacy and quality of life (QOL) outcomes after treatment with onabotA in different age groups in a post hoc analysis of a large cohort of OAB pts. Methods Data from two onabotA randomized, placebo-controlled phase 3 trials and a post-marketing study were pooled for analysis (N=1177). Pts treated with onabotA 100U in treatment 1 and placebo pts who received open-label onabotA in treatment 2 were grouped by age: <40 (n=90), 40-49 (n=156), 50-59 (n=263), 60-69 (n=343) and ≥70 (n=325) years. Assessments at week 12 after treatment were: incidence and duration of CIC, mean and % change from baseline (BL) in urinary incontinence (UI) episodes, proportions of pts with ≥50% UI reduction, positive response (urinary symptoms 'improved'/'greatly improved') on the treatment benefit scale (TBS), and change from BL in Kings Health Questionnaire (KHQ) Social Limitations and Role Limitations domains. Adverse events (AEs) were assessed. Results CIC rates after onabotA treatment were lowest in the <40 group (1.1%) and increased slightly with age (3.2%, 5.3%, 5.3% and 7.2% in the 40-49, 50-59, 60-69 and ≥70 groups, respectively). Mean (median) CIC duration in the <40 and 40-49 groups was 3 (3) and 44 (26) days and ranged from 78 (68) to 88 (74) days in the other groups. Mean UI episodes/day at BL were 3.9, 4.8, 5.2, 5.7 and 6.0 in the <40, 40-49, 50-59, 60-69 and ≥70 groups. A robust treatment response was noted in all groups including substantial reductions in UI episodes/day (-2.4, -2.6, -3.1, -3.6 and -2.9) and % change in UI (-60.8%, -50.4%, -62.4%, -64.4% and -46.8%). High proportions of pts in all groups achieved ≥50% UI reduction (range: 58.2%-71.1%), a positive TBS response (range: 66.2%-73.8%) and improvements from BL in KHQ domain scores ~3-6x the minimally important difference (-5 points). Urinary tract infection was the most common AE in all groups. Conclusions In this large cohort of onabotA-treated OAB pts, CIC risk increased slightly with age but was low in all age groups and accompanied by substantial reductions in UI, improvements in QOL and treatment benefit. The <40 group had the lowest rate of CIC (1.1%) with a duration of 3 days. OnabotA was well tolerated in all age groups. Funding Allergan plc
Authors
Victor Nitti
Eric Rovner Marcus Drake Karel Everaert Sidney Radomski Christopher R. Chapple David Ginsberg Tamer Aboushwareb Cheng-Tao Chang Roger Dmochowski |
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PD39-02 |
THE IMPACT OF DETRUSOR UNDERACTIVITY ON PATIENT SATISFACTION AFTER HOLMIUM LASER ENUCLEATION OF THE PROSTATE: A PROSPECTIVE STUDY |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Non-neurogenic Voiding Dysfunction III | 17BOS |
Abstract: PD39-02 Sources of Funding: None. Introduction Detrusor underactivity is a common clinical problem associated with various lower urinary tract symptoms (LUTS). Impaired bladder contractility can affect the outcome of transurethral prostatectomy. The aim of this study is to evaluate the impact of bladder contractility on outcomes of Holmium laser enucleation of the prostate (HoLEP) in objective and subjective parameters. Methods From December 2009 to December 2015, 797 patients with LUTS/BPH were prospectively enrolled in the Seoul National University Benign Prostatic Hyperplasia Database Registry, and underwent HoLEP by a single surgeon. Preoperative evaluation included International Prostate Symptom Score (IPSS), Overactive Bladder Symptom Score (OABSS), urgency perception scale (UPS), PSA, postvoid residual volume (PVR) and urodynamic study. At postoperative 6 months, IPSS, OABSS, uroflowmetry, PSA and self-administered questionnaires regarding satisfaction to treatment questions (STQ), overall response assessment (ORA) and willingness to undergo the surgery again question (WUSAQ) were obtained. Bladder contractility was classified as weak, normal and strong according to the bladder contractility index (BCI) of <100, 100-150 and >150. Detrusor underactivity (DUA) was defined as BCI<100. Subjective and objective parameters were compared according to the degree of contractility. Results Among 768 patients, 351 (45.7%) had DUA and 63 (7.9%) had strong contractility. Mean age, preoperative IPSS, QoL, Qmax and prostate volume were 69.3 years, 19.2, 4.2, 9.2mL/sec and 70.8mL, respectively. Patients having stronger bladder contractility tended to be younger, have larger prostate volume, higher preoperative OABSS, UPS, bladder outlet obstruction index and larger PVR with significant tendency according to the contractility. However, preoperative Qmax and IPSS were not different among 3 groups. At postoperative 6 months, Qmax, IPSS voiding and QoL were significantly improved as the degree of contractility increases, whereas OABSS, PVR and UPS were not different among 3 groups. Overall, 93.9% of patients were satisfied after the surgery and 99.0%, 94.2% of patients reported improvements and willingness in ORA and WUSAQ, respectively. Patient satisfaction were not different by the degree of contractility. Multiple logistic regression analysis showed that the history of neurologic disease (OR 0.23; 95% CI 0.10-0.50, p<0.001) was the only risk factor for decreased satisfaction. Conclusions Patients having DUA tended to have less improvement in voiding symptoms postoperatively than those without DUA. However, patient satisfaction were not affected by the degree of bladder contractility. Funding None.
Authors
Young Ju Lee
Chu Hong Park Chihyun Ahn Bum Sik Tae Seung-June Oh |
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PD39-03 |
Urodynamic analysis of the impact of diabetes mellitus on bladder function. |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Non-neurogenic Voiding Dysfunction III | 17BOS |
Abstract: PD39-03 Sources of Funding: None Introduction We retrospectively analyzed urodynamic data in patients with diabetic mellitus (DM) to assess diabetic cystopathy. Methods Subjects included male DM patients who had a pressure flow study (PFS) in our institution from April 2005 to October 2016. Patients with prostate volume < 30 ml; no previous history of neurological disorder, prostate cancer, or pelvic surgery; no current urinary medication; and bladder outlet obstruction index < 40 were included. Bladder dysfunction was categorized into the following urodynamic patterns: (a) normal: bladder contractility index (BCI) > 100 without detrusor overactivity (DO); (b) DO: BCI > 100 with DO; (c) detrusor hyperreflexia/impaired contractility (DHIC): BCI ≤ 100 with DO; and (d) detrusor underactivity (DU): BCI ≤ 100 without DO. Urodynamic patterns were evaluated based on the presence of diabetic retinopathy (DR) and nephropathy (DN), which tend to be dependent on DM duration. Linear and multiple regression analyses were performed to investigate the relationship between clinical factors and urodynamic parameters. Results Fifty patients (mean age 66 ± 8 years, DM duration 7 ±1 years) were enrolled. Twenty patients without DR or DN showed 5 normal (25%), 4 DO (20%), 4 DHIC (20%), and 7 DU (35%) patterns on PFS; 17 patients with DR but no DN showed 2 normal (11.7%), 9 DHIC (52.9%), and 6 DU (35.2%) patterns; 13 patients with DR and DN showed 3 normal (23.0%), 3 DHIC (23.0%), and 7 DU (53.8%) patterns. Univariate analysis indicated that DM duration, hemoglobin A1c (HbA1c) level, and DR were significantly negatively correlated with BCI (r2 = 0.13, p = 0.02; r2 = 0.11, p = 0.03; r2 = 0.28, p = 0.001, respectively). Multivariate analysis also revealed that DM duration, HbA1c level, and DR were significantly negatively correlated with BCI (r2 = 0.44, p = 0.04, p = 0.02, and p = 0.02, respectively). Furthermore, univariate and multivariate analyses showed that first desire volume (FDV) was significantly positively correlated with post-void residual (PVR) urine (r2 = 0.49, p < 0.001 and r2 = 0.63, p < 0.001) and voiding efficiency (r2 = 0.14, p < 0.001 and r2 = 0.63, p < 0.001). In addition, maximum cystometric capacity (MCC) was significantly positively correlated with PVR (r2 = 0.28, p < 0.001). However, FDV and MCC were not significantly associated with other urodynamic parameters, including BCI. Conclusions Our study indicated that DM patients had diverse progressive bladder dysfunction patterns. Moreover, impaired bladder sensation increased PVR independent of detrusor contractility. Funding None
Authors
Tsuyoshi Majima
Yoshihisa Matsukawa Yasuhito Funahashi Tokunori Yamamoto Momokazu Gotoh |
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PD39-04 |
Sacral Neuromodulation for detrusor hyperactivity with impaired contractility |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Non-neurogenic Voiding Dysfunction III | 17BOS |
Abstract: PD39-04 Sources of Funding: None Introduction Detrusor hyperactivity with impaired contractility (DHIC) is a challenging condition to manage. Sacral neuromodulation (SNM) is a proven treatment modality for both the individual aspects of DHIC. To date, reporting the effect of SNM on a DHIC cohort of patients is lacking. Methods Consecutive patients undergoing SNM for DHIC were followed prospectively, from April 2013 to October 2016. Patient demographics, bladder diaries, subjective response rates, ICIQ-OAB and PGI-I scores were recorded. Success was defined as greater than 50% symptom improvement in urgency, urge incontinence, and a greater than 50% improvement in voided volume or reduction of post-void residual volumes. Results Twenty patients underwent stage 1 trial of SNM. Average age was 68.5 years, IQR (54.25 -76.25). 13 (65%) patients were female. 13/20 (65%) of patients had a response to the detrusor overactivity component. 10/20 (50%) of patients showed an improvement in the voiding component. 9/20 (45%) of patients showed responses to both components. 6/20 (30%) patients had no response whatsoever. Overall, 12/20 (60%) patients proceeded to insertion of an IPG. At follow up of 17 months, IQR (1.5 – 35), 11/12 (91.7%) of patients were still using the SNM device, median PGI score was 2, IQR (2 – 4). In addition, SNM resulted in statistically significant improvement in voided volume (p=0.016), PVR (p=0.0296), ICIQ-OAB score (p<0.0001) and ICIQ-OAB bother score (p=0.016). Conclusions SNM is a potential treatment option for DHIC with an acceptable success rate, treating both the detrusor hyperactivity, and impaired contractility components of this condition. Funding None
Authors
Derek Hennessey
Nathan Hoag Johan Gani |
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PD39-05 |
FACTORS OTHER THAN URGENCY, FREQUENCY AND INCONTINENCE CONTRIBUTING TO PERCEPTION OF CONDITION SEVERITY IN OVERACTIVE BLADDER |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Non-neurogenic Voiding Dysfunction III | 17BOS |
Abstract: PD39-05 Sources of Funding: none Introduction Perception of bother in patients with overactive bladder (OAB) principally contributes to its impact on quality of life, however etiology and contributing lower urinary tract symptoms (LUTS) may differ among patients. We aimed to identify factors associated with perception of condition severity in a population of women with OAB. Methods Women self-identifying lower urinary tract symptoms (LUTS) were invited to participate in an anonymous online survey. Women scoring 4 or above on a 3-item OAB screening tool (OAB-V3) without a history of neurologic condition, pelvic radiation or intestinal diversion were eligible. Participants were grouped based upon a Patient Perception of Bladder Condition score ≤3 (&[Prime]low PPBC&[Prime]) or ≥4 (&[Prime]high PPBC&[Prime]). Statistical comparisons between groups centered on demographic and clinical factors. Multivariate analysis controlling for traditional OAB symptoms assessed the contributions of non-OAB factors on PPBC. Results 125 women with mean age 41.3 ± 13.5 years comprised the study population. 82 (66%) reported low PPBC and 43 (34%) high PPBC. The groups were similar with respect to age, demographic factors, and reported clinical history. Subjects with low PPBC had significantly lower OAB-q (18.9 vs. 26.8, p<0.001) and OAB-q quality of life (25.7 vs. 39.0, p<0.001) scores. The proportion of patients reporting any incontinence did not differ (86% in both groups), however, high PPBC patients were more likely to report: greater urgency, worse frequency, daily incontinence, larger amount leaked, bladder pain, poor physical and mental health and fatigue. Results of the multivariate analysis controlling for age, urgency, frequency, incontinence, nocturia, bladder pain, mental and physical health and fatigue (Table) suggest bladder pain, low perception of physical health, and fatigue contributed as significantly to a high PPBC score as selected measures of typical OAB symptoms. Conclusions Factors other than traditional OAB symptoms contribute significantly to patient perception of condition severity. Patients with pain, fatigue and poor perception of overall health may be predisposed to greater bother from similar objective LUTS. Failure to address these contributing factors may result in suboptimal outcomes. Funding none
Authors
Joshua Cohn
Casey Kowalik Melissa Kaufman Roger Dmochowski W. Stuart Reynolds |
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PD39-06 |
De Novo Urinary Storage Symptoms are Common after Radical Prostatectomy: Incidence, Natural History and Predictors |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Non-neurogenic Voiding Dysfunction III | 17BOS |
Abstract: PD39-06 Sources of Funding: None Introduction After radical prostatectomy (RP), clinical complaints of new onset storage symptoms may be related to anastomotic strictures, however a subgroup of men with normal urinary function at baseline will experience de novo storage symptoms in the absence of this anastomotic pathology. With the advent of multiple treatments for overactive bladder, we sought to assess the prevalence, natural history, and risk factors of de novo storage dysfunction in order to improve our counseling and treatment efforts for these patients. Methods We retrospectively analyzed urinary symptom questionnaires completed by patients who were continent at baseline and did not have post-operative anastomotic strictures at our institution from 2002-2015. De novo storage dysfunction, assessed as new onset or worsening urgency, frequency, or nocturia, was assessed at 6, 12, 18 and 24 months after RP. Fisher’s exact test and Wilcoxon rank-sum test were used to assess association between patient and perioperative characteristics with these voiding symptoms at 12 months. Results 874 patients were included in the final analysis. An initial 34% of patients reported de novo storage symptoms at 6 months, which decreased to 25% and remained stable at 12, 18 and 24 months. Frequency of urination is the most commonly reported symptom at 12 months (62%) followed by difficulty postponing urination (40%), leakage (35%) and nocturia (3.7%). Younger men (median 61 vs 59 year, p=0.032) and those with a higher BMI (27.5 vs 28.2, p=0.049) are more likely to report worsening symptoms. However, differences between groups are small. For example, the probability of storage dysfunction is 23% for a patient with a BMI of 25 compared to 26% for a patient with a BMI of 30. No significant association was identified between prostate volume, prior TURP, EBL, operative time, postoperative leakage or hematoma, ASA, Charlson comorbidity index score or pathologic tumor characteristics. Conclusions There is a subgroup of patients post-RP who will experience de novo storage symptoms in the absence of an anastomotic stricture. Younger patients and those with a higher BMI may be at a higher risk, reflecting a broader clinical picture where patients with little to no urinary bother may be more acutely aware of new storage symptoms and those with a higher pre-operative weight may more commonly develop urinary leakage that stimulates a reflex detrusor contraction. At risk patients should be counseled on the incidence of de novo storage symptoms in the perioperative period. _x000D_ _x000D_ Funding None
Authors
Kathleen M. Kan
Amy L. Tin Gillian L. Stearns Daniel D. Sjoberg Jaspreet S. Sandhu |
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PD39-07 |
PELVIC FLOOR PHYSICAL THERAPY SIGNIFICANTLY IMPROVES PAIN AND VOIDING SYMPTOMS IN WOMEN WITH PELVIC PAIN |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Non-neurogenic Voiding Dysfunction III | 17BOS |
Abstract: PD39-07 Sources of Funding: Philanthropy; Ministrelli Program for Urology Research and Education (MPURE) Introduction Pelvic pain due to pelvic floor dysfunction responds well to pelvic floor physical therapy (PFPT). We compare validated symptom scores at intake and discharge in women undergoing PFPT for pelvic pain at a multidisciplinary Women&[prime]s Urology Center. Methods Retrospective chart review was performed for women presenting to the Center for PFPT primarily for pelvic pain in 2015. 5 pelvic floor physical therapists had performed individualized interventions. Pertinent history, demographics, and Pelvic Floor Distress Inventory Short Form 20 (PFDI) total and domain scores (Pelvic Organ Prolapse Distress Inventory-POPDI, Urogenital Distress Inventory-UDI, Colorectal-Anal Distress Inventory-CRADI), Pelvic Floor Impact Questionnaire (PFIQ), and pain levels on a 0-10 visual analog scale (VAS) collected at intake and discharge were analyzed with descriptive statistics. Results 95 women were treated in 2015. Mean age was 47 yr ± 15 (range, 18 to 80). In addition to pain women reported urinary frequency (53/93, 57%) and urgency (53/93, 57%), difficulty initiating urination (38/93, 41%), and constipation (51/95, 53%). The most common prior intervention was pain medications (70/85; 82%). 46/95 (48%) had previously undergone PFPT. Mean number of visits was 10 ± 6.5. Mean pain level decreased from 5 at the first visit to 3.5 by the last visit (p<0.0001) and 8 on the worst day to 4.8 by the last visit (p<0.0001). Pre and post treatment PFDI and PFIQ questionnaires were completed by 49/95 (51.6%) and 45/95 (47.4%) women respectively. Total and domain scores with the minimally important difference (MID) for PFDI, CRADI, and UDI (MID not available for other scores) are displayed in Table I._x000D_ PFDI scores significantly improved but did not meet the MID. UDI scores significantly improved and met the MID. Although POPDI and CRADI did not significantly improve, CRADI met the MID. PFIQ scores improved significantly._x000D_ Conclusions PFPT improves pelvic pain and symptoms of urinary distress in women with pelvic pain. Funding Philanthropy; Ministrelli Program for Urology Research and Education (MPURE)
Authors
Natalie Gaines
Jacob Henrichsen Laura Nguyen Larry T. Sirls Jason Gilleran Jamie Bartley Priyanka Gupta Kim A. Killinger Robert Petrossian Lisa Odabachian Judith A. Boura Kenneth M. Peters |
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PD39-08 |
ARE NOMOGRAMS BASED ON FREE UROFLOWS HELPFUL TO EVALUATE URETHRAL OBSTRUCTION IN MEN? |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Non-neurogenic Voiding Dysfunction III | 17BOS |
Abstract: PD39-08 Sources of Funding: none Introduction Decrease of Qmax during intubated flow (IF) in women is due to a urethral reflex (foreign material) and has over-estimation of obstruction as consequence [1]. Our hypothesis is that a similar phenomenon could occur in men. Our purpose was to search for a method using results of a free uroflow (FF) preceding an IF to eventually correct the AG number estimation Methods Retrospectively, analysis of 441 urodynamic studies of men suspected of bladder outlet obstruction (BOO) was performed (FF then IF catheter 8F and AG estimation)._x000D_ The VBN model [2] links urethral obstruction (counter-pressure pucp exerted by the prostate) and detrusor contractility (parameter k) to Qmax and pdet.Qmax. AG and pucp are strongly correlated [3]. Iso-contractility curves in the plane [Qmax,pdet.Qmax] are a nomogram fitted by a non-linear approximation._x000D_ Cut off value for occurrence of a urethral reflex is Qmax.FF>1.5*Qmax.IF. Using the nomogram a corrected AG (Cor_AG) was computed. All computations were made in Excel. _x000D_ Results Nomograms were carried out and used (Figure) allowing in step 1 (from IF data) evaluation of detrusor contractility (k), then in step 2 (from FF data and k) to compute pdet.Qmax.FF and Cor_AG. A sketchy pathway for computation of Cor_AG is given in the figure. Only 362 files with Vini.FF>90 ml were included. Cor_AG was compared to AG; for example (O for AG becoming E or NO for Cor_AG)._x000D_ Results are given in table._x000D_ When Qmax.FF>1.5*Qmax.IF there was no significant difference in Vini (375±245 mL for FF vs. 410±139 mL for IF; n.s.). Increased BOO resulted from a urethral reflex during IF and AG gave an overestimation (agreement with AG was only 46.5%). An emended AG (Cor_AG) allowed a better classification of BOO._x000D_ When Qmax.FF < 1.5*Qmax.IF, Vini was significantly different (313±195 mL for FF vs. 431±154 mL for IF; p <.0001). Selection bias has been excluded. Agreement with AG was found in 72.9%._x000D_ Conclusions To obtain a reliable evaluation of BOO in men, it is suitable to perform a FF before IF. An easily usable Excel tool allows computation of a corrected AG (Cor_AG) which value, if lower than AG, indicates the occurrence of a urethral reflex during IF. The proposed nomograms could be helpful for evaluation of BOO in men._x000D_ 1-Int Urogynecol J 2013; 24: 461-7; 2-NAU 2000; 19:153-76; 3- Ann. Readap. Med. Phys. 2005 ; 48 :11-19._x000D_ Funding none
Authors
Francoise Valentini
Peter Rosier Pierre Nelson |
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PD39-09 |
Bladder function recovery after treatment in male patients with detrusor underactivity – clinical results and predictive factors |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Non-neurogenic Voiding Dysfunction III | 17BOS |
Abstract: PD39-09 Sources of Funding: None Introduction Detrusor underactivity is an important yet still under-research issue. The treatment outcome in patients with detrusor underactivity (DU) is usually unfavorable and no better compared to untreated patients. Therefore, we aim to identify the predictive factors of satisfactory treatment in male patients with detrusor underactivity. Methods We retrospectively reviewed 86 cases of men with video-urodynamic proven detrusor underactivity from 2000 to 2015. DU was defined as low voiding pressure, low flow rate, post void residual (PVR)>300mL and a low voiding efficiency (VE) < 33% in this study. VE > 50% after treatment was considered satisfactory outcome. Patient’s demographics and urodynamic parameters include first sensation of filling (FSF), full sensation of filling (FS), urgency sensation (US), compliance at capacity, maximal flow rate (Qmax), detrusor voiding pressure (Pdet), voided volume, cystometric bladder capacity (CBC) and PVR were compared between the satisfactory group and unsatisfactory group. Various treatment options including transurethral resection of prostate (TURP), transurethral incision of prostate (TUIP) and medication (include botulinum toxin injection) were performed according to clinical and video-urodynamics findings. Results After a mean follow up of 31 months, 63 patients had satisfactory outcome. Satisfactory group has significantly higher detrusor pressure and compliance at capacity than unsatisfactory group. There was significant improvement in FSF, FD, US, Pdet, Qmax, voided volume, PVR and CBC after treatment in satisfactory group meanwhile in unsatisfactory group there were only significant changes in US, PVR and CBC. Conclusions A higher detrusor pressure and compliance at capacity at baseline were predictive of satisfactory treatment outcomes in male patient with detrusor underactivity. Funding None
Authors
Kau Han Lee
Hann-Chorng Kuo |
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PD39-10 |
Development and validation of a novel pictogram-based urinary symptom score: the Visual Urinary Symptom Score (VUSS) for Women |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Non-neurogenic Voiding Dysfunction III | 17BOS |
Abstract: PD39-10 Sources of Funding: none Introduction Symptoms score are integral tools in urology allowing for assessment of severity of symptoms, progression of symptoms and efficacy of therapy, though they inherently depend on literacy and language interpretation. To extend the concept of the male Visual Prostate Symptom Score (VPSS), we proposed a female specific visual score that would circumvent literacy comprehension and provide validated symptom information on frequency, nocturia, urgency, stress urinary incontinence (SUI), dysuria and quality of life (QoL)._x000D_ Objectives: Develop the Visual Urinary Symptom Score for Women (VUSS) score and content validity by: (1) evaluate construct validity through patient understanding of each pictogram (2) comparing VUSS pictograms responses to the Urinary Distress Inventory (UDI-6) and the American Urological Associated Symptom Inventory (AUA-SI) (3) obtain patient input to enhance information capture._x000D_ Methods English speaking women were recruited by posters in the Greater Vancouver Area. They completed the VUSS, the UDI-6 and the AUA-SI independently, described their interpretations of each pictogram and provided feedback for each image to improve comprehension. Statistical analysis: Students t, Fishers exact, and Spearmans correlation tests. Results 300 scores in N=100 were collected (mean age 46, range 21-91); 25 had grade 8-12 high school education; 75 with postsecondary education (mean 4.2 years, range of 0 years to 8 years). All surveys were completed independently. VUSS Q1 and Q2, indicating daytime frequency and nocturia, had the best inherent recognition of concept with 97% correct interpretation. QoL had the poorest inherent recognition of concept with 72% correct interpretation. VUSS Q5, indicating dysuria, was thought by the participants to be the clearest. VUSS and UDI-6 totals had 0.878 correlation, while VUSS AUA-SI had 0.72 correlation. Conclusions VUSS content correlated well with UDI-6 total scores. Comprehension would benefit from increasing contrast details in pictograms. Further development can add to the ability to measure womens LUTS on a global scale to reduce language and literacy barriers to urologic history taking. Next steps will incorporate changes from this validation and testing in a low resource environment. Funding none
Authors
Catherine Lovatt
Lynn Stothers Andrew Macnab Darren Lazare |
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PD39-11 |
PREDICTORS OF URINARY RETENTION IN MALE PATIENTS RECEIVING INTRADETRUSOR BOTULINUM TOXIN INJECTIONS |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Non-neurogenic Voiding Dysfunction III | 17BOS |
Abstract: PD39-11 Sources of Funding: none Introduction Intradetrusor onabotulinumtoxinA (BTX?A) BTX?A injections are an established third?line therapy for the treatment of overactive bladder (OAB). Incomplete bladder emptying requiring clean intermittent catheterization (CIC) is a side effect that limits patient acceptability of BTX-A. There are studies that have evaluated risk factors that predispose to need for CIC, but few have looked at parameters that may confer protection against CIC. Herein we present an initial report of a cohort of men who have undergone prostatectomy and subsequent BTX?A for OAB. _x000D_ _x000D_ _x000D_ Methods A retrospective chart review of patients receiving BTX?A for OAB refractory to antimuscarinics and/or beta 3agonists from 2010 to 2016 was performed. We sought to identify predictors of elevated post?void residual (PVR) leading to CIC in patients not expected to CIC post treatment. A subset of men who had undergone prostatectomy for benign or malignant disease (open or robotic radical prostatectomy (RP), or transurethral procedure (TUR) for BPH were identified. All men received 100 units of onabotulinumtoxinA under local anesthesia by flexible cystoscope. PVR was measured 2 weeks after the procedure. We generally recommend CIC for PVR 200 ? 349 ml with symptoms or greater than 350mL with or without symptoms. Clinical variables were correlated with PVR/CIC at their subsequent evaluations. Patients with neurogenic DO and those performing CIC prior to BTX-A injection were excluded._x000D_ _x000D_ Results 71 men were identified. Of these, 45 (63.4%) had surgical interventions on their prostate; 23 (32.4 %) had open or robotic RP and 22 (31 %) had a TUR for BPH. The overall rate of CIC was 12.7%. Three (13.6%) men in the TUR group required CIC vs. 6 (23%) who had an intact prostate No men in the RP group required CIC. The median post BTX-A PVR in the RP group was 44 ml when compared to 104 in the TUR group and 197ml in the group with intact prostates. (Table)_x000D_ Conclusions The rate of CIC in men receiving BTX?A for OAB in our cohort was 12.7%, somewhat higher than is seen in women. Prior RP appears to have a protective effect against CIC (p=0.02) and elevation of PVR (p=0.001). No man required CIC after RP. Prior TUR does not confer protection against CIC (p=0.5) but may protect against elevation of PVR (p=.03). A proposed mechanism for better emptying after surgery may be the ability to Valsalva void._x000D_ Funding none
Authors
Daniel Hoffman
Ekene Enemchukwu Victor Nitti |
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PD39-12 |
Risk Factors Related to Post-prostatectomy Incontinence and Development of Predictive Nomograms |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Non-neurogenic Voiding Dysfunction III | 17BOS |
Abstract: PD39-12 Sources of Funding: This study was supported by Award Number 8157101445 from National Natural Science Foundation of China. Introduction To investigate and summarize clinical presentations and characteristics of post-prostatectomy incontinence (PPI), and to analyze the relationship between patients’ clinicopathological features and PPI incidence, severity and recovery as well. Methods Clinical and pathological data of 364 patients who underwent radical prostatectomy in Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine between February 2013 and February 2015 were prospectively collected, including 7 lifestyle and comorbidity factors (age, BMI, smoking, etc.), 11 preoperative clinical factors (prostate volume, biopsy approaches, preoperative lower urinary symptoms, etc.), surgeon and surgical method, 4 postoperative clinical factors (complications, postoperative PSA, etc.) and 9 pathological factors (pT, pN, Gleason score, etc.). The incidence, severity and recovery of PPI was followed up by phone call and email. Logistic regression analysis and Cochran’s and Mantel-Haenszel Chi-square test were used to analyze the relationship between all the features and PPI incidence and severity, respectively. A Kaplan-Meier curve was created to clarify recovery of incontinence after prostatectomy. Cox regression analysis was performed in the analysis of influence factors of PPI recovery. Nomograms were formulated based on the results of multivariate analysis and by using the package of rms in R version 2.14.1. Results All 364 patients had complete data and the medium follow-up time was 17 months. The total immediate incontinence rate was 61.8%. The incontinence rate was 10.4% at the 12th month after the surgery. Risk factors related to PPI incidence included smoking, hypertension, preoperative incontinence, preoperative dysuresia and chief surgeon. Risk factors related to PPI severity included age, preoperative PSA, neutrophil-to-lymphocyte ratio, postoperative urinary stricture and Gleason score. Risk factors related to PPI recovery included age, BMI, diabetes, hernia, biopsy approaches, prostate volume, preoperative incontinence, preoperative dysuresia, preoperative PSA, postoperative urinary stricture and PPI severity. Age, BMI and PPI severity were independent predictor of PPI recovery. Conclusions Incontinence is a very common complication after radical prostatectomy, which adversely affects patients’ quality of life. According to the nomograms developed by this study, now it is possible to predict the incidence of PPI and PPI recovery probabilities, which offers a strong evidence to the establishment of personalized prostate cancer management. Funding This study was supported by Award Number 8157101445 from National Natural Science Foundation of China.
Authors
Liang Dong
Jiayi Li Yinjie Zhu Jiahua Pan Baijun Dong Wei Xue Yiran Huang |
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PD40-01 |
Are there regional tendencies toward controversial screening practices? A study of prostate and breast cancer screening in a Medicare population |
Prostate Cancer: Detection & Screening V | 17BOS |
Abstract: PD40-01 Sources of Funding: The Hitchcock Foundation Introduction Prostate and breast cancer screening in older patients continue to be controversial based on competing and at times contradictory guidelines. Indeed, the appropriate balance between useful, early detection and avoiding over-diagnosis remains elusive for these conditions. There is a gap in knowledge regarding regional factors associated with high rates of screening for either practice in the elderly. In this study, we investigated to what extent these practices are related to each other, and to the intensity of local healthcare practices. Methods We performed a retrospective cross-sectional study of fee-for-service Medicare beneficiaries in 2012 (100% sample). We calculated rates of prostate-specific antigen (PSA) screening for males by hospital referral region, adjusted for age and race, using a coding algorithm. Rates of screening were compared with regional rates of screening mammography in older women (75+ years old), as well as measures of care aggressiveness (e.g. spending on tests and procedures) and intensity of end-of-life care, which is considered to reflect physician-driven care within regions. Results The mean adjusted rate of PSA screening was 22% (range 13-30%). The mean age of screened and unscreened patients was 75.0 and 77.4 years, respectively (p<0.0001). HRR-level PSA screening rates were independent of screening mammography rates in older women (r=0.058, p=0.31). PSA screening rates were associated with spending on testing and procedures (r=0.42, p<0.0001) and various measures of intensity of end-of-life care (r=0.32, p<0.0001). Screening mammography had low correlation with these intensity measures. Conclusions Regional rates of PSA screening rates were independent of screening mammography, thus these practices appear to be driven by different factors. Unlike mammography, PSA screening was associated with local enthusiasm for testing and treatment. This suggests that policies to reduce over-use of PSA in elderly patients may dovetail with efforts to reduce high healthcare utilization generally. Continued recognition of the risk of over-screening in the elderly is needed, and future research should examine the factors motivating these screening practices. Funding The Hitchcock Foundation
Authors
Eric Raffin
Tracy Onega Julie Bynum Andrea Austin Donald Carmichael Philip Goodney Elias Hyams |
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PD40-02 |
Re-Examining PSA Density: Defining the Optimal PSA Range and Patients for Using PSA Density to Predict Prostate Cancer Using Extended Template Biopsy |
Prostate Cancer: Detection & Screening V | 17BOS |
Abstract: PD40-02 Sources of Funding: None Introduction Previous guidelines to screen for prostate cancer (PCa) using serum PSA levels led to millions of unnecessary prostate biopsies that revealed no PCa or low-risk PCa that was unlikely to affect survival. PSA density has shown promise as a better marker to indicate prostate biopsy and has been well investigated in the past using sextant or octant biopsies. While most prior studies only showed that PSA density could distinguish between BPH and PCa, we compared the sensitivity and specificity of PSA density versus PSA to detect any and significant PCa across different PSA ranges using the current standard of extended template prostate biopsies. Methods Participants were a prospective cohort of men referred for prostate biopsy using an extended template biopsy scheme to evaluate PCa at 26 sites throughout the US. We analyzed the area under the receiver operating characteristic curve to assess the predictive accuracy of PSA density versus PSA across three PSA ranges (<4, 4-10, >10 ng/mL) and in men with or without a prior negative biopsy. We assessed the detection of any and significant (Gleason score ≥ 7) PCa. Results Among 1,290 patients with available data, 585 (45%) and 284 (22%) men had any PCa and significant PCa, respectively. PSA density was significantly more predictive than PSA for detecting any and significant PCa in the PSA ranges of 4-10 and >10 ng/mL. AUC for significant prostate cancer was 0.72 (0.68, 0.77), p<0.0001 for PSA 4-10 ng/mL and 0.82 (0.75, 0.89), p<0.0001 for PSA >10 ng/mL. PSA density was significantly more predictive than PSA in detecting any and significant PCa in men with and without a prior negative biopsy. However, the incremental AUC value was larger for significant PCA than any PCA in men who had a prior negative prostate biopsy (AUC 0.81 vs 0.70, p = 0.0042), and those who did not (AUC 0.77 vs 0.73, p = 0.0026). Conclusions In contrast to previous studies, we found that PSA density outperformed PSA most within the PSA range >10 ng/mL, suggesting that PSA density will save large volume prostate patients from the costs associated with the over-diagnosis of PCa. Additionally, PSA density performed best among men with a prior negative biopsy, saving these men from the burden of repeated biopsies that are likely to be negative in this population. With the current need for better markers to indicate prostate biopsy, PSA density may have significant value as a more sensitive and specific test than PSA to detect PCa when used with an extended template biopsy scheme. Funding None
Authors
Joshua Jue
Marcelo Panizzutti Nachiketh Prakash Vivek Venkatramani Varsha Sinha Nicola Pavan Bruno Nahar Pratik Kanabur Michael Ahdoot Ramgopal Satyanarayana Dipen Parekh Sanoj Punnen |
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PD40-03 |
Effect of 5-alfa reductase inhibitor usage on outcomes of prostate cancer screening |
Prostate Cancer: Detection & Screening V | 17BOS |
Abstract: PD40-03 Sources of Funding: Pirkanmaa Hospital District, memorial fund of Seppo Nieminen. Introduction Prostate cancer (PCa) screening with prostate-specific antigen (PSA) reduces PCa mortality, but leads to overdiagnosis of indolent PCa. Use of 5-alpha reductase inhibitors (5-ARIs) lowers PSA and in theory could affect performance of PSA-based screening. We evaluated outcomes of PCa screening among 5-ARI users. Methods The study was performed within the Finnish Randomized Study of Screening for Prostate Cancer. Of 80,454 men, 31,866 were randomized to be screened at four-year intervals during 1996-2004. Information on 5-ARI reimbursements before PCa during 1995-2009 was collected from the national prescription database for 78,615 men. We evaluated the effect of screening on PCa risk and mortality by 5-ARI usage using Cox regression. Results Men using 5-ARIs had higher median PSA and were more often screen-positive compared to non-users. Despite this, screening did not significantly affect PCa detection (HR 0.89, 95% CI 0.79-1.01) or mortality (HR 0.82, 95% CI 0.51-1.32) compared to the control arm among 5-ARI users. In ROC analysis, PSA and age did not predict Gleason 7-10 prostate cancer as accurately in 5-ARI users as among the non-users (AUC = 0.88 versus 0.79 in the first screening round). Conclusions PSA-based screening among men using 5-ARIs does not improve detection of high-grade or metastatic PCa or prevention of PCa deaths. Targeted screening should focus on men not using 5-ARIs. Funding Pirkanmaa Hospital District, memorial fund of Seppo Nieminen.
Authors
Teemu Murtola
Anniina Virkku Kirsi Talala Ulf-HÃ¥kan Stenman Kimmo Taari Teuvo Tammela Anssi Auvinen |
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PD40-04 |
Community-based prostate cancer screening in Japan: Predicting factors for positive repeat biopsy. |
Prostate Cancer: Detection & Screening V | 17BOS |
Abstract: PD40-04 Sources of Funding: None. Introduction There have recently been a number of reports on predictors for a positive repeat prostate biopsy in patients on an outpatient-referral basis. On PSA prostate prostate cancer screening, unlike outpatient referral basis, a clarification to select screened patients for repeat biopsy needs to be balanced by cost and survival benefit. For this purpose, a validation of the screening system and its modification, if necessary, are extremely important. The aim of this study is to assess possible predictors in determining criteria for repeat biopsy in a prostate cancer screening population. Methods A total of 93553 men over 55 years-of-age have participated in a prostate cancer screening program in Otokuni district, Kyoto, Japan for 21 years. Transperineal systematic biopsy with 8-12 cores was carried out in the cases of positive digital rectal examination (DRE) or positive transrectal ultrasonography (TRUS) or a prostate specific antigen (PSA) value greater than 10.0 ng/mL. For those with a PSA level from 4.1 to 10.0ng/mL, and negative DRE and TRUS findings, biopsy was indicated only when PSA density (PSAD) was greater than 0.15. The same indication was applied for the repeat biopsy. Results A repeat biopsy after an interval of more than 1 years was carried out in 401 patients and was positive in 167 (41.6%) patients. The PSA value at the diagnosis of cancer declined from the initial value in 26 men (15.6%). The assessment parameters are as follows: age at the final biopsy, change of PSA value, PSA velocity, DRE finding and PSAD value at the latest screening. In multivariate analysis, age, PSAD and positive DRE finding are independent parameter in predicting positive repeat biopsy. The odds ratio in Age>72, PSA>0.30 and positive DRE are 1.86 (1.18 - 2.96), 3.91 (2.47 - 6.24), 2.35(1.09 -5.25), respectively. Of those 3 parameters, when repeat biopsy definition is determined in either positive of 3 parameters, unnecessary biopsy can be decreased in 17.0 %, while localized cancer with low risk group will be missed in 10.1%. Conclusions A decrease in the repeated PSA value cannot predict a negative biopsy outcome under the consecutive and established biopsy criteria. The combination of these three parameters (age, positive DRE and PSAD) might help to reduce unnecessary repeat biopsies in the high-risk cohort of patients with negative initial biopsies._x000D_ _x000D_ Funding None.
Authors
So Ushijima
Koji Okihara Koji Kitamura Kazumi Kamoi Osamu Ukimura |
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PD40-05 |
Determinants of Default from Follow-Up Care in a Prostate Cancer Screening Program |
Prostate Cancer: Detection & Screening V | 17BOS |
Abstract: PD40-05 Sources of Funding: None Introduction The curability of high-risk prostate cancer (PCa) may depend on early diagnosis and compliance with management modalities. Delayed or incomplete treatment for PCa may result in inferior clinical outcomes and lower survival rates. We sought to identify the proportion of and predictors of loss of follow-up care after positive prostate biopsy in a single-institution, retrospective cohort study Methods Patients who did not follow up for or so-called ‘defaulted’ treatment were defined as those who had failed to return for treatment or follow-up discussion after diagnosis of PCa. This did not include patients who elected to be treated at other hospitals. Demographic and clinical characteristics, were compared between defaulters and non-defaulters. A multiple linear regression was performed to predict those individuals likely to default. Results From October 2008 to April 2013, 6182 patients received 12,930 PSA tests at a single institution. Of these patients, 574 (9%) patients had at least one PSA test level greater than 4 ng/mL. A total of 210 patients had subsequent biopsy, of which 141 had a PSA test >4 ng/mL. PCa was detected in 85 (41%) patients, of which 17 (20%) patients failed to follow up. The majority (88%) of defaulters were made aware of their biopsy results prior to self-cessation of care. Defaulters were significantly younger (61.8 ± 2.0y) at time of biopsy compared to non-defaulters (65.8 ± 1.0y), t(83) = 1.8, p = 0.04. Those individuals with an unspecified primary care provider (65%) were more likely to default than those who had primary care doctor at our institution (p<.001). Defaulters were more likely to be uninsured (24%) as compared to those with continued care (4%) (p=.01). Defaulters were more likely to self-identify as Latino (41%) as compared to those with continued care (9%) (p=.01). A multiple regression predicted default from age, insurance status, race and PCP access, p < .0005, R2 = .430. Conclusions At our institution men at highest risk of being lost to follow-up after the diagnosis of prostate cancer were younger, uninsured, Latino, and without centralized care. In our cohort, defaulters had high-risk disease (81% of Gleason >=7), which is crucial to identify in a timely and aggressive fashion so as to prevent future treatment failure. Development of strategies to encourage prompt and continued attendance is needed in addition to qualitative research to better understand the reasons for default and underpinning risk factors. Funding None
Authors
Mark Ferretti
Michael Goltzman Akhil Saji Neel Patel Denton Allman Sean Fullerton Gerald Matthews John Phillips |
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PD40-06 |
A four-kallikrein panel in predicting high-grade prostate cancer on biopsy: an independent replication from the Finnish section of the European Randomized Study of Screening for Prostate Cancer. |
Prostate Cancer: Detection & Screening V | 17BOS |
Abstract: PD40-06 Sources of Funding: The work was supported in parts by grants from the Finnish Funding Agency for Technology and Innovation Finland Distinguished Professor program, the Academy of Finland, the Cancer Society of Finland, the Sigrid Juselius Foundation, the Medical Research Fund of Tampere University Hospital, National Cancer Institute [R01CA160816, R01 CA175491, P50-CA92629, and P30-CA008748], the Sidney Kimmel Center for Prostate and Urologic Cancers, and David H. Koch through the Prostate Cancer Foundation, the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre Program in UK, and the Swedish Cancer Society (project no. 14-0722). _x000D_ The Finnish screening trial was supported by grants from the Academy of Finland (grant #260931), Cancer Society of Finland and Competitive Research Funding (Pirkanmaa Hospital District)._x000D_ Introduction A panel of four kallikrein markers (total, free and intact prostate-specific antigen (PSA), human kallikrein-related peptidase 2 (hK2)) improves predictive accuracy for Gleason score 7 or higher (high-grade) prostate cancer among men biopsied for elevated PSA. A four kallikrein panel model was originally developed and validated on the Dutch center of the European Randomized Study of Screening for Prostate Cancer (ERSPC). The kallikrein panel is now commercially available as the 4Kscoretm. We assessed whether these findings could be replicated among participants in the Finnish section of ERSPC (FinRSPC). Additionally, we assessed whether beta-microseminoprotein (MSP), a candidate prostate cancer biomarker, adds predictive value. Methods Among 4861 biopsied screening-positive participants in the first three screening rounds of the FinRSPC, a case-control subset was selected which included 1632 biopsy positive cases individually matched based on age at biopsy to biopsy negative controls Markers were measured in serum or plasma collected before biopsy. Predictive accuracy of pre-specified prediction models were compared with biopsy outcome. Results Our main analysis included men with PSA 4.0-25 ng/mL, 1111 of whom had prostate cancer, 318 with high-grade disease. Total PSA and age predicted high-grade cancer with an area under the curve (AUC) of 0.648 (95% CI 0.614, 0.681) and the four-kallikrein panel increased discrimination to 0.746 (95% CI 0.717, 0.774). Adding MSP to the four kallikrein panel led to a statistically significant (Wald test; p=0.015) but small additional increase (0.003) in discrimination. Conclusions Four kallikrein markers and MSP in blood improve discrimination of high-grade cancer from Gleason grade 6 cancer or no evidence of cancer at biopsy in men with elevated PSA. These findings provide further evidence that kallikrein markers can be used to inform biopsy decision making. Further studies are needed to define the role of MSP. Funding The work was supported in parts by grants from the Finnish Funding Agency for Technology and Innovation Finland Distinguished Professor program, the Academy of Finland, the Cancer Society of Finland, the Sigrid Juselius Foundation, the Medical Research Fund of Tampere University Hospital, National Cancer Institute [R01CA160816, R01 CA175491, P50-CA92629, and P30-CA008748], the Sidney Kimmel Center for Prostate and Urologic Cancers, and David H. Koch through the Prostate Cancer Foundation, the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre Program in UK, and the Swedish Cancer Society (project no. 14-0722). _x000D_ The Finnish screening trial was supported by grants from the Academy of Finland (grant #260931), Cancer Society of Finland and Competitive Research Funding (Pirkanmaa Hospital District)._x000D_
Authors
Melissa Assel
Liisa Sjöblom Kirsi Talala Paula Kujala Ulf-Håkan Stenman Kimmo Taari Anssi Auvinen Andrew Vickers Tapio Visakorpi Teuvo Tammela Hans Lilja |
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PD40-07 |
Does early PSADT (ePSADT) after Radical Prostatectomy, Calculated prior to PSA Recurrence, Correlate with Prostate Cancer (PC) Outcomes? Results from the SEARCH Database |
Prostate Cancer: Detection & Screening V | 17BOS |
Abstract: PD40-07 Sources of Funding: none Introduction A short PSA doubling time (PSADT), calculated using PSA values ≥0.2 ng/ml, after biochemical recurrence (BCR) post radical prostatectomy (RP) portends a poor prognosis. We tested if ePSADT, calculated from the first detectable PSA after RP and including all values up to and including the first BCR value, predicts castration-resistant PC (CRPC), metastases, all-cause mortality (ACM) and PC-specific mortality (PCSM). Methods Cox proportional hazards were used to test the association between ePSADT and CRPC, metastases, ACM, and PCSM in 674 men in the SEARCH database who underwent RP between 1988-2015 and later recurred. Men had to have at least 2 PSA values separated by at least 3 months to calculate ePSADT. Men who started salvage therapy within this time were censored and did not have ePSADT calculated. Thus, all PSA values used were prior to subsequent therapy. ePSADT was examined as a log-transformed continuous and categorical variable. Results During a median 69-month follow-up (IQR 35-117) after BCR, 43 developed CRPC, 59 metastases, 236 all-cause deaths, and 30 PC-specific deaths. After adjusting for multiple clinicopathological variables, log-transformed ePSADT was not associated with any outcome. However, when ePSADT was categorized as ≥15, 9-14.9, 3-8.9, and <3 months, those with ePSADT <3 months were at increased risk of CRPC (HR 6.20, p=0.004), metastases (HR 5.26, p=0.002), PCSM (HR 5.06, p=0.017), and ACM (HR 1.63, p=0.070) vs. ePSADT ≥15 months, though the association with ACM was not significant. Similarly, ePSADT 3-9 months increased risk of CRPC (HR 3.56, p=0.015), metastases (HR 1.92, p=0.13), PCSM (HR 3.17, p=0.044), and ACM (HR 1.67, p=0.006) vs. ePSADT ≥15 months, though the association with metastases was not significant. See figure for CRPC risk by ePSADT. Conclusions Shorter ePSADT, particularly ePSADT <9 months, calculated using PSA values before and up to BCR, is associated with increased risk of CRPC, metastases, PCSM, and ACM among men with BCR after RP. ePSADT allows for risk-stratification at the time of BCR and before PSADT is calculable allowing these men to receive early aggressive secondary treatment and/or be enrolled on clinical trials. Funding none
Authors
Anna Teeter
Kagan Griffin Lauren Howard William Aronson Martha Terris Christopher Kane Christopher Amling Matthew Cooperberg Stephen Freedland |
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PD40-08 |
Combining 4KScore and MRI for prostate biopsy decision making |
Prostate Cancer: Detection & Screening V | 17BOS |
Abstract: PD40-08 Sources of Funding: none Introduction Multiparametric Magnetic Resonance Imaging (mp-MRI) and the 4Kscore blood test (OPKO: Miami FL) have both been shown to identify significant prostate cancer in men with elevated PSA. In comparison to a blood test, mp-MRI is resource intensive, thus is difficult to apply at a population level. Moreover, results from the PROMIS MRI trial show that 11% of men with normal MRI harbor high-grade disease. One possibility is selective application of mp-MRI to men at intermediate risk as defined by the 4Kscore: this would reduce the number of MRIs and lower the chance of missed high-grade disease. The aim of this study was to evaluate mp-MRI as a follow-up test to the 4Kscore in prostate cancer early detection. Methods The 4Kscore results from the US prospective validation study were combined with mp-MRI data available from the PROMIS study. Using the likelihood ratios for MRI detecting high grade disease and applying them to probabilities of 4Kscores, four different populations were identified based on a threshold for biopsy of 7.5% risk of high grade disease: 1. men with very low 4Kscore for whom risk would not be ≥7.5% even with positive MRI; 2. men with 4Kscores < 7.5% whose risk would be ≥7.5% if MRI were positive; 3. men with 4Kscores ≥7.5% whose risk would be <7.5% if MRI were negative; 4. men with high 4Kscores whose risk would remain ≥7.5% even if MRI were negative. In this strategy, group 1 would not be biopsied; groups 2 and 3 would receive MRI and then biopsy if MRI was positive; group 4 would be biopsied without MRI. Net benefit was calculated for each strategy using a threshold of 7.5%. Results In the 4Kscore validation study, 1012 men underwent prostate biopsy with 231 (23%) diagnosed with ≥Gleason 7 disease. PROMIS gave a positive and negative likelihood ratio of 1.58 and 0.17 for MRI. The range of 4Kscores that could be influenced by the results of MRI was 5-32%, i.e. group 1: 26% of the population with risk <5%; group 2: 10% with risk 5-7.4%; group 3: 45% with risk 7.5-32%; group 4: 21% with risk > 32%. Net benefit of using 4Kscores alone was 17.7%, mp-MRI 17.6%, and combined strategy 18.2%. A difference of 0.5% between the combined strategy and 4Kscore alone is equivalent to 62 fewer biopsies per 1000 for the same number of high grade cancers detected or about 9 MRI per biopsy avoided. Results were similar using a 10% threshold. Conclusions Using mp-MRI in the setting of low-intermediate 4Kscores results in a biopsy strategy with higher net benefit compared to using either modality alone. The proposed risk stratification minimizes the utilization of resources and reduces the excessive rate of missed high-grade disease associated with use of mp-MRI. Funding none
Authors
Karim Marzouk
Behfar Ehdaie Stephen Zappala Andrew Vickers |
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PD40-09 |
Evaluation of prebiopsy magnetic resonance imaging combined with prostate-specific antigen density in the diagnosis of prostate cancer in men aged 75 years and older with elevated PSA |
Prostate Cancer: Detection & Screening V | 17BOS |
Abstract: PD40-09 Sources of Funding: none Introduction This study was designed to investigate the effectiveness of magnetic resonance imaging (MRI) in diagnosing prostate cancer (PCa) before transrectal needle biopsy of the prostate (PBx) for elderly men who were aged 75 years old or older. Methods The medical records of 141 elderly patients over the age of 75 years who underwent MRI before PBx at our institutions were reviewed retrospectively. MRI reports were compared with pathological reports. The factors that were used to detect PBx included age, PSA level, lesion size, prostate volume, and PSA density on MRI. Results PCa was positive in 103 (73.0%) and negative in 38 (27.0%) patients. Between the PCa-positive and PCa-negative groups, almost all factors except serum PSA level were significant predictors of PCa. MRI-based PSA density was more significant than the others. Of the 38 patients without PCa, 30 cases were not PCa patients on PBx even though they had been judged to be cancer positive on MRI before PBx. The specificity of MRI was 21.1% (8/38). Multivariate logistic regression analysis showed that MRI-based TZ-PSA density was the best independent predictor of PCa. When an MRI-based TZ-PSA density cut-off value of 0.42 was used, sensitivity was 83.5% and specificity was 71.1%. Of the 30 false-positive cases on MRI, PBx might not have been needed in 19 cases considering an MRI-based TZ-PSA density cut-off value of 0.42. We stratified the PCa-positive group according to Gleason score (GS<6, 7, and >8). The accuracy of MRI for detecting PCa was 84.6% (GS<6), 91.7% (GS=7), and 96.7% (GS>8). The cancer detection rate on MRI for high GS PCa was higher than low GS PCa. Conclusions These results indicated that MRI before PBx combined with PSA density, especially with MRI-based TZ-PSA density, is helpful to select candidates for PBx. MRI can also detect high GS PCa, so urologists should consider MRI before PBx for elderly men aged 75 years and older with elevated PSA. Funding none
Authors
Yoshinori Yanai
Takeo Kosaka Yu Teranishi Seiya Hattori Kazuhiro Matsumoto Shinya Morita Kazunobu Shinoda Toshiaki Shinojima Ryuichi Mizuno Eiji Kikuchi Shuji Mikami Masahiro Jinzaki Akira Miyajima Mototsugu Oya |
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PD40-10 |
EFFECTS OF THE 2012 USPSTF PSA SCREENING RECOMMENDATIONS ON PROSTATE BIOPSY PRACTICES IN AN INNER CITY HOSPITAL WITH A HIGH RISK PATIENT POPULATION |
Prostate Cancer: Detection & Screening V | 17BOS |
Abstract: PD40-10 Sources of Funding: None Introduction In the 2012 US Preventative Services Task Force (USPSTF) recommendation against prostate specific antigen (PSA) screening, it was acknowledged that African American men represented a disproportionately small minority of the population analyzed. We sought to describe the prostate biopsy practice patterns before and after the recommendation in an inner city hospital that serves a high risk patient population of predominantly Afro Caribbean descent. Methods A retrospective chart review of patients who underwent prostate biopsy from 10/27/2008 to 12/15/2015 was performed. Patients were grouped into those who underwent biopsy prior to, and after the new USPSTF guidelines (5/22/2012). Patient and clinical characteristics were compared between the two time periods. Bivariate analyses included two sample t tests, chi square tests, and the Mann Whitney U tests. Results Our analysis revealed no significant differences in the age, percent of positive biopsies, or type of physician initiating screening. There was a significant difference in median PSA (p= 0.05) and a trend toward significance in the difference in racial distribution between the two groups (p=0.06). Among those with positive biopsies, patients biopsied after the recommendation had significantly greater core positivity, and a borderline significantly higher incidence of clinically significant disease defined by D Amico criteria (p=0.24) Conclusions In a high risk patient population, we found that men biopsied after the USPSTF recommendation were more likely to have a higher PSA level, more likely to be African American, had greater core positivity, and a higher incidence of clinically significant disease. These results suggest that high risk patients in an inner city setting are also being negatively affected by the implementation of the task force recommendations. Further research is required to determine whether the practice pattern change occurred at the level of PSA screening or rather at patient selection for prostate biopsy. Such research will allow clinicians to provide more granular counseling with regards to PSA screening and prostate biopsies for high risk patients. Funding None
Authors
Johnathan A. Khusid
Igor Inoyatov Adan Beccera Llewellyn Hyacinthe Brian K. McNeil Andrew G. Winer |
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PD40-11 |
Impact of Primary Care Physician Factors on Adherence to United States Preventative Services Task Force Recommendation Against PSA Screening |
Prostate Cancer: Detection & Screening V | 17BOS |
Abstract: PD40-11 Sources of Funding: None Introduction We examined the association of primary care physician (PCP) length of practice and prostate specific antigen (PSA) screening opinions on the differential effect of the United States Preventative Services Task Force (USPSTF) recommendation against PSA screening in 2012. Methods 54,684 resulted PSA orders at our institution were reviewed from 2010-2015. Tests were excluded if they were performed by a non-PCP, if the provider ordered <4 tests/year, had a practice break >6 months, or if the provider was not employed at the institution for the entire period. Relative proportions of PSA orders per overall unique male ambulatory clinic volume were assessed for 2010-2011 (first period) and 2013-2015 (second period). Changes on a per-provider basis were assessed as a scatterplot, linear regression, and ANOVA. PCPs were surveyed on their attitudes towards the USPSTF recommendation and responses compared to physician seniority and actual PSA ordering habits. Results 228,731 unique male non-oncology care patients were assessed. From an initial cohort of 88 PCPs, 22 PCPs met inclusion criteria. Mean time between completion of residency and beginning of period was 16 years (range 2-43). There was a significant inverse relationship (Fig 1) between years since completion of residency and change in the overall proportion of patients who underwent PSA screening, with more senior physicians noted to have a larger relative decline in screening rates after the USPSTF recommendation (R2 = 0.308, p=0.007). Eighteen PCPs completed a survey on the USPSTF and PSA which revealed no correlation between stated attitudes toward PSA screening and observed practice, however senior PCPs were more likely to claim greater current PSA screening (p=0.037). Conclusions Greater time since residency completion was significantly associated with screening proportionally fewer men over the period. PCPs’ stated opinion on PSA screening did not appear to have a strong influence on actual observed practice. Funding None
Authors
Ryan Hutchinson
Nirmish Singla Solomon Woldu Abdulhadi Akhtar Justin Haridas Deepa Bhat Claus Roehrborn Yair Lotan |
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PD40-12 |
Do sicker people have worse prostate cancer-specific outcomes after radical prostatectomy? Results from SEARCH |
Prostate Cancer: Detection & Screening V | 17BOS |
Abstract: PD40-12 Sources of Funding: none Introduction Previous studies showed that higher Charlson comorbidity index increased the risk of overall mortality after radical prostatectomy. However, the relationship between comorbidities and prostate cancer-specific outcomes is less well established. While Charlson comorbidity index is a good measurement of health status, it is difficult to capture in retrospective data. Thus, we tested whether a man's overall health status, as reflected by the ASA (American Society of Anesthesiology) score, at the time of radical prostatectomy was associated with more distant prostate cancer-specific outcomes, such as biochemical recurrence (BCR), metastasis, and prostate cancer-specific mortality (PCSM). Methods Data were retrospectively collected on 3102 men who underwent RP between 1992 and 2015 at six Veterans Affairs hospitals in the SEARCH database. Cox proportional hazards analysis was used to test the association between ASA score and BCR, metastasis, all-cause mortality, and PCSM. Models were adjusted for age, race, year of surgery, surgical center, BMI, PSA, biopsy Gleason score, and clinical stage. As 98% of men had a ASA score of 2 or 3, we categorized ASA score as 1-2 vs. 3-4. Results There were 1419 (46%) men with ASA score 1-2 and 1683 (54%) men with ASA score 3-4. Men with ASA score 3-4 were older (mean 62 vs. 61), had more recent year of surgery (median 2009 vs. 2007), higher BMI (median 28.6 vs. 27.8), and higher biopsy Gleason score, versus men with ASA score 1-2 (all p<0.001). Men in the higher ASA group had an increased risk of all-cause mortality compared to men in the lower ASA grouping (HR 1.59, p<0.001). There was no increased risk of BCR (p=0.23), metastasis (p=0.22), or PCSM (p=0.83). Conclusions We found that men who underwent radical prostatectomy for prostate cancer with worse baseline health, as reflected by a higher ASA score (3-4 vs. 1-2), had a higher risk of all-cause mortality but did not have higher risk of the adverse prostate-cancer specific outcomes of BCR, metastasis, or death from prostate cancer. Whether similar results would be obtained if a more granular measure of comorbidity had been used remains to be tested. Funding none
Authors
Anna Teeter
Xizi Sun Lauren Howard William Aronson Christopher Kane Christopher Amling Matthew Cooperberg Martha Terris Stephen Freedland |
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PD41-01 |
Improved surgical outcomes after preoperative rehearsal using 3D printed patient specific simulation for percutaneous nephrolithotomy (PCNL) |
Surgical Technology & Simulation: Training & Skills Assessment II | 17BOS |
Abstract: PD41-01 Sources of Funding: none Introduction Surgical simulation is known to enhance technical skills and this effect is typically strongest for novices because complex procedures such as the PCNL have a steep learning curve. While the benefit of simulation is evident for cases when residents participate, it is unclear how preoperative rehearsal can impact patient safety in the hands of experienced practitioners. We present our initial experience using a high fidelity 3D printed simulation for surgical rehearsal in patients undergoing a PCNL. Methods A total of 15 consecutive patients underwent PCNL by a single Urologist. Before the live procedure, 7 patient specific simulations were performed for preoperative rehearsal. These models were created by converting DICOM images into stereolithography files and 3D printing components for assembly. In addition to the patient&[prime]s pelvicalyceal system and staghorn calculi, their kidney, spine, and posterior abdominal wall were also fabricated to create a complete procedural simulation. All steps of a PCNL were practiced including fluoroscopic access, nephroscopy, and lithotripsy. Procedure specific metrics such as radiation time and number of needle attempts were collected for live and simulation events. Outcomes from the first 8 patients without prior rehearsal were compared to the next 7 patients with preoperative practice. Results The mean fluoroscopy time was significantly lower in the rehearsal group (6.2 vs 12.7 mins, p = 0.03). The average combined time of fluoroscopy for simulation and live cases was still lower than the mean time for unrehearsed group (10.2 vs 12.7 mins, p = 0.22). Similarly, the average number of percutaneous needle access attempts was lower in the rehearsed group (1.8 vs 5 attempts, p < 0.001). The total number of complications and additional procedures was higher in the unrehearsed group (5 vs 1 and 9 vs 1, respectively). There were no differences in mean patient age, body mass index, or stone size between the two groups. Conclusions This study demonstrated that patient specific rehearsal improved surgeon performance for a complex endourological procedure. There was a significant reduction in fluoroscopy time, percutaneous needle access attempts, additional procedures and complications, with an improved stone clearance rate. There was no significant increase in radiation dose to the surgeon despite rehearsal. Advances in 3D printing technology permit it&[prime]s routine use for simulation of complicated operations and possess the ability to directly impact patient outcomes. Funding none
Authors
Jonathan Stone
Rebecca Bonamico Erdal Erturk Ahmed Ghazi |
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PD41-02 |
Train the trainer: a novel course for the standardization of robotic training |
Surgical Technology & Simulation: Training & Skills Assessment II | 17BOS |
Abstract: PD41-02 Sources of Funding: none Introduction Robotic training is fundamental to improve surgical outcomes. Although the robotic mentor is usually selected as a surgeon with extensive experience in robotic surgery, the specific criteria for selecting trainers are poorly defined. We developed the novel "Train The Trainer" course aimed at standardizing robotic surgical training through the assessment of trainers, proctors, and mentors performance Methods "Train The Trainer" was a 2-day course endorsed by EAU Robotic Urology Section (ERUS) and directed to experts in robotic surgery who aim to be certified trainers. The course included a theoretical and a practical part. During the theoretical part, the participants had on overview on training models, and defined presentations on non-technical skills were held by experts in this field. During the practical part, both technical and non-technical skills of the participants were evaluated. Technical skills were tested using DaVinci skill simulator (dVSS) and dry-lab anastomosis. Specifically, participants were asked to achieve at least 80% overall score at three different advanced exercises on the dVSS, whereas dry-lab anastomosis was assessed using the Global Evaluative Assessment of Robotic Skills (GEARS) score. Non-technical skills were evaluated during a simulated training session, where each participant was asked to train (on the dVSS and during dry-lab suture exercises) two medical students who did not have any previous experience with the robotic system. The objective for the medical students was an overall score on the dVSS ≥70% at three different basic exercises and a GEARS score during dry-lab ≥16. The simulated training sessions were video recorded. Non-technical skills were evaluated using the validated Non-Technical Skills for Surgeons (NOTSS) score Results The first "Train The Trainer" course included 14 participants aiming at becoming certified robotic trainers. Median participant age was 39 years. Overall, 13 (93%) of them showed the requested technical skills that consisted of overall score at dVSS ≥80% and GEARS score ≥24 during dry-lab anastomosis. One participant did not show the requested non-technical skills (NOTSS score <12). Therefore, 12 out 14 (86%) participants showed the requested characteristics to become a certified trainer in robotics Conclusions We developed the first robotic course dedicated to trainers, proctors, and mentors. Overall, 86% of the participants achieved the requested technical and non-technical skills. The future validation of this "Train The Trainer" course is mandatory for certified training and improved standardization Funding none
Authors
Nicola Fossati
Justin Collins Kamran Ahmed Peter Wiklund Alexandre Mottrie |
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PD41-03 |
Validation of the European SIMULATE Ureterorenoscopy Training Curriculum |
Surgical Technology & Simulation: Training & Skills Assessment II | 17BOS |
Abstract: PD41-03 Sources of Funding: SIMULATE is primarily funded by The Urology Foundation. The authors are most grateful for support from the following companies: Coloplast, Olympus, Karl Storz, Boston Scientific, ProMed, Simbionix, Limbs and Things, and Mediskilss, without whom the delivery of the educational program would not be possible. KA and PDG also acknowledge support from the NIHR Biomedical Research Centre and MRC Centre for Transplantation, King’s Health Partners. Introduction Recent developments in surgical education suggest that training using a range of simulators of different modalities, within a curriculum, may be much more effective. Furthermore, emphasis must also be placed on nontechnical skills training. The aim of this study is to assess the face, content, construct and transfer components of validity of the newly-developed SIMULATE ureterorenoscopy (URS) training curriculum. Methods A comprehensive training curriculum was developed by experts (n=21) and residents (n=25) using the Delphi process. The curriculum consists of virtual reality, dry-lab and full immersion simulation modalities. Upon completion, 30 residents were invited for training using the curriculum on two separate occasions in the UK (n=15) and Austria (n=15). The former cohort were also given the opportunity to use fresh frozen cadavers with fluoroscopy. Participants were taught and assessed, using OSATS, by endourology and education specialists, all of whom were also invited for an evaluation survey following the training program. Construct validity was assessed using a One-way ANOVA test to evaluate the level of progress throughout the training. Residents were followed up at their institutions and assessed for technical skills, using OSATS, and nontechnical skills, using a modified NOTSS score for URS on their first (n=12) and fourth (n=11) cases to evaluate transfer validity. Results Participants rated that the training significantly improved their skills (mean: 4.2/5) and that they gained transferrable skills (mean: 4.2/5). A One-way ANOVA test revealed significant improvement in both semi-rigid URS (p<0.0001) and flexible URS (p=0.0003) skills, with consecutive cases throughout the course of the curriculum and the first operating room performance (n=12). Statistically significant improvement was observed in non-technical skills from between the training and first operating room performance (p<0.0001). Of the used modalities, flexible URS (mean: 4.3/5) and stone fragmentation (mean: 4.3/5) were rated to be the strongest aspects of the UroMentor. In contrast, both the dry-lab models scored the highest with regards to instrument handling, laser stone fragmentation and stone extraction. C-arm control was the most highly rated aspect of fresh frozen cadavers (mean: 4.7/5). Conclusions The SIMULATE URS curriculum revealed face, content, construct and validity. Participants are currently being followed up in the operating room for 25 URS procedures and will compared to an arm with no simulation experience, as part of the on-going SIMULATE randomised controlled trial. Funding SIMULATE is primarily funded by The Urology Foundation. The authors are most grateful for support from the following companies: Coloplast, Olympus, Karl Storz, Boston Scientific, ProMed, Simbionix, Limbs and Things, and Mediskilss, without whom the delivery of the educational program would not be possible. KA and PDG also acknowledge support from the NIHR Biomedical Research Centre and MRC Centre for Transplantation, King’s Health Partners.
Authors
Abdullatif Aydin
Kamran Ahmed Takashige Abe Thomas Kunit Nicholas Raison Oliver Brunckhorst Thomas Wood Talisa Ross Karl-Dietrich Sievert Muhammad Shamim Khan Prokar Dasgupta |
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PD41-04 |
Development and Validation of a Non-Technical Skills Assessment Tool for Robotic Surgery |
Surgical Technology & Simulation: Training & Skills Assessment II | 17BOS |
Abstract: PD41-04 Sources of Funding: Vattikuti Foundation Introduction The importance of non-technical skills (NTS) for safe, effective surgery is being increasingly recognised. Yet surgical training remains focussed on technical proficiency. Given the unique challenges of robotic surgery with the surgeon distanced from the immediate operating field, effective NTS training is vital._x000D_ _x000D_ This study aimed to develop and validate Interpersonal and Cognitive Assessment for Robotic Surgery (ICARS), the first NTS assessment tool specifically for robotic surgery. Methods An initial framework for NTS assessment was developed through observation of robotic surgery, identifying relevant behaviours and skills. A draft assessment tool comprising all identified skills and behaviours was circulated amongst an international panel of 16 expert surgeons. A delphi methodology was used to refine the assessment checklist and provide content validation until a saturation of new information was achieved. _x000D_ _x000D_ The resultant ICARS tool was validated against the performances of 75 of novice, intermediate and expert robotic surgeons who completed simulated tasks within a distributed operating room environment using the da Vinci Xi surgical robot. During the assessment, participants were taken through 3 clinical scenarios to test NTS. NTS performance was assessed post hoc by 6 expert surgeons using ICARS and the gold standard NOTSS tool. Results Following expert consultation, ICARS was refined from 45 to 28 key components divided into 7 categories and 4 domains . ICARS was highly rated by the expert panel with strong support of face and content validation. 86% felt ICARS was appropriate tool for robotic surgery, 77% thought ICARS was relevant to robotic surgery and 74% felt it would be very beneficial robotic training. Significant differences were seen in scores of novice, intermediate and expert subjects. Bland-Altman plot showed a strong correlation with NOTSS. ICARS also showed robust inter-rater reliability with a mean interclass correlation coefficient of 0.81. Strong internal consistency was demonstrated for all principle domains of the rating system with a mean Cronbach Alpha 0.90 (range 0.83-0.93). Conclusions We have developed the first NTS assessment tool for robotic surgery. Comprehensive validation of ICARS has demonstrated equivalence to the current gold standard, generic assessment tool, extensive internal structure reliability and a high degree of acceptance by expert robotic surgeons. Structured NTS training needs to be integrated within the robotic curriculum and ICARS has been demonstrated to be a valid tool with which this can be supported. Funding Vattikuti Foundation
Authors
Nicholas Raison
Thomas Wood Oliver Brunckhorst Takashige Abe Abdullatif Aydin Andrea Gavazzi Giacomo Novara Nicolo Buffi Declan Murphy Shamim Khan Ben Challacombe Henk Van Der Poel Craig McIlhenny Prokar Dasgupta Kamran Ahmed |
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PD41-05 |
Transfer of flexible ureteroscopic stone-extraction skill from a virtual reality simulator to the operating theatre: A pilot study |
Surgical Technology & Simulation: Training & Skills Assessment II | 17BOS |
Abstract: PD41-05 Sources of Funding: This work was partially sponsored by Fonds de la Recherche Sante du Quebec (FRSQ) grants to Dr Mehdi Aloosh and Dr Sero Andonian and by a grant from the Urology Care Foundation Research Scholars Program and the Boston Scientific Corporation, The Endourological Society, and the_x000D_ &[Prime]Friends of Joe&[Prime] and the Canadian Urological Association-Societe Internationale d&[prime]Urologie (CUA-SIU) Scholarship to Dr Yasser Noureldin. Introduction Ureteroscopic stone extraction is the gold standard for management of ureteral and some renal stones. To_x000D_ achieve competency in performing this minimally invasive procedure and decrease the chance of potential complications adequate training is essential. However,_x000D_ there are concerns whether training exclusively in the operating theatre is adequate to achieve competency. Thus, simulators were introduced for training in a_x000D_ radiation and stress-free environment. UroMentorTM simulator (Simbionix, Cleveland, Ohio, USA) has been validated for training ureteroscopy. However there is no data on the learning curve of ureteroscopic stone extraction on the simulator. Moreover, it is unknown whether skills acquired on this simulator are transferable to the operating theatre. Therefore, the aim of this study was to assess the learning curve of flexible ureteroscopic stone extraction and transfer of the skill obtained from the simulator to the operating theatre. Methods After obtaining ethics approval, Post Graduate Trainees (PGTs) from PGY1-4 were recruited. During phase I, participants completed three weekly one-hour training sessions on the UroMentorTM simulator practicing task 10, where two small stones from the left proximal ureter and renal pelvis were extracted using a basket. Assessments from the simulator and the validated Ureteroscopy-Global Rating Scale (URS-GRS) were used to establish the learning curve. During phase II, the URS-GRS tool was used to assess performance of participants in the operating theatre. Results In phase I, eight right-handed urology PGTs (PGY1-4) with mean age of 27.8±2 (25-31) years participated. PGTs practiced a total of 52 times, with a mean fluoroscopy time of 10.4±12 seconds and a mean operative time of 14.6±4.3 minutes. Competency in the task was achieved after seven trials on the simulator. In phase II, five PGTs were assessed while performing 55 consecutive flexible ureteroscopic stone extraction procedures in the operating room. The mean operative time was 51.4±15.2 minutes and the mean fluoroscopy time was 29±6 seconds. There was a significant correlation between URS-GRS scores obtained on the simulator and in the operating theatre (r=0.9, p=0.03). Conclusions Competency in performing flexible ureteroscopic stone-extraction on the UroMentor simulator was achieved after seven trials. Since there was a strong correlation between URS-GRS scores on the simulator and in the operating theatre, this skill could be transferred from the simulator the_x000D_ operating theatre. Funding This work was partially sponsored by Fonds de la Recherche Sante du Quebec (FRSQ) grants to Dr Mehdi Aloosh and Dr Sero Andonian and by a grant from the Urology Care Foundation Research Scholars Program and the Boston Scientific Corporation, The Endourological Society, and the_x000D_ &[Prime]Friends of Joe&[Prime] and the Canadian Urological Association-Societe Internationale d&[prime]Urologie (CUA-SIU) Scholarship to Dr Yasser Noureldin.
Authors
Mehdi Aloosh
Yasser A Noureldin Sero Andonian |
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PD41-06 |
Robot-assisted training - expert performance in full immersion simulation, setting the benchmark (concurrent validity) |
Surgical Technology & Simulation: Training & Skills Assessment II | 17BOS |
Abstract: PD41-06 Sources of Funding: none Introduction To evaluate surgical trainee performance, technical and non-technical skills can be assessed during full immersion simulation. This study aimed to define the benchmark that novices must attain before achieving competency in urethro-vesical anastomosis (UVA). Benchmark scores are important to reflect when a trainee is safe to perform the task on a real patient by providing an objective assessment of a trainee's performance. Methods 14 expert and intermediate robotic surgeons were assessed for technical and non-technical skills whilst performing UVA in full immersion simulation, with actors playing the roles of scrub nurse and anaesthetist. UVA requires suturing the urethra to the bladder. A series of stressors were applied during the task to enable full assessment of non-technical skills. Data was compared to the performance of 22 medical student novices to establish construct validity. Video footage was assessed by an international expert using GEARS and NOTSS. Mean expert scores were then used to define a competency benchmark. Results There was a statistically significant difference in technical and non-technical skills between novices, intermediates and experts (p = 0.031, p = 0.047 respectively). As construct validity was displayed, mean expert scores were used to define a benchmark score of 2.9 for technical skills and 2.8 for non-technical skills. There was no significant difference between laparoscopic and robotic experts, suggesting there may be some transference of skill from previous laparoscopic experience. Conclusions Trainees should aim to achieve a mean GEARS score of 2.9 and a mean NOTSS score of 2.8 to achieve competency in performing UVA. Using these benchmark scores will help to deem whether a trainee is competent to perform an unassisted UVA on a patient and can be incorporated into robot-assisted surgery training programmes to monitor progression. Future work must be carried out to further evaluate whether there is a role for transference of skills from laparoscopic experience to robot-assisted surgery. Funding none
Authors
Talisa Ross
Nicholas Raison Lauren Wallace Thomas Wood Catherine Lovegrove Henk Van der Poel Prokar Dasgupta Kamran Ahmed |
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PD41-07 |
The Evaluation of a Silicone Renal Tumor Model for Partial Nephrectomy Training |
Surgical Technology & Simulation: Training & Skills Assessment II | 17BOS |
Abstract: PD41-07 Sources of Funding: Research reported in this abstract was supported by the Washington University Institute of Clinical and Translational Sciences grant UL1TR000448, sub-award TL1TR000449, from the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health (NIH). The content is solely the responsibility of the authors and does not necessarily represent the official view of the NIH. Additional support was provided by the Washington University in St. Louis Division of Urology. Introduction Every year more partial nephrectomies are performed as a surgical treatment for kidney cancer. However, this procedure remains technically challenging and no established practice model exists for partial nephrectomy training. We created silicone renal tumor models using 3D printed molds of a patient's kidney with a mass. In this study, we seek to validate these silicone models using multiple simulations with urologists of different training levels. Methods This study is ongoing and recruitment began in late October 2016. Medical students, urology residents, fellows, and attending surgeons are recruited to perform simulated partial nephrectomies on silicone renal tumor models. Four trials are performed with a da Vinci surgical robot on two different days. Operation specific metrics including renal artery clamp time and surgical margins are recorded for each trial. Validated measures of self-assessed operative demand (NASA TLX) and reviewer-assessed surgical performance (GEARS) are also recorded across trials. Results The preliminary results of two medical students, four urology residents, two endourology fellows, and one attending urologist are reported here. Between trials one and four we saw a mean reduction of 3.26 minutes in renal artery clamp time, and a 75% reduction in positive margins. We also saw reduced incidence of positive surgical margins with advanced training stage. Fellows, residents, and medical students had positive margin incidences of 25%, 50%, and 75% respectively. Model face validity was surveyed on a 0-100 sliding scale anchored at unrealistic and realistic. Mean results thus far are 77.5 for overall feel, 79 for needle driving, and 77.5 for cutting. We expect to recruit 20 additional subjects for this study. Upon completion of data acquisition, more robust statistical comparisons and measures will be reported. Conclusions Preliminary data indicate a trend in improved surgical performance over the course of the training and better performance in urologists of higher training levels. Face validity measures indicate the model adequately represents reality. This model may have potential for broader application and integration into minimally invasive surgery training programs. Funding Research reported in this abstract was supported by the Washington University Institute of Clinical and Translational Sciences grant UL1TR000448, sub-award TL1TR000449, from the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health (NIH). The content is solely the responsibility of the authors and does not necessarily represent the official view of the NIH. Additional support was provided by the Washington University in St. Louis Division of Urology.
Authors
Steven Monda
Jonathan Weese Barrett Anderson Ramakrishna Venkatesh Baisong Cheng Robert Figenshau |
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PD41-08 |
Skill Acquisition and its Retention after Simulation-based Practice during Robot-Assisted Surgery: Can functional Brain States Help us Forge Forward? |
Surgical Technology & Simulation: Training & Skills Assessment II | 17BOS |
Abstract: PD41-08 Sources of Funding: Roswell Park Alliance Foundation Introduction Patient safety is fundamental to surgical practice and it is critical to ensure surgical training and competence. Little has been published on brain cognitive states during learning and retention of basic Robot-Assisted Surgical skills. We sought to evaluate the feasibility of utilizing a novel brain functional states to evaluate surgical competency. Methods 27 medical students were evaluated while performing four key tasks of the validated Fundamental Skills of Robot Surgery (FSRS) Curriculum and one advanced surgical module - the Hands-on Surgical Training (HoST) over six sessions, utilizing the robotic Surgery Simulator (RoSS). The four FSRS tasks evaluated were - Instrument Control Task, Ball Placement Task, Spatial Control II Task, Threading string through a series of hoops and 4th Arm Tissue Retraction. Tool –based metrics were assessed and recorded by RoSS. Brain states are extracted using the pairwise phase synchronization between EEG channels and are presented as functional brain networks. The functional brain networks are then quantified using network statistics, and spectral density of signals for all channels (mental workload). Results The average mental workload initially increases before significantly decreasing across sessions(Fig 1). This trend is also observed in functional brain states during the four tool-based metrics, as integration and segregation features increase at the beginning of learning and later decrease (Fig 2). We observed significant correlations between brain state and tool-based metrics (RoSS), while performing HOST task, where brain states do not correlate. Conclusions We report to our knowledge, the first study that evaluates brain states during skill acquisition and learning after simulation-based training. Various brain areas are functionally activated and integrated while acquiring new skills but these interactions decrease after preliminary learning. Funding Roswell Park Alliance Foundation
Authors
Somayeh Shafiei
Thomas Fiorica Ahmed Hussein Youssef Ahmed Sarah Muldoon Khurshid Guru |
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PD41-09 |
Teaching and Evaluation of Basic Urodynamic Skills: Quebec Urology Resident Experience |
Surgical Technology & Simulation: Training & Skills Assessment II | 17BOS |
Abstract: PD41-09 Sources of Funding: none Introduction Recognizing the growing role of urodynamics (UDS) in advanced urology, residency programs have rapidly incorporated it into their training curriculum. However, there is no consensus on the best methods of teaching UDS application. Therefore, we aimed to determine the most appropriate teaching method with objective evaluation to enhance urodynamic skills, in order to improve quality of teaching and patient care. Methods Urology residents (n = 20) were randomized according to postgraduate year and training institution to either review a video training module or a teaching document, on UDS, prior to an objective structured clinical examination (OSCE). Participants were given a basic questionnaire evaluating age, training level, adequacy of training, estimated UDS interpretation proficiency. The OSCE contained 12 UDS tracings with questions and assessing level of certainty. Two urologists independently established the correct answers. Two blinded, independent graders scored each UDS question to determine competency (0=incorrect, 1=partially correct, 2=correct). Certainty was scored on a scale of 0 to 4 (0 representing a guess and 4 representing 100% certainty). Results The median self-reported proficiency was 5 out of 10, mean total score was 13.3 of 24, and overall certainty was 27 of 48. There was significant difference in overall competency between both groups (video: 15.1 ± 2.08, document: 11.4 ± 2.41, P<0.01). Also, the video training module group achieved a higher score on overall certainty (30.7 ± 4.99 versus 22.4 ± 10.3, P<0.05). When analyzing each diagnosis, we found that the mean score for correctly identifying proper calibration and bladder outlet obstruction was significantly higher in the video training module group, while approaching significance for detrusor sphincter dyssynergia (P<0.05) respectively. Overall competency was significantly correlated with self-reported proficiency (r = 0.502, P<0.05), total certainty (r = 0.531, P<0.05), and overall urodynamic experience (r = 0.503, P<0.05). Conclusions A urodynamic video training module improved residents UDS knowledge and interpretation skills. These findings highlight the need to incorporate multimedia teaching for UDS interpretation into urology curriculum. Future research should focus on curriculum standardization and optimal learning methods to improve UDS competency. Funding none
Authors
Samer Shamout
Sero Andonian Hani Kabbara Lysanne Campeau |
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PD41-10 |
Evaluation of the feasibility of remotely manufactured low-cost three-dimensionally printed laparoscopic trainers and comparison to standard laparoscopic trainers |
Surgical Technology & Simulation: Training & Skills Assessment II | 17BOS |
Abstract: PD41-10 Sources of Funding: none Introduction We have previously documented the feasibility of the local three-dimensionally (3D) printed manufacture and efficacy of a low cost, portable laparoscopic trainer (UCi Trainer) that utilizes an electronic tablet for video and optics. In the current study, we evaluate the feasibility of remote 3D manufacture of the UCi Trainer with commercially available “home” printers. We also compared the performance of the UCi Trainer and a standard pelvic trainer (SPT) (Karl Storz, Tuttlingen, Germany) (Richard Wolf, Vernon Hills, Illinois, USA). Methods We created computer-aided designs for nine components to be assembled into a laparoscopic training device. These files were provided to four institutions to 3D print using an inexpensive “home” 3D printer (Flashforge Creator 3D printer), assemble, and use the trainer. All institutions were provided standardized instructions for printing and assembly of the components, and were asked to rate the 3D printing and assembly process. Participants were assigned to perform timed peg transfer and intracorporeal knot tying tasks with the UCi Trainer and SPT, as well as rate each trainer on image quality, resolution, brightness, comfort, and overall performance on a 5-point Likert scale. A local instructor evaluated trainee performance on the peg transfer and knot tying tasks. Results The printer cost was $876.48, and the total materials cost was $26.50 for each UCi Trainer manufactured. Initial set up of the 3D printer was challenging to all participants but with adjustments, successful printing and assembly of the components was accomplished. All participants recommended 3D printing as a method for disseminating surgical education tools. A total of 16 subjects participated in the trainer comparison assessment. There was no significant difference between peg transfer and intracorporeal knot tying task scores completed on the UT when compared with the SPT (p > 0.05). Participants rated the SPT significantly higher compared to the UCi Trainer (p<0.05): image quality (3.19 vs 4.25), resolution (3.56 vs 4.31), brightness (3.19 vs 4.38), delay (3.25 vs 4.38), overall comfort (3.13 vs 3.88), and overall performance (3.19 vs 4.06). In the questionnaire participants agreed that the UCi Trainer is similar to laparoscopy (44%), comfortable to use (56%), good practice format (88%), would purchase the UCi Trainer (69%), and would recommend the UCi Trainer for residents (88%). Conclusions The UCi Trainer can be remotely manufactured in a cost-effective manner. It appears to be a valuable tool for facilitating resident training in laparoscopy. Funding none
Authors
Renai Yoon
Zhamshid Okhunov Benjamin Dolan Michael J. Schwartz Paras H. Shah Hannah Bierwiler Aldrin Joseph Gamboa Roberto Miano Stefano Germani Dario Del Fabbro Alessio Zordani Salvatore Micali Kamaljot Kaler Ralph V. Clayman Jaime Landman |
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PD41-11 |
SAFETY OF LIVE SURGERY IN UROLOGY. PROPENSITY SCORED MATCHED ANALYSIS |
Surgical Technology & Simulation: Training & Skills Assessment II | 17BOS |
Abstract: PD41-11 Sources of Funding: None Introduction Live surgery events (LSE), have become one of the most attended activities at surgical meetings, providing a unique opportunity for surgeons to observe in real time, the decision-making process by skilled and experienced surgeons. However, there is an ongoing discussion on whether patients who are treated during LSE are at a higher risk for complications._x000D_ The purpose of this study is to examine the safety of live robotic-assisted radical prostatectomy (RARP) cohort, performed in our institution by a single surgeon and to provide evidence on this practice._x000D_ Methods From January 2008 through April 2016, >9000 patients underwent RARP at our institution, performed by a single surgeon. From this group, 36 patients underwent live transmission via video link from our institution to an external cogress of RARP. A propensity-matched analysis was conducted, in a 1:3 proportion, comparing outcomes of live transmission cases to those operated under regular circumstances. Postoperative outcomes were analyzed between the live surgery (LS) group (n=36) and the propensity-matched group (control group; n=108). Results There were no significant demographic differences between the two groups regarding the comorbidities, clinical tumor stage, pre-operative PSA, biopsy Gleason score, body mass index (BMI), pre-operative SHIM score and AUA symptoms score and D&[prime]Amico class. The only significant difference in the demographic was the age: 55.42 ± 7.33 y.o for the LS group vs. 58.76 ± 6.24 y.o for the control group (p= 0.016). The operative time was longer in the LS group when compared to the control: 136.14 min ± 24.29 vs. 122.43 min ± 23.72, respectively (p= 0.0036), however, the console time was shorter for the LS group 72.6 min ± 10.41 compared to the 76.48 min ± 9.42, of the control group (p= 0.0402). No major complications were reported in any of the groups, and only 4 minor complications were observed in the control group (p= 0.2415). After a median follow-up of 31.17 ±[ge] 19.17 months, only one patient (2.77%) in the live surgery group presented biochemical recurrence vs. four (3.71%) in the control group (p= 0.7927). No differences were seen in the continence rate, 97.22% for both groups, and no differences were observed in the potency rate for either group: 69.44% for the LS group vs. 67.59% in the control group (p=0.4034). Conclusions In this series of live transmission of RARP, the perioperative results (oncological/ functional outcomes and complications) were similar to those found in daily practice. These findings suggest that LS of this procedure in selected patients and selected centers is safe. Funding None
Authors
Gabriel Ogaya
Eduardo Hernandez-Cardona Hariahran Palayapalayam Xavier Bonet Cathy Jenson Vipul Patel |
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PD41-12 |
The quantified surgeon: defining and validating clinical performance metrics during robotic radical prostatectomy |
Surgical Technology & Simulation: Training & Skills Assessment II | 17BOS |
Abstract: PD41-12 Sources of Funding: None Introduction More attention has been directed to surgeon performance and surgical outcomes. A novel recording solution (&[Prime]dVLogger&[Prime]) for direct capture of surgeon manipulations on the da Vinci surgeon console has been deployed to explore and validate automated surgeon performance metrics. Herein, we present an initial construct validation (expert vs novice) of metrics during select steps of the robotic radical prostatectomy (RRP)._x000D_ Methods We recorded performance data from da Vinci Si systems for training (<200 console cases) and expert (≥200 cases) surgeons performing 4 RRP steps: bladder mobilization (BM), seminal vesicles dissection (SVD), anterior vesicourethral anastomosis (AA) and right pelvic lymph nodes dissection (RLD). The performance metrics, including instrument movements, hand controller movements, and system events, were computed and compared between expert/training groups using the Kruskal-Wallis test._x000D_ Results We evaluated 40 RRP cases. Eight experts (median 450 (200-2000) console cases experience) and 8 novices (median 50 (30-150) cases) participated. For all 4 steps, experts outperformed trainees in total moving time of all instruments (28 vs 49 min, 16 vs 28 min, 15 vs 27 min, 25 vs 52 min respectfully, p<0.01), and total distance traveled by all instruments (33.2 vs 52.6 m, 15.7 vs 25.4 m, 14 vs 20.1 m, 30 vs 59.4 m respectfully, p<0.01). For BM, SVD, AA, experts moved instrument controlled by their dominant hand faster than trainees (2.8 vs 2.3 cm/s, 2.2 vs 1.9 cm/s, 1.8 vs 1.4 cm/s respectfully, p<0.02). Experts applied energy more often than novices during BM, SVD, and RLD (9 vs 6.6 times/min, 8.4 vs 5.4 times/min, 7.2 vs 3.6 times/min respectfully, p<0.01). During AA and RLD, experts adjusted camera position more often than trainees (6 vs 4 times/min, 6.6 vs 5.4 times/min, p<0.05). During BM, experts adjusted hand controller position (i.e. master clutch) more often (2.4 vs 1.8 times/min, p=0.007). Experts were more efficient during the RLD than trainees (1.75 vs 3.3 min/node, p=0.001)._x000D_ Conclusions Experts were more efficient and directed in their movement. Further correlation of metrics to clinical outcomes would further validate their clinical significance. This data can also help establish standardized metrics for surgeon assessment, credentialing, and workflow efficiency._x000D_ Funding None
Authors
Andrew Hung
Jian Chen Anthony Jarc Inderbir Gill |
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PD42-01 |
Impact of preoperative alpha-adrenergic antagonists on ureteral access sheath insertion force and the upper limit of force to avoid ureteral mucosal injury: A randomized-controlled study |
Surgical Technology & Simulation: Instrumentation & Technology II | 17BOS |
Abstract: PD42-01 Sources of Funding: none Introduction Primary access of the ureteral access sheath (UAS) is not always possible and often excessive force is exerted, thereby increasing the risk of ureteral injury. A randomized controlled trial was performed to investigate the efficacy of preoperative α-blockade on reducing UAS insertion forces (UASIF) and to appreciate the upper limit of UASIF to avoid ureteral injury. Methods From December 2015 to October 2016, 88 patients with ureteropelvic junction or renal pelvis stones planned for retrograde intrarenal surgery (RIRS) were prospectively enrolled. Patients were randomly assigned to a control group (n=37) or to an experimental group who received α-blockade with tamsulosin 0.4 mg q.d. for seven days prior to RIRS (n=39). Pre-stented patients were excluded from randomization (n=12). A homemade UASIF gauge was adapted to measure the maximal UASIF at the ureterovesical junction (UVJ) and the proximal ureter. The degree of mucosal injury was recorded. Results UASIF of the α-blockade group was significantly lower than controls at the UVJ (260.1±180.2 g vs. 524.2±237.5 g; p=0.017), however, not at the proximal ureter (367.2±175.2 g vs. 647.7±294.3 g; p=0.054). The α-blockade group exhibited comparable UASIF with the pre-stented group at the UVJ (260.1±180.2 g vs. 99.8±19.9 g; p=0.149) and the proximal ureter (367.2±175.2 g vs. 131.4±75.2 g; p=0.081). The rate of mucosal injury was lower in the α-blockade group compared to controls (p=0.028). Mucosal injury (≥grade 2) did not occur in cases with UASIF <600 g. UASIF was lower in females and patients aged ≥70 years compared to the counterparts (p=0.008 and p=0.021, respectively). Female gender and preoperative α-blockade were independent predictors of lower risks of ureteral injury. Conclusions Preoperative α-blockade mimics the effect of pre-stenting and reduces maximum UASIF and consequent risk of ureteral injury. If the UASIF exceeds 600g, the procedure could be terminated with stent placement and followed later by pre-stented RIRS. Funding none
Authors
Kyo Chul Koo
Joon Ho Yoon No-Cheol Park Jongsoo Lee Jong Won Kim Jae Yong Jeong Sung Ku Kang Jong Chan Kim Kwang Suk Lee Do Kyung Kim Chang Hee Hong Byung Ha Chung |
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PD42-02 |
Development and validation of a homemade device for the measurement of ureteral access sheath insertion force |
Surgical Technology & Simulation: Instrumentation & Technology II | 17BOS |
Abstract: PD42-02 Sources of Funding: none Introduction Excessive ureteral access sheath insertion force (UASIF) during retrograde intrarenal surgery (RIRS) poses risk of ureteral mucosal injury. However, the optimal UASIF has not yet been defined. Our aim was to develop a homemade UASIF measurement gauge and to validate its feasibility before application to clinical practice. Methods Our homemade UASIF measurement gauge consisted of four parts: (A) a V-block jig to secure the UAS, (B) a linear jig to offset torque at sheath exertion, (C) a commercial digital force gauge (IMADA ZTA-50N, IMADA instruments, Korea) capable of 1 g readability ranging from 1.0 to 5,000 g at a millisecond frequency, and (D) an aluminum linear shaft to install and secure all jigs (Fig.1). A 12/14Fr diameter UAS (NavigatorTM HD, Boston Scientific, USA) and biologic material were used to measure the UASIF at various experimental settings. Results To evaluate measurement deviations that may arise from coaxial forces induced by buckling and kinking of the UAS, serial weights (1 g - 170 g) were applied and measured at two locations on the V-block jig: at the UAS fixation groove and at parallel to the linear shaft (Fig.2). Linear measurements at both locations showed excellent concordance (r=0.989, p<0.001). To analyze the reproducibility of UASIF measurement, a vice grip was applied to a biologic material at four different friction settings. UASIF was measured at each friction setting by four operators (Fig.3). UASIF increased linearly to friction increment, and showed excellent reproducibility for maximal UASIF values with a mean standard deviation of 4.24 g (Fig.3). At a fixed friction, higher insertion velocity resulted with greater maximal UASIF (Fig.4). Conclusions Our homemade UASIF measurement gauge would be applicable to clinical practice. It can be utilized to help better elucidate which parameters, or combinations of parameters, will predict successful UAS deployment. Funding none
Authors
Kyo Chul Koo
Joon Ho Yoon No-Cheol Park Kwang Suk Lee Do Kyung Kim Jong Chan Kim Sung Ku Kang Jae Yong Jeong Jong Won Kim Jongsoo Lee Chang Hee Hong Byung Ha Chung |
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PD42-03 |
Efficacy of single uretral stent versus two stent insertions after bilharzial uretral stricture managed by laser endouretrotomy: A randomized Controlled Study |
Surgical Technology & Simulation: Instrumentation & Technology II | 17BOS |
Abstract: PD42-03 Sources of Funding: none Introduction Stricture ureter due to bilharzias is characterized by focal destruction of ureteral muscle. With the advancements of endourologic techniques and increasing in experience made endouretrotomy the treatment of choice for surgical repair for most benign ureteral strictures._x000D_ There is debate about the optimal size of uretral stent size after endouretrotomy. However, many studies recommend larger caliber stents (12-14 Fr)._x000D_ We evaluate our initial experience of insertion of single uretral stent versus two stent after management of bilharzial uretral stricture by laser endouretrotomy._x000D_ Methods Within 2.5 years, 54 patients under went retrograde laser endouretrotomy for bilharzial stricture ureter (diagnosed by positive history of bilhaziasis, positive serology test, bilhazial cystocopic finding, no history of stone, or urologic or pelvic surgery). Patients were randomized into two group, group I (27 patients) have two DJ (7 Fr each) while group II (27 patients) those have single DJ 7 Fr (after endouretrotomy). DJ was removed after 8 weeks. Follow-up was done regularly for 1 year by clinical interpretation and imaging studies. _x000D_ Patients' characters, operative data, operative results (subjectively and objectively) were compared in both groups._x000D_ Results Fifty one complete follow-up >12 month, mean age 46.3 (16-70) Vs 45.2 (18-62) years, mean stricture length 1.48 (0.5-3) Vs 1.27 (0.5-2.5) cm, mean follow-up 20.6 (12-30)Vs 19.4 (12-30) month for group 1 and 2 respectively, (with no significant difference between both group). Success proved by relief of symptoms and radiographic resolution of obstruction. The success rate was significantly better in group (I) Vs group (II) (84% Vs 57.7%) p <0.039. _x000D_ Conclusions Insertion of two DJ, post laser endoureterotomy for bilharzial stricture ureter associated with long term success rate then insertion of single DJ._x000D_ Funding none
Authors
Khaled Mohyelden
Mahmoud Shoukry Hussein Aldaqadossi Hossam Shaker Hamdy Ibrahem |
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PD42-04 |
Ureteral access sheath use associated with loss of reusable ureteroscope flexion and increased need for repair: a multi-institutional prospective cohort study |
Surgical Technology & Simulation: Instrumentation & Technology II | 17BOS |
Abstract: PD42-04 Sources of Funding: the NIH NIDDK K12-DK-07-006: Multidisciplinary K12 Urologic Research Career Development Program as well as an educational grant from the Boston Scientific Foundation. Introduction While technical advances have improved durability and functionality of reusable flexible ureteroscopes, device use and maintenance can involve high costs and administrative burden. The fragility of these instruments necessitates eventual repair and can render the scope inaccessible during refurbishment. We conducted a multi-institutional prospective cohort study to identify perioperative factors influencing flexible ureteroscope durability. Methods This study was a collaboration of the Western Endourology STone (WEST) research consortium consisting of six United States tertiary care centers. Consecutive patients undergoing flexible ureteroscopy were enrolled, and scope performance parameters as well as patient characteristics and intraoperative data were collected between August 2014 and June 2015. Surgeon self-reported concern and satisfaction with each scope were queried following each procedure. Upward and downward angles of deflection of each scope tip were measured before and after procedures. The need for scope repair was determined by the operating surgeon at the time of the procedure and recorded. Results 386 ureteroscopic procedures using 63 flexible ureteroscopes were identified. 300 cases (77.7%) were performed for stone disease treatment. Scope repair was required in 25 cases (6.5%) and 23 scopes (36.5%). Upon univariate analysis, female gender, shorter patient height, absence of guidewire use, presence of a ureteral access sheath, longer laser time, lithotrite type, surgeon training level, self-reported concern, and degree of scope upward flexion both pre- and postop were associated with need for scope repair. Upon multivariate analysis, access sheath use (OR=3.09, p=0.0127) and decreased degree of upward flexion at the end of the case (OR=0.972, p=0.0171) were associated with need for scope repair (Table 1). Access sheath use, patient height, and surgeon concern were associated with loss of scope upward flexion. Conclusions The use of a ureteral access sheath is associated with the loss of upward ureteroscope flexion, which may lead to the need for scope repair. These factors should be considered when evaluating means of optimizing reusable ureteroscope durability. Funding the NIH NIDDK K12-DK-07-006: Multidisciplinary K12 Urologic Research Career Development Program as well as an educational grant from the Boston Scientific Foundation.
Authors
Kazumi Taguchi
Manint Usawachintachit David T Tzou Matthew D Sorenson Jonathan D Harper Brian D Duty Roger L Sur David L Wenzler Dylan Isaacson Carissa Chu Marshall L Stoller Thomas Chi |
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PD42-05 |
First clinical evaluation of a new single use flexible cystoscope dedicated to double-J stent removal (Isiris™): a European prospective multicenter study |
Surgical Technology & Simulation: Instrumentation & Technology II | 17BOS |
Abstract: PD42-05 Sources of Funding: None Introduction We evaluated a new single use digital flexible cystoscope with an integrated grasper designed for double-J stent removal, Isiris® addressing success rate, image quality, deflection, maneuverability and grasper functionality. Methods In September 2015 a prospective cohort study was conducted in six tertiary European reference centers. All consecutive patients included underwent double-J stent removal with Isiris® (Figure 1) and were 18 years or older. Success rate was defined by complete stent removal. Image quality, deflection, maneuverability and grasper functionality were rated with a Likert scale. Results A total of 83 procedures were performed. 82% of procedures were performed in the endoscopy room while the others were in the operating room since a consecutive endourological intervention was planned. The median duration of stent implantation was 28 days [14; 60], Table 1. In five patients, stent removal was not possible. Four patients had an incrusted double-J stent and in one patient the stent migrated into the ureter. After unsuccessful attempts of stent removal with conventional flexible cystoscope and grasper, the five patients had to be scheduled for an ureterorenoscopy procedure to remove the stent. In the other 78 patients all double-J stents were removed successfully. Image quality, deflection, maneuverability and grasper functionality were rated as “very goodâ€� in 72.3%, 78.3%, 72.3% and 73.5% respectively, Table 2. Conclusions This multicenter clinical evaluation of Isiris® displayed good image quality, active deflection, maneuverability and grasper functionality. Further evaluation of stent removal outcomes, cost analysis and microbiology will help to delineate the possible place of Isiris® in the current practice. Funding None
Authors
Steeve Doizi
Guido Kamphuis Guido Giusti Jose Luis Palmero Jake Patterson Silvia Proietti Michael Straub Jean de la Rosette Olivier Traxer |
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PD42-06 |
Assessment Of New Technology In Ureteroscopy: A Comparison Of Digital, Fiberoptic, And Disposable Digital Ureteroscopes Using A Novel Evaluation Instrument |
Surgical Technology & Simulation: Instrumentation & Technology II | 17BOS |
Abstract: PD42-06 Sources of Funding: None Introduction Currently there is no standardized evaluation instrument for evaluation and comparing flexible ureteroscopes for clinical or research purposes. Our goals were to test a novel evaluation instrument in order to assess the performance of flexible ureteroscopes including a new disposable digital flexible ureteroscope during clinical use._x000D_ Methods We designed a novel evaluation instrument comprised of 9 questions designed to provide a comprehensive assessment of a flexible ureteroscope. Response options were presented as an interval scale ranging from 0 to 5 with 5 being the best response possible. We tested the instrument at our institution by administering it after routine upper tract stone cases utilizing a flexible ureteroscope. Three flexible ureteroscope categories were evaluated including: fiberoptic (Olympus URF-P5/P6), reusable digital (Storz Flex Xc), and the LithoVue disposable digital (Boston Scientific). Any urologist or trainee who used the ureteroscope during the procedure was allowed to evaluate the ureteroscope. The instrument was completed independently of each other and opinions about the ureteroscope were not discussed during the procedure. Internal consistency was assessed with Cronbach’s alpha and Pearson correlation coefficients were calculated to describe the linear relationship between items. Multivariate analyses were done to assess responses. Results A total of 34 upper tract stone cases were performed resulting in 79 evaluations. The Storz digital scored the highest of the three ureteroscopes. The image quality was very good on the LithoVue outside the patient, but we did notice some distortion when performing laser lithotripsy that impaired vision. We found no difference in the ease of ureteral access between the ureteroscopes. The instrument demonstrated internal consistency (Cronbach’s alpha = 0.85). The mean inter-item Pearson correlation coefficient was 0.46 (0.10 to 0.88), the highest of which related maneuverability to overall satisfaction (0.88). Respondents who had completed residency scored the ureteroscopes significantly lower in the areas of maneuverability, intuitiveness and overall satisfaction (P = 0.019, 0.003, and 0.046 respectively). Conclusions We report our results from a pilot study evaluating a novel flexible ureteroscope evaluation instrument during clinical use. All ureteroscopes performed well on our evaluation instrument during clinical use. Further validation is needed to assess the quality of this evaluation instrument._x000D_ Funding None
Authors
John Roger Bell
Sara L Best Kristina L Penniston Stephen Y Nakada |
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PD42-07 |
Comparative In Vitro Study of Ho:YAG and Tm Fiber Laser Lithotripters in Dusting Mode of Operation |
Surgical Technology & Simulation: Instrumentation & Technology II | 17BOS |
Abstract: PD42-07 Sources of Funding: IPG Medical Introduction Laser lithotripsy (LL) has become a first-line modality for treatment of many diagnoses of urinary tract _x000D_ stones. The de facto gold standard laser source for LL systems is a Ho:YAG (Ho) laser emitting at the wavelength of 2.10 µm. _x000D_ Dusting mode of operation (i.e., reduction of stones to fragments < 1÷2 mm in size) has been recognized as the most clinically _x000D_ desired regime. Recently, a high peak power pulsed Tm fiber laser emitting at 1.94 µm has been proposed as a viable alternative to _x000D_ Ho laser. In this work, we present for the first time a detailed in vitro performance comparison between top-of-the line Ho system _x000D_ and the new super-pulse Tm system in the dusting mode._x000D_ Methods A top-of-the-line Ho system (up to 120 W average power) was compared with a prototype pulsed Tm system capable of _x000D_ operation with up to 50 W average and 500 W peak power. The in vitro experimental setup included a specially designed cuvette _x000D_ allowing quantitative assessment of size distribution of stone fragments. A precisely controlled flow of water was pumped through _x000D_ the cuvette. The setup was also equipped with a high-resolution optical camera and several needle thermocouples. Post-surgery _x000D_ human stones (both bladder and kidney) as well as phantoms were used for the experiments._x000D_ Results Treatments with the two LL systems were matched in terms of average power (4, 8, 16, 32, 40 W) and/or pulse energy (0.2_x000D_ to 1.0 J), as appropriate. At least three stone specimens were used in each experiment. The following parameters have been _x000D_ evaluated: ablation rate (down to “dust” fragments < 1 mm), magnitude of the retropulsion effect (after a single pulse), temperature _x000D_ rise at water outlet vs inlet, and maximum temperature rise in the cuvette during treatment. For the ablation rate, the following _x000D_ values were measured with Ho laser: 0.62 ± 0.04 mg/s at 8 W, 40 Hz setting; 0.89 ± 0.06 mg/s at 16 W, 80 Hz; and 1.37 ± 0.48 _x000D_ mg/s at 40 W, 50 Hz. The respective numbers with Tm laser, at identical settings, were: 1.0 ± 0.2 mg/s, 2.13 ± 0.13 mg/s, and 3.64 _x000D_ ± 0.29 mg/s. The temperature rise in the cuvette was nearly equal for the two lasers. The average retropulsion distance after a _x000D_ single pulse was substantially shorter with the Tm laser. Similar tendencies were observed for the entire range of tested parameters._x000D_ Conclusions For all average power levels investigated, Tm laser demonstrated a significantly (~2 times) higher ablation rate than _x000D_ Ho laser, while maintaining equivalent thermal regime. The retropulsion effect of Tm laser was considerably less pronounced than _x000D_ that of Ho laser at equal energy settings._x000D_ Funding IPG Medical
Authors
Petr Glybochko
Gregory Altshuler Ilya Yaroslavsky Andrey Vinarov Leonid Rapoport Dmitry Enikeev Nikolay Sorokin Alym Dymov Victoria Vinnichenko |
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PD42-08 |
Introducing a combined ultrasound and electromagnetic tracking device for navigated sonographic kidney puncture. |
Surgical Technology & Simulation: Instrumentation & Technology II | 17BOS |
Abstract: PD42-08 Sources of Funding: none Introduction Precise sonographically guided puncture remains a challenge especially in gaining access to undilated renal pelvises or for biopsy of very small renal masses. Existing systems for navigated ultrasound (US) guided punctures are rarely used due to their complex setup and the increased cost. Most of the systems use electromagnetic tracking facilitating a separate field generator (FG) to be placed next to the patients. We present a novel approach for navigated renal puncture using a mobile lightweight electromagnetic FG that is combined with a conventional US probe into one compact apparatus. The system's feasibility and accuracy for renal puncture was evaluated in an in-vitro and an in-vivo model. Methods The mobile FG has a rectangular frame shaped configuration, that allows for a centered mounting of the US probe. In-vitro evaluation took place in a biological model to teach percutaneous kidney access. Therefore, 10 porcine kidneys freshly removed after commercial slaughtering were used. Their ureters were canalized to simulate hydronephrosis, and then placed inside chicken carcasses of about 1 kg. Puncturing of the renal pelvis were performed both, with and without the assistance of navigation. In case of unsuccessful puncture attempts the puncture was repeated after the renal pelvis was dilated stepwise first to a diameter of 2 mm and if still necessary to 1cm. The correct placement of the needles was checked by CT afterwards._x000D_ For in-vivo evaluation of the system a ventilated porcine model was used. First a puncture without navigation was done to place a cylindric metal bead (1x2mm) within the renal parenchyma. Then a second puncturing was performed using navigation to guide the biopsy needle as close as possible to the bead. This procedure was done twice for each kidney of the model. For verification, a CT scan was performed after every sub-step. The accuracy was calculated as the distance between the metal bead and the biopsy needle's tip. Results In 0-2 mm dilated renal pelvises of the biological model successful puncture took place in 100% vs. 60% (navigated vs. conventional) of the cases (n=10, p≤0.021). The puncture duration was 49 vs. 40 sec. In the porcine model the mean distance of metal bead and biopsy needle (n=4) was 6.36±2.18 mm. Conclusions The innovative combination of FG and US probe enables reproducible and accurate needle navigation without having to use a separate FG. Navigated punctures are superior compared to conventional sonographic punctures. Funding none
Authors
Tobias Simpfendörfer
Alfred Franz Alexander Seitel Nasrin Bopp Claudia Gasch Markus Hohenfellner Lena Maier-Hein Dogu Teber |
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PD42-09 |
Clinical Comparison of Conventional and Mobile Endockscope Videocystoscopy Using an Air or Fluid Irrigant |
Surgical Technology & Simulation: Instrumentation & Technology II | 17BOS |
Abstract: PD42-09 Sources of Funding: None Introduction Conventional videocystoscopy (CVC) requires sterile fluid irrigant, a high power external light source, a cystoscope, and a video monitor/camera system. The high equipment cost makes the widespread use of videocystoscopy prohibitive in underserved populations. We developed the Endockscope (ES), a novel and affordable videocystoscopy system, which utilizes a mobile phone for image display and a solar-rechargeable LED-flashlight as a light source and sought to compare the resultant endoscopic view with CVC in real clinical settings using both air and fluid as an irrigant. Methods Patients scheduled for in-office videocystoscopy for either bladder tumor surveillance or stent removal were considered eligible. Each patient first received CVC visualizing the bladder in a systematic manner using normal saline, a video monitor, external light source, and flexible fiberoptic cystoscope. Without removing the cystoscope, the ES was attached to the cystoscope using the iPhone 6S as a video monitor/camera and the flashlight as the light source. The cystoscopy was then repeated with fluid irrigant (Endockscope-Fluid, ES-F) and then the fluid was drained and replaced with the same volume of air (Endockscope-Air, ES-A). All three exams were recorded and then sent to 11 expert endourologists for grading on a variety of metrics (1-5 scale, 5 being best): image quality/resolution, brightness, color quality, sharpness, overall quality, and whether the video was acceptable for diagnostic purposes (yes/no). Results Ten patients underwent CVC, ES-F, and ES-A cystoscopy (J.L. or R.V.C.). Six of the 10 patients had CVC videos deemed acceptable for diagnostic purposes and thus were compared with ES. The CVC videos scored higher on every metric relative to both the ES-F and ES-A (p < 0.05). The largest difference noted between CVC and ES videos was brightness (p < 0.0001). ES-F videos trended toward higher ratings than ES-A on all metrics, although none reached statistical significance (p > 0.05); 52% and 44% of the ES-F and ES-A videos, respectively, were considered acceptable for diagnostic purposes (p = 0.384). Conclusions The Endockscope mobile cystoscopy system using a fluid irrigant may be a reasonable option in settings where electricity or access to conventional videocystoscopic equipment is unavailable. Funding None
Authors
Renai Yoon
Rahul Dutta Roshan Patel Kyle Spradling Zhamshid Okhunov William Sohn Hak Lee Jaime Landman Ralph V Clayman |
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PD42-10 |
Comparison of long-term non-metallic stents for malignant vs. non-malignant ureteral obstruction |
Surgical Technology & Simulation: Instrumentation & Technology II | 17BOS |
Abstract: PD42-10 Sources of Funding: None Introduction Ureteral stents for malignant obstruction have been noted to have failure rates as high as 40%. In the last decade metallic long-term stents have been studied as an alternative with high cost and patient discomfort. We compared outcomes using a non-metallic long-term stent for malignant versus non-malignant ureteral obstruction. Methods Since 2008 we placed Bard Optima (Covington, GA) stents for ureteral obstruction in patients not deemed suitable for definitive surgical management. Goal was to exchange stents annually. Indications included – malignant obstruction (11), calculus stricture (10), retroperitoneal fibrosis (5), radiation injury (3), ileal-ureter anastomotic stricture (2) and ureteral pelvic junction (2). Patients underwent placement of long term stents with a goal to eventually maintain stents for 365 days. Patency was evaluated by passage of wire through the stent lumen. We then compared malignant vs. non-malignant obstruction to determine any differences in outcomes. Results A total of 24 patients and 32 renal units underwent long-term stent placement from 2008 to 2016. Eleven (34%) renal units were managed for malignant obstruction versus 21 (66%) for benign reasons. The malignant group underwent 28 stent exchanges during this period. Each patient had on average 2 exchanges with a mean dwell time of 269 days. Three patient had bilateral stents. Patency rate was 100%. The non-malignant group underwent 84 stent exchanges, and on average had 4 stent exchanges per patient with a mean dwell time of 285 days. Five patients had bilateral stents Patency rate was 89%. Conclusions To our knowledge this is the first long term series evaluating non-metallic ureteral stents for long-term placement for ureteral obstruction. The Bard Optima stent is a good alternative to long-term metallic stents in patients with malignant obstruction. Compared to metallic stents, our patency rate was higher than historical series. Cost is substantially lower and patient comfort has been exceptional. Funding None
Authors
Amar P. Patel
Jeffrey Pearl John G. Pattaras |
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PD42-11 |
Tele-cystoscopy: Feasibility of equipment and training |
Surgical Technology & Simulation: Instrumentation & Technology II | 17BOS |
Abstract: PD42-11 Sources of Funding: Cancer Center Without Walls Introduction Urology workforce shortages in rural areas limit access to surveillance cystoscopy for patients with bladder cancer. With expansion of the role of urologic allied health professionals (AHP), we developed a tele-cystoscopy model in which AHPs perform cystoscopies that are interpreted and directed in real-time by board-certified urologists at a remote location. The conceptual model is comprised of three pillars: 1) development of the technical infrastructure, 2) creation of AHP cystoscopy training curriculum and skill assessment, and 3) evaluating outcomes. The purpose of this phase of the study was to assess the learning curve for an AHP and patient satisfaction with a tele-cystoscopy program. Methods Our prior work evaluated eight combinations of equipment variables - cystoscope type, compressor-decompressor (codec) version, and wireless internet speed to determine the optimal clarity. Crowd sourcing and experts agreed on the best system. Our training program includes background reading, hands-on-training, and proficiency testing. A diagnostic cystoscopy checklist was modified from gynecology literature to determine proficiency; a score of 27/35 to demonstrates competence. Patient satisfaction was measured with the Client Satisfaction Questionnaire (CSQ-8). A score of 32 indicates the highest satisfaction with care. Results We trained one nurse practitioner to perform flexible cystoscopy and quantitatively captured improvement in her competency with increasing number of cystoscopy performed using the scored diagnostic cystoscopy checklist (Figure 1). We found that 30 cystoscopies appear to be necessary to attain minimal competence but regular repetition is necessary to maintain the skill. Eighteen patients have completed the CSQ-8. Patients were almost universally satisfied with a mean score of 31/32 (std. dev. 1.09). Conclusions We have operationalized the technical infrastructure for tele-cystoscopy and demonstrated the ability to train an AHP. The high satisfaction rates suggest that tele-cystoscopy is a feasible model to project urologic manpower to underserved areas. Funding Cancer Center Without Walls
Authors
Haerin Lee
Jessica Jackson James Mills Kathleen D Lee Terran Sims Jennifer M Lobo Corey Thomas Noah S Schenkman Randy A Jones Tracey L Krupski |
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PD42-12 |
Design, fabrication, and testing of patient-specific concentric tube robots for nonlinear renal access and mass ablation |
Surgical Technology & Simulation: Instrumentation & Technology II | 17BOS |
Abstract: PD42-12 Sources of Funding: None Introduction To address limitations of current commercial, mass-produced robot-assisted surgical systems widely used in urology and other surgical specialties, we propose to develop patient- and procedure-specific dexterous robots. Our focus is on a class of continuum robots known as concentric tube robots, which are comprised of a series of hollow, nesting, precurved tubes that are individually inserted and rotated with respect to one another in order to change the shape of the overall robot. We aim to develop a method for designing, fabricating, and driving a patient-specific concentric tube robot as an alternative paradigm to traditional robotic surgical systems in order to improve procedures for specialized patient groups. As a test case we focus here on nonlinear renal access, for example, subcostal punctures into the upper pole calyces of the kidney to ablate an endophytic renal mass. Methods To enable patient-specific design of these robots, a virtual-reality based interface was developed. The interface leverages the expertise of a surgeon by immersing him or her in a 3-D virtual environment that includes a reconstructed model of the patient’s thoracoabdominal anatomy based on CT scans. Once the surgeon designs the set of concentric tubes, we generate a 3-D model and subsequently 3-D print each tube using a biocompatible polycaprolactone (PCL) filament. The printed tubes are then nested one inside the next and attached to the compact, modular actuation and control system we built for driving these robots. The surgeon controls the movement of the concentric tube robot through a teleoperation control scheme. Results A board-certified urologist performed a preliminary test of the entire system. After an explanation of the interface and its features, the surgeon was immersed in the virtual environment (using 3D reconstructions of an actual patient's upper abdominal anatomy, including kidney and an associated upper caliceal lesion) and tasked with designing a set of tubes to access the lesion. Based on his intuition and expertise, he designed three different sets, which were then 3-D printed with PCL. The surgeon then performed mock procedures by driving each concentric tube robot into a phantom model of the patient's thoracoabdominal anatomy in order to reach the lesion. The lesion was generated using a thermochromic dye which changes color when heated. Once the target was reached, a radiofrequency ablation (RFA) probe was passed through the concentric tube robot and successful ablation confirmed by color change of the lesion. Conclusions This work proposes a framework for integration of the surgeon into design and fabrication of a set of patient- and procedure- specific concentric tubes. Preliminary results demonstrate that a surgeon can use the interface to design a concentric tube robot to access and ablate renal lesions by RFA. Funding None
Authors
Tania Morimoto
Joseph Greer Elliot Hawkes Allison Okamura Michael Hsieh |
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PD43-01 |
Assessment of tumour-aggressiveness in transperineal MRI/ultrasound-fusion biopsy in comparison to transrectal systematic prostate biopsy in patients with and without prior biopsy |
Prostate Cancer: Detection & Screening VI | 17BOS |
Abstract: PD43-01 Sources of Funding: none Introduction Multiparametric magnet resonance imaging (mpMRI) plays an important role in the diagnostic of prostate cancer (PCa). However, systematic prostate biopsy (sysPbx) is still the reference method for diagnosing PCa in first and repeat biopsy setting. We compared MRI/ultrasound-fusion biopsy (fusPbx) to sysPbx in patients with and without prior biopsy. Methods 1060 consecutive patients with suspicion of PCa were investigated (first biopsy: n=222, repeat biopsy: n=838). All patients were examined by mpMRI applying the criteria of the European Society of Urogenital Radiology. Lesions were classified according PI-RADS. All patients underwent a transperineal fusPbx (mean 4 cores/lesion) and, additionally, a transrectal sysPbx (mean 12 cores) during the same session. Results In patients undergoing repeat biopsy (n=838), PCa detection rate was 51% (n=426) (GS≥7(3+4): 39% (n=325)). In fusPbx, PCa detection rate was 41% (n=345) compared to 34% (n=288) in sysPbx (p<0.0001). Also here, fusPbx showed a higher detection rate of GS ≥7(3+4) than sysPbx (33% (n=276) vs. 26% (n=214), p<0.0001). In repeat biopsy, sysPbx alone would have missed 35% (115/325) of GS ≥7(3+4) and fusPbx alone would have missed 17% (54/325) of GS ≥7 (3+4)._x000D_ In first biopsy setting (n=222), PCa detection rate was 53% (n=118) (GS ≥7(3+4): 44% (n=98)). FusPbx detected more PCa than sysPbx (49% (n=108) vs. 40% (n=89); p=0.003). Furthermore, fusPbx showed a higher detection rate of GS ≥7(3+4) than sysPbx (38% (n=85) vs. 33% (n=74), p=0.099). Missing rate of GS ≥7 (3+4) tumours was 24% (24/98) in sysPbx and 13% (13/98) in fusPbx._x000D_ Conclusions Especially patients undergoing repeat biopsy benefit of fusPbx due to a significant higher detection rate of GS≥7 tumours. In patients without prior biopsy, the combination of both biopsy modalities was associated with a higher detection rate of GS≥7 tumours. However in both groups, a relatively high portion of additional GS≥7 tumours was detected by sysPbx alone. Therefore, the combination of both biopsy modalities should be still performed in patients with repeat biopsy and should be offered in first biopsy setting. Funding none
Authors
Angelika Borkowetz
Ivan Platzek Marieta Toma Theresa Renner Martin Baunacke Michael Froehner Stefan Zastrow Manfred Wirth |
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PD43-02 |
Multicentre comparison of target and systematic biopsies using magnetic resonance and ultrasound image-fusion guided transperineal prostate biopsy in patients with a previous negative biopsy |
Prostate Cancer: Detection & Screening VI | 17BOS |
Abstract: PD43-02 Sources of Funding: N Hansen has received a research grant from RWTH Aachen University Hospital (Aachen, Germany). T Barrett acknowledges support from Cancer Research UK, National Institute of Health Research Cambridge Biomedical Research Centre, Cancer Research UK and the Engineering and Physical Sciences Research Council Imaging Centre in Cambridge and Manchester and the Cambridge Experimental Cancer Medicine Centre. C Kastner acknowledges that he has received speaker or mentorship fees from Siemens Healthcare and MedCom GmbH. The Department of Urology, Addenbrookes Hospital, Cambridge, UK, also received sponsorship of various industry for organising Prostate MRI workshops. B Hadaschik acknowledges support from the German Research Foundation. Introduction To evaluate the detection rates of targeted and systematic biopsies in magnetic resonance (MRI) and transrectal ultrasound (US) image-fusion transperineal prostate biopsy for patients with previous benign transrectal US guided biopsies in two high-volume centres. Methods Two centre, prospective outcome study of 487 patients with previous benign biopsies that underwent transperineal MRI/US fusion-guided target and systematic saturation biopsy from 2012 to 2015. MRI was reported according to PIRADS Version 1. Detection of Gleason score (GS) 7-10 cancer (PCa) on biopsy was the primary outcome. Positive (PPV) and negative (NPV) predictive values including 95% confidence intervals were calculated. Detection rates of targeted and systematic biopsies were compared using McNemar test. AUCs were calculated for PIRADS, PSA-Density and the combination of the both. Results Median PSA was 9.0 (IQR 6.7-13.4) ng/ml. PIRADS 3-5 MRI lesions were reported in 343 (70%) patients. GS 7-10 PCa was detected in 149 (31%). PPV for detecting GS 7-10 PCa was 0.20 (+/-0.07) for PIRADS 3, 0.32 (+/-0.09) for PIRADS 4, and 0.70 (+/-0.08) for PIRADS 5. NPV of PIRADS 1-2 was 0.92 (+/-0.04) for GS 7-10 and 0.99 (+/-0.02) for GS 4+3 or higher cancer. Systematic biopsies alone found 125/138 (91%) GS 7-10 cancers. In patients with suspicious lesions (PIRADS 4-5) on MRI, systematic biopsies would not have detected 12/113 significant PCa (11%), while targeted biopsies alone would have failed to diagnose 10/113 (9%). In equivocal lesions (PIRADS 3), targeted biopsy alone would not have diagnosed 14/25 (56%) of GS 7-10, whereas systematic biopsies alone would have missed 1/25 (4%). Combination with PSA-density improved the AUC of PIRADS from 0.822 to 0.846. Conclusions In patients with high probability MRI lesions, combined targeted and systematic MRI/TRUS image-fusion biopsy is still required, however, systematic biopsy alone may be sufficient in patients with equivocal lesions. Repeated prostate biopsies may not be needed at all for patients with a low PSA-density and a negative MRI read by experienced radiologists. Funding N Hansen has received a research grant from RWTH Aachen University Hospital (Aachen, Germany). T Barrett acknowledges support from Cancer Research UK, National Institute of Health Research Cambridge Biomedical Research Centre, Cancer Research UK and the Engineering and Physical Sciences Research Council Imaging Centre in Cambridge and Manchester and the Cambridge Experimental Cancer Medicine Centre. C Kastner acknowledges that he has received speaker or mentorship fees from Siemens Healthcare and MedCom GmbH. The Department of Urology, Addenbrookes Hospital, Cambridge, UK, also received sponsorship of various industry for organising Prostate MRI workshops. B Hadaschik acknowledges support from the German Research Foundation.
Authors
Claudia Kesch
Nienke Lynn Hansen Tristan Barett Jan Philipp Radtke David Bonekamp Heinz-Peter Schlemmer Anne Warren Kathrin Wieczorek Markus Hohenfellner Christoph Kastner Boris Hadaschik |
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PD43-03 |
Risk of prostate cancer diagnosis following a low-suspicious prostate MRI or benign MRI-targeted biopsies: A 3-year follow-up study of men with prior negative transrectal ultrasound guided biopsies |
Prostate Cancer: Detection & Screening VI | 17BOS |
Abstract: PD43-03 Sources of Funding: none Introduction Multiparametric MRI (mp-MRI) is a non-invasive imaging technique that is increasingly used to stratify patients and lesions according to suspicion and risk of having significant prostate cancer (sPCa). Whereas, high suspicious findings on mp-MRI often appear to be PCa, a low-suspicious mp-MRI is assumed to predict the absence of sPCa. However, the clinical outcome after a low-suspicious mp-MRI or benign mp-MRI targeted biopsies of a suspicious lesion in a longer term is uncertain. The objective was to assess the clinical impact and the time-varying risk of being diagnosed with sPCa following either a low-suspicious mp-MRI or benign mp-MRI targeted biopsies (mp-MRI-bx) in men with prior negative transrectal ultrasound biopsies (TRUS-bx). Methods 289 patients were included and underwent mp-MRI followed by re-TRUS-bx and mp-MRI-bx of suspicious lesions at baseline. Of these, 194 patients had either a low suspicious mp-MRI or benign mp-MRI-bx and were selected for this analysis. Men diagnosed with PCa by re-TRUS-bx were classified as mp-MRI false-negative. Men without cancer were followed for at least three years to assess how many had another re-biopsy and a subsequent diagnosis of PCa within follow-up (see flow diagram). The negative predictive values (NPV) of mp-MRI and mp-MRI-bx for ruling out any PCa, significant grade (Gleason score≥7) PCa and clinical sPCa were calculated. Results PCa was detected in 38/194 (20%) patients during the entire follow-up period of median 44 (range 36-59) months. The overall NVP of mp-MRI and mp-MRI-bx to rule out any PCa and significant grade PCa was 80% (156/194) and 95% (185/194), respectively. In addition, the NPV of clinical sPCa was 88% (170/194) caused by 15 patients with Gleason score 6 cancer having a PSA-density > 0.15 ng/ml/cc. No patients with low suspicious mp-MRI features had significant grade PCa detected Conclusions A low suspicious mp-MRI in patients with previous negative TRUS-bx has a high NPV for ruling out sPCa in a longer term. Thus, immediate repeated biopsies have only diminutive clinical impact and could be avoided even in men with persistent elevated PSA-levels. Funding none
Authors
Lars Boesen
Nis Nørgaard Vibeke Løgager Ingegerd Balslev Henrik S. Thomsen |
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PD43-04 |
Combination of version 2.0 prostate imaging reporting and data system (PI-RADS) and periprostatic fat thickness on multiparametric MRI to predict the presence of prostate cancer |
Prostate Cancer: Detection & Screening VI | 17BOS |
Abstract: PD43-04 Sources of Funding: None. Introduction To evaluate the auxiliary function of periprostatic fat thickness (PPFT) on MRI to Prostate Imaging Reporting and Data System (PI-RADS) in predicting the presence of prostate cancer (PCa) and high grade prostate cancer (HGPCa). Methods The demographic data and the clinical information of 683 patients received transrectal ultrasound- (TRUS-) guided biopsy and multi-parametric magnetic resonance imaging (mp-MRI) were retrospectively reviewed. In addition, the PPFT was measured as the shortest perpendicular distance from the pubic symphysis to prostate on midsagittal T1-weighted MR images. The univariate and multivariate analyses were performed for determing independent predictors of PCa and HGPCa in whole study cohort and subgroups according to PI-RADS score. We also constructed two nomograms for predicting PCa and HGPCa based on binary logistic regression results. Results Overall, there were 371 patients (54.3%) having PCa and 292 patients (42.8%) having HGPCa. The mean value of PPFT was 4.04mm. Multivariate analysis revealed that age, PSA, TPV, PI-RADS score, PPFT were independent predictors of PCa. All factors plus DRE were independent predictors for HGPCa. The PPFT was the independent predictors of PCa (OR 2.56, p = 0.004) and HGPCa (OR 2.70, p = 0.014) for subjects with the PI-RADS score of 3. The present two nomograms based on multivariate analysis outperformed the single PI-RADS on aspects of predicting accuracy for PCa (aurea under the curve [AUC]: 0.922 vs 0.883, p= 0.029) and HGPCa (0.919 vs 0.873, p = 0.007). Decision-curve analysis also indicated superior net benefits and wide predicting ranges of the present two nomograms. Conclusions The PPFT on mp-MRI is an independent predictor of PCa and HGPCa, especially for patients with the PI-RADS score of 3. The nomograms incorporated predictors of PPFTÂ and PI-RADS demonstrate good performance in predicting the prsence of PCa and HGPCa. Funding None.
Authors
Yudong Cao
Min Cao Yuke Chen Wei Yu Xiaoying Wang Jie Jin |
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PD43-05 |
Absence of evidence is not evidence of absence: Normal areas on MRI could harbour significant tumour |
Prostate Cancer: Detection & Screening VI | 17BOS |
Abstract: PD43-05 Sources of Funding: None Introduction Accurate prostate cancer risk stratification is essential to guide decision making on active surveillance and interventional therapy. The aim of this study was to determine if a targeted biopsy strategy to sample only MRI detected lesions could replace standard practice of systematic prostate biopsies. Methods Prostate MRI scans of all patients undergoing RARP for prostate cancer between 2013 and 2016 were prospectively analysed with a uro-radiologist as part of an established quality assurance program. MRI scans were graded as optimal or suboptimal by the radiologist. Localisation of MRI detected prostate cancer (represented in a diagram) was compared to histopathological mapping of cancer following RALP. Significant out of MRI field cancer was defined as Gleason ≥3+4. Location was analysed according to 5 different zones: Anterior, left posterolateral, right posterolateral, apex and base. Results The median Age, PSA and Gleason score were 62.9 (4576), 10.67 (156) and 7 (610) respectively. 778 (89.7%) of patients had ? pT2c. Significant prostate cancer was found in 2418/4335 zones (55.8%) on final postoperative pathology. MRI was able to pick up 1797/2418 (74.3%) of the significant lesions and missed 25.7%. Of these significant lesions, 34.7% were ≥4+3. Optimal MRI scans picked up more significant lesions than suboptimal scans (79.6% vs 71.4%). The overall sensitivity of MRI to detect significant prostate cancer was 71.2%, specificity 84.9%, PPV 85.6% and NPV 63.4%. Cohen's Kappa coefficient varied from 0.12 (poor) to 0.44 (moderate)? Area under the ROC curve ranged from 0.572 to 0.722 with apical and anterior lesions having lower values. Individual zonal accuracy data is as per table 1. Conclusions Our results show that in a population of men with significant prostate cancer, MRI can reliably detect significant prostate cancer in in 85.6% of the time. A targeted strategy using MRI will have a 36.6% chance of non detection of significant invisible cancer. Funding None
Authors
Ashwin Sridhar
Ben Lamb Gerald Busuttil Mohammed Zahran Keren Zaccai Maria Davari Imran Ahmad Anna Mohammed Greg Shaw Prabhakar Rajan Senthil Nathan Timothy Briggs Navin Ramachandran Clare Allen John Kelly |
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PD43-06 |
A multivariate logistic regression investigating which factors influence detection of clinically significant cancer by MRI-targeted prostate biopsy |
Prostate Cancer: Detection & Screening VI | 17BOS |
Abstract: PD43-06 Sources of Funding: National Institute for Health and Research UK Introduction MRI-targeted prostate biopsy (MRI-TB) is a promising diagnostic test option for the detection of clinically significant prostate cancer. There is limited data on what the key radiological, surgical and patient factors are that influence detection of clinically significant cancer by MRI-TB. Knowledge of these factors will help optimise the conduct of this diagnostic strategy. Methods 604 men with clinical suspicion of prostate cancer underwent multiparametric MRI (scored on a 1-5 Likert scale) followed by cognitively registered transperineal MRI-TB at a single centre in a 30-month period. Multi-parametric MRI included T2-weighted, diffusion-weighted and dynamic-contrast enhanced sequences reported by an expert uro-radiologist. Factors influencing detection of clinically significant cancer by MRI-TB were investigated with a multivariate logistic regression using STATA. Multiple imputation was carried out to account for missing data. Results In the 604 men, mean age was 65 and median was PSA 7.1. Significant cancer was detected in 390 men (65%). The multivariate analysis adjusting for key confounders showed that factors significantly associated with clinically significant cancer detection included MRI-Likert score (p<0.0001), MRI coil strength (p=0.0013), prior biopsy status (biopsy naive, previous negative biopsy, previous positive biopsy, p=0.0016) and PSA (p=0.0135). Factors not associated with detection of significant cancer included anaesthetic (general versus local,p=0.1274), abnormal digital rectal examination (p=0.0918), surgeon (p=0.1724) and location of tumour (anterior vs posterior, p=0.5825; basal vs apical, p=0.9204). Conclusions Key factors that influence the odds of detection of clinically significant cancer have been identified. This study validates the MRI-Likert score as one of the strongest predictors of clinically significant cancer detection. It highlights the importance of presenting PSA and MRI coil strength. Notably, this data also highlights that digital rectal exam finding is not very reliable, consistent with previous studies. Of particular importance, this data supports the feasibility of a local anaesthetic-only approach for transperineal targeted biopsy which has major healthcare delivery and health resource use benefits. Funding National Institute for Health and Research UK
Authors
Veeru Kasivisvanathan
Osayuki Nehikhare Sara Renshaw Susan Charman Jan van der Meulen Shonit Punwani Alistair Grey Henrietta Mair Esmee van der Saar Ross Warner Hashim Ahmed Mark Emberton Caroline Moore |
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PD43-07 |
Rectal swab cultures and targeted prophylactic antimicrobial regimes do not reduce the risk of sepsis following transrectal prostate biopsy |
Prostate Cancer: Detection & Screening VI | 17BOS |
Abstract: PD43-07 Sources of Funding: none Introduction Sepsis is a significant complication following transrectal ultrasound-guided prostate biopsy (TRUSBx). Ciprofloxacin and gentamicin are commonly used for prophylaxis, however there is emerging evidence for an increase in incidence of resistant enteric organisms observed worldwide. We investigate the effect of rectal swab cultures and sensitivities for targeted prophylactic antimicrobial regimes in reducing the risk of sepsis following TRUSBx Methods All patients had confirmed negative urinalysis prior to biopsy. 609 patients (Group A) received a prophylactic antimicrobial regime of a single intravenous dose of gentamicin 240mg, rectal metronidazole 1g and oral ciprofloxacin 500mg twice daily for 3 days._x000D_ Due to a significant incidence of ciprofloxacin and gentamicin resistance in patients admitted with sepsis following TRUBx, our local antibiotic recommendations changed. The subsequent 231 patients (Group B) had rectal swab cultures and sensitivities performed prior to biopsy. Patients with rectal flora organisms resistant to ciprofloxacin or gentamicin received targeted antimicrobial prophylaxis consisting of a single dose oral fosfomycin 3g, intravenous amikacin 750mg and rectal metronidazole 1g. _x000D_ Data was collected for rectal swab cultures, antibiotic regime used, readmission with sepsis within 14 days and blood or urine cultures results on admission. Results In group A (standard ciprofloxacin-based regime), 12 of 609 (1.9%) patients were admitted with sepsis following biopsy. E.coli was the most common pathogen detected. Of the 7 patients with positive urine or blood cultures, 4 (57%) were ciprofloxacin- and gentamicin-resistant and 2 (29%) were ciprofloxacin-resistant only._x000D_ In group B, 38 of 231 (16.5%) patients had ciprofloxacin or gentamicin resistant rectal flora and received the targeted antimicrobial prophylaxis regime (25 ciprofloxacin-resistant only, 3 gentamicin-resistant only, 10 ciprofloxacin- and gentamicin-resistant). _x000D_ Overall in group B, 5 of 231 (2.1%) patients were readmitted with sepsis despite receiving targeted combination of prophylactic antibiotics based on their rectal swab cultures. Of these patients, 2 had grown ciprofloxacin-resistant organisms on rectal swab and received the appropriate antimicrobial prophylaxis regime. The difference between the two groups was not statistically significant (p=0.86). Conclusions The incidence of ciprofloxacin-resistant flora in our community is significant (15.2%). The risk of sepsis following TRUSBx was overall low, however the use of rectal swab cultures and targeted combination of antibiotic regimes did not seem to reduce the risk any further. Funding none
Authors
Waseem Mulhem
Marios Hadjipavlou Mazin Eragat Charlott Kenny Martino Dallantonia Christopher Wood Mohamed Hammadeh |
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PD43-08 |
Complication Rates for Outpatient,Transrectal, In-bore MRI-guided Biopsy: Seven Years' Experience |
Prostate Cancer: Detection & Screening VI | 17BOS |
Abstract: PD43-08 Sources of Funding: None Introduction The morbidity and mortality associated with TRUS biopsy has been well documented over the past three decades. Acute urinary retention, rectal bleeding, hematuria and hematospermia, uncomplicated urinary tract infection and urosepsis have all been reported at rates between 2-4%. Mortality is rare at less than 0.4%. The purpose of this study is to assess the rates of morbidity with reduced number of cores, targeted to only the tumor suspicious region under MRI-guidance in an outpatient setting. Methods From 2009 to 2016, 3000 men received mpMRI of the prostate. Of those men, 700 underwent in-bore, MRI-guided biopsy in an outpatient setting. All MR guided biopsies were performed using a 1.5 Tesla Philips Achieva XR system (Philips Healthcare, Best, The Netherlands) for both mpMRI image acquisition and in-bore MRI-guided biopsy. DynaCAD and DynaLOC (Invivo, Orlando, FL, USA) software were used for image analysis and biopsy planning. A fully-automatic, titanium biopsy gun was inserted using the DynaTRIM positioning hardware (Invivo, Orlando, FL, USA). Two thirds of the patients undergoing mpMRI were recommended to undergo MR guided biopsy. Of those, 700 underwent MR guided in-bore biopsy. One third of the patients did not undergo prostate biopsy as a result of a negative mpMRI, reducing the number of prostate biopsies in this population. Results Of the 700 men who underwent MRI-guided biopsy, only 0.8% experienced complications. Targeting the lesion and reducing the number of cores acquired may reduce morbidity associated with random, systematic biopsy. The average number of tumor suspicious regions identified on mpMRI was1.8 and the average number of core biopsies taken with each MRI-GB was 3.5 cores as opposed to the 12-18 cores taken on average with systematic TRUS Bx. The MRI-GB procedure time on average did not exceed 30 min. Conclusions In the current cost-containment environment in healthcare, any reduction in hospital admissions is welcomed. Transrectally delivered, outpatient MRI-guided biopsy may be a means to that end. Limiting the number of cores acquired by targeting biopsy only to MR-visible tumor suspicious regions results in a 0.8% complication rate in our experience. The MRI-GB procedure can be performed quickly and safely in an outpatient setting with or without conscious sedation. Funding None
Authors
John Feller
Bernadette Greenwood Stuart May |
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PD43-09 |
Cost Analysis of Different Prostate Biopsy Modalities |
Prostate Cancer: Detection & Screening VI | 17BOS |
Abstract: PD43-09 Sources of Funding: None Introduction The cornerstone of prostate cancer diagnosis remains the transrectal ultrasound guided biopsy (TRUS), which most frequently occurs in the office setting under local anesthesia. However there are now at least 4 other techniques of prostate biopsy aimed at improving outcomes such as patient comfort, significant cancer detection, and infectious complications: TRUS under IV sedation, TRUS with MRI/fusion, transperineal template (TP), and in-bore MRI. In this study, we explored the cost implications of these modalities with TRUS as the standard. The long-term purpose is to determine how to maximize results and cost-savings. Methods Basic costs of 4 prostate biopsy modalities such as standard biopsy under local anesthesia, standard biopsy under sedation anesthesia, transperineal and MRI-fusion biopsies performed at MD Anderson Cancer Center were investigated. From September 2010 to December 2015, data of 25-30 patients for each group were analyzed retrospectively. Costs were categorized as pre-procedure, anesthesia pharmacy and recovery, urology and pathology including both technical and professional costs. MR and complication costs were not included in the analysis. Results Compared to standard prostate biopsy performed under local anesthesia, the cost of standard biopsy under sedation, transperineal and MRI-fusion biopsy increased significantly x1.8 (78%), x2.7 (173%) and x2.6 (159%) times, respectively (p < 0.001). Cost analysis results and details are shown in table 1. Although transperineal and MRI-fusion biopsy total charge seem close to each other transperineal cost is significantly higher than MRI-fusion biopsy (p= 0.004). Conclusions Compared to the TRUS standard, the addition of imaging, anesthesia, TP increase costs significantly, but have known benefits in sensitivity and reduced sepsis. Therefore, future techniques should aim to combined these methods into a platform feasible for outpatient/local anesthesia. Funding None
Authors
Muammer Altok
John Ward Brian Chapin Louis Pisters Curtis Pettaway John Davis |
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PD43-10 |
Repeat Prostate Biopsy Practice Patterns In A Statewide Quality Improvement Collaborative |
Prostate Cancer: Detection & Screening VI | 17BOS |
Abstract: PD43-10 Sources of Funding: Blue Cross Blue Shield of Michigan Introduction To understand how well urologists adhere to guidelines recommending repeat prostate biopsy in patients with multifocal high-grade prostatic intraepithelial neoplasia (MF-HGPIN) or atypical small acinar proliferation (ASAP), we examined re-biopsy practice within the Michigan Urological Surgery Improvement Collaborative (MUSIC)._x000D_ Methods We analyzed data of all men undergoing a first-time prostate biopsy at 36 MUSIC practices. We examined variation in repeat biopsy and cancer detection rates. We fit a multivariate regression model to calculate the proportion of patients undergoing re-biopsy in each practice adjusting for patient characteristics. We used claims data to validate treatment classification in the MUSIC registry. To better understand reasons for not undergoing re-biopsy, we reviewed records of a random sample of patients with ASAP. _x000D_ Results We identified 5,375 men with a negative biopsy, of which 411 (7.6%) had a repeat biopsy. Men with HGPIN (n=718), ASAP (n=350) or MF-HGPIN and/or ASAP (n=587) at initial biopsy had re-biopsy rates of 20.7%, 42.5% and 55.6%, respectively. The adjusted proportion of patients undergoing re-biopsy in each practice ranged from 0% to 17.2% (p<0.001). Overall cancer detection at re-biopsy was 39.3%, and was highest after ASAP (OR:0.39; 95% CI:0.30-0.48), or both MF-HGPIN and ASAP (OR:0.50; 95% CI:0.35-0.65). Gleason ≥7 detection was greatest in patients with both MF-HGPIN and ASAP (41.1%). Chart review revealed that 45.5% of ASAP patients underwent PSA monitoring instead of re-biopsy, while 36% failed to undergo a re-biopsy despite a recommendation (Figure). _x000D_ Conclusions Repeat prostate biopsy rates vary across MUSIC practices with relatively low utilization in men with MF-HGPIN and/or ASAP. Quality improvement strategies should target patients with ASAP or both ASAP and MF-HGPIN, as these have the highest likelihood of cancer detection._x000D_ Funding Blue Cross Blue Shield of Michigan
Authors
Jonathan C. Hu
Khurshid R. Ghani Dinesh Telang Alice Liu Scott Hawken Zack Montgomery Susan Linsell James E. Montie David C. Miller Frank N. Burks for the Michigan Urological Surgery Improvement Collaborative |
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PD43-11 |
Lack of Sustainable Response to the 2012 United States Preventive Services Task Force (USPSTF) Recommendation Against Prostate Cancer (PCa) Screening |
Prostate Cancer: Detection & Screening VI | 17BOS |
Abstract: PD43-11 Sources of Funding: none Introduction In 2012, the USPSTF recommended against prostate specific antigen (PSA)-based PCa screening in all men, regardless of age and/or race. Initial reports showed a substantial drop in PSA screening in response to these recommendations, which was mainly evident in younger patients (aged <75 years old). Our objective was to determine if the downward trend continued past the immediate response to the recommendation, and if it varied by age and race. Methods We evaluated a total of 17,554 men aged 50 years or older, who were interviewed by the National Health Interview Survey 2010, 2013, and 2015. PSA screening was defined as men undergoing PSA testing in the past 12 months preceding survey year for reasons other than prostate cancer/disease. Prevalence of PSA screening per survey year was assessed in the entire cohort, and after stratifying according to age and race. Multivariate logistic regression model calculated the odds of receiving PSA screening in 2013 and 2015 compared to 2010. Interaction analysis were performed using age and race, to examine if these variables modify the effect of survey year on the odds of PSA screening. Covariates consisted of age, race, region, marital status, education, insurance, smoking status, health status, primary care physician visit in the past year and income. Results Mean (median) age was 63.4 (61.2) years. Men age was 50-69, 70-74, and ?75 years in 74.2%, 10%, and 15.8% of cases, respectively. Most patients were White (77%), Married (58%), had Private insurance (47%), and had a household income <$35,000 (34%). The prevalence of PSA screening in 2010 was 35.1% (95% confidence interval [CI]: 31.5%-39.5%). This decreased to 30.5% (95%CI: 33.5%-36.6%) in 2013 and 30.1% (95%CI: 28.8 %-31.4%) in 2015. After adjusting for covariates, in comparison to survey year 2010, 2013 (odds ratio [OR]: 0.79; 95%CI: 0.72 – 0.87) and 2015 (OR: 0.71; 95%CI: 0.64 – 0.78) was associated with lower odds of PSA screening (both p<0.001). On interaction analysis, neither age (p=0.8) nor race (p=0.3) was statistically significant. Conclusions Our findings show that the initial significant drop (4.6%) in PSA screening, which occurred in the first year following the 2012 USPSTF recommendation, was not maintained in the subsequent years (drop of 0.4% only). This might be, at least partially, attributed to the controversy regarding the validity of these recommendations. Conversely to previous report, age does not seem to have an impact on the changes in PSA screening. Likewise, PSA screening seems to drop equally in White and Black men. This last finding might be worrisome, given that the 2012 USPSTF recommendations were mainly based on the PLCO trial, in which only 4% of the population was Black. Funding none
Authors
Haider Rahbar
Deepansh Dalela Akshay Sood Luigi Nocera Patrick Karabon Craig Rogers James Peabody Mani Menon Quoc-Dien Trinh Firas Abdollah |
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PD43-12 |
PSA Screening, Prostate Biopsy, and Treatment of Prostate Cancer in the Years Surrounding the USPSTF Recommendation Against Prostate Cancer Screening |
Prostate Cancer: Detection & Screening VI | 17BOS |
Abstract: PD43-12 Sources of Funding: None Introduction The 2012 USPSTF recommendation against screening for prostate cancer has impacted rates of PSA screening and appears to be associated with declining prostate cancer incidence. Our objective was to examine a large, national claims-based database to characterize health care utilization that may explain these trends. We evaluate rates of PSA testing, prostate biopsy, prostate cancer detection, and treatment in the years surrounding the USPSTF recommendation. Methods MarketScan (which captures > 30 million privately insured patients in the United States) claims were queried for all men age 40-64 years between 2008-2013. The at-risk population consisted of men without a diagnosis of prostate cancer. PSA testing, prostate biopsy, prostate cancer diagnosis and treatment were determined using ICD-9 and CPT codes. Prostate cancer cases were defined as men who underwent prostate biopsy and then had ≥ 2 encounters within 6 months with a prostate cancer diagnosis. Treatments ascertained included treatments for curative intent of localized prostate cancer (i.e., radical prostatectomy, external beam radiation, brachytherapy) and systemic treatments. _x000D_ Results There were 5.27 - 6.79 million qualifying men in MarketScan each year. PSA testing, prostate biopsy, and prostate cancer detection declined significantly from 2009 to 2013 (Figure), most notably between 2011 and 2012. Prostate biopsy rate per 100 patients with a PSA test decreased from 2.31 to 1.85 (p < 0.01). Prostate cancer incidence per prostate biopsy increased from 0.356 to 0.380 (p < 0.01). Treatment for localized prostate cancer decreased from 2009 to 2013 from 154 per 100,000 men to 112 per 100,000 men (p < 0.01). Over the same study period, systemic treatment also decreased from 5.64 per 100,000 men to 4.70 per 100,000 men, p < 0.01). Of new prostate cancer diagnoses, the proportion managed with treatment for curative intent decreased from 67% to 60% (p < 0.01)._x000D_ Conclusions PSA testing, prostate biopsy, prostate cancer incidence, and treatment for prostate cancer decreased in the years surrounding the USPSTF recommendation against prostate cancer screening. The changes in incidence following the USPSTF statement may be driven by different practice patterns around PSA-based referral and prostate biopsy. Funding None
Authors
James Kearns
Sarah Holt Jonathan Wright Daniel Lin Paul Lange Jonathan Gore |
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PD44-01 |
CHARACTERISTICS AND OUTCOMES OF WOMEN PRESENTING TO A MULTIDISCIPLINARY WOMEN’S UROLOGY CLINIC |
Sexual Function/Dysfunction: Female | 17BOS |
Abstract: PD44-01 Sources of Funding: None Introduction We report on women with a variety of complex, often pain-based pelvic floor conditions managed in a comprehensive multidisciplinary Women’s Urology Center (WUC) that offers urological, gynecological, colorectal, psychological, pelvic floor physical therapy and integrative medicine treatments. Methods Women presenting 2011-2015 were reviewed. Descriptive statistics were performed. A mailed survey to patients presenting in 2013-2014 assessed current status and satisfaction with treatment. Baseline and follow up Pelvic Floor Distress Inventory (PFDI-20) overall and subscale scores (Pelvic Organ Prolapse Distress Inventory (POPDI-6), Colorectal and Anal Distress Inventory (CRADI-8) and Urinary Distress Inventory (UDI-6)) were analyzed. Results 693 new patients were seen in the specified time period. Mean age was 51 (range 17-91). Most common chief complaints were pelvic pain (219/687, 32%), urine incontinence (110/687, 16%), and overactive bladder (75/687, 11%). WUC treats women with complicated pelvic floor issues, provides 30-90 minute appointments including multidisciplinary care, yet even with this careful, tailored personal management only 89/567 (16%) patients returned the follow up survey. 85% (71/84) of responders were satisfied with the care and 35% (31/88) were still managed at the WUC. Of those who did not return, 44% (19/43) were improved / satisfied and did not need to return, 49% (21/43) had logistical reasons (live out of area, insurance issues, or inconvenient appointment times) and only7% (3/43) were unhappy with their care. Compared to non-responders, survey respondents had similar age and chief complaint, were more educated (p=0.02), and were less likely to smoke (p<0.01) but more likely to have diabetes (p=0.04). Rates of anxiety and depression were similar between groups (p=0.25, p=0.67). Most common treatments included pelvic floor physical therapy (55%), pelvic floor trigger point injections (15%), medications (24%), and coping strategies (58%). Mean PFDI-20 scores improved (82 to 64), all subscale scores improved (POPDI-6 from 24 to 17, CRADI-8 from 19 to 17 UDI-6 from 37 to 29) however, only the CRADI-8 met the minimally important difference. Conclusions Complex pelvic floor issues are difficult. Many patients were outside our catchment area, had seen multiple providers and were refractory to standard therapies. Although survey response was low, the majority of patients were pleased with their care. A multidisciplinary clinic providing individualized, comprehensive care is effective for pelvic floor symptoms. Funding None
Authors
Laura Nguyen
Kim Killinger Natalie Gaines Priyanka Gupta Larry Sirls Jason Gilleran Jamie Bartley Judith Boura Kenneth Peters |
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PD44-02 |
Sexual function outcomes in patients and patients&[prime] spouses after midurethral sling procedure for stress urinary incontinence: Data from a minimum of 3 years of follow-up |
Sexual Function/Dysfunction: Female | 17BOS |
Abstract: PD44-02 Sources of Funding: None Introduction The midurethral sling (transobturator tape [TOT]) procedure has been widely performed for treatment of urinary incontinence; however, little has been reported regarding sexual function after surgery. Our previous study reported sexual function in couples after TOT procedure. In this prospective study, we investigated the sexual function follow-up outcomes in these patients and their spouses. Methods Between September 2012 and June 2013, 65 patients undergoing TOT and their sexual partners were enrolled. The validated self-administered questionnaires, Female Sexual Function Index (FSFI) and satisfaction domain of the Male Sexual Health Questionnaire (MSHQ), were used to evaluate the couples&[prime] sexual function. They completed the questionnaires before the procedure, at 3, 6, and 12 months after the procedure and every year for 3 years. Results Of 65 couples, 48 couples completed this study. The mean ages of the patients and their partners were 44.7 ± 5.8 and 47.2 ± 6.1 years, respectively. The mean follow-up period was 38.4 ± 2.4 months. A significant decrease in the total FSFI score was observed at 3 postoperative months (P = 0.003), which recovered at 6 postoperative months. A significant improvement was observed in the total FSFI score from baseline to 36 postoperative months (P < 0.001). There were significant improvements in desire, arousal, orgasm, and satisfaction in the FSFI domains (P = 0.014, 0.011, 0.015, and < 0.001, respectively). For the male partner, there was no statistically significant correlation between 12 and 36 postoperative months although the MSHQ satisfaction domain scores tended to increase over the long-term follow-up. Conclusions Over 3 years of follow-up, the outcomes suggest that sexual satisfaction for patients and their partners improved following the TOT procedure, and was relatively well maintained. Funding None
Authors
Phil Hyun Song
Jae Young Choi Young Hwii Ko Ki Hak Moon Hee Chang Jung |
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PD44-03 |
The Impact of Cycling on Women’s Sexual and Urinary Functions |
Sexual Function/Dysfunction: Female | 17BOS |
Abstract: PD44-03 Sources of Funding: none Introduction Cycling health benefits are well known; however, concerns have been raised about its effect on the genitourinary tract, due to prolonged perineal pressure. We conducted an international survey of female athletes to determine the impact of cycling on sexual and urinary function. Methods Cyclists were recruited to complete a survey through Facebook advertisements and outreach to English speaking sporting clubs across the world. Swimmers and runners were recruited as controls. Participants were queried on their physical activities, sexual function with the Female Sexual Function Inventory (FSFI), urinary symptoms with the International Prostate Symptom Score (I-PSS), history of urinary tract infections (UTI), and perineal numbness. High intensity cycling was defined as cycling for more than 2 years, more than 3 times/week, and with a daily average cycling of more than 25 miles. Results Of 4,879 respondents, 2,691 (55%) completed the survey. Of these, we compared cyclists who do not regularly swim or run (658, 39%), and swimmers or runners who do not regularly cycle (1,013, 61%). After adjusting for age, body mass index, history of hypertension, diabetes, ischemic heart disease and/or tobacco use, there were no significant differences between cyclists and non-cyclists in the mean storage and voiding subscores of I-PSS nor the total I-PSS score (6.9 vs 7.4, p=0.12). Cyclists had significantly higher mean total FSFI scores (22.7 vs 21.3, p<0.01) as well as higher mean scores in each FSFI domain, except for satisfaction and pain (Table 1). After adjusting for age, cyclists had higher odds of having a self-reported UTI Odds Ratio (OR) 1.4 (95% 1.1-1.7), and perineal numbness OR 7 (5.3-9.3). High intensity cyclists had no significant differences in the mean I-PSS score (6.8 vs 6.9, p =0.69), nor mean FSFI score (22.9 vs 23.2, p= 0.68) compared to lower intensity cyclists. High intensity cyclists were more likely to develop perineal numbness, OR 1.6 (95% CI 1.3-2), and saddle sores, OR 2.2 (95% CI 1.8-2.8). Bike seat type had no significant effect in any of the above mentioned results. Conclusions Contrary to previous literature, we demonstrate that cycling has no appreciable effect on female sexual or urinary function. However; our study suggests that cycling may increase the risk of UTI and perineal numbness. Funding none
Authors
Mohannad Awad
Thomas Gaither Thanabhudee Chumnarnsongkhroh Ian Metzler Thomas Sanford Gregory Murphy E. Charles Osterberg Benjamin Breyer |
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PD44-04 |
Successful Treatment of Interstitial Cystitis/Bladder Pain Syndrome (IC/PBS) in Women with Provoked Vestibulodynia (PVD) |
Sexual Function/Dysfunction: Female | 17BOS |
Abstract: PD44-04 Sources of Funding: None Introduction There is wide clinical overlap between PVD and IC/BPS as both conditions may include dyspareunia, chronic pelvic pain, and lower urinary tract symptoms. Unlike with IC/BPS evaluation, PVD patients are distinguished by having confined vestibular pain and positive cotton swab (Q-tip) testing, often with erythema and tenderness at 1:00 and 11:00 peri-urethral Skene's vestibular glands. Successful treatment of PVD has been anecdotally observed to resolve IC/BPS patient bladder symptoms. In addition, treatment of PVD often leads to resolution of gland pathology. The goal of this study was to advance our knowledge concerning the association of successful treatment for PVD and subsequent bladder symptom improvement. Methods An IRB-approved anonymous multi-question internet-based survey was sent to 233 consecutive women who were diagnosed and successfully treated for PVD by two sexual medicine physicians. Results 73 (31%) women responded: 55% were 21 - 35 years old. Most common symptoms were dyspareunia (93%), feelings of burning, raw or cutting in the pelvis (75%), pain with tampons (52%), urinary frequency (38%), urgency (30%), bladder pain (26%), and relief of bladder pain with voiding (10%). Prior to being diagnosed with PVD, 71% were seen by 3-10 physicians; 89% were managed by a urologist. Of the 37% diagnosed with IC/BPS, 67% reported <20% improvement in bladder symptoms with various IC/BPS treatments: 74% followed behavioral modifications, 70% used pentosan polysulfate sodium or amitriptyline, and 59% underwent bladder instillations or hydrodistention. 52% of patients were diagnosed with hormonally associated PVD treated with cessation of hormonal contraceptives (if currently using), and topical estradiol/testosterone creams. Other PVD pathophysiologies included neuro-proliferative PVD (30%) treated with vulvar vestibulectomy, and pelvic floor hypertonicity (74%) treated in part with physical therapy. Successful treatments for PVD improved bladder symptoms by ≥ 80% in 56% of patients and by ≥ 40% in 93% of patients. 78% of patients felt misdiagnosed with IC/BPS. Conclusions Women with IC/BPS may have underlying PVD as pathophysiology and not an intrinsic bladder pathology. Urologic training should include vestibular examination and cotton swab testing, along with education concerning PVD management options (hormone treatment, pelvic floor physical therapy, and vestibulectomy) to best manage women with IC/PBS symptoms. Funding None
Authors
Rachel Rubin
Leia Mitchell Ashley Winter Andrew Goldstein Irwin Goldstein |
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PD44-05 |
WRITING IN THE MARGINS OF SEXUAL FUNCTION QUESTIONNAIRES: A QUALITATIVE ANALYSIS FROM WOMEN WITH PELVIC FLOOR DISORDERS |
Sexual Function/Dysfunction: Female | 17BOS |
Abstract: PD44-05 Sources of Funding: None Introduction Pelvic floor disorders (PFDs) are associated with sexual dysfunction related to impaired arousal, absent or diminished orgasm, and pain, as well as lowered rates of sexual activity. As a result, it is a challenge to assess sexual function in women who are not sexually active. Many decline to answer questions, or may write comments in the margins of forced-choice surveys. "Marginalia" can offer rich, novel sources of data that validated surveys fail to capture. We sought to more comprehensively capture women's experiences by analyzing how women with PFDs respond to sexual function questionnaires. Methods Women with PFDs completed validated written sexual function questionnaires [Study of Sexual Attitudes and Behaviors survey (SSABS), Female Sexual Function Index (FSFI), and Sexual Function for Women with POP, Urinary Incontinence and/or Fecal Incontinence (PISQ-IR)]. Marginalia, or the additions, eliminations, and changes subjects made (by hand) to survey items, were collected. Data were coded and analyzed using grounded theory methodology (Charmaz, 2006). Results Ninety-four women completed surveys, the majority of whom experienced FSD (mean FSFI scores were 26.4±5.8 for women <60 and 18.1±12.4 for women 60+; 26.55 or less indicates FSD). Fifty-one (54%) subjects left marginalia, grouped into 4 types: narrative (n=20), clarification (n=65), elimination (n=86), and confusion (n=6). Narrative comments were unsolicited feedback or personal details. Clarifications were explanations or changes to survey items. Eliminations were "not applicable" notations or deletions. Confusion marginalia included question marks. Qualitative analysis revealed several themes (See Table 1). Elimination marginalia were commonly made on survey items addressing sexual activity or satisfaction. Fifty-nine (62.8%) subjects left one or more questions blank. Conclusions Analysis of marginalia from sexual function questionnaires amongst women with PFDs revealed critical, previously undocumented information about patients' histories, concerns, thoughts, and factors affecting sexual function. Further in-depth qualitative investigations along with the development of more effective, robust, and specific evaluation tools are key future directions needed to better address patient needs. Funding None
Authors
Pooja Parameshwar
Jenna Borok Lauren Wood A. Lenore Ackerman Karyn Eilber Jennifer Anger |
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PD44-06 |
OVERACTIVE BLADDER IS RELATED TO SEXUAL WELL-BEING IN JAPANESE WOMEN. |
Sexual Function/Dysfunction: Female | 17BOS |
Abstract: PD44-06 Sources of Funding: None Introduction Female lower urinary tract symptoms (LUTS) affect quality of life and sexual activity. This study aimed to evaluate the influences of LUTS on sexual well-being in Japanese women, as little is known on this topic. Methods We investigated 514 women recruited between August 6 and August 17, 2007, from the outpatient departments (except the departments of pediatrics, psychiatry and ophthalmology) at our hospital, regardless of the reason for visiting._x000D_ All participants were asked to answer a standardized self-reported questionnaire. Using the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) and the overactive bladder symptom score (OABSS), we evaluated urinary symptoms, including stress urinary incontinence, urgency, day time frequency, and nocturia._x000D_ To assess satisfaction with sexual function, we asked the question "If you were to spend the rest of your life with your sexual function the way it is today, how would you feel about this?", with answer choices of "very satisfied", "somewhat satisfied", "neither satisfied nor dissatisfied", "somewhat dissatisfied" and "very dissatisfied", from part of a questionnaire from the Global Study of Sexual Attitudes and Behaviors (GSSAB) study. The top two categories for each aspect were collapsed to identify positive answers as being very or somewhat satisfied with the level of sexual function._x000D_ We analyzed relationships between dissatisfaction with sexual function and other variables, including age, stress urinary incontinence, urgency (? once a day), daytime frequency (≥8 times/day), and nocturia (? once a night). The chi-square test and logistic regression models were used for statistical analyses. Values of P<0.05 were considered statistically significant. Results A total of 360 individuals completed the questionnaire (response rate, 70.0%). The mean (±standard deviation) age of respondents was 48.3 ± 13.2 years. Prevalences of stress urinary incontinence, urgency, daytime frequency, and nocturia were 35.4%, 3.1%, 39.6%, and 55.0%, respectively. Overall, the prevalence of dissatisfaction with sexual function was 55.4%. In univariate analysis, age, urgency, and nocturia were associated with dissatisfaction with sexual function. In multivariate analysis, a significant correlation was found between dissatisfaction with sexual function and both age (odds ratio (OR), 1.05; p<0.001) and urgency (OR, 9.19; p=0.047). Conclusions Our study confirmed age and urgency as independent risk factors for dissatisfaction with sexual function. These results suggest that urgency can offer a predictor of sexual dysfunction among Japanese women. Funding None
Authors
YOSHITAKA AOKI
Kikuko Sasaki Yosuke Matsuta Hideaki Ito Chieko Matsumoto Yukinori Kusaka Osamu Yokoyama |
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PD44-07 |
FEMALE SEXUAL DYSFUNCTION: A WEST VIRGINIA UNIVERSITY CLINICAL EXPERIENCE |
Sexual Function/Dysfunction: Female | 17BOS |
Abstract: PD44-07 Sources of Funding: None Introduction 40% of women in the United States experience concern with regard to sexual function. Female sexual function (FSF) can be broken down into different categories based on the domain involved, including desire, arousal, orgasm, and pain. There are multiple causes for FSF including physical, hormonal, and psychological etiologies, and patients may have additional risk factors that contribute to the dysfunction experienced including depression, obesity, and hypertension. This is especially relevant in West Virginia, which ranks among the highest for several of these risk factors. The presence of sexual dysfunction in patients with interstitial cystitis (IC) is significant and well documented. Herein, we report the data on 362 subjects indexed by the presence or absence of IC and compare the degree of sexual dysfunction associated with the disease. Methods Domain values were obtained by employing the Female Sexual Function Index (FSFI), developed by Rosen, et. al,. This 19-item questionnaire evaluates FSD in six domains. Data was analyzed on an item-for-item basis and by the six domains of sexual dysfunction for our patients and compared to two control groups. The first consisted of 131 healthy volunteers (Rosen, 2000) and the second consisted of 127 patients with Female Sexual Arousal Disorder (FSAD). Statistical significance was determined with one-way ANOVA testing (P<0.05). Results The table below compares our data with two comparison groups across the 6 domains measured by the FSFI. WVU patients with IC scored the lowest in arousal, lubrication, and orgasm, and had the lowest scores in each category compared with all other groups (P < 0.001). WVU patients without IC scored the lowest in arousal and desire, and had worse scores than the control in all categories. Conclusions This study is the first exploration of the Urologic patients in West Virginia with regard to FSF, and it highlights a vastly significant amount of sexual dysfunction within this population. West Virginia in 2015 had the 47th worst health ranking in the United States, with especially high prevalence of smoking, obesity, physical inactivity, heart disease and diabetes. Understanding the physical and psychological causes of female sexual dysfunction as well as the category of sexual function affected is critical for properly treating patients for their specific need. Funding None
Authors
Tyler Overholt
Dale Riggs Barbara Jackson Alex Battin Henry Fooks Mohammad Salkini Adam Luchey Stanley Kandzari Stanley Zaslau |
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PD44-08 |
Effects of fractional microablative CO2 laser therapy on sexual function in postmenopausal women and women with a history of breast cancer treated with endocrine therapy |
Sexual Function/Dysfunction: Female | 17BOS |
Abstract: PD44-08 Sources of Funding: none Introduction To evaluate the effects of fractional microablative CO2 laser therapy on sexual function and the symptoms of the genitourinary syndrome of menopause (GSM) in postmenopausal women and women with a history of breast cancer treated with endocrine therapy._x000D_ _x000D_ Methods From July 2015 to October 2016, 25 women underwent fractional microablative CO2 laser therapy at a single institution by a single provider. The primary objective of the study was to evaluate changes in sexual function and symptoms of GSM in women who underwent treatment by using several validated questionnaires including the Female Sexual Function Index (FSFI), Wong-Baker Faces Scale (WBFS), Female Sexual Distress Scale - Revised (FSDS-R), and the Patient Health Questionnaire (PHQ-9). Differences in outcomes between postmenopausal women and women with a history of breast cancer treated with endocrine therapy were also evaluated. Results For the 25 patients, mean age was 55.2 ± 9.5 years, average onset of menopause was 47.3 ± 6.3 years, and average duration of symptoms was 9.4 ± 7.6 years. Eight of the 25 patients had a history of breast cancer treated with endocrine therapy. Symptoms were assessed at baseline prior to treatment and six weeks after each treatment. Pre-treatment mean total FSFI score was 12.8 and post-treatment was 23.6 (P = 0.004). The largest average improvements from baseline were 1.70 for arousal (P = 0.021), 1.93 for lubrication (P = 0.031), 2.27 for orgasm (P = 0.004), and 2.53 for pain (P = 0.001). No significant differences in outcomes were observed between postmenopausal women and women with a history of breast cancer treated with endocrine therapy. Additionally, statistically significant improvements were observed in vaginal itching (P = 0.013), burning (P = 0.004), dryness (P < 0.001), painful intercourse (P < 0.001), and overall sexual distress (P = 0.001). Depression was not observed to have any significant effect on outcomes. Conclusions Fractional microablative CO2 laser therapy is effective in treating the symptoms of GSM by improving sexual function and decreasing sexual distress in both postmenopausal women and women with a history of breast cancer treated with endocrine therapy. Funding none
Authors
Paul Gittens
Gregory Mullen |
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PD44-09 |
Effect of Flibanserin on Sexual Functioning: An Analysis of Female Sexual Function Index Domains |
Sexual Function/Dysfunction: Female | 17BOS |
Abstract: PD44-09 Sources of Funding: Funding support provided by Valeant Pharmaceuticals North America LLC. Introduction Flibanserin, a 5-HT1A agonist and 5-HT2A antagonist, is indicated for the treatment of acquired, generalized hypoactive sexual desire disorder (HSDD) in premenopausal women. The Female Sexual Function Index (FSFI) is a validated self-report questionnaire comprising 6 domains of sexual functioning: desire, arousal, lubrication, orgasm, satisfaction, and pain. This post hoc analysis evaluated the effect of flibanserin treatment across the 6 FSFI domains. Methods Patient-level data were pooled from three 24-week, double-blind, placebo-controlled studies of flibanserin 100 mg once daily (qhs) in premenopausal women with HSDD. Between group differences in change from baseline to week 24 (last observation carried forward [LOCF]) on FSFI domain and total scores were evaluated using analysis of covariance. Results This analysis included 2368 women (flibanserin, n=1165; placebo, n=1204) who had at least one on-treatment efficacy assessment. The least-squares mean differences (standard error of the mean) in change scores from baseline to week 24 (LOCF) for flibanserin versus placebo were 0.3 (0.1) for the FSFI desire domain, 0.4 (0.1) for the arousal domain, 0.3 (0.1) for the lubrication domain, 0.3 (0.1) for the orgasm domain, 0.3 (0.1) for the satisfaction domain, 0.2 (0.1) for the pain domain, and 1.9 (0.3) for the total score; all P less than 0.0001 except P less than 0.01 for pain. Conclusions Treatment with flibanserin produced significant improvement not only in the FSFI desire domain (a key outcome in clinical trials of HSDD) but also across the other domains of sexual function assessed by the FSFI. Funding Funding support provided by Valeant Pharmaceuticals North America LLC.
Authors
Michael Krychman
James Yuan Krista Barbour Robert Kissling Leonard Derogatis |
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PD44-10 |
Thematic Analysis of Reflections of Women Successfully Treated with Flibanserin at a Single Center |
Sexual Function/Dysfunction: Female | 17BOS |
Abstract: PD44-10 Sources of Funding: None Introduction With flibanserin's approval October 2015 for women with hypoactive sexual desire disorder (HSDD), clinicians at our center have prescribed this medication to appropriate women with HSDD. We examine themes of women's reflections who experienced positive changes on treatment. Methods Clinicians at our site regularly ask patients to update them on their health and progress managing their sexual dysfunction. Patients currently prescribed flibanserin were asked from time to time to disclose their experiences on the medication. Twenty-two e-mail responses met the criteria that they could be collated and examined for themes regarding flibanserin use, including time to response, initial HSDD improvement, longer-term changes, and other general observations. Results Among responders, average age was 53.5 years (range 24-75). First recognition of response to medication came on average at 3.2 weeks (range 1-6). Of the 22 responders, improvements were identified in libido (11), orgasm timing/intensity (7), sexual thoughts (6), initiation of sexual activity (4), receptivity (4), ability to be multi-orgasmic (4), responsiveness (2), and sexual dreams (2). A total of 15 of the 22 women sent additional comments at 8.5 weeks (range 5-11) and 13 at 5.2 months (range 2.5-11) with continued or additional improvements in the following areas: libido (11), orgasm timing/intensity (7), arousal (5), lubrication (4), initiation (4), receptivity (4), sexual thoughts (3), sexual dreams (3) and ability to be multi-orgasmic (2). They also talked about enjoyment (2), being more open sexually (2) and positive anticipation of sexual activity (2). Non-sexual themes noted by 14 women responding longer term were feeling happy (8), experiencing less stress, anxiety or feeling more easy going (5), weight loss (4), feeling generally like a sexual being (4), feeling more connected to their spouse (3) and feeling more energetic or alive (2). Many noted improved sleep, as somnolence is an expected adverse event therefore this is a medication taken at night. No serious adverse events were noted. Conclusions For some women flibanserin has been life-changing in the quality of their sexual response (including desire, arousal and orgasm), their self-image, and their relationship. These positive changes observed are both sexual and non-sexual, resulting in more sexual satisfaction and overall happiness. _x000D_ _x000D_ Funding None
Authors
Sue Goldstein
Irwin Goldstein |
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PD44-11 |
SURVEY OF SEXUAL FUNCTION AND PORNOGRAPHY IN FEMALES |
Sexual Function/Dysfunction: Female | 17BOS |
Abstract: PD44-11 Sources of Funding: None Introduction Sexual dysfunction has a significant impact on quality of life. The use of pornography among females and its impact on sexual dysfunction is poorly described. As an exploratory outcome of a study primarily investigating the relationship between pornography and erectile dysfunction, we attempt to better define pornography use and any contribution to sexual dysfunction in women. Methods After IRB approval, all patients presenting to a urology clinic of ages 20-40 years between February and August, 2016 were offered an anonymous survey consisting of self-reported medical history and demographic questions, validated questionnaires and novel questions addressing sexual function, pornography use and addictive behavior. Accrual continues, and we report a planned interim analysis. Descriptive data was compiled, and strength of correlation between subdomains of female sexual function, obsessive or craving behaviors and pornography use were examined. All variables were analyzed with linear regression. Results Of the first 48 females who agreed to take the survey included in the analysis, the mean age was 28 years. The subjects reported minimal medical comorbidities or risk factors with the most common being depression (16%), PTSD (12%) and smoking (31%). The sample was primarily white (62%), married (60%), heterosexual (81%), and active duty military (58%). The majority of respondents denied pornography use (61%) and 25% used less than weekly. Of those that used pornography, 72% reported duration of 15 minutes or less. The primary access was internet (68%) and phone (55%). The mean Female Sexual Function Inventory total score was 64. There was no observed correlation between female sexual function and pornography use. Conclusions Interim results better describe pornography use among females. In a sample of women ages 20-40, pornography use is not uncommon with the main access being through internet or phone. There does not appear to be any correlation between its use and sexual dysfunction as determined by self-reported questionnaire. Further study may better elucidate any relationship between pornography and female sexual dysfunction. Funding None
Authors
John Kehoe
Jonathan Berger Michael Marshall Andrew Doan Matthew Christman |
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PD44-12 |
FEMALE SEXUAL DYSFUNCTION TREATMENT: A META-ANALYSIS OF THE PLACEBO EFFECT ACROSS RANDOMIZED CONTROLLED TRIALS |
Sexual Function/Dysfunction: Female | 17BOS |
Abstract: PD44-12 Sources of Funding: None Introduction Female Sexual Dysfunction (FSD) is a highly prevalent disease that has an immense impact on personal relationships and quality of life. The literature describes various treatment modalities with mixed effects across the four domains: hypoactive sexual desire disorder, arousal disorder, orgasmic disorder, and sexual pain disorder. The limited efficacy of medical treatment likely speaks to a significant psychological component of the disease. The purpose of this meta-analysis of randomized controlled trials (RCTs) was to quantify the placebo effect of various pharmacologic modalities for FSD. Methods Utilizing MOOSE guidelines, we conducted a systematic review of PubMed®, EMBASE®, clinicaltrials.gov, and the Cochrane Review databases. Using search terms &[Prime]female sexual dysfunction&[Prime] and &[Prime]treatment,&[Prime] in combination with &[Prime]vulvovaginal atrophy,&[Prime] &[Prime]vaginismus,&[Prime] &[Prime]vaginal atrophy,&[Prime] &[Prime]vulvodynia,&[Prime] and &[Prime]vestibulitis,&[Prime] 603 relevant articles were retrieved. Twenty-two RCT&[prime]s met initial inclusion/exclusion criteria and included a placebo arm. Of these, eight studies that utilized the primary outcome measure, the Female Sexual Function Index (FSFI), were ultimately selected for meta-analysis. The placebo effect on FSFI was compared to the respective study&[prime]s treatment effect using inverse-variance weighting in a random effects analysis model. Results Across the eight studies, 1,723 women with clinical pretreatment FSD received placebo. 2,236 women were in the treatment arm of the respective studies and received various pharmacologic interventions including flibanserin, bupropion, onabotulinum toxin A, intravaginal Prasterone, intranasal oxytocin, ospemifene, and bremelanotide. Women receiving placebo improved 3.62 [95% CI: (3.29-3.94)] on the FSFI (Figure 1). The treatment arm had a corresponding increase of 5.35 [95% CI: (4.13-6.57)]. Conclusions This meta-analysis of Level 1 evidence demonstrates that 67.7% of the treatment effect for FSD is accounted for by placebo. This is consistent with the current literature. Further, this study suggests that the current treatments for FSD are, overall, minimally superior to placebo alone which reinforces the significant psychosocial element of the disease process in women. Funding None
Authors
James M. Weinberger
Justin Houman Ashley Caron Avi S. Baskin A. Lenore Ackerman Karyn S. Eilber Jennifer T. Anger |
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PD45-01 |
Change of categories of the International Prostate Symptom Score (IPSS) in hypogonadal patients with and without testosterone therapy for up to 12 years: real-world data from two pooled controlled registry studies |
Sexual Function/Dysfunction: Evaluation I | 17BOS |
Abstract: PD45-01 Sources of Funding: none Introduction Long-term effectiveness and safety of TU in hypogonadal men are investigated since 2004 in two urological centers in Germany. Among the concerns regarding testosterone therapy (TTh) in elderly men, perceived effects on urinary function often prevent the initiation of TTh in men with a diagnosis of hypogonadism. Severe voiding problems (defined by an IPSS >19) are a relative contra-indication according to most guidelines for TTh. Methods Two observational, prospective, cumulative registry studies were pooled and provided data for 1,176 patients with baseline total testosterone (T) levels ≤350 ng/dL and symptoms of hypogonadism. 696 men received parenteral TU 1000 mg/12 weeks following an initial 6-week interval for up to 12 years. 480 men opted against TTh for a variety of reasons and served as controls. IPSS scores at baseline and last visit were categorized into mild (1-7), moderate (8-19) and severe (20-35). Statistical analyses have not yet been performed. Results In the testosterone group, 346 men (49.7%) had mild symptoms, 345 (49.6%) moderate and 5 (0.7%) severe symptoms at baseline. At the last recorded visit, 598 men (85.9%) were categorized as having mild symptoms, 98 men (14.1%) moderate symptoms._x000D_ All of the 5 patients in the “severe” category improved to at least “moderate”._x000D_ In the control group, 307 patients (64.0%) had fell into the &[Prime]mild&[Prime] category, 162 (33.8%) had moderate and 11 (2.3%) had severe symptoms. At the last recorded visit, 171 men (35.6%) had mild, 269 (56.0%) moderate and 39 (8.1%) severe symptoms. _x000D_ Concomitant medication (alpha-blockers and/or 5-alpha-reductase inhibitors) were not changed and equally distributed between groups as treatment decisions were made by the same urologists (AY, AH). _x000D_ Conclusions Long-term TTh with TU in hypogonadal men resulted in improvements in IPSS categories, even in patients with severe symptoms at baseline. Untreated hypogonadal men experienced a worsening of IPSS categories. Concerns about use of TTh regarding urinary function may be overrated. Funding none
Authors
Aksam Yassin
Dany-Jan Yassin Karim Haider Ahmad Haider |
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PD45-02 |
Validation Study of the Male Androgen Deficiency Syndrome (MADS) Screening Questionnaire |
Sexual Function/Dysfunction: Evaluation I | 17BOS |
Abstract: PD45-02 Sources of Funding: PCEC Introduction To validate the MADS questionnaire which was developed to identify men with hypogonadism. Methods A simplified instrument was developed to identify men with hypogonadism and was introduce in 2014 utilizing the Prostate Conditions Education Council (PCEC) Screening Questionnaire which was designed to collect information on age, race (AA-African American, W-white and H-Hispanic), presence on adult onset diabetes (AODM), Exercise frequency (Ex), overweight status (OS) and erectile function (EF) (Stone, NN et al, J. of Mens Health,11,2014). Based on regression analysis of 5071 men a number of groups were identified as being associated with a >60% likelihood of having a testosterone (T)< 300 ng/dL (Figure). The 3 questions comprising the MADS questionnaire were added to the PCEC questionnaire and utilized during Prostate Cancer Awareness Weeks (PCAW) in 2014 and 2015 to validate them. Associations between the questions and T < 300 ng/dL were tested by chi-square analysis (Pearson) and between T level by ANOVA. Results 2405 men presented to PCAWs 2014 and 2015 and filled out the MADS questionnaire of which 1376 also had serum T levels determined. Mean age was 61.1 years (median 62, range 20-92) and mean T was 353.3 ng/dL (median 323, range 28-1319). Mean T with 95%CI for AODM, OS, EX and EF are shown in the table. There were no significant associations between T level and age and race. Responses to the MADS questionnaire and T<300 ng/dL resulted in positive correlation for AODM and OS (>20 lbs or less) 67.4% vs. 42.3% (OR 2.82, 95%CI 1.5-5.4, p=0.001), AA and OS vs no OS 62.5% vs. 42.8% (OR 2.22, 95%CI 1.22-4.03, p=0.007) and W/H, no EX, OS and low EF 60% vs 42.6% (OR 2.02 95%CI 1.14-3.61, p=0.015). Conclusions The study validates the use of the MADS questionnaire which identifies more than 60% of men with a T<300 ng/dL. Men with AODM and overweight by 20 pounds or more, AA men overweight by 20 pounds or more, and white/hispanic men who don't execise and are overweight by 20 pounds or more, have no or low confidence to get and keep and erection have a 2 fold or greater likelood compared to others of having a testosterone level < 300 ng/dL. This instrument can be utilized to screen for hypogonadal men. _x000D_ _x000D_ Funding PCEC
Authors
Nelson Stone
Martin Miner Wendy Poage E. David Crawford |
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PD45-03 |
Voiding function improves under long-term treatment with testosterone undecanoate injections (TU) in hypogonadal men for up to 12 years independent of prostate size |
Sexual Function/Dysfunction: Evaluation I | 17BOS |
Abstract: PD45-03 Sources of Funding: none Introduction Long-term effectiveness and safety of TU in hypogonadal men were studied in a urological setting. One of the concerns regarding testosterone therapy (TTh) in elderly men remains increasing prostate volume and worsening urinary function parameters. Methods Observational, prospective, cumulative registry study in 321 men (age: 58.9 ± 9.8 years, range: 19-84) with total testosterone (T) levels ≤350 ng/dL and symptoms of hypogonadism. All men received parenteral TU 1000 mg/12 weeks following an initial 6-week interval for up to 12 years (T-group). In 147 men, TTh had been temporarily discontinued between years 6 and 8, due to reimbursement issues or diagnosis of prostate cancer, as published previously (Yassin et al. Aging Male 2016; 19: 64-69; Yassin et al. Clin Endocrinol 2016; 84:107-114). Parameters related to voiding function were measured between one and four times per year. Results Total T rose from 223±62 to trough levels between 460 and 535 ng/dL (p<0.0001)._x000D_ IPSS decreased from 10.1±5.0 to 8.3±4.5 after 1 year, 7.6±4.2 after 2 years, 7.2±3.8 after 3 years, 6.8±3.6 after 4 years, 6.9±3.6 after 5 years, 7.5±3.7 after 6 years, 8.6±4.0 after 7 years, 8.4±3.9 after 8 years, 7.3±2.9 after 9 years, 7.3±2.6 after 10 years, 7.3±2.7 after 11 years, and 6.6±2.7 after 12 years (p<0.0001 vs. baseline)._x000D_ Post-voiding residual bladder volume decreased from 23.8±16.2 to 16.7±6.4 mL (p<0.0001 vs. baseline) with a temporary increase in years 6 to 8._x000D_ Prostate volume increased steadily from 28.7±8.3 to 39.0±6.4 mL (p<0.0001 vs. baseline) without deviation from the trend during years 6 to 8, when TTh was interrupted in 147 men._x000D_ The Aging Males&[prime] Symptoms scale (AMS), a quality of life (QoL) instrument, improved from 53.7±9.5 to 27.5±4.0 (p<0.0001 vs. baseline) with a temporary increase in years 6 to 8._x000D_ Medication adherence in the T-group was 100 per cent as all injections were administered in the office and documented. 3 patients were lost to follow-up and considered drop-outs. _x000D_ Conclusions Long-term TTh with TU in an unselected hypogonadal men resulted in improvement of voiding function which seemed to be independent of prostate volume. QoL, closely related to voiding function, developed in parallel. All parameters except prostate volume worsened in those patients in whom TTh was temporarily interrupted. Funding none
Authors
Aksam Yassin
Dany-Jan Yassin Gheorge Doros Abdulmaged Traish |
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PD45-04 |
SERUM ESTRADIOL IS INDEPENDENTLY ASSOCIATED WITH ERECTILE FUNCTION |
Sexual Function/Dysfunction: Evaluation I | 17BOS |
Abstract: PD45-04 Sources of Funding: none Introduction The role that estrogens play in male sexual function remains incompletely understood. We sought to explore whether or not serum estradiol is associated with patient-reported sexual function, independent of serum testosterone levels and BMI. Methods We retrospectively reviewed the records of men presenting to a single urologist with subspecialty practice in andrology over an 18 month period. Serum testosterone and estradiol levels were assessed prior to 10:30 AM by immunoassay. All patients filled out the Male Sexual Health Questionnaire (MSHQ) at the initial consultations, a validated, self-reported 25-question survey on 5 domains of male sexual function (erectile, ejaculatory, libido, satisfaction, and activity). Scores for each domain were obtained by calculating the average response to the questions in the domain. The following exclusion criteria were applied: Peyronie's disease, radical prostatectomy, inflatable penile prosthesis, and pelvic radiation therapy. The association of serum estradiol with sexual function was assessed using multivariate linear regression controlled for serum testosterone level and BMI. Results 261 men met inclusion criteria and had complete data available. When controlling for total testosterone and BMI, serum estradiol was negatively associated with erectile function (p=0.036) [Figure 1]. We did not observe independent associations of serum estradiol with any other domains of sexual function. Men with estradiol levels above 40 pg/mL had significantly worse average erectile function scores on MSHQ than men with estradiol levels below 40 pg/mL (median 1.5 vs. 2.0, p=0.003, Wilcoxon rank-sum test) [Figure 2]. Conclusions Elevated estradiol in men is independently associated with poor erectile function when controlling for total testosterone and BMI. Men with ED who have serum estradiol levels higher than 40 pg/mL may be candidates for treatment with aromatase inhibitors. Funding none
Authors
Anika Ackerman
Ezra Margolin Peter Stahl |
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PD45-05 |
The Impact of Cycling on Men’s Sexual and Urinary Functions |
Sexual Function/Dysfunction: Evaluation I | 17BOS |
Abstract: PD45-05 Sources of Funding: none Introduction Cycling provides many health benefits. Previously, concerns have been raised about cycling's impact on sexual and urinary health due to prolonged perineal pressure. We conducted an international survey of male athletes to determine the impact of cycling on urinary and sexual health. Methods Cyclists were recruited to complete a survey through Facebook advertisements and outreach to English speaking sporting clubs across the world. Swimmers and runners were recruited as controls. Participants were queried about their physical activity and answered validated questionnaires including: The Sexual Health Inventory for Men (SHIM), International Prostate Symptom Score (I-PSS), and the National Institute of Health Chronic Prostatitis Symptom Index (NIH-CPSI). High intensity cycling was defined as cycling for more than 2 years, more than 3 times/week, and a daily average of more than 25 miles. Results Of the 5,851 respondents, 3,919 (67%) completed the survey. Of these, we included cyclists who do not regularly swim or run 1,642 (63%), and swimmers or runners who do not regularly cycle 975 (37%). After adjusting for age, body mass index, hypertension, diabetes, ischemic heart disease and tobacco use, cyclists had a higher mean SHIM score (20.1 vs 18.9) p<0.01, compared to non-cyclists. There were no statistically significant differences in I-PSS or NIH-CPSI scores between the two groups. High intensity cyclists had a significantly higher mean SHIM score compared to lower intensity cyclists (20.6 vs 19.5) p<0.01, but no significant differences were found in I-PSS and NIH-CPSI scores. After adjusting for age, cyclists had significantly higher odds of perineal numbness compared to non-cyclists, odds ratio=10.6 (95% confidence interval 8.3-13.7). Bike seat type had no significant effect in any of the above mentioned results. Conclusions Contrary to prior studies suggesting that cycling may cause ED, our study shows that cyclists have no worse erectile function than non-cyclists. We also showed that cycling does not affect LUTS. Further research is warranted to gain insight into these results, but this study suggests that cardiovascular benefits of exercise may outweigh any theoretical deterrent of cycling. Funding none
Authors
Mohannad Awad
Thomas Gaither Thanabhudee Chumnarnsongkhroh Ian Metzler Thomas Sanford Gregory Murphy E. Charles Osterberg Benjamin Breyer |
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PD45-06 |
A large-scale investigation of the prevalence and patterns of depression and anxiety in outpatients in the clinics of andrology |
Sexual Function/Dysfunction: Evaluation I | 17BOS |
Abstract: PD45-06 Sources of Funding: none Introduction To illustrate the prevalence and patterns of depression and anxiety in outpatients in the clinics of andrology. Methods The executive outpatients referred to the clinics of andrology of a large medical center from 2014 to 2015 were investigated. The presence and severity of depression and anxiety were evaluated by Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder 7 (GAD-7). The data of primary disease, age, height, weight, educational background and occupation were also reviewed. Results 1489 patients were included. The most common symptom for depression was "feeling tired", while for anxiety was "easily irritated". 57% patients were diagnosed with depression, and the ratio of mild depression was 31%, while severe depression were only 3%; 42% patients were diagnosed with anxiety, with mild anxiety 27% and severe anxiety 1%. Patients who received higher education and who participated in mental labor were less likely to suffer from depression. Patients with Late-onset Hypogonadism (LOH), Erectile Dysfunction (ED) and Chronic Prostatitis (CP) exhibited higher risk for depression and anxiety, while less prevalence was found in patients with BPH and infertility. 535 patients (35.9%) were diagnosed with both diseases, with a percentage of 56.4% in the cohort of patients who had at least one of the disease. Conclusions The prevalence of depression and anxiety in outpatients in clinics of andrology was high. Patients with LOH, ED, CP and those who had poor educational background or participated in physical work had higher risk. Most patients were diagnosed with mild to moderate stage, and it's important to evaluate the primary disease and the combined psychogenic problems objectively. Funding none
Authors
Dong Fang
Yiming Yuan Zhichao Zhang Wei Zheng Yuan Tang Wanshou Cui Jing Peng Weidong Song Bing Gao Zhongcheng Xin Liqun Zhou |
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PD45-07 |
Critical Analysis of Penile Duplex Doppler Ultrasound (PDDU) in Erectile Dysfunction (ED): Technical And Interpretation Deficiencies |
Sexual Function/Dysfunction: Evaluation I | 17BOS |
Abstract: PD45-07 Sources of Funding: None Introduction PDDU is used as a diagnostic tool in patients with ED to define etiology and prognosticate. However, technical challenges result in difficulty standardizing its performance and interpretation. This study aims to evaluate recent literature on this topic, addressing technical and interpretation limitations. Methods A PubMed literature search was performed in August 2016 and included papers published in the English language from 2005 onwards. Review articles were excluded. In our analysis, each study was evaluated for the presence of the following elements pertaining to reporting of PPDU technique and interpretation criteria: (i) agents used (ii) use of a redosing protocol, (iii) reporting of maximum rigidity during study (iv) normative criteria for peak systolic velocity (PSV) and end diastolic velocity (EDV) (v) discrepancy in rigidity between sides (vi) presence of negative EDV values (vii) need for reversal of erection reversal Results From a total of 109 published studies, 55 were considered eligible for analysis. 51% reported using PGE1 as the vasoactive injection agent, 20% trimix, 11% papaverine, 7% bimix, 4% used multiple drugs and 7% failed to mention the agent. Only 38% reported using a dosing strategy and 4% reported the percentage of patients requiring multi-dosing. Only 40% mentioned rigidity assessment in their routine, while 55% used a time-based protocol. Discrepancy in between-side rigidity was mentioned in only 4%, while 2% had unilateral cavernosal artery insufficiency reported. Great variability in normative criteria was observed. For normal peak systolic velocity (PSV): 13% used peak systolic velocity (PSV) of ≥35cm/s, 42% ≥30cm/s, 24% ≥25cm/s and 22% failed to report the cut-off used. EDV cut-offs were less heterogeneous: 65% ≤5cm/sec, 4% ≤6cm/sec and 31% failing to report the cut-off. Only 4% reported the presence of negative EDV values. Finally, only 5% mentioned the need for reversal agents after the procedure. Conclusions Despite its generalized use, analysis of current literature on PDDU is notable for the lack of standardization in its performance and interpretation. Redosing and rigidity assessment were under-reported, and cut-off values were extremely heterogeneous. There is thus a need for standardization in performing PDDU and reporting results. Funding None
Authors
Eduardo P. Miranda
Jean E. Terrier Bruno Nascimento John P. Mulhall |
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PD45-08 |
International Variability in Penile Duplex Ultrasound Practice Patterns, Technique and Interpretation |
Sexual Function/Dysfunction: Evaluation I | 17BOS |
Abstract: PD45-08 Sources of Funding: None Introduction Penile duplex ultrasound (PDU), combined with pharmacologic stimulation of erection, is the gold standard approach to evaluating multiple penile conditions. The utility of PDU is hindered by a lack of standard approaches to performing and interpreting this study. We examined the variability in international practice patterns, technique and interpretation among practitioners who perform PDU. _x000D_ Methods A 30-question electronic survey was distributed to members of the International Society for Sexual Medicine (ISSM). The survey assessed current PDU practice patterns, technique and interpretation. Chi-square test was used to determine association between categorical variables. _x000D_ Results The survey was completed by 9.5% of all 1996 current ISSM members. Of ISSM members surveyed, 80% reported using PDU, with more North American practitioners utilizing PDU than their European counterparts (94% vs. 69%, p < 0.01). Urologists performed 62% of all PDU studies, and more than 76% were interpreted by a urologist. Although 90% of practitioners reported using their own standardized protocol, extreme variation in technique existed among respondents. Over 10 different pharmacologic mixtures were used to generate erections, and 17% of respondents did not repeat dosing for insufficient erection. Urologists personally performing PDU were more likely to report assessing cavernosal artery flow in appropriate fashion with the probe at the proximal penile shaft (73% vs 40%) and at a 60-degree angle (29% vs 5%) compared to urologists who do not perform PDU (p < 0.01). Large differences in PDU diagnostic thresholds were apparent. Only 38% of respondents defined arterial insufficiency with a peak systolic velocity < 25 cm/sec; while 53% of respondents defined venous occlusive disease with an end diastolic velocity > 5 cm/sec. _x000D_ Conclusions PDU is used by a greater proportion of North American sexual medicine practitioners than European counterparts. Although most respondents report using a standardized PDU protocol, widespread variation exists among practitioners in terms of both technique and interpretation. This variation prevents comparison of PDU results and may impair accurate diagnosis and appropriate treatment of penile conditions. _x000D_ Funding None
Authors
Mark Hockenberry
Will Kirby Alexander Pastuszak Larry Lipshultz |
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PD45-09 |
Early Detection of Cardiovascular Disease (CVD) Risk in Men with Erectile Dysfunction (ED) is Facilitated Using Next Generation Immunodiagnostics |
Sexual Function/Dysfunction: Evaluation I | 17BOS |
Abstract: PD45-09 Sources of Funding: A.S.H. is a National Institutes of Health (NIH) K12 Scholar supported by a Male Reproductive Health Research (MHRH) Career Development Physician-Scientist Award (HD073917-01) from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Program (to Dolores J. Lamb). Introduction Next generation immunodiagnostic assays offer the ability to quantify single-molecule cardiovascular and inflammatory related biomarkers with high sensitivity. It is known that patients with erectile dysfunction (ED) are at a greater risk for CVD. Additional highly predictive testing, however, is needed to distinguish ED patients at the greatest risk of CVD. We sought to characterize clinically relevant biomarkers that associate with poor erectile function. _x000D_ Methods A retrospective review was performed on men with sexual dysfunction presenting to a single academic andrology clinic. Patients who underwent diagnostic evaluation for sexual dysfunction, completed the International Index of Erectile Function (IIEF) questionnaire, and underwent high sensitivity cardiovascular biomarker testing (Singulex, CA, USA) were included. Electronic medical records were reviewed to collect demographic information. Descriptive statistics and the non-parametric Kruskal-Wallis one-way ANOVA were performed. _x000D_ Results A total of 56 men were included in the study, with a control group of 24 men with normal erectile function scores on the IIEF, 14 with mild ED, 5 with mild-moderate ED, 4 with moderate ED, and 9 with severe ED. Mean age for the entire cohort was 42.2 years (SD 14.9) and mean age of the controls was 39.2 (SD 12.5). Serum levels of 22 biological markers of cardiovascular risk were assessed. Of these 22, HDL2B and cTn-I were significantly associated with IIEF scores, with higher HDL2B biomarker levels associated with severe ED (p=0.038) and lower cTn-I levels associated with severe ED (p=0.040). Conclusions High sensitivity biomarkers of cardiovascular disease, specifically HDL2B and cTn-I, can facilitate early detection of cardiovascular risk in men with ED, corroborating the known relationship between CVD and ED. Further validation of the clinical relevancy of these biomarkers is necessary to confirm the early risk of CVD risk in men with ED. _x000D_ Funding A.S.H. is a National Institutes of Health (NIH) K12 Scholar supported by a Male Reproductive Health Research (MHRH) Career Development Physician-Scientist Award (HD073917-01) from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Program (to Dolores J. Lamb).
Authors
Amin Herati
Peter Butler Alexander Pastuszak David Skutt Larry Lipshultz |
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PD45-10 |
Extracorporeal shock-wave therapy (ESWT) in treatment of ED: first results of ongoing sham-controlled study. |
Sexual Function/Dysfunction: Evaluation I | 17BOS |
Abstract: PD45-10 Sources of Funding: none Introduction Clinical and experimental data shows that shock-wave therapy can stimulate angiogenesis, improving blood flow and endothelial function, and thus improve erectile function. There is not enough clinical data showing the improvement of erectile function following ESWT in randomized sham-controlled studies. The aim of the study is to determine the efficacy and safety of ESWT in men with ED by performing a prospective randomized double-blind sham-controlled study. Primary endpoint: increase in Sexual Health Inventory for Men (SHIM or IIEF-5) score. Methods ESWT was performed on patients above 18 years old diagnosed with vascular ED all in stable relationships, with SHIM<20. No PDE-5 inhibitors or any other treatment of ED was allowed. Six treatment sessions were applied twice a week in three consecutive weeks using Omnispec Model ED1000. The intensity of shockwaves was predefined by the manufacturer. Patient received 300 shocks to each of the 5 locations: 3 spots along the penile shaft and 2 spots on the penile crus. Follow-up visits were performed in 1 and 3 months after the end of treatment. After the end of the follow-up period patients randomized in sham-control group were invited for open treatment. Urologist from the unblinded team was responsible for changing treatment applicator and sham applicator according to patients' randomization numbers, whereas the blind team performed the procedure and collected all data from patients. Results In total, 51 men with ED were included in the study at the moment of publication. 34 patients completed the study: 11 in control and 23 in treatment group. Mean age was 44 (25-67) years. Average time of ED was 13 (6-27) months. SHIM score total in both groups before treatment was 16 (12-20); 17 (12-20) in treatment group and 16 (14-20) in control group. The efficacy of treatment was assessed by comparing SHIM score results before and immediately after treatment, 1 month and 3 months after the treatment. During the treatment period there were no adverse events in both groups. All patients received 6 procedures. In total, 34 men completed the SHIM score questionnaire after the end of treatment period. The result in treatment group was 22 (18-25). Pairwise comparison demonstrated significant increase of the score (p=0.001). Control group did not show any significant increase of the SHIM score, neither in total comparison, where it remained at 17 (12-20), nor in pairwise comparison (p=0.001). Conclusions First results of the study demonstrate good efficacy and excellent tolerability of ESWT in treatment of erectile dysfunction. Funding none
Authors
Andrei Vinarov
Leonid Spivak Darina Platonova Yury Demidko |
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PD45-11 |
Improved diagnosis and treatment of patients through accurate and standardized testosterone tests |
Sexual Function/Dysfunction: Evaluation I | 17BOS |
Abstract: PD45-11 Sources of Funding: Centers for Disease Control and Prevention Introduction _x000D_ Accurate T measurements are needed to assess a patient&[prime]s hormone status and ensure correct diagnosis and treatment of diseases and disorders, such as hypogonadism. CDC Hormone Standardization Program (HoSt) is improving the accuracy of T testing._x000D_ _x000D_ Methods _x000D_ HoSt is assisting clinical, research, and public health laboratories in improving T measurements by _x000D_ _x000D_ &[middot]assessing measurement accuracy in the context of clinical needs to identify potential sources of inaccurate results_x000D_ _x000D_ &[middot]creating measurement results that are traceable to one accuracy base and comparable across methods, time, and location _x000D_ _x000D_ &[middot]monitoring the measurement performance over time and certifying participants testing in patient care, research studies, and clinical trials_x000D_ Results _x000D_ Participation in HoSt is voluntary. Since 2010, the CDC has had 89 enrollments, which include reenrollments. Laboratories meeting the performance criteria are listed on the CDC website (www.cdc.gov/labstandards/hs.html). _x000D_ _x000D_ 76% of HoSt participants have met analytical performance criteria. T calibration bias has improved with an among laboratory bias decreasing from 16.5% in 2007 to 2.7% in 2016. Through the HoSt program&[prime]s quarterly challenges participant performance is monitored at regular intervals and laboratories maintaining annual certification through HoSt have high accuracy over time. _x000D_ _x000D_ HoSt provides unique measurements and services. Additional sources of bias, such as sample-to-sample variability, can now be detected and corrected through the availability of single-donor serum reference materials. Assay variability in well calibrated T methods has been detected with HoSt reference materials. This variability appears to be concentration dependent, with higher bias in low concentration samples, typically found in women and men with hypogonadism (<300 ng/dL). The source of the bias seems to be related to method sensitivity and analytical interferences. Additional evaluations are underway to identify and address the source of bias. _x000D_ _x000D_ CDC is expanding its programs by including free testosterone and SHBG. Furthermore, it increases its services by providing new sets of reference samples to participants to better evaluate the analytical test performance and to better monitor the accuracy of research studies. _x000D_ Conclusions _x000D_ CDC Clinical Standardization Programs ensure that laboratory results in research and patient care are accurate, reliable, and continue to meet the needs defined by stakeholders such as The Partnership for Accurate Testing of Hormones (PATH). Funding Centers for Disease Control and Prevention
Authors
Julianne Cook Botelho
Krista Poynter Ashley Ribera Otoe Sugahara Hubert W Vesper |
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PD45-12 |
Sexual Health Care Practitioner&[prime]s Evaluation of Men who have Sex with Men |
Sexual Function/Dysfunction: Evaluation I | 17BOS |
Abstract: PD45-12 Sources of Funding: A.S.H. is a National Institutes of Health (NIH) K12 Scholar supported by a Male Reproductive Health Research (MHRH) Career Development Physician-Scientist Award (HD073917-01) from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Program (to Dolores J. Lamb). Introduction The National Institute of Health (NIH) has officially designated sexual and gender minorities as health care disparity research populations. The Institute of Medicine Report and Department of Health and Human Services Healthy People 2020 Initiative have called for steps to address these health care disparities. We sought to characterize the practice patterns of sexual health specialists as they relate to Men who have Sex with Men (MSM). Methods In order to assess the attitudes of sexual health practitioners, a survey study was sent to 696 members of the Sexual Medicine Society of North America (SMSNA). Surveys were electronically mailed to members to determine the practitioners&[prime] demographics, their assessment of their patients&[prime] sexual orientation, and adaptation of care to address the specific needs of their MSM patients. Responses were compared using descriptive statistics and chi-squared analysis with Yates correction where appropriate. _x000D_ Results Of 696 SMSNA members surveyed, 92 (13.2%) responded. The plurality of the respondents practiced in an academic setting (43.8%), whereas the remainder practiced in either private or community hospital based settings. While 93.3% of respondents reported treating MSM patients, only 51.7% routinely asked about their patients&[prime] sexual orientation. Of those that don&[prime]t ask, 41.9% responded that sexual orientation is irrelevant to their patients&[prime] care and 25.6% responded that patients will disclose this information if the patient thinks it&[prime]s important. Of all respondents, 51.7% agree that MSM patients have unique sexual healthcare needs, while 48.3% either did not think this population had special needs or did not pay attention to the distinction. Subgroup analyses performed based on practice location showed practitioners in urban locations were significantly more likely to ask their patient&[prime]s orientation compared to suburban and rural settings (p=0.03). _x000D_ Conclusions Despite the near ubiquity of MSM patients in sexual health clinics, only about half of practitioners ask their patients&[prime] sexual orientation. The most common reason for not asking was the belief that sexual orientation is not relevant to sexual health care. However, the majority of respondents agree that these are special healthcare needs pertinent to this population. _x000D_ Funding A.S.H. is a National Institutes of Health (NIH) K12 Scholar supported by a Male Reproductive Health Research (MHRH) Career Development Physician-Scientist Award (HD073917-01) from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Program (to Dolores J. Lamb).
Authors
Amin Herati
Billy Cordon Peter Butler Mark Hockenberry Larry Lipshultz |
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PD46-01 |
Can Surgical Mentor’s Trust Hold the Key to Trainee Performance? |
Surgical Technology & Simulation: Training & Skills Assessment III | 17BOS |
Abstract: PD46-01 Sources of Funding: Roswell Park Alliance Foundation Introduction Although robot-assisted surgery (RAS) provides many advantages in terms of ergonomics, visualization, and perioperative outcomes, it adds complexity to the surgical environment, due to its remoteness. Cognition-based trust is related to performance-relevant understandings such as competence, responsibility, reliability, integrity, and dependability. We sought to develop an objective method for evaluation of cognition-based trust during RAS. Methods We examined EEG data from a mentor who observed 116 Urethro-vesical anastomoses (UVAs) and 98 pelvic lymph node dissections (PLNDs) performed by 3 trainees. The mentor assessed trainee performance using NASA-TLX questionnaires at the end of each step. Procedures were classified as Trustworthy (mentor satisfied) or Concerning (mentor not satisfied) based on the performance score given by the mentor. We tested 68 features extracted from EEG data and applied Kernel Target Alignment (KTA) method to find the most discriminative features. The outcome of the classification was evaluated using the accuracy, sensitivity and specificity of these objective features in their ability to distinguish between trustworthy and concerning procedures. Results Of all features tested, we found that the five most predictive features were Stress, mental workload (MW), Frustration, Surprise and Modularity. These features were significantly different between Trustworthy and Concerning performances, showing higher frustration, stress, MW, surprise and lower modularity while mentoring concerning as opposed to trustworthy performances. Conclusions Cognition-based Trust can be objectively evaluated using EEG features. This is the first reported study to objectively evaluate trust during RAS by featuring cognitive and brain functioning features. Funding Roswell Park Alliance Foundation
Authors
Somayeh Shafiei
Ahmed Hussein Justen Kozlowski Youssef Ahmed Sarah Muldoon Khurshid Guru |
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PD46-02 |
Looking for your Own Reflection: Assessing Brain Functional State of Surgical Mentor During Robot-Assisted Surgery |
Surgical Technology & Simulation: Training & Skills Assessment III | 17BOS |
Abstract: PD46-02 Sources of Funding: Roswell Park Alliance Foundation Introduction Mentorship is fundamental to the existence of any surgical training. During robot-assisted surgery, the involvement of a mentor (dual console or remote based) has changed the interaction and process of mentorship necessary to ensure learning. No study to date has evaluated the impact of cerebral functional connectivity (brain states) when a mentor observes a surgery. Methods The 'Mind Maps' project database aimed at evaluating cognitive function of surgical environment. 87 Urethro-Vesical Anastomoses (UVA) and 74 Pelvic Lymph Node Dissections (PLND) performed by 3 trainees, mentored by a single surgeon (mentor) were assessed and compared to the mentor's performance of 24 LND and 26 UVA. The study included all electroencephalogram (EEG) recordings from the mentor's brain on all procedures enrolled in this study. The mentor subjectively assessed trainees' performance using NASA-TLX questionnaires at the end of each step. We developed a statistical framework to investigate the dynamic change of the mentor's brain network during operation performance. The mentor's brain state during each surgery was extracted as four separate functional brain networks by calculating the pairwise phase synchronization between EEG signals in the alpha, theta, beta, and gamma bands. Network statistics assessing the topology of the functional brain networks were extracted and properties of network structure were compared with organization of known cognitive brain regions. Results We observed a modular organization of functional brain networks that differs in structure across frequency bands. The mentor's functional connectivity is higher when observing surgeries with a low quality of performance of trainees in comparison with observing high quality performance or performing the surgery himself. Additionally, observing the performance of a novice trainee is associated with a higher functional connectivity between and within cognitive areas. Conclusions The brain states of a surgical mentor vary based on the surgical performance of the trainee. The first of its kind, this study opens new horizons for assessment and surgical mentorship. This study lays the foundations to a shared control environment between surgeons, trainees, and the robotic surgical systems. Funding Roswell Park Alliance Foundation
Authors
Somayeh Shafiei
Ahmed Hussein Justen Kozlowski Youssef Ahmed Sarah Muldoon Khurshid Guru |
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PD46-03 |
Is Crowdsourcing Surgical Skill Assessment Reliable? An Analysis of Robotic Prostatectomies |
Surgical Technology & Simulation: Training & Skills Assessment III | 17BOS |
Abstract: PD46-03 Sources of Funding: Blue Cross Blue Shield of Michigan Introduction Crowdsourcing has demonstrated the ability to provide accurate surgical skills assessments correlating with expert surgeon reviewers. We studied whether crowdsourcing skills assessment of robotic prostatectomy performances would yield reliable scoring across a range of days and times of day. We also sought to characterize the agreement of video review among peer robotic surgeons reviewing the same urethrovesical anastomosis videos. Methods We used five urethrovesical anastomosis videos previously assessed by faculty-level surgeons within the Michigan Urological Surgery Improvement Collaborative (MUSIC) using the Global Evaluative Assessment of Robotic Skills (GEARS), (highest score 25). The bottom and top scoring videos and three videos evenly distributed across a range of peer rater scores were selected from a larger pool of videos. Each video was assessed through the C-SATS platform (C-SATS, Inc. Seattle, WA) by n=32 random crowdworkers at one of ten different days/times over one week. A C-SATS GEARS average score was generated for each video; reliability was assessed using intraclass correlation coefficient (ICC). We then evaluated the 5 anastomosis videos with n=23 faculty experts as a comparative example of expert rating performance. Experts were not subjected to the same repeated trials of reviews. Expert reviewers saw each performance once and responded within 14 days of the review process. Ten different groups of crowds reviewed each video over the course of the week. Results A total of 342 unique crowdworkers provided 1,640 ratings in a median completion time of 1 hour and 22 minutes for each of the ten review sessions. The C-SATS ICC was found to be 0.92 (95% CI: 0.79 to 0.99), indicating a very high level of reliability of the C-SATS rating process (Figure 1a). Reliability was lower for the 23 faculty experts (ICC=0.68; 95% CI: 0.42 to 0.95), with the range of expert scores spanning more than half of the GEARS scale on each video (Figure 1b). Conclusions We demonstrated that crowdsourcing to assess technical skills is repeatable and reliable across multiple times of the week providing evidence that such a method could be used to assess the skill of surgeons. Furthermore, expert video review could potentially be enhanced through repeated trials with workshops to build consensus on scoring standardization. Funding Blue Cross Blue Shield of Michigan
Authors
Thomas S. Lendvay
Khurshid R. Ghani James O. Peabody Susan Linsell David C. Miller Bryan Comstock |
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PD46-04 |
Video Analysis of Skill and Technique (VAST): Machine Learning to Assess Surgeons Performing Robotic Prostatectomy |
Surgical Technology & Simulation: Training & Skills Assessment III | 17BOS |
Abstract: PD46-04 Sources of Funding: Blue Cross Blue Shield of Michigan; Intuitive Surgical Introduction A surgeon's technical skill may be a major determinant of patient outcomes. Because robotic surgery can be recorded, computer-vision video analysis of skill and technique (VAST) methods may have advantages for assessment that is objective and scalable. To test the hypothesis that specific features in a video can categorize skill, we studied crowdsourced annotated videos of surgeons performing robotic prostatectomy and applied machine learning to determine skill. Methods Videos of the anastomosis from 12 surgeons in the Michigan Urological Surgery Improvement Collaborative underwent blinded review by 25 peer surgeons using the Global Evaluative Assessment of Robotic Skills (GEARS) tool (max score 25). Surgeons were categorized into low and high skill based on &[prime]bimanual dexterity&[prime] and &[prime]efficiency&[prime]. Robotic instruments were annotated by crowdworkers via a custom-designed Mechanical Turk platform. Using the videos we trained a linear support vector machine (SVM), sampling consecutive frames to study VAST metrics for instruments including velocity, trajectory, smoothness of movement, and relationship to contralateral instrument. We applied the SVM to learn and classify videos into high/low skill. To evaluate performance we used 11 videos as training, and tested on the remaining 1 video, repeating it 12 times and averaged the accuracy. Results GEARS scores ranged from 15.75 to 23.11, with 9 and 3 surgeons categorized into high and low skill, respectively. In total, 146,309 video frames were annotated by 925 crowdworkers. Instrument annotation included individual points as well as wristed joint movement (Figure). SVM accuracy in skill categorization using individual points on an instrument was 83.3%. Accuracy improved to 91.7% when we assessed joint movement. When we combined assessment with the contralateral instrument, accuracy was 100% in categorizing binary skill level. Instrument metrics most closely related to skill prediction were relationship between needle driver forceps and joint, acceleration, and velocity. Conclusions Computer video analysis can be used to predict skill in practicing robotic surgeons. In the future, methods utilizing deep learning to track instruments and calculate skill, may have significant implications for credentialing and quality improvement. Funding Blue Cross Blue Shield of Michigan; Intuitive Surgical
Authors
Khurshid R. Ghani
Yunfan Liu Hei Law David C. Miller James Montie Jia Deng for the Michigan Urological Surgery Improvement Collaborative |
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PD46-05 |
A Randomised Controlled Trial of Cognitive Training for Technical and Non-Technical Skills in Robotic Surgery |
Surgical Technology & Simulation: Training & Skills Assessment III | 17BOS |
Abstract: PD46-05 Sources of Funding: none Introduction Cognitive training techniques such as mental imagery (MI) have been successfully used as training aids for sport, music and rehabilitation medicine. By stimulating similar neural pathways to motor tasks, MI practice leads to improved motor performance. Studies have shown that MI may be effective in surgery although so far this has been limited to laparoscopic technical skills training. Given the unique training challenges posed by robotic surgery, the potential for MI to supplement training outside of the costly and stressful operating room environment is considerable._x000D_ _x000D_ This studies aims to establish the feasibility of cognitive training for technical and non-technical skills training in robotic surgery. Methods A double blind, randomised controlled trial of 61 robotic novices was performed. ISRCTN registry ID ISRCTN47552076. All participants underwent initial basic robotic skills training using a robotic virtual reality simulator. Baseline ability was recorded. Participants were randomised to either MI or standard training in robotic technical and NTS skills. _x000D_ _x000D_ Participants performed 3 dry-lab warm-up exercises before completing a urethrovesical anastomosis (UVA) within a simulated operating room environment. Alongside completion of the UVA task, subjects were required to manage 3 NTS scenarios. Performances were video-recorded and analysed post hoc by blinded, expert robotic surgeons. Technical skills were assessed using GEARS and NOTSS was used for NTS. Results 28 subjects underwent cognitive training and 33 underwent standard training. No significant differences in surgical experience or baseline ability between the 2 study groups. Cognitive training resulted in a significantly better technical performance compared to standard training (total GEARS score 13.37 vs 10.94, p = 0.007). No difference was seen in NTS performance (mean total NOTSS score for MI and standard training respectively 23.5 vs 27.0 p = 0.18). Conclusions This RCT provides strong evidence for the role of cognitive training in technical skills training in robotic surgery but not in NTS training. Further assessment of cognitive training in more experienced robotic surgeons is now required to determine the optimal integration of cognitive training into the robotic surgical curriculum. Funding none
Authors
Nicholas Raison
Kamran Ahmed Takashige Abe Abdullatif Aydin Oliver Brunckhorst Haleema Aya Husnain Iqbal David Eldred-Evans Andrea Gavazzi Giacomo Novara Nicolo Buffi Ben Challacombe Craig McIlhenny Shamim Khan Henk Van Der Poel Prokar Dasgupta |
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PD46-06 |
Analysis the posture pattern during robotic simulator task using optical motion capture system |
Surgical Technology & Simulation: Training & Skills Assessment III | 17BOS |
Abstract: PD46-06 Sources of Funding: none Introduction Robotic surgery has recently become popular in various surgical fields. Although the high degree of instrument maneuverability in robotic surgery reduces surgeon stress and muscle fatigue, surgeons are also forced to maintain uncomfortable joint positions intraoperatively. In this study, we used an optical motion capture system to analyze the differences in the posture pattern during robotic simulator tasks between surgeons at two skill levels. Methods This study included 20 participants;10 were expert surgeons and 10 were novices. We selected two exercises based on a needle driving task in a da Vinci Skills Simulator (DVSS): the Suture Sponge 1 task (SP), and the Tubes task (TU). The participants&[prime] upper body motion during each simulated surgical task was captured with the commercially available optical motion tracking system._x000D_ We evaluated the automated score of the DVSS, task time (second), the joint angles/motion range (shoulder, elbow, wrist), the percentage of time when the wrist height was lower than the elbow height (PTW, %), and the height of the elbow/wrist relative to the armrest._x000D_ Results Experts had significantly better results than novices in overall score (SP 87.9 ± 7.4 vs 62.0 ± 15.1, p = 0.001, TU 72.4 ± 13.56 vs 56.6 ± 10.9, p = 0.028), and in task time (SP 185.9 ± 22.3 vs 283.5 ± 73.8, p = 0.002, TU 209.0 ± 20.0 vs 264.5 ± 40.6, p = 0.006). Figure 1 shows the differences in the PTW, which differed significantly between groups in both task. The features of the novice are that both the elbow joint and wrist joint tend to stretch, the height of the elbow relative to the armrest was significantly higher than experts, and the height of the wrist relative to the armrest was significantly lower. With respect to motion range, in the SP, the novices were significantly larger than the experts for the elbow, wrist, right shoulder, and left shoulder. And in the TU, the novices were significantly larger than the experts for the wrist and the shoulder on the right side. Conclusions Optical motion capture system detected differences in the posture patterns of novice versus expert surgeons during robotic simulator tasks. There are differences between novices and experts in the positional relationship between the elbow and wrist and joint angle of the upper limb, indicating that experts may have less posture stress. Funding none
Authors
Kenta Takayasu
Kenji Yoshida Tadashi Mastuda |
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PD46-07 |
Simulated ward rounds- a unique approach to teach non-technical surgical skills for newly appointed residents in Urology |
Surgical Technology & Simulation: Training & Skills Assessment III | 17BOS |
Abstract: PD46-07 Sources of Funding: The simulation bootcamp was funded by Health Education England- Yorkshire and Humber, Karl Storz, Coloplast and Allergen. Introduction Residents encounter a step change in responsibility during their entry into speciality training and are often expected to run a ward round but are seldom given a formal training for its effective conduct. Along with technical skills, it is increasingly recognised that non-technical skills such as communication, team working and leadership play a vital role in reducing adverse events in surgery. Simulation based learning can be used to complement training. Methods A ward round scenario was designed as one of the modules during a urology simulation boot camp for newly appointed trainees in urology. This module comprised simulated patients with typically encountered urological problems along with a nurse and intern. To test the non-technical skills, various interruptions and distractions were introduced. We assessed this module using structured feedback forms; self-reported confidence scores (5 point Likert scale) and also uniquely performed a cognitive load assessment using the NASA- Task load index (NASA TLX) multi-dimensional assessment tool. Results 32 delegates attended the boot camp of which 19 were males. _x000D_ At the conclusion of this module, 83% delegates felt 'more confident' in running an acute urology ward round. 90% delegates felt challenged in decision making skills during the simulation and believed that they would change their behaviour in ward settings. A vast majority felt that the scenario helped them think critically, develop better insight into teamwork, improved communication skills and learn the importance of handover. 96% delegates enjoyed the exercise and would recommend to other trainees at their level. _x000D_ The cognitive load assessment using the NASA TLX (table 1) showed that among the six domains, performance and mental demand were the most challenging aspects in this module with mean scores of 12.1 and 11.9 respectively. Physical demand scored the least with mean score of 6.3._x000D_ _x000D_ Conclusions We have demonstrated that simulation can improve the confidence of newly appointed residents in leading the ward rounds which in turn could result in improved patient care and better team working. The NASA TLX scale helps to identify the residents cognitive workload in different working environments and can facilitate learning technical and non-technical skills. _x000D_ _x000D_ _x000D_ Funding The simulation bootcamp was funded by Health Education England- Yorkshire and Humber, Karl Storz, Coloplast and Allergen.
Authors
Sanjay Rajpal
Uwais Mufti Andy Myatt Craig Mcllhenny Chandra Shekar Biyani Sunjay Jain |
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PD46-08 |
Following the Crowd: Patterns of Crowdsourcing on Social Media among Urologists |
Surgical Technology & Simulation: Training & Skills Assessment III | 17BOS |
Abstract: PD46-08 Sources of Funding: None Introduction One proposed advantage of urologists' use of social media is efficient knowledge exchange by "crowdsourcing" clinical advice and community solutions to local challenges. This study examines patterns and functions of Twitter-based crowdsourcing among urologists. Methods A sample of Twitter users was developed using a list of U.S. urologists on Twitter from the AUA. Twitter feeds were reviewed for primary (ie, not in reply to another post) posts seeking clinical advice or input, as well as reply posts linked to primary posts of this nature. Posts by trainees and posts using the poll function were excluded. Authors' 50 most recent posts were reviewed, and eligible posts were included for analysis. Authors' demographic data were collected from public sources. When patient data was posted, we noted whether permission was cited. Content analysis was conducted by 2 reviewers; differences were resolved by consensus among all authors. Results After review of 98 urologists' Twitter feeds, 276 posts in 23 crowdsourcing threads were collected for analysis. The reasons for crowdsourcing fell into 4 categories: urologists requesting ideas or solutions to a clinical dilemma (82 posts, 30%); urologists requesting advice about a surgical plan (77 posts, 28%); urologists requesting colleagues' experiences with a device, medication, or finding (64 posts, 23%); and urologists wondering if colleagues would agree with a specific course of action (53 posts, 19%). Topics spanned oncology, stone disease, endourology, and reconstructive surgery. A bidirectional exchange was achieved in most queries; mean number of replies per thread was 11 (range 0-30), and mean number of authors replying to each thread was 5 (range 0-10). In threads with ≥1 reply, the author of the primary post wrote a follow-up question or comment 82% of the time. Recent completion of training (as a proxy for inexperience) did not appear to disproportionately motivate crowdsourcing; median time in practice among authors of primary posts was 7 years (range 1-22), and authors with ≤7 years in practice initiated 13 (57%) requests. Most requests were prompted by a specific patient; of the 23 threads, 15 (65%) referenced a patient or case. Among these patient-specific threads, 7 (47%) also included photos or radiographs, yet only 1 (7%) mentioned having obtained the patient's permission. Conclusions Urologists are now leveraging social media to crowdsource clinical guidance and experiential knowledge. As urologists' Twitter use expands, these exchanges may grow in breadth and sophistication. Public dissemination of patient data remains a concern. Funding None
Authors
Kevin Koo
Kevin Shee E. Ann Gormley |
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PD46-09 |
Variability & Interpretation of Communication Taxonomy during Robot-assisted Surgery: Do we all speak the same language? |
Surgical Technology & Simulation: Training & Skills Assessment III | 17BOS |
Abstract: PD46-09 Sources of Funding: Roswell Park Alliance Foundation Introduction Communication inaccuracies are a major cause of surgical errors in the operation room. The incorporation of relatively new technology such as robot-assisted surgery (remoteness) may render communication even more challenging. We sought to investigate and analyze the different ways the surgeon communicates with bedside assistants during Robot-assisted Surgery. Methods We retrospectively reviewed video and audio recordings of 9 robot-assisted radical prostatectomies enrolled in “Techno-fields” project. Surgical environment was recorded by 3 cameras and lapel microphones recorded the audio from surgical team members. We identified 5 common tasks carried out by console surgeon and categorized the commands used for each request based on the information delivered (Table 1). We also determined the frequency, time to complete each requests, inconveniences and repetitions. Inconveniences were reported if further clarification was needed to perform required action. The most efficient request was the one that with the shortest duration to accomplish the task. Requests were grouped as complete or incomplete. Complete instructions were identified as the most comprehensive detailed request. Results 431 requests were identified during the study. For instrument change, the most frequently and most efficient request was specifying the instrument and the arm (66%) (Mean time 16 seconds). For clipping and suction, the command without further instructions (e.g. “clip” or “suck”) were the most efficient (9.3 and 4.0). For retraction specifying the direction of retraction showed the least repetitions and inconveniences and was also the most efficient. While comparing complete vs incomplete requests, complete requests had shorter time to perform (7.93 vs 9.24) fewer inconveniences (14 vs 20) but needed more repetitions (8 vs 4). Conclusions Properly crafted codes of communications were efficient, took shorter time to accomplish and were associated with less inconveniences and repetitions. Funding Roswell Park Alliance Foundation
Authors
Sana Raheem
Youssef Ahmed Ahmed Hussein Paul May Khurshid Guru |
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PD46-10 |
Validation of the Digital Rectal Exam Clinical Tool (DiRECT) |
Surgical Technology & Simulation: Training & Skills Assessment III | 17BOS |
Abstract: PD46-10 Sources of Funding: University of Virginia Academy of Distinguished Educators Introduction There is increased emphasis on the measurement of competency in medical education and in maintenance of certification. The digital rectal exam (DRE) is an essential and important component of the physical examination but medical students are graduating with minimal experience due to the intimate nature of the exam and difficulty articulating the skill. We previously used a modified Delphi method with 10 experts to create a novel, validated assessment instrument for measuring medical student DRE proficiency, termed the Digital Rectal Exam Clinical Tool (DiRECT). We sought to demonstrate construct validity of the DiRECT in medical students and residents at different training levels. Methods The DiRECT instrument was developed using a modified Delphi method with 5 radiation oncologists and 5 urologists. The consensus panel identified 5 pertinent domains and determined levels of distinction for each. To validate the instrument, patients gave consent for paired digital rectal exams. The attending and trainee (medical student or resident) independently completed the DiRECT and the trainee's responses were referenced against the expert's. The DiRECT was scored using a partial credit model assigned by the study team. Training years were assigned to all participants, beginning at 1 for 3rd year medical students. The relationship between DiRECT score and training years was analyzed with linear regression. Results The DiRECT was completed 34 times by medical students and 15 times by urology resident physicians (PGY2-6). One of five attending urologists completed the corresponding DRE for scoring reference. Each trainee's result as a percent score using our partial credit model is seen in Figure 1. The relationship between training years and partial credit score was statistically significant (p = 0.0141) and with a medium to large effect size (r2 = 12.4%). As level of training increased, the scores closely approximated those of the attending physician. When adjusting for attending physician, training level approached but did not reach statistical significance (p = 0.087). Conclusions We previously showed the ability of the DiRECT to reflect the nuances of complex versus benign exams in second year medical students. These additional data suggest validity of the instrument to differentiate between trainees of differing experience levels. Funding University of Virginia Academy of Distinguished Educators
Authors
Matthew Clements
Karen Schmidt Tracey Krupski |
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PD46-11 |
Utilization of Robotic Anastomosis Competency Evaluation (RACE) for Evaluation of Surgical Competency during Urethro-vesical Anastomosis |
Surgical Technology & Simulation: Training & Skills Assessment III | 17BOS |
Abstract: PD46-11 Sources of Funding: Roswell Park Alliance Foundation Introduction Urethrovesical Anastomosis (UVA) is a challenging and critical surgical step performed during Robot-assisted Radical Prostatectomy (RARP). Robotic Anastomosis Competency Evaluation (RACE) is a composite real-time surgical scoring system which measures surgical skills during UVA. Methods 41 UVAs were performed by 5 surgical trainees during RARP over two academic years at Roswell Park Cancer Institute. The trainees were supervised by experienced robotic surgeons with over 1500 RARP experience. Outcomes included duration of UVA, return of urinary continence, UVA-related complications, and proportions of the UVA performed. Time was measured from the first day of the trainees' clinical fellowship. The trainees began by performing only the anterior portion of the UVA in surgeries before advancing to performing the posterior plate towards the latter half of their fellowship. Effect significance was determined using linear regression analysis. Results RACE score improved with time from 20 to 22 (p=0.17) (Figure 1A). Higher RACE scores were associated with fewer number of pads and with improved continence at both 6 weeks (from 4 to 2, p=0.39) and 6 months (from 2 to 1, p=0.75) (Figure 1B). With time, trainees performed a greater percentage of the UVA (Figure 2A). Meanwhile UVA time increased towards the end of the fellowship possibly due to the trainee performing majority portions (Figure 2B). No significant UVA related complications occurred possibly due to strict mentor supervision. Conclusions As the fellowship progressed, RACE scores improved and were associated with performing greater proportion of UVA. Higher RACE scores were associated with improved continence. RACE can be used to monitor and mentor the progress of trainees resulting in quality care of patients. Funding Roswell Park Alliance Foundation
Authors
Justen Kozlowski
Ahmed Hussein Mohamed Sharif Youssef Ahmed Paul May Thomas Fiorica Sana Raheem James Mohler Khurshid Guru |
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PD46-12 |
Virtual simulation improves a novice&[prime]s ability to localize renal tumors in 3D physical models – a multi-institutional prospective randomized controlled study |
Surgical Technology & Simulation: Training & Skills Assessment III | 17BOS |
Abstract: PD46-12 Sources of Funding: Research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number T32GM088129. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health._x000D_ Introduction Efficient robotic partial nephrectomy requires a precise understanding of tumor location and relationship to vital structures. Translating standard imaging into a reliable 3D mental model is challenging, especially for inexperienced surgeons. We sought to determine if renal tumor visualization and manipulation within a robotic virtual simulator improves the ability of novices to accurately identify tumor location in 3D space. Methods We recruited medical students from Baylor College of Medicine and UT McGovern Medical School. Using a custom-built algorithm, two volumetric reconstructions from CT imaging were generated and imported into the dV-Trainer. For each tumor, 9 different model variations were 3D printed (1 real, 8 with modified tumor locations). Subjects were randomized 1:1 into two groups, dV-Trainer and non dV-Trainer, and were given 5 minutes to review CT images. Subjects in the dV-Trainer group were allowed to manipulate the virtual model for an additional 5 minutes. They were then asked to identify the model corresponding to the real tumor in each case and to assign a nephrometry score. The primary outcome was distance of the tumor selected from the correct location. Results 100 subjects participated and all were included for analysis. There was no difference in subject age (mean: 23.6 ± 2.2) or training year between groups. Subjects in the dV-Trainer group more accurately visualized tumor location (Normalized distance: Model 1: sim 0.17 ± 0.23 vs. no-sim 0.31 ± 0.31, p=0.012; Model 2: sim 0.12 ± 0.28 vs. no-sim 0.34 ± 0.39, p=.001). These findings were not affected by age or year of training. Surprisingly, subjects in the dV-Trainer group had more difficulty assigning the correct nephrometry score than those in the non-dV-Trainer group. Conclusions In this prospective randomized trial, exposure to a patient-specific virtual model improves the novice ability to accurately visualize tumor location when compared to interpreting standard planar CT images alone. This workflow, including our novel reconstruction algorithm, provides a streamlined method for generating patient-specific kidney anatomic simulations which may be valuable for teaching surgical trainees and visualizing complex tumor cases before surgery. Funding Research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number T32GM088129. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health._x000D_
Authors
Arun Rai
Jason Scovell Adithya Balasubramanian Ang Xu Ryan Siller Taylor P. Kohn Young Moon Naveen Yadav Richard Link |
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PD47-01 |
THE EFFECT OF PROSTATE CANCER TREATMENT ON PATIENT REPORTED URINARY AND SEXUAL FUNCTION VARIES BY DISEASE SEVERITY: 3?YEAR RESULTS FROM THE CEASAR STUDY |
Prostate Cancer: Epidemiology & Natural History III | 17BOS |
Abstract: PD47-01 Sources of Funding: This work was supported by the National Cancer Institute at the National Institutes of Health (5T32CA106183 to M.D.T.); by the American Cancer Society (MSRG-15-103-01-CPHPS to M.J.R.); by the US Agency for Healthcare Research and Quality (1R01HS019356, 1R01HS022640-01); and through a contract from the Patient-Centered Outcomes Research Institute. No conflicts of interest. Introduction Disease severity may modulate the effects of prostate cancer treatment on patient-reported functional outcomes. The objective of this study is to determine how the effects of contemporary prostate cancer treatments on functional outcomes vary by disease risk. Methods The Comparative Effectiveness Analysis of Surgery and Radiation (CEASAR) study is a prospective, population-based, observational study which enrolled men with localized prostate cancer in 2011 and 2012. Patient-reported function was measured using the 26-item Expanded Prostate Index Composite (EPIC) at baseline, 6, 12, and 36 months after treatment. To identify differences in the effect of treatment on EPIC domain scores by disease risk, we fit a set of longitudinal models with interactions between disease risk and treatment type (radical prostatectomy [RP] or external beam radiotherapy [EBRT]) with adjustments for the following factors: time since treatment, pre-treatment function, age, race, comorbidity, educational attainment, insurance type, employment, marital status, physical function score, social support, depression score, participatory decision-making score, and study site. Results Among the 2544 participants, 1144 (45%) had low-risk, 983 (39%) had intermediate-risk, and 417 (16%) had high-risk disease. Among low-risk patients, RP causes more severe decreases in sexual function compared to EBRT at 3 years (mean difference in EPIC score: -14.30 [95% CI: -18.56, -10.53]); however, among high-risk patients, this difference becomes both clinically and statistically insignificant (-4.46 [-9.79, 0.88]). With respect to incontinence, RP leads to even greater declines in function among high-risk patients compared to EBRT at 3 years (difference in treatment effects among low risk: -14.60 [-18.00, -11.19] and high risk: -19.25 [-23.87, -14.62]). No clinically significant interactions between treatment and risk were detected among the bowel, hormone, or urinary irritative domains. Conclusions These data suggest that the effect of treatment on urinary incontinence and sexual function vary by disease risk. Namely, high-risk patients report similar sexual function at 3 years regardless of treatment type but more drastic declines in urinary incontinence after surgery. Funding This work was supported by the National Cancer Institute at the National Institutes of Health (5T32CA106183 to M.D.T.); by the American Cancer Society (MSRG-15-103-01-CPHPS to M.J.R.); by the US Agency for Healthcare Research and Quality (1R01HS019356, 1R01HS022640-01); and through a contract from the Patient-Centered Outcomes Research Institute. No conflicts of interest.
Authors
Mark Tyson
JoAnn Alvarez Tatsuki Koyama Matthew Resnick David Penson Daniel Barocas |
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PD47-02 |
Fasting blood glucose and prostate cancer risk in the Finnish Randomized Study of Screening for Prostate Cancer |
Prostate Cancer: Epidemiology & Natural History III | 17BOS |
Abstract: PD47-02 Sources of Funding: Pirkanmaa Hospital District, memorial fund of Seppo Nieminen Introduction Diabetes has been associated with lowered overall risk of prostate cancer (PCa), yet the risk of high-grade tumors may be elevated. The role of hyperglycemia as PCa risk factor is unclear. We estimated PCa risk overall and by tumor grade and stage among men with diabetic fasting blood glucose level in a population-based cohort of Finnish men. Methods The study population of the Finnish Randomized Study of Screening for Prostate Cancer (FinRSPC) was linked to the Fimlab laboratory database to obtain information on fasting plasma/blood glucose measurements since 1978. The data was available for 17,860 men. Based on the average yearly glucose level men were categorized as normoglycemic, prediabetic or diabetic for each follow-up year separately. Follow-up started at the FinRSPC baseline in 1996-1999 and continued until prostate cancer diagnosis, death, or the end of 2014._x000D_ Cox regression with adjustment for age, FinRSPC study arm and use of statins, antihypertensive drugs, NSAIDs, aspirin, 5α-reductase inhibitors and alpha-blockers was used to calculate hazard ratios (HRs) and 95% confidence intervals (95%CIs) for prostate cancer overall and separately for Gleason 6, Gleason 7-10, localized and metastatic tumors._x000D_ Results During the median follow-up of 14.7 years a total of 1,663 new PCa cases were diagnosed. Compared to normoglycemic men, men with diabetic blood glucose level had increased risk of PCa (HR 1.52; 95% CI 1.31-1.75). The risk increase was observed for all tumor grades, but the risk of being diagnosed with metastatic PCa was not elevated. The risk increase was observed if the blood glucose level was diabetic in the 1990s (HR 1.39; 95% CI 1.16-1.67). Blood glucose level measured in the 1980s was not associated with the risk. Use of diabetic drugs removed the risk association; p for interaction by antidiabetic drug use < 0.001. Conclusions Men with diabetic fasting blood glucose level have an increased prostate cancer risk. The risk increase is long-term, initiating approximately a decade before the diagnosis. Use of antidiabetic drugs attenuates the risk increase. Funding Pirkanmaa Hospital District, memorial fund of Seppo Nieminen
Authors
Teemu Murtola
Ville Vihervuori Kirsi Talala Kimmo Taari Teuvo Tammela Anssi Auvinen |
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PD47-03 |
Family History and Increased Risk of Clinically Significant Prostate Cancer in the PLCO Cancer Screening Trial |
Prostate Cancer: Epidemiology & Natural History III | 17BOS |
Abstract: PD47-03 Sources of Funding: none Introduction A family history (FH) of prostate cancer (CaP) is associated with an increased risk of CaP. However, it remains unclear how this association impacts the need for screening. The aim of this study is to evaluate the impact of FH of the diagnosis of clinically significant CaP in a large national cohort. Methods The study included 73,045 men from the control and screening arms of the Prostate Lung Colorectal and Ovarian (PLCO) trial, which had complete information regarding FH and CaP diagnosis. Incidence of clinically significant cancer (CS; intermediate or high risk disease) was compared by FH. The relationship between number of relatives diagnosed and age at CaP diagnosis was evaluated. Multivariable logistic regression was used to estimate odds rato (OR) and 95% confidence intervals (CI). _x000D_ Results FH was associated with a significantly increased risk of both CaP [OR 1.6, (95% CI 1.5-1.8)] and CS-CaP [OR 1.7 (95% CI 1.5-1.8), respectively]. Furthermore, the impact of FH on CS-CaP increased with the number of family members with CaP; for participants with one relative, the OR was 1.6 (95% CI 1.5-1.8); for those with multiple relatives, the OR increased to 2.2 (95% CI 1.6-3.2). Men with younger relatives with prostate cancer (< 65 vs ≥65 years) were more likely to be diagnosed with CS-CaP, [OR 1.6, (95%CI 1.3-2.0)]. FH, number of affected relatives and age of relatives remained significant on multivariable analysis controlling for ages, race, smoking history, history of BPH, marital status employment status and study arm. Conclusions Detailed FH, including the number of relatives and relatives&[prime] age of at diagnosis significantly affect a man&[prime]s risk of CS-CaP and should be taken into consideration during individualized counseling about the frequency and intensity of screening. Funding none
Authors
Adrien Bernstein
Ron Golan Jonathan Shoag Brian Dinerman Jim C. Hu |
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PD47-04 |
Statin use, serum lipid levels and prostate inflammation; results from the REDUCE study |
Prostate Cancer: Epidemiology & Natural History III | 17BOS |
Abstract: PD47-04 Sources of Funding: American Institute for Cancer Research, NIH 1K24CA160653, GlaxoSmithKline Introduction Statin use is associated with lower risk of advanced prostate cancer, but mechanisms are not completely understood. In addition to cholesterol-lowering, statins also have systemic anti-inflammatory properties, but the effect of serum cholesterol levels and statin use on benign prostate inflammation has not been explored. The aim of this study was to examine associations between serum lipid levels, statin use, and histological prostate inflammation among men with a negative prostate biopsy. Methods We conducted a retrospective analysis of data from 6,655 men with a negative baseline prostate biopsy in the REduction by DUtasteride of prostate Cancer Events (REDUCE) trial. Statin use and serum lipid levels [total cholesterol, low and high density lipoprotein (LDL and HDL, respectively), triglycerides] were assessed at baseline. Prostate inflammation was classified as chronic (lymphocytes, macrophages) or acute (neutrophils) following central histological review of negative baseline prostate biopsies. Multinomial logistic regression was used to examine the effect of serum lipid levels and statin use on presence and extent of chronic and acute prostate inflammation [none, moderate (<20% biopsy cores), severe (≥20% biopsy cores)], adjusting for potential confounders. Results Chronic and acute prostate inflammation was found in 5,152 (77%) and 1,005 (15%) men, respectively. Serum lipid levels were not associated with presence or extent of chronic prostate inflammation. Total cholesterol, LDL and triglycerides were not associated with presence or extent of acute prostate inflammation. However, men with high HDL (≥60 vs. <40 mg/dl) had reduced presence of any acute inflammation (OR 0.79; 95% CI 0.63-0.99), and were less likely to have severe acute inflammation (OR 0.66; 95% CI 0.45-0.97). Statin users had reduced presence of any chronic prostate inflammation (OR 0.81; 95% CI 0.69-0.95), and were less likely to have severe chronic inflammation and severe acute inflammation (OR 0.80; 95% CI 0.68-0.95 and OR 0.73; 95% CI 0.53-1.00, respectively), relative to non-users. Conclusions In a cohort of men with a negative prostate biopsy, those with high HDL had lower presence and extent of acute prostate inflammation and statin users had reduced presence and extent of chronic inflammation. These findings support an effect of HDL and statin use on benign prostate inflammation. As we have shown inflammation is correlated with prostate cancer risk, this work suggests a mechanism linking serum lipid levels, statins and prostate cancer risk. Funding American Institute for Cancer Research, NIH 1K24CA160653, GlaxoSmithKline
Authors
Emma Allott
Lauren Howard Adriana Vidal Daniel Moreira Ramiro Castro-Santamaria Gerald Andriole Stephen Freedland |
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PD47-05 |
Elderly prostate cancer patients have a worse prognosis than younger patients: a population-based study in the Netherlands. |
Prostate Cancer: Epidemiology & Natural History III | 17BOS |
Abstract: PD47-05 Sources of Funding: none Introduction Annually over 10,000 men are diagnosed with prostate cancer (PC) in the Netherlands and almost half are older than 70 years. As the effect of treatment might differ for older patients, we examined the clinical features, applied treatments, and prognosis for older PC patients in the Netherlands. Methods All patients diagnosed with PC in 2013 were retrieved from the database of the nationwide population-based Netherlands Cancer Registry. We examined the clinical characteristics, treatment, and 5-year relative survival (as approximation of PC specific survival) of patients aged 0-60, 60-69, 70-79, and ≥80. Results Approximately 46% (n=5001) of diagnosed PC patients in 2013 were ≥70 years and 10% (n=1164) ≥80 years. PSA level at diagnosis and Gleason score progressively increased with age. Also, older patients were more often diagnosed with advanced stage of PC (cT4/N+/M+) compared to younger patients; 12% of patients aged <60 years versus 39% of patients aged ≥80 years had an advanced stage. For all disease stages combined, the proportion of patients that underwent curative treatment decreased with increasing age. Within the group of cT2 patients, 70% of patients aged 70-79 years and 16% of patients aged ≥80 years were treated with curative intent compared to 85% of younger patients. The vast majority of cT3 patients received radiotherapy in combination with hormonal therapy, regardless of age. However, in the eldest patients (≥80 years) hormonal monotherapy was applied most frequently (>60%). In the patients with cT4/N+/M+ PC, the use of hormonal therapy as monotherapy increased strongly with increasing age. The 5-year relative survival decreased with increasing age: 92% for the patients aged <70 years, 87% for patients aged 70-80 years, and 68% for patients aged ≥80 years. The 5-year relative survival of low stage PC appeared to be similar for patients aged <70 years versus ≥70, whereas the survival of advanced PC (≥T3) was worse for older patients: 5-year relative survival is 97% versus 91% for the cT3 patients and 53% versus 43% for the cT4/N+/M+, respectively for patients aged <70 years versus ≥70 years. Conclusions Elderly men with PC are more often diagnosed with advanced disease, possibly as a result of patients' or doctors' delay. After adjusting for disease stage, older patients have a worse prognosis than younger patients. Further research should elucidate whether elderly PC patients are treated optimally while taking the increased life expectancy and the trade-off between the beneficial effects and adverse events of the treatments into account. Funding none
Authors
Robin W.M. Vernooij
Inge M. van Oort Theo M. de Reijke Katja K.H. Aben |
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PD47-06 |
Lower Risk of Prostate Cancer in Asian Men: From Less Screening or True Racial Differences? |
Prostate Cancer: Epidemiology & Natural History III | 17BOS |
Abstract: PD47-06 Sources of Funding: This study was supported by GlaxoSmithKline (GSK). Introduction Global prostate cancer incidence rates are lower in Asian men than white men. To what degree this relates to less aggressive screening in Asian men or inherent differences by race remains to be determined. Our aim was to determine whether Asian race was associated with lower prostate cancer diagnosis in a study of all men who received prostate-specific antigen (PSA) screening and systematic prostate biopsies independent of PSA levels. Methods REDUCE was a 4-year, multicenter, randomized, double-blind, placebo-controlled study that followed biopsy-negative men with protocol-dictated PSA-independent biopsies at 2- and 4-years. Eligible men were aged 50-75 years, had serum PSA between 2.5-10 ng/mL, and a prior negative prostate biopsy. We tested the association between race and receipt of prostate biopsy as well as race and prostate cancer diagnosis using multivariable logistic regression. Results Of 8,122 men in REDUCE, 7,296 were of white or Asian race and had complete data for analysis. Asian men had lower BMI (24.8 vs 26.9, p<0.001) and smaller prostate volumes (34.2 vs 43.4 cc, p<0.001) but were similar in baseline age, PSA, family history of prostate cancer, and digital rectal exam findings compared to white men. There was no difference in rate of receiving a prostate biopsy between Asian and white men (p=0.634). After adjusting for various clinical and demographic characteristics, Asian men were less likely to be diagnosed with cancer during the 4-year study compared to white men (OR 0.56, p=0.011). When testing for differences in cancer grade, Asian race was significantly associated with decreased risk of low-grade cancer compared to white race (OR 0.43, p=0.016). This risk reduction was also observed for high-grade cancer (OR 0.63, p=0.290) though the association was not statistically significant. Conclusions Among men with a negative pre-study biopsy who all underwent biopsies largely independent of PSA, Asian race was associated with reduced risk of prostate cancer diagnosis. These data suggest less screening among Asian men globally cannot completely explain the lower risk of prostate cancer among Asian men. Further studies are needed to explore the inherent differences attributed by race in prostate cancer diagnosis. Funding This study was supported by GlaxoSmithKline (GSK).
Authors
Tom Feng
Alexis Freedland Lauren Howard Adriana Vidal Daniel Moreira Ramiro Castro-Santamaria Gerald Andriole Stephen Freeland |
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PD47-07 |
The effect of a preference sensitive online decision aid on localized prostate cancer treatment: first results of a randomized cluster controlled trial |
Prostate Cancer: Epidemiology & Natural History III | 17BOS |
Abstract: PD47-07 Sources of Funding: none Introduction Decision aids (DAs) support shared decision making for the treatment of localized prostate cancer by providing balanced evidence based information, eliciting preferences and by structuring the decision making process. Studies have shown that the use of a DA may increase minimal/non-invasive treatment options. However, the current literature is uncertain about the effect on treatment choice in localized prostate cancer using DAs. Our objective is to study the effect of a preference sensitive web based DA on treatment decision making. Methods A randomized cluster controlled trial was performed among 18 hospitals between 2014-2016. _x000D_ In the intervention arm (nine hospitals) the DA was offered following diagnosis (N=332). Patients in the control arm (another nine hospitals) received care and information as usual (N=128). After treatment decision-making but before treatment start, patients in both arms received a questionnaire measuring treatment choice, decisional conflict and knowledge. Analyses were performed using t-tests, ANOVA and Pearson correlations._x000D_ Results Response rate was 72% (intervention N=273, control N=109). No differences were found in PSA and Gleason score between groups. The decision aid led to more patients choosing active surveillance (AS) in comparison with standard information (28% vs. 17%, P=0.03). In the control arm we found significantly more external beam radiotherapy (EBRTx) (16% vs 8%, P=0.02) and brachytherapy (BT) ( 33% vs. 19%, P=0.005). No differences were found in decisional conflict and knowledge. One in five patients indicated to prefer a decision aid in a paper form instead of online. Conclusions Patients made different treatment choices after DA use. The online DA supported shared decision making and this may lead to significantly more AS. More radiotherapy was found in the control arm. The decision aid did not lead to more decisional conflict. However, a minority of the patients prefers a paper form of the decision aid. The most optimal DA form needs to be determined. We currently collect post-treatment measures to determine regret and treatment satisfaction levels. Funding none
Authors
Romy Lamers
Maarten Cuypers Marieke de Vries Lonneke vd Poll-Franse Ruud Bosch Paul Kil |
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PD47-08 |
Variation and trends in prostate cancer care at Commission on Cancer designated facilities |
Prostate Cancer: Epidemiology & Natural History III | 17BOS |
Abstract: PD47-08 Sources of Funding: none Introduction Contemporary treatment trends for prostate cancer show increased rates of active surveillance. However, nationwide applicability of these reports is limited. Additionally, the impact of Commission on Cancer facility type on prostate cancer treatment patterns is unknown. Methods We used the National Cancer Data Base between 2004 and 2013 to identify men diagnosed with prostate cancer. Our cohort was stratified based on the National Comprehensive Cancer Network prostate cancer risk-classes. Cochran-Armitage tests evaluated temporal trends. Random effects hierarchical logit models assessed treatment variation at Commission on Cancer-facility and institution level._x000D_ Results In 825,707 men, utilization of radiation therapy declined and utilization of radical prostatectomy increased for all prostate cancer risk-groups between 2004-2013 (p<0.0001). Observation for low-risk prostate cancer increased from 16.3% in 2004-2005 to 32.0% in 2012-2013 (p<0.0001). Significant treatment variation was observed based on Commission on Cancer-facility type. For all risk-groups, rates of treatment according to facility type ranged from 28.4% to 76.9% for radical prostatectomy, 3.6% to 16.2% for brachytherapy, 13.7% to 28.1% for external beam radiation therapy, 1.3% to 7.3% for androgen deprivation therapy, 4.6% to 19.1% for observation, and 0% to 2.1% for cryotherapy. The highest rates of observation for low-risk disease were observed in academic centers. After adjusting for sociodemographic and facility factors, the highest proportions of treatment variation attributable to the single institution were observed for CT (59%, 95%CI 0.45-0.73) and BT (46%, 95%CI 38-53%), while the lowest proportion of treatment variation was observed for ADT (14%, 95%CI 12-15%), and Observation (15%, 95%CI 14-17%). The results were consistent in the sensitivity analysis and in all NCCN risk-groups. _x000D_ Conclusions Regardless of tumor characteristics, significant variations in treatment modality exist among different facility types and institutions.The increased utilization of observation in low-risk prostate cancer is an encouraging finding, which appears to be mainly derived by a decrease in radiotherapy utilization in this risk group. Funding none
Authors
Björn Löppenberg
Akshay Sood Deepansh Dalela Patrick Karabon Jesse Sammon Malte Vetterlein Joachim Noldus James Peabody Quoc-Dien Trinh Mani Menon Firas Abdollah |
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PD47-09 |
Influence of statin intake on PSA values, risk of prostate cancer development and survival in a prospective screening trial cohort (ERSPC Aarau) |
Prostate Cancer: Epidemiology & Natural History III | 17BOS |
Abstract: PD47-09 Sources of Funding: None Introduction Chemoprevention of prostate cancer (PCa) has been extensively investigated in the last decades. So far only 5-alpha-reductase-inhibitors (5-ARI) are supported by clinical evidence to have chemopreventive effect on PCa incidence, hence unclear in terms of prevention of aggressive PCa. Evidence for an effect of statins on PCa is conflicting. The interaction between dyslipidemia and carcinogenesis is still to be established. The aim of the study was to analyse the influence of statins intake on PSA values and PCa development. Methods A population-based analysis including 4314 men from the European Randomized Study of Screening for Prostate Cancer (ERSPC) database was conducted. Data about drug intake, age, family history and symptoms was obtained by a self-administered questionnaire. A transrectal ultrasound guided prostate biopsy was performed in men with a PSA-level > 3ng/ml. Tumor stage and grade were registered, incidence and mortality data were obtained through registry linkages. PCa incidence and grade, total PSA value, free-to-total PSA and overall survival were compared between statin users and non-users, respectively. Results Over a follow-up period of 9.6 years men with statin (n=761) exposure had insignificantly lower risk to be diagnosed with PCa ([stat+] hazard ratio (HR) 0.77, 95 % confidence interval (CI) 0.58 to 1.02. Statin users had less low risk PCa compared to non-users (p<0.05) at baseline visit while there was no difference in other PCa risk groups (according to d'Amico risk groups classification) or at follow-up visit. Interestingly, total PSA values were lower in statin users both for baseline (1.5 vs. 1.8 ng/ml, p<0.001) and follow-up-visits (after four years) (1.8 vs. 2.1ng/ml, p<0.001). Overall mortality was higher among statin users compared to non-users ([stat+] HR 1.67, 95% CI 1.36 to 2.04, however the competing risk analysis could demonstrate that PCa incidence was not influenced by overall-mortality. Conclusions In our study population we could demonstrate that statins intake did not alter overall PCa risk in a statistically significant manner. However, the finding of persistently lower PSA values in statin users is of potential clinical importance. It suggests that PSA cutoff values should be lowered in statin users otherwise it may introduce potential bias towards delayed PCa detection in this group, especially outside screening setting. On the other hand lower PSA values may suggest a durable protective effect of statins on PCa development. Funding None
Authors
Maciej Kwiatkowski
Elena Lang Ashkan Mortezavi Lukas Prause Stephen Wyler Rainer Grobholz Andreas Huber Lukas Manka Tullio Sulser Franz Recker Daniel Eberli |
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PD47-10 |
The Research Implications of PSA Registry Errors |
Prostate Cancer: Epidemiology & Natural History III | 17BOS |
Abstract: PD47-10 Sources of Funding: None Introduction Errors in prostate specific antigen (PSA) values included in prostate cancer registries have called into question clinical research studies that rely on this information. We sought to characterize the potential effects of PSA registry errors on clinical research by comparing cohorts based on registry PSA values with those based on laboratory values extracted from an integrated national health care system._x000D_ Methods We defined three example cohorts of men with prostate cancer using data from the VA integrated health care system: those with &[Prime]very low&[Prime] (<4.0 ng/mL), &[Prime]low&[Prime] (<10.0 ng/mL), and &[Prime]high&[Prime] (20-100 ng/mL) PSA values. We compared the composition of each cohort when using the cancer registry versus the electronic health record PSA values. We compared overall survival for each cohort as an example clinical outcome. We fit multivariable proportional hazards models to determine the importance of the PSA source in each cohort._x000D_ Results There was significant discordance when using cancer registry versus electronic health record PSA values to identify a cohort of patients with &[Prime]very low PSA&[Prime] values. While 7,286 were included in both cohorts, one third (n=3,515) of the cohort defined using cancer registry PSA values was misclassified and 1,800 additional patients were identified when using electronic health record data. The concordance was highest for patients with &[Prime]low&[Prime] PSA values, with 21,860 (98%) of patients identified in both the cancer registry and electronic health record based cohorts. Cancer registry PSA values misclassified 41% (604) of the &[Prime]high&[Prime] PSA cohort, and 133 additional patients were identified using electronic health record data. Comparisons of overall survival in the examples cohorts identified a difference in overall survival in the &[Prime]very low&[Prime] (log rank P=0.03), but not the &[Prime]low&[Prime] or &[Prime]high&[Prime] PSA cohorts. Conclusions Patient cohorts based on cancer registry PSA values may have high rate of misclassification, particularly among patients with &[Prime]very low&[Prime] or &[Prime]high&[Prime] PSA values. In some cases, differences in cohorts resulted in measurable differences in overall survival. Attempts should be made to validate cancer registry PSA data to ensure accurate and reproducible results._x000D_ Funding None
Authors
David Guo
I-Chung Thomas Harsha Mittakanti Jeremy Shelton Danil Makarov Ted Skolarus Matthew Cooperberg Geoffrey Sonn Benjamin Chung James Brooks John Leppert |
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PD47-11 |
Optimum tools for predicting clinical outcomes in prostate cancer patients undergoing radical prostatectomy: a systematic review of prognostic accuracy and validity |
Prostate Cancer: Epidemiology & Natural History III | 17BOS |
Abstract: PD47-11 Sources of Funding: Movember Foundation Introduction Prostate cancer progresses slowly, but its therapies often have adverse effects. Informed patient counselling regarding clinical outcomes is therefore important. The objective of this study was to identify all external validations of tools that predict clinical outcomes in prostate cancer patients undergoing radical prostatectomy, and evaluate which are optimum for clinical implementation. Methods PubMed and Embase were systematically searched from 2007 to 2016. Search terms related to the inclusion criteria: prostate cancer, clinical outcomes, radical prostatectomy and prognosis. Titles/abstracts were screened and relevant studies were advanced to full-text review. The references of full-texts were reviewed for further studies. The Centre for Evidence-Based Medicine prognostic study tool was used for critical appraisal and the online tool Covidence was used for data extraction. Results Seventy-three studies externally validated 41 post- and 13 pre-operative tools for the prediction of biochemical recurrence (BCR), aggressive BCR, metastasis, and prostate cancer specific mortality (PCSM). Recommendations for clinical implementation were made based on accuracy, cohort sizes, number of validations, and consistency. The accuracy of recommended tools ranged from 72-92% and 68-79% amongst the largest validation cohorts for post- and pre-operative tools, respectively. For post-operative prognosis we recommend the CAPRA-S, Stephenson, Kattan, DPC and the Suardi nomograms for the prediction of BCR, the DPC nomogram for aggressive BCR, the CAPRA-S and Eggener nomograms for metastasis, and the Eggener nomogram for PCSM. For pre-operative prognosis we recommend the CAPRA and Stephenson nomograms for BCR, the D&[prime]Amico criteria for aggressive BCR, the CAPRA nomogram for metastasis, and the D&[prime]Amico criteria for PCSM. Conclusions We identified all tools that can be used to predict clinical outcomes for prostate cancer patients undergoing radical prostatectomy. While many were inaccurate or not well validated, we recommend the best available tools to help clinicians give patients accurate predictions. Use of these tools should help clinicians deliver accurate, evidence based counselling to patients undergoing radical prostatectomy. Funding Movember Foundation
Authors
Jared Campbell
Elspeth Raymond Michael O'Callaghan Andrew Vincent Kerri Beckmann David Roder Sue Evans John McNeil Jeremy Millar John Zalcberg Martin Borg Kim Moretti |
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PD47-12 |
Incidence Rates and Cancer Control Outcomes of Contemporary Primary Neuroendocrine Prostate Cancer: Analysis of SEER Database |
Prostate Cancer: Epidemiology & Natural History III | 17BOS |
Abstract: PD47-12 Sources of Funding: none Introduction Neuroendocrine carcinoma of the prostate (NEPC) is an uncommon histologic type, described only in few reports. The present study provides population-based incidence rates and oncological outcomes for NEPC. Methods The current analysis relied on a total of 309 individuals diagnosed with histologically-confirmed NEPC between 2004 and 2013 within the Surveillance, Epidemiology, and End Results (SEER) registries. Patients with unknown metastatic stage (Mx) were not considered. Age-adjusted incidence rates (AAI) was calculated after correction according to the 2000 United States standard population and plotted according to the year of diagnosis. Temporal trend for AAI was quantified using the annual percentage change (APC) with the least squares linear regression. Among NEPC individuals, those with small cell carcinoma (SCC) histological subtype were identified and stratification was performed according to SCC vs. non-SCC (NSCC) histological variant. Kaplan-Meier estimate plots described overall survival (OS) in the entire cohort, as well as after stratification according to metastatic status and histological subtype. Results A total of 309 patients harboured NEPC. Of those, 60.2% (n=186) harboured SCC. A total of 64.1% (n=198) harboured metastatic disease. Annual AAI rates ranged from 0.23/1,000,000 person years in 2004 to 0.40/1,000,000 person years in 2013, with a statistically-significant increase over the study period (p=0.02; Figure 1). Median survival in the overall population was 10 months, with a difference between SCC and NSCC that only bordered statistical significance (10 vs. 12 months; p=0.05). Median survival was 13 versus 8 months for M0 vs. M1 disease (p<0.001). In SCC individuals, median survival was 12 versus 8 months for M0 vs. M1 disease (p<0.001). In NSCC, median survival was 15 vs. 9 months for M0 vs. M1 disease (p=0.01) Conclusions Despite a small but statistically-significant increase in NEPC incidence, it still represents a very rare entity. Most cases are represented by SCC. Survival is very poor, regardless of histological variant. While metastatic status at diagnosis confers worse survival rates, the absolute survival difference remains negligible. Funding none
Authors
Emanuele Zaffuto
Marc Zanaty Helen Davis Bondarenko Raisa S. Pompe Paolo Dell'Oglio Giorgio Gandaglia Nicola Fossati Armando Stabile Kevin C. Zorn Francesco Montorsi Alberto Briganti Pierre I. Karakiewicz |
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PD48-01 |
Is restaging transurethral resection (TUR) necessary in patients with non-muscle invasive bladder cancer (NMIBC) and focal Lamina Propria Invasion? |
Bladder Cancer: Non-invasive III | 17BOS |
Abstract: PD48-01 Sources of Funding: None Introduction Repeat TUR is both diagnostic and therapeutic in patients with T1 NMIBC. The depth of lamina propria invasion was shown to have the largest impact on T1 tumors prognosis. We intended to evaluate the influence of lamina propria invasion type at initial TUR on the re-staging pathology._x000D_ Methods We reviewed from our prospectively maintained database all patients with a high-grade pT1 disease who underwent a re-staging TUR within 6 weeks at our center from January 2015 to May 2016. All pathology specimens were reviewed by a dedicated uro-pathologist. The characteristics of the lamina propria invasion were assessed according to the pathological report to identify focal invasion. The pathology of the second TUR was analyzed regarding the characteristics of the initial resection._x000D_ Results We included 198 patients, with a median age of 70 years (interquartile range: 63-79). Muscle was present in the initial TUR specimen in 107 patients (54%). Pathology restaging was pT0 in 73 patients (37%), pTis in 44 (22%), pTa in 27 (14%), pT1 in 50 (25%) and pT2 in 4 (2%). Eighty-seven patients (44%) had tumors with minimal lamina propria invasion at initial TUR (53 specimens (27%) with focal invasion, 15 (7.6%) with superficial invasion and 19 (10%) with multifocal superficial invasion). Focal invasion was defined as few malignant cells in the lamina propria, superficial invasion as T1a and multifocal superficial invasion as multiple areas of T1a. Of the patients with minimal lamina propria invasion, residual disease was found in 20 patients (23%). However, none of those patients had T2 disease (Table 1)._x000D_ Conclusions A significant number of patients with T1 tumors have residual disease at restaging TUR. This is not any different among patients with minimal lamina propria invasion. All patients with T1 tumors should undergo restaging TUR irrespective of the depth of penetration into the lamina propria._x000D_ Funding None
Authors
François AUDENET
Caitlyn RETINGER Christine CHIEN Nicole BENFANTE Bernard BOCHNER Machele DONAT Harry HERR Guido DALBAGNI |
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PD48-02 |
The effect of immediate second resection of tumor bed after complete transurethral resection of bladder tumor : A comparative study using propensity score matching |
Bladder Cancer: Non-invasive III | 17BOS |
Abstract: PD48-02 Sources of Funding: None Introduction This study aimed to evaluate the immediate second resection of tumor bed after complete transurethral resection (TUR) could improve the quality of the initial TUR. Methods We retrospectively collected the data from 304 patients (immediate second resection group; ISR group) who had underwent immediate second resection as previously reported (Kim et al. J Endourol 2008) and 232 patients (non-second resection group; NSR group) who had not undergone immediate second resection by other surgeon. Confounding variables including age, gender, multiplicity of tumor, tumor size, pathologic tumor stage, pathologic tumor grade were matched in the two study groups using propensity score matching. Results The propensity score matched model included 6 variables, and matching by propensity score yielded 170 patients in ISR group matched to 170 patients in NSR group. (ISR group; 97 Ta, 6 CIS and 67 T1, NSR group; 94 Ta, 7 CIS and 69 T1). Of the patients who received restaging TUR (ISR group; 46 vs. NSR group; 39), the absence of residual tumors was significantly greater in ISR group than NSR group (74.3% vs. 47.8%, p=0.002). Among the patients with non-muscle invasive bladder tumor, ISR group demonstrated significantly better outcomes compared to NSR group in terms of 2-year RFS (82.9% vs.66.1%, p<0.001). The patient with high risk disease showed that the 2-year RFS was better for those who underwent immediate second resection than those who did not (83.7% vs. 56.6. p<0.001). Conclusions After controlling for variables affecting disease recurrence, the immediate second resection of tumor bed after complete TUR of bladder tumor improved recurrence free survival in patients with non-muscle invasive bladder tumor._x000D_ _x000D_ Funding None
Authors
Myungchan Park
Sang Hyun Park Myung Kim Jong Keun Kim Cheryn Song Bumsik Hong Hanjong Ahn |
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PD48-03 |
RISK FACTORS FOR RESIDUAL DISEASE AT RE-TUR IN T1G3 BLADDER CANCER |
Bladder Cancer: Non-invasive III | 17BOS |
Abstract: PD48-03 Sources of Funding: None Introduction Goals of transurethral resection of a bladder tumour (TUR) are to completely resect the lesions and to make a correct diagnosis in order to adequately stage the patient. It is well known that the presence of detrusor muscle in the specimen is a prerequisite to minimize the risk of under staging._x000D_ Persistent disease after resection of bladder tumours is not uncommon and is the reason why the European Guidelines recommended a re-TUR for all T1 tumours. It was recently published that when there is muscle in the specimen, re-TUR does not influence progression or cancer specific survival._x000D_ We present here the patient and tumour factors that may influence the presence of residual disease at re-TUR._x000D_ Methods In our retrospective cohort of 2451 primary T1G3 patients initially treated with BCG, pathology results for 934 patients (38.1%) who underwent re-TUR are available. 75.4% had multifocal tumours, 42.7% of tumours were more than 3 cm in diameter and 25.8% had concomitant CIS._x000D_ We analyse this subgroup of patients who underwent re-TUR: there was no residual disease in 267 patients (28.6%) and residual disease in 667 patients (71.4%): Ta in 378 (40.5%) and T1 in 289 (30.9%) patients. Age, gender, tumour status (primary/recurrent), previous intravesical therapy, tumour size, tumour multi-focality, presence of concomitant CIS, and muscle in the specimen were analysed in order to evaluate risk factors of residual disease at re-TUR, both in univariate analyses and multivariate logistic regressions._x000D_ Results The following were not risk factors for residual disease: age, gender, tumour status and previous intravesical chemotherapy. The following were univariate risk factors for presence of residual disease: no muscle in TUR, multiple tumours, tumours > 3 cm, and presence of concomitant CIS _x000D_ Due to the correlation between tumor multi-focality and tumor size, the multivariate model retained either the number of tumors or the tumor diameter (but not both), p < 0.001. The presence of muscle in the specimen was no longer significant, p = 0.15, while the presence of CIS only remained significant in the model with tumor size, p < 0.001._x000D_ _x000D_ Conclusions The most significant factors for a higher risk of residual disease at re-TUR in T1G3 patients are multifocal tumours and tumours more than 3 cm. Patients with concomitant CIS and those without muscle in the specimen also have a higher risk of residual disease. Funding None
Authors
Joan Palou
Richard Sylvester Francesca Pisano Steven Joniau Kathy Vander Eeckt Marco Oderda Vincenzo Serretta Stephane Larrè Savino Di Stasi Bas Van Rhijn Alfred J Witjes Anne Grotenhuis Renzo Colombo Alberto Briganti Amrek Babjuk Viktor Soukup Per Uno Malmstrom Jaques Irani Nuria Malats Jack Baniel Roy Mano Tommaso Cai Eugene Cha Peter Ardelt John Varkarakis Riccardo Bartoletti Martin Sphan Guido Dalbagni Shahrokh F Shariat Evangelous Xylinas R Jeffrey Karnes Paolo Gontero |
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PD48-04 |
Clinical benefits of combined technique transurethral En-bloc + endoscopic mucosal resection for non-muscle invasive bladder cancer, especially in large tumor. |
Bladder Cancer: Non-invasive III | 17BOS |
Abstract: PD48-04 Sources of Funding: None. Introduction Transurethral resection (TUR) is standard therapy for non-muscle invasive bladder cancer (NMIBC). Radical resection is an important predictor for outcome, and accurate pathological diagnosis is the key determinant factor to decide treatment strategy after TUR. In short, TUR are expected to complete excision and accurate pathological diagnosis for improved the prognosis in patients with NMIBC. Although TUR methods are established, pathological diagnosis is difficult because of heat denaturation and burn mark. In recent years, transurethral En-bloc resection technique is reported to be useful for judging cancer invasion in NMIBC. However, such method has disadvantage in prolongation of surgical time, particularly in large tumors. In this study, we investigated the usefulness and safety of combination therapy of electrical En-bloc resection and endoscopic mucosal resection (En-bloc + EMR) in NMIBC patients. Methods We analyzed 30 patients who were clinically diagnosed with NMIBC. The median of the tumour diameter was 30 (15–55) mm. At first, a tumour mass was cut by using CAPTIVATOR II (Boston Scientific) in the same way as EMR. Subsequently, a circular incision was created around the residual tumour, maintaining a distance of approximately 5–10 mm from the tumour edge, for the En-bloc resection. For the control, TUR was performed in 16 patients that were matched for tumour diameter and clinical stage. All surgeries were performed by one urologist. Before the patients were enrolled, the institutional ethical committee approved the study, and written informed consent was obtained. Results The mean operation time for EMR and En-bloc resection was 1.2 and 13.9 min respectively and total operation time was 15.0 min. That was similar to that for TUR (P = 0.94, mean = 16.2 and SD = 3.8 min). One patients had mild perforation of the bladder. However, no severe complications were observed and no significant difference was found regarding periods of catheterization and hospitalization. The pathologists can diagnose the invasion status with considerable certainty in all specimens obtained by En-bloc + EMR, compared to by TUR because of less heat denaturation and burn mark._x000D_ _x000D_ Conclusions Our results showed En-bloc + EMR technique is a useful and safe. We believe that this technique is particularly suitable for large tumors because control of bleeding and visual field are clearly better than TUR. In addition, this technique has an advantage in accurate pathological diagnosis to distinguish pTa and pT1. Funding None.
Authors
Yasushi Hayashida
Yasuyoshi Miyata Tomohiro Matsuo Keisuke Taniguchi Hideki Sakai |
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PD48-05 |
Metric Sub-stage According to Micro and Extensive Lamina Propria Invasion Improves Prognostics in T1 Bladder Cancer |
Bladder Cancer: Non-invasive III | 17BOS |
Abstract: PD48-05 Sources of Funding: None Introduction Management of T1 bladder cancer (BC) is controversial and reliable prognostics are urgently needed. We evaluated the clinical impact of two systems to sub-stage T1-BC on a large series of T1-BC patients treated with Bacillus Calmette-Guerin (BCG). Methods We included 601 patients with primary (first tumor) T1-BC, who were treated with at least one induction schedule of BCG instillations and followed in four university hospitals. The slides were reviewed by 3 uro-pathologists and sub-staged according to two classifications: Metric sub-stage according to T1micro-invasive (T1m - lamina propria invasion <0.5mm) vs. T1extensive-invasive (T1e - invasion ≥0.5mm) and secondly, according to presence or absence of muscularis mucosae invasion (MM - T1a vs. T1b). Prognostic value for progression-free survival (PFS) and cancer-specific survival (CSS) were analyzed for each system with a multivariable step-wise cox-regression model. We corrected for sex, age, size (>3cm vs. ≤3 cm), concomitant CIS, WHO 1973 and WHO 2004 grade. Results Median follow-up was 5.9 (IQR 3.3-9.0) years. Median age was 71 (IQR 15) years, 150 (25%) patients were female. Concomitant CIS was found in 196 (33%) cases. Metric sub-staging was possible in all cases. T1m was found in 213 (35%) tumors vs. 388 (65%) T1e. Based on MM invasion, 281 (47%) tumours were staged T1a vs. 320 (53%) T1b. MM was identified at the invasion front in 466 (78%) tumors. During follow-up, progression (≥cT2 and/or N1 and/or M1) was found in 148 (25%) patients and 95 (16%) patients died of BC. On univariable analysis, both sub-staging systems were significantly associated with PFS and CSS. On multivariable analysis, metric (T1m/e) sub-stage (T1e vs. T1m; HR 3.8, 95%CI 2.3-6.0, p<0.001) and WHO 1973 grade (G3 vs. G2; HR 1.8, 95%CI 1.2-2.7, p=0.006) were prognostic for progression. Independently associated with worse CSS were T1e (HR 2.7, 95%CI 1.6-4.8), WHO 1973 G3 (HR 2.6, 95%CI 1.4-4.7, p=0.002), increasing age (HR 1.03, 95%CI 1.01-1.05, p=0.002) and tumor size >3 cm (HR 1.8, 95%CI 1.2-2.9, p=0.008). _x000D_ Conclusions In this multi-center study, metric (T1m/e) sub-stage proved a very reliable and strong prognosticator for progression and cancer-specific survival. Our results suggest that metric T1 sub-stage may aid in treatment decision-making between conservative treatment and radical cystectomy for clinical T1-BC. T1a/b sub-stage has inferior prognostic value and reproducibility. Ultimately, metric sub-stage (T1m/e) may be incorporated in the TNM classification system for urinary BC. Funding None
Authors
Elisabeth Fransen van de Putte
Theodorus van der Kwast Simone Bertz Stefan Denzinger Quentin Manach Eva Compérat Joost Boormans Michael Jewett Robert Stöhr Alexandre Zlotta Kees Hendricksen Morgan Rouprêt Wolfgang Otto Maximilian Burger Arndt Hartmann Bas van Rhijn |
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PD48-06 |
2 YEAR CLINICAL AND IMMUNOLOGIC OUTCOMES OF INTRADERMAL BCG PRIMING PRIOR TO INTRAVESICAL INDUCTION IMMUNOTHERAPY FOR HIGH RISK NON-MUSCLE INVASIVE BLADDER CANCER |
Bladder Cancer: Non-invasive III | 17BOS |
Abstract: PD48-06 Sources of Funding: 1. Max and Minnie Tomerlin Voelcker Fund_x000D_ 2. NIH 5K23CA178204-03_x000D_ 3. The Roger L. and Laura D. Zeller Charitable Foundation Chair in Urologic Cancer_x000D_ Introduction Intravesical induction immunotherapy with Bacille Calmette-Guerin (BCG) is the standard of care treatment for high risk non-muscle invasive bladder cancer (NMIBC). Despite this, rates of recurrence and progression to muscle-invasion remain unacceptably high. We sought to optimize immunologic response to intravesical induction immunotherapy with standardized BCG intradermal vaccination prior to induction, and herein report our two year outcomes._x000D_ Methods BCG-naive patients with high-risk NMIBC who were candidates for BCG therapy were prospectively enrolled from 2014-2015. Patients who were PPD-negative were subsequently vaccinated with BCG in standard intradermal fashion, and 3 weeks later, standard induction immunotherapy with Tice BCG was performed. Urinary cytokines, BCG-specific T and mononuclear cells, and clinical outcomes were analyzed. Results 15 patients were enrolled and 13 completed the study; 5 controls were also enrolled. The median follow-up was 20.4 months (range: 28.1 to 14.8m). No patient experienced dose-limiting toxicity or a Grade 3+ adverse event. No patients progressed to muscle-invasive disease. 9 patients successfully converted PPD. 9 of 13 patients recurred in the lower tract (69.2%) and all were successfully salvaged. Immunologically, BCG-specific T cell lymphoproliferation was increased, as was IFN-γ secretion, IFN-γ ELISPOT response, and direct ex vivo IFN-γ response. Â Flow cytometry demonstrated that BCG significantly enhanced CD4+ and CD8+ T cells in most patients. Â Compared to controls, primed patients exhibited an increase in IFN-γ release in response to BCG ex vivo at both 3 months and 6 months after therapy. Â Priming resulted in an earlier and more robust increase in urinary IL-2, IL-17, and IL-8 compared to control patients suggesting a potential benefit from earlier and higher activation of local immune response. Conclusions Vaccination with BCG prior to induction immunotherapy results in improved immunologic measurements and increased urinary cytokines associated with control of high-risk NMIBC. Priming may represent a method to increase the efficacy of BCG immunotherapy for high-risk NMIBC. Further study with dedicated multi-center clinical trials and long term follow-up is warranted._x000D_ Funding 1. Max and Minnie Tomerlin Voelcker Fund_x000D_ 2. NIH 5K23CA178204-03_x000D_ 3. The Roger L. and Laura D. Zeller Charitable Foundation Chair in Urologic Cancer_x000D_
Authors
Niannan Ji
Edwin E. Morales Neelam Mukherjee Vincent Hurez Tyler J. Curiel Getahun Abate Daniel F. Hoft Robert S. Svatek |
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PD48-07 |
RECURRENCE AND PROGRESSION ACCORDING TO STAGE AT RE-TUR IN T1G3 BLADDER CANCER PATIENTS TREATED WITH BCG: NOT AS BAD AS PREVIOUSLY THOUGHT |
Bladder Cancer: Non-invasive III | 17BOS |
Abstract: PD48-07 Sources of Funding: None Introduction The goals of transurethral resection of a bladder tumour (TUR) are to completely resect the lesions and to make a correct diagnosis in order to adequately stage the patient. Persistent disease after TUR is not uncommon and is the reason why re-TUR is recommended in T1G3 patients. When there is T1 tumour in the re-TUR specimen, very high risks of progression (82%) have been reported1 and therefore cystectomy is considered to be mandatory._x000D_ We analyse the tumour stage at re-TUR and the risk of recurrence, progression to muscle invasive disease and cancer specific mortality (CSM) in T1G3 patients treated with BCG._x000D_ Methods In our retrospective cohort of 2451 T1G3 patients initially treated with BCG, pathology results for 934 patients (38.1%) who underwent re-TUR are available._x000D_ There was no residual disease in 267 patients (28.6%) and residual disease in 667 patients (71.4%): Ta in 378 (40.5%) and T1 in 289 (30.9%) patients. 310 patients (33.2%) received more than 6 instillations of BCG. Event rates in the 3 groups were compared using the chi-square statistic on 2 degrees of freedom_x000D_ Results Table 1 shows the observed results with a median follow up of 5.2 years and a maximum follow up of 18.7 years._x000D_ Similar trends were seen in both patients with and patients without muscle in the original TUR specimen. Conclusions Patients with T1G3 tumours treated with BCG and no residual disease or Ta tumour at re-TUR have better recurrence, progression and CSM rates than those with T1 tumour. The 25.3% progression rate of patients with T1 disease after re-TUR is far lower than that previously reported, with a CSM rate of 13.1%. Funding None
Authors
Joan Palou
Paolo Gontero Francesca Pisano steven Joniau Kathy Vander Eeckt Marco Oderda Vincenzo Serretta Stephane Larrè Savino Di Stasi Bas Van Rhijn Alfred J Witjes Anne Grotenhuis Renzo Colombo Alberto Briganti Amrek Babjuk Viktor Soukup Per Uno Malmstrom Jaques Irani Nuria Malats Jack Baniel Roy Mano Tommaso Cai Eugene Cha Peter Ardelt John Varkarakis Riccardo Bartoletti Martin Sphan Guido Dalbagni Shahrokh F Shariat Evangelous Xylinas R Jeffrey Karnes Richard Sylvester |
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PD48-08 |
Clinical and Pathological Outcomes for Patients with High Risk T1HG Bladder Cancer Managed with either Upfront Cystectomy or Primary BCG and Delayed Cystectomy |
Bladder Cancer: Non-invasive III | 17BOS |
Abstract: PD48-08 Sources of Funding: National Cancer Institute SPORE Introduction _x000D_ In muscle invasive bladder cancer (BC) there is an increased risk for systemic disease identified for patients with certain high risk features (HRF). We sought to identify the effect of HRF in the T1HG population who were managed with either primary BCG or upfront radical cystectomy (RC). Methods _x000D_ With IRB approval, a single center retrospective review was performed on all patients with BC at MDACC from 1995-2013. All patients included underwent a re-resection for T1HG disease and had presence of HRF as defined by: presence of hydronephrosis, thickening or induration felt at exam under anesthesia, presence of lymphovascular invasion, presence of prostatic ductal involvement or the presence of variant histology. Patients were considered to have had BCG therapy if they underwent 6 weeks of induction therapy and started a maintenance course. Primary outcome included overall survival (OS) and disease specific survival (DSS). Secondary outcomes include pathological outcome at RC. Results _x000D_ 209 patients with T1HG bladder cancer and HRF were identified, 64 patients (31%) had primary BCG and 145 (70%) had upfront RC. For patients with primary BCG, 2 had died and did not receive RC, 12 had BCG response and 50 patients had BCG failure and had a delayed RC (DRC). Median OS for primary BCG patients was 130 months vs. 137 for URC (p=0.0467 on KM). _x000D_ _x000D_ A total 195 patients underwent RC. Time from diagnosis of T1HG to RC was 1.4 months for upfront RC compared to 10.3 months for DRC (p<0.001). 22% (32/145) of URC patients, and 10% (5/50) of DRC patients extravesical disease (p=0.09). There was no significant difference in OS between RC patients who had upfront RC vs. DRC (p=0.2117). 10 year DSS post RC was 74.5% for upfront RC vs. 78% for DRC (p=0.122)._x000D_ Conclusions _x000D_ T1HG BC with HRF is amenable to either upfront RC or primary BCG. Primary BCG is associated with worse OS compared to upfront RC. However, this includes patients who did not make it to RC. Of patients treated with BCG, 78% received RC. There was no adverse effects on outcome at DRC. This study validates the use of upfront RC in T1HG with HRF. As well, it demonstrates that primary BCG is a reasonable option as long as diligent follow up is maintained and a low threshold to proceed with RC upon recurrence is followed. Funding National Cancer Institute SPORE
Authors
Michael Metcalfe
James Ferguson Roger Li Xiao Lianchun Neema Navai Ashish Kamat Jay Shah Colin Dinney |
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PD48-09 |
Purified protein deprivation skin test reaction is associated with clinical outcome of patients with non-muscle invasive bladder cancer treated with bacillus-Calmette Guerin |
Bladder Cancer: Non-invasive III | 17BOS |
Abstract: PD48-09 Sources of Funding: none Introduction The association between the purified protein derivative (PPD) skin test reaction before intravesical BCG therapy and clinical outcomes of patients with non-muscle invasive bladder cancer (NMIBC) has not been adequately investigated. Methods A total of 288 patients with NMIBC who underwent complete TURBT and adjuvant intravesical BCG therapy between 1987 and 2015 were included. In all patients, skin reactivity to a PPD of mycobacterium tuberculosis was tested before BCG therapy. The PPD skin test reaction was classified into 3 categories; negative, erythema or induration. Erythema reaction of 10 mm or less in diameter was considered to be negative. We evaluated the association between the PPD skin test reaction and tumor recurrence as well as the occurrence of major side effects due to BCG. Results The PPD skin test results were induration in 66 (23%) patients, erythema in 149 (52%), and negative in 73 (25%). The 5-year recurrence-free survival rates in patients with induration, erythema, and negative to PPD skin test were 89.4%, 65.5%, and 56.4%, respectively, with significant differences between the 3 groups. Univariate analysis demonstrated that tumor multiplicity (p=0.025) and induration to PPD skin test (p<0.001) were significantly associated with tumor recurrence. On multivariate analysis only induration to PPD skin test was independently associated with tumor recurrence (Hazard ratio: HR of 0.321, p=0.002). Seventy two (25%) patients experienced major side effects, including macrohematuria in 16 patients, high grade fever in 28, severe lower urinary tract symptoms in 19, and others in 19. Major side effects were observed in 22 (33%) patients with induration, in 40 (27%) with erythema, and in 10 (14%) with negative to PPD skin test, with significant difference between the 3 groups. On multivariate analysis only erythema to PPD skin test was independently associated with occurrence of major side effect (HR of 2.309, p=0.03) Conclusions The PPD skin test reaction before BCG therapy was highly associated with clinical outcome of tumor recurrence and occurrence of major side effects in patients with NMIBC treated with BCG therapy. Funding none
Authors
Naoya Niwa
Eiji Kikuchi Kazuhiro Matsumoto Koichiro Ogihara Hiroshi Hongo Takeo Kosaka Ryuichi Mizuno Akira Miyajima Mototsugu Oya |
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PD48-10 |
Preoperative neutrophil-to-lymphocyte ratio and smoking history are independently associated with BCG relapsing tumor recurrence in non-muscle invasive bladder cancer patients |
Bladder Cancer: Non-invasive III | 17BOS |
Abstract: PD48-10 Sources of Funding: none Introduction We have previously reported smoking status (2015 AUA) and an elevated preoperative neutrophil-to-lymphocyte ratio (pre-NLR) (2016 AUA) were predictive factors for tumor recurrence in overall non-muscle invasive bladder cancer (NMIBC) cases. However, there are still no reliable indicators for identifying BCG relapsing tumor recurrence in NMIBC patients treated with BCG therapy. We examined here whether elevated pre-NLR and/or smoking status could be associated with BCG relapsing tumor recurrence. Methods We identified 1759 cases treated by TURBT for initially diagnosed NMIBC between 1999 and 2015 at our 4 institutions. Detailed information concerning smoking status and a full set of blood data were available for 947 of these 1759 cases. After excluding patients who were BCG refractory and BCG intolerant, 438 cases treated with BCG therapy were included in the present study. We evaluated the predictive factors for identifying BCG relapsing tumor recurrence, defined as recurrence after achieving a disease-free status by initial BCG instillations for 6 months. We assigned patients to the elevated pre-NLR group using a cut-off of NLR of more than 2.095 according to a calculation by receiver-operating curve analysis. Results A total of 208 patients (47.5%) had elevated pre-NLR and 264 patients (60.3%) had a previous history of smoking. Patients with elevated pre-NLR were significantly older and had higher tumor stage as compared to their counterparts. A higher population of male patients was observed in the smoker group. The 5-year recurrence free survival (RFS) rate in patients with elevated pre-NLR was 63.2 ± 3.7%, which was significantly lower than that in those without elevated pre-NLR (77.9 ± 3.0%, p<0.001). The 5-year RFS rate in patients with a previous history of smoking was 66.0 ± 3.3%, which was significantly lower than that in that in the non-smoker group (78.2 ± 3.4%, p=0.003). Multivariate analysis demonstrated that an elevated pre-NLR (hazard ratio: HR, 1.98, p<0.001) and a previous history of smoking (HR, 1.81, p=0.003) were independently associated with BCG relapsing tumor recurrence. Conclusions Pre-NLR level and smoking status before BCG therapy might be useful information for predicting BCG relapsing tumor recurrence. Patients with a high pre-NLR level and positive smoking history are highly recommended to undergo early cystectomy due to their higher rate of BCG relapsing tumor recurrence. Funding none
Authors
Koichiro Ogihara
Eiji Kikuchi Yoshinori Yanai Kimiharu Takamatsu Suguru Shirotake Kazuhiro Matsumoto Masafumi Oyama Hirohiko Nagata Akira Miyajima Mototsugu Oya |
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PD48-11 |
Next Generation Sequencing of Non-Muscle Invasive Bladder Cancer Reveals Potential Biomarkers and Rational Therapeutic Targets |
Bladder Cancer: Non-invasive III | 17BOS |
Abstract: PD48-11 Sources of Funding: Supported by the Sidney Kimmel Center for Prostate and Urologic Cancers at Memorial Sloan Kettering Cancer Center, Pin Down Bladder Cancer, and the Michael A. and Zena Wiener Research and Therapeutics Program in Bladder Cancer. Introduction To identify genetic alterations with potential clinical implications through next generation sequencing of index pretreatment non-muscle invasive bladder cancer (NMIBC) tumors. Methods We analyzed index pretreatment NMIBC tumors and matched germline DNA of 105 patients with a 341 cancer-associated gene panel in a CLIA-certified clinical laboratory. Representative hematoxylin and eosin slides were reviewed by a genitourinary pathologist to confirm grade, stage, and urothelial histology. Restaging TUR was performed in all HGT1 tumors. Results To characterize the genomic landscape of NMIBC, we analyzed 105 tumors across the disease spectrum including LGTa (n=23), HGTis (n=12), HGTa (n=32) and HGT1 (n=38). The most frequently mutated genes in NMIBC tumors were TERT promoter (74%), FGFR3 (50%), KDM6A (47%), ARID1A (28%), PIK3CA (27%), KMT2D (24%), STAG2 (21%), and CDKN2A (17%). Of 105 tumors, 81% harbored at least one inactivating alteration in a chromatin-modifying gene. Alterations in the RTK/RAS/PIK3 pathway were present in 83% of tumors, including 58% of high-grade NMIBC tumors with either ERBB2 or FGFR3 alterations in a mutually exclusive pattern. Of 105 patients, 62 were treated uniformly with a 6-week induction course of BCG without maintenance. Genes altered with ≥5% frequency on the 341-gene panel were investigated for an association with recurrence after Bacillus Calmette-Guerin (BCG) therapy. On cox-regression analysis, only truncating mutations in the chromatin-modifying gene ARID1A were associated with recurrence after BCG (HR=3.14 [95%CI=1.51-6.51] p=0.002) (Table 1). This remained significant when adjusting for multiple comparisons (p=0.04) and when including ARID1A missense mutations of unknown significance (HR=3.08 [95%CI=1.49-6.35] p=0.002). Conclusions Next Generation Sequencing of index pretreatment NMIBC tumors showed an association between ARID1A mutations and recurrence after BCG therapy. Whether ARID1A mutations in NMIBC can serve as potential predictive or prognostic biomarkers or as therapeutic targets warrants further investigation. Moreover, the majority of NMIBC tumors had at least one potentially &[Prime]actionable&[Prime] alteration that could serve as a target in rationally designed trials of intravesical or systemic therapy. Funding Supported by the Sidney Kimmel Center for Prostate and Urologic Cancers at Memorial Sloan Kettering Cancer Center, Pin Down Bladder Cancer, and the Michael A. and Zena Wiener Research and Therapeutics Program in Bladder Cancer.
Authors
Eugene Pietzak
Eugene Cha Aditya Bagrodia Esther Drill Gopa Iyer Priscilla Baez Sumit Isharwal Qiang Li Ahmet Zehir Maria Arcila Michael Berger Nikolaus Schultz Irina Ostrovnaya Jonathan Rosenberg Dean Bajorin Guido Dalbagni Hikmat Al-Ahmadie David Solit Bernard Bochner |
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PD48-12 |
METHOD OF DETECTING BLADDER CANCER BY OPTICAL ANALYSIS OF BODILY FLUIDS |
Bladder Cancer: Non-invasive III | 17BOS |
Abstract: PD48-12 Sources of Funding: Non available _x000D_ Introduction Cystoscopy remains the main stay of surveillance employed for the follow up of Bladder cancer patients. The present study aims to provide a new detection method which is completely non-invasive, does not require additional surgery, and which is more accurate than visual inspection techniques, using a new photodynamic diagnostic procedure to quantify certain cancer specific biomarker called Porphyrin, which selectively binds on to the bladder cancer tissues. Methods Twenty bladder cancer patients and twenty healthy controls (all confirmed by cystoscopy) were invited to participate in the current clinical trial (NCT02101931), where 5 mg of 5-Aminolevulinic Acid (ALA) per kilogram body weight were administered for each subject. ALA gets metabolized into certain types of porphyrins which selectively bind on to the tumor tissues (for a longer time than the normal tissues which is two hours). At two hour intervals after administration, blood and urine sample were collected from the patients and were optically analyzed to measure a concentration of porphyrin therein. Optical analysis is performed by laser-induced fluorescence spectroscopy using a blue diode laser with a power rating about 100 mW and a wavelength of 405 nm. Results The laser-induced fluorescence spectroscopy results for the detected porphyrin in the blood and urine samples shows that approximately 90% of porphyrin were eliminated through urine for a healthy person after four hours. However, in cancer patients’ blood and urine samples, the prophyrin were retained up to eight hours, which indicates that healthy controls shows low signal intensity than bladder cancer patients in both urine (Fig 1) and blood (Fig 2) samples. Conclusions The present technique offers a viable, easy and reliable tool for diagnosis and continual monitoring of disease regression through blood and urine, based on optical analysis. Further studies on a large scale are warranted for conformation of these results. Funding Non available _x000D_
Authors
Danny Rabah
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PD49-01 |
Adjuvant pelvic radiation is associated with improved survival and decreased disease recurrence in pelvic node-positive penile cancer after lymph node dissection: a multi-institutional study |
Sexual Function/Dysfunction: Penis/Testis/Urethra: Benign Disease & Malignant Disease I | 17BOS |
Abstract: PD49-01 Sources of Funding: none Introduction Few studies have examined the role of adjuvant radiation therapy (AXRT) in advanced penile squamous cell carcinoma. We sought to evaluate the association of pelvic AXRT with survival and recurrence for patients with penile cancer and positive pelvic lymph nodes (PLN) after lymph node dissection. Methods Data were collected retrospectively across 4 international centers of patients with penile squamous cell carcinoma (PeCa) undergoing lymph node dissections from 1980 to 2013. 92 patients with positive PLN were analyzed. Variables recorded included age, stage, histological grade, PLN status, pelvic extranodal extension (ENE), chemotherapy status, disease-specific survival, overall survival, and recurrence. Results 43% (n=40) patients received AXRT after a positive PLN dissection. Median follow up was 9.3 months (IQR 5.2-19.8). The median number of positive PLN was 2 (IQR 1-3). Patients receiving AXRT had an improved median overall survival (OS) of 12.2 months versus 8 months in those who did not receive radiation (p=0.0447). Median disease-specific survival (DSS) was 14.4 months versus 8 months in the AXRT and non-AXRT group respectively (p=0.0232). Patients not receiving AXRT was associated with worse OS (HR: 1.9; 95% CI: 1.11-3.26; p=0.0195) and DSS (HR: 2.08; 95% CI: 1.18-3.66; p=0.0112) on multivariable analysis. Median time to recurrence was 7.7 months versus 5.3 months in the radiation and non-radiation arm respectively (p=0.0425). Patients not receiving AXRT was also independently associated with higher overall recurrence on multivariable analysis (HR: 1.98; 95% CI: 1.15-3.42; p=0.0131). Conclusions AXRT is associated with improved OS and DSS, and decreased recurrence in this population of PeCa patients with positive PLN. Further studies with a prospective design and larger data sets are required to validate this finding. Funding none
Authors
Dominic Tang
Rosa Djajadiningrat Gregory Diorio Zhenjun Ma Braydon Schaible Mario Catanzaro Dingwei Ye Yao Zhu Nicola Nicolai Simon Horenblas Peter Johnstone Philippe Spiess |
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PD49-02 |
Prediction of Postoperative Complications after Inguinal Lymphadenectomy for Penile Cancer Using a Novel Classification Tool |
Sexual Function/Dysfunction: Penis/Testis/Urethra: Benign Disease & Malignant Disease I | 17BOS |
Abstract: PD49-02 Sources of Funding: none Introduction To develop and validate a preoperative radiological assessment tool for predicting complications following inguinal lymph node dissection (ILND) in penile cancer patients. _x000D_ Methods Patients treated at Fudan University Shanghai Cancer Center (n=175) and Moffitt Cancer Center (n=28) were used for prediction assessment and repetition, respectively. The ILN complexity score (ILCS) included 5 radiological features of ILNs and surrounding adipose tissue. A tertiary (low/moderate/high) classification was assigned according to the sum score. Postoperative complications were graded according to the Clavien-Dindo system. Logistic regression analyses were used to assess the odd ratios (ORs) of the ILCS for predicting overall and major (grade?2) complications._x000D_ Results In the primary cohort, overall and major complications were observed in 47.4% and 20.5% of patients, respectively. Controlling for covariates, the moderate and high scores had 2.73 (p=0.02) and 4.61-fold (p=0.01) increased risks of overall complications compared with the low score. For predicting major complications, the adjusted OR was 3.48 for the moderate score (p=0.02), and 17.01 for the high score (p<0.01), using the low score as a reference. The predictive accuracy of the ILCS for overall and major complications was 0.63 (0.56-0.70) and 0.73 (0.64-0.82), respectively. In the repetition cohort, the ILCS was significantly associated with major complications (OR=17.33, p=0.02) and showed a predictive accuracy of 0.79 (0.64-0.93)._x000D_ Conclusions Using structured radiological measurements of the inguinal nodal basin, the ILCS provided accurate risk estimation of overall and major complications after ILND for penile cancer._x000D_ Funding none
Authors
Yao Zhu
Wei-Jie Gu Philippe Spiess Ding-Wei Ye |
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PD49-03 |
Adherence to Guidelines: Surgical Staging of Inguinal Lymph Nodes in High-Risk Clinically Localized Penile Cancer and Survival Implications |
Sexual Function/Dysfunction: Penis/Testis/Urethra: Benign Disease & Malignant Disease I | 17BOS |
Abstract: PD49-03 Sources of Funding: none Introduction Oncologic guidelines recommend surgical staging of inguinal lymph nodes (ILN) for high-risk, clinically node negative penile squamous cell carcinoma (SCC) due to the significant risk of ILNs harboring micrometastatic disease and significant survival advantage noted in those who undergo prophylactic ILN dissection. As penile SCC is rare in the US, we sought to use population-level data to determine adherence to guidelines, factors associated with adherence, and survival implications. Methods Starting in 2012, the National Cancer Database (NCDB) has reported on regional lymph node staging procedures. We queried the NCDB from 2012-2014 for all patients diagnosed with pT1b-T3, cN0 penile SCC who, by guidelines, should receive ILN sampling. Binomial logistic regression analysis was performed to determine predictors of ILN sampling. Variables included were facility type, geographic region, age, race, insurance status, income/education level of region, urban vs rural, patient distance from hospital, comorbidity, and pT-stage. Multivariate Cox regression analysis was performed for overall survival (OS) utilizing the aforementioned variables in addition to the performance of ILN staging. Results Of the 765 pT1b-T3, cN0 penile SCC patients identified, only 28.2% underwent surgical staging of ILNs - with the following pathologic staging: pN0 73.5%, pN1 10.6%, pN2 6.9%, pN3 4.6%, and unknown 4.2%. Overall, 22.2% of patients who underwent ILN sampling were node positive. Binomial logistic regression analysis to determine statistically significant predictors of performance of ILN sampling identified that patients with higher comorbidities, lower pT-stage, and those treated at non-academic hospitals were less likely to receive ILN sampling. On both univariate (Log Rank 11.56, p<0.01) and multivariate survival analysis, lack of ILN sampling was independently associated an increased risk of death (HR 1.72, p=0.03). Conclusions Adherence to guidelines to perform ILN staging in high-risk, clinically node negative penile SCC in the United States is low; and significantly lower in community vs. academic hospitals. Omission of ILN sampling is independently associated with worse OS. Funding none
Authors
Solomon Woldu
Ryan Hutchinson Nirmish Singla Boyd Viers Laura-Maria Krabbe Arthur Sagalowsky Yair Lotan Aditya Bagrodia Vitaly Margulis |
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PD49-04 |
ONCOLOGICAL OUTCOMES AND PATTERNS OF RECURRENCE OF PENILE SPARING APPROACHES FOR CARCINOMA OF THE PENIS: A RETROSPECTIVE, MULTICENTER COHORT ANALYSIS |
Sexual Function/Dysfunction: Penis/Testis/Urethra: Benign Disease & Malignant Disease I | 17BOS |
Abstract: PD49-04 Sources of Funding: none Introduction Use of penile sparing surgery (PSS) for penile carcinoma (PC) has been well characterized for low stages of the disease. In this present study we analyzed the outcomes of patients treated with circumcision, partial/total glansectomy, laser ablation, or wide local excision (WLE) for primary PC. Methods We included 1260 consecutive patients who underwent PSS at 5 academic institutions from July 2000 to June 2015. Tumor and patient characteristics such as age, tumor size (cm), tumor grade and pathological stage were recorded and analyzed. Kaplan-Meier analysis was performed to evaluate 1 year, 2 year and 5 year recurrence free survival (RFS) among the groups. Multivariable Cox proportional hazards regression was used to assess prognostic factors for RFS and overall survival (OS). Results Glansectomy patients had higher size, grade and pathologic stage tumors at time of surgery (p < 0.05). At a median follow up of 39.9 months, 37.1 % of patients treated with laser ablation had a local recurrence vs. those who underwent glansectomy or WLE alone (7.6 and 19.5%, respectively; p < 0.001). Patients who had laser procedures also had worse 1-yr, 2-yr and 5-yr RFS (74.4, 65.1 and 51%) vs. glansectomy (81.2, 72.4 and 68.8%, respectively) or WLE (80.3, 66.7 and 55.4%, respectively) (p = 0.056). Mutlivariable analysis found tumor grade (HR = 1.5, p <0.001) and corporal invasion (HR = 1.4, p = 0.05) to be significant, independent predictors for disease recurrence. Age was a significant prognosticator for OS (HR = 1.1, p < 0.001). Conclusions Tumor grade and corporal invasion were found as independent predictors of disease recurrence after penile sparing treatments. Patients treated with laser ablative techniques had worse recurrence outcomes. Strict surveillance guidelines for these patients are greatly needed. Funding none
Authors
Juan Chipollini
Adam Baumgarten Dominic Tang Sylvia Yan Sarah Ottenhof Yao Zhu Ding-wei Ye Chris Protzel Simon Horenblas Nicholas Watkin Philippe Spiess |
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PD49-05 |
Pathological Nodal Involvement in Patients with Penile Cancer in the National Cancer Data Base (NCDB) Using the Updated AJCC Staging Guidelines for T2 and T3 Disease |
Sexual Function/Dysfunction: Penis/Testis/Urethra: Benign Disease & Malignant Disease I | 17BOS |
Abstract: PD49-05 Sources of Funding: None Introduction The AJCC recently proposed new TNM staging for penile cancer, splitting the orginal T2 group (tumor invading corpus spongiosum or cavernosum) into T2 (invading corpus spongiosum) and T3 (invading corpus cavernosum). We sought to validate the new T staging system for predicting pathologic nodal involvement using the National Cancer Data Base (NCDB). Methods Invasive penile cancer cases from 2010-2012 were identified from the NCDB. Pathologic tumor stage was recorded including spongiosal versus carvernosal involvement. Differences in demographic (age, race, comorbid status) and pathologic features (size of tumor, grade, nodal status, LVI, histology, and extranodal extension) between T2 and T3 tumors were compared using χ2 and t-tests. Univariate and multivariate logistic regression was performed to determine the odds of positive lymph nodes (pN+) at inguinal lymph node dissection (ILND) relative to T-stage. Results There were 367 T2 and 507 T3 patients with penile cancer. The proportion of cases with pN+ disease was 15%, 32%, 46% and 58% for T1, T2, T3 and T4 cases, respectively. Compared to T2 tumors, T3 tumors were larger (mean size 5.8 cm vs. 4.3 cm), more often treated with radical penectomy (36% vs 17%), had higher positive surgical margin rates (12% vs 9%), more aggressive pathology (32% vs 27% poorly differentiated), and were more likely to have lymphovascular invasion (42% vs 31%) (all p < 0.05). In univariate analysis, compared to T1 tumors, T2 (OR 2.8, 95% CI 1.9-4.2) and T3 (OR 4.7, 95% CI 3.3-6.8) were both associated with an increased risk of positive lymph nodes. Although in multivariate analysis, both T2 (OR 2.0, 95% CI 1.2-3.3) and T3 (OR 2.3, 95% CI 1.4-3.6) remained significantly associated with risk of positive lymph nodes compared to T1 disease, there was no increase in risk between T2 and T3 disease (OR 1.1, 95% CI 0.7-1.8, p = 0.56). Conclusions The proposed new AJCC staging system for the penile cancer distinguishes spongiosal (T2) from cavernosal (T3) involvement and identifies significant differences in pathologic features of the tumors (grade, LVI and size). There does not appear to be a difference in positive lymph node status between the two grades when other clinical and pathological variables are considered. Further study is required to confirm these findings and the prognostic implications of the proposed new staging system. Funding None
Authors
James Kearns
Brian Winters Daniel Lin Jonathan Wright |
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PD49-06 |
The adherence to the EAU Guidelines on penile cancer treatment could influence the survival: multicenter, retrospective, European study. |
Sexual Function/Dysfunction: Penis/Testis/Urethra: Benign Disease & Malignant Disease I | 17BOS |
Abstract: PD49-06 Sources of Funding: none Introduction Penile Cancer (PC) is uncommon in Western countries. Due to its low incidence and low volume of surgical series it is difficult to achieve good quality guidelines with robust recommendations. Aims of this study were 1) to evaluate the adherence to the EAU guidelines on PC in terms of primary treatment and lymphadenectomy; 2) to weight the impact of the adherence on survival outcomes._x000D_ _x000D_ _x000D_ Methods We retrospectively reviewed the clinical charts of 176 patients underwent penile surgery for cancer in 8 European Centres. Demographics, circumcision, site of primary lesion, perioperative and histopathological data were collected and analysed. The follow-up was updated by recall of all patients._x000D_ A comparison between theoretical and practical surgical and lymphoadenectomy approach was done in order to evaluate the adherence rate. Descriptive, univariate and multivariate analyses were performed to evaluate the impact of the adherence on survival with Kaplan-Meier curves._x000D_ _x000D_ _x000D_ Results 176 patients were enrolled (median age 66.5 y +/- 11.3). The lesions were located at the glans, the prepuce and on both sites in 55%, 11% and 34%, respectively. The surgical approaches adopted were radical circumcision, tumor excision, glansectomy, penile partial amputation, total emasculation in 7%, 24%, 15%, 39%, 15%, respectively.The staging was 16% Conclusions Our data showed that the adherence to the EAU Guidelines on PC strongly influences the survival outcomes._x000D_
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Funding none |
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PD49-07 |
Engineering of corporal tissue constructs using non-human primate corpus cavernosal smooth muscle and endothelial cells for clinical applications |
Sexual Function/Dysfunction: Penis/Testis/Urethra: Benign Disease & Malignant Disease I | 17BOS |
Abstract: PD49-07 Sources of Funding: U.S. Department of Defense Introduction Numerous conditions exist, both congenital and acquired, that threaten male sexual health through changes in form and/or function. Efforts in penile reconstruction are often limited by poor availability of functionally intact penile tissue. We have previously demonstrated the ability to reconstruct functional corporal tissue via autologous cell-seeded collagen matrix in a rabbit model. In this study, we investigated the feasibility of engineering corporal constructs using cavernosal smooth muscle (SMCs) and endothelial cells (ECs) from non-human primates (NHPs) seeded onto 3D acellular corporal collagen matrices._x000D_ _x000D_ Methods Corpora cavernosa were isolated from NHPs. These specimens were then subjected to an established decellularization process to create acellular corporal collagen matrices. Autologous corporal SMCs and ECs were isolated, expanded in vitro, and seeded onto matrices via a multistep static/dynamic procedure._x000D_ Results Histologic and immunohistochemical analyses were performed. The corporal construct treated with the TritronX-100 protocol was effectively decellularized based on results of both DAPI (4,6 diamidino 2 phenylindole) staining and DNA assay (< 50 ng dsDNA/mg dry sample weight). Scanning electron microscopy demonstrated highly porous 3D structure and structural integrity. Evenly distributed cellular attachment and phenotype of corporal ECs and SMCs before/after dynamic culture conditioning were evaluated by immunohistochemical staining with anti-von Willebrand factor and anti-alpha smooth muscle actin. Conclusions We have demonstrated the feasibility of engineering viable and well-organized corpora cavernosa using tissue from NHPs. This represents an important achievement toward clinical utility for humans. Such technology may have application for congenital anomalies, penile cancer, traumatic penile injury, and selected cases of erectile dysfunction and Peyronies disease._x000D_ _x000D_ Funding U.S. Department of Defense
Authors
Joao Zambon
Young-Min Ju Koudy Williams Ryan Terlecki SIta Somara Alexander Baume Ashley Dean John Jackson Julie Allickson James Yoo Anthony Atala |
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PD49-08 |
The impact of routine frozen section analysis during penectomy on surgical margin status and long-term oncologic outcomes |
Sexual Function/Dysfunction: Penis/Testis/Urethra: Benign Disease & Malignant Disease I | 17BOS |
Abstract: PD49-08 Sources of Funding: None Introduction Intraoperative frozen section analysis (FSA) of biopsy or resection specimens often provides critical information for appropriate surgical management. However, to the best of our knowledge, there are no recent studies focusing on assessing the role of FSA in the status of surgical margins (SMs) relating to the outcomes of penectomy cases. Instead, a few review articles discourage its use in the intraoperative assessment of SMs during penectomy, mainly because lesions often show well differentiated squamous proliferation that can mimic non-neoplastic conditions. The current study aims to investigate the utility of routine FSA of the SMs in men undergoing penectomy for squamous cell carcinoma. Methods A retrospective review identified consecutive patients (n=38) who underwent partial (n=26) or total (n=12) penectomy for squamous cell carcinoma at our institution from 2004 to 2015. FSA findings were correlated with the diagnosis of the frozen section control, the status of final SM, and patient outcomes. Results FSA of the SMs was performed in 20 (77%) partial penectomies and 9 (75%) total penectomies, while no FSA was done for SMs in other cases. FSAs were reported as positive (n=3, 10%), negative (n=24, 83%), and atypical (n=2, 7%). All of the positive or negative FSA diagnoses, including those in 7 cases of well differentiated carcinoma, were confirmed accurate on the frozen section controls, whereas the 2 cases with atypical FSA had non-malignant and carcinoma cells, respectively, on the controls. Final SMs were positive in 5 (13%) penectomies (2 partial and 3 total), including 3 (10%) FSA cases versus 2 (22%) non-FSA cases (P=0.574). Furthermore, 2 initially FSA-positive/atypical cases achieved negative conversion by excision of additional tissue sent for FSA. In contrast, 2 FSA-negative cases showed carcinoma at the final SM where FSA was not submitted. During follow-up (mean: 41.2; median: 42; range: 1-136 months), 3 patients (non-FSA/final SM-negative, non-FSA/final SM-positive, FSA-negative/final SM-negative) developed tumor recurrence, and one of them (non-FSA/SM-positive) died of cancer. Kaplan-Meier analysis revealed that the number or diagnosis of FSA was not significantly associated with disease progression. Conclusions Overall, performing FSA during penectomy does not appear to have any significant impact on final SM status nor long-term oncologic outcomes. However, as seen in at least 2 cases, select patients may benefit from the routine FSA. Meanwhile, diagnostic accuracy of FSA of the SMs was found to be quite high. Funding None
Authors
Alexandra Danakas
Caroline Bsirini Hiroshi Miyamoto |
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PD49-09 |
Survival Analysis of patients with T2 penile cancer who received inguinal lymph node dissection: Results from the National Cancer Database |
Sexual Function/Dysfunction: Penis/Testis/Urethra: Benign Disease & Malignant Disease I | 17BOS |
Abstract: PD49-09 Sources of Funding: none Introduction Penile cancer (PC) is an uncommon disease with little level I evidence to guide therapy. The NCCN guidelines advocate for inguinal lymph node dissection (LND) for all patients with pT2 disease. Using a large national cancer registry, we assessed temporal trends in LND performance for patients with T2 disease, and evaluated survival outcomes between those who underwent LND and those who did not. Methods The National Cancer Database (NCDB) was queried for all non-metastatic PC patients with T2 squamous cell carcinoma of the penis from 2004-2014. Temporal trends for receipt of LND were assessed using Cochran-Armitage tests. , We used multivariable logistic regression models to examine the association between demographic and clinicopathologic characteristics and receipt of LND. Kaplan Meier analyses with log-rank tests and multivariable Cox regressions with time-varying covariates were used to assess overall survival (OS). Results A total of 1699 patients met inclusion criteria, of which 617 (36.3%) underwent LND. LND rates increased significantly from 2004 to 2014 (27 versus 46%, p<0.001). Significant differences in rates of LND were observed with regards to receipt of radiation (59% in treated vs 34% in not treated, p<0.001) chemotherapy (69% in treated vs 33% in not treated, p< 0.001), age (53% for ?50 yrs vs 22% for >70 yrs, p<0.001), and facility type (21% at community hospitals vs 48% at academic centers, p < 0.001). Following adjustment, the likelihood of receiving of LND decreased with increasing age (71 + year OR 0.30 [CI 0.23-0.64]), and increased with year of diagnosis (OR 2.30 for 2014 vs 2004[CI 1.19-4.43]) and treatment in an academic/research facility (OR 2.92 [CI 1.84-4.62] ). In survival analyses, patients receiving LND had a significantly longer median overall survival (113.9 months vs. 46.2 months, p<0.001). The survival benefit of LND was stronger 2+ years from surgery (HR 0.62 [CI 0.44-0.89]) compared 0-2 years (HR 0.85 [CI 0.68-1.06]) (see figure 1). Conclusions In hospitals reporting to NCDB, the rate of LND for patients with T2 penile cancer was only 36.3%. The observed survival benefit indicates that LND utilization is an important quality metric in patients with invasive penile cancer. Funding none
Authors
Andres Correa
Elizabeth Handorf Benjamin Ristau Haifler Haifler Shreyas Joshi Robert Uzzo Rosalia Viterbo Richard Greenberg David Chen Alexander Kutikov Daniel Geynisman Marc Smaldone |
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PD49-10 |
Changes in penile length after radical prostatectomy: Investigation of anatomical mechanism |
Sexual Function/Dysfunction: Penis/Testis/Urethra: Benign Disease & Malignant Disease I | 17BOS |
Abstract: PD49-10 Sources of Funding: none Introduction Several studies have shown penile shortening after Radical prostatectomy (RP); however, the underlying mechanism of this phenomenon is not well-elucidated. In the current study, chronological changes in penile length (PL) before and after RP were measured and the underlying mechanisms were investigated for the same. Methods Stretched PL (SPL) of 102 patients was measured before, 10 days after, and at 1, 3, 6, 9, 12, 18, and 24 months after RP. The perpendicular distance from the distal end of the membranous urethra to the midline of the pelvic outlet was measured on mid-sagittal magnetic resonance imaging (MRI) slice at three time-points: preoperatively, 10 days after RP and 12 months after RP. Pre- and postoperative SPLs were compared using paired Student’s t-test. Predictors of PL shortening at 10 days and at 12 months after RP were evaluated on univariate and multivariate analyses. Results The SPL was shortest at 10 days after RP; it gradually recovered thereafter (Fig.1). SPL at 12 months after RP was not significantly different from preoperative SPL. On MRI examination, the distal end of membranous urethra was found to have moved proximally (mean proximal displacement: 3.9 mm) at 10 days after RP, and to have returned to the preoperative position at 12 months after RP. Only the volume of the removed prostate was a predictor of SPL change at 10 days after operation on univariate analysis; on multivariate analysis, the association was not statistically significant. No predictor of SPL change was shown at 12 months after RP. Conclusions The SPL was shortest at 10 days after RP and gradually recovered thereafter in this study. Anatomically, glans and corpus spongiosum surrounding urethra is an integral structure, and the proximal urethra is drawn into pelvis during urethrovesical anastomosis (Fig.2). This is the first report showing that slight vertical repositioning of the membranous urethra after RP causes chronological changes in SPL. The information is useful for patients to know penile appearance changes after RP. Funding none
Authors
Yoshifumi Kadono
Kazuaki Machioka Kazufumi Nakashima Masashi Iijima Kazuyoshi Shigehara Takahiro Nohara Kazutaka Narimoto Kouji Izumi Yasuhide Kitagawa Hiroyuki Konaka Atsushi Mizokami |
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PD49-11 |
Survival Among Female Urethral Cancer Patients 2004-2013, a National Cancer Database Analysis |
Sexual Function/Dysfunction: Penis/Testis/Urethra: Benign Disease & Malignant Disease I | 17BOS |
Abstract: PD49-11 Sources of Funding: none Introduction Primary urethral cancers account for less than 1% of all GU cancers. Due to the rarity of this condition, the literature is limited to retrospective case series and case reports. Therefore we sought to characterize female urethral cancer in a contemporary cohort. Methods Years 2004?2013 of the National Cancer Database (NCDB) were used to identify primary urethral neoplasms among women. Clinicopathologic variables including age, race, tumor histology, grade, and treatment modality were analyzed. Overall survival (OS) was estimated using the Kaplan-Meier method. Associations with survival were evaluated using Cox regression models. Results Between 2004 and 2013 there were 1,088 cases of primary female urethral cancer in NCDB. The median age at diagnosis was 66 years (IQR 56, 77) and the majority of women were Caucasian (66%) or African-American (30%). Adenocarcinoma (AC) was the most common histologic subtype (34%), followed by squamous (SCC) (26%) and urothelial cell carcinoma (UC) (25%). Women with AC were younger (63 years vs 69 for UC and 67 for SCC, p<0.001) and more likely to be African American (56.0 % vs 24.2%, p<0.001). _x000D_ At diagnosis 45% of all patients were ≥cT3 and 38% were clinical stage III or higher. 16.6% had clinical node positive disease while 8.8% had distant metastatic disease. Among those with AC 56.8% were ≥cT3 compared to 48.2% of SCC and 35% with UC (p<0.001). Patients with AC were most likely to undergo definitive surgery (72% vs 68% for UC and 59% for SCC, p=0.0067). Conversely, those with SCC were more likely to be treated with primary chemo-radiation (16% vs 7% of AC and 5% of UC, p<0.0001). Nearly 44% of patients with SCC received radiation therapy during treatment compared to 37% and 21% of AC and UC patients respectively (p<0.0001). _x000D_ Median survival for those living was 47 months while 5 year OS was 41%. By subtype, 5 year OS for AC was worse than SCC or UC (Figure 1) (Log-Rank 0.013). On multivariate analysis, after adjusting for clinical TNM stage, race, age, and treatment modality, histology was no longer significantly associated with overall survival (p=0.57)._x000D_ Conclusions Patients with AC are younger, more likely to be African American, and present at a later stage than those with SCC or UC. Five year overall survival is poor regardless of histology, but worse among those with AC. Funding none
Authors
Mary E. Westerman
Vidit Sharma Derek J. Gearman Matthew K. Tollefson Stephen A. Boorjian Deborah J. Lightner R. Jeffrey Karnes |
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PD49-12 |
Primary Malignant Melanoma of the Female Urethra: Management and Long-term Outcomes at a Tertiary Referral Center |
Sexual Function/Dysfunction: Penis/Testis/Urethra: Benign Disease & Malignant Disease I | 17BOS |
Abstract: PD49-12 Sources of Funding: None Introduction Malignant melanoma of the female urethra is a rare tumor. There is limited data regarding management and outcomes of this condition. We therefore sought to evaluate the management and outcomes of urethral melanoma in females at our institution. Methods A retrospective analysis was performed of all women presenting to a tertiary referral center with primary malignant melanoma of the urethra from 1950 to 2016. All patients with identifiable metastatic disease at time of diagnosis were excluded. We evaluated pathology, tumor characteristics, presenting symptoms, initial and subsequent treatments, tumor recurrences, and survival. Results A total of 23 women (median age 71; range 51, 86) were identified with a pathologic diagnosis of malignant melanoma of the urethra. Median width of the urethral mass was 2.2 cm (IQR 1.4, 3.0) with a median depth of invasion of 7 mm (IQR 3, 12). The majority of masses involved the distal urethra (83%, 19/23), while four involved the entire urethra (17%). Concurrent vaginal involvement (pathologic T3) was present in 65% of patients (15/23). Reason for presentation to clinic include bleeding (74%, 17/23), mass (17% 4/23), pain (13%, 3/23), and voiding difficulty (4%, 1/23). All patients underwent surgical resection as first line therapy (65% partial urethrectomy, 26% radical urethrectomy, 9% anterior exenteration). Fifteen (65%) patients had recurrence of disease at a median of 7 months (IQR 4, 13). Local recurrence occurred in 80% of patients (12/15). Metastatic disease was identified in 60% of patients (9/15) with lungs being the most common site (78%, 7/9), followed by inguinal lymph nodes (44%, 4/9) and brain (33%, 3/9). Metastatic disease occurred at a median of 5 months (IQR 3, 25). A total of thirteen patients died secondary to melanoma (65%, 13/20). Median overall survival is 25 months (IQR 9, 53) and cancer specific survival is 53 months (IQR 12, 72). Conclusions Malignant melanoma of the urethra in females commonly recurs (65%) with a large proportion of those patients progressing to metastatic disease (80%) at a median of 5 months after initial surgical resection. These patients should be closely monitored for development of systemic disease with timely initiation of adjuvant therapies. Funding None
Authors
Brian Montgomery
Derek Lomas Vidit Sharma Deborah Lightner |
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PD50-01 |
The Value of Repair of Asymptomatic Grade II Pelvic Organ Prolapse during Mid Urethral Sling Surgery for Stress Urinary Incontinence: A prospective randomized study of 72 cases |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Female Incontinence: Therapy II | 17BOS |
Abstract: PD50-01 Sources of Funding: "none" Introduction To compare the clinical outcome between midurethtral sling procedure for stress urinary incontinence with and without concomitant repair of asymptomatic grade II pelvic organ prolapse (cystocele) repair._x000D_ _x000D_ _x000D_ _x000D_ _x000D_ Methods _x000D_ Seventy two female patients with stress urinary incontinence (SUI) and asymptomatic grade II cystocele were included in a randomized study between June 2014 and June 2015. They were divided equally into two groups. Group (A) treated only with trans-obturator tape (TOT) without treatment of the cystocele while in group (B) TOT was associated with cystocele repair by a tailored proline mesh. Postoperative follow up was performed after 3, 6 and 12 months. The two groups were compared regarding clinical outcome of SUI (cure, improvement or failure) and development of any denovo events._x000D_ Results _x000D_ For clinical outcomes based on patients’ subjective symptoms, the cure rate of group (A) was 77.8%.66.7% and 66.7% meanwhile for group (B) was 85%,90% and 90% at 3,6 and 12 months, respectively (p<0.05). Cystocele was cured in all patients in group (B). Six patients (17%) with asymptomatic cystocele grade II in group (A) became symptomatic or with a higher grade at 6 months duration that required surgical repair. Denovo urgency with or without UUI was 12.5% in group (A) increasing up to 50% at 6 months follow up which was treated with anticholenergic medications, but was 5% in group (B) with highly stastistically significant difference (p<0.05)._x000D_ Conclusions _x000D_ Concomitant asymptomatic cystocele repair with midurethral sling improve the cure rate of stress urinary insentience, reduce the incidence of denovo urgency incontinence and worsening of existing cystocele._x000D_ Funding "none"
Authors
Samer Morsy
Hussein Hussein Ahmed Abdel Aziz Dalia Abdel Azim Sarah Hassan Eman Hussein Mohamed Abdel Azim |
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PD50-02 |
OBESITY DOES NOT WORSEN URINARY INCONTINENCE FOLLOWING SACRAL COLPOPEXY |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Female Incontinence: Therapy II | 17BOS |
Abstract: PD50-02 Sources of Funding: none Introduction Obesity has been associated with urinary incontinence and may worsen incontinence related complaints following robotic sacral colpopexy (RSC). Elevated Body Mass Index (BMI) may confer an increased risk of denovo stress urinary incontinence (SUI) even when mid urethral sling (MUS) is performed. We sought to determine the risk of denovo stress incontinence following robotic sacral colpopexy in patients with elevated BMI and assess the impact of BMI on postoperative Quality of Life (QoL) metrics. Methods Retrospective chart review was undertaken and continence and BMI are noted. BMI was stratified according to the NIH classification. Outcomes were patient reported SUI and pad use, development of denovo SUI after colpopexy, and decision to undergo MUS after RSC. Incontinence was defined as any mention of SUI at any one of the follow up visits when asked directly by the examiner, SUI in the bladder diary, or evidence of SUI on the supine stress test. Results Between 2009 and 2015 134 women underwent RSC. 52 patients complained of urinary incontinence pre operatively (38.5%). As BMI increased, the number of pads recorded on preoperative bladder diary also increased, however, following concomitant mid urethral sling there was no difference in number of patients reporting incontinence or pad use at the last postoperative visit (Table 1) over 21.3 months follow up. The denovo rate of urinary incontinence did not increase as the BMI increased and failed to meet statistical significance, with normal BMI having a de?novo SUI rate of 26%, overweight 17%, obese 23%, and extreme obesity 25%, p>0.05. Conclusions Obese patients undergoing RSC have increased preoperative pad use and SUI rates but have similar SUI cure rates and denovo SUI rates compared with nonobese patients. Funding none
Authors
Charles Powell
Bridget Eckrich Jeffrey Rothenberg Thomas Gardner |
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PD50-03 |
EFFECTS OF BARIATRIC SURGERY ON FEMALE PELVIC FLOOR DISORDERS |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Female Incontinence: Therapy II | 17BOS |
Abstract: PD50-03 Sources of Funding: None Introduction Data regarding the effects of overweight on various aspects of pelvic floor function, as well as the potential reversibility of pelvic floor disorders following significant weight loss, are scarce. The aim of this prospective study was to assess the effect of surgically-induced weight loss on female urinary incontinence (UI), pelvic organ prolapse (POP), colorectal-anal complaints and sexual dysfunction. Methods 160 consecutive women (age>18 years), who underwent bariatric surgery in a single university-affiliated medical center, were prospectively enrolled. Four validated questionnaires (ICIQ-UI, BFLUTS-SF, PFDI-20, PISQ-12) were used to evaluate pelvic floor disorders and sexual dysfunction before, and 3-6 months after surgery.The study protocol was approved by the local hospital Helsinki committee. Results 150 women (mean age 43±12.8) completed all pre- and postoperative questionnaires. Mean BMIs before, and 3-6 months after surgery were 42±4.6 and 32±4.6 kg/m2, respectively. Preoperatively, 56 (37.3%) women had UI, 44 (29.3%) women had POP symptoms, and 66 (44%) women had colorectal-anal symptoms. Pre and postoperative results of the 56 preoperatively incontinent women are presented in Table. Postoperative weight loss was associated with statistically significant improvement in UI (mean ICIQ score 9.3±3.9 vs 3.3±3.8, P<0.001). Incontinence was either improved or entirely resolved in 30/33 (91%) women with stress UI, 15/17 (88%) women with mixed UI, 3/4 (75%) women with urgency UI. Overall, weight loss was also associated with statistically significant improvement in POP symptoms (mean PFDI score 19±13.2 vs 11±12.8, P<0.001), and colorectal-anal symptoms (mean PFDI score 21±15.9 vs 14±14.9, P=0.004). Moreover, half of preoperatively incontinent women, and more than 25% of women who had either POP, or colorectal-anal symptoms, reported complete resolution of their symptoms. Statistically significant improvement in sexual function was suggested by both BFLUTS-SF (0.3±0.8 to 0.1±0.6; P=0.011) and PISQ-12 (37.9±6.1 to 39.5±5; P=0.003) questionnaires. Conclusions Surgically-induced weight loss was associated with a significant improvement in pelvic floor disorders, including all major types of UI, POP and colorectal-anal symptoms; as well as improved sexual performance. Funding None
Authors
Asnat Groutz
Avner Leshem David Gordon Mordechai Shimonov |
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PD50-04 |
Which patients can expect improvement in Stress Urinary Incontinency after bariatric surgery? |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Female Incontinence: Therapy II | 17BOS |
Abstract: PD50-04 Sources of Funding: none Introduction Stress Urinary Incontinency (SUI) is a prevalent dysfunction encountered in obese patients. Although SUI is not a formal indication for bariatric surgery, patients who underwent this intervention report clinical improvement. The goal of this study is to characterize the epidemiological, antropometric and clinical profile of patients diagnosed with SUI before and after bariatric surgery. Methods Women in program of bariatric surgery of the Department of Surgery of Irmandade da Santa Casa de Misericórdia de São Paulo during the year of 2015-2016 were included, and only patients who did not complete the protocol questionnaire were excluded. The main variables evaluated: urinary stress test, weight, Body Mass Index (BMI), abdominal circumference (AC); number of pregnancies and parturition, POP-Q prolapse status, menopause status; smoking, diabetes, Visual Analog Scale (VAS) of satisfaction, International Consultation on Incontinence Questionnaire- Short Form (ICIQ-SF), Patient Global Impression of Improvement (IGP-I). Patients were submitted to this evaluation before and after 6 months of Roux-en-Y gastric bypass surgery. According to the result of the stress test, patients were divided in 3 groups: A- negative test before and after surgery, B- positive before and negative after surgery, C- positive test before and after surgery. Results Among the total of 46 patients enrolled in the study, 3 did not concluded the post-operation evaluation and were excluded. Patients were categorized in group A, group B and group C with 21, 16 and 6 patients respectively. In the preoperative period the factors to explain SUI were age and waist circumference. Each year of age increases the chances of SUI by 11,8%, each 10 centimeters more in abdominal circumference, increase the chances of SUI by 73,4%. Before the surgery, 22 (51,2%) were incontinent , 16 (72,7%) showed improvement and 6 (27,3%) remained incontinent (p=0,021). After the logistic regression analysis of groups B and C, there was a correlation with the variables ages over 52 years (p = 0.041), menopause (p = 0.029) were the most susceptible to IUE permanence. ICIQ-SF variation average in group B was 9,625 points and in group C was 6,5 points. Presence of uterine prolapse implicated in increasing up to 4,75 points in average on post-operation ICIQ-SF (p=0,03). VAS satisfaction average was higher in group B (8,84±1,12) than in group C(5,5±3,27). IGP-I showed better results in group B when compared to group C (p=0,065). Conclusions Weight loss through bariatric surgery completely improves SUI and its repercussions on quality of life in the vast majority of patients. Increased age and abdominal circumference raises the chance of SUI in obese women, and the age over 52 years and menopause are strongly related to the persistence of SUI after weight loss. Funding none
Authors
Antonio Rodrigues
Luís Gustavo Toledo John Chii Chao Thiago Loiro Tagliari Danielle Briza |
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PD50-05 |
Long-term outcomes from TVT procedures for treatment of female stress urinary incontinence: Data from a minimum of 15 years of follow-up |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Female Incontinence: Therapy II | 17BOS |
Abstract: PD50-05 Sources of Funding: None Introduction To evaluate the long-term outcomes of the tension-free vaginal tape (TVT) procedure, we investigated the data from female patients with stress urinary incontinence (SUI) who had a minimum of 15 years of follow-up to determine the predictive risk factors affecting the treatment efficacy. Methods A total of 192 female patients (mean ± SD age: 62.1 ± 7.8 years) who had undergone the TVT procedure for SUI were selected and followed-up for at least 15 years (mean ± SD duration: 191.4 months, range: 187-196 months). We analyzed the long-term results and the predictive parameters for success rates, and patients&[prime] satisfaction. Results At 15 years after surgery, the overall cure rate was 84.5%, with a satisfaction rate of 68.4%. Univariate analysis showed an association between the SUI symptom grade and the cure rates, while the presence of frequency, urgency, and urge incontinence showed an association with the patients&[prime] satisfaction. However, in the multivariate logistic regression model, none of these variables were identified as an independent risk factor related to the cure and satisfaction rates. Twenty patients (10.0%) had postoperative complications at 1 year after surgery. However, at 15-years after surgery, only 2 patients (1.0%) had a postoperative complication, such as de novo urgency. Conclusions Our long-term data show that the TVT procedure is a reliable method for the treatment of female SUI, regardless of any independent predictive factors. Funding None
Authors
Phil Hyun Song
Jae Young Choi Young Hwii Ko Ki Hak Moon Hee Chang Jung |
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PD50-06 |
Mid-urethral position: Is this critical to achieving continence following sling placement for stress incontinence? |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Female Incontinence: Therapy II | 17BOS |
Abstract: PD50-06 Sources of Funding: None Introduction Since the widespread adoption of the synthetic mesh mid-urethral sling (MUS) for the treatment of stress urinary incontinence (SUI), proper placement of the sling at the mid urethra has been emphasized. There is limited and conflicting evidence on the importance of the mid-urethral position with regards to continence outcomes, however. We aimed to describe our experience of sling position in women presenting for MUS excision. Methods We retrospectively reviewed our database of patients who underwent translabial ultrasound (TLUS) prior to MUS excision for mesh-related complications between January 2013 and May 2014 at UCLA. Patients were excluded if they had a history of pelvic radiation, neurogenic voiding dysfunction, transvaginal mesh placement for prolapse, urethral erosion, multiple slings, prior revision of an anti-SUI surgery, post-void residual > 150 cc, or did not undergo preoperative urodynamics (UDS). Patients were stratified into 2 cohorts based on absence or presence of SUI on UDS. Sling position was categorized as proximal urethra or bladder neck, mid urethra, or distal urethra based on sagittal images of the TLUS. Sling position was assessed by a radiologist. For cases in which the sling position overlapped between more than one location, the dominant location was determined by a FPMRS fellow (JO). Results 96 patients were identified. Median age was 56.4 years old (range 32-83). Median time from last mesh placement to MUS excision was 4.76 years (1.4-13.6). Among 19 patients without SUI on UDS, the sling was located in the distal, mid, and proximal urethra in 19 (24.7%), 43 (55.8%), and 15 (19.5%) patients, respectively. Among 77 patients with SUI on UDS, the sling was located in the distal, mid, and proximal urethra in 4 (21.1%), 13 (68.4%), and 2 (10.5%) patients, respectively. Comparing the distribution of slings located at the mid urethra versus outside of the mid urethra, there was no significant difference between the cohorts (p=0.4). There were also no significant differences in age, prior vaginal deliveries, or time to MUS excision. Patients presenting with SUI had a significantly higher body mass index (p=0.02), however. Conclusions Many patients who have a successful outcome following MUS as defined as resolution of SUI have a sling located outside of the mid urethra. Thus, mid-urethral position may not be as critical to achieving continence with a MUS as previously thought. We hypothesize that it is the ability of a MUS to provide a &[Prime]hammock&[Prime] of support, regardless of position, that contributes to successful continence outcomes. Funding None
Authors
Janine Oliver
Taylor Sadun Claire Burton Lauren Wood Evgeniy Kreydin Ja-Hong Kim Shlomo Raz |
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PD50-07 |
LOW SERUM TESTOSTERONE IS ASSOCIATED WITH INCREASED STRESS AND MIXED INCONTINENCE IN WOMEN |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Female Incontinence: Therapy II | 17BOS |
Abstract: PD50-07 Sources of Funding: None Introduction Androgen receptors are present in the levator ani and testosterone administration has been shown to result in levator hypertrophy and improvement of surgically induced incontinence in a rodent model.1 However, the association between serum testosterone levels and incontinence in humans has not been extensively studied. We sought to examine the relationship between serum total testosterone levels and self reported urinary incontinence among women participating in a national survey. Methods Data were analyzed for 2123 females who participated in the 2012 cycle of National Health and Nutrition Examination Survey and underwent measurement of serum total testosterone. Incontinence was defined as self-reported stress, urge, or mixed incontinence. Serum testosterone concentrations were log-transformed, assigned to quartiles, and examined first in a weighted variance-corrected univariate model for association with incontinence, and then in a weighted variance-corrected model adjusted for age, body mass index, diabetes, race, parity and time of venipuncture (morning, day, or evening). Results Univariate analysis revealed a strong inverse correlation between serum testosterone level and each type of incontinence in females. However, after adjustment for age, decreased serum testosterone was associated only with increased likelihood of stress and mixed incontinence. In the multivariate model, women in the lowest quartile of serum testosterone concentration were more likely to complain of stress (OR 1.49, 95%CI 1.07-2.06) and mixed incontinence (OR 1.61, 95%CI 1.18-2.18). Conclusions This is the first study to demonstrate a relationship between serum testosterone level and stress and mixed incontinence in women. Given the role of pelvic musculature in maintaining urethral support and the anabolic effect of androgens on skeletal muscle, a physiologic mechanism for this relationship can be proposed and further evaluated in prospective and translational studies. Funding None
Authors
Michelle Kim
Zaid Chaudhry Janine Oliver Evgeniy Kreydin |
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PD50-08 |
AUTOLOGOUS MUSCLE DERIVED CELLS FOR URINARY SPHINCTER REPAIR FOR RECURRENT OR PERSISTENT STRESS URINARY INCONTINENCE AFTER CONTINENCE SURGERY |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Female Incontinence: Therapy II | 17BOS |
Abstract: PD50-08 Sources of Funding: Cook MyoSite, Incorporated Introduction We describe the effect of Autologous Muscle Derived Cells for Urinary Sphincter Repair (AMDC-USR) on women with recurrent or persistent stress urinary incontinence (SUI) after continence surgery. Methods Analysis includes data from women enrolled in Cook MyoSite-sponsored SUI studies who underwent prior continence surgery (e.g., urethral sling, bladder neck suspension) and presented with incontinence episode frequency (IEF) of ≥3 stress leaks over 3 days and ≥3 g 24-hour pad test. Twenty-one women who received 1 treatment of 10 (n=5), 50 (n=2), 100 (n=4), or 200 x 106 (n=10) AMDC-USR were treated in open-label studies (NCT00847535, NCT01008943) and 17 women who were randomized 2:1 to receive 150 x 106 AMDC-USR (n=11) or placebo (n=6) and 1:1 for 1 or 2 treatments were treated in a double-blind trial (RCT, NCT01382602). SUI was assessed by 3-day diaries at baseline and 1, 3, 6, and 12 months for all studies and at 2 years in the RCT. RCT patients were unblinded after 12-month visits. Results Median baseline stress IEF per 3 days was 12 leaks for open-label studies, and 11 leaks for AMDC-USR and 27.5 leaks for placebo in the RCT. In the RCT, the AMDC-USR group tended to be younger (51 yr vs. 64 yr), had a lower percentage with stage 1-2 pelvic organ prolapse (9% vs. 67%), and better 24-hour pad tests (45 g vs. 76 g) than placebo. In open-label studies, 18 women completed 12-month visits; 67% (12/18) had ≥50% IEF reduction, 44% (8/18) had ≥75% IEF reduction, and 39% (7/18) reported ≤1 leak over 3 days. Similarly, 12-month responder rates for the RCT AMDC-USR group were 73% (8/11) for ≥50% IEF reduction, 64% (7/11) for ≥75% IEF reduction, and 36% (4/11) for ≤1 leak per 3 days. During the RCT, a higher percentage of the AMDC-USR group met IEF reduction endpoints than placebo (Figure). Eight AMDC-USR RCT patients completed 2-year diaries; 100% (6/6) of women with ≥50% IEF reduction at 12 months also met the endpoint at 2 years. All (6/6) RCT placebo patients elected to receive open-label AMDC-USR after unblinding; at final follow-up, 3 patients had ≥50% IEF reduction compared to 12-month diaries. No AMDC-USR safety signals were identified._x000D_ Conclusions AMDC-USR may be a novel, safe, durable therapy for the challenging patient population with recurrent or persistent SUI after continence surgery. Funding Cook MyoSite, Incorporated
Authors
Lesley Carr
Le Mai Tu Magali Robert David Quinlan Kevin Carlson Sender Herschorn Roger Dmochowski Kenneth Peters Melissa Kaufman Ron Jankowski Michael Chancellor |
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PD50-09 |
A POTENTIAL NEW TARGET FOR STRESS URINARY INCONTINENCE: A μ-OPIOID RECEPTOR IN THE SPINAL CORD BY TRAMADOL, IN RATS |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Female Incontinence: Therapy II | 17BOS |
Abstract: PD50-09 Sources of Funding: Grant-in-Aid for Scientific Research (15K01377 and 15K01376) Introduction Stress urinary incontinence (SUI) is the most common type of urinary incontinence in women. As the efficacy of pharmacotherapy for SUI is generally unsatisfactory, surgery seems to be the best option for achieving long-term continence. Thus, new effective drugs for SUI should be developed. Tramadol is widely used as an analgesic. It combines the effects of μ-opioid receptors with inhibition of serotonin and noradrenaline reuptake inhibitors. Both effects may be useful for treatment of SUI, but the efficacy of tramadol for SUI has not been examined yet. We previously established a rat model that can be used for examining the active urethral closure mechanism during sneezing. We therefore investigated the effect of tramadol on urethral continence reflex by using this model. Methods Healthy female rats and rats with SUI induced by vaginal distension (VD) were used. (1) The effects of tramadol on tilt leak point pressure (tilt LPP) were examined before and after intravenous (i.v.) injection of tramadol under urethane anesthesia in both rats. (2) To investigate the effect of tramadol on mid-urethral responses during sneezing, the amplitude of the urethral responses during sneezing (A-URS) and urethral baseline pressure (UBP) were measured by inserting a microtip transducer catheter in the middle urethra in both rats. (3) To confirm the effects of tramadol on μ-opioid receptors in the spinal cord, the effect of tramadol in the presence of intrathecal (i.t.) cyprodime, a selective μ-opioid receptor antagonist, was examined in the healthy rats. Results (1) Tilt LPP was lower in the VD rats than in the healthy rats (43.9 vs 48.6 cmH2O). Tramadol (i.v.) significantly increased the tilt LPP by 25.9% and 21.2% in the healthy and VD rats, respectively. (2) In the healthy rats, tramadol (i.v.) enhanced the A-URS and UBP by 37.0% and 74.9%, respectively. In the VD rats, tramadol administration also enhanced UBP by 11.1% but did not affect A-URS. (3) Administration of cyprodime alone (i.t.) did not affect A-URS and UBP. However, in the presence of cyprodime, tramadol-induced increases in A-URS were suppressed, while UBP was elevated significantly._x000D_ _x000D_ Conclusions These results indicate that tramadol, a μ-opioid agonist, is effective for enhancing the active urethral continence reflex during sneezing at the spinal level (a microtip transducer catheter measurement), thereby preventing SUI (a LPP measurement). Therefore, activation of μ-opioid receptors in the spinal cord may be a new candidate treatment for SUI in humans. Funding Grant-in-Aid for Scientific Research (15K01377 and 15K01376)
Authors
Asuka Ashikari
Minoru Miyazato Takuma Oshiro Seiichi Saito |
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PD50-10 |
Gene Expression and Patterns of Scarring Response in Human Fibroblasts in Response to Mesh and Catheter Materials Using a Novel 3-D Collagen Model |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Female Incontinence: Therapy II | 17BOS |
Abstract: PD50-10 Sources of Funding: International Collaboration on Repair Discoveries (ICORD) Introduction Scarring secondary to mesh and prosthetic materials is a serious clinical problem within the GU tract. Fibrotic matrices contain fibronectin; and alpha-smooth muscle actin contributes contraction. Metalloproteinases (MMPs) such as MMP-1 and -3 can modulate matrix protein accumulation through degradation. Results from our institution have shown that silica materials can directly induce scarring through the interaction with tissue fibroblasts in vitro. By extension, we hypothesized that other materials may induce fibrotic changes through cellular matrix gene expression. Objectives: 1) to establish a 3D model of human fibroblasts to study patterns of fibroblast response to materials and 2) measure gene expression in human fibroblasts exposed to prosthetic and mesh materials compared to a control. Methods Collagen gel was prepared by using 3 mg/ml in final concentration with 0.5% of polyvinyl alcohol (PVA). Mesh or catheter materials and human dermal fibroblasts (70,000 /ml) were added to a collagen gel and seeded in a 24-well plate (0.5 ml of gel in each well) to create a 3D environment for fibroblast response. After polymerization of collagen, another 250,000 cells in 0.5 ml medium were added on the top of gel. Cells were cultured at 37 0C, 5% CO2 for indicated time point. Images of cells were taken under reverse microscopy to determine the pattern of the scarring contraction. Gel cell matrix was harvested and digested with 1 mg/ml of collagenase for 15 minutes, pelleted by centrifugation and RNA was extracted. RT-PCR was performed for 32 cycles to analyze gene expression. Results After 5 days, fibroblast contractions were identified surrounding prosthetic materials but not within the control. There were increases in type 1 collagen, ?-smooth muscle actin and fibronectin expression in fibroblasts exposed to prosthetic materials compared to fibroblasts grown in collagen gel alone. MMP-1 and MMP-3 were also detected. Conclusions Fibroblasts exposed to mesh and catheter materials responded with an increase in fibronectin, alpha smooth muscle actin and type 1 collagen that is increased compared to controls. This may indicate why in vivo these materials induce fibrosis. Because fibronectin, type 1 collagen and alpha smooth muscle actin are main components of scarring and their gene expression is elevated, future directions include development of medical devices that could induce downregulation of these genes. Funding International Collaboration on Repair Discoveries (ICORD)
Authors
Li Yunyuan
Lynn Stothers Aziz Ghahary |
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PD50-11 |
Management of urinary incontinence following sub-urethral sling removal |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Female Incontinence: Therapy II | 17BOS |
Abstract: PD50-11 Sources of Funding: None Introduction We sought to evaluate de novo and persistent urinary incontinence outcomes following synthetic sub-urethral sling removal (SSR) in women. Methods We reviewed a prospectively maintained database of 360 consecutive women who underwent SSR between 2005 and 2015. We excluded patients who had neurogenic bladder, non-synthetic or multiple slings, prior mesh for prolapse, concomitant surgery at the time of sling excision, urethral erosion or urethrovaginal fistula, post-operative retention, or less than 6 months follow-up. Demographics, type of sling, indications for removal, time to removal, and patient-reported outcomes were recorded. All SSR were performed transvaginally under general anesthesia with removal of as much sling as possible. Post-operative outcomes were stratified by type of incontinence (stress-predominant (SUI), urge-predominant (UUI), and mixed (MUI)). Subsequent management (observation/medications, minimally-invasive intervention (urethral bulking agent, sacral neuromodulation, onabotulinumtoxinA injection), or more invasive surgery (sling, bladder suspension)) was evaluated. Success or "dry" was defined by response of 0 (none) or 1 (rarely) on UDI-6 questions 2 and 3 and self-reported satisfaction with continence at last visit, and no further anti-incontinence intervention. Results 99 patients met study criteria. Mean follow-up was 24 months (range 6-114). Mean duration from sling placement to SSR was 58 months (range 5-156). Median age and BMI were 55 years and 25.3 kg/m2, respectively. 78% underwent prior hysterectomy and 64% were post-menopausal. 71% of slings were retropubic. Of 99 women, 27 (27%) denied any subjective leakage following SSR alone, while 72 (73%) experienced some degree of incontinence post-operatively: 26 with SUI (7 persistent, 19 de novo), 14 with UUI (6 persistent, 8 de novo), and 32 with MUI (13 persistent, 19 de novo). However, following a single minimally-invasive intervention, success rates rose to 81% in women with SUI, 86% in those with UUI, and 75% in those with MUI (Table). Conclusions Patients undergoing SSR may experience cure (>25%) or de novo or persistent urinary incontinence, with a higher predilection for UUI or MUI. However, after a single minimally-invasive intervention following SSR, success rates reached 75-86%. Funding None
Authors
Nirmish Singla
Himanshu Aggarwal Jeannine Foster Feras Alhalabi Gary Lemack Philippe Zimmern |
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PD50-12 |
High catastrophizing in patients with self-reported painful mesh complications have poorer outcomes |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Female Incontinence: Therapy II | 17BOS |
Abstract: PD50-12 Sources of Funding: none Introduction The pain catastrophization scale (PCS) was developed to help identify those patients likely to have an exaggerated negative mental thought process in response to pain. Catastrophizing has been shown to be a risk factor for chronicity of pain, disability, and depression. Patients who catastrophize after surgery have worse outcomes and longer duration of pain. Given this, we sought to identify the rate of catastrophizing in cohort of patients with mesh complications and chronic pain. Methods Patients throughout the US with self-described complications of vaginal mesh were recruited through advertisements to complete an internet-based anonymous survey. All patients filled out the PCS and the Genitourinary Pain Index (GUPI) questionnaire. The PCS is a 13-question survey with scores ranging from 0-52. Previous studies have established distribution of scores from subjects with chronic pain, with a score of 30 or higher representing the highest quartile, thus a score ≥30 was used to define high pain catastrophizing. Additional data was abstracted including age, number of previous pelvic surgeries, and intent to sue. Statistical analysis was performed using χ2 test and t-test for categorical and continuous variables, respectively. Results A total of 133 patients were included in the study, of which 78 patients (59%) were found to have high pain catastrophizing. There was no significant difference between baseline age, intent to sue, or number of previous pelvic surgeries between those who catastrophized and did not. Patients who catastrophized were significantly more likely to have a higher GUPI score (33.8 vs. 27.7, p<0.001) along with significant differences in pain (16.3 vs. 13.0, p<0.001) and quality of life (10.8 vs. 9.1, p<0.001) subdomains. Furthermore, patients who catastrophized tended to have less hope that they would recover (38.5% vs. 23.6%) which approached but did not reach statistical significance (p=0.072). Conclusions Patients with self-described mesh complications have a high rate of pain catastrophizing, which is associated with significantly worse quality of life and pain scores. Given that previous studies have also shown catastrophizing is associated with higher pain intensity, disability, and psychological distress (Weber et al, 2001), identifying high catastrophizing patients in the setting of chronic pelvic pain from mesh complications may help guide treatment and be an indicator for early or adjunctive psychosocial intervention. Funding none
Authors
Juzar Jamnagerwalla
Karyn S. Eilber Jennifer T. Anger A. Lenore Ackerman |
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PD51-01 |
Are the Results of the ProtecT Trial Applicable to Contemporary Prostate Cancer Patients Treated at Two High-Volume European Institutions? |
Prostate Cancer: Localized: Surgical Therapy VI | 17BOS |
Abstract: PD51-01 Sources of Funding: none Introduction The ProtecT trial reported excellent outcomes for patients with localized prostate cancer (PCa) treated with radical prostatectomy (RP). We aimed at assessing the generalizability of the ProtecT trial in men treated with RP at two high-volume institutions. Methods 20,391 PCa patients aged 50-69 years treated with RP at two centers were included. We evaluated changes in disease characteristics over the study period and we identified patients who fulfilled the ProtecT criteria (cT1-cT2 and PSA <20ng/ml). Kaplan-Meier analyses assessed time to biochemical recurrence (BCR), clinical recurrence (CR), cancer-specific mortality (CSM), and overall mortality. A graphical illustration of the 10-year CSM and other-cause mortality (OCM) rates was generated using competing-risks Poisson regression analyses after stratifying patients according to eligibility in the ProtecT trial. Results The proportion of biopsy Gleason 8-10, PSA >20 ng/ml, and high-risk disease increased over time (5.1 vs. 18.8% and 6.9 vs. 9.1% and 13.3 vs. 24.6% for 1999-2005 vs. 2014-2016; all P<0.001). Overall, 18,555 (91.0%) patients fulfilled the ProtecT criteria. The proportion of eligible individuals decreased over time (91.2 vs. 89.7% for 1999-2005 vs. 2014-2016, respectively; P=0.02). The median PSA and the proportion of biopsy Gleason 8-10 were higher among men treated at referral centers compared to what reported in ProtecT (6.5 vs. 4.9 ng/ml and 9.0 vs. 2%; P<0.001). When considering patients eligible for the ProtecT, the proportion of biopsy Gleason score 8-10 and median PSA increased over time (3.8 vs. 15.7% and 6.3 vs. 7.1ng/ml for 1996-2005 vs. 2014-2016; all P<0.001). Median follow-up was 50 months. The 10-year BCR-, CR-, and CSM-free survival rates were higher in men eligible for the ProtecT trial as compared to those not eligible (74.2 vs. 42.6% and 95.4 vs. 79.0% and 98.8 vs. 91.4%; all P<0.001) and comparable to what observed in the ProtecT. The risk of dying from OCM was substantially higher than the risk of dying from PCa among men eligible for the ProtecT (6.9 vs. 2%). Conversely, in non-eligible patients the 10-year CSM and OCM rates were 9.7 vs. 7.8%. Conclusions A migration towards higher Gleason scores and PSA levels at diagnosis occurred over recent years. More than 10% of men treated at referral centers should have been excluded from the ProtecT trial due to less favourable characteristics. These patients are more likely to die from PCa than from OCM thus being the optimal candidate for testing the role of primary treatment in randomized trials. Funding none
Authors
Giorgio Gandaglia
Emanuele Zaffuto Nicola Fossati Paolo Dell'Oglio Vito Cucchiara Raisa S. Pompe Nazareno Suardi Patrizio Rigatti Markus Graefen Francesco Montorsi Derya Tilki Alberto Briganti |
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PD51-02 |
Identifying the optimal candidate for early salvage radiation therapy after radical prostatectomy for prostate cancer: a long-term multi-institutional analysis |
Prostate Cancer: Localized: Surgical Therapy VI | 17BOS |
Abstract: PD51-02 Sources of Funding: none Introduction The effectiveness of salvage radiation therapy (SRT) may be limited to specific categories of patients. We aimed at identifying the optimal candidate for SRT. Methods The study included 693 node-negative patients who received SRT at six tertiary referral centres for either PSA rising after RP, or PSA persistence after surgery that was defined as PSA level ≥0.1 ng/ml at 1 month after RP. The study outcome consisted of distant metastasis after SRT: retroperitoneal (M1a), skeletal (M1b), and visceral metastasis (M1c). Regression tree analysis was used to develop a distant metastasis risk-stratification tool. Covariates consisted of pT stage (≤pT3a vs. ≥pT3b), pathologic Gleason (≤7 vs. ≥8), surgical margins (negative vs. positive), post-operative undetectable PSA (no vs. yes), and PSA level at SRT. Results At a median follow-up of 96 months, 82 (12%) patients developed distant metastasis. The metastasis location was retroperitoneal, skeletal, and visceral in 18 (2.6%), 33 (4.8%), and 9 (1.3%) patients, respectively. Using regression tree analysis, 5 risk groups for distant metastasis were identified: 1) very low-risk: undetectable PSA after RP, Gleason sum ≤7, and ≤pT3a; 2) low-risk: undetectable PSA after RP, Gleason sum ≤7, and ≥pT3b; 3) intermediate-risk: undetectable PSA after RP, and Gleason sum ≥8; 4) high-risk: PSA persistence after RP, and Gleason sum ≤7); 5) very high-risk: PSA persistence after RP, and Gleason sum ≥8. Frequencies and proportions of the five groups were 294 (42%), 211 (30%), 110 (16%), 58 (8%), 20 (3%), respectively. Metastasis-free survival at 8 years of the five groups was 86%, 75%, 74%, 72%, and 60%, respectively (p=0.003). The PSA level at SRT was significantly associated with the risk of distant metastasis in low-, intermediate-, and high-risk patients, where an early SRT was associated with better cancer control (all p<0.01). Conversely, this effect was not evident in the very low- and very high-risk patients, where PSA level at SRT was not significantly associated with the risk of metastasis (all p>0.05) Conclusions We developed a risk stratification tool that identified five prognostic risk groups. The early SRT administration provides better cancer control in low-, intermediate-, and high-risk patients. On the other hand, very low- (undetectable PSA after RP, Gleason score ≤7, and ≤pT3a) and very high-risk patients (PSA persistence after RP and Gleason score ≥8) do not benefit from an early treatment administration. Funding none
Authors
Nicola Fossati
R. Jeffrey Karnes Stephen Boorjian Michele Colicchia Alberto Bossi Thomas Seisen Cesare Cozzarini Claudio Fiorino Barbara Noris Chiorda Giorgio Gandaglia Thomas Wiegel Shahrokh F. Shariat Gregor Goldner Steven Joniau Antonino Battaglia Karin Haustermans Gert De Meerleer Valérie Fonteyne Piet Ost Hein Van Poppel Francesco Montorsi Alberto Briganti |
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PD51-03 |
Predicting competing mortality in patients undergoing radical prostatectomy at an age of 70 years or older |
Prostate Cancer: Localized: Surgical Therapy VI | 17BOS |
Abstract: PD51-03 Sources of Funding: none Introduction Estimating the risk of competing mortality is of importance in tailoring optimal individual management strategies in patients with early prostate cancer. Patients selected for radical prostatectomy at an age of 70 years or older, a stricter selection for good risks may influence the prognostic significance of individual risk factors for competing mortality. No generally accepted tool is available in order to predict competing mortality in in this particular population. Methods Using proportional hazard models for the subdistribution of competing risks according to Fine and Gray, we studied 2961 consecutive patients treated at our institution between 1992 and 2007 in order to determine which parameters predict competing mortality in patients selected for radical prostatectomy at an age of 70 years or older and compared the prognostic impact of individual parameters with that in their younger counterparts. The mean follow-up was 11.2 years. Results Three common diseases (diabetes mellitus, chronic lung disease and other cancer) which predicted competing mortality in younger men were no predictors of competing mortality in men selected for radical prostatectomy at an age of 70 years or older (hazard ratios, HRs, lower than 1). Beside age (HR per year 1.08, p=0.0255), peripheral vascular disease (HR 2.33, p=0.0195), cerebrovascular disease (HR 2.23, p=0.0242), American Society of Anesthesiologists (ASA) physical status class 3 (HR 2.19, p<0.0001), current smoking (HR 2.18, p=0.0098) and lower or unknown level of education (HR 2.07, p=0.0002) were independent predictors of competing mortality in patients aged 70 years or older. With adding one risk point for each of these parameters, the resulting score compared favorably with five conventional comorbidity measures (Akaike information criterion 1425 versus a range between 1452 for the unweighed Charlson score and 1460 for the modified Lee mortality index). Conclusions Conclusions: Combining these five conditions in a score might provide a superior comorbidity measure in patients undergoing radical prostatectomy at an age of 70 years or older. Funding none
Authors
Michael Froehner
Rainer Koch Matthias Hübler Stefan Zastrow Manfred P. Wirth |
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PD51-04 |
The impact of anxiety and depression on functional outcome in patients who underwent radical prostatectomy |
Prostate Cancer: Localized: Surgical Therapy VI | 17BOS |
Abstract: PD51-04 Sources of Funding: none Introduction Urinary incontinence (UI) and erectile dysfunction (ED) represent the most quality of life restricting complications after radical prostatectomy (RP). The aim of our study was to assess the impact of depression and anxiety on functional outcome in patients undergoing RP for prostate cancer (PCa). Methods A total of 3890 patients who underwent RP between 2004 and 2016 were analyzed. Patients with adjuvant radiation within three or twelve months after RP were excluded. For erectile function (EF) assessment, additional exclusion criteria consisted of androgen deprivation therapy (ADT) within three or twelve months after RP, preoperative erectile dysfunction and none or only unilateral nerve sparing. Baseline depression and anxiety were assessed using the Patient Health Questionnaire- (PHQ-) 4 and categorized into 0-2 (normal), 3-5 (mild) and ≥6 (moderate to severe) points. Urinary continence (UC) was defined as the use of zero or 1-safety pad per 24 hours. Recovery of EF was defined as a score of ≥3 points in the second question of the IIEF-5 questionnaire: &[Prime](...)how often were your erections stiff enough for penetration?&[Prime]. Multivariable logistic regression analyses adjusted for age, BMI, pathological tumor stage and nerve-sparing technique (bi- vs. unilateral vs. none; only in UC analysis) were used to assess the impact of depression and anxiety on UC and EF. Results Overall 1-week UC rates were 20.6%, 18.5% and 13.1% for PHQ-4 scores 0-2, 3-5 and ≥6. For the same groups, the rates were 75.1%, 73.7% and 69.4% for 3-months and 84.2%, 86% and 75% for 1-year UC. Multivariable regression analyses confirmed the adverse impact of a higher PHQ-4 score on 1-week and 1-year UC. Odds ratio for 1-week, 3-months and 1-year UIC were 1.86, 1.42 and 1.99 for patients with PHQ-4 scores ≥6 (p= 0.003, 0.1 and 0.02). EF rates at 3-months were 47.9 %, 43.1% and 47.4% for PHQ-4 scores 0-2, 3-5 and ≥6. For the same groups, 1-year EF recovery rates were 63.7%, 57.9% and 58.6%. No statistically significant difference was found either in uni- or in multivariable analyses. However, we observed a significantly higher use of PDE-5-inhibitors (PDE-5-I) and intracavernous injection therapies (ICI) among men with PHQ-4 score of ≥6. Conclusions A higher PHQ-4 score, representative for depression and anxiety, is significantly associated with worse 1-week and 1-year UC. We did not found a correlation between depression and anxiety and EF recovery, however men with higher PHQ-4 scores were more likely to use erectile dysfunction treatment. Therefore, further studies and higher patient samples are necessary. Funding none
Authors
Raisa Sinaida Pompe
Alexander Krueger Pierre I. Karakiewicz Philipp Mandel Philipp Gild Sami-Ramzi Leyh-Bannurah Georg Salomon Hartwig Huland Markus Graefen Derya Tilki |
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PD51-05 |
Survival associated with radical prostatectomy versus radiotherapy for high-risk prostate cancer: a contemporary, nationwide observational analysis |
Prostate Cancer: Localized: Surgical Therapy VI | 17BOS |
Abstract: PD51-05 Sources of Funding: None Introduction The optimal primary treatment for men with clinically high-risk prostate cancer (PCa) is controversial as both radical prostatectomy (RP) and radiotherapy (RT) are associated with potential advantages and disadvantages. Our objective was to compare the overall mortality-free survival of high-risk PCa patients treated with primary RP vs. primary RT with neoadjuvant/adjuvant androgen deprivation therapy [ADT], within the National Cancer Data Base (NCDB). Methods Within the NCDB, a total of 87,875 high-risk PCa patients fulfilled our pre-specified inclusion criteria (53,197 in RP group and 34,678 in RT+ADT group). We employed an instrumental variable analysis (IVA) approach using the yearly rate of RP as the instrument, to mitigate the impact of both observed and unobserved confounders. Multiple sensitivity analyses were performed, including stratification for age, comorbidity, ADT utilization and high dose (>75.6 Gy) RT. In addition, the overall mortality-free survival of RP was compared to that of RT reported in three recently published randomized controlled trails (RCTs), after selecting only RP patients who fitted inclusion/exclusion criteria of these RCTs Results On IVA adjusting for socio-demographic, facility- and tumor-specific covariates, RP was associated with lower overall mortality compared to RT+ADT (hazard ratio (HR) 0.52; 95% CI, 0.47-0.57; p<0.001) in the overall analysis, in patients with age ?65 years with CCI 0 (HR 0.48; p<0.001), in patients >65 years with CCI 0 (0.53; p<0.001), those receiving RT with neoadjuvant (HR 0.52; p<0.001) or adjuvant ADT (HR 0.47; p<0.001), or treated with high dose (?75.6 Gy) RT (HR 0.54; p<0.001). While the survival outcomes for patients treated with RT (+/-ADT) in the RCTs were not statistically different from similarly treated and appropriately selected patients within the NCDB, RP was associated with greater overall mortality-free survival than any of the arms represented in the RCTs. Conclusions Our results suggest that in patients with clinically high-risk PCa, primary RP is associated with greater overall mortality-free survival than primary RT+ADT in patients with clinically high-risk PCa, regardless of baseline characteristics. These findings, in lieu of a randomized trial, can guide the clinicians to carefully choose the primary modality of treatment for patients with high-risk PCa. Funding None
Authors
Tarun Jindal
Deeoansh Dalela Patrick Karabon Malte Vetterlein Thomas Seisen Akshay Sood Quoc-Dien Trinh Wooju Jeong Mani Menon Firas Abdollah |
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PD51-06 |
Salvage Robot Assisted Radical Prostatectomy after Primary Radiation or Ablation Treatment: What have we learned? Assessing the Learning Curve in Terms of Morbidity, Oncological and Functional Outcomes. |
Prostate Cancer: Localized: Surgical Therapy VI | 17BOS |
Abstract: PD51-06 Sources of Funding: None Introduction Among the different approaches to treat recurrent prostate cancer only 2% of the patients undergo salvage RP because, despite good cancer control, historically, salvage RP has been associated with significant morbidity and poor functional outcomes_x000D_ _x000D_ To analyze the learning curve in terms of morbidity, oncological and functional outcomes in Salvage Robotic Assisted Radical Prostatectomy (sRARP) patients in a single surgeon tertiary-referral center._x000D_ Methods In our IRB approved retrospective analysis >9000 patients underwent RARP for localized prostate cancer (PCa) by a single surgeon (V.P) between January 2008 and March 2016. Among those patients, 80 underwent sRARP due to a local recurrence after primary treatment. Within the current learning curve analysis, all of the 80 sRARP patients were then sub-divided in 4 equal groups of 20 consecutive patients based on date of surgery. Functional and oncological outcomes were measured at 12 months post-sRARP in Groups 1-3 only, as group 4 had limited follow-up. Potency was defined as the ability to achieve a successful erection with penetration over 50% of the time, while full and 0-2 continence was defined as 0 pads and ?2 pads/day, respectively. Results Preoperatively; a trend to decrease was observed through the 4 groups in terms of operative time (137 to 125 min; p=0.022), estimated blood loss (137 to 117ml; p=0.346) and catheterization time (16.95 to 12.2; p=0.182). Radiographic anastomotic leaks trended towards a decline (from 50% to 20%; p=0.126), while morbidity remained stable thorough the groups (5%; p>0.05). Biochemical failure was similar between 3 groups (30%, 31.3%, and 21.4% respectively: p=0.797) and all patients were alive at 12 months of follow up. Potency rates tended to increase from 10% in GI to 28.6% in GIII (p=0.378). Full and 0-2pads continence rates were similar among the groups (50-57.9%; p=0.859 and 60-68.4%: p=0.860 respectively). Lastly; a clinical reduction in time to continence was observed from GI to GIII (112.3 to 71.28 days; p=0.393). Conclusions The learning curve over the course of ~8 years demonstrated a decrease in operative time and suggested a trend for decreases in intraoperative blood loss, catheterization time and anastomotic leaks, while nerve sparing increased significantly through the groups. Therefore, a slightly higher potency rate and lower time to continence through the learning curve was shown. However, longer term studies are needed to confirm these results. Funding None
Authors
Xavier Bonet
Gabriel Ogaya Tracey Woodlief Eduardo Hernández-Cardona Hariharan Ganapathi Travis Rogers Rafael Coelho Bernardo Rocco Vipul Patel |
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PD51-07 |
Impact of the time interval between biopsy and robotic-assisted radical prostatectomy on biochemical recurrence: a propensity score matching analysis |
Prostate Cancer: Localized: Surgical Therapy VI | 17BOS |
Abstract: PD51-07 Sources of Funding: none Introduction The impact of the time interval (TI) between prostate biopsy and robot-assisted radical prostatectomy (RARP) on the risk of biochemical recurrence (BCR) has been controversial so far. It is possible that clinicians empirically decide on curative treatments earlier for patients who are expected to have a worse prognosis, resulting in a so-called treatment selection bias. Therefore, we performed propensity score matching analysis to investigate the potential impact of treatment delays in patients with localized prostate cancer._x000D_ Methods We retrospectively reviewed the medical records of 812 patients who were treated with RARP at our institution. A multivariate Cox analysis was used to identify the independent significant preoperative risk factors for BCR. Using these preoperative risk factors, a propensity score matching analysis was conducted to adjust for the preoperative characteristics between two patient groups: Group A, TI ≤ 6 months; Group B, TI ≥ 6 months). Clinicopathological outcomes and BCRFS between the two groups were compared to investigate the impact of TI ≥ 6 months on oncological outcomes after RARP. Results The median follow-up period after RARP was 32.2 months (6.1-104.9 months). The multivariate analysis revealed that PSA, primary (pGS) and secondary (sGS) Gleason score, and a positive prostate biopsy were independent preoperative risk factors for BCR. One hundred and two patients with Group B were matched with an equal number of patients with Group A based on propensity scores by using six preoperative factors: PSA, pGS and sGS, clinical T stage, age, and positive prostate biopsy. The propensity adjusted 5-year BCRFS for patients with TI ≥ 6 months was 85.5%. This was not worse than that of patients with TI ≤ 6 months (85.0%, p = 0.85). Similarly for D&[prime]Amico low-risk patients, the propensity adjusted 5-year BCRFS rates for Group A and Group B were 99.2% and 99.4%, respectively (p = 0.84); for intermediate-risk patients, 89.1% and 79.6%, respectively (p = 0.19); and for high-risk patients, 69.9% and 89.1%, respectively (p = 0.36). There were no significant differences with regards to Gleason upgrading (p = 0.46) or upstaging (p = 0.11) after propensity adjustments between the two groups._x000D_ Conclusions In our cohorts, a delay in the time from biopsy to RARP did not significantly affect BCR. Therefore, hasty treatment decisions are unnecessary for at least 6 months after biopsy of early prostate cancer. However, we suppose that our results may not be same for patients with very high-risk/locally advanced cancer. Funding none
Authors
Yosuke Hirasawa
Makoto Ohori Naoto Kaburagi Takashi Mima Tatsuo Gondo Kunihiko Yoshioka Jun Nakashima Yoshio Ohno |
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PD51-08 |
Assessing the 20-year outcomes of radical prostatectomy for high risk prostate cancer: results from a large, multi-institutional series |
Prostate Cancer: Localized: Surgical Therapy VI | 17BOS |
Abstract: PD51-08 Sources of Funding: none Introduction Data on the oncologic outcomes of high-risk prostate cancer (HRPCa) patients at 20 years after radical prostatectomy (RP) are lacking. The aim of our investigation was to evaluate the long-term patterns of biochemical (BCR), clinical recurrence (CR), cancer specific mortality (CSM) and other-cause mortality (OCM) in a multi-institutional database of surgically-treated HRPCa patients. Methods We evaluated 2280 patients with HRPCa treated with RP and pelvic lymph node dissection at 3 tertiary care centers between 1986 and 2015. High-risk prostate cancer was defined according to D'Amico criteria. We estimated BCR and CR rates using the Kaplan-Meier method. The CSM and OCM rates were obtained using competing risk analyses. BCR, CR, and CSM were assessed after 20 years from surgery. Cox regression analyses assessed predictors of long-term oncological outcomes. Results Median follow-up was 210 months. Median age was 66 years. The 20-year overall BCR-free survival and CR-free survival rates were 36.7% and 76.3%. Overall, 1050 experienced BCR. The latest BCR was registered at 237 months after RP. Out of 1230 patients who experienced BCR, 394 (37.5%) developed CF, while 656 (62.5%) were CF-free at last follow-up. The latest CF was registered at 244 months from RP. Overall, 394 and 172 patients experienced OCM and CSM. The competing risk 20 years CSM and OCM rates were 12.4 and 30.8%. Overall, 74 patients (3.5%) had a follow up ≥20 years. Of those, 7 (9.2%) and 1 (1.3%) experienced CSM and OCM. The 25-year competing-risks OCM and CSM-free survival rates were 77.9 and 98.5%. Age at RP (HR=0.97), pathological Gleason score 6 (HR=3.73), time to BCR (HR=1.01) and number of nodes removed (HR=1.06) were predictors of being free from overall mortality at 20-year follow up (all p≤0.04). Among patients with a follow-up ≥20 years (n=74), 39 (51.3%) experienced BCR at a median follow-up of 214 months. No patient developed BCR after 20 years from RP. Moreover, 12 (33.3%) developed CF within 20 years (median follow-up 231 months), while only 1 (1.5%) developed CF after 20 years from RP. Conclusions Among HRPCa patients, CSM may still occur even after 20 years from RP. Therefore, long monitoring and follow-up should be prolonged even after this time point. Moreover, time to BCR was a strong predictor of reaching a long follow-up after surgery and should be considered as a main criterion to further stratify patients according to their risk of CF and mortality over time. Funding none
Authors
Marco Bianchi
Michele Colicchia Giorgio Gandaglia Stefania Munegato Nicola Fossati Marco Bandini Armando Stabile Paolo Dell'Oglio Nazareno Suardi Paolo Gontero R. Jeffrey Karnes Steven Joniau Martin Spahn Francesco Montorsi Alberto Briganti |
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PD51-09 |
Conditional Probability of Biochemical recurrence-free survival and Cancer-specific mortality after radical prostatectomy at long term follow-up |
Prostate Cancer: Localized: Surgical Therapy VI | 17BOS |
Abstract: PD51-09 Sources of Funding: none Introduction To estimate the conditional probability of biochemical recurrence (BCR) free survival and cancer-specific mortality (CSM) for men with clinically localized prostate cancer (PCa) treated with radical prostatectomy (RP)._x000D_ Methods The study population consisted of 3576 consecutive patients who underwent laparoscopic radical prostatectomy (LARP) and 2619 men treated with robotic radical prostatectomy (RARP) in the last 15 years at our institution. BCR was defined as PSA≥0.2 ng/dl. PCa death was defined as patients who died with metastasis in an androgen independent setting. Kaplan Meier and Cox regression methods was used to estimate BCR and CSM conditional probabilities. _x000D_ Results Median follow-up was 8.49 years (IQR 4.01-12.97). Positive surgical margins (PSM) were identified in 1202 patients (19.4%); of these, 664 (55.24%) had organ confined disease and 523 (43.51%) had extraprostatic extension (EPE). BCR-free survival rate was significantly higher with RARP (83% vs 77% for laparoscopic surgery at 10 years; p<0.001). Patients with PSA<10 ng/dl BCR-free survival at 10 years was 80% vs 64% for PSA 10-20 ng/dl, and 59% for PSA >20ng/dl; p>0.001.Negative margins, Gleason≤6 and no extracapsular extension in the specimen were found to have higher BCR-free survival (all p< 0.001)._x000D_ Conditional probability of BCR after surgery 1st year is 6.7%. Those who reach the 2nd year without recurrence have a relapse probability of 4%, (cumulative probability 9.8%) That probability falls to 3.5% after the 3rd year (cumulative probability 13%), 2% after the 4th year (cumulative probability 15%) and is 2.1% after the 5th year (cumulative probability 17%). After 10 years of follow-up without recurrence, the subsequent probability of relapse is 0.8%, (cumulative probability 21%)._x000D_ A total of 92 (1.48%) patients died of disease. Among patients with BCR, those who recur within the first three years of follow-up had higher CSM (9% vs 4% for BCR after 3 years; p=0.04). The table shows the variables associated with CSM in multivariable analysis._x000D_ Conclusions We found a 50% decrease in BCR probability in patients who had not recurred with the first 3 years. Similar drop was identified for CSM. This is not only useful for patients counseling but also to optimize postoperative follow-up strategies._x000D_ Funding none
Authors
Silvia Garcia-Barreras
Rafael Sanchez-Salas Igor Nunes-Silva Fernando Secin Victor Srougi Mohammed Baghdadi Eric Barret François Rozet Marc Galiano Xavier Cathelineau |
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PD51-10 |
Survival after Radical Prostatectomy in Patients with PSA Persistence: the Impact of Competing Causes of Mortality |
Prostate Cancer: Localized: Surgical Therapy VI | 17BOS |
Abstract: PD51-10 Sources of Funding: none Introduction We aimed to assess the risk of cancer-specific mortality (CSM) in patients with PSA persistence after radical prostatectomy (RP) after accounting for other-cause mortality (OCM). We hypothesized that a non-negligible proportion of patients is at risk of dying from other causes and would not benefit from additional cancer therapies. Methods We included 829 patients with localized PCa undergoing RP at two referral centers between 1994 and 2014. All patients had PSA persistence after RP defined as a PSA ≥0.1 ng/ml at 8 weeks after surgery. A graphical illustration of the 10-year CSM and OCM rates was generated using competing-risks Poisson regression analyses. Patients were stratified according to age (<65 vs. ≥65 years) and according to their probability of dying from PCa at 10-years (stratified as <10% vs. 10-30% vs. >30%), which was developed from a Cox regression model based on pathologic characteristics and first PSA after surgery. For each strata, survival estimates were calculated. Competing-risks regression models were used to test the effect of age and disease characteristics on CSM after accounting for OCM Results Overall, 223 (26.9%), 331 (39.9%), and 275 (33.2%) patients had pathologic Gleason score ≤6, 7, and ≥8, and 400 (48.3%), 215 (25.9%), 214 (25.8%), and 172 (20.7%) patients had pT2, pT3a, pT3b/4, and pN1 disease. The median first PSA after surgery was 0.33 ng/ml. Median follow-up was 107 months, during which time 90 and 136 patients died from PCa and from OCM. The 10-year CSM and OCM rates were 12.6% and 11.9%. When considering men with a risk of dying from PCa <10%, the 10-year rate of OCM was higher as compared to the CSM rate (8 vs. 1.6%), regardless of age. The proportion of patients who died from OCM at 10-year was 4.2% in men <65 years with a probability of dying from PCa >30% vs. 18.2% in patients ≥65 years with a probability of CSM between 10 and 30%. In men with a calculated risk of dying from PCa >30% the 10-year CSM rates were 43.7 vs. 34.1% for those aged <65 vs. ≥65 years old. At multivariable regression analyses, the number of positive nodes, first PSA after surgery, and pathologic Gleason score 8-10 (all p<0.001) were associated with the risk of CSM after accounting for the risk of dying from other causes. Conclusions Up to 20% of men with PSA persistence after RP will ultimately die from other causes. Conversely, patients with Gleason score 8-10, higher PSA after surgery, and a higher number of positive nodes are at increased risk of CSM. These patients might benefit from additional cancer therapies, while men less likely to die from PCa may be spared such treatments. Funding none
Authors
Giorgio Gandaglia
William Parker Nicola Fossati Paolo Dell'Oglio Armando Stabile Carlo Andrea Bravi Luigi Nocera Francesco Pellegrino Emanuele Zaffuto Nazareno Suardi Francesco Montorsi R. Jeffrey Karnes Stephen Boorjian Alberto Briganti |
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PD51-11 |
Pathological findings at radical prostatectomy after initial active surveillance in low-risk prostate cancer patients. Did we miss the chance to cure? |
Prostate Cancer: Localized: Surgical Therapy VI | 17BOS |
Abstract: PD51-11 Sources of Funding: none Introduction No previous study calculated tumor volume (TV) at pathology in patients enrolled in active surveillance (AS) programs who are eventually treated with radical prostatectomy (RP). We assessed pathological characteristics in these patients as compared to those found in patients eligible for AS but chosen to undergo immediate RP Methods Between 2009 and 2016, 235 consecutive patients were enrolled into our AS program for low-risk PCa according to the PRIAS criteria. During AS, 88 (37.4%) patients were switched to active treatment because of rising PSA, pathological upgrading (Gleason>6 or >2 positive cores) or patient preference. Of these, 48 patients (55%) were submitted to RP at our center. We examined the pathological characteristics of RP in these patients. TV was calculated as prostate weight x percentage of cancer at whole mount pathology. Finally, we compared these figures with those found in the pathological examination of 274 consecutive patients who could have been considered eligible for AS at the time of diagnosis that were instead submitted to immediate RP Results Median time from AS entry to RP (n=48) was 14 months (IQR: 11-25.5). Median TV in patients treated with RP after AS was 3.4 ml vs. 2.07 ml in immediate RP patients (p=0.002). In patients who progressed during AS and then received RP (n=48), 38 (79.2%), 11 (22.9%), 2 (4.2%), and 3 (6.3%) had Gleason score >6, extracapsular extension (ECE), seminal vesicles invasion (SVI) and nodal invasion (LNI), respectively. In patients submitted to immediate RP, 85 (30.9%), 13 (4.7%), 1 (0.4%) and 0 (0%) had Gleason score >6, ECE, SVI and LNI, respectively. Patients initially managed with AS had higher rates of Gleason >6 (7.7% vs. 35.4%), ECE (22.9 vs. 4.7%), SVI (4.2 vs. 0.4%), LNI (6.3 vs. 0%) and higher (all p<0.001). However, when the rates of adverse pathology of patients who progressed during AS (n=48) were recalculated on the total number of patients who entered the AS program (n=235), these figures were virtually identical to those of patients submitted to immediate RP (all p: n.s.), suggesting that time on AS did not worsen pathological outcomes. Conclusions Patients initially managed with AS seem to show higher rates of adverse pathology compared to similar patients treated with immediate RP. However, when applied to the overall population of AS patients, the rate of upstaging and upgrading at diagnosis remained stable during AS. The findings of adverse pathology at RP seem to be more related to initial misclassification instead of real clinical progression Funding none
Authors
Nazareno Suardi
Stefano Luzzago Paolo Dell'Oglio Nicola Fossati Giorgio Gandaglia Emanuele Zaffuto Franco Gaboardi Claudio Doglioni Massimo Freschi Vincenzo Scattoni Umberto Capitanio Armando Stabile Francesco Montorsi Alberto Briganti |
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PD51-12 |
Oncological and functional outcomes after RP for high or very high-risk prostate cancer – European validation of the current NCCN guideline |
Prostate Cancer: Localized: Surgical Therapy VI | 17BOS |
Abstract: PD51-12 Sources of Funding: none Introduction To validate the current NCCN-classification of very high-risk (VHR) patients and compare the pathological, functional and oncological outcomes between surgically treated high- (HR) and VHR patients. Methods We retrospectively analyzed 4041 patients stratified into HR or VHR who underwent RP between 1992 and 2016. Multivariable logistic regression and Kaplan-Meier survival analyses compared outcomes between the two groups. Results After RP, the rate of adverse pathological features was higher in 1369 VHR vs. 2672 HR patients. Functional outcomes were similar between both groups, with 1-year continence (UC) and potency rates of 83.5% and 59.5% in the VHR compared to 82.7% and 42% in the HR group (p = 0.8 and p = 0.1). Accordingly, no difference was found in multivariate logistic regression predicting UC at three and twelve months after RP. In a subset of 1835 patients who underwent RP between 1992-2011 (median follow-up 58.8 months), VHR patients had significantly worse five- and eight-year biochemical recurrence-free survival (BFS), metastatic progression- free survival (MP-FS), prostate cancer-specific mortality-free survival (PCSM-FS) and overall survival (OS) rates. Eight-year BFS and MP-FS rates were 25.4% and 71.5% for VHR vs. 43.1% and 86.1% for HR patients. For the same time point, PCSM-FS and OS rates were 87% and 76.1% for VHR vs. 93.2% and 83.7% for HR patients, respectively (all p < 0.001). Conclusions Despite the relatively poor prognosis of HR PCa patients, RP provides favorable five- and eight-year MP, PCSM and OM-free survival rates. Relative to HR patients, their VHR counterparts harbor significantly worse pathological and oncological outcomes and more frequently require additional therapies. These observations validate the stratification between HR and VHR in European PCa patients. Interestingly, functional outcomes are similar between the two groups. Funding none
Authors
Raisa Sinaida Pompe
Philipp Gild Felix K. Chun Zhe Tian Jonas Schiffmann Georg Salomon Hartwig Huland Markus Graefen Pierre I. Karakiewicz Derya Tilki |
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PD52-01 |
Differential Gene Expression in Patients with Indolent versus Aggressive Chromophobe Renal Cell Carcinoma: An Analysis of The Cancer Genome Atlas Database |
Kidney Cancer: Epidemiology & Evaluation/Staging III | 17BOS |
Abstract: PD52-01 Sources of Funding: None Introduction Chromophobe subtype of renal cell carcinoma (chRCC) makes up approximately 5% of all RCC. It has a better prognosis compared to clear cell and papillary subtypes and shares similar traits to oncocytoma. However, a minority of these tumors behave aggressively. We sought to evaluate genomic differences between patients with indolent and aggressive chRCC. Methods We analyzed The Cancer Genome Atlas (TCGA) database and found 63 chRCC patients. RNA expression analysis compared deceased (n=9, 14.2%) and alive patients (n=54, 85.8%). Supervised whole genome differential expression analysis of RNA-Seq data for 20,536 genes was conducted using the SAMSeq package in R. Functional annotation analysis to evaluate biological significance of differentially expressed genes (FDR<0.05; Fold Change >2) was conducted in DAVID 6.8. Results Compared to patients who were alive, we identified 200 significantly overexpressed genes in the deceased group (FDR<0.05). 139 (75.1%) genes were involved in protein phosphorylation, 116 (62.7%) in alternative splicing, 108 (54.8%) in protein binding, and 103 genes (55.7%) were identified as nucleus proteins. _x000D_ _x000D_ The majority (56%) of genes were related to cell replication & cell cycle, followed by DNA repair (9%), intracellular metabolism (7.5%), transcription\translation (4.5%), signaling mechanisms (4%), transport proteins (2.5%) and others (6.5%). _x000D_ _x000D_ Interestingly, 5 genes associated with breast cancer were overexpressed in the deceased group (FDR<0.05). These genes included KIF15, BRCA2, RAD51, BRIP1 and HMMR. HMMR and BRIP1 proteins interact with BRCA1 in breast carcinogenesis. BRCA1 was overexpressed, but not significant (FDR=0.126). Furthermore, Cyclin A2, Cyclin B1, Cyclin B2, Cyclin E2 and Cdk1 (cyclin-dependent kinase) were overexpressed (FDR <0.05). Cyclin A1, B1 and B2 are known mitotic regulators. Cyclin A2 regulates mitosis by activating Cyclin B1/Cdk1 complex. _x000D_ Conclusions We identified several known genes that are differentially overexpressed in patients who died from chRCC. These expression profiles will need validation, but may be used as biomarkers to identify aggressive variants of chRCC. Funding None
Authors
Alp Tuna Beksac
David Paulucci John Sfakianos Ketan Badani |
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PD52-02 |
Renal cell carcinoma associated with Xp11.2 translocation/TFE3 gene fusions: differential diagnosis with clear cell renal cell carcinoma on contrast-enhanced ultrasound |
Kidney Cancer: Epidemiology & Evaluation/Staging III | 17BOS |
Abstract: PD52-02 Sources of Funding: none Introduction To evaluate the significance of contrast-enhanced ultrasound(CEUS) in diagnosis and differential diagnosis of renal cell carcinoma associated with Xp11.2 translocation/TFE3 gene fusions (Xp11.2 RCC) and clear cell renal cell carcinoma (CCRCC). Methods We retrospectively analyzed the conventional ultrasound (CUS) and CEUS data of 15 cases proved to be Xp11.2 RCC and 72 cases proved to be CCRCC by pathology after surgery. Results Xp11.2 RCC more frequently affected young (32.3± 12.6 years) women (9/15, 60%) with gross hematuria (7/15, 46.7%), while CCRCC more frequently involved middle-aged (51.0 ± 14.1 years) men (47/72, 65.3%). In CUS, both Xp11.2 RCC and CCRCC tended to be quasiccircular and hypo-echoic. Lesion sizes between Xp11.2 RCC (4.6±1.6 cm) and CCRCC (5.0±1.8 cm) were unsignificant difference. In CEUS, the arrival time (AT) and time to peak intensity (TTP) of most Xp11.2 RCCs (12/15, 80%) were slower than adjacent renal cortex, while AT and TTP of most CCRCCs (52/72 80.6%) were faster than adjacent renal cortex.The difference of peak intensity (PI) between Xp11.2 RCC(hypo-enhancement 9/15, 60%) and CCRCC (hyper-enhancement 53/72, 73.6%) were significant. Contrast agent in most CCRCCs (48/72, 66.7%) was rapid-fading, but all of Xp11.2 RCCs were rapid-fading, there was significant difference between them. Conclusions CEUS provide a new and effective method in diagnosis of Xp11.2 RCC. CEUS are useful in differential diagnosis of Xp11.2 RCC with CCRCC. Funding none
Authors
Zhang Fan
Wang Wei Gan Weidong Guo Hongqian |
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PD52-03 |
Patients With RCC And Pathologic Nodal Disease Should Be Reclassified As Stage IV |
Kidney Cancer: Epidemiology & Evaluation/Staging III | 17BOS |
Abstract: PD52-03 Sources of Funding: none Introduction Patients with locally advanced (pT3) renal cell carcinoma (RCC) and pathologic nodal disease may have worse survival than those without nodal disease, although they are currently all considered stage III. Our aim was to compare the survival of stage III RCC patients with pathologic nodal disease (pT123N1M0) to stage III patients without nodal disease (pT3N0M0), and stage IV patients. Methods We retrospectively studied a cohort of patients who underwent retroperitoneal lymph node dissection at the time of nephrectomy from 1993 to 2012. Stage III with (pT123N1M0) and without (pT3abcN0M0) pathologic nodal disease was noted in 115 (7.7%) and 275 (18.4%) patients. In order to compare outcomes of stage III patients to those with stage IV disease, we included 523 pT123N0M1 and 222 pTanyN1M1 patients. Cancer-specific survival (CSS) was estimated using the Kaplan-Meier Method. Univariate and multivariate Cox proportional hazards regression models were fit to identify factors significantly associated with clinical outcomes. Results Clear cell RCC was present in 86.9% and 60.0%, and high grade tumor (grade 4) was present in 26.5% and 50.4% of pT3N0 and pT123N1, respectively. Median tumor size was 9 cm and 10 cm in pT3N0 and pT123N1 patients, and median number of lymph nodes removed was 6 (range1-45) and 8 (range1-37), respectively. Cancer-specific survival was better in patients with pT3abcN0M0 than those with pT123N1M0 (5-year CSS rate: 74.8% vs 38.6%, p<0.001); however, similar 5-year CSS rates were noted in pN1M0 and pN0M1 (38.6% vs 29.8%, p=0.13), while pTanyN1M1 had the worst 5-year CSS (7%). On multivariate Cox regression analysis, high-grade tumor (HR 2.96, 95% CI 2.11-4.14, p<0.0001), and pathologic lymph node involvement (HR 2.83, 95% CI 2.03-3.95, p<0.0001) were significantly associated with cancer-specific survival. Conclusions Patients with pN1M0 disease have significantly worse survival than those with pT3N0M0 disease, although both groups are currently classified as stage III. In addition, patients with pN1M0 have survival similar to those with pN0M1 disease (stage IV), suggesting that pN1M0 patients should be reclassified as stage IV. Funding none
Authors
Kai-Jie Yu
Sarp K. Keskin Firas G. Petros Xuemei Wang Leonardo D. Borregales Yara Aboshady Cindy Gu Surena F. Matin Christopher G. Wood Jose A. Karam |
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PD52-04 |
Surgical Histopathology for Suspected Oncocytoma on Renal Mass Biopsy: Retrospective Institutional Cohort with Systematic Review and Meta-Analysis |
Kidney Cancer: Epidemiology & Evaluation/Staging III | 17BOS |
Abstract: PD52-04 Sources of Funding: None Introduction The proportion of oncocytic renal neoplasms diagnosed on renal mass biopsy (RMB) with discordant surgical pathology is unknown. We aimed to estimate the proportion confirmed as oncocytoma after surgery, the discordant pathologic findings, and indications leading to intervention. Methods A retrospective institutional cohort (2006-2015) identified patients with localized renal masses diagnosed with an oncocytic renal neoplasm on RMB suggestive of an oncocytoma. Concordance of surgical histopathology was evaluated for patients undergoing surgery. Additionally, a systematic review and meta-analysis of the literature (1997-July 1, 2016) was conducted to quantify all cases in the reported literature. Indications for intervention, when available, were assessed. Results A total of 31 (13.2%) of 234 core RMBs suggested oncocytoma, with 6 masses in 5 patients proceeding to surgery with none (0%) identified as oncocytoma, 3 (50%) diagnosed as renal cell carcinoma (RCC), and 3 (50%) diagnosed as other benign or indolent tumors. Nine additional studies were included in the meta-analysis for a total of 205 RMBs identifying oncocytic renal neoplasms with 46 (22.4%) proceeding to surgery. One additional study identified 2 neoplasms not captured by the primary RMB series for a total of 48 unique lesions included in the analysis. Surgical pathology showed oncocytoma (64.6%), chromophobe RCC (12.5%), other RCC (12.5%), hybrid oncocytic/chromphobe tumor (6.3%), and other benign lesions (4.2%). Positive predictive value of oncocytoma on RMB was 67% (95% confidence interval 34% to 94%) with significant heterogeneity between studies (I2=71.8%, p<0.01). Risk of bias was judged to be low for 4 of the 10 series. Conclusions Confidently diagnosing a localized renal mass as a benign lesion, such as an oncocytoma, has implications for the ultimate management strategy a patient will undergo. RMB was found to be unreliable in confidently diagnosing a localized renal mass as an oncocytoma with 1 in 4 found to be RCC on surgical pathology. Patients and physicians should be aware of the uncertainty in diagnosis when considering management strategies. Funding None
Authors
Hiten Patel
Sasha Druskin Steven Rowe Phillip Pierorazio Michael Gorin Mohamad Allaf |
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PD52-05 |
When to Perform Preoperative Bone Scintigraphy for Kidney Cancer Staging |
Kidney Cancer: Epidemiology & Evaluation/Staging III | 17BOS |
Abstract: PD52-05 Sources of Funding: None Introduction In absence of objective criteria for staging bone scintigraphy [BS], the decision to perform preoperative BS for patients diagnosed with renal cell carcinoma [RCC] remains a subjective practice. We aimed at identifying an objective and reproducible strategy for preoperative bone staging in RCC patients. Methods We evaluated 2,008 RCC patients treated with surgery and prospectively included into an institutional database. The study outcome was the presence of one or more lesions suspicious for bone metastases at staging BS. In case of uncertain result, BS was considered negative in case of no-evidence of progression during follow-up or positive in all other cases. Patients without a pre-operative BS but with a negative post-operative BS were considered negative by definition. A multivariable logistic regression model was fitted to predict positive BS. Predictors consisted of preoperative platelet/haemoglobin [PLT/HB] ratio, clinical tumour stage [cT], clinical nodal stage [cN] and presence of systemic symptoms. A 2000-sample bootstrap validation was used to estimate H-index. Decision curve analysis [DCA] was used to compare the performance of the proposed model with the prediction based on symptoms only, as recommended by guidelines. Results BS resulted negative in 1927 (96%) patients and positive in 81 patients (4%). Preoperative PLT/HB ratio was associated with higher risk of positive BS (Odds Ratio [OR] 1.04; p<0.001). Similarly, cT (cT2 vs cT1a; OR 2.13; p=0.02), cN (cN1 vs cN0; OR 2.5; p=0.001) and presence of systemic symptoms (OR 4.26; p<0.001) were all associated with higher risk of positive BS. Following a 2000-sample bootstrap validation, H-index of the proposed model was 0.76 whereas the H-index of the prediction based on systemic symptoms only resulted 0.63. At DCA, the net benefit of the proposed model was superior than the net benefit of the prediction based on symptoms only. Conclusions Based on the proposed model, it is possible to accurately estimate the risk of positive BS at kidney cancer staging using pre-operative characteristics. If BS is performed only when the risk of positive result is >5%, a negative BS is spared in 80% of the population and a positive BS is missed in 2% of the population only. When compared to decision-making based on symptoms only, which represents the strategy recommended by available guidelines, the proposed model resulted more objective, statistically more accurate and clinically associated with higher net benefit. These figures support an update of the available guidelines. Funding None
Authors
Fabio Muttin
Alessandro Larcher Nicola Fossati Paolo Dell’Oglio Alessandro Nini Armando Stabile Francesco Ripa Francesco Trevisani Cristina Carenzi Alberto Briganti Andrea Salonia Alexandre Mottrie Roberto Bertini Francesco Montorsi Umberto Capitanio |
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PD52-06 |
Capturing Renal Cell Carcinoma Recurrences When Asymptomatic Improves Patient Survival |
Kidney Cancer: Epidemiology & Evaluation/Staging III | 17BOS |
Abstract: PD52-06 Sources of Funding: None Introduction Oncologic surveillance is an integral part of renal cell carcinoma (RCC) care. Whether this practice affords a survival benefit remains unclear. Our objective was to determine whether detection of RCC recurrences in an asymptomatic vs. symptomatic manner influenced all cause mortality following kidney cancer surgery. Methods We identified 737 patients who underwent partial or radical nephrectomy for non-metastatic RCC at our institution between 1998 and 2016. Overall survival in patients with recurrence stratified by the type of detection (asymptomatic vs symptomatic) was estimated using Kaplan-Meier probabilities and compared with the log rank test. Cox proportional hazard regression models were used to evaluate the impact of the type of recurrence detection on survival. Results A total of 78 patients (10.6%) experienced recurrence after surgery at a median interval of 17 months (range, 0 - 172). Median postoperative follow-up for all recurrences was 47 months (range, 3 - 230). Recurrences were detected in 63 (80.8%) patients using routine surveillance (asymptomatic) and in 15 (19.2%) patients due to symptoms. There were no significant differences in clinicopathological features of the primary tumors between the two types of detection. Five and 10-year overall survival among patients with asymptomatic vs. symptomatic recurrences was 56% and 37% vs. 24% and 8%, respectively (p = 0.0003) (Figure). On multivariable analysis, patients in whom recurrences were detected from symptoms showed a 3-fold increased risk of death as compared to those in whom recurrences were detected asymptomatically via routine surveillance (HR 3.15, 95% CI 1.33, 7.46; p = 0.009). Conclusions Capturing RCC recurrences in an asymptomatic manner during routine surveillance is associated with improved patient survival. Further investigation to optimize a surveillance protocol which balances the benefit of early detection with the cost of follow-up is needed. Funding None
Authors
Suzanne Merrill
Ashiya Hamirani Matthew Kaag Erik Lehman Kathleen Lehman Jay Raman |
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PD52-07 |
Medication Use and Kidney Cancer Risk: A Population-Based Study |
Kidney Cancer: Epidemiology & Evaluation/Staging III | 17BOS |
Abstract: PD52-07 Sources of Funding: This research was supported in part by the CUA-Pfizer Urology Resident Research Grant and the Canadian Drug Safety and Effectiveness Network. Introduction Exposure to commonly-prescribed medications may be associated with cancer risk. However, there is limited data in kidney cancer. Furthermore, methods of classifying cumulative medication exposure in previous studies may be prone to bias. Methods We conducted a population-based case-control study utilizing health care databases in Ontario, Canada. Individuals enrolled as cases were aged ≥66 with an incident diagnosis of kidney cancer. For each individual enrolled as a case, we identified up to four individuals without kidney cancer as controls matched on age, sex, history of hypertension, comorbidity score, and geographic location. Cumulative exposure to commonly prescribed medications hypothesized to modulate cancer risk were obtained using prescription claims data. We modelled exposure in four different fashions: 1) as continuous exposures using a) fractional polynomials (which allow for non-linear relationship between a continuous exposure and outcome) or b) a linear relationship; and 2) as dichotomous exposures denoting a) 3 years or greater vs. less than 3 years of cumulative exposure; or b) &[prime]ever&[prime] vs. &[prime]never&[prime] exposure. We used conditional logistic regression to estimate the association of medication exposure on incident kidney cancer. Results We identified 10,377 incident cases of kidney cancer and 35,939 matched controls. When utilizing fractional polynomials, increasing cumulative exposure to aspirin, selective serotonin reuptake inhibitors, and proton-pump inhibitors were associated with significantly reduced risk of developing kidney cancer, while increasing exposure to anti-hypertensive drugs was associated with significantly increased risk (Table 1). The directions of association were relatively consistent across analyses; however, the magnitudes were sensitive to the method of analysis (Table 2). Conclusions Our study provides impetus to further explore the effect of commonly-prescribed medications on carcinogenesis to identify modifiable pharmacological interventions to reduce the risk of kidney cancer. Funding This research was supported in part by the CUA-Pfizer Urology Resident Research Grant and the Canadian Drug Safety and Effectiveness Network.
Authors
Madhur Nayan
David Juurlink Peter Austin Erin Macdonald Antonio Finelli Girish Kulkarni Robert Hamilton |
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PD52-08 |
Can looks deceive? Not all clinically "cystic" renal masses harbor indolent biology |
Kidney Cancer: Epidemiology & Evaluation/Staging III | 17BOS |
Abstract: PD52-08 Sources of Funding: None Introduction Cystic renal cell carcinomas (RCC) are suggested to be clinically indolent. As such, a distinct pathologic staging category for these lesions was recently proposed. While not without merit, these recommendations fail to account for limitations in the ability of modern imaging to differentiate cystic RCC from more biologically aggressive mimics. We evaluated the frequency of high grade kidney cancer in the highly selected cohort of surgically resected renal masses having cystic appearance on pre-operative radiographic imaging. Methods A prospectively maintained institutional database was queried for clinically cystic renal masses that underwent surgery from January 2000 - June 2016 (n=2,729 kidney surgeries). Patient and tumor characteristics including age at surgery, smoking history, Charlson comorbidity index (CCI), gender, race, BMI, surgery date, laterality, Bosniak classification, histology, grade, size, and nearness to the collecting system were tabulated. Associations between tumor grade and patient/tumor characteristics were evaluated using generalized estimating equations. Results Eighty-nine patients (n=101 cystic lesions) met strict inclusion criteria; the majority (77%) were older than 50 years of age and the mean Charlson comorbidity index was 1.15 (SD1.48) (Table 1). Of the 101 clinically cystic renal masses, 23% were confirmed pathologically as high grade RCC while 77% were low grade RCC (n=56) or benign (n=22). CCI was associated with high grade surgical pathology (OR 1.37, 95% CI 1.05-1.79, p = 0.02). There was no association between tumor grade and the remainder of the patient/tumor characteristics analyzed. Conclusions Recently proposed changes to the kidney cancer staging system define a tumor's cystic nature based on pathologic examination. Proceeding with surgery for a radiographically "cystic" renal mass was a rare event in our cohort; however, among those that went onto surgery, nearly a quarter harbored high grade pathology. Before making changes to the clinical RCC staging system, a better understanding of the limitations inherent to radiographic determination of low malignant potential, cystic renal masses is necessary. Funding None
Authors
Benjamin Ristau
Lyudmila DeMora Eric Ross Randall Lee Michael Haifler Shreyas Joshi Andres Correa David Chen Richard Greenberg Rosalia Viterbo Marc Smaldone Robert Uzzo Alexander Kutikov |
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PD52-09 |
Thromboembolic Events During Treatment for Renal Cell Carcinoma: Must We Prevent? |
Kidney Cancer: Epidemiology & Evaluation/Staging III | 17BOS |
Abstract: PD52-09 Sources of Funding: None Introduction Renal mass detection has been on a steady incline over the past decade and subsequently, surgery for solid renal masses has also increased. 900,000 Americans are diagnosed with a VTE each year with the average cost being $56,000 to treat each incident. VTE is the number two cause of death behind the primary malignancy itself. As quality indicators and outcomes are more frequently being linked with reimbursement, venous thromboembolism (VTE) prevention has gained increased attention. Increasing the number of surgeries will also increase the incidence of VTE. The purpose of this study is to identify the incidence of VTE among renal cell carcinoma patients that have undergone definitive surgical therapy and to see if pharmacological prophylaxis following surgery is warranted. Methods Over a fourteen year period (2000-2014), all patients who had surgery for renal cell carcinoma were examined. A total of 900 patients had either open, laparoscopic or robotic surgery. This included partial, radical and cytoreductive nephrectomies. All VTE incidents that had occurred up until 2015 were documented. Patient demographics and comorbidities were analyzed for risk factors for VTE. All VTE incidents were documented in adjunct with known risk factors for each patient. Results Of the 900 patients that were evaluated, 10 were documented to have VTE, making the incidence 1.1%. 40% of these patients had a prior history of VTE. 20% of the patients with a VTE had metastatic disease at time of surgery. 90% of patients were obese with a mean BMI of 32.3. 50% of patients with postoperative VTE had tobacco use. 100% of patients with documented VTE had at least 1 risk factor for VTE while 80% of patients had greater than 2 risk factors. Conclusions VTE incident following renal cell carcinoma surgery was found to be 1.1%. All patients had at least one risk factor in addition to surgery. The rate of significant postoperative bleeding following surgical therapy for renal cell carcinoma requiring transfusion is noted to be 3-6%. Risks of postoperative bleeding and other complications outweigh the benefit pharmacological VTE may have with such a low incidence of VTE. Early ambulation and mechanical VTE prophylaxis are warranted following surgery. Although VTE was a rare event, those with multiple risk factors may warrant special consideration and more aggressive VTE prophylaxis following surgery. Funding None
Authors
Jamie Olsen
Steven Jubelirer Samuel Umstot Samuel Deem |
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PD52-10 |
Shorter telomere length increases age-related tumor risks in Chinese von Hipple-Lindau disease |
Kidney Cancer: Epidemiology & Evaluation/Staging III | 17BOS |
Abstract: PD52-10 Sources of Funding: Supported by National Natural Science Foundation of China(Grand number 81572506) Introduction Von Hipple-Lindau(VHL) disease is a rare autosomal dominant familial cancer syndrome with age relatived cancer onset in patients' life. The five common tumors are central nervous system (CNS) hemangioblastoma, renal cell carcinoma(RCC) ,retinal angioma(RA), pancreatic cyst and tumor(PCT), and pheochromocytoma(Pheo). Until now, no reliable markers are found to predict the age-related tumor risks in VHL patiens. The present study has evaluated the influence of peripheral leukocyte telomere length on age-related tumor risks in a large group of VHL patients. Methods Genomic DNA was extracted from peripheral blood of 187 VHL patients. Tumor onset age was defined as the age when any symptom or imaging sign of the tumor first occurred. Age-related risks of the five tumors were evaluated using Kaplan-Meier plot and Cox regression model. Relative telomere length(RTL) was measured with qRT-PCR method. Results The main death-causing tumor CNS hemangioblastoma occurred in 53.5%(100/187) VHL patients in our study, and the mean onset age was 30.2±11.3 years old. In the shorter RTL group(RTL<0.44), the first tumor onset age was 7.7 years earlier than the longer one(25.2±8.6y vs 32.9±12.3y, p<0.001). The shorter RTL group displayed a statistically higher age-related risks than the longer RTL group for CNS(HR1.99, p=0.001), RCC(2.02, p=0.0030), PCT(2.11, p<0.001) and Pheo(3.13, p=0.005). Conclusions We for the first time propose that peripheral leukocyte telomere length may be associated with risks of VHL-related tumors, which may be helpful for establishing personalized surveillance plan for VHL patients and for further understanding the pathogenesis of VHL disease. Funding Supported by National Natural Science Foundation of China(Grand number 81572506)
Authors
Jiangyi Wang
Shuanghe Peng Xianghui Ning Teng Li Jiayuan Liu Shengjie Liu Kan Gong |
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PD52-11 |
A Molecular Scoring Algorithm to Predict Survival in Metastatic Renal Cell Carcinoma |
Kidney Cancer: Epidemiology & Evaluation/Staging III | 17BOS |
Abstract: PD52-11 Sources of Funding: R21CA176422, R01CA134466 Introduction Multiple prognostic algorithms exist for patients with renal cell carcinoma (RCC). Models for localized disease, especially those that incorporate pathologic features, are highly accurate, while models for metastatic disease have inferior predictive ability. Thus, we investigated the gene expression profile in metastatic RCC to improve prognostication and provide a rationale for future biologic studies. Methods A custom Nanostring panel was used to evaluate 124 candidate genes on specimens from 111 patients with resected primary and matched metastatic clear cell RCC between 1990 and 2005., No patient received systemic therapy prior to metastasectomy. After initial candidate genes were identified, a multivariable gene expression model was built using the lasso method and a scoring algorithm to predict likelihood of death was developed using the coefficients. Multivariable Cox regression used to determine if the scoring algorithm was predictive after adjusting for our previously published algorithm for metastatic RCC. Results Nanostring assay was successful in 91 of 111 primary clear cell RCC tumor specimens. Median follow-up for survivors was 108.0 months, during which 79 patients died from RCC. In primary tumors, 18 of 124 genes interrogated were univariately associated with RCC-specific survival (false discovery rate <0.10) and five genes were retained in the multivariable model. After adjusting for clinical and pathological indices previously shown to be predictive of survival in metastatic clear cell RCC, the five gene scoring algorithm remained highly significant (p<0.0001). When expression levels were determined in metastatic tissue, rather than the primary tumor tissue, the five gene scoring algorithm remained significantly associated with survival. Conclusions We have identified a panel of genes that predict prognosis in patients with metastatic clear cell RCC and provides significant risk stratification after adjusting for existing models. These genes may provide insight into the biology of metastatic RCC and warrant further investigation. Funding R21CA176422, R01CA134466
Authors
Bradley Leibovich
Daniel Serie Thai Ho John Cheville Richard Joseph Mansi Parasramka R. Houston Thompson Alexander Parker Jeanette Eckel-Passow |
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PD52-12 |
A novel pre-operative model to predict 90-day surgical mortality in patients being considered for extirpative surgery for renal cell carcinoma |
Kidney Cancer: Epidemiology & Evaluation/Staging III | 17BOS |
Abstract: PD52-12 Sources of Funding: None Introduction Older patients are more likely to be diagnosed with renal cell carcinoma and to have a lower overall survival based on age and associated co-morbidities. Decisions regarding the pursuit of surgical therapy are impacted by competing risks for perioperative mortality. We utilized the National Cancer Database (NCDB) to evaluate 90-day mortality and developed a nomogram predicting short-term mortality after renal cell carcinoma surgery. Methods The NCDB for kidney cancer was queried to identify all patients with clinically localized, non-metastatic disease who were treated with partial or radical nephrectomy. Those patients with incomplete data were excluded. Logistic regression was performed on a random sample of 60% of the dataset to identify preoperative variables associated with 90-day mortality. Variables included age, sex, race, comorbidity score, tumor diameter, and presence of tumor thrombus. A nomogram was built from the logistic regression model and tested on the remaining 40% of the patients in the dataset for the ability to predict 90-day mortality. Results 183,407 patients were identified that met inclusion criteria (median age 61.1). Overall 90-day mortality for the cohort was 1.9%. Odds ratios for 90-day mortality using preoperative variables are shown in Table 1. The nomogram ranged from 0-14 (Table 1). Median (IQR) nomogram score was 2 (1-4). Twelve percent of patients had nomogram score of 6 or higher. Compared to patients with 0-1 points, those with 2-3 (OR 2.69, 2.26-3.20; p < 0.001), 4-5 (OR 5.98, 5.06-7.06; p < 0.001), and 6+ (OR 12.34, 10.46-14.55; p < 0.001) were at incrementally significantly higher odds of 90-day mortality (Figure 1). Being greater than 80 years of age placed patients into the highest category of mortality. Conclusions Management of localized kidney cancer must consider competing causes of mortality, especially in elderly patients with multiple co-morbidities. We present a preoperative tool to calculate risk of surgical short-term mortality to aid in surgeon-patient counseling. Funding None
Authors
Adam Calaway
Maria Francesca Monn Clint Bahler Clint Cary Ronald Boris |
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PD53-01 |
Non-guideline concordant treatment of testicular cancer |
Sexual Function/Dysfunction: Penis/Testis/Urethra: Benign Disease & Malignant Disease II | 17BOS |
Abstract: PD53-01 Sources of Funding: none Introduction The management of testicular cancer requires a complex multimodal therapeutic approach. Despite the availability of regularly updated national and international guidelines on testicular cancer, treatment still differs between the institutions probably affecting the patients' outcome. Our study aims to investigate frequently occurring errors regarding the diagnosis and therapy of testicular cancer in consideration of the current EAU guidelines. Methods We performed a retrospective analysis including 129 patients diagnosed with testicular cancer that were referred to our department between 09/2015 and 10/2016. Patients' age, histology, clinical stage, IGCCCG risk classification, treatment (surveillance, chemotherapy, radiotherapy, surgery) and follow-up were investigated and compared to the EAU guidelines' recommendations. Results Of the eligible 129 patients, 34 (26%) patients displayed a non-guideline concordant care. The most common error was undertreatment (47%), mostly due to missing chemotherapy cycles. Modified treatment and overtreatment occurred in 20% and 16% respectively, while inappropriate treatment (9%) and misdiagnosis (6%) were rarely seen (Table 1). In secondary treated patients, non-guideline concordant therapy was observed more frequently compared to those patients receiving primary therapy (59% vs. 41 %). Almost all patients (93%) receiving a non-guideline concordant therapy suffered a relapse in contrast to 67% of patients that were treated according to the EAU guidelines. Conclusions Non-adherence to the current EAU guidelines on testicular cancer appears to be a major problem in various testicular cancer treating institutions. In our study, the most frequent error was undertreatment, followed by modified treatment and overtreatment. Inappropriate therapy leads to a higher relapse rate and morbidity associated with a worse curative outcome. Funding none
Authors
Pia Paffenholz
David Pfister Axel Heidenreich |
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PD53-02 |
Histology and Clinical Outcomes in Patients with Elevated Serum Tumor Markers at the Time of Post-Chemotherapy Retroperitoneal Lymph Node Dissection for Advanced Germ Cell Malignancy |
Sexual Function/Dysfunction: Penis/Testis/Urethra: Benign Disease & Malignant Disease II | 17BOS |
Abstract: PD53-02 Sources of Funding: Supported by the Sidney Kimmel Center for Prostate and Urologic Cancers, the Richard Capri Foundation and Support Grant/Core Grant P30 CA008748, T32 CA082088 Introduction Post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) is rarely performed in patients with advanced germ cell tumors (GCT) and elevated serum tumor markers (STM). Few studies have assessed the therapeutic benefit of PC-RPLND in the setting of elevated STM. Methods From 2001 to 2014, 63 patients with elevated STM (alpha-fetoprotein ?15.0 ng/mL and/or human chorionic gonadotropin ?2.2 IU/L) underwent PC- RPLND. We evaluated associations between patient characteristics, histology, and cancer-specific survival (CSS) using descriptive statistics and univariable Cox regression models. Results Median age at the time of RPLND was 28 years (IQR 22, 37). Sixteen patients (25%) received two or more courses of chemotherapy prior to RPLND. RP histology revealed viable cancer in 20 patients (32%), teratoma only in 24 (38%), and fibrosis/necrosis only in 19 (30%). Viable cancer was more common among patients treated with second-line chemotherapy than those receiving only first-line chemotherapy (63% vs. 21%, p=0.004) and in those with rising STM at RPLND compared with those with stable/declining STM levels (73% vs. 19%, p=0.001). Concordance rates between retroperitoneal and extra-retroperitoneal sites were 100% for fibrosis, 67% for teratoma, and 43% for viable cancer. Five-year CSS was 83% (95% CI 69-91%) during a median follow-up of 4.5 years for survivors. Persistent STM elevation after RPLND was associated with worse CSS (HR 9.73; 95% CI 2.95-32.07; p<0.001). This study is limited by retrospective data collection and small sample size. Conclusions Our findings showed the potential curative benefit of bilateral PC-RPLND and resection of all residual ERP diseases in GCT patients with elevated STM. This suggests that post-chemotherapy surgery should be considered in a subset of patients with low and stable STM levels after first or second-line chemotherapy in order to possibly avoid the long-term toxicity of additional salvage chemotherapy. Funding Supported by the Sidney Kimmel Center for Prostate and Urologic Cancers, the Richard Capri Foundation and Support Grant/Core Grant P30 CA008748, T32 CA082088
Authors
Qiang Li #
Piotr Zareba # Brett Carver George Bosl Darren Feldman Dean Bajorin Robert Motzer Joel Sheinfeld |
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PD53-03 |
Total lymph node yield impacts overall survival following post-chemotherapy retroperitoneal lymph node dissection for non-seminomatous testicular cancer |
Sexual Function/Dysfunction: Penis/Testis/Urethra: Benign Disease & Malignant Disease II | 17BOS |
Abstract: PD53-03 Sources of Funding: None Introduction For patients undergoing post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND), the dual goals are to maximize therapeutic efficacy while minimizing morbidity. A prior institutional study showed > 40 lymph nodes (LN) improves the diagnostic efficacy of the operation. Our study evaluates the prognostic significance of LN yield at time of PC-RPLND using the National Cancer Database (NCDB). Methods NCDB was used to identify patients who underwent PC-RPLND for non-seminomatous germ cell tumour (NSGCT) from 2004-2013. To ensure proper sequencing of chemotherapy and RPLND, only patients with Stage III NSGCT were included. Patients were stratified by ≤ 20, 21-40, and > 40 LN examined. A multivariable Cox proportional hazards model was constructed to evaluate the association of LN yield at PC-RPLND with overall survival (OS). Results A total of 645 patients underwent PC-RPLND for Stage III NSGCT. Patients with > 40 LN, were more likely to have private insurance than those with 21-40 or ≤ 20 (77% vs 74% vs 64%, p = 0.014), pure embryonal (18% vs 15% vs 15%) or teratoma (13.7% vs 12.5% vs 5.8%) histology. On univariate analysis, insurance status (p = 0.015), M1b stage (p = 0.006), positive LN status (p = 0.018), LN metastasis size (<2cm, p = 0.017 & 2-5cm, p = 0.021) and LN count, both as a continuous (p = <0.001) and categorical (p = 0.015) variable, predicted OS (Table 1). Five-year OS was 96% for the > 40 LN group, compared to 91% and 77% for the 21- 40 and ≤ 20 LN groups (Figure 1). Risk-adjusted multivariable Cox model showed an 83% reduction in hazard of death for patients with > 40 LN examined (hazard ratio [HR] 0.17; 95% CI, 0.04- 0.71) (Table 1). Conclusions The results from our study demonstrate LN yield appears to be an independent predictor of OS in patients undergoing PC-RPLND. These results suggest that the removal and review of more than 40 LN improves the therapeutic efficacy of PC-RPLND for NSGCT. Funding None
Authors
Raj Bhanvadia
Joseph Rodriguez III Scott Eggener |
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PD53-04 |
The features and management of late relapse of non-seminomatous germ cell tumours |
Sexual Function/Dysfunction: Penis/Testis/Urethra: Benign Disease & Malignant Disease II | 17BOS |
Abstract: PD53-04 Sources of Funding: None Introduction Late relapse (LR) of nonseminomatous germ cell tumours (NSGCTs), defined when this occurs > 2 years following successful treatment, is uncommon. We have examined the features and management of LR in NSGCT’s presenting to our institution. Methods Of 2490 patients, 90 were referred with LR of NSGCT. LR occurred at a median of 84 months (range 25-504, mean 131.7) following treatment. With their initial disease 23 had stage 1 disease with the other 67 all receiving chemotherapy for metastatic disease. Of these, 38 also had a post chemotherapy retroperitoneal lymph node dissection (PC-RPLND) for residual mass with histology showing 31 teratoma differentiated (TD) only, 3 necrosis and 3 had TD with viable tumour and 1 with TD and de-differentiated (DD) cancer. Results In 30 cases patients presented with symptoms of LR, with the remainder detected by markers and imaging. Of the 38 patients who had prior PC-RPLND 12 experienced a LR exclusively in the retroperitoneum with 7 relapsing in the retroperitoneum and other sites. Surgical resection was undertaken in 74 cases of LR with 11 receiving chemotherapy prior. In patients who had surgical resection initially - 38 had TD only, 22 had cancer with 7 having viable GCT and 4 viable GCT with TD and 11 having DD elements, 2 were benign and 1 not available. In those who had chemotherapy prior to resection - 5 had pure TD with 4 having cancer (2 of these were associated with TD or DD) and 2 had fibrosis/necrosis. To date 19 patients have died of disease (13 represented with symptoms and 11 occurred in multiple sites). Conclusions LR in NSGCT is rare and presents > 5 years in the majority of cases. Mortality is strongly linked to symptomatic and/or multiple sites of recurrence. TD is the predominant component of LR - related to incomplete surgical clearance following PC-RPLND where pathology demonstrates TD as well radiologically unrecognised foci of TD in stage 1 disease or following systemic disease. This reinforces the need for an aggressive surgical approach for PC residual masses in terms of completeness of the templates as well as closer scrutiny of equivocal nodal enlargement in surveillance and following chemotherapy. Funding None
Authors
Alexander Jay
Mohammed Aldiwani Suranga Wijayarathna Robert Huddart Erik Mayer David Nicol |
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PD53-05 |
Risk of Secondary Malignancy and Causes of Death after Radiation Therapy for Testicular Seminomas |
Sexual Function/Dysfunction: Penis/Testis/Urethra: Benign Disease & Malignant Disease II | 17BOS |
Abstract: PD53-05 Sources of Funding: none Introduction Testicular seminoma is the most radiosensitive genitourinary malignancy and affects relatively young men with excellent survival outcomes. Given the long life expectancy among survivors, there has been increasing concern regarding the impact of radiation therapy on development of secondary malignancies and potential mortality. We aimed to quantify the impact of radiation after orchiectomy for seminoma on survival, incidence of secondary malignancy, and eventual causes of death. Methods A national sample of men (1988-2013) diagnosed with stage 1A, 1B, 1S, 2A, 2B, and 2C testicular seminomas from Surveillance, Epidemiology, and End Results Program registries were evaluated. Kaplan-Meier curves estimated 5, 10, and 15-year overall (OS) and cancer-specific survival (CSS). Men receiving frontline radiation therapy were identified, and Cox proportional hazards models estimated impact on OS and CSS. Log-binomial regression estimated risk of secondary malignancy after radiation therapy. Causes of death were quantified, and excess deaths from secondary malignancies associated with radiation therapy were identified. Results A total of 17830 men (median age 37, 76% Caucasian, 15% Hispanic) with testicular seminomas were included for survival analysis of whom 16969 (95%) had data on radiation therapy and no prior history of malignancy. Over 50% of men with stage 1A, 1B, and 2A seminoma underwent radiation therapy. Survival rates were generally excellent (10-year CSS 1A (99.5%), 1B (99.5%), 2A (98.2%), 2B (97.3%), 2C (96.8%), 1S (99.1%)); improvement in OS was observed with radiation therapy for stage 1 (HR 0.59 (95%CI 0.50-0.70), p<0.001)) and stage 2A (HR 0.29 (95%CI 0.13-0.67), p<0.004) disease. No benefit was observed for stage 2B (p=0.70) and 2C (p=0.91) disease. The most common causes of death were cardiovascular/peripheral vascular disease (N=131), testicular cancer (N=116), other cancer (N=115), and accident/suicide/homicide (N=107). Radiation increased risk of secondary malignancy (RR 1.78 (1.56-2.04), p<0.001) and relative proportion of deaths from other cancers (0.90% vs. 0.41% for no radiation) with most notable differences for respiratory (prevalence ratio (PR) 2.5), gastrointestinal (PR 1.7), lymphoma/leukemia (PR 1.5), and other visceral cancers. For stage 1A (radiation vs. no radiation), the increase in absolute proportion of deaths from other cancers (0.98% vs. 0.28%, p<0.001) was not offset by any reduction in cancer deaths (0.55% vs. 0.46%, p=0.502). Conclusions In a national sample of men, survival rates for testicular seminoma were excellent with increased incidence of secondary malignancies associated with radiation therapy. While deaths due to other cancers was increased, the relative survival benefit of radiation therapy for stage 1B, 1S, and 2A testicular seminoma appeared to outweigh the risks but not for stage 1A. Funding none
Authors
Hiten Patel
Arnav Srivastava Ridwan Alam Gregory Joice Zeyad Schwen Alice Semerjian Mohamad Allaf Phillip Pierorazio |
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PD53-06 |
Histologic Findings of Late Relapsed Seminoma Managed with Retroperitoneal Lymph Node Dissection |
Sexual Function/Dysfunction: Penis/Testis/Urethra: Benign Disease & Malignant Disease II | 17BOS |
Abstract: PD53-06 Sources of Funding: none Introduction The overall survival for men diagnosed with pure seminoma is excellent. We sought to detail the retroperitoneal pathologic findings and treatment of men with pure seminoma who experienced a late relapse after their initial therapy. Methods The Indiana University Testis Cancer Database was queried for patients with a diagnosis of pure seminoma from 1987 to 2016. Patients with a late relapse who underwent a retroperitoneal lymph node dissection (RPLND) were included. Late relapse was defined as the dates between orchiectomy and RPLND being > 3years. This timeframe was used to account for treatment in the initial year for those who presented with metastatic disease. Patient charts were reviewed to identify patient demographics, tumor, and treatment characteristics. Categorical variables were assessed using Fisher’s exact test. Results A total of 16 patients met inclusion criteria. Twelve patients initially presented with clinical stage I disease. Of these, 6 (50%) were treated with adjuvant radiotherapy, 5 (42%) were managed with surveillance, and 1 (8%) received 2 cycles of adjuvant carboplatin. The remaining 4 patients initially presented with metastatic disease and were treated with combination platinum-based chemotherapy. The median time between radical orchiectomy and RPLND was 64 months (range 32-415). The location of recurrent disease was the retroperitoneum in 14 patients (88%) and the pelvis in 2 patients (12%). Recurrent seminoma was identified at the time of RPLND in 5 patients (31%). Three patients (19%) had necrosis only. The remaining 8 (50%) patients were found to nonseminomatous components in the retroperitoneal specimen. Of the 6 patients with clinical stage I initially treated with radiotherapy, 1 patient had recurrent seminoma, 1 was found to have a Leydig cell tumor, 2 patients demonstrated a malignant transformation to sarcoma and rhadomyosarcoma, and 2 were found to have nonseminoma. Patients initially treated with radiotherapy for clinical stage I disease required more induction and salvage chemotherapy as well as more additional procedures (i.e. nephrectomy, bowel resection, etc) at the time of RPLND (66% vs. 33%, p=0.09). Conclusions Patients who received radiotherapy for clinical stage I disease have an unpredictable retroperitoneal histology and require a higher burden of treatment at the time of relapse compared to those without radiotherapy. Overall, 50% of patients were found to have malignant transformation or nonseminoma at the time of late relapse. Funding none
Authors
Clint Cary
Joseph Jacob Richard Foster |
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PD53-07 |
Conditional Risk of Relapse in 3,601 Patients Managed with Surveillance for Stage I Testicular Cancer |
Sexual Function/Dysfunction: Penis/Testis/Urethra: Benign Disease & Malignant Disease II | 17BOS |
Abstract: PD53-07 Sources of Funding: none Introduction The baseline risk of relapse following orchiectomy is approximately 15% in patients with clinical stage I (CSI) seminoma and 30% in patients with CSI non-seminoma (NSGCT). Surveillance has been widely adopted for initial management. However, the baseline relapse risk does not reflect how prognosis may change the longer a patient has survived without relapse. This dynamic relapse risk is referred to as conditional risk of relapse and can provide important prognostic information for physicians and patients. Methods We performed a retrospective review of patients managed with surveillance for CSI testicular cancer in Denmark and the Princess Margaret Cancer Center, Toronto, Canada, between 1980 and 2014. Conditional risk of relapse was estimated using the Kaplan-Meier method. We stratified patients based on validated risk factors for relapse. We used linear regression to determine trends of conditional risk over time. Results We identified 3,601 patients of which 2,462 (68.6%) had seminoma and 1,139 (31.6%) had NSGCT. Median follow-up in those without relapse was 12.1 (interquartile range 8.0 to 19.5) years and 9.4 (interquartile range 5.1 to 17.1) years in seminoma and NSGCT, respectively. At orchiectomy, the baseline risk of relapse at 5 years was 53.2%, 22.1%, 21.2%, and 12.4% in patients with high-risk NSGCT (CSIB with pure embryonal carcinoma), low-risk NSGCT (CSIA without pure embryonal carcinoma), seminoma with tumour size ≥ 3cm, and seminoma with tumour size less than 3cm, respectively. The conditional relapse risk decreased over time in all groups (p<0.001), but did so at different rates (Figures 1 and 2). For patients without relapse at 3 years, the corresponding risk of relapse within the next 5 years was 6.6%, 0.9%, 3.5%, and 2.0%, respectively (Figures 1 and 2). Conclusions Our pooled study is the largest to date to provide conditional risk of relapse for patients with CSI testicular cancer on surveillance. These results can be used to provide patients with prognostic information and tailor surveillance protocols to reduce the intensity of follow-up in patients with a low risk of future relapse. Funding none
Authors
Madhur Nayan
Gedske Daugaard Michael Jewett Jakob Lauritsen Mikkel Bandak Mette Saksoe Mortensen Maria Gry Gundgaard Kier Philippe Bedard Aaron Hansen Padraig Warde Peter Chung Eshetu Atenafu Robert Hamilton |
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PD53-08 |
Clinical implications of serum N-glycan profiling as a diagnostic and prognostic biomarker in germ-cell tumors |
Sexual Function/Dysfunction: Penis/Testis/Urethra: Benign Disease & Malignant Disease II | 17BOS |
Abstract: PD53-08 Sources of Funding: None Introduction Serum biomarker monitoring is essential for management of germ-cell tumors(GCT). However, not all GCT are positive for conventional tumor markers. We examined whether serum N-glycan-based biomarkers can be applied for detection and prognosis in patients with GCT._x000D_ Methods We performed a comprehensive N-glycan structural analysis of sera from 54 untreated GCT patients and 103 age-adjusted healthy volunteers using glycoblotting methods and mass spectrometry. Candidate N-glycans were selected from those with the highest association; cutoff concentration values were established, and an N-glycan score was created based on the number of positive N-glycans present. The validity of this score for diagnosis and prognosis was analyzed using a receiver operating characteristic (ROC) curve._x000D_ Results We identified 5 candidate N-glycans significantly associated with GCT_x000D_ patients (A). The accuracy of the N-glycan score for GCT was significant with an area-under-the-curve (AUC) value of 0.87 (B). Diagnostically, the N-glycan score detected 10 of 12 (83%) patients with negative conventional tumor markers (C). _x000D_ Prognostically, the N-glycan score was comprised 4 candidate N-glycans (D). The predictive value of the prognostic N-glycan score was significant, with an AUC value of 0.89 (E). A high value prognostic N-glycan score was significantly associated with poor prognosis (F)._x000D_ Finally, to identify a potential carrier protein, immunoglobulin (Ig) fractions of sera were subjected to N-glycan analysis and compared to whole sera. Candidate N-glycans in Ig-fractions were significantly decreased; therefore, the carrier protein for candidate N-glycans is likely not an immunoglobulin. Conclusions Our newly developed N-glycan score seems to be a practical diagnostic and prognostic method for GCT. Funding None
Authors
Takuma Narita
Shingo Hatakeyama Tohru Yoneyama Shintaro Narita Shinichi Yamashita Koji Mitsuzuka Toshihiko Sakurai Sadafumi Kawamura Tatsuo Tochigi Ippei Takahashi Shigeyuki Nakaji Yuki Tobisawa Hayato Yamamoto Takuya Koie Norihiko Tsuchiya Tomonori Habuchi Yoichi Arai Chikara Ohyama |
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PD53-09 |
Men with testicular cancer have lower semen quality compared to those with other malignancies |
Sexual Function/Dysfunction: Penis/Testis/Urethra: Benign Disease & Malignant Disease II | 17BOS |
Abstract: PD53-09 Sources of Funding: none Introduction It is suggested that semen quality is already impaired in testicular cancer (TC) patients. However, the impact of type of malignancy on semen quality remains unclear. The aim of this study is to investigate the semen parameters and associated malignancies of men with cancer who cryopreserved sperm before undergoing therapy. Methods We reviewed the database from our cryopreservation laboratory between January 1994 and May 2016, and identified 114 patients who have banked their sperm before undergoing treatment. Age at banking, semen volume, sperm density, percent motile sperm and type of cancer were recorded. Semen parameters were compared between TC and other malignancy (non-TC). Results A total of 114 semen samples included 25% with testicular cancer (seminoma: 8.8% and non-seminoma: 17%), 25% with lymphoma, 18% with leukemia, 7.0% with myelodysplastic syndrome, 4.4% with solid cancer, 3.5% with urological cancer, 1.8% with immune system diseases, and unspecified 13%. Median patient age, semen volume, sperm density and sperm motility were 29 years, 2.9 mL, 28 x 106/mL, and 43%, respectively. Patients with TC had significantly lower total sperm concentration (P=0.008) and motile sperm rate (P=0.012) compared with other malignancies. The fertile range of the sperm from cancer patients were significantly poor in the TC (fertile 0%, intermediate 31%, and subfertile 69%) compared with other malignancies (12%, 42%, and 46%, respectively) (P=0.044). In TC patients, the ratio of oligozoospermia was significantly higher in comparison with other malignancies (P<0.001). There were no significant differences in sperm parameters between seminoma and non-seminoma, whereas ratio of oligozoospermia was significantly greater in non-seminoma group than seminoma group (P<0.001). Among 29 TC patients, 3 patients (10%) had undergone infertility treatment, and 2 patients (7%) archived pregnancy and resulted in 2 deliveries. Conclusions Men with testicular cancer have lower semen quality compared to those with other malignancies. The rate of using cryo-thawed sperm from cancer patients for fertility treatments in our unit was 10%. Funding none
Authors
Daisuke Noro
Shingo Hatakeyama Itsuto Hamano Toshikazu Tanaka Takuma Nairta Tohru Yoneyama Atsushi Imai Yasuhiro Hashimoto Takuya Koie Chikara Ohyama |
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PD53-10 |
Impact of Adjuvant Treatment on Long-Term Quality of Life of Testicular Cancer Survivors |
Sexual Function/Dysfunction: Penis/Testis/Urethra: Benign Disease & Malignant Disease II | 17BOS |
Abstract: PD53-10 Sources of Funding: None Introduction Issues of survivorship of testicular cancer are emerging due to excellent results from treatment. Treatment generally consists of orchidectomy followed by active surveillance or adjuvant therapy with chemotherapy, radiotherapy or retroperitoneal lymph node dissection. The 10-year overall survival rate for testicular cancer is 95%. The objective of this project is to determine the effect of adjuvant therapy, education, cancer stage and age of diagnosis on the long-term quality of life of testicular cancer survivors. Methods 144 patients were identified to have received treatment for testicular cancer at St Vincent’s Hospital in Melbourne from 2001-2016. Patients were contacted by phone and mail. A validated cancer questionnaire (EORTC QLQ-C30) with a testicular cancer module (EORTC QLQ-TC26) was used. Questionnaire answers were recorded on a Likert scale and converted to a score from 0-100 according to the official scoring manual. Independent t-tests compared domain scores between different treatments, educational levels, cancer stages and age groups. Results The response rate was 40% (57/144). Nine patients were deceased, and the median follow-up after orchidectomy was 42 months. Patients who received adjuvant therapy reported more financial difficulties than those who received surveillance alone (Figure 1). However, there were no differences in global quality of life or other domains between different treatments (Figure 2). Those who were tertiary educated were more comfortable communicating with their partners about their disease and sexuality. Men with stage 2 disease or above reported lower social functioning than those with stage 1 disease. Finally, men who were older at the time of diagnosis reported a more positive outlook about the future and fewer concerns about infertility. Conclusions Clinicians could tailor counselling according to age, educational level, cancer stage and financial status at diagnosis. Importantly, patients could be reassured that the treatment chosen will not have a significant impact on long-term quality of life. Funding None
Authors
Trung Q Ngo
Jeremy R Goad Anthony J Dowling Lih-Ming Wong |
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PD53-11 |
Primary retroperitoneal lymph node dissection (RPLND) in Stage II A/B seminoma patients without adjuvant treatment: a phase II trial (PRIMETEST) |
Sexual Function/Dysfunction: Penis/Testis/Urethra: Benign Disease & Malignant Disease II | 17BOS |
Abstract: PD53-11 Sources of Funding: None Introduction To evaluate progression-free survival of stage II A/B seminoma patients (pts) undergoing primary retroperitoneal lymph node dissection (RPLND) without adjuvant treatment. To date there are only few publications reporting primary RPLND in Stage II seminoma. Aim is to present initial data of a feasibility study and a prospective phase II trial._x000D_ Methods Before starting the phase II trial, 9 pts have been treated within a pilot feasibility study including one CS IIC patient and one patient with atypical inguinal recurrence. Since 3.2016 additional 2 pts were treated within the prospective phase II design (NCT 2015053664) with a primary retroperitoneal lymph node dissection (open or daVinci robot assisted) in Stage II A/B seminoma in a single center. All patients including those within the feasibility study were evaluated for peri- and postoperative outcome and oncologic data including recurrence free survival. The trial is designed to exclude a > 30% recurrence to standard treatment and will have to accrue 30 pts._x000D_ Results Eleven patients with seminomatous germ cell tumors have been included in both cohorts since 5.2014. Two patients received RPLND after inguinal orchiectomy as a primary treatment, 5 patients (46%) after early relapse and 4 patients (36%) after late relapse. 6/9 (67%) patients were under active surveillance, 3/9 (22%) patients received one cycle of carboplatin. Mean tumor size was 2.6 cm at a mean patient age of 43 years. 7 conventional, 1 inguinal and 3 DaVinci robot assisted RPLNDs were performed, mean OR time was 144 min with a mean blood loss of 109 cc. One patient after DaVinci RPLND developed ureteral stricture requiring an ileal ureter substitute. The mean follow-up of all pts is 18 month (4 – 28 month). 7/11 (64%) patients are recurrence free. So far, four patients (including the CS IIC patient and the patient with atypical inguinal lymph nodes) developed recurrences 3, 3, 3 and 9 month after surgery (3x outside field and 1x inside field relapse). 1 patient received radiotherapy (36Gy) and 3 patients received CTX with 4xPE, 3xBEP and 3xBEP, 3/4 (75%) patients are currently recurrence free._x000D_ Conclusions Primary retroperitoneal lymph node dissection (RPLND) in stage II A/B seminoma is an experimental treatment alternative with promising short term results. RPLND should be performed only within clinical trials and in specialised high volume referral centers. _x000D_ Funding None
Authors
Achim Lusch
Laura Gerbaulet Christian Winter Peter Albers |
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PD53-12 |
Centralization of care promotes training disparities with regard to the teaching of Retroperitoneal Lymphadenectomy |
Sexual Function/Dysfunction: Penis/Testis/Urethra: Benign Disease & Malignant Disease II | 17BOS |
Abstract: PD53-12 Sources of Funding: None Introduction In 2007, Lowrance et al published a manuscript in the Journal of Urology, which stated that the majority of United States trained urology residents have minimal experience with Retroperitoneal Lymphadenectomy. The purpose of our study is to evaluate if the current trend in retroperitoneal lymphadenectomy training has declined further. Methods After permission from the American Board of Urology, a retrospective review of operative log reports from 2005-2015 was performed. Using CPT code designation, total cases performed were quantified and further stratified by log year, practice region, practice type and recertification versus primary certification. Results A total of 1227 open retroperitoneal transabdominal lymphadenectomy; extensive, including pelvic, aortic and renal nodes (CPT 38780) were logged by 500 physicians. 247 (49.4%) physicians applying for primary certification logged at least 1 lymphadenectomy compared to 253 (50.6%) applicants for recertification. Of the 500 certifying physicians, 321 (64.2%) reported only 1 lymphadenectomy, 144 (28.8%) reported 2-5 procedures and 35 (7.0%) performed more than 5. When stratified by geographic location, most procedures were recorded in the North Central (27.5%) and Western section (24.4%). There were 793 (64.6%) cases performed in an Academic hospital setting. Conclusions A significant number of recently trained urologists continue to demonstrate minimal experience with retroperitoneal lymph node dissection. With limited exposure to an operation that was once considered an index case, there is a significant negative impact on the quality of urologic resident education. Additionally, this review demonstrates an already visible trend toward the centralization of care with the majority of procedures performed at major academic institutions. Funding None
Authors
Ryan Owen
Stephanie Dresner James Bienvenu W. Bedford Waters |
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PD54-01 |
BRAIN ACTIVITY CHANGES ON FUNCTIONAL MAGNETIC RESONANCE IMAGING DURING SACRAL NERVE STIMULATION FOR OVERACTIVE BLADDER |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Female Incontinence: Therapy III | 17BOS |
Abstract: PD54-01 Sources of Funding: Medtronic Unrestricted Research Grant Introduction Sacral nerve stimulation(SNS) is used for refractory overactive bladder(OAB). Its mechanism of action is unknown, but likely involves spinal reflexes and afferent signaling to the brain. This study used functional magnetic resonance imaging(fMRI) to measure real-time SNS effects on brain activity in OAB. Methods Following IRB approval, women with non-neurogenic refractory OAB who responded to SNS via InterStim II device, had a stable program for 3 or more months, and received no adjuvant OAB treatment were recruited. Enrolled patients completed pre-fMRI validated symptom and quality of life instruments[UDI-6, IIQ-7, PGI-S, Perceived Urgency Intensity(PUI)]. Stimulus settings were recorded, devices switched off for a 5-day washout, and instruments repeated. Three fMRI scans below, at, and above stimulus sensory threshold were done. Images were 2-dimensional gradient echo-planar imaging blood oxygenation level dependent contrast(EPI-BOLD) acquired over 5 stimulator-off and 4 on cycles of 42 seconds each. Output images use single voxel p-value 0.05 with false positive error of 0.05 (cluster-analysis determined). Results A total 13 patients were enrolled (3 did not undergo fMRI, 4 were excluded for poor OAB symptom control or low image quality), 6 completed fMRI. The sample had a median age 52[36-64] years. Urinary bother significantly worsened with 'washout' while symptoms worsened with a trend toward significance. Voiding diary data supported this. _x000D_ An overall pattern of brain activation generally progressed with increasing stimulation, but activation of the right inferior frontal gyrus remained stable, while deactivation of the pons and periacqueductal gray matter was only noted with sub-sensory stimulation. Sensory stimulation activated the insula but deactivated the medial and superior parietal lobes. Suprasensory stimulation activated multiple structures and the expected S3 sensory region. All devices had normal impedances after fMRI and PUI(p0.36) nor PGI-S(p0.36) changed from baseline. Conclusions Varying SNS stimulus influences fMRI signal intensity. These results suggest sacral nerve stimulation may have a centrally-mediated mechanism of action. Funding Medtronic Unrestricted Research Grant
Authors
Bradley Gill
Javier Pizarro-Berdichevsky Pallab Bhattacharyya Brian Marks Adrienne Quirouet Sandip Vasavada Stephen E Jones Howard B Goldman |
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PD54-02 |
Removal of Sacral Nerve Stimulation Devices for Magnetic Resonance Imaging: What Happens Next |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Female Incontinence: Therapy III | 17BOS |
Abstract: PD54-02 Sources of Funding: none Introduction Sacral neuromodulation (SNS) is an effective therapy; however, these devices are not approved to undergo magnetic resonance imaging (MRI) of sites other than the brain. Therefore, when non-brain MRIs are required, devices are often removed prior to imaging. We assessed the frequency of device removal for MRI and the subsequent clinical course of these patients. Methods A retrospective review of all SNS procedures in the urology department at a tertiary care center from 2010-2015 was performed and explants identified. Cases explanted for MRI were analyzed to collect demographics, clinical characteristics, and post-removal management. Descriptive statistics were calculated and presented as mean(standard deviation) or median[interquartile range] as appropriate. Results A total of 90 patients underwent SNS device removal, with 21(23%) occurring for MRI, of which all devices were implanted in 2012 or before. At explant, patients were 95%(N=20) female, 66[52-72] years of age, and had a 29.6[23.8-34.6] kg/m2 body mass index. Suboptimal symptom control from SNS was noted in 7(33%) patients prior to explantation and 4 patients in the cohort (19%) had Multiple Sclerosis. _x000D_ _x000D_ Of those explanted, 24% required MRI for neurologic and 57% for orthopedic concerns. The remaining MRI indications included abdominal masses (10%), genitourinary disease (5%), surveillance for prior spinal cord malignancy (5%), and cardiac disease (5%). Only 16 (76%) patients explanted ultimately underwent MRI, a median of 13[3-16] days after device removal. MRI results actively impacted clinical management in half of the imaged patients, with no pharmacologic interventions, but instead surgical evaluation (5), physical therapy/rehabilitation (1), an outpatient procedure (1), and a headache diary (1) being recommended. Only 10%(N=2) of explanted patients underwent device replacement, while 7 patients resumed medical therapy, 3 utilized intermittent self-catheterization or an indwelling catheter, 2 patients pursued Botulinum toxin, 1 sought care with a local urologist, and 1 underwent cystectomy and ileal conduit urinary diversion. Of the remainder, 1 is deceased and 4 were lost to follow-up. _x000D_ Conclusions In patients receiving SNS therapy, device removal for MRI is a rare event, most commonly due to orthopedic and neurologic pathologies. About half of the MRIs performed impacted clinical management. As SNS replacement was rare in this cohort, research is needed on the safety of various MRI types with SNS devices in vivo. Funding none
Authors
Jessica Lloyd
Bradley Gill Javier Pizarro-Berdichevsky Elodi Dielubanza Juan Guzman Henry Okafor Howard Goldman |
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PD54-03 |
Optimizing lead placement during staged sacral neuromodulation (SNM): factors associated with progression to stage 2 |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Female Incontinence: Therapy III | 17BOS |
Abstract: PD54-03 Sources of Funding: SUFU neuromodulation grant Introduction Current practice at our high-volume tertiary referral hospital aims to optimize lead placement at the superior medial aspect of the S3 foramen and achieve lead thresholds under 2mA for all four electrodes sites. This analysis aims to summarize our experience with optimized technique, and evaluate the impact of baseline factors on progression to stage 2 SNM implant. Methods This is a cross sectional analysis of all stage 1 lead placement SNM cases from August 2014-October 2016. After a 2 week trial period, patients received a stage 2 SNM pulse generator implant if voiding diaries reflected ≥50% symptom improvement. Otherwise, the lead was removed. We performed univariate analysis on demographic, clinical and intraoperative factors comparing patients who progressed to stage 2 with those whose leads were removed after the trial period. Multivariate analysis with logistic regression was performed using R version 3.2.1. Results 89% of the total 108 stage 1 lead placements progressed to stage 2. 91% of subjects were female. Cumulative indications for SNM were 95% refractory urgency/urgency incontinence, 16% idiopathic urinary retention, and 29% fecal incontinence. Several factors were associated with progression to stage 2 implant (see table 1). Multivariate analysis revealed that history of prior failed 3rd line therapy was independently associated with lead removal (OR 17, CI 2.9-132, p=0.003), and there was a trend toward significance for pelvic pain (OR 4.8, CI 0.9-27, p=0.06). Conclusions Optimized lead placement technique can achieve motor and sensory thresholds <2mA in all electrodes and 89% conversion rate to stage 2 SNM. Our analysis was limited by small lead removal group size, but history of pelvic pain and prior SNM implant appear to be associated with lead removal after the 2 week trial. Funding SUFU neuromodulation grant
Authors
Sarah A Adelstein
Kevin Gioia Jonathan Wingate Alvaro Lucioni Kathleen C Kobashi Una J Lee |
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PD54-04 |
NEUROMODULATION FOR CHRONIC UROGENITAL PAIN: A COMPARISON OF PUDENDAL AND SACRAL NERVE STIMULATION |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Female Incontinence: Therapy III | 17BOS |
Abstract: PD54-04 Sources of Funding: Funding: Philanthropy; Ministrelli Program for Urology Research and Education (MPURE) Introduction Introduction and Objective: Little evidence exists regarding the effect of chronic neuromodulation on urogenital pain. We evaluated outcomes between pudendal vs. sacral nerve neuromodulation. Methods Methods: Adults in our prospective database with primary/secondary diagnosis of pelvic pain (excluding interstitial cystitis) and quadripolar lead placed at the pudendal or sacral nerve were reviewed. History, pain scores (0-10; none to severe), Global Response Assessment (GRA), Interstitial Cystitis Symptom/Problem Index (ICSIPI) and Overactive Bladder symptom severity (OABq ss)/health related quality of life (HRQOL) collected at baseline, 3 and 6 months, and 1 and 2 years were analyzed with descriptive statistics and repeated measures over 1 year. Results Results: Of 87 that had a lead placed, 72 (83%) had generator implantation and 65 had complete baseline data. 37/65 had a pudendal (12/37 had failed sacral stimulation) and 28 had a sacral lead. Group characteristics were similar except for pudendal had lower body mass index (median 24.8 vs. 28.6; p=0.009) and fewer with primary urinary urgency/frequency (8.1% vs. 39.3%; p=0.003). Pudendal patients more commonly had a primary diagnosis of pelvic pain that approached but was not statistically significantly (62.2% vs. 38.5%; p=0.06). Median follow up was 1.2 vs. 2.6 years in the pudendal and sacral groups respectively (p=0.0011). Median pelvic pain scores were similar between pudendal and sacral groups at baseline and each follow up, and both improved significantly over 1 year (p=0.0003 and p<0.0001). The pudendal group had lower ISCIPI and OABq/ss scores at baseline (p=0.007 and p=0.035, respectively), but both groups improved over 1 year on the ICSIPI (p<0.0001 for both groups), OABq/ss (p=0.005 and p=0.0002 respectively), and OABq HRQOL (p=0.027 and p<0.0001, respectively). Similar proportions in the pudendal and sacral groups had pain at each follow up except for at 6 months (17/19; 90% vs. 8/14; 57%; p=0.047); for those with pain, similar proportions (between 33% and 50%) had moderate/marked improved in pain on the GRA at each time point. Conclusions Conclusions: Both groups experienced modest but similar improvements in pelvic pain. Pudendal was effective in those who failed sacral neuromodulation and was used preferentially in patients with a primary diagnosis of pain. Neuromodulation should be considered in the management of chronic pelvic pain. Funding Funding: Philanthropy; Ministrelli Program for Urology Research and Education (MPURE)
Authors
Austin Fan
Kim A. Killinger Kenneth M. Peters Judith Boura |
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PD54-05 |
Demographic and Clinical Variables Associated With Treatment Response in Women Undergoing OnabotulinumtoxinA and Sacral Neuromodulation |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Female Incontinence: Therapy III | 17BOS |
Abstract: PD54-05 Sources of Funding: Eunice Kennedy Shriver National Institute of Child Health and Human Development Introduction Refractory urgency urinary incontinence (UUI) can be treated with onabotulinumtoxinA and sacral neuromodulation but it is unclear whether treatment response differs based on patient characteristics. The objective was to identify clinical and demographic factors associated with treatment response in women participating in a randomized trial comparing efficacy of these two therapies. Methods These data were obtained from the Refractory Overactive Bladder: Sacral Neuromodulation vs Botulinum Toxin Assessment (ROSETTA) trial. Adjusting for clinical site, age stratum and treatment, univariable analyses were performed to identify baseline participant characteristics and clinical variables associated with each treatment using two definitions of response: 1) a reduction of mean daily UUIE longitudinally over 6 months 2) ≥50% decrease in UUIE across 6 months. Variables with p≤0.1 were included in multivariable analyses. Linear and logistic regression models were fit to estimate each outcome and reported as mean reductions and adjusted odds ratios (OR) with 95% confidence intervals (CI), respectively. Results Variables significantly associated with treatment response on univariable and multivariable analyses are noted in the table. Increasing age, higher BMI and higher baseline IIQ score significantly reduced the chances of achieving ≥50% decrease in UUIEs at 6 months for both treatments with a significantly greater effect noted with age in the onabotulinumtoxinA group. A mean reduction in daily UUIE over 6 months was independently associated with higher baseline HUI scores and greater baseline UUIE per day. Higher health utility index scores also had a greater effect on participants in the onabotulinumtoxinA group. Increasing age was associated with less reduction in UUIE per day. Conclusions Six months after treatment, age, BMI, baseline UUIE, IIQ and HUI were similarly associated with treatment response in women undergoing sacral neuromodulation and onabotulinumtoxinA with interesting differential effects noted with age and HUI. This information may assist in counseling patients regarding the efficacy and expectations of these treatment modalities for women with refractory UUI. Funding Eunice Kennedy Shriver National Institute of Child Health and Human Development
Authors
Holly E Richter
Cindy Amundsen Eric Jelovsek Stephen Erickson Yuko Komesu Christopher Chermansky Norbert Kadima Deborah Myers Heidi Harvie Michael Albo Dennis Wallace |
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PD54-06 |
A prospective randomized clinical trial comparing two doses of AbobotulinumtoxinA for idiophatic overactive bladder |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Female Incontinence: Therapy III | 17BOS |
Abstract: PD54-06 Sources of Funding: none Introduction Cystoscopic administration of BoNT-A has been reported to be effective for patients with idiopathic overactive bladder refractory. Most of studies ranging doses have reported OnabotulinumtoxinA. The purpose of our study was to compare 300U versus 500U of AbobotulinumtoxinA in this patients. Methods This is a prospective, randomized, blind study. Adult female patients, with symptoms of OAB, who had failed conservative treatment or discontinued pharmacotherapy due to intolerability or contraindications were included. Patients who had any neurological disease, tumors, pelvic abnormalities or voiding dysfunction were excluded. Detrusor overactivity was not required for inclusion. They were assessed at 4,12 and 24 weeks after injection. Treatment consisted of 30 injections distribuited into the detrusor muscle, avoiding trigone. The primary outcome was change in clinical status, including urinary frequency, urgency and urinary urgency incontinence (UUI) episodes. Secondary outcomes were changes in maximum cystometric capacity (MCC), volume at first desire to void (FDV) and post-void residual (PVR). Quality of life (QoL) was assessed using a visual analogue scale (VAS,0-10) and a patient global impression of improvement (PGI-I).Urinary retention, urinary tract infection (UTI) and required clean intermitent catheterization (CIC) were adverse events. Results A total of 22 patients were randomized to either 300U (n=11) or 500U (n=11) groups. Baseline demographics characteristics were comparable for both groups. All 21 patients reported urgency, with 90% of UUI before treatment. At 12 w, an important reduction in daily UUI episodes was observed in two groups, with 90% of them being dry. Decrease in mean episodes of nocturia and urinary frequency, increase FDV and CCM and a mean reduction in total ICIQ-OAB were observed. At 24 w, episodes of UUI had returned in 50% (300U) and 0% (500U) (p=0,013). Patients had an impression of significant improvement in 70% (300U) and 88,9% (500U) at 12w; and 50% (300U) and 100% (500U),at 24w. Score of VAS was manteined higher in 500U group. There was a significant increase in mean PVR after treatment (4w) in both groups. Our incidence of UTI was 36,7% (300U) and 34,6% (500U). One patient (500U) required CIC for 2 weeks. Conclusions Data from this study suggest 500U improves symptoms and quality of life for longer time than 300U. However, results are not significantly differents to determine which dose is safer. As far we know this is the first study to compare two doses of AbobotulinumtoxinA for refractory idiophatic OAB._x000D_ _x000D_ Funding none
Authors
Danielle de Sa Dantas Bezerra
Luis Gustavo Morato Toledo Jose Eduardo Vetorazzo Filho Antonio Pedro Flores Auge |
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PD54-07 |
Expression of miR221 and miR125b in Bladder Biopsy Predict the Risk of High PVR Following Intradetrusor Onabotulinumtoxin-A Injection: Implications for Clinical Decision Making |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Female Incontinence: Therapy III | 17BOS |
Abstract: PD54-07 Sources of Funding: Internal Funding from the Department of Urology at the University of Pittsburgh School of Medicine Introduction Micro RNAs (miRs) are non-coding strands of RNA involved in gene expression. Because of their relative stability in urine and serum, miRs are widely researched as promising biomarkers that may better help understand chronic diseases. The role of miRs in the pathology and treatment outcomes of onabotulinumtoxin-A (onaBoNT-A) in overactive bladder (OAB) patients is unknown. Here, we identified the miRs associated with elevated post-void residual volumes (PVRs) >200ml following intradetrusor injection of onaBoNT-A 100IU._x000D_ _x000D_ Methods 14 female OAB patients with urgency urinary incontinence refractory to OAB drugs were consented for this study. Cystoscopic-guided punch bladder biopsy was obtained at the time of injecting 100 units of onaBoNT-A. RNA was extracted from the biopsy for measuring the expression of 13 miR species using TaqMan Universal PCR Master Mix in quantitative PCR. The miR species were selected for their known effect on neurotrophin expression and smooth muscle function. Relative expression for each miR was determined after normalizing to U6 small nuclear RNA. PVRs and urine Nerve Growth Factor (NGF) levels were measured at baseline and at the follow-up visit 3 weeks later. Results Consented 14 patients had a mean age of 66 years (Range 46-80 years). Of these patients, 9 maintained PVRs < 200mL (0-120 mL) after injection of onaBoNT-A to comprise the low PVR group. The other 5 patients developed PVRs > 200mL (213-391mL), and they comprise the high PVR group. The mean pre-procedure PVR was similar in both groups. Relative expression of miR221 and miR125b (see Figure 1) was upregulated by 11 and 2 fold, respectively (*p<0.05, Mann-Whitney U test) in patients who maintained low PVRs after onaBoNT-A. The expression of other 11 miR species and urine NGF levels at baseline were not significantly different between the two groups. Even though the NGF levels were similar in two groups but the 11 fold downregulation of miR221 may attenuate the action of NGF in high PVR group. Conclusions This study suggests that deficiency in the pretreatment expression of miR221 and miR125b may predispose OAB patients to high PVRs following intradetrusor onaBoNT-A. Additional studies are needed to understand the role of each miR in OAB pathology and treatment outcomes. Funding Internal Funding from the Department of Urology at the University of Pittsburgh School of Medicine
Authors
Christopher J Chermansky
Brian T Kadow Mahendra Kashyap Pradeep Tyagi |
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PD54-08 |
What is the ideal antibiotic prophylaxis for intravesical Botox injection? A comparison of two different regimens |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Female Incontinence: Therapy III | 17BOS |
Abstract: PD54-08 Sources of Funding: none Introduction Intravesical onabotulinum toxin A (Botox®) is an effective treatment for idiopathic detrusor overactivity of which urinary tract infections (UTIs) are a common complication. We previously identified a UTI rate of 35.1% in patients who received a single intramuscular (IM) dose of a third-generation cephalosporin (ceftriaxone) at the time of Botox injection. Given this high rate of infection despite single-dose antibiotic prophylaxis, we changed our practice pattern to determine if a longer course of antibiotic treatment would decrease the UTI rate following intravesical Botox injection. Methods We retrospectively evaluated patients undergoing intravesical Botox injections from May 2012 to November 2016. All procedures were performed at the same office location. One group of patients, with negative pre-procedure urine cultures, was given an IM dose of a third-generation cephalosporin. A second group, also with negative pre-procedure cultures, received a 3-day course of an oral fluoroquinolone starting the day before Botox injection. Data abstracted included age, BMI, history of diabetes, pre/post procedure urine culture. Pre-procedure UTI was defined as asymptomatic bacteriuria. The post-procedure UTI rate was examined using a χ2 test. A secondary analysis was performed using logistic regression modeling to test the association between clinical characteristics and antibiotic regimen and risk of post-procedure UTI. Results 284 Botox injections were performed over the study period - 236 patients received a single IM dose of ceftriaxone and 48 patients received three days of oral ciprofloxacin. There was no difference in the baseline age, BMI, diabetes, or rate of pre-procedure positive culture between the two groups. Overall, the UTI rate was significantly lower in the fluoroquinolone group (20.8%) vs. the cephalosporin group (36%), p=0.042. On multivariable regression analysis, predictors of post-procedure UTI included single IM dose of prophylaxis (OR 2.80, 95% CI 1.2-6.5, p=0.016) and positive pre-procedure urine culture (OR 1.31, 95% CI 1.03-1.66, p=0.027). Age, BMI and diabetes were not associated with post-procedure UTI. Conclusions In our series comparing two different antibiotic prophylaxis regimens for Botox injection, we found a significantly lower rate of UTI when patients received a three-day course of an oral fluoroquinolone as opposed to a single IM dose of a third-generation cephalosporin. Patients with a positive pre-procedure culture may benefit from longer duration of antibiotics at the time of Botox injection. Funding none
Authors
Justin Houman
Juzar Jamnagerwalla Ariel Moradzadeh Kian Asand Devin Patel Jennifer Anger Karyn Eilber |
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PD54-09 |
First results – the Urge 1 study - randomized trial to compare solifenacin and bilateral mesh replacement of the uterosacral ligaments in the treatment of urgency urinary incontinence |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Female Incontinence: Therapy III | 17BOS |
Abstract: PD54-09 Sources of Funding: None Introduction The etiology of urinary incontinence is unknown. Beside stress urinary incontinence (SUI), current treatment options are based on a neurological disorder or the detrusor. In the early 90s Ulmsten and DeLancey hypothesized an anatomical defect of the anterior vaginal wall: laxity of the 3 levels (the paraurethral tissue, the apical end and vesicourethral junction). Except SUI, and in regard to materials (length/width) and fixation/implantation sides no standardized surgical treatment for these levels were developed. _x000D_ We introduced a standardized apical fixation: a bilateral mesh augmentation of the uterosacral ligaments: the cervicosacropexy (CESA) or vaginosacropexy (VASA). In order to evaluate the different hypotheses we compared the standard pharmacological treatment with the surgical approach of CESA or VASA in the treatment of urgency urinary incontinence (UUI) in women. _x000D_ _x000D_ _x000D_ Comparison of therapeutic efficacy between solifenacin and CESA or VASA surgeries in women with involuntary urinary leakage. Methods Women with UUI symptoms and without previous treatment were eligible for this study. The study was approved by the local ethical committee (ClinicalTrails.gov Identifier: NCT01737411). UUI symptoms were assessed according to validated questionnaires. Urodynamics were performed before and after each treatment arm. Patients were randomized either in the solifenacin therapy arm (10mg) or in the surgical procedure arm. After 4 months the efficacy of each treatment arm was assessed. Cure was defined as voiding frequency <8 times/day and no involuntary leakage of urine. Polyvinylidene fluoride (PVDF) tapes of identical length were used for open abdominal USL augmentation and named cervicosacropexy (CESA) or vaginosacropexy (VASA) depending on the site of fixation. These tapes were sutured either on the cervix or vaginal stump and placed under the left and right peritoneal fold of the USL from the rectum and attached to the prevertebral fascia of the S1/S2 sacral vertebra. Results 77 patients were evaluable for analysis. In total, after primary and secondary solifenacin treatment 3 out of 58 patients (5%) were cured. After primary and secondary CESA or VASA surgical treatment 26 out of 65 patients (40%) were cured of their UUI symptoms. Conclusions The CESA and VASA surgical procedures provide a therapy to cure 40% of patients from involuntary urinary leakage. Compared to the standard pharmacological treatment these surgical procedure depicts an option in the treatment of UUI. Funding None
Authors
Sebastian Ludwig
Martin Stumm Peter Mallmann Wolfram Jäger |
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PD54-10 |
THE VALUE OF COMBINING LOW DOSE TROSPIUM CHLORIDE WITH TRANSCUTANEOUS POSTERIOR TIBIAL NERVE STIMULATION IN THE TREATMENT OF OVERACTIVE BLADDER IN FEMALES |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Female Incontinence: Therapy III | 17BOS |
Abstract: PD54-10 Sources of Funding: none Introduction This study was done to verify whether the combination of transcutaneous posterior tibial nerve stimulation (TPTNS) with low dose trospium chloride in the treatment of females with overactive bladder (OAB) would be more effective than TPTNS alone after failure of behavioral therapy. Methods We randomized 30 women with OAB, in two groups: G I (15 patients) received 30 minutes TPTNS, three times a week; GII (15 patients) received TPTNS plus Low dose trospium chloride (20 mg once daily); all for 8 weeks. Patients were evaluated using Overactive Bladder Symptom Score questionnaire (OABSS) which includes 3 categories (score < 5 = mild symptoms, 6-11 = moderate symptoms, > 12 = severe symptoms), Incontinence Impact Questionnaire-short form 7 (IIQ-7) which includes 3 categories (score < 50% = good quality of life, 50-70% = moderate quality of life and > 70 = poor quality of life), 3 day voiding diary and urodynamics at weeks 0 and 8. Results The groups were similar before treatment. After treatment both groups improved regarding all the parameters, however group II showed more significant improvement. The OABSS was reduced from 13.0 ± 1.31 to 8.53 ± 1.30 (p<0.001) and from 12.67 ± 1.95 to 10.0 ± 2.0 (p<0.001) in GII and GI respectively. Improvement (change from one category to a better one) occurred in 8 (53.3%) and in 14 (93.3%) patients in GI and GII respectively. The mean IIQ-7 was reduced from 63.38 ± 8.81 to 31.99 ± 9.26 (p<0.001) for GII vs. 64.33 ± 8.57 to 51.86 ± 17.26 (0.002) for GI. Before treatment, 11 (73.3%) and 4 (26.7%) patients in each group had moderate and poor quality of life respectively. After treatment, 6 (40%) and 14 (93.3%) had good quality of life, 7 (46.7%) and 1 (6.7%) had moderate quality of life in GI and GII respectively. Two (13.3%) in GI had poor quality of life. The mean frequency for GII after treatment was 8.60 ± 0.83 instead of 12.87 ± 1.85 (p<0.001) before treatment, while it was reduced from 13.13 ± 1.64 to 10.60 ± 2.32 (p=0.003) in GI. The cystometric capacity improved from 263.40 ± 50.45 ml to 377.80 ± 112.92 ml (p=0.001) for GII Vs. 250.13 ± 56.24 ml to 296.40 ± 99.0 ml (p=0.026) for GI. Conclusions TPTNS combined with low dose trospium chloride proved to be more effective than TPTNS alone in the treatment of OAB in females. Funding none
Authors
Amr Abulseoud
Gaber Ali Mohamed Hassouna Ahmed Moussa Ibrahim Ibrahim Emmanuel Saba |
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PD54-11 |
Electrical Stimulation of Afferent Nerves in the Foot with Transcutaneous Adhesive Pad Electrodes in Women with Refractory Overactive Bladder: Defining Ideal Stimulation Duration |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Female Incontinence: Therapy III | 17BOS |
Abstract: PD54-11 Sources of Funding: Colter Foundation Grant at the University of Pittsburgh Introduction A non-invasive and convenient overactive bladder (OAB) treatment with no major adverse events would be ideal. We previously showed that stimulation of afferent nerves in the foot for 3 hours daily with transcutaneous adhesive pad electrodes (FootStim) decreased urgency urinary incontinence (UUI) and urgency frequency in women with refractory OAB. Yet, the ideal stimulation duration remains unknown. In this study, we sought to define the ideal stimulation duration in women with refractory OAB who underwent FootStim for either 30 minutes or 3 hours daily for 1 week._x000D_ Methods Women with refractory OAB were recruited onto the study. All these patients with UUI stopped OAB drug therapy 2 weeks prior to study initiation. A 3-week voiding diary was obtained, and FootStim was applied during week 2. The patients underwent FootStim for either 30 minutes or 3 hours daily. Baseline voiding parameters were measured during week 1, and the post-stimulation effect was measured during week 3. Adhesive pad electrodes were attached to the bottom of the foot and connected to a transcutaneous electrical nerve stimulator. Stimulation parameters included pulse frequency of 5 Hz, pulse width of 0.2 ms, and intensity of 2-4 times the minimal stimulation necessary to induce a toe twitch. Responder was defined as having a statistically significant improvement in 1 or more OAB symptoms. Results 33 women completed the study, of which 19 underwent stimulation for 3 hours and 14 underwent stimulation for 30 minutes. The response rates were 16/19 (84%) in the 3 hour group and 10/14 (71%) in the 30 minute group. In the 3 hour group incontinence frequency decreased from 3.7 to 2.8 leaks/day (p=0.04) and urgency frequency decreased from 7.6 to 6.6 episodes/day (p=0.03). Daytime voiding frequency (n=8) and nocturia (n=7) decreased in the 3 hour group. In contrast, only incontinence frequency decreased in the 30 minute group, and this dropped from 5.3 to 4.3 leaks/day (p=0.03). In the 30 minute group urgency frequency improved in 2, nocturia improved in 1, and daytime urinary frequency improved in none. FootStim effects persisted in both groups for 4 days after treatment ended. There were no adverse events in either group. Conclusions FootStim for either 30 minutes or 3 hours daily decreased UUI frequency in women with refractory OAB; however, FootStim for 3 hours better improved the other OAB symptoms. Our results support further testing of FootStim to determine long-term efficacy and stimulation schedule. Funding Colter Foundation Grant at the University of Pittsburgh
Authors
Christopher J Chermansky
Bing Shen Janet Okonski William C de Groat Changfeng Tai |
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PD54-12 |
Statewide Trends of InterStim® Implantation Across Different Surgical Specialties in New York |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Female Incontinence: Therapy III | 17BOS |
Abstract: PD54-12 Sources of Funding: none Introduction With the number of indications increasing for sacral neuromodulation (SNM), multiple surgical specialties are now performing the procedure. However, it is unknown what proportion of implants are being performed by each specialty. The level of training of those performing SNM implants has also never been studied. We aim to assess trends in Interstim® generator implants and subsequent revisions or removals performed in New York state._x000D_ Methods The Statewide Planning and Research Cooperative System (SPARCS) is a comprehensive all payer data reporting system that collects patient level details on hospital and outpatient visits in New York State. We queried all SNM generator implantations from 2011 to 2014 (CPT code 94590) as well as device revision or removal (CPT codes 94585 and 94595). Results From 2011-2014, a total 1,454 implants were performed in NYS. 60.5%, 14.8%, and 19.2% were performed by urologists, gynecologists, and colorectal surgeons (CRS), respectively. 44% (408/931) of urology implants and 64% (146/228) gynecology implants were performed by Female Pelvic Medicine and Reconstructive Surgery (FPMRS) trained physicians. The number of cases performed by urologists decreased significantly in 2014 while CRS nearly doubled the number of implants performed each year from 2011 to 2013 (Figure 1). 8.5% of implants required subsequent revision or removal during this time period. There were no statistical differences in Interstim® revision or removal rates between implants performed by urologists (9.0%), gynecologists (10.1%), or CRS (5.4%, p=0.097). There was also no statistical difference in revision or removal rates when comparing implants performed by those with a fellowship in FPMRS (9.9%) and those without (11.4%, p=0.414). Conclusions In recent years, SNM implantation has been primarily performed by urologists in NYS. Following FDA approval of Interstim® for fecal incontinence in 2011, CRS have dramatically increased the number of cases they perform. Neither surgical specialty nor FPMRS fellowship training appear to affect revision or removal rates in the short term. Funding none
Authors
Wai Lee
Andrew Chen Olga Povcher Kailash Kapadia Wei Hou Jason Kim |
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PD55-01 |
Dutasteride and active surveillance in prostate cancer: are visible lesions less conspicuous at magnetic resonance imaging? A pilot randomized controlled trial |
Prostate Cancer: Localized: Active Surveillance III | 17BOS |
Abstract: PD55-01 Sources of Funding: None Introduction Dutasteride 0.5mg daily is licensed for lower urinary tract symptoms (LUTS) in men with an enlarged prostate, and some men on active surveillance will be taking dutasteride for LUTS. _x000D_ This study was designed to describe the effects of daily 0.5 mg dutasteride for 6 months, compared to placebo, on men with biopsy proven prostate cancer and an MR lesion at baseline. We report here the effect of dutasteride on the conspicuity of tumor on diffusion-weighted imaging (DWI) sequences to answer the question: does dutasteride make visible lesions less conspicuous on DWI?._x000D_ Methods Institutional review board approval and patient informed consent were obtained. We retrospectively analyzed 37 men, randomized to 6 months of daily dutasteride 0.5 mg (n=18) or placebo (n=19), undergoing 3T multi-parametric Magnetic Resonance Imaging (mpMRI) scans at baseline and 6 months. Images were reviewed by 2 experienced uro-radiologists in consensus blind to treatment allocation and clinical information. Mean apparent diffusion coefficient (ADC) from DWI of peripheral (PZ) and transition (TZ) zones, and MR-suspicious lesions were compared between the dutasteride and placebo groups at baseline and 6 months (T test; p < 0.05 significant). _x000D_ We defined the term conspicuity as the mean ADC of the PZ divided by the mean ADC of the lesion. We assessed the change in conspicuity over 6 months and analyzed the differences in the dutasteride and placebo groups._x000D_ Results All men had at least one visible lesion at baseline and 6 months on DWI. There were no significant differences at 6 months for ADC values in the PZ, TZ and lesions between the two groups (placebo vs dutasteride). There was a significant decrease in mean conspicuity in the dutasteride group (1.54 at baseline vs 1.38 after 6 months; p = 0.025)._x000D_ Changes in mean absolute tumor ADC and conspicuity between the placebo and dutasteride groups were demonstrated (- 0.03 vs 0.08, p =0.033) and (0.11 vs - 0.16, p = 0.012), respectively. _x000D_ There was a significant percentage increase in tumor ADC and a significant decrease in the conspicuity for the dutasteride group when compared to men in the placebo group (8.6% vs - 2.3%, p = 0.048) and (- 9.9% vs 9.3, p = 0.013), respectively. _x000D_ Conclusions Dutasteride reduces tumor ADC and conspicuity. A lower biopsy threshold would make sense in men who are on dutasteride for LUTS and are undergoing MRI assessment for prostate cancer. Funding None
Authors
Francesco Giganti
Caroline Moore Nicola Robertson Alex Freeman Mark Emberton Clare Allen Alex Kirkham |
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PD55-02 |
The Use of Five-Alpha Reductase Inhibitors and their Association with Reclassification and Pathologic Outcomes in the Canary Prostate Active Surveillance Study (PASS) |
Prostate Cancer: Localized: Active Surveillance III | 17BOS |
Abstract: PD55-02 Sources of Funding: Canary Foundation, Department of Defense (PC130355), and Institute for Prostate Cancer Research Introduction The outcomes of patients who enroll in active surveillance (AS) programs for prostate cancer (PCa) while currently taking five-alpha reductase inhibitors (5-ARIs) have not been well defined. Previous studies suggest that the initiation of 5-ARIs after enrolling in AS decreases the rate of reclassification and/or treatment for PCa, but there is still an FDA black box warning about the risk of grade risk prostate cancer while on 5-ARI. The objective of this study was to evaluate the safety of remaining on a 5-ARI after initiating AS for PCa. Methods All men were enrolled in PASS. Inclusion criteria were current or never 5-ARI user, Gleason 3+3 or 3+4 PCa at diagnosis, ≤ 34% core ratio at diagnosis and ≥ 1 surveillance biopsy. Reclassification was defined as an increase in Gleason score and/or ratio of biopsy cores positive for cancer to ≥ 34%. Results 1045 men were included in this study, 938 who had never used a 5-ARI and 107 5-ARI users. 5-ARI users had larger prostate volume (51 cc vs 40 cc, p < 0.01), a higher rate of BPH (77% vs 29%, p < 0.01) and older age (65 vs 62 years, p < 0.01). All other clinical parameters, including serum PSA, were statistically similar._x000D_ _x000D_ There was no significant difference in any reclassification (p = 0.12). The use of 5-ARI at diagnosis was significantly protective for reclassification in a proportional hazards model (HR 0.68, p = 0.03); this difference was not significant after accounting for serum PSA, BMI, prostate size and positive cores ratio at diagnosis (HR 0.78, p = 0.18) (Table). There was no significant effect on adjusted analysis when evaluating for disease upgrading._x000D_ _x000D_ 171 patients underwent radical prostatectomy (RP), 158 never 5-ARI users and 13 5-ARI users. There were no statistically significant differences when evaluating for Gleason grade or adverse pathology. 5-ARI users had a longer median time to RP (3.6 vs 2.1 years, p = 0.045). Conclusions There is no association between 5-ARI use at diagnosis and reclassification on AS for men in the Canary PASS cohort. 5-ARI users have a longer median time to RP and do not have more severe PCa at RP. Funding Canary Foundation, Department of Defense (PC130355), and Institute for Prostate Cancer Research
Authors
James Kearns
Anna Faino Lisa Newcomb James Brooks Peter Carroll Atreya Dash William Ellis Michael Fabrizio Martin Gleave Todd Morgan Peter Nelson Ian Thompson Andrew Wagner Yingye Zheng Daniel Lin |
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PD55-03 |
Active surveillance for low-risk prostate cancer in men under 60 years of age |
Prostate Cancer: Localized: Active Surveillance III | 17BOS |
Abstract: PD55-03 Sources of Funding: None Introduction Active surveillance (AS) is increasingly used in managing low-risk prostate cancer. Data on outcomes of AS in younger men are limited. We present characteristics and outcomes of two cohorts of men who began AS at under 60 years of age. Methods We reviewed our institutional AS databases at the Massachusetts General Hospital (MGH) (n = 990) and Sunnybrook Health Sciences Centre (n =1162) of men diagnosed with low-risk prostate cancer between 1990-2016 to identify 432 men under age 60 (n = 181, MGH; n = 251, Sunnybrook). Clinical outcomes were analyzed, including repeat biopsy data, progression to treatment, and pathologic staging in those who had surgical treatment. Survival estimates were generated by Kaplan-Meier analysis. Results At diagnosis, median age was 55 years (IQR 53-57) and median PSA was 4.6 ng/mL (IQR 3.1-5.9), with only 11 of 432 men with PSA ≥10 ng/mL. The vast majority of patients had Gleason ≤6 (97.7%) and clinical stage T1 (91.9%) disease. With a median follow-up of 5.1 years (range: 0.05-21.7; IQR: 3.1-8.4), 84.3% (364/432) had a repeat biopsy with 62.6% (228/364) showing prostate cancer, 24.5% (89/364) benign, 7.7% (28/364) with PIN, and 5.2% (10/364) with atypia. Kaplan-Meier actuarial freedom-from-treatment was 74.3% at 5 years and 55.4% at 10 years. Of all 432 patients, 131 (30.3%) progressed to treatment for the following reasons: pathologic progression (64.1%), PSA progression (18.3%), patient preference (11.5%), volume progression (3.1%) and other reasons (3.1%). Among the 131 treated patients, 62.6% underwent radical prostatectomy, 13.0% underwent high-intensity focal ultrasound therapy, 12.2% underwent external beam radiation and 10.7% had brachytherapy. On pathologic review after surgery, 88.2% (60/68) were pT2, and 11.8% (8/68) pT3. Five patients developed metastasis (2 with positive lymph nodes at time of radical prostatectomy, 3 with distant metastasis). Metastasis-free survival was 99.7% and 97.5% at 5 and 10 years, respectively. There were no prostate-cancer specific deaths. Conclusions Active surveillance is a reasonable option for carefully selected men under 60 with low-risk prostate cancer. However, patients must be surveyed closely and understand the significant risk of ultimately needing treatment. Funding None
Authors
Keyan Salari
David Kuppermann Mark Preston Douglas Dahl Jason Efstathiou Michael Blute Danny Vesprini Andrew Loblaw Anthony Zietman Laurence Klotz Adam Feldman |
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PD55-04 |
The ERSPC versus the ProtecT study: outcomes after active surveillance compared to surgery and radiotherapy for localized prostate cancer. |
Prostate Cancer: Localized: Active Surveillance III | 17BOS |
Abstract: PD55-04 Sources of Funding: None Introduction The safety of active surveillance (AS) remains topic of debate, but must be evaluated in light of results from the &[prime]golden standard&[prime] therapies, e.g. radiotherapy (RT) and radical prostatectomy (RP). The ProtecT study published 10-yr outcomes after randomization to active monitoring (AM), RT or RP; with higher risk patients and a less strict follow-up protocol than contemporary AS. In the European Randomized study of Screening for Prostate Cancer (ERSPC) Rotterdam, a subgroup of patients also received AM/AS, although more often according to a strict protocol (e.g. PRIAS). Methods We evaluated death rates among men with low to intermediate risk prostate cancer (PC) treated with AS, RT or RP in the ERSPC and compared these to ProtecT. Men with low risk (Gleason score (GS) 6, cT1C/cT2A) and intermediate risk (GS ≤3+4, cT1c/cT2) PC, diagnosed in the 1st and 2nd screening round (1993-2003) were included. Controlling for age, PSA, clinical stage, GS and comorbidities, we performed cox proportional hazard analyses. Results Of the 2280 PC patients, 905 and 1275 had low and intermediate risk PC, resp. Median age and PSA were 66.4 yrs and 4.3 ng/mL; 66,6 yrs and 4.5 ng/mL, resp. Median follow-up was 13 yrs._x000D_ In the low risk group, the hazard ratio (HR) for PC specific death for RT/RP (n=370/312) vs AS (n=223) was 0.61 (95%CI 0.18-2, p=0.41). The HR for overall death was 1.29 (95% CI 0.97-1.72). _x000D_ In the intermediate risk group, the HR for PC specific death for RT/RP (n=501/526) vs AS (n=248) was 0.65 (95%CI 0.25-1.64, p=0.36). The HR for overall death was 1.23 (95% CI 0.95-1.59). See Figure 1._x000D_ In the ProtecT study, the HR for PC specific death for RT vs. AM was 0.51 (95% CI 0.15-1.69) and for RP vs. AM 0.63 (95% CI 0.21-1.93), p=0.48. The HR for overall death was not specified (p=0.87 across treatment groups)._x000D_ Conclusions The HR for PC specific death for AS vs immediate active therapy, between the ERSPC Rotterdam and ProtecT, seem comparable. Although the ERSPC was not randomized, but includes 13 yr complete follow-up and consensus based cause of death assignment, these data confirm that AS as an initial treatment, as compared to immediate active therapy, results in similar low PC specific death rates. In the end, quality of life and hence the personal treatment preference of the patient should be decisive. Funding None
Authors
Frank-Jan Drost
Arnout Alberts Chris Bangma Monique Roobol for the ERSPC Rotterdam group |
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PD55-05 |
Active surveillance is a viable option for men with borderline low-risk prostate cancer |
Prostate Cancer: Localized: Active Surveillance III | 17BOS |
Abstract: PD55-05 Sources of Funding: None Introduction Eligibility criteria for active surveillance (AS) for low-risk prostate cancer have been defined by multiple series reported in the literature. In clinical practice occasional patients who do not meet all criteria may choose AS. We investigated outcomes in borderline cases. Methods We investigated our institutional database of 990 men on AS between 1997-2014. Our guidelines for AS eligibility, formalized in 2008, include Gleason ≤6, stage ≤cT2a, PSA ≤10 ng/mL, ≤3 of 12 cores positive at diagnosis, and ≤20% of any core involved at diagnosis. For this analysis, we defined borderline cases for AS as those patients with one or more of either Gleason score 7, PSA >10, stage cT2a, >33% of cores positive at diagnosis, or >20% of any core involved at diagnosis. Survival analyses were conducted using Kaplan-Meier and Cox proportional hazards. Results In the entire cohort (n=990), mean age at diagnosis was 66.9 years (±7.9) and median PSA 5.1 (IQR 4-6.87). While the majority met all AS criteria, 310 patients (31.3%) met at least one of the borderline AS criteria; 2.4% of patients had Gleason 7, 7.6% had PSA >10, 8.0% were cT2a, 3.9% (37/943) had >33% of cores positive at diagnosis, and 18.4% (156/848) had >20% of any core involved. With mean follow-up 4.5 years, univariate survival analysis demonstrated no difference in freedom from treatment (FFT) between patients with Gleason 7 vs. ≤6, >33% vs. ≤33% cores involved, or PSA >10 vs. ≤10. Lower FFT was noted among patients with cT2a vs. ≤cT1c disease (62.0% vs. 70.8%, P=0.04), patients with >20% vs. ≤20% of any core involved (61.5% vs. 71.8%, P=0.009), as well as those with PSA density ≥0.15 vs. <0.15 (61.1% vs. 72.0%, P = 0.0006). In multivariate analysis, >20% core involvement and PSA density ≥0.15 remained a significant predictor for treatment (P=0.003), adjusting for PSA >10, Gleason >6, >33% cores involved, and stage. Among the 310 borderline AS cases, there were only 6 (1.9%) cases of metastasis and 1 (0.3%) prostate cancer-specific death. These adverse outcomes were equivalent to the remainder of the cohort meeting strict AS criteria, which included 10 (1.5%) cases of metastasis and 2 (0.3%) prostate cancer-specific deaths. Conclusions Active surveillance remains a viable option for select patients who are borderline cases per current AS criteria. However, patients with higher volume disease and higher PSA density may be more likely to progress to treatment. Long-term clinical outcomes in these patients should continue to be investigated. Funding None
Authors
Keyan Salari
David Kuppermann Mark Preston Douglas Dahl Aria Olumi Jason Efstathiou Richard Lee Chin-Lee Wu Michael Blute Anthony Zietman Adam Feldman |
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PD55-06 |
PSA velocity in men starting 5-alpha-reductase inhibitors at the time of starting active surveillance is a predictor of pathological progression in Low-Risk Prostate Cancer |
Prostate Cancer: Localized: Active Surveillance III | 17BOS |
Abstract: PD55-06 Sources of Funding: none Introduction 5-alpha-reductase inhibitors (5ARI) are being increasingly used among low-risk active surveillance (AS) patients. The REDUCE trial suggested that 5ARIs may reduce the rate of pathological progression in men on AS. However, limited work has been done to assess the predictive value of prostate-specific antigen (PSA) velocity (PSAV) during time to PSA nadir in patients on 5ARI. _x000D_ _x000D_ We examined the predictive value of PSAV for pathological outcomes at confirmatory biopsy among low-risk prostate cancer patients taking 5ARI during AS. Methods A total of 240 patients (between 1994-2015) taking 5ARI were captured from the Princess Margret Hospital Active Surveillance database. A total of 43 (18%) patients were excluded (17 started 5ARI after diagnosis and 26 patients missing PSA) and n=197 patients had at least 3 PSA values to determine PSAV. The nadir PSA was defined as the lowest value achieved by patients after initiation of 5ARI. PSAV was calculated using the general linear mixed-model method. We subsequently examined pathological progression on confirmatory biopsy using multivariate logistic regression adjusting for patient and disease characteristics. Results Of 240 patients, we identified 197 low-risk PC patients (median age 63 y) undergoing AS, who had a confirmatory biopsy at a median of 12 months (IQR 7-18). 76% of patients on 5ARI had PSA declines; maximum nadir PSA was over 6 months, with 34 percent PSA decline from baseline. _x000D_ _x000D_ The overall pathological progression rate was 25 (11.2%) and 16 (7.2%) patients had grade progression on confirmatory biopsy among patients with 5ARI use. PSAV was significantly greater (i.e. larger decline, median -1.46 ng/ml/year) in those who did not experience overall pathological progression compared to those who did (median -0.45 ng/ml/year, p=0.02). Similarly, PSAV was significantly greater in men without grade progression (median - 1.54 and -0.57 ng/ml/year for non-progressors versus progressors, respectively, p=0.03). In multivariate logistic regression, PSAV during nadir was a statistically significant predictor of the overall pathological progression, odds ratio (OR) 1.17 (95%CI 1.01-1.38, p=0.04) and grade progression (OR 1.22, 95%CI 1.00-1.51, p=0.05). Conclusions 5ARI use significantly decreased PSA levels within 6 months of starting AS. The PSAV was lower (smaller) in patients who progressed compared to those who did not progressed with 5ARI use. PSAV is a significant predictor of both overall and grade progression among low-risk AS patients. Funding none
Authors
Narhari Timilshina
Shabbir Alibhai Maria Komisarenko Lisa Martin Ruby Grewal Rob Hamilton Girish kulkarni Alexandre Zlotta Neil Fleshner Antonio Finelli |
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PD55-07 |
Very low risk and low risk patients in active surveillance: Is the distinction relevant? |
Prostate Cancer: Localized: Active Surveillance III | 17BOS |
Abstract: PD55-07 Sources of Funding: PCORI ME-1408-20318 Introduction Active Surveillance (AS) of localized prostate cancer (PCA) has been shown to be a safe alternative to immediate curative treatment for men with favorable risk diagnoses; very low risk (VLR) and low risk (LR). The relevance of stratifying patients into VLR and LR categories for the purposes of enrollment and analysis is in question. Our objective was to compare the difference in cancer risk for men with VLR and LR disease. Methods We used the clinical data from 1,032 VLR and 446 LR patients enrolled in the Johns Hopkins prospective AS program to predict the pathologic Gleason score (PGS) as the outcome of interest. Predictions were obtained by extending a statistical model developed in the VLR cohort (SITE PUBLICATION HERE), to estimate different probability distributions of PGS between VLR and LR groups. This approach leverages 1) repeated PSA and biopsy measurements taken in the course of AS, 2) post-prostatectomy PGS findings in AS patients to identify patterns of clinical measurements associated with more aggressive pathology. The model is agnostic with regard to differential risk a priori (i.e., biopsy extent of cancer). Results LR patients were significantly more likely than VLR patients to have a PGS above 6 (p<0.01). The estimated probability of PGS=6 for VLR and LR patients was 71% and 57%, respectively (Table). Both VLR and LR patients were unlikely to have predicted PGS of >4+3; 9.2% and 10%, respectively._x000D_ _x000D_ Conclusions As compared to VLR, men with LR PCA were more likely to harbor pathologically significant disease, suggesting that this distinction is clinically relevant. Long term cancer specific outcomes will be necessary to confirm the clinical significance of these findings. Funding PCORI ME-1408-20318
Authors
R. Yates Coley
Scott Zeger Mufaddal Mamawala H. Ballentine Carter |
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PD55-08 |
Introducing mpMRI into contemporary UK active surveillance for localised prostate cancer |
Prostate Cancer: Localized: Active Surveillance III | 17BOS |
Abstract: PD55-08 Sources of Funding: None Introduction Active surveillance (AS) of localized prostate cancer (PCa) in the UK involved protocol-driven (P) transrectal repeat biopsies (RB) plus serial digital rectal examination & PSA-testing, until NICE 2014 guidelines recommended multi-parametric magnetic resonance imaging (mpMRI) should drive RB where needed or replace P-RB. Interrogating our AS follow-up (F/U) data, we hypothesized that mpMRI reduces the number of RB required to drive therapeutic intervention (TI). Methods 445/461 (97%) AS patients had complete F/U data. Cohort features at diagnosis include median age 68.9 years (interquartile range IQR 63.7-74.8), median PSA 7.2ng/mL (IQR 5.6-9.6), median PSAD 0.11 (IQR 0.08-0.18), ≤cT1c in 80%, 54% unilateral Gleason 3+3, 23% unilateral 3+4, 2% unilateral ≥4+3, 18% bilateral ≥3+3, and median Charlson Comorbidity score 3.1 (IQR 2.5-4.2). We examined the drivers for TI and compared the utility of mpMRI prior to potential RB in AS. Results 132/445 (30%) patients underwent TI (59% external beam radiotherapy/brachytherapy, 22% radical surgery, 19% other) over a median AS (inter-quartile range IQR) F/U of 2.4 (1.2-3.73) years (maximum F/U 11.3 years). Median (IQR) time to TI was 1.55 (0.71-2.4) years. Reasons for TI included rising PSA, patient choice, mpMRI abnormality alone and/or RB Gleason upgrading. Where TI was driven by RB, 43/71 (61%) had undergone mpMRI, and 39% had P-RB without mpMRI. 49/97 (51%) demonstrated upgrading on RB following mpMRI versus 38/115 (33%) for P-RB without mpMRI. Time to TI was similar for those undergoing RB following mpMRI versus P-RB without mpMRI (P=0.877). Of those upgraded at RB, the number of RB procedures needed to upgrade one patient was 1.9 if prior mpMRI was used versus 3.3 for P-RB alone._x000D_ Conclusions In this UK cancer centre AS cohort, replacement of P-RB with mpMRI ± RB where indicated, benefitted patients by reducing the number of invasive interventions needed to identify disease progression (characterized by Gleason upgrade), leading to treatment intervention. Funding None
Authors
Richard Bryant
Bob Yang Yiannis Philippou Karla Lam Maureen Obiakor Jennifer Ayers Fergus Gleeson Ruth MacPherson Clare Verrill Ian Roberts Thomas Leslie Jeremy Crew Prasanna Sooriakumaran Freddie Hamdy Simon Brewster |
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PD55-09 |
Role of mpMRI PSA Density and PIRADS Score in Predicting Upstaging in Men on Active Surveillance |
Prostate Cancer: Localized: Active Surveillance III | 17BOS |
Abstract: PD55-09 Sources of Funding: None Introduction Active surveillance (AS) has gained increased popularity for its role in reducing overtreatment of low-risk prostate cancer. One major concern about AS is the potential for understaging more aggressive disease. Additionally, men on AS are often subject to numerous prostate biopsies which also carries morbidity risk. Multiparametric MRI (mpMRI) of the prostate has demonstrated its ability to better detect clinically significant prostate cancer (CSPC) versus standard TRUS-biopsy alone. Using mpMRI, we aim to determine which men on AS are at risk of being upstaged, and which men could potentially avoid repeat biopsy while safely remaining on AS. Methods We reviewed men on AS who underwent mpMRI of the prostate followed by MRI-TRUS (Uronav) fusion biopsy between January 2014 and May 2016. All men had a standard 12-core biopsy simultaneously or within the past 12 months. For this study, CSPC is defined as Gleason score ≥7. Using univariate and multivariate logistic regression analyses, we examined the effect of age, race, PSA, PSA density (PSAD), prostate volume by MRI, PIRADS score, lesion size, number of lesions, and DRE to determine the likelihood of upstaging to CSPC. The multivariate model was selected using Akaike Information Criterion to optimize model parsimony and fit. Results A total of 101 men on AS underwent MRI-TRUS fusion biopsy. Patients had a median age of 66.5 years, PSA of 6.5ng/mL, prostate volume of 47.9mL, and PSAD of 0.14. Univariate analysis revealed that PSA, PSAD, increasing PIRADS score, lesion size >2cm, and 3 or more lesions on MRI increased the odds of CSPC. Multivariate logistic regression demonstrated that PSAD ≥0.15 (OR 2.66, CI 1.0-7.03, p=0.049) and increasing PIRADS score (PIRADS 4: OR 10.6, CI 2.1-53, p=0.004; PIRADS 5: OR 15, CI 2.8-80, p=0.002) were independent predictors of CSPC. Men with a PIRADS score of ≥3 with a PSAD ≥0.15 had a 55% chance of being upstaged to CSPC. Conversely, in men with PIRADS score ≤3 with a PSAD <0.15, no upstaging was seen (Figure). Conclusions In men on AS, the combination of mpMRI PSAD and PIRADS score predicts upstaging when PIRADS score is ≥3 with a PSA density ≥0.15. When this criteria is not met, men may potentially forgo repeat biopsy while safely maintaining them on AS. Further prospective study is warranted. Funding None
Authors
Michelle Van Kuiken
Robert H. Blackwell Bryan Bisanz Joseph Yacoub Ari Goldberg Steven Shea Marcus Quek Gopal N. Gupta |
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PD55-10 |
Oncologic Outcomes after Radical Prostatectomy in Favorable Intermediate Risk Group Active Surveillance Candidates |
Prostate Cancer: Localized: Active Surveillance III | 17BOS |
Abstract: PD55-10 Sources of Funding: None. Introduction NCCN active surveillance (AS) guidelines have recently expanded to include select intermediate-risk prostate cancer patients, but data supporting the safety of AS in these patients are limited. We compare the pathologic and oncologic outcomes of these favorable intermediate-risk patients to very low, low, and unfavorable intermediate-risk patients in a cohort of radical prostatectomy (RP) patients. Methods Patients in our prospectively maintained database meeting NCCN very low (T1c, Gleason ≤6, ≤3/12 cores, ≤50% core volume, and PSA density <0.15), low (T1-T2a, Gleason ≤6, PSA <10), favorable intermediate (major pattern grade 3, ≤3/12 cores, ≤50% core volume, and only ONE intermediate risk factor [T2b/c, Gleason 7, or PSA 10-20]), or unfavorable intermediate (all other intermediate) risk criteria were identified. Incidence of adverse pathologic findings at RP (Gleason score upgrading to primary pattern 4 or 5, non-organ confined disease) was compared between favorable intermediate and very low / low-risk groups (chi-squared test). Kaplan-Meier analysis compared biochemical progression free survival among all groups. Results 3669 patients underwent RP between 1/1/04 and 12/31/15. Of these, 1454, 251 and 1361 patients fulfilled criteria for very low/low, favorable intermediate, and unfavorable intermediate-risk groups, respectively. Median follow-up was 37 months. Patients in the favorable intermediate group had significantly higher rates of Gleason score upgrading (16% vs 6%; p<0.001) and non organ-confined disease (16% vs 11%; p=0.035) than those in low risk group. Time to biochemical recurrence for the favorable intermediate group did not differ significantly from the low risk group (p=0.057), but was significantly longer than unfavorable intermediates (p=0.003) (Figure 1). Conclusions Compared to very low/low risk prostate cancer patients, men with favorable intermediate-risk disease had significantly higher rates of more aggressive, non-organ confined disease at RP, and trended toward worse biochemical progression free survival. However, when compared to unfavorable intermediate risk patients, it appears the magnitude of these differences would not preclude AS as a reasonable option for appropriately selected patients with favorable intermediate risk prostate cancer. Funding None.
Authors
Monty Aghazadeh
Jason K Frankel MD Matthew Belanger Tara McLaughlin PhD Ilene Staff, PhD Joseph Wagner, MD |
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PD55-11 |
Is favorable intermediate risk prostate cancer really favorable? Implications for Active Surveillance Strategies |
Prostate Cancer: Localized: Active Surveillance III | 17BOS |
Abstract: PD55-11 Sources of Funding: None Introduction Select patients with Gleason 7 prostate cancer (CaP) are managed by active surveillance (AS) at our institution. In fact, the most recent National Comprehensive Cancer Network (NCCN) guidelines have endorsed use of AS in patients with favorable-intermediate risk (FIR) CaP. The aim of this study is to assess oncologic and pathologic findings at radical prostatectomy (RP) in men classified by the NCCN risk strata. Methods This is an observational study of prospectively collected data of patients undergoing RP from 2005 to 2015. FIR CaP was defined as: Gleason grade 3+4, ≤50% of cores positive, and no more than one of the following: PSA >10 or clinical stage >T2a. Rates of adverse pathology at RP and biochemical recurrence (BCR) were compared in stratified analysis by NCCN risk grouping: very-low risk (VLR), low-risk (LR), FIR, and those with intermediate risk disease not meeting FIR criteria, termed unfavorable intermediate risk (UIR). Adverse pathology was defined as Gleason grade >3+4, extracapsular extension (ECE), seminal vesicle invasion (SVI), lymph node invasion (LNI), or a composite adverse pathology variable (AP). Results There were 1413 patients identified, of which 353 met criteria for FIR. The mean age of the entire cohort was 60.8 ± 6.7 years. with median follow-up time of 30.0 (IQR 11.7-42.2) months. Rates of AP increased accordingly with risk group (Table 1). The FIR group showed rates of AP between LR and UIR. On age-adjusted logistic regression analysis, risk grouping significantly correlated with AP (p<0.05). The cumulative survival-free BCR probabilities are also listed in Table 1, with the FIR group demonstrating rates more similar to VLR/LR than UIR. A Cox regression analysis controlling for age, ethnicity and prior biopsy status demonstrated similar hazard ratios (HR) for developing BCR in the LR (OR 6.1, 9% CI 1.3,28.8) and FIR (OR 5.88, 95% CI 1.3,25.8) groups, as opposed to higher HR in UIR ( OR 14.3, 95% CI 3.5, 59.1), when compared to the reference group (VLR). Conclusions Patients with FIR CaP have proportional rates of adverse pathology compared with lower risk CaP. However, intermediate-term clinical outcomes suggest more favorable clinical behavior, which may be related to the biology of these tumors. This has significant implications when considering patients for AS. Funding None
Authors
Samuel Haywood
Yaw Nyame Helen Liang Eric Klein Andrew Stephenson |
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PD55-12 |
Older age at diagnosis and disease volume predict upgrading on confirmatory biopsy in prostate cancer patients being considered for active surveillance |
Prostate Cancer: Localized: Active Surveillance III | 17BOS |
Abstract: PD55-12 Sources of Funding: None Introduction Prior single-institution retrospective studies suggest that age may independently predict risk of Gleason progression on repeat biopsy following a diagnosis of low risk prostate cancer (PCa). Older men experience higher rates of PCa-specific mortality; therefore, the appropriateness of active surveillance may differ in an older patient population and is influenced by the probability of undersampling for occult higher grade disease. Furthermore, the clinicopathologic features most useful in guiding decisions to re-biopsy remain poorly defined. We therefore sought to investigate the risk of Gleason upgrading on repeat biopsy, as well as the features most suggestive of potential Gleason misclassification. Methods We retrospectively reviewed charts of 635 men on active surveillance at our institution between 2002 to 2015. Demographic and clinicopathologic features including age, race, initial PSA, prostate volume, clinical staging, and biopsy findings were collected. Within this population, we identified 556 men who were diagnosed with Gleason 3+3 disease on initial biopsy, of whom 406 received a documented confirmatory biopsy within 1 year of diagnosis. Logistic regression modeling was performed to determine features associated with detection of Gleason 7 or higher disease on confirmatory biopsy. Results Eighty-five of 406 patients (21%) with initial Gleason 6 disease who received a repeat confirmatory biopsy were found to have grade reclassification. On multivariable analysis, older age (per year OR 1.07; 95% CI 1.02-1.11; p = 0.003) and number of positive cores (per core, OR 1.38, 95% CI 1.10-1.73; p = 0.05) were significantly associated with reclassification on confirmatory biopsy (Table 1). Initial prostate volume, clinical stage, and PSA were not found to be associated with this risk. Conclusions Older age and the number of positive cores on diagnostic biopsy appear to predict for risk of misclassification of Gleason 7 or greater disease. Therefore, in this setting, a repeat biopsy may be particularly warranted to minimize the chances of diagnostic misclassification. Funding None
Authors
Charles Dai
Vishnu Ganesan Nima Almassi Yaw Nyame Daniel Greene Daniel Hettel Alice Crane Joseph Zabell Anna Zampini Samuel Haywood Hans Arora Chad Reichard Ahmed El-Shafei Robert Stein Khaled Fareed Michael Gong J. Stephen Jones Andrew J. Stephenson Eric Klein |
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PD56-01 |
Long-Term Outcomes of Salvage Cryoablation for Recurrent Prostate Cancer Following Radiation Therapy: A Combined Analysis of Two Centers |
Prostate Cancer: Localized: Ablative Therapy II | 17BOS |
Abstract: PD56-01 Sources of Funding: None Introduction There is a paucity of long-term data following local recurrences from radiation refractory prostate cancer (RRPCa). We analyzed the long-term survival outcomes of salvage cryoablation (Cryo) for RRPCa cancer across two centers. Methods Patients undergoing salvage Cryo for biopsy proven, localized RRPCa from 1990 to 2004 were prospectively accrued. Preoperative characteristics, perioperative morbidity and postoperative data were reviewed from a prospectively maintained database. The primary outcome was overall survival (OS). Secondary outcomes were metastasis-free survival (MFS) and disease specific survival (DSS). Results 268 patients were identified with a median follow up of 115 months (55.25-151 IQR). Median age is 70 yrs. (65.8-73 IQR). Median PSA nadir was 2 (1-4.25 IQR) and median pre-salvage PSA was 6 (3.5-10.4 IQR). 20% (54/268) had Gleason score <7 at time of recurrence, 10% (28/268) had a Gleason score of 7, and 69% (184/268) had Gleason score >7. Out of 268 patients, 15 (5.6%) underwent repeat cryotherapy and neoadjuvant hormones were used in 29% of patients (77/268). _x000D_ Of the 268 patients, 123 (45%) experienced some form of morbidity. 101 (38%) had mild-moderate incontinence (0-1 pad/day), 43 (16%) had severe incontinence (≥2 pad/day), 43 (16%) experienced pelvic/perineal pain, 4 (1.5%) had rectourethral fistula, 68 (25%) had urinary retention, 38 (14%) had gross hematuria, and 28 (10.4%) had a bladder neck contracture, 12 (4.4) had urethral stricture disease. There were 176 Clavien 1-2, and 48 Clavien 3 events in the cohort. 4 (1.4%) patients were SP tube dependent and 3 (1.1%) patients went on to cystoprostatectomy.48% (130/268) of patients died by study follow up, 22% (59/268) died of RRPCa, and 31% (84/268) developed metastasis. Median OS was 163 mo., DSS 210 mo. and MFS was 199 mo. There was a significantly worse OS (p=0.027) and MFS (p=0.0114) for patients with a pre-cryotherapy PSA > 10 than those with a PSA <5, and those with PSA 5-10 – Figure 1. _x000D_ Conclusions Cryo for RRPCa provides long term MFS, DSS and OS with an acceptable degree of morbidity and is a viable treatment option of localized RRPCa following radiation therapy. Pre-Cryo PSA appears to serve as a prognostic tool for patient selection, and further prospective trials are required for validation. Funding None
Authors
Michael Metcalfe
Khurram Siddiqui Malcolm Dewar John Ward Joseph Chin Louis Pisters |
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PD56-02 |
Avoidance of Androgen Deprivation Therapy in Radiorecurrent Prostate Cancer as a Clinically Meaningful Endpoint for Salvage Cryoablation |
Prostate Cancer: Localized: Ablative Therapy II | 17BOS |
Abstract: PD56-02 Sources of Funding: Healthtronics Introduction Success of salvage cryoablation (SCAP) for radiorecurrent prostate cancer is typically measured by the ability to control serum PSA. However, slight elevations in PSA are typically asymptomatic and likely unimportant especially considering that most SCAP patients have a limited life expectancy based on comorbidities and advancing age. We propose that a more clinically meaningful endpoint would be the ability of SCAP to avoid the need for androgen deprivation therapy (ADT). Using the Cryo On-Line Database (COLD) registry, we investigated the ability of SCAP to delay or avoid ADT in local recurrence after radiation therapy. Methods The COLD registry is comprised of retrospectively and prospectively collected data on patients undergoing primary and SCAP. Patients with local recurrence after curative radiation to the prostate were identified. Kaplan-Meier analysis was used to calculate ADT-free survival. Results 998 patients were identified in the COLD database that had undergone SCAP. Median follow up was 19 months. 171 (17.1%) had been started on ADT post-SCAP. Overall, the calculated 5-year ADT-free survival was 71.7%(Figure 1). When stratified by D&[prime]Amico risk group, 301 high-risk patients (74.5%), 263 intermediate-risk (88.0%) and 261 low-risk (89.1%) were free of ADT post-SCAP. This correlates with a 5-year ADT-free survival of 61.2%, 74.3%, and 82.7%, respectively (Figure 2). Preoperative ADT use or full vs. partial gland SCAP did not have an effect on ADT use postoperatively. Of 213 patients with recurrence based on serum PSA elevations (Phoenix definition), ADT was avoided in 118 (55%). Conclusions For the patient with local recurrence after radiation, SCAP is an option that provides a high chance of avoiding ADT. The potential to avoid ADT and its associated side effects should be a part of counseling sessions between the patient, family, and urologist when discussing treatment options for locally radiorecurrent prostate cancer. Avoidance of ADT is more clinically relevant endpoint than biochemical recurrence. Funding Healthtronics
Authors
Kevin Ginsburg
Ahmed ElShafei Changhong Yu J. Stephen Jones Michael Cher |
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PD56-03 |
Predictors of recto-urethral fistula after primary, whole gland cryoablation of prostate cancer: results from the Cryo-On-Line Database (COLD) Registry. |
Prostate Cancer: Localized: Ablative Therapy II | 17BOS |
Abstract: PD56-03 Sources of Funding: none Introduction While recto-urethral fistula is a rare complication following salvage cryoablation for radiorecurrent prostate cancer, less is known about the development of recto-urethral fistula after primary whole gland cryoablation. We define the incidence and risk factors for recto-urethral fistula in a multicenter, centralized registry. Methods The Cryo-On-Line Data (COLD) Registry was queried for men undergoing primary whole gland cryotherapy between 1990 and 2014 who developed a recto-urethral fistula. Patient factors and disease parameters were correlated with the recto-urethral fistula using chi-squared tests for categorical variables and t-test for continuous variables. Variables with p<0.25 were entered into a binary logistic regression with stepwise backward elimination to determine the factors associated with formation of urethral fistula. Results We identified 4,102 men who underwent primary whole gland cryotherapy between 1990 and 2014. Median age was 71 years (IQR:66-76). Median PSA was 6.5 (IQR: 4.8-9.8). Available Gleason Score included 8-10:500 pts, 7:1,194 pts and 6:1,601 while pretreatment clinical stage included T1:1539, T2:1,503 T3:328 and T4:20. 1,508 pts received neoadjuvant androgen deprivation. 805 cases were performed at academic centers and 3297 were performed in the private setting. Post-operative recto-urethral fistula was identified in 50 (1.2%) men. On univariate analysis, pre-operative Gleason score, pre-operative incontinence and post-operative urinary retention were statistically significant predictors for development of recto-urethral fistula. On multivariate analysis, post-operative urinary retention (OR 7.26, 95%CI 4.06-13.03, p<0.001) pre-operative Gleason score of 7 (OR 1.92, 95%CI 1.08-3.43, p=0.027) and pre-operative incontinence (OR 2.95, 95% CI 1.12-7.76, p=0.028) predicted urethral fistula. Conclusions In a large, mixed cohort of patients undergoing primary whole gland cryoablation for prostate cancer, the incidence of urethral fistula was very low at 1.2%. The strongest association was present in men with post-procedural urinary retention. Further study regarding instrumentation of the lower tract for retention following cryotherapy in the early post-operative setting is warranted. Funding none
Authors
Ariel Schulman
Kae Jack Tay Ghalib Jibara Efrat Tsivian Ahmed Elshafei Thomas Polascik J. Stephen Jones |
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PD56-04 |
Salvage Prostate Cryoablation in Older Men |
Prostate Cancer: Localized: Ablative Therapy II | 17BOS |
Abstract: PD56-04 Sources of Funding: None Introduction Outcomes of salvage prostate cryosurgery in older men remain undefined. We evaluated oncological and functional outcomes after salvage full gland prostate cryoablation in men over age 75 years. Methods We identified 923 men who underwent salvage full gland prostate cryoablation for recurrent prostate cancer after primary radiotherapy, including 240 (26%) > 75 years at time of surgery. Primary outcomes were progression-free survival (PFS) using Phoenix criteria and post-treatment biopsy status. Secondary outcomes included post-treatment urinary incontinence, erectile dysfunction (ED), rectal fistulae, and urinary retention. Results Mean follow-up was 26 months (SD±30). Compared to men ≤ 75 years, men > 75 years were more likely to have pre-treatment Gleason sum ≥7 disease (71% vs.63%, p=0.03) and less likely to have undergone neoadjvuant androgen deprivation therapy (29% vs. 37%, p=0.02) (Table 1). In Kaplan Meir analyses, there were no significant differences in 5-year PFS between groups: 61% versus 57% for men > 75 and ≤ 75 years, respectively (p=0.43) (Figure 1). Post-treatment biopsy was positive in 34% versus 29% of men >75 years and ≤ 75 years, respectively (p=0.5). Older men were more likely to have post-treatment urinary retention (23% versus 15%, p=0.003). There were no significant differences in recto-urethral fistulae (3% versus 2%, p=0.62), urinary incontinence (32% versus 30%, p=0.48), or new onset ED (54% versus 49%, p=0.63) between groups (Table 1). Conclusions Salvage whole gland cryoablation of the prostate in men > 75 years is associated with robust progression-free survival and functional outcomes comparable to younger men. Prostate cryoablation should be considered in older men with recurrent disease after primary radiotherapy. Funding None
Authors
J. Kellogg Parsons
Ashley Ross Ahmed El Shafei Asmaa Hatem Britney Cotta Kae Jack Tay Thomas Polascik Robert Given Vladimir Mouraviev J Stephen Jones |
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PD56-05 |
Eliminating risk of upgrade from MRI-TRUS fusion biopsy to radical prostatectomy: Could Saturation biopsy of the index tumor be the solution? |
Prostate Cancer: Localized: Ablative Therapy II | 17BOS |
Abstract: PD56-05 Sources of Funding: This research was made possible through the NIH Medical Research Scholars Program, a public-private partnership supported jointly by the NIH and generous contributions to the Foundation for the NIH by the Doris Duke Charitable Foundation (Grant #2014194), the American Association for Dental Research, the Colgate-Palmolive Company, Genentech, and other private donors. For a complete list, visit the foundation website at http://www.fnih.org. Introduction Several studies have demonstrated the risk of upgrade from prostate biopsy (PBx) to radical prostatectomy (RP) pathology to be as high as 40%. The objective of the current study is twofold: to evaluate the prostate cancer upgrading on RP in a cohort of patients who underwent MRI-TRUS fusion biopsy (FBx) prior to RP and to determine if saturation of index tumor (IT) during PBx decreases this risk of upgrading. Methods Clinical and pathologic data from a prospectively maintained single institution database was analyzed for patients who underwent both FBx and standard 12-core biopsy (Sbx) followed by RP (2010-16). Index tumor was defined as the tumor with the largest diameter on T2W MRI. Patients were considered to have a saturated index tumor (SIT) if they had a fusion target (consisting of one axial and one sagittal biopsy) taken for every 6mm of IT diameter, and were considered to have a nonsaturated index tumor (NSIT) if they had only one target assigned regardless of the size of IT. Gleason 6, Gleason 7 and Gleason 8 or above were defined as low, intermediate and high risk respectively. Gleason Upgrade was defined as a higher Gleason score on RP specimen compared to PBx. Risk category upgrade was defined as higher risk category on RP specimen. Chi square and McNemar&[prime]s test were used to compare rates of upgrade. Results 206 patients (91 with SIT and 115 with NSIT) were included in the study with median age and PSA of 61.5 (IQR 9.3) yrs and 7.38 (IQR 8) ng/ml respectively. Median number of biopsy cores per index tumor was 4 in the SIT group and 2 in the NSIT group (p<0.001) . For the entire cohort, highest Gleason score from combined Fbx/Sbx was upgraded on final pathology in 36 (17.5%) patients vs 95 (46.1%)patients when compared to Sbx only (p=0.001). Risk category upgrade from combined Fbx/Sbx vs Sbx only was found in 26 (12.6%) vs 83 (40.3%), p<0.0001. Patients with SIT had lower Gleason upgrade (12.1% vs 21.7% , p =0.07) and significantly lower risk category upgrade (6 (6.6%) and 20 (17.4%), p=0.02) compared to patients with NSIT. Conclusions Ensuring that high risk cancer is not missed on biopsy is crucial to treatment planning in patients with prostate cancer. Our results demonstrate that the addition of mpMRI-TRUS Fbx significantly decreases the risk of upgrade on RP pathology, proving the efficacy of Fbx in accurately characterizing PCa preoperatively. Saturation of the index tumor further decreases the risk of upgrade on final pathology by extensive sampling and minimizing the impact of tumor heterogeneity. Funding This research was made possible through the NIH Medical Research Scholars Program, a public-private partnership supported jointly by the NIH and generous contributions to the Foundation for the NIH by the Doris Duke Charitable Foundation (Grant #2014194), the American Association for Dental Research, the Colgate-Palmolive Company, Genentech, and other private donors. For a complete list, visit the foundation website at http://www.fnih.org.
Authors
Brian Calio
Abhinav Sidana Dordaneh Sugano Amit Jain Mahir Maruf Maria Merino Peter Choyke Bradford Wood Peter Pinto Baris Turkbey |
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PD56-06 |
New frontiers ahead focal therapy postoperative follow-up: What is the real role of MRI in this setting? |
Prostate Cancer: Localized: Ablative Therapy II | 17BOS |
Abstract: PD56-06 Sources of Funding: None Introduction Magnetic resonance imaging (MRI) plays an important role as a treatment-monitoring tool along focal therapy (FT) follow-up. This is the first study to assess MRI accuracy to predict prostate cancer (PCa) local T-stage in the FT postoperative scenario. We aimed to describe MRI effectiveness in predicting upstaging in two groups of men: 1) men who presented failure after primary FT and underwent salvage robotic-assisted radical prostatectomy (S-RARP); and 2) men who underwent RARP as primary treatment (P- RARP). Methods Prospective data of 2775 men underwent RARP for localized PCa from 2000 to 2016 were reviewed. Twenty-two men underwent S-RARP after FT failure (S-RARP group). Total 2750 underwent RARP as first treatment. Matched-pair 1:2 selection of 44 out of 2750 patients by age defined primary RARP group (P-RARP). All patients underwent MRI immediately before RARP. MRI findings were confronted with final surgical pathology. Primary endpoint: sensitivity, specificity, positive and negative predictive values; positive (+LR) and negative (-LR) likelihood ratio regarding upstaging analysis on S-RARP. Secondary endpoint: same effectiveness analysis on P-RARP. Results Preoperative MRI failed in predicting upstaging in 80&[permil] versus 91.7&[permil] of patients (p=0.515) that presented final pathological status ≥pT3a on S-RARP and P-RARP groups, respectively. On the other hand, when final pathology described a localized disease T2a-T2c, MRI correctly predicted the final pathological status in 81.8&[permil] versus 95.2&[permil] of patients (p=0.27) on S-RARP and P-RARP groups, respectively. Between-group analysis, showed sensitivity and specificity rates of 20&[permil] versus 8.33&[permil] and 81.8&[permil] versus 95.23&[permil], respectively; Positive and negative predictive values of 33.33&[permil] versus 50&[permil] and 69.23&[permil] versus 64.51&[permil], respectively; Positive (+LR) and negative (-LR) likelihood ratio of 1.1 versus 1.74 and 0.98 versus 0.96, respectively. Conclusions MRI has shown to be a weak diagnostic tool for predicting extra-prostatic disease along FT follow-up. Urologists may be warned about the risk of underdiagnosis and undertreatment in patients presenting failure after FT. Funding None
Authors
Igor Nunes-Silva
Eric Barret Mohammed Baghdadi Victor Srougi Silvia Garcia-Barreras Ariê Carneiro Paolo Capogrosso Gregorie Rembeyo Rafael Sanchez-Salas François Rozet Marc Galiano Xavier Cathelineau |
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PD56-07 |
Can focal therapy impact on perioperative, oncological and function outcomes in men underwent focal therapy salvage robotic-assisted radical prostatectomy? A retrospective matched-pair comparative study |
Prostate Cancer: Localized: Ablative Therapy II | 17BOS |
Abstract: PD56-07 Sources of Funding: None Introduction Salvage surgery is an option for recurrent prostate cancer(PCa) after focal therapy(FT). This is the first study to assess the impact of FT on surgical outcomes comparing salvage robotic-assisted radical prostatectomy(S-RARP) versus primary-RARP(P-RARP). We aimed to compare the impact of FT on perioperative, oncological and functional outcomes in men underwent S-RARP versus P-RARP. Methods Prospective data of 2775 men underwent RARP for localized PCa from 2000 to 2016 were reviewed. Twenty-five men underwent S-RARP after FT failure(S-RARP group). Total 2750 underwent RARP as primary treatment. Matched-pair 1:2 selection of 44 out of 2750 patients by age, IPSS and IIEF5 defined P-RARP group. Primary endpoint was between-groups differences on functional outcomes. Secondary endpoint was oncological data. p<0.05 was significant. Results Surgical time, transfusion and complication rates were comparable(p≥0.05). Rates of continence probability[49.5%(SE 0.13) versus 62.4%(SE 0.08), p=0.8 and 73%(SE 0.14) versus 76.5%(SE 0.07), p=0.8, at 1 and 2 years, respectively] and the chance for achieving continence[HR 1.062, 95%CI 0.54-2.08, p=0.861] were comparable between-groups. Potency recovery was significant lower on S-RARP at 1 year follow-up[3±2 versus 9.22±6.55, p=0.008]. S-RARP showed significant lower rates of cumulative BCR-free survival probability[67.6%(SE 0.12) versus 95.1%(SE 0.03), p=0.001 and 56,3%(SE 0.15) versus 92,4%(SE 0.04), p=0.001, at 1 and 2 years, respectively]. S-RARP presented significant increased risk of BCR[HR 4.8, 95%CI 1.67-13.76, p=0.004]. Upstaging was an independent predictor factor for BCR on S-RARP[HR 14.65, 95%CI 1.46-146.37, p=0.022]. Conclusions Salvage-RARP following FT failure is feasible and safe with acceptable complications rates. Patients assigned to FT should be previously advised about lower erectile recovery rates in case of a salvage surgery. Urologists may be warned about the risk of undertreatment in patients presenting failure along FT follow-up. Funding None
Authors
Igor Nunes-Silva
Eric Barret Victor Srougi Mohammed Baghdadi Silvia Garcia-Barreras Paolo Capogrosso Gregorie Rembeyo Ariê Carneiro Rafael Sanchez-Salas François Rozet Marc Galiano Xavier Cathelineau |
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PD56-08 |
The PART trial - A phase III study comparing Partial prostate Ablation versus Radical prosTatectomy (PART) in intermediate risk prostate cancer – early data from the feasibility study |
Prostate Cancer: Localized: Ablative Therapy II | 17BOS |
Abstract: PD56-08 Sources of Funding: None Introduction Recent findings from the ProtecT trial suggest that survival in clinically localised prostate cancer is very high, and that radical treatments half the incidence of metastatic disease progression but at the cost of significant side effects. Using minimally invasive technology, such as HIFU or cryotherapy, for partial gland ablation (PA) could reduce these side effects. _x000D_ _x000D_ Partial prostate Ablation versus Radical prostatectomy (PART trial) is the first phase III study to compare PA and radical surgery (RP) in intermediate risk prostate cancer. PART is a prospective, multi-centre, parallel group randomised controlled trial to assess the clinical effectiveness and cost-utility of PA or RP in patients with intermediate risk, unilateral clinically significant localised prostate cancer. Our hypothesis is that PA of the prostate using minimally invasive therapies can achieve organ preservation, reduce side effects, maintain good voiding and sexual function, without compromise to oncological outcomes. We report the outcomes of our successful feasibility study which will now drive the establishment of the main multi-centre randomised controlled trial. _x000D_ Methods Participants were eligible when diagnosed with intermediate risk, unilateral clinically significant localised prostate cancer, fit for either RP or PA. Pre-biopsy mpMRI and targeted biopsy or template guided biopsies were compulsory before randomization to either RP or PA. Target accrual for the feasibility phase was 80 patients over 18 months. Follow-up involved regular PSA measurements and, in the focal therapy arm, mpMRI and targeted biopsies of any suspicious areas. Quality of life data were measured at six weeks and three monthly intervals. Results The table below summarises recruitment data. Baseline demographics of men randomised to date are Mean age: 66.7yrs (48.4-78.2); BMI: 26.4 (22.0-32.3); PSA: 7.60 (2.5-16.20) and Gleason score: 3+4=7 75.6%, 4+3=7 24.4%._x000D_ Conclusions A randomised controlled trial of partial ablation of the prostate versus radical treatment with surgery is feasible. The full trial is being developed, and will provide key data to inform men when making the treatment decision for intermediate risk unilateral prostate cancer. Funding None
Authors
Tom Leslie
Lucy Davies Daisy Elliott Simon Brewster Prasanna Sooriakumaran Derek Rosario Jim Catto Tim Dudderidge Hashim Ahmed Mark Emberton Richard Hindley Jenny Donovan Richard Gray Freddie Hamdy |
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PD56-09 |
PSA Trends following Primary Focal Cryosurgery for early stage prostate cancer |
Prostate Cancer: Localized: Ablative Therapy II | 17BOS |
Abstract: PD56-09 Sources of Funding: Department of Urology, Winthrop University Hospital. Introduction Determination of biochemical (BCR) recurrence in patients who undergo primary focal cryosurgery (PFC) for organ confined prostate cancer (PCa) is controversial. We aim to evaluate prostate specific antigen (PSA) trends in post PFC patients. Methods A single-center retrospective review of patients from our IRB-approved database who underwent PFC was performed. Patients were followed with serial PSAs and BCR was determined using the Phoenix (PD: PSA nadir + 2 ng/ml) and Stuttgart (SD: PSA nadir + 1.2 ng/ml) definitions. PSA bounce was assessed using 2 different definitions (B1: increase in PSA of 0.4 in first 6 months and any drop thereafter, B2: increase in PSA of ≥0.2 above nadir and then a drop to/below nadir) Age, prostate volume, D&[prime]Amico risk, Gleason score, PSA variables and kinetics overtime were assessed between those who experienced BCR versus not. Various PSA permutations were analyzed. Results 123 (94.6%) consecutive patients who had >1 PSA follow-up values were included in our analysis. Median (range) age and follow-up time was 66 (48-82) years and 19 (6.3-68.6) months respectively. 11 (8.9%, 7B1; 4B2) patients experienced PSA bounce and a median percent drop in first post-PFC PSA of 80.0 (0.0-98.7) was not associated with BCR, p=0.301. PSA values in both groups increased over time but the rate of change was significantly higher in patients who experienced BCR compared to those who did not [median PSA velocity: 0.1 vs 0.04, p=0.003]. Other PSA variables associated with experiencing BCR were higher pre-PFC PSA (7.2 vs 5.4 ng/ml, p=0.003) and higher PSA nadir (1.3 vs 1 ng/ml, p=0.012). Conclusions Higher PSA velocity, nadir and pre-PFC PSA may help raise suspicion for BCR. In the future with validation, these variables could serve as the components of PFC-specific BCR criteria. Funding Department of Urology, Winthrop University Hospital.
Authors
Michael Kongnyuy
Shahidul Islam Daniel Halpern Kaitlin Kosinski Jose Salcedo Jeffrey Schiff Anthony Corcoran Aaron Katz |
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PD56-10 |
Urologist's Practice Patterns And Preferences Regarding Focal Therapy For Prostate Cancer |
Prostate Cancer: Localized: Ablative Therapy II | 17BOS |
Abstract: PD56-10 Sources of Funding: This research was funded by the Intramural Research Program of the National Institutes of Health (NIH), National Cancer Institute, Center for Cancer Research. Introduction Focal therapy (FT) for localized prostate cancer (PCa) has been shown to have encouraging short term oncological outcomes, excellent preservation of functional outcomes and is increasing in popularity in Urologic community. We aim to evaluate the preferences and practice trends among urologists regarding this upcoming treatment strategy. Methods A 20 item online questionnaire was designed to collect information on urologists' views and use of focal therapy. The survey was sent to the members of the Endourological Society (ES) and the American Urological Association (AUA). Multivariate logistic regression analysis was done to determine predictors for utilization of FT. Results A total of 425 responses were received [AUA: 342, ES: 83]. Mean age of respondents was 53(±11.3) years. Although half of the respondents (50.8%) believed FT to be moderate to extremely beneficial in the treatment of PCa, only 24.2% (103) of the respondents currently utilize FT in their practice. Of the respondents who were fellowship trained in urologic oncology were more likely to consider FT to be moderately to extremely beneficial (p<0.001). Surgeon's experience (practice for more than 15 years) (p = 0.031) was the only independent predictor for utilizing FT in localized PCa. While the most common setting for utilization of FT was in patients with unilateral intermediate risk (72.8%) PCa, a small percentage of respondents also used FT for patients with unilateral high risk PCa and bilateral intermediate risk (21.3% and 10.6% respectively). The most common FT modality was Cryoablation in 58% followed by High Intensity Focused Ultrasound in 44.6%. Most common reasons for not using focal therapy were the lack of belief in 'index lesion theory' (203) (63%) followed by the lack of experience (133) (41.3%). About 57.6% would use FT more often in an office or outpatient setting if they had access to reliable and cost effective options. Conclusions Only a quarter of our respondents utilize FT in their practice with surgeon's experience being the only independent predictor for utilizing FT. Majority of respondents though consider FT to be beneficial in prostate cancer management and would use it more often if provided more reliable and cost effective options. Over time, experience and accessibility to reliable methods to perform FT may lead to further utilization of this novel treatment strategy. Funding This research was funded by the Intramural Research Program of the National Institutes of Health (NIH), National Cancer Institute, Center for Cancer Research.
Authors
Amit L Jain
Abhinav Sidana Mahir Maruf Brian Calio Dordaneh Sugano Bradford Wood Peter Pinto |
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PD56-11 |
Development of convective water vapor energy for treating localized prostate cancer: First-in-man early clinical experiences. |
Prostate Cancer: Localized: Ablative Therapy II | 17BOS |
Abstract: PD56-11 Sources of Funding: NxThera Inc._x000D_ Maple Grove, Minnesota, USA Introduction Earlier work has confirmed the unique thermodynamic properties of phase-change convective radiofrequency (RF) ablation using water vapor (steam) to conform to the anatomical zones of the prostate. The objective of this study was to assess in vivo treatment of prostate cancer and the early clinical effects using convective RF water vapor. Methods A total of 20 patients have been treated at 2 centers using the Reviv System and 6 have completed 6 month follow up biopsy. All patients had clinically localized prostate cancer as determined by biopsy, DRE, PSA and prostate MRI (non mp3). Treatment was performed using a urethral cooling catheter and a transperineal, ultrasound guided approach for needle placement and water vapor delivery. Several doses of thermal energy were tested depending on prostate size. Follow-up monitoring included serial, gadolinium enhanced MRIs performed pre-procedure and at 1 week, 1, 3, and 6 months post-procedure and a surveillance biopsy at 6 months post-procedure. Standard AE reporting was used to evaluate clinical outcomes. Results 20 patients have been treated. 11 patients underwent hemiablation, 6 whole gland ablation (3 staged), 2 unilateral PZ treatment and 1 hemiablation with contralateral PZ ablation. Serial MRIs confirmed tissue ablation in all patients. Ablation was seen to the prostatic apex, capsular boundaries and the anterior zones of the prostate. Six-month surveillance biopsies have been completed on 6 patients. Four had completely negative biopsies for cancer and two had positive biopsies that were in untreated zones. Catheterization and adverse events will be reviewed. There has been no incontinence, bladder neck contractures or rectal injuries. Conclusions The zonal anatomy of the prostate is ideal for phase change convective RF ablation using water vapor. The thermodynamics and physical principles validated by MRI indicate that effective ablation can be safely delivered anywhere in the prostate including the apex, capsular margins and anterior prostate. Partial, focal, zonal or whole gland ablation can be performed. These early and limited data confirm that effective tissue ablation to all areas of the prostate is feasible using convective thermal water vapor. Funding NxThera Inc._x000D_ Maple Grove, Minnesota, USA
Authors
Christopher Dixon
Ramon Rodriguez Lay Cesar Cabanas Edwin Rijo Thayne Larson |
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PD56-12 |
SURVEY OF ABDOMINAL ACCESS AND ASSOCIATED MORBIDITY FOR ROBOT-ASSISTED RADICAL PROSTATECTOMY (RARP)- DOES PALMER’S POINT WARRANT FURTHER AWARENESS AND STUDY? |
Prostate Cancer: Localized: Ablative Therapy II | 17BOS |
Abstract: PD56-12 Sources of Funding: None Introduction Laparoscopic access for RARP is often initiated in the peri-umbilical location. Palmer’s Point, located in the left upper quadrant, has been reported as an alternative access site for pelvic laparoscopy to reduce morbidity, but not widely reported among urologists. Furthermore, there are no published articles specifically addressing vascular injuries during RARP access within the literature. To better understand surgeons’ preferences for access and its associated morbidity during RARP, we surveyed surgeons from two urological organizations. Methods An anonymous online questionnaire (Survey Monkey) consisting of 17 questions that assessed training, experience, and preferences for RARP was emailed in December 2014 and collected until February 2015 to members performing RARP of the Endourology Society (ES) and the Michigan Urological Society Improvement Collaborative (MUSIC) . Surgeons were also asked to share their personal experience with a vascular event or bowel injury during RARP. Results Questionnaires were answered by 111 surgeons in total (ES, n=71 and MUSIC, n=40) with an estimated total response rate of 5.5% In total, 77% reported prior experience with the Veress needle method before exposure to RARP and 71% of respondents primarily use the Veress needle for RARP, with 73% reporting access primarily at the peri-umbilical location. A personal experience with a vascular or a bowel injury during veress needle insertion was reported in 18% and 9% of surgeons, respectively; furthermore 26% of respondents were personally aware of at least 1 death or life-threatening event among colleagues (5% reported 3 or more). The majority (56%) of respondents were unaware of Palmer’s Point, while among the minority aware of Palmer’s Point, only 33% reported ever using this location. Conclusions In this survey, surgeons most commonly access the abdomen at the peri-umbilical location with a Veress needle for RARP with the majority not aware or utilizing Palmer’s Point. Nearly 1 in 5 surgeons reported a personal experience with a vascular injury and over 1 in 4 reported a death or life-threatning injury among colleagues during access for RARP. Palmer’s Point, located away from major vasculature, may reduce the morbidity of access for RARP and warrants further awareness and study, Funding None
Authors
William K Johnston III
David Miller Susan Linsell Khurshid Ghani |
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PD57-01 |
Hematuria Risk Index - risk of urothelial malignancy in patients with asymptomatic microscopic hematuria |
Bladder Cancer: Epidemiology & Evaluation III | 17BOS |
Abstract: PD57-01 Sources of Funding: none Introduction To determine the incidence and predictors for malignancy in patients who undergo workup for microscopic hematuria. Methods We conducted a prospective cohort study of patients undergoing evaluation for asymptomatic microscopic hematuria from January 2009 to July 2016 in an integrated managed care organization in Southern California. Patients' accompanying diagnoses and baseline cohort characteristics were determined and identified using our comprehensive electronic health record system. Cancers indicated in the workup were validated by chart review. Additional cancers documented in the institutional cancer registry through July 2015 were included if diagnosed within 1 year of initial workup. Bivariate associations were assessed using the chi-square test; multivariable logistic regression was used to build a predictive risk model and create a hematuria risk index. Results Within a cohort of 6417 patients with microscopic hematuria, a total of 177 (2.8%) were diagnosed with a neoplasm. On multivariate analysis, age between 50-59 (OR=1.96, 2 points), age over 60 (OR=5.21, 4 points), history of gross hematuria (OR=3.15, 3 points), current or past smoking history (OR=1.51, 1 point), male gender (OR=2.57, 2 points), >25 red blood cell per high power field (OR=2.94, 2 points), Non-Hispanic Black (OR=1.73, 1 point), and Non-Hispanic White (OR=2.31, 2 points) were all significant predictors of malignancy. A modified Hematuria Risk Index (0 to 14 points) was developed from these factors, which demonstrated an improved area under the receiver operating characteristic curve of 0.841 compared to our previous model at 0.807. We observed natural breaks in the scores that grouped the patients into low (0-4 points, 41.7%), moderate (5-9 points, 49.0%), and high-risk of cancer (10-14 points, 9.2%). Malignancy was found in 0.4%, 2.5% and 15.0% of patients from the low, moderate and high-risk groups, respectively. Conclusions Advance age, history of gross hematuria, current or past smoking history, male gender, >25 red blood cell per high power field, and certain ethnic groups are significant predictors for malignancy in the setting of microscopic hematuria. Classification of patients into low, moderate and high-risk groups will improve patient counseling and will hopefully reduce the need for invasive endoscopy and ionizing radiation exposure for patients within the low-risk category. Funding none
Authors
Ronald Loo
Casey Ng Jeff Slezak Steven Jacobsen |
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PD57-02 |
Characterization of Urothelial Cancer Circulating Tumor Cells with a Novel Selection-Free Method |
Bladder Cancer: Epidemiology & Evaluation III | 17BOS |
Abstract: PD57-02 Sources of Funding: This work is supported by NCI grant nos. U54CA143803, CA163124, CA093900, CA143055 to K.J.P as well as the Prostate Cancer Foundation, the Patrick C. Walsh Fund, and a gift from the Stutt family. E.E.vdT is supported by the Cure for Cancer Foundation. H.J.C. is supported by the Urology Care Foundation's Resident Research Award. T.J.B. received funding from the Greenberg bladder cancer institute. Introduction The majority of work performed to date investigating circulating tumor cells (CTCs) as biomarkers of urothelial carcinoma (UC) has utilized the CellSearch test (Jansen Diagnostics, Raritan, NJ). One factor limiting the sensitivity of this assay is its reliance on positive selection of CTCs expressing the cell surface protein EpCAM. In this study, we used a novel selection-free method to enumerate and characterize CTCs in patients with UC across a range of stages. Methods Blood samples from 38 patients (9 controls, 8 with non-muscle invasive bladder cancer [NMIBC], 12 with muscle-invasive bladder cancer [MIBC] and 9 with metastatic UC) were processed with the AccuCyte-CyteFinder system (RareCyte, Inc., Seattle, WA). Slides were stained for the white blood cell (WBC) markers CD45 and CD66b, and the epithelial markers EpCAM and pan-cytokeratin (CK). CTCs were defined as nucleated cells positive for CK but negative for the WBC markers. Separately, the more restrictive CellSearch definition was also applied, with the additional requirement of EpCAM positivity. The Kruskal-Wallis ANOVA test was used to compare CTC counts between cancer stage groups. Results CTCs were detected in 2/8 (25%) patients with NMIBC, 7/12 (58%) with MIBC, and 6/9 (67%) with metastatic disease. No CTCs were found in any control. Comparing CTC counts between groups, the only statistically significant comparison was between controls and patients with metastatic UC (p=0.009, Fig 1A). Using EpCAM positivity as a requirement for defining a CTC, no CTCs were detected in any patient with NMIBC, and only 2 (17%) patients with MIBC (Fig 1B). CTCs tended to be larger in patients with metastatic UC (Fig 2). Conclusions CTCs were detected at all UC stages and exhibited phenotypic diversity for cell size and EpCAM expression. EpCAM negative CTCs that would be missed with the CellSearch test were detected in patients with NMIBC and MIBC. Funding This work is supported by NCI grant nos. U54CA143803, CA163124, CA093900, CA143055 to K.J.P as well as the Prostate Cancer Foundation, the Patrick C. Walsh Fund, and a gift from the Stutt family. E.E.vdT is supported by the Cure for Cancer Foundation. H.J.C. is supported by the Urology Care Foundation's Resident Research Award. T.J.B. received funding from the Greenberg bladder cancer institute.
Authors
Heather Chalfin
Max Kates Emma van der Toom Stephanie Glavaris James Verdone Noah Hahn Kenneth Pienta Michael Gorin Trinity Bivalacqua |
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PD57-03 |
Assessment of the ecological association between tobacco smoking exposure and bladder cancer incidence over the past half-century in the United States |
Bladder Cancer: Epidemiology & Evaluation III | 17BOS |
Abstract: PD57-03 Sources of Funding: none Introduction Tobacco smoking is recognized as the most established risk factor for bladder cancer. As such, we aimed to assess the ecological association between tobacco smoking prevalence and bladder cancer incidence in the US over the past half-century, and to contrast it with that observed for lung cancer, which represents the most established tobacco-related malignancy. Methods The annual overall tobacco smoking prevalence rates were extracted from the Report of the Surgeon General (1950-1978) and the Center for Disease Control website for the years 1953-1983. The overall age-adjusted incidence rates of bladder and lung cancers were derived from the Surveillance, Epidemiology, and End Results database for the years 1983-2013 (30-year time-lag). All analyses were stratified according to gender. Weighted least square regression models were used to assess the bladder and lung cancer incidence rate differences (IRD) and the proportion of changes in incidence of each malignancy related to tobacco smoking prevalence variations. Additional comparisons between the associations of tobacco smoking prevalence with bladder vs. lung cancer incidence rates were performed using a Wald test. Results The associations between tobacco smoking prevalence and bladder cancer incidence were not significant in the overall (IRD=+0.04; 95%CI: from -0.14 to +0.22; P=0.631), men (IRD=+0.07; 95%CI: from-0.09 to +0.23; P=0.374) and women (IRD=+0.12; 95%CI: from -0.01 to +0.25; P=0.061) populations. In contrast, the associations between tobacco smoking prevalence and lung cancer incidence were significant in the overall (IRD=+3.55; 95%CI: from +3.09 to +4.00; P<0.001), men (IRD=+4.82; 95%CI: from +4.44 to +5.20; P<0.001) and women (IRD=+3.55; 95%CI: from +3.12 to +3.99; P<0.001) populations. The difference between the observed associations of tobacco smoking prevalence with bladder vs. lung cancer incidence was significant in all examined populations (all P<0.001). Tobacco exposure accounted for an estimated 0.81%, 2.74% and 11.59% of the variation in bladder cancer incidence vs. 89.72%, 95.80% and 90.69% of the variation in lung cancer incidence in the overall, men and women populations, respectively. Conclusions In contrast to lung cancer, our study showed that variations in tobacco smoking prevalence were not associated with the incidence trends of bladder cancer in the US population over the past half-century._x000D_ Funding none
Authors
Thomas Seisen
Stuart R. Lipsitz Joaquim Bellmunt Mani Menon Nicolas von Landenberg Philipp Gild Morgan Rouprêt Toni K. Choueiri Quoc-Dien Trinh Maxine Sun |
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PD57-04 |
Prognostic Value of the WHO 1973 and 2004 Classification Systems for Grade in Non-Muscle-Invasive T1 Bladder Cancer |
Bladder Cancer: Epidemiology & Evaluation III | 17BOS |
Abstract: PD57-04 Sources of Funding: None Introduction Management of T1 bladder cancer (T1-BC) is a therapeutic challenge. Tumor grade is an important prognostic factor to aid in treatment decision making. Currently, the AUA guidelines advise use of WHO 2004 grade over the 1973 classification, although in the literature, neither has been proven superior over the other. In this study, we compared the prognostic value of these WHO classifications in T1-BC. Methods Three uro-pathologists revised the slides of 601 primary (first diagnosis) T1-BCs from patients treated with BCG in four university hospitals between 1983 and 2006. Grade was defined according to WHO 1973 (grade 1-3) and 2004 (low-grade; LG and high-grade; HG). Association with progression-free survival (PFS) and cancer-specific survival (CSS) was analysed for each system with multivariable cox-regression models. We corrected for age, sex, multiplicity, size (>3cm vs. ≤3 cm) and concomitant CIS. Results Median age was 71 (IQR 15) years and 196/601 (33%) tumors had concomitant CIS. After revision, 188 (31%) tumors were grade 2 and 413 (69%) grade 3 (WHO 1973). According to WHO 2004, 47 (8%) tumors were LG and 554 (92%) were HG. At a median follow-up of 5.9 (IQR 3.0) years, progression (≥cT2 and/or N1 and/or M1) occurred in 148 (25%) patients and 94 (16%) patients died of BC. Grade 3 tumors were associated with a worse PFS (HR 2.1, p<0.001) and CSS (HR 3.4, p<0.001) than grade 2 tumors. WHO 2004 grade had no prognostic value for progression (HG vs. LG HR 2.0, p=0.077) or CSS (HG vs. LG HR 1.6, p=0.292). The only prognostic factor for progression on multivariable analysis was WHO 1973 grade (HR 2.0, p=0.001). Grade 3 tumors (HR 3.0, p<0.001), increasing age (HR 1.03, p=0.003) and tumor size >3cm (HR 1.8, p=0.008) were all independently associated with worse CSS. Conclusions In T1-BC, WHO 1973 grade has a strong prognostic value, whereas the 2004 system is not prognostic. The superior value of WHO 1973 grade in T1-BC suggests that the 1973 system should be recommended by clinical non-muscle-invasive BC guidelines. Funding None
Authors
Elisabeth Fransen van de Putte
Theodorus van der Kwast Simone Bertz Stefan Denzinger Quentin Manach Eva Compérat Joost Boormans Michael Jewett Robert Stöhr Alexandre Zlotta Kees Hendricksen Morgan Rouprêt Wolfgang Otto Maximilian Burger Arndt Hartmann Bas van Rhijn |
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PD57-05 |
Universal Point of Care Testing for Lynch Syndrome in Patients with Upper Tract Urothelial Carcinoma |
Bladder Cancer: Epidemiology & Evaluation III | 17BOS |
Abstract: PD57-05 Sources of Funding: _x000D_ Supported by the Monteleone Family Foundation for Research in Bladder and Kidney Cancer and the Eleanor and Scott Petty Fund for Upper Tract Urothelial Cancer Research Introduction _x000D_ Lynch Syndrome (LS) is an autosomal dominant inherited syndrome that places patients at risk for upper tract urothelial carcinoma (UTUC). Our goal was to identify the most reliable means of screening for LS in patients with UTUC at the point of care (POC). Methods _x000D_ Patient information was retrospectively collected in an IRB-approved protocol on patients treated for UTUC. Screening was universally performed on all patients presenting during the study period. We evaluated patient and family history (Amsterdam I and II criteria; AMS1 and AMS2, respectively), tumor immunohistochemistry (IHC) for 4 mismatch repair proteins (MMRP), tumor and normal tissue polymerase-chain reaction for microsatellite instability (MSI), and clinical genetic analysis and counseling (GAC), in those with undiagnosed LS. Patients who were AMS 2 positive, MSI positive of IHC positive were considered as presumed lynch syndrome (pLS). Results _x000D_ From 1/2013-7/2016, 101 UTUC patients without a history of LS were universally screened during clinical follow-up. A total of 15/101 (15%) patients were pLS. 7/101 (7%) patients met AMS2 criteria. 4 patients meeting AMS2 criteria had intact expression of MMRP and no MSI instability. 11 (11%) patients had either loss of one or more MMRP. There were two cases of MSI high instability, both in patients with MMRP loss. There were no cases of MSI-high instability and negative IHC. Insufficient tissue was found in 1/101 (1%) of IHC and 8/88 (9%) of MSI tests (p=0.0164). All patients with any positive screen were referred for GAC, 5 followed-up and all 5 patients had a confirmed germline mutation. The remaining did not follow through with GAC because of financial/insurance barriers. _x000D_ Conclusions _x000D_ We identified 15% of universally screened UTUC as pLS at the POC using IHC and AMS2 criteria. IHC and AMS2 criteria appear to provide the most reliable screening, outperforming AMS1 and MSI. MSI is limited by requirement for normal tissue and a greater amount of tumor tissue, and can miss cases of MMRP loss, especially MSH6. Most patients did not have a personal history of a classic LS-related cancer. Our findings of a 15% rate of LS-related UTUC has significant implications for universal POC testing of UTUC patients. _x000D_ _x000D_ Funding _x000D_ Supported by the Monteleone Family Foundation for Research in Bladder and Kidney Cancer and the Eleanor and Scott Petty Fund for Upper Tract Urothelial Cancer Research
Authors
Michael Metcalfe
Firas Petros Priya Rao Maureen Mork Xiao Lianchun Russell Broaddus Surena Matin |
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PD57-06 |
OUTCOMES OF UROTHELIAL BLADDER CANCER PATIENTS WHO HAD PREVIOUS UPPER TRACT UROTHELIAL DISEASE |
Bladder Cancer: Epidemiology & Evaluation III | 17BOS |
Abstract: PD57-06 Sources of Funding: None Introduction Upper tract urothelial carcinoma (UTUC) accounts for <5% of all urothelial cancers. Studies show that urothelial bladder carcinoma recurrence (UBCR) occurs in 22–47% of deNovo UTUC (dNUTUC) patients. Our goal was to compare UBCR rates, predictors and disease specific mortality (DSM) in different dNUTUC locations. Methods The SEER database was queried for all patients with dNUTUC from 1988-2013, who developed UBCR. Data collected consisted of demographic, clinical parameters including tumor location, pathological and survival data. Patients were stratified according to their dNUTUC location (renal pelvis [RENPEL] vs. ureteral [UL]) and compared for time to UBCR and bladder cancer (BC) DSM. Results This cohort included 15,298 patients with dNUTUC. UBCR was diagnosed in 51.6% and 51.2% of RENPEL and UL tumors, respectively (p=0.639), (N=7179). Table 1 presents the demographic, pathologic and median follow-up data of the UBCR patients, stratified according to dNUTUC location. Approximately a fifth of these UBCRs are muscle invasive. Covariates associated with UBCR include RENPEL tumors (OR=1.318, 95% C.I. 1.027-1.691. p=0.03), less advanced disease (OR=0.587, 95% C.I. 0.434-0.793, p=0.001) and dNUTUC surgical treatment (OR=5.78, 95% C.I. 1.846-18.106, p=0.003). Interestingly, 50% and 75% of the dNUTUC patients are diagnosed with UBCR within 67 and 133 months, respectively, with higher grade UBCRs being diagnosed earlier. Survival data shows age, black race and more advanced disease being predictors of BC DSM (table 2). Conclusions These data suggest that RENPEL dNUTUC tumors consist of a higher risk for developing UBCR, especially when less advanced and treated surgically. Postoperative follow-up of dNUTUC patients should include routine cystoscopies for at least 11 years, to diagnose 75% of UBCR. Worse BC DSM is associated with black race and older patients with a more advanced disease. Funding None
Authors
Hanan Goldberg
Thenappan Chandrasekar Zachary Klaassen Robert Hamilton Girish Kulkarni Neil Fleshner |
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PD57-07 |
Race and Finasteride Use: Differential Impact on Bladder Cancer Risk |
Bladder Cancer: Epidemiology & Evaluation III | 17BOS |
Abstract: PD57-07 Sources of Funding: None Introduction A recent subset analysis of the Prostate, Lung, Colorectal, and Ovarian cancer (PLCO) study has suggested that Finasteride use was associated with a reduced incidence of bladder cancer (HR=0.634, 95% confidence interval=0.493-0.816; p = 0.0004). We sought to validate this finding in a multiracial population in our tertiary care center. _x000D_ Methods We identified patients in our institutional database with Benign Prostatic Hyperplasia (BPH) based on International Classification of Diseases (ICD) 9 and 10 codes assigned between 2000 and 2016. From this cohort we then identified patients who were on Finasteride and those that developed bladder cancer. All demographic and clinical variables including age, race, smoking history, finasteride use were collected via an institutional database that prospectively extracts data from electronic medical records (EMR). Finasteride use was based on the documented prescriptions. Chi-square test was used to compare the proportion of bladder cancer patients between two groups (i.e. users and non-users of Finasteride). Multivariate logistic regression analysis was performed to determine the association of finasteride use and diagnosis of bladder cancer controlling for age, smoking history and race._x000D_ Results We identified 42,774 patients with BPH. The median follow-up was 87 months. There were 11,864 (27.7%) African Americans (AA), 11,863 (27.7%) Caucasians, and 6,340 (14.8%) Hispanics in this population. 5,698 (13.3%) patients were prescribed Finasteride. Bladder cancer was diagnosed in 84 of 5,698 (1.5%) patients who were prescribed Finasteride compared with 863 of 37,076 (2.3%), who were not prescribed Finasteride (p<0.001). Multivariate logistic regression analysis showed that Finasteride use was protective of bladder cancer (OR: 0.57, CI: 0.45-0.71, p<0.001). When we stratified the data based on race, Finasteride use was protective of bladder cancer in Caucasians (2.1% vs. 3.8%, p=0.001) and Hispanics (0.8% vs. 1.6%, p=0.042), but not in AA (1.7% vs. 1.7%, p=0.854)._x000D_ Conclusions Our study confirms previous findings from the PLCO study that men who are on Finasteride have lower incidence of bladder cancer but only in Caucasians and Hispanics. Future research and randomized controlled studies may be needed to confirm these findings. _x000D_ Funding None
Authors
Abhishek Srivastava
Ethan Fram Ilir Agalliu Mark Schoenberg Alexander Sankin |
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PD57-08 |
CENTRALIZATION OF RADICAL CYSTECTOMY FOR BLADDER CANCER IN A UNIVERSAL HEALTHCARE SYSTEM: EARLY RESULTS FROM A CANADIAN ACADEMIC CENTER |
Bladder Cancer: Epidemiology & Evaluation III | 17BOS |
Abstract: PD57-08 Sources of Funding: None Introduction Radical cystectomy for bladder cancer is a complex surgical oncology procedure. Accumulating data suggest variation in outcomes based on hospital and surgeon characteristics. Centralization of this procedure to high volume, fellowship-trained surgeons may improve clinical outcomes. High quality data examining the impact of radical cystectomy centralization are lacking. At the University of Alberta, radical cystectomy was centralized at a single institution and performed by 1 of 2 urologic oncologists starting in August 2013. Our objective was to compare outcomes of radical cystectomy before and after centralization of care._x000D_ Methods A retrospective analysis of data from the University of Alberta Radical Cystectomy Database was performed. Eligible subjects were those with histologically proven urothelial carcinoma of the bladder (cTanyN1-3M0) undergoing curative intent surgery. Patients were classified into pre-centralization era (1994-2007; N=523) and post-centralization era (2013-present; N=134) cohorts for analyses. Pre-centralization era patients were treated by 1 of 11 urologic surgeons at 2 academic teaching hospitals. Post-centralization era patients were treated by 1 of 2 fellowship-trained urologic oncologists at 1 academic teaching hospital. Outcomes were overall survival, 90-day mortality rate, positive surgical margin (R1) resection rate, total number of lymph nodes evaluated, and 90-day blood product transfusion rate. The Kaplan-Meier method and multivariable regression analyses were used to analyze survival outcomes. Statistical tests were two-sided (p≤0.05)._x000D_ _x000D_ Results The median follow-up duration in the pre- and post-centralization era was 33 months and 16 months, respectively. The predicted 2-year overall survival rate was 62% in the pre-centralization era and 84% in the post-centralization era (Log rank P=0.0007; multivariable HR 0.40, 95% CI 0.24 to 0.68, P<0.0001). Treatment in the post-centralization era was associated with lower 90-day mortality (6.3% versus 1.5%, multivariable OR 0.23, 95% CI 0.06 to 0.99, P=0.049), R1 resection (13.0% versus 1.5%; multivariable OR 0.07, 95% CI 0.01 to 0.51, P=0.009), and 90-day blood product transfusion (59% versus 6%, P<0.0001) as well as higher total number of lymph nodes evaluated (7 versus 30 lymph nodes, P<0.0001)._x000D_ Conclusions Surgical treatment in the post-centralization era was associated with superior survival, cancer control, and perioperative outcomes._x000D_ _x000D_ Funding None
Authors
Jan Rudzinski
Niels Jacobsen Eric Estey Sunita Ghosh Scott North Naveen Basappa Michael Kolinsky Adrian Fairey |
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PD57-09 |
NATIONAL SURGICAL QUALITY IMPROVEMENT PROGRAM SURGICAL RISK CALCULATOR POORLY PREDICTS COMPLICATIONS IN PATIENTS UNDERGOING RADICAL CYSTECTOMY WITH URINARY DIVERSION: THE CASE FOR A PROCEDURE-SPECIFIC RISK CALCULATOR |
Bladder Cancer: Epidemiology & Evaluation III | 17BOS |
Abstract: PD57-09 Sources of Funding: University of Chicago Institute of Translational Medicine, Core Subsidy Grant Introduction The American College of Surgeons&[prime] National Surgical Quality Improvement Program (NSQIP) Risk Calculator is commonly used in the preoperative setting. The risk profile generated is often used during the informed consent process and may in the near future be used as a quality measure linked with reimbursement. We aimed to evaluate the accuracy of this NSQIP risk calculator in patients undergoing radical cystectomy with urinary diversion. Methods We retrospectively reviewed our institutional database to identify patients undergoing radical cystectomy with urinary diversion between 2010 and 2015. We used the proprietary NSQIP online calculator, which incorporated the procedure-specific CPT code, to obtain a 30-day postoperative risk profile for each of eleven outcomes, which were then compared to actual outcomes for each patient. Brier scores (BS) were calculated as a measure of NSQIP calculator accuracy. Consistent with prior studies, we selected a threshold of BS <0.01 (90% accuracy) as an acceptable calculator. Results We included 567 patients who underwent radical cystectomy, of whom 364 (64%) received an ileal conduit (IC) and 203 (36%) received orthotopic neobladder diversion (ONB). Mean age was 68.24 years (±10.40) and 435 (76%) were male. BS exceeded the threshold of 0.01 (indicating poor predictive value) for serious complications, any complications, surgical site infection, urinary tract infection, deep venous thrombosis, renal failure, readmission, return to operating room, and discharge to rehabilitation facility, regardless of diversion type (see Figure 1) - risk was underestimated for each of these complications. Length of stay was underestimated by 17% and risk of serious complication was underestimated by 31%. The calculator did adequately predict the risk of death for patients receiving ONB and overall. Conclusions The universal NSQIP surgical risk calculator inaccurately predicts most postoperative complications in patients undergoing radical cystectomy with urinary diversion. This highlights the need for a procedure-specific risk calculator in order to better counsel patients in the preoperative setting and generate realistic quality measures._x000D_ _x000D_ Funding University of Chicago Institute of Translational Medicine, Core Subsidy Grant
Authors
Melanie Adamsky
Shay Golan Chuanhong Liao Scott Johnson Nimrod Barashi Raj Bhanvadia Norm Smith Gary Steinberg Arieh Shalhav |
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PD57-10 |
A prospective study on the impact of radical cystectomy on sexual function in females with bladder cancer |
Bladder Cancer: Epidemiology & Evaluation III | 17BOS |
Abstract: PD57-10 Sources of Funding: none Introduction Patient reports of health related quality of life (HRQoL) are being used to facilitate understanding of the physical and psychological impacts of surgery in patients with bladder cancer. Presently, the true effect of radical cystectomy (RC) on female sexual function is poorly described. The aim of this study is to prospectively report baseline and post-operative sexual function in a group of females undergoing RC. Methods Seventy-four females undergoing RC for bladder cancer were enrolled from 2008-2014 in a prospective HRQoL study. The Female Sexual Function Index (FSFI) was administered 1 month prior to RC, 6- and 12-months post-operatively. Latent Transition Analysis (LTA) was conducted at all 3 points in time to assign patients to homogeneous groups based on their survey responses (i.e., patients with similar responses were grouped together). Group membership was modeled by marital status, type of urinary diversion, vaginal reconstruction, and administration of neoadjuvant chemotherapy. LTA was also used to estimate transitions between groups over time. Results Sixty patients completed baseline surveys and 47 (64%) one year following cystectomy. Median age of the cohort was 66 (IQR 59,72) and 62 patients (84%) underwent vaginal reconstruction with RC. LTA revealed that at baseline, 65% of patients provided responses that were characterized as having &[prime]no sexual activity&[prime] (group 1), 17% &[prime]limited sexual function&[prime] (group 2), and 18% &[prime]adequate sexual function&[prime] (group 3). The distributions were stable one year after RC (65%, 21%, and 14% for the 3 groups, respectively). Analyzing transitions between preop grouping and at 1 year revealed that 44% of patients with adequate sexual function (group 3) remained unchanged. In group 2, 33% remained in the same category, while 21% transitioned to group 3. For patients reporting no sexual activity pre-op, 87% remained in the same category at 1 year, but 8% and 5% transitioned to groups 2 & 3 respectively. Being married was significantly associated with sexual function after surgery (p<0.001). No significant association was found based on the type of urinary diversion, vaginal reconstruction, or neoadjuvant chemotherapy. Conclusions Although a large proportion of females are not sexually active either before or after RC, one third of patients in this study maintained sexual function, with a small proportion demonstrating improvement at 1 year. Enhanced understanding of pre-op and post-op sexual function can lead to improved peri-operative counseling & surgical planning for sexually active females undergoing RC. Funding none
Authors
Karim Marzouk
Bruce Rapkin Yuelin Li Thomas Atkinson Alan Thong Leah Goldstein Dahlia Sperling Carolyn Schwartz Harry Herr Machele Donat Vincent Laudone Jonathan Coleman Guido Dalbagni Bernard Bochner |
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PD57-11 |
Cross-sectional study evaluating long-term bowel issues in bladder cancer patients: Diarrhea as a limiting factor of quality of life after radical cystectomy |
Bladder Cancer: Epidemiology & Evaluation III | 17BOS |
Abstract: PD57-11 Sources of Funding: None Introduction A significant number of patients after radical cystectomy (RC) suffer from changes in bowel habits and defecation, as we had previously shown. Reports addressing long-term bowel disorders following RC are rare. This cross sectional study evaluates long-term bowel issues in a large cohort with the help of an issue-tailored questionnaire. Methods A questionnaire assessing changes in bowel function and its impact on daily life was developed and distributed in collaboration with the German bladder cancer support group. A total of 431 patients after RC were evaluated. Symptoms such as diarrhea, constipation, urge to defecate, sensation of incomplete defecation, flatulence, and impact on quality of life (QoL) were evaluated. Results A total of 324 patients were followed ≥1 year, 43% of the patients reported current bowel disorders, 40% life restriction and 60% dissatisfaction. Most frequent bowel symptoms were flatulence (49%), followed by diarrhea (30%) and the sensation of incomplete defecation (23%). The highest prevalence rate of diarrhea is reported in year 3 after surgery: 3 months after surgery 14%, 3-11 months 21%, 12-23 months 18%, 24-35 months 44%, 36-59 months 36%, ≥60 months 27% (p<0.01). Flatulence is also a long-term bowel symptom with a prevalence of 50% ≥1 year vs 37% <1 year after surgery (p=0.0334). The prevalence of the remaining bowel symptoms did not change over time. After 12 months, diarrhea significantly correlated with flatulence, uncontrolled stool loss, urge to defecate, younger age at time of surgery, and the size of bowel segment used for urinary diversion (all p<0.01). Patients suffering from diarrhea report a higher defecation frequency, a lower QoL, a higher dissatisfaction level, a lower energy level (all p<0.01), and a lower health state (p=0.0488). Conclusions To our knowledge this is the largest cohort evaluating long-term bowel issues after RC. Diarrhea is a prominent long-term bowel symptom after RC with a high impact on daily life. A better understanding of long-term bowel symptoms can be translated into daily clinical management, such as optimized surgical procedures, post-operative medication/nutrition and patient education. Funding None
Authors
Marie Hupe
Winfried Vahlensieck Martin Hennig Tomasz Ozimek Julian Struck Hossein Tezval Axel Merseburger Markus Kuczyk Mario Kramer |
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PD57-12 |
A comparison of post-cystectomy recurrence and survival in NAC-responsive MIBC vs. high-risk NMIBC patients: similar pathologic stage yet different outcomes |
Bladder Cancer: Epidemiology & Evaluation III | 17BOS |
Abstract: PD57-12 Sources of Funding: Greenberg Bladder Cancer Institute Introduction Patients with muscle-invasive bladder cancer (MIBC) who are down-staged after neoadjuvant chemotherapy (NAC) have improved survival over those who remain ≥pT2. It is uncertain whether subgroups of patients with high-risk non-MIBC (NMIBC) would also benefit from NAC. We compared post-surgical outcomes in high-risk NMIBC patients who did not receive NAC with MIBC patients who were down-staged with NAC and without NAC. Methods We identified 334 patients with urothelial bladder cancer who were pT0, pTis, pTa, or pT1 and N0 at cystectomy from 2005-2015: 111 with cT2 who received NAC (NAC-responsive), 37 with cT2 who did not receive NAC (non-NAC-responsive), and 186 with high-grade cTis, cTa, or cT1 (high-risk NMIBC). Comparisons were made using Kruskal-Wallis for continuous and chi-squared for categorical variables. Log-rank and Cox regression analyses were used to evaluate survival. Results Compared to NAC-responsive and non-NAC-responsive patients, high-risk NMIBC patients had higher prevalence of intravesical therapy (70.4% vs. 14.1% and 13.5%, p<0.01), pure urothelial histology (92.5% vs. 80.2% and 64.9%, p<0.01), tumor ≥2 cm (19.9% vs. 6.6% and 10.8%, p<0.01), and lower prevalence of pT0 pathology (11.8% vs. 41.3% and 46%, p<0.01). Location of recurrence did not differ significantly between the groups (p=0.53), and 23.5% of recurrences in high-risk NMIBC patients occurred outside of the pelvis. Log-rank comparisons showed improved recurrence-free and overall survival in NAC-responsive vs. high-risk NMIBC patients (p<0.02 and p<0.02) but not in non-NAC-responsive vs. high-risk NMIBC patients (p=0.34 and p=0.43). In Cox regression, tumor ≥2 cm was independently associated with increased risk of cancer recurrence (HR=2.31, p=0.02) and overall mortality (HR=2.10, p=0.02) Conclusions Patients with NAC-responsive MIBC had better post-surgical outcomes than patients with high-risk NMIBC. High-risk NMIBC patients had a higher prevalence of tumor ≥2 cm, which was an independant predictor of cancer recurrence. Despite being node negative, almost a quarter of recurrences in patients with high-risk NMIBC occurred distantly. Further work is needed to identify whether patients with unresectable or high volume NMIBC could benefit from NAC. Funding Greenberg Bladder Cancer Institute
Authors
Aaron Brant
Max Kates Meera Chappidi Nikolai Sopko Trinity Bivalacqua |
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PD58-01 |
Validation of Venous Thromboembolism Risk Assessment Score in Major Urologic Cancer Surgery: A Population Based Study |
General & Epidemiological Trends & Socioeconomics: Quality Improvement & Patient Safety I | 17BOS |
Abstract: PD58-01 Sources of Funding: None Introduction The Caprini Risk assessment model is widely used to risk stratify patients for the occurrence venous thromboembolism (VTE), and has been validated for non-urologic surgery. We sought to validate the Caprini risk assessment model in a contemporary cohort of patients undergoing major urologic cancer surgery. Methods A population-based cohort study comprised of a weighted sample of 1,099,093 patients from 490 United States hospitals undergoing radical prostatectomy, radical nephrectomy, partial nephrectomy, or radical cystectomy for malignancy from 2003 to 2013. The primary outcome was 90-day symptomatic VTE (pulmonary embolism or deep vein thrombosis). Patients were scored according to the Caprini risk assessment model. The association of risk factors with VTE was determined with logistic regression. The performance of the Caprini score, as a predictor of VTE, was quantified using receiver operating characteristic (ROC) curves. Results There were no patients in the low risk category, 0.9% in the moderate risk category, and 99.1% were high risk (38.1% high risk, 48.5% higher risk, and 12.5% highest risk). The incidence of postoperative VTE was 1.2% (0.6%, radical prostatectomy; 1.9%, radical nephrectomy; 1.0%, partial nephrectomy; 5.4%, radical cystectomy). Old age, obesity, central venous access, acute MI, abnormal pulmonary function, hypercoagulable states, past history of VTE, recent surgery, and immobilization were independent risk factors for VTE. While the Caprini score was generally associated with increased risk of VTE (odds ratio [OR] 1.21, 95% confidence interval [CI] 1.17-1.25, p<0.001), the Caprini score demonstrated poor discrimination in the prediction of VTE no matter if they received VTE chemoprophylaxis (ROC area 0.53, 95% CI 0.50-0.56) or did not receive VTE chemoprophylaxis (ROC area 0.58, 95% CI 0.56-0.59) (Figure). Conclusions While the Caprini risk assessment model has been validated in other surgical specialties, it is not a good predictor of venous thromboembolism in patients undergoing major urologic cancer surgery. It should not be used to risk stratify patients undergoing major urologic cancer surgery. Funding None
Authors
Ross Krasnow
Mark Preston Benjamin Chung Adam Kibel Steven Chang |
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PD58-02 |
A Quality Improvement Foley Project to Reduce Catheter Related Trauma in a Large Community Hospital |
General & Epidemiological Trends & Socioeconomics: Quality Improvement & Patient Safety I | 17BOS |
Abstract: PD58-02 Sources of Funding: None Introduction Indwelling catheter placement is a modifiable risk factor for urethral trauma. We describe the various aspects of an educational system that was implemented at our hospital with the primary goal of reducing Foley catheter trauma. Methods A multidisciplinary Foley Project protocol was implemented in June 2015, which consisted of a system-wide catheter education program, difficult urinary catheterization (DUC) algorithm, and skilled catheter nursing (SCN) team to improve patient outcomes. The catheter education program consisted of a didactic presentation, supplemented with hands-on teaching, presented by urology residents. The DUC algorithm (Figure 1) provided nurses with step-by-step instructions to follow when a DUC is encountered. A retrospective review of male DUC consults between June 2014 and September 2015 was then performed. The pre-protocol group includes consults received from June 2014 to May 2015. The post-protocol group includes consults received from June 2015 to September 2015. Results There were 74 patients in the pre-protocol (median age 71 years, median BMI 26.0) and 18 patients in the post-protocol group (median age 75 years, median BMI 27.4). The overall incidence of catheter-associated trauma during placement was 30/71 (41.1%) in the pre-protocol and 1/17 (5.9%) in the post protocol groups (p=0.005). The total incidence of false passage in the pre and post-protocol groups was 19/73 (26.0%) and 0/17 (0%), respectively (p=0.02). In the pre-protocol group, 39/73 (53.4%) required a procedure by a urologist, while only 2/17 (11.8%) of patients in the post-protocol group required a procedure (p=0.002). Conclusions Implementation of a Foley Project protocol consisting of system-wide nursing education, DUC algorithm, and SCN team reduced the frequency of catheter-associated trauma and subsequent procedures. Funding None
Authors
Kassem Faraj
Chirag Dave Paras Vakharia Judy Boura Jay Hollander |
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PD58-03 |
Is Compliance to an Enhanced Recovery Protocol After Radical Cystectomy Associated With Improved Post Operative Outcomes? |
General & Epidemiological Trends & Socioeconomics: Quality Improvement & Patient Safety I | 17BOS |
Abstract: PD58-03 Sources of Funding: None Introduction Enhanced recovery after surgery (ERAS) protocols have been shown to shorten length of stay and improve outcomes in patients undergoing radical cystectomy. In this study, we investigate the importance of compliance within our protocol on post-operative outcomes. Methods Using an IRB approved, prospectively maintained database, 303 consecutive patients were identified who underwent open radical cystectomy with ERAS pathway from 7/2013 to 12/2015. Compliance was measured by a Composite Compliance Score (CCS) constructed from 18 interventions (Table 1). Median CCS was 85%, and 157 patients with lower overall compliance (CCS< 85%) were compared to 146 with higher compliance (CCS>=85%). Results Patients in the more compliant group were younger, more likely to have orthotopic urinary diversion, received less blood transfusions and had shorter operative times (Table 2). On univariate analysis, more compliant patients had shorter hospital stays, significantly less GI related and high grade (clavien III or higher) complications at 30 and 90 days (Table 3). Multivariable linear regression modeling showed that higher compliance was significantly associated with shorter hospital stay ( β= -1.11, p<0.01,). Logistic regressions also revealed that higher compliance reduced the risks of GI related complications (OR=0.47, p<0.01), and 30-day high-grade complications (OR=0.39, p=0.026). Conclusions Patients with better compliance to our ERAS protocol have decreased length of stay by more than one day following cystectomy, reduced risk of high-grade and GI complications when compared to those with lower compliance. Our results strengthen the evidence for implementation of enhanced recovery protocols. Funding None
Authors
Saum Ghodoussipour
Brian Cameron Clara Wang Jie Cai Nariman Ahmadi Siamak Daneshmand Hooman Djaladat |
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PD58-04 |
The role of patient factors on urology operating room turnover |
General & Epidemiological Trends & Socioeconomics: Quality Improvement & Patient Safety I | 17BOS |
Abstract: PD58-04 Sources of Funding: None. Introduction Surgical quality improvement literature has historically focused on strategies in cost reduction, outcome improvement, and increasing operating room (OR) efficiency. To this point, a vast majority of available literature on OR turnover has focused on institutional factors: role of the surgeon, lean-thinking practices, and team perception of turnover. However, a paucity of research exists on patient-specific factors that may ultimately affect OR duration and turnover. Our objective was to determine the role of patient characteristics on urology OR turnover in both a hospital and ambulatory setting. Methods Patients undergoing urology procedures at our institution have routine prospective data collection, including preoperative ASA classification, as well as various time landmarks before, during, and between procedures (time patient enters the OR, time of intubation, etc). Retrospective collection of OR start and end times from an OR scheduling software was conducted. Emergency cases were excluded. Analysis of variance with effects of hospital vs. ambulatory location and ASA class (I-IV) was performed on logarithmically transformed times (to correct skew), followed by Tukeys test for multiple comparisons. Results A total of 1766 patients undergoing 1788 urology procedures over a 9 month period (January-September 2016) were stratified by ASA class I-IV. Both ASA class and location significantly affected time from OR start to procedure start, and time from procedure end to OR end; these times increased as ASA class increased. All OR times were significantly less in the ambulatory setting for any given ASA. Conclusions Though patient characteristics have long been known to effect intra-operative duration, prior literature has not properly determined the role of patient factors in OR turnover times. Our data demonstrate that turnover times were shorter in our ambulatory setting and that, as ASA class increases, OR start and end times are prolonged. Future quality improvement studies should focus on patient-specific factors that may affect OR efficiency. Funding None.
Authors
David Kozminski
Matthew Cerf Daniel Loman Paul Feustel Barry Kogan |
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PD58-05 |
Contributing to a crisis? Defining national patterns in opioid prescribing after outpatient vasectomy |
General & Epidemiological Trends & Socioeconomics: Quality Improvement & Patient Safety I | 17BOS |
Abstract: PD58-05 Sources of Funding: Grant 1T32-CA180984 from the National Cancer Institute Introduction Prescribing surplus opioids after minor surgery can increase risks of misuse in the community. Surgeons may be well positioned to decrease these risks through modification of post-operative prescribing practices. In this context, we define national practice patterns and surgeon-specific differences in opioid prescriptions after outpatient vasectomy. Methods Using the de-identified ClinformaticsTM Data Mart Database (OptumInsight, Eden Prairie, MN) from a large, national US health insurer, we identified patients who underwent outpatient vasectomy between 1/2012 and 12/2014. Men were excluded if they received any concurrent operation or filled an opioid prescription in the 6 months prior to vasectomy. For this cohort, we determined the proportion of men filling an opioid prescription in the 7 days after surgery, and evaluated the type and quantity of opioids prescribed, standardized to morphine milligram equivalents (MME). Finally, we quantified surgeon-specific variation in MMEs prescribed for surgeons with 10 or more patients in the cohort, and at least 5 filling an opioid prescription post-operatively. Results We identified 25,102 men who received a vasectomy during the study interval. Among this group, 10,442 (41.6%) patients filled an opioid prescription after surgery. Hydrocodone was the most common medication, comprising 66.7% of filled prescriptions. The median number of MMEs prescribed was 112.5 [IQR 82.5-150]; equivalent to twenty-three, 5 mg hydrocodone tablets per prescription [IQR 16.5-30 tablets/ prescription]. Across 360 surgeons meeting criteria for surgeon-specific analysis, the average number of MMEs prescribed after vasectomy varied substantially (range: 29.2-390 MMEs (p<0.001); corresponding to a range of six to seventy-eight, 5 mg hydrocodone tablets per prescription (Figure). Conclusions Less than half of men fill an opioid prescription following vasectomy, indicating that non-opioid pain strategies may be sufficient for most patients. Nonetheless, surgeon-specific analyses revealed a 13-fold difference in the average quantity of opioids supplied. Because patient necessity is unlikely to entirely explain this variability, efforts to reduce excess opioid prescribing after vasectomy are warranted. Funding Grant 1T32-CA180984 from the National Cancer Institute
Authors
Gregory Auffenberg
Rodney Dunn Yongmei Qin Tyler Winkelman James Dupree Brent Hollenbeck Ted Skolarus David Miller Tudor Borza |
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PD58-06 |
Surgical skill and patient outcomes after robot-assisted radical prostatectomy |
General & Epidemiological Trends & Socioeconomics: Quality Improvement & Patient Safety I | 17BOS |
Abstract: PD58-06 Sources of Funding: Blue Cross Blue Shield of Michigan Introduction The empirical relationship of surgical skill on patient outcomes after robotic surgery is unknown. In the Michigan Urological Surgery Improvement Collaborative (MUSIC), we assessed the association between peer review of technical skill and short-term operative outcomes following robot-assisted radical prostatectomy (RARP). Methods Surgeons performing RARP in MUSIC were invited to submit a representative video of a nerve-sparing procedure. Edited video clips of the vesico-urethral anastomosis from 29 surgeons underwent blinded review by 56 peer surgeons for global robotic skill using the Global Evaluative Assessment of Robotic Skills (GEARS) tool (maximum score 25) using a custom-designed web-based secure registry. Each surgeon underwent video review by at least 9 peer surgeon reviewers. Surgeons were ranked on GEARS scores and sorted into quartiles of skill. Using a mixed logistic regression model adjusted for surgeon as a random effect, we then assessed the relationship between the highest (Q4) and lowest (Q1) skill quartiles and risk-adjusted peri-operative complication rates at the patient level using data from a prospective registry involving 2,256 patients. Results Compared to surgeons in the lowest 25% (Q1) of skill ratings, surgeons in the top 25% (Q4) for skill had lower rates of excess blood loss (>400 cc) (OR=0.47, p=0.01), and less events of urethral catheter replacement after its removal (OR=0.62, p=0.07) (Figure). There were no differences between Q1 and Q4 performance quartiles when comparing readmission rates (OR=1.16, p=0.58) or prolonged urethral catheter (>16 days) duration outcomes (OR=1.41, p=0.27). Conclusions The technical skill of practicing robotic surgeons performing the anastomosis during RARP varied widely, and better skill was associated with superior results for selective patient outcomes. Future work will need to study the relationship between skill and long-term patient reported outcomes to determine if quality improvement initiatives focused on surgical skill lead to improved patient care. Funding Blue Cross Blue Shield of Michigan
Authors
James O. Peabody
Rodney L. Dunn Andrew Brachulis Tae Kim Susan Linsell Brian R. Lane Richard Sarle James Montie David C. Miller Khurshid R. Ghani for the Michigan Urological Surgery Improvement Collaborative |
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PD58-07 |
MUSIC OCTAVE – Composite Measures to Assess Surgeon Performance for Robotic Prostatectomy |
General & Epidemiological Trends & Socioeconomics: Quality Improvement & Patient Safety I | 17BOS |
Abstract: PD58-07 Sources of Funding: Blue Cross and Blue Shield of Michigan Introduction The Michigan Urological Surgery Improvement Collaborative (MUSIC) collects patient-reported outcomes (PRO), peri-operative outcomes, and surgeon-level video assessments of technical skill as a means to facilitate quality improvement for prostate cancer patients in the state of Michigan. In this study, we defined composite measures that could be used to identify better performing surgeons across a variety of outcomes for robot-assisted radical prostatectomy (RARP)._x000D_ Methods For the urethro-vesical anastomosis, an Outcomes, Competency, and Technical Assessment Video Evaluation (OCTAVE-Anas) score was created by combining PRO urinary function score changes at 3-months post-RARP, percentage of patients having a urethral catheter duration >16 days, percentage of patients readmitted, and blinded peer-review Global Evaluative Assessment of Robotic Skill (GEARS) scores of videos of the anastomosis technique. Similarly, for nerve sparing (NS), OCTAVE-NS score was created based on differences in erectile function at 6-months post-RARP, percentage of organ-confined patients with positive margin, and GEARS assessment of NS technique. All component measures were standardized to represent number of standard deviations better (positive values) or worse (negative values) than population averages, and the OCTAVE score was calculated as the sum of these standardized values._x000D_ Results From 4/2014 through 4/2016, 20 surgeons from 14 different practices (2,774 total patients) sent video clips of their surgical techniques and had at least 50% of their patients participating in MUSIC PRO. OCTAVE-Anas scores ranged from -6.4 to 3.5, while OCTAVE-NS scores ranged from -3.7 to 3.5. Construct validity was demonstrated with moderate correlation between OCTAVE and the video assessment scores (Anas r=0.59, NS r=0.56, Figure 1). _x000D_ Conclusions OCTAVE successfully incorporates multi-dimensional assessments to reliably determine better performing surgeons for the anastomosis and nerve-sparing aspects of RARP. This method may be used to identify surgeons to provide peer surgical skill quality improvement, with the aim to advance care for prostate cancer patients in the state of Michigan._x000D_ Funding Blue Cross and Blue Shield of Michigan
Authors
Rodney L Dunn
James O Peabody Brian R Lane Richard Sarle Tae Kim Andrew Brachulis Todd Morgan Benjamin Stockton Khurshid R Ghani for the Michigan Urological Surgery Improvement Collaborative |
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PD58-08 |
The Utility of Standardized Weekly Intradepartmental Conference in Detecting Preoperative Issues and Concerns |
General & Epidemiological Trends & Socioeconomics: Quality Improvement & Patient Safety I | 17BOS |
Abstract: PD58-08 Sources of Funding: _x000D_ none Introduction Unrecognized pre-operative issues and concerns negatively impact operating room utilization and patient safety. The objective of this study is to evaluate the utility of standardized weekly Intradepartmental Conference in detecting pre-operative issues and concerns. Methods We implemented a pre-operative conference involving 14 urology staff (4 faculty urologists, 3 residents, 4 physician assistants and 3 nurses) to review operative cases 1 week prior to their scheduled dates. Each case was discussed in detail regarding the condition, procedure, indications, history and physical examination, laboratory and radiological findings, risk factors and social issues. An independent provider who did not directly participate in the conference recorded all concerns and issues as well as all corrective actions and changes. Data was collected in a prospective manner. Results Data on 330 cases were collected prospectively over a 12-month period. The operative workload included stone procedures (42%), transurethral resections (32%), open/laparoscopic oncology procedures (10%) and others (15%). American Society of Anesthesiologists (ASA) Physical Status was class 3 in 70% and class 2 in 23%. The majority (88%) of patients had at least 1 medical comorbidity, and 68% (n=225/330) had at least one issue or concern identified during the pre-operative conference; 1 issue (37%), 2 (18%), 3 (10%), 4 (2%) and 5 (2%). Abnormal, missing or pending labs were collectively the most common issue (36%) followed by issues relating to consent (24%), anesthesia and surgical risks (14%), imaging (10%), other work-up (10%), OR resources or equipment (4%), and socio-economical (3%). Such issues required corrective/mitigating actions in 53% (174/330) of cases that related the procedure (18%), pre-operative investigations and optimization including pre-admission (14%) and case order (6%). In addition, 8.7% (29/330) of the cases were cancelled/rescheduled purposefully to allow time to correct the issues. Such practice resulted in improved OR access that allowed earlier dates for 4% of the cases awaiting surgical treatment. Conclusions Standardized pre-operative review of surgical cases identifies issues and concerns, and provides an opportunity to implement corrective actions. Such practice has the potential to positively impact OR utilization and patient safety. Funding _x000D_ none
Authors
Al-Qassab Usama
Jeffrey Pearl Louis Aliperti Dean Laganosky Vitaly Zholudev Lorentz Adam Maggie Dear Jennifer Lindelow Donald Finnerty John Petros Filson Christopher Muta Issa |
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PD58-09 |
The impact of a teaching hospital on fundamental general urologic procedures: do residents help or hurt? |
General & Epidemiological Trends & Socioeconomics: Quality Improvement & Patient Safety I | 17BOS |
Abstract: PD58-09 Sources of Funding: none Introduction There has been increased focus on supervision and quality of care in resident education. Studies suggest trainee involvement in complex urologic procedures results in increased operative time with decreased complications. We wanted to examine the effects of trainee involvement in fundamental urology procedures. Methods Current Procedural Terminology codes were used to identify patients within the National Surgical Quality Improvement Program database who underwent a selection of fundamental general urology procedures (2005-2013). Operative time and perioperative complications (30-day) were examined and compared between cases with and without resident/fellow (R/F) involvement. Results 29,488 patients had general urology procedures with information regarding trainee involvement, 13,251 (44.9%) with R/F involvement and 16,237 (55.1%) without. Overall patients who underwent procedures with trainee involvement were younger and had fewer comorbidities (table 1). R/F involvement showed significant increase in operative time in all procedures included in the study (table 2.) On multivariate analysis trainee involvement increased the risk of complications (OR 1.61, 95% CI 1.45-1.78, p<0.001). Other factors that increased the risk of complications were: ASA class 3-4 (OR 2.01, 95% CI 1.46-2.77, p<0.001), partially/totally dependent functional status (2.22, 95% CI 1.68-2.94, p<0.001), diabetes mellitus (OR 1.21, 95% CI 1.05-1.39, p=0.008), heart disease (OR 1.19, 95% CI 1.02-1.38, p=0.027), and respiratory disease (OR 1.33, 95% CI 1.09-1.63, p=0.027). Laparoscopic approach showed a decreased risk in complications (OR 0.44, 95% CI 0.39-0.49, p<0.001). Conclusions While R/F are valuable members of the urology team at teaching hospitals and training is necessary, their involvement in urologic surgery appears to increase operative time and complications. Further research needs to be done on how to mitigate these effects while preserving surgical education quality. Funding none
Authors
Carrie Mlynarczyk
Maxwell James Henry Tran Doreen E Chung |
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PD58-10 |
Quality Improvement Education and Participation in Urology Residency Programs: Preliminary Survey Results of Program Directors |
General & Epidemiological Trends & Socioeconomics: Quality Improvement & Patient Safety I | 17BOS |
Abstract: PD58-10 Sources of Funding: None Introduction One of the key physician competencies outlined in the Urology Milestone project is engagement in quality improvement (QI). Despite this mandate, little is known about how QI education and participation by residents is integrated into their training. Therefore, we performed a national survey of urology residency program directors (PD) in partnership with the Society of Academic Urologists (SAU). Methods A 37-item electronic survey was developed to assess QI education, mentorship, and participation within a urology residency program. The survey was tested by an assistant program director and revised based on the feedback received. The survey was sent via email (11/1/2016) to all PD affiliated with the SAU (n=116; 94% of ACGME programs). Included in this analysis are only the completed responses received from the initial survey invitation at 1 week (censor date 11/7/2016). Results A total of 22 respondents returned a completed survey for a response rate of 19% (22/116). Table 1 outlines program characteristics. All PD reported they participate in direct patient care, but 36% (8/22) also listed QI leader and educator as an additional role. Only 27% (6/22) of PD have received formal training in QI methodology, but 59% (13/22), 55% (12/22), and 32% (7/22) are directly involved in QI education, serve on a QI committee, and lead a QI team, respectively. Only 45% (10/22) of programs have a formal curriculum for teaching QI to residents with 90% (9/10) using didactic sessions focusing on Six Sigma (5/10; 50%) and root cause analysis (5/10; 50%) methodology. Table 2 lists PD attitudes towards QI education and participation for residents. The majority of PD (19/22; 86%) would like to see the American Urological Association develop a urology-oriented QI curriculum. Conclusions A minority of programs have QI education available for residents. However, PD agree that QI is an integral part of residency training, which should be promoted by our profession. Responses from additional PD will allow us to validate these initial trends. Funding None
Authors
Justin Ziemba
Brian Matlaga Christopher Tessier |
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PD58-11 |
The Fragility of Statistically Significant Results from Randomized Trials in Urology |
General & Epidemiological Trends & Socioeconomics: Quality Improvement & Patient Safety I | 17BOS |
Abstract: PD58-11 Sources of Funding: None Introduction Randomized controlled trials (RCTs) have the potential of providing high quality evidence to inform clinical practice. This quality relies not only on safeguards against bias, but also on statistical power. In this study, we determined the Fragility Index of urological RCTs as a novel metric (Walsh M et al, JCE 2014) to assess the robustness of statistically significant results. Methods Statistical significance implies that an observed event is unlikely to occur by chance alone. The fragility index is defined as the minimum number of patients in an arm of a trial whose status would have to change from "non-event" to "event" in order to turn a statistically significant result into a non-significant one. All RCTs published in the 4 major urology journals between 2011-2015 were identified. We excluded studies not reporting dichotomous outcomes, as well as those with non-significant results and non-parallel designs. We applied the Fisher exact test to determine fragility index values. Results 332 RCTs were identified, and 42 studies met inclusion criteria. Median sample size (IQR) was 99 (65, 179), while median event rate per study outcome was 38 (24, 65). The median fragility index was 3 (1, 4.5), indicating that an addition of only three alternate events to an arm of the average trial would have eliminated its statistical significance. There was statistically significant correlation between the fragility index and events per study (ρ=0.552, p=0.01) as well as sample size (ρ=0.493, p=0.01). Conclusions Statistically significant results in urology RCTs are often fragile, with significance hinging on few events. This is of particular concern in studies that may have large loss to follow-up numbers. Urologists should therefore interpret RCTs cautiously. There may be a role for reporting fragility index values routinely alongside the p-value to provide additional guidance as to the statistical robustness of findings. Funding None
Authors
Vikram Narayan
Shreyas Gandhi Kristin Chrouser Nathan Evaniew Philipp Dahm |
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PD58-12 |
PSA screening at the intersection of Politics and Policy |
General & Epidemiological Trends & Socioeconomics: Quality Improvement & Patient Safety I | 17BOS |
Abstract: PD58-12 Sources of Funding: None Introduction The implementation of health care policy in the U.S. may be impacted by conflicting political philosophies. A &[Prime]conservative&[Prime] view of health care emphasizes an individual&[prime]s right to self-determination, while a &[Prime]liberal&[Prime] view holds that government can effectively utilize strategies to balance the needs of the community with those of an individual. Federal screening guidelines promoting population health may be perceived to conflict with conservative values. The aim of this study was to assess the inter-relationship of a states percentage of &[Prime]conservative&[Prime] men and the impact that the 2012 USPSTF recommendation against PSA-based prostate cancer (PCa) screening on screening probability. Methods Data from the 2012 and 2014 Behavioral Risk Factor Surveillance System was used to identify asymptomatic men (age ≥ 50) without PCa who reported PSA screening in the past 12 months. Odds ratios were determined by multivariate logistic regression analysis, adjusting for age, race, education, income, insurance, healthcare access, and marital status. The change in PSA screening rates were assessed as a function of the percentage of adults in a state describing themselves as &[Prime]conservative&[Prime] or &[Prime]very conservative&[Prime] in Gallup U.S. Daily (accessed 4/4/16). Results Among 222,475 survey respondents, the prevalence of PSA screening decreased between 2012 and 2014 (OR=0.87, p<0.001; Fig 1a). In the most conservative states (upper tertile of self-described conservatives) screening prevalence was unchanged (OR=0.92, CI 0.84-1.00), and in the least conservative states (lowest tertile) there was a significant decline (OR=0.72, CI 0.64-0.81; Fig 1b)._x000D_ Up to 22% of the variation in PSA screening rates may be ascribed to a state&[prime]s dominant political leaning (coefficient of determination=0.22), a moderate and significant correlation (ρ= 0.47, P<0.001)._x000D_ Conclusions The changes in PSA screening rates appear to reflect the political divide in the U.S. Despite the 2012 USPSTF guideline and subsequent overall decrease in PSA screening, there was no decline in PSA screening in the most conservative states. This is a hypothesis-generating finding, as it is predicated on observational data that may be affected by other factors. Nonetheless, this finding suggests that a state&[prime]s dominant political ideology influences the implementation of federal health care screening policy. Funding None
Authors
Jesse Sammon
Emily Serrel Malte Vetterlein Patrick Karabon Gregory Mills Moritz Hansen Mani Menon Quoc-Dien Trinh Firas Abdollah |
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PD59-01 |
Active Surveillance for Small Renal Masses is Safe and Non-Inferior: Intermediate-Term Results from the DISSRM Registry |
Kidney Cancer: Localized: Active Surveillance | 17BOS |
Abstract: PD59-01 Sources of Funding: National Institutes of Health (NIH), Grant Number TL1 TR001078. Introduction Active surveillance is an alternative to primary intervention aimed at reducing the overtreatment of small renal masses, defined as solid renal masses ≤4.0 cm (clinical stage T1a). We sought to describe intermediate-term outcomes in patients with small renal masses enrolled in a multi-institutional, prospective study. Methods Since 2009, the Delayed Intervention and Surveillance for Small Renal Masses (DISSRM) registry prospectively enrolled 615 patients with small renal masses who chose to undergo primary intervention or active surveillance. Primary outcomes were cancer-specific survival and overall survival; secondary outcomes included progression-free survival. Progression was strictly defined as growth rate >0.5 cm/year, greatest tumor diameter >4.0 cm, metastatic disease, or elective crossover. Outcomes were evaluated using Kaplan-Meier survival analysis and comparisons were performed using the log-rank test. Results Of the 615 enrolled patients, 298 (48.5%) chose primary intervention and 317 (51.5%) chose active surveillance. From the active surveillance cohort, 45 (14.2%) patients underwent delayed intervention. Median follow-up time for the entire registry was 2.9 years, with 203 (33.0%) patients followed for 5 years or more. At baseline, patients who chose active surveillance were older (P < 0.001) and had higher comorbidity status (P < 0.001) than those who chose primary intervention. There was no difference in cancer-specific survival at 7 years between primary intervention and active surveillance (99.0% vs 100%, respectively, P = 0.3) [Figure 1A]. However, overall survival was higher in patients with primary intervention when compared to active surveillance at 5 years (93.0% vs 80.2%, respectively) and 7 years (91.7% vs 65.9%, respectively, P = 0.002) [Figure 1B]. The 5-year and 7-year progression-free survival rate in the active surveillance cohort was 83.9% and 71.4%, respectively. Conclusions In the intermediate-term, active surveillance appears to be as safe as and not inferior to primary intervention for carefully selected patients with small renal masses. As the registry matures, further studies will elucidate the effectiveness of active surveillance in the long-term. Funding National Institutes of Health (NIH), Grant Number TL1 TR001078.
Authors
Ridwan Alam
Hiten D. Patel Mark F. Riffon Bruce J. Trock Peter Chang Andrew A. Wagner James M. McKiernan Mohamad E. Allaf Phillip M. Pierorazio |
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PD59-02 |
Variability in growth kinetics of small renal masses on active surveillance: Results from the DISSRM Registry |
Kidney Cancer: Localized: Active Surveillance | 17BOS |
Abstract: PD59-02 Sources of Funding: Research reported in this abstract was supported by the TL1 Predoctoral Training Program of the National Institutes of Health under award number TL1200008._x000D_ _x000D_ The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Introduction Active surveillance (AS) is emerging as a safe and effective strategy for the management of small renal masses, which are defined as solid masses with a maximum diameter less than 4.0cm. We conducted this prospective multi-institutional study involving patients with small renal masses in order to characterize the growth rates of these masses and their pertinence to clinical outcomes. Methods Beginning in 2009, the Delayed Intervention and Surveillance for Small Renal Masses (DISSRM), a prospective multi-institutional registry of patients with small renal masses, has enrolled patients who chose either primary intervention or AS. Patients electing active surveillance received regularly scheduled imaging, with tumor characteristics collected throughout their enrollment in the registry. Results 615 patients were prospectively enrolled, of which 317 patients (51.5%) elected AS. 284 had follow-up imaging at time of this analysis, with a mean follow-up of 2.91 years. Overall mean growth rate was -0.11 cm±0.31cm/year (median: -0.07 cm/year). Growth rate and variability decreased with time, with the mean growth rates at 6, 12, 24, and 48 months of -0.10±0.09, -0.08± 0.07, -0.05±0.056, and -0.04±0.02 cm/year, respectively (Figure 1). GR was not predictive of adverse pathological features. No patient developed metastatic disease or died of kidney cancer. Conclusions Growth kinetics of SRM is highly variable upon entrance into AS, with both growth rate and growth rate variability decreasing with time. Early in AS, worrisome growth rates should not trigger reflex crossover to intervention as growth rates are highly variable within the first 6-12 months of surveillance. Instead we recommend re-assessment of risk stratification with additional imaging or consideration of biopsy prior to treatment. The role of GR in decision making for SRM on AS requires further refinement. Funding Research reported in this abstract was supported by the TL1 Predoctoral Training Program of the National Institutes of Health under award number TL1200008._x000D_ _x000D_ The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Authors
Akachimere Uzosike
Michael Johnson Hiten Patel Mark Riffon Michael Gorin Christian Pavlovich Peter Chang Andrew Wagner Bruce Trock Mohamad Allaf Phillip Pierorazio |
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PD59-03 |
Growth kinetics in von Hippel-Lindau-associated renal tumors: Defining the influence of germline mutation type |
Kidney Cancer: Localized: Active Surveillance | 17BOS |
Abstract: PD59-03 Sources of Funding: none Introduction Renal cell carcinoma develops in 25-60% of patients von Hippel-Lindau (VHL), which is characterized by germline mutations in the VHL gene. The paradigm for treating renal tumors in VHL includes active surveillance for lesions less than 3 cm, and surgical resection for lesions greater than 3 cm. Knowledge of growth rates for renal lesions in VHL guide surveillance schedules. While the risk of developing RCC is related to VHL genotype, it is unknown if VHL genotype can influence tumor growth rate. We sought to characterize growth rate for VHL-associated renal tumors and to determine if the type of germline mutation in VHL influences tumor growth kinetics._x000D_ Methods Patients with solid, enhancing renal tumors with at least 3 cross sectional imaging studies and known germline mutation status were retrospectively reviewed. In patients with multiple index lesions, all lesions were analyzed. Renal tumor size was measured as the largest single-dimension diameter. Growth rates were calculated using linear regression. Germline mutations were categorized into missense, partial deletion, frameshift, deletion, splice donor, amino acid insertion, and splice acceptor. The effect of germline mutation type on renal tumor kinetics was assessed with the Wilcoxon-ranksum or Kruskall Wallis tests. _x000D_ Results A total of 246 tumors in 161 patients and 1341 time-point measurements were included for analysis. Median growth rate for the entire cohort was 3.5 mm (interquartile range 2.4-5.1 mm). Median growth rates were similar for all mutation categories: 3.4 mm for missense (n=111), 3.5 mm for partial deletion (n=71), 3.2 mm for nonsense (n=28), 4.5 mm for frameshift (n=16), 2.5 mm for deletion (n=8), 3.4 mm for splice donor (n=4), 3.9 mm for amino acid insertion (n=3), and 4.9 mm for splice acceptor (n=3) (Figure 1). There was no difference in growth rates between missense and non-missense tumors (p=0.1) _x000D_ Conclusions The majority of VHL-associated renal tumors have a growth rate of less than 5 mm per year. Where no association was identified between germline mutation type and single-dimension VHL renal tumor growth kinetics, further study is needed to determine the impact of somatic mutations on tumor development and growth kinetics. _x000D_ Funding none
Authors
Mark Ball
Shawna Boyle Kiranpreet Khurana Rabindra Gautam Gennady Bratslavsky W. Marston Linehan Adam Metwalli |
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PD59-04 |
Natural history and predictors of growth of small renal masses in a prospective cohort with a median follow-up of five-years |
Kidney Cancer: Localized: Active Surveillance | 17BOS |
Abstract: PD59-04 Sources of Funding: None Introduction Active surveillance (AS) has become the preferred treatment for small renal masses (SRM) in elderly and the infirm. The vast majority of data comes from small retrospective series with short-term follow-up. We report the natural history of SRM in patients with a five-year median follow-up. Methods This prospective cohort included patients undergoing AS for SRMs diagnosed between 2001 and 2011 in Nova Scotia. Age, sex, symptoms at presentation, diameters at diagnosis (cm), tumour location (central, peripheral), degree of endophytic component (1-100%), tumour consistency (solid, cystic), and renal mass biopsy were evaluated. Outcomes observed included progression to treatment or metastatic disease and death, as well as tumor growth rate and its predictors. Results The total cohort included 324 patients. Of those, we included 103 patients with 107 SRMs with a diagnosis prior to 2012. Median follow-up time for patients on continued AS was 59.2 months with a median age at diagnosis of 75 years. The median maximum diameter and volume at diagnosis were 2.1 cm (IQR=1.2 cm) and 4.8 cm^3, respectively. 69.9% of population had peripheral masses and 82.5% has solid masses. Biopsies were in 10.7% of patients (36.4% malignant histology). Surgery was performed in 15.5% of patients for tumour growth, gross hematuria, renal vein thrombus, or personal request (68.8% malignant histology). 1.9% of patients developed metastatic disease. In total, 45.6% of the population died from other causes and 1.9% died from kidney cancer. Of the patients on continued AS, 51.5% were alive without metastatic disease and 1.0% were alive with metastatic disease. The average growth rate of all SRMs was 6.2 cm^3/year with an average volume at diagnosis of 9.3 cm^3 (p= 0.0043). Tumor growth rate was significantly different between peripheral and central SRMs (p= 0.0007) with peripheral masses growing at a rate of 1.8 cm^3/year (initial volume at diagnosis= 7.9 cm^3) and central masses growing at a rate of 17.3 cm^3/year (initial volume at diagnosis= 11.4 cm^3). Tumor growth rate of masses that were >3 cm at initial diagnosis was approximately 15 times greater than masses that had an initial diameter of <1 cm (23.5 cm^3/year versus 3.0 cm^3/year; p= 0.0067). Conclusions In this cohort with a median follow-up of five years, 45.6% of patients died from other causes and only 1.9% developed metastatic disease. This demonstrates that AS is the preferred treatment for patients who are elderly or infirm. Tumor growth rate can be predicted by initial tumour size and tumor location. Funding None
Authors
Emily Whelan
Jeffrey Himmelman Ross Mason Kara Thompson Ricardo Rendon |
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PD59-05 |
Active Surveillance for renal masses with > 5 years of follow-up: Tumor growth, delayed intervention rates, and clinical outcomes |
Kidney Cancer: Localized: Active Surveillance | 17BOS |
Abstract: PD59-05 Sources of Funding: None Introduction We reviewed our large single center experience with active surveillance (AS) for localized renal masses focusing on patients with > 5 years (yrs) of follow-up. Methods We queried our prospectively maintained kidney cancer database (n = 2574) for patients (pts) enrolled on AS. Estimated tumor volume (ETV) was calculated using a standard formula and linear growth rate (LGR) was evaluated. Wilcoxon rank sums and Chi-squared tests were used to assess for demographic differences in growth rates and cross-over to DI. Kaplan-Meier curves were used evaluate clinical outcomes. A sub-set analysis (n = 156) was performed of pts with ≥5 yrs follow-up and no cross-over to DI. Results We identified 601 pts enrolled in our AS program (60.1% male, mean age 67.3 yrs, mean ETV of 22.9 cm3). The median follow-up for the entire cohort was 62.6 months (mo). Mean change in ETV was 6.9 cm3/yr (IQR -0.03 to 4.14 cm3/yr) and mean LGR was 2.6 mm/yr. Mean change in ETV of solid masses was more rapid than cystic masses (11.4 vs. 5.8 cm3/yr, p <0.04). Of the entire cohort, 190 pts (32%) crossed over to DI (Figure 1). Among those who crossed over, median time to DI was 16.4 mo (IQR 9.2 to 32.6 mo). Cross over to DI was uncommon after 24 mo whereas nearly two-thirds of patients who crossed over to DI did so within 2 yrs and 77% crossed over within 36 mo of enrolling in AS. Younger pts (63.6 vs. 69.0 yrs, p < 0.0001) and pts with solid versus cystic masses (33.9% vs. 23.3%, p < 0.016) were more likely to cross-over to DI. A majority of pts (89.5%) were still alive at 60 mo follow-up. A subset of 156 pts had ≥5 years of follow-up without crossing over to DI (62.9% men and mean ETV at presentation of 4.26 cm3). 16 pts died, however, only 6 pts (1.5%) exhibited disease progression. One pt died from RCC and 5 developed lymph node or distant metastasis. Mean ETV growth rate for this sub-set was 2.81 cm3/year and mean LGR was 1.4 mm/yr. Conclusions AS with or without DI is a successful strategy in well selected pts with localized renal masses. Most patients who cross over into DI are likely to do so within the first 2 yrs on AS. Metastasis and death from disease are rare in well selected pts who have been followed for ≥5 yrs. AS of localized renal masses is a sound oncologic practice in select pts beyond 5 yrs of follow-up. Funding None
Authors
Andrew McIntosh
Pranav Parikh Anthony Tokarski Eric Ross David Chen Richard Greenberg Alexander Kutikov Marc Smaldone Rosalia Viterbo Robert Uzzo |
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PD59-06 |
Quality of life scores in patients with small renal masses who have undergone renal mass biopsy compared to those who have not: analysis of the DISSRM Registry. |
Kidney Cancer: Localized: Active Surveillance | 17BOS |
Abstract: PD59-06 Sources of Funding: None Introduction Renal mass biopsy (RMB) can be employed as an adjunct to the decision-making process for patients with small renal masses. It is hypothesized that the pathological diagnosis provided by RMB purports a QOL advantage by alleviating cancer-related uncertainty and anxiety. This study evaluates the influence of RMB on QOL in a large prospective registry of patients with SRM. _x000D_ _x000D_ Methods The DISSRM (Delayed Intervention and Surveillance for Small Renal Masses) Registry is a multi-institutional study that prospectively follows patients with SRM who elect primary intervention (PI) or active surveillance (AS). Patients complete SF12 QOL questionnaire at enrollment, 6 and 12 months, and subsequently on an annual basis. SF12 scores, MCS (Mental Component Summary) and PCS (Physical Component Summary) were compared between patients who had RMB versus those who did not in the PI, AS, and crossover groups separately using ANOVA and linear regression mixed modeling. Results 619 patients were identified in the DISSRM Registry, of whom 320 were in the AS arm and 299 in the PI arm. 84 patients (13.6%) underwent biopsy, 34 (40.6%) in the PI group, 35 (41.6%) in the AS group, and 15 (17.8%) in the AS group who crossed over. Median age, ECOG performance status and Charlson comorbidity Index (CCI) were similar regardless of biopsy status among the AS and PI groups. In PI patients, there were no significant differences between SF12, MCS or PCS (p>0.092) or changes in SF12, MCS, or PCS (p>0.162) in patients who underwent biopsy and those who did not across all time points up to 84 months. In the AS patients who did not crossover, no differences in SF12, MCS and PCS were seen between patients who had biopsy and those who did not (p>0.0564). PCS declined over time in patients who stayed on AS without biopsy (p<0.001), but all other measures were unchanged over time (p>0.7291). In the crossover group, SF12, MCS, and PCS were lower at 24 and 48 months in patients who had not undergone biopsy (p=0.002). These patients were older (72.5 vs 67.2, p=0.003), had higher CCI (p=0.004), and lower ECOG performance status (p=0.045). There were no changes to SF12, MCS, or PCS scores in crossover patients regardless of biopsy status over time (p>0.1513). _x000D_ _x000D_ Conclusions AS and PI patients who underwent RMB during follow-up in DISSRM did not have significant changes in quality of life scores over time, nor did they have worse scores than their counterparts who did not undergo biopsy. A pathological diagnosis through RMB did not appear to have a beneficial or detrimental effect on QOL while on AS. Funding None
Authors
Alice Semerjian
Ridwan Alam Hiten Patel Mark Riffon Michael Johnson Peter Chang Andrew Wagner James McKiernan Bruce Trock Mohamad Allaf Phillip Pierorazio |
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PD59-07 |
Using Mathematical Modeling to Define the Role of Active Surveillance in the Management of Patients with Clinical T1 Renal Masses |
Kidney Cancer: Localized: Active Surveillance | 17BOS |
Abstract: PD59-07 Sources of Funding: American Cancer Society Institutional Research Grant, 81-001-26, Lobo (PI), 12/01/2015-11/30/2016, "A Model to Optimize use of Biopsies and Treatment for Small Renal Masses" Introduction A considerable proportion of small renal masses (SRMs) are either benign or demonstrate indolent behavior, yet guidelines stop short of recommending active surveillance (AS) over definitive treatment for any subset of patients with SRMs. Because coding does not easily capture AS, outcomes data is limited and secondary data analysis is difficult. Given these limitations, we developed a mathematical model to determine when AS can be recommended over definitive treatment. Methods We developed a Markov Decision Process (MDP) model to maximize life years and quality-adjusted life years (QALYs) for patients with SRMs over a ten year horizon, comparing AS, ablation, and surgical treatments. Patient demographics, pre-existing comorbidities, mass characteristics, degree of renal impairment, and treatment-associated morbidity were incorporated. A Markov model was used to simulate the size progression of SRMs. All model inputs were extrapolated from current literature. Results Table 1 shows results for one patient subset: 65 year old patients with no comorbidities. To maximize life years, the model recommended AS over definitive treatment for patients with SRMs up to 3 cm in diameter. Partial nephrectomy (PN) was recommended for patients with masses 3 cm and larger. Ablation was recommended as a secondary option to PN due to the assumption of a higher recurrence rate with ablation compared to PN. For patients with a central mass where nephron sparring treatment was less feasible, radical nephrectomy (RN) was only recommended for patients with 4 cm masses and larger without advanced chronic kidney disease (CKD Stage 4 and 5). To maximize QALYs, the model recommended AS for more subsets of patients, including older patients. Conclusions Clinicians are increasingly advising patients with SRMs to undergo active surveillance over definitive treatment. In the absence of large prospective trials, mathematical modeling can help frame the decision making process for patients and inform future guidelines on the management of patients with SRMs. Our model can give personalized recommendations for patients based on demographics, comorbidities, and mass characteristics._x000D_ Funding American Cancer Society Institutional Research Grant, 81-001-26, Lobo (PI), 12/01/2015-11/30/2016, "A Model to Optimize use of Biopsies and Treatment for Small Renal Masses"
Authors
Devang Sharma
Jennifer Lobo Noah Schenkman Tracey Krupski |
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PD59-08 |
Proposal and validation of a dynamic criterion for patient inclusion in kidney cancer active surveillance protocols |
Kidney Cancer: Localized: Active Surveillance | 17BOS |
Abstract: PD59-08 Sources of Funding: None Introduction Overtreatment of older patients with a small renal mass is a relevant concern and active surveillance [AS] represents an attractive management. However, current criteria for AS eligibility lack of validation. The aim of the study was to validate a criterion for AS eligibility based on tumour clinical size and age on a cohort of patients treated with surgery. Methods 1922 patients diagnosed with a cT1cN0cM0 renal mass elected for surgical treatment and collected into a prospective database were assessed. Under the assumption that older patients with smaller tumours are optimal candidates for AS relative to younger patients with larger tumours, we relied on the ratio [R] between tumour clinical size and age in order to differentiate patients suitable for AS (R<5) from patients unsuitable for AS (R≥5). X2 test was used to compare the rate of malignant histology, stage pT3-pT4 and grade G3-G4 at final pathology in patients suitable vs. unsuitable for AS. Smoothed Poisson?s incidence plots were used to examine the rate of cancer specific [CSM] and other cause mortality [OCM] in patients suitable vs. unsuitable for AS. Results According to the proposed definition, the rate of patients suitable for AS was 34%. Patient suitable for AS had a lower rate of malignant histology (78 vs. 87%; p<0.001), pT3-pT4 (4 vs. 10% p=0.001) and grade G3-G4 (7 vs. 17% p<0.001) relative to patients unsuitable for AS. In patients suitable for AS, the 10-year rates of CSM and OCM were 1.7 and 19%, respectively (Fig. 1A). In patients unsuitable for AS, the 10-year rates of CSM and OCM were 6.7 and 11% (Fig. 1B), respectively. Conclusions When validated in a cohort of surgically treated patients, the ratio between tumour clinical size and age is a useful parameter to differentiate patients with adverse pathologic outcomes from patients with more favourable pathologic outcomes. These differences translate into critically different relative rates of CSM and OCM. These findings suggest that the proposed strategy criterion deserve further examination as a potential criterion for AS. Funding None
Authors
Alessandro Larcher
Fabio Muttin Francesco Ripa Armando Stabile Francesco Trevisani Alessandro Nini Francesco Cianflone Cristina Carenzi Alexandre Mottrie Andrea Salonia Alberto Briganti Francesco Montorsi Roberto Bertini Umberto Capitanio |
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PD59-09 |
Management of Small Renal Masses in Renal Transplant Recipient Candidates: A Multi-Institutional Survey Analysis |
Kidney Cancer: Localized: Active Surveillance | 17BOS |
Abstract: PD59-09 Sources of Funding: None Introduction Radical nephrectomy (RN) is the preferred treatment of small renal masses (SRM) in renal transplant candidates. Given the high risk of surgical complications in this cohort, active surveillance (AS) may be an option as many lesions are indolent. Since data on the use of AS in this setting is lacking, we surveyed transplant surgeons across the US on their institutional practice patterns for treatment of SRM. Methods A 21-question online survey designed to analyze practice patterns of SRM management in renal transplant recipient candidates was sent to active transplant centers in the US. The list of recipients to whom the survey was distributed was obtained with permission from the American Society of Transplant Surgeons. All respondents were de-identified and consented to participate. Results We received 62 responses from 53 US Transplant Centers. All 11 United Network of Organ Sharing (UNOS) regions were represented. 38.7% (n=24) indicated that their institution does not follow formal guidelines for treatment of SRM. The majority (85.5%, n=53) indicated that their institution screens for renal masses in candidates for renal transplantation. RN was the preferred treatment (59%, n=61), followed by AS (21.3%, n=13), partial nephrectomy (14.8%, n=9) and focal ablative therapy (4.9%, n=3). Additionally, 14.5% (n=9) respondents routinely perform renal mass biopsy before any decision is made._x000D_ _x000D_ Although the majority of centers prefer definitive treatment, 27% allow AS prior to transplantation. For those institutions that allow AS, 95.5% felt comfortable if mass was <1 cm, 41.7% if <2 cm and 20.8% if 2-4 cm. Among institutions that allow AS, none alter their immunosuppressive regimen. _x000D_ _x000D_ Amongst the responders whose institutions did not allow active surveillance, 77.4% indicated that if presented with long-term data showing safety of AS, they would perform immediate transplantation and monitor SRM in these patients. _x000D_ Conclusions Variations in practice patterns suggest the need for standardized guidelines in the management of SRM in renal transplant candidates. Though RN is the preferred treatment, most transplant surgeons would consider AS if long term safety data were available. Funding None
Authors
Alp Tuna Beksac
David Paulucci John Sfakianos Balaji Reddy Susan Lerner Jared Winoker Harry Anastos Jorge Pereira Ketan Badani |
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PD59-10 |
The Natural History of Large Renal Masses on Active Surveillance & Expectant Management |
Kidney Cancer: Localized: Active Surveillance | 17BOS |
Abstract: PD59-10 Sources of Funding: none Introduction Surgical intervention is the standard of care for large renal masses; however patients with competing risks may not be suitable candidates for immediate intervention. This study illustrates our experience with active surveillance (AS) and expectant management of large renal masses (LRM) ≥ 4cm. We describe the growth rate of LRM under surveillance, factors associated with growth rate, and overall outcomes. Methods Our institutional database identified 101 patients with renal masses ≥ 4.0cm between 1993 and 2016. Inclusion criteria were those followed with serial imaging for at least 6 months without surgical intervention. Bosniak 1-2 cysts and clinically benign renal masses such as angiomyolipomas were excluded from analysis. We used ordinal least squares regression to calculate LRM growth rate (cm/year) for each patient based on maximal diameter. Univariate linear regression was used to assess whether clinical factors were associated with growth rate and competing risk methods were used to estimate the probability of developing RCC metastasis in the setting of death from other causes. Results The median age at diagnosis was 73 (IQR 64, 80) with a median LRM size of 4.9cm (IQR 4.0, 6.7). Median follow up was 4 years (IQR 2.2, 7.3). Charlson comorbidity index was ≥2 in 59% of patients, and 32% had other non-renal malignancies. 19% of patients had or developed non-RCC metastasis from another malignancy. Median LRM growth rate was 0.4 cm/year (IQR 0.1, 0.8). We did not find a significant association between clinical factors and LRM growth. AS was discontinued in 34 patients who underwent surgical intervention after a median follow up of 1.9 years, 88% had malignant disease. Among 56 patients who underwent surgery or biopsy during AS, 82% had malignant histology. Median follow up for patients who did not undergo surgery was 3.3 years (IQR 1.9, 5.0). In total, 10 patients developed metastatic RCC (3 of whom died from RCC), and 29 patients died from other causes. Four treated patients progressed to RCC metastases, and 3 RCC-related mortality. Median follow up for metastasis free survivors was 4 years (IQR 2.2, 6.8). The 5-year probability of non-RCC related death and RCC metastasis was 26% and 7%, respectively. Conclusions In highly comorbid patients, such as those with other advanced malignancies, active surveillance and expectant management of LRM has a low likelihood for RCC progression which is overshadowed by the risk of non-RCC related death. This data supports the use of surveillance of LRM as an acceptable strategy for selected patients with competing risks from other serious illnesses. Funding none
Authors
Karim Marzouk
Amy Tin Nick Liu Daniel Sjoberg A. Ari Hakimi Paul Russo Jonathan Coleman |
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PD59-11 |
The Natural History of Observed Large Renal Masses |
Kidney Cancer: Localized: Active Surveillance | 17BOS |
Abstract: PD59-11 Sources of Funding: None Introduction The natural history of small renal masses (T1a) has been well defined leading to the recommendation of considering active surveillance as a viable option for the management of such masses in the elderly. Less clear, however, is the management of larger masses in such patients. The treatment of masses over 4 cm in the elderly and infirm is often contingent on a competing risk of death analysis with other comorbidities. The objective of this study is to define the natural history, including the growth rate and metastatic risk, of large and untreated renal masses in order to better council patients on their competing risks. Methods A search was conducted into the imaging database at our centre for renal masses between 2005 and 2016. The search results were then reviewed by a radiologist. Renal masses concerning for renal cell carcinoma by imaging measuring over 4 cm and that had at least 2 cross-sectional imaging studies greater than 6 months apart were included. The 3 dimensional measurements of each renal mass were performed by one radiologist. A retrospective review of each patient's clinical chart was also conducted. Growth rates of the maximal tumor dimension were calculated. 95% confidence intervals using t-test were completed. Metastatic rates, cancer specific and overall mortality were also evaluated. Results We found 68 patients who met the inclusion criteria. Mean age at study entry was 75.5 years, mean eGFR was 57.5 ml/min/1.73m2. Mean tumor maximal dimension at study entry was 5.6cm and mean follow up was 2.5 years. 46 patients did no develop metastasis during the follow-up period and showed a growth rate of 0.67 cm/year (95% CI: 0.34 cm/yr to 1 cm/yr). 15 patients (22%) developed metastasis during follow-up with a mean tumor growth rate of 0.98 cm/year (95% CI: 0.33 cm/yr to 1.63 cm/yr). 7 patients had metastasis at presentation and were not treated and they showed a growth rate of 1.47 cm/year (95% CI: 0.37 cm/yr to 2.57 cm/yr). _x000D_ 10 patients progressed to radical nephrectomy; 2 progressed to partial nephrectomy. 17 (25%) patients died of metastatic RCC, 17 (25%) died of other causes. Overall and cancer specific survival were 50% and 75%, respectively._x000D_ Conclusions Large renal masses (> 4cm) have a higher growth rate than that reported for small renal masses. There is a tendency for the growth rate to increase in those who are likely to develop metastasis. Cancer specific survival in our cohort was 75% at a mean follow up of 2.5 years. Selection criteria for recommending observation of larger renal masses (>4cm) need to be more stringent than small renal masses reserving it only for much sicker and older patients. _x000D_ _x000D_ Funding None
Authors
Robert Leslie
Louisa Ho Alexandre Menard Robert Siemens Naji Touma |
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PD59-12 |
Predicting low metastatic potential tumors using clinical radiographic size: a systematic review of the literature. |
Kidney Cancer: Localized: Active Surveillance | 17BOS |
Abstract: PD59-12 Sources of Funding: None Introduction As detection of renal masses occurs earlier and at smaller sizes with widespread use of cross-sectional imaging, a significant portion of patients with small renal masses undergo intervention and are found to have benign or low-grade pathology. There is an inverse relationship between the incidence of these masses that have low metastatic potential and size on pre-operative imaging. The purpose of this study is to quantify proportion of low risk masses based on size, and quantify number of low risk masses being surgically removed Methods We systematically reviewed the literature for studies that included pathologic findings after surgical removal of renal masses. The studies must state tumor grade and number of benign masses removed stratified by radiographic size. Studies that did not include surgical pathology were excluded. Results A total of 602 titles were reviewed for relevance. 144 abstracts were selected and reviewed according to inclusion criteria. Six full text articles that included tumor grade and benign versus malignant histology stratified by tumor size were included. Pooled estimates of low risk renal masses (benign and grade one) were 43.1%, 38.8%, 28.3%, 26.6%, and 15.7% for size groupings 0-2cm, 2-3cm, 3-4cm, 4-6cm and >6cm, respectively. If including grade 2 tumors, the percentages increase, leaving only 6.9%, 11.1%, 17%, 25%, and 33.5% high-grade (grade 3 or 4) tumors in respective size groupings (Figure 1). Conclusions The pooled estimates of patients with low grade or benign surgical pathology that had been resected clearly demonstrate a substantial portion of patients with small renal masses that have low metastatic potential are undergoing surgery for removal. As the diameter of a renal mass on preoperative cross sectional imaging decreases, the tumor grade and proportion of malignant pathology does as well. This information is essential to patient counseling and decision-making regarding placement on active surveillance. These findings could be especially helpful in the growing population of elderly patients with significant medical comorbidities. Funding None
Authors
Alice Semerjian
Hiten D. Patel Michael A. Gorin Michael H. Johnson Mohamad Allaf Phillip M. Pierorazio |
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PD60-01 |
Incidence and Predictors of Complications due to Urethral Stricture in Patients Awaiting Urethroplasty |
Trauma/Reconstruction/Diversion: Urethral Reconstruction (including Stricture, Diverticulum) IV | 17BOS |
Abstract: PD60-01 Sources of Funding: None Introduction Urethroplasty is usually a definitive treatment for recurrent urethral stricture. However, patients often wait a significant period of time for urethroplasty, especially in a universal healthcare system, and may incur further risk of complications due to urethral stricture. The purpose of this study is to examine the incidence and predictors of complications due to urethral stricture in patients awaiting urethroplasty. Methods A retrospective review of patients undergoing urethroplasty from Sept 2009-2013 in a single center was performed. Patients treated outside of the regional health authority were excluded to minimize unidentified complications and interventions. The primary outcome was complication due to urethral stricture, defined as any unplanned intervention with the health care system during the period between decision to perform surgery and urethroplasty date. These complications included urinary tract infection (UTI), urolithiasis, acute urinary retention, genitourinary pain related to stricture, and catheter-related issues. Results 276 patients met study criteria. Mean stricture length was 4.5 cm, and most strictures were bulbar (67.4%) or penile (15.2%) in location. Idiopathic (47.8%), traumatic (15.9%), and iatrogenic (10.9%) were the most common stricture etiologies. Overall, 44 (15.9%) patients presented with a complication with a mean time to complication of 65.9 days. The mean surgical wait time was 164 days. Complications included urinary tract infection (56.8%), acute urinary retention (20.5%), genitourinary pain requiring intervention (5.8%), and catheter related events (15.9%). Univariate analysis for factors predicting complications yielded catheter dependency (clean-intermittent catheterization or suprapubic catheter)(p<0.001) and number of prior endoscopic treatments (p=0.005) as significant, with prior urethroplasty (p=0.06) trending towards significance. Multivariate Cox regression analysis found catheter-status (p<0.001; H.R. 2.3, 95% CI:1.5-3.4) and prior urethroplasty (p=0.013; H.R. 1.7, 95% CI: 1.1-2.5) to be significantly associated with complications. Conclusions Our study is the first to examine and quantify the morbidity of urethroplasty wait times. Approximately 16% of patients presented with a complication while awaiting urethroplasty at a mean of 66 days after the decision for surgery. Urethroplasty wait time should be less than 66 days and patients whom are catheter dependent or failed prior urethroplasty should be prioritized, as they are more likely to develop complications. Funding None
Authors
Hoy Nathan
Nick Dean Dave Chapman Jon Witten Keith Rourke |
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PD60-02 |
DELAY OF URETHROPLASTY IS ASSICIATED WITH LONGER STRICTURES AND MORE COMPLICATED REPAIRS |
Trauma/Reconstruction/Diversion: Urethral Reconstruction (including Stricture, Diverticulum) IV | 17BOS |
Abstract: PD60-02 Sources of Funding: none Introduction Bulbar urethral strictures ≤ 2 cm are generally amenable to excision and primary anastomosis (EPA) and associated with excellent outcomes. We hypothesized that men having repeated endoscopic treatments of urethral strictures developed increased spongiofibrosis, thus leading to longer strictures requiring more complex repairs. The objective of this study was to analyze clinical characteristics of patients having bulbar strictures > 2 cm requiring complex repairs in comparison to those with shorter strictures. Methods We retrospectively reviewed our urethroplasty database of over 1200 patients from 2007-2016. We identified 365 patients undergoing first-time urethroplasty for bulbar urethral stricture disease with complete data available and at least 2 years of follow-up. Penile strictures and posterior urethral stenosis were excluded. Pretreatment characteristics were evaluated to identify associations with intraoperative bulbar urethral stricture length. A cutpoint of 2 cm was used to identify preoperative characteristics associated with shorter strictures more amenable to EPA versus those requiring substitution urethroplasty. Results Of the 365 (64%) primary bulbar urethral strictures treated, 160 (44%) were > 2 cm in length. These longer bulbar urethral strictures > 2 cm (LBUS) were associated with a greater delay between stricture diagnosis and urethroplasty (mean 117 vs 81 months, p=0.01) and greater total number of prior endoscopic interventions (mean 8 vs 3, p=0.005) compared to shorter strictures. Accordingly, LBUS were less likely to undergo EPA relative to those with strictures ≤ 2 cm (64% vs 99%, p<0.0001). When stratified by time from initial diagnosis to definitive urethroplasty (≤ 5 years, 5-10 years, and >10 years), a clear incremental increase was identified in procedures performed (p<0.0001) and stricture length (p=0.004) (Fig 1). Men with strictures >2 cm were more likely to experience urethroplasty failure (18% vs 9%, p=0.01). Specifically, each additional endoscopic stricture incision was associated with a 1.25-fold increased risk of urethroplasty failure (p=0.007). On multivariable analysis, only increasing number of endoscopic interventions (OR 1.02, 95%CI 1.00-1.05; p=0.04) was independently associated with bulbar urethral stricture length >2 cm. Conclusions Delay between initial stricture diagnosis and definitive reconstruction is associated with increasing numbers of endoscopic treatments, lengthening of strictures, and greater risk of urethroplasty failure. Funding none
Authors
Boyd Viers
Travis Pagliara Charles Rew Lauren Folgosa-Cooley Christine Shiang Jeremy Scott Allen Morey |
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PD60-03 |
Pre- and post-treatment urethrograms show that transurethral treatments increase the complexity of urethral strictures |
Trauma/Reconstruction/Diversion: Urethral Reconstruction (including Stricture, Diverticulum) IV | 17BOS |
Abstract: PD60-03 Sources of Funding: none Introduction We examined the association of urethral stricture complexity at urethroplasty with previous transurethral manipulation including urethral dilation, urethrotomy, and urethral stenting, which are the most commonly performed procedures for treating male urethral strictures but have alarmingly high failure rates. Methods We retrospectively reviewed the records of 249 patients with urethral stricture disease who had undergone urethroplasty between 2004 and 2015. Patients with a history of lichen sclerosus, hypospadias, phalloplasty, and/or prior urethroplasty were excluded from analysis. Of the remaining 197 patients, we analyzed the records of 45 patients who had a history of transurethral treatments including self- or office- dilation, urethrotomy with a cold knife or laser, and/or urethral stenting using temporary thermo-expandable stents at least once and whose urethrography results at initial stricture diagnosis and at urethroplasty were available. We considered stricture complexity increased if the number of strictures and/or stricture length on the urethrography at urethroplasty was greater than that at initial diagnosis, and/or if a false passage was newly identified. Results Thirty-nine of the patients (87%) had been subjected to urethral dilation, 32 (71%) to urethrotomy, and 13 (29%) to temporary urethral stenting, and 39 (87%) had received repeated and/or multiple kinds of transurethral treatments. Disease duration (defined as the period between the initial stricture diagnosis and urethroplasty) in patients with repeated transurethral treatments (mean 102 months) was more than four times that in patients with a single transurethral treatment (mean 24 months, p = 0.006). Stricture complexity was increased in 22 (49%) and was significantly associated with a history of urethrotomy (p = 0.03), urethral stenting (p = 0.0002), and repeated transurethral treatments (p = 0.01). Notably, twelve (92%) of 13 patients with history of urethral stenting showed increased stricture complexity, and multivariate logistic regression analysis revealed that history of urethral stenting was an independent predictor of increased stricture complexity (OR 13.7, p = 0.01). Of the 22 patients with increased stricture complexity, seven (32%) were forced to change the type of urethroplasty to one more complex than the predicted repair type based on the urethrography at initial diagnosis. Conclusions Repeated transurethral manipulation is associated with increased stricture complexity and is potentially counterproductive. Funding none
Authors
AKIO HORIGUCHI
MASAYUKI SHINCHI KEIICHI ITO RYUICHI AZUMA TOMOHIKO ASANO |
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PD60-04 |
Predictive Factors of Success in Adult Patients Treated for Urethral Stricture after Primary Hypospadias Repair Failure: a Multivariable Analysis of a Single-Surgeon Series |
Trauma/Reconstruction/Diversion: Urethral Reconstruction (including Stricture, Diverticulum) IV | 17BOS |
Abstract: PD60-04 Sources of Funding: None Introduction The repair of urethral strictures after hypospadias repair still represent a challenging problem. Although the number of surgeries for the correction of primary hypospadias may represent a risk factor for surgical failure, no evidence for this currently exists in the current literature. Therefore, we investigated the predictive factors of success in adult patients treated for urethral stricture after primary hypospadias repair failure._x000D_ Methods The study was an observational, retrospective, descriptive study of adults with urethral strictures following hypospadias surgery. We included only patients with complete clinical data regarding the type of primary hypospadias, the number of operations needed for repair and the surgeon who performed the repair. The primary outcome of the study was treatment failure, defined as the need for any post-operative instrumentation. Secondary outcomes consisted of the relationships between the site of hypospadias, the site of the stricture and patient demotivation, defined as patient refusal of further treatments. Statistical analyses were performed using Stata (StataCorp LP, College Station, TX, USA) version 12.0. Tests were two-sided with a significance level set at p<0.05. Results Overall, 408 patients were included in the study. The most frequent type of primary hypospadias was penile (56%), whereas the most frequent site of secondary stricture was penile (49%). A concordance between the site of primary hypospadias and the site of the secondary stricture was observed.A Kaplan Meier analysis revealed that two-stage techniques were significantly associated with lower treatment failure-free survival compared to one-stage techniques (p=0.001).At multivariable analysis, the number of previous operations needed for initial hypospadias repair was not associated with the risk of treatment failure (hazard ratio 0.95; 95% Confidence Interval: 0.88 - 1.03; p=0.2). Conversely, length of stenosis, with a cut-off of 3 cm (HR 1.42; CI 1.09 - 1.74; p=0.003), and presence of lichen sclerosus (HR 1.92; CI 1.01 - 3.65; p=0.047) were associated with an increased risk of treatment failure. Age (HR 1.03; CI 1.01 - 1.05; p=0.003), diabetes (HR 6.68; CI 1.38 - 32.3; p=0.018), penile hypospadias (HR HR 0.40; CI 0.24 - 0.68; p<0.001) and presence of lichen sclerosus (HR 2.51; CI 1.24 - 5.09; p=0.011) were associated with increased risk of patient demotivation for further surgeries. Conclusions Stricture length, but not the number of previous operations needed for primary hypospadias repair, was associated with the risk of failure. Funding None
Authors
Guido Barbagli
Nicola Fossati Alessandro Larcher Francesco Montorsi Salvatore Sansalone Denis Butnaru Massimo Lazzeri |
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PD60-05 |
Double Faced (Inlay And Onlay) Buccal Mucosa Urethroplasty Offers Better Long Term Results For Long And Narrow Urethral Strictures |
Trauma/Reconstruction/Diversion: Urethral Reconstruction (including Stricture, Diverticulum) IV | 17BOS |
Abstract: PD60-05 Sources of Funding: none Introduction Buccal Mucosa Augmentation Urethroplasty has proved to be a standard of care for treatment of non-traumatic urethral strictures. However, appropriate augmentation requires a substantially wide native urethral plate in order to prevent graft- plate discrepancy, which is vital for long term success. Long urethral strictures with a very narrow urethral usually require a staged treatment due to a possible fear of failure due to graft-plate mismatch. We studied the long term results of Double faced buccal mucosa urethroplasty for long and narrow strictures. Methods 86 patients between the age group of 24 to 72 years (Mean age 53.45 years) were subjected to double faced buccal mucosa urethroplasty from the year 2011 to 2015. 27 out of 86 (31.39%) patients had a pan-urethral stricture due to Lichen Sclerosus (LS). 38 out of 86 (44.18) patients had a post-TURP proximal bulbar stricture. 7 patients (8.13%) had a recurrent bulbar stricture after a previous BMG urethroplasty. 5 patients had a long penile urethral stricture and 9 patients had a long bulbar stricture due to LS. The mean stricture length was 7.45cm. Urethral plates less than 3mm wide were selected for double faced BMG. In pan-urethral and penile strictures dorsal onlay and ventral inlay grafts were applied. In the bulbar strictures dorsal inlay and ventral onlay grafts were applied. 16Fr Foley was placed in all patients for 3 weeks. _x000D_ Inlay grafting was done by incising the urethral plate deep enough to expose a healthy spongiosal tissue. Results The longest follow-up was about 54 months and the mean follow-up duration was 37.65 months. All patients had a maximum flow rate > 18ml/Sec (Mean 15.62ml/Sec). 4 patients with LS had meatal restenosis which was treated by ventral meatotomy. 2 patients with bulbar stricture had urethro-cutaneous fistulae from the incision site which closed spontaneously with prolonged catheterization. 8 patients with ventral onlay BMG complained of post void dribbling which was corrected with an advise of perineal compression after urination. Inlay BMG widened the diseased urethral plate from an average of 2mm to 7.5mm. This prevented the discrepancy between the onlay graft and the urethral plate. _x000D_ Conclusions Application of an inlay BMG widens the narrow urethral plate and prevents significant graft-plate mismatch. Widening of the urethral plate offers tension free urethral closure and better long term results. Double faced BMG urethroplasty offers better results in long and narrrow strictures by preventing graft-plate discrepancy. Funding none
Authors
ASHISH PARDESHI
VIJAY RAGHOJI RAJESH RAJENDRAN |
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PD60-06 |
Double Faced Buccal Mucosal Graft Urethroplsty For Near Obliterative Inflammatory Urethral Stricture: A Retrospective Study. |
Trauma/Reconstruction/Diversion: Urethral Reconstruction (including Stricture, Diverticulum) IV | 17BOS |
Abstract: PD60-06 Sources of Funding: None Introduction To compare the perioperative outcomes of double faced buccal mucosal graft (BMG) urethroplasty for near Obliterative inflammatory urethral stricture and to compare the results with historical controls that underwent one sided (dorsal/ventral) BMG urethroplasty for similar strictures. Methods Between August 2010 and October 2015, 255 patients who underwent BMG urethroplasty at our centre were retrospectively reviewed. Out of these 46 patients, who presented with near Obliterative urethral stricture of length more than 2 cm and underwent patch urethroplasty, using a dorsal plus a ventral, double BMG were included in this study. In addition 44 patients with similar urethral stricture who underwent one sided (dorsal/ventral) buccal graft urethroplasty were also included in the study for comparison of results. The patients were divided into two groups based on the operative technique; Group A with 46 patients, 24 patients Enzo Palminteri technique (dorsal inlay with ventral onlay) and 22 patients Joel Gelman technique (dorsal onlay with ventral inlay), and Group B with 44 patients, dorsal/ventral urethroplasty. Results With a mean follow up of 36 months (range 12 – 62 months) failure was found to be in 2 patients in Group A (success rate 95.6% and 100% after 1 urethrotomy) and 10 patients in Group B (success rate 77.2 %) Conclusions The result of this study showed that double phase BMG urethroplasty is successful for management of near Obliterative stricture. The result also showed an improved success rate and lesser complications in comparison with dorsal/ventral urethroplasty. Funding None
Authors
Prarthan Joshi
Tarun Javali Horahalli Nagaraj S.M.L. Prakash Babu Kuldeep Aggarawal Arjun Nagaraj |
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PD60-07 |
Outcome of dorsal onlay buccal mucosal graft versus ventral onlay local penile skin flap in complex anterior urethral strictures; a prospective randomized study |
Trauma/Reconstruction/Diversion: Urethral Reconstruction (including Stricture, Diverticulum) IV | 17BOS |
Abstract: PD60-07 Sources of Funding: none Introduction Anterior urethral stricture is a challenging disease. Multiplicity of surgical techniques denotes that none is ideal. Very few prospective randomized studies are available to compare different techniques. _x000D_ Our aim is to compare the use of buccal mucosal graft (BG) versus local penile skin flaps (PF) in patients with complex anterior urethral strictures. Methods A total of 34 adult patients with complex anterior urethral stricture were included. A complex anterior urethral stricture was defined as a stricture length of > 2 cm and/or previous failed procedures, including urethral dilatation, internal optical urethrotomy (OU) and urethroplasty. We randomised patients to undergo either buccal mucosa dorsal onlay graft or ventral onlay local penile skin flap urethroplasty. Successful treatment outcome was defined as no further treatment of the urethral stricture required after urethroplasty and peak flow rate > 15 ml/s. We compared operative time, estimated blood loss, complications, and recurrence rates in both groups. Results Mean follow up was 22.3 months in BG group vs 18.9 months in PF group. The number of penile, bulbar and bulbo-penile strictures as well as median stricture length (40 mm in BG group Vs. 50 mm in PF group) were not statistically different between the two groups._x000D_ Mean operative time was 185.9 min and 190.6 min in BG group and PF group respectively. Estimated blood loss was significantly higher in PF group, (median 400 ml and 300 ml in PF and BG group respectively, p= 0.003). _x000D_ Regarding complications, two patients (11.8%) in each group developed wound infection, one patient (5.9%) in PF group had urinary fistula, and one patient (5.9%) presented by ventral chordee post operatively. In BG group, only one patient (5.9%) developed mild limitation of mouth opening. _x000D_ The success rates in the buccal mucosal (88.2%) and penile flap (88.2%) groups were similar. Conclusions On intermediate follow up, dorsal onlay buccal mucosa and ventral onlay penile skin flap urethroplasty provide similar success rates. PF group had significantly higher blood loss, but no blood transfusion was required in both groups. Since no statistically significant difference in outcomes and complication rates were observed between BG and PF, both techniques are recommended for the treatment of complex anterior strictures, based on the surgeon's expertise. Further studies with longer term follow-up periods & higher sample sizes are needed to elucidate subtle differences between both techniques. Funding none
Authors
Ahmed Tawakol
Mohammed Abdel-Rassoul Mohamed El-Ghoneimy Mohamed El-Gammal |
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PD60-08 |
Investigation of traumatic urethral catheterization and evaluation of a novel safety syringe after correlating trauma with urethral distension and catheter balloon pressure: A prospective multi-institutional study. |
Trauma/Reconstruction/Diversion: Urethral Reconstruction (including Stricture, Diverticulum) IV | 17BOS |
Abstract: PD60-08 Sources of Funding: None Introduction To highlight the dangers inherent in traumatic urethral catheterization we prospectively monitored the incidence, cost and clinical outcomes of urethral catheter related injuries. We also investigated urethral diametric strain and threshold maximum inflation pressure for rupture during inadvertent inflation of a catheter anchoring balloon in the urethra and evaluated a novel safety device to prevent trauma. Methods The incidence of urethral catheter related injuries was prospectively monitored at 2 tertiary referral teaching hospitals for 6 months. Recorded data included method and extent of urethral catheterization injury, number of catheterization attempts, urological management provided, additional bed days due to urethral injury and clinical outcomes after follow-up. In addition, inflation of a urethral catheter anchoring balloon was also performed in the bulbar urethra of porcine and cadaver models using 16Fr catheters (n=28). Extent of urethral trauma was characterised with retrograde urethrography. Urethral rupture was correlated with internal urethral diametric strain and maximal urethral pressure threshold values in kPa to develop a &[prime]safety threshold&[prime] pressure valve. Results A total of 37 iatrogenic urethral injuries were recorded. The incidence of traumatic urethral catheterization was 6.7 per 1,000 catheters inserted. Thirty (81%) patients sustained a complication Clavien-Dindo grade 2 or greater. The additional length of inpatient hospital stay was 9.4 ± 10 days (range 2 to 53). The additional cost of managing iatrogenic urethral injuries was $371,790. In porcine and cadaver models, retrograde urethrography demonstrated that urethral rupture consistently occurred at an internal urethral diametric strain greater than 40% and a maximum inflation pressure greater than 150 kPa. Based on these parameters a safety valve that reliably activated at a threshold inflation pressure of 150 kPa was developed. Conclusions Iatrogenic urethral catheterization injuries represent a significant cost and cause of patient morbidity. Urethral injuries will continue to occur unless urinary catheter safety mechanics are altered. Internal urethral diametric strain and threshold maximum inflation pressures are important parameters for designing a safer urethral catheter system with lower intrinsic threshold inflation pressures. Funding None
Authors
Niall Davis
Eoghan Cunnane Mark Quinlan Rustom Manecksha John Thornhill David Mulvin Michael Walsh |
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PD60-09 |
Analysing 5-year Memokath outcomes for malignant and benign ureteric obstruction: A proposed update to clinical guidelines |
Trauma/Reconstruction/Diversion: Urethral Reconstruction (including Stricture, Diverticulum) IV | 17BOS |
Abstract: PD60-09 Sources of Funding: none Introduction Patient and disease characteristics influence ureteric stricture management with DJ stents, metallic stents, endoscopic, or reconstructive surgery. Memokaths are an option with reported 90-100% patency and 14-30% complication rates, but the published literature is limited by small sample size and short follow-up duration up to 22 months._x000D_ _x000D_ Objective: To independently analyse 5-year Memokath stent outcomes, identifying variables associated with good outcomes to update clinical guidelines._x000D_ Methods Management of obstructed ureteric stricture patients with Memokath stents was reviewed independently using electronic patient records. Outcomes included time to first complication, complications' incidence and severity._x000D_ Multiple linear regression was performed identifying variables linked with particular outcomes. _x000D_ Results 100 patients aged 23-87 years (mean 57) received Memokath stents for ureteric obstruction, 59% for malignant strictures, with 20% bilateral. Only 25 patients had no complications: either alive with, or dying of their primary malignancy with their original Memokath. Median time to complication in the remaining 75 patients was 12.5 months with Memokaths lasting longer in patients with malignancy (p=0.02). _x000D_ _x000D_ Multiple linear regression analyses showed that increased eGFR (p=0.005) and age (p=0.0001) independently significantly predicted greater Memokath lifespan, while co-morbidities, stricture length and location, and underlying pathology, did not. _x000D_ _x000D_ 5 year outcomes: 25 patients had a Memokath in situ: 14 still alive with the original. 22 had other stents, while 12 required major surgery. 66% of patients with most severe complications (need for major surgery or dialysis) were in the benign group._x000D_ Conclusions Memokaths are a reasonable option for patients with malignant ureteric obstruction and life expectancy up to 1 year. Age and eGFR greater than 45 predicted longer Memokath duration. Patient and stricture variables other than aetiology did not affect Memokath durability, but should be considered for delivery of the most appropriate patient-centred individualised care. 5 year complication rates were significantly higher than previously reported (75 vs 25%). _x000D_ _x000D_ Updated practice guidelines would aid future patient selection and counselling, as well as encouraging protocolled follow-up and patient reported outcomes assessment, when considering metallic stent drainage for ureteric obstruction._x000D_ Funding none
Authors
Luke Forster
Laura Watson Charles Breeze Antonina Di Benedetto Stuart Graham Prasad Patki Anup Patel |
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PD60-10 |
Substitution urethroplasty with closure versus non-closure of the buccal mucosa graft harvest site: final results of a randomized controlled trial with a detailed analysis of pain and morbidity |
Trauma/Reconstruction/Diversion: Urethral Reconstruction (including Stricture, Diverticulum) IV | 17BOS |
Abstract: PD60-10 Sources of Funding: None Introduction The optimal surgical management of the donor site during buccal mucosa graft urethroplasty (BMGU) remains controversial. To analyze in detail intensity and quality of pain as well as oral morbidity following closure (C) versus non-closure (NC) of the donor site. Methods This randomized controlled trial included 135 patients who were treated with BMGU between 2014 and 2015. The buccal mucosa graft was harvested from the inner cheek. Following computer-based randomization, 63 and 72 patients received C and NC of the donor site. Preoperatively, at postoperative day (POD) one, 5, 21 as well as 3 and 6 months postoperatively, patients completed standardized questionnaires. The intensity of oral pain and of the perineogenital region, respectively, was assessed with a numeric rating scale (NRS). The quality of oral pain was evaluated using the Short-Form McGill Pain Questionnaire (SF-MPQ), consisting of a sensory and affective pain subscale. The co-primary endpoints were intensity and quality of oral pain. Secondary endpoints included oral morbidity as well as intensity of pain of the perineogenital region. Generalized linear mixed models evaluated the effect of C versus NC on intensity and quality of oral pain, oral morbidity as well as intensity of pain of the perineogenital region. Results Oral pain intensity mean scores on the NRS were 0.15 (standard deviation (SD): 0.531; range: 0-3), 3.16 (SD: 2.10; range: 0-10), 2.89 (SD: 2.16; range: 0-9), 1.30 (SD: 1.72; range: 0-8), 1.00 (SD: 1.42; range: 0-6) and 0.77 (SD: 1.33; range: 0-6), respectively, at baseline, POD one, 5, 21 as well as 3 and 6 months. The most frequent sensory dimension of pain was &[prime]tender&[prime]. The most common affective dimension of pain was &[prime]tiring-exhausting&[prime] on POD one, 5 and 3 months. On POD 21 and 6 months, the most frequent affective pain was &[prime]fearful&[prime]. Oral morbidity and complications included pain, bleeding, swelling, numbness, alteration of salivation and taste, as well as impairment of mouth opening, smiling, diet and speech. C versus NC of the donor site had no effect on intensity and quality of oral pain as well as morbidity and complications. Time from BMGU and length of buccal mucosa graft had significant effects on intensity and quality of oral pain (p-values<0.042). Mean NRS cores of the pain intensity of the perineogenital region were 0.86 (SD: 1.74; range: 0-8), 3.94 (SD: 2.24; range: 0-10), 2.70 (SD: 2.08; range: 0-8), 1.81 (SD: 1.63; range: 0-8), 1.37 (SD: 1.71; range: 0-8) and 1.18 (SD: 1.76; range: 0-7), respectively, at baseline, POD one, 5, 21 as well as 3 and 6 months. C versus NC had no effect on intensity of pain of the perineogenital region. Time from BMGU, length of the buccal mucosa graft and perioperative analgesic medication had significant effects on the intensity of pain of the perineogenital region (p-values<0.035). Conclusions In conclusion, C versus NC of the donor site has no effect on intensity and quality of oral pain, morbidity and complications. Both, C and NC of the buccal mucosa harvest site, are feasible and safe procedures. Funding None
Authors
Armin Soave
Roland Dahlem Hans Pinnschmidt Sascha Ahyai Michael Rink Jessica Langetepe Oliver Engel Luis Kluth Philip Reiss Margit Fisch |
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PD60-11 |
Population-based Management of Male Urethral Stricture Disease |
Trauma/Reconstruction/Diversion: Urethral Reconstruction (including Stricture, Diverticulum) IV | 17BOS |
Abstract: PD60-11 Sources of Funding: None Introduction Male urethral stricture disease is a common condition with significant quality of life and economic implications. While endoscopic treatment with incision or dilation is the most common treatment approach, the AUA guidelines (www.auanet.org/guidelines) recommend urethroplasty based on increased long-term success rates. However, the extent to which this procedure is performed relative to endoscopic treatment in real-world practice in the USA is unknown. Thus, we conducted a population-based study of patients treated for urethral stricture disease to examine management patterns and opportunities for improvement. _x000D_ Methods We identified male patients who underwent procedures for urethral stricture disease between 2001 and June 2015 based on ICD-9 codes and administrative claims from a large, national US health insurer (ClinformaticsTM Data Mart Database, OptumInsight, Eden Prairie, MN). We assessed utilization and standardized cost of endoscopic treatments (urethrotomy and dilation) and urethroplasty. We examined patient factors associated with endoscopic treatment versus urethroplasty using multivariable logistic regression._x000D_ Results We identified a total of 75,522 patients treated for male urethral stricture disease with 125,498 total procedures. This is the largest reported cohort of urethral stricture procedures in the literature. The majority of patients were treated with endoscopic surgery (98.8%), with only 1,515 patients undergoing urethroplasty. After adjustment, younger age (adjusted odds ratio (aOR), age ≤ 40 vs. age ≥ 60 years, 8.2; 95% CI, 7.2-9.4) and higher annual income (aOR, income ≤ $40K vs. ≥ $100,00K, 0.7; 95% CI, 0.5-0.9) were each associated with receipt of urethroplasty. Total standardized costs for endoscopic treatment was $115,724,899 compared to $3,678,066 for urethroplasty._x000D_ Conclusions Our population-based study of insured patients demonstrated very low use of urethroplasty in real-world practice, despite recommendations for use and superior success rates. Income disparities in urethroplasty utilization is concerning and may indicate health access disparity. Strategies to increase the use of high value surgery for patients with urethral stricture disease include increasing referrals to reconstructive urologists, and knowledge and technique transfer to community urologists interested in providing this service rather than repeated, low-value endoscopic treatment._x000D_ Funding None
Authors
Robert Goldfarb
Steven Brandes Peter Kirk Tudor Borza Yongmei Qin Ted Skolarus |
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PD60-12 |
GERIATRIC URETHROPLASTY: LESSONS LEARNED FROM URETHRAL RECONSTRUCTION IN ELDERLY MEN |
Trauma/Reconstruction/Diversion: Urethral Reconstruction (including Stricture, Diverticulum) IV | 17BOS |
Abstract: PD60-12 Sources of Funding: none Introduction While urethroplasty remains safe and effective in younger populations, little data exists evaluating outcomes of urethroplasty in elderly men. We report treatment outcomes, complications, and stricture characteristics among men having urethral reconstruction who were ≥ 70 years of age. Methods A retrospective review of over 1000 urethroplasty cases by a single surgeon from 2007-2014 was performed to identify elderly men ≥70 years undergoing urethral reconstruction. Men were stratified by age and differences were assessed including stricture characteristics, postoperative complications, and surgical outcomes. Mutivariable logistic regression models evaluated the association between age and surgical outcome. Men with a history of hypospadias were excluded. Results Among 514 men having urethroplasty for which complete data was available, 85 (17%) were ≥70 years. Elderly men were more likely to have a history of radiation therapy (63% vs 5%, p<0.0001) and experience treatment failure (30% vs 12%, p=0.001) during follow up (mean 20 months). Accordingly, the 24-month stricture recurrence-free survival was 61% vs 78% (p=0.03). In men ≥70, the success rates of excision and primary anastomosis (EPA), substitution urethroplasty, and urethrostomy were 75%, 67%, and 80%. While stricture length, location, and prior endoscopic treatments were similar between cohorts, elderly men were more likely to have obliterative strictures (44% vs 28%), a shorter duration between diagnosis and treatment (median 46 vs 61 months), and undergo EPA (80% vs 66%). Following surgery there was no difference in overall <90 day complications (22% vs 18%); however elderly men were more likely to have a Clavien 3 or greater complication (13% vs 5%; p=0.005). Among treatment failures, men ≥70 failed earlier (8 vs 18 months; p=0.04) and were more likely to fail on subsequent intervention (55% vs 30%; p=0.05). On multivariable analysis, radiation (OR 2.91, 95% CI 1.36-6.24; p=0.006) and increasing age (OR 1.03, 95%CI 1.01-1.05; p=0.006) were independently associated with risk of treatment failure. Conclusions While advanced age is independently associated with urethroplasty failure, urethroplasty is a safe and effective treatment option for aging men with urethral stricture disease. Funding none
Authors
Boyd Viers
Travis Pagliara Charles Rew Lauren Folgosa-Cooley Christine Shiang Jeremy Scott Allen Morey |
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PD61-01 |
18F fluciclovine PET/CT in comparison with 11C- choline PET/CT for nodal staging in prostate cancer patients: preliminary diagnostic accuracy analysis |
Prostate Cancer: Staging II | 17BOS |
Abstract: PD61-01 Sources of Funding: none Introduction To evaluate the diagnostic performance of 18F-fluciclovine (FACBC) - positron emission tomography/computer tomography (PET/CT) in nodal staging prior to pelvic lymph node dissection (PLND) during radical prostatectomy (RP) in primary prostate cancer (PCa) patients. Methods Overall, 60 patients were consecutively and prospectively enrolled and underwent 18F-FACBC-PET/CT. Inclusion criteria were: intermediate and high-risk biopsy-proven PCa according to D’Amico risk group classification; standard staging workup (including 11C-Choline-PET/CT); absence of previous or ongoing androgen deprivation therapy; eligible for PLND in course of RP. Any nodal uptake greater than surrounding background was interpreted with a visual 5-point-scale (confidence of disease): 1-2 probably negative; 4-5 probably positive; 3 equivocal. Lesions’ number, site and size, SUV max and target-to-background-ratio were also recorded. PET/CT results using both tracers were compared, on a per-patient basis analysis, with histopathology from extended PLND (60 patients). Results Main characteristics of the population are shown in Table 1. Overall, 1342 lymph nodes were retrieved and 32 (2%) LNMs were counted. At final pathologic results, we found 9 and 15 false positive (FP) results with FACBC and Choline, respectively; while 5 false negative (FN) results were found with both tracers. The diagnostic performance of both tracers in detecting LNMs are summarized in Table 2: sensitivity, specificity and accuracy were 58%, 69% and 67% vs. 58%, 81% and 77% for 11C-Choline PET/CT vs. 18F-fluciclovine PET/CT, respectively._x000D_ Conclusions Conclusion: 18F-fluciclovine demonstrated suboptimal sensitivity, equal to Choline, suggesting that neither tracer is ideal for PCa nodal staging. However, our preliminary data show encouraging slightly better overall diagnostic performance and practical/technical advantages in favor of 18F-fluciclovine as compared with the routine tracer. Enrolment and further analyses (region-based/semi-quantitative/uni-multivariate-logistic-regression to evaluate predictive factors) are ongoing. Funding none
Authors
Cristian Vincenzo Pultrone
Lorenzo Bianchi Lucia Zanoni Cristina Nanni Francesca Giunchi Michelangelo Fiorentino Angelo Porreca Marco Borghesi Valerio Vagnoni Stefano Fanti Riccardo Schiavina Eugenio Brunocilla |
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PD61-02 |
68Ga-PSMA PET/CT for detection of early recurrent prostate cancer after radical prostatectomy with PSA values up to 1ng/mL |
Prostate Cancer: Staging II | 17BOS |
Abstract: PD61-02 Sources of Funding: none Introduction With current standard cross-sectional imaging (CT or MRI) detection of prostate cancer lesions in patients with biochemical recurrence (BCR) after radical prostatectomy remains challenging, especially at low PSA values. Recently, 68Ga-PSMA PET imaging has been shown to improve detection rates. However, up to now published case series include only a limited number of patients at low PSA values. Methods For this retrospective analysis 272 pts with BCR after radical prostatectomy were extracted from the institutional database who presented with a PSA value from 0.2 up to 1ng/ml at the time of 68Ga-PSMA PET/CT imaging. 68Ga-PSMA PET/CT was evaluated by one experienced reader for lesions suggestive for prostate cancer recurrence and site of suspicious lesions was reported. Patients were grouped according to PSA value, from 0.2 – 0.5ng/mL and from >0.5 – 1.0ng/mL. Primary T-, N-stage, Gleason-Score, D´Amico-Classification, previous local radiation therapy as well as concurrent androgen deprivation therapy (ADT) was correlated to detection rates. Results In total, in 54.5 % (73/134) of patients with PSA from 0.2 – 0.5ng/mL and in 76.1% (102/134) of patients with PSA >0.5 – 1.0ng/mL suspicious findings on 68Ga-PSMA PET/CT imaging were noted. Sites of recurrence were local (37.0% and 41.2%), pelvic or retroperitoneal lymph nodes (45.2% and 54.9%), bone (24.7% and 29.4%), supradiaphragmal lymph nodes (6.8% and 6.9%) as well as others (4.1% and 2.0%). In patients with primary locally advanced tumors (pT>3a), primary N+ disease, Gleason-Scores >8, primary higher D´Amico-Classification, previous radiation therapy as well as with concurrent ADT positive findings on 68Ga-PSMA PET/CT were more likely compared to patients without these characteristics. Conclusions 68Ga-PSMA PET/CT is able to identify sites of recurrent prostate cancer after radical prostatectomy even at low PSA values up to 1ng/ml in a significant number of patients – especially in patients with primary more aggressive tumor characteristics, previous local radiation therapy or concurrent ADT – and thus will very likely present the future imaging technique in these patients. As salvage therapies (local radiation therapy, salvage lymph node dissection or PSMA-radioguided surgery) are most effective at low PSA-levels, early detection of cancerous foci by 68Ga-PSMA PET might even improve oncological results. Funding none
Authors
Tobias Maurer
Charlotte Düwel Berhard Haller Jürgen E. Gschwend Markus Schwaiger Matthias Eiber |
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PD61-03 |
Evaluation of recurrent prostate cancer after primary radiation therapy as defined by Phoenix criteria by 68Ga-PSMA PET/CT |
Prostate Cancer: Staging II | 17BOS |
Abstract: PD61-03 Sources of Funding: none Introduction The aim of this retrospective study was to evaluate the detection rate of 68Ga-PSMA PET/CT in a homogeneous patient population with biochemical recurrent prostate cancer defined by Phoenix criteria after external beam radiotherapy (EBRT) or brachytherapy as primary treatment and who had not undergone previous salvage prostatectomy. Methods After screening of our institutional database 118 patients were finally eligible for this retrospective analysis with a median PSA of 6.4 ng/mL (range: 2.2 - 158.4 ng/mL). 77 and 41 patients had been treated by EBRT or brachytherapy, respectively. Of the 118 patients, 45 were receiving androgen deprivation therapy (ADT) within at least 6 months prior to 68Ga-PSMA PET/CT. The detection rates were stratified by PSA (2 to <5, 5 to <10 and ?10 ng/mL). The influence of primary Gleason score at diagnosis and ADT was assessed. Correlations between standardized uptake values (SUV) and Gleason score or ADT in patients with positive findings were analyzed. Results 90.7% (107/118) patients showed pathological findings indicative for tumor recurrence in 68Ga-PSMA PET/CT. The detection rates were 81.8% (36/44), 95.3% (41/43) and 96.8% (30/31) for PSA ranges of 2 to <5, 5 to <10 and ?10 ng/mL, respectively. 68Ga-PSMA PET/CT indicated local recurrence in 68/107 patients (63.5%), only distant lesions in 64/105 patients (59.8%) and local recurrence as well as distant lesions in 25/107 patients (23.4%). The detection rate was significantly higher in patients with ADT (97.7%) vs. without ADT (86.3%, p=0.0381), but independent from primary Gleason score ?8 (92.0%) vs. ?7 (90.2%, p=0.6346). SUVmax and SUVmean were significantly higher in patients with ADT (p=0.0025 and 0.0044, respectively) and a clear trend to higher values was observed for patients with Gleason score ?8 (p=0.0502 and 0.0514, respectively). Conclusions 68Ga-PSMA PET/CT demonstrates high detection rates in patients with biochemical recurrence of prostate cancer after primary radiation therapy as defined by Phoenix criteria. The detection rate positively correlated to increasing PSA as well as concomitant ADT. 68Ga-PSMA PET/CT enables discrimination of local vs. systemic disease and thus might have a crucial impact on further clinical management. The high observed detection rates even at very low PSA values questions the definition of recurrence by the current Phoenix criteria. A limitation of this study is the lack of histopathological proof in the majority of patients. Funding none
Authors
Tobias Maurer
Ingo Einspieler Isabel Rauscher Christoph Rischpler Charlotte Düwel Markus Krönke Gregor Habl Sabrina Dewes Jürgen E. Gschwend Hans-Jürgen Wester Markus Schwaiger Matthias Eiber |
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PD61-04 |
Comparison of Gleason upgrading rates in transrectal ultrasound systematic random biopsies versus US-MRI fusion biopsies for prostate cancer. |
Prostate Cancer: Staging II | 17BOS |
Abstract: PD61-04 Sources of Funding: None Introduction US-MRI fusion biopsy (FB) showed that it improves the detection of clinically significant prostate cancer (PCa). A more accurate diagnostic method is desirable to avoid misclassification, which in turn is particularly important in appropriate decision making on treatment for PCa (active surveillance or focal therapy or radical treatment). We aimed to compare the Gleason upgrading (GU) rates and the concordance of the Gleason scores in the biopsy versus final pathology after the surgery in patients who underwent only TRUS systematic random biopsies versus US-MRI FB for PCa. Methods A retrospective analysis of patients&[prime] prospective collected data that underwent prostate biopsy and subsequent radical prostatectomy were included from January 2011 to June 2016 at our institution. The study cohort was divided into: US-MRI FB (Group A) and only TRUS systematic random biopsy (Group B). US-MRI FB was performed in patients who had a previous MRI with a focal lesion classified by Likert score ≥ 3, otherwise a TRUS systematic random biopsy was performed. All biopsies and surgical specimens were analyzed by the same uropathologist and MRIs were analyzed by two expert urological radiologists. Results 73 men underwent US-MRI FB and 89 TRUS systematic random biopsy. The GU rate was higher in group B (31.5% vs 16.4%; p = 0.027). GU according to Gleason grade pattern was higher in Group B against Group A (40.4% vs 23.3%; p = 0.02). Analyses from separate Gleason grade pattern showed that Gleason score 3+4 presented less GU in group A (24.1% vs 52.6%; p = 0.043)(table 1). The Bland-Altman plot analysis showed a higher bias in Group B compared to group A (-0.27 [-1.40 to 0.86] vs -0.01 [-1.42 to 1.39]). In the multivariable logistic regression the only independent predictor of GU was the use of TRUS systematic random biopsy (2.64 [1.11 - 6.28]; p = 0.024). Conclusions The US-MRI FB appears to be related to a decrease in GU rate and an increase in the concordance between biopsy and final pathology in comparison to TRUS random biopsy, that leads to greater accuracy on diagnosis and better treatment decision. Funding None
Authors
Arie Carneiro
Paulo Kayano Tiago Castilho Arjun Sivaraman Oliver Claros Ary Neto Renee Filippi Ronaldo Baroni Gustavo Lemos |
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PD61-05 |
Outcomes of Repeat MRI-US Fusion-Targeted Biopsy in Men with Initially Low Risk or Negative Fusion Biopsy |
Prostate Cancer: Staging II | 17BOS |
Abstract: PD61-05 Sources of Funding: Joseph and Diane Steinberg Charitable Trust Introduction While the value of MRI-US Fusion-targeted biopsy (MRF-TB) in the identification of occult, clinically significant prostate cancer (csPCa), has been well described, the accuracy of targeting using available fusion platforms is not as clear. As the need for repeat biopsy among men with negative or low risk MRF-TB remains to be defined, we evaluated the outcomes of repeat MRF-TB among men with initially negative or low risk MRF-TB. Methods Between 6/2012 and 9/2016, 1,584 consecutive men undergoing pre-biopsy prostate MRI followed by MRF-TB and systematic biopsy (SB) were enrolled in prospective date registry. 195 men underwent repeat MRI and MRF-TB for continued suspicion of csPCa. 76 men were excluded from analysis due to outside facility or 1.5T MRI, hip implant or interval focal therapy. Upgrade was defined as an increase in Gleason score (GS) from 3+3 to ≥3+4 or from 3+4 to ≥4+3 among men with PCa noted on first MRF-TB, or any cancer among men with no cancer on first MRF-TB. Biopsy outcomes were stratified per MRI findings and progression. Results 119 men (mean age 65.9±7.7 years, mean PSA 5.8±4.5 ng/mL) underwent repeat MRF-TB. The median interval between initial and repeat biopsy was 17.1±8.9 months. On repeat biopsy, 50% (59) had concordant GS, 17% (20) were downgraded, and 34% (40) were upgraded. Of the 40 upgrades, 42% (17) were due to an increase in GS and 58% (23) were due to newly detected PCa, as illustrated in Table 1._x000D_ _x000D_ PI-RADS score was predictive of the likelihood of upgrade on repeat MRF-TB (Table 2). 53% of men with PI-RADS 4 and 5 demonstrated upgrade on repeat biopsy compared to 26% of men with PI-RADS 3. 82% (9/11) of upgrades in men with PI-RADS 1 and 2 were due to newly detected GS 6 disease. Conclusions 53% of men with PI-RADS 4 and 5 lesions were upgraded on repeat MRF-TB, suggesting a need for repeat sampling among men with low risk or negative MRF-TB and persistent PI-RADS 4 and 5 regions noted on follow-up MRI. Among men with PI-RADS 1 or 2 on repeat imaging, continued observation may be reasonable given the low likelihood (5%) of csPCa on repeat MRF-TB. Funding Joseph and Diane Steinberg Charitable Trust
Authors
Xiaosong Meng
Andrew Rosenkrantz Fang-Ming Deng Richard Huang James Wysock Marc Bjurlin William C. Huang Herbert Lepor Samir S. Taneja |
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PD61-06 |
Diagnostic Performance and Reproducibility of a Likert Scale Versus Qualitative Descriptors For Determination of Extraprostatic Tumor Extension With Multiparametric Magnetic Resonance Imaging of the Prostate |
Prostate Cancer: Staging II | 17BOS |
Abstract: PD61-06 Sources of Funding: This investigation was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under award number UL1TR001105. Introduction _x000D_ Preoperative detection of extraprostatic extension (EPE) in prostate cancer (PCa) may affect clinical management and surgical planning. Qualitative descriptors commonly used in multiparametric magnetic resonance Imaging (mpMRI) reports have not been systematically validated and are potentially difficult to reproduce. This study aimed to determine the inter-reader agreement and diagnostic performance of qualitative descriptors versus a 5-point Likert scale for determination of EPE._x000D_ Methods _x000D_ This was an IRB-approved, HIPAA-compliant, single-center, retrospective study with 3 experienced and 2 non-experienced readers. Men who underwent mpMRI of the prostate followed by radical prostatectomy between Nov/2015 and Jul/2016 were eligible. Whole-mount prostatectomy specimen processed with a 3D-printed, patient-specific mold for precise anatomical registration was the standard of reference. Reviewers chose one or more of 8 qualitative descriptors (e.g., capsular bulging, irregular margin) and, after a washout period, assigned a Likert score for the likelihood of EPE: 1, highly unlikely; 2, unlikely; 3, indeterminate; 4, likely; 5, highly likely. Reproducibility among reviewers was assessed with weighted kappa statistics (<0,no agreement; 0-0.20 slight, 0.21-0.40 fair, 0.41-0.60 moderate, 0.61-0.80 substantial, and 0.811 almost perfect). Cochran-Armitage Trend test was used to test the association bewteen pathology-proven EPE and MRI-based Likert score._x000D_ Results _x000D_ Eighty men met eligibility criteria; mean age: 64 years, PSA: 8.0 ng/mL; prostate volume: 39.9 cc; Histologic index lesion size: 22±9 mm; Gleason score≤ 3+4, 62.5%; ≥4+3, 37.5%. EPE was present in 40(50%) men. Qualitative descriptors had inconsistent reproducibility (kappa as low as 0.33 for experienced and -0.02 for inexperienced readers) and poor accuracy (as low as 0.41). Agreement was moderate for experienced (k=0.56) and non-experienced (0.46) readers with the Likert scale. There was significant increase in the likelihood of EPE with higher Likert scores (Figure 1). _x000D_ Conclusions _x000D_ A 5-point Likert scale improves inter-reader reproducibility and the diagnostic performance of mpMRI compared to qualitative descriptors of EPE, facilitating informed decision making, treatment planning and patient counseling._x000D_ _x000D_ Funding This investigation was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under award number UL1TR001105.
Authors
Daniel Costa
Niccolo Passoni Yin Xi John Leyendecker Alberto Diaz de Leon Susana Otero-Muinelo Harpreet Grewal Franto Francis Claus Roehrborn Yair Lotan Payal Kapur Aditya Bagrodia Neil Rofsky Ivan Pedrosa |
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PD61-07 |
Accuracy of preoperative multiparametric magnetic resonance imaging for prediction of unfavorable pathology in patients with localized prostate cancer undergoing radical prostatectomy |
Prostate Cancer: Staging II | 17BOS |
Abstract: PD61-07 Sources of Funding: None Introduction We investigated the accuracy of multi-parametric MRI (mpMRI) for preoperative staging and its influence on the determination of neurovascular bundle sparing and disease prognosis in patients with localized prostate cancer. Methods We reviewed 1,045 patients who underwent radical prostatectomy with preoperative mpMRI at a single institution. Clinical local stages determined from mpMRI were correlated with preoperative and postoperative pathological outcomes. Results The sensitivity and specificity to diagnose seminal vesicle invasion (SVI) on mpMRI were 43.8% and 95.4%, respectively. The negative predictive value was 78.9%. The sensitivity and specificity to diagnose extracapsular invasion (ECE) were 54.5% and 80.5%, respectively. The overall sensitivity and specificity of diagnosing pathological T3 or higher were 52.6% and 82.1%, respectively. Non-organ-confined disease determined by mpMRI was significantly associated with positive surgical margin and pathological T3 disease on multivariate analysis. Preoperative adverse findings on mpMRI were significantly associated with performance of the non-nerve-sparing technique. Conclusions The mpMRI did not show outstanding diagnostic accuracy relative to our expectations in predicting SVI or ECE preoperatively. However, adverse findings on preoperative mpMRI were significantly related with worse postoperative pathological outcomes as well as postoperative biochemical recurrence. Funding None
Authors
Hakmin Lee
Ohseong Kwon Sangchul Lee Sung Kyu Hong Seok-Soo Byun Hwang Gyun Jeon Byong Chang Jeong Seong Il Seo Seong Soo Jeon Han-Yong Choi Hyun Moo Lee |
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PD61-08 |
Does Gleason Score at the Site of Positive Surgical Margin Predict Recurrence Following Radical Prostatectomy? |
Prostate Cancer: Staging II | 17BOS |
Abstract: PD61-08 Sources of Funding: none Introduction Multiple pathologic features have been shown to predict biochemical recurrence (BCR) in patients after radical prostatectomy (RP) for prostate cancer. While positive surgical margins (PSM) have been shown to increase the likelihood of BCR, little data exists on the clinical significance of the tumor Gleason grade at the site of PSM. This study aims to assess if the Gleason grade at the PSM is predictive of BCR, and whether its predictive value differs from that of other commonly referenced risk factors. Methods We performed a retrospective review of a prospectively maintained database of all patients who underwent RP at our institution from 2009 to 2015. We identified 403 patients, 58 (14.4%) of whom were noted to have PSM. These cases were reviewed by an attending Pathologist who assigned a Gleason grade (3, 4 or 5) to the tumor at the site of PSM. The predictive value for BCR was compared to that of final pathology Gleason score and presence of PSM alone. Results We found that 34.5% (20/58) of patients with PSM had BCR, which was greater than the overall BCR rate of 19.9% (80/403) (p < 0.0001). Patients with Gleason 4+ disease at the PSM had a higher BCR rate (57.9%, 11/19) compared to those with Gleason 3 (23.1%, 9/39, p = 0.009) and those with a negative margin (17.4%, 60/345, p < 0.0001). Interestingly, patients with Gleason 3 at the PSM did not have a significantly higher BCR rate than those with a negative margin. Gleason grade at the PSM was an independent predictor of BCR compared to presence of PSM alone. In patients with Gleason sum 7 disease on traditional final pathology, those with Gleason 3 at the PSM had a lower BCR rate (25.0%, 8/32) compared to those with Gleason 4+ (58.8%, 10/17, p = 0.02). Conclusions Our data suggests that Gleason score at the site of PSM independently predicts BCR in patients following RP with accuracy similar to traditional pathologic staging. However, in patients with a PSM and Gleason 7 on traditional pathologic staging, the presence of Gleason 4 or tertiary 5 disease at the margin can serve as an independent predictor of BCR, relative to patients with Gleason 3 at the margin. Routine reporting of the Gleason score at the site of a positive surgical margin may aid in postoperative risk stratification following RP. Funding none
Authors
Goran Rac
Lawrence Dagrosa Laura Spruill Thomas Keane |
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PD61-09 |
Index Tumor Volume on MRI as a predictor of pathologic outcomes following radical prostatectomy |
Prostate Cancer: Staging II | 17BOS |
Abstract: PD61-09 Sources of Funding: This research was supported by the Intramural Research Program of the National Cancer Institute, NIH Introduction Tumor volume measured on radical prostatectomy (RP) specimen has been shown to be associated with adverse pathologic and oncologic outcomes; however, it is difficult to calculate and cannot contribute to preoperative decision making. Advances in imaging technology may facilitate the prediction of prostate cancer outcomes prior to surgery. In this study, we evaluated the predictive value of the index tumor volume (ITV) calculated from prostate MRI in analyzing adverse pathologic outcomes following RP in a higher risk cohort. Methods Clinical and pathologic data from a prospectively maintained, single-institution database were analyzed for patients who underwent 3T MRI prior to RP (without prior therapy) between 2007 and 2016, with an index tumor defined as a T2-visible lesion with the longest diameter. ITV was calculated from T2W MRI by multiplying length by width by depth by 0.52 to generate the volume of an ellipse. Adverse pathologic outcomes were determined on whole mount RP specimens, and defined as positive margins (PM), extracapsular extension (ECE), positive lymph nodes (LNI), and seminal vesicle invasion (SVI). Logistic regression was used to assess associations of clinical, imaging, and histopathological variables with adverse pathologic features. Receiver operating characteristic curves were used to characterize and compare ITV performance with Partin tables. Results In our study period, 464 patients met our inclusion criteria. In our cohort, median age and PSA were 60 years (IQR 10) and 6.21 ng/ml (IQR 6), and 24.4% were &[Prime]high risk&[Prime] (Gleason 8-10) on biopsy . 15.6% of patients had PM, 23.5% ECE, 6.3% LNI, and 6.5% SVI. Patients with adverse outcomes were found to have larger median ITV (PM: 1.236cc vs 0.832cc, p=0.045; ECE: 1.388cc vs 0.771cc, p<0.001; LNI: 2.750cc vs 0.801cc, p<0.001; SVI: 2.269cc vs 0.806cc, p<0.001). On multivariate analysis, ITV was found to be an independent predictor of ECE (OR: 1.211, p=0.005), LNI (OR: 1.366, p<0.001), and SVI (OR: 1.305, p=0.002), but not PM (OR: 1.052, p=0.300). ITV alone and ITV+PSA were found to have predictive ability comparable to that of Partin tables (ECE: ITVAUC: 0.660 vs. ITV+PSAAUC:0.721 vs. PartinAUC: 0.717, LNI: ITVAUC: 0.802 vs. ITV+PSAAUC:0.881 vs. PartinAUC: 0.873, SVI: ITVAUC: 0.749 vs. ITV+PSAAUC:0.762 vs. PartinAUC: 0.806). Conclusions We demonstrate that Index Tumor Volume measured on T2W MRI is an independent predictor of ECE, LNI, and SVI following RP. We believe this easily calculated preoperative marker provides additional prognostic information, particularly in higher risk cohorts. Funding This research was supported by the Intramural Research Program of the National Cancer Institute, NIH
Authors
Dordaneh Sugano
Abhinav Sidana Brian Calio Sonia Gaur Amit Jain Mahir Maruf Maria Merino Peter Choyke Baris Turkbey Bradford Wood Peter Pinto |
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PD61-10 |
Does the number of Gleason 6 positive cores on prostate biopsy predict adverse pathology at radical prostatectomy in patients who are candidates for active surveillance? |
Prostate Cancer: Staging II | 17BOS |
Abstract: PD61-10 Sources of Funding: None Introduction Patients with low-risk prostate cancer (PCa) at diagnosis are at risk for upgrading or upstaging on radical prostatectomy (RP). The possibility of occult aggressive disease is a concern for active surveillance (AS). Accordingly, AS is commonly restricted to men with 3 or fewer positive cores. The goal of this study was to model the relationship between the number of positive cores and the risk of adverse pathology in order to determine a threshold number of cores for AS._x000D_ Methods We identified a cohort of 1,820 men who underwent RP at Memorial Sloan Kettering Cancer Center (MSKCC) between January 2000 and August 2016, and had low risk PCa. A comparable cohort of 1,469 French patients treated between December 2004 and November 2012 was identified. Adverse pathology was defined as Gleason score ≥ 4+3, seminal vesicle invasion or lymph node involvement. The association between number of biopsy cores and the risk of adverse pathology was analyzed using locally weighted scatterplot smoothing._x000D_ Results In the MSKCC cohort, 171 (9.4%) patients had adverse pathology at RP, compared to 48 (3.3%) in the French cohort. There was a small increase in the risk of adverse pathology with the number of positive cores: patients with 1 positive core had a 4% risk which increased to 8% for patients with 12 positive cores. The increase in risk was smooth, with no discontinuities suggesting an obvious threshold for AS eligibility (Figure 1). There were some differences between cohorts, with the change in risk with increasing cores being flatter in MSKCC cohort. However, even in the French cohort, there were not large differences in risk by number of cores._x000D_ Conclusions There is no number of positive cores threshold associated with a sharp increase in the risk of adverse pathology. Consequently, patients should not be excluded from AS solely based on the number of positive cores. _x000D_ Funding None
Authors
François AUDENET
Emily VERTOSICK Samson FINE Rafael SANCHEZ-SALAS Marc GALIANO Eric BARRET Xavier CATHELINEAU François ROZET James EASTHAM Peter SCARDINO Karim TOUIJER |
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PD61-11 |
The new Epstein Gleason score classification significantly reduces upgrading in prostate cancer patients |
Prostate Cancer: Staging II | 17BOS |
Abstract: PD61-11 Sources of Funding: none Introduction Aim of our study was to evaluate differences between the old and the new classification systems in upgrading and downgrading rates in a cohort of patients undergoing radical prostatectomy (RP) for PCa. Methods Between 2012 and 2016, 636 patients with clinically localized PCa were treated with RP at two tertiary referral centers. Blood samples were collected and tested for total PSA. All the patients included in the study presented a biopsy performed in the same center where the RP was performed. Biopsy specimens as well as RP specimens were graded according to both 2005 Gleason and 2015 Epstein Gleason grading systems. Upgrading and downgrading rates on RP were recorded for both classifications and then compared. Clinically significant upgrading was defined as: Epstein score raising from ≤2 to ≥3 or from 3 to 5 and Gleason (2005) raising from ≤6 to ≥7 or from 7 to ≥9. As well clinically significant downgrading was defined as: Epstein score decreasing from ≥3 to ≤2 or from 5 to ≤3 and Gleason (2005) decreasing from ≥7 to ≤6 or from ≥9 to ≤7. The accuracy of the biopsy for each Gleason score classification was determined using the kappa coefficient of agreement: <0.4 poor agreement, 0.4-0.75 good agreement and > 0.75 excellent agreement. Results Median age and preoperative PSA levels were 66 years (IQR: 61-69) and 7.1 ng/ml (IQR: 5.2-10.0), respectively. Overall 247/636 (39 %) had advanced disease (pT≥3a). Pathological grading of biopsies and RP specimens according to both classifications are described in table 1. The Epstein Gleason score presented a lower upgrading rate (93/636:15% vs 150/636:24%; p=0.000) and a similar downgrading rate (36/636:6 % vs 28/636:4% p=0.194) when compared to the 2005 one. The kappa-statistics measures of agreement between needle biopsy and RP specimens was better for the Epstein score when compared to the 2005 Gleason score (k= 0.569±0.034 vs k= 0.481±0.033). Conclusions The new Epstein Gleason score classification significantly reduces upgrading events in patients with PCa treated with RP. The implementation of this new classification could better define prostate cancer aggressiveness with important clinical implications particularly in PCa management. Further studies with a pathological review and reclassification of the specimens are needed to confirm our data. Funding none
Authors
Cosimo De Nunzio
Giuseppe Simone Costantino Leonardo Riccardo Mastroianni Devis Collura Giovanni Muto Michele Gallucci Riccardo Lombardo Carlo De Dominicis Andrea Tubaro Andrea Vecchione |
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PD61-12 |
Impact of surgical technique on the performance of pelvic lymph node dissection at radical prostatectomy: Results from a German multicenter database |
Prostate Cancer: Staging II | 17BOS |
Abstract: PD61-12 Sources of Funding: none Introduction Pelvic lymph node dissection (PLND) is the gold standard for LN staging in localized prostate cancer. The prevalence of LN involvement (LNI) is directly related to the number of dissected LNs or extent of PLND. Most published outcomes of PLND are based on single-center series. Unselected data on current PLND practice and influence of different surgical approaches on the performance of PLND are rare. The present study aims to assess the differential LN counts and rates of LNI detection depending on different PLND techniques by analysis of data from a multicenter German database. Methods We identified men in a German internet-based multicentre database (www.prostata-ca.net) who had open PLND, open radioisotope guided sentinel PLND (sPLND), robotic-assisted PLND (rPLND) or laparoscopic PLND (lPLND) and radical prostatectomy from 2005 to 2015. Differences in demographic characteristics, clinicopathological features, N-stage, LN counts and rates of LNI detection were examined using Mann-Whitney U-test or Pearson Chi-square test. Results A total of 6892 men (median age 67 years, median PSA 8ng/ml) from 17 hospitals met inclusion criteria. The patients were subjected to open PLND (59.4%), sPLND (28.2%), lPLND (11.2%) and rPLND (1.3%). sPLNDs and rPLNDs were carried out only by one center each. Except for a trend (p<0.0001) towards better differentiated Gleason-Scores in men with sPLND, there were no differences in patient characteristics comparing the groups. The median number of LNs removed was 10 (IQR 7-14) with no significant differences between PLND techniques: open PLND 11 (IQR 7-15), sPLND 10 (8-14), lPLND 10 (6-15) and rPLND 11 (8-13.5). Overall, 12.33% of patients had LNI. In sPLND, the LNI rate (18.9%) was significantly (p<0.001) higher than in open (10.26%), lPLND (7.27%) and rPLND (7.95%). In open PLND techniques, the rate of LNI was significantly higher (p<0.001) than in the two minimal invasive approaches. Overall, the median number of positive LNs was 2 (IQR 1-4) without significant difference between the techniques. Conclusions In current practice in Germany, using open PLND techniques results in a higher LNI rate than minimal invasive approaches. The use of targeted sPLND results in by far the highest rate of LNI despite better differentiated tumors. More LN+ patients were detected by sPLND than expected according to the data of single-center extended PLND series, too. These results should stimulate a reevaluation of patient selection or type of PLND. Funding none
Authors
Alexander Winter
Lutz Brautmeier Attyla Drabik Tom Fischer Mario Zacharias Robert Kössler Björn Volkmer Jan Roigas Ulrich Witzsch Holger Heidenreich Manfred Beer Marcus Horstmann Wolfgang Stollhoff Wolfgang Diederichs Mike Lehsnau Mark Schrader Steffen Weikert Christian Klopf Jan Fichtner Friedhelm Wawroschek Annette Reinecke Martin Schostak Kurt Miller |
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PD62-01 |
Comparative effectiveness of selective adjuvant versus systematic neoadjuvant chemotherapy-based strategy for muscle- invasive urothelial carcinoma of the bladder |
Bladder Cancer: Invasive VI | 17BOS |
Abstract: PD62-01 Sources of Funding: none Introduction There is evidence supporting the use of neoadjuvant (NAC) or adjuvant chemotherapy (AC) in combination with radical cystectomy (RC) for muscle-invasive urothelial carcinoma of the bladder (UCB). However, no study has been devised to compare upfront RC followed - performance status and absence of surgical contraindications permitting - by the selective delivery of AC in patients with adverse pathological features, while watching those with organ-confined disease (selAC-based strategy) vs. the systematic delivery of NAC in all eligible individuals followed by surgery if amenable (sysNAC-based strategy). We hypothesized that a selAC-based strategy is associated with an overall survival (OS) benefit when performing an "intention-to-treat" analysis._x000D_ Methods Within the National Cancer Data Base (2003-2011), we identified 10,056 patients who received selAC- vs. sysNAC-based strategy for cT2-T4N0M0 UCB. Inverse probability of treatment weighting (IPTW)-adjusted Kaplan-Meier and Cox regression analyses with time-varying covariate were used to compare OS of patients who received selAC- vs. sysNAC-based strategy. Exploratory analyses according to baseline characteristics were additionally performed. Results Overall, 8,312 (82.7%) vs. 1,744 (17.3%) patients underwent selAC- vs. sysNAC-based strategy, respectively. IPTW-adjusted Kaplan-Meier curves showed that median OS was significantly longer in the selAC- vs. sysNAC-based strategy group (42.0 [95%CI, 39.5-44.6] vs. 33.7 [95%CI, 29.4-38.1] months; P=0.001). The 5-year IPTW-adjusted rates of OS for selAC- vs. sysNAC-based strategy were 42.98% [95%CI, 41.8-44.2] vs. 37.45% [95%CI, 34.8-40.1], respectively. In IPTW-adjusted Cox regression analyses with time-varying covariate, selAC-based strategy was associated with a significant OS benefit after 17 months of follow-up (HR=0.79; 95%CI=[0.70-0.90]; P<0.001). In exploratory analyses, this benefit was significant in cT2 patients (HR=0.78; 95%CI=[0.67-0.88]; P<0.001) while there was no difference between treatment groups in >=cT3 patients (HR=1.18; 95%CI=[0.95-1.47]; P=0.129). Conclusions We report an OS benefit for individuals treated with a selAC- vs. sysNAC-based strategy for muscle-invasive UCB - especially cT2 disease. Our findings warrant further consideration in randomized controlled trials to explore this hypothesis. Funding none
Authors
Thomas Seisen
Guru Sonpavde Naveen Kachroo Stuart R. Lipsitz Jeffrey J. Leow Mani Menon Philipp Gild Nicolas von Landenberg Morgan Rouprêt Adam S. Kibel Maxine Sun Sumanta K. Pal Joaquim Bellmunt Toni K. Choueiri Quoc-Dien Trinh |
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PD62-02 |
Adjuvant chemotherapy vs. observation following radical cystectomy for pT3-4 and/or pN+ urothelial carcinoma of the bladder previously treated with neoadjuvant chemotherapy |
Bladder Cancer: Invasive VI | 17BOS |
Abstract: PD62-02 Sources of Funding: none Introduction Neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) is the standard of care for clinically localized muscle-invasive urothelial carcinoma of the bladder (UCB). Approximately 20% of patients who received NAC + RC have adverse features on pathology, specifically pT3-4 and/or N+ disease. Against this backdrop, we examine the role of adjuvant chemotherapy (AC) following RC for those pretreated with NAC. Methods Within the National Cancer Data Base (2004-2012), we identified 800 patients who received AC vs. observation following NAC plus RC for pT3/T4N0 or pN+ UCB. Multiple imputation using chained equations was used to handle missing data. We further performed inverse probability of treatment weighting (IPTW)-adjusted Kaplan-Meier and Cox regression analyses with a 6-month conditional landmark to compare overall survival (OS) between the two treatment groups. Specifically, propensity scores derived from a logistic regression model predicting the receipt of AC vs. observation were used to weigh each patient to balance observable characteristics. Results Overall, 190 (23.8%) vs. 610 (76.2%) patients underwent AC vs. observation following NAC + RC, respectively. Independent predictors of receiving AC vs. observation included facility type (Non-academic vs. academic: OR=2.08, 95%CI=[1.45-2.97]; P<0.001) and location (West vs. Est; OR=1.84; 95%CI=[1.12-3.01]; P=0.016), as well as disease stage (pTanyN+ vs. pT3N0: OR=2.18; 95%CI=[1.47-3.22]; P<0.001), while older age (OR=0.97; 95%CI=[0.94-0.99]; P=0.008) predicted the opposite. IPTW-adjusted Kaplan-Meier curves showed that median OS was significantly improved in the AC vs. observation group (29.9 [IQR, 15.1-85.4] vs. 24.2 [IQR, 12.9-58.9] months; P=0.031; Figure 1). The 5-year IPTW-adjusted rates of OS for AC vs. observation were 36.8% vs. 24.7%, respectively. In IPTW-adjusted Cox regression analyses, AC was associated with a significant OS benefit (HR=0.76; 95%CI=[0.60-0.97]; P=0.031). Conclusions We report an OS benefit for individuals treated with AC vs. observation for pT3-4 and/or N+ UCB following NAC + RC. Our findings warrant further consideration in randomized controlled trials to explore this hypothesis. Funding none
Authors
Thomas Seisen
Asha Jamzadeh Malte W. Vetterlein Nicolas von Landenberg Philipp Gild Mani Menon Morgan Rouprêt Maxine Sun Toni K. Choueiri Joaquim Bellmunt Quoc-Dien Trinh |
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PD62-03 |
The Effect of Intrinsic Subtype on Response to Neoadjuvant Chemotherapy for Muscle Invasive Bladder Cancer |
Bladder Cancer: Invasive VI | 17BOS |
Abstract: PD62-03 Sources of Funding: National Cancer Institute SPORE & VF Foundation Introduction _x000D_ Gold standard treatment for muscle invasive bladder cancer (MIBC) is radical cystectomy (RC) with neoadjuvant chemotherapy (NAC). However, the survival benefit of NAC in unselected patients is considered modest (5-15%). Recently genomic studies identified intrinsic basal, p53-like, and luminal molecular subtypes of MIBC which identify the genetic heterogeneity of bladder cancer. We hypothesized that tumor intrinsic subtype at the time of staging transurethral resection (TURBT) could be associated with clinical benefit from NAC. Methods _x000D_
We identified patients with MIBC who underwent RC with or without NAC between 2000 and 2010 at three different institutions. Whole-genome analysis was performed on TURBT specimens and were classified into basal, luminal or p53-like subtypes. Primary outcome is overall survival (OS). Secondary outcome is response is tumor downstaging ( Results _x000D_
273 TURBT specimens were analyzed. There were no significant differences in the subtypes between age, sex and stage (P<0.05). 87 (32%) were basal, 95 (35%) were p53-like, and 91 (33%) were luminal. 127 (46%) did not get NAC, and 146 (54%) received NAC. _x000D_
_x000D_
Downstaging occurred in 69 of 273 patients (26%), 2% (2/127) did not receive NAC and 47% (69/146) received NAC (p<0.001). Of patients that received NAC, 51% (25/49) of basal, 33% (16/48) p53-like, and 57% (28/49) of luminal tumors were downstaged (p=0.033)._x000D_
_x000D_
Median OS for patients who did not receive NAC was 33 mo. vs. 102 mo. for those who did (p<0.0001). OS was improved for patients who did vs. those who did not get NAC in basal subtypes (17 mo. vs. 271 mo., p<0.001). However, there was no significant difference in OS for p53-like (58 mo. vs. 70 mo., p=0.3137), and for luminal (43 mo. vs. 85 mo., p=0.0629). For patients that did get NAC, patients with basal tumors had a significant increase in OS over to the other subtypes (p=0.0239) (Figure 1). _x000D_
Conclusions _x000D_
Basal tumors in the absence of NAC are high risk, but they have a favorable response to NAC which results in an increased OS. Luminal tumors have a favorable downstage rate at RC, but this does not translate into increased OS. P53-like tumors have a poor prognosis regardless of use of NAC. We demonstrate that the intrinsic molecular subtypes of MIBC identified at TURBT have variable response to NAC with significant implications on OS. Funding National Cancer Institute SPORE & VF Foundation |
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PD62-04 |
Safety and efficacy Gemcitabine-Cisplatin split dose as a neoaduvant chemotherapy for muscle invasive bladder cancer |
Bladder Cancer: Invasive VI | 17BOS |
Abstract: PD62-04 Sources of Funding: None Introduction Neoadjuvant chemotherapy (NAC) (Cisplatin based) and radical cystectomy are currently level 1 recommendation for muscle invasive bladder cancer. Gemcitabine-Cisplatin regimens are gaining popularity as (NAC). Only few data at present about splitting the doses in order to decrease toxicity, used with patients with lower renal function and achieve more patient compliance. The objective of this study is to study the effectiveness and safety of split dose Gemcitabine and Cisplatine as a NAC for muscle invasive bladder cancer. Methods All consecutive patients from 2004 to 2015 that received Gemcitabine and Cisplatine split doses and followed by open radical cystectomy for T2-T4 bladder cancer were included in the study. All patients administered 1,000 mg/m2 of gemcitabine and 35 mg/m2 of Cisplatin given on days 1 and 8 of a 21 days cycle for 4 cycles. Preoperative patients` clinical parameters, need for dose reduction, number of cycles complications of NAC and pathologic response were recorded. Patients with unavailable follow up data were excluded from the study. Fisher exact test was used for univariate analysis to detect preoperative factors affecting pathologic response. Results Eighty two patients met the inclusion criteria. Only 10 patents (12 %) couldn't complete 4 cycles because of complications. 38 patients (46%) were down staged (pT≤ 1) and 32 achieved complete response (pT0). Median follow up time was 29 months. Univariate analysis for detecting factors affect pathologic response showed no significant effect of Gender (p=0.742), race (p=0.783), Age (p=0.377), BMI (p=0.821), T stage (0.982), N stage (0.615), presence of Cis (0.096), squamous differentiation (p=0.229) and presence of lymphovasular invasion (p=0.749). Conclusions Splitting the dose of Gemcitabine and Cisplatine as a NAC for muscle invasive bladder cancer has a good pathologic response with high safety profile. Patients with different preoperative characters can get benefit from this regimen. Funding None
Authors
Mohamed Abdelhafez
Michael Williams |
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PD62-05 |
NEOADJUVANT CHEMOTHERAPY IN MUSCLE-INVASIVE BLADDER CANCER: DIFFERENCES IN CLINICAL AND PATHOLOGICAL RESPONCE |
Bladder Cancer: Invasive VI | 17BOS |
Abstract: PD62-05 Sources of Funding: none Introduction Neoadjuvant cisplatin-based chemotherapy prior to radical cystectomy (RC) for muscle invasive bladder cancer is underutilized beside has been supported by guidelines. This study was undertaken to determine the rate of neoadjuvant gemcitabine and cisplatin (NGC) use before radical cystectomy (RC) and lymphadenectomy and to assess its effect on the pathologic response rates, surgical outcome and complication rate. Methods This retrospective study examined all patients having a RC between January 2012 and September 2016. We collected patient demographics, pre-treatment clinical stage, post-RC pathologic data and survival data. Response Evaluation Criteria in Solid Tumors (RECIST, ver. 1.0) was used to asses clinical response to NGC (CR for complete response, PR for partial response, PD for progression of disease and SD for Stable disease on CT). Pathological Tumor Regression Grade (TRG) was evaluated (AJSP). Results A total of 84 RC were performed of which 74 (88%) were for stage cT2-T4 urothelial carcinoma of the bladder. Salvage cystectomy were excluded (n=10). Of the 74 patients, 30 (40.5%) received NGC. Based on CT scan, clinical response to NGC was evaluated (RECIST criteria): CR was observed in 2 pts (6%), PR in 18 (60%); PD in 1 (3%) and SD in 9 (30%) regarding primary bladder tumor. In 12 pts with enlarged lymph-nodes, the response to NGC was CR in 1, PR in 10 and SD in 1. Patients receiving neoadjuvant GC had a greater chance of achieving a pathologically lower stage compared to the untreated population: organ-confined cancer in 53,3% (16/30) vs. 33% (p < 0.001). Lymph-node metastasis resulted in 25% patients after GC (n=10) vs 45.5% of untreated patients (n=20; p < 0.001). Considering patients resulted CR and PR after NGC (n=20), 70% had down-staging on pathologic report after RC. Complication rates were higher in NGC group (4 thromboembolisms; 2 sepsis; 12 hematologic complications); all complications were not related to surgery. Pathological TRG after NGC was not correlated to clinical regression grade. The OS (mean follow-up 30 months) of patients who received NGC resulted of 66.6% compared with 56% of patients undergoing cystectomy alone (p<0,001). Fifty percent of patients in NGC group were alive without cancer vs 40,1% in cystectomy alone group (p<0,001). Conclusions Neoadjuvant chemotherapy for muscle-invasive bladder cancer increases the rate of down-staging and cancer specific survival. NGC is associated with an increased risk of complications that may be prevented using tailored strategies. Pathological regression grades after NGC are not correlated to RECIST criteria based on CT. Funding none
Authors
Andrea Benedetto Galosi
Giulio Milanese Lucio Giustini Giulia Sbrollini Isabella Chiodega Guevar Maselli Luciano Burattini Rossana Berardi Rodolfo Montironi |
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PD62-06 |
Neoadjuvant chemotherapy for elderly patients with locally advanced or early nodal disease: Are we doing enough? |
Bladder Cancer: Invasive VI | 17BOS |
Abstract: PD62-06 Sources of Funding: none Introduction The administration of neoadjuvant chemotherapy (NAC) for patients with muscle invasive urothelial carcinoma improves overall survival and is a category 1 NCCN recommendation. Recent reports have shown that the survival benefit may be greater in patients with locally advance disease and nodal involvement. Here we aim to assess the NAC administration trends in patients with locally advanced and low stage nodal disease using a large national tumor registry. Methods Patients treated for muscle invasive urothelial carcinoma were selected from the National Cancer Data Base. Patients with clinical stage T2-T4 and low stage nodal disease (N0-N2), treated between 2004 and 2014, where included in the study. Patients who underwent chemotherapy as the only treatment where excluded from the analysis. A multivariate analysis was constructed to identify factors that affected administration of NAC. Covariates included in the model were clinical stage, age, race, sex, insurance status, income, Charlson comorbidity index, pathological stage, demographic location, facility location, and diagnosis year. Results A total of 19,299 patients met inclusion criteria for the study. NAC utilization increased over the study period with 35.6% of patients receiving NAC in 2014 compared to 10.1% in 2004. Decreasing NAC utilization was noted with increasing age (< 65 years: 28.0%; 65-74 years: 23.9%; ≥75 years: 12.3%, p<0.001). On multivariate analysis age, clinical stage and patient age were found to be significantly associated with administration of NAC. Increasing clinical stage and early nodal disease was found to be associated with an increase in the administration of NAC, using cT2N0 as a reference, the likelihood of NAC administration of T3N0 and T4N0 and Tany/N1-2 was 1.31 (95% CI 1.14 to 1.50) and 1.63 (95% CI 1.43 and 1.87) respectively (p< 0.001, both). Increasing age was associated with a decrease in the use of NAC, using <65 years as a reference, the likelihood of NAC administration for patients 65-74 years and ≥75 years was .89 (95% 0.82 to 0.91) and 0.39 (95% CI 0.34 to 0.44), respectively (p=0.32 and p< 0.001). On interaction analysis between age and clinical stage, the likelihood of receiving NAC still increased with increasing clinical stage in patients < 65 to 74 years old but this effect was non-existent in patients 75 years or older. Conclusions Although the administration of NAC has increased over the last 10 years, the use of NAC in septa and octogenarians remains low; even, in those presenting with advance stage and early nodal disease. Funding none
Authors
Andres Correa
Elizabeth Handorf Benjamin Ristau Haifler Haifler Shreyas Joshi Robert Uzzo Rosalia Viterbo Richard Greenberg David Chen Alexander Kutikov Daniel Geynisman Marc Smaldone |
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PD62-07 |
Utilization of chemotherapy and radiation for muscle invasive urothelial carcinoma |
Bladder Cancer: Invasive VI | 17BOS |
Abstract: PD62-07 Sources of Funding: None. Introduction Trimodal therapy (TMT) with transurethral resection, followed by chemotherapy and radiation for muscle invasive urothelial carcinoma (UC) is typically reserved for patients deemed unfit for radical cystectomy (RC). Recently, some studies have demonstrated reasonable oncologic outcomes after TMT for select patients with muscle invasive UC. We assessed practice patterns for TMT in patients with muscle invasive UC using data from the National Cancer Database (NCDB). Methods We identified patients with muscle invasive UC of the bladder treated with either RC or TMT between 2004 and 2013. TMT was defined by patients who had transurethral resection plus chemotherapy and radiation therapy within 90 days. Trends in utilization of TMT over time were measured. We compared socioeconomic and clinical variables including age, race, distance from residence to treatment center, urban vs rural residence, median county income, facility type and volume, Charlson comorbidity score (CCS), tumor size and grade, and clinical nodal status between patients receiving RC and TMT and identified predictive factors for receipt of TMT with logistic regression modeling. Results Using the NCDB, we identified 18,084 patients that underwent RC (15,722) or TMT (2,362) for cT2 UC of the bladder. TMT patients were older (median 76 vs 68 years), had higher CCS, and higher rates of clinical node positive disease (for all comparisons, p < 0.001). Tumor size was similar between groups. On multivariable analysis, significant predictors of TMT included increasing age (OR = 4.48 [4.05 – 4.96]), rural residence (OR = 1.27 [1.11 – 1.45]), and facility type (those in an integrated network cancer program were 1.44 times as likely to undergo bladder sparing as those treated at community cancer centers [1.11-1.88]).Negative predictors for TMT were treatment at an academic center (OR = 0.59 [0.48 – 0.73]), treatment at a high volume center (OR = 0.35 [0.29 – 0.43]), and longer distance of residence from treatment center (OR = 0.30 [0.29 – 0.37]). The proportion of patients receiving TMT decreased over the study period. Conclusions Older patients who live in rural areas were more likely to undergo TMT. Treatment at high volume, academic centers and distant residence from treatment center were all negative predictors for receipt of TMT. Further analyses of these two groups is necessary to determine whether these patterns of treatment impact survival of patients with muscle invasive UC. Funding None.
Authors
Jen-Jane Liu
Ann Martinez Acevedo Mark Garzotto Michael Conlin Jeremy Cetnar Arthur Hung Christopher Amling Ryan Kopp |
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PD62-08 |
Changes in lean muscle mass associated with neoadjuvant chemotherapy in patients with muscle invasive bladder cancer |
Bladder Cancer: Invasive VI | 17BOS |
Abstract: PD62-08 Sources of Funding: none Introduction Baseline sarcopenia is independently associated with increased mortality after cystectomy for muscle-invasive urothelial carcinoma (MIUC). Cytotoxic chemotherapy is associated with variable changes in lean muscle mass in other malignancies, however, its impact on muscle mass in MIUC patients is undefined. As neoadjuvant chemotherapy (NC) prior to radical cystectomy is the current standard of care in MIUC, our objective was to describe preoperative changes in body composition in patients receiving platinum-based NC. Methods Patients with cT2-4, N0-1, M0 UC of the bladder who underwent NC were retrospectively identified. Skeletal muscle index (SMI, cm^2/m^2) was calculated using validated methodology (cross sectional area of skeletal muscle/height^2 at L3) from pre- (pre-NC) and post-NC (post-NC) computed tomography images. Patients were classified as being sarcopenic according to consensus definitions: Male: SMI <55 cm^2/m^2, Female: SMI <38.5 cm^2/m^2. Pre-NC and post-NC median body mass index (BMI) and SMI were compared using paired Wilcoxon signed rank tests. Results The cohort consisted of 26 patients, with a median age 70 years, including 7 females (27%). Chemotherapy regimens included dose-dense methotrexate, vinblastine, doxorubicin and cisplatin in 8 (31%), gemcitabine/cisplatin in 16 (62%) and gemcitabine/carboplatin in 1 (3.8%). Median number of cycles was 3.5 (range 2-6). Median pre- and post-NC BMI were 27.1kg/m^2 and 27.2kg/m^2 (p=0.36). Median pre- and post-NC cross-sectional lumbar muscle area were 141 and 129.4 cm^2 (p<0.001). Median pre- and post-NC SMI were 49.2 and 44.5 cm^2/m^2 (p<0.001). Median % change in SMI was -6.4% (Figure). Pre-NC, 18 (69%) patients were sarcopenic vs. 21 (81%, p=0.002) post-NC. Percent change in SMI did not differ according to baseline sarcopenia status or number of chemotherapy cycles. Conclusions Although BMI remained stable, we observed a significant decrease in lean muscle mass among MIUC patients treated with platinum-based NC prior to cystectomy, with an associated increase in the prevalence of sarcopenia. These patients may benefit from pre-habilitative interventions to mitigate lean muscle loss prior to cystectomy. The association of change in SMI with surgical outcome in this cohort is under investigation. Funding none
Authors
Kalen Rimar
Alexander Glaser Edward Schaeffer Joshua Meeks Shilajit Kundu Sarah Psutka |
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PD62-09 |
Pathological examination extemporary of lymph nodes using frozen section (fs) during radical cystectomy (rc) is useful to select patients who need super extended lymph node dissection (se-lad) : results of a prospective study |
Bladder Cancer: Invasive VI | 17BOS |
Abstract: PD62-09 Sources of Funding: none Introduction The value of extemporary pathological examination of lymph nodes during RC using FS has been debated and is still controversial. In the majority of tertiary centers an extended or super-extended lymphadenectomy(E-SE-LAD) without intra-op evaluation of the nodes is performed. However this approach has drawbacks: 1. longer time of surgery 2. possible higher complication rate . To prevent this an intra-op path evaluation of the nodes removed can help in reducing the extent and time of surgery and complications. The objective of the study was to evaluate the path diagnosis on FS of lymph nodes during RC and to compare it to the final path report. Finally the impact of FS results on the extent of surgery was analized. Methods The last 74 patients who received RC with ELAD for TCC of the bladder at our center were included. Obturator, internal, external, common, pre-sacral and perivesical nodes were removed bilaterally before RC and sent immediately for FS. When 1 pos. node was detected LAD was extended to the aortic bifurcation bilaterally . If none or more than 1 node was pos. at FS LAD was stopped. Mean age was 63.5 year (58-78). Male/female ratio was : 51/23. 148 LADs were performed and nodes sent in separate containers (pelvic:obturator + internal , external, common iliac , pre-sacral,peri-vesical) for FS during RC. Pathological preparation An established path protocol for extemporary diagnosis was followed in all cases. It consisted of different passages: 1. freezing (cryostat) 2. first staining (hematossilin-Eosin) 3. cutting (5 nm thickness sections) 4. quick re-staining with hematossilin-Eosin 5. reading. Results The median N of nodes sent for FS was 18 from each side (36 in total) . 14/74 pts (19%) had pos. nodes at FS and all were confirmed at the final path evaluation . 3/14 pts. had only one pos. node (2 R, 1 L) and LAD was extended to the aortic bifurcation. The final path report confirmed the FS report and no further pos.nodes were detected. In one case (1/148 LADs) a node was suspicious at FS and pos. at the final path report: patient received ELAD. 10/14 pts. had more than one pos node: LAD was not extended further. The concordance between FS and final path report was 99.3% (147/148 LADs). In 2 patients the N of pos nodes at the final path examination was greater than the one found on FS (+ 5 and + 2). In both cases surgery was not changed. Conclusions A high concordance between intra-op FS diagnosis of lymph nodes and final path report was observed (99.3%). In 4% of patients (3/74) the surgical procedure was changed (ELND) due to the FS results. In 96% of our pts. an extended surgery was not necessary . FS resulted a valuable method for the detection of pos. nodes during RC. A well defined and strict path protocol and path/uro cooperation is the key. Funding none
Authors
Maurizio Brausi
Giancarlo Peracchia Giuseppe De Luca |
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PD62-10 |
Identification of Molecular Biomarkers of Cisplatin-based Chemosensitivity in Patients Undergoing Neoadjuvant Chemotherapy for Muscle-Invasive Bladder Cancer |
Bladder Cancer: Invasive VI | 17BOS |
Abstract: PD62-10 Sources of Funding: None Introduction Although survival benefit of cisplatin-based neoadjuvant chemotherapy for muscle-invasive bladder cancer has been demonstrated, a significant proportion of patients do not respond. Identification of chemoresponsive cohorts would avoid morbidity and prevent delayed surgical intervention in patients who are unlikely to benefit. We evaluate the role of miRNA and mRNA expression profiles in initial TURBT specimens of patients who receive neoadjuvant chemotherapy prior to radical cystectomy. Differences in TURBT specimen expression patterns between complete responders (pT0) and nonresponders (pT2≤) at time of cystectomy may help stratify patients for possible neoadjuvant chemotherapy. Methods FFPE tissue was isolated from initial TURBT specimens of patients with clinically localized MIBC treated with cisplatin-based neoadjuvant chemotherapy. Tissue from 9 patients with T2≤ disease was compared with samples from 10 pT0 patients at time of cystectomy. Differential expression of 754 miRNAs and mRNA was analyzed utilizing RT-qPCR. miRNA expression profiles were compared between complete responders and nonresponders. mRNA in tumor specimens was sequenced from both groups with 76 base pair paired-end reads using NextSeq technology. KEGG Pathway analyses were used to identify differential gene expression patterns between the two groups. Results Significant upregulation of miRNA 485-3p, miRNA 520d, miRNA 410, miRNA 872, and miRNA 1304 was observed in nonresponders versus complete responders. KEGG pathway analysis revealed significant upregulation of the hsa03430 pathway, implicated in DNA mismatch repair, the hsa03420 pathway, implicated in nucleotide excision repair, and the hsa03410 pathway, involved in base excision repair, among pT0 patients. Conclusions Differential miRNA and mRNA expression within the initial tumor specimen of patients with complete pathologic regression versus progression indicates a possible role in determining-neoadjuvant chemo-sensitivity. Upregulation of DNA repair mechanisms in the primary tumor may signify chemo-sensitivity and help stratify MIBC patients being considered for neoadjuvant chemotherapy. Funding None
Authors
Paras Shah
Zachary Kozel Annette Lee Ilya Korsunsky Andrew Shih Oksana Yaskiv Manish Vira Thomas Bradley Xinhua Zhu |
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PD62-11 |
PREDICTIVE ROLE OF EPITHELIAL TUMOR MARKER LEVEL ELEVATION AT FOLLOW-UP FOR TUMOR RECURRENCE AND ONCOLOGICAL OUTCOMES IN UROTHELIAL BLADDER CANCER |
Bladder Cancer: Invasive VI | 17BOS |
Abstract: PD62-11 Sources of Funding: None Introduction We have previously reported that elevated pre-cystectomy serum levels of epithelial tumor markers (TM) and lack of TM response to neoadjuvant chemotherapy (NAChT) are associated with worse oncological outcome in patients with invasive urothelial bladder cancer (UBC). Herein, we evaluate elevation of TM levels during follow-up and their predictive role in tumor recurrence. _x000D_ Methods Under IRB approval, serum levels of Carbohydrate Antigen 125 (CA-125), Carbohydrate Antigen 19-9 (CA 19-9) and Carcinoembryonic Antigen (CEA) were prospectively measured in 409 patients with invasive UBC between August 2011 and August 2016. Excluded from the study were metastatic (13), palliative or inoperable (5) cases. Markers were measured at different time points during follow-up. Results A total of 391 cystectomy patients were included in the study with median age of 71 years and 79% males. Pathology was organ-confined in 59% and NAChT was given in 35% of population. Elevated precystectomy level of any of the tumor markers (31% of patients) was independently associated with worse RFS (p<0.001; HR=2.81) and OS (p<0.001; HR=3.97). After completion of cystectomy, we were able to document normal serum marker levels from 288 cases, of whom 26 patients (9%) developed tumor marker relapse later during follow up. This subset showed significantly more clinical recurrences (89% in elevated vs. 12% in stable group, RR= 7.41), and death (24% vs. 7%, RR=3.4). Median time from tumor marker relapse to clinical recurrence was 46 days (IQR 0-179), and median time to mortality was 308 days (IQR 119-574). Details of tumor markers course in the 23 patients with marker relapse followed by clinical recurrence is shown in figure 1. Further Survival analysis using landmark time-point with log rank showed there is a significant difference in cancer-specific survival between the groups (median 284 vs 547 days; p=0.01) (Figure 2). Conclusions To our knowledge, this is the first pilot study showing predictive role of epithelial tumor marker for recurrence of invasive urothelial bladder cancer. Patients with marker relapse following cystectomy are at significant increased risk of recurrence and mortality. A larger, controlled study with longer follow up is needed to determine their role in predicting survival. Funding None
Authors
Soroush T Bazargani
Hooman Djaladat Anne Schuckman Gus Miranda Jie Cai Sarmad Sadeghi Tanya Dorff David Quinn siamak Daneshmand |
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PD62-12 |
Comparative effectiveness of trimodal therapy versus radical cystectomy for localized muscle-invasive urothelial carcinoma of the bladder |
Bladder Cancer: Invasive VI | 17BOS |
Abstract: PD62-12 Sources of Funding: none Introduction The only randomized controlled trial comparing trimodal therapy (TMT) vs. radical cystectomy (RC) for muscle-invasive urothelial carcinoma of the bladder (UCB) failed to meet its accrual target. We sought to examine the comparative effectiveness of TMT vs. RC for muscle-invasive UCB in an observational cohort study. Methods Within the National Cancer Data Base (2004-2011), we identified 12,843 individuals who received TMT or RC for definitive treatment of cN0M0 muscle-invasive UCB. Inverse probability of treatment weighting (IPTW) adjusted Kaplan-Meier and Cox regression analyses with time-varying covariate were used to compare overall survival (OS) of patients who received TMT vs. RC. Exploratory analyses according to patient characteristics were also performed. Results Overall, 1,257 (9.8%) and 11,586 (90.2%) patients received TMT and RC, respectively. IPTW-adjusted Kaplan-Meier curves showed that median OS was similar between TMT and RC groups (39.6 [95% CI, 33.7-45.5] vs. 43.0 [95% CI, 40.9-45.1] months; P=0.290; Figure 1). In IPTW-adjusted Cox regression analysis with time-varying covariate, TMT was associated with a significant adverse effect on OS after 25 months of follow-up (HR=1.37;95%CI=[1.16-1.59];P<0.001). In exploratory analyses (Figure 2), there was no significant difference between TMT and RC with regard to long-term OS in individuals aged >=70 (HR=1.21;95%CI=[0.83-1.60];P=0.225), of female gender (HR=1.28;95%CI=[0.83-1.74];P=0.170), with Charlson comorbidity index >=1 (HR=1.10;95%CI=[0.83-1.38];P=0.439) and/or >=cT3 disease (HR=1.16; 95%CI=[0.80-1.52];P=0.338. Conclusions We generally observed that TMT was associated with worse long-term OS compared to RC for muscle-invasive UCB. However, selected subgroups of patients may choose TMT over RC to avoid surgical toxicities with minimal impact on OS._x000D_ Funding none
Authors
Thomas Seisen
Maxine Sun Stuart R. Lipsitz Firas Abdollah Jeffrey J. Leow Mani Menon Nicolas von Landenberg Philipp Gild Morgan Rouprêt Mark Preston Lauren C. Harshman Adam S. Kibel Paul L. Nguyen Joaquim Bellmunt Toni K. Choueiri Quoc-Dien Trinh |
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PD63-01 |
Severe Penile Injuries Sustained During Operations Iraqi and Enduring Freedom: Evaluating the TOUGH Cohort for Penile Transplantation |
Trauma/Reconstruction/Diversion: External Genitalia Reconstruction and Urotrauma (including transgender surgery) II | 17BOS |
Abstract: PD63-01 Sources of Funding: none; The view(s) expressed herein are those of the author(s) and do not reflect the official policy or position of Brooke Army Medical Center, the U.S. Army Medical Department, the U.S. Army Office of the Surgeon General, the Department of the Army or the Department of Defense or the U.S. Government. Introduction In our initial review of the Trauma Outcomes and Urogenital Health (TOUGH) cohort, we identified 423 male US service members (SMs) who sustained penile injuries (PI) while deployed in support of Operations Iraqi Freedom and Enduring Freedom (OIF/OEF). Conventional penile reconstruction is challenged by the unique structure and function of the penile tissues. Thus, penile transplantation is being investigated as a potential means for penile replacement after severe PI. We have made the clinical observation that many SMs who sustained severe PI during OIF/OEF presented with complex polytrauma which may have excluded them from enrollment in existing penile transplantation protocols. The objective of this study was to evaluate the injury patterns among members of the TOUGH cohort who sustained PI with a focus on comorbid conditions which may impact candidacy for penile transplantation. Methods The previously identified members of the TOUGH cohort who sustained PI were further characterized based on injury severity as well as the presence of comorbid conditions which may impact eligibility for penile transplantation. Severe PI was defined as an Abbreviated Injury Scale severity of 3 or greater (cutaneous avulsion, laceration through glans/cavernosum/urethra, or partial/total penectomy). Five comorbid conditions were identified which may negatively impact penile transplant candidacy: traumatic brain injury (TBI), massive blood transfusion, colorectal injury, pelvic fracture, and extremity amputation(s). SMs with severe PI were stratified by the number of comorbid conditions diagnosed. Results Among the 423 men with PI identified in the TOUGH cohort, 86 (20.3%) sustained severe PI. SMs with severe PI were largely young (median age: 23) and injured during battle (n=81; 94%) by explosive mechanisms (n=77; 90%) resulting in severe polytrauma (median ISS=29). Comorbid conditions which could impact penile transplantation candidacy were common, including massive transfusion (n=56; 65%), lower extremity amputation(s) (n=55; 64%), TBI (n=34; 40%), colorectal injury (n=29; 34%), and pelvic fracture (n=27; 31%). Overall, 83% of SMs (n=71) had at least one of these conditions and 47% (n=41) had ≥ 3. Conclusions Severe PI was relatively rare during OIF/OEF. Life-threatening polytrauma was common and nearly all SMs with severe PI had comorbid immunologic, physical, and/or neurologic diagnoses which could disqualify them from penile transplantation given the current restrictions identified in existing transplant protocols. Funding none; The view(s) expressed herein are those of the author(s) and do not reflect the official policy or position of Brooke Army Medical Center, the U.S. Army Medical Department, the U.S. Army Office of the Surgeon General, the Department of the Army or the Department of Defense or the U.S. Government.
Authors
Steven Hudak
Judson Janak Jean Orman Michael Davis |
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PD63-02 |
Compliance with AUA guidelines with excretory phase imaging for evaluation of high-grade renal trauma: Results from the American Association for Surgery of Trauma (AAST) Genitourinary Trauma Study |
Trauma/Reconstruction/Diversion: External Genitalia Reconstruction and Urotrauma (including transgender surgery) II | 17BOS |
Abstract: PD63-02 Sources of Funding: None Introduction In AAST grade IV and V injuries or grade III injury with perinephric fluid, current guidelines recommend obtaining a CT scan of abdomen and pelvis with intravenous contrast, followed by a delayed excretory phase to look for collecting system injury. Our aim was to evaluate compliance with excretory phase imaging recommendations in a contemporary multi-center study of high-grade renal trauma._x000D_ Methods From 2014 to 2016, data on high-grade renal trauma (AAST grade III-V) was gathered from 10 participating trauma centers. Demographics, trauma characteristics, management, outcomes, and imaging studies, were collected. Compliance with imaging recommendations was defined as obtaining delayed excretory images within 24 hours of admission for any grade IV or V injury, or grade III injuries with perinephric fluid, in those patients not undergoing immediate laparotomy. Follow-up images and data were reviewed to determine if there were cases of delayed diagnosis of urinary extravasation. _x000D_ Results There were 217 high-grade renal injuries (grades III [118], IV [69], V [30]). Initial CT scans were missing in 49 patients due to: patient transfer and unavailable initial imaging (15), or immediate laparotomy (34). 168 patients had an initial CT scan for review. From these, 161 had CT findings indicating the need for excretory imaging due to perinephric fluid in grade III (98), or grade IV (48) or V (15) injury. 112 (70%) of these patients had excretory imaging within 24 hours of admission, an additional 10 (6%) had one obtained during their initial hospital stay (range 2-6 days post injury). Of the patients with excretory imaging 37 (31%) had a collecting system injury diagnosed in initial CT scan with additional 3 (2%) diagnosed in CT scans obtained later during their initial hospital stay. Overall compliance with imaging recommendations ranged between 20%-100% (median: 81%) for different centers. Of 39 patients who did not have an excretory imaging, 5 underwent a CT with excretory phase later, and 2 had a delayed diagnosis of urinary leakage._x000D_ Conclusions There is discrepancy between centers in compliance with obtaining excretory phase CT scans for evaluation of high-grade renal trauma. Despite the variation in compliance with imaging recommendations, the rate of clinically significant delayed diagnosis of urinary extravasation is low in the overall management of high-grade renal injury. _x000D_ Funding None
Authors
Brandi Miller
Sorena Keihani Brian P. Smith Patrick M. Reilly Xian Luo-Owen Kaushik Mukherjee Bradley J. Morris Sarah Majercik Peter B. Thomsen Bradley A. Erickson Benjamin N. Breyer Gregory Murphy Richard A. Santucci Timothy Hewitt Frank N. Burks Erik S. DeSoucy Scott A. Zakaluzny LaDonna Allen Jurek F. Kocik Raminder Nirula Jeremy B. Myers |
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PD63-03 |
Recovery of the Function of the Kidney following Renal Trauma and Conservative Management |
Trauma/Reconstruction/Diversion: External Genitalia Reconstruction and Urotrauma (including transgender surgery) II | 17BOS |
Abstract: PD63-03 Sources of Funding: none Introduction The majority of patients with renal trauma are managed conservatively regardless of grade of injury once they are stable with resuscitation. However, it is not known what happens to the function of the affected kidney following initial loss due to trauma._x000D_ _x000D_ Methods In this prospective study conducted from July 2014 to December 2015 patients with unilateral renal injury and contra-lateral normal kidney were included. Their renal injury was graded according to American Association for the Surgery of Trauma. They underwent first DMSA renal scan within 7 days and second DMSA scan 3 months after trauma for assessment of early and delayed relative function of injured kidney respectively. Patients requiring any surgical and radiological intervention were excluded from the study Results Total 32 patients fulfilled the inclusion and exclusion criteria and completed the study. The mean early relative function of the injured kidney (35.7 ± 15.8 %) improved significantly at 3 months (39.6 ± 17.7%, p < 0.001). When we considered grade I to grade III as low grade we observed that the improvement was significant in kidneys with low grade injury (from 46.1 ± 3.2% to 50.4 ± 2.7%, p < 0.01) and grade IV injury. There was no improvement of function of kidney with grade V injury (Table I). The preserved function and improvement of function was associated with low grade injury, low degree of parenchymal loss and no vascular injury (p<0.01, Table 2). On multivariate analysis only vascular injury was associated with no significant improvement in function. The relative renal function improved in 25 patient remained almost the same in 3 patients and decreased in 4 patients. Significantly a high proportion of kidney with high grade injury, more than 50% of parenchyma loss and vascular injury had loss of relative function more than 5 %. Conclusions Retained renal function following conservative management depends on grade of renal injury, degree of parenchymal loss and vascular injury. The improvement of function of injured kidney occurs with passage of time in the majority except those with vascular injury. Funding none
Authors
Kanishka Kumar
Shrawan Singh BR Mittal Shivanshu Singh Arup K Mandal |
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PD63-04 |
Role of repeat imaging in renal trauma management : results of a French multicentric study (TRAUMAFUF) |
Trauma/Reconstruction/Diversion: External Genitalia Reconstruction and Urotrauma (including transgender surgery) II | 17BOS |
Abstract: PD63-04 Sources of Funding: none Introduction Renal trauma is the most common type of genitourinary injury. In the management of renal trauma, a repeat imaging is recommended two to seven days after the initial trauma to seek for missed complications. However, the data on which this recommendation is based are scarce and controversial._x000D_ The aim of this study was to evaluate the impact of the routine use of repeat imaging after renal trauma. Methods A nationwide multicentric retrospective study including all patients referred for renal trauma has been conducted in fifteen trauma centers between 2005 and 2015. Patients were divided into three groups : no routine repeat Imaging (NRIM), repeat imaging in asymptomatic patient (SYSTIM), repeat imaging in symptomatic patient (SYMPTIM)._x000D_ The three groups were compared, and multivariate analysis were performed to seek for predictive factors of secondary surgery/interventional radiology, change in patient management and readmission. Results Out of 927 patients who were treated fo renal trauma, 758 had repeat imaging (81.8 %) : 583 (76.9 %) had routine repeat imaging while asymptomatic (SYSTIM), 175 (23,1 %) had repeat imaging due to symptoms (SYMPTIM)._x000D_ The median interval between trauma and repeat imaging was five days if there were no symptoms, and seven days if patients had symptoms. A relevant finding was made more frequently in the SYMPTIM group than in the SYSTIM group (57.1 % vs. 24.1 %, p<0.0001)._x000D_ In thirty patients who had routine repeat imaging (5.1 %), secondary surgery/interventional radiology was needed based on imaging findings, : 19 ureteral stent, 4 percutaneous drainage, 6 embolization and a diaphragmatic tear repair._x000D_ Initial management was modified in 64 (38.2 %) patients from the SYMPTIM group. There was no significative difference in terms of readmission in the NRIM group vs. the SYSTIM group (2.9 % vs. 3.6 %, p = 0.81). Conclusions In our study, repeat imaging within 10 days following renal trauma was performed in 81.8% of patients but did change the management in only 5.1% of asymptomatic patients. _x000D_ Repeat imaging after renal trauma could be proposed only to symptomatic patients, with active bleeding or urinary extravasation on the initial CT and patients at risk of renal pseudo-aneurysm. Funding none
Authors
Reem BETARI
Gaelle FIARD Marine RUGGIERO Ines DOMINIQUE Lucas FRETON Jonathan OLIVIER Quentin LANGOUET Clémentine MILLET Sébastien BERGERAT Paul PANAYATOPOULOS Xavier MATILLON Ala CHEBBI Thomas CAES Pierre-Marie PATARD Nicolas SZABLA Nicolas BRICHART Laura SABOURIN Kerem GULERYUZ Charles DARIANE Cédric LEBACLE Jérôme RIZK François-Xavier MADEC François-Xavier NOUHAUD Benjamin PRADERE Xavier ROD Marine HUTIN Benoit PEYRONNET |
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PD63-05 |
Blunt Renal Trauma: Validation of a conservative follow-up imaging strategy |
Trauma/Reconstruction/Diversion: External Genitalia Reconstruction and Urotrauma (including transgender surgery) II | 17BOS |
Abstract: PD63-05 Sources of Funding: none Introduction AUA guidelines suggest that follow-up imaging post-renal trauma is not routinely required for American Association for the Surgery of Trauma (AAST) grade I-III renal injuries but early CT imaging is prudent for grade IV-V renal injuries. Our aim was to determine the yield of follow-up imaging in patients sustaining renal trauma at our major trauma unit and prospectively validate a new conservative follow-up imaging strategy. Methods All patients who attended Cork University Hospital with a diagnosis of blunt renal injury from 2000-2016 were identified. Review of all charts and imaging was undertaken with relevant patient demographics recorded. Operative records, complications, date and results of follow-up imaging were also reviewed. Injuries were graded by a staff radiologist using the AAST Organ Injury Scale and were grouped as low-grade (I, II, III) or high-grade injuries (IV, V). We correlated clinical outcomes with repeat imaging results. A new conservative follow-up imaging strategy was introduced in 2012. Results One hundred and fifty patients (155 renal units) were identified with a median age 23 years (IQR 18-38 years), 86% were male. Low-grade injuries accounted for 69% of cases, all were managed conservatively with a complication rate of 3% (n=3 pain). Forty-six patients (31%) had high-grade injuries; 3 cases required nephrectomy and 1 case required angio-embolisation, 87% were managed conservatively with a complication rate of 17% (n=2 urinoma; n=2 hypertension; n=2 pain; n=1 febrile episode; n=1 secondary haemorrhage). All patients with complications were symptomatic, prompting repeat imaging. Results of routine repeat imaging did not independently predict any complication or prompt urologic intervention. Following the introduction of a conservative follow-up imaging strategy in 2012 (validation cohort n=48, high grade injuries n=22), we have safely reduced repeat CT imaging in high grade injuries by 41% (p=0.018). Conclusions Selective reimaging of renal injuries based on clinical and laboratory criteria would have detected all complications in our series. Routine follow-up imaging for renal injuries grades I-III is unnecessary in the absence of clinical deterioration. Follow-up imaging of high grade renal injuries (IV,V) should be guided by the presence of urine extravasation in addition to clinical and laboratory criteria. AUA guidelines are clinically appropriate in a major tertiary trauma unit in Ireland but can be tailored further to reduce repeat CT imaging of Grade IV renal injuries. Funding none
Authors
Kieran J Breen
Eanna O'Corragain Paul Sweeney Eamonn Rogers Eamonn A Kiely Frank M O'Brien |
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PD63-06 |
Nonoperative management has significantly increased for both blunt and penetrating renal trauma: data from the National Trauma Data Bank |
Trauma/Reconstruction/Diversion: External Genitalia Reconstruction and Urotrauma (including transgender surgery) II | 17BOS |
Abstract: PD63-06 Sources of Funding: None Introduction Management of blunt renal trauma has evolved to favor a conservative approach. Penetrating trauma, however, has traditionally involved surgical intervention. The purpose of this study is to compare the trends in operative and nonoperative management following blunt and penetrating renal trauma. Methods A retrospective cross sectional analysis was performed using data from 2002-2012 within the National Trauma Data Bank (NTDB). Cases were identified by ICD-9 diagnosis codes. Codes 866.00 through 866.03 and 866.10 through 866.13 were queried for blunt and penetrating renal trauma, respectively. Only cases requiring interventions were included. Treatments were identified using ICD-9 procedure codes for nephrectomy (55.5x), renal laceration repair (55.81), arteriography (88.45) or endovascular repair (39.79). Results 4296 cases were reported during the study period. Of these, 2635 involved blunt trauma and 1661 involved penetrating injury. Following blunt trauma, there was a significant increase in the percentage of cases managed by endovascular means (R2=0.92, p<0.01) with a corresponding decrease in the amount of patients undergoing both nephrectomy (R2=0.32, p=0.068) and laceration repair (R2=0.54, p<0.01) [Figure 1a]. Following penetrating trauma, there was also a significant decrease in nonoperative management (R2=0.69, p<0.01) largely explained by a decline in nephrectomy (###). Endovascular interventions significantly increased (R2=0.87, p<0.01) [Figure 1b]. These cases, however, were predominantly managed with laceration repair with no significant change over the study period. Conclusions Surgical intervention for blunt and penetrating trauma continues to decrease. Procedural intervention for blunt renal trauma largely consists of endovascular management. Although most interventions for penetrating trauma involve repair, nephrectomy has significantly decreased while endovascular management has increased. Future efforts should aim to characterize whether the current trends in surgical intervention following penetrating renal injuries is appropriate and if outcomes data warrants a change in guidelines that may allow for quality improvement and decreased morbidity. Funding None
Authors
Marc Colaco
Susan MacDonald Ryan Terlecki |
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PD63-07 |
PERINEPHRIC HEMATOMA SIZE IS INDEPENDENTLY ASSOCIATED WITH THE NEED FOR UROLOGIC INTERVENTION IN BLUNT RENAL TRAUMA |
Trauma/Reconstruction/Diversion: External Genitalia Reconstruction and Urotrauma (including transgender surgery) II | 17BOS |
Abstract: PD63-07 Sources of Funding: AHS Surgery Strategic Clinical Network Summer Surgical Research Studentship (SSRS) Award Introduction Although the American Association of the Surgery for Trauma Organ Injury Scale (AAST-OIS) can help predict the need for urologic intervention, this grading system does not include other potentially important factors such as devitalized renal fragments, laceration location and perinephric hematoma characteristics. The objective of this study is to examine predictors of urologic intervention in the setting of blunt renal trauma. Methods The Alberta Trauma Registry was used to identify renal trauma patients at the University of Alberta from October 2004-December 2014. Penetrating trauma and patients without complete datasets were excluded from analysis. Hospital records and diagnostic imaging were reviewed to identify the need for intervention related to the renal injury including ureteral stenting, percutaneous drainage, angiographic embolization, nephrectomy or renorraphy. Clinical and radiographic factors examined included patient age, gender, length of stay, ISS, AAST-OIS grade, laceration length/number, perinephric hematoma characteristics (number, length, location, area), intravascular contrast excretion (ICE) and devitalized segment status. Descriptive statistics and binary logistic regression were performed where appropriate. Results 328 patients with blunt renal trauma met study criteria. Mean patient age was 37.0 years with a mean ISS of 31.7. 27 patients (8.2%) required a total of 31 interventions including ureteral stenting (38.7%; 12/31), angiographic embolization (32.3%; 10/31), nephrectomy (22.6%; 7/31), renorraphy (3.2%; 1/31) and percutaneous drainage (3.2%; 1/31). On univariate analysis AAST grade (p<0.001), hematoma diameter (p<0.001), hematoma area (p<0.001), ICE (p<0.001), laceration length (p<0.001), laceration number (p<0.001), devitalized fragment presence (p<0.0001) and degree of devitalization (p<0.001) were associated with the need for intervention. On multivariate regression analysis only AAST grade (p<0.001; O.R. 69.4; 95%C.I. 6.4-748.3), hematoma diameter (p=0.004; O.R.1.5; 95%C.I. 1.1-1.9) and/or hematoma area (p=0.012; O.R. 1.03; 95% C.I. 1.01-1.06) remained associated with the need for intervention. Conclusions Although the AAST-OIS is strongly associated with the need for urologic intervention, perinephric hematoma diameter and area are also independently associated with this occurrence. Perinephric hematoma size should be considered during clinical decision-making and should be incorporated into a revised injury grading system. Funding AHS Surgery Strategic Clinical Network Summer Surgical Research Studentship (SSRS) Award
Authors
Logan Zemp
Uday Mann Keith Rourke |
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PD63-08 |
Early mobilization is safe after renal trauma : a multicenter study |
Trauma/Reconstruction/Diversion: External Genitalia Reconstruction and Urotrauma (including transgender surgery) II | 17BOS |
Abstract: PD63-08 Sources of Funding: none Introduction Renal trauma is the most frequent genitourinary trauma. Current guidelines recommend bed-rest in patients with renal trauma. However, there is no data in the literature to support this recommendation. The aim of this study was to assess the impact of early vs. delayed mobilization on the outcomes of renal trauma management. Methods A retrospective multicenter study was conducted including all patients treated for renal trauma in 17 hospitals between 2005 et 2015. Iatrogenic trauma were excluded. Patients were divided in two groups : early mobilization (within the first 24 hours after admission, EM) and delayed mobilization (> 24 hours after admission, DM). The choice of the day of mobilization was made on an individual basis, according to local protocols and was not standardized. Patients’ characteristics and outcomes were compared between the two groups Results _x000D_ Out of 1799 patients, data regarding the day of mobilization was found in the medical records of 918 patients : 153 in the EM group and 765 in the DM group. There was less grade 4 of 5 trauma in the EM group (11.4% vs. 32.3%; p<0.0001), less concomittant solid organ injuries (19.1% vs. 49.7% ;p<0.0001) and less concomittant bone injuries (18.7% vs. 45.8%;p=0.0001). The rates of transfusion and of surgery/interventional radiology after mobilization were similar in both groups (2% vs. 2.4% ;p=0.99 and 2.7% vs. 4.1% ;p=0.49 respectively). In contrast, interval between admission and return of bowel function was shorter in the EM group (0.7 vs. 4 days ;p<0.0001) as was lenght of hospital stay (4.1 vs. 14.8 days ; p<0.0001)_x000D_ In multivariate analysis, EM was not associated with the risk of surgery/interventional radiology nor with transfusion after mobilization (OR=0.86 ; p=0.82 et OR=1.1 ; p=0.87 respectively). In contrast, EM remained associated with shorter time to return of bowel function (?=0.35 ; p<0.0001) and shorter length of stay (?=0.17 ; p<0.0001)._x000D_ Conclusions In this multicenter study, early mobilization after renal trauma did not increase the risk of secondary transfusion nor secondary surgery/interventional radiology an was associated with shorter time to return of bowel function and length of stay. Funding none
Authors
benoit peyronnet
jonathan olivier marine hutin francois-xavier nouhaud quentin langouet marina ruggiero ines dominique lucas freton clémentine millet sebastien bergerat paul panayotopoulos reem betari xavier matillon ala chebbi thomas caes pierre-marie patard nicolas szabla nicolas brichart axelle bohem laura sabourin kerem guleryuz charles dariane cedric lebacle jerome rizk alexandre gryn xavier rod francois-xavier madec gaelle fiard benjamin pradère |
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PD63-09 |
Postoperative complications following primary penile inversion vaginoplasty among 330 male-to-female transgender patients |
Trauma/Reconstruction/Diversion: External Genitalia Reconstruction and Urotrauma (including transgender surgery) II | 17BOS |
Abstract: PD63-09 Sources of Funding: None Introduction Studies of surgical complications from penile inversion vaginoplasty are limited to small sample sizes. Risk factors for complications are unknown. We aim to describe postoperative complications after penile inversion vaginoplasty and evaluate risk factors for complications. Methods We conducted a retrospective review of all male-to-female (MTF) patients presenting for primary penile inversion vaginoplasty to a high-volume surgeon (MLB) from 2011-2015. We classified complications using Clavien-Dindo grades. A multivariate logistic regression was performed to determine the independent effects of age, BMI, and hormone replacement therapy (HRT) on postoperative surgical complications. Results In the study period, 330 patients presented for primary penile inversion vaginoplasty. The median age at time of surgery was 35 years, range (18-76). The median number of years on HRT before gender reassignment surgery (GRS) was 3 (interquartile range, IQR 2-6). The median follow-up time was 3 months (range 3 -73 months). Ninety-five patients (28.7%) presented with a postoperative complication. The median time to a complication was 4 months (IQR 1-12). The most common complication was the formation of granulation tissue in 24 (7.3%) patients. Recto-neovaginal fistulae occurred in 6 (1.8%) patients. Of the patients who presented with a surgical complication, 24 (25.3%) required a second operation. There were no complications greater than Clavien-Dindo grade IIIB. Of the 41 (12.4%) patients who presented with wound separation or granulation tissue, the adjusted odds ratio for each additional year of HRT was 1.05 (1.00-1.11), p=0.04. No preoperative or intraoperative risk factors were associated with fistulae formation. Conclusions The majority of complications due to MTF penile inversion vaginoplasty occur within the first four months after surgery. Years on HRT may be an independent risk factor for wound complications. Long-term use of HRT may alter tissue plasticity and healing; and therefore, puts one at risk for complications. Future prospective studies are required to investigate the long-term effects of feminizing hormones on male genital tissue. Funding None
Authors
Thomas Gaither
Mohannad Awad E. Charles Osterberg Gregory Murphy Angelita Romero Marci Bowers Benjamin Breyer |
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PD63-10 |
One-stage gender confirmation surgery (metoidioplasty) for female-to-male transsexuals |
Trauma/Reconstruction/Diversion: External Genitalia Reconstruction and Urotrauma (including transgender surgery) II | 17BOS |
Abstract: PD63-10 Sources of Funding: None Introduction Female-to-male gender confirmation surgery (GCS) includes removal of breasts and female genitalia, as well as complete genital and urethral reconstruction. With multidisciplinary approach, all these procedures can be performed in one stage, enabling avoidance of multi-staged surgeries. Our aim was to present our experience in one-stage sex reassignment surgery in female-to-male transsexuals. Methods During the period of 8 years (2008-2016), totally 485 patients (mean age 29.5 years) underwent metoidioplasty. Out of them, 140 (29%) had also a hysterectomy performed, and 79 (16.3%) underwent one-stage GCS comprising of bilateral mastectomy, total transvaginal hysterectomy with bilateral adnexectomy, vaginectomy, metoidioplasty, urethral lengthening, scrotoplasty and implantation of bilateral testicular prostheses. All surgeries were performed by gynecology and gender surgeons team, simultaneously. Results The mean follow-up was 44 months (ranged from 14 to 92). Mean surgery time was 260 minutes (range 215-325). Postoperative hospital stay was 3-6 days (mean 4 days). Complications occurred in 22 patients (27.8%) in total. There were 8 cases (10%) with complications related to mastectomy: one patient had revision surgery because of the breast hematoma, 3 patients experienced partial nipple graft necrosis and 4 patients developed hypertrophied scars. Two patients underwent conversion of transvaginal hysterectomy to abdominal approach. One patient received blood transfusion due to excessive bleeding caused by the newly discovered Von Willebrand disease. There were 8 complications (10%) related to urethroplasty, including 4 fistulas, 3 strictures and 1 diverticulum. Two patients had testicular implant rejection, while one patient had testicular implant displacement. In the group of patients who experienced urethral complications, 5 patients required minor revision surgery along with the ones having complications with testicular implants. Conclusions Through multidisciplinary approach of experienced teams, one-stage gender confirmation surgery presents a viable, time and cost saving procedure. Complication rates do not differ from reported rates in multi-staged surgeries. Funding None
Authors
Marta Bizic
Borko Stojanovic Vladimir Kojovic Miroslav Djordjevic |
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PD63-11 |
Surgical and Functional Outcomes following Adult Buried Penis Repair with Limited Suprapubic Panniculectomy and Split-Thickness Skin Grafting |
Trauma/Reconstruction/Diversion: External Genitalia Reconstruction and Urotrauma (including transgender surgery) II | 17BOS |
Abstract: PD63-11 Sources of Funding: none Introduction Adult buried penis is an acquired disorder that can result in secondary manifestations including phimosis, lichen sclerosis, lower urinary tract symptoms, and/or sexual dysfunction. Few published data exist regarding surgical repair, with no universally-accepted technique. We describe our technique for surgical management and report postsurgical clinical and functional outcomes. Methods Patents at Harborview Medical Center were assessed between 6/1/2005 - 6/1/2016. Surgical reconstruction included limited suprapubic panniculectomy with pubic symphysis fixation, excision of penile shaft skin with split-thickness skin graft (STSG), and scrotoplasty if needed. Patient demographic and surgical data were abstracted via chart review. All patients were attempted to be contacted by phone for updated followup. Uni- and multi-variate analysis was examined for association with any complication (p < 0.05 considered significant). Results 42 men underwent buried penis repair. Demographic and surgical characteristics by complication are shown (Table). There was a 33% complication rate (24 events), with the majority related to the pannus wound (8), genital wound (6), or graft loss (5). In univariate analysis, BMI (p = 0.02) and no history of gastric bypass (p = 0.03) were significant predictors of a complication. Upon multivariate analysis, only BMI remained significant (OR 1.1 for each unit increase of BMI, 95% CI 1.01 - 1.27)._x000D_ _x000D_ 24 patients were reached for long-term followup (mean 35.5 ± 36.7 months). There was long-term improvement in every functional domain that was assessed (Figure). 79% reported they would undergo buried penis surgery again, 68% reported that surgery led to a positive change in their lives, and 79% reported that the surgery had remained a long-term success. _x000D_ Conclusions Surgical correction of buried penis results in functional long-term improvements. Higher BMI is associated with an increased likelihood of a perioperative complication, and this risk may be reduced by preoperative weight loss following gastric bypass. Funding none
Authors
Lindsay Hampson
Wade Muncey C.C. Ma Jeffrey Friedrich Hunter Wessells Bryan Voelzke |
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PD63-12 |
EXCISION AND PRIMARY ANASTOMOSIS RECONSTRUCTION FOR TRAUMATIC STRICTURES OF THE PENILE URETHRA |
Trauma/Reconstruction/Diversion: External Genitalia Reconstruction and Urotrauma (including transgender surgery) II | 17BOS |
Abstract: PD63-12 Sources of Funding: none Introduction Anastomotic urethroplasty has long been recognized as a reliable method of reconstruction for focal, severe bulbar urethral strictures. The role of excision and primary anastomosis (EPA) is less well defined for penile urethral strictures due to concerns for potential compromise of sexual function. We report a multi-institutional experience with functional outcomes among men undergoing EPA of pendulous urethral strictures. Methods A retrospective review was conducted of over 2000 urethroplasty patients from two tertiary referral centers from 1995-2016. We identified 13 men treated with EPA for isolated penile urethral strictures, with radiographically confirmed location between the penoscrotal junction and urethral meatus. Clinical characteristics and outcomes are described. Validated questionnaires were utilized to evaluate overall improvement (PGI-I), urinary bother (I-PSS), sexual function (IIEF-5), as well as symptoms related to penile curvature (PDQ). Results Among the 13 men who underwent EPA for penile urethral strictures, strictures were focal (median length 1cm, IQR 1-1.4) and median follow-up was 31 months (IQR 5-110). Only 1/12 (8%) men experienced a treatment failure requiring further instrumentation. None reported new onset penile curvature or curvature related bother (PDQ) following treatment. The majority of men had stricture etiology reported as trauma (10/13, 77%), of which 4 had a history of urethral disruption secondary to penile fracture and 6 iatrogenic trauma. Median patient age was 51 years (IQR 30-60); and 8/12 (67%) had normal preoperative erectile function. After stricture treatment, 75% of men reported a significant global improvement in condition (PGI-I). Sexually active men reported normal erectile function (median IIEF 21 (IQR 19-25), and the majority had only mild urinary bother (median IPSS 4 (IQR 2-14)). The single treatment failure had a history of hypospadias with multiple prior procedures who now requires intermittent catheterization. Conclusions Among selected patients with focal traumatic strictures involving the penile urethra, EPA appears to be highly effective with negligible impairment of erectile function. Funding none
Authors
Boyd Viers
Billy Cordon Travis Pagliara Jeremy Scott Noel Armenakas Allen Morey |
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PD64-01 |
The Neurogenic Bladder Symptom Score (NBSS): An assessment of its external validity and ability to detect change |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Neurogenic Voiding Dysfunction II | 17BOS |
Abstract: PD64-01 Sources of Funding: PCORI grant CER14092138. Introduction The Neurogenic Bladder Symptom Score (NBSS) has been validated as a tool to assess bladder quality of life and symptoms. The objective of this study was to externally validate the NBSS and assess responsiveness (ability of a questionnaire to detect change). Methods Data from the "Patient reported outcomes for bladder management strategies in spinal cord injury" study was used. Adult SCI patients were eligible for enrollment through direct recruitment or an open online portal. At the initial visit, patients provided an extensive medical history, and completed the NBSS. Responsiveness was assessed in a separate prospective cohort of patients undergoing their first injection of onabotulinum toxin. Medians, interquartile range (IQR), and Pearson correlation coefficient (r) are reported. Results 609 patients had complete NBSS scores. Median age was 48 (IQR 36-57), and 67% were male. The majority had thoracolumbar lesions (51%) and managed their bladder by CIC (63%). The median NBSS total score was 22 (IQR 15-30, possible range 0 (no symptoms) to 74 (severe symptoms)), and median quality of life was 'mixed'. The Cronbach's alpha of the total score was 0.85, and 0.93, 0.76, and 0.49 for the incontinence, storage/voiding, and consequences domains respectively. All item to domain correlations were moderate to strong (r≥0.3) aside from 3/7 of the items from the consequences domain. Appropriate hypothesized correlations between the NBSS domains and external variables (such as the number of prior urinary infections and the NBSS consequences domain (r=0.51, p≤0.01) were observed. There was no significant correlation between overall quality of life and prior hospitalizations for urinary infections, or incontinence pad usage._x000D_ _x000D_ A separate cohort of 15 patients with neurogenic bladder competed the NBSS pre and post onabotulinum toxin injection, and the mean change in the total NBSS score was -12 (IQR -2 to -25). The mean change of the incontinence domain was -9 (IQR -1 to -15) and -3 (IQR -2 to -5) for the storage/voiding domain. The change scores had a large to moderate effect size (total NBSS (0.91), incontinence domain (1.03), storage/voiding domain (0.69)) suggesting appropriate and clinically relevant responsiveness. Conclusions The NBSS demonstrated good validity in a large cohort of SCI patients. Similarly, the total NBSS score and relevant domains were responsive to change, and can be used to assess the impact of an intervention. Funding PCORI grant CER14092138.
Authors
Blayne Welk
Sara Lenherr Sean Elliott John Stoffel Angela Presson Chong Zhang Richard Baverstock Kevin Carlson Jeremy Myers |
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PD64-02 |
IS NEUROGENIC BLADDER A RISK FACTOR FOR FEBRILE URINARY TRACT INFECTION AFTER URETEROSCOPY, AND IF SO, WHY? |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Neurogenic Voiding Dysfunction II | 17BOS |
Abstract: PD64-02 Sources of Funding: NONE Introduction Ureteroscopy is commonly used to treat kidney and ureteral stones. While generally considered safe and effective, there is a small but growing body of evidence suggesting that patients with neurogenic bladder are at an increased risk of infectious complications following ureteroscopy. We sought to characterize the rate of febrile urinary tract infections (UTI) after ureteroscopy in patients with neurogenic bladder compared to those with physiologically normal bladders. We also investigated whether it is the neurogenic bladder itself or the neurogenic bladder in the context of bacterial colonization due to catheterization that might be the root cause. Methods We retrospectively reviewed a cohort of patients from a single academically affiliated hospital system who underwent ureteroscopy between June 2013 and May 2016. Information regarding the patient’s neurogenic bladder status, preoperative culture results, bladder management method and presence of upper tract decompression (ureteral stent or nephrostomy) was collected. Postoperative febrile UTI was defined as a hospital admission within 1 week of surgery due to fever not attributable to another source. Results During the study period we identified 467 ureteroscopies, of which 44 (9.5%) were performed on patients with a neurogenic bladder. Postoperative febrile UTI rates were higher in patients with neurogenic bladder as compared to control patients (9% vs 1.4%, respectively, p= 0.01). The risk of febrile UTI after ureteroscopy did not appear to be equally distributed among those with neurogenic bladder. Postoperative febrile UTIs were not seen in neurogenic bladder patients who were catheter independent (0/12). Interestingly, the presence of a nephrostomy tube in patients with physiologically normal bladders increased the risk of postoperative febrile UTI to levels comparable to neurogenic bladder patients who were catheter dependent (10.5% vs 12.5%, respectively). Conclusions While the presence of a neurogenic bladder may increase the risk of infectious complications after ureteroscopy, the reliance on intermittent or indwelling catheters for bladder management appears to be a more important factor. Interestingly, a similar risk of postoperative febrile UTI also appears to be present in non-neurogenic patients with nephrostomy tubes. These data suggest that bacterial colonization, which is prevalent in patients with neurogenic bladder, may be a significant underlying risk factor for febrile UTI after ureteroscopy. Funding NONE
Authors
Craig Stauffer
Elizabeth Snyder Tin Ngo Chris Elliott |
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PD64-03 |
Demonstration of Levator Ani EMG Activity Below the Level of Injury in Complete Spinal Cord Injury (SCI) Using Over Ground Robotic Exoskeleton Walking |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Neurogenic Voiding Dysfunction II | 17BOS |
Abstract: PD64-03 Sources of Funding: None Introduction Detailed studies from our institution have revealed sparing of motor function in trunk muscles below the level of injury and that use of an over ground robotic exoskeleton, which requires weight shifting to initiate stepping, can elicit core EMG activity below the level of injury. By extension, since PFM can often be co-contracted with core muscle activity, we hypothesized that PFM activity may also be demonstrable during exoskeleton-assisted gait training in motor complete SCI below the level of injury. Objective: characterize activation patterns of core and levator ani muscles during exoskeleton-assisted over ground walking vs treadmill walking with body-weight support in motor complete SCI vs able bodied controls. Methods Surface EMG were recorded from the rectus abdominis, external oblique, erector spinae (ES) and levator ani bilaterally. Foot switch signals linked heel strike to EMG activity (Biometrics Ltd, Newport, UK). Baseline, quiescent EMG activity were recorded for 20 sec. during sitting and support (by exoskeleton) standing. EMG activity during exoskeleton-assisted walking were recorded over ground with the Eksoâ„¢ and on the treadmill with Lokomatâ„¢. 40-60 steps were recorded during each walking trial, and walking speed was matched. Protocol was matched in controls. Bladder diaries and validated LUTS scores were completed. Results 3 SCI (ASIA A levels T4, T4,C7; 2 male 1 female, age 33-39 yrs, 2-25 yrs since injury) participated. EMG from PFM, abdominal and ES showed heightened activity during over ground exoskeleton-assisted walking compared to treadmill in both complete SCI and controls. Robust rhythmic bursting was observed in PFM with exoskeleton walking, but not during supported standing or sitting. Fig MVC % exoskeleton (red) vs supported treadmill (black) vs quiet rest (grey). Conclusions EMG activity of PFM was demonstrable using over ground exoskeleton-assisted walking in motor complete SCI below the level of injury. Assisted gait training may reveal this preservation of function by imposing a higher demand on PFM compared to standing only. Potential activation of PFM with robotic gait training supports a novel direction in urologic management of SCI to challenge the levator ani; an important aspect in urinary tract function. Funding None
Authors
Lynn Stothers
Chisholm Amanda Raid Alamro A Williams Tania Lam |
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PD64-04 |
Quality of Life Associated with Bladder Management Strategy after Spinal Cord Injury |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Neurogenic Voiding Dysfunction II | 17BOS |
Abstract: PD64-04 Sources of Funding: PCORI CER14092138 Introduction Little is known about the relative quality of life (QoL) benefits of different bladder management strategies after spinal cord injury (SCI). We sought to describe bladder-related symptoms and QoL using a national sample of SCI patients. Methods Data from a national prospective observational survey was used. Demographic and clinical information were obtained by interview. The Neurogenic Bladder Symptom Score (NBSS), a validated tool to measure urinary symptoms, was administered electronically. Patient demographics, NBSS total score and the NBSS QoL question (&[Prime]If you had to live the rest of your life with the way your bladder (or urinary reservoir) currently works, how would you feel?&[Prime]) were compared with bladder management method using chi-squared, Fisher&[prime]s exact, ANOVA and Kruskal-Wallis tests as appropriate. Results Since January 2016, 780 participants completed the baseline interview. Median age was 46 (interquartile range, IQR: 35-56) with median 27 (IQR: 20-41) years since injury. 39% of participants were recruited in clinic and 55% online/remote. SCI level was: 49% paraplegia, 43% tetraplegia, and 8% unknown/other. Current bladder management was: 63% clean-intermittent catheterization (CIC), 23% indwelling suprapubic/urethral catheter or stoma, 9% spontaneous voiding, and 5% condom catheter. Those using CIC were significantly younger than those using other bladder management methods (p<0.001) and those using spontaneous voiding had the longest median time since injury (p<0.001). The total NBSS score was lowest for indwelling catheter/stoma (18.3 ± 10.5) as compared to condom catheter (22.9 ± 9.3), CIC (24.5 ± 9.9) and spontaneous voiding (28.1 ± 11.9) (p <0.001). Similarly, bladder QoL was &[Prime]pleased&[Prime] or &[Prime]mostly satisfied&[Prime] in 43% of people with an indwelling catheter/stoma, 35% for CIC, 27% for condom catheter, and 26% for spontaneously voiding (chi-square test with permutation, p=0.012; Figure 1). Conclusions In a large cohort of SCI patients, indwelling catheters or stoma drainage was associated with reduced bladder-related symptoms and consequences and best QoL among bladder management methods. This patient-centered outcome differs from the urologists preference for CIC based on medical benefits. Further exploration is needed to understand the patient-reported QoL and clinical outcomes. Funding PCORI CER14092138
Authors
Shyam Sukumar
Sara Lenherr Jeremy Myers Darshan Patel Ronak Gor Amitabh Jha Angela Presson Chong Zhang Jeffrey Rosenbluth John Stoffel Blayne Welk Sean Elliott |
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PD64-05 |
Switch to Abobotulinum toxin A may be useful in the treatment of neurogenic detrusor overactivity when intradetrusor injections of Onabotulinum toxin A failed |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Neurogenic Voiding Dysfunction II | 17BOS |
Abstract: PD64-05 Sources of Funding: none Introduction To assess the outcomes of switching to a different brand of botulinum toxin A (BTA), from Onabotulinum toxin A (OTA) (Botox) to abobotulinum toxin A (ATA) (Dysport) in case of failure of intradetrusor injections (IDI) of OTA in the treatment of neurogenic detrusor overactivity (NDO). Methods The charts of all patients who underwent a switch to IDI of ATA after failure of an IDI of OTA at six departments of neurourology were retrospectively reviewed. The main outcomes of interest were the bladder diary data and four urodynamic parameters: maximum cystometric capacity (MCC), maximum detrusor pressure (PDET max) and volume at first uninhibited detrusor contraction (UDC). Data were compared before and after treatment with OTA and ATA, using Stuart, Wilcoxon and paired-t tests for paired samples and univariate logistic regression was performed to seek for predictors of switch success. Results Out of 57 patients included, 38.6% were primary non-responders to Botox, and in secondary non-responder a median number of 5 OTA IDI were performed before failure (range 1-17). Persistent urinary incontinence was observed in 84.2% patients, and 75.4% had persistent detrusor overactivity. Six weeks after the first injection of Dysport, no adverse events were reported. A significant decrease in number of urinary incontinence episodes per day was observed in 52.63% of patients (p <0.001) and all patients experienced a reduction in PDET Max (-8.1 cmH20 on average; p=0.003). MCC significantly increased by a mean of 41.2 ml (p=0.02). The proportion of patients with no UDC increased significantly at after ATA injections (from 15.79% to 43.9%; p=0.0002). Hence, 32 patients draw clinical and/or urodynamic benefits from the botulinum toxin switch from OTA to ATA (56.14%). After a median follow up of 21 months, 87% of responders to BTA switch were still treated successfully with BTA. In univariate analysis, three variables were associated with BTA switch success: low MCC before first ATA IDI (OR=20.4;p=0.01) and dose of ATA (OR= 10.9; p=0.048) were predictive of increased success rates; poor compliance was predictive of lower success rate (OR=0.2; p=0.04). Conclusions Most patients refractory to OTA (Botox) (56.14%) draw benefits from the switch to ATA (Dysport). Low MCC and dose of ATA were predictive of success of BTA switch while poor compliance was predictive of failure. Funding none
Authors
benoit peyronnet
florie bottet romain boissier andrea manunta benedicte reiss jean-gabriel previnaire jacques kerdraon alain ruffion loic lenormand brigitte perrouin-verbe sarah gaillet xavier gamé gilles karsenty |
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PD64-06 |
Multi-institutional experience with Onabotulinumtoxin-A in patients with prior augmentation cystoplasty |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Neurogenic Voiding Dysfunction II | 17BOS |
Abstract: PD64-06 Sources of Funding: NIH grant K12 DK0083014 Introduction Augmentation cystoplasty has been used in the treatment of refractory neurogenic and overactive bladder. In some patients, symptoms may persist or recur after the surgery, and there is little guidance on management in this setting. In this study, we reviewed the use of Onabotulinum Toxin A (BTX-A) in patients with prior bladder augmentation. Methods Retrospective chart review was performed at two institutions, identifying patients with history of augmentation cystoplasty who underwent intravesical BTX-A injection. Data collected included demographics, preoperative and postoperative findings. Results 22 (17 female, 5 male) patients with mean age 36.8 years (range 18-65) and history of prior augmentation cystoplasty were identified. Etiology of bladder dysfunction included: congenital neurogenic bladder (59%), spinal cord injury (14%), multiple sclerosis (4%), and idiopathic (23%). Indications for BTX-A were urge urinary incontinence and refractory storage symptoms in 15 and 7 patients, respectively. 18/22 patients completed urodynamic studies (UDS) prior to BTX-A injections. Mean maximum cystometric capacity was 298 cc. Decreased compliance and detrusor overactivity were noted in 6 (33%) and 9 (50%) patients, respectively. Patients underwent injection of 200-300 units of BTX-A. Combined intradetrusor and intra-augment injections were done in 11 patients, the remaining 18 patients received only intradetrusor injections. 18 patients (82%) reported improvement in subjective parameters (frequency, urgency, incontinence). There was no significant difference in subjective outcome associated with site of injection (p=0.5, chi-square). No patients had adverse events associated with systemic absorption of BTX-A. One patient had persistent detrusor overactivity, poor compliance, and hourglass configuration on post-BTX-A UDS, and required repeat augmentation cystoplasty. 17 (77%) patients underwent repeat injections; on average, patients underwent 3.3 injections with interval of 8.8 months between injections. Conclusions BTX-A injection was shown to subjectively improve refractory storage symptoms and continence after augmentation cystoplasty in the majority of patients. In this multi-institutional cohort, patients had good subjective response regardless of site of injection (combined versus intradetrusor only), and most patients went on to undergo repeat injections. Prospective studies are needed to better evaluate the efficacy and ideal sites of BTX-A injection in the setting of augmentation cystoplasty. Funding NIH grant K12 DK0083014
Authors
Laura Martinez
Ryan Tubre Robyn Roberts Timothy Boone Julie Stewart Tomas Griebling Rose Khavari Priya Padmanabhan |
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PD64-07 |
Intradetrusor injections of botulinum toxin A in adult patients with spinal dysraphism: results of a multicenter study |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Neurogenic Voiding Dysfunction II | 17BOS |
Abstract: PD64-07 Sources of Funding: none Introduction The DIGNITY randomized controlled trials have lead botulinum toxin A to be licensed for neurogenic detrusor overactivity (NDO) but included only spinal cord injured and multiple sclerosis patients. To date, no data has been published regarding the efficacy of intradetrusor botulinum toxin injections (IDBTI) in patients with spinal dysraphism while these patients are injected in numerous centers in daily practice. The aim of the present study was to report the outcomes of IDBTI in spina bifida patients. Methods All patients with spinal dysraphism who had undergone at least one IDBTI from 2002 ro 2016 in 14 centers were included retrospectively. Patients bleow the age of 16 years old were excluded to focus on an adult population. The primary endpoint was the success of injections, defined as as the combination of urgency, urinary incontinence and detrusor overactivity resolution. Datas collected included patients’ characteristics, adverse events, and urodynamics parameters before and 6 weeks after IDBTI. The impact of poor compliance (defined as bladder compliance < 20 ml/cm H2O) and type of spinal dysraphism on outcomes was assessed through univariate analyses. _x000D_ Results After exclusion of 53 children, 125 patients who underwent a total of 561 IDBTI courses were included (1 to 17 courses per patient). The urodynamic patterns were detrusor overactivity in 48.6% of patients, isolated poor compliance in 33.6% of patients and combination of poor compliance and detrusor overactivity in 17.8%. The toxin used was in the vast majority onabotulinum toxin A at a dosage of 200 U in 43 patients (34.7%) and 300 U in 62 patients (49.2%). Twenty patients (16.1%) received initially abobotulinum toxin A 750 injections. Global success rate of the first injection was 68.8% with resolution of urinary incontinence in 73.5% of patients. Ninety-six patients (76.8%) underwent a second injection and the mean interval between the first and second injections was 7.5 months. Success rate was significantly lower in case of poor compliance (49% vs. 87%; p<0.0001). In contrast, success rates did not differ significantly between open and closed spinal dysraphism (66.7% vs. 72.3%; p=0.51). The two other predictors of success were female vs. male gender (83.3% vs. 51.7%; p=0.0002) and age (OR=0.1; p=0.005). Out of 561 injections, 20 adverse events were noted (3.6%) including three fatigue/muscular weakness. Conclusions IDBTI seems effective in spina bifida patients showing detrusor overactivity regardless of the type of spinal dysraphism (open or closed). In contrast, the effectiveness is much lower in spina bifida patients with poor compliance bladder. The safety of IDBTI in patients with spinal dysraphism is statisfactory Funding none
Authors
benoit peyronnet
alexia even alix verrando gregoire capon marianne de sèze juliette hascoet claire lenormand charlotte maurin xavier biardeau laure monleon jacques kerdraon evelyne castel-lacanal francois marcelli maximilien baron marie-aimée perrouin-verbe clément allenet pascal mouracade boutin jean-michel christian saussine philippe grise loic lenormand emmanuel chartier-kastler jean-nicolas cornu gilles karsenty brigitte schurch pierre denys gerard amarenco andrea manunta xavier gamé |
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PD64-08 |
Can we avoid bladder augmentation in case of failure of a first intradetrusor botulinum toxin injections in patients with spinal dysraphism? |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Neurogenic Voiding Dysfunction II | 17BOS |
Abstract: PD64-08 Sources of Funding: none Introduction For long, bladder augmentation has been considered as the gold standard treatment in neurogenic detrusor overactivity (NDO) patients who failed intradetrusor injections of botulinum toxin A (IDBTI). Several reinjections strategies have been described over the past few years (e.g. botulinum toxin switch, reinjection to a higher dosage,….) to avoid this last resort. Moreover, several studies have suggested that the optimal effectiveness of IDBTI could be obtained only after several injections. Patients with spina bifida are a high risk population regarding upper tract damage. There is currently no data regarding the management of failure of a first IDBTI in spina bifida patients. The aim of this study was to report the outcomes of botulinum toxin reinjections and to compare the outcomes of various reinjections strategies in patients with spinal dysraphism who failed a first IDBTI. Methods All patients with spinal dysraphism who had undergone at least one IDBTI from 2002 ro 2016 in 14 centers were included retrospectively. Patients below the age of 16 years old were excluded to focus on an adult population. The primary endpoint was the success of injections, defined as as the combination of urgency, urinary incontinence and detrusor overactivity resolution. The choice to perform either a repeat injection of the same toxin to the same dosage or a repeat injection of the same toxin to a higher dosage or a botulinum toxin switch or a bladder augmentation was left to the physician’s discretion. The outcomes of these various strategies were compared using the Fisher exact test. Results Out of a 125 patients cohort, 40 patients with spinal dysraphism who failed a first IDBTI were included (32%). Nine patients underwent augmentation cystoplasty directly after the first failed injection. At the end of the study period, two patients were lost to follow-up and two had just undergone their second IDBTI (outcomes not yet known). Out of 27 patients left, repeat injections remained uneffective in 17 patients (63%) despite one to four courses of reinjections. Two other patients had transient effectiveness before the injections failed again. Hence, 19 patients finally underwent bladder augmentation (70.4%). Thirteen patients had effective injections at least once during their management (48.1%) and 11 had still effective injections at the end of the study period (40.7%) but 3 of them were only improved without complete success (clinical but not urodynamic success). Thus only seven patients had a durable and satisfactory effectiveness of IDBTI (25.9%). Six botulinum toxin switch from onabotulinum toxin to abobotulinum toxin were performed with only two success (33%). In contrast, five out of six patients (83%) who underwent a repeat injection of onabotulinum toxin 300 U after failure of onabotulinum toxin 200 U had a complete success (difference: p=0.62). Finally, six out of 16 patients who underwent a repeat injection of onabotulinum toxin 200 U to the same dosage had a complete success (37.5%; difference with reinjection to a higher dosage: p=0.43). None of the patients in whom the first three injections failed finally responded to the toxin. Conclusions Reinjection strategies seem poorly effective in spina bifida patients who failed a first IDBTI with success in only 25.9% of them. _x000D_ Despite a lack of statistical power, reinjection of onabotulinum toxin to a higher dosage (300 U after failure of 200 U) seem to be the more effective option in these patients._x000D_ Funding none
Authors
benoit peyronnet
gerard amarenco alexia even marianne de sèze gregoire capon maximilien baron alix verrando juliette hascoet claire lenormand charlotte maurin xavier biardeau laure monleon jacques kerdraon evelyne castel-lacanal francois marcelli marie-aimée perrouin-verbe clément allenet pascal mouracade boutin jean-michel christian saussine philippe grise loic lenormand emmanuel chartier-kastler jean-nicolas cornu gilles karsenty brigitte schurch pierre denys andrea manunta xavier gamé |
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PD64-09 |
Long-term outcome of adenosine A2A receptor antagonist on lower urinary tract symptoms in male Parkinson's disease patients |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Neurogenic Voiding Dysfunction II | 17BOS |
Abstract: PD64-09 Sources of Funding: none Introduction In addition to motor symptoms, bladder dysfunction is a major clinical issue in patients with Parkinson's disease (PD). Istradefylline, a novel non-dopaminergic selective adenosine A2A receptor antagonist, was approved in 2013. We previously reported that Istradefylline improved not only motor symptoms, but also lower urinary tract symptoms (LUTS) in patients with PD in a short-term period. However, the long-term effects of istradefylline for LUTS has not yet been clarified. The aim of this study was to determine the effects of 1 year istradefylline treatment on LUTS in PD patients. Methods We enrolled male 12 male PD patients. The mean of age of patients was 66 (61-80) years old, the Hoehn-Yahr stage was 2 (2-3), and disease duration was 9 (4-26) years. The effects of istradefylline (20 mg/day) on LUTS in PD patients with motor complications after 3, 6 months and 1 year of therapy were evaluated based on the International Prostate Symptom Score (IPSS), Overactive Bladder Symptom Score (OABSS), King's Health Questionnaire (KHQ) score, 3-day voiding diary, and urinary flow rate and post-voiding residual urine volume before and after its administration. Results Motor symptoms significantly improved after 1 year evaluating movement disorder rating scale (P<0.01). Significant improvements were also observed in the answers provided on urinary questionnaires after 1 year treatment (IPSS: 14.4 ± 7.6 vs. 8.5 ± 6.8, OABSS: 6.9 ± 2.8 vs. 5.5 ± 3.7; P<0.05) [breakdown: Table]. Data from the KHQ revealed that the domain of impact on life had significantly improved after 1 year treatment [Table]. And in 3-day voiding diary, nighttime urinary frequency (3.0 ± 1.6 vs. 2.4 ± 0.7; P<0.05). However, no significant changes were observed in the urinary flow rate (Qmax) or post-voiding residual urine volume (RU) between before and after 1 year administration of istradefylline (Qmax (ml/s): 10.7 ± 3.9 vs. 8.0 ± 2.8, RU (ml): 51.0 ± 60.0 vs. 40.5 ± 30.8). No adverse urological effects were observed in any patient. Conclusions Istradefylline effectively improved not only motor symptoms, but also LUTS in patients with PD in a long-term period. And the results of the present study confirmed that adenosine A2A receptor antagonists are useful as a new pharmacological treatment for OAB in patients with PD. Funding none
Authors
Takeya Kitta
Ichiro Yabe Yukiko Kanno Ouchi Mifuka Kimihiko Moriya Ikuko Takahashi Masaaki Matsushima Hidenao Sasaki Nobuo Shinohara |
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PD64-10 |
Long term outcome following bladder neck artificial urinary sphincter implantation |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Neurogenic Voiding Dysfunction II | 17BOS |
Abstract: PD64-10 Sources of Funding: none Introduction Implantation of the artificial urinary sphincter (AUS) around the bladder neck (or prostate in men) remains the goldstandard treatment for women with refractory sphincter weakness incontinence (SWI) or patients with neuropathic pathology. This study evaluates long-term outcomes of the AMS800 device in this patient population. Methods Over a 20 year period (January 1995 - December 2014), 140 bladder neck (BN) AUS were implanted in 111 patients (mean age 39.1 years) by a single surgeon. Aetiology of incontinence: Spina bifida n=53, neuropathic (other) n=15, failed female incontinence surgery n=22, pelvic fracture n=18, extrophy/epispadias n=15, following undiversion cystoplasty n=6, other n=4. 73 were primary procedures, 18 revision after previous infection/erosion and 49 replacement for malfunction. Mean follow-up was 112.8 months (range 12.4 - 243.7 months). Results 55 of 140 (39.3%) devices were explanted at a mean of 39.1 months; 26 for erosion (50.4 months), 22 for malfunction (65.1 months), 7 for infection (1.5 months). 30 of 73 (41.1%) primary, 8 of 18 (44.4%) revision and 17 of 49 (34.7%) replacement implants were explanted. 118 devices were implanted in a single stage (n=51, 43.2% explanted) while 22 were done as a staged procedure (n=4, 18.2% explanted). In 68 cases patients performed self catheterisation (ISC) with the device explanted in 25 (37.3%) compared to 30 of 72 (41.4%) with no ISC. Interestingly, with ISC there was a much lower rate of erosion then no ISC (10% vs 26%) but a much higher malfunction rate (24% vs 8%). Cystoplasty was present in 67 cases of which 26 (38.8%) were explanted compared to 73 with no cystoplasty in which 31 (42.3%) were explanted. _x000D_ _x000D_ 85 devices (66.6%) remain in situ (42 primary, 10 revision, 33 replacement). 78 (91.8%) are keeping their users continent and happy with the outcome of their surgery. 2 of these, done as a staged procedure, are continent with only the cuff in situ. The other 7 are incontinent due to failure of the surgery or de novo detrusor overactivity. _x000D_ Conclusions Apart from being more surgically challenging, implantation of a bladder neck AUS is associated with excellent functional outcomes albeit with a significantly higher explantation rate when compared to bulbar AUS. Contrary to what we have previously demonstrated with bulbar AUS, we have hereby shown no difference in explantation rate between primary and non-primary bladder neck AUS. The overall explantation rate is no difference whether a cystoplasty is present or not or whether patients performing ISC. ISC is nonetheless associated with a significantly higher rate of device malfunction. Funding none
Authors
Simon Bugeja
Stella Ivaz Stacey Frost Mariya Dragova Daniela E Andrich Anthony R Mundy |
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PD64-11 |
New novel chronic tibial neuromodulation (CTNM) treatment option for OAB significantly improves urgency (UI)/Urge Incontinence (UUI) and normalizes sleep patterns |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Neurogenic Voiding Dysfunction II | 17BOS |
Abstract: PD64-11 Sources of Funding: StimGuard supplied the stimulation devices. Introduction Percutaneous tibial nerve stimulation (PTNS) has been successfully used to treat symptoms of overactive bladder_x000D_ (OAB). PTNS currently relies on episodic stimulation of the tibial nerve once/week for 30min in an outpatient setting using an acupuncture needle and a ground pad to create electrical stimulation. We investigated CTNM in OAB patients using this new minimal invasive chronic implantable device (StimGuard LLC). Methods In 2014, two male patients (82y old with Parkinson's disease for 6y and 69y old with MS for 16 years) with neurogenic lower urinary tract dysfunction (nLUTD) received those implants. Both patients suffered from refractory UI and nocturia; detrusor overactivity and detrusor sphincter dyssynergia._x000D_ In February-April 2016, six additional patients (1 male: spina bifida; 5 female: iOAB) received the implants through a <5mm skin incision. Patients were asked to use the device while sleeping (max 8h). Patients were followed with bladder diary, maximum flow rate (ml/sec), post void residual (PVR) and questionnaires on a regular basis (1 month prior to surgery and 2, 4 weeks, 3 and 6 months postop). Results Implantation of the electrode was well-tolerated by all patients and performed as an outpatient procedure without perioperative complication. The initial two patients reported significant improvement of nLUTD within 48 hours. Both neurogenic patients were completely dry two months post-op; UI and nocturia disappeared (bladder diary). Both patients stopped CTNM due to the progression of their comorbidity, though a causal correlation could not be drawn. After 1.5 years the electrode of one patient migrated through the implantation path._x000D_ In the second group, the male was excluded due to lack of improvement and required an alternative treatment. Five female iOAB patients documented major improvements in their bladder diaries. UUI episodes significantly decreased (base: 2.1/day vs. 2.5/month 6 months post-op) and nocturia vanished. Mean voided volume significantly increased by 70ml, without or increased PVR. In the five iOAB patients, all implants are currently in place and their efficacy confirmed._x000D_ Conclusions CTNM offers a promising treatment option using a novel chronic implantable device using an external charger. The new minimal_x000D_ invasive technology might revolutionize neuromodulation and offers those patients suffering from refractory OAB an opportunity to perform CTNM over several hours, even while sleeping with low or no stimulation related morbidities._x000D_ Funding StimGuard supplied the stimulation devices.
Authors
Karl-Dietrich Sievert
Lilliana Milinovic Esra Foditch Stefan DeWachter Anne Roggenkamp Thomas Kessler |
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PD64-12 |
Urodynamic findings of patients with brain tumor classified by location of affected area |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Neurogenic Voiding Dysfunction II | 17BOS |
Abstract: PD64-12 Sources of Funding: none Introduction With advancement of treatment modalities, the survival of patients with brain tumor has been increased, and the management of lower urinary tract symptom of brain tumor patients emerged as a new challenge. Although several brain imaging studies have been introduced with healthy brain parenchyma, identifying fundamental brain region involved, the correlation of each areas is not proved distinctively. Especially, the effect of intracranial space occupying lesions on bladder and urethra is not clearly demonstrated until now. We have evaluated urological symptoms and urodynamic findings of patients with brain tumor, and made comparison of the urodynamic patterns according the affected brain areas. Methods Brain tumor patients with urological symptom who received urodynamic test at our tertiary referral center from May 2007 to March 2016 were evaluated. To minimize confounding variables, patients with accompanying degenerative neurological disorders, spinal cord injury, diabetes mellitus, prostatic hyperplasia, history of pelvic organ surgery were excluded. And patients with multiple brain lesions were also excluded. The localization of brain tumor was based on the magnetic resonance imaging or computed tomography imaging taken same time of urodynamic study. Results Finally, twenty six patients (male 8 female 18) were assessed. The median age at urodynamic study was 46.5 (21.3~76.5) years old. Twenty four patients received urodynamic study at median period of 3.6 (0.9~74.3) months after brain surgery, and two patients had not received operation at the time of urodynamic study. Involuntary detrusor contraction was observed in 13 (50%) patients, acontractile detrusor was observed in 7 (36.9%) patients, and detrusor sphincter dyssynergia was observed only in one patient with frontal lobe tumor. The urological symptom and urodynamic findings showed different pattern according to the affected territory (Figure 1.) Conclusions We could observe diverse urodynamic patterns according the affected areas. Our results suggest complexity of micturition circuit in central nervous system. Further study with large cohort in correlation with functional brain imaging might solve the mysterious role of brain on bladder, suggesting management guide according to the affected brain area. Funding none
Authors
Hee Seo Son
Mark Benson Gamo Jongsoo Lee Jong Won Kim Sang-Hyeon Cheon Ju Tae Seo Jang Hwan Kim |
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PD65-01 |
Germline mutations in the Kallikrein 6 region and predisposition for aggressive prostate cancer |
Prostate Cancer: Markers II | 17BOS |
Abstract: PD65-01 Sources of Funding: Canadian Institutes of Health Research (CIHR; project numbers: MOP-94845 and MOP-97733)_x000D_ Ontario Institute for Cancer Research (OICR; project number: 08Nov-163)_x000D_ Prostate Cancer Canada Movember Foundation (RS2014-01) Introduction Prostate Cancer (PCa) is a highly heterogeneous disease, ranging from indolent tumors to rapidly progressing life-threatening metastatic disease. There is a need for markers that can specifically identify individuals at increased risk of harboring aggressive forms of PCa. Methods We surveyed the Kallikrein (KLK) region (KLK1-15) for single nucleotide polymorphisms (SNPs) associated with aggressive PCa (defined as Gleason Score ≥8) in 1858 PCa patients. Discovery cohorts (Swiss arm of the European Randomized Study of Screening for PCa, n=379, and Toronto, Canada, Princess Margaret Cancer Centre, n=540) and a validation cohort (Prostate, Lung, Colorectal, and Ovarian (PLCO) screening trial, n=939) were analyzed. Fine-mapping within the KLK region was carried out by genotyping and imputation in the discovery cohort whereas PLCO data was provided through DbGaP. The influence of SNPs of interest on biochemical free survival was evaluated in an intermediate-risk disease patient cohort from the International Cancer Genome Consortium (ICGC; n=130) treated for localized PCa and analyzed with next generation sequencing. Single-, multi-SNP association studies, and haplotype analyses were performed. All statistical tests were two sided. Results Several SNPs in very strong linkage disequilibrium in the KLK6 region and located within the same haplotype (rs113640578, rs79324425, rs11666929, rs28384475, rs3810287), identified individuals at increased risk of aggressive PCa in both discovery (OR=3.51-3.64; 95%CI=2.01-6.36; p=1.0x10-5-8.4x10-6) and validation (OR=1.89-1.96; 95% CI 0.99-3.71; p=0.04-0.05) cohorts. The validation cohort revealed another important haplotype with 2 SNPs at the same locus (rs28665094, p=0.006 and rs268890, p=0.005) associated with aggressive PCa. The overall test of haplotype association was highly statistically significant in the discovery cohort (p=3.5x10-4), in the PLCO cohort (p=0.006) and in the three data sets combined (p=2.3x10-5). These germline SNPs predicted relapse independently of standard clinical and molecular factors in the ICGC cohort (HR=3.15, 95%CI=1.57-6.34 p=0.001). Conclusions Our fine-mapping study has identified novel loci in the KLK6 region strongly associated with aggressive PCa. Additional sequencing studies might help identify rare variants with major effect in this KLK6 region. Funding Canadian Institutes of Health Research (CIHR; project numbers: MOP-94845 and MOP-97733)_x000D_ Ontario Institute for Cancer Research (OICR; project number: 08Nov-163)_x000D_ Prostate Cancer Canada Movember Foundation (RS2014-01)
Authors
Laurent Briollais
Hilmi Ozcelik Jingxiong Xu Maciej Kwiatkowski Emilie Lalonde Dorota H Sendorek Neil E Fleshner Franz Recker Cynthia Kuk Ekaterina Olkhov-Mitsel Sevtap Savas Sally Hanna Tristan Juvet Geoffrey A Hunter Matt Friedlander Hong Li Karen Chadwick Ioannis Prassas Antoninus Soosaipillai Marco Randazzo John Trachtenberg Ants Toi Yu-Jia Shiah Michael Fraser Theodorus van der Kwast Robert G Bristow Bharati Bapat Eleftherios P. Diamandis Paul C Boutros Alexandre R Zlotta |
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PD65-02 |
Oncosomes as a Novel Liquid Biopsy Biomarker for Quantifying Metastatic Cancer Dynamics in Real-Time |
Prostate Cancer: Markers II | 17BOS |
Abstract: PD65-02 Sources of Funding: Prostate Cancer Canada, OICR, AMOSO, CUOG Introduction Tumor cells acquire qualities that enable them to succeed at key steps of the metastatic cascade, but very little is known about how individual cells accomplish these feats in a challenging hemodynamically active environment. Using intravital imaging, we observe that oncosome release is a key event during cancer cell extravasation in various prostate cancer cell lines. Oncosomes are large cell fragments released by cancer cells at various stages of cancer progression. Having observed their release in vivo during cancer cell extravasation, we sought to determine at what other stages of metastasis oncosomes were released. _x000D_ _x000D_ Methods Using PC-3, LnCAP, Du145 cells, intravenous injection into the chorioallantoic membrane (CAM) of chick embryos, a gold standard of visualizing cancer cell extravasation, was employed and confocal resonance scanning microscopy was used to visualize the release of oncosomes and other smaller extracellular vesicles in vivo. Blood at various timepoints was also collected to enumerate the number of CD9+ve and STEAP1+ve oncosomes released by extravasating cells. Primary tumors were also formed and blood collected in the same manner to ascertain the extent of oncosome release in vivo. Results At the key step of extravasation, arrested cancer cells release oncosomes into the microcirculation which are observed to exhibit a diameter >900 nm and expressing surface antigens found on the surrogate prostate cancer cell such as CD9 and STEAP1. We explored the abundance and biophysical characteristics (size diameter range) of extracellular vesicles (EVs) released during the metastatic cascade and found that oncosomes are not consistently released by primary tumors or metastases and that these large cancer cell fragments are specifically released by actively extravasating cancer cells. Conclusions Circulating oncosome levels in patient plasma are a novel biomarker or “liquid biopsy� for actively metastasizing cells in the body, representing a powerful tool for monitoring metastatic cancer dynamics. We show that oncosome biogenesis is a specific byproduct of extravasating cells and not by primary tumors or metastatic deposits even in the presence of pro-apoptotic or pro-necroptotic stimuli. Our findings in plasma samples from patients on first-line treatment for metastatic prostate cancer support the concept of oncosomes as a promising biomarker for monitoring cancer metastasis dynamics in real-time, a novel &[Prime]liquid biopsy&[Prime] for metastatic prostate cancer treatment response. Funding Prostate Cancer Canada, OICR, AMOSO, CUOG
Authors
Florence Deng
Yohan Kim Andrew Poon Tom Liao Hon Leong |
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PD65-03 |
Decipher Gene Expression Levels Do Not Correlate With Pathologic Features of Aggressive Prostate Cancer in African Americans |
Prostate Cancer: Markers II | 17BOS |
Abstract: PD65-03 Sources of Funding: None Introduction Genomic testing is used with increasing frequency as part of a personalized approach to managing prostate cancer. Decipher is one such test that analyzes the expression of 22 RNA biomarkers from archival prostate tissue and predicts risk of metastatic progression and prostate cancer specific mortality. The company also provides microarray analysis to characterize additional markers from the Decipher Genomic Resource Information Database (GRID) that have been implicated in prostate cancer. Traditionally, adverse pathologic features at prostatectomy have been used to predict risk of biochemical recurrence and guide adjuvant therapy after prostatectomy, but it is not clear to what extent these features correlate with genetic markers of disease aggressiveness. In this study, we sought to determine patterns of biomarker expression in African Americans, who are at higher risk of developing aggressive prostate cancer, and whether these biomarkers correlate with adverse pathologic features at prostatectomy. Methods We ran the Decipher test retrospectively on radical prostatectomy specimens obtained between December 2008 and April 2016 from a cohort of 72 African American men at a single institution. Data obtained included Decipher GRID expression levels of additional RNA biomarkers as well as the pathologic features at prostatectomy of each specimen. Fisher's Exact Test analysis was used to determine correlations between biomarkers and the following pathologic features: perineural invasion (PNI), extraprostatic extension (EPE), seminal vesical invasion (SVI), lymphovascular invasion (LVI), and margin positivity. Results The most common biomarkers expressed were SPINK1 (37.5%, n=27), ERG (18.1%, n=13), NKX3 (13.95, n=10), and PCA3 (11.1%, n=8). The triple negative genotype (ERG-/ETS-/_x000D_ SPINK-) was 38.9% (n=28). There were no statistically significant relationships between any biomarker expression levels and pathologic features associated with aggressive prostate cancer. PCA3 did show a nonsignificant association with LVI (p = 0.09). _x000D_ Conclusions Our study employed one of the largest African American cohorts to date and failed to show a relationship between adverse pathologic features and the RNA expression patterns of markers implicated in prostate cancer. Further studies are necessary to determine the impact of these abnormal expression patterns on clinical outcomes and whether they are better predictors of disease recurrence than traditional clinicopathologic variables. Funding None
Authors
Jordan Alger
Rohit Patil Anna Chichura Filipe La Fuente Carvalho Jonathan Hwang Lambros Stamatakis |
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PD65-04 |
Nucleolin staining may aid in the identification of circulating prostate cancer cells |
Prostate Cancer: Markers II | 17BOS |
Abstract: PD65-04 Sources of Funding: This work was supported by the Urology Care Foundation's Resident Research Award (H.J.C.), NCI grant numbers. U54CA143803, CA163124, CA093900 and CA143055 (K.J.P.), and by the Prostate Cancer Foundation (K.J.P.). Introduction Circulating tumor cells (CTCs) have great potential as circulating biomarkers for solid malignancies. Currently available assays for CTC detection rely on epithelial markers with somewhat limited sensitivity and specificity. Here we report that the staining pattern of nucleolin, a common nucleolar protein in proliferative cells, separates CTCs from white blood cells (WBCs) in men with metastatic prostate cancer. Methods Whole peripheral blood from three men with metastatic prostate cancer was processed with the AccuCyte CTC system (RareCyte, Inc., Seattle, WA). Slides were immunostained with DAPI, anti-pan-cytokeratin, anti-CD45/CD66b/CD11b/CD14/CD34, and anti-nucleolin antibodies and detected using the CyteFinder system. DAPI nucleolin co-localization and staining pattern wavelet entropy was measured with novel image analysis software. Results 33,718 DAPI-positive cells were analyzed with the novel imaging software, of which 45 (0.13%) were known CTCs based on the established AccuCyte system criteria. Nucleolin staining pattern for segmentable CTCs demonstrated greater wavelet entropy than that of WBCs (median wavelet entropy: 6.86 x 107 and 3.03 x 106, respectively; p-value = 2.92 x 10-22; approximated z-statistic: 9.63). Additionally, the total nucleolin staining of CTCs was greater than that of WBCs (median total pixel intensity: 1.20 x 105 and 2.55 x 104 integrated pixel units, respectively; p-value = 2.40 x 10-21; approximated z-statistic: 9.41). Conclusions Prostate cancer CTCs displayed unique nucleolin expression and localization as compared to WBCs. This finding has the potential to serve as the basis for a sensitive and specific CTC detection method. Funding This work was supported by the Urology Care Foundation's Resident Research Award (H.J.C.), NCI grant numbers. U54CA143803, CA163124, CA093900 and CA143055 (K.J.P.), and by the Prostate Cancer Foundation (K.J.P.).
Authors
Heather Chalfin
James Verdone Emma van der Toom Stephanie Glavaris Michael Gorin Kenneth Pienta |
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PD65-05 |
Urine expression of TIMP1, serpinB1, and semenogelin 2 may differentiate men with low-risk or no evidence of prostate cancer from men with high-risk or metastatic disease |
Prostate Cancer: Markers II | 17BOS |
Abstract: PD65-05 Sources of Funding: Department of Defense Introduction While serum PSA and other available diagnostic biomarkers can provide valuable guidance for assessing the risk of prostate cancer (PCa), limitations in accuracy persist. Novel biomarkers with improved performance characteristics are needed. Using mass spectrometry-based proteomics, we have identified three urinary proteins with significantly different expression patterns across PCa stages. This study evaluates the expression of these potential biomarkers in urine. Methods Urinary protein concentrations of three proteins, TIMP1, serpinB1, and semenogelin 2, were assessed via Western blot and ELISA for 160 total urine samples. Each patient group (control, Gleason 6 PCa, Gleason ≥8 PCa, and metastatic PCa) had 40 samples. Urine protein was isolated using Amicon Ultra-15 Centrifugal Filter Units for Western blotting. ELISAs were performed using untreated raw urine samples. Immunohistochemistry (IHC) was performed on prostate tissue sections for all three proteins of interest. Results TIMP1 levels were statistically higher in control and Gleason 6 PCa urine samples than for Gleason ≥8 and metastatic disease (2.19 ± 1.7 vs. 1.23 ± 1.13 ng/mL; p = 0.002). Expression of serpinB1 was significantly higher in men with Gleason 6 PCa than those with high-grade Gleason ≥8 PCa (0.71 ± 0.49 vs. 0.23 ± 0.33 ng/mL; p = 0.003). Metastatic PCa had significantly higher semenogelin2 concentrations in urine than healthy men (155.68 ± 74.3 vs. 81.55 ± 55.6 pg/mL; p = 0.02), and expression levels seem to rise with disease progression. IHC staining of tissue sections corroborated these findings. Conclusions Our results indicate differences in urinary concentrations of TIMP1, serpinB1, and semenogelin 2 across PCa stages. These novel biomarkers allowed distinction between men without prostate cancer or low-risk disease and those with high-risk or metastatic disease. These proteins represent potentially valuable non-invasive prostate cancer biomarkers and warrant further investigation. Funding Department of Defense
Authors
Sarah Prophet
Adam Feldman Mary Fergus Bruce Zetter |
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PD65-06 |
Patient NCCN Risk Classification Based on Combined Clinical Cell Cycle Risk (CCR) Score |
Prostate Cancer: Markers II | 17BOS |
Abstract: PD65-06 Sources of Funding: none Introduction Improved prognostic tools for newly diagnosed prostate cancer are needed to more appropriately match treatment to a patient&[prime]s risk of progression. The cell cycle progression (CCP) score is a highly validated prognostic RNA expression signature which has been combined with CAPRA (CCR, combined clinical cell cycle risk score) to generate an estimate of prostate cancer mortality (PCM) within 10-years of diagnosis. Here, we evaluate how the prognostic information from CCR can reclassify patients compared to their initial assignment to an NCCN risk category based on clinicopathologic features alone. Methods The CCR score was previously validated and is calculated as a linear combination of CAPRA and CCP score (0.39 x CAPRA + 0.57 x CCP). A risk reclassification scheme was applied to patients tested by the Myriad Genetics commercial laboratory (N=16,442). First, PCM risk was assigned based on the patient&[prime]s CCR score. Next, patients whose PCM risks were outside the interquartile range (IQR) of their NCCN risk category were reclassified according to whether their PCM risks fell within the IQR of another NCCN risk category. Finally, patients whose PCM risks were below (or above) the IQR of the NCCN low (or high) category were reclassified as low (or high). Results Based on clinicopathologic features alone the commercial cohort was classified according to NCCN Guidelines as low (N=8,695), favorable intermediate (N=3,347), intermediate (N=3,086), or high risk (N=1,224). After calculating patient risk of PCM based on CCR, 25% of the NCCN low risk men were reclassified to favorable intermediate or intermediate risk; 47% of the NCCN favorable intermediate risk men were reclassified (24% lower and 23% higher); 49% of the NCCN intermediate risk men were reclassified (24% lower and 25% higher); and 25% of the NCCN high risk were reclassified to favorable intermediate or intermediate risk. There is no outcome data associated with commercial samples. Conclusions The prognostic information in the CCR score results in significant amounts of risk reclassification for all patients with localized disease when compared to stratification based only on NCCN risk categories. Funding none
Authors
E. David Crawford
Steve Stone Julia Reid Michael Brawer |
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PD65-07 |
IsoPSA™: INTERIM CLINICAL PERFORMANCE EVALUATION OF A NOVEL STRUCTURE-BASED BIOMARKER FOR PROSTATE CANCER IN A MULTICENTER PROSPECTIVE TRIAL FOR GLEASON ≥7 |
Prostate Cancer: Markers II | 17BOS |
Abstract: PD65-07 Sources of Funding: Cleveland Diagnostics, Inc. Introduction We provide interim evaluation of a multivariate model centered on IsoPSATM, a novel structure-focused protein biomarker, to assess potential discrimination of high-grade (Gleason≥7) from benign or low-grade (Gleason=6) patients. In this multicenter prospective trial we provide performance data compared with biopsy reports. Methods 226 plasma samples were obtained from multiple clinical sites, collected within 30 days prior to prostate biopsy from patients with blood PSA between 2 and 44 ng/ml. IsoPSATM was evaluated against 12 core TRUS biopsy results as the gold standard comparator. The prevalence of high-grade patients in the sample cohort was 33.2%. Multivariate logistic regression model included only the IsoPSATM test parameter, K, and age. Results The model predictions are subdivided into low risk with high NPV, medium risk, and high risk with high PPV. The overall ROC analysis for IsoPSATM showed an AUC=0.82. For the low risk cohort, with the previously determined value of the test statistic, KP<15%, we note very high NPV=96%. Conversely, patients with KP>64% are at high risk, with PPV=79%. In comparison, serum PSA ROC analysis showed AUC=0.67, NPV=85%, PPV=36%, at PSA=4.0. Current standard selection practice resulted in 67% negative biopsies. Using IsoPSATM KP for patient selection would have resulted in 96% avoided biopsies for the low risk cohort, while improving biopsy yield to 79% at the high risk cohort. Conclusions Combining only IsoPSATM with patient age allows for clinically actionable stratification of patients into low and high risk cohorts to improve patient selection for biopsy. Funding Cleveland Diagnostics, Inc.
Authors
Eric Klein
Mark Stovsky Jason Hafron Kenneth Kernan Kannan Manickam Hui Zhu Matthew Wagner |
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PD65-08 |
Distinguishing low versus high risk prostate cancer lesions using radiomic features derived from multi-parametric magnetic resonance imaging (MRI) |
Prostate Cancer: Markers II | 17BOS |
Abstract: PD65-08 Sources of Funding: Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under award numbers _x000D_ R21CA179327-01, _x000D_ R21CA195152-01, _x000D_ U24CA199374-01_x000D_ the National Institute of Diabetes and Digestive and Kidney Diseases under award number R01DK098503-02, _x000D_ the DOD Prostate Cancer Synergistic Idea Development Award (PC120857); _x000D_ the DOD Lung Cancer Idea Development New Investigator Award (LC130463),_x000D_ the DOD Prostate Cancer Idea Development Award; _x000D_ the Case Comprehensive Cancer Center Pilot Grant_x000D_ the VelaSano Grant from the Cleveland Clinic_x000D_ the Wallace H. Coulter Foundation Program in the Department of Biomedical Engineering at Case Western Reserve University_x000D_ the I-Corps@Ohio Program_x000D_ Case Urology Translational Research Training Program (CUTRTP)_x000D_ Hartwell Foundation_x000D_ Introduction Multi-parametric magnetic resonance imaging (mp-MRI) based prostate imaging reporting and data system (PIRADS) is limited in confidently and robustly distinguishing clinically significant and insignificant prostate cancer (PCa). Radiomic features employ image processing methods to characterize specific patterns in images and have been shown to better characterize PCa than mp-MRI signal intensities alone. For example, gradient features quantify the appearance of edges, Haralick features distinguish homogenous low intensity (PCa) from normal regions and Gabor features quantify appearance of PCa at multiple orientations and scales. In this study, we aim to identify which of the mp-MRI derived radiomic features can distinguish high and low risk PCa as defined by the D’Amico criteria. Methods A retrospective cohort of 452 PCa patients who underwent a 3 Tesla mp-MRI scan was considered for this study. A subset of 72 patients comprising 153 lesions was chosen chronologically based on PIRADS to obtain a statistically balanced cohort. D’Amico criteria were available for 83 lesions and was used to categorize into low (N= 26), intermediate (N = 43) and high (N = 14) risk groups. A balanced dataset of N = 28 lesions with 14 lesions from each of high and low risk categories was finally assembled for radiomic feature analysis. Results A set of 101 radiomic features were extracted on a voxel-wise basis within the lesion region of interest (ROI) from each of T2w and ADC MRI sequences. First order statistics (mean, variance, skewness and kurtosis) were computed within each ROI to obtain 808 features per ROI. Of these, 44 features showed statistically significant differences between high and low risk lesions. Specifically, variance and skewness of T2w gradient and Gabor features, skewness and kurtosis of ADC Haralick and Laws features showed p<0.05 using Wilcoxon Rank-Sum test (representative results are shown in Figure). A random forests classifier trained using these radiomic features within a 3-fold cross validation framework resulted in an AUC of 0.96. Conclusions Radiomic features derived from mp-MRI distinguish high and low risk prostate cancer lesions as defined by D’Amico criteria. An independent validation of these features is required on a separate test set. Funding Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under award numbers _x000D_ R21CA179327-01, _x000D_ R21CA195152-01, _x000D_ U24CA199374-01_x000D_ the National Institute of Diabetes and Digestive and Kidney Diseases under award number R01DK098503-02, _x000D_ the DOD Prostate Cancer Synergistic Idea Development Award (PC120857); _x000D_ the DOD Lung Cancer Idea Development New Investigator Award (LC130463),_x000D_ the DOD Prostate Cancer Idea Development Award; _x000D_ the Case Comprehensive Cancer Center Pilot Grant_x000D_ the VelaSano Grant from the Cleveland Clinic_x000D_ the Wallace H. Coulter Foundation Program in the Department of Biomedical Engineering at Case Western Reserve University_x000D_ the I-Corps@Ohio Program_x000D_ Case Urology Translational Research Training Program (CUTRTP)_x000D_ Hartwell Foundation_x000D_
Authors
Rakesh Shiradkar
Soumya Ghose Robert Villani Eran Ben-Levi Ardeshir Rastinehad Anant Madabhushi |
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PD65-09 |
Does 4K and/or Michigan Prostate Score Change Cancer Detection Rates in Multi-Parametric MRI discovered PIRADS 3 or Lower Lesions? |
Prostate Cancer: Markers II | 17BOS |
Abstract: PD65-09 Sources of Funding: none Introduction A multifaceted approach using commercially available prostate biomarkers to aid in the decision making for diagnosing and treating prostate cancer has taken place in recent years. We aim to determine if the 4K score and Michigan Prostate Score (MIPS) change cancer detection rates in PIRADS 3 or lower disease. Methods A retrospective review of 58 consecutive patients who underwent multi-parametric magnetic resonance imaging (mpMRI) of the prostate, 4k score and MIPS test between December 2015 and September 2016 was performed. Indications for mpMRI, 4k score and MIPS test included an abnormal digital rectal examination, elevated PSA, PSA velocity > 0.75 ng/ml/year, and patients on active surveillance. All 3 tests were ordered during the same clinic visit prior to knowing the results of the other test. We excluded patients with PIRADS score 4 or 5. Clinically significant cancer was defined as GS ? 7. Results A total of 17 patients (32 lesions) with PIRADS ? 3 and 4k score test underwent MRI/US guided fusion biopsy. Median PSA was 5.6 ng/ml (1st quartile: 4.49 ng/ml, 3rd quartile 10.14 ng/ml). Median age was 63.5 (1st quartile 57.5, 3rd quartile 67.25). Median 4k score was 21% (1st quartile 9%, 3rd quartile 62%). A total of 8 patients (47%) were diagnosed with prostate cancer. 7/8 patients (88%) had biopsies that were positive for clinically significant cancer (Grade group 2= 5) and 2/7 patients (29%) had high grade cancer GS?8 (Grade group 4= 1, Grade group 5= 1). 5 patients had 4k scores > 60% and all 5 patients were diagnosed with clinically significant prostate cancer on same session sextant biopsy. 2 of the 5 (40%) of patients had cancer diagnosed on both mpMRI/US guided fusion and random sextant biopsy. 3 of the 5 patients (60%) did not have clinically significant prostate cancer on mpMRI/US guided fusion biopsy but had CaP on same session sextant biopsy (Table 1), p < 0.001. There was no significant difference between the patients with high MIPS and MRI fusion biopsy cores or sextant biopsy cores, p = 0.61. Conclusions The 4K score may be a useful adjunct to mpMRI of the prostate in patients with PIRADS ? 3. In this series, patients with high 4k score were found to have high grade prostate cancer on same session random prostate biopsy that was missed on mpMRI guided fusion biopsy. Funding none
Authors
Wei Phin Tan
Patrick Whelan Jessica Phelps Andrea Strong Megan Lowe Stephanie Shors Gregory White Shahid Ekbal Charles McKiel Leslie Deane |
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PD65-10 |
Using mp-MRI guided prostate needle biopsy samples to improve prostate cancer diagnosis. |
Prostate Cancer: Markers II | 17BOS |
Abstract: PD65-10 Sources of Funding: Prostate Cancer UK_x000D_ European Urological Scholarship Programme Introduction Prostate cancer is a heterogeneous disease both in terms of clinical presentation and pathology which can lead to very different clinical outcomes. Conventional prognostic factors, including serum PSA levels, Gleason score and pathological stage are often inaccurate and histological biomarkers could be useful in distinguishing indolent from aggressive prostate cancers. Tissue microarrays (TMAs) are useful for validating protein biomarker expression in large cohorts of patient samples using immunohistochemistry (IHC) but are often created from radical prostatectomy specimens which do not accurately represent diagnostic biopsies. The limited tumour availability in biopsy samples has led us to develop an improved method for constructing TMAs to study multiple biomarkers simultaneously on biopsy tissues. Objectives: Validate a new method of constructing TMA blocks from prostate needle biopsies and study the link between well known biomarkers (PSA, PSMA, p63,MSMB and AMACR) and mp-MRI data_x000D_ Methods Patients attending UCLH with suspected prostate cancer were recruited to the PICTURE study and underwent a diagnostic mp-MRI scan and subsequent image-guided biopsy. This was analysed by a pathologist to confirm tumour Grade. Clinical and MRI data were routinely collected. We extracted the regions of tumour within biopsy samples and re-embedded them so that they could easily be repositioned into a recipient TMA block. Blocks were sectioned and stained using automated IHC for established prostate cancer biomarkers including p63, AMACR, PSMA, MSMB and PSA. Results We have successfully produced TMA blocks containing representative regions of benign and tumour samples for 200 patients. 99.4% of the cores included were recovered in the TMAs slides. Biomarker expression correlates with Grade of cancer for PSA (p=0.01), MSMB (p=0.016) p63 (p<0.0001), AMACR (p<0.0001) and PSMA (p<0.0001). Expression also correlates with Likert score for PSMA (p=0.009), p63 (p=0.023) and AMACR (p<0.0001). Conclusions This new method of constructing TMA blocks is effective at utilising interesting regions of biopsy tissue. It allows multiple biomarkers to be assessed quickly from large cohort studies that accurately represent the tissue routinely used for diagnosis. Funding Prostate Cancer UK_x000D_ European Urological Scholarship Programme
Authors
Jonathan OLIVIER
Jonathan Kay Vasili Stravinides Freeman Alex Hashim Ahmed Caroline Moore Emberton Mark Whitaker Hayley |
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PD65-11 |
Does PI-RADS v2 Scores Predict Adverse Surgical Pathology at Radical Prostatectomy? |
Prostate Cancer: Markers II | 17BOS |
Abstract: PD65-11 Sources of Funding: none Introduction In recent years, multi-parametric MRI (mpMRI) has gained increased acceptance and utilization as a diagnostic and staging tool for early - stage prostate cancer. Reporting systems, in particular the Prostate Imaging - Reporting and Data System (PI-RADS), now in its second version, has been advanced as means to standardize the grading and reporting of MRI findings. However, it remains to be determined whether PI-RADS scores independently predict the risk of adverse pathology, i.e. high-grade and/or high-stage disease. _x000D_ Objective: To evaluate the association of surgical pathological findings assessed on whole-mount pathology analysis and pre-operative mpMRI suspicion assessed using PI-RADS v2 scores._x000D_ Methods We retrospectively analyzed 121 patients who had radical prostatectomy within 12 months of their staging endorectal 3T mpMRI. We examined the association of the PI-RADS v2 scores with adverse surgical pathology, defined as advanced pathologic stage (≥ pT3a) or high-grade disease (primary Gleason pattern ≥ 4) or both, using frequency tables (diagnostic accuracy and chi-square) and logistic regression models. Results Of 121 patients, 73 (60%) had adverse surgical pathology; 9 men (7%) had high-grade, 64 (29%) had ≥ pT3 disease, and 29 (24%) had both high-grade and high-stage disease. 106 (88%) had PI-RADS mpMRI score 4 or 5 findings, of whom, 65% had adverse pathology compared to 15 (12%) patients with PI-RADS ≤3, of whom 27% had adverse pathology. Conversely, 95% (69/73) of patients with adverse pathology had positive MR studies (PI-RADS score 4 or 5). Accordingly, mpMRI PI-RADS 4 or 5 demonstrated 95% sensitivity (95% CI 87-98), 23% specificity (95% CI 12-37), 65% PPV (95% CI 55-74), 73% NPV (95% CI 45-92), and 66% accuracy (95% CI 57-75) for the detection of adverse surgical pathology. In the multivariable logistic regression analysis, adjusted for PSA density and age, PI-RADS score 4 or 5 (odds ratio (OR) 4.1, 95% CI 1.2-14.2, p=0.027) and clinical CAPRA score (OR 1.4, 95% CI 1.0-1.9, p=0.026) were significantly and independently associated with higher risk of adverse pathology. This study is limited by its retrospective nature. _x000D_ Conclusions PI-RADS v2 score 4 or 5 on mpMRI is highly sensitive for the detection and prediction of adverse pathology. PI-RADS v2 may help improve the detection and staging of prostate cancer and allow for tailored intervention. _x000D_ Funding none
Authors
Hao Nguyen
Antonio Westphalen Ameli Niloufar Michael Leapman Janet Cowan Jeff Simko Katsuto Shinohara Peter Carroll |
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PD65-12 |
THE ANDROGEN RECEPTOR BECOMES A NOVEL PREDICTIVE BIOMARKER OF PROSTATE CANCER PROGRESSION WHEN POST TRANSLATIONALLY ACTIVATED BY THE FER KINASE ON TYROSINE 223 |
Prostate Cancer: Markers II | 17BOS |
Abstract: PD65-12 Sources of Funding: Prostate Cancer Canada and McGill Urology Research Funds Introduction Prostate cancer (PCa) is a leading cause of cancer deaths in USA. There is no cure for advanced disease; patients failing surgery or radiations invariably fail androgen-deprivation therapy (ADT) and further progress once castrate-resistant (CRPC). Studies point to anomalies in the androgen/androgen receptor (AR) axis in advanced PCa. We reported on the Fer tyrosine kinase directly activating AR on Y223 in PCa cells and becoming its partner in the tumor cell nucleus of CRPC patients (Rocha et al 2013). We aimed to assess the pY223AR fate in PCa._x000D_ Methods Sections of human prostate tissues and metastases were stained using pY223AR antibodies (Abs) we raised, and N- and C- terminal Abs to detect all AR forms vs wild-type, respectively. Results were expressed in percentages (%) and H scores. The cohort included 450 cases ranging from healthy men to benign hyperplasia, prostatectomies, neo-adjuvant hormone therapy, advanced on ADT, primary/lymph nodes, bone metastases and seminal vesicles. _x000D_ Results AR and pY223AR-negative tumor cells constituted up to 15% in ADT/CRPC cases. In AR positive epithelial cells of normal and benign cases, the AR staining was mainly nuclear but negative for pY223AR. In primary tumors, the AR intensity and H scores increased with Gleason (p<0.01), being most elevated in ADT/CRPC. A shift in intensity from 1+ to +3 and +2 was observed with progression when all forms of AR were detected, whereas wild-type nuclear AR remained at 1+. Similar observations were made for all forms and wild-type AR in seminal vesicles, lymph nodes and bone metastases. Nuclear AR levels (all forms and wild-type) did not correlate with patient outcome. The nuclear intensity and H score of pY223AR also increased with Gleason of primary tumors (p<0.01), being most elevated in ADT/CRPC. Again, the pY223AR shifted from 1+ to +3 and +2 in the cell nucleus of primary tumors and metastases. Of interest, nuclear pY223AR correlated with biochemical recurrence (BCR) (Kaplan-Meier; log rank, p<0.0001 at H score?160). In univariate and multivariate analyses, pY223AR H scores predicted BCR (p<0.0001), PCa specific death (p=0.002) and overall survival (p=0.0002), independently of Gleason, stage and PSA. Also, combining pY223AR H score with PSA, GS and stages improved prognostication (ROC curves). Conclusions These findings suggest that activation of Y223 in all forms of AR is key for progression. Also, pY223AR represents a novel biomarker predicting outcome of prostate cancer._x000D_ Funding Prostate Cancer Canada and McGill Urology Research Funds
Authors
Turki Altaylouni
Fatima Zouanat Eleonora Scarlata Tarik Benidir Lucie Hamel Fadi Brimo Louis Bégin Armen Aprikian Simone Chevalier |
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PD66-01 |
Renal cell carcinoma with perirenal fat invasion: is partial nephrectomy as good as radical surgery? |
Kidney Cancer: Localized: Surgical Therapy VI | 17BOS |
Abstract: PD66-01 Sources of Funding: None Introduction Partial nephrectomy (PN) is the standard of care in the management of cT1a tumors, while radical nephrectomy (RN) is indicated in more advanced tumors. Recent studies provided evidence that PN could be performed in patients with tumors greater that 7 cm with complication rates and oncological outcomes comparable with those undergoing RN. _x000D_ The objective of the presenting study is to compare the recurrence-free survival (RFS), overall (OS) and cancer-specific survival (CSS) of PN and RN in patients with non-metastatic pathological T3a renal cell carcinoma (RCC) with perirenal fat invasion only. Methods We retrospectively reviewed 1202 patients undergoing RN (n=653) and PN (n=549), at a oncological referral center, from January 2003 to June 2016. Of all patients, we identified 25 RN and 41 PN pT3a tumors with exclusively perirenal fat invasion. None had nodal or distant metastasis at pre-treatment clinical staging. Patients characteristics were compared with Mann-Whitney U test and Student t-test for categorical and numeric variables with normal distribution, respectively. Both groups were compared for RFS, OS and CSS with a Kaplan-Meier survival analysis. Results All patients included had pT3a stage with isolated perirenal fat invasion. Groups undergoing Radical and Partial nephrectomy were not significantly different regarding Charlson Comorbidity Index (Median 3 for RN vs 4 for PN, p=0.24) or Age (Mean 65.3 for RN vs 62.0 for PN, p=0.99). Patients undergoing RN had bigger tumors (7.9 cm vs 4.6, p<0.001) and higher Fuhrman grade (p=0.01). Median follow-up was 36 months for RN and 34 months for PN. At the end of follow-up, recurrence was seen in 3 patients undergoing RN (12%) and 2 undergoing PN (5%), p=0.36. Mortality was similar across groups (16% for RN vs 15% for PN, p=0.99) as well as Cancer-specific mortality (4% for RN vs. 5% for PN, p=0.99). At the end of follow-up, RFS was 80% (20/25) for RN and 82% (34/41) for PN. (Figure 1) Conclusions In our data, renal cell carcinoma with T3 stage due to perirenal fat invasion exclusively had similar outcomes when treated with Radical or Partial Nephrectomy. OS as well as RFS were comparable for both surgical modalities, suggesting that, although RN is currently the gold standard for this staging, PN may provide similar oncologic results. Funding None
Authors
Fabio Gallucci
Mauricio Cordeiro Joao Barbosa Paulo Afonso Carvalho Henrique Nonemacher Eder Ilario Arnaldo Fazoli Daniel Abe Valter Cassao Romulo Mattedi William Nahas |
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PD66-02 |
Are all renal oncocytic neoplasms created equally? |
Kidney Cancer: Localized: Surgical Therapy VI | 17BOS |
Abstract: PD66-02 Sources of Funding: none Introduction Chromophobe and oncocytoma represent two distinct renal tumor subtypes stemming from a similar line of differentiation. Apparent overlap in morphology can make definitive diagnosis difficult. A variety of histologic descriptions for these tumors - oncocytic neoplasm, hybrid oncocytic, and unclassified renal cell carcinoma (RCC) with oncocytic features - create both treatment and surveillance dilemmas for the practicing urologist. Are these descriptive nuances important? We hypothesized that recurrence and survival of patients whose tumors exhibit predominantly oncocytic features would be similar, regardless of pathologic variation, and would compare favorably to those tumors defined as pure chromophobe RCC. Methods Using data from three high volume institutions, we grouped tumors into four categories: pure oncocytoma, oncocytic neoplasms, renal cell carcinoma unclassified with predominantly oncocytic features, and pure chromophobe tumors. Tumor characteristics and oncologic outcomes were then collected. Results A total of 367 patients were identified. Tumor characteristics, demographic information, and oncologic outcomes are reported below (table 1). 168 radical and 199 partial nephrectomies were performed. Median follow-up time for the overall cohort was 25 months (IQR 6 - 65 months). Deaths were rare, and no patients developed recurrence, metastasis, or was felt to have died as a result of their tumor in the non chromophobe groups. In the chromophobe cohort, 4 patients (3%) experienced disease recurrence. A total of 6 patients (4%) died during follow up and 4 patients (3%) were felt to have died of disease. In chromophobe patients who developed disease recurrence, tumors were predominantly larger (mean 12.3cm) with sarcomatoid differentiation in 50%. Conclusions Variant tumors with oncocytic features behave more like oncocytoma than renal cell carcinoma. "Atypical features", when present, are permissible as long as the gross appearance remains compatible with oncocytoma. These tumors require little to no post-operative surveillance as opposed to chromophobe RCC, where follow up is warranted. Whether surgery can be obviated altogether when these tumors are diagnosed on preoperative renal mass biopsy requires further evaluation. Funding none
Authors
Chandra K. Flack
Adam C. Calaway Brady L. Miller Maria M. Picken E. Jason Abel Gopal G. Gupta Ronald S. Boris |
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PD66-03 |
Survival in patients with end stage renal disease as a result of kidney cancer |
Kidney Cancer: Localized: Surgical Therapy VI | 17BOS |
Abstract: PD66-03 Sources of Funding: none Introduction Kidney cancer treatment resulting in significant parenchymal loss may lead to end stage renal disease (ESRD) requiring hemodialysis. ESRD is associated with significant medical comorbidity and a high risk of mortality. Emerging data suggests that surgically induced chronic kidney disease (CKD) may portend a better prognosis than medical CKD, but it is unknown whether mortality in patients with surgically induced ESRD differs compared to medical ESRD. We sought to compare demographics and overall survival between patients with ESRD as a result of kidney cancer (KC) and with ESRD from other causes. Methods Retrospective review of patients with ESRD as a result of KC in the United States Renal Data System was performed for years 1999-2013. Demographic information and survival was compared to those patients with alternative causes of ESRD. Cox regression was used to identify independent predictors of survival. Results During the time period 1,586,104 patients with ESRD were evaluated, 9,116 (0.6%) of which were as a result of kidney cancer (KC). KC patients were more likely to be male (74.0% vs 55.6%, p<0.001) and older (67.9 vs 62.3 years, p<0.001), but were less likely to have diabetes (16.6% vs 42.1%, p<0.001), congestive heart failure (18.1% vs 31.7%, p<0.001), or cardiovascular disease (5.1% vs 9.3%, p<0.001). KC patients were significantly less likely to receive a kidney transplant (6.0% vs 12.8%, p<0.001). 5-year unadjusted mortality rates were 22.0% for those with KC compared to 31.8% for those with other causes of ESRD. On multivariate analysis, ESRD secondary to KC remained a predictor of mortality; as did older age, female sex, congestive heart failure, and chronic obstructive pulmonary disease. Conclusions ESRD as a result of KC is associated with less comorbidity than other causes, yet survival remains worse. This may be a result of increased mortality from malignancy in this population. Funding none
Authors
Joseph Rodriguez
Scott Johnson Zachary Smith Gary Steinberg |
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PD66-04 |
Some Minutes Count More Than Others: Variation in Warm Ischemia Time ≤ 25 Minutes has No Effect On Kidney Function in Patients Without Impaired Renal Function |
Kidney Cancer: Localized: Surgical Therapy VI | 17BOS |
Abstract: PD66-04 Sources of Funding: None Introduction Warm ischemia time (WIT) is one of the primary determinants of post partial nephrectomy (PN) renal function, with conflicting data about the importance of every minute or a duration threshold beyond which renal damage occurs. We aimed to explore whether variation within short warm ischemia time (<25 minutes) affects renal functional outcome. Methods A multi-institutional database of robotic partial nephrectomy (RPN) patients comprising five high volume surgeons at five U.S. institutions was used to identify 703 patients with two kidneys undergoing main renal artery clamping RPN. Multivariable regression analysis assessing the impact of WIT on acute kidney injury (AKI) and progression of chronic kidney disease (CKD) stage, adjusting for underlying factors such as comorbidities, tumor size, RENAL Nephrometry Score (RNS), surgeon RPN number, and baseline eGFR was performed. WIT was treated as a continuous variable and as a categorical variable using specified cut points derived from the interquartile range and median WIT, and WIT of >25 min. Results WIT continuous (OR=1.08; 95% CI = 1.04, 1.12, p<.001) and WIT > 25 vs. WIT 20 – 25 minutes (OR=5.08, 95% CI = 1.94 – 14.36, p=.001) were associated with an increased likelihood of AKI at discharge in multivariable analysis (Table I., Figure I.), but not an increased likelihood of CKD at median 6.8 or 11.5 months follow up. No other threshold below 25 minutes was significantly more likely to increase the likelihood of AKI (p>.05). Higher baseline eGFR (HR=1.01, p=.002), larger tumors (HR=1.15, p=.018), higher RNS (HR=1.18, p=.029), history of abdominal surgery (HR=1.53, p=.05), as well as AKI at discharge (HR=1.94; p=.002) were associated with an increased risk of CKD stage progression. Conclusions Variability of WIT within 25 minutes does not appear to increase the risk of AKI or progression of CKD. Extended WIT beyond 25 minutes is highly correlated with an increased likelihood of AKI, supporting previously reported literature. Techniques to reduce or eliminate warm ischemia may not be necessary when WIT is expected below 25 minutes. Funding None
Authors
Daniel Rosen
David Paulucci Ronney Abaza Daniel Eun Akshay Bhandari Ashok Hemal Ketan Badani |
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PD66-05 |
Use of Intraoperative Mannitol during Partial Nephrectomy Fails to Provide Short-term or Long-term Renal Function Benefit – Even in High Risk Populations |
Kidney Cancer: Localized: Surgical Therapy VI | 17BOS |
Abstract: PD66-05 Sources of Funding: None Introduction Mannitol has been shown in animal models to have a renoprotective effect during warm ischemia, but these potential benefits have yet to be demonstrated in clinical studies. Despite this, mannitol is still used in about 75% of partial nephrectomies (PN). Using the largest PN series to date, we sought to identify any short-term or long-term preservation in renal function through the use of intraoperative mannitol, with a particular focus on high risk groups. Methods We retrospectively reviewed 1,415 robotic and open PN patients over a period of 6 years. Doubly robust inverse probability of treatment weighting (DR-IPTW) was applied to attempt to equilibrate treatment groups with regards to clinicodemographic characteristics. Acute kidney injury (AKI) was defined as a change in preop GFR >25% within 72 hours of surgery, or stage 1 of the RIFLE criteria. GFR preservation (GFR-P) was defined as 100*GFR at 3-12 months/Preop GFR. A propensity-weighted adjusted logistic regression was employed to determine the relationship between the treatment group, renal functional outcomes, and baseline covariates. Subgroup analyses were performed on patients with baseline CKD, prolonged ischemia time (>25 vs <25 min), cold and warm ischemia, and solitary kidneys. Results 73.5% of patients received mannitol. After weighting, there were no statistical differences in baseline characteristics (p>0.05). In the cohort at large, 34.8% developed AKI and global GFR-P was 90.4% at a median 6 month follow-up. There were no differences in the outcomes of AKI (OR 1.14 [95% CI, 0.84-1.54]) and GFR-P (β = 1.34 [95% CI, -1.41-4.09]) between treatment groups. In subgroup analyses, there were no differences in the outcomes of AKI (OR 1.03 [95% CI, 0.51-2.10]) or GFR-P (β =1.28 [95% CI, -9.77-7.21]) in patients with preexisting CKD, prolonged ischemia time (AKI, OR 1.16 [95% CI, 0.64-2.11] ; GFR-P, β =1.76 [95% CI, -3.96-7.47]), cold ischemia (AKI, OR 1.02 [95% CI, 0.54-1.91] ; GFR-P, β =1.39 [95% CI, -4.62-7.40]), warm ischemia (AKI, OR 1.14 [95% CI, 0.77-1.69] ; GFR-P, β =1.16 [95% CI, -2.10-4.42]), and in solitary kidneys (AKI, OR 0.21 [95% CI, 0.24-1.20] ; GFR-P, β =13.2 [95% CI, -5.73-32.2]). Conclusions Mannitol use in PN failed to provide any short-term or long-term renoprotective benefit. This held true within subgroup analyses including patients with preexisting CKD, prolonged ischemia times, cold and warm ischemia groups and in solitary kidneys. Despite evidence from animal models, there does not appear to be a role for mannitol use clinically during PN. Funding None
Authors
Jeremy Reese
Julein Dagenais Matthew Maurice Pascal Mouracade Onder Kara Ryan Nelson Jihad Kaouk |
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PD66-06 |
Randomized, Controlled, Double Blinded, Prospective Evaluation of Renal Function Following Mannitol Administration during Minimally Invasive Robotic-Assisted Laparoscopic Partial Nephrectomy |
Kidney Cancer: Localized: Surgical Therapy VI | 17BOS |
Abstract: PD66-06 Sources of Funding: None Introduction Mannitol solution has been an agent utilized to improve kidney circulation and decrease reperfusion injury to attempt to maintain renal function. With the development of partial nephrectomy (PN) as the preferred surgical approach, the use of mannitol was adopted as a way to theoretically prevent damage during the kidney’s ischemic time. After oncologic outcomes, maintenance of renal function is a principal goal. With advancements in minimally invasive techniques, the utilization of mannitol has been called into question. Robotic-assisted laparoscopic partial nephrectomy (RALPN) has been shown to decrease warm ischemia time, which may potentially minimize the benefit of mannitol. To date, no prospective, randomized, controlled trials have investigated the use of mannitol in the robotic procedure. We hypothesize that the intra-operative mannitol use during RALPN provides no statistically significant benefit for post-operative renal function outcomes. Methods We conducted a randomized, controlled, double blinded, single surgeon, prospective study to assess renal function after RALPN. Patients were randomized into a control group with intravenous normal saline infusion prior to clamping of the vessels or to an experimental group with an infusion of mannitol. Monitoring of Creatinine (sCr) and estimated glomerular filtration rate (eGFR) were obtained prior to the surgery as well as post operatively at 24 hours, 1 week, and 30 days. A descriptive analysis of the study groups was performed using means, standard deviations, ranges and percentages. Subgroup comparisons examined differences in the percent change of eGFR and sCR post-surgery. Continuous variables were analyzed using the Student’s t-test and categorical variables using Fisher’s Exact Test with a p < 0.05 considered statistically significant. Results Patient demographics as well as tumor characteristics were similar between the two groups other than patient BMI. Preoperative sCR and eGFR showed no statistical differences between the groups and evaluation of percent change in sCR and eGFR after surgery did not indicate a significant difference between the groups after RALPN (p>0.05). Conclusions After prospective analysis of the change in post-operative renal function of randomized groups following RALPN, we determined no statistically significance. Further evaluation with increased numbers, long term follow-up, and expansion to multiple institutions may further support this conclusion. Based on this evaluation, infusion of mannitol does not provide significant improvement of maintenance of renal functions after RALPN. Funding None
Authors
Stephen Phillips
Kellen Choi Sharon Hill Deem Samuel |
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PD66-07 |
CREATION OF A PREDICTION TOOL FOR RENAL FUNCTION AFTER PARTIAL AND RADICAL NEPHRECTOMY: PERSONALIZING DECISION-MAKING FOR RENAL CANCER SURGERY |
Kidney Cancer: Localized: Surgical Therapy VI | 17BOS |
Abstract: PD66-07 Sources of Funding: none Introduction While a nephron-sparing approach for renal tumors is desired in order to maximize renal function, technical factors related to tumor complexity can make the decision challenging. We therefore created a preoperative prediction tool for renal function outcomes at various time points following partial nephrectomy (PN) and radical nephrectomy (RN) to help guide the choice of surgical approach. Methods The Mayo Clinic Nephrectomy Registry was queried for patients who underwent PN or RN for a renal tumor between 1997-2013. Exclusions were nodal or distant metastases, venous tumor thrombus on imaging, and preoperative estimated glomerular filtration rate (eGFR) <15 mL/min. Parsimonious linear regression models predicting eGFR were created for PN and RN using backward selection of candidate preoperative predictors, and eGFR predictions at 1 year are presented. Adjusted R2, a value ranging from 0-1 that represents the proportion of total variation in eGFR explained by the model, was used to quantify predictive ability. Results The analytic cohort included 1525 and 935 patients undergoing PN and RN, respectively. Mean (SD) preoperative eGFR and tumor size were 72 (20) mL/min and 3.4 (1.9) cm, respectively, for patients undergoing PN, and were 65 (18) mL/min and 7.1 (3.8) cm, respectively, for patients undergoing RN. The model for PN included age, presence of a solitary kidney, smoking status, performance status, BMI, preoperative eGFR, tumor size, and open vs lap surgical approach (R2=0.78), while the model for RN included age, diabetes, BMI, preoperative eGFR, tumor size, and surgical approach (R2=0.68). Using the models, a 68 year-old, non-smoking, non-diabetic, ECOG 0, binephric patient with a BMI of 20kg/m2, a preoperative eGFR of 100mL/min, and a 6.5cm renal mass will have a predicted eGFR of 85 mL/min following open PN and 63 mL/min following laparoscopic RN at 1 year. If the patient was instead 50 years old, diabetic, with a preoperative eGFR of 80mL/min and a 2.5cm mass, predicted eGFR would be 78 mL/min following laparoscopic PN and 56 following laparoscopic RN at 1 year. Conclusions We created a prediction tool for renal function following RN and PN. If validated, this tool may be useful during patient counseling by providing personalized predicted renal function outcomes. Funding none
Authors
Bimal Bhindi
Christine Lohse Ross Mason John Cheville Stephen Boorjian Bradley Leibovich R. Houston Thompson |
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PD66-08 |
Partial Nephrectomy is Associated with Increased Recurrence Risk Among Clinical Stage T1 Upstaged to Pathologic T3a Renal Cell Carcinoma |
Kidney Cancer: Localized: Surgical Therapy VI | 17BOS |
Abstract: PD66-08 Sources of Funding: None Introduction To compare recurrence-free survival (RFS) of partial nephrectomy (PN) versus radical nephrectomy (RN) for clinical stage T1 (cT1) renal cell carcinoma (RCC) with pathologic upstaging to T3a among all comers and stratified by pT3a histologic subgroups. Methods A retrospective analysis of 1250 patients undergoing PN or RN for cT1 RCC upstaged to pT3a was performed. Baseline characteristics were compared between treatment groups with chi-square and Student t test. RFS was estimated with the Kaplan-Meier method and evaluated as a function of treatment with log-rank test and Cox models adjusting for clinicopathologic variables. Results A total of 140 (11.2%) cT1 cases were upstaged to pT3a, 49 (3.9%) after PN and 91 (7.3%) RN. RN cases had greater mean tumor size (5.5cm vs 4.2cm, P<0.001), were more likely to be of moderate/high anatomic complexity (78% vs 45%, P<0.001) and clear cell histology (95 vs 84%, P=0.035), and less likely to demonstrate positive margins (0% vs 15%, P<0.001, Table). Upstaging in RN was more frequent due to sinus fat (53% vs 14%, P<0.001) or venous invasion (45% vs 8%, P<0.001) and less frequent due to perinephric fat invasion (35% vs 80%, P<0.001, Table 1) compared to PN. PN was associated with higher recurrence risk in pT3a RCC (HR=2.04, P=0.019, Figure). Similar results were found in multivariable analysis (HR=3.17, P=0.003). After stratification by pT3a histology, PN was associated with lower RFS in perinephric (P=0.002) and sinus fat invasion (P=0.046, Figure). Conclusions PN is associated with higher recurrence risk in cT1 RCC upstaged to pT3a. Patients at high risk for pT3a upstaging may benefit from RN. Funding None
Authors
Paras Shah
Daniel Moreira Vinay Patel Arvin George Geoffrey Gaunay Manaf Alom Michael Schwartz Manish Vira Lee Richstone Louis Kavoussi |
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PD66-09 |
Utilization of Robotic versus Open Partial Nephrectomy for Management of cT1 and cT2 Renal Masses |
Kidney Cancer: Localized: Surgical Therapy VI | 17BOS |
Abstract: PD66-09 Sources of Funding: none Introduction Partial nephrectomy is widely utilized for surgical management of small renal masses. Robotic partial nephrectomy (RPN) has demonstrated improved postoperative morbidity and comparable oncologic outcomes compared to open partial nephrectomy (OPN). However, there is limited data regarding the utilization of RPN across different socio-economic strata and racial groups in the United States. We investigated trends and disparities in utilization of RPN for management of cT1 and cT2 renal masses. Methods Patients who underwent RPN and OPN for clinical stage T1 and T2, N0, M0 renal masses from 2010 to 2013 were identified in the National Cancer Data Base (NCDB). Univariate and multivariable logistic regression analyses were performed to evaluate differences in receiving RPN across various patient groups. Results A total of 23,681 patients fulfilled inclusion criteria. Utilization of RPN for management of cT1/cT2 renal masses significantly increased from 2010 to 2013 compared to OPN (Figure.1). Black (aOR=0.91, 95%CI: 0.84-0.99) and Hispanic (aOR=0.85, 95% CI: 0.76-0.94) patients were less likely to undergo RPN in favor of OPN. RPN was less likely to be performed in rural counties (aOR= 0.81, 95% CI: 0.66-0.98) and in patients with no insurance (aOR=0.52, 95% CI: 0.45-0.61) or patients covered by Medicaid (aOR=0.81, CI: 0.73-0.89). No significant difference was seen with respect to utilization of RPN between academic and non-academic facilities. Patients with higher clinical stage and co-morbidities were also less likely to undergo RPN (aOR=0.23, 95% CI: 0.15- 0.36 and 0.79, 95% CI: 0.71-0.87 respectively). Conclusions Utilization of RPN continues to increase over time; however, there is significant disparity in utilization of RPN based on socio-economic status and race. Black or Hispanic patients and patients in rural communities and with limited insurance were more likely to be treated with OPN instead of RPN. Funding none
Authors
Mahmoud Alameddine
Tulay Koru-Sengul Feng Miao LuÃs Felipe Sávio Ian Zheng Vivek Venkatramani Nachiketh Soodana Prakash Joshua S Jue Bruno Nahar Chad Ritch Sanoj Punnen Dipen J. Parekh Mark L. Gonzalgo |
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PD66-10 |
Bulb suction drainage is not necessary after routine robotic-assisted partial nephrectomy: A large case-control analysis |
Kidney Cancer: Localized: Surgical Therapy VI | 17BOS |
Abstract: PD66-10 Sources of Funding: None Introduction Bulb suction drain placement is routinely done following robotic-assisted partial nephrectomy secondary to concern for post-operative urine leak. We explore the necessity of bulb suction drain placement and the rate of post-operative urine leaks in patients who underwent robotic-assisted partial nephrectomy at our institution. Methods We performed a retrospective chart review to analyze the occurrence of urine leaks following robotic-assisted partial nephrectomy performed by two fellowship trained surgeons between January 2012 to July 2016. Urine leak was defined as drain body fluid creatinine to serum creatinine ratio greater than 5 or any patient with symptomatic urinary ascites within 90 days post-operatively. Results Our review included 208 patients who underwent robotic-assisted partial nephrectomy. A total of 124 patients had intra-operative 10 French bulb suction drain placement and 84 patients had drain placement omitted. The mean length of stay for patients who had drain placement versus those who did not was 3.0 and 2.4 days, respectively. In patients who had bulb suction drains, the mean duration the drain was left in place and drain output was 1.7 days and 180.2 mL, respectively. On post-operative day 1, drain-fluid creatinine (ng/dL) was measured, resulting in a mean drain-fluid creatinine to serum creatinine ratio of 0.97 (range 0.73-3.12). The mean tumor size (cm) and R.E.N.A.L. nephrometry score (range score 4-12) in patients with drain placement vs. those without was 3.3, 5.9 and 2.7, 5.2, respectively. There was a statistically significant difference (p= .007) in R.E.N.A.L. score between the two groups, but was ultimately inconsequential in our population. The collecting system was entered in 61 patients (29.3% of cases) resulting in zero urine leaks within this subgroup. No patients were re-admitted 30 to 90 days post-operatively for symptomatic urinary ascites or related complications. Conclusions Routine bulb suction drain placement, even in the event of collecting system entry, can safely be omitted following robotic-assisted partial nephrectomy. _x000D_ _x000D_ Funding None
Authors
Christopher Winter
Wesley White Ryan Pickens |
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PD66-11 |
Oncological Outcomes Comparing Intravesical and Extravesical Bladder Cuff Excision Following Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma |
Kidney Cancer: Localized: Surgical Therapy VI | 17BOS |
Abstract: PD66-11 Sources of Funding: None Introduction Radical nephroureterectomy (RNU) with excision of a bladder cuff remains the standard treatment for upper tract urothelial carcinoma (UTUC). However, the approach to surgical excision of the distal ureter remains understudied with studies reporting conflicting results. Herein, we report oncologic outcomes for two approaches to resection of the distal ureter using a large single-center database. Methods We reviewed 372 patients treated with RNU for UTUC who underwent intra- or extravesical bladder cuff excision from 1995 to 2009. Intravesical excision was defined as a separate anterior cystotomy with circumferential excision of the distal ureter, while extravesical excision was a lateral cystotomy encompassing the ipsilateral ureteral orifice. Patients with metastatic disease at RNU, neoadjuvant chemotherapy, and non-urothelial primary were excluded. Multivariable Cox regression analysis was performed to evaluate characteristics associated with patients’ risk of cancer-specific mortality (CSM). Kaplan-Meier analysis was used to evaluate recurrence free survival (RFS). Results Median patient age at RNU was 73.7 years (IQR 65.4, 79.5); 67% (n=249) were male and 64% (n=238) underwent extravesical excision. Median follow-up was 47 months (IQR 16.4, 101.4), during which time 52.4% (n=195) experienced a bladder or systemic recurrence and 17.5% (n=65) died due to metastatic urothelial carcinoma. There was no statistically significant difference for 5-year RFS between the two groups (p=0.29). On multivariable analysis features independently associated with increased risk of CSM included smoking history (HR 2.31; p=0.03), high grade (HR 4.23; p<0.001), pT2 or higher (HR 2.51; p=0.01), lymph node positive disease(HR 4.29; p<0.01) and tumor size > 3 cm (HR 2.10; p=0.02). Importantly, approach to the bladder cuff excision was not associated with an increased risk of disease recurrence (HR=1.11; p=0.60) or CSM (HR 1.26; p=0.52). Conclusions Excision of the entire ureter, including the intramural component, is an important part of RNU. However, intra- or extravesical approach to the distal ureter, does not affect RFS or CSM. Therefore, our data validates the oncologic safety of both approaches to the bladder cuff for patients undergoing RNU for UTUC. Funding None
Authors
Amir Toussi
Tanner Miest Stephen Boorjian George Chow R. Houston Thompson Bradley Leibovich Matthew Tollefson |
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PD66-12 |
Outcomes on ileal mucosal cuff management during radical nephroureterectomy |
Kidney Cancer: Localized: Surgical Therapy VI | 17BOS |
Abstract: PD66-12 Sources of Funding: None Introduction Patients who undergo radical cystectomy for urothelial cancer are at risk for upper tract urothelial carcinoma (UTUC). It is well-accepted that the removal of a formal bladder cuff at the time of radical nephroureterectomy (RNU) results in improved oncologic outcomes. However, the effects of ileal mucosal cuff excision in patients undergoing RNU who have had a prior urinary diversion has not been studied. To our knowledge, we present the first report on outcomes of ileal mucosal cuff management for patients undergoing RNU for UTUC. Methods Between 1995 and 2009 we retrospectively reviewed 483 patients at Mayo Clinic who underwent RNU for primary UTUC. We identified 41 patients who underwent RNU after having a previous radical cystectomy. Patients with mucosal cuff excision identified pathologically were analyzed and compared to those without a mucosal cuff. Kaplan Meier analyses were used to estimate recurrence free survival. Results Median age of the cohort was 72 (IQR 66, 77) and 32 (78%) were male. A total of 18 (43.9%) patients underwent ileal cuff excision. Tumor multifocality, non-muscle invasive tumors ( Conclusions We found no significant difference in oncologic outcomes between patients with ileal mucosal cuff excision and those without a mucosal cuff at the time of RNU. Furthermore, there was no significant increase in intra- or post-operative complications by removing the mucosal cuff. In well-selected patients, oncologic outcomes may not be compromised by lack of ileal cuff excision. Funding None |
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PD67-01 |
Long-term functional outcomes and morbidity of prostate sparing cystectomy versus cystoprostatectomy: A case controlled study. |
Bladder Cancer: Invasive VII | 17BOS |
Abstract: PD67-01 Sources of Funding: none Introduction Prostate sparing cystectomy (PSC) is arguably a valid option for management of bladder cancer in selected cases. The majority of reported studies however have short term follow up as well as small sample size.We aimed to evaluate retrospectively our long term experience of prostate sparing cystectomy and compare it with our results of nerve sparing cystoprostatectomy (NSCP) in the laparoscopic/robotic era_x000D_ Methods Between 2001 and 2011, 60 patients were treated with laparoscopic or robotic PSC for muscle invasive or recurrent non muscle invasive bladder cancer. These patients were matched and compared to 47 patients who received laparoscopic or robotic NSCP and orthotopic bladder substitution during the same study period. Regarding continence, surviving patients were postoperatively contacted, at 3 months and 1 year, to answer a questionnaire based on the International Continence Society guidelines for reporting continence after urinary diversion. Potency was accessed by a house made questionnaire addressing the use of any medications or devices to achieve erection. Results Mean patient age was 60.35 and 62.12 for PSC and NSCP respectively. Median follow up was 69.5 months and 62 months for PSC and NSCP respectively. Forty percent of PSC had ? pT1N0, 30% pT2N0, 22% ? pT3N0 while 8% had N+ disease; compared to NSCP patients whom 38% had ?pT1N0, 19% pT2N0, 23% ? pT3N0 and 19% N+. (p=0.74) The overall 3- and 5-year cancer specific survivals were 92% and 90% in the PSC group, and 82% and 79% in the NSCP group respectively. The local recurrence rates were 11.7 % and 21.3 % for the PSC and the NSCP groups respectively, and the respective distant recurrence rate was 17% and 28%._x000D_ Regarding continence; 45% in the PSC showed immediate and full recovery of continence day and night compared to no patient in the NSCP group. After 1 year, 97% and 71% of PSC group were completely leak-free for day and night respectively, compared to 78% and 37% in NSCP (p?0.001). The incidence of self catheterization was equal in both groups at 15%. On long term follow up, 42% of PSC patients developed symptoms secondary to outlet obstruction and 18% of them required endoscopic resection of their prostate. While in NSCP patients, 4% developed anastomotic stricture that required endoscopic fulgration ( p?0.001)_x000D_ Regarding potency; 49% of PSC and 23% of NSCP reported maintaining similar preoperative potency level. Sexual intercourse was achievable without any treatment in 68% of PSC compared to 37% in NSCP. The incidence of intracavernosal injection was higher in the NSCP arm compared to the PSC (41% vs.17%) Four patients (9%) in the NSCP group failed all conservative management and required penile prosthesis compared to no patient in the PSC group. ( p?0.001)_x000D_ Conclusions Prostate sparing cystectomy is superior to nerve-sparing cystoprostatectomy regarding continence and potency. However, candidate patients who wish to retain their prostate should be informed about the long term need to manage outflow obstructive symptoms. Funding none
Authors
Mohamed Saad M.
Rafael Sanchez-Salas Eric Barret Marc Galiano François Rozet Nathalie Cathala Annick Mombet Dominique Prapotnich Xavier Cathelineau |
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PD67-02 |
Critical evaluation of the selection criteria for Prostate sparing cystectomy: do we need to tighten them? |
Bladder Cancer: Invasive VII | 17BOS |
Abstract: PD67-02 Sources of Funding: none Introduction Prostate Sparing cystectomy is a valid option for the treatment of patient with bladder cancer provided that strict selection criteria are used. Although that there is a uniform agreement on excluding patients with bladder neck tumors as well as patients with suspicious prostate that may harbor prostatic carcinoma, there has not been a standardized consensus on how to safely exclude them. Furthermore, the exclusion of other criteria such as carcinoma in situ, tumor characteristics and presence of preoperative hydronephrosis have not been clearly elucidated. Methods We retrospectively reviewed our laparoscopic/robotic assisted laparoscopic prostate sparing cystectomy series to evaluate our method of selecting patients. Results Between 2001 and 2011, 60 patients were treated with laparoscopic or robotic PSC for muscle invasive or recurrent non muscle invasive bladder cancer. Mean follow up time was 76.9 months ±33.3SD. When the preoperative PSA cut off value for biopsy was ? 4ng/dl; prostatic adenocarcinoma was detected on final pathology in 2 patients and arised de novo in 1 patient. When the value was lowered to 2.5ng/dl, no patient had incidental prostatic carcinoma and none developed de novo carcinoma. Distant/solitary carcinoma in situ was associated with more recurrences and so did preoperative hydronephrosis. Tumor grade, size and number were not associated with more recurrences. Conclusions The presence of any carcinoma in situ should be a contraindication to prostate sparing cystectomy. In addition to standard prostatic evaluation, a cut off PSA value of ? 2.5ng/dl for biopsy can eliminate any chance of harboring or developing a prostatic cancer. Funding none
Authors
Mohamed Saad M.
Rafael Sanchez-Salas Eric Barret Marc Galiano François Rozet Nathalie Cathala Annick Mombet Dominique Prapotnich Xavier Cathelineau |
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PD67-03 |
The oncological impact of transurethral endoscopic resection of the prostate versus Millin’s adenomectomy in prostate sparing cystectomy cases |
Bladder Cancer: Invasive VII | 17BOS |
Abstract: PD67-03 Sources of Funding: none Introduction Prostate sparing cystectomy (PSC) is a controversial subject in the management of bladder cancer. Some authors believe it is a valid option in certain selected cases, while others believe that it carries significant risks. One of the arguments against sparing the prostate was the observation that it has unusually high rate of distant metastasis when compared to radical cystectomy. It was speculated that metastatic diffusion through prostatic veins can occur during endoscopic prostatic resection prior to surgery._x000D_ we aimed to evaluate retrospectively, whether the different approaches to the prostatic adenoma prior to prostate sparing cystectomy have an impact on the rate of metastasis._x000D_ Methods Between October 1992 and December 2011, 160 cases with bladder cancer were treated with prostaste sparing cystectomy at our institution. Out of these; 100 patients (62.5%) had their prostate managed with TURP while 60 patients (37.5%) were managed by prostatic enucleation during cystectomy using Millin’s technique. A minimum of 5 years follow up was available. Results Mean patient age was 62 years for the TURP group and 60 years for the Millin’s group. Mean postoperative follow up available was 64 months and 78 months for TURP and Millin’s group respectively. Postoperative pathological stage for the TURP group was ? pT1N0 in 24% , pT2N0 in 40%, ? pT3N0 in 23% and N+ in 13% ; compared to the Millin’s group where the pathological stage was ? pT1N0 in 40 %, pT2N0 in 30%, ? pT3N0 in 22% and N+ in 8%. Overall survival rates at 5 years were 67% and 88% for the TURP and the Millin’s groups respectively. The 5 years recurrence free survival rates for the TURP group were 77% for pT2 N0 or less, 44% for pT3 N0 or greater and 22% for pN+ disease. Regarding the Millin’s group, the recurrence free survival rates were 86% for pT2 N0 or less, 75% for pT3 N0 or greater and 40% for pN+ disease. The local recurrence rates were 6.2 % and 11.7 % for the TURP and the Millin’s groups respectively, and the respective distant recurrence rate was 34% and 16.7% .( p?0.001) Conclusions These results further support previous suggestions that TURP may contribute to the dissemination of tumor cells in bladder cancer patients. Funding none
Authors
Mohamed Saad M.
Rafael Sanchez-Salas Eric Barret Marc Galiano François Rozet Nathalie Cathala Annick Mombet Dominique Prapotnich Xavier Cathelineau Mohamed Saad M. Rafael Sanchez-Salas Eric Barret Marc Galiano François Rozet Nathalie Cathala Annick Mombet Dominique Prapotnich Xavier Cathelineau |
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PD67-04 |
EARLY AND LATE COMPLICATIONS OF ROBOTIC RADICAL CYSTECTOMY AND INTRACORPOREAL URINARY DIVERSION |
Bladder Cancer: Invasive VII | 17BOS |
Abstract: PD67-04 Sources of Funding: none Introduction To present 90 day perioperative complications stratified by urinary diversion type in patients undergoing robotic radical cystectomy (RRC) and completely intracorporeal urinary diversion (ICD). Methods An IRB approved protocol allowed for review and analysis of data from 216 patients undergoing RRC-ICD between July 2010 to March 2016 from a single institution’s bladder cancer database. Perioperative complications were categorized as early (<30 days) or late (0-90 days) and complication severity was classified using the Clavien-Dindo system. Results A total of 174 men and 42 women with a median age (range) of 71 (35-94) years and a median body mass index (range) of 26.8 (16.0-44.5) kg/m2 underwent RRC-ICD. Orthotopic neobladder was performed in 68 patients (31.5%). The median postoperative length of stay (range) was 6 days (2-47). Early (<30 days) and late complications (0-90 days) occurred in 147 (68.1%) and 175 (81.0%) patients, respectively. A total of 30 patients (13.9%) required perioperative blood transfusion(s). Of those, 24 (16.2%) had ileal conduits and 6 (8.8%) had neobladders. The perioperative mortality was 1.9%. Moreover, 7.9 % patients developed an uretero-enteric stricture over a median follow-up (range) of 11.8 months (0.0-65.3). Complications are detailed in the corresponding table. Conclusions Robotic radical cystectomy with complete intracorporeal urinary diversion is safe and technically feasible with acceptable perioperative morbidity. Prospective randomized trails comparing intracorporeal urinary diversion versus open diversion are necessary to compare peri-operative morbidity. Funding none
Authors
Sameer Chopra
Fatima Hussain Andre Abreu Nariman Ahmadi Andre Berger Inderbir Gill Monish Aron Mihir Desai |
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PD67-05 |
Facility Volume and Type is Associated with Receipt of Continent Diversion for both Open and Robotic Radical Cystectomy |
Bladder Cancer: Invasive VII | 17BOS |
Abstract: PD67-05 Sources of Funding: Department of Urology and Department of Biostatistics, Winthrop University Hospital Introduction Continent urinary diversion (CUD) can offer improved quality of life in select patients follow in radical cystectomy (RC). We aim to evaluate the rate of receipt of CUD in robotic assisted RC (RARC) and open RC (ORC) based on hospital volume and facility type in the National Cancer Data Base. Methods We divided all cystectomy cases into volume categories (defined as: 1-2.9, 3-4.9, 5-9.9, 10-19.9 and 20+ cystectomies/year) and facility type (academic/research (AR), comprehensive community (CC) and other), type of surgery (ORC or RARC) to assess the patterns in the rate of receipt of CUD. To assess the relationship between facility characteristics and receipt of CUD, chi-square was used. Univariate and multivariable logistic regression models for CUD rates were used to adjust for patient, tumor and facility characteristics. Results 16,923 RC cases were identified (ORC = 13,236, RARC=3,687). Overall, 5.7% of ORC (754) and 7.1% of RARC (261) received CUD (p=0.003). RARC had higher rates of receiving CUD compared to ORC in all volume categories except for the highest volume centers (10.2% vs 9.7%). Rates of receipt of CUD increased with increasing RC volume centers (p=0.01); in the ORC group (2.8 vs. 10.2%), and in the RARC group by (5.7% vs. 9.7%; p for interaction=0.10). In adjusted models, center volume remained a highly significant predictor of CUD receipt (p<0.001). Rates of receipt of CUD were higher in RARC vs. ORC in CC and other facility types, but were equal in AR facilities. The difference in the rate of CUD receipt between facility types was significant for ORC (p=0.001) but not for RARC (p=0.09). CUD receipt was observed to decrease linearly over time in both ORC (6.9% in 2010 vs. 4.7 in 2013; p=0.001) and RARC (9.4% in 2010 vs. 6.0% in 2013; p=0.06). Conclusions Increasing facility cystectomy volume was associated with increased rates of receipt of CUD in both open and robotic cystectomy while facility type was only significant for open surgeries. The overall rate of receiving CUD was higher in RARC versus ORC surgeries but the overall rate of patients receiving continent diversions remains low and may be decreasing. Funding Department of Urology and Department of Biostatistics, Winthrop University Hospital
Authors
Kaitlin Kosinski
Melissa Fazzari Michael Kongnyuy Daniel Halpern Marc Smaldone Jeffrey Schiff Aaron Katz Anthony Corcoran |
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PD67-06 |
Pathologic Metrics of Surgical Quality in Open and Robotic Radical Cystectomy Improved at Higher Volume and Academic Centers |
Bladder Cancer: Invasive VII | 17BOS |
Abstract: PD67-06 Sources of Funding: Department of Urology and Department of Biostatistics, Winthrop University Hospital Introduction Pathologic findings including surgical positive margin(PM) rates and lymph node(LN) yield have been used as metrics of surgical quality in radical cystectomies(RC) dissections. We aim to evaluate these measures in RC reported in the National Cancer Data Base(NCDB) stratified by hospital cystectomy volume and facility type to assess surgical quality for both robotic and open RC. Methods The NCDB was queried for primary RC cases (2010-2013). Stratified by institutional volume (1-2.9, 3-4.9, 5-9.9, 10-19.9 and 20+ RC/year), facility type (academic/research(AR),community, and other), type of surgery [open (ORC) and robotic assisted(RARC)] surgical quality was measured using trends of PM rates, LN dissection rates, and number of dissected LN. We performed chi-square tests for association and tests for trend to assess the relationship between facility characteristics and surgical quality measures. Univariate and multivariable logistic regression models for PM and LN dissection rates were examined. Results 16,923 RC cases were identified. Using the above volume categories, we observed a significant increase in RARC PM rates in centers performing less than 10 RARC per year(12% vs. 9%; p=0.01). In adjusted models, low center volume was associated with a higher PM rate(p=0.02). ORC PM rate in the lowest volume(LV) category was 13.9% vs. 12.0% in the highest volume(HV) category. RARC PM rate in the LV category was 10.4% vs 9.3% in the HV category. Receipt of a LN dissection was significantly higher in HV compared to LV centers for ORC(91 vs. 84%, p=0.03) not for RARC(96.6 vs 92%; p=0.07). In adjusted models, volume association with LN dissection approached but did not reach significance(p=0.06). Median LN yield increased with higher facility volume in both ORC(17 vs. 7; p<0.001) and RARC(21 vs. 10.5; p<0.001). AR facility type was associated with lower PM rates (p=0.05), higher LN dissection rates (p=0.05), and higher median LN dissected (p<0.0001) in ORC. For RARC, AR facility type was only associated with higher median number of LN dissected in RARC (p<0.0001). Conclusions Several metrics of oncologic surgical quality were improved at higher cystectomy volume and academic centers for both open and robotic cystectomy. Databases capturing cancer specific survival should be queried to evaluate the downstream oncologic influences of these findings. Funding Department of Urology and Department of Biostatistics, Winthrop University Hospital
Authors
Kaitlin Kosinski
Melissa Fazzari Michael Kongnyuy Daniel Halpern Marc Smaldone Jeffrey Schiff Aaron Katz Anthony Corcoran |
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PD67-07 |
Open versus robot assisted radical cystectomy and intracorporeal urinary diversions: Mid-term propensity score matched analysis of perioperative and oncologic outcomes |
Bladder Cancer: Invasive VII | 17BOS |
Abstract: PD67-07 Sources of Funding: none Introduction To compare oncologic outcomes of propensity score matched (PSM) cohorts of patients treated with either ORC or RARC and intracorporeal urinary diversion (UD). Methods The IRB approved bladder cancer databases of two centers were queried for &[Prime]cystectomy with curative intent&[Prime]. A 1:2 PSM analysis was used to minimize the biases of retrospective analysis of data. Kaplan-Meier method was used to compare the oncologic outcomes of the PSM cohorts. Survival rates were computed at 2, 3 and 4 years after surgery and the log rank test was applied to assess statistical significance between groups. Univariable and multivariable Cox regression analyses were performed to identify predictors of disease-free survival (DFS). Results Overall 631 patients with a minimum 2 yr follow-up were included, (478 ORC and 153 RARC). _x000D_ Patients treated with ORC had significantly higher ASA scores (p=0.007) and pT stages (p=0.001), lower lymph node count (LNc) (p<0.001) and lesser adoption of neoadjuvant chemotherapy (p<0.001). After applying the PSM, the two groups (193 ORC, 110 RARC patients) did not differ for any clinical or pathologic variable (all p ≥0.627), except than for LNc (p=.004) (Table 1). _x000D_ At Kaplan-Meier analysis ORC and RARC cohorts displayed comparable DFS (p=0.73), cancer specific survival (p=0.7) and overall survival probabilities (p=0.12). _x000D_ At multivariable Cox regression analysis in the postPSM cohort, age (p=0.048), pT stage >2 (p=0.003) and nodal metastasis (p<0.001) were independent predictors of DFS (Table 2)._x000D_ Conclusions RARC with intracorporeal UD and ORC provide comparable mid term oncologic outcomes. Funding none
Authors
Giuseppe Simone
Leonardo Misuraca Andre Luis De Castro Abreu Gabriele Tuderti Mariaconsiglia Ferriero Salvatore Guaglianone Gus Miranda Francesco Minisola Monish Aron Inderbir Singh Gill Michele Gallucci Mihir Desai |
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PD67-08 |
Long term oncological outcome of robotic assisted versus open cystectomy |
Bladder Cancer: Invasive VII | 17BOS |
Abstract: PD67-08 Sources of Funding: none Introduction There is currently lack of sufficient data on the long-term oncological outcomes after robot-assisted radical cystectomy.The aim of this study is to compare the long-term oncological outcomes of robot-assisted with open radical cystectomy. Methods We retrospectively analysed the oncological outcomes of robot-assisted (RARC) versus open radical cystectomy (ORC) from prospectively collected database, between 2003 and 2011 to evaluate recurrence free (RFS) and cancer specific survival (CSS). Data including patient age, gender post-operative histology and time to recurrence were collected prospectively and analysed using the Kaplan Meier method and log rank testing. Patients were stratified as having organ confined (?pT2) or non-organ confined (?pT3 or LN+ve) disease. Results A total of 182 patients were identified during the study period: 65 (men 53, women 12) underwent RARC and 117 (men 82, women 35) patients had an ORC. Median age was 67 (35-82) and the median follow up for all the cases was 55.5 months (range 3-154months). Histologically-proven organ-confined disease was found in 74% of RARC patients compared with 59% of patients having ORC. Positive margins were reported in 4/65 (6%) RARC cases compared with 7/117 (5.98%) open cases. Median lymph node yield was similar for both surgical approaches (11 for ORC vs 10 for RARC), but the percentage of positive LNs was higher in the ORC group (17% vs 8%). _x000D_ Overall, 37% (24/65) of RARC patients and 41% (48/117) of ORC patients developed recurrence. For organ-confined disease, 5-year RFS was 75% vs 74.9% for RARC and ORC respectively. This difference was not statistically different (p= 0.7435). For non-organ confined disease 5 year RFS was 39.2% vs 31.2% for RARC and ORC respectively. This difference was statistically non-significant (p= 0.89)._x000D_ For patients with organ confined disease, there was no statistically significant difference in 5-year CSS between RARC and ORC (84% and 82.6% respectively, p=0.74). There was also no significant difference in 5-year CSS between RARC and ORC for non-organ confined disease (39% and 38.9% respectively, p=0.85)._x000D_ Conclusions This data shows that the long term oncological outcomes of open vs robot assisted cystectomy are equivalent. Thus technology is unlikely to have significant impact on oncological outcomes. Funding none
Authors
Kawa Omar
Brian Parsons Martina Smekal Rajesh Nair Ramesh Thurairaja Shamim Khan |
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PD67-09 |
Comparative effectivness of robot-assisted vs. open radical cystectomy |
Bladder Cancer: Invasive VII | 17BOS |
Abstract: PD67-09 Sources of Funding: none Introduction Over the past decade, robotic-assisted radical cystectomy (RARC) has slowly gained acceptance in the urology community. However, the benefits of RARC over ORC remain controversial. Our objective was to conduct a comparative effectiveness analysis between RARC and ORC using data from the National Cancer Data Base (NCDB). Methods Within the NCDB, we identified patients with non-metastatic muscle-invasive bladder cancer (BC) who underwent RC between 2010 and 2013. Patients were stratified according to surgical approach: ORC or RARC. Oncologic endpoints measured included the presence of positive surgical margins, the performance of a pelvic lymph node dissection, and number of lymph nodes removed. Perioperative outcomes measured included length of stay (LOS), 30-day and 90-day postoperative mortality rates, as well as 30-day readmission following surgery. To minimize selection bias, observed differences in baseline characteristics between patients who received RARC vs. ORC were controlled for using a weighted propensity score analysis. Using weighted data, all endpoints were assessed using propensity-adjusted logistic regression analyses. Results Of 9,561 patients who underwent RC, 2,048 (21.4%) and 7,513 (78.6%) underwent RARC and ORC, respectively. The use of RARC has increased over time, from 16.7% in 2010 to 25.3% in 2013. With regard to oncologic outcomes, RARC was associated with similar positive surgical margins (9.4% vs. 10.7% OR:0.86, 95%CI 0.72-1.04, p=0.12), higher rates of lymphadenectomy (96.4% vs. 92.0%, OR: 2.31, 95%CI 1.68-3.19, p<0.001), higher median lymph node count (17 vs. 12, p<0.001) and higher rates of lymph node count above the median (56.8% vs. 40.4%, OR: 1.95, 95%CI 1.56-2.43, p<0.001). With regard to postoperative outcomes, receipt of RARC was associated with a shorter median LOS (7 vs. 8, p<0.001), lower rates of pLOS (45.1% vs. 54.8%, OR: 0.68, 95%CI 0.58-0.79, p<0.001), lower 30-day (1.5% vs. 2.8%, OR: 0.49, 95%CI 0.29-0.82, p=0.007) and 90-day postoperative mortality (5.0% vs. 6.8%, OR: 0.72, 95%CI 0.54-0.95, p=0.023). Conclusions Our large contemporary study shows the increased adoption of RARC between 2010 and 2013, with currently more than 1 out of 4 patients undergoing RARC. RARC was associated with higher LN counts, shorter LOS and lower postoperative mortality. Funding none
Authors
Nawar Hanna
Jeffrey J. Leow Maxine Sun Nicolas von Landenberg Philipp Gild Firas Abdollah Mani Menon Adam S. Kibel Joaquim Bellmunt Toni K. Choueiri Quoc-Dien Trinh |
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PD67-10 |
Incidence and Risk Factors for Peritoneal Carcinomatosis Following Open Radical Cystectomy |
Bladder Cancer: Invasive VII | 17BOS |
Abstract: PD67-10 Sources of Funding: none Introduction Recently, there has been increased interest in the incidence of peritoneal carcinomatosis (PC) following radical cystectomy (RC). Particularly, pneumoperitoneum and robotic RC have been implicated as potential risk factors for peritoneal seeding. However, little has been reported on the rates of PC in open RC patients. Herein, we characterized the frequency and risk factors of PC in open RC patients in our institutional cystectomy registry. Methods We identified patients with urothelial carcinoma of the bladder treated for curative intent from 1980 to 2015. Patients were categorized based on recurrence pattern through our institutional cystectomy registry. We defined PC as tumor recurrence involving the omentum, small bowel and mesentery. Clinicopathologic variables were compared using 2 sample t-test and F test. Overall and cancer-specific survival was evaluated using Kaplan-Meier methodology and log rank test. Results Between 1980 and 2015, 3,285 patients underwent open RC. One hundred and twenty nine (3.9%) patients experienced PC, 1148 (34.9%) patients had other forms of recurrence, and 2008 (61.1%) had no recurrence. Median time to PC and other recurrence were 1.3 (IQR 1.3, 2.3) and 0.9 (IQR 0.5, 2.1) years respectively (p=0.042). Patients with PC had higher pathologic tumor and nodal stage than those with other recurrences and no recurrences (p<0.0001). Pathologic factors associated with PC include lymphovascular invasion (29.5% vs 16.7%, p=0.0002) and positive tumor margin (5.4% vs 2.9%, p=0.0093). Patients with PC experience worse overall and cancer specific survival than other types of recurrence (Figure). Conclusions PC occurred in almost 4% of our patients undergoing open RC. Worsening pathologic stage was associated with PC. Cancer death in patients with PC was almost universal at 5 years. Further analysis will be needed to determine risk factors for developing PC following RC. Funding none
Authors
David Y Yang MD
Igor Frank MD Ross A Avant MD Prabin Thapa Stephen A Boorjian MD Matthew K Tollefson MD |
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PD67-11 |
Enhanced Recovery After Radical Cystectomy Reduces Cost and Length of Stay: The Johns Hopkins Experience. |
Bladder Cancer: Invasive VII | 17BOS |
Abstract: PD67-11 Sources of Funding: None Introduction Many centers have adapted Enhanced Recovery after Surgery (ERAS) pathways to decrease hospital length of stay (LOS) and peri-operative complications. We report the Johns Hopkins ERAS experience, specifically evaluating complication rate, LOS, 30- and 90-day readmissions, and for the first time in an ERAS cohort, cost. Methods ERAS protocol (Table 1) was implemented for radical cystectomy (RC) patients in November 2015. Outcomes. readmissions and cost were compared to a matched group of 54 RC patients from an 8-month period prior to the use of ERAS. Patients were excluded if indication was not for bladder cancer or if they underwent adjunct procedures. _x000D_ Results 58 consecutive ERAS patients were compared to 54 pre-ERAS patients (Table 2). Cost of index hospitalization was $30,450 in the ERAS group and $35,411 in the pre-ERAS group; readmission LOS and costs were comparable between groups. Median LOS was 5 days for the ERAS group and 8.5 days for the pre-ERAS group (p=<0.001). The pre-ERAS group had a significantly increased use of nasogastric tube (30% vs. 13.8%) and parenteral nutrition (20.4% vs. 6.9%). A trend towards increased complications occurring during index hospitalization in the pre-ERAS group was observed, although not reaching statistical significance. The ERAS group experienced a slightly higher rate of 30-day readmission, though two were for ostomy appliance issues. The most common reason for readmission was infection in both groups; there was a higher rate of GI related readmissions in the ERAS group (Figure 1). Conclusions Implementation of the ERAS protocol at our center resulted in significantly reduced length of hospital stay and decreased cost, with comparable rates of complication and readmission. Funding None
Authors
Alice Semerjian
Niv Milbar Max Kates Michael Gorin Heather Chalfin Cary Stimson William Yang Steven Frank Deb Hobson Lindsay Robertson Ken Lee Michael Johnson Phillip Pierorazio Trinity Bivalacqua |
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PD67-12 |
Safety & Feasibility of Bladder and Prostate Robotic Surgery After Radiation Therapy |
Bladder Cancer: Invasive VII | 17BOS |
Abstract: PD67-12 Sources of Funding: none Introduction Open surgery for removing the bladder and/or prostate after radiation therapy is a challenging procedure with a high complication rate. We wanted to assess the feasibility and complication rates in similar cases utilizing robotic surgery. Methods We identified 13 patients undergoing robotic surgery after radiation therapy in our robotic surgery database. Ten underwent a cystectomy and 3 radical salvage prostatectomy. We collected demographic, surgery and post-surgery data during their hospital stay. Results In the cystectomy group there were 6 females and 4 males, mean age 68 years. Three of the patients were 81, 84 and 85 years old. Two female patients had prior brachytherapy due to cervical cancer and developed a small contracted bladder with vesico-vaginal fistula. Two males with external beam radiation and one male with brachytherapy for prostate cancer developed TCC. One male with squamous cell carcinoma and 4 others with TCC that received chemo-radiation in the past, were sent to salvage cystectomy due to local recurrence. Five patients received neoadjuvant chemotherapy prior to surgery._x000D_ Mean operating time was 6:53 hours. Mean operative blood loss 461 ml. Three patients received 2 units of packed cells apiece during surgery due to blood loss of 800 ml each. The mean blood loss for the others was 291 ml._x000D_ One female patient with prior multiple open abdominal surgeries had adhesions that required conversion to open surgery which ended with bowel injury and cystectomy was aborted. Post-operative complications consisted of transient ileus in 3 patients. Mean hospital stay was 6 days (range 4-8 days). Six patients were discharged with a drain due to increased serous drainage, which was later removed in our clinic. In the radical prostatectomy group mean operative time was 2:46 hours, mean blood loss was 133 ml, there were no intra-operative or post-operative complications. Mean hospital stay was 5 days (range 3-8 days). Conclusions Robotic cystectomy and/or prostatectomy after radiation therapy to the pelvis is an effective and safe procedure. Nonetheless, it has the risk of increased blood loss during surgery, increased hospital stay and more serous secretions through the drains compared to robotic surgery in patients without prior radiation therapy. Funding none
Authors
Tareq Aro
David Kakiashvili Kamil Malshy Valentin Shabataev Gilad Amiel |
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PD68-01 |
Pilot study results using fluorescence activated cell sorting of spermatozoa from testis tissue: a novel method for sperm isolation after TESE |
Infertility: Therapy II | 17BOS |
Abstract: PD68-01 Sources of Funding: None Introduction Testicular sperm extraction (TESE) is successful in identifying a small number of sperm in 50% of men with non-obstructive azoospermia (NOA). Traditionally, sperm are isolated from testicular tissue using a combination of standard light microscopy, tissue digestion and time analyzing the specimen in hope to isolate rare spermatozoa. Here we discuss our results utilizing fluorescence-activated cell sorting (FACS) of testis tissue to increase the efficiency in the isolation of spermatozoa. Methods Testicular tissue was obtained from 10 patients: 2 cadaveric specimens with normal spermatogenesis and 8 specimens from wasted testicular tissue from microTESE. The specimens were prepared by sharp cutting followed by mechanical disaggregation with a Medimachine (BD Biosciences, USA) and passed through a 50- and 30-micron filter. The specimens were then stained with DNA-stains To-Pro-3 or SYTO 17(ThermoFischer, USA) and incubated. Sperm from a normal semen sample were stained similarly and used as controls for gating during flow cytometry . Then, cell sorting was completed using a FACSAria II (BD Biosciences, USA) to isolate spermatozoa. Each sorted specimen underwent standard light microscopy to identify spermatozoa. Results Using this technique, spermatozoa were successfully isolated and recovered in both cadaveric specimens. Of the 8 patients undergoing microTESE , 3 (38%) had spermatozoa recovered using standard tissue processing and 4 (50%) had spermatozoa recovered using FACS. Notably, in our cohort, both patients with maturation arrest had a negative microTESE with standard tissue processing, but had successful isolation of spermatozoa using FACS. Conclusions Our initial experience using fluorescence-activated cell sorting for rare spermatozoa isolation from testicular tissue proves the technical feasibility of this process. As this research continues to be refined and implemented, the clinical application of this technique has the potential to increase the rate of successful TESE to isolate spermatozoa. Funding None
Authors
Sameer Mittal
Anna Mielnik Alexander Bolyakov Peter Schlegel Darius Paduch |
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PD68-02 |
Sperm Extraction Location Can Affect Early Embryo Morphokinetics |
Infertility: Therapy II | 17BOS |
Abstract: PD68-02 Sources of Funding: none Introduction The sperm centrosome plays an important role in early embryo development. Paternal effect on embryonic cleavage and blastocyst formation can be affected in cases of severe male infertility where spermatogenesis is abnormal. We compared morphokinetics of embryonic development in patient embryos created from sperm extracted from the testis and epididymis. Methods The charts of 72 men with severe oligospermia or azoospermia who underwent successful IVF/ICSI were retrospectively reviewed. _x000D_ Demographics, endocrine labs, semen analysis, genetic testing data, pathologic diagnosis and location of sperm extraction were analyzed. Zygotes were cultured in the Embryscope time lapse imaging chamber. Kinetic data and cycle outcome data were analyzed. Clinical pregnancy rate (CPR), implantation rate (IR) and blastulation rate were calculated. Results 41 men (56.9%) underwent sperm extraction from the testis with 28 (68.3%) having a microTESE. 31 men (43.1%) had epididymal sperm extraction, with the 74.2% having a percutaneous extraction. The most common diagnosis in the epididymal group was presence of vasectomy (61.3%) and idiopathic nonobstructive azoospermia (63.4%) in the testicular group. The average FSH (mU/mL) in the epididymal group was 3.8 and was 17.6 in the testicular group (p = 0.051). There was no difference in LH (p = 0.88), testosterone (p = 0.46) or estradiol (0.725) between the two groups. CPR and IR in the testicular sperm group (51% and 31%, respectively) was similar to that of the epididymal group (57% and 37%, respectively). Embryos in the testicular sperm group were significantly slower in reaching early kinetic endpoints (t2,t4,t8), though tM, tSB and tEBL from both groups were similar. The mean day 3 embryo cell count was lower with testicular (7.69 +/- 2.09) vs epididymal derived (8.65 +/- 2.73; p=0.03) embryos. There was an increased percentage of embryos in the testicular group that failed to compact (TESE 31%,vs PESA 16%; P<0.0001). Conclusions Delayed developmental times were observed in embryos derived from testicular sperm up until the stage of compaction (an early indicator of embryonic genomic activation). Embryos from the testicular group arrested at a higher rate prior to this stage but after this stage, they had similar kinetics as epididymal derived embryos. _x000D_ Larger, prospective studies examining sperm quality in testicular extraction patients and its relationship to embryo kinetics may help to further elucidate these results. Funding none
Authors
Nicholas Tadros
Pavinder Gill Edmund Sabanegh Nina Desai |
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PD68-03 |
Impact of injected testicular sperm characteristics on reproductive outcomes in intracytoplasmic sperm injection |
Infertility: Therapy II | 17BOS |
Abstract: PD68-03 Sources of Funding: Supported by The Frederick J. and Theresa Dow Wallace Fund of the New York Community Trust. Introduction Microdissection testicular sperm extraction (microTESE) with intracytoplasmic sperm injection (ICSI) is an important treatment option for men with non-obstructive azoospermia (NOA). Although men with NOA have 0% normal forms, laboratory staff will commonly avoid ICSI of individual sperm because of subjective considerations of sperm &[Prime]quality&[Prime] based on morphologic evaluation. We report the effect of injected sperm characteristics on fertilization and pregnancy rates in ICSI following microTESE in men with NOA. Methods We conducted a retrospective review of all men at a single institution who had successful sperm retrieval at microTESE and then proceeded to ICSI between 05/13 and 06/16. Information was collected on demographics, injected sperm characteristics at ICSI, fertilization, and pregnancy rates. Comparisons were done using Fisher&[prime]s test, gamma test, one-way ANOVA, and multivariable analysis (MVA), with significance set at p<0.05. Results A total of 198 men (mean age 35±8 years) were included. Fertilization and pregnancy rates were 44% and 38%, respectively. On univariable analysis, sperm motility and the lack of acrosome defects were associated with higher fertilization and pregnancy rates while an increasing number of total sperm abnormalities was negatively associated with fertilization, but not pregnancy, rates (Table). On MVA, only sperm motility was associated with fertilization rates (p<0.001) while both sperm motility (p=0.004) and the lack of acrosome abnormalities (p=0.018) were associated with pregnancy rates. Female age (mean age 31±5 years) was not associated with fertilization or pregnancy rates on MVA. Conclusions This study is the first to assess the relationship between injected testicular sperm characteristics and reproductive outcomes in ICSI. All men with NOA have abnormal sperm morphology and our experience suggests that no specific sperm abnormality, including injection of non-motile sperm, precludes the chance of pregnancy. Further study of sperm characteristics may influence how aggressively surgeons should seek better sperm quality during microTESE procedures. Use of elongating spermatids (blunt-tailed sperm) did not adversely affect the chance of pregnancy despite concerns for lower fertilization with severely blunt-tailed sperm. Funding Supported by The Frederick J. and Theresa Dow Wallace Fund of the New York Community Trust.
Authors
Phil V. Bach
Ryan Flannigan Bobby Najari Nikica Zaninovic Gianpiero Palermo Zev Rosenwaks Peter Schlegel |
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PD68-04 |
Impact of CFTR mutations on phenotype and reproductive outcomes in men with congenital absence of the vas deferens |
Infertility: Therapy II | 17BOS |
Abstract: PD68-04 Sources of Funding: Supported by The Frederick J. and Theresa Dow Wallace Fund of the New York Community Trust. Introduction Congenital absence of vas deferens (CAVD) causes obstructive azoospermia in 1% of infertile men and can be treated using epididymal sperm aspiration (MESA) coupled with intracytoplasmic sperm injection (IVF/ICSI). CAVD can be seen in patients with and without mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. There is an ongoing debate about whether CFTR mutations affect spermatogenesis. We hypothesized that CFTR mutations in men with CAVD would negatively affect reproductive outcomes. Methods We retrospectively reviewed a database of 78 infertile men with CAVD who were treated by a single surgeon from 1990 to 2016. Information on demographics, phenotype, CFTR mutations, and IVF/ICSI outcomes were collected. Patients with CFTR mutations (CFTR+) and without CFTR mutations (CFTR-) were compared using Fisher test and unpaired t-test, with significance set at p<0.05. Results We identified 65 men with CAVD who were screened for CFTR mutations, of whom 34 had bilateral CAVD and underwent MESA and IVF/ICSI at our institution. Average patient and partner ages were 33±6 years and 31±5 years, respectively. 36 patients (55%) were CFTR+ while 29 patients (45%) were CFTR-. 92% of CFTR+ patients presented with bilateral CAVD compared to 79% of CFTR- patients (p=0.27). Renal anomalies were only seen in CFTR- patients (Table). Amongst CFTR- patients, 50% with unilateral CAVD and 35% with bilateral CAVD had renal anomalies (p=0.65). The most common CFTR mutation detected was δf508 (50%), followed by w1882x (22%) and 5t (17%). 24 CFTR+ couples underwent 47 IVF/ICSI cycles and 10 CFTR- couples underwent 13 IVF/ICSI cycles. While fertilization rates were higher in CFTR- patients, there was no difference in clinical pregnancy or live birth rates (Table). Conclusions Men with CAVD present evenly with and without CFTR mutations. CFTR- patients are more likely to harbor renal anomalies and should be screened while CFTR+ patients do not need to be screened for renal anomalies. While CFTR mutations negatively affect fertilization rates, there was no difference in clinical pregnancy or live birth rates after IVF/ICSI. Further studies with larger populations that examine the relationship between specific CFTR mutations and reproductive outcomes are warranted to substantiate our findings. Funding Supported by The Frederick J. and Theresa Dow Wallace Fund of the New York Community Trust.
Authors
Phil V. Bach
Filipe Neto Bobby Najari Ryan Flannigan Miriam Feliciano Philip Li Marc Goldstein |
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PD68-05 |
The outcomes of scrotal exploration with vasoepididymostomy in patients with non-iatrogenic, non-traumatic obstructive azoospermia |
Infertility: Therapy II | 17BOS |
Abstract: PD68-05 Sources of Funding: none Introduction Non-iatrogenic, non-traumatic obstructive azoospermia (OA) includes causes like congenital bilateral absence of vas deferens (CBAVD), blockage at rete testis, or obstruction distal to internal inguinal rings. The blockage could be potentially identified at scrotal exploration and corrected with vasoepididymostomy (VE). The purpose of this study is to analyze patients with non-iatrogenic, non-traumatic OA who underwent scrotal exploration with or without VE anastomosis in our institution. Methods Retrospective chart review was done for patients treated from 2000 to 2015. OA was confirmed by semen analysis and normal spermatogenesis at testis needle biopsy in all patients. The operation method for VE anastomosis was two-stitch longitudinal intussusception technique. Patients who had prior vasectomy or history of vas deferens trauma/injury were excluded. The age, hormone profile, semen parameters, obstruction level, semen quality at proximal vas deferens cutting end and patency rates were analyzed. Results Totally 96 patients with mean age 35.4±5.6 y/o were collected. The obstruction level was: bilateral rete testis blockage (n= 17), bilateral epididymis (49), bilateral intra-abdominal blockage (7), CBAVD variants (3). There were 68 patients received VE anastomosis. The patency rates 6 months after operation for patients with bilateral epididymal blockage were 88%. They were 90.9% for blockage at both epididymal tails, 88.9% at body, and 83.3% at head. Motile sperm in peri-operational cutting end fluid aspiration had patency rates at 80.6%, in contrary they were 50% in cases showing only immotile sperm. The mean patency rates were 79.5% for all cases 6 months after operation. There were 28.1% of patients failed to have correction procedure, including 25% of high or low blockage, and 3.1% of CBAVD variants. Patients with CBAVD variants showed lower semen pH (6.67±0.1, P= 0.001). Conclusions For patients with non-iatrogenic non-traumatic OA receiving scrotal exploration, 28.1% are not eligible for correction. The mean patency rates for all patients 6 months after micro-anastomosis were 79.5%. They were 90.9% and 88% for cases with obstruction at bilateral epididymal tails and body respectively. Motile sperm in proximal end predict higher patency rates. Funding none
Authors
Chin Heng Lu
William J.S. Huang I-Shen Huang Alex T.L. Lin Kuang-Kuo Chen |
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PD68-06 |
Teaching the teachers: An educational program for management of infertility in men with spinal cord injury |
Infertility: Therapy II | 17BOS |
Abstract: PD68-06 Sources of Funding: Craig H. Neilsen Foundation Grant #365254 Introduction Spinal cord injury (SCI) occurs most often to young men. Infertility is a major sequela of SCI. Anejaculation and abnormal semen parameters are seen in 90% of the cases. Currently there is no established standard of care for the management of infertility in these men, largely due to a lack of education of healthcare providers at all levels. Consequently, couples with SCI male partners are often over-treated with expensive and unnecessary procedures. A 3 year educational program funded by the Craig Neilsen Foundation has been developed to train practitioners in methods and techniques for managing infertility in this population. Methods A teaching curriculum was developed based on our 27 years of experience in the management of infertility in men with SCI. The training is performed at our center or at outside centers if requested and is comprised of the following items:_x000D_ 1) The core of the curriculum is a half day of lectures and videos _x000D_ 2) Two half-days of hands-on training on the techniques of penile vibratory stimulation (PVS) and electroejaculation (EEJ) as well as management of autonomic dysreflexia and retrograde ejaculation. This is part of the training curriculum at our site and can be performed at other sites if the users so wish. _x000D_ 3) A syllabus, copy of the PowerPoint presentation and instructional videos will be supplied to trainees which may be used to teach future healthcare providers of all types._x000D_ 4) The program offers Continuing Medical Education (CME) credits (7.5 hours for the full course) for physicians. _x000D_ 5) Limited travel reimbursement is available for professionals who train at our center in Miami._x000D_ Results During our first year (December 2015 - December 2016), educational materials (syllabus and comprehensive 30 minute instructional video) were developed. The program was presented at the Academy of Spinal Cord Injury Professionals (ASCIP) 2016 meeting and has been selected as an instructional course for the 2017 annual AUA meeting. A total of 9 physicians from the USA, Canada, Spain, Brazil and Israel have been trained to date at our center. Multiple requests for training have been received and are scheduled for future dates. Conclusions This educational program addresses a gap in knowledge among health care professionals on the topic of management of infertility in men with SCI. We encourage interested professionals to take advantage of this training opportunity, which will be available through December 2018. Funding Craig H. Neilsen Foundation Grant #365254
Authors
Emad Ibrahim
Teodoro Aballa Charles Lynne Nancy Brackett |
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PD68-07 |
Policy on Posthumous Sperm Retrieval: Survey of 75 Major Academic Medical Centers |
Infertility: Therapy II | 17BOS |
Abstract: PD68-07 Sources of Funding: None Introduction Very few studies have addressed attitudes on posthumous sperm retrieval due to the ethical and legal ramifications of the use of gametes after death. We evaluated the presence and content of a policy on posthumous sperm retrieval at the 75 major academic medical centers in the U.S. Methods We surveyed the 75 major academic medical centers as ranked for research in 2016 by U.S. News & World Report using a questionnaire based telephone/web survey. We gathered data on presence and content of posthumous sperm retrieval policies. If not published, we contacted the legal counsel for the medical center, the ethics and compliance offices, the Urology Department, as well as the infertility center for each institution, in that order. Results Out of the 75 major academic medical centers, we gathered data on posthumous sperm retrieval from 25 (33.3%). Of the 25 institutions, nine (36%) had policies regarding posthumous sperm retrieval, fifteen (60%) did not have a policy, and one center remained undisclosed. Five of the fifteen medical centers without policies have discussed development of a policy but did not formalize it due to lack of legal guidance as a barrier to policy adoption. Out of the nine centers that had a policy, four required prior written consent, while five allowed for verbal or inferred consent from the surviving life partner. Conclusions Very few, about 1/3, of the surveyed academic medical centers have policies on posthumous sperm retrieval. Medical centers can adopt individualized policies based on guidelines published by the American Society for Reproductive Medicine. Funding None
Authors
Nicholas Waler
Ranjith Ramasamy |
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PD68-08 |
Efficacy of Anastrozole in Oligozoospermic Hypoandrogenic Subfertile Men – The Significance of Post Treatment Testosterone to Estradiol Ratio |
Infertility: Therapy II | 17BOS |
Abstract: PD68-08 Sources of Funding: None Introduction We aim to determine the effect of anastrazole on hormonal and seminal parameters in hypoandrogenic subfertile men. We also aim to assess whether seminal parameter changes are correlated to the magnitude of increase in testosterone to estrogen ratio in men responding to treatment. Methods A retrospective review was performed of all hypogonadal subfertile men attending a male infertility clinic and treated with anastrazole. Hormone analysis before treatment, 2 weeks after starting treatment and 4 months after were performed. Hormone analysis included measurements of total testosterone, estradiol, sex-hormone binding globulin, albumin, FSH and LH, and bioavailable testosterone was calculated. Semen analyses before treatment and 4 months after treatment were recorded. Total motile sperm count was calculated from the semen analysis. For statistical analysis, variables are presented as median interquartile range or mean ± standard error. A matched pairs analysis estimated significance of change in laboratory values and semen analyses with treatment. A sub-group analysis was performed of men with baseline oligozoospermia. In this group, we used linear regression to identify correlations between changes in hormone concentrations and increase in semen parameters. Results The study group consisted of 86 subfertile hypoandrogenic men with low testosterone to estradiol ratio (n=78) or a prior aversive reaction to clomiphene citrate (n=8). 95.3% of patients had an increased serum testosterone and decreased serum estradiol following treatment with anastrozole. Sperm concentration and total motile counts improved in 18 out of 21 subfertile hypoandrogenic oligozoospermic men treated with anastrozole. In these men, the magnitude of total motile count increase was significantly correlated with the change in the testosterone to estradiol ratio. None of the men with azoospermia or cryptozoospermia experienced an improvement in sperm in the ejaculate and microTESE recovery rates were 72.7% in these men. Conclusions Approximately 95% of men with hypoandrogenism responded with improved endocrine parameters, and a subset of oligozoospermic men (approximately 25% of all patients) displayed significantly improved sperm parameters. In that subset, increase in sperm parameters was correlated with the change in the testosterone to estradiol ratio, which argues for a physiological effect of treatment. Funding None
Authors
Nikita Abhyankar
Ohad Shoshany Daniel Garvey Craig Niederberger |
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PD68-09 |
Demographics, Usage Patterns, and Safety of Male Users of Clomiphene in the United States |
Infertility: Therapy II | 17BOS |
Abstract: PD68-09 Sources of Funding: None Introduction Infertility affects 15% of all couples in the United States (US) with up to half having a male etiology. There are currently no oral treatments of male infertility approved for use by the Food and Drug Administration. The selective estrogen receptor modulator Clomiphene is the most commonly prescribed such agent, however its usage is only described in case series. We sought to characterize the demographics and usage patterns of Clomiphene for male infertility across the United States. Methods This is a retrospective cohort study of individuals in the Truven Health MarketScan® claims database from 2001 to 2009. This US database provides information of insurance claims filed for the care of privately insured individuals with employment-based insurance. While the number of enrollees varies between years, recent years contained up to 30 million people. Pharmacy claims were used to identify the usage patterns of Clomiphene among male enrollees. Associated diagnoses and treatments were identified by utilizing International Classification of Diseases, 9th edition (ICD-9) and Current Procedural Terminology (CPT) codes. Rates of side effects previously reported for Clomiphene were compared 6 months before and 6 months after medication usage. Results 3,922 men took Clomiphene and represented the primary study cohort, with a mean age of 35 years. Usage varied between 0.3% to 0.8%, with the highest prevalence among men 30-39 years old. No trend of usage was noted during the study period. Associated diagnoses of Clomiphene users included male infertility (59%), testicular hypofunction (32%), erectile dysfunction (8.6%), and low libido (0.6%). Infertility evaluation with semen analysis was performed in 55% of men. Testing for testosterone, LH, and FSH was done in 38%, 31%, and 35%. The median time of use was 2.4 months, with 73% of men stopping within 6 months, 17% stopping within the first year, and 3% continuing for more than 2 years. No increased risk of reported Clomiphene side effects (thrombotic events, vision problems, gynecomastia, mental disorders, liver disease, nausea, or skin problems) were apparent in men taking the medication. Conclusions The current report is the first to characterize the demographics and national usage patterns of Clomiphene, the most commonly prescribed oral agent for male infertility. Knowledge of adjuvant testing and prescribing practices for Clomiphene may inform and improve patient care. No increased risk of reported side effects was detected. Additional studies are needed to further understand indications, efficacy, and safety of Clomiphene use in men. Funding None
Authors
Dimitar V. Zlatev
Shufeng Li Laurence C. Baker Michael L. Eisenberg |
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PD68-10 |
The Effect of Sperm Morphology on Intrauterine Insemination Pregnancy Success Rate: A Systematic Review and Meta-Analysis |
Infertility: Therapy II | 17BOS |
Abstract: PD68-10 Sources of Funding: None Introduction Multiple studies have demonstrated a higher intrauterine insemination (IUI) pregnancy success in men with >4% normal morphology compared to men with ≤4% normal sperm morphology; other studies have not demonstrated this relationship. We performed a systematic review and meta-analysis to assess the effect of abnormal sperm morphology on pregnancy success for couples undergoing IUI._x000D_ Methods We performed a systematic search of MEDLINE, EMBASE, and Clinicaltrial.gov for studies evaluating semen morphology using the strict criteria and IUI success rates (measured by clinical pregnancies per cycle of IUI) published through April 2016. Studies were eligible for inclusion if they assessed IUI pregnancy success rate for percent sperm morphology >4% and ≤4% or percent sperm morphology ≥1% and <1%. Estimates were pooled using random-effects meta-analysis. Differences by study-level characteristics were estimated using meta-regression._x000D_ Results Data were extracted from 22 trials involving 25,817 cycles. 19 trials reported sperm morphology >4% and ≤4% and 13 trials reported sperm morphology ≥1% and <1%. Average pregnancy success rates for couples with a normal sperm morphology >4% was 15.29% [95% CI: 12.89% to 18.05%; I2=91.5%]. There was no significantly difference when compared to the pregnancy success rate for couples with normal sperm morphology ≤4%: 13.00% [95% CI: 10.76% to 15.63%; I2=88.9%]; between-group difference, P = 0.205. No significant difference was seen between the average pregnancy success for couples with a sperm morphology ≥1%: 14.06% [95% CI: 12.47% to 15.81%; I2=80.1%] compared to the pregnancy success for couples with sperm morphology <1%: 13.33% [95% CI: 9.93% to 17.68%; I2=28.9%]; between-group difference P = 0.739. Using meta-regression, no within-group confounders were noted for wither 1% threshold and 4% threshold when potential confounders such as female age, average total motile count (TMC), minimum TMC required for IUI, and average year of study (P > 0.05)._x000D_ Conclusions Neither the threshold of sperm morphology between >4% and ≤4% and ≥1% and <1% was statistically significant nor clinically significant. Thus for couples with abnormal morphology, IUI ought to be trialed prior to proceeding to significantly more expensive in vitro fertilization. We recommend that men with isolated abnormal sperm morphology should not be counseled against trial of IUI even if sperm morphology is <1%. _x000D_ Funding None
Authors
Taylor P. Kohn
Jaden R. Kohn Samuel A. Shabtaie Nancy L. Brackett Charles M. Lynne Ranjith Ramasamy |
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PD68-11 |
FATE OF RECURRENT OR PERSISTENT VARICOCELE IN THE ERA OF ASSISTED REPRODUCTION TECHNOLOGY: MICROSURGICAL SUBINGUINAL REDO VARICOCELECTOMY VERSUS OBSERVATION |
Infertility: Therapy II | 17BOS |
Abstract: PD68-11 Sources of Funding: None Introduction The role of redo varicocelectomy in infertile males with recurrent or persistent varicocele is controversial in the era of assisted reproductive technology (ART). The aim of the study was to compare sperm parameters, pregnancy and miscarriage rates between the men with recurrent or persistent varicocele who underwent redo microsurgical subinguinal varicocelectomy or had observation only. Methods The study included 217 infertile men with recurrent or persistent varicocele. The patients were divided into two groups: 120 men underwent redo microsurgical subinguinal varicocele repair, and 97 had observation only, as the control group. All patients had clinical varicoceles, and recurrences were confirmed with color Doppler ultrasound. Indications for redo varicocelectomy were no improvement in semen parameters and not achieving pregnancy after at least 6 months of initial varicocelectomy. Difference in total motile sperm count (TMSC), serum follicle stimulating hormone (FSH) and total testosterone levels from the beginning to the end of the study, pregnancy (spontaneous or with the use of ART) and miscarriage rates were compared between the two groups. Results Baseline mean patient and female partners ages, recurrent varicocele sites, TMSC, serum FSH and total testosterone levels, time to recurrence and follow-up period did not significantly differ between the two groups. The mean TMSC increased from 20.93±2.87 to 45.54±6.28 million in the microsurgical redo varicocelectomy group, and decreased from 16.62±2.75 to 15.6±2.81 million in the control group, revealing significant difference between the two groups (p=0.000). Increase in total testosterone was significantly higher in the microsurgical redo varicocelectomy group (+1.36±0.32 ng/ml) than in the control group (-0.23±0.1 ng/ml) (p=0.000). Of the couples, 63 (52.5%) achieved to pregnancy in the redo microsurgical varicocelectomy group, and 38 (39.2%) had pregnancy in the control group (p<0.05). Spontaneous pregnancy rate was significantly higher in the microsurgical varicocelectomy group (39.7%) than in the control group (15.8%) (p<0.01). Use of ART to achieve pregnancy was significantly lower in the microsurgical varicocelectomy group (60.3%) than in the control group (84.2%) (p<0.01). Conclusions Microsurgical subinguinal redo varicocelectomy improves postoperative semen parameters, serum total testosterone level and spontaneous pregnancy rates, compared to the controls. It also decreases need for use and level of ART. Funding None
Authors
Selahittin Çayan
Erdem Akbay |
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PD68-12 |
Study to analyse the fertility potential of varicocelectomy in non-obstructive azoospermia (NOA), virtual azoospermia (VA) and severe oligospermia (SO) |
Infertility: Therapy II | 17BOS |
Abstract: PD68-12 Sources of Funding: None Introduction Varicocele occurs in 35% and 75% of primary and secondary infertility. Azoospermia and SO occurs in 4.3% and 13.3% patients with varicocele._x000D_ Primary objective was to analyse improvement in semen parameters after varicocelectomy in NOA, VA, SO groups. _x000D_ Secondary objective was to analyse the pregnancy outcomes after varicocelectomy. _x000D_ Methods Single centre study over 6 years of 25 adult patients of primary infertility with NOA, SO (< 5 million/ml), VA (< 1 milion/ml) with clinical varicocele and testicular size >10cc, semen volume >1.5 ml, pH >7.2 and normal FSH, testosterone levels and normal female evaluation. Patients were operated by loupe guided microsurgical subinguinal artery, lymphatic sparing varicocelectomy followed by needle aspiration biopsy (NAB) of bilateral testes. Semen analysis was done at 3, 6 months. Response was evaluated by improvement in sperm counts, progressive motility and pregnancy outcome. Results Mean age and mean duration of infertility were 30.64 years, 4.36 years. 18 patients had grade 2 varicocele, 4 had grade 1, 3 had grade 3 with mean grade of 1.96. Average testicular size was 19.16 cc. Mean counts improved from 1.052 to 8.456 (million/ml) (p<0.0001). Mean progressive motility improved from 15.76% to 24.4% (p<0.001). Twenty-one (84%) patients responded and four patients (16%) did not respond. Between two groups age, duration and grade were not significantly different. Amongst NOA, VA, SO groups; age, duration, grade, testicular size were not significantly different. 5 patients had pregnancy (2 spontaneous, 3 IUI). Mean time was 15 months (spontaneous), 4.5 months (IUI). They had significant improvement in motility (p 0.003). Grade was significantly different in pregnant (2.4) and non-pregnant (1.85) groups (p 0.048). On NAB 4 had hypospermatogenesis, 1 had late MA. In follow up no-one had recurrence, 1 patient had unilateral hydrocele. Limitations were small sample size and non-randomisation. _x000D_ _x000D_ Conclusions Significant improvement in sperm counts and motility occurred after varicocelectomy in general (NOA, VA, SO). Age >33 years, duration >7.75 years, abnormal testicular histology were risk factors for non-responsiveness. Hypospermatogenesis was relatively better and early MA was worst for pregnancy outcome. Funding None
Authors
Ashwin Tamhankar
Ajit Sawant Vijay Kulkarni Prakash Pawar Shankar Mundhe Sunil Patil |
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PD69-01 |
A Phase IIa Study to Investigate the Efficacy and Safety of the Selective Oxytocin Receptor Antagonist, IX-01, in Men with Lifelong Premature Ejaculation |
Sexual Function/Dysfunction: Medical, Hormonal & Non-surgical Therapy II | 17BOS |
Abstract: PD69-01 Sources of Funding: Ixchelsis Ltd. Introduction Premature Ejaculation (PE) is associated with rapid ejaculation, inability to delay ejaculation and distress. There are no approved pharmacological treatments in US. The objective was to test the efficacy and safety of IX-01, an orally administered selective oxytocin receptor (OTR) antagonist with potential to treat PE. Methods A double-blind, placebo-controlled trial (NCT02232425) was performed in US and Australia. Eligibility criteria included lifelong PE, ≥4 intercourse attempts during a 4 week run-in, with intravaginal ejaculatory latency time (IELT) ≤1 minute measured by stopwatch on ≥75% occasions and none > 2 minutes. Men were randomized (2:1) to receive IX-01 or placebo taken 1-6 hours before intercourse during 8 weeks treatment. The starting dose was 400 mg and could be increased to 800 mg or equivalent placebo. Efficacy was assessed by IELT, Clinical Global Impression of Change (CGIC), and Premature Ejaculation Profile (PEP). Safety assessments included adverse events (AEs), vital signs, laboratory tests, electrocardiograms, and depression scales. Results Eighty-six men (mean age 43 years) received ≥1 dose of study drug. Men took a mean of 14.6 (range 1-59) and 13.0 (range 1-51) doses of IX-01 and placebo respectively. Fifty (89.3%) men took the maximum 800 mg dose of IX-01 at least once during the study. The main efficacy results are depicted in Table 1. IX-01 showed clinically and statistically significant improvements in IELT and patient reported outcomes compared to placebo. A summary of the AE&[prime]s is presented in Table 2. The AE profile of IX-01 was similar to placebo. No other safety signals were detected. Conclusions This is the first study to demonstrate the efficacy of an OTR antagonist to treat PE. IX-01 was well tolerated and prolonged IELT, and improved ejaculation control and diminished distress in men with lifelong PE. Funding Ixchelsis Ltd.
Authors
Christopher McMahon
Ian Osterloh Raymond Rosen Stanley Althof Gary Muirhead Brian Harty Francois Giuliano Martin Miner Bronwyn Stuckey Marc Gittelman Laurence Belkoff Wayne Hellstrom Allen Seftel Irwin Goldstein |
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PD69-02 |
Double-Blind, Randomized Controlled Trial of Topical 4% Benzocaine Wipes for Management of Premature Ejaculation: Interim analysis |
Sexual Function/Dysfunction: Medical, Hormonal & Non-surgical Therapy II | 17BOS |
Abstract: PD69-02 Sources of Funding: PREBOOST &[reg] : Veru Healthcare / The Female Health Company Introduction Premature ejaculation (PE) is the most common form of sexual dysfunction in men yet few safe and effective therapies exist. A variety of local anesthetics have been studied, but lack of efficacy has restricted widespread use. We performed a randomized, double-blind controlled trial to evaluate the use of a novel topical 4% benzocaine wipe for management of PE. Methods We enrolled men aged ≥ 18 years in a heterosexual, monogamous relationship with PE as defined by self-reported poor control over ejaculation, personal distress related to ejaculation, and average intravaginal ejaculatory latency time (IELT) ≤ 2 minutes on stopwatch measurement. Subjects were randomized in a 2:1 fashion to treatment with benzocaine wipes or placebo. One month after randomization, men in the placebo group were crossed over to the treatment group. Primary outcome was change in IELT at two months. Secondary outcomes included change in questionnaire assessments including global rating of distress, medication assessment, and Index of Premature Ejaculation (IPE). Wilcoxon rank-sum test was used for comparison of all outcomes. Results An interim analysis was conducted in 21 men who were randomized (15 treatment, 6 placebo) and had complete follow-up data. Baseline mean ± standard deviation IELT was 74.3 ± 31.8 vs 84.9 ± 29.8 seconds among the treatment and placebo groups, respectively (p=0.39). After 2 months, men in the treatment group had significant improvement in IELT with a mean increase of 231.5 ± 166.9 seconds (95% confidence interval of 139-323 seconds) which was significantly greater than men on placebo (94.2 ± 67.1 seconds, p= 0.043). A greater proportion of men in the treatment group after one and two months achieved IELT of at least 2 minutes vs placebo (60%, 80.0% vs 33.3% respectively). Compared to placebo, men in the treatment group reported greater improvement in distress relating to intercourse, control of ejaculation, and satisfaction with sexual intercourse over the study period (p<0.01, p=0.01, and p<0.01, respectively). Treatment was well tolerated and no transference was reported. Conclusions Topical 4% benzocaine wipes improved both objective and subjective symptoms of PE compared to placebo. Funding PREBOOST &[reg] : Veru Healthcare / The Female Health Company
Authors
Ridwan Shabsigh
Jed Kaminetsky Michael Yang Michael Perelman |
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PD69-03 |
Comparison of efficay and safety for erectile dysfunction of mirodenalfil 50mg once daily and 100mg on-demand in patients with radical prostatectomy : Multicenter, Randomized trial. |
Sexual Function/Dysfunction: Medical, Hormonal & Non-surgical Therapy II | 17BOS |
Abstract: PD69-03 Sources of Funding: SK chemicals Korea Introduction To compare the improvement of erectile dysfunction (ED) as well as safety of mirodenalfil 50mg once daily and 100mg on-demand in patients with radical prostatectomy due to prostate cancer. Methods Prospective study was done with 166 patients who had ED after taken radical prostatectomy due to prostate cancer from June 2013 to October 2014. Out of 184 individuals, 171 met inclusion criteria and 153 finished the research. Patients were divided into two groups. Group 1 had mirodenafil 50mg daily and Group 2 had mirodenafil 100mg on-demand. The ?ve-item version of the International Index of Erectile Function (IIEF-5), SEP Q2, Q3 were assessed immediately before initiation of treatment (V1) and after two (V2), six (V3) and twelve months of treatment (V4). Also, to investigate the safety, blood pressure, pulse, and side effect were evaluated. Results Out of 171 individuals, 153 (89.4%) finished the research (group 1: n=74, 48.4%, group 2: n=79, 51.6%). Statistically, there were no difference of IIEF-5 at V1 between two groups. Both groups had meaningful improvement on IIEF-5 in V2,V3, V4 and group 1 had better improvement than group 2 (10.9±4.1 vs. 8.0±5.3, δ4.0±2.6, p=0.01) (Table1). Group 1 had larger improvements than Group 2 in SEP Q2 and Q3 significantly (V4-Q2: 60.1% vs. 50.7%, p=0.01, Q3: 58.4% vs.48.8%, p=0.01). There was no drop out patients due to cardiovascular problems and other side effects. Conclusions The administration of a 5 mg dose of mirodenafil daily to patients who had erectile dysfunction that had undergone a radical prostatectomy due to prostate cancer had batter effect on the recovery and maintenance of erectile function than 100mg dose of mirodenafil. The side effects were insignificant for both dosing schedules._x000D_ _x000D_ Funding SK chemicals Korea
Authors
Kyu Shik Kim
Tae Hyo Kim Joon Hwa Noh Jae Hyun Bae Cheol Young Oh Jin Sun Cho Ho Song Yu Seung Hwan Lee Sung Yong Cho Hee Ju Cho Jeong Man Cho Jae Duck Choi June Hyun Han U-Syn Ha Sung Hoo Hong Yong Tae Kim Hong Yong Choi Seung Wook Lee |
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PD69-04 |
Safety and Efficacy of Low-intensity Extracorporeal Shockwave in the Treatment of Vasculogenic Erectile Dysfunction: a multi-center, double-blind, randomized sham-controlled clinical trial |
Sexual Function/Dysfunction: Medical, Hormonal & Non-surgical Therapy II | 17BOS |
Abstract: PD69-04 Sources of Funding: None. Introduction To evaluate the safety and efficacy of Low-intensity Extracorporeal Shockwave (LI-ESWT) in the Treatment of Vasculogenic Erectile Dysfunction. Methods A multi-center, double-blind, randomized sham-controlled clinical trial was conducted. 70 patients (46 cases for LI-ESWT treatment group and 24 cases for the placebo group) at age 20-70 years, who had mild or moderate Vasculogenic ED evaluated with the International Index of Erectile Function erectile function domain (IIEF-EF) were recruited for this study. Screening, treatment and results were performed in sequence. 4 weekly sessions for the treatment stage: A total of 5000 shockwaves were applied for each treatment and 4 areas were conducted including: 900 shockwaves in right and left crura, and 1600 shockwaves in each site. Effectiveness was assessed according to the International Index of Erectile Function erectile function domain (IIEF-EF), questions 2 and 3 of the Sexual Encounter Profile (SEP), Global Assessment Question (GAQ) scores, and Erection Hardness Scale (EHS) at baseline and at 1 and 3 months after treatment. The study was approved by Peking University First Hospital ethics committee, and all patients signed an informed consent form. Results For Full Analysis Set (FAS) and Per-Protocol Set (PPS), the average IIEF-EF increased significantly from 18.04±3.94 (17.90±3.77) at baseline to 22.02±4.13 (21.95±4.06) at 1 months post treatment, and was 22.54±3.98 (22.49±3.90) at the 3 months follow-up. The success rate by LI-ESWT is 67.39% (73.17%) after 1months post treatment VS 20.83% (23.81%) in the placebo group and is 69.57% (73.17%) after 3 months post treatment VS 20.83% (23.81%) in the placebo group by FAS (PPS). SEP, GAQ, EHS analysis were also significantly improved compared to the placebo controls (p<0.05). No side effects were reported in this study. _x000D_ _x000D_ Conclusions LI-ESWT in patients with mild or moderate Vasculogenic ED is a feasible, noninvasive and effective way for improving male ED. Funding None.
Authors
Zhongcheng Xin
Ruili Guan Wanshou Cui Xiaodong Zhang Long Tian Yi Xie Hongen Lei Jihong Liu Tao Wang |
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PD69-05 |
Efficacy and safety of fixed dose combination of tamsulosin and tadalafil in patients with benign prostatic hyperplasia and erectile dysfunction |
Sexual Function/Dysfunction: Medical, Hormonal & Non-surgical Therapy II | 17BOS |
Abstract: PD69-05 Sources of Funding: Hanmi Pharmaceutical Co., Ltd., Seoul, Korea Introduction Lower urinary tract symptoms (LUTS) resulting from benign prostatic hyperplasia (BPH) and erectile dysfunction (ED) are commonly occurred in aged men and known to be mechanistically associated each other. The aim of this study was to evaluate the efficacy and safety of once-daily fixed dose combination (FDC) of tamsulosin and tadalafil in patients with BPH and ED in comparison to tadalafil mono-therapy. Methods In a phase III, multi-center, randomized, double-blinded and placebo-controlled clinical trial, participants were randomly assigned to active treatment groups of either FDCs consisting tamsulosin 0.4 or 0.2mg in combination of tadalafil 5mg or mono-component of tadalafil 5mg for 12-week treatment period, followed by an open-label extension period that continued up to week 24, while being treated with FDC of tamsulosin 0.4 mg and tadalafil 5mg. The primary efficacy variables of the study were assessed after 12 weeks of treatment using the international prostate symptom score (IPSS) and International Index of Erectile Function (IIEF). Other assessments included Sexual Encounter Profile, Global Assessment Question, Qmax, PSA, and PVR at every visit with four- or six-week interval. Eligible patients were men aged over 45 years with BPH confirmed by total IPSS greater than or equal to 13 and ED persistent for longer than 3 months. Results Total 510 subjects were enrolled. The mean decrease from baseline in total IPSS at week 12 of the treatment period was significantly greater in the FDC of tamsulosin 0.4 mg group compared to the tadalafil 5mg group (p=0.0320). The lower limit of one-sided 97.5% confidence interval of changes from baseline in IIEF-Erectile Function (EF) domain score was greater than the pre-specified non-inferiority margin (-3.22) for both FDCs of tamsulosin 0.4 and 0.2mg. Treatment change from tadalafil 5 mg mono-therapy to FDC of tamsulosin 0.4mg and tadalafil 5mg made significant improvement in total IPSS at week 24 of the extension period after treatment change at week 12 (p<0.0001). The most frequent adverse drug reactions included headache, flushing, nasal congestion and ocular hyperaemia, all of which were of mild or moderate intensity and both FDCs of tamsulosin 0.4 and 0.2mg were well tolerated. Conclusions The FDC of tadalafil 5mg and tamsulosin 0.4mg substantiated superiority for BPH/LUTS treatment and non-inferiority for ED treatment over tadalafil 5mg mono-therapy without showing any clinically significant safety issues, supporting favorable benefit-risk balance of the FDC for the treatment of comorbid BPH and ED. Funding Hanmi Pharmaceutical Co., Ltd., Seoul, Korea
Authors
Sae Woong Kim
Jina Jung Yong-Il Kim Jae Seog Hyun Du Geon Moon Nam Cheol Park Sung Won Lee Soo Woong Kim Tai Young Ahn Ki Hak Moon Kweon Sik Min Ji-Kan Ryu Kwangsung Park Jong Kwan Park Sang-Kuk Yang Dae Yul Yang Seung Wook Lee |
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PD69-06 |
Clinical Improvements in Erectile Function and Mood in Hypogonadal Men Treated with 4.5% Nasal Testosterone Gel |
Sexual Function/Dysfunction: Medical, Hormonal & Non-surgical Therapy II | 17BOS |
Abstract: PD69-06 Sources of Funding: Support from Trimel/Acerus Pharmaceuticals for the Phase 3 clinical trial. Introduction Male hypogonadism is a clinical syndrome resulting from failure of the testis to produce physiologic levels of testosterone (T) due to disruption of the hypothalamic-pituitary-gonadal axis. Hypogonadism is characterized by many ill-effects including mood disturbances, reduced energy levels, and impaired sexual function. A Phase 3 study investigated the safety and efficacy of a 4.5% testosterone gel administered intranasally (nasal testosterone gel - NTG). Herein we describe the efficacy of NTG administration outcomes on erectile function and mood correlations using validated questionnaires. Methods The study was a 90-day, randomized, open-label, dose-ranging study in hypogonadal men with sequential safety extensions out to 1 year. 4.5% NTG (125 uL/nostril, 11.0mg testosterone/dose) was self-administered using a multiple-dose dispenser either twice daily (BID) or 3 times a day (TID) for a total dose of 22.0mg or 33.0mg, respectively. Titration was performed based on blood levels so as to achieve the eugonadal range (300 -1050 ng/dL). Erectile function and mood were assessed at baseline (day 0), and 30 day intervals through the 90-day treatment period using the International Index of Erectile Function (IIEF) and Positive and Negative Affect Schedule (PANAS), respectively. Results Treatment with NTG led to statistically significant improvements in each of the 5 domains of erectile function (F(3,813) = 83.96 p < .001). Most of the benefit was evident by Day 30 (t = -9.8714, df = 288, p-value < .001) with much smaller increases until study completion (Figure 1). Similar to erectile function, NTG produced clinically and statistically significant improvements in mood (PANAS) by Day 30, with continued (non-significant) improvements seen through study completion (Figure 2). Conclusions NTG achieves large, clinical improvements in erectile function and mood within 30 days of treatment, with the added bonus of improvements in sexual desire. NTG is a safe, effective, and unique form of TTh, and is approved for use in the United States. Funding Support from Trimel/Acerus Pharmaceuticals for the Phase 3 clinical trial.
Authors
Larry Lipshultz, MD
Gerwin Westfield, PhD Margaux Guidry, PhD Nathan Bryson, PhD Mohit Khera, MD |
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PD69-07 |
Erectile Function Outcomes Of Prostate Cancer Patient Treated With Triple Therapy |
Sexual Function/Dysfunction: Medical, Hormonal & Non-surgical Therapy II | 17BOS |
Abstract: PD69-07 Sources of Funding: None Introduction The combination of radical prostatectomy (RP), radiation therapy (RT) and androgen deprivation therapy (ADT) - triple therapy (TT) is reserved for prostate cancer patients of extremely high risk or with PSA recurrence after primary therapy. The combination of these 3 treatments has a significant negative impact upon sexual function. This analysis was conducted to define the effect of TT on long-term erectile function (EF). Methods Study population consisted of patients who (i) were exposed to TT (in any order) (ii) had baseline EF assessed by erection hardness score (EHS) (iii) were at least 6 months after completion of ADT (iv) had an early morning serum total testosterone level ≥6 months (m) after ADT completion and (v) had erectile function assessed (EHS, IIEF) at last follow-up visit. At ≥6m after ADT cessation, patients used maximum dose PDE5 inhibitor (PDE5i) on 4 occasions. If they failed they moved directly to penile injection therapy. Injection therapy was deemed to have failed if patients had been titrated to 100 units of trimix (papaverine/phentolamine/PGE1) without success. Multivariable analysis was performed to define predictors of penetration hardness erections with penile injections. Factors analyzed in the model included: patient age, baseline EF, ADT duration, nerve sparing status at RP and end-of-treatment (EOT) total testosterone Results 436 men met the inclusion criteria. Mean age 68±11 years. Gleason scores: 7 68%, 8 19%, 9 13%. Nerve sparing status at RP: unilateral 12%, non-nerve sparing 88%. RT modality: 3D-conformal 17%, IMRT 51%, brachytherapy 32%. Baseline median EHS score was 3, with 7% grade 2 64% grade 3, 29% grade 4. Mean ADT duration was 9±11 (4-28) months. Mean duration at last visit since cessation of ADT (last dose plus wash-out period) was 9±5 months. Mean total testosterone level at last visit 262±317 (86-742 ng/dl). 6% of men responded to PDE5i while only 49% responded to penile injections. At EOT on injections: median EHS was 2 with no patient achieving a grade 4 erection; mean IIEF EFD score was 14±9 (4-24). Predictors of injection response are listed in the Table. Conclusions Triple therapy for prostate cancer has a devastating effect on erectile function with more than half of the patients failing to respond to penile injection therapy. Funding None
Authors
Jose Torremade
Yanira Ortega Kazuhito Matsushita John P Mulhall |
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PD69-08 |
The Impact Of Androgen Deprivation Therapy On Compliance With Intracavernous Injections |
Sexual Function/Dysfunction: Medical, Hormonal & Non-surgical Therapy II | 17BOS |
Abstract: PD69-08 Sources of Funding: None Introduction Androgen deprivation therapy (ADT) for prostate cancer lowers testosterone to castrate levels resulting in loss of sex drive, difficulty achieving orgasm and erectile tissue structural changes. Intracavernous injections (IC) are well recognized as a strategy for treating ED and are used regularly in erectile rehabilitation programs for men after radical prostatectomy and prostate radiation. There is no available literature on the compliance of men on IC who are concomitantly on ADT. Methods Men with ED who had failed maximum dose PDE5 inhibitor agents; were enrolled in our IC program for ≥12 months (m); men treated with radiation therapy (RT) alone were compared to men who had had RT combined with ADT (and were still using ADT). 12 month follow-up or longer was required to be included in the analysis. Demographic, comorbidity, sexual function and sexual activity data were recorded. IC compliance was defined as use of IC ≥1/month and patients were followed at 3 months (m), 6m and 12 months after initial in-office IC training. Multivariable analysis was performed to define predictors of continued use of IC at 12 m after training completion. Results 410 men were included: 216 RT alone, 194 RT+ADT. Mean age 67±14 years; RT type was IMRT 226, brachytherapy 184; 82% of men were partnered (no difference between groups in any of these 3 factors). IC compliance for RT alone and RT+ADT groups was: @3m 84% vs 41%; @6m 76% vs 22%; @12m 81% vs 10% (all p<0.01). Predictors of IC compliance at 12 m after training are listed in Table. Conclusions RT patients exposed to ADT struggle to comply with IC therapy despite understanding the role it might play in erectile rehabilitation of such patients. Younger, partnered and historically sexually active men were more likely to continue injection therapy long-term. Funding None
Authors
Jose Torremade
Coskun Kagacan Joseph Narus John P Mulhall |
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PD69-09 |
SCROTOX: Salvage Peri-spermatic cord Botulinum-A Toxin injections for patients with refractory chronic scrotal content pain after microsurgical denervation of the spermatic cord. |
Sexual Function/Dysfunction: Medical, Hormonal & Non-surgical Therapy II | 17BOS |
Abstract: PD69-09 Sources of Funding: None Introduction Chronic scrotal content pain is a difficult condition to treat. Microsurgical denervation of the spermatic cord (MDSC) is one surgical treatment option with success rates published in the 60-85% range. However, patients who fail MDSC have limited options. Botulinum-A toxin (Botox) has been shown to modulate the release of neuropeptides leading to inhibition of neurogenic inflammation and chronic pain. This provides an antinociceptive effect. Our goal was to assess the use of peri-spermatic cord Botox injections (Scrotox) to provide prolonged pain relief in men with refractory chronic scrotal content pain after MDSC. Methods Retrospective review of 44 patients who underwent Scrotox (60 procedures: 30 bilateral, 15 right side, 15 left side) from July 2013 to July 2016. All patients had failed prior MDSC. 100 units of Botox diluted in 10cc of saline was injected medial and lateral to the spermatic cord at the level of the external inguinal ring to ablate branches of the genitofemoral, ilioinguinal and inferior hypogastric nerves. The primary outcome measure was the level of pain. Pain was assessed preoperatively and postoperatively using two assessment tools: a) the subjective visual analog scale (VAS) and b) an objective standardized externally validated pain assessment tool (PIQ-6, QualityMetric Inc., Lincoln, RI). Results Median age was 45 years. Median duration of pain prior to the procedure was 9 years. Median follow up post procedure was 7 months. Subjective VAS patient pain outcomes: 62.5% significant reduction in pain (7.5% complete resolution, 55% reported a greater than 50% reduction in pain) by 3 months post-op. Objective PIQ-6 outcomes: significant reduction in pain in 27% of patients at 6 months and 40% at 1 year post-op. There were no complications in our cohort. Conclusions Scrotox is a potentially safe and viable treatment option for the salvage management of persistent chronic scrotal content pain in patients who have failed MDSC. Further studies are warranted to better understand the long-term durability of this treatment modality. Funding None
Authors
Nahomy Calixte
Bayo Tojuola Ibrahim Kartal Ahmet Gudeloglu Jamin Brahmbhatt Sijo Parekattil |
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PD69-10 |
Does Surgical Approach Affect Rates of Erectile Dysfunction Treatment Following Radical Cystectomy: Analysis of a Nationwide Insurance Claims Database |
Sexual Function/Dysfunction: Medical, Hormonal & Non-surgical Therapy II | 17BOS |
Abstract: PD69-10 Sources of Funding: none Introduction As survival following radical cystectomy (RC) improves, it is important to increase focus on survivorship issues such as sexual function. Therefore, our objective was to determine the rates of erectile dysfunction (ED) treatment use in bladder cancer patients prior to and following RC and to determine if surgical approach affects these treatment rates in order to better understand current patterns of care. Methods Male bladder cancer patients undergoing RC were identified in the MarketScan database (2010-2014). ED treatment was defined as use of phosphodiesterase-5 inhibitors, intracavernosal injections, vacuum erection devices, urethral suppositories, or implantable penile prosthesis. ED treatment use was assessed at baseline (in the year prior to RC) and at 6-month intervals (0-6, 7-12, 13-18, 19-24 months) following RC. At each time point, ED treatment use was compared between patients who underwent open RC (ORC) and minimally-invasive RC (MIRC). Multivariable logistic regression models were used to identify predictors of ED treatment use at 6-month intervals following RC. Results In the cohort of 1176 patients, at baseline, 6.5% (n=77) of patients used ED treatments. The rates of ED treatment use at 0-6, 7-12, 13-18, and 19-24 months following RC were 15.2%, 12.7%, 8.1%, and 10.1% respectively. At baseline and all follow-up time points assessed, the rates of ED pharmacotherapy use between the ORC (n=1009) and MIRC (n=167) groups were comparable. In the multivariable model, predictors of ED treatment use in 0-6 months following RC were age <50 (OR=3.17 95% CI [1.68, 6.01]), baseline ED treatment use (OR=5.75 95%CI [3.08, 10.72]), neoadjuvant chemotherapy (OR=1.72 95%CI [1.13, 2.61]), and neobladder diversion (OR=2.40 95%CI [1.56, 3.70]). Baseline ED treatment use continued to be associated with ED treatment use at 6-12 months (OR=5.63 95%CI [2.42, 13.10]) and 13-18 months (OR=8.99 95%CI [3.05, 26.51]) following RC. Surgical approach (MIRC vs. ORC) was not associated with ED treatment use at any of the follow-up points. Conclusions ED treatment use following RC is quite low, and is not associated with surgical approach. The strongest predictor of ED treatment use following RC is baseline treatment use followed by younger age. These findings suggest either ED treatment is of low priority for RC patients or sexual function issues may not be commonly discussed with patients following RC. Urologists should consider discussing sexual function more frequently with their RC patients. Funding none
Authors
Meera Chappidi
Max Kates Gregory Joice Phillip Pierorazio Trinity Bivalacqua |
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PD69-11 |
HIGH?DOSE INTRACAVERNOSAL PHENYLEPHRINE FOR PRIAPISM: IS IT SAFE? |
Sexual Function/Dysfunction: Medical, Hormonal & Non-surgical Therapy II | 17BOS |
Abstract: PD69-11 Sources of Funding: None. Introduction Acute ischemic priapism is considered a medical emergency, and prompt intervention is indicated to prevent potentially permanent erectile dysfunction (ED) and corporal fibrosis. Guidelines recommend using a stepwise approach to manage acute ischemic priapism, which includes corporal aspiration, irrigation, and intracavernous injection of sympathomimetic agents. At our institution, we treat a large number of patients for acute priapism. We sought to evaluate if large doses of phenylephrine (PE) resulted in any significant changes in vital signs or impacted outcomes. Methods After IRB approval, we retrospectively reviewed the charts of patients presenting to our emergency department between May 1, 2014 and August 15, 2016 using ICD9 and ICD10 diagnosis codes for priapism. Baseline variables were explored with categorical data analysis (Chi-Squared and T-tests). Where feasible, linear regression was used to evaluate outcomes. Results We identified 74 different patient encounters of acute priapism. 58 patients received PE during the course of their management. Of this group, the median age was 36.5 years (IQR = 27-47) and the median time to presentation was 5.4 hours (IQR = 4.0-9.6). 31 patients had previously experienced priapism. The median dose of PE given was 1,000 mcg (IQR 500-2,000). Univariate regression found no association between PE dose and change in patient heart rate or blood pressure. Even when considering patients who received a higher dose (greater than the median of 1,000 mcg), phenylephrine did not have a statistically significant effect on patient vital signs (see Figure). 53 of 58 (91%) patients receiving PE experienced detumescence, 2 required shunting in operating room, and 2 refused treatment and left against medical advice. Conclusions We frequently treat patients with high doses of PE and seldom notice adverse effects, typically resulting in resolution of priapism without any additional procedures. Careful administration of high-dose intracavernosal PE in patients presenting with priapism does not appear to affect hemodynamic stability and may help avoid ischemic damage and achieve detumescence effectively and efficiently. Funding None.
Authors
Ajaydeep S. Sidhu
George F. Wayne Bu J. Kim Alexander G. S. Anderson Joan C. Delto Maurilio Garcia-Gil Gustavo A. Diaz-Mercado Billy H. Cordon Jorge R. Caso Alan S. Polackwich |
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PD69-12 |
Survey of Sexual Function and Pornography |
Sexual Function/Dysfunction: Medical, Hormonal & Non-surgical Therapy II | 17BOS |
Abstract: PD69-12 Sources of Funding: None. Introduction In evaluating a male with sexual dysfunction, psychosexual factors should be considered. One potential but not well examined psychosexual factor is the impact of pornography use on sexual function. Given the large proportion of young men in the military and the potential detrimental effects of sexual dysfunction on quality of life, we sought to determine if there exists a correlation between degree of pornography use and sexual dysfunction. Methods After local institutional review board approval, patients aged 20-40 years presenting to a urology clinic were offered an anonymous survey consisting of self-reported medical history, demographic questions, validated questionnaires (including the International Index of Erectile Function [IIEF-15]), and novel questions addressing sexual function, pornography use, craving behavior, and obsessive behavior. For an interim analysis of those surveyed between February and August 2016, descriptive data were compiled and evidence for correlation between domains of the IIEF-15 and various aspects of pornography use was examined using linear regression tests. Results Surveys were completed by 312 respondents. The sample was generally healthy: 12% indicated a comorbidity other than tobacco use, 19.2% indicated tobacco use. The mean age was 31 years (sd=5.9). Common demographics included white race (64.4%), non-Hispanic ethnicity (74.6%), active duty (96.8%), enlisted (77.3%), and married (68.8%)._x000D_ The mean scores of the IIEF-15 domains were: 26.2 (sd=6.0) for erectile function, 8.6 (sd=2.1) for orgasmic function, 8.1 (sd=2.0) for sexual desire, 10.7 (sd=3.4) for intercourse satisfaction, and 7.9 (sd=2.3) for overall satisfaction. _x000D_ When asked how they best satisfied sexual desires, 96.6% indicated intercourse (with or without pornography) versus 3.4% who indicated masturbation to pornography. Weekly pornography use varied: 25.9% indicated less than weekly, 24.6% indicated 1-2 times, 21.3% indicated 3-5 times, 5.0% indicated 6-10 times, and 4.3% indicated greater than 11 times. The typical media for viewing pornography were internet on a computer (72.3%) or a smart phone (62.3%)._x000D_ There were statistically lower scores in all IIEF-15 domains amongst respondents reporting a preference for masturbating to pornography rather than intercourse (p <0.05). However, there were no significant correlations between frequency or duration of pornography use and IIEF-15 domain scores (p > 0.05). Conclusions There appears to be a relationship between pornography use and sexual dysfunction in men who report a preference for masturbation to pornography rather than sexual intercourse. Funding None.
Authors
Jonathan Berger
Andrew Doan John Kehoe Michael Marshall Warren Klam Donald Crain Matthew Christman |
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PD70-01 |
Effects of Water Avoidance Stress on Peripheral and Central Responses During Bladder Filling in the Rat |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology III | 17BOS |
Abstract: PD70-01 Sources of Funding: The NIH Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP, DK082370) Research Network to LV Rodriguez. Introduction Chronic emotional stress plays a role in the exacerbation and possibly the development of functional lower urinary tract disorders. Chronic water avoidance stress (WAS) in rodents is a model with high construct and face validity to bladder hypersensitivity syndromes, such as interstitial cystitis/bladder painful syndrome (IC/BPS), which manifest as urinary frequency and bladder hyperalgesia, which have been shown to be highly responsive to stress. Given the significant overlap of the brain circuits involved in stress, anxiety, and micturition, we evaluated the effects chronic stress has on bladder function and its effects on regional brain activation during bladder filling. Methods 16 adult female Wistar-Kyoto rats were randomized to 10-day WAS (n=8) or handled controls (n=8). On day 11, rats were evaluated by visceromotor reflex (VMR) for bladder hyperalgesia. VMR was obtained during isotonic bladder distention (0-40 cmH2O) with urethral occlusion. Cerebral perfusion was assessed during bladder distention (20 cmH2O) using [14C]-iodoantipyrine autoradiography with regional cerebral blood flow-related tissue radioactivity (rCBF) analyzed in 3-D reconstructed brains with statistical parametric mapping. Results At 20 cmH2O, VMR significantly increased in WAS compared to controls. WAS animals compared to controls showed greater activation in cortical regions of the central micturition circuit, with seed analysis showing increased functional connectivity of the cingulate to the parabrachial/Barrington nucleus complex (PBN), of the PBN to the thalamus and somatosensory and retrosplenial cortices, and of posterior insula to anterior secondary motor cortex. Conclusions The current study demonstrates how stress exacerbation of symptoms seen in the majority of patients with IC/PBS may be centrally mediated and gives us anatomic sites to further evaluate the biological mechanisms by which stress may induce or maintain bladder hyperalgesia and urinary frequency as well as a translational model to evaluate the molecular changes behind the brain differences seen in patients with IC/BPS. Collectively, our physiologic and brain mapping results suggest hypersensitivity during bladder filing in WAS animals, as well as increased engagement of portions of the micturition circuit responsive to urgency and the perception of bladder fullness, including viscerosensory perception and its relay to motor regions coordinating imminent bladder contractions. Funding The NIH Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP, DK082370) Research Network to LV Rodriguez.
Authors
Huiyi Harriet Chang
Zhuo Wang Yunliang Gao Rong Zhang Daniel P Holschneider Larissa V Rodriguez |
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PD70-02 |
cAMP-Dependent Regulation of RhoA/Rho-kinase Attenuates Detrusor Overactivity in a Novel Mouse Experimental Model |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology III | 17BOS |
Abstract: PD70-02 Sources of Funding: This study was supported by a grant from the National Health Institute (R01DK067223)._x000D_ William Akakpo received international mobility grants from the French Association of Urology (AFU) and the French Society of Urodynamics (SIFUD-PP). Introduction The pathophysiology of detrusor overactivity remains unclear. We hypothesized that dysregulation of S-nitrosylation, a process that mediates proteins activity, contributes to the pathogenesis of this disorder. We aim to investigate detrusor function and cAMP activation as a possible treatment for detrusor overactivity in an experimental model lacking a key denitrosylation enzyme, S-nitrosoglutathione reductase (GSNOR). _x000D_ Methods GSNOR-deficient (GSNOR-/-) (n=30) and wild-type (WT) mice (n=26) were treated for 7 days with the cAMP activator, Colforsin (1mg/kg), or vehicle intraperitoneally. Cystometric studies or molecular analyses of bladder specimens were performed. Bladder function indices and expression levels of proteins that regulate detrusor relaxation (nitric oxide synthase pathway) or contraction (RhoA/Rho-kinase pathway) and oxidative stress were assessed. Student t-test and one-way ANOVA were used. _x000D_ Results GSNOR-/- mice showed a significant increase (p<0.05) in voiding and non-voiding contraction frequencies compared to WT mice (figure 1, arrows indicate voiding contractions). Colforsin normalized these abnormalities. Western blot analyses showed an up-regulation of the RhoA/Rho-kinase pathway reflected by a significant increase (p<0.05) of phosphorylated-MYPT1 expression in GSNOR-/- mouse bladders, which was reversed by Colforsin treatment (figure 2). An increased level (p<0.05) of gp91phox expression in bladders of GSNOR-/- mice was observed without significant change after Colforsin treatment. Neuronal and endothelial nitric oxide synthase phosphorylation on Ser-1412 and Ser-1177, respectively, did not differ between GSNOR-/- and WT mouse bladders irrespective of Colforsin treatment. Conclusions Impaired denitrosylation contributes to detrusor overactivity in association with upregulated RhoA/Rho-kinase signaling. Colforsin reverses physiologic and molecular abnormalities. This study describes a novel model of detrusor overactivity and suggests a possible basis for its treatment. _x000D_ Funding This study was supported by a grant from the National Health Institute (R01DK067223)._x000D_ William Akakpo received international mobility grants from the French Association of Urology (AFU) and the French Society of Urodynamics (SIFUD-PP).
Authors
William Akakpo
Biljana Musicki Arthur Burnett |
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PD70-03 |
Freshly dissociated smooth muscle cells from detrusor overactive human bladders show abnormal expression of TREK-1 channels and caveolae membrane microdomains. |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology III | 17BOS |
Abstract: PD70-03 Sources of Funding: NIH/NIDDK RO1-DK095817 Introduction Detrusor Overactivity (DO) is the abnormal response of the urinary bladder to physiological stretch during the filling phase of the micturition cycle. Although the mechanisms underlying this response are poorly understood, increasing evidence suggest that TREK-1 channel, a mechanosensitive member of the two-pore potassium channel family (K2P, KCNK), is a key regulator of detrusor response to stretch. We hypothesized that changes in detrusor TREK-1 protein expression underlie excitability and force transduction alterations in DO. We aimed to: 1) study the changes in expression and function of TREK-1 channels and, 2) explore the basis of TREK-1 force transduction under pathological conditions associated with detrusor overactivity (DO) in the human detrusor. Methods We performed immunocytochemistry labeling, qRT-PCR, whole cell patch-clamp electrophysiological recordings and detrusor muscle strip contractility studies on freshly dissociated bladder smooth cells isolated from normal (AUA SS <8; n= 15) and DO (AUA SS >22; n= 33) human bladders. Results A two-fold depletion in TREK-1 channel protein expression was observed in specimens obtained from DO bladders in comparison to controls (4.6±2.1 vs 9.1±2.7. ≤ 0.05). This change was associated with a significant reduction of whole cell patch-clamp recorded TREK-1 currents (Control, 1087.0±99.3 pApF vs DO, 98.6±66.3 pApF at 60 mV, n=6 each. ≤0.001). Further, detrusor strips obtained from DO patients failed to relax when exposed to 10 µM of arachidonic acid, a TREK-1 channel opener. To study how the mechanical force is transduced, we performed confocal analysis of immunocytochemically labeled freshly dissociated detrusor smooth muscle cells against cytoskeletal elements. Our results revealed colocalization of TREK-1 channels with members of the caveolin protein family and cytoskeletal proteins. Interestingly, caveolae microdomains were severely disrupted in DO specimens. Conclusions Our data demonstrate a significant reduction of TREK-1 channel expression and function in human smooth muscle cells obtained from DO bladders. Further, we provided evidence of close association between TREK-1 channels, different elements of the cell cytoskeleton and caveolins suggesting the presence of TREK-1 enriched caveolae microdomains. Funding NIH/NIDDK RO1-DK095817
Authors
Ricardo Pineda
Balachandar Nedumaran Joseph Hypolite Shandra Wilson Randall B Meachan Anna P Malykhina |
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PD70-04 |
Optogenetic Modulation of Bladder Function |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology III | 17BOS |
Abstract: PD70-04 Sources of Funding: This work was funded by a grant from the NIH Common Fund - SPARC program, U18EB021793 to RG. McDonnell Center for Cellular and Molecular Neurology Postdoctoral Fellowship supported AM. Introduction Millions of people in the United States suffer from bladder dysfunction and pain caused by interstitial cystitis/bladder pain syndrome and overactive bladder. The underling pathologies for many of these diseases are poorly understood. To better delineate the role of sensory nerve fibers in bladder function, we have utilized optogenetics to spatially and temporally control bladder afferent activity. Methods Optogenetics involves the use of optically activatable pumps, channels or receptors (opsins) expressed in neurons to modulate their activity. We crossed mice expressing the Cre-dependent genes for the excitatory opsin channelrhodopsin-2 (ChR2) and the inhibitory archaerhodopsin (Arch) with mice that express Cre recombinase in Nav 1.8 or TRPV1 populations to restrict expression to nociceptive neurons (TRPV1-ChR2 and Nav 1.8-Arch). These opsins were activated be either blue (ChR2) or green (Arch) laser or LED illumination of the bladder. We then measured the influence of opsin activation on bladder function using continuous infusion cystometry. In order to translate this into a more clinically relevant gene delivery system, bladder wall injection of herpes simplex viral vector (HSV) with a pan-neuronal promotor controlling expression of ChR2 or Arch were used in rats. Results In TRPV1-ChR2 mice, ChR2 activation with blue light resulted in voiding events in a half full bladder that increased in magnitude with increase of light intensity. Activation of Arch with green light could delay regular cystometric contractions in Nav 1.8-Arch mice. In rats transduced with HSV-ChR2, we were able to evoke voiding events with ChR2 activation by blue light illumination of the bladder, after less filling than under normal conditions (non-stimulated). These effects were not seen in rats injected with the control viral vector, HSV-eYFP. Finally, illumination of the bladder with green light delayed regular cystometric contractions in rats injected with HSV-Arch but not in animals injecting with HSV-eYFP. Conclusions Here we demonstrate bidirectional modulation of bladder function using optogenetics.. This bidirectional control of bladder function can be induced by selective targeting of nociceptive afferents. Further restriction of opsin expression to specific populations of bladder sensory fibers could lead to a better understanding of their role in bladder function and disease. The refinement of virally delivery methods for optogenetic proteins, together with the development of medical devices for light delivery could lead to development of future therapies for bladder dysfunction. Funding This work was funded by a grant from the NIH Common Fund - SPARC program, U18EB021793 to RG. McDonnell Center for Cellular and Molecular Neurology Postdoctoral Fellowship supported AM.
Authors
Aaron Mickle
Vijay Samineni Kate Meacham Jangyoel Yoon Jose Grajales-Reyes Melanie Pullen John Rogers Henry Lai Robert Gereau |
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PD70-05 |
Mitochondrial mutations contribute to increased voiding frequency and impaired cholinergic contraction in a model of premature aging |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology III | 17BOS |
Abstract: PD70-05 Sources of Funding: TER: HL129632; JMM: HL103797, HL125695 Introduction Aging is associated with increased lower urinary tract symptoms including increased frequency and urgency. Impaired mitochondrial function is characteristic of aging and leads to impaired energy production and reactive oxygen species. These effects are implicated in pathological aging in multiple systems, including the genitourinary system. Knockout (KO) mice lacking polymerase gamma (POLG), a mitochondrial proofreading enzyme, display a premature aging phenotype and have been used to investigate the effects of aging on skeletal muscle and brain. This study characterized the accumulation of mitochondrial mutations on voiding function and bladder smooth muscle response in POLG KO mice. Methods Twelve month old male POLG KO (-/-) and genetically matched wild-type (WT) mice were evaluated for urinary voiding function. Bladders were weighed, urothelium removed and strips cut from the distal detrusor for tissue bath experiments. Contraction to carbachol and relaxation to norepinephrine (NE) were measured via concentration response curves. Contraction to electric field stimulation (EFS) was performed in the presence and absence of the cholinergic antagonist atropine. Results POLG KO mice exhibited increased bladder to body weight ratios (WT: 0.08% ± 0.003, KO: 0.10% ± 0.003; p<0.01). The prematurely aged mice demonstrated increased frequency (WT: 4 ± 0.7, KO: 6 ± 0.7; p<0.05) and total void area relative to body weight (WT: 1.3 cm2/g ± 0.22, KO: 2.1 ± 0.25; p<0.05), and smaller voids (WT: 14.4 cm2 ± 2.47, KO: 10.2 ± 0.86). Detrusor relaxation to NE and contraction to EFS was unchanged. However, sensitivity and maximal contraction to carbachol was decreased in KOs (p<0.05). Furthermore, cholinergic inhibition blunted EFS contraction 62% in WT and 35% in KOs indicating a greater purinergic neurotransmitter release was responsible for KO bladder contraction. Conclusions Aged bladders with accumulated mitochondrial mutations, are enlarged and exhibit smaller, more frequent voids and greater urine output. Additionally, KOs demonstrated less cholinergic mediated contraction and a shift to purinergic mediated EFS contraction. These findings signify the importance of further investigating the role of purinergic signaling and mitochondria in aging bladder dysfunction. Funding TER: HL129632; JMM: HL103797, HL125695
Authors
Shelby A. Powers
Terence E. Ryan Michael R. Odom Joseph M. McClung Johanna L. Hannan |
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PD70-06 |
The role of urothelial ATP signaling in micturition reflex |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology III | 17BOS |
Abstract: PD70-06 Sources of Funding: none Introduction Urothelial ATP signaling has been believed to have an essential role in micturition reflex. To clarify the exact role of urothelial ATP signaling in micturition reflex, we performed detailed in vivo functional analyses in purinergic receptor-deficient mice (Takezawa et al., Sci Rep, 2016). Methods Male C57BL/6J mice, P2X2-/-, and P2X3-/- mice were used. For the bladder functional analyses, the voided volume per micturition of free-moving mice was assessed by automated voided stain on paper method (Negoro et al., Nat commun, 2012), and the bladder capacity, post-voiding residual volume and intercontraction intervals were evaluated by mouse video-urodynamics testing (Takezawa et al., Am J Physiol Renal Physiol, 2014). (1) Bladder function under normal conditions was examined in wild-type (WT), P2X2-/-, and P2X3-/- mice. (2) Lipopolysaccharide (LPS)-induced changes of bladder function and increases in c-Fos-positive cells in the L6 spinal cord were analyzed in WT, P2X2-/-, and P2X3-/- mice. Results (1) Unexpectedly, a lack of P2X2 or P2X3 receptors did not affect bladder function under normal conditions (Figure 1). (2) In contrast, the LPS-induced bladder hyperactivity and an increase in c-Fos-positive cells in the L6 spinal cord were attenuated in P2X2-/-, and P2X3-/- mice (Figure 2). Conclusions These findings indicate that urothelial ATP signaling is not essential for normal micturition reflex under physiological conditions, but plays an important role in bladder hyperactivity under pathological conditions. Funding none
Authors
Kentaro Takezawa
Makoto Kondo Hiroshi Kiuchi Norichika Ueda Tetsuji Soda Shinichiro Fukuhara Tetsuya Takao Yasushi Miyagawa Akira Tsujimura Kazumasa Matsumoto-Miyai Yusuke Ishida Hiromitsu Negoro Shoichi Shimada Norio Nonomura |
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PD70-07 |
Role of Cannabinoid Receptor Type 1 in Tibial and Pudendal Neuromodulation of Bladder Overactivity in Cats |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology III | 17BOS |
Abstract: PD70-07 Sources of Funding: This study is supported by the National Institutes of Diabetes, Digestive and Kidney Diseases under Grants DK-094905, DK-102427, and DK-091253. Introduction Overactive bladder (OAB) affects more than 30 million adults in United States with a significant impact on the quality of life. Percutaneous tibial nerve stimulation (TNS) is a treatment option for OAB. Currently the mechanism underlying bladder neuromodulation is uncertain. Cannabinoid type 1 (CB1) is a cannabinoid G protein-coupled receptor which has been shown in previous animal studies to be involved in micturition control. This study attempts to identify the role of CB1 receptors in tibial and pudendal neuromodulation. Methods 17 cats' bladders were irritated with 0.5% acetic acid (AA) to activate the nociceptive bladder C-fiber afferents and induce bladder overactivity. Electrical stimulation was applied to the tibial or pudendal nerve to inhibit the bladder overactivity. Then AM251 (a selective CB1 receptor antagonist) was administrated intravenously (IV) to determine the involvement of CB1 receptors in the two types of neuromodulation. AM251 was also given intrathecally (IT) to determine the central site of action. Results AA irritation significantly (p<0.01) reduced bladder capacity to 36.6±4.8% of saline control capacity. TNS at 2 or 4 times threshold (T) intensity for inducing toe movement inhibited bladder overactivity and significantly (p<0.01) increased bladder capacity to 69.2±9.7% and 79.5±7.2% of saline control, respectively. AM 251 IV at 0.03 or 0.1 mg/kg significantly (p<0.05) reduced the inhibition induced by 2T or 4T TNS, respectively, without changing prestimulation bladder capacity. Intrathecal AM 251 (0.03 mg) had no effect on TNS inhibition. Pudendal nerve stimulation (PNS) also inhibited bladder overactivity induced by AA irritation, but AM 251 at 0.01-1 mg/kg IV had no effect on PNS inhibition or the prestimulation bladder capacity. Conclusions This study suggests that CB1 receptors at supraspinal sites play a critical role in TNS but not PNS inhibition of bladder overactivity. Further studies are required to help assess if CB1 receptor has clinical application in neuromodulation therapies for OAB. Funding This study is supported by the National Institutes of Diabetes, Digestive and Kidney Diseases under Grants DK-094905, DK-102427, and DK-091253.
Authors
Xuewen Jian
Michelle Yu Jamie Uy Thomas W. Fuller Cameron Jones Bing Shen Jichen Wang James R. Roppolo William C. de Groat Changfeng Tai |
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PD70-08 |
KV7 Channel Pharmacological Modulation in Human Detrusor: A Promising Two-Way Street for the Potential Treatment of Overactive and Underactive Bladder |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology III | 17BOS |
Abstract: PD70-08 Sources of Funding: Supported by NIH R01DK084284 grant to Georgi V. Petkov and NIH F31DK104528 fellowship to Aaron Provence Introduction Recent studies on rodents suggest that voltage-gated KV7 channels (KV7.1-KV7.5) are functionally expressed in detrusor smooth muscle (DSM). Here, we sought to validate the KV7 channels as potential novel targets in the pharmacological treatment of overactive bladder and/or underactive bladder by elucidating their functional role in human freshly-isolated DSM cells and tissues. Methods Human DSM tissues were collected from patient-donors undergoing routine open bladder surgeries in accordance with IRB protocol Pro00045232. Combined methodology including isometric DSM tension recordings, ratiometric fluorescence Ca2+ imaging, and perforated patch-clamp electrophysiology, was applied to ascertain the role of the KV7 channel subtypes in human DSM function. Results The KV7 channel activator, retigabine, decreased global Ca2+ concentrations in DSM isolated strips, while the KV7 channel inhibitor XE991 increased global DSM Ca2+ concentrations. Retigabine decreased spontaneous phasic and nerve-evoked contractions in DSM isolated strips. On the contrary, XE991 increased spontaneous phasic and nerve-evoked contractions in DSM isolated strips. Retigabine-induced DSM relaxation was attenuated in the presence of XE991. The KV7.2/KV7.3 channel activator ICA-069673 and KV7.1 activator L-364,373 also inhibited DSM spontaneous phasic contractions. In freshly-isolated DSM cells, retigabine hyperpolarized the DSM cell membrane potential, while XE991 induced membrane depolarization. Consistent with retigabine, the novel and selective KV7.4/KV7.5 channel activator ML213, also hyperpolarized the DSM cell membrane potential. Conclusions Collectively, these data provide promising evidence for the potential therapeutic utility of selective KV7 channel pharmacological modulators. DSM KV7 channels appear to be a universal therapeutic switch for bladder dysfunction treatment. Pharmacological opening of KV7 channels may be an effective novel approach to treat overactive bladder, whereas KV7 channel inhibitors can potentially be used as novel therapeutics for underactive bladder. Funding Supported by NIH R01DK084284 grant to Georgi V. Petkov and NIH F31DK104528 fellowship to Aaron Provence
Authors
Aaron Provence
Damiano Angoli Eric Rovner Georgi Petkov |
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PD70-09 |
Effects of nerve growth factor (NGF) neutralization on TRP channel expression in laser-captured bladder afferent neurons of mice with spinal cord injury (SCI) |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology III | 17BOS |
Abstract: PD70-09 Sources of Funding: NIH P01 DK093424 Introduction NGF is reportedly involved in changes in C-fiber bladder afferent pathways to induce detrusor overactivity (DO) following SCI. The expression of TRP channels such as TRPV1 and TRPA1 are known to be involved in sensitization of C-fiber afferent pathways. Also, TRPC channels such as TRPC1, TRPC3 and TRPC6 are shown to be expressed in dorsal root ganglia (DRG) although their roles in the control of bladder afferent function have not been well clarified. Therefore, we investigated the effects of anti-NGF antibody treatment on TRP channel expression in laser-captured bladder afferent neurons using SCI mice. Methods SCI was produced by Th8/9 spinal cord transection in female C57BL/6N mice. Two weeks later, an osmotic pump was placed subcutaneously to administer vehicle in spinal intact (SI), vehicle in SCI and 10µg/kg/hr of anti-NGF antibody in SCI mice for two weeks. Four weeks after SCI, L6 DRG were removed bilaterally, and gene expression of TRPA1, TRPV1, TRPC1, TRPC3 and TRPC6 was analyzed by real-time PCR in bladder afferent neurons which were labeled by Fast Blue injected into the bladder wall one week earlier and collected by laser-capture microdissection from L6 DRG sections. Results The mRNA expression of TRPV1, but not TRPA1, increased in vehicle-SCI mice compared to SI mice. The expressions of TRPC3 and TRPC6 in vehicle-SCI mice decreased compared to SI. However, in SCI mice treated with anti-NGF antibody, the mRNA expression of TRPV1 decreased and the mRNA levels of TRPC3 and TRPC6 increased compared to vehicle-SCI mice (Figure). Conclusions The anti-NGF antibody treatment reversed the changes in expressions of TRPV1 and TRPC3/TRPC6 which increased and decreased, respectively, after SCI in the mouse model. These results suggest that the NGF-dependent changes in specific genes such as TRPV1, TRPC3 and TRPC6 could be involved in SCI-induced DO, and that TRPC3/TRPC6 might have an inhibitory role in the control of bladder afferent activity while TRPV1 overexpression is involved in C-fiber sensitization to induce DO after SCI. These findings help to understand the TRP-mediated mechanism underlying neurogenic lower urinary tract dysfunction. Funding NIH P01 DK093424
Authors
Nobutaka Shimizu
Shun Takai Naoki Wada Takahisa Suzuki Ei-ichiro Takaoka Takahiro Shimizu Akihide Hirayama Hirotsugu Uemura Anthony J. Kanai Naoki Yoshimura |
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PD70-10 |
Abnormal resting-state inter-network coupling in patients with non-neurogenic OAB |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology III | 17BOS |
Abstract: PD70-10 Sources of Funding: Swiss National Foundation Introduction Recent fMRI studies using bladder filling tasks demonstrated alterations in supraspinal LUT control networks (NT) in women with OAB, particularly regarding NT connectivity and white matter changes. It is unclear if patients with OAB show altered supraspinal responses during empty bladder conditions and if resting-state (RS) activity is altered by catheterization usually require for bladder filling tasks._x000D_ We applied a functionally-motivated NT approach, using RS functional NT connectivity (RS-FNC) analysis, to examine RS related NT interactions in age-matched controls and OAB patients. Based on previous publications we hypothesize lower FNC in OAB patients. Methods We examined 10 healthy females (37±9y) and 10 with OAB (38±8y) and DO in urodynamics. For RS-fMRI whole brain images, using a multi-slice EPI sequence were acquired in a 3T scanner. Using SPM8, we estimated the RS NTs using the GIFT toolbox and independent component analysis (ICA) across all subjects. IC dimension estimation was performed using the minimum description length criteria, modified to account for spatial correlation. All non-neuronal ICs (e.g. cardiac-induced pulsatile artifact and head motion) were removed, resulting in a total of 9 neuronal ICs (including the default mode NT, DMN). Prior to FNC analysis, IC time courses were bandpass (0.013 Hz & 0.24 Hz). Group differences in FNC strength were calculated using the FNC toolbox for both conditions. The temporal lags between ICA-derived NTs were computed to gain directed FNC. Significant between-group FNC (and lag) results are shown at p < 0.05 FDR corrected. Results Healthy controls showed significantly higher (directed) FNC than OAB patients for: DMN (left-dominant) &[rarr] DMN (right-dominant) and fronto-parietal attention NT &[rarr] DMN (left-dominant). OAB patients show lower inter-networkcoupling, especially between the DMN(IC1) and the left-dominant fronto-parietal attention NT (FPN,IC4)._x000D_ Further, FNC differed between groups in temporal synchronicity. E.g., lag time between the DMN and FPN is shorter than between the right and left DMN in OAB patients. Conclusions We conclude that the interplay between neuronal NTs is altered in OAB patients compared to healthy subjects already during RS. Aberrant coupling of the fronto-parietal attention NT might indicate a general neuronal deficit that impairs adequate LUT control, i.e. suppression of premature micturition reflex, consequently resulting in OAB and incontinence. These novel findings can be an important link to the underlying pathophysiology of OAB in otherwise neurological unimpaired patients. Funding Swiss National Foundation
Authors
Lorenz Leitner
Ulrich Mehnert Matthias Walter Thomas M. Kessler Spyros Kollias Lars Michels |
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PD70-11 |
Circadian rhythm coordinates ATP release in the urothelium via connexin43 hemichannels. |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology III | 17BOS |
Abstract: PD70-11 Sources of Funding: none Introduction We have previously reported that a peripheral circadian clock exists in the bladder and that connexin 43 (Cx43), a major gap junction protein, oscillates and is a regulator of circadian functional bladder capacity. On the other hand, it has been reported that Cx43 forms hemichannels involved in the release of adenosine triphosphate (ATP) in other cell types. Moreover, it has been also known that extracelluar ATP activates the afferent nerves, which leads to the sensation of bladder fullness. We thus hypothesized that the urothelium had circadian rhythm, which regulated the Cx43 oscillation and function as the hemichannels for ATP release to coordinate the diurnal urination rhythm. Methods We measured bioluminescence of cultured urothelium from Per2::luc clock gene reporter mice to identify whether the urothelium had circadian rhythms. We also quantified the expression levels of the major clock genes and Cx43 in the urothelium of 11-week-old C57BL/6 female mice at seven consecutive points every 4 hours by real-time polymerase chain reaction and immunoblotting methods. The concentrations of ATP released into the bladder were measured after bladder distention with 30 cm H2O for 10 minutes at zeitgeber time (ZT) 7, a sleeping phase, and ZT19, an active phase for mice. Additionally, we analyzed the circadian rhythm and Cx43 functions with immortalized human urothelial cells. Results The cultured urothelium from Per2::luc mice showed robust oscillations of bioluminescence, while such rhythms were completely lost in that from Per2::luc mice with Bmal1 knockout having a dysfunctional clock. Cx43 in the urothelium demonstrated a circadian rhythm in conjunction with major clock genes with a peak time at ZT19 and with a nadir time at ZT7. The concentration of ATP released into the bladder showed diurnal changes along with the Cx43 expression. In addition, the circadian rhythms of major clock genes and Cx43 were also observed in immortalized human urothelial cells. The concentration of mechanically-induced ATP release had oscillations in correlation with the Cx43 expression. Furthermore, it was significantly higher in the Cx43-overexpressed cells, whereas it was significantly lower in Cx43- knockdown ones or in the presence of GAP19 peptide, a selective Cx43 hemichannel blocker. Conclusions A functional circadian rhythm existed in the urothelium, and coordinated the Cx43 expression and function as hemichannels which provided a direct pathway of ATP release for mechanotransduction and signaling in the urothelium. Funding none
Authors
Atsushi Sengiku
Hiromitsu Negoro Takeshi Sano Masakatsu Ueda Jin Kono Louis Liou Hitoshi Okamura Osamu Ogawa |
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PD70-12 |
Impairment of micro blood flow in the bladder mucosa and dermis up-regulates TRPM8 channels and induce cold stress related frequency in ovariectomized rats. |
Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology III | 17BOS |
Abstract: PD70-12 Sources of Funding: none Introduction Cold stress produced by sudden change or continuous exposure to low temperature exacerbates lower urinary tract symptoms (LUTS), such as urinary urgency, frequency, and nocturia. Stimulation of C-fibers and TRPM8 channels have been reported as mechanisms of cold stress related LUTS. Menopause women are known to be sensitive to cold stress, but the mechanism is not clearly known. The aim of this study is to show that menopause causes impairment of micro blood flow in the bladder mucosa and dermis under the skin and up-regulates TRPM8 channels which induces cold stress related frequency in rats. Methods A total of 18 Spontaneously Hypertensive rats at postnatal week 10 were used in the experiments. The rats were randomly divided into 2 groups, including 9 with sham operation and 9 with bilateral ovariectomy. At 4 weeks after surgery, cystometography (CMG) was performed. CMG was first performed in room temperature (RT) for 20 minuets. Rats were then put into low temperature (LT) for 40 minutes. After LT, rats were put into RT for 20 minutes. After CMG, the whole bladder and dermis under the lumbar skin was harvested and real-time RT-PCR was performed. Immunohistochemistry was also performed and impairment of micro blood flow was evaluated by hypoxia-inducible factor-1 (HIF-1) staining. Results Results of the CMG are shown in Fig 1. Basal pressure and micturition pressure did not show a difference between control rats and ovariectomy rats, but change rate with cold stress in voiding interval and micturition volume showed a significant exacerbate. Results of real-time RT-PCR are shown in Fig 2. Up-regulation of TRPM8 in the dermis and TRPV1 in the bladder mucosa was seen in ovariectomy rats. Immunohistochemistry showed increase of HIF-1 in the bladder mucosa and dermis. Conclusions Ovariectomy causes impairment of micro blood flow in the bladder mucosa and dermis which induces cold stress frequency by up-regulating TRPM8 channels. Funding none
Authors
Tetsuichi Saito
Tetsuya Imamura Takashi Nagai Toshiro Suzuki Tomonori Minagawa Teruyuki Ogawa Osamu Ishizuka |
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PD71-01 |
Decipher Test Impacts Decision-Making among Patients Considering Adjuvant and Salvage Treatment following Radical Prostatectomy: Interim Results from the Multicenter Prospective PRO-IMPACT Study |
Prostate Cancer: Markers III | 17BOS |
Abstract: PD71-01 Sources of Funding: GenomeDx Biosciences Inc. Introduction Prostate cancer patients and providers have tremendous uncertainty as they decide on the appropriate timing for intervention with adjuvant or salvage radiation therapy (ART, SRT) after radical prostatectomy (RP). We prospectively evaluated the impact of the Decipher test (GenomeDx Biosciences Inc., San Diego), which predicts metastasis risk after RP, on providers' decision-making for ART and SRT. Methods 150 patients considering ART and 115 patients considering SRT were enrolled. Participating providers submitted a management recommendation prior to processing the Decipher test and again upon receiving the Decipher test results. Patients completed validated surveys on prostate cancer-specific quality of life, decision quality, and prostate cancer-related anxiety. Results Pre-Decipher, observation was recommended for 89% of adjuvant patients and 58% of salvage patients. Post-Decipher, 18% (95% CI 12-25%) of treatment recommendations changed in the adjuvant arm, including 31% of high-risk Decipher patients, and 32% (95% CI 24-42%) of management recommendations changed in the salvage arm, including 56% of high-risk Decipher patients. Decisional Conflict Scale (DCS) scores decreased (indicating higher decision quality) after exposure to Decipher results (median DCS pre-Decipher 25 [IQR 8-44], median DCS post-Decipher 19 [IQR 2-30], p<0.001 in the adjuvant arm, pre-Decipher 27 [IQR 16-41], post-Decipher 23 [IQR 4-30], p<0.001 in the salvage arm). Prostate cancer-specific anxiety changed following exposure to Decipher test results: fear of prostate cancer recurrence in the adjuvant arm (p=0.02) and prostate cancer-specific anxiety in the salvage arm (p=0.05) decreased significantly among Decipher low-risk patients. Decipher results were associated with the decision to pursue ART (OR 1.48; 95% CI 1.19-1.85) and SRT (OR 1.41; 95% CI 1.09-1.81) in multivariable logistic regression. _x000D_ Conclusions Knowledge of Decipher results was associated with treatment decision-making and improved decision quality among men with prostate cancer considering adjuvant or salvage radiation therapy. Funding GenomeDx Biosciences Inc.
Authors
John L. Gore
Marguerite du Plessis Maria Santiago-Jiménez Kasra Yousefi Darby J.S. Thompson Lawrence Karsh Brian Lane Michael Franks David Chen Mark Bandyk Fernando Bianco Gordon Brown William Clark Adam Kibel Hyung Kim William Lowrance Murugesan Manoharan Paul Maroni Scott Perrapato Paul Sieber Edouard Trabulsi Robert Waterhouse Elai Davicioni Yair Lotan Daniel W. Lin |
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PD71-02 |
PROSTATE HEALTH INDEX DENSITY IMPROVES DETECTION OF CLINICALLY-SIGNIFICANT PROSTATE CANCER |
Prostate Cancer: Markers III | 17BOS |
Abstract: PD71-02 Sources of Funding: A.R. is supported by a DOD PRTA award (W81XWH-13-1-0445) as well as a PCF Young Investigator Award and Patrick C. Walsh Investigator Grant. Introduction The prostate health index (PHI) is superior to PSA and other PSA-derivatives for the detection of prostate cancer (PCa). We sought to explore the utility of PHI density for the detection of clinically-significant PCa in a contemporary cohort of men presenting for diagnostic workup of PCa. Methods The study cohort included patients with elevated PSA (>2 ng/mL) and negative digital rectal examination who underwent PHI testing and prostate biopsy at our institution in 2015. Serum markers were prospectively measured per standard clinical pathway. PHI was calculated as [([-2]proPSA/free PSA) x (PSA)1/2], and density calculations were performed using prostate volume as determined on transrectal ultrasound. Logistic regression was used to assess the ability of serum markers to predict clinically-significant PCa, defined as any Gleason score ≥7 cancer or Gleason score 6 cancer in >2 cores or >50% of any positive core._x000D_ Results Of 118 men with PHI testing who underwent biopsy, 47 (39.8%) were found to have clinically-significant PCa on biopsy. The median PHI density was 0.70 (IQR 0.43-1.21); it was 0.53 (IQR 0.36-0.75) in men with negative biopsy or clinically-insignificant PCa and 1.21 (IQR 0.74-1.88) in men with clinically-significant PCa (p<0.001). Clinically-significant PCa was detected in 3.6% of men in the first quartile of PHI density (<0.43), 36.7% of men in the interquartile range (0.43-1.21) of PHI density, and 80.0% of men with PHI density >1.21 (p<0.001). Using a threshold of 0.43, PHI density was 97.9% sensitive and 38.0% specific for clinically-significant PCa, and 100% sensitive for Gleason score ≥7 disease. Compared to PSA (AUC 0.52), PSAD (AUC 0.70), %free PSA (AUC 0.75), and PHI (AUC 0.76), PHI density demonstrated the highest discriminative ability for clinically-significant PCa (AUC 0.84). Conclusions Based on this prospective single-center experience, PHI density could be used to avoid 38% of unnecessary biopsies while failing to detect only 2% of clinically-significant cancers. Funding A.R. is supported by a DOD PRTA award (W81XWH-13-1-0445) as well as a PCF Young Investigator Award and Patrick C. Walsh Investigator Grant.
Authors
Jeffrey Tosoian
Sasha Druskin Darian Andreas Patrick Mullane Meera Chappidi Sarah Joo Kamyar Ghabili Mufaddal Mamawala Joseph Agostino H. Ballentine Carter Alan Partin Lori Sokoll Ashley Ross |
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PD71-03 |
Novel DNA Methylation Markers for Accurate Prognostic Assessment of Prostate Cancer: Discovery and Early Validation |
Prostate Cancer: Markers III | 17BOS |
Abstract: PD71-03 Sources of Funding: Mayo Foundation Introduction Current prognostic classification of prostate cancer (PCa) is based on Gleason scoring, which is subjective & lacks precision. We sought to identify discriminant methylated DNA markers with potential to enhance prognostic assessment. Methods For discovery, whole methylome sequencing was applied to DNA extracted from 54 frozen archival tissues [36 PCa cases (18 Gleason 3+3, 18 Gleason ≥7) and 18 normal-appearing prostate controls]. For tissue validation, top candidate markers were assayed by methylation-specific PCR on an independent set of 50 case and 35 control tissues. Tissues were obtained from radical prostatectomies done between 2003-2007; all were reviewed pathologically and micro-dissected prior to DNA extraction and bisulfite treatment. Marker levels were standardized to total human DNA. From the discovery set, marker distributions in cases and controls were assessed to identify discriminant candidates. Markers were correlated with progression (PSA >0.4 ng/ml or confirmed recurrence) using regression partitioning trees (rPart) in PCa cases. From the rPart model, subjects were categorized as low, medium, and high risk progression groups. The prognostic value of methylation markers relative to Gleason scoring was assessed with the likelihood ratio test of competing cox proportional hazards models. Results In the discovery set, 120 candidate markers exceeded filtering criteria (AUC>0.95, fold-change >10, p<0.005). Of these, the top 72 candidate markers were evaluated in the independent set. Numerous markers were identified that highly discriminated PCa from normal-appearing prostate controls, with some achieving AUCs > 0.99. Five prognostic markers (FAM78A, WNT3A, GAS6, LOC100129726, and MAXchr727) were selected by the rPart modeling. The risk grouping defined by methylated DNA markers added significant prognostic content in predicting progression-free survival relative to Gleason scoring (p<0.0001) whereas Gleason scoring had no added value relative to methylated DNA marker risk grouping (p=0.43) (figure)_x000D_ Conclusions Based on these discovery and early validation data, we identify novel methylated DNA markers with potential to accurately predict progression in PCa. Further exploration is clearly warranted to corroborate and extend these intriguing findings. Funding Mayo Foundation
Authors
Matthew T. Gettman
Brian A. Dukek William R. Taylor Tracy C. Yab Xiaoming Cao Patrick H. Foote Calise K. Berger Thomas C. Smyrk John C. Cheville Douglas W. Mahoney R. Jeffrey Karnes John B. Kisiel David A. Ahlquist |
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PD71-04 |
An Independent, Multi-Institutional, Prospective study in the Veterans Affairs Health System confirms the 4Kscore accurately predicts aggressive prostate cancer |
Prostate Cancer: Markers III | 17BOS |
Abstract: PD71-04 Sources of Funding: OPKO Diagnostics Introduction The 4Kscore test was previously validated in a large, prospective trial to predict aggressive prostate cancer, however, the study population had a limited number of African American (AA) men. We conducted an independent multi-institutional, prospective trial to validate the 4Kscore test within the Veterans Affairs (VA) Health System, where a large proportion of the men getting care are AA. Methods We prospectively enrolled men who were referred for biopsy of their prostate at 8 diverse VA sites throughout the nation. All men underwent phlebotomy for 4Kscore ascertainment prior to prostate biopsy. We assessed the discrimination, calibration, and clinical utility of the 4Kscore test for predicting Gleason 7 or higher (G7+) prostate cancer, and compared it to a base model consisting of age, digital rectal exam findings, and PSA. Additionally, we compared the performance of the 4Kscore test in AA and non-AA men. Results Among 403 men who were enrolled in the trial, we had 366 men with a 4Kscore and complete data available for analysis. Among these men, 208 (56%) were AA, and 134 (36%) had G7+ prostate cancer. The 4Kscore exhibited better discrimination (AUC: 0.81 vs. 0.74, p=0.011) and higher clinical utility on decision analysis than the base model for deciding on the need for biopsy. Calibration plots of the 4Kscore for the entire cohort afforded predictions that closely matched the observed risk of G7+ prostate cancer in the population (Figure 1). There was no difference in the discrimination of the 4Kscore test between AA and non-AA men (0.80 vs. 0.84; p=0.32). While we found some evidence that the 4Kscore underestimates the risk of G7+ prostate cancer in AA men, discrimination (0.80 vs. 0.72, p = 0.013) and clinical utility for the 4Kscore test were still higher than the base model. Conclusions In an independent, multi-institutional, prospective trial of the 4Kscore test in the VA health system, we confirmed that the 4Kscore accurately predicts the likelihood of aggressive prostate cancer and outperforms standard clinical information for biopsy decision making in both AA and non-AA men. Funding OPKO Diagnostics
Authors
Sanoj Punnen
Stephen Freedland Thomas Polascik Stephen Savage Stacy Loeb Edward Uchio Sharad Mathur Michael Risk Yan Dong Jonathan Silberstein |
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PD71-05 |
Validation of GEMCaP as a DNA based biomarker to predict prostate cancer recurrence after radical prostatectomy |
Prostate Cancer: Markers III | 17BOS |
Abstract: PD71-05 Sources of Funding: NIH Introduction There are currently no validated DNA based biomarkers available for routine clinical use to predict prostate cancer recurrence after prostatectomy. The Genomic Evaluators of Metastatic Cancer of the Prostate (GEMCaP) assay was developed to predict recurrence using a tumor genotype derived from copy number for a set of genomic loci. We aim to validate the GEMCaP assay using a separate cohort from the development cohort. Methods We randomly selected 203 patients who had undergone radical prostatectomy at the Cleveland Clinic (CC) or the University of Rochester (UR) Cancer Centers from 2000-2005 and had tumor tissue available for research. After pathology review cancer tissues were macrodissected and DNA was extracted and subjected to high resolution array comparative genomic hybridization (aCGH). A high GEMCaP score was defined as >20% of the genomic loci exhibiting copy number gain or loss in a given tumor, as in previous studies. Cox regression was used to evaluate associations between the GEMCaP score and risk of biochemical recurrence. Results We report the results from 140 patients, 54 from the CC cohort and 86 from the UR cohort. Overall, 38% of patients recurred with a median time to recurrence of 45 months. Based on the CAPRA-S score, 39% were low-risk, 42% were intermediate-risk and 19% were high-risk. Thirty-one percent of the cohort had a high GEMCaP score (?20%). A high GEMCaP score was associated with higher risk of biochemical recurrence (HR 2.69, 95% CI 1.51-4.77) and remained associated with biochemical recurrence after adjusting for the CAPRA-S score (HR 1.91, 95% CI 1.05-3.48). The C-index for GEMCaP alone was 0.64, and improved when combined with CAPRA-S (C-index = 0.76). Conclusions In this validation study, a high GEMCaP score was associated with biochemical recurrence in two external cohorts. This remained true after adjusting for clinical and pathologic factors as accounted for by the CAPRA-S score. The GEMCaP biomarker could be an efficient and effective clinical risk assessment tool to identify prostate cancer patients for early adjuvant therapy. Funding NIH
Authors
Hao Nguyen
Christopher Welty Karla Lindquist Vy Ngo Elizabeth Gilbert Henrik Bengtsson Cristina Magi-Galluzzi Jerome Jean Gilles Jorge Yao Matthew Cooperberg Edward Messing Eric Klein Peter Carroll Pamela Paris |
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PD71-06 |
CTC-based gene expression for predicting resistance to abiraterone and enzalutamide in mCRPC |
Prostate Cancer: Markers III | 17BOS |
Abstract: PD71-06 Sources of Funding: This work was supported by the Prostate Cancer Foundation and Department of Defense. Introduction There is a continued need to develop liquid biomarkers that predict response to 2nd generation hormonal therapies. While circulating tumor cell (CTC)-based detection of AR-V7 has been shown to be one potential marker, the apparent rarity of AR-V7 positivity is indicative of the importance of other drivers of resistance in this setting. We sought to utilize a multiplex gene expression platform for assessing CTCs in order to determine other potential predictive biomarkers of response to abiraterone and enzalutamide. Methods Whole blood (~5mL) was obtained from 37 patients with metastatic castration resistant prostate cancer (mCRPC) starting enzalutamide (n=16) or abiraterone (n=21). CTCs were isolated using anti-EpCAM-conjugated magnetic beads, and following cell lysis, mRNA was extracted followed by multiplex qRT-PCR for 44 prostate cancer-related genes plus internal controls. Gene expression was normalized to controls, and samples were considered CTC-positive based on a previously established set of epithelial markers (EpCAM, EGFR, DSG2, KRT8, KRT18 and KRT19). The primary endpoint was PSA progression-free survival (PFS), with PSA progression defined as an increase of 25% or more above the nadir. Univariable Cox regression analyses were performed to assess for genes associated with PFS at false discovery rate (FDR) < 0.20. Results We identified 27 (73%) patients with detectable CTCs among the 37mCRPC patients. The median age of the cohort was 73 years (IQR 64-78), and patients were followed for a median of 7.4 months (IQR 3.8-18.5). A total of 22 (81.5%) patients suffered PSA progression at a median time of 3.3 months (IQR 1.5-6.8). In the Cox analysis, PSMA (HR 3.83, 95%CI 1.62-9.03, p=0.002), TSPAN8 (HR 2.04, 95%CI 1.21-3.46, p=0.008), BMP7 (HR 1.46, 95%CI 1.09-1.95, p=0.017), and GAS6 (HR 2.29, 95%CI 1.16-4.51, p=0.017) were independent predictors of shorter PFS. Conclusions We identified four prostate cancer-related genes that can be identified in CTCs and appear to predict short PFS in men with mCRPC being treated with enzalutamide or abiraterone. While this is a small cohort and prospective validation is needed, these findings highlight the potential role for this approach in helping guide therapy choice. Funding This work was supported by the Prostate Cancer Foundation and Department of Defense.
Authors
Jae-Seung Chung
Yugang Wang Henderson James Udit Singhal Yuanyuan Qiao Alexander Zaslavsky Dan Hovelson Felix Feng Ganesch Palapattu Taichman Russell Arul Chinnaiyan Scott Tomlins Todd Morgan |
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PD71-07 |
GAS6, KLK2, and BMP7 detected in circulating tumor cells predict resistance to chemotherapy in mCRPC |
Prostate Cancer: Markers III | 17BOS |
Abstract: PD71-07 Sources of Funding: This work was supported by the Prostate Cancer Foundation and Department of Defense. Introduction Docetaxel or cabazitaxel-based chemotherapy continues to have a critical role in the treatment of men with metastatic castration-resistant prostate cancer (mCRPC). However, responses are heterogeneous and resistance to therapy is a pressing clinical problem. With the goal of developing liquid biomarkers to aid in treatment selection, we sought to identify genes associated with resistance to chemotherapy using a circulating tumor cell (CTC)-based approach. Methods Whole blood (~5mL) was obtained from 25 patients with mCRPC starting docetaxel (n=21) or cabazitaxel (n=4). CTCs were isolated using anti-EpCAM-conjugated magnetic beads, and following cell lysis, mRNA was extracted followed by multiplex qRT-PCR for 44 prostate cancer-related genes plus internal controls. Gene expression was normalized to controls, and samples were considered CTC-positive based on a previously established set of epithelial markers (EpCAM, EGFR, DSG2, KRT8, KRT18 and KRT19). The primary endpoint was PSA progression-free survival (PFS), with PSA progression defined as an increase of 25% or more above the nadir. Univariable Cox regression analyses were performed to assess for genes associated with PFS at false discovery rate (FDR) < 0.20. Results Among 25 patients with mCRPC, we identified 84% (21/25) with detectable CTCs. The median age of the cohort was 62 years (IQR 58-70). At a median (IQR) follow up of 5.4 (3.4-9.3) months, 47.6 % (10/21) of patients showed a PSA decrease of at least 30% following treatment initiation. 18/21 patients (85.7%) experienced PSA progression at a median of 2.8 months (IQR 1.7-4.8). In the Cox analysis, KLK2 (HR 2.54, 95%CI 1.24-5.21, p=0.011), GAS6 (HR 3.50, 95%CI 1.30-9.42, p=0.013), and BMP7 (HR 2.01, 95%CI 1.15-3.52; p=0.014) were associated with shorter PFS._x000D_ _x000D_ Conclusions We have identified three genes associated with progression in mCRPC patients initiating chemotherapy. While these early results need further confirmation, they suggest that CTCs may be utilized to help guide precision-based treatment strategies in patients with mCRPC. Additionally, these results corroborate our recent in vitro and in vivo findings (Lee et al, J Cell Biochem, 2016) indicating that GAS6 protects prostate cancer cells from docetaxel-induced apoptosis. Funding This work was supported by the Prostate Cancer Foundation and Department of Defense.
Authors
Jae-Seung Chung
Yugang Wang Henderson James Udit Singhal Yuanyuan Qiao Alexander Zaslavsky Dan Hovelson Felix Feng Ganesh Palapattu Taichman Russell Arul Chinnaiyan Scott Tomlins Todd Morgan |
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PD71-08 |
ANDROGEN RECEPTOR SPLICE VARIANT 7 (AR-V7) IN PATIENTS WITH LOCAL ADVANCED, METASTATIC AND CRPCM: A NOVEL CAPILLARY NANO-INMUNOASSAY TECHNIQUE |
Prostate Cancer: Markers III | 17BOS |
Abstract: PD71-08 Sources of Funding: None. Introduction The androgen receptor (AR) splice variant 7 (AR-V7), has been associated with increased risk of prostate cancer (PC) and with the possibility of progression and responsiveness to the various lines of hormonal treatment and chemotherapy._x000D_ The aim of this study was to investigate the feasibility of a novel capillary nano-immunoassay in detecting AR-V7 variant in plasma from PC patients_x000D_ Methods 72 patients with PC were enrolled. Localized, locally advanced, metastasic and CPRC status were allowed due to represent all the PC biological spectrum. _x000D_ Capillary Electrophoresis with immunoassay methodology were performed using the WES (TM) machine according to the manufacturer&[prime]s protocol. With this technique, proteins are separated by size, immobilized and probed with specific antibodies. Signal intensity is detected by a horseradish peroxidase-conjugated chemiluminescence system and the data is shown as an electropherogram. The primary antibody used was AR-V7. Quantitative analysis for AR-V7 protein peak was done automatically as area under the peak. Dates from the human prostate cell lines PC3 and VCaP and from 17 healthy donors were used to standardize the assays for AR-V7._x000D_ The study was carried out in accordance with the ethical standards of the Declaration of Helsinki and was approved by the Institutional Review Board of the University Hospital of Salamanca (Spain)._x000D_ _x000D_ _x000D_ Results AR-V7 signal was detected in 21 (29%) patients: 17 (81%) had a Gleason score ≥ 7, 15 (71%) castration-resistant prostate cancer (CRPC) and 18 (86%) metastatic disease. The complete results are shown in the table 1. _x000D_ _x000D_ Conclusions This study describes the feasibility of detecting AR-V7 expression from plasma of PC patients by using an automated capillary nano-immunoassay technique WESTM. We provide evidence about this technique, simpler, faster and we have automated platform to make it in comparison with traditional CTCs techniques. AR-V7 has been observed more frequently in aggressive tumors._x000D_ These findings lay the foundations for liquid biopsy as a means of obtaining biological data in a more convenient way for the patient. These data are needed for personalized treatment decisions, which can prevent patients from receiving inefficient systemic therapy._x000D_ Funding None.
Authors
ALVARO RODRIGUEZ
JUAN LUIS GARCIA JAVIER GARCIA GARCIA REBECA LOZANO MEJORADA IRENA MISIEWICZ-KRZEMINSKA MANUEL HERRERO POLO JUAN JESUS CRUZ FRANCISCO GOMEZ VEIGA |
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PD71-09 |
Quantitative Digital Image Analysis and Machine Learning Accurately Classifies Primary Prostate Tumors of Bone Metastatic Disease Based on Histomorphometric Features in Diagnostic Prostate Needle Biopsies |
Prostate Cancer: Markers III | 17BOS |
Abstract: PD71-09 Sources of Funding: DOD PC131996, PCF-Movember GAP1 Unique TMAs Project, Prostate Cancer Foundation (PCF) Creativity Award, Jean Perkins Foundation, NIH/NCI P01 CA098912-09, NIH R01CA131255 and P50CA092131, Stephen Spielberg Team Science Award. Introduction Prostate cancer (PC) with de novo bone metastases (M1) has a 5-year survival of 28%. Pathological features of primary M1 tumors are generally indistinguishable from those of high-grade localized (M0) cases, however 5-year survival for M0 PC is nearly 100%. Digital image analysis is an evolving &[Prime]OMICS&[Prime] platform for biomarker development that can be applied to diagnostic histopathology. We hypothesize that novel software analysis tools and machine learning can systematically interrogate digitized prostate needle biopsy (PNBX) slides to extract histomorphometric features that identify discrepant architecture and nuclear texture of M0 and M1 tumors. Herein, algorithms that measure these features were developed in a training set of digital images and then validated in an independent patient cohort._x000D_ _x000D_ Methods We created a biorepository of diagnostic PNBX specimens from 2150 PC patients from the Greater Los Angeles VA Healthcare System between 2000 and 2016. The biorepository was mined to create a matched cohort of M0 (n=44) and M1 (n=61) cases. Slides were digitized at 40X magnification and two pathologists annotated all cancer foci. ~30 image tiles were obtained from each case (n=2857) and 88 features were extracted. Segmentation based fractal texture descriptors (SFTA), Gabor (GF), grey level run length (GLRL), and nuclear texture (CP) features were used to train a classifier to distinguish M0 from M1 tiles. Results After conversion of M0 and M1 image tiles to digital nuclear masks, training features were used to classify nuclear texture or tissue architecture. The majority vote from nuclear classification was transferred to the tile level and the majority classification of tiles was used to classify each case. For tissue architecture, 45 STFA and 60 Gabor features classified M1 and M0 cases with an accuracy of 71.8% and 80%, respectively. For nuclear features, 44 GLRL and 8 CP classified M0 versus M1 cases with an accuracy of 63% and 75.4%, respectively. A classifier trained with a combined 88 features achieved 86% accuracy in distinguishing M1 from M0 cases. Conclusions We applied digital imaging technology and machine learning to extract 88 novel features that accurately differentiate high-grade M0 from M1 PC. The quantification of tissue architecture and nuclear morphology provides an orthogonal approach for biomarker development, which can be applied to prognostication and potential treatment decisions in patients with high-risk localized or metastatic PC._x000D_ Funding DOD PC131996, PCF-Movember GAP1 Unique TMAs Project, Prostate Cancer Foundation (PCF) Creativity Award, Jean Perkins Foundation, NIH/NCI P01 CA098912-09, NIH R01CA131255 and P50CA092131, Stephen Spielberg Team Science Award.
Authors
Eric Miller
Hootan Salemi Sergey Klimov Michael Lewis Isla Garraway Beatrice Knudsen Arkadiusz Gertych |
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PD71-10 |
Serum N-glycomics predicts in patients who developed castration resistant prostate cancer |
Prostate Cancer: Markers III | 17BOS |
Abstract: PD71-10 Sources of Funding: none Introduction There are several systemic agents for metastatic castration-resistant prostate cancer (CRPC) result in a complicated decision-making while selecting an appropriate treatment. Therefore, there is a need to identify more powerful predictive biomarkers of CRPC to decide on therapeutic strategy. In the present study, we performed serum N-glycomics between healthy volunteer (HLT) and various stages of PC patients and evaluated its potential as a predictive serum-based glycobiomarkers of CRPC. Methods N-glycomics in serum were performed total 850 patients in randomly selected 128 healthy volunteer (HLT) and 286 benign prostatic hyperplasia (BPH), 258 PC before radical prostatectomy (RP), 29 PC after RP, 41 hormone sensitive PC who treated androgen deprivation therapy (HSAPC with ADT) and 68 CRPC patients. Candidate N-glycans for prediction of CRPC were selected from those with the highest area-under-the-curve (AUC) and used to create an N-glycan score (NGScore) based on presence and amount. The validity of this score for prediction of CRPC was analyzed using a receiver operating characteristic (ROC) curve. Results N-glycomics reveled that tri- and tetra-antennary N-glycans level of CRPC was significantly higher than that of HSPC with ADT group, while high mannose, hybrid and bi-antennary typed N-glycan of CRPC was significantly lower than that of HSPC with ADT. We identified 5 candidate N-glycans (high mannose; m/z 1565, bi-antennary; m/z 1752 and 2058, tri-antennary; m/z 2744 and 3414, respectively) significantly associated with CRPC patients. The accuracy of the NGScore for prediction of CRPC was significant with an AUC value of 0.7588. The positive and negative predictive value of NGScore at cutoff ≥2.0 was 77.1% and 71.2% respectively. A high value NGScore was significantly associated with CRPC. Finally, we prospectively investigated NGScore, PSA and testosterone levels of 13 HSPC with ADT patients who treated androgen deprivation therapy (ADT) and revealed that 66.6% of NGScore ≥2 points patients (4/6) was developed CRPC or experienced PSA failure. NGScore less than 2 points patients (7/7) was not developed CRPC during follow-up period. Conclusions Our newly developed NGScore seems to be a practical predictive method for CRPC. Funding none
Authors
Tohru Yoneyama
Yuki Tobisawa Shingo Hatakeyama Kazuyuki Mori Yasuhiro Hashimoto Takuya Koie Chikara Ohyama |
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PD71-11 |
p53 focal protein expression in primary prostate tumors and lymphatic vessel invasion predict biochemical recurrence and metastatic progression |
Prostate Cancer: Markers III | 17BOS |
Abstract: PD71-11 Sources of Funding: CPDR Program HU0001 10-2-0002 to I.R. Introduction p53 has been widely studied in prostate cancer (CaP). Next-Gen Sequencing (NGS) studies of prostate tumors reveal that p53 mutations are frequently observed in castration resistant CaP genomes. Recently, Haffner et al. (JCI, 2013) reported data on a single patient with a p53 mutation in a primary, well differentiated tumor at time of radical prostatectomy (RP) that was linked to future metastatic lesions. Lymphatic vessel invasion (LI) has also been demonstrated to predict poor CaP outcomes. The study purpose was to evaluate independent and combined roles of p53 and LI status in predicting CaP progression in a RP patient cohort with long-term follow-up. Methods This retrospective RP cohort study was comprised of CaP patients (50 metastatic; 138 randomly sampled, non-metastatic) enrolled at the Walter Reed National Military Medical Center between 1993 and 2013. Representative sections of whole mounted RP specimens were examined. LI and p53 status were assessed using immunohistochemistry staining with Biocare Medical D2-40 & p53 Tumor Suppressor Protein monoclonal antibodies. In CaP index tumors, p53 status was evaluated as percent p53 positive (+) tumor cells divided by total index tumor area (0%, 1-5%, >5%). Kaplan Meier (KM) estimation curves were used to examine time to biochemical recurrence (BCR) and distant metastasis as a function of p53 and LI status. Results Of the 188 eligible patients, median age at RP and follow-up time were 60.4 and 12.7 years, respectively. Nearly half (49.2%) of tumors stained focally as p53+ while 26.6% of patients had evidence of LI. p53+ patients had higher pathologic T stage (61.6% p53+ vs. 38.4% p53-, p = 0.0068). In KM models, p53+ >5% alone predicted BCR (p = 0.0075) and distant metastasis (p = 0.0053). When p53 status was examined in combination with LI, the poorest CaP outcomes were observed for those jointly LI+/p53 >5% (Figure 1a-b, p < 0.0001). Conclusions p53 protein expression, alone and in combination with LI status, predicts CaP progression after RP. These data suggest that determination of p53 alterations is warranted for improved prognostication of CaP progression. Funding CPDR Program HU0001 10-2-0002 to I.R.
Authors
William Gesztes
Jennifer Cullen Denise Young Yongmei Chen Allen Burke Albert Dobi Gyorgy Petrovics Inger Rosner Shiv Srivastava Isabell Sesterhenn |
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PD71-12 |
Biological Pathways Identified from our Functional Driver Gene Marker Network that Activate the Androgen Receptor |
Prostate Cancer: Markers III | 17BOS |
Abstract: PD71-12 Sources of Funding: DOD Introduction We reported functional driver genes and network interaction of race specific and differentially expressed genes by use of bioinformatics among a large population of African American men (AAM) and European American men (EAM) (Powell, I et al 2013, Cancer Epid Bio Prev.). Within this network we subsequently identified biological pathways reported elsewhere that activate directly or indirectly the androgen receptor. We will present these pathways from our interactive network. Methods In our initial microarray analysis from formalin fixed radical prostatectomy specimens, we examined 227 genes from 517 genes associated with PCa showing significantly greater expression in PCa from AAM and EAM, and a subset of these genes was identified by bioinformatics and the network from Ingenuity Pathways to be functionally interrelated and driver genes. Genes associated with inflammatory cytokines (blue) and lipid metabolism (yellow) were expressed among AAM and EAM respectively. SEE FIGURE1 Results Biological Pathways identified in our functional driver gene network that activate the androgen receptor: 1. ALOX12/ALOX15 ?TNF ?IL6/IL1B (Fairfax et al,2010) 2. IL1B? MAPK ? IL8 (Tsai et al 2009) 3. IL6 ?mediators AKt, MAPK and STAT3? activated androgen receptor (Jia et al 2004) 4. IL8 binds to CXCR ½ receptors at the cell surface and activate the androgen receptors through multiple mediators of cell signaling in the PCa cell (Waugh and Wilson 2008). Conclusions These biomarker pathways may be useful markers in diagnosing aggressive prostate cancer and in the development of targeted biologic therapy. Further analyses may reveal additional pathways. Funding DOD
Authors
Isaac Powell
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PD72-01 |
LONG-TERM ANDROGEN DEPRIVATION, WITH OR WITHOUT RADIOTHERAPY, IN LOCALLY-ADVANCED PROSTATE CANCER: RESULTS FROM A PHASE III RANDOMIZED STUDY |
Prostate Cancer: Localized: Radiation Therapy II | 17BOS |
Abstract: PD72-01 Sources of Funding: Takeda Introduction Data comparing androgen-deprivation therapy (ADT) combined with external beam radiation therapy (EBRT) versus EBRT-alone have clearly demonstrated a survival benefit for the combined strategy in localized prostate cancer. Data comparing ADT alone with ADT+EBRT combinations are scarcer and this study aims to investigate oncological outcomes with long-term follow-up. Methods This multicenter phase III trial included 273 patients with biopsy-proven locally advanced prostate cancer (T3-4) randomly assigned to ADT alone or ADT+EBRT. Luteinizing hormone-releasing hormone (LHRH) agonist (leuprorelin 11.25 mg, subcutaneous) was started within seven days of randomization and continued every three months for three years in both arms. Oral flutamide (750 mg/day) was administered during the first month. The whole pelvis was treated at a dose of 46+/-2 Gy and the prostate with a boost from 20 Gy to 28 Gy. The primary objective was 5-year progresion-free Survival (PFS) according to clinical or biochemical criteria, using the ASTRO-Phoenix definition. Secondary endpoints consisted of overall survival (OS), disease-specific survival (DSS), locoregional progression free survival (LPFS), metastasis-free survival (MFS), time to metastatic progression, biochemical progression free survival (BPFS) and tolerance. Results With a median follow-up of 7.3 years, 263 patients were included in the Intent-to-treat analyses. The 8-year PFS rate was significantly higher in the ADT+EBRT arm than in the ADT-alone arm (47.9% versus 7.0%; hazard ratio: 0.27, log-rank p<0.0001). The risk of death from prostate cancer was significantly reduced in the ADT+EBRT arm as compared to the ADT-alone arm (sub-hazard ratio (SHR): 0.48; Gray’s test p=0.02). The 8-year OS rate was respectively 56.8% in the ADT-alone arm and 65.1% in the ADT+EBRT arm (log-rank p=0.43). LPFS was significantly in favor of ADT+EBRT arm (SHR = 0.61; Gray’s test p=0.01). MFS was comparable between both arms (Gray’s test p=0.88). Analysis of toxicities revealed acute lower tolerance (mainly gastro-intestinal and genito-urinary) in the ADT+EBRT arm with a gradual decrease in intensity during follow up from 6 months after the end of EBRT. Conclusions These long-term results confirm the oncological benefit of combining EBRT with ADT in the treatment of locally advanced prostate cancer. Funding Takeda
Authors
Paul Sargos
Nicolas Mottet Pierre Richaud |
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PD72-02 |
Genomic Classifier augments the role of pathological features in identifying optimal candidates for adjuvant radiation therapy in patients with prostate cancer: Development and internal validation of a multivariable prognostic model |
Prostate Cancer: Localized: Radiation Therapy II | 17BOS |
Abstract: PD72-02 Sources of Funding: none Introduction Despite documented oncological benefit, postoperative adjuvant radiotherapy (aRT) utilization in prostate cancer (PCa) patients is still limited in the US. We aimed to develop and internally validate a risk stratification tool incorporating the Decipher genomic score, along with routinely available clinicopathologic features, to identify patients who would benefit the most from aRT Methods 512 PCa patients treated with RP at four US academic centers between 1990-2010. All patients had pT3a disease, positive margins, and/or pathologic lymph node invasion (LNI). Multivariable Cox regression analysis tested the relationship between available predictors (including Decipher score) and clinical recurrence (CR), which were then used to develop a novel risk stratification tool. Our study adhered to the TRIPOD guidelines for development of prognostic models Results Overall, 21.9% patients received aRT. Median follow-up in censored patients was 8.3 years. The 10-year CR rate was 4.9% vs. 17.4% in patients treated with aRT vs. initial observation (p<0.001). Pathological T3b/T4 stage, Gleason score 8-10, LNI and Decipher score >0.6 were independent predictors of CR (all p<0.01). A novel nomogram (Figure 1) based on these risk factors had a c-index of 0.85, with optimal calibration characteristics. Cumulative number of risk factors was 0, 1, 2, and 3-4 in 46.5, 28.9, 17.2, and 7.4% of patients respectively. aRT was associated with decreased CR rate in patients with ≥2 risk factors (10-year CR rate 10.1% in aRT vs. 42.1% in initial observation, p=0.008, number needed to treat=3.1), but not in those with <2 risk factors (p=0.23, Figure 2). Conclusions Utilizing the novel model to indicate aRT might reduce overtreatment, decrease unnecessary side effects, and reduce risk of CR in the subset of patients (~25% of all patients with aggressive pathological disease) who really benefit from this therapy. _x000D_ Funding none
Authors
Deepansh Dalela
Maria Santiago-Jimenez Kasra Yousefi Jeffrey Karnes Ashley Ross Robert Den Edward Schaeffer Adam Dicker Mani Menon Alberto Briganti Elai Davicioni Firas Abdollah |
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PD72-03 |
Timing of salvage radiation therapy and use of concomitant hormonal therapy for patients with PSA rising after radical prostatectomy: a long-term survival analysis |
Prostate Cancer: Localized: Radiation Therapy II | 17BOS |
Abstract: PD72-03 Sources of Funding: none Introduction Recent prospective randomized studies showed that concomitant use of hormonal therapy (HT) increased outcomes after salvage radiation therapy (SRT). However, these studies were limited by the inclusion of a significant proportion of patients treated in a late salvage setting. We hypothesized that the beneficial effect of concomitant use of HT decreases when patients are treated with early SRT. Methods The study included 706 patients who received SRT at six tertiary referral centres for PSA rising after RP. The irradiation of the pelvic lymph nodes area was left at the discretion of the treating physician. The study outcome consisted of distant metastasis developed after SRT, including retroperitoneal nodal metastasis (M1a), skeletal (M1b), and visceral metastasis (M1c). Multivariable Cox regression analysis was used to test the association between the study outcome and the following predictors: patient age, pT stage (≤pT3a vs. ≥pT3b), pathologic Gleason (≤7 vs. ≥8), surgical margins (negative vs. positive), PSA level at SRT, and concomitant hormonal therapy (HT) administration. Non-parametric curve fitting method was used to plot the risk of distant metastasis over PSA level at SRT. Results were stratified according to the use of HT (no vs. yes). Results Median age and PSA level at SRT were 66 years and 0.40 ng/ml. Overall, 214 (30%) patients received concomitant HT. At a median follow-up of 84 months, 15 (2.1%), 54 (7.7%), and 9 (1.3%) patients developed retroperitoneal, skeletal, and visceral metastasis, respectively. At multivariable analysis, PSA level at SRT (HR: 1.19, p=0.004) was a significant predictor of distant metastasis. The association between distant metastasis and PSA level at SRT significantly differed by concomitant HT (p<0.0001 by an interaction test). Specifically, the benefit of HT was minimal for PSA level <1 ng/ml, and it increased exponentially for PSA level >2 ng/ml (Figure 1). Conclusions The oncological benefit of concomitant HT greatly depends on PSA level at SRT. Our retrospective data suggest a clear benefit of adding HT to SRT only in patients with PSA >2 ng/ml, whereas hormonal therapy had minimal effect on progression in men receiving SRT at a PSA <1 ng/ml at SRT. Funding none
Authors
Nicola Fossati
R. Jeffrey Karnes Stephen Boorjian Michele Colicchia Alberto Bossi Thomas Seisen Cesare Cozzarini Claudio Fiorino Barbara Noris Chiorda Giorgio Gandaglia Thomas Wiegel Shahrokh F. Shariat Gregor Goldner Steven Joniau Antonino Battaglia Karin Haustermans Gert De Meerleer Valérie Fonteyne Piet Ost Hein Van Poppel Francesco Montorsi Alberto Briganti |
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PD72-04 |
Cancer-specific mortality among men with localized prostate cancer treated with radical prostatectomy versus radiotherapy: A multi-center study using propensity score matching and competing risk regression analyses |
Prostate Cancer: Localized: Radiation Therapy II | 17BOS |
Abstract: PD72-04 Sources of Funding: none Introduction Retrospective studies comparing outcomes of radical prostatectomy (RP) versus radiotherapy (RT) for patients with clinically localized prostate cancer (PCa) have conflicting conclusions and are limited by methodological biases arising from distinct baseline patient and cancer features. We used propensity score-matched analysis and consequent competing risk regression analysis to compare cancer-specific mortality (CSM) and other-cause mortality (OCM) outcomes of RP versus RT ± androgen deprivation therapy (ADT). Methods The multi-center Severance Urological Oncology Group PCa registry was utilized to identify 3,028 consecutive patients with localized PCa treated by RP (n=2,521) or RT±ADT (n=507) between 2005 and 2016. 339 RT±ADT cases were matched with an equal number of RP cases by propensity scoring based on patient age, preoperative prostate-specific antigen, biopsy Gleason score, clinical tumor stage, and Charlson Comorbidity Index (CCI). Competing risk regression analysis was used to evaluate CSM and OCM during the median follow-up of 68.9 months. Results Five-year OS rates for patients treated with RP and RT±ADT were 94.7% and 92.6%, respectively (p=0.105). Both treatments conferred comparable metastasis-free survival (p=0.778) and progression to CRPC survival (p=0.071), respectively. Cumulative incidence estimates revealed comparable CSM rates following both treatments within all NCCN risk groups (p=0.155). Gleason score ≥8 was associated with higher risk of CSM (HR=8.107, 95% CI 1.676-39.21; p=0.009). OCM rates were comparable between both treatment groups in the low and intermediate risk categories (p=0.354 and p=0.643, respectively). For high risk patients, RT±ADT was associated with higher OCM rates compared to RP (13.9% vs. 4.3%; p=0.001). Predictors of OCM were age ≥75 years (HR=2.382, 95% CI 1.363-4.164; p=0.002) and CCI ≥2 (HR=3.244, 95% CI 1.731-6.084; p<0.001). Conclusions RP and RT±ADT provide comparable CSM outcomes for all localized risk group patients with PCa. The risk of OCM should be cautiously considered when making treatment decisions for old aged high risk patients with significant comorbidities. Funding none
Authors
Jae Young Jeong
Kyo Chul Koo Woo Jin Bang Seung Hwan Lee Sung Yong Cho Sun Il Kim Se Joong Kim Jin Seon Cho Koon Ho Rha Sung Joon Hong Byung Ha Chung |
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PD72-05 |
Natural history of patients treated with salvage radiation therapy for rising PSA after radical prostatectomy: a long-term survival analysis |
Prostate Cancer: Localized: Radiation Therapy II | 17BOS |
Abstract: PD72-05 Sources of Funding: none Introduction A potential risk of significant competing causes of mortality in men submitted to salvage radiation therapy (SRT) might be present. We aimed at reporting the natural history of patients treated with SRT from a large multi-institutional series. Methods The study included 715 patients who received SRT at six tertiary referral centres for either PSA rising after RP, or PSA persistence after surgery that was defined as PSA level ≥0.1 ng/ml at 1 month after surgery. The irradiation of the pelvic lymph nodes area was left at the discretion of the treating physician. The study outcomes were cancer-specific (CSM) and other cause mortality (OCM). Cox regression analyses were used to predict the risk of CSM and OCM. Predictors consisted of patient age, pT stage (≤pT3a vs. ≥pT3b), pathologic Gleason (≤7 vs. ≥8), surgical margins (negative vs. positive), PSA level at SRT, and concomitant hormonal therapy (HT) administration. Competing-risks Poisson regression methodologies were performed. Results Median patient age and PSA level at SRT were 66 years and 0.30 ng/ml, respectively. At a median follow-up of 102 months (inter-quartile range: 61, 135), local recurrence was detected in 14 (2.0%) patients, whereas 30 (4.3%), 16 (2.3%), 64 (9.2%), and 13 (1.9%) developed pelvic, retroperitoneal, skeletal, and visceral metastasis, respectively. Overall, 154 patients were died at last follow-up: 39 patients succumbed to prostate cancer, and 115 died from other cause. At 10 years follow-up, CSM and OCM rates were 13% and 37%, respectively. At multivariable competing-risks regression analyses, pathologic stage ≥pT3b (HR: 3.16, p=0.006) and Gleason score ?8 (HR: 3.56, p=0.003) were independent predictors of CSM, after accounting for the risk of dying from other cause. Conversely, age (HR: 1.08, p<0.0001) and concomitant HT (HR: 1.15, p=0.001) represented independent predictors of OCM, after accounting for the risk of dying from prostate cancer. When patients were stratified by age (≤65 vs. >65), the risk of OCM at 10 years was significantly higher in older patients (77% vs. 50%, p<0.0001). Conclusions This is the first study assessing the long-term natural history of SRT after accounting for the risk of OCM. We showed that roughly a third of men submitted to SRT died from other cause rather than from PCa and this rate increased in older men receiving concomitant HT. These results should be taken into account when deciding on the use of SRT after radical prostatectomy according to each patient profile in order to avoid potential overtreatment. Funding none
Authors
Nicola Fossati
R. Jeffrey Karnes Stephen Boorjian Michele Colicchia Alberto Bossi Thomas Seisen Cesare Cozzarini Claudio Fiorino Barbara Noris Chiorda Giorgio Gandaglia Thomas Wiegel Shahrokh F. Shariat Gregor Goldner Steven Joniau Antonino Battaglia Karin Haustermans Gert De Meerleer Valérie Fonteyne Piet Ost Hein Van Poppel Francesco Montorsi Alberto Briganti |
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PD72-06 |
Adjuvant versus early salvage radiation therapy in node positive prostate cancer patients: a long-term survival analysis |
Prostate Cancer: Localized: Radiation Therapy II | 17BOS |
Abstract: PD72-06 Sources of Funding: none Introduction The role of post-prostatectomy radiation therapy (RT) in patients with pN1 prostate cancer is still under debate. However, whether adjuvant RT (aRT) is equal to early salvage RT (esRT) at long term in this setting is still unknown. In this study, we aimed at comparing the long-term effectiveness of aRT versus esRT. Methods Using a multi-institutional cohort from six tertiary referral centres, we identified 171 pN1 patients who were treated with radical prostatectomy and pelvic lymph node dissection. Patients were stratified into two groups: aRT (Group 1) versus initial observation followed by esRT in case of PSA relapse (Group 2). Specifically, aRT was administered at undetectable PSA level within 6 months after RP, whereas esRT was administered at a PSA level ≤0.5 ng/ml. The clinical target volume included the pelvic lymph nodes area, prostatic and seminal vesicle bed in all patients receiving RT. The evaluated outcomes were metastasis-free and overall survival. Multivariable Cox regression analyses tested the association between groups (aRT vs. observation ± esRT) and the study outcomes. Covariates consisted of pathologic stage (≤pT3a vs. ≥pT3b), pathologic Gleason score (≤7 vs. ≥8), and surgical margin status (negative vs. positive). Results Overall, 85 (50%) and 86 (50%) patients underwent aRT and initial observation, respectively. Median follow-up was similar among groups: 84 vs. 92 months (p=0.9). In group 2, 69 (80%) patients experienced PSA relapse and underwent esRT. Patients characteristics were not significantly different in terms of pathologic stage (≥pT3b: 60% vs. 53%, p=0.2), Gleason score (≥8: 44% vs. 41%, p=0.9), and positive surgical margins (59% vs. 55%, p=0.6). Overall, 26 patients developed distant metastasis with the following distribution: retroperitoneal nodes (n=5), bone (n=19), and other organs (n=2). At last follow-up, 13 patients succumb to prostate cancer and 13 patients died for other cause. Metastasis-free survival (67% vs. 72% p=0.2) and overall survival (78% vs. 74%, p=0.8) at 8 years after RP were not significantly different among groups. These results were confirmed at multivariable analyses for both distant metastasis (HR: 0.77; p=0.7) and overall survival (HR: 1.94; p=0.3). Conclusions At long-term follow-up, timely administration of esRT showed comparable metastasis-free and overall survival to aRT. Even in pN1 patients, esRT may not thus compromise cancer control, while significantly reducing potential over-treatment associated with aRT. Funding none
Authors
Nicola Fossati
R. Jeffrey Karnes Stephen Boorjian Michele Colicchia Alberto Bossi Thomas Seisen Cesare Cozzarini Claudio Fiorino Barbara Noris Chiorda Giorgio Gandaglia Thomas Wiegel Shahrokh F. Shariat Gregor Goldner Steven Joniau Antonino Battaglia Karin Haustermans Gert De Meerleer Valérie Fonteyne Piet Ost Hein Van Poppel Francesco Montorsi Alberto Briganti |
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PD72-07 |
Multiparametric MRI after radical prostatectomy predicts salvage radiotherapy outcomes for prostate cancer |
Prostate Cancer: Localized: Radiation Therapy II | 17BOS |
Abstract: PD72-07 Sources of Funding: none Introduction The Stephenson Nomogram estimates the success of salvage radiotherapy (sXRT) after radical prostatectomy (RP) but does not include multiparametric pelvic MRI (mpMRI). Here, we evaluate the utility of mpMRI in predicting sXRT failure after RP. Methods Men undergoing RP at Mayo Clinic from 2003-2015 who had biochemical recurrence and received sXRT were included in a retrospective chart review. Men who underwent prostate cancer treatment prior to RP, received adjuvant XRT, or who were hormone refractory at sXRT were excluded. Patients with mpMRI within 12 months of sXRT were retained. mpMRI lesions were grouped according to location: vesicourethral, seminal vesical (SV) bed / prostate fossa, pelvic nodes, pelvic bones. If no lesion was present, the mpMRI was categorized as negative. Standard descriptive statistics and multivariable cox regression analyses were performed to assess the impact of mpMRI on PSA recurrence after sXRT. Models were adjusted for the variables in the Stephenson Nomogram: PSA at RP, PSA prior to sXRT, PSA doubling time, hormone therapy with sXRT, sXRT dosage, extracapsular extension, SV invasion, pathologic Gleason score, margin status, and pN stage. Results Overall, 473 men had mpMRI prior to sXRT (median PSA at sXRT 0.45ng/ml). Of these, 56.9% (204) had an indeterminate or suspicious lesion on MRI: 25.6% (124) vesicourethral, 27.8% (135) SV bed / prostatic fossa, 7.0% (34) pelvic node, and 0.6% (3) pelvic bone. Median PSA with a visible lesion on mpMRI was 0.45ng/ml. At a median follow up of 42 months after sXRT, 29.3% (142) had PSA recurrence and 14.0% (68) had distant metastasis. Patients without a mpMRI lesion or with a suspicious nodal/bone lesion had higher rates of PSA recurrence at 4 years compared to those with vesicourethral/SV/prostate fossa lesions alone: 39.5% vs 21.9% (p<0.001), Figure 1. On multivariable analysis, patients without a mpMRI lesion or a suspicious nodal/bone lesion were significantly more likely to have PSA recurrence (HR 2.41, 95% CI 1.52-3.83, p<0.001) after adjusting for variables in the Stephenson Nomogram. Conclusions Pre-sXRT mpMRI is a valuable tool in risk stratifying men undergoing sXRT. The median PSA with a visible lesion on mpMRI was 0.45ng/ml, supporting the use of mpMRI in the early sXRT setting._x000D_ Funding none
Authors
Vidit Sharma
Avinash Nehra Michele Colicchia Mary E Westerman Adam T Froemming Lance A Mynderse R. Jeffrey Karnes |
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PD72-08 |
Distant recurrence patterns in patients with prostate cancer initially treated with brachytherapy who experienced biochemical failure. |
Prostate Cancer: Localized: Radiation Therapy II | 17BOS |
Abstract: PD72-08 Sources of Funding: None Introduction To examine the patterns of distant recurrence in patients with biochemical failure after treatment with brachytherapy for prostate cancer. Methods We identified 4,036 patients treated with brachytherapy with or without external beam radiation (EBRT) and/or androgen deprivation therapy (ADT) for their diagnosis of prostate cancer. These patients were treated between 1992 to 2012 at a single institution. Of those patients, 266 had a PSA recurrence as defined by the Phoenix criteria. Of those patients, 92 were found to have distant failure as defined by metastases to bones, visceral organs, or lymph nodes. Kaplan Meier analysis was used to estimate 5-year freedom from distant failure. Univariable and multivariable cox regression analysis was performed to identify factors associated with distant failure. Results Median age on presentation for our cohort was 67.5 with a median Gleason score of 7 and PSA of 9.3 ng/ml. We identified a 5-year freedom from distant failure rate of 65.7% with a median follow up of 8.17 years and a median time to BCR of 2.9 years after initial treatment with brachytherapy. Of those patients with distant metastases, 73.9% of patients showed metastases to the bone alone, 16.3% showed metastases to lymph nodes alone, 3.2% showed metastases to visceral organs alone, and 6.5% exhibited multiple sites of metastatic spread simultaneously. On multivariate analysis, Gleason score was significantly associated with increased risk of distant failure (HR=1.30, P=.045). Conclusions Patients who experience distant metastatic disease after BCR following brachytherapy are most likely to exhibit metastatic disease to bones, although metastases to visceral organs and lymph nodes were also observed. Gleason score was significantly associated with increased risk of distant failure. Our study is the first to look at patterns of metastatic recurrence within a cohort of patients specifically treated with brachytherapy as the primary modality for prostate cancer therapy. The above findings can be used when counseling patients with prostate cancer who are seeking brachytherapy treatment as well as when considering which imaging modalities to obtain for detection of metastatic disease. Funding None
Authors
Matthew Goland-Van Ryn
Richard Stock David Paulucci Nelson Stone Ketan Badani John Sfakianos |
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PD72-09 |
Early outcomes of focal brachytherapy for localized prostate cancer: comparison with whole gland brachytherapy. |
Prostate Cancer: Localized: Radiation Therapy II | 17BOS |
Abstract: PD72-09 Sources of Funding: None Introduction Focal brachytherapy (FBT) emerged as a reasonable option to treat patients with favorable prostate cancer (PCa). The aim of this study is to evaluate the early functional and oncological outcomes of FBT in the treatment of localized PCa._x000D_ Methods A retrospective review was performed at our prospective collected PCa database, searching for patients treated with FBT between 2010 and 2015. A cohort of 100 individuals treated with whole gland brachytherapy (WBT) in the same period was assessed in order to perform a comparison. IPSS, ICS and IIEF5 questionnaires were used to evaluate urinary symptoms, continence and sexual function, respectively, at 6, 12 and 24 months. All patients in the FBT group had a control prostate biopsy; PCa recurrence was defined as positive biopsy at the same treatment site. In the WBT group, PCa recurrence was defined by PSA increase > nadir + 2. Results Forty patients were included in the FBT group with complete oncological follow-up. Twenty-seven patients had completed questionnaires with 24 months of follow-up (included in the functional assessment). Initial presentation and treatment characteristics are exhibited on table 1. Median follow-up for FBT and WBT groups were 34 months (range: 10-68 months) and 24 months (range: 24-36 months), respectively. There was no difference in recurrence rates between-groups (FBT 7.5% vs. WBT 3%, p = 0.35) (fig. 1). WBT group had significant worsening of urinary symptoms when compared to FBT group at 6 months (p = 0.003), but not with 12 and 24 months. Urinary continence and sexual function was similar between-groups. Conclusions FBT has satisfactory oncological outcomes and less urinary symptoms at early follow-up when compared to WBT. Urinary continence and sexual functional is the same as WBT. Funding None
Authors
Victor Srougi
Eric Barret Mohammed Baghdadi Igor Nunes-Silva Silvia Garcia-Barreras Gregory Rembeyo François Rozet Marc Galiano Rafael Sanchez-Salas Jean Cosset Xavier Cathelineau |
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PD72-10 |
Assessing the risk of early and late toxicity of post-prostatectomy radiation therapy: a long-term multi-institutional analysis |
Prostate Cancer: Localized: Radiation Therapy II | 17BOS |
Abstract: PD72-10 Sources of Funding: none Introduction The risk of complications after radiation therapy (RT) is still controversial. Therefore, we aimed at reporting early and late genito-urinary (GU) and gastro-intestinal (GI) toxicity of post-prostatectomy RT using a large multi-institutional series. Methods The study included 1196 patients treated at six tertiary referral centres with either: (i) adjuvant RT (aRT); (ii) salvage RT (sRT); (iii) RT for PSA persistence (pRT), delivered at PSA level ≥0.1 ng/ml within 6 months after RP. The irradiation of the pelvic lymph nodes area was left at the discretion of the treating physician. Acute and late radio-induced GU and GI complications were classified according to the RTOG/EORTC scoring system. Multivariable logistic regression analysis was used to predict the risk of grade ≥2 early and late GU and GI toxicity. Covariates consisted of: radiation dose, radiation field (prostatic bed vs. whole pelvis), time from RP to RT, concomitant hormonal therapy (HT), and number of lymph nodes removed during RP. Results Overall, 281 (23%), 729 (61%), and 186 (16%) patients received aRT, sRT, and pRT, respectively. Median follow-up was 72 months. Overall, 658 (55%) patients had an early GU complication, of which 170 (14%) and 11 (1%) were grade 2 and 3, respectively. Similarly, 796 (67%) had an early GI complication, of which 287 (24%) and 3 (0.3%) were grade 2 and 3, respectively. Late GU complications were observed in 449 (38%) patients, of whom 140 (12%) and 72 (6%) had grade 2 and 3 events, respectively. Similarly, late GI complications were observed in 362 (30%) patients, of whom 120 (12%) and 19 (1%) had grade 2 and 3 events, respectively. At multivariable analysis, the concomitant HT administration was the only predictor that was significantly associated with both GU and GI early (OR: 2.03, p=0.002; and OR: 1.54, p=0.037) and late complications (OR: 2.08, p<0.001; and OR: 1.52, p=0.01). Whole pelvis irradiation was a significant predictor only for early GU (OR: 1.77; p=0.006) and early GI complications (OR: 3.20; p<0.001). Finally, the number of lymph nodes removed was associated with both early and late GI complications (OR: 1.12, p=0.02; and OR: 1.18, p=0.01). Conclusions At long-term follow-up, the risk of complications is not negligible, despite being mostly low grade. Concomitant HT represents a significant predictor of both early and late high-grade complications. Whole pelvis irradiation is a significant risk factor for early high-grade complications, whereas number of nodes removed is significantly associated with late high-grade complications Funding none
Authors
Nicola Fossati
R. Jeffrey Karnes Stephen Boorjian Michele Colicchia Alberto Bossi Thomas Seisen Cesare Cozzarini Claudio Fiorino Barbara Noris Chiorda Giorgio Gandaglia Thomas Wiegel Shahrokh F. Shariat Gregor Goldner Steven Joniau Antonino Battaglia Karin Haustermans Gert De Meerleer Valérie Fonteyne Piet Ost Hein Van Poppel Francesco Montorsi Alberto Briganti |
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PD72-11 |
Urethral strictures after radiotherapy for prostate cancer - 5 Year data of a certified prostate-cancer-centre |
Prostate Cancer: Localized: Radiation Therapy II | 17BOS |
Abstract: PD72-11 Sources of Funding: None Introduction Urethral strictures are scars of urethral epithelium, which can cause an obstructive voiding dysfunction with consecutive damage of the upper urinary tract. Almost 45% of all strictures are iatrogenic. Strictures occur in up to 2-9% after radical prostatectomy, but can also occur after radiotherapy for prostate cancer. This study provides 5-year data of a certified prostate-cancer-centre (PKZ) for the endpoint urethral stricture. Methods Between 01/2008 and 12/2012 a total of 519 men were irradiated for prostate cancer (LDR- and HDR-brachytherapy as well as external beam radiation). The entire cohort was followed-up prospectively according to a standardized protocol (stratified by type of irradiation). Short segment urethral strictures were treated by urethrotomy, recurrent and long segment stenosis with buccal mucosa urethroplasty. Results Overall, 18 out of 519 (3.4%) patients developed a urethral stricture post-therapeutically, which recurred in 66% of cases after the first operative treatment. The largest risk for developing a urethral stricture is attributed to the HDR-brachytherapy (8.9%). 2/82 (2,4%) patients after LDR-brachytherapy developed urethral strictures; 2/279 (0,7%) patients after external beam radiation suffered from strictures. Conclusions Urethral strictures after radiotherapy for prostate cancer should be diagnosed and treated in a timely fashion to prevent loss of renal function. The rate of radiogenic urethral strictures (3.4%) is equivalent to those after radical prostatectomy. Due to a high rate of recurrences, urethrotomy has a limited importance after irradiation. Funding None
Authors
Jennifer Kranz
Uwe Maurer Gerlinde Maurer Oliver Deserno Joachim Steffens |
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PD72-12 |
SEER ANALYSIS OF RISK OF BLADDER, RECTUM AND COLON CANCER AFTER RADIOTHERAPY FOR PROSTATE CANCER IN YOUNGER AND OLDER MEN |
Prostate Cancer: Localized: Radiation Therapy II | 17BOS |
Abstract: PD72-12 Sources of Funding: None Introduction Despite improvements in various forms of radiotherapy for prostate cancer over the past 20 years, secondary malignancies remain a concern, especially amongst younger patients. We analyzed a population-based cancer database to compare the risk of bladder, rectum and colon cancer after definitive treatment of prostate cancer with external beam radiotherapy (EBRT) or brachytherapy (BT) compared to surgery; and assessed its differential impact by age at diagnosis. _x000D_ Methods We analyzed a cohort of 198,738 men from the SEER database diagnosed with localized prostate cancer between 1993 and 2013. We used Cox regression models and to assess the association between BT and EBRT vs. surgery and the likelihood of developing subsequent bladder, rectum or colon cancer 2 or more years after treatment. For subgroup analyses, we separately analyzed these associations in men who were below and above the age of 65 years using a similar analysis. To help account for multiple comparisons p values < .005 were considered statistically significant._x000D_ Results The incidence of secondary malignancies was low in all groups (~ 4.3%). All three sites showed a statistically significant (p < 0.0001) increase in the hazard of secondary cancers compared to surgery (colon HR: 1.46, 95%, CL: 1.36 - 1.57; rectum HR: 1.78, 95%, CL: 1.59 - 1.99; bladder HR: 2.19, 95%, CL: 2.05 - 2.34). While exposure to radiation was associated with increased hazards in both younger and older men, consistently higher hazards were seen in the younger cohort. We found that EBRT was associated with a higher risk of cancer at all sites in both younger and older men, but BT was not associated with an increased risk of colon or rectal (Table 1). _x000D_ Conclusions Incidence of bladder, rectum and colon cancer is significantly increased after treatment of prostate cancer with radiotherapy compared to surgery. Effects are observed regardless of age, and worse in men who are younger and those receiving EBRT. _x000D_ Funding None
Authors
Diana Lopategui
Raymond Balise Marcelo Panizzutti Sanoj Punnen |
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PD73-01 |
Renal mass biopsy is associated with increased incidence of pathological upstaging to perinephric fat invasion in patients with clinically localized renal cell carcinoma |
Kidney Cancer: Localized: Surgical Therapy VII | 17BOS |
Abstract: PD73-01 Sources of Funding: None Introduction Renal mass biopsy (RMB) provides important information about the aggressiveness of renal tumors and helps urologists in the treatment decision-making process. Although tumor tract seeding is exceedingly rare, we questioned whether tumor capsule violation from RMB is associated with increased risk of perinephric fat invasion. In this study, we evaluated the association between RMB and perinephric fat invasion in patients with localized RCC who underwent partial or radical nephrectomy. Methods We reviewed the National Cancer Database from 2004-2013 and identified patients who underwent partial nephrectomy (PN) or radical nephrectomy (RN) for clinical T1a, T1b, and T2a tumors. Patients were classified as upstaged if final pathology demonstrated perinephric invasion only. Patients who received neoadjuvant systemic treatment, those with clinically node positive disease, and tumors with renal sinus fat invasion were excluded. Logistic regression analysis was used to identify predictors of perinephric fat invasion. Descriptive statistics were then used to compare patient demographics and tumor characteristics between those with RMB and those without RMB. Results A total of 56,557 patients met our inclusion criteria. Pathologic upstaging to pT3a disease occurred in 3.7% of patients, of which 2.1% (1,191/56,557) had perinephric fat invasion only. RMB was performed in 3,740 (6.6%) patients. Age ≥70, Caucasian race, Charlson-Deyo score ≥2, and tumor size ≤4cm were associated with higher utilization of RMB. Perinephric fat invasion was identified in 2.0% of patients without RMB and in 2.9% of patients with RMB. Logistic regression demonstrated a significant association between RMB and perinephric fat invasion (OR 1.51, 95% CI 1.24 - 1.85) after controlling for confounders. As an additional control, RMB was not found to be associated with risk of upstaging to renal sinus fat invasion. Conclusions Perinephric fat invasion on final pathology is a rare finding in patients with clinically localized renal tumors. Although performed for relatively smaller tumors, RMB is associated with risk of upstaging to pT3a disease and this is limited to perinephric fat invasion. This finding may be secondary to pathologic artifact or confounding variables not accounted for in our multivariable model. Prospective studies to evaluate cancer specific outcomes, such as recurrence, are warranted to further investigate the clinical relevance of these findings. Funding None
Authors
Amirali Salmasi
Andrew Lenis Izak Faiena Nicholas Donin Allan Pantuck Karim Chamie |
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PD73-02 |
Grading the Non-Neoplastic Kidney Predicts Post-operative Renal Function in Radical Nephrectomy Specimens |
Kidney Cancer: Localized: Surgical Therapy VII | 17BOS |
Abstract: PD73-02 Sources of Funding: None Introduction Existing pre-operative measures of kidney function have limitations. We utilize clinical and histopathologic changes in the non-neoplastic kidney (NNK) to predict post-operative renal function one and two years post radical nephrectomy (RN) for renal cell carcinoma (RCC). Patients were followed for up to 5 years. Methods This retrospective review included all patients undergoing RN for RCC measuring <10 cm with a normal contralateral kidney between January 1, 2011 - May 1, 2015. All slides were independently re-reviewed for histopathologic changes using the Banff 97 criteria by two blinded nephropathologists for any chronic glomerular (G), tubulointerstitial (IFTA), arterial (Art), and arteriolar changes (Arl). Univariate analyses were conducted with Spearman correlation coefficients and ANOVA. Factors significantly associated with post-operative eGFR were entered into multivariable regression (MVR) models. Separate regression models were created for the clinical and histological factors. Predictive performance was evaluated with the r-square statistic. Estimated glomerular rate (eGFR) was calculated using chronic kidney disease epidemiology collaboration formula. Results The 167 patients had a mean age, Charlson comorbidity score, and tumor size of 61, 2.6, and 6.2cm, respectively. The group consisted of diabetics (26%), hypertensives (60%), and smokers (35%). Mean pre-op eGFR and 24-month eGFR were 78 and 51mL/min/1.73m2, respectively. Severe histopathologic changes were discovered in 11% of patients despite normal pre-operative eGFRs. New kidney disease was common (54%); 8 patients progressed to dialysis and 20 died during follow-up. NNK changes were significantly associated post-op eGFR at 1 year (R2=0.52) and 2 years (R2=0.5). Severe G and IFTA were associated with an independent eGFR change of decline of -28 (p<0.001) and -16 mL/min/1.73m2 (p=0.0005). Art (p=0.08) and Arl (p=0.387) changes were not associated with eGFR changes. Age (p<0.0001), body mass index (p=0.0039), and age-adjusted Charlson co-morbidity (p=0.0434) were significantly associated with post-op eGFR. Using MVR modeling a calculator was developed and accurately predicted post-op eGFR. Conclusions Using age, glomerular, and tubulointerstitial histopathologic variables alone, the post-operative eGFR can be accurately calculated. This calculator may guide studies on subsequent therapeutic intervention following radical or partial nephrectomy. Funding None
Authors
Deepak Pruthi
Vivian Lu Ruchi Chhibba Evan Weins Ian Gibson Thomas McGregor |
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PD73-03 |
Impact of renal vein invasion on the outcomes in patients with renal cell carcinoma and caval tumor thrombus |
Kidney Cancer: Localized: Surgical Therapy VII | 17BOS |
Abstract: PD73-03 Sources of Funding: none Introduction Invasion of main renal vein (RV) wall is not defined as an adverse pathological feature in the current TNM staging in patients with renal cell carcinoma (RCC) & inferior vena cava (IVC) tumor thrombus. In some recent studies, RV wall invasion is suggested as a predictor of poor outcomes. In this study, we sought to determine the impact of renal vein wall invasion on the risk of recurrence and death in patients with RCC and caval tumor thrombus._x000D_ Methods A cohort of 257 patients with non-metastatic RCC and level II-IV IVC thrombus who underwent surgery between 1990-2015 at our institution were studied. Patient demographics, clinical, pathological features including renal and IVC wall invasion, and outcomes information were obtained. Univariable and Multivariable Cox-proportional hazard model were used for analysis. Results Median age of the cohort at surgery was 64 years. A total of 45% patients had renal artery embolization prior to surgery. On preoperative imaging tumor thrombus level was noted as level 2 in 112 patients (42%), level 3 in 90 patients (35%) and level 4 in 51 patients (20%). A total of 35% had recurrence with mean time to recurrence of 15 months. At mean follow up time of 21 months, 53% were alive. Main RV and IVC wall invasion was present in 57% and 15% patients respectively._x000D_ _x000D_ On univariable analysis, microscopic main RV wall invasion was not significantly associated with increased risk of recurrence (Hazard ratio[HR]=1.13) or death (HR=1.07) (both p>0.05). Invasion of IVC wall was associated with increased risk of recurrence (HR=1.9, p<0.05) but was not significantly associated with increased risk of death (HR=0.87, p=0.7). Lower preoperative hemoglobin, need for bypass, need for blood transfusion, older age, and longer operative time were associated with poor survival (all p<0.05)._x000D_ Conclusions Main RV wall invasion is present in significant proportion of patients with non-metastatic RCC with IVC tumor thrombus, however, in our cohort it was not associated with increased risk of recurrence or death. Main RV wall invasion should be reported by the pathologist until the impact of this finding is clearly defined. Funding none
Authors
Sudhir Isharwal
Joseph Zabell Scott Lundy Sarah Vij Venkatesh Krshnamurthi |
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PD73-04 |
A Comparison of Overall Survival Between Partial and Radical Nephrectomy for T1 Renal Masses: A Report from the National Cancer Database |
Kidney Cancer: Localized: Surgical Therapy VII | 17BOS |
Abstract: PD73-04 Sources of Funding: None Introduction Partial nephrectomy (PN) is the recommended treatment for cT1a renal masses. Compared to radical nephrectomy (RN), PN offers comparable cancer specific survival, with better functional outcome. However, there are conflicting results regarding the benefit of PN on overall survival (OS). We sought to compare the OS of patients with a T1 renal mass who underwent PN or RN. Methods The American College of Surgeons National Cancer Database of 351,112 patients with kidney cancer was utilized to identify patients 39,346 patients who underwent RN (n=32,665, 83.1%) or PN (n=6,681, 16.9%) for a pT1N0M0 clear cell, chromophobe or papillary renal cell carcinoma from 2003 to 2012. OS for PN vs. RN for at a median follow-up of 4.1 years (IQR 2.3-6.2 years) was compared overall and separately for T1a and T1b renal masses. OS was specifically compared in a multivariable cox proportion hazards regression model adjusting for age, Charlson-Deyo score, race, ethnicity, histology, stage, treatment facility type and other socioeconomic factors. Results Patients who underwent RN were more likely to have a T1b renal mass, (48.8% vs. 42.2%, p<.001), be of Hispanic ethnicity (p=.002) and have clear cell vs. chromophobe or papillary RCC (p<.001) There were no differences in age (p=.131), insurance status (p=.927), gender (p=.431), race (p=.076), income (p=.565), year of diagnosis (p=.525), margins (p=.216) between groups. The 5-year OS was 83.0% for RN 82.8% for PN (p=.850). In multivariable analysis, no difference in OS between PN and RN was found for T1 overall (HR=1.01; 95% CI=0.94, 1.08; p=.782), for T1a (HR=1.05; 95% CI=0.96, 1.19; p=.331) or for T1b (HR=0.97; 95% CI=0.87, 1.07; p=.520). Furthermore, OS for PN did not differ for patients ? 75 years old with a T1 renal mass (HR=1.06; 95% CI=0.96, 1.19; p=.251) or patients < 75 years old with a Charlson-Deyo score of 0 and a T1 renal mass (HR=1.01; 95% CI=0.89, 1.09; p=.806). Conclusions There was no difference in overall survival between PN and RN with a median follow up of 4.1 years. Longer-term studies are required to determine any impact on OS between PN and RN. Funding None
Authors
David Paulucci
Alp Tuna Beksac John Sfakianos Ketan Badani |
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PD73-05 |
A Multi-Institutional Propensity Score Matched Comparison of Transperitoneal vs. Retroperitoneal Robotic Partial Nephrectomy for Posterior Clinical T1 Renal Masses |
Kidney Cancer: Localized: Surgical Therapy VII | 17BOS |
Abstract: PD73-05 Sources of Funding: None Introduction A retroperitoneal approach compared to transperitoneal during partial nephrectomy (PN) can provide superior access to posteriorly located renal tumors. To elucidate any benefit to this approach, we compared perioperative and renal functional outcome in the largest comparison to date of transperitoneal and retroperitoneal robotic PN (TP-RPN and RP-RPN) for posterior tumors. Methods The present study identified 1684 patients who underwent RPN for a solitary clinical T1 renal tumor from 6 different surgeons from 2006 to 2016. Patients with a tumor anterior (n=519) or neither anterior nor posterior to the coronal plane (i.e., lateral, n=253) were excluded from the analysis. There were 519 patients who underwent either TP-RPN (n=357, 68.8%) or RP-RPN ( n=162, 31.2%) for a posteriorly located tumor that met inclusion for this analysis. TP-RPN and RP-RPN patients were 1 to 1 propensity score matched on pre-operative and tumor-specific characteristics. Perioperative outcome and renal function outcome at 22 months (IQR 8.9-41.6 months; Range 3.2-95.9 months) were compared with Mann-Whitney U tests and Chi-squared tests of independence. Results Between the propensity score matched TP-RPN (n=157, 50%) and RP-RPN (n=157, 50%) patients, no significant differences in age (p=.481), age adjusted CCI (p=.053), body mass index (p=.996), baseline eGFR (p=.502), tumor size (p=.741) or R.E.N.A.L. Nephrometry score (p=.308) were identified. Operative time (185.0 vs. 157.0, p<.001) was longer in TP-RPN vs. RP-RPN patients. No significant differences in warm ischemia time (p=.618), estimated blood loss (p=.178), positive surgical margins (p=.501), medical post-operative complications (7.0% vs. 2.5%, p=.064), major complication rates (p=.295), or progression of Chronic Kidney Disease stage at 22 months (p=.550) were identified. Conclusions RP-RPN for posterior tumors resulted in reduced operative time when compared to TP-RPN. All other measures including ischemia time, blood loss, margin rates, complications, and renal function did not differ between the two approaches, both of which are safe to treat posterior tumors. Funding None
Authors
David Paulucci
Ronney Abaza Daniel Eun Akshay Bhandari Ashok Hemal James Porter Ketan Badani |
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PD73-06 |
COMPARATIVE TRIFECTA OUTCOMES AFTER LAPAROSCOPIC PARTIAL NEPHRECTOMY (LPN): CLAMPING VERSUS OFF-CLAMPING FOR HIGH COMPLEXITY RENAL SCORE TUMORS |
Kidney Cancer: Localized: Surgical Therapy VII | 17BOS |
Abstract: PD73-06 Sources of Funding: None Introduction The duration of renal ischemia is the largest modifiable risk factor during partial nephrectomy. The shorter the warm ischemia time during LPN the lower the effect on long-term renal function. Real advantages of off-clamping LPN compared with clamping surgery are not yet sufficiently studied. Few studies reported results of off-clamping LPN for high RENAL score cases. We compared Trifecta outcomes of the LPN with and without clamping stratifying cases through nephrometric RENAL score. Methods A total of 109 cases classified as low-complexity (54), intermediate-complexity (33) and high-complexity (22) underwent clamping (55) or off-clamping (54) laparoscopic partial nephrectomy and were compared in each group (clamping x off-clamping LPN). Clamping technique was performed with cold scissors intended to obtain 0.5cm of free surgical margins. Off-clamp technique was performed with harmonic scalpel close to the plane of enucleating to achieve minimal surgical margins. Renal function was measured at 1, 6 and 12 months postoperatively. All enrolled patients had normal contra-lateral kidney. Trifecta (Trifecta criteria: Clavien ≤ 2, negative-margins, and warm ischemia time ≤ 20 min) outcomes were analyzed and compared between the groups stratified by the nephrometric RENAL score. Results Trifecta achievement was similar in both groups for low complexity tumors (p < 0.31). The off-clamping group achieved higher trifecta rates for the intermediate (87.5% x 23.5%, p < 0.001) and high (83% x 0%, p < 0.005) complexity tumors. Patients with off-clamp technique had higher mean blood loss (150 X 400 ml) with no difference in blood transfusions. In the clamping group, significant higher proportion did not achieve trifecta (45.5% x 7.4%, p < 0.001). After 1 year, the difference of remnant renal function was 10% more for patients with off clamp surgery with high complexity RENAL score Conclusions Off-clamping pure LPN was associated to accomplish higher trifecta rates for intermediate and high complexity RENAL score tumors. Long-term renal function was slightly better for off clamp group. It is unclear if off-clamp technique or differences in the amount resected of renal parenchyma were responsible for observed differences. Funding None
Authors
Marcos Tobias-Machado
Jônatas Pereira Alexandre Hidaka Igor Nunes-Silva Sidney Glina Hamilton Zampolli Eliney Faria |
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PD73-07 |
Analysis of Risk Factors Associated with Infections Complications Following Partial Nephrectomy |
Kidney Cancer: Localized: Surgical Therapy VII | 17BOS |
Abstract: PD73-07 Sources of Funding: Stephen Weissman Kidney Cancer Research Fund Introduction Partial nephrectomy (PN) is the standard for management for cT1a renal mass and is increasingly used for larger tumors. Compared to radical nephrectomy, however, it may carry a higher risk of procedure-specific complications, including perioperative infections. We determined to identify risk factors for infectious complications after PN Methods Single-center retrospective analysis of patients who underwent PN from 7/2008-1/2015. Demographics, disease and operative characteristics (including surgical approach and length of antibiotic coverage), and occurrence and site of infectious complications were reviewed. Rate of infectious complications following PN at the 30 day and 90 day postoperative mark was calculated. Multivariable analyses (MVA) for risk factors associated with infectious complications during the first 30 and 90 days postoperatively were performed Results 481 patients were analyzed (mean age 63.1 years, 61.3% male/38.7% Female). Median tumor size was 3.5 cm (IQR 1.9-4.7). Minimally invasive PN was performed in 63.1% (N=299) and open PN was performed in 36.9% (N=175). Urine leak occurred in 21 (4.4%). Infection in first 30 days postoperatively occurred in 29 patients (6%), while infection in first 90 days postoperatively occurred in 42 patients (8.7%). Infection sites during the first 30 day period were wound (N=9), urinary tract (N=8), respiratory (N=7), abscess/sepsis (N=4), and C. difficile (N=3). De novo infectious events >30 and < 90 days were wound (N=6), urinary tract (N=4), and abscess/sepsis (N=4). MVA for infectious complications in first 30 days revealed duration of antibiotic therapy >24 hours (OR 1.91, p=0.01) as being the only independent risk factor for development of infectious complication. MVA for infectious complications during first 90 days postoperatively revealed urine leak (OR 6.21, p<0.001) and increasing delta GFR (OR 1.02, p=0.006) as being independent risk factors Conclusions Postoperative infectious complications occurred in less than 10% of patients undergoing PN, with most occurring in the first 30 days. Overall wound and urinary tract infections were most common throughout, while abscess/sepsis increased over time, and respiratory and GI/C. difficile decreased over time. Perioperative antibiotics should be limited to <24 hours as part of strategies to reduce risk of infectious sequelae Funding Stephen Weissman Kidney Cancer Research Fund
Authors
Richmond Owusu
Michael Liss Sean Berquist Abd-elrahma Hassan Charles Field Aaron Bloch Unwanaobong Nseyo Fang Wan Zachary Hamilton Ithaar Derweesh |
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PD73-08 |
The impact of intra vs. post-operative blood transfusion on cancer recurrence and survival following nephrectomy for renal cell carcinoma |
Kidney Cancer: Localized: Surgical Therapy VII | 17BOS |
Abstract: PD73-08 Sources of Funding: none Introduction The effects of perioperative blood transfusion (PBT) on morbidity, mortality following cancer surgery have previously been demonstrated in several malignancies including renal cell carcinoma (RCC). However, the significance of transfusion timing is still unclear. The purpose of this study is to evaluate whether intraoperative BT (InBT) differ from postoperative BT (PoBT) in regards to oncological outcomes in patients treated with nephrectomy for RCC. Methods Study included 1159 patients with RCC who underwent radical (RN) or partial nephrectomy (PN) between 1988 and 2013. PBT was defined as receipt of packed red blood cells either during surgery or during the postsurgical hospitalization. Univariate and multivariate models were used to evaluate the association of BT with cancer-specific survival (CSS), disease-free survival (DFS) and overall survival (OS). Results Of 1159 patients undergoing nephrectomy, 198 patients (17.1%) received a PBT. Patients were next divided into 3 groups; no PBT, InBT alone (n=117) and PoBT alone (n=60). Twenty one patients of the PBT group (10.6%) received both intra and post-operative transfusion. Given the small number of patients, this sub-group was excluded. On multivariate analyses, receipt of InBT was associated with significantly increased risk of local disease recurrence (HR: 2.3; P=0.025), metastatic progression (HR: 2.2; P=0.006), cancer- specific mortality (HR: 2.95; P=0.009) and all-cause mortality (HR: 2.05; P=0.007); while receipt of a PoBT did not independently bear an increased risk of local recurrence (p = 0.1), metastatic progression (P=0.095) or kidney cancer death (P=0.53), yet did significantly increase the risk of overall mortality (HR: 2.6; P=0.002). Conclusions In the current cohort, InBT but not PoBT was associated with significantly increased risk of cancer recurrence and cancer-specific mortality._x000D_ This observation requires further studies to assess the impact and management of more restrictive intraoperative blood management strategies._x000D_ Funding none
Authors
Yasmin Abu-Ghanem
Zohar Dotan Issac Kaver Dorit Zilberman Jacob Ramon |
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PD73-09 |
Big renal angiomyolipoma: The 4 cm size limit for conservative management should be revisited? |
Kidney Cancer: Localized: Surgical Therapy VII | 17BOS |
Abstract: PD73-09 Sources of Funding: None Introduction The 4 cm size of renal anagiomyolipoma (AML) has been reported to increase the risk of pain and bleeding. It was our observation that many patients with renal AML of size > 4 cm are asymptomatic and are safely followed up without intervention. Here, we report 11 patients (pts) with renal AML of size of 10 cm or more, with the majority being treated conservatively. Methods Eleven pts with giant renal AML with size of 10 cm or more were identified in our records. Medical records of these patients were reviewed as regards to diagnosis, association with tuberous sclerosis, management and outcome. Results These were 7 females and 4 males with median age of 43 years (ranage:29-71). Five pts had tuberous sclerosis (TS) and 6 has sporadic renal AML. The 5 patients with TS have bilateral and multiple renal AML while 5 of the sporadic AML are unilateral and single and only one had 2 lesions in one kidney and a small one in the other kidney. The greatest diameter of the biggest lesion had a median of 15.5 cm (range: 10-32). Only one patient had significant pain associated with a lesion of 16 cm while the remaining patients were asymptomatic or had slight pain. Serum creatinine was normal in all patients with a median of 68 umol/L (range, 39-109). Big Aneurysms (>10 mm) were seen in 3 renal units (2 pts) with TS and required selective angioembolization that was successful. Partial nephrectomy was needed in 2 patients, one with significnat pain not relieved by selective embolization and another one explored for suspicious retroperitoneal liposarcoma. Everolimus was given to 4 patients, one of them , initially with huge bilateral multiple AML, extending from the diaphragm down to the pelvis, and with big hemorrhagic cystic lesion responded reasonably well with decrease of the size of AML and the associated hemorrhagic cyst. In the remaining 3 patients, the drug was discontinued because of side effects in 1, and no response in 2. At last follow up with a median duration of 68 months, all patients were asymptomatic and serum creatinine (median, 60 umol/L) remained within normal range, except mild increase in 2 pts, with no significant difference compared to its level at presentation (P =0.45). The CT at last follow up showed no significant big aneurysms and the greatest diameter of the biggest lesion is not significantly different from the one at presentation (p=0.9). Conclusions Big AML >10 cm remained stable in the majority of patients with conservative management. Renal function remained normal in the majority of these patients with long term follow up. Big aneurysms within AML can be successfully treated by superselective embolization. Nephron-sparing surgical excision of AML can be done for those with significant pain. The 4 cm cut off limit for conservative treatment should be revisited. Funding None
Authors
Mohamed Gomha
Magdy Al-Gahwary Yousef Alsowayan |
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PD73-10 |
Comparison Between Laparoendoscopic Single Site Nephrectomy and Conventional Laparoscopic Nephrectomy: A Randomized Control Single Institution Experience |
Kidney Cancer: Localized: Surgical Therapy VII | 17BOS |
Abstract: PD73-10 Sources of Funding: none Introduction Laparoendoscopic single site nephrectomy (LESS-N) has been shown to offer better cosmetic outcomes on the expense of longer operative times compared to laparoscopic nephrectomy (LN). It was also associated with debatable improvement in blood loss, pain scores, hospital stay and postoperative recovery. The aim of this study is to present an operative and postoperative outcome comparison between LN and LESS-N in all patients with different nephrectomy indications. Methods This single blinded prospective randomized control trial was conducted at the Urology department of Cairo University from 2012 to 2014. 54 Patients indicated for nephrectomy were randomized to either LESS-N or LN. The main outcomes analyzed included operative time, blood loss, hospital stay, complications and visual analogue pain scores. We used the days off work and the days needed to reach 100% of previous physical activity as clinical end points to compare convalescence. We also compared body image satisfaction scores and the overall rating of the experience. Results The mean age at nephrectomy was 35 years in the LESS-N group and 40 in the LN group (p=0.2). Indications for nephrectomy were recurrent urinary tract infections in nonfunctioning kidneys (n=36), malignant renal masses (n= 10), Donor nephrectomy (n=6) and renovascular hypertension (n=2). Compared to LN the mean operative time was longer in the LESS group (157 vs 182 min, p=0.046). There was no statistically significant difference in the mean blood loss (115 vs 148 ml, p=0.331), hospital stay (2.9 vs 3.2 days, p=0.14) or pain scores. Four patients (14.8%) from the LESS-N group suffered from complications compared to only 1 patient (3.7%) from the LN group. The patient’s mean scar satisfaction score was higher in the LESS group (9.3 vs 8.3, p=0.003). The mean days off work (20.7 vs 27.3 days, p=0.07), the mean number of days to 100% activity (53.7 vs 70.6, p=0.14) and the score given to the overall experience by the patient (8.8 vs 8.4, p=0.3) did not differ significantly between the 2 groups Conclusions LESS-N offers a superior cosmetic outcome compared to LN on the expense of operative time and surgical difficulty. However, the LN group also enjoyed excellent scar satisfaction. Many studies showed that the importance of cosmesis is more evident in younger patients and those with non-oncological conditions. We believe that the choice for LESS nephrectomy should be tailored to each specific patient according to his age, individual perception of scar importance, indication for nephrectomy and size of kidney to be removed rather than offering it unanimously to all our nephrectomy population Funding none
Authors
Mohamed Eltemamy
Mahmoud Abdel Hakim Ahmed El-feel Ahmed Elshafei Omar Abdel-Razzak |
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PD73-11 |
Management of contralateral recurrence after radical nephroureterectomy for upper tract urothelial carcinoma |
Kidney Cancer: Localized: Surgical Therapy VII | 17BOS |
Abstract: PD73-11 Sources of Funding: None Introduction Contralateral recurrence after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) is rare and difficult to manage. Clinicians and patients are faced with the difficult decision of balancing oncologic control while preserving renal function. We report our experience on management and outcomes of contralateral recurrence in patients after RNU for UTUC. Methods Between 1995 and 2009 we retrospectively reviewed 480 patients who underwent RNU at Mayo Clinic. We identified 21 (4.3%) patients who developed UC recurrence in the contralateral system following initial RNU. Patients with metastatic disease before or at the time contralateral recurrence and patients with non-UC primary tumors were excluded. Charts were retrospectively reviewed. Progression to metastatic disease from the time of contralateral recurrence was investigated as the primary outcome of interest. Results The median age of the cohort was 72 years. Of the 21 patients, 14 (70%) were male, 19 (91%) were smokers, 13 (62%) had a history of bladder cancer and 10 (77%) had previously undergone a cystectomy. The urine cytology was positive in 15 (71%) prior to the initial RNU. During the initial RNU, 17 (81%) had non-muscle invasive disease; 10 (48%) had high grade pathology; 7 (33.3%) had concomitant CIS and 10 (48%) had multifocal disease. Median time to contralateral recurrence from the initial RNU was 12 months. Over a median follow up of 42 months, the overall median number of endoscopic procedures to manage contralateral recurrence was 3 (IQR 2, 4.5). 11 (52%) patients had intrapelvic instillation either via a nephrostomy tube or reflux through a stent. 6 (29%) patients eventually underwent definitive treatment with a second RNU. Of these, 5 had attempts at endoscopic control before second RNU; and the median number of endoscopic procedures was 2. The 3-year metastasis free survival was 68% and there was no statistically significant difference in progression to metastatic disease between patients undergoing RNU and those managed with only endoscopic approach (p=0.31). Progression to metastasis was seen more frequently in patients with a history of bladder cancer (p=0.01). Conclusions Approximately, 5% of patients with UTUC following RNU develop contralateral recurrence. Patients with a history of bladder cancer who develop contralateral recurrence are more likely to die of metastatic disease. Therefore, more studies are needed to elucidate the role of early definitive treatment in this unique patient population. Funding None
Authors
Amir Toussi
Vidit Sharma Tanner Miest George Chow Bradley Leibovich Matthew Tollefson |
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PD73-12 |
Pathologic predictors of muscle invasive urothelial carcinoma of the bladder following radical nephroureterectomy |
Kidney Cancer: Localized: Surgical Therapy VII | 17BOS |
Abstract: PD73-12 Sources of Funding: None Introduction Intravesical recurrence after radical nephroureterectomy (RNU) ranges from 15% to 50%. However, only a few studies have investigated pathologic characteristics of bladder tumor recurrence, and even fewer have evaluated risk factors for muscle invasive bladder cancer (MIBC) after RNU for primary treatment of upper tract urothelial carcinoma (UTUC). Therefore, we present our data on the clinical course of intravesical recurrence and pathologic features for MIBC following RNU. Methods Between 1995 and 2009 we identified 395 patients who underwent RNU at Mayo Clinic for urothelial carcinoma. We identified 113 patients who subsequently developed intravesical recurrence. Patients with a prior radical cystectomy were excluded. Charts were retrospectively reviewed. Kaplan Meier analysis and Cox Proportional hazard regression models were used to estimate predictors and the risk of intravesical recurrence and MIBC from the time of RNU. Results Of the 395 patients, 28.6% (113) developed intravesical recurrence and 4.5% (18) had MIBC following RNU. Over a median follow up period of 43.4 months, 18.5% (21) of patients underwent radical cystectomy for intravesical recurrence; of these 52% (11) was for MIBC. Median time to intravesical recurrence was 7.8 months and median time to development of MIBC was 17.9 months. The 5-year probability of developing intravesical recurrence was 37.5%; while the 2, 5, and 10-year estimates of MIBC were 1.1%, 6.0%, and 6.7%, respectively. The 5-year cancer specific survival for patients who developed intravesical recurrence and MIBC after RNU was 86.1% and 65.2%, respectively (p=0.01). Specifically, high grade pathology, ureteral tumors and concomitant CIS were associated with an increased risk of MIBC (HR 3.4, p=0.01; HR 6.7, p<0.01; and HR 2.7, p=0.05; respectively). Conclusions Approximately 5% of patients develop MIBC following RNU for primary UTUC. High grade pathology, ureteral tumors and concomitant CIS at the time of RNU are predictive of MIBC on subsequent intravesical recurrence. Funding None
Authors
Amir Toussi
Tanner Miest Vidit Sharma George Chow Bradley Leibovich Matthew Tollefson |
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PNFBA-01 |
Convective Radiofrequency Water Vapor Energy Ablation (Rezum®) Effectively Treats Lower Urinary Tract Symptoms Due to Benign Prostatic Enlargement regardless of Obesity while Preserving Erectile and Ejaculatory Function |
Best Abstracts: Next Frontier, Sunday, Afternoon Session | 17BOS |
Abstract: PNFBA-01 Sources of Funding: NxThera Introduction To assess the impact of convective RF water vapor thermal therapy (WaVE) to treat LUTS due to BPE (LUTS/BPE) on subjective and objective voiding and sexual function parameters and to compare results between obese (BMI > 30) and non-obese subjects. Methods Men ≥ 50 years old with IPSS ≥ 13, peak flow rate (Qmax) between 5 and 15 mL/s, and prostate size 30 to 80cc were randomized 2:1 between WaVE and sham procedure with cystoscopy and simulated treatment sounds. Blinded comparison was done at 3 months and the treatment arm was followed for 12 months for IPSS, Qmax, and sexual function via IIEF-15 and Male Sexual Health Questionnaire for Ejaculatory Function (MSHQ-EjF). Percentage of subjects who achieved minimal clinically important difference in erectile function perceived by subjects as beneficial (MCID) was determined. Treatment outcomes for obese and non-obese subjects were compared. Results 197 men were randomized, 136 in WaVE group, 61 in sham group. WaVE group and control group IPSS reduced by 11.2 and 4.3 at 3 months (p<0.0001). WaVE group IPSS decreased by 50% or greater at 3, 6, and 12 months (p<0.0001). Peak flow rate in WaVE group increased by 6.2 mL/s at 3 months and sustained through 12 months (p<0.0001). 42 treatment subjects had a median lobe, 30 had the median lobe treated with similar outcomes to treated subjects without median lobes. Obese subjects had similar improvement in IPSS as compared to non-obese subjects, including both storage and voiding domains. IIEF-15 and MSHQ-EjF scores were not different between WaVE or control groups at 3 months and were not different in WaVE group from baseline at 12 months. Ejaculatory bother improved 31% in WaVE group over baseline (p=0.0011). 32% of subjects in WaVE group achieved MCID at 3 months and 27% at 1 year, in all ED categories. Obese subjects were more likely to have severe ED but experienced similar rate of MCID and improvement in ejaculatory bother as non-obese subjects. Adverse effects included hematuria, irritative voiding symptoms, hematospermia, and UTI and all resolved within 3 weeks. There were no serious adverse effects. Decreased ejaculatory volume occurred in 6 men and anejaculation was reported by 4 men. Conclusions Convective RF water vapor thermal therapy provides a rapid and sustainable improvement in LUTS/BPE through 1 year, can be applied to all zones including the median lobe, and preserves erectile and ejaculatory function. Results are similar for both obese and non-obese subjects. Funding NxThera
Authors
Nikhil Gupta
Tobias Köhler Kevin McVary |
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PNFBA-02 |
Technical Skill Assessment of Surgeons Performing Robot-Assisted Radical Prostatectomy: Relationship Between Crowdsourced Review and Patient Outcomes |
Best Abstracts: Next Frontier, Sunday, Afternoon Session | 17BOS |
Abstract: PNFBA-02 Sources of Funding: Blue Cross Blue Shield of Michigan Introduction Pilot work from the Michigan Urological Surgery Improvement Collaborative (MUSIC) showed that crowdsourced (i.e. lay-person) video ratings of skill for surgeons performing robot-assisted radical prostatectomy (RARP) demonstrated strong correlation with peer surgeon ratings. In this project, we assessed the association between crowd review of surgeon skill with patient outcomes following RARP. Methods Surgeons in MUSIC were invited to submit a representative video of a nerve-sparing RARP. Edited video clips of the urethrovesical anastomosis from surgeons underwent evaluation of global skill by crowdworkers via C-SATS Inc, (Seattle, WA) using the Global Evaluative Assessment of Robotic Skills (GEARS) tool (maximum score 25). A mean GEARS score for each video clip was derived using a linear mixed effects model. Surgeons were ranked on their skill scores and sorted into quartiles of skill. Using data from a prospective registry involving 2,256 patients, we compared risk-adjusted peri-operative complication rates at the patient level between surgeons (n=7) in the lowest (Q1) skill quartile to surgeons (n=8) in the highest (Q4) quartile (n=8). Odds ratios (OR) were calculated using logistic regression models. Likelihood ratio tests were used to statistically assess whether outcomes differed between ratings quartiles. Results Crowdworkers (n=285) provided 867 video ratings on anastomosis procedures from 29 MUSIC surgeons within 3 hours and 48 minutes. Crowd ratings for global robotic skill of the anastomosis ranged from 16.5 to 18.0 in the lowest quartile (Q1), and from 20.2 to 21.9 in the highest quartile (Q4). Compared to surgeons in Q1 for anastomosis skill, surgeons in Q4 for skill had significantly lower rates of urethral catheter replacement (OR=0.45, p<0.001) and readmission rates (OR=0.54, p=0.002) after RARP, but not lower rates of excess (>400 cc) blood loss (OR=1.03, P=0.901) (Table). Conclusions Crowdsourced assessments of technical skill for practicing robotic surgeons performing the anastomosis varied widely, and correlated with clinically relevant post-surgical outcomes for RARP. In the future, the technical ability of a surgeon may become a significant performance measurement directly linked to patient outcomes. Funding Blue Cross Blue Shield of Michigan
Authors
Khurshid R. Ghani
Bryan Comstock David C. Miller Rodney L. Dunn Tae Kim Susan Linsell Brian R. Lane Richard Sarle Thomas Lendvay James Montie James O. Peabody for the Michigan Urological Surgery Improvement Collaborative |
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PNFBA-03 |
RANDOMIZED, DOUBLE?BLIND, PLACEBO-CONTROLLED STUDY OF AUTOLOGOUS MUSCLE DERIVED CELLS FOR URINARY SPHINCTER REPAIR |
Best Abstracts: Next Frontier, Sunday, Afternoon Session | 17BOS |
Abstract: PNFBA-03 Sources of Funding: Cook MyoSite, Incorporated Introduction This multicenter study (NCT01382602) assessed the safety and efficacy of Autologous Muscle Derived Cells for Urinary Sphincter Repair (AMDC-USR) in women with stress urinary incontinence (SUI). Methods Women with predominant SUI who experienced ≥3 stress leaks over 3 days were randomized 2:1 to receive intrasphincteric injection of 150 x 106 AMDC-USR or vehicle placebo and 1:1 to receive 1 or 2 treatments. Second treatments were administered 6 months after first treatments. At baseline and follow-up, SUI was monitored by 3-day diaries of stress incontinence episode frequency (IEF), 24-hour pad tests, in-office pad tests, and quality of life (QOL) questionnaires. The primary composite efficacy endpoint was the percentage of patients with ≥50% IEF reduction or ≥50% reduction in either pad test 12 months post-treatment. Patients were unblinded after completing 12-month visits, and patients who received placebo could opt to receive an open-label AMDC-USR treatment. Patients were followed for 2 years after initial treatment. Results Overall, 143 patients were treated (50 placebo; 93 AMDC-USR), 141 patients completed 12-month visits (50 placebo, 91 AMDC-USR), 127 patients completed 2-year visits, and 3 patients remain in follow-up. Both placebo and AMDC-USR groups had similar baseline characteristics. No AMDC-USR safety signals were identified and no urinary retention was reported. Due to an unexpectedly high placebo responder rate with the composite endpoint, which included pad tests, enrollment was halted at 61% (150/246) of the planned study size. In post hoc analyses, IEF reduction correlated with QOL score improvement and suggested that ≥50% IEF reduction, ≥75% IEF reduction, and ≤1 leak per 3 days may be clinically meaningful endpoints. With these alternate endpoints, placebo rates were reduced and a potential treatment effect was detected (Figure). Further, 84% (37/44) of AMDC-USR patients with ≥50% IEF reduction at 12 months and available 2-year diaries also met this endpoint at 2 years. At final follow-up, 56% (20/36) of patients who received open-label AMDC-USR and had ≥3 stress leaks at 12 months had ≥50% IEF reduction compared to the 12-month diary collected before unblinding. Conclusions In women with SUI, AMDC-USR is safe and may provide durable reduction in IEF. Funding Cook MyoSite, Incorporated
Authors
Lesley Carr
Le Mai Tu Magali Robert David Quinlan Kevin Carlson Sender Herschorn Roger Dmochowski Ron Jankowski Michael Chancellor |
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PNFBA-04 |
Association between urinary symptom severity and automated segmentation of white matter plaque in women with multiple sclerosis |
Best Abstracts: Next Frontier, Sunday, Afternoon Session | 17BOS |
Abstract: PNFBA-04 Sources of Funding: Funding provided by the National Institute of Health (NIH), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) grant number P20 DK097819-01. Introduction Multiple sclerosis (MS) is characterized by demyelinated white matter plaque throughout the central nervous system. Patients with MS frequently experience a range of bothersome urinary symptoms. The cingulate cortex, insula cortex, and prefrontal cortex are three cortical brain regions that regulate micturition, and plaque involvement in these regions may be associated with urinary symptom severity. The aim of this study is to investigate the relationship between cerebral plaque volume, location, and urinary symptoms in women with MS. Methods We conducted a prospective case control study of women with MS undergoing routine yearly brain MRI. Women were administered the AUA Symptom Score (AUASS) and divided into two groups: women with severe urinary symptoms (AUASS ≥20) and women with mild symptoms (AUASS ≤7). MS plaque volume and location in the brain were determined using a validated automated white matter lesion segmentation algorithm. Mann Whitney U and Spearman's rank tests were used to investigate the relationship between plaque volume, location, and AUASS subscale scores. Results The study included 36 women with a median age of 50.1 years (IQR 27.1) and BMI 26.6 kg/m2 (IQR 5.8) with no significant differences between groups, p>0.05. The median total plaque volume was 2523.5mm3 (IQR 11705.5) and did not differ between the groups, p=0.52. Women with severe urinary symptoms had larger median plaque volume in the left frontal lobe (LFL) (623.5mm3 IQR 2652 vs. 184mm3 IQR 908; p=0.04) and right limbic lobe (RLL) (1.5mm3 IQR 10 vs. 0 IQR 0; p=0.02) compared to women with mild urinary symptoms. Within the RLL, women with severe symptoms had larger median plaque volume in the cingulate gyrus (median 1 IQR 4 vs. median 0 IQR 0; p=0.02). There was moderate correlation between LFL lesion volume and the AUA voiding symptom subscore (coefficient 0.4, p=0.03) as well as RLL lesion volume and the AUA voiding symptom subscore (coefficient 0.5, p=0.002). However, these regions did not correlate with the storage subscore. There were no significant relationships between symptoms severity and plaque volume in the insula, cerebellum, corpus callosum, occipital or parietal lobes (p>0.05). Conclusions Urinary symptom severity in women with MS is associated with plaque in the cingulate gyrus and LFL, and not total cerebral plaque volume. The voiding symptom subscore of AUASS correlated with the volume of plaque in these locations. Further research to assess spinal cord plaque characteristics is underway. Funding Funding provided by the National Institute of Health (NIH), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) grant number P20 DK097819-01.
Authors
Siobhan Hartigan
Steven Weissbart Michel Bilello Diane Newman Alan Wein Ariana Smith |
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PNFBA-05 |
SPECIFIC CHANGES IN BRAIN ACTIVITY IN WOMEN WITH OVERACTIVE BLADDER AFTER SUCCESSFUL SACRAL NEUROMODULATION WITH INTERSTIM®: AN FMRI STUDY |
Best Abstracts: Next Frontier, Sunday, Afternoon Session | 17BOS |
Abstract: PNFBA-05 Sources of Funding: SUFU Neuromoduation Grant Award Introduction Sacral neuromodulation (SNS) with InterStim® is efficacious for the treatment of overactive bladder (OAB); however, its mechanism of action is unclear, and there are no objective markers of response. Prior functional neuroimaging studies have suggested that women with OAB have increased brain activity in the cingulate cortex, insula, and frontal cortex, in response to bladder filling. The aim of this study was to investigate the effect of SNS on brain activity in women with OAB. Methods We conducted a prospective mechanistic study of women with OAB (measured on validated questionnaire) undergoing InterStim®. Prior to stage 1 InterStim®, women underwent BOLD fMRI during bladder filling. During filling, women were asked to signal the experience of urgency. Women who completed stage 2 InterStim® underwent a 2nd BOLD fMRI during bladder filling 6 weeks after InterStim® implantation. Brain activity during urgency was compared to no urgency, and analysis was stratified according to response to InterStim®. _x000D_ Results The study included 12 women with idiopathic OAB with normal emptying (median age 63.5, IQR 11 years). All women underwent pre-InterStim® fMRI, and 7 completed stage 2 InterStim® and underwent post-InterStim® fMRI (i.e. 7 responders, 5 non-responders). Among responders, brain activity decreased in the left cingulate gyrus (x,y,z coordinates: -5, 23, 39, p=0.048) and left frontal gyrus (-5, 23, 39, p=0.04) after InterStim® implantation (figure 1). There were no areas of increased brain activity after InterStim® implantation. Women who responded to InterStim® had increased brain activity on their pre-InterStim® fMRI in multiple cortical regions, including the cingulate cortex, inferior frontal gyrus, insula, and thalamus. There were no differences in ICIQ-FLUTS filling scores or pre-InterStim® fMRI filling volumes between responders and non-responders (p>0.05). _x000D_ Conclusions SNS with InterStim® appears to attenuate increased brain activity in women with OAB. Women with OAB and increased brain activity during bladder filling may experience greater treatment response. fMRI has preliminarily detected a phenotype of OAB that may predict therapeutic response to InterStim®. _x000D_ Funding SUFU Neuromoduation Grant Award
Authors
Steven Weissbart
Rupal Bhavsar John Detre Hengyi Rao Alan Wein Lily Arya Ariana Smith |
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PNFBA-06 |
askMUSIC&[copy]: leveraging a clinical registry to inform patients |
Best Abstracts: Next Frontier, Monday, Morning Session | 17BOS |
Abstract: PNFBA-06 Sources of Funding: Blue Cross and Blue Shield of Michigan and grant 1T32-CA180984 from the National Cancer Institute. Introduction Clinical registries increasingly provide physicians with a means for making data-driven decisions; however, few opportunities exist for patients to interact with registry data to support their own decisions. Herein, we report a web-based system that uses a prostate cancer (CaP) registry to provide newly-diagnosed men with a platform to understand treatment decisions made by others with similar characteristics. Methods The Michigan Urological Surgery Improvement Collaborative (MUSIC) is a consortium of 43 diverse urology practices that maintains a prospective registry of men with CaP. We developed a patient-facing, web-based tool that uses self-reported information and registry data to generate a personalized prediction of the likelihood of receiving a given treatment for CaP (Figure 1). The treatment predictions rely on registry data from 1/2011 to 12/2015 and were generated using a random forest machine learning model derived in a 2/3 random sample of the data. Predictive performance was measured in this derivation cohort (using 10-fold cross validation) and verified in the remaining data using multinomial area-under-the-curve (AUC) and calibration plots. Results Between the included dates, 11,456 men were diagnosed with CaP and 44.7% underwent prostatectomy, 22.0% surveillance, 19.5% radiation (RT), 8.8% androgen deprivation, and 3.6% watchful waiting (WW). The predictive model demonstrated consistent discrimination between treatments in the derivation and validation cohorts (AUCs 0.762 and 0.744, respectively). The predicted likelihood of receiving a given treatment was accurate for the most common treatment types in the derivation and validation cohorts although the model overpredicted the likelihood of receiving WW in both cohorts and RT in the validation cohort (Figure 2). Conclusions With MUSIC registry data and machine learning methods, we were able to create a tool, designed for patients, that generates accurate predictions for most CaP treatments. As a newly diagnosed man considers treatment options, this tool will provide insight into choices made by similar men. Funding Blue Cross and Blue Shield of Michigan and grant 1T32-CA180984 from the National Cancer Institute.
Authors
Gregory Auffenberg
Shreyas Ramani Khurshid Ghani Brian Denton Craig Rogers Benjamin Stockton David Miller Karandeep Singh for the Michigan Urological Surgery Improvement Collaborative |
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PNFBA-07 |
The current management of prostate cancer in the United States: Data from the AQUA Registry |
Best Abstracts: Next Frontier, Monday, Morning Session | 17BOS |
Abstract: PNFBA-07 Sources of Funding: none Introduction Prostate cancer management trends have been described previously using a variety of data sources, but none has captured actual national data across a broad range of practice types and locations. We explored management trends in the new AUA Quality (AQUA) Registry. Methods The AQUA Registry collects data from participating practices via automated data extraction from local electronic health record systems. Data are collected from both structured (e.g., billing codes, prescriptions) and unstructured (e.g., pathology reports, physician notes) chart elements. We identified newly diagnosed prostate cancer cases using a series of data rules and algorithms. Results From Jan. 2014 to Jun. 2016, the AQUA Registry collected data on 35,437 men with prostate cancer from 64 practices. Localized prostate cancer disease was found in 22,861. The median number of localized cases per site was 112 (range 1-2768, IQR 36-315). A total of 16,485 (72%) had sufficient data to calculate risk; the missing data rate fell from 33% in 2014 to 23% in 2016. Of men with sufficient data, 42%, 35%, and 23% had low, intermediate, and high-risk disease, respectively. The proportion of low-risk cases fell from 45% in 2014 to 40% in 2016, the differences are reflected in rising rates of high-risk disease (p<0.001). The Figure below illustrates treatment trends over time for 15,825 men with identified primary treatment. The rate of active surveillance for low-risk disease rose from 41% in 2014 to 54% in 2016. Medication data were available for 5154 men receiving advanced disease medications; 32.5% of these received more than one medication. In total, 2089 men received abiraterone, 2289 enzalutamide, 320 docetaxesl, 81 cabazitaxel, 334 sipuleucel-T, 108 radium-223, and 2290 denosumab. Among 738 men receiving both abiraterone and enzalutamide, 66% received abiraterone first; the median time starting these two medications was 232 days. Conclusions We confirmed prior reports from less representative registries in terms of shifting prostate cancer risk distribution and high and rising rates of active surveillance for low-risk disease. The AQUA Registry provides unique data on patterns of use for advanced prostate cancer medications. Many more urology practices have recently joined the registry and therefore, the numbers of men represented will grow rapidly. Funding none
Authors
Matthew Cooperberg
Raymond Fang J. Stuart Wolf, Jr Heddy Hubbard Sanyog Pendharkar Sunil Gupte Kimberly Ross Mary Nolin Steven Schlossberg J. Quentin Clemens |
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PNFBA-08 |
Novel in vitro organoid technology to facilitate a precision medicine approach in the management of men with biochemical recurrence of prostate cancer |
Best Abstracts: Next Frontier, Monday, Morning Session | 17BOS |
Abstract: PNFBA-08 Sources of Funding: ANZUP Tolmar Clinical Research Fellowship Introduction Precision medicine aims to provide the right treatment for the right patient at the right time with treatment directed on the basis of the targetable tumoral aberrations rather than just a traditional histologic subtype. However to facilitate this approach, clinicians require patient derived samples. Prostate cancer is challenging to culture in vitro. Recent development of novel organoid in vitro culture technology has led to the development of multiple new in vitro prostate cancer cell line models. We aim to apply organoid culture technology to develop novel in vitro prostate cancer cell line models and propagate patient derived samples to allow drug testing and next generation sequencing as part of a precision medicine approach to early recurrent prostate cancer. Methods Patient derived metastatic tissue samples were collected as part of a larger clinical trial. These were digested in Type II Collagenase (Gibco) for 2 hours and seeded directly onto Collagen Type I coated plates in novel media. Samples were cultured in vitro for a minimum of 2 weeks prior to validation. PSA ELISA (GenWay Biotech) of conditioned media along with RT-qPCR comparison of various gene products of interest between cultured patient samples and established prostate cancer cell lines was performed. In vitro samples were subsequently utilised for therapeutic screening. Results A total of 5 patient samples were available for culture with histologically proven metastatic prostate cancer. Tissue from a 67 year old male with biochemical recurrence of prostate cancer following retro-pubic radical prostatectomy was obtained fresh at time of salvage lymph node dissection (PSA was 1.5 ng/ml). Tissue was successfully cultured for a minimum of 4 weeks prior to validation. PSA ELISA of conditioned media was positive. RT-qPCR confirmed expression of Prostate specific genes PSA, AR, FKBP5 and TMPRSS. Drug screen revealed a marked response to Docetaxel, Cabazitaxel and Enzalutamide and minimal effect to Bicalutamide. Conclusions We have successfully cultured patient derived samples for precision medicine. Further therapeutic screening and next generation sequencing of derived cultures is ongoing in order to potentially inform therapeutic strategies. Organoid in vitro culture technology could provide a vital stepping stone towards precision medicine in the future, involving the rapid generation of patient specific in vitro models for therapeutic screening to guide individualized treatment. Funding ANZUP Tolmar Clinical Research Fellowship
Authors
Andre Joshi
Cheryl Nicholson Handoo Rhee Alexander Hutchinson Stephen McPherson Jennifer Gunter Elizabeth Williams Colleen Nelson Ian Vela |
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PNFBA-09 |
The diverse genomic landscape of low-risk prostate cancer |
Best Abstracts: Next Frontier, Monday, Morning Session | 17BOS |
Abstract: PNFBA-09 Sources of Funding: DOD W81XWH-13-2-0074 Introduction Active surveillance (AS) is becoming standard of care for men with low-risk prostate cancer; however a need exists for better tools to assess which men are optimal candidates for AS. In this study we compare genomic expression profiles of AS candidates against higher-risk radical prostatectomy (RP) patients to characterize the genomics of clinically low-risk prostate cancer. Methods Biopsies from 473 UCSF patients potentially suitable for AS (stage≤cT2N0M0, PSA≤10 ng/ml, Gleason 3+3 or low-volume 3+4) were profiled using the Affymetrix HuEx microarray to generate RNA expression data. These cases were compared to 2043 RP cases previously profiled on the same microarray platform. Scores for 21 published prognostic signatures were calculated and pathway associated genes were summarized to provide levels of patient risk and pathway activity. Results Of the 473 AS biopsies profiled, 408 (86%) passed quality control and were used for analysis. Based on the quartiles of average scores for 21 prognostic signature risk models, 49%, 36%, 11%, and 4%, respectively, were classified into the 1st, 2nd, 3rd, or 4th score quartiles. Considering only the clinically low-risk patients at diagnosis, 356 (87%) were low, 45 (11%) were intermediate and 7 (2%) were high risk. Genomic risk was positively associated with cell cycle related pathways (p<0.001) and negatively associated with apical junction (p<0.001), epithelial-mesenchymal transition (p<0.001), and androgen receptor (p<0.05) pathways. Clustering of patients based on the expression of 36 pathways revealed two biologic groups corresponding to putative basal and luminal subtypes. Compared to higher risk RP patients, the low risk prostate cancer tumors at diagnosis were enriched for basal-like tumors (20% vs 33%, p<0.001). Conclusions Although only 2% of low risk AS candidates have high risk genomic characteristics, very substantial genomic heterogeneity exists in this population, and pathway activation overlaps significantly with higher-risk RP patients. These results suggest that even in potential AS candidates, genomic profiling could eventually be used to better guide management. Funding DOD W81XWH-13-2-0074
Authors
Matthew R. Cooperberg
Nicholas Erho June M. Chan Felix Y. Feng Janet E. Cowan Kaye Ong Mohammed Alshalalfa Tyler Kolisnik Jennifer Margrave Maria Aranes Marguerite du Plessis Christine Buerki Shuang G. Zhao Imelda Tenggara Elai Davicioni Peter R. Carroll |
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PNFBA-10 |
Focal Therapy of Prostate Cancer: Defining Appropriate Treatment Margins Using MRI:Whole Mount Co-Registration |
Best Abstracts: Next Frontier, Monday, Morning Session | 17BOS |
Abstract: PNFBA-10 Sources of Funding: The project described was supported by Award Number R01CA158627 from the National Cancer Institute; Jean Perkins Foundation; Steven C. Gordon Family Foundation. Introduction Focal therapy of prostate cancer (partial gland ablation, PGA) is of keen interest. To determine treatment margins required for complete tumor ablation, we studied men who were eligible for PGA, but underwent radical prostatectomy. The present work differs from prior studies in that accurate co-registration between pre-op multiparametric MRI (mpMRI) slices and whole-mount findings was enabled through use of patient-specific prostate molds to obtain uniform, standardized processing of specimens. _x000D_ Methods 35 men with localized, organ-confined prostate cancer (CaP) who underwent 3 Tesla mpMRI prior to radical prostatectomy from 2013 to 2015 were subjects. Mean patient age was 63 yrs; median PSA 6.7 ng/ml; and mean prostate volume 37.6 cc. Criteria for focal therapy eligibility were Gleason score ≤4+3 within MRI-visible index tumor, pathologic stage ≤T3a, and no contralateral clinically significant disease. Using T2-weighted images from pre-operative mpMRI, the prostate capsule and suspicious regions of interest (ROIs) were contoured. 3D patient-specific molds, printed in advance of prostatectomy from MRI specifications, were then used to align prostatectomy specimens with mpMRI (Priester et al., J. Urol, 2016). Digitized whole mount sections, sliced at 4.5 mm intervals, provided 3D reconstruction of prostate tumors. Tumors were matched with ROIs and the relative 3D surfaces were compared to determine appropriate treatment margins. _x000D_ Results 39 of 62 (63%) prostate tumors found on whole-mount sections were detected by MRI. 90% of tumors were in PZ, 10% in TZ. Of the 23 tumors not MRI visible, 22 were low volume, Gleason score 3+3. Mean index tumor volume on MRI was 0.59 cc and 1.59 cc on prostatectomy specimen (p<0.001). Median treatment margin required was 10.7mm (FIGURE). Average treatment volume required for complete tumor ablation was 11.4 cc, which comprised 30% of average prostate volume. All subjects would have been successfully treated with hemi-gland ablation. _x000D_ Conclusions MRI consistently and dramatically underestimates the extent of prostate tumors. In this population, uniformly employing 1cm treatment margins during focal therapy would have resulted in incomplete tumor ablation in 50% of patients. A patient specific treatment plan incorporating tumor size, geometry, and adjacent tissue sampling is a future research priority. _x000D_ Funding The project described was supported by Award Number R01CA158627 from the National Cancer Institute; Jean Perkins Foundation; Steven C. Gordon Family Foundation.
Authors
Tonye Jones
Alan Priester Shyam Natarajan Pooria Khoshnoodi Warren Grundfest Leonard Marks |
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PNFBA-11 |
E-cigarette smoke is potentially bladder carcinogenic – it induces tumorigenic DNA adducts and inhibits DNA repair in urothelial cells. |
Best Abstracts: Next Frontier, Monday, Morning Session | 17BOS |
Abstract: PNFBA-11 Sources of Funding: This research was supported by grants from NIH (R01CA190678, 1P01CA165980, and ES00260) and Center of Excellence for Urological Research at New York University School of Medicine. Introduction E-cigarette (E-cig) is designed to deliver stimulant nicotine, similar to the conventional cigarette, through an aerosol state. Nicotine is dissolved in harmless organic solvents and then aerosolized with solvents by electric heating. Hence, E-cig smoke (ECS) contains nicotine and the gas phase of the solvents. ECS contains neither carcinogens, allergens, nor odors that result from incomplete combustion in conventional tobacco smoke (TS). E-cig has been advertised as an invention that can deliver a TS &[prime]high&[prime] without TS&[prime]s ill effects. The question, &[prime]Is ECS as harmful as TS or not, particularly its carcinogenicity?&[prime] deserves careful examination. Since 90% of inhaled nicotine and its major metabolite cotinine are excreted to urine, it is possible bladder is a major target of ECS. Using a mouse model, we addressed three questions on E-cig induced effects. 1) Does ECS induce DNA damage in bladder mucosa? 2) If it does, then what is the chemical nature of the DNA damage? 3) Where are the DNA damaging agents coming from? We also examined the effect of nicotine and its metabolites, nitrosamines and formaldehyde (FAL), on DNA adduct induction and their effects on DNA repair and mutational susceptibility in cultured human urothelial cells. Methods 1.Twenty male mice were randomized into 2 groups. Mice were exposed to ECS (10 mg/ml) or filtered air 6 h/d, 5 d/week for 12 weeks. _x000D_ 2.PdG and O6-meth-dG adducts were determined by an immunochemical method and the 32P post-labeling 2D-TLC/HPLC method. _x000D_ 3.DNA repair activity was determined by an in vitro DNA-damage-dependent repair synthesis method. Mutational susceptibility were determined by the supF system._x000D_ Results 1.ECS induces γ-OH-PdG adducts and O6-meth-dG adducts in mouse bladder mucosa. _x000D_ 2.Nicotine, nitrosamine and FAL induce γ-OH-PdG; nicotine and nitrosamine also induce O6-meth-dG in urothelial cells._x000D_ 3.Nicotine, nitrosamine and FAL inhibit DNA repair and suppress XPC and OGG1 in urothelial cells._x000D_ 4.Nicotine, nitrosamine and FAL enhance urothelial cell mutational susceptibility. _x000D_ Conclusions ECS induces tumorigenic γ-OH-PdG and O6-meth-dG in bladder mucosa. Nicotine, nitrosamine and FAL can induce the same types of DNA damage in human urothelial cells and also inhibit DNA repair and enhance mutational susceptibility. We conclude that nicotine can be nitrosatized in human and mouse urothelial cells, then further metabolized into carcinogenic nitrosamines and FAL. We predict that E-cig smokers have a high bladder cancer risk. Funding This research was supported by grants from NIH (R01CA190678, 1P01CA165980, and ES00260) and Center of Excellence for Urological Research at New York University School of Medicine.
Authors
Hyun-Wook Lee
Sung-Hyun Park Mao-wen Weng Hsing-Tsui Wang William Huang Herbert Lepor Xue-Ru Wu Lung-Chi Chen Moon-shong Tang |
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PNFBA-12 |
Liquid Biopsy for Renal cell carcinoma |
Best Abstracts: Next Frontier, Monday, Morning Session | 17BOS |
Abstract: PNFBA-12 Sources of Funding: Supported by:_x000D_ The John and Mary Brock Foundation_x000D_ The Claude P. Cook Foundation_x000D_ Veterans Affairs Merit award to Dr. Petros_x000D_ The Coca?Cola Company Research Award_x000D_ Philanthropic award given by the Emory University Winship Cancer Institute Introduction Circulating tumor DNA (ctDNA) has characteristics of an ideal biomarker. We sought to develop whole exome sequencing of ctDNA to interrogate commonly mutated genes in renal cell carcinoma for early tumor detection through a single blood sample. Methods Patients with solid renal tumors and healthy controls gave 40 mL blood and plasma cell free DNA was prepared. A multiplex bar coded polymerase chain reaction amplification using the Fluidigm Access Array was performed to prepare sequencing libraries for the Illumina HiSeq platform. Galaxy workflow was used to identify mutations and results were compared to buffy coat sequencing. The following genes were queried: VHL, PBRM1, SETD2, BAP1, KDM5C, KIT, NFE2L2, MET, TP53, CDKN2A, FGFR3, PIK3CA, BRAF, MUC4. Criteria for calling mutations included adequate frequency by overall count and percentage of reads, identification in all overlapping sequences, and presence of buffy coat for comparison with <0.5% containing the mutation. Results Thirty preoperative test patients with RCC and 32 healthy controls were analyzed using the gene panel. Of the 32 patients analyzed in the healthy control cohort, 27 (84%) failed to yield sequence of the genes of interest. Of the pre operative RCC patients, 20/30 (67%) had detectable somatic mutations, resulting in nonsynonymous, frameshift, stopgain, or splice site mutations, compared to 1/32 (3.1%) controls. Mutations were detected in both early and advanced stage disease, including a patient with a 1.1 x 0.7 x 0.5 cm tumor. Mutations were seen in all genes assayed. Conclusions These data demonstrate feasibility of gene-specific whole exome sequencing of ctDNA for diagnosis of RCC in patients with solid renal tumors. The majority of RCC patients of various stages and histology had ctDNA detected in a single preoperative blood sample. A single control gave a positive test. Non invasive detection of RCC shows promise for not only initial diagnosis but also disease monitoring and guidance of targeted therapies throughout a wide spectrum of disease severity, including small lesions. Funding Supported by:_x000D_ The John and Mary Brock Foundation_x000D_ The Claude P. Cook Foundation_x000D_ Veterans Affairs Merit award to Dr. Petros_x000D_ The Coca?Cola Company Research Award_x000D_ Philanthropic award given by the Emory University Winship Cancer Institute
Authors
Usama Al-Qassab
C. Adam Lorentz Dean Laganosky Kenneth Ogan Viraj Master John Pattaras Muta Issa Christopher Keith David Roberts Michael Rossi Sharon Bergquist Jeremy Goecks Rebecca Arnold John Petros |
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PNFBA-13 |
Are the current follow-up guidelines after treatment for organ confined renal cancer sufficient? |
Best Abstracts: Next Frontier, Monday, Morning Session | 17BOS |
Abstract: PNFBA-13 Sources of Funding: none Introduction Follow-up algorithms following surgical treatment for localized renal cell carcinoma (RCC) have been a matter of debate for years. Our objective was to determine the long-term oncological outcome of localized RCC ( Methods We identified 880 patients with complete long-term follow-up data, surgically treated for RCC ( Results After a median follow-up was 74.33 months (range 2.67-289) 38 patients had disease recurrence (4.35% of all patients). 73.5 % of these were distant metastasis and 26.5% showed local recurrence.. 42.1% of events occurred after the recommended follow-up period of 60 months. There was a trend towards later metastasis in patients with low grade (G1) and low stage (Ta) tumors. Patients with lung metastasis and patients with multiple metastatic locations, developed metastasis earlier than those with bone metastasis. The time point of metastasis did not correlate with age, in contrast to an increased risk of dying of other causes. (Figure 1) Conclusions Current guidelines recommend a follow-up of five years. Our data shows that over 42% of recurrences happen after this time point. We suggest that age adjusted strategies might be appropriate for future follow-up strategies weighing up life expectancy and the risk of developing a tumor recurrence. Funding none |
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PNFLBA-01 |
Current Anti-Retroviral Treatments Do Not Eliminate HIV From Semen |
Plenary: Next Frontier, Sunday, Morning Session | 17BOS |
Abstract: PNFLBA-01 Sources of Funding: None Introduction Infected semen fuels the HIV pandemic. Despite the development of highly effective anti-retroviral drugs, more than 30,000 new cases are diagnosed annually in the U.S., only a 10% drop since 2005. Although it is recognized that semen infection is compartmentalized from blood, little is known about infection sites or effective treatment for semen HIV. To begin to develop treatment guidelines to eliminate HIV from semen, we have examined semen virus detection according to treatment regimen of HIV-infected men. Methods Review of a recently compiled blinded dataset of antiretroviral drug therapy, blood levels of HIV RNA and CD4+ lymphocytes, and HIV RNA or HIV proviral DNA in semen specimens submitted by 230 HIV-infected men undergoing semen screening from 2012 to 2015. Semen HIV was detected by RT-PCR. Results All men on antiretroviral therapy had undetectable levels of HIV RNA in blood. Overall, 112 (18%) of the specimens tested positive for virus, with 81 (35%) of men producing at least one positive specimen. Ten of fourteen men not on antiretroviral therapy because of persistently low blood virus levels produced at least one positive semen specimen with 13 (36%) of 36 specimens testing positive for HIV._x000D_ Average CD 4 blood count (634) for men producing positive semen specimens was not significantly different from those producing no HIV-positive semen specimens (683). _x000D_ Twenty eight (20%) of the 137 men taking combinations of reverse transcriptase inhibitors produced at least one HIV-positive semen specimen; of the total of 403 specimens in this treatment group, 74 (18%) were positive._x000D_ Nine (23%) of the 39 men whose treatment regimen included a protease inhibitor produced at least one positive specimen, with only 11 (10%) of the total of 107 specimens in this group testing HIV positive._x000D_ Eighteen (41%) of the 44 men whose treatment included an integrase inhibitor with no protease inhibitor produced at least one positive specimen, with 23 (18%) of the total of 128 specimens testing HIV positive. Conclusions Current antiretroviral treatment strategies do not eliminate HIV from semen as effectively as they eliminate HIV RNA in blood. These findings suggest anti-viral combinations containing a protease inhibitor may be more effective in reducing HIV in semen. A larger study cohort is urgently needed to test this possibility. Funding None
Authors
Robert Eyre
Ann Kiessling |
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PNFLBA-02 |
A head to head comparative Phase II trial of standard urine culture and sensitivity versus DNA next generation sequencing testing for urinary tract infections |
Plenary: Next Frontier, Sunday, Morning Session | 17BOS |
Abstract: PNFLBA-02 Sources of Funding: None _x000D_ _x000D_ Introduction The aim of our study was to conduct a Head to Head Comparative Phase II trial of standard urine culture and sensitivity versus DNA next generation sequencing testing for diagnosis and treatment efficacy in patients with urinary tract infections (UTI) based on short-term outcomes. Methods Between January 2016 and December 2016, 56 patients were entered into this study with symptoms of an UTI, 44 patients completed the study. All subjects completed a standardized UTI symptom score questionnaire on day 0-7 and day 14. Twenty-two volunteers were entered as controls in this study without symptoms of a urinary tract infection. The Level 1 Panel as a quantitative real-time Polymerase chain reaction (PCR) test for bacteria and fungi and the Level 2 test which detects virtually all microbial organisms and fungal pathogens were used versus routine culture and sensitivity test. Results The symptom scores were statistically significantly better for those patients whose diagnosis and treatment was based on DNA results versus traditional culture studies. For instance, all 44 patients showed positive results in DNA sequencing tests, while only 13/44 patients had positive urine culture tests. The difference in average improvement of 8.5 is highly significant (p<0.0001) (Fig.1). Especially in the cohort of patients with DNA positive test and culture negative the treatment outcomes were improved with respect to symptom scores when they started treatment on day 8. That ultimately led to faster recovery times and decreased the cost of treatment. Advantages of the DNA test also include an increased sensitivity for the diagnosis of anaerobic flora. _x000D_ _x000D_ Conclusions In this study DNA testing demonstrated a more accurate diagnosis of UTI than standard urine culture tests. In addition, DNA next generation testing led to better treatment outcomes in patients treated with antibiotics for primary anaerobic, aerobic or a combination of bacteria. Therefore, DNA testing allowed for the improved diagnosis and treatment based on symptoms of a UTI especially when urine cultures are negative._x000D_ _x000D_ Figure 1. Box-plot of Symptom Severity Reduction at Day 14 in Treatment Arms (group 1- based on culture and sensitivity, group 3 and 4- based on DNA results) Funding None _x000D_ _x000D_
Authors
Michael McDonald
Darien Kameh Mark E. Johnson Vladimir Mouraviev |
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PNFLBA-03 |
WATER Study Clinical Results – Phase III double-blind randomized control trial of Aquablation vs. Transurethral Resection of the Prostate for Moderate-to-Severe Benign Prostatic Hyperplasia |
Plenary: Next Frontier, Sunday, Afternoon Session | 17BOS |
Abstract: PNFLBA-03 Sources of Funding: WATER was sponsored by PROCEPT BioRobotics. (NCT02505919). Introduction Prostate resection for patients with LUTS remains the gold standard for surgical treatment of BPH. Gilling et al. reported a prospective single-arm multicenter trial at 3 centers in Australia and New Zealand with 1-year follow-up on 21 men with a similar profile as WATER. Prostate volume dropped from 57 ml at baseline to 35 ml (P<0.0001). Mean IPSS score improved from 23.0 at baseline to 6.8 at 12 months (P<0.0001) and maximum urinary flow increased from 8.7 mL/sec to 18.3 mL/sec (P<0.0001). There were no important perioperative adverse events. No subject developed urinary incontinence and sexual function was preserved postoperatively. In this report, we compared the safety and efficacy of prostate resection using a high-pressure waterjet vs. electrocautery from the WATER study._x000D_ Methods In this randomized, double-blind, multicenter phase III trial, patients with moderate-to-severe lower urinary tract symptoms related to benign prostatic hyperplasia were assigned to transurethral resection of the prostate using either standard electrosurgery (TURP) or robotic waterjet (Aquablation)._x000D_ The trial has a co-primary safety and efficacy endpoint designed to show non-inferiority. With a minimum enrollment of 177, the estimated power for safety was 99% and efficacy was 80%. The primary safety endpoint is the occurrence of Clavien-Dindo persistent grade 1 or Grade 2 or higher operative complications at 3 months. The primary efficacy endpoint is the reduction at 6 months in IPSS score. _x000D_ Results The geographic enrollment from the OUS (Australia, New Zealand, United Kingdom) sites and US sites was 91 and 93 subjects, respectively. The baseline IPSS score (TURP 22.2, Aquablation 22.9, p=0.47), demographic profile (Table 1), and prostate volume (TURP 52.0 mL, Aquablation 54.3 mL, p=0.31) were similar in both arms. Operative time was equivalent between the two groups, but resection time was lower in the Aquablation group (28 vs. 4 minutes, p<.0001). The length of stay and length of stay by geography was similar for both arms that averaged 1.4 days. Conclusions The first report of the primary safety and efficacy endpoints will be available and ready for presentation at AUA in May 2017. Funding WATER was sponsored by PROCEPT BioRobotics. (NCT02505919).
Authors
Claus Roehrborn
Peter Gilling |
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PNFLBA-04 |
Randomized Clinical Trial of Treatment with Tamsulosin Begun in the Emergency Department to Promote Passage of Urinary Stones |
Plenary: Next Frontier, Sunday, Afternoon Session | 17BOS |
Abstract: PNFLBA-04 Sources of Funding: The STONE Study is supported by cooperative agreement U01 DK096037 from the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (Pilot Study RO1 DK071603, Planning Grant U34 DK090957). The study is registered at clinicaltrials.gov (NCT00382265). Introduction Urinary stone disease (USD) is common, increasing with many patients first presenting to the emergency department (ED). Use of alpha-adrenergic receptor antagonists (alpha-blockers) has been advocated to promote passage of urinary stones. We conducted a multi-center, double-blind, placebo-controlled clinical trial of the alpha-blocker tamsulosin in ED for ureteral stones less than 9 mm in diameter. Methods Patients presenting to five EDs with USD confirmed by non-contrast spiral computed tomography (CT) were randomized equally to receive tamsulosin 0.4 mg daily or placebo. The primary outcome was stone passage, determined by either visualization or capture by the study participant, within 28 days of randomization. The primary outcome analysis compared binomial proportions for each of the two treatment groups using a chi-square test statistic. Secondary outcomes were confirmation of stone passage on follow-up CT in a subgroup (n=237), need for surgical intervention, crossover to open-label tamsulosin, and days of work lost. Results We randomized 512 participants. The mean ± standard deviation (SD) age was 40.6 ± 13.3 years. Symptomatic urinary stones were identified in the following locations: 45% ureterovesical junction, 24% distal ureter, 10% mid-ureter, 17% proximal ureter and 3% renal pelvis. The mean ± SD diameter of the symptomatic stone was 3.8 ± 1.4 mm (range, 1 mm to 8 mm). The proportion of study participants who had passed a stone by day 28 (outcome determined in 97% of those randomized) was 52% in the tamsulosin group and 49% in the placebo group (relative risk 1.07, 95% confidence interval 0.90-1.28; p=0.447). Conclusions The proportion of patients who had passed their urinary stones at day 28 did not differ significantly between tamsulosin and placebo. The trial was not designed to detect stone passage according to stone location. Our results do not support the use of this drug to promote passage of urinary stones less than 9 mm in diameter. Funding The STONE Study is supported by cooperative agreement U01 DK096037 from the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (Pilot Study RO1 DK071603, Planning Grant U34 DK090957). The study is registered at clinicaltrials.gov (NCT00382265).
Authors
Andrew C. Meltzer
Judd E. Hollander Allan B. Wolfson Michael C. Kurz Stephen V. Jackman Ziya Kirkali John W. Kusek Pamela K. Burrows |
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PNFLBA-05 |
Polyurethanes for Urinary Stents: A study on materials’ stone encrustation performances |
Plenary: Next Frontier, Sunday, Afternoon Session | 17BOS |
Abstract: PNFLBA-05 Sources of Funding: Teleflex Inc. Introduction Many studies have looked at infection and encrustation resistance capabilities of commercial 'polyurethane' (PU) compared to silicone [Tunney et al., 1996; Gorman et al., 1998; Bithles, 2004], but few have specified the exact PU composition [Park et al., 2002] and none have considered multiple subtypes. _x000D_ _x000D_ The objective of this study was to determine the amount of encrustation formed on multiple PU subtypes compared to silicone._x000D_ Methods A continuous flow in vitro model of the bladder was built and validated, and the widely accepted artificial urine formulation by Tunney et al was chosen [5]. Experiments were done in duplicate, testing commercial polycarbonate PU, polyether PU, and polyester PU against silicone, the gold standard (n = 4). Over five days with daily solution refresh, measurements for calcium encrustation content were taken via o-Cresolphthalein (oCPC) method. One-way ANOVA and Fisher's Pairwise Comparison were used for statistical analysis. Results Results showed significant reductions of encrustation on polyether PU and polyester PU compared to silicone (p-values < .0001) and similar levels of encrustation on polycarbonate PU compared to silicone (p-values < .510). Conclusions This study showed how polycarbonate PU encrusted much more than polyether and polyester PU, though all three are called 'polyurethane.' Furthermore, results suggest polyester and polyether PU perform better than silicone in terms of encrustation resistance. Future work includes clinical trials to confirm results. _x000D_ _x000D_ Note: The first experiment was done before the submission deadline and the duplicate experiment was done after the submission deadline to confirm findings. Funding Teleflex Inc.
Authors
Gary Li
Jun Li Zheng Zhang Morgan Tierney |
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PNFLBA-06 |
The impact of scribes on office productivity in urology practice |
Plenary: Next Frontier, Sunday, Afternoon Session | 17BOS |
Abstract: PNFLBA-06 Sources of Funding: none Introduction The advent of electronic health records (EHR) has been determined to be a major cause of physician frustration and burnout. One strategy has been the use of scribes to assist with completion of medical records during office visits. Although data suggests that patients accept the presence of scribes and scribes can improve physician satisfaction, there is conflicting data on whether scribes improve productivity and no studies on the impact of scribes specifically in urology. We sought to determine whether the use of scribes improved provider productivity in our urology practice. Methods We instituted a voluntary scribe program at our multi-site large urology practice. A total of 20 providers participated in the scribe program (user group, UG). 18 providers practicing in the same physical offices who declined the use of scribes served as a control group (non-user group, NUG). Provider productivity as measured by total evaluation and management (E&M)visits and relative value units (RVUs) visits were aggregated and compared for the 6 months pre- and post-adoption of the scribe. The month the scribe started was considered a training month and excluded from analysis. Coding patterns were assessed for UG and NUG pre- and post-scribe as well. Statistical analysis pre- and post-scribe for each provider was performed using Student's paired t-test. Results Pre-scribe E&M visits for UG and NUG were 1613.8 and 1661.1, respectively (difference 47.3, p=0.72). Pre-scribe RVUs for UG and NUG were 11567.7 and 10475.6, respectively (difference 1092.1, p=0.22). For UG post-scribe, significant increases in both E&M visits and total RVUs were observed (E&M visits 1836.9, +13.8%, p=0.00; RVUs 12467.7, +7.8%, p=0.05). Conversely, there was no significant change in either E&M visits or RVUs for NUG (E&M visits 1651.6, -0.6%, p=0.76; RVUs 10576.0, +1.0%, p=0.67). Post-scribe, the difference in RVUs between UG and NUG was significant (1891.7, p=0.05) while the difference in RVUs approached, but did not reach, significance (185.3, p=0.08). Conclusions To date, there has been no analysis on the impact that the addition of scribes has on productivity in the urology office. Our data suggests that productivity as measured by both office E&M visits as well as total RVUs is significantly improved by the addition of scribes. When combined with other data regarding scribe acceptance by patients and improvements in physician satisfaction, the utilization of scribes is a viable option for urology practices seeking to manage EHR fatigue in their providers. Funding none
Authors
Deepak Kapoor
Karen Hohlman |
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PNFLBA-07 |
Bladder Injury Activates Innate Immunity During Short-term Foley catheterization in a Swine Model |
Plenary: Next Frontier, Sunday, Afternoon Session | 17BOS |
Abstract: PNFLBA-07 Sources of Funding: Washington University St, Louis Anesthesiology Department_x000D_ World Wide Technology and The Steward Family Foundation Introduction Bladder instrumentation by a foreign body (foley catheter) induces inflammation mediated by neutrophil cells. Damage associated molecular patterns (DAMPs); in particular toll-like receptor 9 (TLR9) activate neutrophil production of cytokines. We hypothesized that activation of toll-like receptor 9 (TLR9) induced by necrotic cells may lead to tissue damage. Methods After approval by the Animal Care Committee at Washington University in St. Louis, we studied 5 domestic swine receiving a foley catheter. Urine samples were collected over 6 hours. Following cell counts urine neutrophils were labeled with monoclonal antibodies. IL-1?, IL-6, IL-8, IL-10 and TNF-? (figure 1), TLR9, and mitochondrial DNA (mtDNA) (Figure 2), were analyzed by qPCR. Neutrophil Elastase was detected by spectrometry. Specimens from areas of direct contact (urethra, bladder neck and fundus) were stained with H&E (Figure 3). Mann-Whitney U test was performed, p<0.05 was considered significant._x000D_ Results Foley catheter placement resulted in neutrophilia (p<0.01). Elevated cytokine transcription during the first 3 hours for IL-6, IL-8 (p<0.01), TNF-? (p<0.01), and IL-1? was evident. At 6 hours a noticeable elevation of the anti-inflammatory cytokine IL-10 appeared to reverse proinflammatory cytokine transcription. TLR9 (p<0.001) and mtDNA (p<0.05) transcription was significant. Histology of the bladder at urethra (A), bladder neck (B), and fundus (C) shows diffuse epithelial injury. _x000D_ Conclusions Cystitis induced by tissue damage is evident by 3 hours of exposure to a foley catheter resulting in elevated neutrophil cytokines, and TLR9 transcription. Therapies to ameliorate early neutrophil activation may prevent inflammation and infection_x000D_ Funding Washington University St, Louis Anesthesiology Department_x000D_ World Wide Technology and The Steward Family Foundation
Authors
Alexander Earhart
Nicholas Staten Alana Desai Henry Lai Ramakrishna Venkatesh Carlos Puyo |
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PNFLBA-08 |
Is Group Learning Behavioral Modification Program Effective and Safe in Reducing Geriatric Urinary Incontinence? A Multi-Center Randomized Controlled Trial. |
Plenary: Next Frontier, Sunday, Afternoon Session | 17BOS |
Abstract: PNFLBA-08 Sources of Funding: NIH/NIA # RO1AG043383 Introduction Primary aim: to compare the effectiveness and safety of a group-administered behavioral treatment program (GBT) to no treatment in older women with stress, urgency, or mixed urinary incontinence (UI). _x000D_ Methods Recruitment letters were mailed to women 55 years and older at three sites (Alabama, Michigan & Pennsylvania) seeking UI naïve to previous therapy. Responders were screened by phone and eligible respondents were referred to sites for clinical screening and randomization. Inclusion/exclusion criteria included age 55+, International Consultation on Incontinence questionnaire (ICIQ-SF) score at least 3 (1 for frequency, 2 for severity), minimum 3-months duration, no prolapse, previous bladder surgery or pelvic cancers. Primary outcome: ICIQ-SF. Secondary outcomes: 3-day voiding diary (VD), paper towel test, 24-hr pad test, Brink test, Patient Global Impression of Improvement (PGI-I) and other UI questionnaires. GBT group received a one-time 2-hour bladder health class whereas control received usual care. Both received behavioral education brochure, monitored every 3 months for 12-months; clinic visits at 3 & 12 months and mailed questionnaires at 6 & 9 months._x000D_ Results 463 subjects were randomized to GBT (232) or control (231). 34 withdrew (GBT=22 & Control =12). Demographics were not significantly different between groups. Outcomes at 3, 6, 9 & 12 months showed significant differences in favor of GBT over control including ICIQ (p<0.0001) (Fig 1), # leaks @ VD (p0.0002), paper towel test (p0.0008), 24-hr pad weights (p0.0007), Medical, Epidemiologic & Social aspects of Aging questionnaire (MESA) (p<0.0001), Incontinence Quality of Life (IQOL) (p<0.0001) & PGI-I (p<0.0001) but not the Brink test for pelvic floor strength (p0.09-.9). No significant difference in adverse events or serious events were encountered in each group. (all p values at 12 months) _x000D_ _x000D_ _x000D_ _x000D_ _x000D_ _x000D_ _x000D_ _x000D_ _x000D_ _x000D_ _x000D_ _x000D_ _x000D_ _x000D_ _x000D_ _x000D_ Conclusions This novel GBT bladder health education program was safe & effective in reducing UI frequency, severity and bother and improving quality of life for older women with UI in the community. This easily scaled intervention increases opportunity to reach larger populations beyond clinical into community settings. _x000D_ Funding NIH/NIA # RO1AG043383
Authors
Ananias C Diokno
Lisa Kane Low Diane K Newman Kathryn Burgio Tomas L Griebling Michael Maddens Leslee Subak Carolyn Sampselle Ann Robinson Trevillore Raghunathan Judith Boura Donna McIntyre |
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PNFLBA-09 |
Long-term combination treatment with solifenacin and mirabegron is effective and well tolerated in patients with overactive bladder |
Plenary: Next Frontier, Sunday, Afternoon Session | 17BOS |
Abstract: PNFLBA-09 Sources of Funding: This study was funded by Astellas Pharma Europe B.V. Introduction The objective of this Phase III study was to evaluate the safety and efficacy of long-term solifenacin and mirabegron combination (COMBN) treatment compared with solifenacin (SOLI) and mirabegron (MIRA) alone. Methods This was a randomized, double-blind, parallel-group study. Adult patients with symptoms of overactive bladder (OAB) for ≥3 m and ≥3 incontinence episodes in 7 d were eligible. After a 2-wk washout period, patients were randomized (4:1:1) to receive COMBN (SOLI 5 mg + MIRA 50 mg), SOLI (5 mg), or MIRA (50 mg) for a duration of 12 m. The primary safety variable was frequency of treatment-emergent adverse events (TEAEs). The change from Baseline to end of treatment (EoT) in mean number of incontinence episodes/24 h and micturitions/24 h were primary efficacy variables. Key secondary efficacy variables were change from Baseline to EoT in mean volume voided per micturition, OAB questionnaire Symptom Bother score, and treatment satisfaction-visual analog scale score. All efficacy variables were evaluated using analysis of covariance models. Results In total, 1,819 patients received COMBN (n=1,210), SOLI (n=303), or MIRA (n=306) and all groups had similar demographics. Overall, 856 (47.2%) patients experienced ≥1 TEAE (Table 1). A slightly increased frequency of TEAEs was observed in the COMBN group. The most common TEAEs in each group were dry mouth (COMBN and SOLI) and nasopharyngitis (MIRA). The changes from Baseline to EoT in the mean number of incontinence episodes and micturitions were significantly greater with COMBN treatment compared with SOLI and MIRA (Table 2). COMBN treatment was also significantly superior to SOLI and MIRA for all key secondary efficacy variables. Conclusions COMBN (SOLI + MIRA) treatment over 12 m was well tolerated and no new safety concerns were apparent. Clinically relevant improvements in efficacy were observed with COMBN treatment compared with each monotherapy over the 12 m study period. Funding This study was funded by Astellas Pharma Europe B.V.
Authors
Christian Gratzke
Rob van Maanen Christopher Chapple Paul Abrams Sender Herschorn Dudley Robinson Arwin Ridder Matthias Stoelzel Asha Paireddy Elizabeth R. Mueller |
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PNFLBA-10 |
A phase III blinded study of immediate post-TURBT instillation of gemcitabine versus saline in patients with newly diagnosed or occasionally recurring grade I/II non-muscle invasive bladder cancer: SWOG S0337 |
Plenary: Next Frontier, Monday, Morning Session | 17BOS |
Abstract: PNFLBA-10 Sources of Funding: Support: NIH/NCI grants CA180888, CA180819 and in part by Eli Lilly and Company_x000D_ _x000D_ Clinical Trials.gov Registry Number: NCT00445601_x000D_ _x000D_ Introduction Gemcitabine (G) is a frequently used and effective systemic agent for advanced urothelial cancer (UC). However, its utility for low grade (LG) non-muscle invasive (NMI) disease when administered intravesically has not been studied extensively. This trial tested the impact of one instillation of G (2 gm/100 ml saline) versus saline (S) alone (100 ml), held for one hour immediately following transurethral resection of bladder tumor (TURBT), on time to recurrence (TTR). Methods Patients had suspected LG NMI UC based on cystoscopic appearance. Patients could not have a prior history of muscle invasive, upper tract or prostatic urethral UC, non-UC bladder cancer or prior HG UC or > 2 UC episodes within 18 months before index TURBT. Patients were followed quarterly with cystoscopies for 2 years, then semiannually for 2 more years. Design: Primary endpoint: TTR. Randomize 340 eligible patients, one-sided ?=0.025, 89% power to detect a hazard ratio (HR) of 0.65 (G vs S) for time to recurrence. Participants were stratified by new vs recurrent tumor and 1 vs > 1 lesion(s). Results From July 2007 to August 2012, 416 (406 eligible) patients were randomized to G or S. Median age was 66 yrs, 85% were male, 91% were white, 37% had recurrent disease, and 68% had one lesion at entry. 33 patients assigned to G and 28 to S did not receive instillation, primarily because of complications at TURBT or patient refusal. In the primary ITT analysis (n=406), there was a significant 34% reduction in risk of recurrence in the G arm compared to S (HR=0.66, 95% CI 0.48, 0.90, p=0.010). For the per-protocol target population, LG NMI UCs, TTR even more strongly favored G (HR 0.50 95% CI 0.33, 0.76; p=0.001). Few muscle invasive events (G 2.5%, S 4.9%) or deaths from any cause (G 8.5%, S 12.2%) occurred. Adverse events (AEs) were infrequent. There were no Grade 4 or 5 complications, and no difference in Grade 3 AEs (G 2.4%, S 3.4%). Conclusions Immediate post TURBT intravesical instillation of G was safe, well tolerated and significantly reduced recurrence of LG NMI UC in these participants. Funding Support: NIH/NCI grants CA180888, CA180819 and in part by Eli Lilly and Company_x000D_ _x000D_ Clinical Trials.gov Registry Number: NCT00445601_x000D_ _x000D_
Authors
Edward Messing
Cathy Tangen Seth Lerner Deepak Sahasrabudhe Theresa Koppie David Wood Philip Mack Robert Svatek Christopher Evans Khalid Hafez Daniel Culkin Timothy Brand Lawrence Karsh Jeffrey Holzbeierlein Shandra Wilson Guan Wu Melissa Plets Nicholas Vogelzang Ian Thompson |
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PNFLBA-11 |
Radical Prostatectomy Versus Observation for Early Prostate Cancer: Follow-up Results of the Prostate cancer Intervention Versus Observation Trial (PIVOT) |
Plenary: Next Frontier, Monday, Morning Session | 17BOS |
Abstract: PNFLBA-11 Sources of Funding: Source of Funding:Department of Veterans Affairs, Agency for Healthcare Quality and Research and the National Cancer Institute. Introduction We previously found no mortality differences between surgery and observation in men with localized prostate cancer through 12 years. Uncertainty persists regarding nonfatal health outcomes and long-term mortality. We evaluated clinically important outcomes for men with early stage prostate cancer diagnosed during the early PSA era who were randomly assigned to treatment with either surgery or observation._x000D_ _x000D_ _x000D_ Methods Between 1994 and 2002, we randomly assigned 731 men with localized prostate cancer to radical prostatectomy or observation. We extended follow-up through August 2014 for our primary outcome, all-cause mortality, and main secondary outcome, prostate cancer mortality. We describe disease progression, additional treatments received and patient reported outcomes through the original follow-up of January 2010._x000D_ Results During 19.5 years of follow-up (Median=12.7 years), 223 of 364 men (61.3%) assigned to surgery died compared to 245 of 367 (66.8%) assigned to observation; (Absolute risk reduction(ARR)=5.5%, 95% Confidence Interval[CI], -1.5, 12.4); Hazard ratio(HR)=0.84, 95%CI, 0.70, 1.01; P=0.06). Prostate cancer mortality occurred in 27 men (7.4%) randomized to surgery versus 42 men (11.4%) randomized to observation; (ARR = 4.0, 95%CI, -0.2 to 8.3; HR=0.63, 95% CI, 0.39 to 1.02; P=0.06). The effect of surgery on mortality did not vary by baseline patient characteristics. Radical prostatectomy may have reduced all-cause mortality among men with intermediate (ARR=14.5%, 95%CI, 2.8 to 25.6) but not low (ARR=0.6%, 95%CI, -10.5 to 11.8) or high risk disease (ARR=2.3%, 95%CI, -11.5 to 16.1)(P for interaction = 0.08). Surgery reduced disease progression treatment, primarily androgen deprivation for asymptomatic, local or PSA progression, by 26.2 percentage points(95%CI, 19.0 to 32.9). Urinary incontinence, erectile and sexual dysfunction were each greater by more than 30 percentage points with surgery. Disease or treatment related bother and limitations in activities of day-to-day living were greater with surgery though 2 years but not at later follow-up. _x000D_ _x000D_ Conclusions After nearly 20 years, surgery did not significantly reduce all-cause or prostate cancer mortality compared with observation. Surgery had more adverse effects, but reduced disease progression and subsequent treatments; most asymptomatic, local or biochemical and may have reduced all-cause mortality in men with intermediate risk disease. _x000D_ Funding Source of Funding:Department of Veterans Affairs, Agency for Healthcare Quality and Research and the National Cancer Institute.
Authors
Timothy Wilt
Karen Jones Michael Barry Gerald Andriole Daniel Culkin Thomas Wheeler William Aronson Michael Brawer |
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PNFLBA-12 |
Targeting Epidermal Growth Factor Receptor (EGFR) and Human Epidermal Growth Factor Receptor 2 Expressing Bladder Cancer Using Combination Photoimmunotherapy (PIT) |
Plenary: Next Frontier, Monday, Morning Session | 17BOS |
Abstract: PNFLBA-12 Sources of Funding: Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. This research is also made possible through the NIH Medical Research Scholars Program, a public-private_x000D_ partnership supported jointly by the NIH and generous contributions to the Foundation for the NIH from the Doris Duke Charitable Foundation, the American Association for Dental Research, the Colgate-Palmolive Company, Genentech, and other private donors. For a complete list, visit the foundation website at http://www.fnih.org Introduction Bladder cancer (BC) is heterogeneous, expressing various cell surface targets, such as EGFR and Her2. Photoimmunotherapy (PIT) involves antibodies (Abs) conjugated to a photoabsorber (PA), IR Dye 700Dx, and then activated by Near infra-red light (NIR) to specifically target tumors. Our lab has previously shown that tumors expressing high levels of EGFR can be efficiently targeted with PIT. However, PIT is less effective when a tumor lacks “overwhelming� expression of a single target. Here, we present a novel, combinatorial PIT approach for such tumors expressing EGFR and Her2, using Panitumumab-IR700 (PanIR700) and Trastuzumumab-IR700 (TraIR700) antibodies, respectively. Methods BC cell lines were analyzed for expression of EGFR and Her2 using flow cytometery. Concurrent and optimal binding of both PA-labeled Abs were determined using flow cytometery. NIR LD50 of multiple treatment regimens were determined to analyze in vitro efficacy of combination PIT. Results The SW780 and RT112 cell lines showed low to moderate expression of EGFR and Her2. The EGFR expression was 143 fold higher in SW780 and 83 fold higher in RT112 over the isotype control. The Her2 expression was 42 fold higher in SW780 and 27 fold higher in RT112 over the isotype control. Hence, the ratio of cell surface EGFR to Her2 expression in both cell lines was about 3:1. For SW780, NIR LD50 was 28.66 J/cm2 for the combination PIT compared to 71.55 J/cm2 for the PanIR700 alone therapy. The NIR LD50 for RT112 was 14.66 J/cm2 for the combination PIT, with LD50 for PanIR700 alone therapy indeterminate from insufficient cell death. In both cases, the LD50 for TraIR700 alone therapy could not be determined from lack of sufficient cell death. Conclusions PIT is a new targeted treatment for bladder cancer that can be effectively used either locally or for metastatic lesions accessible by the NIR light. We demonstrate a novel and promising approach to treating BC by selectively inducing cell death in BC cell lines with low to moderate expression of cell surface markers of EGFR and Her2 using combination PIT. This will be further evaluated in a xenograft model. Funding Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. This research is also made possible through the NIH Medical Research Scholars Program, a public-private_x000D_ partnership supported jointly by the NIH and generous contributions to the Foundation for the NIH from the Doris Duke Charitable Foundation, the American Association for Dental Research, the Colgate-Palmolive Company, Genentech, and other private donors. For a complete list, visit the foundation website at http://www.fnih.org
Authors
mohammad siddiqui
Reema Railkar Thomas Sanford Peter Choyke Hisataka Kobayashi Piyush Agarwal |
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PNFLBA-13 |
Interim Results from A Single-Arm Multicenter Phase II Trial of CG0070, an Oncolytic Adenovirus, for BCG-Unresponsive Non-Muscle-Invasive Bladder Cancer (NMIBC) |
Plenary: Next Frontier, Monday, Morning Session | 17BOS |
Abstract: PNFLBA-13 Sources of Funding: Cold Genesys Introduction CG0070 is a replication selective oncolytic adenovirus that destroys bladder tumor cells through their defective retinoblastoma pathway. Prior reports have shown promising activity in patients with high-grade NMIBC who previously did not respond to BCG. However, limited accrual has hindered analysis of efficacy, particularly for pathologic subsets. We evaluated interim results of a phase II trial for intravesical CG0070 in patients with BCG-unresponsive NMIBC who refused cystectomy. Methods At interim analysis, thirty-six patients with residual high grade Ta, T1, or CIS ± Ta/T1 had 6 month follow-up in this phase II single arm multicenter trial (NCT02365818). All patients received at least 2 prior courses of intravesical therapy for CIS, with at least 1 of them being a course of BCG. Patients had either failed BCG induction therapy within 6 months or had been successfully treated with BCG with subsequent recurrence. Complete response (CR) at 6 months was defined as absence of disease on cytology, cystoscopy, and random biopsies. Results Of 36 patients there were 18 CIS, 4 CIS + Ta, 3 CIS + T1, 8 Ta, 3 T1 (Figure 1). Overall 6 month CR was 44%. Considering 6 month CR for pathologic subsets: pure CIS was 72.2%, CIS ± Ta/T1 52%, CIS + Ta/T1 0%, pure Ta/T1 27%. In non-responders with CIS, there were 4 patients (22%) with persistent CIS at 6 months, and 1 (5.6%) that progressed to CIS + T1. No patients with pure T1 or CIS + Ta/T1 had 6-month CR. In patients with both CIS + Ta/T1 (n=7), 5 had persistent Ta/T1 ± CIS, while 2 had CIS on biopsy at 6 months. All treatment related adverse events (AEs) at 6 months were Grade 1-3, most commonly urinary: dysuria (47%), bladder spasms (44%), hematuria (36%), and urgency (33%). Immunologic treatment related AEs included fatigue (11%) and chills (5.6%). Grade 3 treatment related AEs included dysuria (5.6%) and hypotension (2.7%). There were no Grade 4/5 treatment related AEs. Conclusions This phase II study demonstrates that intravesical CG0070 yielded an overall 44% complete response rate at 6 months for all patients and 52% for patients with CIS, with an acceptable level of toxicity for patients with high-risk BCG-unresponsive NMIBC. There is a particularly strong response and limited progression in patients with pure CIS. Funding Cold Genesys
Authors
Vignesh T. Packiam
Daniel A. Barocas Karim Chamie Ronald L. Davis III A. Karim Kader Donald L. Lamm Dominic Curran Alex W. Yeung Gary D. Steinberg |
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PNFLBA-14 |
Early In Vivo Detection of Metastatic Bladder Cancer in Mice using Molecular MRI |
Plenary: Next Frontier, Monday, Morning Session | 17BOS |
Abstract: PNFLBA-14 Sources of Funding: Funds from Stephenson Cancer Center Introduction Early detection of bladder cancer metastases might provide the potential for early treatment of metastatic disease. We previously reported on the use of a bladder tumor-binding peptide (BTBP)2 coupled to a Gd-DOTA MRI contrast agent (BTBP-probe)3 delivered intravesically to visualize bladder cancer growing on the bladder surface of an orthotopic mouse model, In this new report we demonstrated the use of this probe delivered intravenously to detect micrometastic spread of cancer to distant organs._x000D_ Methods MRI Studies: MRI experiments were done on a Bruker Biospec 7.0 Tesla/30 cm horizontal-bore imaging system. Multiple abdominal region 1H?MR image slices were taken using a RARE multislice (repetition time (TR) 1.3 s, echo time (TE) 9 ms, 256x256 matrix, 4 steps per acquisition, 3x3 cm2 field of view, 0.75 mm slice thickness). Mouse abdominal organs were imaged at 0 (pre-contrast) and at 3-4 hours post-contrast agent injection. Mice were injected intravenously with the BTBP-Gd-DOTA contrast agent (100µl/mouse; 50µmol/L). T1-weighted images were obtained using a variable TR (repetition time) spin-echo sequence (TR, 200-1600 ms; TE, 15 ms; NA, 2). Pixel-by-pixel relaxation maps were reconstructed from a series of T1-weighted images using a nonlinear two-parameter fitting procedure. The T1 value of a specified region-of-interest (ROI) was computed from all the pixels in the identified ROIs. MRI scans were obtained 6-7 weeks post-implantation of bladder tumors to identiy metastatic lesions. _x000D_ Results Molecular MRI (mMRI) was used to detect the presence of the BTBP-probe via a substantial decrease in T1 relaxation, measured as T1 relaxation difference, within tumor regions of mice administered the BTBP-probe (p<0.05) compared to the controls. Both primary and metastatic tumors were detected._x000D_ Conclusions We used mMRI to show for the first time non-invasive in vivo early detection of bladder tumor metastases in a mouse model for bladder carcinoma. Using mMRI with a bladder tumor-binding peptide targeted probe provides the advantage of in vivo image resolution and spatial differentiation of regional events in early detection of bladder cancer metastases._x000D_ Funding Funds from Stephenson Cancer Center
Authors
Joel Slaton
Nataliya Smith Debra Saunders Robert Hurst Rheal Towner |
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PNFLBA-15 |
Interim results of a novel ‘adaptive’ registration-utility trial assessing the performance of ExoDx® (Prostate) IntelliScore (EPI); a non-DRE urine exosome gene expression assay to predict high grade disease on initial biopsy. |
Plenary: Next Frontier, Monday, Morning Session | 17BOS |
Abstract: PNFLBA-15 Sources of Funding: Private Introduction Overdetection and overtreatment of indolent prostate cancer (PCa) remains a significant health issue requiring noninvasive assays to guide the prostate biopsy decision process. We previously demonstrated that a non-DRE urine exosome gene expression assay (ExoDx Prostate (IntelliScore) (EPI) discriminates GS 7 PCa from GS 6 and benign disease, potentially reducing the number of unnecessary biopsies. We initiated a novel prospective, phase-adaptive two cohort trial design: Group 1 (G1), men scheduled for a biopsy and Group 2 (G2), men for which the decision to biopsy is uncertain. The G1 consensus results including EPI cut-point recommendation will be applied to G2 patients with clinical utility, ease of adoption, patient response and health economic data collected. Here we report interim results from G1 with initial cut-point comparison to the original validation trial._x000D_ _x000D_ Methods The trial was activated on Sept. 2016 at 9 sites (8 community practice, 1 academic), geographically distributed across the U.S. We plan to enlist up to 20 sites by April 2017. Enrollment is limited to initial biopsy patients only, >/=50 years with PSA 2-10 ng/mL. The EPI test is performed at Exosome Diagnostics’ CLIA laboratory in Cambridge, MA; G1 results are collected for consensus review and G2 recommendation. Results The average biopsy rate across all sites is 1-2 / week. Demographics of the 96 (of targeted) 500 G1 patients enrolled thus far are comparable to the validation study (mean age 64 years, mean PSA 5.78; 75% white, 17% African American, 23% positive family history of PCa, 81% non-suspicious DRE). Of note, we have observed a higher positive biopsy rate of 59% (vs. 47% in validation study); 22% ISUP 1 (GS 3+3) and 37% >/=ISUP 2. The EPI test validated (15.6) vs. adjusted (20) cut-points both result in NPV 90, with sensitivity of 94% and 92%, respectively. The number of avoided biopsies is greater (30%) with the adjusted cut-point of 20 vs. the original validated cut-point (21%); while missing only 1>/=ISUP 3 case. The original validated cut-point would have avoided biopsies in 30% of men with GS6 or benign disease while the adjusted cut-point would have avoided 43% of biopsies in this population. Conclusions Interim results from a prospective adaptive trial of the EPI test demonstrate consistent performance as identified in the original validation study. The adjusted cut-point continues to provide added benefit without risk of missing significant disease. Funding Private
Authors
Alan Partin
Phillipp Torkler Mikkel Noerholm Johan Skog Michael Donovan |
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PNFLBA-16 |
First results of A-PREDICT: A Phase II Study of Axitinib in Patients with Metastatic Renal Cell Cancer (RCC) Unsuitable for Nephrectomy |
Plenary: Next Frontier, Monday, Morning Session | 17BOS |
Abstract: PNFLBA-16 Sources of Funding: Pfizer Introduction Axitinib is a potent oral vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI) not previously tested in the UK in metastatic RCC patients with their primary tumour in situ. A-PREDICT aims to determine whether axitinib has activity in this population and explore biomarkers of activity and resistance Methods A-PREDICT is a phase II single group study (maximum n=99) of axitinib (starting dose 5mg BID) in patients with metastatic clear cell RCC unable to have immediate cytoreductive nephrectomy. Participants consented to provide biosamples (tumour, blood, urine) at baseline, on treatment and at progression. The primary endpoint is proportion of patients alive and free from disease progression (RECIST v1.1) at 6 months. Secondary endpoints include toxicity (CTCAE v4), progression free, overall survival and correlation of biomarkers with clinical endpoints. Results 65 participants were recruited between 10/10/2012 and 23/12/2016. In December 2016 the Independent Data Monitoring and Steering Committee recommended that the trial close to recruitment as the pre-defined threshold level of activity had been reached. As of 19/12/2016 tumour samples were available for 92% participants at baseline, 87% on treatment and 13% at progression with equivalent return rates for blood and for urine samples._x000D_ Final data on response and toxicity will be available Q2 2017._x000D_ Conclusions Recruitment to translational studies is challenging. Due to close cooperation of oncologists, urologists, radiologists and pathologists, A-PREDICT represents the largest UK translational therapeutic study of first line treatment using axitinib in metastatic RCC, presenting a unique opportunity to study mechanisms of sensitivity and resistance to axitinib. Importantly, axitinib met predefined activity thresholds. Funding Pfizer
Authors
Grant Stewart
James Morden Ekaterini Boleti Naveen Vasudev Fiona Thistlethwaite Agnieszka Michael Lucy Kilburn Rebecca Lewis David Nicol Linda Pyle Claire Snowdon Rachel Todd Lucy Tregellas Samra Turajlic Charlie Swanton Judith Bliss James Larkin |
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PNFLBA-17 |
Detection of circulating tumor cell in the patients with prostate cancer using novel viral marker OBP-1101 |
Plenary: Next Frontier, Monday, Morning Session | 17BOS |
Abstract: PNFLBA-17 Sources of Funding: None Introduction Circulating tumor cell (CTC) is reported in several studies as a promising predictor of survival or treatment response. However, CTC detection by using immunohistochemical techniques some limitations, such as dead cancer cells could be detected, insufficient sensitivity, or inability to detect epithelial-mesenchymal transformation (EMT). OBP-1101 is a novel adenovirus-derived detection marker for cancer cells. Green Fluorescent Protein (GFP) protein gene expression is controlled by telomerase promoter in OBP-1101 and might be resolve above-mentioned problems. Methods After IRB approval, 15 ml blood samples were collected from 49 patients with prostate cancer at Kobe University Hospital. Detection of CTC using OBP-1011 was performed and these results were compared with patient demographics. Clinical stage, Gleason score, PSA, NCCN risk classification were analyzed whether they correlate with GFP positivities. In addition, results of immunohistochemical staining using EpCAM antibody and PSMA antibody were compared with GFP positivities. Results GFP positive CTC was detected in 26 cases (53.1%). EpCAM positive CTC was detected in 28 cases (57.1%). Among 28 EpCAM positive cases, PSMA positive CTCs were detected in 25 cases (89.3%). On the other hand, PSMA positive CTCs were detected only in 4 cases (8.2%). None of the Clinical stage, Gleason score, PSA, risk classification correlated with GFP positivity or EpCAM positivity. Conclusions The CTCs detected by using OBP-1101 could have different characteristics from those detected by using epithelial markers. These characteristics to detect EMT might be markers of worse clinical outcomes and change clinical decision making. Funding None
Authors
Nobuyuki Hinata
Yukari Bando Akira Miyazaki Tomoaki Terakawa Junya Furukawa Kenichi Harada Masato Fujisawa |
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PNFLBA-18 |
A Prospective, Multicenter, Randomized Trial of Open versus Robotic Radical Cystectomy (RAZOR) |
Plenary: Next Frontier, Monday, Morning Session | 17BOS |
Abstract: PNFLBA-18 Sources of Funding: National Cancer Institute - 5RO1CA155388 Introduction Over 3 million surgeries have been performed globally using the surgical robot since its inception without level 1 evidence. We present the first phase 3 multicenter prospective randomized trial comparing an open to robotic approach for any organ site. Open radical cystectomy (ORC) and urinary diversion remains the gold standard management for invasive bladder cancer, however it is a complex procedure with significant perioperative morbidity. Robotic assisted RC (RARC) is a minimally invasive alternative to ORC with the promise of reducing perioperative morbidity without compromising oncological principles. The RAZOR trial compares open versus robotic cystectomy using oncologic, perioperative, functional and QOL endpoints. Methods Across 15 participating institutions in the United States, patients with biopsy proven bladder cancer; clinical stage T1-T4, N0-N1, M0 or carcinoma in situ (CIS) refractory to intravesical treatments were randomized to ORC or RAsRC in a 1:1 ratio. The trial was designed as a non-inferiority comparison with RARC being considered inferior if the 2-year progression-free survival (PFS) was >15% lower than ORC [Power = 80% and 2-sided significance level (alpha) = 5%]. Other endpoints included blood transfusion rate, estimated blood loss (EBL), length of stay (LOS), complications (Clavien-Dindo system), lymph node yield and margin status. Results A total of 350 patients were randomized. After exclusions, 150 in the RARC and 156 in the ORC arms were analyzed. Follow-up data is currently being reviewed and the 2-year PFS comparison is under analysis. Results are presented in Table 1. Estimated blood loss was significantly lower in the robotic arm translating into significantly lower blood transfusion rates. Major complications (Grade III and above) were similar in both groups. The number of lymph nodes removed was comparable and there was no significant difference in overall positive margin status. Positive bladder soft tissue margins were more common in the robotic arm. There was a trend to shorter LOS for RARC._x000D_ Conclusions The 2 year oncologic outcomes will be ready for the AUA meeting. The robotic approach is associated with significantly lower EBL and transfusion rates than ORC with a trend to shorter LOS. There is no difference in the perioperative morbidity between the 2 approaches._x000D_ Funding National Cancer Institute - 5RO1CA155388
Authors
Dipen Parekh
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PPTLBA-01 |
Quality of life after penile prosthesis implantation – 1 year follow-up data of the italian prospective registry INSIST-ED |
Plenary: Prime Time, Sunday, Morning Session | 17BOS |
Abstract: PPTLBA-01 Sources of Funding: None Introduction The impact of penile prosthesis implantation (PPI) on the overall patient's quality of life (QoL) has been scantly analyzed. The aim of this study was to assess the QoL of patients submitted to PPI, using the validated questionnaire Quality of Life and Sexuality with Penile Prosthesis (QoLSPP). Methods Data were collected from the multi-institutional database directly filled out by 43 different surgeons after the surgical procedure on a dedicated website (www.registro.andrologiaitaliana.it) and revised by a data-manager from December 2014 to December 2016. Clinical characteristics of patients, etiology of erectile dysfunction (ED) and type of implanted prosthesis were analyzed. In order to simultaneously evaluate perceived penile prosthesis function and QoL, all patients were re-assessed at 1-yr follow-up with the QoLSPP questionnaire. Descriptive statistics and linear regression analysis were applied to assess the impact of the type of implanted prosthesis (hydraulic vs. non-hydraulic) on functional outcomes and QoL. Results Overall, 560 patients were included in the database. Follow-up data were available for 84 (15%) of them [median age 62yrs (IQR: 55 – 67 yrs)]. Of them, 85.1% (71) received an hydraulic penile prosthesis and 14.9% (13) a non-hydraulic model. 52.1% (44) of patients were submitted to PPI for post-radical prostatectomy ED, while 22.5% (19) and 16.9% (14) were affected by Peyronie's disease and vasculogenic ED, respectively. Overall, all patients reported high scores of the QoLSPP domains Functional (F:20.3/25), Personal (P:16.7/20), Relational (R:15.8/20) and Social (S:12.6/15) at 1-yr follow-up. Patients implanted with a non-hydraulic prosthesis reported significantly lower mean scores for all the QoLSPP domains as compared to hydraulic prosthesis (F:21.6 vs 17.7; P:17.6 vs 23.9; R:16.7 vs 13.8; S:13.2 vs 10.4; all p<0.02). At multivariable linear regression analysis, the hydraulic model was significantly associated with higher scores of the QoLSPP domains, after accounting for patient's age and ED etiology. Conclusions This is the first study reporting QoL data after PPI using the validated QoLSPP questionnaire. Our results showed a significant advantage of the hydraulic model as compared to the non-hydraulic model in terms of both perceived prosthesis function and QoL, irrespective of patient's age and ED etiology. Funding None
Authors
Paolo Capogrosso
Giovanni Alei Gabriele Antonini Antonio Avolio Antonio Barbieri Carlo Bettocchi Marco Bitelli Francesco Boezio Masssomo Capone Enrico Caraceni Maurizio Carrino Carlo Ceruti Sandro Ciampalini Fulvio Colombo Enrico Conti Antonio Corvasce Giuseppe Dachille Diego Pozza Stefano Fiordelise Alessandro Franceschelli Giulio Garaffa Nicola Ghidini Franco Giorgio Emilio Italiano Giuseppe La Pera Antonino Laganà Giovanni Liguori Lilia Utizi Matteo Matera Nicola Mondaini Alessandro Natali Carlo Negro Fabrizio Palumbo Matteo Paradiso Edoardo Pescatori Massimo Polito Gaia Polloni Andrea Salonia Mauro Silvani Aldo Tamai Massimiliano Timpano Francesco Varvello Patrizio Vicini Antonio Vitarelli Antonio Palmieri Federico Dehò |
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PPTLBA-02 |
Blue Light Flexible Cystoscopy (BLFC) with hexaminolevulinate (HAL) and white light flexible cystoscopy: a prospective, comparative, within-patient controlled multi-center Phase 3 study in the detection of bladder cancer during surveillance |
Plenary: Prime Time, Sunday, Afternoon Session | 17BOS |
Abstract: PPTLBA-02 Sources of Funding: Photocure Inc Introduction White light (WL) cystoscopy is the current standard of care for bladder cancer surveillance. Multiple studies have demonstrated that blue light cystoscopy (BLC) with HAL in the operating room (OR) improves detection of bladder cancer with reduction in recurrence rates when compared to WL TURBT. The objective of this study was to determine if Blue Light Flexible cystoscopy (BLFC) in the office setting can improve detection of tumors in the surveillance setting when compared to WL cystoscopy alone. Methods Patients with a high risk of recurrence based on history of multiple tumors, recurrent tumors and/or high grade tumors were included for their first surveillance visit. Patients who had received intravesical therapy within 6 weeks were excluded. In the clinic setting, all patients received intravesical HAL, which was retained for 1 to 3 hours before examination. The bladder was inspected under WL using flexible cystosocpy, and all suspicious lesions were documented. Some patients were randomised to WL only, in order to avoid observational bias. The rest underwent immediate subsequent investigation with BLFC. The first four patients enrolled at each site were training patients and not included in the efficacy analysis. Those suspected of recurrence were referred to the OR within 6 weeks, where WL and BLC were repeated. All suspected lesions underwent biopsy or resection. A panel of independent pathologists blinded to the origin of the specimen achieved a consensus read. The primary endpoint was the proportion of patients with histologically confirmed malignancy which was detected with BLC only. Additional endpoints included false positive rates, detection of CIS and number of additional tumors detected with BLC only. Results Seventeen academic institutions in the US participated in the study and 304 patients were enrolled. Of the 234 non-training patients who proceeded through randomization, 103 patients were referred to the OR with a suspected recurrence for WL and BLC. Approximately 80% of the patients had a history of CIS or HG Ta/T1 tumor. Full results are expected by end of April, 2017. Conclusions In the surveillance setting, an increase in detection of tumor recurrence using BLFC may provide a significant advantage for patients potentially leading to less extensive and more cost effective management. Funding Photocure Inc
Authors
Siamak Daneshmand
Sanjay Patel Yair Lotan Kamal Pohar Edouard Trabulsi Michael Woods Tracy Downs William Huang Jennifer Taylor Michael O'Donnell Trinity Bivalacqua Joel DeCastro Gary Steinberg Ashish Kamat Matthew Resnick Badrinath Konety Mark Schoenberg Stephen Jones |
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V10-01 |
Reconstruction of Two Concurrent Ipsilateral Ureteral Strictures with Appendiceal Onlay and Non-Transecting Ureteral Reimplant |
Reconstruction Upper Tract | 17BOS |
Abstract: V10-01 Sources of Funding: none Introduction The management of concurrent ipsilateral ureteral strictures is challenging as the ureter cannot be transected in two places. The mainstays of reconstruction in this clinical scenario include renal autotransplant or ileal ureter, both of which are associated with morbid short and long-term complications. The concept of an onlay graft or flap to increase the size of the lumen is a well-established technique for urethral reconstruction. We demonstrate the feasibility of this concept to the ureter by placing an onlay of bladder and appendix to manage concurrent ureteral strictures. Methods A 66-year-old man with bilateral proximal ureteral stones developed a 3cm right distal ureteral stricture and a 6cm right proximal ureteral after undergoing ureteroscopy and laser lithotripsy at an outside institution. These strictures were refractory to endoscopic management. The patient had an elevated creatinine. Robotic reconstruction was performed with simultaneous intraoperative ureteroscopy to delineate the stricture. As the ureteroscope was passed retrograde, the 3cm distal and 6cm proximal ureteral strictures were incised using the robot along the anterior aspect of the ureter. The patient’s appendix was mobilized, detubularized, and placed as an onlay flap onto the proximal stricture. The distal ureteral stricture was repaired by marsupializing a flap of bladder onto the ureter for a non-transecting reimplant. Results The patient had an uneventful postoperative course and went home on postoperative day 4. Nephrostogram performed at 6 weeks post op demonstrated prompt drainage of contrast after stent removal. At 6 months post op, he had no urinary infections or flank pain. Ureteroscopy at this time demonstrated patency throughout the entire course of the right ureter. Conclusions For the appropriate patient, ureteral reconstruction using onlay of appendix and bladder is a feasible option for multiple ureteral strictures. Six-month outcomes are favorable, but long-term outcomes need to be elucidated. Funding none
Authors
Dmitry Volkin
Kiranpreet Khurana Aaron Weinberg Mark Ferretti Marc Bjurlin Michael D. Stifelman Lee C. Zhao |
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V10-02 |
Robotic buccal mucosal ureteroplasty for ureteral stricture after robotic ureterolysis |
Reconstruction Upper Tract | 17BOS |
Abstract: V10-02 Sources of Funding: none Introduction Long strictures involving the proximal ureter pose a reconstructive challenge. Recently, robot-assisted ureteroplasty with buccal mucosa graft (BMG) has been described. We present a patient who received both robotic ureterolysis followed by a robotic ureteroplasty the following year, in order to describe both robotic techniques on video. Methods A 58 year-old male on medication for a pituitary tumor presented with left ureteral obstruction and underwent a robotic ureterolysis/omental wrap procedure for presumed retroperitoneal fibrosis after failed medical management. Fibrosis was isolated to the region of a tortuous left iliac artery, which was likely due to trauma from a prior femoral artery catheterization during a cardiac procedure. The ureter was freed of fibrotic attachments and covered with an omental wrap. The patient did well for 1 year, but eventually developed recurrent ureteral obstruction with a 6cm mid/upper ureteral stricture requiring nephrostomy drainage and stent. He elected to undergo BMG ureteroplasty._x000D_ _x000D_ For both robotic procedures, the patient was positioned in modified lateral decubitus lithotomy position with ports similar to a pyeloplasty. For the ureteroplasty, the mouth was prepped separately for BMG harvest. Ureteroscopy and near-infrared fluorescence were used to define the proximal and distal extent of the stricture. The stricture was measured and the BMG was harvested accordingly. A ureterotomy was made along the length of the stricture over the ureteroscopy. The BMG was sewn to the ureteral edges as an onlay patch. Ureteroscopy was used to confirm patency and a stent was placed. An omental wrap was sutured over the ureter and BMG for blood supply._x000D_ _x000D_ Results The patient underwent an uncomplicated ureterolysis procedure with an EBL of 75cc, OR time of 280 minutes, and a hospital stay of 3 days. He is doing well with followup <1 year with no complications or evidence of obstruction. Conclusions We describe a case of robotic ureterolysis followed by robotic BMG ureteroplasty in the same patient. Robotic BMG ureteroplasty is an option for patients with long ureteral strictures with proximal extent, and is an alternative to autotransplantation or ileal ureter. Funding none
Authors
Chase Heilbronn
Logan Campbell Mouafak Tourjman Dan Pucheril Lamont Jones Craig Rogers |
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V10-03 |
Robot Assisted Bilateral Ureteral Reimplantation on Studer Neobladder with Exposure of Iliac Artery Prosthesis |
Reconstruction Upper Tract | 17BOS |
Abstract: V10-03 Sources of Funding: None Introduction The Studer type neobladder is an orthotopic vesical substitution alternative that provides a continent reservoir that works at low pressure and is easy to void. One possible complication of this diversion is the uretero-intestinal stenosis. The presence of vascular prosthesis can cause an inflammatory reaction that might affect the ureters. The standard treatment for the stenosis is the surgical repair. This ureteral reconstruction is a demanding surgery in the open approach._x000D_ Robotic sugery enhaces vision of the surgical field while maintaining a high freedom of movement and facilitates a successful repair. Methods We present the case of a 72-year-old male, with a history of hypertension, diabetes and hyperuricemia, who’s urological history began in April 2015 with a Transurethral Resection of Bladder (TURB) that showed a High Grade cT1 bladder tumor and Carcinoma in situ (Cis) with an early recurrence. In November 2015, he underwent a Robotic Assisted Laparoscopic Radical Cystoprostatectomy with bilateral lymphadenectomy and Studer type Neobladder. After removing ureteral catheters (1 week after surgery) the patient present urinary leaks at the level of uretero-neovesical anastomosis. Bilateral Nephrostomy catheters where placed. After conservative treatment with ureteral catheters, an antegrade pyelography showed resolution of the urinary leaks but presence of bilateral distal ureteral stenosis _x000D_ In March 2016 the patient presented in the emergency room with severe bleeding due to a fistula between the left common iliac artery and the Studer neobladder, requiring percutaneous placement of two arterial prostheses. _x000D_ _x000D_ In April 2016, a Robotic Assisted Laparoscopic Bilateral ureteral reimplantation on Studer Neobladder was performed. _x000D_ Local Bioglue was used to cover the area of exposure of vascular prosthesis. Results The surgical time was 210 minutes. The preoperative hemoglobin was 120 mg/dL and the postoperative one was 100 mg/dL. No blood transfusions were necessary. There were no postoperative complications. The patient was discharged at the 8th day after surgery. Nephrostomies were removed 15 days after surgery. Conclusions Robot assisted surgery is a good approach for the treatment of ureterointestinal stenosis, even in cases of concomitant vascular disease. Funding None
Authors
Joan Palou
Lluís Gausa Ivan Schwartzmann Laura González Pérez Juan Antonio Peña Enver Moncada Pablo Juárez del Dago Humberto Villavicencio |
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V10-04 |
Early Robotic Repair of Multifocal Ureteral Perforation After Ureteroscopy |
Reconstruction Upper Tract | 17BOS |
Abstract: V10-04 Sources of Funding: none Introduction As urologists become more comfortable with robotic surgery, new techniques surface. Minimally invasive approaches for management of iatrogenic ureteral injuries, mostly secondary to gynecologic procedures, have been described previously. Traditional conservative management of ureteral injury, including stent placement, nephrostomy tube, or delayed repair can be morbid and require significant patience on behalf of both the patient and surgeon with potential for a prolonged course to definitive repair. We present a case which demonstrates the feasibility of early robotic repair of a multifocal ureteral injury within 24 hours of ureteroscopic insult, expediting resolution of the patient’s injury. Methods A 73-year-old male was transferred to our institution with a reported ureteral avlusion with subsequent failure to place a stent or nephrostomy tube. We performed our own retrograde pyelogram and identified what appeared to be a devastating injury to the mid ureter. We were fortunate to pass a wire across the injuries, and a stent was placed to aid with intraoperative identification. A 4-port laparoscopic robotic approach was taken to identify the left kidney and subsequently the left ureter. Gentle dissection around the ureter in the area concerning for injury identified two separate full thickness injuries. The ureter was repaired using running absorbable suture in a tension free, watertight fashion. A drain was placed in the vicinity of the repair bed._x000D_ Results The patient's discharge was delayed due to postoperative fevers. Workup was negative. He was ultimately discharged with a stent and Foley catheter in place on postoperative day 3. The Foley catheter was removed on postoperative day 7. He underwent cystoscopy with stent removal and retrograde pyelogram 4 weeks after surgery, which revealed a patent ureter. Renal ultrasound at 6 weeks demonstrated no hydronephrosis, and the patient is asymptomatic._x000D_ Conclusions Based on our initial experience, early robotic repair is a safe and effective modality for management of iatrogenic ureteral injury. The approach and principles of reconstruction are similar to already established techniques. In this case, it also allowed for simultaneous management of the patient’s ureteral stone disease. The initial increased risk of proceeding to a more invasive treatment modality is likely offset by the shortened timeline to stent or nephrostomy tube free status. Further investigation of this approach as well as evaluation of long term outcomes will be critical to establishing this as a standard option for management of iatrogenic ureteral injuries._x000D_ Funding none
Authors
Andrew Radtke
Kenneth Jacobsohn |
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V10-05 |
Robotic Salvage Pyeloplasty with Buccal Mucosal Onlay Graft – A Simplified Technique |
Reconstruction Upper Tract | 17BOS |
Abstract: V10-05 Sources of Funding: none Introduction Surgical management of recurrent ureteral pelvic junction (UPJ) obstruction is limited by our ability to create a tension free anastomosis due to ureteral devascularization, fibrosis with renal fixation, and dense stricture formation. A high rate of recurrence leads to progressively complex repairs. Herein, we present the use of buccal mucosal graft (BMG) in a salvage robotic laparoscopic pyeloplasty in the management of recurrent UPJ obstruction. Methods We present two patients with recurrent left UPJ obstruction. Both previously underwent multiple failed open or robotic pyleoplasties, attempted endoscopic treatment and subsequent management with ureteral stent exchanges. At the time of surgery patients were placed in left lateral flank position and a Foley catheter inserted. Transperitoneal access was obtained with a Veress needle. Extensive adhesiolysis was required. The colon was reflected medially, the kidney, ureter and renal pelvis were exposed and the UPJ identified. The area surrounding the UPJ and proximal ureter were circumferentially dissected. The UPJ was entered and the ureter incised longitudinally from the renal pelvis until healthy, normal caliber ureter was demonstrated distally, with spatulation for at least 1 cm on either end. The defects were measured and found to be 3.5 and 4 cm. 8 Fr double J ureteral stents were placed. Single buccal grafts were harvested from the right inner cheek and measured for the length of the stricture and 1.5-2cm wide. A stay suture was placed to maintain orientation and minimize handling of the ureteral tissue. The graft was delivered to the abdomen and placed as an anterior onlay, over the ureteral and UPJ defect, with two 4-0 running Vicryl sutures. The tension free repair and surgical field was wrapped in omentum after confirming a water tight anastomosis. A JP drain was placed. Results Operative times were 280 and 411 minutes. Estimated blood loss was 25-50 mls. The hospital stay was 2 days. Foley catheters and JP drains were removed in the immediate post-operative period. The ureteral stents were removed at 6 and 9 weeks, with retrograde pyelograms confirming patency. Both patients have been asymptomatic since stent removal and anticipate follow-up functional renal scans with Lasix in 6 months. Conclusions Robotic salvage pyeloplasty with BMG is an attractive alternative technique in the management of recurrent UPJ obstruction demonstrating a tension free, water tight and patent repair. Short term follow up has demonstrated that it is an effective and feasible approach when compared to more extensive and invasive surgical procedures. Funding none
Authors
Ryan J. Nelson
Anna Zampini Jeremy Reece Kenneth Angermeier Georges-Pascal Haber |
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V10-06 |
Robotic-assisted Laparoscopic Calyceal Diverticulectomy |
Reconstruction Upper Tract | 17BOS |
Abstract: V10-06 Sources of Funding: None Introduction A calyceal diverticulum is a cystic cavity within the kidney that is lined by transitional epithelium and communicates with a calyx, or less commonly, with the renal pelvis. A calyceal diverticulum forms as a result of the failure of the degeneration of the ureteric bud. 0.2 – 0.5% are congenital; 40% are associated with calculi. This is a video demonstrating a robot assisted laparoscopic calyceal diverticulectomy._x000D_ Methods This video demonstrates two cases of robotic calyceal diverticulectomy the first patient is a 19 year-old caucasian female and the second patient is a 25 year-old caucasian female. Who both had sudden onset of flank pain and abdominal pain. Initial work up was consistent with infection; however on repeat imaging, both patients were found to have a calyceal diverticulum. Both patients underwent a robot assisted laparoscopic diverticulectomy. Initial dissection was similar to a partial nephrectomy with mobilization of the large bowel and exposure of the renal hilum. The diverticulum is then incised, drained, and excised to the infundibulum to prevent recurrence. Any remaining urothelium was fulgurated. Results Both patients who underwent a robot assisted laparoscopic calyceal diverticulectomy are complication and re-admission free to date. Conclusions Robotic-assisted laparoscopic calyceal diverticulectomy is a feasible and safe option in the management of large persistent calyceal diverticulum. Funding None
Authors
Hugh Smith
Nathan Jung Juan Class Amar Singh Darryl Turner Dana Butler Chris Keel |
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V10-07 |
Robotic repair of right uretero-ileal anastomotic stricture following prior robotic radical cystectomy and intracorporeal conduit diversion |
Reconstruction Upper Tract | 17BOS |
Abstract: V10-07 Sources of Funding: none Introduction Uretero-ileal anastomotic stricture is a well-known complication following radical cystectomy and urinary diversion with a rate of 8-12% in open and robotic series. Some strictures can be managed endoscopically but many require revision of the uretero-ileal anastomosis. With increased utilization of robotic radical cystectomy we have started revising these strictures with a robotic approach as well. Methods From September 2014 - October 2016 we have performed 75 robotic radical cystectomies with 60 undergoing robotic intracorporeal ileal conduit urinary diversion._x000D_ We found 6 patients that developed a uretero-ileal stricture. In the following video we highlight the technique for robotic revision of a right-sided uretero-ileal anastomotic stricuture in a patient following prior robotic radical cystectomy and intracorporeal ileal conduit urinary diversion. Results Our uretero-ileal anastomotic stricture rate following robotic radical cystectomy with intracorporeal conduit urinary diversion was 10%. _x000D_ Of these four were involving the left and two were involving the right ureter. Three patients were able to be managed with endoscopic dilation_x000D_ and three patients required revision of their uretero-ileal anastamotic stricture. All 3 patients were able to be managed with robotic uretero-ileal anastomotic revision._x000D_ Mean time to diagnosis of stricture was 182 days. For the patient in the video operative time was 62 minutes, EBL was 100cc, and length of stay was 1 day. The other two patients had other concomitant operations (parastomal hernia repair in one and takedown of pre-existing colon conduit in another) that significantly impacted operative time and length of stay and were not including in analysis of perioperative outcomes. Conclusions Uretero-ileal anastomotic strictures following robotic radical cystectomy and intracorporeal conduit urinary diversion can safely and effectively be managed with a robotic approach. Funding none
Authors
Mehrdad Alemozaffar
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V10-08 |
Total laparoscopic ureteral substitution using appendix |
Reconstruction Upper Tract | 17BOS |
Abstract: V10-08 Sources of Funding: None Introduction Complex ureteral injuries have challenging repair, involving renal autotransplantation or ureteral substitution, which was first described in 1911, using bowel segments (Shoemaker), and in 1912, using the appendix (Melkianof). We report a post-pyeloplasty complex ureteral injury that was laparoscopically repaired by an appendix interposition. Methods A 17 year-old boy with right ureteropelvic junction (UPJ) obstruction was scheduled for pyeloplasty. During surgery, an obstruction on the ureterovesical junction was discovered, making impossible the use of a double-J stent, causing local trauma. So, Anderson-Hynes pyeloplasty was performed and he was left only with a nephrostomy tube. Twenty days later, an anterograde pyelogram demonstrated a stricture on the UPJ level. A cystoscopy showed a scar on right ureteral meatus. It was impossible to identify the right ureteral meatus, during cystoscopy. Then an exploratory laparoscopy was scheduled on the fortieth postoperative day, and as the renal drainage was not possible by two points of obstruction, ureteral substitution was decided. Because of an intraoperative favorable anatomy, the appendix was chose and it was made laparoscopically. Results The operation lasted about 350 minutes and the estimated blood loss was 200ml, so the patient received no blood transfusion. Postoperatively, the patient developed urinary tract infection and was discharged in the tenth postoperative day. Double-J stent was removed on the sixtieth postoperative day. Follow-up 6 months after surgery showed a satisfied patient, with no limitations on quality of life, asymptomatic, but with a residual hydronephrosis on image studies. Conclusions We support the use of the appendix for ureteral substitution (as a ureteral substitute) on selected cases, and we advice for the possibility of laparoscopic approach of complex injuries. We believe this is the first video of a total laparoscopic ureteral substitution using appendix. Funding None
Authors
Paulo Medeiros
Cesar Britto Daniel Ferreira MaurÃcio Júnior Rodolfo Alves Ronnie Lima Thiago Grossi Carla Santos John Heyder Galvão |
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V10-09 |
Tips for Surgical Technique During Robotic Ureteral Reconstruction for Various Segments of Ureter |
Reconstruction Upper Tract | 17BOS |
Abstract: V10-09 Sources of Funding: None Introduction Ureteral reconstruction for different segments of ureter can be extremely challenging. There are many methods for reconstruction, most of which are typically performed using an open approach. Standard techniques such as boari flap and psoas hitch have been around for many years and are traditionally not performed using a minimally invasive approach. In this video we present multiple advanced techniques and alternatives during robotic ureteral reconstruction for various segments of ureter. Methods We present techniques for distal ureterectomy with reimplantation, segmental ureterectomy with end to end anastomosis, buccal mucosal patch and ileal patch for midureteral stricture, and ileal ureteral replacement for panureteral stricture. We demonstrate these techniques as well as the use of indocyanine green injection to help with identification of the level of obstruction. Results To date, 24 cases of ureteral reconstruction have been performed. Robotic console times have ranged form 60 minutes to 194 minutes. Estimated blood loss has ranged from 10-150ccs. Length of stay has ranged from 1-4 days. Follow up has ranged from 2-60 months. To date, there is no evidence of recurrent obstruction in any patient. Conclusions Robotic ureteral reconstruction can be successfully performed on any segment of ureter and is a feasible option to more invasive open surgery. The use of indocyanine green can help delineate segments of ureter for excision. Ileal and buccal patches are good alternatives to segmental ureterectomy or more complicated flaps for midureteral strictures. Funding None
Authors
Manish Patel
Ashok Hemal |
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V1-01 |
Radial Forearm Free Flap Substitution Urethroplasty for the Treatment of a Long Urethral Defect |
Reconstruction Lower Tract (I) | 17BOS |
Abstract: V1-01 Sources of Funding: None Introduction We describe the surgical steps for performing a radial forearm free flap (RFFF) substitution urethroplasty in a patient with an obliterated urethral defect after failing an excision and primary anastomotic (EPA) urethroplasty for a pelvic fracture urethral injury (PFUI). Methods A 9-year old male involved in an all-terrain vehicle accident was initially treated at an outside hospital for non-operative pelvic fractures and a urethral disruption. He was managed with a suprapubic catheter. The patient was referred 5 months after the injury with a 3 cm obliterated bulbar urethral defect. We performed a posterior EPA urethroplasty with corporal splitting and partial inferior pubectomy. One month after surgery, an anastomotic leak was identified on retrograde urethrogram (RUG) imaging. The urethral catheter was removed and the patient was managed with a SPT. Two months after surgery, repeat imaging was performed and an obliterated urethral defect was identified. Due to the early failure of the repair, suggesting vascular compromise and/or technical failure, we proceeded with RFFF substitution urethroplasty. Results The patient underwent RFFF urethroplasty under the coordinated care of the urology and microvascular plastic surgery team. Major steps included the following: 1) dissecting the urethra and measuring the length of the urethral defect, 2) harvesting the radial forearm free flap, 3) tubularizing the flap over a catheter, 4) preparing the recipient femoral vessels in the inguinal region, 5) performing the urethral-flap anastomoses, and 6) performing the microvascular anastomoses. Following excision of scar, the urethral defect measured 10 cm. The flap was harvested from the left forearm which was closed primarily. The operation was 8:45 with 180 cc of blood loss. During the microvascular anastomoses, an acoustic microvascular coupler was placed to audibly monitor the vascular flow of the flap during the post-operative period. The patient was kept on bed rest for 48 hours, and the patient was discharged home on post-operative day 4. After 3 weeks, the urethral catheter was removed and the SPT was kept to drainage since a small leak was visualized at the proximal anastomosis on RUG imaging. The SPT was removed 3 weeks later following no visual evidence of leak on imaging. The patient continues to void without obstructive symptoms 3 months after surgery. Conclusions Radial forearm free flap urethroplasty is a treatment option for long, obliterated urethral defects and should be performed in a multidisciplinary manner with the assistance of a microvascular plastic surgeon. Funding None
Authors
Paul H Chung
Jonathan T Wingate Jeffrey B Friedrich Bryan B Voelzke |
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V10-10 |
Combination of Endo-GIA with laparoscopic pyeloplasty for the treatment of a 19 year-old man of horseshoe kidney with ureteropelvic junction obstruction |
Reconstruction Upper Tract | 17BOS |
Abstract: V10-10 Sources of Funding: None Introduction The horseshoe kidney is a renal fusion anomalies which occurs in 0.25% of the population. The ureteropelvic junction obstruction (UPJO) with horseshoe kidney is uncommon. We reported that a 19 year-old man with horseshoe kidney and UPJO was underwent laparoscopic pyeloplasty and the horseshoe kidney was cut using Endo-GIA in its isthmus. Methods The patient presented with symptom of left flank pain with severe hydronephrosis. The diuretic renal dynamic imaging showed the complete mechanical obstruction for the upper urinary tract. The glomerular filtration rates were 34 ml/min for the left side and 40 ml/min for the right side. The computerize tomography showed the horseshoe kidney with the right-side UPJO. The ureteropelvic junction was compressed upwardly by the isthmus of horseshoe kidney. For the complete relief of the obstruction, the isthmus of the horseshoe kidney was cut using Endo-GIA combining with the laparoscopic pyeloplasty. Results The surgery was done with expected post-operative results. The operative time was 125 minutes. The post-operative hospitalization was 3 days and the double-J stent was removed 3 months after surgery. The patient is asymptomatic with complete relief of obstruction. Conclusions When UPJO complicated with horseshoe kidney which may be the potential reason to cause hydronephrosis, cutting the horseshoe kidney using Endo-GIA combining with the laparoscopic pyeloplasty may be a feasible alternative. Funding None
Authors
Xuesong Li
Kunlin Yang Liqun Zhou |
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V10-11 |
Intracorporeal Robotic-Assisted Laparoscopic Appendiceal Interposition for Ureteral Stricture Disease |
Reconstruction Upper Tract | 17BOS |
Abstract: V10-11 Sources of Funding: None Introduction Management of complex ureteral strictures greater than 1 cm in length are traditionally treated with open or laparoscopic ureteral reconstruction. In the setting of long segment strictures not amenable to simple ureteroureterostomy, ureteral replacement with ileum classically has been described as a suitable option. Aside from ileum, a buccal mucosa graft and the appendix have been described as alternative replacement tissues. To date, there are no reports in the literature of a robotic-assisted laparoscopic (RAL) ureteral reconstruction utilizing the appendix. We report, to our knowledge, the first case of a completely intracorporeal RAL appendiceal interposition for ureteral stricture disease in a 33 year old Caucasian male with a 5 cm obliterative right-sided ureteral stricture secondary to recurrent urolithiasis. Methods The DaVinci Xi was docked to the patient in a fashion comparable to right nephroureterectomy. Extensive renal descensus was performed and it was determined that tension-free primary ureteroureterostomy was not feasible. Given the ideal position, length and orientation of the appendix, along with the added morbidity of bowel harvest, we elected to perform an appendiceal interposition. The appendix with its mesentery was isolated and interposed between the remaining healthy proximal and distal ends of the ureter. The ureteroappendiceal anastomoses were performed in an end-to-end fashion. A ureteral stent was left in place to allow for postoperative healing. The entire case was done intracorporeally. Results The ureteral stent was removed two weeks postoperatively. Antegrade nephrostogram showed patency of the ureter down to the bladder one month postoperatively. Lasix renal scan confirmed preservation of renal function and no obstruction three months postoperatively. Conclusions In carefully selected patients with long-segment right-sided ureteral strictures and favorable anatomy, appendiceal interposition is a good option for ureteral reconstruction. This procedure can be done safely and effectively with robotic-assistance._x000D_ Funding None
Authors
Vidhush K Yarlagadda
Jeffrey W Nix J Patrick Selph |
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V10-12 |
Robotic (Da Vinci Xi) ureteral reimplant with Boari flap |
Reconstruction Upper Tract | 17BOS |
Abstract: V10-12 Sources of Funding: none Introduction Ureteral reimplant is most commonly performed due to trauma and oncologic disease affecting the distal ureter necessitating removal and reconstruction. The most commonly utilized procedures to aid in ureteral reimplant are the psoas hitch and the Boari bladder flap repair (BFR). Both maneuvers allow more proximal lesions to be treated with implantation instead of nephrectomy. Psoas hitch involves mobilizing the contralateral bladder attachments and securing the bladder dome to the psoas tendon of the affected side. BFR, most commonly performed in conjunction with a psoas hitch, involves incising a section of bladder, rotating it toward the affected ureter and tubularizing it for anastomosis with the remaining healthy ureter. With the open BFR first performed on humans in 1947, minimally invasive techniques have been described in recent years with similar outcomes. Recent advances in robotic technology may increase the feasibility and safety of robotic assisted laparoscopic BFR in selected patients. Methods We present our experience utilizing the Da Vinci Xi robotic system to perform a robotic assisted BFR. Results Our patient is a 64 year-old white male with history of high grade T1 bladder cancer who was found to have blood emanating from the left ureteral orifice on surveillance cystoscopy as well as two filling defects at the junction of the mid and distal ureter on retrograde pyelogram. Due to his baseline history of hypertension, diabetes, and marginal baseline renal function; he elected to undergo robotic left distal ureterectomy with left pelvic lymph node dissection, psoas hitch, BFR and stent placement. Intraoperative cystoscopy and ureteroscopy aided the robotic procedures, and the operation went without complication with an EBL of 200mL. At follow up visit 2 weeks post-operatively, our patient was recovering well, however, cystogram revealed a small leak. At post-operative week 3, CT-Urogram and repeat cystogram revealed leak resolution, and the foley catheter was removed. Ureteral stent was removed at post-operative week 6. Conclusions Robotic Boari bladder flap repair is safe and effective in carefully selected patients. Due to the ability to side dock the robot, the Da Vinci Xi robotic system enabled concurrent intraoperative cystoscopy and ureteroscopy. This allows for more accurate identification of the lesion and precise division of the ureter. Funding none
Authors
John DiBianco
Christopher Bayne Dan Su Ami Kilchevsky Jeffery Sparenborg Les Folio Piyush Agarwal |
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V1-02 |
Robot Assisted Laparoscopic Placement of Bladder Neck Artificial Urinary Sphincter. |
Reconstruction Lower Tract (I) | 17BOS |
Abstract: V1-02 Sources of Funding: None Introduction We present our technique of robot assisted laparoscopic placement of bladder neck artificial urethral sphincter (Robot-AUS). Compared to the open approach, the robot assisted laparoscopic technique allows for excellent visualization of the posterior dissection. Methods Our patient is a 49-year-old male with history of L1 spinal cord injury with stress urinary incontinence between intermittent catheterizations. Using the Da Vinci Xi surgical system, the bladder neck was circumferentially dissected. A 9cm AMS 800 AUS cuff was placed around the bladder neck after confirming appropriate sizing with simultaneous cystourethroscopy. The pressure-regulating balloon was placed in the recreated space of Retzius. Tubing connections were created extracorporeally at the right lower quadrant port site; the pump was passed subcutaneously from this port site to the right hemi-scrotum. Results The patient was discharged home on post-operative day #1, performing intermittent catheterization through a deactivated cuff. His stress urinary incontinence persisted until his device was activated at post-op week 4. Six months post-operatively, he is dry without the use of pads and is able to easily pass his catheter after cycling the AUS. Conclusions Bladder neck artificial urinary sphincter is effectively placed in a minimally invasive fashion with a robot assisted laparoscopic approach; the approach provides excellent visualization of the posterior dissection. _x000D_ Funding None
Authors
John Schomburg
Mya Levy Sean Elliott |
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V1-03 |
Membranous urethroplasty using dorsal onlay buccal mucosal graft for strictures associated with TURP or radiation therapy |
Reconstruction Lower Tract (I) | 17BOS |
Abstract: V1-03 Sources of Funding: none_x000D_ Introduction To present the application of buccal mucosa graft dorsal onlay urethroplasty for membranous urethral stricture caused by TURP or radiation therapy. Methods All patients were confirmed to have membranous involvement using radiographic and endoscopic evaluation. Dorsal onlay urethroplasty via a one-sided urethral dissection as described by Kulkarni and Barbagli was performed in all patients. This technique was modified by carrying dorsal urethrotomy proximally through the membranous urethra and sharply excising a wedge of intracrural tissue beyond stricture area to make adequate room for buccal mucosa grafting. _x000D_ All patients were followed at 4, 8, 12 months and then yearly for assessment of functional and patient-reported outcomes. Results Fifteen consecutive men with a mean age 68 years (47-72) post membranous urethral stricture repair were included. Seven patients had prior TURP, 6 had prior radiation therapy with prostate in situ, and 2 patients had radical prostatectomy followed by adjuvant radiation therapy. At a mean of 17 months (4-37) follow up, one patient required an additional procedure for stricture recurrence. No patient developed de novo incontinence. Improvement was seen with respect to mean maximum flow rate (4 to 21 cc/sec), PVR (90 to 50 cc), and International Prostate Symptom Scores (23 to 9). Conclusions Membranous urethral strictures can be effectively treated using this buccal mucosa graft dorsal onlay technique which avoids extensive urethral mobilization, urethral transection, and perirectal dissection. The described technique did not compromise continence in this group of patients. Additionally, in this series dorsal buccal mucosal graft take is demonstrated in patients with prior history of radiation therapy. _x000D_ _x000D_ Funding none_x000D_
Authors
Stephen Blakely
Daniela Kaefer Michael Daugherty Dmitriy Nikolavsky |
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V1-04 |
RECONSTRUCTION OF BULBO-MEMBRANOUS URETHRAL STRENOSIS AFTER SURGERY FOR BENIGN PROSTATIC HYPERPLASIA WITH PRESERVATION OF CONTINENCE |
Reconstruction Lower Tract (I) | 17BOS |
Abstract: V1-04 Sources of Funding: none Introduction Bulbo-membranous urethral stenosis after surgery for benign prostate hyperplasia (BPH) are challenging because the internal sphincter has been removed and continence depends on the function of the external sphincter, which is located just at the site of the stenosis; any attempt for reconstruction may jeopardize continence. Anatomical studies have shown that the rhabdosphincter is separated from the membranous urethra by a sheath of connective tissue. We developed a novel technique performing a meticulous dissection of this sheath to separate the muscle from the urethral wall, thus performing an intra-sphincteric anastomosis without disturbing the sphincteric function Methods A 67 year old patient underwent a transvesical simple prostatectomy for BPH. He developed an early bulbo-membranous stenosis managed initially with repeated dilation until he went into complete retention needing a suprapubic tube. _x000D_ The bulbar urethra is exposed through a vertical perineal incision with splitting of the bulbo-spongiosum muscle and then separated from the corpus cavernosum. Opening of the perineal membrane and splitting of the intercrural space in the midline, provides access to the dorsal aspect of the bulbo-membranous junction. The bulb is then mobilized to the left side, without detachment from the perineal body and the bulbar vessels are retracted. The sheath of the membranous urethra is now opened circumferentially at the bulbo-membranous junction, carefully reflecting the circular muscle fibers of the external sphincter until exposure of the urethral wall is obtained and the connecting tissue plane is identified. Gentle blunt proximal dissection along this plane allows separating the muscle away from the urethra towards the prostatic apex until healthy urethra is found to perform the bulbo-prostatic anastomosis, which is completed with a standard parachute technique. Finally the sphincteric muscle ring is anchored to the anastomosis with interrupted absorbable stitches_x000D_ Results The patient was discharged on PO day 3 and the urethral catheter was removed at 3 weeks. He recovered normal continent micturition and is voiding symptoms free at 3 months of follow-up Conclusions Excision and bulbo-prostatic anastomosis with sphincter sparing for bulbo-membranous stenosis after BPH surgery is feasible and safe. Our technique allows repairing the urethra preserving continence and to our knowledge it has not been described before. A larger series and reproduction in other centers are needed to validate this technique Funding none
Authors
Cristina Baeza
Reynaldo Gomez Rodrigo Campos Laura Velarde |
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V1-05 |
Redo bulbo-prostatic anastomotic (BPA) urethroplasty for recurrent pelvic fracture-related urethral strictures |
Reconstruction Lower Tract (I) | 17BOS |
Abstract: V1-05 Sources of Funding: None Introduction Surgical reconstruction of bulbomembranous urethral strictures following traumatic disruption of the pelvic ring requires careful assessment of both urethral edges, incision/excision of scar tissue and a tension-free anastomosis. Revision surgery is complicated by further loss of urethral length and often requires certain maneuvers to straighten the course of the proximal urethra and bridge longer defects. These techniques, achieved via a transperineal approach, are demonstrated in this video. The outcomes of redo-BPA are presented. Methods A 35 year old man developed stenosis of the bulbomembranous urethra associated with a pelvic fracture sustained during a fall from height. This recurred after anastomotic urethroplasty. During revision surgery the midline perineal incision was re-opened.The bulbar urethra was mobilised proximally off the central tendon up the point of obliteration and transected at this level. The proximal end was identified by means of a sound introduced suprapubically and spatulated. The scar tissue was excised until healthy mucosa was exposed. The distal end was mobilised and spatulated. The intercrural plane was developed, inferior wedge pubectomy performed and the urethra rerouted around the left crus of the penis to facilitate fashioning a tension-free anastomosis. _x000D_ _x000D_ Between January 2006 and December 2014, 117 patients with pelvic fracture-related urethral injuries were treated in our unit. 29 patients (24.8%) had previous attempts at repair (one attempt n=24; two attempts n=1; more than two previous repairs n=4)._x000D_ Results The procedures performed (in a stepwise fashion) were: anastomotic urethroplasty n=10; corporal separation n=4; wedge pubectomy n=3; rerouting of the urethra n=6. Abdomino-perineal exposure was necessary in 6 patients in order to carry out entero-urethroplasty or repair associated bladder neck injuries or fistulae. _x000D_ A successful outcome (unobstructed voiding with no evidence of radiological recurrence and no need for further surgery or instrumentation) was achieved in 22 patients (75.9%) compared to 85% in those having a primary procedure. _x000D_ Conclusions The best outcome after BPA is seen in previously un-operated patients and recurrences are more difficult to salvage. Revision surgery is technically challenging but is nonetheless feasible and associated with favourable outcomes in a specialised high-volume centre. Funding None
Authors
Enrique Fes Ascanio
Simon Bugeja Stella Ivaz Felix Campos Juanatey Anastasia Frost Daniela Andrich Anthony Mundy |
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V1-06 |
The Urethral Pull-Through: Reconstructing the Devastated Posterior Urethra and Bladder Neck After Radiation |
Reconstruction Lower Tract (I) | 17BOS |
Abstract: V1-06 Sources of Funding: None Introduction Recurrent posterior urethral stenosis secondary to radiation-induced damage poses a significant challenge to the reconstructive surgeon. Reconstructive options are limited. Using an IRB-approved database, we present our contemporary experience of 20 patients with radiation-induced proximal urethra/bladder beck stenosis who underwent urethral pull-through urethroplasty and staged artificial urinary sphincter (AUS) placement from 2007-2016. Methods With the patient in lithotomy position, a midline incision is made from the penoscrotal junction to the posterior perineum. The bulbospongiosus muscle is identified and reflected off of the urethra. The urethra is mobilized posteriorly until the point of obstruction where it is then transected. With the proximal urethra and bladder neck visible, the stenosis is incised and the lumen dilated to size 14 Hegar. The urethra is trimmed and spatulated until healthy tissue is encountered. A Lowsley retractor is used to place a 22-Fr Foley as a suprapubic tube (SP) and a 22-Fr Red Robinson as the pull-through catheter. The pull-through catheter is then advanced into the urethra a length that is dependent on the length needed to span the area of stenosis into the bladder neck. The pull-through catheter is secured to the urethra with chromic suture and is then used to bring the urethra up through the proximal urethra which is allowed to heal by secondary intention. The bulb muscle is then split and placed around the urethra to serve as a vascularized layer around the repair. A large AUS cuff is placed to facilitate subsequent AUS placement. After 4 weeks the SP and pull-through catheters are removed. 12 weeks after urethroplasty, an AUS is placed. We initially use a low pressure 51-60 reservoir and the system is activated 12 weeks after placement. Results No high-grade intraoperative complications were observed. 16 patients maintained urethral patency with no further dilation and 17 patients were socially continent at a median follow-up of 22 months (6.6-105 months). A median of 1 sphincter revision surgery was required to establish social continence. 4 patients had recurrent stenosis. There were 4 AUS complications (2 infections and 2 erosions). Two of these patients subsequently had new devices placed and are continent at last follow-up. Two are pending AUS reimplantation. Conclusions The urethral pull-through combined with placement of an AUS offers patients urinary continence and durable urethral patency. Our technique can be highly beneficial in the patient that traditionally would have limited desirable options. Funding None
Authors
Jeffrey Loh-Doyle
Mukul Patil Stuart Boyd |
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V1-07 |
Clampo-Tractor. A novel self retaining clamp retractor for penile urethral reconstruction: Improving surgeon ergonomics |
Reconstruction Lower Tract (I) | 17BOS |
Abstract: V1-07 Sources of Funding: None Introduction Constant, steady retraction and exposure are important for penile surgery - including hypospadias repair, urethral reconstruction, and correction of penile curvature. We set out to develop a retractor that would improve surgeon and assistant ergonomics and provide compression at the base of the penis to reduce blood loss. We describe this novel self-retaining penile retractor and our initial experience in its use. Methods This retractor is made of medical grade stainless steel. It has three components – a fixed hemostatic clamp attached to a scale, with also houses an artery forceps. This forceps moves along the scale to adjust the traction on the penis. The clamp is flat and compressive. The arms are non-traumatic and do not cause circumferential constriction. A stay suture taken through the glans is engaged by the artery forceps, and the height adjusted according to the penile length. The retractor has been used by reconstructive urologists in India, Turkey, Australia, Kuwait, Indonesia, and the United States of America. Results A total of 37 reconstructive cases were performed using this penile retractor (23 redo hypospadias repairs, 7 complex penile urethroplasties, 4 penile urethrocutaneous fistula repairs, and 3 surgeries for correction of Peyronie’s disease). For each case, surgeons were asked to score the retractor on a 4 point scale: 1. Extremely Non satisfactory, 2. Not Satisfactory, 3. Satisfactory, 4. Extremely Satisfactory. The average score was 3.65._x000D_ Advantages noted were ease of application, reduction of assistant fatigue, stable operative exposure and non-traumatic tissue compression conferring a bloodless field. There were no complications attributable to the device. The main limitation is that it cannot be used for hypospadias proximal to the penoscrotal junction. _x000D_ This retractor is inexpensive, durable and easy to sterilize and can be used on adult and pediatric patients alike._x000D_ Conclusions In our experience this retractor has high utility in reconstruction of the penis and penile urethra. It affords improved ergonomics for the surgeon and assistant, which results in shorter operative times and reduced blood loss while avoiding tissue damage. Funding None
Authors
Pankaj Joshi
Sanjay Kulkarni |
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V1-08 |
Surgical Correction of Urorectal Fistula (URF) following Radical Prostatectomy for the Treatment of Prostate Cancer. |
Reconstruction Lower Tract (I) | 17BOS |
Abstract: V1-08 Sources of Funding: None Introduction Urorectal fistula is the least common, but probably the most incapacitating complication associated with the surgical treatment of localised prostate cancer. There has been a considerable rise in the reported incidence of URF after the treatment of prostate cancer, presumably due to new and evolving multimodal treatments. The majority of patients with URF present with urine leakage through the rectum as the flow gradient is predominantly from the urinary to the intestinal tract. Methods This video describes a transperineal approach for surgical correction of URF following radical prostatectomy for the treatment of prostate cancer. We explain in detail the surgical technique and emphasise the key steps. The essential anatomical landmarks are identified including access via an inverted U-shaped, peri-anal incision, exposure of the perineal body, fistula exposure and division with independent closure of both sides of the fistula. Results Over the past 10 years we have repaired URF transperineally in 62 patients with a minimum of 1 year follow-up (these exclude abdomino-perineal repairs). 44 (71%) were purely post-surgical fistulae while the remaining 18 (29%) had adjuvant radiotherapy. There were 10 failures (5 in each group), 8 of which were salvaged by an abdomino-perineal repair, giving an overall fistula closure rate of 96.8%._x000D_ _x000D_ Via a transperineal approach the rectum can be accessed easily, and the rectal defect closed in two layers, with relatively few problems. The bladder defect is more difficult to close because there is less mobility and flexibility of the tissues, and is therefore usually closed in one layer. Preservation of the levator ani muscles allows them to be interposed between the urinary and rectal suture lines longitudinally, closing the space between them and doing away with the need for a gracilis interposition flap._x000D_ Conclusions URF at the level of the anastomosis or bladder base can be managed via a transerineal approach without the need for a trans-anorectal sphincter-splitting approach, a covering colostomy or an interposition flap when the circumstances are appropriate, and the surgeon is sufficiently experienced. Funding None
Authors
Enrique Fes Ascanio
Simon Bugeja Stella Ivaz Felix Campos Juanatey Anastasia Frost Daniela Andrich Anthony Mundy |
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V1-09 |
Repair of Adult Buried Penis with Removal of Suprapubic Fat Pad and Split Thickness Skin Graft: Emphasis on Patient Body Habitus |
Reconstruction Lower Tract (I) | 17BOS |
Abstract: V1-09 Sources of Funding: None Introduction Repair of adult acquired buried penis is a challenging surgical problem with potential for substantial morbidity when complications occur. Just a few of the post-operative problems can include: recurrence of buried penis, damage to genitourinary structures, wound breakdown / infection, and loss of split thickness skin graft. We present a technique for buried penis repair with removal of suprapubic fat pad, penile split thickness skin graft, emphasizing the importance of patient body habitus._x000D_ Methods We reviewed records of patients undergoing a consistent technique for adult buried penis repair from 2014-2016. Information was gathered on patient demographics, past medical history, concomitant problems (such as urethral stricture, and lymphedema), and outcomes. Important aspects of surgical technique involve complete resection of the suprapubic fat pad, removal of scarred penile skin, reconstruction of the peno-abdominal and peno-scrotal junction, and split thickness skin graft of the penis._x000D_ Results Seven men were identified. Mean age and BMI were 40 (range 21-65 years) and 48 kg/m2 (range 39-65 kg/m2). Four patients had distal urethral stricture and required 1st stage urethroplasty of the meatus and fossa navicularis. Two patients had concomitant scrotal lymphedema and required scrotectomy with reconstruction with local flaps. Some graft loss occurred in 57%. Graft loss ranged from 20% to 50%. All patients were managed conservatively and no patients required re-grafting or additional peri-operative procedures. No patients had recurrence of buried penis or required further intervention. _x000D_ Conclusions Anatomic attachment of the abdominal pannus above the supra pubic fat pad is variable among patients and an important pre-operative consideration potentially mitigating the risk of recurrence of buried penis. Wound complications are common, but generally heal with conservative measures. Funding None
Authors
Jeremy B. Myers
Bradley A. Erickson Sorena Keihani |
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V1-10 |
Is continence possible in patients with double block at bladder neck -prostate and membrano -bulbar urethra after pelvic fracture urethral injury? |
Reconstruction Lower Tract (I) | 17BOS |
Abstract: V1-10 Sources of Funding: none Introduction Rarely, pelvic fracture urethral injury can cause simultaneous transection of bladder neck and membrano-bulbar junction. Mundy reported sequestration of prostate. In another report, they found 85% of patients of PFUI have functioning external urethral sphincter mechanism after successful anastomotic repair. This information helped in our development of a new technique for repair in such cases to preserve continence. Methods We present a retrospective review of 8 patients .Preoperative evaluation requires MCU and RGU. Urethroscopy evaluates the membrano-bulbar obliteration. Antegrade cystoscopy confirms the bladder neck obliteration. Pelvic MRI is also obtained to check for the prostate. Perineal incision- bulbar urethra is mobilized and transected proximally. Suprapubic incision- posterior pubectomy is performed. An endoscope passed through SPC tract and blocked bladder neck area is opened from outside. Semen collected in the sequestrated prostatic urethra is aspirated with needle over which prostatic urethra is opened .A 6Fr endoscope is passed through the prostatic urethra distally to visualize the membranous urethra. The membranous urethra is opened perfectly under vision as distally as possible. Excision of the scar at the apex of membranous urethra is kept to minimum to preserve continence. Bulbo-Membranous Anastomosis (BMA) and bladder neck–prostatic anastomosis is performed . Results Mean age 14 (5 to 36) yrs ,mean follow up 26 (14 to 72) months .Initial 2 adults are 100% incontinent . We then modified our technique of identifying membranous urethra through intraprostatic scopy and bulbo membranous anastomosis. The video is of an adult who underwent transpubic urethroplasty at age 7 for double block. As prostatic urethra was rudimentary bulbo vesical anastomosis was performed. He presented at age 18 years with pain after ejaculation. He was reoperated using our modified technique.1 adult and all 5 children were approached through the above improved technique. 2 (40%) children required redo surgery with for revision of the bladder neck anastomosis. as we had tried narrow anastomosis to help continence. All children are continent and have good flow, 2 have occasional nocturnal dribbling. Conclusions Double transection with injury at membrano-bulbar and prostate bladder neck junction requires two separate anastomoses to be performed. Postoperative continence is possible .Our step wise technique improved continence rates to ensure proper preservation of the external sphincter. Funding none
Authors
Pankaj Joshi
Devang Desai Sandesh Surana Hazem Orabi Craig Hunter Sanjay Kulkarni |
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V11-01 |
Complications of Percutaneous Access during Percutaneous Nephrolithotomy |
Urolithiasis | 17BOS |
Abstract: V11-01 Sources of Funding: None. Introduction The rate of access-related complications for percutaneous nephrolithotomy (PCNL) has been estimated to be approximately 12.5% . Often, complications are the result of inadequate pre-operative preparation for PCNL or incorrect operative methods. In this video, we discuss several important risk factors as well as several tips to address access-related complications of PCNL. Methods Intraoperative risk factors for access-related complications are discussed at length. These include pre-operative considerations and anatomic considerations that would necessitate alternative forms of access, including CT-guided or laparoscopically-guided access. Next, techniques to avoid problems at the time of establishing access are demonstrated and discussed in detail. Results Access-related complications are often encountered in patients who require pre-operative anticoagulation or in whom a urinary tract infection may be identified pre-operatively. Addressing these issues preemptively is imperative to patient safety. Further, several risk factors for bowel injury may be addressed with meticulous knowledge of the patient&[prime]s anatomy pre-operatively. In certain cases, anatomic abnormalities necessitate laparoscopic or CT-guided access. Finally, the main difficulties at the time of obtaining access for PCNL are discussed at length, including inadvertent vascular access, extravasation of contrast, guidewire kinking, obstruction of the access tract by a staghorn calculus, bowel injury, and pleural injury. Inadvertent vascular access is often addressed by redirecting the guidewire into the collecting system. In rare cases, use of the access sheath, or balloon, to tamponade bleeding, may be required. Extravasation often necessitates re-puncture, while guidewire kinking may be rectified with the assistance of a rigid, open-ended catheter. Access for staghorn calculi may be achieved with the assistance of retrograde ureteroscopy, or maneuvering past the stone edge with a grasping forceps. Bowel injury should be addressed with drainage of the urinary tract separate from the bowel and broad spectrum antibiotics. Finally, pleural injury necessitates rapid identification to ensure expedient placement of a chest tube. Conclusions Access-related complications can introduce significant morbidity to an otherwise successful PCNL. We demonstrated some crucial skills to avoid the difficulties that are often encountered at the time of obtaining access, as well as several techniques that can be used in a timely fashion to address access-related injuries. Funding None.
Authors
Vinaya Vasudevan
Zeph Okeke Arthur Smith |
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V11-02 |
Avicenna Roboflex, For Robotic Assisted Retrograde Intrarenal Laser Lithotripsy of The Kidney Stones, Larger Than 2 Cm. |
Urolithiasis | 17BOS |
Abstract: V11-02 Sources of Funding: none Introduction Robotic assisted retrograde intra-renal surgery (RA-RIRS) with the Avicenna Roboflex allows safe, comfortable, and remote control, of all commercially available flexible ureteroscopes functions. Continuous development of Avicenna Roboflex’s ergonomics and surgeon user friendliness, and precise large intra-renal stone laser fragmentation, has increased flexible endoscope durability. _x000D_ The impact of these incremental improvements on fragmentation efficiency of different stone volumes, density and compositions are unknown._x000D_ Methods The Avicenna Roboflex allows user adjustable deflection scaling for greater tip control precision than is possible with manual flexible ureteroscope operation, where every 5 degrees of deflection movement deflects the tip 30 degrees. For optimal ergonomics, a central wheel for deflection mechanism control was eliminated, assigning this function to a new grooved thumb-wheel incorporated into the bulb of the right hand control._x000D_ Moreover, a new universal remote pedal control unit allows remote laser and fluoroscopic activation control, while laser fiber advancement and retraction from the endoscope tip, irrigation flow rate with pulsed flush options, and the ability to influence renal respiratory excursion by adjusting an inflatable compression belt balloon, which are all possible from the Master Control Console, give the operator greater control of many different aspects of the surgical procedure. In this video, these capabilities of RA-RIRS treatment are demonstrated with the Avicenna Roboflex coupled to a Storz digital flexible ureteroscope, for upper tract stones of different volumes, densities and compositions, and for the first time, in an upper tract urothelial tumor._x000D_ Results Of sixty-eight consecutively treated patients, 62 met stone volume eligibility criteria (<4400mm3 ) for possible single session treatment, with 24% pre-stented. Stones had HU <1500, and were treated in <2 hours without complications. Non-contrast 3 months CT showed only one significant (4mm) stone residual needing a 2nd intervention in a triple phosphate infection stone, giving an overall 98% stone free rate. Conclusions The incremental improvements incorporated into the Avicenna Roboflex Master control console have increased operator control of key surgical procedural aspects, resulting in excellent single stage treatment outcomes for a wide range of stone compos?t?ons, while releasing precious operating room resources and avoiding endoscope breakage for additional cost savings. Funding none
Authors
Anup Patel
Jan Klein Yasser Farahat Nida Zafer Tokatli Ahmet Sinan Kabakci Remzi Saglam |
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V11-03 |
Applying Urolithiasis Techniques to Biliary Stones: Percutaneous Transhepatic Lithotripsy |
Urolithiasis | 17BOS |
Abstract: V11-03 Sources of Funding: None Introduction Choledocolithiasis is a significant problem that can lead to severe cholangitis. Endoscopic retrograde cholangiopancreatography (ERCP) is firstÂline treatment. However, this is not always possible when the patient has surgically altered anatomy or very large stone burden. Urologists can use our skills and technology to assist in these situations. We report our technique and outcomes from our 15 years of experience with percutaneous transhepatic endoscopic biliary lithotripsy. Methods Patients are selected by our gastroenterology colleagues who approach us for assistance when ERCP is not possible. We utilize a percutaneous transhepatic endoscopic approach in a combined procedure with interventional radiology. Most patient have a transhepatic biliary drain already in place. A wire is then placed through the tube into the biliary system and into the common bile duct. A 14-French ureteral access sheath is placed under fluoroscopic guidance into the common bile duct. A flexible ureteroscope is then guided through the access sheath into the biliary system. A holmium laser is used to fragment the stones. The stones can be subsequently retrieved or flushed into the intestinal tract. Results Over the 16-year time period, a total of 26 procedures were performed on 18 patients (mean age 55.8 years). The indications were surgically altered anatomy in the majority of the cases that did not allow access via ERCP. Two of the patients had a large biliary stone burden which was too large to be managed by ERCP. Stone clearance was achieved in 16 of the 18 (89%) patients after a mean of 1.1 procedures. Most of these patients (61%) required only one procedure to become stone free. There were no Clavian grade III or higher complications. One patient developed cholangitis that resolved with administration of intravenous fluids and antibiotics. There were no instances of injury to the biliary system, pancreatitis, or need for urgent re-intervention at our institution. Conclusions With a multidisciplinary approach and the correctly selected patient, percutaneous transhepatic biliary endoscopic lithotripsy is a safe and effective intervention for complex biliary stones. Endourologic urolithiasis techniques can play a role in the treatment of patients with choledocolithiasis not amenable to ERCP. This improves patient care by decreasing the need for invasive surgery when ERCP is ineffective. Funding None
Authors
Brett Johnson
John Roger Bell Prasad Dalvie John McDermott Stephen Nakada |
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V11-04 |
Dusting Utilizing Suction Technique (DUST) for Percutaneous Nephrolithotomy: Dedicated Laser Handpiece to Treat a Staghorn Stone |
Urolithiasis | 17BOS |
Abstract: V11-04 Sources of Funding: None Introduction Dusting, use of high frequency and low pulse energy holmium laser settings, is performed during ureteroscopy but reports on this method to treat complex renal calculi via percutaneous nephrolithotomy (PCNL) are limited. We report the first clinical feasibility of a dusting technique during PCNL with the assistance of a specially designed laser suction handpiece (LSHP). Methods We performed PCNL on a patient with spinal cord injury, urinary tract infection and a computed tomography scan demonstrating a left complete staghorn stone (5x3.5x2.5 cm; 1000 Hounsfield units). Prone PCNL was performed via a 30 Fr Amplatz sheath with access in the lower pole. A 120-Watt holmium laser (P120H, Lumenis) was used as the lithotripsy source to perform Dusting Utilizing a Suction Technique (DUST) for PCNL. A 550um laser fiber was inserted into the LSHP (Lumenis, Israel) which was connected to a suction pump in the P120H. The LSHP weighs 135 grams, and has a stainless steel cannula with an inner lumen diameter of 3.25 mm. Laser fiber length is controlled via a manipulation wheel, with the fiber positioned in a working channel on top of the cannula. Suction is activated on the LSHP, and fragments are sucked into a collection container. We used &[Prime]automatic&[Prime] mode where suction occurred only during laser activation. Results We successfully performed DUST-PCNL using settings of 0.6 J x 70 Hz, and 1.0 J x 60 Hz, both on long pulse mode. PCNL took 110 minutes to complete; total lasing time was 21.29 mins, and laser energy usage was 47.68 kJ. The fiber tip was easily visible at the tip of the LSHP, with no failure of the device. We did not encounter any difficulty with fragment aspiration or clogging of the steel cannula or suction tubing. Ancillary devices included a basket to retrieve large fragments, and flexible nephroscopy was performed to dust an upper pole branch of the staghorn. At the end, a 22F Malecot re-entry tube was placed. A nephrostogram on post-operative day (POD) 1 demonstrated a 4 mm residual fragment. Patient was discharged on POD 2. There were no complications; stone analysis demonstrated a struvite stone. Conclusions Utilizing a 120-Watt holmium system, we confirmed initial clinical feasibility and safety of DUST-PCNL to perform simultaneous lithotripsy and aspiration for effective stone clearance. An advantage of this method is versatility in treating a stone with both rigid and flexible endoscopy using a lightweight energy source. Further clinical evaluation is needed to understand the efficacy of this technique in comparison to alternate lithotripsy sources. Funding None
Authors
Khurshid Ghani
William Roberts |
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V11-05 |
RENAL CALYCEAL DIVERTICULUM WITH STONES - SINGLE-STAGE PERCUTANEOUS APPROACH |
Urolithiasis | 17BOS |
Abstract: V11-05 Sources of Funding: None Introduction In this video, we demonstrate single-stage percutaneous approach to a calyceal diverticulum (CD) with stones. Methods Video of surgical technique accompanied by slides and voiceover explanation of the steps Results A hemostat and then an 18G diamond-tipped needle are used to line up to the target stone. If the stone is visible on KUB, a ureteral catheter is not required. An infracostal puncture is preferred to reduce the risk of lung injury even if the CD is located in the upper pole. The needle is advanced into the CD. A 0.035-inch J-tipped movable core wire is advanced through the needle and carefully coiled, avoiding back wall perforation with the stiffer portion of the wire. Guidewire control is essential - utmost attention must be paid to keeping the guidewire secure when passing dilators to prevent loss of access. An 8/10 French coaxial dilator is passed over the J-wire and a second J wire is coiled inside the diverticulum as a safety wire. The tract is balloon dilated over the working wire. Advancing the dilator too far into the diverticulum can cause posterior wall perforation and bleeding and should be avoided. A 30F Amplatz sheath is passed over the balloon dilator. In a small diverticulum, we only place the tip of the balloon dilator into the diverticular cavity with the access sheath remaining just outside._x000D_ _x000D_ A rigid nephroscope is advanced and 11F alligator forceps are used to manually dilate the remaining tract until the diverticular cavity is visualized. Grasping forceps or a lithotripter are used to remove the stone. After removal of all stone material, the cavity is inspected for presence of a flattened renal papilla. Papilla presence would indicate an obstructed hydrocalyx rather than a calyceal diverticulum. The diverticular cavity is fulgurated with a resectoscope and a rollerball electrode using 1.5% glycine irrigant. Low energy electrocautery settings are used - 20 W coagulation and 0W cut. An 18F red rubber catheter is placed in the cavity with position confirmed on fluoroscopy. The catheter is removed on post-operative day 1 if drainage is minimal. _x000D_ Conclusions This single-stage technique allows quick and effective treatment of calyceal diverticulum stones. Funding None
Authors
Nadya E. York
Hazem M. Elmansy Marcelino E. Rivera James E. Lingeman |
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V11-06 |
Step by Step Ultrasound-guided Percutaneous Nephrolithotomy: A Single Hospital Experience |
Urolithiasis | 17BOS |
Abstract: V11-06 Sources of Funding: none Introduction Percutaneous nephrolithotomy is effective for patient who has large renal stone > 2cm in size. Ultrasound-guided percutaneous nephrolithotomy can be performed safely without radiation exposure. We describe how we performed ultrasound-guided percutaneous nephrolithotomy step by step according to our experience. Methods We conducted a retrospective study of patients received percutaneous nephrolithotomy from January 2012 to October 2016. In total, 205 patients were enrolled. One-hundred and thirty-six patients received ultrasonic-guide operation and 69 received fluroscopic-guided operation. Patients' clinical characteristics, operation time, hospital stay, complication, hematocrit and renal function data were recored and analyzed. We performed ultrasound-guided by following steps:(1) Double-J catheter insertion (2) Three-way Foley insertion (3) Normal saline instillation and Foley clumping (4) Needle puncture (5) Incision and Dilatation (6) Balloon dilatation and insert sheath. Results Among two groups, the patient clinical characteristics do not have significant difference. There were also no difference during hospital stay, hematocrit and renal function change. However, shorter operation time (62mins vs. 87mins, p< 0.05), was noted in ultrasound-guided group maybe due to shortened puncture time. In the other hand, complete stag-horn stone patients had higher stone free rate (75% vs 90%, p< 0.05) in fluroscopic group. Complication rate is similar in two groups but one patient in ultrasound-guided group had developed bladder rupture while normal saline instillation by pressure pump. Conclusions ultrasound-guided percutaneous lithotomy is feasible for patient who has large renal stones. The outcome is similar compared to traditional fluroscopic-guided procedure. In our experience, ultrasound-guide may shorten puncture time and decrease the radiation exposure to patients and staffs. Double-J catheter insertion before puncture to create dilated calyces may help puncture easier. Funding none
Authors
Yite Chiang
Kaiyi Tzou |
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V11-07 |
ECIRS (Endoscopic Combined IntraRenal Surgery) in the Galdakao-modified supine Valdivia position |
Urolithiasis | 17BOS |
Abstract: V11-07 Sources of Funding: None Introduction ECIRS (Endoscopic Combined IntraRenal Surgery) is a combined rigid and flexible antegrade and retrograde approach for the treatment of large and/or complex urolithiasis, usually performed in the Galdakao-modified supine Valdivia (GMSV) position. The aim of the present video is to describe the main distinctive and standardized steps of this surgical procedure, and to highlight the relatedadvantages in terms of safety and efficacy. Methods From 2004 until 2016 more 750 ECIRS have been performed in our Department. Year after yearall the procedure has been standardized step-by-step, starting from patient positioning in the GMSV position (part 1 of the video). Since ECIRS involves manypeople and a number of devices the operating room is very crowded, and a meticulous organization is needed (part 2 of the video). Being a suitable percutaneous access key to the success of any percutaneous nephrolithotomy (PNL), a combined and reproducible guidancemethod for the renal puncture has been developed, performing an ultrasound-assisted, fluoroscopy-guided and endoscopy-checked percutaneous access (part 3 of the video). Retrograde semirigid and flexible ureteroscopy before and during PNL has both a diagnostic and active role, contributing to improve safety and efficacy of ECIRS (part 4 of the video). Results All the team in the operating room (urologists, anaesthetist, nurses) shares the responsability of positioning the patient correctly in the GMSV position, combining the supine Valdivia position with a modified arrangement of the lower limbs. This position presents a variety of anaesthesiological, urological and management advantages, optimally supporting ECIRS. The diagnostic role of retrograde ureteroscopy includes the preliminary evaluation of the dynamic anatomy of both lower and upper urinary tract, for a tailoringof the intraoperative choices (calyx of access, tract size, dilation method) on the single clinical case. Endovision control of each step of the renal access reduces radiation exposure and the risk of complications due to the insufficient introduction of the devices or to their overadvancement. Retrograde ureteroscopy allows treatment of stones in calyces parallel to the access tract. Final flexible nephroscopy and ureteroscopy optimize stone-free rates. Conclusions ECIRS represents a safe, effective and comprehensive approach to PNL, allowing a versatile personalized stone management, and a perfect tailoring of all the intraoperative choices on the real-time situation of the patient._x000D_ _x000D_ Funding None
Authors
Cesare Marco Scoffone
Manuela Ingrosso Cecilia Cracco |
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V11-08 |
Complete Supine Percutaneous Nephrolithotomy from the Surgeon&[prime]s Point of View with a GoPro®. Ten Steps for Success. |
Urolithiasis | 17BOS |
Abstract: V11-08 Sources of Funding: None Introduction To show a video of a complete supine Percutaneous Nephrolithotomy (csPNL) performed for the treatment of a kidney stone, from the surgeon&[prime]s point of view. The procedure was recorded with a GoPro® camera placed on the surgeon&[prime]s forehead, didactically demonstrating the 10 essential steps for a successful procedure. Methods The patient was a 38 years-old female patient with 2.4 cm of left kidney lower pole stone burden who presented with 3 months of lumbar pain and recurrent urinary tract infections. She had a previous diagnosis of polycystic kidney disease and chronic renal failure stage 2. CT scan showed two 1.2 cm stones in the lower pole (Guy&[prime]s Stone Score 2). She had a previous ipsilateral double J insertion due to an obstructive pyelonephritis. The surgeon had a Full HD GoPro Hero 4 Session® camera mounted on his forehead, controlled by the surgical team with a remote control. All of the mains steps were recorded, as well the cystoscopic, nephroscopic and fluoroscopic images. Informed consent was obtained prior to the procedure. Results The csPCNL was uneventful with a single access in the lower pole. The surgical time was 90 minutes. Hemoglobin drop was 0.5g/dL and creatinine levels rose from 1.8mg/dL to 1.9mg/dL. A post-operative CT scan was stone-free. The patient was discharged 36 hours after surgery. The camera worked properly and didn&[prime]t cause pain or muscle discomfort to the surgeon. The quality of the recorded movie was excellent Conclusions GoPro 4 Session® camera proved to be a very interesting tool to document surgeries without interfering with the procedure and with great educational potential. More studies should be conducted to evaluate the role of this equipment in the operative room. Funding None
Authors
Fabio Vicentini
Hugo Santos Evaristo Oliveira Neto Carlos Batagello Julia Amundson Miguel Srougi Eduardo Mazzucchi |
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V11-09 |
The parallel guidewire rapid release percutaneous tract dilation |
Urolithiasis | 17BOS |
Abstract: V11-09 Sources of Funding: none Introduction The parallel rapid release ureteral access sheath is a good way to transform the working wire into a safety wire. The guide is passed in the first 4 cm of the dilator which has a lateral slit. When the dilator is retrieved, the wire is released from the dilator through the lateral slit, and stays outside the access sheath. _x000D_ We present a video of percutaneous tract dilation parallel to the guidewire, using the same principle. The working guidewire becomes safety guidewire outside the Amplatz sheath, at the end of the dilation. Methods Between February 2016 and October 2016, 15 PCNL have been performed with dilation of the tract beside the guidewire._x000D_ Technique: A stiff 8 Fr ureteral catheter or JJ-stent pusher is used. The Amplatz catheter can also be used. Its tip is held with a forceps. With a &[Prime]lancet&[Prime] blade scalpel, beginning from the tip, a 4-5 cm longitudinal slit is performed in one side of the catheter. At the end of the slit, the scalpel is turned on its self to perform a small hole to accommodate the guidewire. It will be the egress point of the guidewire. After calyx puncture, a guidewire is inserted down the ureter or it is coiled in an opposite calyx. A pre-dilation to 12 Fr is performed. The catheter is bent just after the slit. Thus, the small hole will be in the apex of the bend. The tail of the guidewire is inserted into the slit tip of the catheter. After transiting in the 4 cm of the catheter with the slit, the guidewire will egress through the hole, in the summit of the bend. The catheter is advanced over the guidewire until reaching the calyceal cavity. &[Prime]One shot&[Prime] dilation is performed over the catheter with a 24 Fr Amplatz dilator and sheath. The long part of the catheter, Amplatz dilator and sheath are beside the working guidewire. When the Amplatz sheath reaches the calyx, the catheter is attracted and the guidwire is released from the first part of the catheter through the slit. Thus, the working guidewire become safety guidewire outside the Amplatz sheath._x000D_ Results 15 patients had PCNL with dilation with this technique, 9 males and 6 females. The mean age was 39 (56-23). 8 right kidneys and 7 left. The main stone burden was 43 mm (32-56). The dilation beside the guidewire was possible in all cases. Operative time was 70 min (45-95). The tract dilation time was 4.5 min (3.5- 7). The hemoglobin drop was 0.89 (0.5-1.8). There was no complication noted during this dilation. Conclusions The dilation beside the guidewire is safe and feasible in this small series. It allows the economy of a guidewire. However, the catheter has to be very stiff to allow having a straight path to guide the dilator into the calyx. More studies are necessary to develop the technique. Funding none
Authors
Mohammed Lezrek
Hicham Tazi adil slimani khalil bazine Amoqurane Beddouch abdeghani ammani mohammed alami |
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V1-11 |
Staged Urethroplasty for Penile Urethral Strictures after Hypospadias Repair and Lichen Sclerosus |
Reconstruction Lower Tract (I) | 17BOS |
Abstract: V1-11 Sources of Funding: None Introduction Staged urethroplasty with oral mucosa graft is a versatile and reliable technique that allows patients with severe penile urethral strictures from lichen sclerosus, repeated failed urethroplasties and trauma to resume standing physiologic voiding. We present our technique for staged urethroplasty in this patient population. Methods From 2013-2016, staged urethroplasty was performed by a single surgeon (BF) on 20 men. During first-stage surgery, the urethra is divided in the midline and lateralized. Oral mucosa graft is applied to the exposed corpora cavernosa. A bolster dressing and urethral catheter are left in place for 5-7 days. Second-stage urethroplasty is performed 6-9 months later. The urethra is tubularized over a urethral stent, which remains in place for 10 days. Results Stricture etiology was lichen sclerosus (9, 45%), failed hypospadias surgery (8, 40%), trauma (2, 10%), and penile calciphylaxis (1, 5%). Twelve men (60%) underwent second stage urethroplasty at a median of 277 days (range 167-738). No patient required additional grafting after first stage. Complications after second stage surgery included wound dehiscence (2, 17%), fistula (1,8%), and stricture (1, 8%). Conclusions Staged urethroplasty is an effective treatment for patients with severe penile urethral strictures from lichen sclerosus, repeated failed urethroplasties and trauma. Funding None
Authors
Andrew Gomella
Logan Hubbard Hong Truong Bradley Figler |
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V11-10 |
Mini-percutaneous nephrolithotomy using an integrated ultrasonic and mechanical lithotripter (Olympus ShockPulse-SE Lithotripter) |
Urolithiasis | 17BOS |
Abstract: V11-10 Sources of Funding: none Introduction Mini-percutaneous nephrolithotomy (mini-PCNL) was initially described in the late 1990s. Many variations on the technique have been described since that time focusing on differing access sizes. Lithotripsy through a mini-PCNL tract has traditionally been accomplished through laser or electro-hydraulic/pneumatic energy. We sought to explore the feasibility of lithotripsy through a mini-PCNL tract with the Olympus ShockPulse-SE Lithotripter which combines both ultrasonic and mechanical energy to optimize lithotripsy. Methods A 58 year male patient with a 2.5 cm left lower pole stone was identified as the initial candidate for our technique. He was positioned in the standard prone position and access was obtained into his lower pole with an 18-gauge Cook LS access needle. We proceeded to dilate a 16-French tract using a one-step dilator with the Storz Modular Minimally Invasive PCNL (MIP) System. With the Storz MIP M nephroscope and a 1.5 mm Olympus ShockPulse-SE probe, we then broke the stone into minute fragments which were initially suctioned and collected with the StoneCatcher (Boston Scientific) system. Remaining fragments were removed with an endoscopic grasper and a nitinol stone basket. The procedure was performed tubeless with a stent. After five days, a follow-up plain film was obtained and the stent removed. Results The dual modality lithotripter was efficient with stone fragmentation and extraction through suction. The total operative time was 110 minutes. The patient was discharged on post-operative day one after an uncomplicated stay of 30 hours total duration. Post-operatively, his hemoglobin declined 2.3 g/dl and his creatinine rose 0.2 mg/dl. On return, his large 2.5 cm stone showed good clearance on KUB though dust like fragments (< 2 mm) remained in his lower pole. Conclusions This is the first report of using integrated ultrasonic and mechanical energy lithotripsy in a mini-PCNL. The combination of the Olympus ShockPulse-SE Lithotripter with the Storz MIP system proved efficient in terms of operative duration and stone breakdown. It was also effective at clearing a large stone burden through a small 16-French tract. This method is feasible and provides an alternative to laser or pneumatic lithotripsy and offers the benefits of suction. Funding none
Authors
Joshua Ebel
Nathaly François Bodo Knudsen |
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V11-11 |
Thulium lithotripsy: from experiment to clinical practice |
Urolithiasis | 17BOS |
Abstract: V11-11 Sources of Funding: none Introduction To date Holmium (Ho) laser is one of the most popular and effective tools_x000D_ for lithotripsy. It emits very short pulses (0.1 – 1 ms) with high peak power (0.5-10 kW) that allows to efficiently fragment any type of urinary stones. Series of articles show Ho laser wavelength of 2.1 µm is significantly off the peak of water absorption, and so can negatively affect efficiency of stone fragmentation._x000D_ They also stressed that the thulium (Tm) fiber laser with diode laser pumping can improve stone fragmentation, because emission of Tm laser with wavelength 1.94 µm is 4.5 times stronger absorbed by water than that of Ho laser._x000D_ _x000D_ There is a lot of data on feasibility and efficacy of Tm laser application for stone fragmentation in vitro. _x000D_ _x000D_ Nevertheless, Thulium laser lithotripsy hasn’t been widely utilized in the clinical settings._x000D_ _x000D_ A prototype Tm fiber laser with a peak power up to 500 W were developed by NTO «IRE – Polus» Methods We have evaluated in vitro performance of a prototype Tm fiber laser with a peak power up to 500 W as a potentially alternative for modern Ho laser system._x000D_ The in vitro experimental setup for measuring the stone fragmentation rate (ablation rate) included a specially designed cuvette with several levels of meshes allowing for precise quantification of size distribution of stone fragments (for the modes of fragmentation and dusting). Post – surgery human stones and BegoStone phantoms were used. The laser parameters (pulse energy and average power) were identical._x000D_ Also retropulsion effect caused by a single pulse has been evaluated. Lateral shift of a stone after a single pulse of laser energy was measured._x000D_ Results ¥ Proposed experimental technique offers relatively simple and reliable method of comparing performance of laser lithotripters under controlled ex vivo conditions_x000D_ ¥ The Tm system, at identical laser parameters, produced about 2.3 and 1.3 times greater average ablation rate than the Ho system does in dusting and fragmentation modes, respectively_x000D_ ¥ The ratio of ablation rates on BegoStone phantoms correlated well with human stone data and varied between 1.6 and 2.3_x000D_ ¥ The effect of retropulsion of the Tm laser (at 500 W) was 75%, 60%, and 29% of that of the Ho laser for equal pulse energies of 1, 2, and 3 J, respectively. The retropulsion onset threshold was significantly higher for Tm laser_x000D_ Conclusions Supported by this experimental data we assessed the clinical effectiveness of Tm fiber Urolase system with peak power of 120 W for lithotripsy. Several bladder stones with the average size about 1.9 cm were successfully destroyed. _x000D_ Further investigation in to the clinical applicability of Thulium lithotripsy is required._x000D_ Funding none
Authors
Alim Dymov
Petr Glybochko Yuri Alyaev Andrey Vinarov Gregory Altshuler Viktoria Zamyatina Nikolay Sorokin Dmitri Enikeev Vladimir Lekarev Alexandra Proskura Alexey Koshkarev |
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V11-12 |
HOLMIUM LASER SETTINGS DURING LITHOTRIPSY OF DIFFERENT TYPES OF KIDNEY STONES |
Urolithiasis | 17BOS |
Abstract: V11-12 Sources of Funding: None Introduction Currently, holmium laser is the most versatile energy source for the treatment of intrarenal stones by intracorporeal lithotripsy since it may be used with both flexible and rigid endoscopes, permitting access to all parts of the kidney. High-power laser enables the destruction of all kinds of stones, but the settings most suitable for the treatment of individual types remain to be defined. Methods In the operation theatre we used a pelvic trainer into which we introduced six different types of urinary stones from our stone library: uric acid, cystine, struvite, brushite, calcium oxalate monohydrate, and calcium oxalate dihydrate._x000D_ Ex vivo lithotripsy was performed by means of continuous serum irrigation with the Lumenis VersaPulse 120 W high-power laser, with a 550-micron fibre. Power, frequency, and potency parameters, as well as the short-pulse/long-pulse variable, were varied among the six different types of stones. Results In all cases lithotripsy was commenced using low power and frequency: 0.2 J and 10 Hz. Power and frequency were raised up to a maximum of 3 J and 40 Hz, according to the type of stone, and until maximum potencies close to 120 W were obtained._x000D_ The difference in hardness of the investigated types of stones required differing power settings according to whether fragmentation into large pieces or pulverisation was desired. The different power settings used for the various types of stones are described, and the fragmentation ability and speed of the holmium laser are appraised. Conclusions High-power laser is useful for destruction of any type of urinary stone. The harder the stone, the greater is the potency needed; however, the frequency is not so important. Low power is able to yield good results on soft stones, and excellent pulverisation can be obtained by increasing the pulse frequency. The long pulse is very useful for lowering the stone retropulsion and increasing pulverisation, particularly in the case of softer stones. Funding None
Authors
Oriol Angerri
Juan Manuel López Pavel Gavrilov Francisco Sánchez-Martín Félix Millán Humberto Villavicencio |
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V1-12 |
Surgical Management of Adult Acquired Buried Penis (AABP) |
Reconstruction Lower Tract (I) | 17BOS |
Abstract: V1-12 Sources of Funding: none Introduction Adult acquired buried penis as a result of obesity is a morbid condition. Affected patients have poor sexual function, urinary dribbling, mood disturbance, and poor quality of life (QoL). Weight loss is ineffective due to chronic skin changes and suprapubic fat pad (termed the escutcheon) lymphedema. Previous efforts have described limited repairs including isolated resection of the escutcheon which unfortunately often leads to reburying. We present a surgical repair including escutcheonectomy, scrotoplasty, and penile degloving with split-thickness skin graft (STSG) to provide definitive repair and halt the progression of the disease process. Methods A retrospective chart review was conducted of patients managed surgically for adult acquired buried penis in 2015-2016. Twelve patients were identified that underwent escutcheonectomy, scrotoplasty, penile degloving and STSG repair. All patients had morbid obesity as a sole etiology or significant contributing factor. Outcomes evaluated were surgical complications, reburying of the penis, graft take rate, and urinary symptoms. Results Twelve patients underwent repair of adult acquired buried penis. All patients had good cosmetic results and durable unburying at intermediate term follow-up. Mean patient body mass index (BMI) was 45.4 ± 3.7. Fifty percent of the patients in the series were diabetics and 50% had hypertension and hyperlipidemia (Table 1). Mean operative time, length of stay (LOS), and estimated blood loss (EBL) were 312 ± 59 min, 5.3 ± 1.1 days, and 304 ± 133 cc respectively. STSG take rate was 80-100% (mean 92%) (Table 2). Conclusions Adult acquired buried penis is a challenging condition to treat. Limited surgical repairs can lead to reburying of the penis, need for further procedures, and the progression of urethral disease with voiding dysfunction. Escutcheonectomy, scrotoplasty, and STSG has encouraging intermediate term outcomes with durable unburying of the penis and good STSG take rates. Further follow-up in larger series is needed but results are thus far encouraging. Funding none
Authors
Thomas Fuller
Katherine Theisen Paul Rusilko |
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V12-01 |
Multimodal Enhanced Cystoscopy for Improved Bladder Tumor Resections |
Bladder Oncology and Diversion | 17BOS |
Abstract: V12-01 Sources of Funding: none Introduction Conventional transurethral resection of bladder tumor (TURBT) with white light cystoscopy (WLC) has recognized shortcomings including missed small tumors, inadequate assessment of resection margins and depth, and difficulty in differentiating cancerous from benign lesions. These limitations contribute to cancer recurrences and compel the need for repeat TURBT to ensure adequate cancer staging. Adjunctive optical imaging technologies including photodynamic diagnosis (PDD), narrow band imaging (NBI), and confocal laser endomicroscopy (CLE) improve tumor identification and characterization. Given their respective strengths and complementary characteristics, we postulate that combining wide-field (PDD and NBI) with microscopic (CLE) imaging technologies will further enhance TURBT. Towards that goal, we report our preliminary experience with multimodal enhanced cystoscopy. Methods The study received IRB approval. PDD was performed using hexaminolevulinate (Photocure) in combination with blue light cystoscope (Storz). NBI (Olympus) was performed with an NBI-enabled camera head attached to the standard resectoscope. Probe-based CLE was performed with fluorescein as the contrast agent along with 2.6 or 0.85 mm endomicroscopes (Cellvizio, Mauna Kea Technologies). Following TURBT with PDD or NBI, the resection bed was imaged with CLE. Imaging features of the resection bed were characterized by 3 urologists and achieved consensus. _x000D_ Results To date, 10 subjects have undergone multimodal imaging. No adverse events were noted due to the combination of instruments or imaging agents used. Confocal imaging features of the resection bed including elastin fibers (network of thin, interwoven strands), muscle fibers (sheets of straight, connected columns) and perivesical fat (collection of dark, round globules) were observed. Muscularis propria was present in the resected tissue on pathology assessment, confirming adequate resection. Patients are currently undergoing follow-up for cancer recurrence._x000D_ Conclusions We report real-time microscopic inspection of the resection bed to assess for adequate depth of resection with CLE in combination with the macroscopic imaging technologies PDD and NBI. Further studies are needed to determine if multimodal enhanced cystoscopy results in improved TURBT with adequate depth and margins of resection and decreased recurrence rate, which may eventually translate to a decreased need for repeat TURBT._x000D_ Funding none
Authors
Timothy Chang
Dharati Trivedi Mario Sofer Joseph Liao |
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V12-02 |
Confocal Laser Endomicroscopy for bladder cancer diagnosis: how to do it & our preliminary results |
Bladder Oncology and Diversion | 17BOS |
Abstract: V12-02 Sources of Funding: This study was supported by the Cure for Cancer foundation (http://www.cureforcancer.nl). Introduction Cystoscopy is the cornerstone in bladder cancer diagnosis and monitoring. Although very effective, conventional white light cystoscopy has its limitations. New techniques have been developed to improve visualisation of tumours and suspicious lesions. However, no information can be given on grade of the disease during cystoscopy or per-operatively as no histopathologic information can be obtained real time. Confocal Laser Endomicroscopy (CLE) is a unique new imaging technique. It allows in vivo optical sectioning of tissue and provides real time microscopic images with high resolution. The objective of this study is to assess if we can take &[prime]optical biopsies&[prime] of the bladder using CLE. Methods We performed CLE in 19 patients with a bladder tumour, during transurethral resection of the bladder tumour (TURB). At the beginning of the procedure, after initial evaluation of the bladder, 360 ml of 0.1% Fluorescein, a fluorescent contrast agent, was administered intravesical via an indwelling catheter. After 5 minutes CLE was performed using the Cystoflex UHD R (Cellvizio, Mauna Kea, Paris, France), which has a resolution of 1 μm, a field of view of 240 μm, and an imaging depth of 50-65 μm. The CLE probe was introduced via the working channel of the cystoscope (Olympus or Storz 0 - 12°). CLE images were obtained of healthy tissue and tumours, and correlated with histopathology and analysed afterwards. After obtaining CLE images, the tumour was resected en-bloc. Tumour grade was assessed according to the WHO 2004 classification. Results We were able to obtain good CLE images when the probe was correctly positioned. The probe has to be in good contact with the tissue, and perpendicular to the surface. Of the 19 patients; 2 had a benign lesion, 12 low-grade urothelial carcinoma, and 5 high-grade carcinoma. Differences in CLE images could be seen between healthy tissue and tumour (figure 1). Conclusions During TURB it was possible to take &[prime]optical biopsies&[prime] of the bladder. The obtained CLE images could give real time histopathologic information, and has the potential to differentiate in tumour grade during cystoscopy. These &[prime]optical biopsies&[prime] may assist urologist in future clinical practice in bladder cancer diagnosis and follow-up. Funding This study was supported by the Cure for Cancer foundation (http://www.cureforcancer.nl).
Authors
Esmée Liem
Jan Erik Freund Theo de Reijke Joyce Baard Guido Kamphuis Pilar Laguna Pes Martijn de Bruin Jean de la Rosette |
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V12-03 |
robotic uteretal reimplantation for uretero-enteric anastomotic strictures |
Bladder Oncology and Diversion | 17BOS |
Abstract: V12-03 Sources of Funding: none Introduction Uretero-enteric anastomotic strictures occur in about 2-10% of patients treated with radical cystectomy and urinary diversion (UD). In this study we report the outcomes of robotic ureteral reimplantation for ureteroenteric anastomotic strictures in patients previously treated with robot assisted radical cystectomy (RARC) and UDs. Methods From April 2013 to July 2016 12 patients underwent robotic ureteral reimplantation in three tertiary referral centers. Out of 12 patients, 7 had orthotopic neobladder, 4 ileal conduit and 1 Indiana pouch. All patients had prior RARC and all but one had intracorporeal UD. _x000D_ Surgical steps include a careful ureteral dissection on the surface of the ureter/s to avoid injuring the iliac vessels, spatulation of the ureters, JJ stent insertion and finally uretero-ileal anastomosis._x000D_ Baseline, perioperative and early functional outcomes data are reported._x000D_ Results Mean time from RARC to uretero-anastomotic stricture diagnosis was 174 days (33-674). Mean stricture length was 2 cm (range 0.5-3), median operative time was 201 minutes (83-310) and median length of stay was 2 days (2-12)._x000D_ All cases were completed robotically. Intraoperative blood loss was negligible. Four patients experienced a Clavien grade II complication (urinary tract infection requiring antibiotics). At a median follow-up of 320 days (55-907) no recurrences occurred._x000D_ Conclusions Robotic ureteral reimplantation for uretero-enteric strictures is a safe and highly effective procedure. Given the suboptimal success rate of endoscopic treatment, robotic repair has become a first treatment option in our centers. Funding none
Authors
Carlos Fay
Daniel Melecchi Freitas Sameer Chopra Nariman Ahmadi Andre Berger Mihir Desai Inderbir Gill Alvin Goh Leonardo Misuraca Salvatore Guaglianone Mariaconsiglia Ferriero Gabriele Tuderti Michele Gallucci Giuseppe Simone Monish Aron |
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V12-04 |
Robot assisted orthotopic modified Studer neobladder |
Bladder Oncology and Diversion | 17BOS |
Abstract: V12-04 Sources of Funding: None Introduction Robotic intracorporeal orthotopic neobladder after radical cystectomy and extended lymphadenectomy is a technically challenging procedure. So far, only a few centers worldwide have taken this procedure into routine. After over 1000 procedures and routinely performed intracorporeal Bricker urinary deviation, the swiss team started with the intracorporeal neobladder technique carefully. The video presents our standardized technique in 10 patients after one first proctored surgery by a mentoring team (AH/PW). Methods A daVinci SI-system with 4 arms and 6-port access was used. The left ureter is drawn unter the mesorectum to the right side. 50cm are needed for the pouch. The urethro-ileal anastomosis with a 3-0 barbed suture is performed after an approximation of rectoprostatic fascia and the ileal sling. A 60mm/45mm stapler ileo-ileostomy is established. Two holding sutures are placed 10cm proximal from the urethroileal anastomosis, marking the deepest point of the pouch. The ileum is opened at the antimesenteric side over 40cm and the posterior wall is closed using 3-0 barbed running suture. Than, the distal ventral pouch is closed. The distal ureters were incised and a Wallace plate was formed. The ureters are stented through the abdominal wall and the chimney with Ch8 mono-J catheters. The ileo-ureteral anastomosis is performed with a 3-0 double arm running suture. The last anterior segment of the pouch is closed and than proved for water tightness. Results Operative time (skin-skin) was 575(420-725) minutes, bleeding 600(200-1000)ml. 1 patient required invasive ventilaton more than 24h. Time to flatus was 2(1-5) days, to bowel movement 4(3-10) days. The in-hospital stay was 15(9-27) days. There were no reoperations within 30days and no 30d- mortality. There were no positive margins nor positive lymph nodes in 22(15-43) removed nodes. The indwelling catheters remained 26(17-40) days, all pouches voided subsequently without residual urine. Conclusions Robotic intracorporeal urinary diversion with a modified orthotopic Studer neobladder is a technically demanding procedure. With a standardized setting, the procedure is feasable in experienced robotic teams with promising intraoperativ and early postoperative results.Still, long termin pouch function, metabolism and oncological follow-up have to be observed critically. Funding None
Authors
Hubert John
Christian Padevit Kevin Horton Abolfazl Hosseini Peter Wiklund |
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V12-05 |
Revisiting the Abdomen after Robot-Assisted Radical Cystectomy: Tips and Tricks for Robot-Assisted Repair |
Bladder Oncology and Diversion | 17BOS |
Abstract: V12-05 Sources of Funding: Roswell Park Alliance Foundation Introduction Reoperations following robot-assisted radical cystectomy (RARC) are challenging owing to technical complexity (abdominal adhesions and altered anatomy after cystectomy). We sought to describe our experience in robot-assisted (RA) reoperations following RARC. Methods We retrospectively review 406 RARCs performed by a single surgeon between 2005 and 2015. Data were reviewed for demographics, preoperative disease, and operative and perioperative outcomes. Surgical interventions for RARC-specific complications were identified and RA technique described. Results For ureteroileal complications: 12 RA versus 7 open. Both had comparable perioperative outcomes. Fistula repair: 5 RA versus 6 open. Although patients in the RA group had longer operative times, they had shorter hospital stay (4 versus 10 days) and none of them required further intervention (4 in the open group did). Bowel obstruction that failed conservative treatment: 4 RA versus 7 open. Further intervention was required in 2 patients in the RA. Parastomal hernia repair: 4 RA and 2 open (one failed). Conclusions Our initial experience with RA management of RARC complications appears safe and feasible, although the decision to proceed is determined primarily by surgeon experience. Funding Roswell Park Alliance Foundation
Authors
Ahmed Hussein
Justen Kozlowski Youssef Ahmed Khurshid Guru |
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V12-06 |
Utilization of Indocyanine Green Fluorescence Angiography During Intracorporeal Uretero-ileal Anastomosis Following Robotic Radical Cystectomy |
Bladder Oncology and Diversion | 17BOS |
Abstract: V12-06 Sources of Funding: none Introduction Indocyanine-green (ICG) is an exogenous tracer approved by he FDA and is currently used in several urological procedures such as partial nephrectomies to reveal vascular anatomy and tissue perfusion. Methods In this video we report our initial experience and proof-of-concept in 10 patients who underwent robotic-assisted radical cystectomy with intracorporeal diversion where ICG was utilized prior to perform uretero-ileal anastomosis to assess ureteric vascularity. _x000D_ _x000D_ _x000D_ Results In our cohort of 10 patients, 7 patients required resection of distal ureter in at least one ureter. Three patients required bilateral distal ureteral resection, three patients required left and one patient required right distal ureter resection._x000D_ The median resected ureteral lenght was 2cm. The median operation time 510 minutes. Complications were found in 3 patients, fever in two and ileus in one (Clavien II). The median length of stay was 5.5 days and the median follow-up was 81 days._x000D_ Conclusions Intravenous injection of ICG before ureteroileal anastomosis is useful to evaluate distal ureteral vascularity. It helps to identify and excise the non-vascularized ureteral segment. Long term follow-up will be necessary to evaluate the benefits of ICG-use to prevent ureteroileal strictures. Funding none
Authors
Daniel Melecchi Freitas
Carlos Fay Nariman Ahmadi Andre Abreu Toshitaka Shin Inderbir Gill Andre Berger Mihir Desai Monish Aron |
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V12-07 |
Robotic intracorporeal “Padua Ileal Bladder”: Surgical technique, perioperative, oncologic and functional outcomes |
Bladder Oncology and Diversion | 17BOS |
Abstract: V12-07 Sources of Funding: none Introduction Robot-assisted radical cystectomy (RARC) with intracorporeal neobladder reconstruction is a challenging procedure. The need for surgical skills and long operative times have led to concern about its reproducibility. The aim of this video is to illustrate our technique for RARC and totally intracorporeal orthotopic “Padua Ileal Bladder�. Methods From August 2012 to February 2014, 45 patients underwent RARC, extended pelvic lymph node dissection and intracorporeal partly stapled neobladder at a single tertiary referral centre. Surgical steps are demonstrated in the accompanying video. Demographics, clinical and pathological data were collected. Perioperative, 2-yr oncologic and 2-yr functional outcomes were reported. Results Intraoperative transfusion or conversion to open surgery was not necessary in any case and intracorporeal neobladder was successfully performed in all 45 patients. Median operative time was 305 minutes (IQR 282-345). Median estimated blood loss was 210 ml (IQR 50-250). Median hospital stay was 9 days (IQR7–12). The overall incidence of perioperative, 30-d and 180-d complications were 44.4%, 57.8% and 77.8%, respectively, while severe complications occurred in 17.8%, 17.8% and 35.5%, respectively. Two-yr daytime and night-time continence rates were 73.3% and 55.5%, respectively. Two-yr disease free survival, cancer specific survival and overall survival rates were 72.5%, 82.3% and 82.4%, respectively. The small sample size and high caseload of the centre might affect the reproducibility of these results. Conclusions Our experience supports the feasibility of totally intracorporeal neobladder following ?RARC. Operative times and perioperative complication rate are likely to be reduced with increasing experience. Funding none
Authors
Giuseppe Simone
Rocco Papalia Leonardo Misuraca Gabriele Tuderti Francesco Minisola Mariaconsiglia Ferriero Giulio Vallati Salvatore Guaglianone Michele Gallucci |
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V12-08 |
Ureteroileal bypass: a new robotic technic to treat ureteroentereric strictures in urinary diversion |
Bladder Oncology and Diversion | 17BOS |
Abstract: V12-08 Sources of Funding: none Introduction Bladder cancer is the ninth most frequently cancer diagnosed worldwide. The standard definitive treatment for MIBC is radical cystectomy (RC) and urinary reconstruction._x000D_ Complications of RC and diversion can appear after months or years of surgical treatment. Ureteroentereric strictures are a late complication after cystectomy and diversion that occur in 2% to 15% of patients.4-6 Multiple treatment alternatives have been proposed to those strictures with variable success rates, ureteral reimplantation is still considered the gold standard surgical treatment7. However, the surgical approach to the ureteroenteric anastomosis can be challenging due to fibrosis and adhesions. We propose herein a technical modification aiming to minimize ureteral dissection; the technique involves a latero-lateral anastomosis of the dilated ureter with the ileal conduit without detaching de ureter from the intestinal segment. Our experience with this technical modification is described._x000D_ Methods We reported a patient submitted to uretero-ieal bypass to treat uretero-enteric stricture in Bricker implant._x000D_ The technique was made robot-assisted, and it is shown in the figure. Results The case reported is a 70 years-old man, without any comorbities, diagnosed with muscle invasive bladder cancer after transuretral ressection. _x000D_ He was subbmited to Robot-Assisted RC with intracorporeal Bricker diversion, without any major complications._x000D_ The pathologic report of cistectomy was high grade urothelial carcinoma pT2 N0._x000D_ With 3 months of follow-up, patient refered left flank pain, without any report of urinary infecction._x000D_ Serum Creatinine before cistetomy was 0.8 mg/dL, and 3 months after surgery it increased to 1.33 mg/dL._x000D_ The CT scan showed the right kidney without any change, there was no limphnode or visceral metastasis, the left kidney had adequate contrast enhancement, and there was ureteral hydronephrosis till the implant in the Bricker, without patency for contrast. There was no sign of metastasis in the implant._x000D_ With a follow-up of one year after the uretero-ileal bypass, patient is assimptomatic, serum creatinine decreased to 0,92 mg/dL, and image control shows total resolution of hydronephrosis._x000D_ Conclusions Latero-lateral ureteroenteric anastomosis is a feasible treatment option for benign anastomotic strictures. It can be performed either by open or minimally invasive approaches with good perioperative outcomes Funding none
Authors
Guilherme Padovani
Rubens Park Marcos Mello Rafael Coelho Leonardo Borges Adriano Nessralah Miguel Srougi William Nahas |
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V12-09 |
Anatomic robot assisted radical cystectomy in female: step by step technique |
Bladder Oncology and Diversion | 17BOS |
Abstract: V12-09 Sources of Funding: none Introduction Robot assisted radical cystectomy in female for bladder cancer is a challenging urologic surgical procedure. We describe step by step surgical technique and present perioperative outcomes of a single patient who underwent a robot assisted radical cystectomy (RARC) with totally intracorporeal orthotopic neobladder (iON). Methods A 66 yr-old female patient with a cT1/N0/M0 high grade BCG refractory recurrent bladder cancer, underwent RARC and iON.?Key steps of surgery include: the ligation of gonadic pedicles, meticulous dissection of the umbilical and uterine artery and the ureter, dissection of the bladder pedicle, opening of the vagina and creation of the plane between vagina and bladder. Cut of the urethra and securing the Foley catheter with the entire specimen placed into an Endocatch bag to minimize any urine spillage. Removal of the specimen into an endocatch bag through the vagina. Extended pelvic lymph node dissection. Suture of the vagina and creation of a peritoneal flap as posterior neobladder support. Results The procedure was successfully completed. Operative time was 295 minutes, EBL was 250 mL, time to flatus was 3 days, time to bowel was 7 days. Hemoglobin and creatinine at discharge were 10.3 g/dL and 0.76 mg/dL, respectively. The hospital stay was 8 days. The pathologic stage was pT0 pN0. The number of nodes removed was 26. Postoperative course was uneventful. The patient recovered daytime continence 45 days after surgery. Conclusions A meticulous dissection of vascular suppliers of the bladder, a natural orifice specimen retrieval and the ease of posterior neobladder support thanks to a perfect vision of the small pelvis anatomic structures may contribute to minimize invasiveness and to improve perioperative outcomes of radical cystectomy in female patients. Funding none
Authors
Giuseppe Simone
Salvatore Guaglianone Leonardo Misuraca Francesco Minisola Gabriele Tuderti Mariaconsiglia Ferriero Giuseppe Romeo Michele Gallucci |
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V12-10 |
Robot-assisted Laparoscopic Radical Cystectomy and Intracorporeal Neobladder Utilizing a Vaginal-Sparing and Staple-Free Approach |
Bladder Oncology and Diversion | 17BOS |
Abstract: V12-10 Sources of Funding: None Introduction At our institution robot assisted laparoscopy with intracorporeal neobladder has become standard of care for our treatment of patients with muscle invasive bladder cancer. When indicated and feasible we perform a vaginal sparing and staple-free approach for our female patients in order to optimize continence and sexual function. Methods Using a high definition recording system and iMovie software with narrative and annotative editing we created a video illustrating our vaginal-sparing and staple-free approach to the robot assisted laparoscopic radical cystectomy and neobladder. Our Patient is a 66 year old female with high grade bulky urothelial carcinoma of the bladder. Results We have performed vaginal-sparing and staple-free robot-assisted laparoscopic radical cystectomy and intracorporeal neobladder in 12 patients. Patients age range of 41-72 years old. 70% of these patients underwent neoadjuvant chemotherapy. Total operative times range from 4.25 – 5.85 hours. The majority of patients have self-reported good satisfaction with neobladder after surgery. Conclusions In our experience, the robotic staple-free, vaginal-sparing intracorporeal neobladder is a safe and effective method of treatment for muscle invasive bladder cancer. Long term cancer control not yet proven with the robotic approach; however short term control is comparable to other methods. Further study will be needed to demonstrate the long term safely and cancer control with this technique. Funding None
Authors
Christine White
Mark Ferretti Gregory Lovallo Mutahar Ahmed |
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V12-11 |
Laparoscopic repair of ileal conduit parastomal hernia using the modified Sugarbaker technique |
Bladder Oncology and Diversion | 17BOS |
Abstract: V12-11 Sources of Funding: none Introduction Parastomal hernia is a common complication of stoma formation, The reported incidence is variable depending on the degree, the duration of follow-up and the type of stoma. The incidence for ileal conduits ranges from 2% to 6.5%. Modified laparoscopy Sugarbaker technique is a possible method to repair ileal conduit parastomal hernia. Methods We present a case of the laparoscopic modified Sugarbaker technique applied to repair a ileal conduit parastomal hernia in a 67 years-old patient with a history of radical cystoprostatectomy and Bricker uretero-ileostomy for a bladder cancer seven years ago. The procedure is described in detail in this video. Results The patient was positioned supine with both arms tucked. The abdomen was accessed using a 10-mm trocar in the axillary line, in front of the ileostomy , a 10-mm trocar by subxiphoid approach and a 5-mm trocar in the left lower quadrant._x000D_ A tedious lysis of adhesions was performed with minimal use of bipolar energy. Liberation of omental adhesions in the foramen of parastomal hernia and extraction of 40 cm. of small bowel located in parastomal hernia were performed.The parastomal hernia defect were identified and measured. We used a 15 cm x 20 cm physiomesh® mesh. The fine filament design and its macroporous structure flexible, facilitate the scar tissue formation and adaptation to the abdominal wall. The mesh was tacked in position to the abdominal wall in its periphery using the 5-mm tacking device. When we place the takers should make an external pressure on the abdominal wall. Several takers are placed in the abdominal wall, circumferentially around the ileal loop. The patient was discharged after a 2-day stay. After 20 months of follow up, the patient is free of recurrence of parstomal hernia. Conclusions The introduction of prosthetic meshes significantly decreases the recurrence rates of parastomal hernia. Laparoscopic surgery reduces_x000D_ postoperative pain, recovery time and minimize many of the morbidities associated with open procedures. Laparoscopic parastomal hernia repair has a viable option to overcome the challenges that face the hernia surgeon. Funding none
Authors
Dario Garcia-Rojo
Xavier Serra-Aracil Angel Prera Carlos Abad Jesus Muñoz Leticia De Verdonces Marta Capdevila Eduardo Vicente Naim Hannaoui Younes Fadil Jose Luis Gonzalez-Sala Arturo Dominguez Clara Centeno Victor Parejo Mario Rosado Paula Planelles Juan Prats |
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V12-12 |
Robotic Cystoprostatectomy with Pubectomy and Ileal Conduit for Patients with Osteomyelitis Pubis |
Bladder Oncology and Diversion | 17BOS |
Abstract: V12-12 Sources of Funding: Nne Introduction Osteomyelitis pubis is a rare complication of pelvic radiation and prostate surgery. This chronic condition has substantial impact on quality of life. Medical therapy has limited role and surgical resection is usually needed. Open prostatectomy or cystoprostatectomy with pubectomy is associated with difficult post-operative recovery. We report our early experience in robotic cystoprostatectomy with pubis symphysis debridement Methods We present an instructional video of a 77 y.o. male with history of prostate cancer. s/p open radical prostatectomy 19 years prior to his surgery, complicated with multiple Bladder neck contractures over the years. He underwent salvage radiation therapy for biochemical failure. Developed urinary incontinence. Later he underwent an attempted bladder sling placement, followed by AUS and Urolume urethral stent. Due to AUS pump erosion and eventual explanation few months later. Every 6 months thereafter he was repeatedly treated for stones encrusting. He then developed OM of the pelvic bone for the last 4 years, complicated by bacteremia and extended IV antibiotics. Results Up to 2016 four patients with chronic post radiation osteomyelitis pubis underwent robotic cystectomy with pubic symphysis debridement and ileal conduit urinary diversion. One patient needed a temporary loop colostomy. Average robotic operative time: 175 minutes. Average hospital Stay 5.3 days. Median EBL 75 ± 40 ml. Antibiotics were stopped within 4 weeks. One had high grade complication and none had recurrence of the osteomyelitis. Conclusions Robotic cystectomy with pubic symphysis debridement is a feasible alternative to open cystectomy with open resection of pubis symphysis. It may provide faster recovery. Funding Nne
Authors
Ahmad Shabsigh
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V2-01 |
Repair of a complex vaginal J-pouch fistula utilizing a gracilis muscle interposition flap |
Female Pelvic Medicine | 17BOS |
Abstract: V2-01 Sources of Funding: none Introduction Rectovaginal and J-pouch vaginal fistulae are abnormal epithelialized connections between the rectum or J-pouch to the vagina. Symptoms, such as fecal incontinence, can be distressing to patients. These fistulae can be a challenge to repair and multiple repair methods have been described in the literature including transvaginal, transrectal, and flap interposition repairs. Success rates in the literature range from 10-100% and with each subsequent repair the success rate of closure decreases. Methods We present the case of a 35 year-old woman with a history of ulcerative colitis who developed a fistula following a total proctocolectomy and ileal-anal pouch anastomosis. When she presented she had already undergone more than ten attempts at repair. Prior to our fisula repair she had a fecal diversion with a loop ileostomy. We performed a transvaginal repair utilizing a gracilis muscle interposition flap. Indocyanine green was given intravenously and the SPY Elite imaging system was used to enable the visualization of microvascular blood flow and perfusion to the gracilis flap and to the bed of the fistula repair intraoperatively. Results Our patient did well after the procedure. She was discharged home with the foley in place on post-operative day 1. At her one month follow-up the repair was intact and she was healing well. Conclusions In cases of complex rectovaginal and vaginal J-pouch fistulae, especially those that are reoperative cases, fistula repair with a gracilis interposition flap is a viable repair option. Success from this repair can be aided by assuring complete excision of non-viable tissue and a healthy flap. In our case these steps were aided by the use of the SPY Elite imaging system. Funding none
Authors
Gillian Wolff
Jack Christian Winters Ralph Chesson |
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V2-02 |
TOTAL AUTOLOGOUS FASCIA LATA ANTERIOR REPAIR AND APICAL SUSPENSION: A NEW TECHNIQUE |
Female Pelvic Medicine | 17BOS |
Abstract: V2-02 Sources of Funding: None Introduction The reclassification of vaginal mesh to a high risk device for treatment of pelvic organ prolapse prompted our group to consider alternative graft materials. Based on the similar success rates and durability of mesh and autologous fascia in the treatment of female stress urinary incontinence (SUI), our objective was to develop a transvaginal repair for anterior and apical vaginal prolapse with the use of only autologous fascia lata graft thereby avoiding synthetic mesh, allograft and xenograft. _x000D_ Methods The video demonstrates our technique for Autologous Anterior and Apical Pelvic Organ Prolapse (AAA-POP) repair. Autologous fascia lata of suitable size (4 X 12 cm up to 5 X 14 cm) is harvested through a minimally invasive, lateral upper thigh incision. The graft is then cut into 3 strips (1cm X 12cm up to 1.3 cm X 14cm) and reassembled with one strip affixed to the bladder neck and sutured to the obturator internus fascia with 0-vicryl. The other 2 strips are sutured to the strip at the bladder neck with CV-2 Gore-Tex suture, crossed at the level of the vaginal apex, and sutured to the sacrospinous ligaments with 0-PDS. Patients were followed with subjective SEAPI scores, visual analog pain (VAP) scores (range 0-10), pelvic examination (Baden-Walker grading), and examination of the thigh harvest site._x000D_ _x000D_ Results The AAA-POP procedure has been performed on 5 patients with a mean age of 61 and a mean follow-up of 2 months. Apical uterine suspension was performed in 3/5 patients and the other 2/5 patients were status post hysterectomy. Symptoms of pelvic organ prolapse resolved in all 5 patients, but 1 patient had an asymptomatic grade 1 cystocele without apical prolapse at 3 months follow-up. No patients complained of SUI or urge incontinence on SEAPI scoring. 1 patient required lysis of a concurrent pubovaginal sling 2 weeks postoperatively with resolution of urinary retention, and 1 patient had mild obstructive symptoms on SEAPI scoring. 2 patients developed thigh hernias postoperatively, and the mean VAP score at the harvest site was 1.8 for all patients._x000D_ Conclusions Autologous Anterior and Apical Pelvic Organ Prolapse (AAA-POP) repair with fascia lata is a feasible option in the post-mesh era and appears to be safe and efficacious with short-term follow-up. Longer follow-up is needed to determine long term success and possible complications of the procedure. Although self-reported pain scores were low, patients should be aware of the risk of residual pain at the harvest site and possible development of a thigh hernia._x000D_ Funding None
Authors
Christian Twiss
Miguel Craig Frank Lin Joel Funk |
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V2-03 |
Robot-assisted Repair of Supratrigonal Vesicovaginal Fistulae using a Peritoneal Flap Inlay |
Female Pelvic Medicine | 17BOS |
Abstract: V2-03 Sources of Funding: none Introduction Vesicovaginal fistulae (VVF) represent a major health-care problem in low- resourced countries, where most VVF derive from obstetric complications. In the western world, most VVF occur after difficult hysterectomies. A transvaginal approach can be used successfully in low and simple fistulae, while supratrigonal and more complex cases may require a transabdominal approach. To minimize operation trauma laparoscopic or robot-assisted techniques are being used. Though fistulae closure with tension-free, multilayer closure is feasible, the use of tissue interposition can achieve higher closure rates in larger fistulae or where the surrounding tissue is devitalized. Different materials have been described for fistula closure, including peritoneal tissue and gluteal muscle as well as artificial materials._x000D_ Methods Our video presents a robot-assisted technique using a peritoneal flap patch for reconstruction of the VVF. A daVinci SI-system with 4 arms and 6-port access was used. Preoperatively a Fogarthy catheter is placed through the fistula to mark the fistula channel , and the ureters are also stented. After initial adhesiolysis and preparation of the vesicovaginal space, the vagina is incised. Then, the fistula is identified and excised with the surrounding tissue both on the vaginal and bladder side. Following the closure of the vagina, a pedicle peritoneal flap is harvested and interposed between vagina and dorsal bladder wall. Finally, the bladder closure is performed with double-layer sutures. The analysis was performed retrospectively including operative parameters, perioperative complications and functional outcome for all patients._x000D_ Results Median operative time (skin to skin) was 219 (181-331) minutes without relevant blood loss. Median length of hospital stay was 8 (4-13) days. The indwelling catheter was removed after 10 days and a normal cystogram. Postoperatively all patients (n=10) showed a recurrence-free total continence (0 pad/day). The highest postoperative complication was fever requiring antibiotic treatment (Clavien grade II). _x000D_ Conclusions Robotic vesicovaginal repair of high vesicovaginal fistulae and peritoneal flap inlay is a safe minimal invasive approach with a high satisfaction rate and no recurrences in this pilot series to date. _x000D_ Funding none
Authors
Christoph Schregel
Beatrice Breu Kevin Horton Hubert John |
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V2-04 |
A Novel Robotic-Assisted Laparoscopic Repair of Posterior Compartment Prolapse: Treating Women with Defecation Dysfunction |
Female Pelvic Medicine | 17BOS |
Abstract: V2-04 Sources of Funding: none Introduction Symptoms associated with posterior compartment prolapse greatly impact a woman&[prime]s quality of life. These symptoms include straining or splinting to defecate, incomplete emptying, and incontinence of feces or gas. Current surgical repair options aim to repair the rectocele, but do not routinely address the size and laxity of the rectum, which may also contribute to defecation symptoms. Methods We present a demonstrative video of a robotic-assisted laparoscopic sacrocolpopexy and laparoscopic posterior colporrhaphy in a woman with a prior supracervical hysterectomy and subsequent robotic sacrocolpopexy with perineorrhaphy. Due to persistent defecation dysfunction combined with physical exam findings consistent with posterior compartment prolapse, the decision was made to proceed with surgical repair after the risks and benefits were discussed. The accompanying video demonstrates a plication using perirectal connective tissue and lightweight polypropylene &[Prime]Y&[Prime] mesh that is ultimately secured to the posterior colporrhaphy for additional support. Results In the short-term, this novel procedure has proven effective in treating a small series of women with posterior compartment prolapse and defecation dysfunction. Those women included within our limited series report subjective improvement with regards to their original ailments of bowel dysfunction. No serious adverse events related to this surgical procedure occurred in the peri-operative period or during short-term follow up. Conclusions While longer follow-up is needed, the robotic-assisted laparoscopic sacrocolpopexy with laparoscopic posterior colporrhaphy represents a technically safe and feasible approach to treating women with posterior compartment prolapse and defecation dysfunction. Funding none
Authors
Ron Golan
Brian Dinerman Adrien Bernstein Kiersten Craig Patrick Culligan |
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V2-05 |
The novel technique of post-hysterectomy vaginal vault prolapse repair: apical sling and &[laquo]neocervix&[raquo] formation |
Female Pelvic Medicine | 17BOS |
Abstract: V2-05 Sources of Funding: None Introduction Frequency of vaginal vault prolapse (VVP) requiring surgical repair is up to 6-8% and 11.6% in patients with prior hysterectomy for uterine prolapse. Sacrocolpopexy is considered the gold standard procedure for VVP correction. Nevertheless, it is associated with long operation time, pneumoperitoneum, Trendelenburg position, and a number of well-known complications. The objective of this study was to evaluate effectiveness of novel technique: bilateral sacrospinous fixation by monofilament polypropylene apical sling (UroSling-1, Lintex) combined with neocervix formation (purse-string suture on the internal surface of the cervical fascia fixed to the tape) in surgical treatment of post - hysterectomy vaginal vault prolapse. Secondary aim was to estimate the impact of the surgery on urinary function and patient&[prime]s quality of life. Methods This prospective study involved 54 women suffering from post-hysterectomy prolapse. Patients underwent hybrid reconstruction of the pelvic floor in accordance with the proposed method. To evaluate the results of surgical treatment, data of a vaginal examination (POP-Q), uroflowmetry, ultrasound measurement of post-voiding residual volume were used, determined before the surgery and at control examinations after treatment. Changes in quality of life were evaluated by comparing the scores according to PFDI-20, PFIQ-7, PISQ-12, ICIQ-SF questionnaires. Results Mean operation time was 35 ± 13 minutes. There were no cases of intraoperative damage to the bladder or rectum, as well as clinically significant bleeding. Median follow-up time was 12 (min-8, max-18) months. There was noted statistically significant improvement in POP-Q points, especially, Ba and C (p<0,001) in all patients. Also statistically significant improvement was found in peak and average flow rate according to uroflowmetry (p<0,05). Recurrent prolapse was noted in anterior compartment in 3.7% (2/54). After 6 months of follow-up stress urinary incontinence de novo was noted in 7.4% (4/54). Most of the patients reported a significant improvement in quality of life after treatment. Conclusions The novel technique: combination of the apical sling and purse-string &[laquo]neocervix&[raquo] formation appears to be effective and safe method for treatment patients with post-hysterectomy prolapse. This technique also provides high functional results and improves quality of life. Funding None
Authors
Dmitry Shkarupa
Alexey Pisarev Ekaterina Shapovalova Anastasia Zaytseva Nikita Kubin |
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V2-06 |
Female Dorsal Onlay Buccal Mucosa Graft Urethroplasty |
Female Pelvic Medicine | 17BOS |
Abstract: V2-06 Sources of Funding: None Introduction Female urethral strictures can present significant challenge which can be further complicated from challenging location or length of stricture. The objective of this video is to demonstrate the use of a buccal mucosa graft in the treatment of female urethral strictures. Methods This video demonstrates the use of a dorsal onlay buccal mucosal graft in a female patient with history urethral stricture and bothersome urinary symptoms. The patient has undergone multiple dilations in the past with recurrence of the stricture. Results The patient underwent successful buccal mucosal graft urethroplasty and now has significant improved urinary symptoms as well as urine flow rates. Conclusions Dorsal onlay buccal mucosa graft is a versatile tool in the Urologist's armamentarium when facing the challenge of a complicated female urethral stricture. Funding None
Authors
Brenton Armstrong
Dan Hoffman Lee Zhao Victor W. Nitti Benjamin Brucker |
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V2-07 |
Female Urethroplasty with Buccal Mucosal Graft for Stricture Disease |
Female Pelvic Medicine | 17BOS |
Abstract: V2-07 Sources of Funding: None Introduction Female urethral strictures are rare and occur in less than 1% of women. Common causes are trauma, iatrogenic injury, inflammatory diseases or idiopathic. Diagnosis is suspected when a patient reports obstructive symptoms, urodynamics shows outlet obstruction and/or cystourethroscopy reveals urethral narrowing or fibrosis. Surgical treatment depends on location and length of the stricture, and the optimal approach is not well established. In this video, the technique for female urethroplasty with a dorsal onlay buccal mucosal graft is demonstrated. Methods A 48-year-old female patient presented with long-standing, symptomatic urethral stricture disease. She previously failed conservative management with urethral dilations and elected to pursue urethroplasty with buccal mucosal graft. Following informed consent, video recording of intraoperative surgical procedure was performed. Video editing and narration was standardized to highlight key steps of the procedure. Results The patient was taken to the OR for urethroplasty with a dorsal onlay buccal mucosal graft. First, a cystoscopy was performed and a suprapubic tube was placed to allow for sufficient postoperative healing. The buccal mucosal graft was harvested, defatted and soaked in normal saline. Circumferentially around the urethral meatus hydrodissection is used with care taken to avoid the clitoral tissue and nerves. The urethra was dissected to the level of the bladder neck and the full extent of the stricture was identified then incised. Stay sutures were placed in the superior and inferior apices to facilitate placement of the graft. Superior apical sutures were threaded through the graft and additional interrupted sutures were placed circumferentially. The graft was trimmed to size, threaded with the inferior apical stay sutures and secured in place. The surgical bed and graft were joined to enhance revascularization. The patient did well postoperatively, with no recurrence of stricture and healthy buccal mucosa graft on cystoscopy. Conclusions Urethroplasty with dorsal buccal mucosal graft placement can be a feasible and effective treatment for female urethral strictures. Funding None
Authors
Alexander Small
Carrie Mlynarczyk Henry Tran Doreen Chung |
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V2-08 |
A New Limited Open Technique for Complete Removal of Retropubic Synthetic Midurethral Sling Mesh |
Female Pelvic Medicine | 17BOS |
Abstract: V2-08 Sources of Funding: none Introduction While synthetic midurethral sling placement is generally a safe and effective treatment for female stress urinary incontinence, a small percentage of patients will require sling excision for post-operative complications including urinary obstruction, mesh exposure, or pain. Though many of these complications can be addressed with suburethral or local sling excision, refractory chronic pain may require total mesh excision._x000D_ _x000D_ One of the greatest concerns for surgeons performing total mesh excision of a retropubic sling is the potential morbidity of the operation, including wound complications associated with extensive retropubic dissection to localize the sling arms. With these concerns in mind, we present a technique for total retropubic sling excision which limits the extent of retropubic dissection._x000D_ Methods A 48 year old female patient underwent retropubic synthetic sling placement in 2010, followed by vaginal, urethral, and suprapubic pain, as well stranguria, incomplete emptying and persistent urgency, frequency and urgency incontinence. After preoperative evaluation, in light of her chronic suprapubic pain, she was offered total retropubic sling excision. She elected to proceed after discussion of risks, benefits, and alternatives. _x000D_ _x000D_ The novelty of our procedure is seen in the limited retropubic dissection. Each arm of the sling mesh is mobilized vaginally to the level of the endopelvic fascia. The retropubic space is entered via a vaginal approach and developed bluntly. Only then is abdominal exposure sought; at this point, gentle traction on the sling arm can be seen from above, allowing for only a tiny fascial incision to be made directly over the sling arm location. The retropubic portion of the mesh is then traced to the vaginal portion, and the sling arm is freed in its entirety. This is repeated on the contralateral side._x000D_ Results At four week follow up, the patient reported greater than 90% improvement in her pain, with improved ease of voiding. She had no wound complications. Conclusions Our novel technique allows for complete retropubic sling mesh removal with limited retropubic dissection, which may minimize the surgical morbidity and decrease the risk of wound complications. Funding none
Authors
Elodi Dielubanza
Jessica Lloyd Howard Goldman |
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V2-09 |
Laparoscopic cervicosacropexy and vaginosacropexy techniques as treatment of pelvic organ prolapse and urinary incontinence |
Female Pelvic Medicine | 17BOS |
Abstract: V2-09 Sources of Funding: None Introduction In the presence of genital prolapse with apical descent, sacrocolpopexy and vaginal sacrospinous fixation are current available procedures. They focus on restoring apical support usually with a piece of mesh made of different materials, undefined length and shape and different fixation sides in the small pelvis. Thereby, non-physiological fixation of cervix/vagina and bladder may result and may be followed by urinary incontinence. _x000D_ Following DeLancey and Ulmsten, we developed a bilateral replacement of the uterosacral ligament (USLs) which are the physiological holding structures. _x000D_ In this study we describe the laparoscopic cervicosacropexy (LACESA) and vaginosacropexy (LAVASA) techniques in the treatment of genital prolapse with apical descent and urinary incontinence. _x000D_ Methods The laparoscopic LACESA) and LAVASA techniques involves substituting both damaged USLs with purpose designed (identical in length and shape) PVDF-structures (polyvinylidene fluoride)._x000D_ The anterior fixation area of the PVDF-structure was centrally placed on the vault / cervical stump with 3 non-absorbable sutures. _x000D_ After identification of the L5-S1, the peritoneum was horizontally blunt dissected and the prevertebral fascial layer of S1/S2 sacral vertebra was prepared. _x000D_ The anatomical path of each USL was tunnelled and the ligament augmentation part of the PVDF-structure was placed. Using a fixation device, the PVDF-structure was attached to the lateral margin of the right and left prevertebral fascial layer of the S1/S2 sacral vertebra with 3 titanium helices on each side._x000D_ Results We report 94 women who underwent the laparoscopic CESA or VASA procedure for apical descent with a medium follow-up of 18 months. Mean age was 68 years. Preoperative, 67 women had POP-Q stage II, 21 women POP-Q stage III and 6 women POP-Q stage IV. Average operating time was 107 minutes (47 - 129 min.). 69 women had coexisting urinary incontinence (UI). No major intraoperative complications were noted except a bladder lesion and one relapse of prolapse. Within follow-up no mesh erosions were noted. Postoperative, all women had POP-Q stage 0. A 74% continence rate for urinary incontinence was noted. Conclusions The LACESA and LAVASA techniques yielded excellent anatomical correction of prolapse. The mesh used is made of PVDF, which cause milder tissue reaction and minimizing the risk of mesh shrinkage/erosions. The unique design of the PVDF structure allows restoration of the USLs with clearly defined surgical steps, making the procedure standardised and reproducible. Funding None
Authors
Sebastian Ludwig
Sokol Rexhepi Wolfram Jäger |
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V2-10 |
SURGICAL TECHNIQUE: TOTAL COLPOCLEISIS |
Female Pelvic Medicine | 17BOS |
Abstract: V2-10 Sources of Funding: none Introduction Total colpocleisis is an excellent treatment option utilizing native tissue for complete vault eversion in older women not interested in coital function. This video illustrates our surgical technique for total colpocleisis. Methods An 88 year-old female presented with pelvic organ prolapse (POP) after failing conservative management. She complained of concomitant storage and voiding lower urinary tract symptoms (LUTS), particularly stress urinary incontinence (SUI) with a pessary in place. Examination revealed complete procidentia and SUI with POP reduction. She elected to undergo total colpocleisis, and transobturator midurethral sling placement. Results The procedure began by marking of four quadrants, from the apex to bladder neck, posterior and lateral vaginal walls. Lidocaine with epinephrine was used for hydrodissection and hemostasis. The vaginal epithelium was dissected and excised in each quadrant. Purse string sutures were placed sequentially at 2-3 cm from each other until the entire prolapse was reduced. Cystoscopy was performed to ensure patency of the ureters. The anti-incontinence procedure (not shown) was performed. The anterior vaginal wall was closed, followed by posterior vaginal wall closure including a tight perineorrhaphy. Conclusions On examination at 6 months, no recurrence of her prolapse was noted. Further, the patient reported that her SUI and LUTS had resolved. Colpocleisis remains an effective and minimally invasive option for women with severe POP who are not interested in maintaining sexual function. Funding none
Authors
Rena Malik
Carlos Finsterbusch Catherine Harris Maude Carmel |
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V2-11 |
High uterosacral hysteropexy for the management of pelvic organ prolapse |
Female Pelvic Medicine | 17BOS |
Abstract: V2-11 Sources of Funding: None Introduction Hysterectomy at the time of pelvic organ prolapse repair is controversial. Uterine preserving procedures for prolapse repair may be beneficial as this allows preservation of fertility, body image and sexual function and potentially avoids an unnecessary procedure. In this video, we present our technique for transvaginal high uterosacral hysteropexy as an alternative mesh-free uterine-preserving procedure for prolapse repair and analyse our institutional outcomes. Methods This video illustrates a step by step video sequence of our technique for high uterosacral hysteropexy in a patient with symptomatic Stage III pelvic organ prolapse. We also performed a single institution, single surgeon retrospective analysis of patients treated by either high uterosacral hysteropexy or hysterectomy with high uterosacral suspension for their prolapse between 2013 and 2015. Institutional Review Board approval was obtained. We directly compared operative blood loss, pre-operative POP Q evaluation with post-operative POP Q evaluation as well as pre and post-operative American Urologic Association (AUA) Symptom scores in these 2 groups. Results Surgery time was 3 hours 24 minutes. No immediate or early complications were noted and repair was successful on follow up. The outcomes of 20 patients were assessed and summarized in the table below. Nine patients underwent high uterosacral hysteropexy alone and 11 patients underwent hysterectomy and high uterosacral suspension. Follow up was for a minimum of 6 months. Blood loss was significantly reduced in the high uterosacral hysteropexy cohort (mean: 88mls vs 232mls, p=0.004) and there was no difference in post-operative AUA symptoms scores or POP Q evaluation between the 2 treatment groups. Conclusions We present our technique of high uterosacral hysteropexy and show that this results in a significantly reduced blood loss compared to non uterine-preserving techniques and comparable post-operative outcomes suggesting that this a suitable option for pelvic organ prolapse management. Funding None
Authors
Naveen Kachroo
Solafa Elshatanoufy Humphrey Atiemo |
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V2-12 |
Vesicovaginal Fistula repair in orthotopic neobladder with pedicled island skin flap |
Female Pelvic Medicine | 17BOS |
Abstract: V2-12 Sources of Funding: none Introduction 51 y/o female patient with history of bladder cancer and subsequent orthotropic neobladder vesicovaginal fistula. She failed two attempts at closure due to necrosis of the vaginal wall. She was averse to using muscle flaps and was considering conversion to urinary diversion. A martius flap with a skin island was used to correct the defect on the anterior vaginal wall. Methods An inverted U incision was made on the vaginal wall. The intestinal mucosa was carefully separated from the anterior vaginal wall. The neobladder defect was closed in an interrupted fashion with 3-0 polyglactin sutures. A 3 x 1.5 centimeter skin island was isolated from the labia and the underlying fibrofatty tissue was mobilized. The anterior portion of the graft is ligated leaving the fibrofatty graft supplied by the posterior labial artery from the internal pudendal artery. A tunnel is developed from the vaginal incision to the labia and the graft is transferred through the tunnel to cover the vaginal wall defect. The skin island was secured to the vaginal defect with interrupted 3-0 polyglactin sutures. An indwelling foley catheter and a suprapubic tube were left in place. Results 8 weeks postoperatively the patients graft had excellent uptake. Cystoscopy was performed and there was no evidence of the neobladder defect. The neobladder was filled with methylene blue and there was no leakage to suggest persistence of the fistulous tract. 12 weeks post operatively the patient did not have recurrence of fistulous tract. Conclusions Transvaginal correction of orthotropic neobladder vesicovaginal wall fistula with martius flap and a skin island is a viable alternative for repair of large complex defects. Funding none
Authors
Daniel Hoffman
Victor Nitti |
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V3-01 |
Technical considerations for a horseshoe kidney and a posteriorly occurring renal mass: The use of intravenous indocyanine green and 4th arm in robot-assisted partial nephrectomy |
Renal Oncology | 17BOS |
Abstract: V3-01 Sources of Funding: None Introduction Horseshoe kidney is a congenital anomaly in which the fused kidneys fail to ascend to their normal position. Anatomic aberrations including renal malrotation and the presence of an isthmus can make access to the posterior renal anatomy challenging. Persistent embryonic arteries combined with variations in origin, number, and size of renal arteries contribute to the increased potential of excess blood loss during surgery. Taken together, these anatomic variations make minimally invasive surgery in horseshoe kidneys technically challenging. Although minimally invasive techniques have been utilized for partial nephrectomy (PN) in horseshoe kidneys, reporting on technical modifications during robot-assisted techniques is minimal. Here, we present a case of a renal mass located in a horseshoe kidney and describe our technique for robot-assisted PN in this patient population. Methods A 65-year-old female presented with an incidental finding of a 5.6 cm posteriorly occurring enhancing renal mass on the left lower pole of her previously undiagnosed horseshoe kidney. Workup included a CT angiogram for further evaluation of renal vasculature. Nephrometry score was 2+1+3+P+2= 8-P-H. The left moiety was fed by two renal arteries with significant distance between them, and a single renal vein inserting more distally into the inferior vena cava. The patient ultimately opted for robot-assisted PN. A fourth arm Grasping Retractor was utilized early for improved hilar retraction, and later for folding the kidney on its isthmus to create posterior access and optimal exposure during tumor enucleation. Intravenous indocyanine green (ICG) instillation was used in conjunction with near infrared fluorescence to attempt selective arterial clamping and improve intraoperative understanding of renal perfusion as well as the renal mass. Results Console time was 157 minutes with an estimated blood loss of 300 mL. Warm ischemia time was 19 minutes. The patient was discharged on post-operative day one. There were no perioperative complications. Pathology revealed a 5.7 cm oncocytoma. Conclusions We demonstrate that using ICG and the 4th arm are technical considerations that can assist with robot-assisted PN in a horseshoe kidney, especially for posteriorly occurring tumors. Funding None
Authors
Randall Lee
Laura Giusto Benjamin Waldorf Daniel Eun |
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V3-02 |
Transperitoneal Robot Assisted Inferior Vena Cava Filter Extraction: You Already Know How to Do This! |
Renal Oncology | 17BOS |
Abstract: V3-02 Sources of Funding: none Introduction In this video we present a technique for robotic removal of an inferior vena cava filter (IVCF) not amenable to endovascular retrieval. Our technique mirrors our established technique for robotic removal of a level I or level II caval thrombus associated with renal cell carcinoma. The index patient is a healthy 31-year old male experiencing epigastric discomfort attributed to a permanent caval filter placed 10 years prior, with radiographic evidence of IVC extrusion. Methods The patient is positioned in the right-side-up modified flank position. The colon is mobilized and athermal Kocherization of the duodenum is performed with awareness that any extruding struts of the IVCF may perforate adjacent organs. The filter is easily visualized within the exposed cava. After circumferential dissection of the cava above and below the IVCF, occlusion of the IVC is accomplished by placing modified Rummel tourniquets in the form of vessel loops doubly wrapped around the IVC and the bilateral renal veins. To avoid significant blood loss, it is crucial to ligate, bipolar, or staple all lumbar veins. Intravascular heparin is given before tightening the tourniquets. Control of the renal arteries is not necessary. Cavotomy is performed once all inflow is controlled so that a bloodless field is maintained during IVCF extraction. Struts of the filter that have eroded through the vena cava may be broken and removed prior to opening the cava, otherwise the struts can be pulled into the lumen of the vena cava once open, with minimal risk of caval tearing. Caval reconstruction is accomplished with a running 4-0 permanent monofilament suture. Heparinized saline is flushed through the cavotomy prior to closure and before releasing tourniquets to reestablish blood flow. Results Operative time was 189 minutes. IVC occlusion time was 25 minutes. Estimated blood loss was 800 ml in this case due to an unrecognized lumbar vein. The patient was discharged to home on postoperative day two. There were no intraoperative or postoperative complications. The patient was continued on 81 mg aspirin at discharge and prophylactic enoxaparin for three weeks. Pain symptoms had improved at 3 month follow up. Conclusions This video demonstrates a stepwise technique for transperitoneal robot assisted IVC filter extraction. Urologists with adequate robotic experience in robotic nephrectomy with level I-II IVC tumor thrombus should feel comfortable approaching robotic IVC filter retrieval. It is important to have multidisciplinary support, adequate preoperative imaging, and be familiar with the IVC filter design. Funding none
Authors
Sean McAdams
Haidar Abdul-Muhsin Victor Davila Sailendra Naidu Samuel Money Erik Castle |
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V3-03 |
Robotic Left-sided Level II Caval Thrombectomy and Nephrectomy: Primary Description of Novel Supine, Single-dock Approach. |
Renal Oncology | 17BOS |
Abstract: V3-03 Sources of Funding: None. Introduction Initial descriptions of robotic management of renal cell carcinoma with Inferior Vena Cava (IVC) thrombus employ a lateral approach predicated on early IVC exposure and control. However, for left-sided renal masses and associated tumor thrombi, this approach requires re-positioning and re-docking steps, as well as pre-operative left renal artery embolization. Herein, we describe a novel supine, single dock technique for robotic left nephrectomy and caval thrombectomy. Methods We perform robotic nephrectomy and caval thrombectomy on a 79 y.o. male with a 6cm left renal mass and level II IVC thrombus. The patient is placed supine, in steep trendelenburg. We employ a 6-port trans-peritoneal technique and dock the robot such that arms are directed cephalad. Key steps critical to the procedure include: 1) Exposure of the retroperitoneum 2) IVC exposure and control 3) Left Renal Hilar Control 4) Cavotomy, thrombectomy, and reconstruction 5) Nephrectomy and lymph node dissection (LND). Peri-operative outcomes are reported and compared to previously published case series. Results Robotic left nephrectomy and level II caval thrombectomy was performed successfully via a single-dock, supine approach. This method yielded excellent and early access to the IVC and left renal hilum, and allowed for concomitant nephrectomy/LND without re-positioning. Total operative time was 420 minutes with 330 minutes robotic console time (174 minutes for exposure, 27 minutes IVC clamp time, 84 minutes for nephrectomy/LND). EBL was 500cc without need for peri-operative transfusions and no intraoperative complications. Length of stay was 5 days and no major perioperative complications were noted. Outcomes compare favorably to previously reported robotic caval thrombectomy procedures employing the lateral approach. Conclusions We demonstrate successful robotic left nephrectomy with Level II caval thrombectomy using a supine, single-dock approach. To our knowledge, this is the first description of this approach for robotic caval thrombectomy. In appropriately selected patients, this versatile approach allows for rapid caval control, bilateral renal hilar access, and obviates the need for patient re-positioning. Funding None.
Authors
Monty Aghazadeh
Spencer Craven Alvin Goh |
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V3-04 |
Precision Surgery in Robotic Partial Nephrectomy |
Renal Oncology | 17BOS |
Abstract: V3-04 Sources of Funding: None Introduction Current paradigms in partial nephrectomy (PN) for localized renal tumor support a minimally-margin size with limited ischemia where possible, even in the most complex of cases. However, there is as yet no standardized assessment or planning procedure for Robotic partial nephrectomy (RPN). Methods Here we present our technique for Robotic Partial Nephrectomy Precision Surgery. This technique combines patient-specific imaging assessment by Virtual PN and surgical navigation intra-operatively with cognitive fusion. Results Case1: The 49-year-old woman, with right non-functional kidney was referred by the 5.2cm left renal tumor located in the renal hilum and tumor thrombus in the renal vein in a functional solitary kidney. The tumor biopsy revealed the clear cell carcinoma. After administration of molecular targeted medicine for 6 months with tumor shrinkage to 4.7cm, R.E.N.A.L. nephrometry score 10a, RPN was conducted. Preoperative Virtual PN revealed that the selecting clamping was not appropriate for this case, and provided the case specific margin size (1-2mm) and anatomical visualization of the intrarenal structures, tumor, renal arteries, veins, tumor thrombus, and renal pelvis, and their location in color-coded manner. RPN was performed with intra-operational image guidance in 19 min warm ischemia time (WIT), 50ml estimated blood loss (EBL), and negative surgical margin. Post-operative creatinine level was same as pre-operative level 0.89, and the dialysis was not required. Case 2: 56-year-old woman with totally endophytic renal tumor sized in 2.5cm and the nephrometry score was 8a was underwent RPN. Prior the operation, the 3rd arterial branch was identified for the point of selective clamping by the Virtual PN. RPN was performed with intra-operational image guidance of the targeted artery, with WIT being 18 min, with EBL being 100ml and with negative surgical margin. Pre-operative creatinine was 0.59 and post-operative creatinine was 0.58. There were no complications in either case. Conclusions Robotic Partial Nephrectomy combined with 3D navigation, Virtual PN, and intra-op surgical navigation may allow “Precision Surgery� to preserve renal function by minimizing the excision margin and limiting ischemic area. Funding None
Authors
Shuji Isotani
Michael Stifelman Shigeo Horie |
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V3-05 |
Robotic assisted laparoscopic tumor enucleation with artery hypothermic perfusion combined with neoadjuvant target therapy for a multifocal solitary kidney cancer |
Renal Oncology | 17BOS |
Abstract: V3-05 Sources of Funding: none Introduction Our patient is a 61 year old female who underwent radical nephrectomy on the right side 8 years ago. Multiple renal masses were found by ultrasound during the latest follow up. Subsequent imaging confirmed 3 tumors in the left kidney with 5.5cm in the greatest dimension. Methods This patient underwent 3 circles of neoadjuvant target therapy with Axitinib. All of three tumors shrinked after therapy with decreased enhancement and clearer tumor capsule in the CT imaging. A balloon was placed into the left renal artery by an interventional radiologist before surgery. We began the procedure by mobilizing the colon. Then we identified the renal vein and all of its branches. After the lumbar vein was disconnected, the renal artery can easily be dissected. After defat, the kidney was totally mobilized. After occlusion of the artery, the renal vein was clamped. During infusion of cold Ringer’s solution, we started enucleation from the largest tumor. The parenchyma close to the tumor was resected until the capsule was identified. The tumor was enucleated by combining sharp and blunt dissection using tumor capsule as the anatomical landmark, with no visible rim of normal parenchyma. Tumor thrombosis was find invading into the branch of the renal vein and was separated from the tumor. The second tumor was identified at the edge of the first tumor and was enucleated with the same technique. The thrombosis was resected and no visible tumor was left on the tumor bed. Collecting system was found ruptured and was closed by running suture with 3-0 monofilament. No additional suture was performed on the tumor bed. The parenchyma defect was closed with horizontal interrupted 2-0 Monocryl sutures with Hem-o-lok clips placed on the kidney capsule. The third tumor at the upper pole was enucleated similarly. Once the stitches were placed, the clamp of the renal vein was removed and occlusion of the artery was released. Results Perioperative date revealed estimate blood loss of 200 ml and warm ischemia time of 68 minutes. The patient underwent anuria for 2 hours and the serum creatinine elevated to 3.4 mg/dl 48 hours after surgery and dropped down to 1.5mg/dl after one month. Final pathology revealed a pT3a clear cell carcinoma. No residue tumor was revealed in the enhanced CT during follow up. Conclusions In summary, complicated renal cancer, especially solitary cancer need individualized treatment. Tumor enucleation assisted with target therapy and robotic technique seems like a feasible strategy to realize tumor free and maintain renal function. Funding none
Authors
Xiaozhi Zhao
Hongqian Guo |
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V3-06 |
Conventional Laparoscopic Radical Nephrectomy with inferior vena cava thrombectomy |
Renal Oncology | 17BOS |
Abstract: V3-06 Sources of Funding: none Introduction In the past decade, the options of targeted therapy agents, for the treatment of advanced and metastatic renal cell carcinoma (RCC) has significantly increased. This increase has lead to a migration of targeted therapy agents from salvage to the neoadjuvant setting for large unresectable masses, venous tumor thrombus involvement, and patients with imperative indications for nephron sparing._x000D_ Venous tumor thrombus involvement of Inferior vena cava (IVC) is a complicating factor that occurs in up to 10% of cases of patients with renal cell carcinoma (RCC), of which nearly one-third of patients also have concurrent metastatic disease. The surgical management with laparoscopic technique for renal cell carcinoma with IVC tumor thrombus remains challenging and technically demanding in urological oncology. Our objective is to describe the surgical technique of a right pure conventional laparoscopic Radical Nephrectomy with (IVC) thrombectomy in a patient with level II thrombus who receive neoadjuvant target therapy. Methods A 78-year-old male with lung metastatic renal cell carcinoma cT3bN1M1, received target therapy in neoadjuvant setting and after improving in the Memorial Sloan-Kettering Cancer Center Score for Metastatic Renal Cell Carcinoma (MSKCC/Motzer) and International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic scores, underwent cytoreductive nephrectomy with thrombectomy of IVC._x000D_ We report one case of right pure conventional laparoscopic radical nephrectomy and thrombectomy of the level II (infrahepatic) tumor thrombus in the IVC._x000D_ To do this, IVC was isolated, the right gonadal and lumbar veins were ligated and transected. The infrarenal IVC, left renal vein and infrahepatic IVC blood flow were controlled with a bulldog clamp. After thrombectomy of the IVC, the wall defect was sutured with continuous Prolene suture and then a laparoscopic radical nephrectomy was performed._x000D_ Results The operative time was 300 min and the IVC clamping time was 15min. The estimated blood loss was 700 ml, and no major intraoperative or postoperative complications occurred. The patient was discharged from hospital 3 days after the surgery without needing critical care unit. Conclusions Laparoscopic radical nephrectomy with thrombectomy for renal cell carcinoma with tumor thrombus level II is a safe, reproducible and technically feasible technique, which can be applied to a specific population of patients but also is challenging and requires advanced laparoscopic skills. Funding none
Authors
Giuliano Guglielmetti
Henrique Nonemacher George Lins de Albuquerque Rafael Coelho Mauricio Cordeiro Willian Nahas |
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V3-07 |
Salvage Robotic Partial Nephrectomy After Cryoablation |
Renal Oncology | 17BOS |
Abstract: V3-07 Sources of Funding: None Introduction Focal therapy with cryoablation (CA) or radiofrequency ablation (RFA) is a treatment option for small renal masses, however reported recurrence rates are 10-13% (Novick, 2009). Salvage partial nephrectomy after CA is challenging due to significant desmoplastic reaction and scarring, which has been noted to be more severe than RFA. Increased complications have also been reported in post CA versus RFA patients. Robotic salvage partial nephrectomy is uncommonly reported. We describe a unique case of salvage robotic partial nephrectomy 5 years after CA. Methods A 60 year old healthy male was found to have a 2.8 cm right lower pole mass and he was treated with cryoablation therapy. He was asymptomatic, but remained on surveillance with periodic imaging. Five years later, he was found to have a 3.2 cm enhancing renal mass with calcifications, concerning for malignancy. He was referred to us for salvage robotic partial nephrectomy. Results We utilized a standard transabdominal approach using a 6 port robotic technique. The colon was reflected medially. The inferior vena cava was identified. The ureter was significantly scarred and was in close proximity to the mass. Hilar dissection revealed a single renal artery and two renal veins. The kidney and mass were exposed. The ureter was adherent to the tumor and was carefully freed. Ultrasound guidance was used to demarcate the tumor. After hilar clamping, the mass was excised using a monopolar scissors. 3-0 v-loc suture was used to repair the calyceal openings and oversew the tumor bed. A 2-0 V-loc suture was used for the renorraphy using the running sliding hem-o-lok clip technique. Clamps were removed and good hemostasis was confirmed. Surgicel and Tisseel were applied to the defect. A JP drain was placed. Operative time was 162 minutes with 34 minutes of warm ischemia time. _x000D_ _x000D_ The foley catheter was removed the day after surgery. The patient was discharged home on postoperative day 1 with the drain despite drain creatinine being consistent with serum. It was removed in the office on postoperative day 3. Final pathology was grade 2 pT1a clear cell renal cell carcinoma with negative margins. Renal function was normal at four and 6 month follow up. Imaging did not reveal any evidence of recurrence. Conclusions In experienced hands, salvage robotic partial nephrectomy after cryoablation is challenging but feasible with acceptable warm ischemia time. As demonstrated in the video, robotic approach allows for adequate visualization and meticulous renorrhaphy. Funding None
Authors
Joan C. Delto
Alan M. Nieder Akshay Bhandari |
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V3-08 |
Partial nephrectomy of an Endophytic Mass in a Horseshoe Kidney |
Renal Oncology | 17BOS |
Abstract: V3-08 Sources of Funding: none Introduction Nephron sparing surgery, specifically robotic assisted laparoscopic partial nephrectomy, has become a widely accepted treatment choice for small renal masses. Renal fusion abnormalities, such as horseshoe kidney, are uncommon congenital findings with a frequency of approximately 1 in 200 in the general population. Renal fusion abnormalities change the position and orientation of the kidney, and complicate the treatment of renal disorders. We demonstrate our technique for the management of a complex, endophytic cT1b renal mass in a horseshoe kidney. Methods A 73-year-old African-American gentleman with a history of CHF as well as COPD and a 50-pack-year history of cigarette smoking had an incidentally discovered horseshoe kidney on a contrasted CT scan of the abdomen ordered for abdominal pain, as well as an endophytic, complex cystic mass within the superior pole of the left portion of the kidney measuring 4.7 x 4.5 x 3.7 cm. This mass was assigned a 10AH on the nephrometry scoring scale. He placed in the modified flank position and the da Vinci Xi surgical system was used to target the left flank. After dropping the colon and the colorenal ligaments, we were able to identify the hilum, including the renal hilum, and the complex vascular anatomy. We used endoscopic ultrasound to target the tumor, and we undertook a circumferential resection of the mass. Final warm ischemia time was 24 minutes 32 seconds. We performed a two layer renorrhaphy, which was hemostatic at the conclusion of the procedure. Results The patient did well postoperatively. His serum creatinine preoperatively was 1.3, and at the time of his discharge on postoperative day 3, it had returned to baseline. Final pathology showed papillary renal cell carcinoma type 1, Fuhrman nuclear grade 3, 4.2cm in maximal dimension. The surgical margin was negative for malignancy. The patient is currently awaiting follow up cross sectional imaging. Conclusions Robotic assisted laparoscopic partial nephrectomy can be a valuable addition to the urologist’s armamentarium for the treatment of complex renal masses identified in horseshoe kidneys. Funding none
Authors
Gregory Mitchell
Russell Libby Jonathan Silberstein Raju Thomas |
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V3-09 |
Nephron-sparing laparoscopic partial nephrectomy after superselective embolization of a renal tumor in a hybrid operating room: a new approach of zero ischaemia |
Renal Oncology | 17BOS |
Abstract: V3-09 Sources of Funding: none Introduction To perform nephron-sparing surgery, arterial clamping is often required. Operative bleeding control is difficult in laparoscopic techniques. We imagined a novel technique for "zero ischemia" nephron-sparing surgery using a hybrid opearating room: clampless laparoscopic partial nephrectomy was performed after superselective tumoral embolization. Our objective is to describe this new technique. Methods The patient is a 46 year old patient with no prior medical history, who had a 3 cm large localized renal tumor on the convexity of the left kidney. The lesion was heterogeneous, medial, partially endophytic and of moderate complexity (RENAL 8p). The procedure was realized in a hybrid operating room by a double team: interventional radiologist and urologist. Results A first renal arteriography was made to visualize the arterial vascularization of the left kidney. With a guidance software, the tumoral artery was catheterized superselectively. The tumor and its arteries were embolized by microspheres and coils. A 3D arteriography showed the exclusion of the tumor from the renal vascularization. Then, the patient was positionned for laparoscopic partial nephrectomy, thas was performed without dissecting the renal pedicule, nor clamping of the renal artery. Operative bleeding was insignificant. No suture was necessary. A final control 3D arteriography showed no arterial bleeding and preservation of healthy renal parenchyma. Follow-up was uneventful. Preoperative renal function was maintained. The tumor was a clear cell renal carcinoma. Surgical margins were negative. Conclusions This is the first experience of superselective tumoral embolization followed immediately by laparoscopic partial nephrectomy in a hybrid operating room. Resection of a localized renal cancer of moderate complexity was performed clampless, sutureless and without intraoperative bleeding. Funding none
Authors
Paul Panayotopoulos
Antoine Bouvier Pierre Bigot |
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V3-10 |
Robotic-assisted laparoscopic nephrectomy of an auto-transplanted kidney for recurrent renal cell carcinoma |
Renal Oncology | 17BOS |
Abstract: V3-10 Sources of Funding: None Introduction Advances in robotic technology continue to expand the boundaries of minimally invasive renal surgery for both benign and malignant conditions. A single report has previously described the use of the robotic approach in transplant nephrectomy for a failed allograft. _x000D_ Herein, we present the first robotic-assisted laparoscopic nephrectomy of an auto-transplant kidney for a tumor recurrence, in a unique case of a solitary kidney that had previously undergone ex vivo partial resection for a complex renal cell carcinoma. Methods The patient is a 64-year-old man with a history of a solitary left kidney after a radical right nephrectomy several years ago for a clear cell renal cell carcinoma. After discovery of a new centrally located left renal mass on surveillance, he underwent nephron-sparing surgery by laparoscopic nephrectomy followed by ex vivo partial nephrectomy and auto-transplant to the right iliac fossa. He subsequently developed a recurrence near the renal pelvis which was initially stable for four years on tyrosine kinase inhibitor therapy. The tumor then increased in size after therapy was discontinued due to toxicity. He was counseled on his surgical options for a radical auto-transplant nephrectomy and elected for a robotic approach. The procedure was completed transperitoneally using the da Vinci Si Surgical System. The patient was positioned supine with the robot side-docked over the right iliac fossa. Three robotic arms were utilized in addition to two assistant ports. Results The total operative time was 387 minutes with an estimated blood loss of 800 mL. The patient received 2 units of packed red blood cells intraoperatively. The patient had an unremarkable postoperative course and was discharged on day 3. There were no perioperative complications. Pathology revealed recurrent 8.2cm clear cell renal cell carcinoma, Grade IV involving the renal vein with negative surgical margins. Conclusions Robotic transplant nephrectomy has previously been shown to be safe and feasible in the management of a failed allograft. We report on our technique and experience with the additional technical demands of a previously operated auto-transplant kidney. A minimally-invasive approach can potentially reduce the morbidity of this uncommon and complex procedure. _x000D_ Funding None
Authors
Belinda Li
Parth Patel Alex Gorbonos |
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V3-11 |
Robotic partial nephrectomy involving intracorporeal cold ischemia for post cryoablation failure |
Renal Oncology | 17BOS |
Abstract: V3-11 Sources of Funding: none Introduction The reference standard treatment for small renal masses is partial nephrectomy, and the robotic approach has become rapidly adopted in this setting. However, minimally invasive approach to partial nephrectomy can be complicated by previous surgery or percutaneous renal ablative therapy. The ideal approach to partial nephrectomy is unknown in this setting. We present a surgical video of a 62 year old female with a previous left renal cryoablation, who developed an ipsilateral recurrent left renal mass in the previous ablative zone. We performed a robotic partial nephrectomy utilizing intracorporeal cold ischemia. Our surgery is technically innovative in that we introduce a method for providing cold ischemia through a minimally invasive robotic approach in the setting of cryotherapy failure. Methods The Da Vinci Xi (Intuitive Inc, Sunnyvale, CA, USA) robotic platform was utilized with a 4 arm approach. Robotic ports were placed in a linear configuration lateral to the rectus muscle and an assistant port near the umbilicus. An additional 15mm accessory port is placed near the 12th rib for introduction of ice slush. Modified 20mL syringes are used to deploy ice slush through the 15mm accessory port. The renal artery is clamped and the tumor completely excised. Renorrhaphy was performed with adequate hemostasis. Results Estimated blood loss was 50mL Cold ischemia time was 83 minutes. Final pathology revealed clear cell renal cell carcinoma, Fuhrman grade 2, 2.0cm, with negative margins, pT1a. Follow up renal functional studies showed a GFR >60 mL/min/1.73m2 at 6 month follow up. Conclusions Robotic partial nephrectomy in the setting of percutaneous ablative failure is technically feasible and can be performed with the addition of ice slush cold ischemia. Further study is requisite to confirm these results. Funding none
Authors
Zachary Hamilton
Omer Raheem Ithaar Derweesh |
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V3-12 |
Robot Assisted Partial Nephrectomies – 12 Tumors, 1 Kidney |
Renal Oncology | 17BOS |
Abstract: V3-12 Sources of Funding: None Introduction Tuberous sclerosis is a rare hereditary disorder caused by the decrease or loss of expression of the TSC1 or TSC2 tumor suppressor gene, resulting in an increase in activation of the mTOR pathway. Renal angiomyolipomas (AMLs) occur in up to 60% of patients with tuberous sclerosis. The risk of hemorrhage from AMLs increases with tumors larger than 4 centimeters. Elective AML treatment includes arterial embolization, ablation or nephron-sparing excision, if possible. Everolimus, an mTOR inhibitor, is FDA approved to reduce angiomyolipoma size in patients with tuberous sclerosis. We hypothesize that Everolimus may decrease the vascularity of the tumors and help minimize bleeding during surgery. Methods An 18 year-old female was referred to our clinic for evaluation of multiple bilateral angiomyolipomas. She had been on Everolimus for several years and had undergone several unsuccessful embolizations at an outside facility. MRI of the abdomen showed more than 30 angiomyolipomas in the left kidney and more than 20 in the right kidney. The largest tumors in the left kidney measure 4 centimeters, 2.7 centimeters, and 2 centimeters. A renal scan indicated relatively equal kidney function. The patient went to the operating room for robot assisted left partial nephrectomies. Twelve tumors were enucleated without hilar clamping. The 2 largest tumor defects were closed with a sliding clip technique renorrhaphy. Hemostatic matrix was placed for additional hemostasis. Total operative time was 3 hours and total robot console time was 2.5 hours. Results Twelve tumors were excised with the largest measuring almost 5 centimeters. There were no intraoperative or postoperative complications. Her hemoglobin nadir was 10.2 g/dL from a preoperative value of 11.7 g/dL. Postoperatively her creatinine stayed stable at 0.6 mg/dL. She was discharged home on postoperative day 2. Conclusions Robot partial nephrectomies for multiple angiomyolipomas is a feasible, safe, and effective option in patients with tuberous sclerosis who wish to preserve renal function while pursuing surgical management. Everolimus may contribute to the lack of vascularity noted in these lesions with minimal bleeding during surgery. Funding None
Authors
Karen Stern
Catherine Chen Gwen Grimbsy Thai Ho Erik Castle |
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V4-01 |
Patient specific rehearsal using 3D printing for complex partial nephrectomy cases |
Imaging/Uroradiology | 17BOS |
Abstract: V4-01 Sources of Funding: none Introduction The benefits of surgical simulation have been previously demonstrated to enhance technical skills with a downstream effect of improved patient outcomes. However, other methods to utilize simulation technology remain under-explored. One area of simulation that has proven to be difficult is the creation of a high fidelity process that accurately and reproducibly simulates individual anatomy and pathology (i.e. patient specific simulators). Advances in 3-D printing and polymer technology, coupled with software that incorporates imaging data into a computer design, make it possible to develop individualized models from patient imaging data. We present the feasibility of patient-specific preoperative rehearsal using 3D processing & printing in complex partial nephrectomy cases. Methods Three patients with enhancing renal lesions suspicious for renal malignancy with complex tumor morphology or significant comorbidities were chosen for preoperative simulation and rehearsal. DICOM files of patients C.T. angiography (CTA) were imported into 3D processing software to create virtual models of kidney parenchyma incorporating the tumor, renal vasculature, and pelvicalyceal system. Surgical phantoms were created using 3D printing and polymer hydrogels, for patient-specific surgical rehearsal. For whole task preoperative surgical rehearsal, other relevant anatomical elements (bowel, perinephric fat, solid organs and bony structures) were incorporated into a replicated hemiabdomen. _x000D_ Results All 3 preoperative simulations were completed prior to the live case. Partial nephrectomy was successful in all 3 cases with an average blood loss of 300cc and WIT of 20 minutes. For the first case, preoperative 3D processing and hydrogel kidney aided in assessing the depth of resection of a completely endophytic tumor and predicted violation of the pelvicalyceal system in the live case. In the 2nd case, the preoperative rehearsals ascertained the feasibility of completing partial nephrectomy in a 9 cm upper pole mass. In the final case, the preoperative rehearsals confirmed the feeding vessel and viability of selective ischemia with his existing coagulopathy and nephropathy. _x000D_ Conclusions This initial trial demonstrates that patient-specific procedural rehearsal is effective for enhancing the performance of surgeons during a complex minimal invasive procedure. This transition from generalized to patient-specific simulation may have the potential to impact patient outcomes by permitting preoperative rehearsal. _x000D_ Funding none
Authors
Jonathan Stone
Rachel Melnyk Guan Wu Hani Rashid Jean Joseph Ahmed Ghazi |
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V4-02 |
Gold Nano-Particle Directed Focal Laser Ablation for Prostate Tumors using US and MR Fusion Technology |
Imaging/Uroradiology | 17BOS |
Abstract: V4-02 Sources of Funding: Funded Trial by Nanonspectra Biopsciences Introduction : A growing collective proficiency in multiparametric magnetic resonance imaging (mpMRI) and targeted biopsies for prostate cancer (PCa) screening has given way to an increasing interest in the application of these technologies for targeted therapy. Various targeted therapies have been developed and evaluated; however, these treatments focus energy at a region of the prostate, as opposed to directly at the tumor. Gold nanoparticle (GNP) therapy is a novel treatment that results in tumor-specific ablation, sparing surrounding tissue and structures. Herein, we report the first two cases in the world using gold nanoparticle-directed focal laser ablation of prostate tumors targeted with ultrasound (US) and MR/US fusion technology. Methods Patients were enrolled in a phase II trial, &[prime]A Study of MRI/US Fusion Imaging and Biopsy in Combination with Nanoparticle Directed Focal Therapy for Ablation of Prostate Tissue.&[prime] Treatment and follow up plan are as follows: intravenous infusion on day 0, which allows GNP deposition into the tumors with the goal of achieving a 15.2 µg/cc tumor concentration required for excitation/ablation. On day 1, the patient presents for focal laser excitation of the GNPs. Laser catheters are placed using a combination of US and a transperineal electromagnetic-tracked MR/US fusion device (Invivo, Gainesville, FL). 48 hours’ post-ablation, the patient is imaged, fig 1, followed by re-imaging and MR/US fusion guided biopsy (FBx) at 3 months. All patient demographics, clinical variables, and complications were recorded. Results To date, 2 patients have been enrolled in the trial, both with localized Gleason 7 PCa diagnosed using MR/US FBx. Mean age was 67 + 4.3 years and mean prostate specific antigen was 6.1 + 0.06 ng/ml. The mean tumor volume was 0.40 + 0.05 cc with a solitary lesion in each patient. The mean PSA decrease was 3.6 + 0.6 ng/ml, a 40.9% decrease at 1 month. No short-term complications were observed. The first patient underwent a follow up FBx at 3 months with no detectable cancer. Conclusions Increasing interest in image guidance technologies and focal therapies has sparked a new generation of PCa treatment modalities. We have demonstrated the first safe and effective use of ultra-focal therapy using MR/US fusion technology in concert with GNP directed therapy to treat prostate tumors. Funding Funded Trial by Nanonspectra Biopsciences
Authors
Jared S Winoker
Pratik A Shukla Michael A Carrick Harry Anastos Cynthia J Knauer Ashutosh K Tewari Bachir M Taouli Sara C Lewis Jon A Schwartz Joshua M Stern Steven E. Canfield Ardeshir Rastinehad |
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V4-03 |
CT/MRI-US Fusion Guided Renal Mass Biopsy: Initial Experience |
Imaging/Uroradiology | 17BOS |
Abstract: V4-03 Sources of Funding: None Introduction The Real-time Virtual Sonography (RVS) system allows image-fusion of real-time live US with pre-operative contrast-enhanced CT/MRI. Both real-time US and fused-image of CT are real-timely displayed in parallel in US-machine. The objectives are to assess the feasibility and safety of a pilot study for offie RVS-guided renal mass biopsy (RMB)._x000D_ Methods Pre-operative: After 8 hours of fasting, the patient is placed in prone position in outpatient facility and monitored. US/CT registration: The DICOM data of a previous CT scan or MRI is loaded into the RVC system. The image is rotate to be at the same orientation of the patient. The kidney of interest and the plane with a reference point that a shows a good window to puncture the renal mass is selected.The kidney of interest is then US-scanned and the images are compared with the CT scan. When the images match to each other the plane with the reference point is fused with pre-operative contrast CT scan using the RVS system. The kidney is scanned and the best location to target the renal mass is selected. Co-axial needle technique: A 17G hollow needle is connected to a needle-guide under 21-degree inclination and attached to the US probe. Under local anesthesia, a 17G hollow-needle, is first placed along the planned puncturing dotted-line toward the renal mass up to the Gerota&[prime]s fascia. Biopsy: A 18G biopsy-gun is inserted through the co-axial-outersheath, advanced along the planned puncturing dotted-line upto the tumor and is fired to obtain the biopsy-tissue from the tumor. Usually two to three cores are taken, all through the hollow needle. Results From April to June of 2014, 13 patients underwent RMB. Only single-use of local anesthesia was required in all cases. Co-axial needle technique facilitated (i) visualization of the biopsy-needle in live US, (ii) multiple-sampling through it, and (iii) decreasing the seeding risk of malignant cells. RVS system facilitated targeting the contrast-enhanced lesion, as it improved visualization of important anatomical landmarks. Intra-operatively accompanied pathology-team was important to determine the adequacy of tissue-sampling. Biopsy histology was concordant with surgical specimen in 7 of 10 patients undergoing surgery. Additionally, 2 patients with histology of oncocytoma chose active surveillance. There were no complications. Conclusions Outpatient RMB performed by urologist is safe and promising. This was achieved using local anesthesia, co-axial needle technique, and intra-operative co-operation with pathology-team, and introduction of real-time image-fusion technology of live US with contrast CT/MRI. Funding None
Authors
Andre Abreu
Sameer Chopra Carlee Beckler Masakatsu Oishi Nariman Ahmadi Toshitaka Shin Andre Berger Mihir Desai Monish Aron Inderbir Gill Osamu Ukimura |
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V4-04 |
Novel Use of Fluorescence Lymphangiography During Robotic Groin Dissection for Penile Cancer |
Imaging/Uroradiology | 17BOS |
Abstract: V4-04 Sources of Funding: none Introduction Indocyanine green (ICG) lymphangiography has been used to detect lymphatic channels under fluorescent light and to aid in the excision of affected lymph nodes. We describe our novel technique of robotic inguinal lymphadenectomy with near infrared fluorescence imaging using ICG to facilitate lymph node identification during robotic groin dissection for penile cancer. Methods Using a high definition recording system and iMovie software with narrative and annotative editing, we created a video of our novel technique for robotic inguinal lymphadenectomy with near infrared fluorescence imaging using the Surgical Intuitive Da Vinci Xi robot. Robotic ports are placed in a V configuration at the tip of the femoral triangle after development of the working space by blunt finger dissection. Intradermal ICG is injected at the penile stump or base (0.5 ml of 2 mg/kg concentration in normal saline) and the lymphatic channels and nodes are visualized with near infrared fluorescence imaging in the robotic console approximately 15 minutes after injection. The surgical template established via the open approach is then replicated. Results A total of 8 groin dissections have been completed using this technique with a mean lymph node yield of 8 per groin (range 5-16 lymph nodes). With a follow up ranging from 3-16 months, there have been no post-operative infections, lymphatic leaks, wound breakdown, or necrosis. All pathologically proven nodes were identified intra-operatively with ICG. Conclusions Our novel technique of robotic inguinal lymphadenectomy with fluorescence lymphangiography using ICG facilitates identification of lymph channels and nodes. It is reproducible, safe, and helps ensure complete excision of both superficial and deep lymph nodes during groin dissection for penile cancer. This technique may dramatically decrease the morbidity compared to the open technique without compromising oncologic efficacy. Further prospective studies are required to assess the long term results of this procedure. Funding none
Authors
Alexander P. Kenigsberg
Marc A. Bjurlin Alon Y. Mass Lee C. Zhao William C. Huang |
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V4-05 |
Impact of the 20 G all-seeing needle and 4.8 Fr micro PCNL with the High Definition Image Guide (HDIG) system |
Imaging/Uroradiology | 17BOS |
Abstract: V4-05 Sources of Funding: None Introduction PCNL is the first-line therapy for large and complex renal calculi. To perform PCNL safely and effectively, the most important step is the formation of a nephrostomy tract and tract dilatation. Furthermore, as fine a nephroscope as possible is required for micro PCNL. In this clinical study, renal puncture using 20 G all-seeing needle and 4.8 Fr micro PCNL were performed for large renal stone using a micro-optic disposable scope. Methods The Φ0.65 mm scope with the High Definition Image Guide (HDIG) system reported in previous WCE held in Taiwan (2014) was adopted. The scope consists of an integrated light lead and the micro fiber optic including a Φ0.5 mm precise object lens and optical glass fiber, where real-time HD images can be seen through the digital image processing device. The scope can be set inside a 20 G puncture needle or 4.8 Fr metal sheath which can simultaneously include the micro-optic scope, 0.018 inch guidewire and 200 µm laser fiber. These devices are developed as part of a collaborative research with Takei Medical & Optical Co. Ltd. (Tokyo, Japan) and Sumita Optical Glass Inc. (Saitama, Japan) funded by Utsukushima Next-Generation Medical Industry Agglomeration Project between 2012 and 2014. After evaluating safety, optical quality and operation performance in an animal study, the clinical study authorized by the ethical committee of Okayama University Hospital was carried out from June 2013. The procedures of micro PCNL are as follows; ultrasound-guided renal puncture using 20 G all-seeing needle, removal of the scope followed by insertion of 0.018 inch guidewire, dilatation by metal introducer, insertion of 4.8 Fr metal sheath into renal calyx, insertion of the HDIG scope into the sheath, complete fragmentation of calculi by Ho-YAG LASER without removal of the fragments. Results A 68-year old male with renal calculi 21 mm in diameter in left lower calyx once underwent the puncture and the micro PCNL. After the operation, spontaneous discharge of fragmented calculi through lower urinary tract was observed and abdominal X-ray on POD 21 showed no fragment in his left kidney. No adverse event was occurred except slight elevation of serum creatinine during only a week postoperatively. Conclusions The micro-optic disposable scope with the HDIG system is extremely useful for safer puncture and finer PCNL. We are now planning to adopt it to percutaneous procedure for urothelial carcinoma in upper urinary tract. Funding None
Authors
Koichiro Wada
Hiromi Kumon Ryuta Tanimoto Yosuke Mitsui Takuya Sadahira Atsushi Takamoto Yasuyuki Kobayashi Katsumi Sasaki Motoo Araki Toyohiko Watanabe Yasutomo Nasu |
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V4-06 |
THE DEVELOPMENT OF A WEB-BASED VIDEO PLATFORM FOR TEACHING THE ROBOTIC SIMPLE PROSTATECTOMY |
Imaging/Uroradiology | 17BOS |
Abstract: V4-06 Sources of Funding: none Introduction The vast majority of resident surgical teaching in the United Sates is performed in the operating room. Instructional feedback on technique is nearly exclusively given at the time of surgery. However, this current model poses problems in the modern era due to pressures for increased surgical throughput and resident duty hour restrictions. We have developed a web-based, interactive platform that uses novel video technology (compatible with most media devices) to enhance surgical teaching. We have taken the first step in implementing the training platform by assessing the platform’s usability to teach the robotic simple prostatectomy and to ensure trainee participation using a validated, industry standard questionnaire. Methods All urology surgical trainees at our institution were given access to a web-based surgical training platform. This platform allows trainees to easily upload video segments of surgeries they performed for expert (attending physician) review. The experts are alerted through email and are prompted to give text based comments as feedback. The feedback is embedded within the video and is time congruent to the task being performed. The trainees are alerted to the reviewer’s comments and are prompted to review the video containing expert feedback. To evaluate the platform as a teaching tool, the trainees were given access to the platform, asked to watch the steps of a robotic simple prostatectomy, leave comments, and then complete the System Usability Survey (SUS). This is a 10 question, survey to assess the perceived usability of web-based products. The SUS is an industry standard and has been proven and validated by a large database of web-based platforms to effectively differentiate usable and unusable products. Results Out of the 21 trainees at our institution, all accessed the website during the study period. A total of 17/21 (81%) used the platform and completed the SUS. The average SUS score was 85 for our platform, which correlates to a usability in the top 10% of technology based systems. The SUS score of 85 also correlates with continued usage and increased likelihood that users would recommend the platform to other trainees. Conclusions Our web-based surgical training platform has shown very favorable usability, which makes it likely to be utilized by residents as a teaching tool. The platform is well equipped for teaching robotic simple prostatectomy or other relatively low volume surgical procedures. Future studies are aimed at tracking and quantifying resident platform utilization and correlating this to resident surgical skill progression. Funding none
Authors
Nicholas Kavoussi
Igor Sorokin Jeffrey Gahan |
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V4-07 |
Contrast-Enhanced Ultrasound (CEUS): Evaluation of High Intensity Focused Ultrasound (HIFU) ablation of the prostate |
Imaging/Uroradiology | 17BOS |
Abstract: V4-07 Sources of Funding: none Introduction No consensus or guidelines exist on imaging follow up for ablation therapies. The objective is to evaluate Contrast-Enhanced Ultrasound (CEUS) in High Intensity Focused Ultrasound (HIFU) ablation of the prostate. Methods We performed CEUS immediately pre- and post-ablation, and during follow up of the patients who underwent HIFU for localized prostate cancer using either Ablatherm® or Sonacare®. After conventional trans-rectal US (TRUS) examination (GE Healthcare, Chicago, IL), a 1.5 cc bolus of the ultrasound contrast agent LUMASON® (sulfur hexafluoride lipid-type A microspheres) was injected intravenously. Two minutes cine images of the regions of interest were obtained and time intensity curves (TIC) were concurrently generated. Results From Dec/2015 to Sep/2016, 12 consecutive patients that underwent HIFU were evaluated by CEUS. Median (range) age, PSA and prostate volume were 64 yr (55-83), 6.25 ng/ml (2.8-19.6) and 29 cc (18-51), respectively. Hemi/subtotal/whole-gland HIFU were performed in 9/1/2 patients, respectively. In a median follow up of 5.3 months (2.2-10), the PSA decreased 88% (35-98). In one patient the PSA did not decrease and biopsy confirmed local recurrence. _x000D_ CEUS findings: 1) On pre-HIFU, the cancer area demonstrated higher peak intensity (PI) and shorter time to peak than the non-cancer area. 2) The PI was at about 25 sec and the wash out continued up to the end of the 2 min recording. 3) The TIC provided quantification of enhancement of treated and untreated prostate, therefore decreasing subjectiveness. 4) CEUS provided real time visualization of ablated area with clear and sharp margins. 5) CEUS provided confirmation that the targeted region of interest was precisely treated as planned. 6) The treated area could be visualized immediately after ablation and the ablation defect persisted on follow up (Figure)._x000D_ Conclusions CEUS provides a real time feedback with visualization and quantification of the actual treated and untreated areas on intraoperative and follow up evaluation of patients undergoing HIFU ablation of the prostate. Funding none
Authors
Andre Luis Abreu
Daniel Freitas Daniel Park Toshitaka Shin Masakatsu Oishi Carlos Fay Suzanne Palmer Frank Chen Andre Berger Rene Sotelo Edward Grant Osamu Ukimura Inderbir Gill Mittul Gulati |
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V4-08 |
Preliminary Results of Advanced Image-Guided Renal Biopsy and Thermal Ablation Utilizing Cone-Beam Computerized Tomography: A Surgeons Procedure. |
Imaging/Uroradiology | 17BOS |
Abstract: V4-08 Sources of Funding: none Introduction Introduction: The diagnosis of incidental small renal masses (SRM) has increased partly due to the use of cross sectional imaging. Partial nephrectomy is now considered the &[Prime]Gold&[Prime] standard whereas thermal ablation (TA) is an alternative option for sub-optimal surgical candidates. TA in most institutions is performed by Interventional Radiologists with little participation by Urologic Oncologists (UO). In this study patients with SRM were treated by TA using cone-beam computerized tomography (CBCT) [Artis-X, Siemens Healthcare, GmbH] coupled with digital fluoroscopy. Using &[Prime]I-Guide&[Prime] software, needle placement is facilitated and simplified. _x000D_ Objective: To demonstrate the CBCT renal biopsy (RB) and TA technique for select patients with SRM as performed by UO. Methods 20 patients with SRM underwent RB and TA between January and September 2016 (Table 1). Procedures were performed under general anesthesia. 1-3 TA probes were placed (Cool-tip radiofrequency needle, Covidien, Boulder CO, USA). The number of ablation cycles, core biopsies, amount of radiation and contrast used, and intra-operative complications were individualized and recorded. Post-operative complications were evaluated using the Clavien-Dindo classification of surgical complications. Results With a median 3 month follow up there were no technical failures and all patients had 6 week contrast enhanced CT demonstrating no enhancement (Table 2). _x000D_ Conclusions With access to appropriate image guidance tools, Urologists can become more involved in the diagnosis and treatment of SRM. Advanced targeting is now simplified making it possible for oncologic surgeons to perform TA on select patients. Further follow up on this cohort is essential. Funding none
Authors
Emily Kelly
Raymond Leveillee |
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V4-09 |
MRI Guided Salvage Cryoablation of Recurrent Prostate Cancer |
Imaging/Uroradiology | 17BOS |
Abstract: V4-09 Sources of Funding: none Introduction Prostate cancer is the most common non-cutaneous malignancy in men in the United States, and cancer recurrence after definitive therapy can be as high as 30%. Recurrent cancer presents many challenges. Finding the site of recurrence is difficult, and once found, the optimal treatment modality must be determined. We present a patient with MRI detected, biopsy proven local recurrence treated with MRI guided salvage cryoablation. Methods A 57 year old man underwent open radical retropubic prostatectomy for a Gleason 3+4 T3a N0 R0 prostate cancer. At his 6 year follow-up, his PSA rose to 1.3 ng/dL and he underwent salvage intensity modulated radiation therapy. 2 years later, his PSA was 1.9 ng/dl and MRI and TRUS biopsy demonstrated a 1.1 by 2 cm mass in the left vesicourethral anastomosis. CT imaging and bone scan demonstrated no evidence of metastatic disease. Results After extensive discussion of therapeutic options, the patient elected to proceed with MRI guided salvage cryoablation. Initial treatment was with four cryoprobes spaced 1 cm apart. Two freezing cycles were performed with 7 minutes of freezing time. Post-ablation, his PSA nadired at 0.22 ng/mL, and repeat MRI demonstrated a residual 7 mm by 7 mm mass in the left vesicourethral anastomosis. Repeat TRUS biopsy demonstrated a Gleason 4+4 prostate cancer. The patient underwent a second ablation separating the cryoprobes by 5 mm and using 3 cycles of freezing. Since then, his PSA has remained undetectable with no evidence of disease for 5 years. Conclusions MRI allows precise placement of the cryoprobes. In addition, active imaging provides ice ball monitoring that improves the safety and precision of cryotherapy. In the appropriate patient, this technique may provide durable cancer-free survival. Funding none
Authors
David Y Yang MD
David A Woodrum MD, PhD Lance A Mynderse MD, FACS |
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V4-10 |
“URODYNAMIC 4D-CT” Evaluation is a Highly Effective Technique for the Assessment of Urinary Conditions. |
Imaging/Uroradiology | 17BOS |
Abstract: V4-10 Sources of Funding: none Introduction Male patients with LUTS have been examined using methods such as UFM, CMG, PFS and VCUG. Although PFS is thought to be specifically effective for assessing the degree of bladder outlet obstruction (BOO), it requires some skill to perform and is invasive to the patient. In addition, it is difficult to evaluate urinary disorders comprehensively in a single examination. Area Detector CT was applied to urodynamic study in a technique we call “Urodynamic 4D-CT”. We have already demonstrated the clinical effectiveness and convenience of “Urodynamic 4D-CT” imaging in the assessment of urinary conditions. In this clinical study, we examined urinary evaluations that combined Urodynamic 4D-CT with PFS. Methods A Toshiba Aquilion ONE 320 CT scanner (running on ZIO STATION 2) was used for scanning dynamic urinary flow images. After normal intravenous administration of a contrast agent as per regular CT scanning, 4D-CT images were taken during urination with the patient maintaining a half-seated position on the CT table. While shooting the X-rays, testis were protected from radiation exposure with a lead plate. Results Using “Urodynamic 4D-CT”, 94 cases with LUTS were assessed to determine details regarding BPH, BNC and urethral stricture. The Bladder / prostate angle and the widest point in the prostatic urethra and bladder neck were demonstrated to be significantly improved after effective Holmium Laser prostatectomy (HoLEP). Movement of the upper bladder had been limited before performing the HoLEP operation, however, it is clear to see how bladder function improved dramatically once supported by the pubo-prostatic ligament post-operation. Urodynamic 4D-CT was shown to be effective at evaluating BOO status before treatment and predicting the outcomes of HoLEP for patients with BPH. Compared to the use of previous techniques, urination disorders were far easier to diagnose and understand when synchronizing PFS with Urodynamic 4D-CT. Conclusions Urodynamic 4D-CT was demonstrated to be a safe, thorough and revolutionary new method for assessment of urinary condition in a single examination. Urodynamic 4D-CT was able to illustrate the dynamic shape transition realized on the entire urinary tract chronologically, simply, and less invasively than other techniques. When used in conjunction with PFS, the possibility was clearly demonstrated for 4D-CT scanning to help accurately evaluate urinary conditions, as well as assess patient operability, with an efficiency superior to previous techniques. Funding none
Authors
Shintaro Mori
Masanori Inoue Masahiro Jinzaki Ryoichi Shiroki |
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V4-11 |
MRI-Guided Transurethral Ultrasound Ablation in Patients with Localized Prostate Cancer: Primary Outcomes of a Prospective Phase I Study |
Imaging/Uroradiology | 17BOS |
Abstract: V4-11 Sources of Funding: This study was sponsored by Profound Medical Inc. Introduction MRI-guided transurethral ultrasound ablation (TULSA) is a novel minimally-invasive technology for ablation of benign and malignant prostate tissue. The transurethral device emits directional ultrasound producing an ablation volume that is shaped to patient-specific anatomy and pathology using active MRI thermometry feedback control. The aim of this multi-center, prospective Phase I study was to assess the safety and feasibility of MRI-guided TULSA for near whole-gland ablation in patients (pts) with localized prostate cancer (PCa). Methods This trial treated 30 pts with biopsy-proven organ confined PCa (T1c-T2a, PSA upto 10 ng/ml, Gleason Score 3+3, and upto 3+4 in Canada only). MRI-guided TULSA was delivered with 3 mm margins at the gland periphery, and expected 10% residual viable prostate tissue around the capsule. Primary endpoints were safety (adverse events), and feasibility (spatial precision of conformal ablation). Exploratory outcomes included PSA, quality of life, MRI and 12-core TRUS-guided biopsy. Results Median (IQR) age was 69 (67-71) years, with 24 (80%) low-risk and 6 (20%) intermediate-risk cancers and PSA 5.8 (3.8-8.0) ng/ml. Treatment time and prostate volume, respectively, were 36 (26 - 44) min and 44 (38 - 48) cc. Spatial control of thermal ablation was +/- 1.3 mm. Adverse events (CTCAE v4) included urinary tract infections (10 pts G2), acute retention (3 pts G1; 5 pts G2), and epididymitis (1 pt G3). There were no rectal injuries or fistulae observed. Pre-treatment IPSS of 8 (5-13) and IIEF of 13 (6-28) were recovered to, respectively, 6 (4-10) at 3 mo and 13 (5-25) at 12 mo. Median PSA decreased 87% at 1 month (mo), stable to 0.8 (0.6 - 1.1) ng/ml at 12 mo. Positive biopsies at 12 mo show 61% reduction in total cancer length, clinically significant disease in 9/29 pts (31%), and any disease in 16/29 pts (55%). Following positive biopsy results at 12 mo, 3 pts underwent salvage radical prostactetomy, and 1 pt opted for investigational MRI-guided focal laser ablation. Conclusions MRI-guided TULSA is a well-tolerated, safe procedure for pts with localized PCa. TULSA can offer a low morbidity profile while keeping post treatment salvage therapy options open if necessary. The multicentre TULSA-PRO Ablation Clinical Trial (TACT) is currently underway, to evaluate safety and effectiveness of whole-gland ablation with reduced margins in 110 pts. Funding This study was sponsored by Profound Medical Inc.
Authors
Joseph Chin
James Relle Michele Billia Valentin Popeneciu Timur Kuru Jason Hafron Matthias Roethke Maya Mueller-Wolf Zahra Kassam Fayruz Kibria Mathieu Burtnyk Heinz-Peter Schlemmer Sascha Pahernik |
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V4-12 |
Simulation model for ultrasound and fluoroscopy guided percutaneous renal access: step by step tutorial |
Imaging/Uroradiology | 17BOS |
Abstract: V4-12 Sources of Funding: none Introduction Percutaneous renal access has been a leading toping in urology for years, given the widespread use of nephrostomy and percutaneous nephrolitotomy (PCNL). Systematic training routine is known to be helpful in laparoscopic and robotic surgery in order to shorten the learning curve. Nevertheless, there is a shortage of training models regarding percutaneous renal access. Methods We present materials and methods to build a percutaneous renal access model. We propose a homemade devise that allows training using simulated fluoroscopy guided puncture, contributing to shorten learning curve and reduce radiation during this period. Using jelly, our model permits practising the ultrasound guided puncture, both combined with simulated fluoroscopy or independently. In order to make our simulator, we use materials available in any home improvement store. Results The materials required to make our model cost less than 130 euros. About 3 hours are required to set up the simulator. We have built a structure that allows rotation and permits fluoroscopy guided puncture at 0 and 30 degrees angle, as the standard technique to identify the position of the needle in the upper-lower and anterior-posterior axis. Furthermore, our simulator permits using simultaneously ultrasound guidance. We have improved imaging using a pinhole system and reflected light in order to avoid magnifying of movements of the needle. With our proposal, we can restore and re-use the jelly puncture model, thereby clearing any puncture tracks. Conclusions There is a scarcity of training models covering renal kidney access, one of the main topics in urological surgical access. The lack of simulation sessions results in longer learning curve and additional exposure to ionizing radiation. We propose a complete, versatile and effective model to train both the fluoroscopy and the ultrasound guided renal access. Funding none
Authors
Manuel Carballo-Quinta
Sabela López-García Máximo Castro-Iglesias Grethel Rivas-Dangel Sheila Domínguez-Almúster Moisés Elías Rodríguez-Socarrás Miguel Pérez-Schoch Jorge Sánchez-Ramos María Elena López-Díez Antonio Ojea-Calvo |
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V5-01 |
Holmium Laser Enucleation of the Prostate as Retreatment after UroLift Device: Feasibility and Technical Considerations |
BPH and Voiding Dysfunction | 17BOS |
Abstract: V5-01 Sources of Funding: none Introduction In this video we demonstrate the feasibility of Holmium laser enucleation of the prostate (HoLEP) for retreatment of persistent lower urinary tract symptoms (LUTS) after previous treatment with the UroLift device. Technical considerations with regards to both enucleation and morcellation of resected tissue are discussed. Benign prostatic hyperplasia (BPH) affects millions of men worldwide. The UroLift system (NeoTract Inc., Pleasanton, CA) was recently introduced as a means to perform prostatic urethral lift (PUL) procedure for lateral lobe hypertrophy in patients with obstructive voiding symptoms. Urolift has been associated with a retreatment rate of 7% at 2 years and 14% at 4 years. Retreatment with TURP, photovaporization of the prostate and repeat UroLift has been described without notable issue, but retreatment with HoLEP has not yet been described. Methods We included two patients who had undergone PUL with UroLift system at outside institutions and presented with recurrent LUTS. Patients were evaluated by cystoscopy, uroflowmetry, transrectal ultrasound of the prostate, and urodynamics to define the etiology of their urinary symptoms and determine appropriate therapy. HoLEP was performed under general anesthesia as previously described. Morcellation of the resected adenoma was performed with the VersaCut reciprocating morcellator (Lumenis Inc, Santa Clara, CA). Results Enucleation was successfully completed in both patients. Monofilament sutures of the Urolift device were easily visualized and transected with the holmium laser. At the bladder neck, both patients were unexpectedly found to have the outer nitinol tab portions of UroLift devices located within the capsule of the prostate, rather than in the intended extracapsular location. Auxiliary maneuvers were required for removal of these nitinol tabs. The inner stainless steel portions of the UroLift device were encountered during morcellation of the resected adenoma. In each instance, the metal tabs became lodged in the reciprocating blades of the morcellator, requiring withdrawal of the morcellator instrument and manual removal of the tab from the morcellator blade. This resulted in brief disruptions in the procedure. There were no operative complications. Conclusions To our knowledge, we present the first description of HoLEP with morcellation of adenoma tissue after previous prostatic urethral lift surgery with the UroLift device. HoLEP can be performed safely and effectively post Urolift, however morcellation of the adenoma tissue is complicated by the metallic implants of the Urolift device. Funding none
Authors
Sean McAdams
Mitchell Humphreys |
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V5-02 |
Voiding urethrocystoscopy: a new concept for benign prostatic obstruction characterization. |
BPH and Voiding Dysfunction | 17BOS |
Abstract: V5-02 Sources of Funding: None Introduction The role of urethrocystoscopy (UC) in male lower urinary tract symptoms (LUTS) assessment regarding benign prostatic obstruction (BPO) is unclear. However, the last EAU guidelines advise to perform an UC prior to minimally invasive/surgical therapies if the findings may change treatment. We assessed the feasibility of voiding urethrocystoscopy (VUC) in males with (LUTS) and describe the characteristics of dynamic movements of the prostatic lobes during micturition, with further implications for surgical approach such as preservation ejaculatory function. Methods All consecutive patients with LUTS and willing to preserve their ejaculatory function scheduled for BPO relief surgery in a tertiary reference center were included in this prospective evaluation. After emptying the bladder, an UC with a 16-Fr flexible endoscope was performed and the bladder was filled up to 500mL to generate a desire to void. The patient was asked to void once the tip of the endoscope facing the veru montanum. Movements of the prostatic lobes during micturition were characterized. Endoscopic movements of the prostatic lobes were video-recorded, and categorized based on the dynamics of the lateral lobes, the posterior lobe and the bladder neck. Results 192 procedures were conducted. In 161 cases (84%), the patient was able to void. Among these patients, 126 cases were stated as “closed� (coalescent), without opening of the initial part of the urethra and the bladder neck. In 38 cases, there was no opening of the lateral lobes (type 1A), and in 47 cases a partial opening of the distal parts of the lateral lobes was seen (type 1B). In 31 cases, a fixed posterior bladder neck was seen (type 2A) and in 10 cases a mobile median lobe, with a rolling ball effect, was seen (type 2B). In 25 cases, the lumen was completely open and equivocal in 10 cases. Conclusions This study demonstrates the feasibility of VUC and describes for the first time the dynamics of prostatic lobes during micturition. This functional description may be useful to evaluate preoperatively the possibility of partial surgery, meaning removal of the only visually obstructive responsible structure to restore correct urinary flow, and subsequently preservation of ejaculatory function. In this study, 70% of patients could benefit of such surgery since the obstruction was partial (types 1B, 2A and 2B). Funding None
Authors
Bertrand Lukacs
Steeve Doizi |
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V5-03 |
Robot-assisted periprostatic artificial urinary sphincter implantation in male patient with neurogenic stress urinary incontinence |
BPH and Voiding Dysfunction | 17BOS |
Abstract: V5-03 Sources of Funding: none Introduction _x000D_ In men with urinary incontinence due to neurogenic intrinsic sphincter insufficiency, it is recommended to place artificial urinary sphincter (AUS) cuff around the bladder neck to spare antegrade ejaculation, to avoid the risk of pressure ulcers at the perineal incision site and to limit the risk of cuff erosion due to clean-intermittent-self-catheterization (CISC). The objective of this study was to describe a surgical technique of periprostatic AUS implantation in neurogenic male patients._x000D_ Methods The technique of periprostatic AUS implantation in men is described in this video. We present the case of a 50 year-old male with a past medical history of cauda equina syndrome and stress urinary incontinence due to neurogenic intrinsic sphincter deficiency. The patient performed 5 to 6 CISC per day due to underactive bladder. The urethral closure pressure was 33 cm H2O on urodynamics and the amount of urine leakage was 350 g/24 hour according to the pad test. Results The procedure is performed under general anesthesia. The patient is placed in a 23° Trendelenburg position. A laparoscopic transperitoneal approach is performed and five ports are placed in total, including three ports for the robotic arms and one 12 mm-port for the assistant surgeon to allow the insertion of the AUS cuff. First, the peritoneum is opened just above the seminal vesicles. The space between the posterior part of the prostate and the seminal vesicles is dissected. The bladder is then released down and the Retzius space is dissected. The lateral sides of the prostate are dissected and the endopelvic fascia is opened on both sides. A Prograsp forceps is used to open the angle between seminal vesicles and bladder on both sides from inside to outside. A measurement tape is then passed around the bladder neck and the AUS cuff is inserted through the 12-mm port. The balloon is implanted in the Retzius space through a 3 cm suprapubic incision and the pump is placed in the scrotum by a subcutaneous passage made from the suprapubic incision_x000D_ Conclusions This video report the feasibility of robot-assisted periprostatic AUS implantation in male patient with neurogenic stress urinary incontinence. The benefits of positionning the AUS cuff around the bladder neck (vs. bulbar urethra) and of the robot-assisted approach to perform this periprostatic implantation (vs. open or laparoscopic approaches) remain to be proven by clinical research studies. Funding none
Authors
benoit peyronnet
sébastien vincendeau pierre grison quentin alimi lucas freton lauranne tondut baptiste gires karim bensalah nelly senal jacques kerdraon andrea manunta |
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V5-04 |
Combined photovaporisation of prostate and laser cystolithotripsy using GreenLight Laser |
BPH and Voiding Dysfunction | 17BOS |
Abstract: V5-04 Sources of Funding: None Introduction Bladder stones in elderly men are commonly associated with bladder outlet obstruction. To date, there are many different treatment modalities have been presented for both these conditions. The aim of this study is to evaluate the safety and feasibility of a novel approach to photovaporise prostate as well as laser cystolithotripsy as an alternative method of utilizing GreenLight laser only. Methods In a prospective study conducted between January 2013 to July 2016, 23 patients with significant bladder outlet obstruction with presence of bladder calculi underwent both photovaporisation of prostate and cystolithotripsy in a single operation using single instrument via GreenLight laser. Patients diagnosed with bladder calculi and concurrent prostate hyperplasia underwent lithotripsy using greenlight photovaporisation side firing after completion of photovaporisation of the prostate were included in this study. Results _x000D_ Twenty five patients underwent simultaneous laser cystolithotripsy and photovaporisation of prostate. The median Median patient age was 67 years (range 59-89). Median pre-operative prostate volume was 70cc (range 38-160). Stone size ranging from 1 - 4cm with variable number of stones (1-18) were fragmented with good results, bladder debris washout. There were no complications. An average of 316000 Joules were used to treat both vesical calculi and BPH. Majority of calculi analysis showed mixture of calcium oxalate, calcium phosphate and uric acid. Laser fiber lasted through both procedures without damage and not requiring replacement throughout the surgery. One case required percutaneous cystostomy for stone extraction. Conclusions The findings on this study shows that GreenLight laser is a minimally invasive and safe technique to treat both enlarged prostate with bladder calculi. This method can be used as an alternative method of treatment by using single instrument approach and could possibly prevent potential open procedure. Funding None
Authors
Darren Ow
Marlon Perera Damien Bolton Nathan Lawrentschuk |
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V5-05 |
Prostate Artery Embolization prior to robotic simple prostatectomy in a patient with high bleeding risk |
BPH and Voiding Dysfunction | 17BOS |
Abstract: V5-05 Sources of Funding: none Introduction Prostate artery embolization (PAE) is an alternative to surgery for patients with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) who are poor surgical candidates. We describe a novel use of PAE as a preoperative measure to reduce perioperative bleeding risk in a high-risk patient undergoing robotic simple prostatectomy. Methods A 61 year-old man presented with LUTS refractory to medication that progressed to hematuria and urinary retention. Cystoscopy and CT urogram demonstrated a markedly enlarged prostate >110gm. The patient elected for robotic-assisted simple prostatectomy. However, he was a Jehovah&[prime]s Witness on chronic anticoagulation and refusing blood transfusions. The decision was made to perform PAE preoperative to reduce bleeding risk. PAE was performed the day prior to surgery. A catheter was inserted into femoral artery to the external iliac artery to the internal iliac artery. Digital Subtraction angiography was used to identify the prostatic arteries, which were embolized with 100-300 and 300-500 µm Tris-acryl Gelatin Microspheres (Embosphere; Merit Medical Systems Inc, South Jordan, Utah, USA), until there was no appreciable flow to the prostate from either artery. Intraprocedural cone beam CT was performed, which yielded detailed vascular anatomy and confirmed targeted embolization. The following day, the patient underwent robotic-assisted simple prostatectomy. _x000D_ Results The prostate enucleation planes were noticeably avascular, allowing for minimal blood loss and good visualization. Console time was 189 minutes with an estimated blood loss of 100mL and no postoperative hematuria. Whole-mount pathology demonstrated mild ischemic changes and confirmed presence of microspheres within prostatic tissue, indicative of successful PAE. The patient had an uneventful postoperative course and was discharged on postoperative day 2 with no complications. He successfully passed a trial of void and reported resolution of urinary symptoms. Conclusions We describe a novel multidisciplinary approach using PAE prior to prostate surgery for BPH as a means of preoperative risk reduction in a high-risk patient. Preoperative PAE could potentially be used for risk reduction in other high-risk patients requiring complex surgery for BPH and could be combined with the surgical approach preferred by the surgeon. Funding none
Authors
Craig Rogers
Dan Pucheril Kaila Wilcher Riaz Rehan Maria Zanini Scott Schwartz |
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V5-06 |
Robot-assisted simple prostatectomy in patients with large volume BPH (>100 ml): indications, technique and results based on 81 procedures |
BPH and Voiding Dysfunction | 17BOS |
Abstract: V5-06 Sources of Funding: none Introduction Open adenomectomy (OSP) is still considered the gold standard surgical treatment for patients with large volume benign prostatic hyperplasia (BPH). Recently, minimally invasive techniques has been proposed in order to reduce the morbidity and complication rates. Here we present the technique and results of our Robot-assisted simple prostatectomy (RASP) series. Methods 81 patients with large volume BPH (>100 ml) underwent RASP through a transperitoneal access. All the procedures were performed with the DaVinci Si robotic system in a four arm configuration. Patients were preoperatively assessed with transrectal ultrasound and uroflowmetry. Baseline functional parameters including International Prostate Symptom Score (IPSS), Maximum Flow Rate (Qmax) and Post-Void Residual (PVR) were assessed postoperatively during the follow-up. Perioperative outcomes included operative time (OR time), catheterization time (CV time) and length of hospital stay (LOS). Complications were recorded and graded according to the Clavien-Dindo classification. Results The median age was 69 years (IQR 66-76) and 48 (62%) of the patients had a Charlson Comorbidity Index of 2 or more. The median prostate volume was 130 ml (IQR 111–190) and 28 (34%) patients had an indwelling catheter prior surgery. Patients showed a significative improvement of functional outcomes, with a median Qmax improvement of +15 ml/s and a decrease of the IPSS and PVR of -20 and -73 ml respectively. The median OR time was 105 min (IQR 85-150) and the median estimated blood loss was 250 ml (IQR 105-320). The median CV time and LOS time was 3 and 4 days respectively. The overall postoperative complication rate was 31% with no grade 4 and 5 complications. Conclusions In our RASP series we obtained a significative improvement of functional outcomes with an acceptable risk of peri-operative complications. This technique could be considered an interesting option for surgeons that have completed their learning curve performing an adequate number of robot-assisted radical prostatectomys and in case of concomitant pathologies needing a surgical approach as vescical stones, bladder diverticula or inguinal hernia. Funding none
Authors
Paolo Umari
Nicola Fossati Alexander Heinze Ruben De Groote Geert De Naeyer Peter Schatteman Alexandre Mottrie |
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V5-07 |
Perineal Artificial Urinary Sphincter (AUS) with High Submuscular (HSM) Placement of Pressure Regulating Balloon (PRB) |
BPH and Voiding Dysfunction | 17BOS |
Abstract: V5-07 Sources of Funding: Educational Grant from Boston Scientific Introduction In patients undergoing Artificial Urinary Sphincter (AUS) placement, with a history of major pelvic surgery, avoidance of the Space of Retzius with traditional placement of the Pressure Regulating Balloon (PRB) may be beneficial. This video presents perineal AUS placement with high submuscular placement (HSM) of the PRB. Methods A perineal incision provides excellent exposure of the bulbar urethra for proximal bulbar urethral cuff placement. Via a separate 2cm high scrotal incision the external inguinal ring is identified. A pediatric Deaver is placed within the superficial ring and blunt finger dissection used above the transversalis fascia develops a space below the rectus that accommodates the PRB. Using one's index finger the PRB is then easily placed in the HSM space without any additional instrumentation. Finally through this same incision a subdartos pouch is created for pump placement. The AUS is cycled and deactivated and the wound is closed in multiple layers. Results There is no difference in revision rates between HSM PRB placement versus Space of Retzius placement. Conclusions HSM placement of the PRB at the time of AUS implantation avoids the Space of Retzius with associated potential bladder, bowel, or vascular injury and/or complications. HSM placement avoids peritoneal placement post-robotic prostatectomy. HSM placement is safe, effective, can easily be learned and implemented, and may be used with concomitant IPP placement. Funding Educational Grant from Boston Scientific
Authors
Billy Cordon
Allen Morey |
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V5-08 |
"TOP-DOWN" HOLMIUM LASER ENUCLEATION OF THE PROSTATE (HoLEP) TECHNIQUE |
BPH and Voiding Dysfunction | 17BOS |
Abstract: V5-08 Sources of Funding: None Introduction In this video, we demonstrate our version of the novel anterior-posterior HoLEP dissection technique. Methods Video of the surgical technique accompanied by slides and voiceover explanation of the steps Results A novel anterior-posterior HoLEP dissection technique allows faster operation time and potential continence improvement. We demonstrate our version of this technique and present early operative outcomes. After cystoscopy a posterior groove is created at the 6 o'clock position in a bilobar gland. If there is a prominent median lobe the groove is cut at either 5 or 7 o'clock. The groove is extended to the veramontanum and to depth of capsule. The edges of the lateral lobes on either side of the veru are incised. The scope is rotated to visualize the anterior commissure and retracted to identify the edge of the lateral lobes and the sphincter. The anterior commissure is then incised at 2 Joules/20 Hz Setting. The dissection plane is located anteriorly with a series of short incisions. We identify this plane on both sides at this point as it can be difficult to find it later once a lateral lobe is completely resected on one side._x000D_ _x000D_ Once the plane is apparent, lateral lobe dissection is begun. The lateral lobe is dissected from the top down, allowing faster dissection time than the traditional technique. The mucosal strip is easily visualized as the apical dissection is performed from top down. This eliminates the need to encircle the mucosal strip reducing enucleation time. Given sphincter proximity, 2 Joules/20 Hz laser setting is again used. Once the entire lobe dissection is completed, the lobe is pushed into the bladder. The residual cavity is inspected and hemostasis controlled. Finally, tissue is morcellated with a Wolf PIRANHA instrument. _x000D_ _x000D_ Retrospective review of HoLEPs from December 2015 to April 2016 was performed. 49 patients who underwent anterior posterior technique were compared with 37 who underwent traditional posterior to anterior enucleation. Mean enucleation time and mean enucleation rate were both faster with the novel, top-down approach. _x000D_ Conclusions We demonstrate a novel top-down HoLEP enucleation technique with promising early operative results. Funding None
Authors
Nadya E. York
Casey A. Dauw Michael S. Borofsky James E. Lingeman |
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V5-09 |
Holmium Laser Enucleation of a Prostatic Abscess |
BPH and Voiding Dysfunction | 17BOS |
Abstract: V5-09 Sources of Funding: None Introduction A prostatic abscess is a commonly encountered localized genitourinary infection, best treated with surgical resection. Traditional transurethral resection places the urinary sphincter in jeopardy of thermal injury in the event of an apically located abscess. Methods We present a 69 year old male with a several week history of dysuria and back pain. He presented to his local physician for evaluation and after CT imaging was diagnosed with a psoas abscess, diskitis/osteomyelitis and a prostatic abscess. The prostatic abscess was noted to be in an extremely apical location posing a significant risk of thermal injury with a standard resection. Therefore, a holmium laser enucleation of the prostatic abscess was performed. Results After initial inspection of the bladder demonstrated asymptomatic ureteroceles, an incision was made at the bladder neck and carried to the depth of the surgical capsule distally to the verumontanum. The lateral dissection expresses purulence almost immediately and a large abscess pocket is encountered during the anterior dissection. The remainder of the enucleation is performed without complication. The patient was spontaneously voiding by POD 2 and discharged with IV antibiotics for 6 weeks to treat his osteomyelitis. Conclusions Holmium laser enucleation of a prostatic abscess can be performed safely and effectively to both maximally reduce the abscess cavity and risk of excessive thermal injury when treating an apically located abscess. Funding None
Authors
Marcelino Rivera
James Lingeman Amy Krambeck |
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V5-10 |
EXTRAPERITEONAL SIMPLE PROSTATECTOMY: A SURGERY FOR BEGINNERS? |
BPH and Voiding Dysfunction | 17BOS |
Abstract: V5-10 Sources of Funding: none Introduction Laparoscopic simple prostatectomy has been introduced with the purpose of reducing the morbidity associated with classical and standard open surgery. The extraperitoneal (pré-peritoneal) approach adds no technical difficulty, and additionally, allows no surgical violation of the peritoneum. The purpose of this work (video), is to show step-by-step a video-endoscopic extraperitoneal simple prostatectomy technique and present a series of cases of patients treated with this approach, with residents as first surgeons. Methods To create an educational video that shows in a didactic way the video-endoscopic extraperitoneal simple prostatectomy procedure. Eighteen consecutive cases performed with this technique were analysed. Demographic data and main perioperative outcomes were registed and analyzed. Pre and post-operative International Prostate Symptom Score and maximum flow rate were registered as indicators of relieving of bladder outlet obstruction (BOO). A questionnaire for surgery feasibility was applied to the surgeons. Results An educational video that shows in a didactic way the simple video-endoscopic extraperitoneal simple prostatectomy is presented. The results of a series of 18 consecutive cases are presented: mean prostate volume was 98 ml; mean estimated blood loss was 150 ml (no transfusions required). No intraoperative complications or conversion were recorded. Mean length of hospital stay was 3,5 days. Post-operative complications occurred in a 5,6% rate (self-limiting prolonged haematuria). A significant improvement was observed of subjective and objective indicators of BOO (p<0.05). Retrospective study design, lack of a control arm, and limited follow-up represent major limitations of the present analysis. The surgeons assessment reveals that the technique was easy to perform. Conclusions This work proves that the video-endoscopic extraperitoneal simple prostatectomy is a safe and effective procedure and certainly a good option for the surgical treatment of high volume benign prostatic hyperplasia. Additionally, in our opinion this surgery appears to be a good procedure for iniciating laparoscopic training, due to the near absence of oncologic concern, and because of its feasibility. Funding none
Authors
Paulo Mota
Nuno Carvalho Emanuel Carvalho-Dias Agostinho Cordeiro João Torres Nuno Morais Mário Cerqueira-Alves Riccardo Autorino Estevão Lima |
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V5-11 |
Robotic simple prostatectomy: the retropubic approach |
BPH and Voiding Dysfunction | 17BOS |
Abstract: V5-11 Sources of Funding: None Introduction Several surgical options for the management of BPH. We present the case of a patient with a large prostate gland on TRUS during prostate biopsy and transient urinary retention. GIven size of the gland and long distance to bladder neck as well as patient's status as Jehovah's witness, decision made to use retropubic approach to robotic simple prostatectomy. Methods Video recorded of surgical procedure Results Patient with minimal blood loss during the procedure, no additional need for transfusion. Patient discharged on post-op day 3 after uncomplicated hospital course. Small leak seen on post-op VCUG resulted in additional week of catheter use and resolution on repeat imaging. Patient with resolution of lower urinary tract symptoms. Conclusions Retropubic approach to robotic simple prostatectomy can be an option for surgical management of large glands and a safe and effective alternative to the transvesical approach. Funding None
Authors
Unwanaobong Nseyo
Yahir Santiago-Lastra Jill Buckley |
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V5-12 |
Holmium Laser Enucleation of the Prostate After Prostatic Urethral Lift |
BPH and Voiding Dysfunction | 17BOS |
Abstract: V5-12 Sources of Funding: None Introduction Prostatic urethral lift (PUL) has emerged as a minimally invasive option for treatment of benign prostatic hyperplasia (BPH) and bothersome lower urinary tract symptoms (LUTS) especially in young males who would like to avoid sexual and ejaculatory dysfunction. To date, there is no long-term data concerning the durability of the PUL in the management of LUTS. The bladder outlet is opened by placement of retention devices which effectively lift the lateral lobes towards the prostatic capsule. This device consists of a nitinol capsular anchor attached to a non-absorbable suture which spans the prostate tissue and is anchored by a stainless steel urethral end piece. Patient selection is critical, and PUL should be avoided in those with obstructing bladder necks, large median lobes or with glands larger than 100g. Holmium laser enucleation of the prostate (HoLEP) is a safe, effective and durable option for management of BPH in any size gland. Also, the powerful cutting effects of the holmium laser and visualization afforded to the surgeon with HoLEP make it an excellent surgical option to deal with urethral foreign bodies after failed PUL. Methods A 51 year old male presented with persistent lower urinary tract symptoms after two prior PUL procedures and urodynamic evidence of obstruction. Cystoscopy showed a high bladder neck. The patient chose to undergo HoLEP, and this was performed using Storz 28 French sheath and 550 micron Boston Scientific holmium laser fiber at 80 watts. Hemostasis was achieved at 40 watts. Morcellation was carried out using the Storz offset nephroscope and the Wolf Piranha morcellator. Results The enucleation time was 23 minutes. Four stainless steel urethral end pieces were removed. 5g of prostate tissue was morcellated in 7 minutes. A urethral end piece did bind the morcellator momentarily, however at this point, the prostate tissue was small enough to be grasped and removed through the scope. The catheter was removed after one day. At four months follow-up, the patient had a post-void residual of 0 mL and subjective improvement in his symptoms with International Prostate Symptom Score of 4 and Quality of Life score of 0. Conclusions HoLEP is an effective option for managing the unique situation of BPH and urethral foreign bodies after failed PUL. Funding None
Authors
Andrew Navetta
Erin Bird Marawan El Tayeb |
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V6-01 |
Midline Extraperitoneal RPLND in Testis Cancer: Minimizing Surgical Morbidity |
Misc. GU Oncology and Transplant | 17BOS |
Abstract: V6-01 Sources of Funding: none Introduction Retroperitoneal lymph node dissection (RPLND) is an important component of the management of testicular germ cell tumor (GCT) but its surgical morbidity is not insignificant. Herein we describe our updated experience with a midline extraperitoneal (EP) approach to RPLND for seminomatous and non-seminomatous GCT. Methods Between 2010 and 2015, from a prospectively collected IRB approved database, 122 consecutive patients underwent RPLND. Patients requiring aortic resection, retrocrural dissection or access to intraperitoneal disease were excluded. The remaining 69 patients underwent midline EP-RPLND. All post-chemotherapy (PC) cases underwent bilateral template dissection; all primary cases underwent extended ipsilateral templates. Perioperative and long-term outcomes were analyzed and a descriptive analysis using SAS was performed. Results 68 patients underwent midline EP-RPLND successfully (98.6%). Median age was 28 years (range=17-55). Median follow up was 15.3 months (IQR: 5.7-24.3). On pre-operative imaging the size of retroperitoneal mass or lymphadenopathy was <2 cm in 29 patients, 2-5 cm in 15 patients, and >5 cm in 24 patients, of which 19 were >10cm. 3 patients underwent cavectomy. Median EBL was 325 mL (IQR: 200-612.5). Median number of lymph nodes (LN) resected was 36 (IQR: 24.5-49); median number of positive nodes was 1 (IQR: 0-4). Median return of bowel function was 2 days (1-3) and LOS was 3 days (2-4). There were no cases of ileus. 13 patients (19.1%) had complications within 90-days: 12 were Clavien grade 2 (17.6%), there was 1 grade 3b complication (1.5%). Antegrade ejaculation rates were 91.6% in the primary group and 96.8% in the PC group. Conclusions Midline EP-RPLND can be performed safely without compromising completeness of resection. This approach is associated with a faster return of bowel function, lower rates of ileus and shorter LOS. Funding none
Authors
Sumeet Syan-Bhanvadia
Soroush Bazargani Thomas Clifford Hooman Djalaat Anne Schuckman Siamak Daneshmand |
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V6-02 |
Post Chemotherapy Robotic Retroperitoneal Lymph Node Dissection for Non-Seminomatous Germ Cell Tumor |
Misc. GU Oncology and Transplant | 17BOS |
Abstract: V6-02 Sources of Funding: None Introduction Retroperitoneal lymph node dissection (RPLND) is indicated for patients with non-seminomatous germ cell tumor (NSGCT) who have completed a primary regimen of chemotherapy and have a residual retroperitoneal mass greater than 1 cm with normal tumor markers. In the post chemotherapy (PC) setting, previous series have reported on the benefits of robotic retroperitoneal lymph node dissection (R-RPLND) with reduced morbidity, reduced hospital stay, and comparable nodal yield when compared to the open approach. Methods We present the technique of R-RPLND using both the daVinci Si and Xi robot. The supine approach is preferable to a lateral approach as it allows a full bilateral dissection to be performed from one position without the need to re-dock or reposition the patient. Nerve sparing technique is performed in patients undergoing bilateral dissection. There is significant reaction and fibrosis surrounding the residual retroperitoneal mass after chemotherapy and special considerations include the complete resection of the adherent mass, avoidance and control of vascular injuries, and nerve sparing techniques. Results All patients were diagnosed with NSGCT and had completed 3-4 cycles of BEP. They were noted to have residual retroperitoneal mass with normal tumor markers. Mean operative time was 339. Mean estimated blood loss was 125cc. Mean number of lymph nodes excised was 28. There were no transfusions and no open conversions. Pathology showed benign fibrosis and necrosis in two (50%), teratoma in two (50%), and no viable germ cells were found. Conclusions R-RPLND in the PC setting is feasible and offers patients the benefits of a minimally invasive approach. The robotic approach, while technically challenging, offers the ability to perform bilateral template dissections and repair vascular injuries if encountered. Funding None
Authors
James Porter
Gerald Heulitt |
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V6-03 |
Synchronous and Simultaneous Posterior Reroperitoneoscopic Bilateral Adrenalectomy. |
Misc. GU Oncology and Transplant | 17BOS |
Abstract: V6-03 Sources of Funding: none Introduction Laparoscopic bilateral adrenalectomy is a challenging procedure that usually requires patient repositioning and long operative time. Posterior retroperitoneoscopic adrenalectomy, by providing direct access to the gland, allows two surgical teams to work together, avoiding patient repositioning. This is an interesting approach in patients with bilateral affection. _x000D_ We describe the technique of synchronous and simultaneous posterior retroperitoneoscopic bilateral adrenalectomy in a patient with neurofibromatosis syndrome type 1 and bilateral pheocromocytomas. Methods A 25-year-old man with neurofibromatosis syndrome type 1 and past medical history of kidney transplant was referred for a 1 year long severe refractory hypertension. A thorough evaluation was performed for possible secondary causes of hypertension. Clinical suspicion of pheochromocytoma was confirmed by 24 hour urinary catecholamines level and CT scan of abdomen. The CT scan showed right sided adrenal mass of 45 mm and left adrenal mass of 43 mm. With patient placed in prone position, using 3 trocars per side and with two surgical teams working simultaneously a posterior retroperitoneoscopic bilateral total adrenalectomy was performed. Results The operation time was 120 minutes, intraoperative blood loss was 300 ml. With no postoperative complications, the patient had a fast postoperative recovery and was discharged on the third postoperative day. Blood pressure became normal from 1st post operative day without any drug. Differed histopathology exam confirmed that both adrenal tumors were pheochromocytomas. There was no clinical or biochemical relapse during a follow up period of 6 months. Conclusions Synchronous and Simultaneous Posterior Retroperitoneoscopic Bilateral Adrenalectomy is a safe and feasible technique in patients with bilateral pheochromocytomas. Funding none
Authors
Patricio Garcia Marchiñena
Miguel Basualdo Oscar Damia Guillermo Gueglio Alberto Jurado |
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V6-04 |
Retroperitoneal compartment syndrome in Renal Transplantation —How do we salvage the graft? |
Misc. GU Oncology and Transplant | 17BOS |
Abstract: V6-04 Sources of Funding: None Introduction Early allograft dysfunction (EAD) can be caused by a number of technical factors including vascular complications such as thrombosis and kinking. Retroperitoneal compartment syndrome (RACS) is an under-recognized vascular cause of EAD with potentially devastating consequences, and may even result in a lost graft. The graft can be salvaged with early recognition and intervention through a mesh hood fascial closure (MHFC) technique. Methods Here we describe, in video, a 23-years-old male recipient diagnosed with renal failure secondary to chronic reflux. He has a 6 months history of peritoneal dialysis and is currently on hemodialysis. The patient received an anonymous living-donor right kidney from our paired exchange program. His BMI is 22. The graft had a single renal artery and single renal vein. A standard anastomosis was performed and subsequent urine output was brisk. The fascia was closed without tension. However, urine production ceased after the fascia was fully closed. A case of RACS was suspected and intraoperative Doppler ultrasound showed no blood flow in the graft. Immediately re-exploration revealed the graft to be abnormal in color and turgor. Results These abnormalities resolved after pressure was relieved. The kidney was then placed in the optimal position within the iliac fossa and a large ellipsoid piece of polypropylene mesh was draped loosely and without tension over the graft. The mesh was attached to the posterior fascial edges using interrupted #1 polypropylene sutures. Skin closure then was completed over a closed suction drain placed in the retroperitoneal space lateral to the kidney. Doppler ultrasound after skin closure showed good flow and the postoperative course was unremarkable. Conclusions RACS could be associated with small android pelvis and lack of compliance in the retroperitoneal cavity secondary to peritoneal dialysis. Suspected RACS require prompt intervention to prevent irreversible graft dysfunction. We have shown that MHFC is an effective and safe method to treat EAD secondary to RACS. Funding None
Authors
Wen Xie
Karen Pineda-Solis Omar Ali Alp Sener Patrick Luke |
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V6-05 |
Robotic partial adrenalectomy for symptomatic aldosterone-secreting adenomas: technique and outcomes |
Misc. GU Oncology and Transplant | 17BOS |
Abstract: V6-05 Sources of Funding: none Introduction Partial adrenalectomy for functioning adrenal masses is significantly underused. Preliminary experiences suggested the effectiveness of partial adrenalectomy for functioning adrenal adenomas. _x000D_ We describe surgical technique and present perioperative and functional outcomes of a two center series including nine symptomatic aldosterone-secreting adenomas treated with robotic partial adrenalectomy (RPA)._x000D_ Methods From June 2014 to October 2016 RPA was performed in 9 consecutive patients with symptomatic aldosterone-secreting adrenal adenomas._x000D_ Surgical steps include: Incision of Gerota' s fascia at the level of the upper pole of the kidney and exposure of the adrenal gland; careful dissection of the medial aspect of the gland, preserving adrenal vessels with a selective control of vessels feeding the adrenal mass; progressive dissection of the mass with a pure enucleation technique in order to maximize the amount of adrenal parenchyma spared; specimen retrieval into an endocatch bag; hemostasis and closure of adrenal defect with a sliding clip technique._x000D_ Two cases are demonstrated in the video._x000D_ Baseline, perioperative and early functional outcomes data are reported._x000D_ Results All cases were completed robotically. Intraoperative blood loss was negligible, postoperative course was uneventful in all cases, except for 1 patient who required antibiotic therapy for post-operative fever (Clavien grade 2 complication). Median hospital stay was 3 days (IQR: 2-3)._x000D_ Patients became normotensive immediately after surgery. Aldosterone and plasmatic renin activity levels decreased and returned within the normal range after surgery as well._x000D_ Conclusions Robotic Partial Adrenalectomy is a safe and feasible technique. Thanks to surgical skills acquired with partial nephrectomy, an increasing adoption of adrenal sparing surgery among minimally-invasive urologists is likely to be anticipated. Funding none
Authors
Giuseppe Simone
Gabriele Tuderti Leonardo Misuraca Antonio Celia Bernardino De Concilio Antonio Stigliano Francesco Minisola Mariaconsiglia Ferriero Giuseppe Romeo Salvatore Guaglianone Michele Gallucci |
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V6-06 |
Robotic-Assisted Thoracoscopic Transdiaphragmatic Adrenalectomy: A Novel Surgical Approach |
Misc. GU Oncology and Transplant | 17BOS |
Abstract: V6-06 Sources of Funding: None Introduction In patients who have previously undergone trans-peritoneal or retroperitoneal surgeries, extensive adhesions may limit the feasibility of conventional transperitoneal laparoscopy. Herein, we introduce the technique of robotic-assisted thoracoscopic transdiaphragmatic adrenalectomy (RATTA) in a patient with a history of transabdominal surgeries. Methods Our patient is a 56-year-old female with a history of clear cell renal cell carcinoma (ccRCC) treated in 2004 with a left hand-assisted laparoscopic total nephrectomy, with negative surgical margins. In 2010, she was found to have enlargement of left retroperitoneal and common iliac lymph nodes and underwent chemotherapy with subsequent retroperitoneal lymph node dissection for a persistent left para-aortic mass. In 2015, she developed a 2.3 cm left (ipsilateral) adrenal nodule and had interval growth of a right lower lung nodule. Biopsy of the adrenal nodule demonstrated metastatic ccRCC. The patient was counseled and elected to undergo concomitant right robotic-assisted thoracoscopic pulmonary wedge resection and left RATTA. After completion of the pulmonary wedge resection by thoracic surgery, the patient was placed in a prone position. A double lumen endo-tracheal tube allowed for single (right) lung ventilation. With the left lung down, an 8 mm (camera) trocar was inserted into the thoracic cavity just superior to the 4th rib and pneumothorax was induced. Under direct vision, two additional 8 mm ports were placed approximately 6 cm on either side of the camera port. A 12 mm assistant port was then placed in a far lateral position. The diaphragm was incised, starting at the left crus and extending laterally through the diaphragmatic muscle exposing the retroperitoneal space and fat. The adrenal gland with mass was identified, dissected from surrounding structures, and extracted. The diaphragm was then closed using Ethibond® suture with PTFE felt pledgets. A 22-Fr chest tube was placed in the thoracic cavity. _x000D_ Results Operative and post-operative courses were uncomplicated. The chest tube was removed on post-operative day (POD) 2 with no residual pneumothorax. The patient was discharged on POD 4. Pathology confirmed metastatic ccRCC in both the left adrenal and right lung nodules with negative surgical margins. Conclusions We present the first described case of robotic-assisted thoracoscopic transdiaphramatic adrenalectomy. This novel technique represents a feasible alternative to transperitoneal or retroperitoneoscopic approaches in patients with previous abdominal and retroperitoneal surgeries. Funding None
Authors
Christopher M. Russell
Simpa S. Salami Amir H. Lebastchi Kiran H. Lagisetty Khaled Hafez Rishindra M. Reddy Alon Z. Weizer |
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V6-07 |
Intracorporeal partly stapled Padua Ileal Bladder using robotic staplers: surgical technique, perioperative and early functional outcomes of a prospective single center series |
Misc. GU Oncology and Transplant | 17BOS |
Abstract: V6-07 Sources of Funding: None Introduction Robot assisted radical cystectomy (RARC) with totally intracorporeal orthotopic neobladders is a challenging surgical procedure. The potentially increased risk of neobladders stone formation consequent to the use of staplers to create the neobladders is still a matter of debate. Robotic staplers have been recently made commercially available. In this prospective study (www.clinicaltrials.gov NCT02665156) we assessed the feasibility, safety and time efficiency of RARC with intracorporeal partly stapled “Padua Ileal Bladder” using robotic staplers. Methods Twenty-two consecutive patients with muscle invasive or high grade recurrent urothelial carcinoma of the bladder were treated between March 2016 and October 2016. Baseline, perioperative and follow-up data were prospectively collected and maintained into an IRB approved database. Key steps of surgery include: selection of 45 centimeters of ileum and division of the distal and proximal part of the ileum using robotic staplers; detubularization of the ileal loop; creation of the neo-bladder neck with one stapler load; double folding of the proximal ileal loop using two-three stapler loads; hand-sewing of the posterior neobladders wall with barbed suture; uretero-ileal anastomoses on JJ stents with a modified split-nipple technique; urethroneobladder anastomos is performed according to Van Velthoven; hand-sewing of the anterior neobladders wall with barbed suture. Results All procedures were successfully completed; open conversion was never necessary. Median total operative time (“skin to skin”) was 270 minutes (IQR:255-295). Operative time was < 300 minutes in all patients but two (345 and 350 minutes, respectively)._x000D_ One patient (4,5%) had wound infection (CLavien grade 1), three patients (13.6%) had Clavien grade 2 complications (blood pack trasfusion, urinary tract infection requiring antibiotics, hypoxaemia requiring oxygen treatment), one patient (4.5%) needed urethral catheter replacement in the OR (Clavien grade 3b) and one patient (4.5%) had acute kidney failure requiring temporary dialysis (Clavien grade 4a). Median hopsital stay was 9 days (IQR 8-11). Three patients (13.5%) required readmission after discharge (Candidaemia requiring medical treatment [Clavien grade 2] and nephrostomy tube insertion in two patients [Clavien 3a]). Overall complication rate was 40.1% and overall severe complication incidence was18.2%; 59.5% of patients did not experience any complication. At a median follow-up of 3 months, no patients developed recurrence, daytime continence rate was 59%._x000D_ Conclusions We first report safety and time efficiency in the use of robotic staplers to create orthotopic neobladder. This preliminary report highlights feasibility of this technique and favorable perioperative and functional outcomes._x000D_ _x000D_ Funding None
Authors
Giuseppe Simone
Salvatore Guaglianone Francesco Minisola Mariaconsiglia Ferriero Leonardo Misuraca Gabriele Tuderti Giuseppe Romeo Michele Gallucci |
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V6-08 |
Robotic Ureteral Reconstruction for Ureteral Complications of Kidney Transplants |
Misc. GU Oncology and Transplant | 17BOS |
Abstract: V6-08 Sources of Funding: None Introduction Urologic complications after kidney transplantation are a significant cause of morbidity leading to decreased graft function or graft loss. Ureteral stricture is the most common complication with a reported incidence ranging between 0.6% to 10.6%. The reported incidence of vesicoureteral reflux (VUR) causing graft pyelonephritis is 0.1% to 3.5%._x000D_ _x000D_ Uretero-pyelostomy and uretero-ureterostomy utilizing the native ureter are well established surgical methods of transplant ureteral reconstruction._x000D_ _x000D_ The aim of this study is to evaluate the technique, feasibility and results of robotic-assisted laparoscopic reconstruction of the transplanted ureter with the native ipsilateral ureter._x000D_ Methods We retrospectively reviewed six patients (3 male, 3 female) who underwent 5 robotic-assisted uretero-pyelostomies and 1 uretero-ureterostomy between 2013 and 2016. Mean follow-up time was 18 months (range 2 to 37 month)._x000D_ _x000D_ Four patients had significant ureteral obstructions and 2 had recurrent pyelonephritis due to VUR. 2 patients with obstruction had nephrostomy tubes (NT) at time of surgery and 2 had double J stents._x000D_ _x000D_ All patients were evaluated preoperatively with a voiding cysto-urethrogram (VCUG), cystoscopy and retrograde pyelography and MAG3 renal scan. 4 patients had a preoperative nephrostogram. Baseline post-transplant serum creatinine, pre-reconstruction serum creatinine, post-reconstruction serum creatinine were evaluated. A MAG3 renal scan was obtained post-operatively in case of increased creatinine._x000D_ _x000D_ All patients had postoperative cystograms and were followed with serum creatinine-GFR._x000D_ Results Each transplant ureteral reconstruction were completed successfully. There was one conversion to an open uretero-pyelostomy. Mean hospital stay was 3 days (range 2-4 days). One patient had a ureteral obstruction due to kinking of the JJ stent requiring a NT placement. _x000D_ After ureteral reconstruction. serum creatinine returned to baseline for all patients. No recurrent strictures were demonstrated by increasing serum creatinine or MAG3 renal scans. No recurrent episodes of pyelonephritis were found. There was no graft loss. _x000D_ Conclusions Robotic-assisted reconstruction of the transplant ureter by uretero-pyelostomy or uretero-ureterostomy using the native ureter is feasible and can be safely performed with graft survival and low complication rates. Funding None
Authors
Kevin Yang
David Canes Alireza Moinzadeh Andrea Sorcini |
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V6-09 |
Novel Robotic Approach to Inguinal and Pelvic Lymphadenectomy for Metastatic Melanoma in a 44 Year Old Male |
Misc. GU Oncology and Transplant | 17BOS |
Abstract: V6-09 Sources of Funding: None Introduction To describe a new approach to pelvic lymphadenectomy designed to reduce complication rates. Methods This case describes the treatment of a 44 year old male requiring an inguinal lymph node dissection. This case was approached robotically in order to minimize complications. This video describes and demonstrates the robotic technique, as well as, the patient’s clinical course and follow-up under the care of one surgeon at a large, academic hospital. Results Complete resection of the inguinal lymph nodes using the Da'Vinci Xi robot resulted in no complications with no signs of recurrence at follow-up. Conclusions Continued expectations to provide exceptional oncological care while minimizing morbidity have lead surgeons to novel treatment approaches for inguinal lymphadenectomy. Open inguinal lymph node dissections continue to have significant rates of complications. The vast majority of complications are due to tissue necrosis, wound dehiscence, seroma formation, and lymphedema. Previously published rates of seroma formation are as high as 32% for the open technique, while the instance of lymphedema may be as high as 40%. Wound infections also comprise a significant portion of morbidity at 24% and skin flap complications are reported at 52%. With this technique our cohort experienced one total Clavien grade II complication (20%) and had an average length of stay under two days which is similar to other minimally invasive techniques. _x000D_ Our oncological outcomes with this technique have been equivalent to the open approach to date. No patients have had recurrent disease. Our lymph node count per side ranges from 1-54; however, 60% of the groins contain 6 or greater lymph nodes. _x000D_ Robotic inguinal lymph node dissection represents a promising alternative to the traditional open technique with the possibility of lower overall morbidity. Additional studies should be conducted evaluating the oncologic efficacy of this approach. _x000D_ Funding None
Authors
Nathan Jung
Hugh Smith Alan Hyde Alvaro Valle Chris Keel |
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V6-10 |
Robotic kidney transplant – our initial experience and technique. |
Misc. GU Oncology and Transplant | 17BOS |
Abstract: V6-10 Sources of Funding: None Introduction Kidney transplant is the treatment of choice for CKD stage 5. Though open surgery is the gold standard, it has disadvantages like pain, wound related morbidity and inferior cosmesis. Therefore, minimally invasive surgical techniques are being established. Our objective is to present our initial experience and technique of robotic kidney transplant. Methods We retrospectively studied twelve procedures conducted from April 2016 to October 2016. The demographic, operative, complication, and outcome data were analysed. Kidney was wrapped in an ice slush jacket and then inserted into the abdomen of the recipient through a midline umbilical (9 patients) or Pfannenstiel incision (three patients). A Gel-point port was used to seal the mid-line incision. The gel point was used to introduce kidney, ice-slush and a vascular punch for arteriotomy. Renal arterial anastomosis was done end to side to external iliac artery and renal venous anastomosis end to side to external iliac vein. Results Age of patients ranged from 9 to 50 years. The combined arterial and venous anastomosis time ranged from 35 to 50 minutes. Mean operative blood loss 120± 20 ml. Mean hospital stay of 8 days. There were no surgical complications and no conversions to open. Mean serum creatinine at discharge, at one & 3 month were 2.6 mg/dl; 1.2 mg/dl & 1.3 mg/dl respectively. Conclusions Robotic approach confers advantages of decreased wound morbidity, better cosmesis and no lymphocele. However, long term follow up of large number of patients is needed to establish its place. It is more expensive than open procedures. Funding None
Authors
Anant Kumar
Anil Gulia Samit Chaturvedi Manoj Kumar Ruchir Maheshwari Karamveer Singh Sabharwal |
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V6-11 |
Laparoscopic Radical Heminephrouretectomy in Horseshoe Kidney with High-Grade Urothelial Cell Carcinoma and Single-Port Bladder Cuff Management: First Case Report. |
Misc. GU Oncology and Transplant | 17BOS |
Abstract: V6-11 Sources of Funding: None Introduction Horseshoe kidney is a renal fusion congenital disorder, affecting up to 0.25% of the general population. High-grade urothelial carcinoma represents about 5-7% of all renal tumors._x000D_ We describe the laparoscopic approach of hemi-nephroureterectomy and lymphadenectomy with the single-port bladder cuff resection in a horseshoe kidney with upper urinary tract urothelial cell carcinoma. Methods Male, 50 years old patient with an incidental endoscopic finding of a right renal pelvic tumoral lesion. The imaging studies revealed a horseshoe kidney._x000D_ _x000D_ The angio-MRI of the abdomen reveals a tumor in the renal pelvis and in the first two-thirds of the ureter. The vascular artery study reveals a renal artery supplying blood to the tumoral lesion and the second artery to the inferior pole of the kidney._x000D_ Results Right laparoscopic radical hemi-nephroureterectomy with Isthmectomy and lymphadenectomy (perihiliar, paraaortic, precaval, and paracaval) whit single-port bladder cuff was performed without complications. The surgical specimen was all removed by the suprapubic incision of the single port._x000D_ _x000D_ The pathology shows a tumor confined to the renal pelvis; ureter tumor extension recognized with partial obstruction in its proximal two-thirds, without recognizing infiltration ureteral wall. lymph node negative for tumor involvement. TNM: pT1 High-Grade N 0 M 0. _x000D_ Six months follow-up is satisfactory without relapse._x000D_ _x000D_ Conclusions This is the first case reported which describes the laparoscopic approach for hemi-nephroureterectomy with lymphadenectomy and simultaneously by single-port bladder cuff in horseshoe kidney with upper urinary tract urothelial cell carcinoma._x000D_ _x000D_ The single-port technique, allows an intravesical approach with a safe surgical margin while still attaining the benefits of a minimally invasive surgery._x000D_ _x000D_ This procedure is viable and safe, inclusive in structural anomalies such as the horseshoe kidney with favorable oncologic short-term results._x000D_ _x000D_ Funding None
Authors
Marino Cabrera
Jose Gustavo Ramos Claudia Lucia Ochoa Angie Ramirez Rodolfo Varela Jorge Forero German Godoy |
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V6-12 |
Transvescicoscopic bladder cuff excision in laparoscopic nephroureterectomy |
Misc. GU Oncology and Transplant | 17BOS |
Abstract: V6-12 Sources of Funding: None Introduction To describe the management of the distal ureter during laparoscopic radical nephroureterectomy with the transvesical laparoscopic approach. Methods The patient was placed in the modified lithotomy position with abducted thighs. The procedure started with cystoscopic examination of the bladder and ureteral orifices. After a small skin incision, a 5-mm-diameter trocar was introduced into the bladder dome. The anterior bladder wall was suspended to the abdominal wall to prevent the trocar from slipping out and 2 more 3-mm-diameter trocars were placed. The ureter was mobilized with hook electrocautery and dissected ureteral end was placed in extravesical space. Bladder was repaired with 4-0 vicryl. Then patient was placed in lateral position and conventional laparoscopic radical nephroureterectomy was performed. While dissection of distal ureter, the distal end of ureter was smoothly removed from perivesical space without any difficulty. Results The patient was a 61-year-old female. The patient’s CT scan showed right proximal ureteral mass and the result of previously performed ureteroscopic biopsy was transitional cell carcinoma, low grade. The operation time of transvesical bladder cuff excision was 50 minutes, and laparoscopic nephroureterectomy was performed for 120 minutes. Estimated blood loss of whole procedure was 300ml and there was no intraoperative or postoperative complication. Foley catheter was removed at 1 week. After 6 months postoperatively, there’s no evidence of recurrence or metastasis. Conclusions Our initial experience with transvesicoscopic bladder cuff excision in laparoscopic radical nephroureterectomy demonstrated that the procedure is feasible and safe. Funding None
Authors
Young Eun Yoon
Sang Woon Kim Hyung Ho Lee Jang He Han Seung Hwan Lee Won Sik Ham Koon Ho Rha Woong Kyu Han |
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V7-01 |
Intraoperative MRI-Guided Navigation of the Pelvic Floor During Exstrophy Closure |
Pediatrics | 17BOS |
Abstract: V7-01 Sources of Funding: none Introduction Radical dissection of the urogenital fibers and the thickened smooth and striated muscle fibers connecting the posterior urethra and bladder plate to the diastatic pubic rami is crucial for adequate placement of the posterior vesicourethral unit deep within the pelvis during classic bladder exstrophy (CBE) and cloacal exstrophy (CE) closure, as well as ensuring successful outcomes. Intraoperative magnetic resonance imaging (MRI) guided navigation of the pelvic floor offers a novel technique for identification of the urogenital diaphragm fibers and the thickened muscular attachments between the posterior urethra, bladder plate and pubic rami during CBE closure. Methods Institutional review board and Food and Drug Administration approval was obtained for use of Brainlab® (Munich, Germany) intraoperative MRI-guided navigation of the pelvic floor anatomy during closure of CBE at the authors’ institution. Pre-operative pelvic MRI was obtained one day prior to exstrophy closure in patients necessitating pelvic osteotomies. Intraoperative registration was performed after pre-operative planning with a pediatric radiologist utilizing five anatomic landmarks immediately prior to initiation of surgery. Accuracy of identification of pelvic anatomy was assessed by three pediatric urologic surgeons and one pediatric radiologist. Results 32 patients with CBE and 2 patients with CE closed at the authors’ institution have successfully utilized Brainlab® technology to navigate and guide the dissection of the pelvic floor intraoperatively. All patients had 100% accuracy in correlation of gross anatomic landmarks with MRI identified landmarks intraoperatively, and all have had successful closure without any complication. Conclusions Brainlab® intraoperative MRI-guided pelvic floor navigation and dissection is an effective way to accurately identify pelvic anatomy during CBE and CE closure. Future assessment of real-time changes in pelvic floor anatomy comparing pre-closure to post-closure MRI will allow quantification of pelvic floor anatomy in these patients and may allow for intra-institutional telementoring in this most important first step of exstrophy reconstruction. Funding none
Authors
Heather Di Carlo
Aylin Tekes John Gearhart |
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V7-02 |
Robotic Assisted Ileovesicostomy & Cecostomy Tube |
Pediatrics | 17BOS |
Abstract: V7-02 Sources of Funding: None Introduction Robotic surgical techniques have been adopted for procedures in pediatric urology but reconstruction for neurogenic bladder has been an area where it is underutilized. The reasons for this may include the need to create a bowel anastomosis, relative inexperience with robotics or perceived limitations of the technology. Our objective is to demonstrate the successful use of robotics in creating an ileovesicostomy incontinent urinary diversion with a complete intra corporeal bowel anastomosis and cecostomy tube placement. Methods A 15 year-old female with myelomeningocele and neurogenic bladder had multiple failed attempts at compliance with clean intermittent catheterization program. She developed acute kidney injury and it was recommended that she undergo incontinent urinary diversion. We utilized the Intuitive Surgical DaVinci® Si robotic surgery system for the operation. Prior to port placement, we performed cystoscopy and injected 300 units of botox into the detrusor muscle. We used a 12mm camera port just superior to the umbilicus and three 8mm robotic ports. A 12mm accessory port was also placed for additional assistance. A cecostomy tube was also placed robotically to manage the patient’s neurogenic bowel. The ileovesicootomy stoma was created in the left lower quadrant by extending the left arm robotic port site. Results The patient was admitted the day prior to the procedure for mechanical bowel prep. The next morning she was taken to the operating room for the procedure. Total operative time was 406 minutes. Anesthesia induction was 17 minutes, cystoscopy and botox injection was 10 minutes and port placement and laparoscopic dissection took 22 minutes. Total console time was 244 minutes and closure time was 14 minutes. The remaining 96 minutes was for patient positioning and preparation. A foley catheter was placed per her urethra temporarily to keep her bladder decompressed to aid in wound healing and was removed prior to discharge. She was started on a clear liquid diet on post-operative day #2 and advanced as tolerated. The patient was discharged home on post-operative day #4 with no surgical drainage tubes except for her urostomy. At 5-month follow-up her creatinine remains at her baseline of 0.9 and her ultrasound shows no hydronephrosis. She has no leakage per urethra. Conclusions Robotic assisted ileovesocostomy is technically feasible in the pediatric population. As experience increases with such techniques, these authors expect that robotic surgery can be utilized in more complex reconstruction and patients can experience the benefits that minimally invasive techniques offer. Funding None
Authors
Christina Ching
Molly Fuchs Christopher Brown Daniel DaJusta |
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V7-03 |
Robotic Partial Nephrectomy with Selective Clamping for Renal Mass in <15kg Pediatric Patient: Techniques Adapted from Adult Urology |
Pediatrics | 17BOS |
Abstract: V7-03 Sources of Funding: None Introduction Robotic partial nephrectomy (RPN) provides for nephron sparing and renal preservation with a minimally invasive approach. Though commonly utilized in adults for resection of renal masses, it is less commonly applied for tumors in children. To optimize outcomes in these patients, techniques from the adult setting were translated to the pediatric realm, with the goals of fostering bi-directional transfer of expertise and knowledge and of achieving safe and effective application of this surgical approach. Methods A collaborative team was formed and consisted of a pediatric urologist trained in minimally invasive and oncologic surgery as primary surgeon with an adult minimally invasive oncologic urologist as proctor. Key aspects for translation to the pediatric setting included: port placement, lower insufflation pressure, choice and size of instruments and supplies, and minimization of potential hemorrhage and ischemia with selective clamping/early unclamping technique. This approach was applied to a 14 kilogram, 3 year old female with a right lower pole lesion with cystic and solid components, concerning for malignancy. Results The mass was resected with negative margins and demonstrated benign pathology. Clamp time was 14 minutes, and EBL was minimal. There were no intra- or post-operative complications. The patient’s creatinine was unchanged, and a follow-up ultrasound demonstrated no residual mass in a normal appearing right kidney. Conclusions Collaboration of experienced pediatric and robotic teams allows for successful adaptation of adult techniques to pediatric patients. Specific considerations must be made in order to achieve safety and feasibility of RPN with selective clamping for renal preservation in cases of pediatric renal masses. Funding None
Authors
Patricia S. Cho
Michael V. Hollis Briony K. Varda Erin R. McNamara Richard N. Yu Andrew A. Wagner Richard S. Lee |
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V7-04 |
Mons Plasty: A Technique for Optimal Aesthetic Outcome |
Pediatrics | 17BOS |
Abstract: V7-04 Sources of Funding: None Introduction It has been suggested that women who have undergone repair for exstrophy-epispadias complex (EEC) have unsatisfactory cosmetic results possibly leading to decreased self-esteem. Here we aim to show a mons plasty technique to be incorporated at the initial EEC closure that creates anatomically correct external female genitalia as well as improves the aesthetic outcome. Methods Briefly, the surgical technique incorporates approximation of the bifid clitoris in the midline, aligning the labia minora along the lateral aspect of the introitus, creation of a clitoral hood, superomedial rotation of the labia majora, and finally mobilization of peripubic adipose to create a mons. Results In our experience the surgical technique was successful in creating anatomically normal appearing external genitalia with subjective parental satisfaction. The patient has not had any complications. A post-operative VCUG showed grade 3 left vesicoureteral reflux. She is not yet potty trained but does have apparent normal voiding with dry periods throughout the day. Conclusions The technique described restores normal anatomic appearance as well as improves the cosmetic outcome. This technique should be considered in one-stage female EEC closure. Funding None
Authors
Kelly Nast
Diana Cardona-Grau George Chiang Antoine Khoury |
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V7-05 |
Robotic Assisted Laparoscopic Adrenalectomy In The Setting Of An Incidental Adrenal Mass |
Pediatrics | 17BOS |
Abstract: V7-05 Sources of Funding: none Introduction Since Rudolf Virchow first described abdominal “glioma� tumors in children, neuroblastoma has come to be recognized as the most common malignancy in infants and the most common solid malignancy in children. Resection in neuroblastomas that are classified as low risk is often curative. Traditionally the standard operative management has been open surgical resection. More recently however, a shift towards minimally invasive approaches has been described. Here we report a case of neuroblastoma managed with robotic assisted laparoscopic adrenalectomy. This is the first robotic adrenalectomy performed at our institution and, to the best of our knowledge, the first performed on a Da Vinci Xi robot. Methods A single case was reviewed and reported. Results A 2-year-old female with a history of a febrile urinary tract infection found to have a poorly functioning left upper pole moiety with ectopic ureter initially underwent a successful robotic assisted left upper pole partial nephrectomy. On her postoperative renal ultrasound, she was found to have a new right sided adrenal mass. This was confirmed with MRI and MIBG scan. Metanephrinies, homovanillic acid, and vanillylmandelic acid levels were obtained to evaluate for pheochromocytoma and were within normal limits. Robotic assisted laparoscopic right adrenalectomy was then performed. Intraoperatively, a small iatrogenic cavotomy was made and repaired. There were no further complications and the patient tolerated the procedure well. She had an uneventful recovery and was discharged home on post-operative day two. Conclusions Robotic assisted laparoscopic adrenalectomy represents a viable option for surgical excision of adrenal tumors and can be accomplished with rapid recovery time, decreased surgical morbidity, and comparable oncologic outcomes. Injury to surrounding vessels presents a known complication to adrenalectomy. Our case demonstrates the advantage of a Da Vinci Xi surgical system for laparoscopic vascular repair and tumor excision. In our experience, while adhering to sound oncologic surgical principles, a robotic assisted laparoscopic approach can be considered as an alternative to traditional open adrenalectomy for select children with neuroblastoma. Funding none
Authors
Eli Thompson
Evalynn Vasquez Andy Chang Paul Kokorowski |
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V7-06 |
PERCUTANEOUS EXTERNALLY ASSEMBLED LAPAROSCOPIC (PEAL) SURGERY FOR FOWLER-STEPHENS ORCHIOPEXY: A VIDEO PRESENTATION |
Pediatrics | 17BOS |
Abstract: V7-06 Sources of Funding: None Introduction Laparoscopy is the gold standard for diagnosis and treatment of boys with non-palpable testicles. In an effort to reduce the invasiveness of laparoscopic orchiopexy, various strategies have been employed including use of laparoendoscopic single site surgery (LESS) and needlescopic surgery. Needlescopic instruments have limited functionality due to their small size and are more prone to intrabdominal organ injury. LESS has been criticized when used in children due to the requirement of a much larger 3 cm incision. In this video we will demonstrate the feasibility of a novel percutaneous externally assembled laparoscopic (PEAL) surgery paradigm for orchiopexy which is designed to reduce the invasiveness of the procedure while maintaining instrument triangulation. Methods The PEAL surgical paradigm is composed of a reusable handpiece and a disposable 2.96 mm instrument shaft and interchangeable disposable 5 mm instrument tips. This video will demonstrate how the PEAL instruments are externally assembled and brought back into the abdomen without a trocar to perform the surgery. Due to their small size and because they are assembled externally, they produce an essentially scarless outcome. This video will demonstrate the PEAL surgical paradigm for the performance of Fowler-Stephens orchiopexy._x000D_ _x000D_ Results Using this innovative new paradigm, a 9 month-old infant underwent first stage and a 9 year-old child underwent second stage successful bilateral Fowler-Stephens orchiopexies. Operative times were 65 minutes for the first stage and 180 minutes for the second stage. Blood loss was minimal in both cases. Both patients were discharged the day of surgery with no complications. At follow up, the objective cosmetic results were excellent and the second patient&[prime]s testis was palpable in the scrotum and well-positioned. Conclusions Due to its improved cosmesis and ease of performance, the PEAL surgical paradigm shows promise in reducing the invasiveness of pediatric Fowler-Stephens orchiopexy. In addition it shows promise with a wide variety of minimally invasive surgical applications. Funding None
Authors
David Ruckle
Samuel Abourbih Minh-Hang T. Chau Mohamed Keheila Jim Shen Patrick Yang Salim Cheriyan Nazih Khater D. Duane Baldwin |
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V7-07 |
Robotic Bladder Neck Reconstruction with Sling and Split Appendix Technique for Appendicovesicostomy and MACE |
Pediatrics | 17BOS |
Abstract: V7-07 Sources of Funding: None Introduction Robotic surgical techniques have been adopted for procedures in pediatric urology even in reconstruction for neurogenic bladder. Our aim was to expand on the previously described bladder neck reconstruction with sling and Appendicovesicostomy (APV), by showing that the well described open split appendix technique can also be perform robotically, allowing for the creation of both APV and MACE. This video is to our knowledge, the first to demonstrate the use of robotic split appendix technique. Methods A 6 year-old male with myelomeningocele, neurogenic bladder and bowel was not able to achieve urinary continence on a standard regiment of IC and anticholinergic. Urodynamic showed adequate bladder capacity at 300 ml with low storage pressure and adequate compliance. Unfortunately he had a low leak point pressure indicating poor outlet resistance. Thus indication for a bladder neck reconstruction with APV was made. There was also a need for implementing a good bowel regiment and after evaluation at our Center for Colorectal and pelvic Reconstruction by the colorectal surgeon, indication for a MACE was also made. We selected to utilize the Intuitive Surgical DaVinci® Si robotic surgery system for the operation. Prior to port placement, we performed cystoscopy and injected 300 units of Botox into the detrusor muscle, we placed ureteral catheter for easy ureteral orifice identification during bladder neck reconstruction and an 8 French Foley catheter. We used a 12mm camera port just superior to the umbilicus and three 8mm robotic ports. A 12mm accessory port was also placed for additional assistance. Results The patient was admitted the day prior to the procedure for mechanical bowel prep. The next morning he was taken to the operating room for the procedure. Total operative time was 7 hours. Total console time was 6 hours. A 10 French Foley catheter was placed through the APV channel and an 8 French feeding tube was placed through the MACE. A 5 French feeding tube was left stenting the urethra and was removed prior to discharge. He was started on a clear liquid diet on post-operative day #2 and advanced as tolerated. The patient was discharged home on post-operative day #4. Conclusions Robotic assisted bladder neck reconstruction with split appendix technique to create both APV and MACE is technically feasible in the pediatric population. As experience increases with such techniques, these authors expect that robotic surgery will continue to be utilized in more complex reconstruction and patients can experience the benefits that minimally invasive techniques offer. Funding None
Authors
Molly Fuchs
Christina Ching Christopher Brown Richard Wood Mark Levitt Rama Jayanthi Daniel DaJusta |
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V7-08 |
Laparoscopic Nephrectomy for Prenatally diagnosed Wilms' Tumor |
Pediatrics | 17BOS |
Abstract: V7-08 Sources of Funding: None Introduction The most common diagnosis of neonatal renal mass is congenital mesoblastic nephroma. However, Wilms' tumor has been reported sporadically in the literature. We report the diagnosis, management and surgical approach to a prenatally diagnosed Wilms' tumor. Methods The patient was a newborn female found to have an abnormal renal ultrasound on routine 2nd trimester prenatal ultrasound. The mass was seen on subsequent ultrasounds at 32 weeks and again 37 weeks. Neonatal ultrasound confirmed the mass. A contrast-enhanced CT scan was performed on day 10 of life, revealing a centrally-located, multifocal, enhancing left renal mass. The remainder of staging work up was negative. She underwent a Laparoscopic radical left nephrectomy with lymph node sampling on day 26 of life. Intraoperative frozen pathology was consistent with Wilms' tumor; therefore, a port-a-cath was placed under the same anesthetic for administration of adjuvant chemotherapy. The case presentation and surgical management are described in the video. Results The final pathology revealed favorable histology Stage II Wilms' tumor. There was extension into the renal sinus. Surgical margins were negative. There was no lymph node involvement. The patient was dismissed on post operative day 1. She received adjuvant chemotherapy with Vincristine and Dactinomycin based on the EE4A regimen. Port placement was performed using the novel HIdES (Hidden Incision Endoscopic Surgery); which renders the scar profile nonvisible if the patient is wearing a bathing suit. Conclusions Although the most common cause of neonatal renal mass is nephrogenic mesoblastic nephroma, Wilms' tumor cannot be excluded. Therefore, a timely management is warranted. A minimally-invasive surgical approach to radical nephrectomy and lymph node sampling is safe and feasible in the neonatal period. Funding None
Authors
Amir Toussi
Candace Granberg Patricio Gargollo |
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V7-09 |
Pediatric Robot-assisted Lower Pole Heminephrectomy with Intraureteral Indocyanine Green in a Duplicated Collecting System Not Following Weigert-Meyer Law |
Pediatrics | 17BOS |
Abstract: V7-09 Sources of Funding: None Introduction Duplicated collecting systems that violate Weigert-Meyer law are rare, and have only been reported in a handful of case reports. Indocyanine green (ICG), a dye that can be visualized under near-infrared fluorescence, may be used as a real-time contrast agent in the surgical management of patients with atypical ureteral anatomy. We describe a robot-assisted lower pole heminephrectomy with intraureteral ICG in a 13 year old pediatric patient with a duplicated collecting system not following Weigert-Meyer law. Methods Magnetic resonance urography demonstrated that the lower moiety renal pelvis was severely dilated proximal to a ureteropelvic junction obstruction and that the ectopic lower moiety ureter inserted into the prostatic urethra. Renal scan demonstrated an essentially functionless left lower moiety. The patient’s family consented to off-label use of ICG after full disclosure. Intraoperatively, 10 milliliters of indocyanine green solution (25 milligrams indocyanine green in 10 milliliters distilled water) was injected into the lower moiety ureter through a ureteral catheter. Near-infrared fluorescence was toggled on and off throughout the procedure to visualize the green-fluoresced ureter throughout the case. Results The patient’s left lower pole moiety kidney and ectopic ureter were removed en-bloc. Use of intraureteral ICG allowed for definitive identification and precise dissection of the lower moiety ureter. Operative time was 235 minutes and estimated blood loss was 450 milliliters. On postoperative day one, the patient’s Foley catheter was removed and the patient was discharged. There were no intraoperative or postoperative complications. Conclusions Exceptions to Weigert-Meyer law are uncommon. In such cases, the use of intraureteral ICG may be used as a contrast agent to definitively delineate ureteral anatomy intraoperatively. Funding None
Authors
Ziho Lee
Michael Packer Gregory Dean Jonathan Roth Daniel Eun |
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V7-10 |
Robotic assisted laparoscopic dismembered tapered ureteral reimplantation for megaureter |
Pediatrics | 17BOS |
Abstract: V7-10 Sources of Funding: None Introduction Children with megaureters may have elements of obstruction, reflux, or both and are at risk for upper tract deterioration if left uncorrected. We present a series of 5 pediatric patients ranging from 14 months old to 11 years old with symptomatic megaureter and describe a novel technique for surgical correction involving a minimally-invasive, robotic-assisted approach with a dismembered extravesical ureteroneocystostomy following extracorporeal ureteral tapering. Methods We retrospectively reviewed 5 pediatric cases of megaureter managed in similar fashion with a novel surgical technique. Outcomes were assessed via chart review with a focus on postoperative improvement in clinical symptoms and in radiographic findings. Results After a mean follow up of 24 months, all patients have demonstrated clinical improvement in their symptoms, radiographic improvement of hydronephrosis, or both. This pattern persists in the two patients with longest follow ups of 44 and 54 months. Repeat voiding cystourethrogram following surgery is done as clinically indicated and has not yet been performed in all patients who had preoperative reflux. Conclusions In conclusion, robotic-assisted laparoscopic dismembered ureteroneocystostomy with extracorporeal ureteral tapering is a feasible, minimally-invasive method for managing patients with symptomatic megaureter who have components of obstruction, reflux, or both. Funding None
Authors
Jared Manwaring
Jonathan Riddell |
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V7-11 |
Robotic-Assisted Laparoscopic Partial Nephrectomy for a Renal Mass in a Two-Year-Old |
Pediatrics | 17BOS |
Abstract: V7-11 Sources of Funding: None Introduction Robotic-assisted laparoscopic extirpative renal surgery has been well described for benign indications in children, primarily for resection of non-functioning renal moieties. However, it has rarely been described for resection of potentially malignant masses. The following clinical case demonstrates successful robotic-assisted laparoscopic partial nephrectomy (RALPN) for a renal mass in a two-year-old child. Because the methods used for neoplasms differ significantly from those employed for benign resection, they have been described in detail and demonstrated in the accompanying video. Methods The patient is a 15kg, otherwise healthy, two-year-old girl with an incidentally discovered 1.2cm left lower pole renal mass. The small size and polar location of the lesion made it particularly amenable to RALPN with plans for frozen section analysis and possible regional lymphadenectomy and conversion to radical nephrectomy. Results The procedure was performed using an 8mm umbilical camera port, two 8mm robotic arm ports, and a 12mm assistant port. After medializing the descending colon, the ureter was traced up to the renal hilum. Renal vessels were encircled with vessel loops. The Gerota’s fascia and fat overlying the lower pole of the kidney was dissected and sent to pathology, exposing the underlying mass. Intra-operative ultrasound confirmed the presence and depth of the mass. The renal artery was clamped with laparoscopic bulldog. The mass was excised with cold scissors. Renorrhaphy was performed using sliding clip technique. Warm ischemic time was 32 minutes. Frozen sections showed narrow margins but was inconclusive regarding the tumor’s malignant potential and so a decision was made to defer further surgery until definitive diagnosis. Estimated blood loss was 10cc. The patient was discharged from the hospital on day two. Final pathology demonstrated adenomatous perilobar nephrogenic rest, a known precursor lesion to Wilms’ tumor. At last follow-up 3.5 months postoperatively, the patient is doing well with renal ultrasound demonstrating a normal appearing and symmetrical left kidney. Conclusions RALPN is a safe and effective modality for resecting potentially malignant renal masses, even in very small children. We believe it offers significant advantages over the large open incisions and radical resections often still utilized for small pediatric renal masses. The accompanying video further illustrates our technique. Funding None
Authors
Ramsey Al-Khalil
Wai Lee April Adams Szafran Wayne Waltzer Ezekiel Young |
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V7-12 |
ROBOTIC-ASSISTED LAPAROSCOPIC LEFT NEPHROURETERECTOMY OF AN ECTOPIC KIDNEY IN THE MALE PEDIATRIC PATIENT |
Pediatrics | 17BOS |
Abstract: V7-12 Sources of Funding: None Introduction Ectopic ureteral insertion is a rare condition. Ectopic ureters in males may present with flank pain, lower urinary tract symptoms, or epididymoorchitis. We present a case of a male patient with a dysplastic, ectopic, left kidney with an ectopic ureter managed with robotic-assisted laparoscopic nephroureterectomy._x000D_ _x000D_ Methods A 10 year old male presented with chronic, left epididymal pain. Urinalysis was unremarkable. The patient was born with a solitary functioning right kidney detected on prenatal ultrasound. Additionally, he had a known left sided pelvic cyst, consistent with a nonfunctioning, ectopic, left kidney. The ectopic, dysplastic, left kidney had been followed with regular ultrasounds and the dilated renal pelvis had increased in size by 8 mm over the last five years. Routine ultrasound demonstrated a 4.5 cm, tubular, cystic structure behind the bladder. Follow up MRI revealed an atrophic, ectopic, dilated left kidney with ectopic ureter inserting into the left seminal vesicle. The patient was taken for robotic assisted laparoscopic left nephroureterectomy. Results Pathologic analysis revealed an ectopic ureter with associated epithelial-lined cyst. No renal parenchyma was identified in the pathologic specimen. There were no complications. Estimated blood loss was 20 milliliters. The patient was dismissed from the hospital on postoperative day 1. Conclusions Robotic-assisted laparoscopy proved to be a safe and efficacious platform for dissection and removal of an ectopic, nonfunctioning kidney with an ectopic ureter draining into the seminal vesicle. All structures were accessed from a single docking point, and the procedure was well-tolerated, providing a minimally-invasive option for management of this congenital abnormality. Funding None
Authors
George Bailey
Candace Granberg |
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V8-01 |
Focal Laser Ablation: Path to a clinic treatment for prostate cancer |
Prostate and Renal Oncology | 17BOS |
Abstract: V8-01 Sources of Funding: Medtronic Navigation, Inc. via Physician-Sponsored Research Agreement with Regents of University of California and National Cancer Institute (R01CA158627). Introduction Focal therapy of prostate cancer (CaP) is of keen interest, but data obtained via clinical trials are scarce. In this video, a path from targeted prostate biopsy to focal laser ablation (FLA) is demonstrated in 4 ensuing chapters: (1)Targeted Biopsy, (2) Preliminary Studies, (3) MRI-guided In-bore FLA, and (4) In-clinic FLA. Clinical trial data are included to support each step along the path. Methods The path started with targeted biopsy via MRI/US fusion (Artemis), now performed in >1500 men at UCLA since 2009; these data laid groundwork for FLA. Preliminary studies using interstitial laser energy (in vitro and in vivo) were then assembled. After that, FLA in-bore was performed in 8 men, using direct MRI guidance for targeting and MR thermometry for temperature monitoring. Then, FLA was performed in-clinic in 10 men using (1) the fixed arm of the Artemis device for stabilization of the intra-prostatic laser fiber, (2) MRI/US fusion for tumor localization and targeting, and (3) direct thermal probes for safety monitoring during treatment. In-clinic FLA was performed using local anesthesia + midazolam. Results Initial work with targeted biopsy showed that index CaP lesions could be accurately defined and other serious lesions ruled out in >80% of cases (Filson, CA, 2015). Preliminary studies showed that interstitial laser energy could ablate prostate tissue safely and effectively. Then, In-bore FLA was shown to be safe and effective in 8 men (Natarajan, J.Urol., 2016), but was cumbersome and expensive. Ultimately, the path led to an FDA-approved Phase I trial of out-of-bore (in-clinic) FLA in 10 men, all with intermediate-risk CaP. Short-term results were similar to those obtained in-bore, but simpler (3 vs 6 personnel), quicker (minutes vs hours), and less expensive (thousands vs tens of thousands of dollars). In-clinic FLA resulted in prostate-confined ablation zones averaging 4.3 cc (range, 2.1-6.0 cc); no man incurred incontinence or ED; and at 6-month targeted biopsies, successful ablation of intermediate-risk CaP was found in 6/10 men. Defining adequate margins of treatment remains a challenge. Conclusions A path from targeted biopsy to focal laser ablation of prostate cancer was followed; the potential for safe and effective treatment of intermediate-risk CaP ---under local anesthesia in a clinic setting---has been established. Funding Medtronic Navigation, Inc. via Physician-Sponsored Research Agreement with Regents of University of California and National Cancer Institute (R01CA158627).
Authors
Leonard Marks
Shyam Natarajan Alan Priester Daniel Margolis |
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V8-02 |
APPLICATION OF CHITOSAN MEMBRANES ON THE NEUROVASCULAR BUNDLES AFTER ROBOT-ASSISTED RADICAL PROSTATECTOMY: PRELIMINARY RESULTS OF A PHASE II STUDY |
Prostate and Renal Oncology | 17BOS |
Abstract: V8-02 Sources of Funding: none Introduction A physical damage can occur to the neurovascular bundles during the procedure, due to the use of cautery and tractions.Nowadays bio-engineeringis developing novel devices with the aim of co-operate the neural renewal.Among them chitosan seems to be promising with neuro-regenerative properties. In our Institution we tried to use chitosan membranes as scaffold for neural renewal after nerve-sparingrobot-assisted radical prostatectomy (RARP)._x000D_ In laboratory setting results were promising so we designed a prospectivestudytrying to confirmchitosanproperties in_x000D_ clinicalpractice._x000D_ Primary end-point: to evaluate the feasibility of the application of chitosan membrane on neuro-vascular bundles after nerve-sparing RARP. Secondary end-point: To evaluate the recovery of erectile function at 1, 2, and 3 months postoperatively by performing a matched-pair analysis comparing the group of patients who underwent chitosan application to a control group who did not. Methods 47patients who underwent nerve sparingRARP (07/2015 - 01/2016) were enrolled. Criteria for inclusion was an IIEF>17._x000D_ A control group of patients was selected. Potency recovery was defined as erection enough for intercourse or masturbation._x000D_ Membranes were adequately prepared by immersion in saline solution and cutting. After that reconstructive phase of RARP was performed,chitosan membranes were introduced and applied on the bundles. Results Baseline data of patients in the Groups were comparable.Concerning intraoperative data, no modifications of operative time was recorded in the Chitosan Group;No intraoperative complications occurred.Postoperative complications rate was not affected by the application of the membrane.Concerning the functional data, a faster erectile function recovery was recorded in the cohort of patients who underwent chitosan application. Conclusions In our experience, the application of chitosan membranes on the neurovascular bundles after robot-assisted RP was easy and safe. Preliminary functional outcomes showed a faster recovery of erectile function in the cohort of patients who underwent the application of the membranes.Larger sample size and randomized trials are needed in order to confirm these preliminary outcomes. Funding none
Authors
Francesco Porpiglia
Riccardo Bertolo Enrico Checcucci Matteo Manfredi Sabrina De Cillis Roberta Aimar Stefano Geuna Cristian Fiori |
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V8-03 |
Robot assisted radical nephrectomy and inferior vena cava thrombectomy: surgical technique, perioperative and oncologic outcomes |
Prostate and Renal Oncology | 17BOS |
Abstract: V8-03 Sources of Funding: none Introduction In this video we highlight surgical steps of a right radical nephrectomy and level IIIb inferior vena cava (IVC) thrombectomy using an occluding balloon Fogarty catheter to control the upper boundary of IVC thrombus under transesophageal ultrasound guidance. Perioperative and oncologic outcomes of our first 35 patients treated with robotic radical nephrectomy and inferior vena cava thrombectomy in two tertiary referral centers were reported. Methods Key surgical steps are higlighted in the video. _x000D_ Preoperative arterial embolization was performed. A right template retroperitoneal lymph node dissection was performed and all lumbar veins were secured to achieve a complete IVC control; the left renal vein and the distal IVC segment were prepared and encircled with Roummel Tourniquet. Short hepatic veins were secured with Ligasure and the posterior aspect of the IVC was prepared. Proximal IVC was encircled and right renal vein was stapled._x000D_ The distal IVC and left renal vein Tourniquets were cinched down and a small cavotomy was performed to insert a Fogarty catheter with an occluding balloon tip. To ensure the correct placement of the catheter tip at the cranial edge of the thrombus we used transesophageal ultrasound. Once the balloon was inflated and distally attracted, cavotomy was performed and the thrombus progressively mobilized and secured into an endocatch bag. IVC lumen was inspected to ensure absence of any residual thrombus fragment and the balloon was deflated to restore IVC flow throw the major hepatic veins. The cava was sutured with a 3/0 Visi black monocryl suture. _x000D_ Thirty-five consecutive patients with renal tumor and IVC thrombus were treated between July 2011 and September 2016 in two tertiary referral centers; perioperative and oncologic data were reported._x000D_ Results Fogarty catheter was successfully used in 7 (20%) cases. Open conversion was necessary in one case (2.8%). Median operative time was 300 minutes. Ten patients (28.6%) required blood transfusion (Clavien grade 2); one patient (2.8%) had a Clavien grade 3a complication (gastroscopy); two patients (5.7%) had Clavien grade 3b complications (reintervention due to bleeding from adrenal gland and subphrenicascess requiring drainage, respectively); one patient (2.8%) experienced a PRESS syndrome requiring ICU admission (Clavien 4a). _x000D_ Out of 13 patients who underwent cytoreductive nephrectomy and IVC thrombectomy, only one patient died of disease progression 14 months postoperatively. Both 2-yr cancer specific and overall survival rates in this subpopulation were 88.9%._x000D_ Twenty-two patients received surgery with curative intent and 5 of these experienced disease recurrence: 2-yr metastasis free, cancer specific and overall survival rates were 56%, 100% and 94.4%, respectively._x000D_ Conclusions The increasing experience with robotic surgery has made nephrectomy and IVC thrombectomy a feasible and safe treatment option in tertiary referral centers, associated with favourable perioperative outcomes and encouraging short term oncologic outcomes. Funding none
Authors
Giuseppe Simone
Leonardo Misuraca Gabriele Tuderti David Hatcher Mariaconsiglia Ferriero Andre Luis De Castro Abreu Francesco Minisola Monish Aron Salvatore Guaglianone Mihir Desai Inderbir Singh Gill Michele Gallucci |
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V8-04 |
Percutaneous Externally Assembled Laparoscopic (PEAL) Nephrectomy |
Prostate and Renal Oncology | 17BOS |
Abstract: V8-04 Sources of Funding: None Introduction Laparoendoscopic single-site nephrectomy (LESS) provides excellent cosmetic outcomes, but is technically challenging due to loss of triangulation and increased instrument collision. A novel Percutaneous Externally Assembled Laparoscopic (PEAL) surgical paradigm was developed to simplify minimally invasive surgery while providing a nearly scarless outcome. In this video, we will demonstrate how PEAL instruments restore triangulation and simplify LESS nephrectomy. Methods The PEAL instrument is composed of a reusable handpiece and a disposable 2.96 mm shaft and interchangeable 5 mm instrument tips. These instruments are inserted without a trocar which minimizes their cosmetic impact. This video will demonstrate a PEAL nephrectomy in a 69 year-old female with a nonfunctional duplicated right kidney. Initially a multi-access port was inserted into the umbilicus and used to take down adhesions from a previous surgery. Adhesions to the liver were left intact to provide liver retraction. A 2.96 mm instrument shaft was introduced in the right mid-clavicular line at the level of the umbilicus using a special introducer tip. It was brought out through the multi access port and switched to a 5 mm grasper tip. This PEAL instrument was able to reestablish triangulation and upon its removal required no wound closure. Results The use of the PEAL surgical paradigm restored triangulation and allowed a nearly scarless nephrectomy despite this patient’s giant duplicated kidney. This 2.96 mm instrument shaft was inserted through a small puncture and maintains the nearly scarless cosmesis of LESS surgery. The 5 mm grasping tip, which can be changed through any conventional laparoscopic port, was robust and allowed for the effective manipulation of this giant kidney. The estimated blood loss was 100 cc and the operative time was 310 min. The patient tolerated the procedure well without any perioperative complications. The patient was discharged home on POD 1 and required no narcotic pain medications. Conclusions The addition of the PEAL instrument facilitated the completion of LESS nephrectomy in a patient with complicated anatomy. By using these externally assembled instruments, PEAL provides a functional, robust 5 mm tip and reestablishes instrument triangulation, thereby greatly simplifying LESS surgery. In addition the <3mm shaft maintains a nearly scarless cosmetic outcome. The PEAL instruments can be used to simplify LESS, reduce the invasiveness of conventional laparoscopic surgery or as stand-alone surgical paradigm. For these reasons we feel that the PEAL paradigm is a promising new surgical approach Funding None
Authors
Jerry Thomas
Mohamed Keheila Samuel Abourbih Patrick Yang Nazih Khater Jim Shen Salim Cheriyan D. Duane Baldwin |
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V8-05 |
Successful endovascular control of renal artery in a transplant kidney during nephron sparing surgery for large centrally located tumor |
Prostate and Renal Oncology | 17BOS |
Abstract: V8-05 Sources of Funding: CryoLife LTD Introduction Renal cell carcinomas (RCC) which comprise 4.6% of malignant neoplasms in patients following kidney transplantation occurs more frequently than in the general population. Native kidneys are affected in 90% of cases compared with 10% of the transplanted kidneys. _x000D_ Nephron Sparing Surgery (NSS) is the treatment of choice, although graft nephrectomy is chosen in cases with large lesion,decreased functioning graft, and locally advanced disease. One of the main technical challenges is obtaining adequate vascular control._x000D_ Herein we present a rare case of large centrally located hilar tumor in a kidney 18 years after transplantation._x000D_ Methods Open Nephron Sparing Surgery (NSS) is described. Considering possible difficulties in approaching the renal pedicle due to adhesions and the location of the tumor, arterial catheterization of the Iliac artery was performed in the operating room prior to surgery. An arterial occlusion balloon catheter was inserted into the renal transplant artery in order to ensure adequate haemostatic control without the need to expose and clamp the friable transplant renal artery.Under general anesthesia, through the previous right lower abdominal transplant's incision the kidney was exposed and freed from the surrounding structures, the ureter was identified and then the arterial balloon located in the transplant artery was inflated. Surface cooling was achieved with ice slush and the centrally located lesion was enucleated intact and opening of the collecting system as well as exposed blood vessels were individually sutured. Tumor bed closure was carried out with 15 ml of BioGlue® tissue adhesive. After the enucleation the arterial balloon was deflated. No signs of bleeding or urinary extravasations were seen. Results Post-operative course was uneventfull, and after one year of follow-up no recurrence was observe an serum creatinine is stable and slightly elevated. Conclusions we demonstrate an unusual case of renal cell carcinoma in transplanted kidney managed by NSS despite the lesion high RENAL score. A novel approach was used to achieve vascular control by using intra arterial balloon catheterization prior to surgery. In order to preserve maximal function tumor bed closure was made with tissue adhesive BioGlue®. We believe that this unique choice of treatment can be used in cases of NSS where the access to the renal pedicle is limited. Funding CryoLife LTD
Authors
Sagi Shprits
Boaz Moskovits Robert Sachner Ofer Nativ |
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V8-06 |
Advanced Reconstruction of Vesico-Urethral Support during Robot-assisted Radical Prostatectomy: experience with 526 cases |
Prostate and Renal Oncology | 17BOS |
Abstract: V8-06 Sources of Funding: none Introduction To date, several modifications of robot-assisted radical prostatectomy (RARP) aimed at improving continence have been introduced. In 2014, we presented Advanced Reconstruction of Vesico-Urethral Support (ARVUS) - innovative reconstruction technique during RARP using fibres of levator ani muscle as support for the anastomosis. We conducted a randomized trial [1], which showed improved continence rates of ARVUS compared to posterior reconstruction of rhabdosphincter according to Rocco. We then implemented the new technique into our daily practice. Here we present functional results on larger group of patients from a single center. Methods Between July 2014 and July 2016, we performed consecutive 526 RARPs using ARVUS technique. We prospectively collected all the oncological and functional data. Continence was defined as using 0 pads per day. The time points for evaluation were 24h after catheter removal, then 4 and 8 weeks and 6 and 12 months. Erection was assessed using International Index of Erectile Function (IIEF-5) questionnaire. Patients who required radiotherapy and patients lost to follow up were excluded from the analysis. Results Median age was 63.2 years with median preoperative PSA 7.4 ng/ml. Median console time was 87 minutes and median blood loss 160 ml. Nerve sparing surgery had 78% of the patients. The positive surgical margin rate was 11.97%. Urinary continence assessed after 24 hours showed 20.91% (110/526) continence rate. In 4 weeks the continence rate was 60.45% (318/526), 68.06% (358/526) in 8 weeks, 73.8% (279/378) in 6 months and 84.94% (220/259) in 12 months. There were no major side effects associated with the reconstruction technique, no patient experienced perineal pain or urinary retention. Erection was evaluated in patients with initial IIEF-5 score ?19. In 12 months the potency rate was 71.04%. Conclusions ARVUS technique in our setting showed good functional results with no major side effects. Nevertheless, we believe that multi-center external validation is needed. _x000D_ _x000D_ 1. Student V Jr, Vidlar A, Grepl M, Hartmann I, Buresova E,Student V. Advanced Reconstruction of Vesicourethral Support (ARVUS) during Robot-assisted Radical Prostatectomy: One-year Functional Outcomes in a Two group Randomised Controlled Trial. Eur Urol. 2016 Jun 6 [Epub ahead of print]._x000D_ Funding none
Authors
Vladimir Jr. Student
Igor Hartmann Ales Vidlar Michal Grepl Eva Buresova Vladimir Student |
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V8-07 |
Modified Milan Sling technique during robot-assisted radical prostatectomy for early recovery of urinary continence without nerve-sparing: A pilot study |
Prostate and Renal Oncology | 17BOS |
Abstract: V8-07 Sources of Funding: The Stiftelsen Japanese Swedish Research Foundation Japanese Section Introduction _x000D_ Urinary incontinence after radical prostatectomy for localized prostate cancer strongly influences patients' quality of life. Postoperative urinary continence tends to recover early since robot-assisted radical prostatectomy has been introduced, but the results of the procedure are still not satisfactory. Various modifications of pelvic floor reconstruction during radical prostatectomy, including pelvic floor structure preservation with nerve-sparing technique, have been reported for the purpose of early recovery of urinary continence. However, wide excision without nerve-sparing is necessary depending on a case, such as high risk stratified group, while it may cause poor recovery of urinary continence. We modified the previously reported Milan vas deferens sling technique by adding reinforcement of under-anastomosis layers during robot-assisted radical prostatectomy, which significantly accelerates early recovery of postoperative urinary continence in cases without nerve-sparing. Methods _x000D_ Modified sling technique;_x000D_ Sling suture was made from autologous vas deferens. After putting the vas deferens sling on the sub-urethral perirectal fat, three independent layers were constructed below the urethrovesical anastomosis, and a single anterior layer was made. Then, both ends of the sling were transfixed to Cooper ligaments bilaterally with adequate sling suspension._x000D_ Between October 2015 and July 2016, consecutive 35 patients who underwent robot-assisted radical prostatectomy without nerve-sparing at our institution with a single surgeon were investigated. The patients were classified into two groups: 15 using the sling technique (sling group) and 20 using the non-sling technique with simple posterior reconstruction (nonsling group). Urinary continence defined as 0 or safety 1 pad use daily was compared between the groups._x000D_ Results _x000D_ Patients' characteristics were comparable between the groups. Urinary continence rate significantly improved in the sling group (60.0%, p=0.0365) as compared to the nonsling group (25.0%) at 1 month despite no difference at 3 months (86.7% in the sling group vs. 65.0% in the nonsling group, p=0.1467) postoperatively. Postoperative complications related to sling procedure were not detected. Conclusions _x000D_ Despite a small sample size in the single-institution study, this sling technique may improve early urinary continence recovery after robot-assisted radical prostatectomy even without nerve-sparing. A larger study is needed to confirm its efficacy. Funding The Stiftelsen Japanese Swedish Research Foundation Japanese Section
Authors
Yuji MAEDA
Toshimitsu MISAKI Osamu UEKI Tetsuyuki KUROKAWA Yukinosuke OSHINOYA Ken-ichi NAGANO Haruo HISAZUMI |
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V8-08 |
Purely off-clamp robotic partial nephrectomy |
Prostate and Renal Oncology | 17BOS |
Abstract: V8-08 Sources of Funding: none Introduction The negative impact of ischemia on renal function (RF) has led surgeons to develop minimally ischemic techniques to perform partial nephrectomy (PN). The aim of this video is to describe our surgical technique and report perioperative, 3-yr oncologic and functional outcomes of a single centre series of 308 patients treated with robotic off-clamp PN (OFF-RPN). Methods A prospective renal cancer database was queried and data of all patients treated with OFF-RPN between 2010 and 2015 in a high-volume centre were collected. _x000D_ Patients were placed in an extended flank position and a 5-port access with a side docking was performed. Hilar vessels were not clamped in any case; pure tumour enucleation or enucleoresection were the resection techniques used; renorraphy was omitted for small and exophytic masses and minimized with a “point specific haemostasis� for hilar tumours. _x000D_ Perioperative complications, 3-yr oncologic and functional outcomes were reported. Univariable and multivariable analyses were performed to identify independent predictors of RF deterioration._x000D_ Results Out of 308 patients treated, 41 (13.3%) experienced perioperative complications, 2.9% of which were Clavien grade ?3. Three-yr local recurrence free survival and renal cell carcinoma specific survival rates were 99.5% and 97.9%, respectively._x000D_ No patient with preoperative CKD-stage ?3B developed severe RF deterioration (CKD-stage 4) at 1-yr follow-up._x000D_ At multivariable analysis, preoperative eGFR (p=0.005) was the only independent predictor of a new onset CKD-stage ?3 in patients with preoperative CKD-stages 1 or 2._x000D_ Conclusions OFF-RPN is a safe surgical approach in tertiary referral centres, with adequate oncological outcomes and negligible impact on RF. Funding none
Authors
Giuseppe Simone
Leonardo Misuraca Gabriele Tuderti Francesco Minisola Mariaconsiglia Ferriero Giuseppe Romeo Manuela Costantini Salvatore Guaglianone Michele Gallucci |
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V8-09 |
Robot Assisted Radical Prostatectomy For Prostates Over 100 Grams: Technique And Outcomes |
Prostate and Renal Oncology | 17BOS |
Abstract: V8-09 Sources of Funding: None Introduction Benign prostatic hyperplasia (BPH) is seen in more than 30% of men over 60 years age. It is not uncommon to encounter men with BPH having significant prostate cancer seeking treatment. Radical prostatectomy is technically challenging in very large prostate. We present our experience of robot assisted laparoscopic radical prostatectomy (RALP) in prostate weighing more than 100 gram. There are few studies reporting varying outcomes for >70 gm prostate. We compared RALP operative parameters and functional outcomes between 70-100 gm prostate with >100 gm prostate Methods We retrospectively reviewed our IRB approved prostate cancer database. RALP specimen weighing more than 100 gram in 183 men (Group 1) and 70 to 100 gram in 647 men (group 2). We compared demographic, operative, oncologic and functional outcomes between these two groups. In this video we describe the technical nuances during RALP for very large prostate with prostate cancer and present their outcomes. Early ligation of dorsal venous complex (DVC) reduces venous blood loss during further dissection. Proper identification of bladder neck and anterior entry favors recognition of median lobe. After visualizing bilateral ureteric orifice, constant upward traction of median lobe by fourth arm is important to enter proper posterior plane. Mobilization of the prostate and retraction can be challenging in these patients. Fish-mouth reconstruction of bladder neck helps watertight vesico-urethral anastomosis and urinary continence Results Patient profile, operative parameters, oncologic and functional outcomes are shown in table 1. Operative time and estimated blood loss was higher in group 1. Many of these patients were not potent or had low SHIM scores and therefore did not have full NS. Chance of achieving bilateral full nerve spare was less in group 1. Higher incidence of extra capsular extension was observed in group 2 but positive surgical margin was similar between groups. At 12 months more than 95% achieved continence and there was no difference in biochemical recurrence, continence and potency between groups Conclusions Very large prostate size has slightly longer operative time and more blood loss. Prostate size >100 gm may challenge bilateral full NS. But, oncological and functional outcomes are not compromised by prostate size in experienced surgeons hands Funding None
Authors
Hariharan Palayapalayam Ganapathi
Gabriel Ogaya-Pinies Eduardo Hernandez Travis Rogers Vipul Patel |
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V8-10 |
Robotic Salvage Retroperitoneal and Pelvic Lymph Node Dissection for "Node-only" Recurrent Prostate Cancer |
Prostate and Renal Oncology | 17BOS |
Abstract: V8-10 Sources of Funding: none Introduction Despite primary treatment of prostate cancer with surgery or external radiation therapy, 20-40% of patients relapse within 5 years and 25-35% progress to metastatic disease. Salvage lymph node dissection has been proposed in patients with biochemical recurrence from prostate cancer and nodal involvement only, although the optimal template remains a question of debate. Herein we describe the technique of robotic high-extended salvage retroperitoneal and pelvic lymphadenectomy (sRPLND+PLND) for "node-only" recurrent prostate cancer. Methods Twenty patients underwent robotic sRPLND+PLND for "node-only" recurrent prostate cancer after definitive primary treatment as identified by carbon-11 acetate PET/CT. Our anatomic template extends from bilateral renal artery and vein cranially up to Cloquets node caudally, completely excising lymphatic-fatty tissue from aorto-caval and iliac vascular trees. Meticulous node-mapping assessed nodes at 4 prospectively-assigned anatomic zones. Results Median age at salvage RPLND was 64 (45-76), median BMI was 26.4 kg/m2 (21.4 - 41.2), previous primary treatment was radical prostatectomy in 17 patients (85%) and external radiation therapy in 4 patients (15%), median time from primary treatment was 32 months (4-160) and median PSA at sRPLND+PLND was 2.1 ng/dl (0.28 - 38.17). Median operative time was 5 hours (3.5-5.8), blood loss was 100 ml (50-300), and hospital stay was 1 day (1-3). No patient had intra-operative complication, open conversion or blood transfusion. Four patients had Clavien II post-operative complications: flank/scrotal ecchymosis in 1 patient (5%), chylous ascites in 2 patients (10%) and neuropraxia/foot drop in 1 patient (5%). Final histology confirmed positive nodes in 16 patients (20%). Mean and median (range) number of nodes excised per patient was 89 and 80 (41-132) respectively. Mean and median (range) number of positive nodes was 21 and 6 (0-109) respectively. At 2 months post-operatively median (range) PSA was 0.76 ng/mL (<0.01-2 ng/mL). Conclusions Herein we describe the detailed technique of robotic high-extended salvage RPLND+PLND for "node-only" recurrent prostate cancer and present the initial experience. Robotic sRPLND+PLND duplicates open surgery, with superior nodal counts and decreased morbidity compared to the published literature. Longer follow-up is necessary to assess oncologic outcomes. Funding none
Authors
Carlos Fay
Andre Abreu Daniel Park Niero Rajarubendra Daniel Melecchi Freitas Giovanni Cacciamani Inderbir Gill |
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V8-11 |
The Use of a Novel Curved-tip Suction Device in Laparoscopic and Robotic Urologic Surgery |
Prostate and Renal Oncology | 17BOS |
Abstract: V8-11 Sources of Funding: none Introduction To describe the merits of a novel curved-tip suction device in laparoscopic and robotic urologic surgery. Methods A prototype for a laparoscopic curved-tip suction device was designed and produced by a manufacturer of laparoscopic instruments. The curve tip is designed to fit 5 mm, 8 mm, 10 mm, 11 mm and 12 mm laparoscopic trocars. The prototype was then used in over 150 laparoscopic and robotic-assisted prostatectomies, cystectomies, partial and radical nephrectomies and pediatric urology cases Results Our experience with the curved-tip suction device for laparoscopic and robotic surgery has been promising in over 150 cases. The concave design facilitates optimal visualization of the focal point of dissection by keeping the working area clear without the suction shaft obscuring the surgical field as with conventional suction devices. This allows laparoscopic and robotic instruments to access tight work spaces without colliding with the suction device. The contour of this suction tip permits suctioning in recesses obscured by organs and bony prominences, which is particularly important when operating in the pelvis as we have seen with robotic prostatectomies and cystectomies. In cases of improper port placement, this device salvages operative conditions by optimizing exposure. Finally, this device allows for more precise and ergonomic tissue retraction without excessive torque that results in tissue injury as with conventional suction devices. Conclusions Based on our experience in laparoscopic and robotic urologic surgery, the use of a curved-tip suction device allows for better visualization of the surgical field, increased space for laparoscopic and robotic instruments to maneuver in the area of dissection and precise atraumatic tissue retraction. Funding none
Authors
Mina Fam
Michael Esposito Gregory Lovallo Thomas Christiano Christopher Wright Mutahar Ahmed |
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V8-12 |
Combining antegrade and retrograde dissection during salvage robotic radical prostatectomy |
Prostate and Renal Oncology | 17BOS |
Abstract: V8-12 Sources of Funding: None Introduction Recently published series of salvage robotic radical prostatectomy for radiorecurrent prostate cancer showed the feasibility and the safety of this complex surgical procedure with favorable perioperative and satisfactory functional outcomes. This video shows surgical steps of a salvage robotic radical prostatectomy with pelvic lymph node dissection for radio recurrent prostate cancer. Methods _x000D_ _x000D_ We present a case of a 60 yr old patient who underwent primary radiation therapy in 2007 for a G7(3+4) prostate cancer. Due to a raising PSA, a prostate biopsy showed a G7(4+3) prostate cancer of the right lobe. A 18F Choline PET/CT was negative for nodal and distant metastasis. _x000D_ With the patient in a steep trendelenburg position a five trocar access was performed. Bilateral extended pelvic lymph node dissection was completed. The Retzius space was developed and the endopelvic fascia bilaterally incised. After sealing the dorsal vein complex with Ligasure, urethral stump was meticulously prepared and transected. The apex was retrogradely dissected up to identifying the Denonvilliers fascia, before moving to bladder neck isolation. Bladder neck was isolated and sectioned and seminal vesicles dissected. The Denonvilliers fascia was identified and opened and the dissection plane, previously prepared retrogradely, was identified. Bilateral extrafascial radical prostatectomy was completed. A Van Velthoven anastomosis with posterior muscolo-fascial reconstruction was performed. _x000D_ _x000D_ Results Operative time was 132 minutes. Blood loss was 300 ml. Postoperative course was uneventful and the patient was discharged on 3rd postoperative day. Pathologic examination showed a pT2bN0 G7(4+3) prostate cancer with negative surgical margins. One-mo PSA levels were 0.01 ng/mL. At 6 month follow up PSA level remained 0 and patient was continent._x000D_ _x000D_ Conclusions Combining retrograde and antegrade dissections during salvage robotic radical prostatectomy may contribute to a safe development of the posterior dissection plane. Salvage robot assisted radical prostatectomy is a feasible treatment option for patients with radiorecurrent prostate cancer. _x000D_ _x000D_ Funding None
Authors
Mariaconsiglia Ferriero
Giuseppe Simone Riccardo Mastroianni Gabriele Tuderti Leonardo Misuraca Francesco Minisola Salvatore Guaglianone Michele Gallucci |
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V9-01 |
Three-Dimensional Photography as a Tool for Characterization of Penile Deformity in Peyronie’s Disease |
Infertility, ED, and Reconstruction Lower Tract (II) | 17BOS |
Abstract: V9-01 Sources of Funding: Columbia University College of Physicians & Surgeons Introduction Non-curvature penile deformities are prevalent and bothersome manifestations of Peyronie's disease (PD) that can result in functional impairment and psychological distress. The quantitative metrics that are currently used to describe these deformities are inadequate and non-standardized, which has historically been a barrier to clinical research and patient care. Our aim is to introduce three-dimensional photography as a technique to improve the evaluation of patients with PD, partially by the measurement of erect penile volume (EPV) and percent erect penile volume loss (EPVL), and to assess the reliability of measurements acquired by 3D photography. Methods Six penis models were constructed using computer-assisted design software, and physical models were produced using a 3D printer. 3D photographs of each model were captured in triplicate by 4 observers using an inexpensive 3D camera (Structure Sensor, Occipital, San Francisco, CA). Computer software (Blender, Amsterdam, Netherlands) was used to generate automated measurements of EPV, penile length, minimum circumference, and maximum circumference. 3D images were then digitally reconstructed to restore each image to a non-deformed shape. Percent EPVL was calculated for each model as the percent difference between the EPV of the original model and the EPV after digital reconstruction. The automated measurements were then statistically compared to measurements obtained using water displacement experiments and a tape measure. Results On average, 3D photography was accurate to within 0.1% for measurement of penile length. It overestimated maximum and minimum circumference by averages of 5.0% and 1.8%, respectively; overestimated EPV by an average of 8.6%; and underestimated percent EPVL by an average of 1.9%. All inter-test, inter-observer, and intra-observer ICC values were greater than 0.75, reflective of excellent methodological reliability. Conclusions Erect penile volume and percent EPVL are novel, highly descriptive metrics that may be useful in describing all variants of non-curvature, volume-loss deformities resulting from PD. These metrics can be quickly, accurately, and reliably determined using computational analysis of 3D photographs. Clinical research using 3D photography for assessment of EPV and percent EPVL will empower clinicians and researchers to better understand the clinical impact of penile volume-loss deformities and to study how these deformities respond to therapy. Funding Columbia University College of Physicians & Surgeons
Authors
Ezra Margolin
Carrie Mlynarczyk Doron Stember Peter Stahl |
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V9-02 |
Complete Vestibulectomy for Neuro-Proliferative Vestibulodynia (NPVD): Urologic Surgical Technique and Outcomes |
Infertility, ED, and Reconstruction Lower Tract (II) | 17BOS |
Abstract: V9-02 Sources of Funding: none Introduction The vestibule, derived from the endodermal urogenital sinus and homologue of the male penile urethra is defined as introital tissue between vulva and vagina and surrounds the female urethral meatus. Vestibular pathology is commonly associated with introital dyspareunia. Women often complain of lower urinary tract symptoms and bladder pain, secondary in part to high tone pelvic floor dysfunction, and are often misdiagnosed with interstitial cystitis. Vestibulodynia is diagnosed by vestibular examination and cotton swab testing. Patients with diffuse vestibular pain may have NPVD, a mast cell disease of endoderm resulting in an increased density of C afferent nociceptors in the vestibule. Successful urologic surgery may require complete excision of the vestibule, from hymen to Hart&[prime]s line, passing within a millimeter of the meatus. Vaginal flap reconstruction is required to cover the defect from excised vestibule. We review a single urologist&[prime]s technique and surgical outcomes over a 7-year period showing complete vestibulectomy to be a safe outpatient urological treatment for NPVD._x000D_ Methods In lithotomy position, the labia minora are retracted laterally. The incision is outlined 1 mm right/left of the urethral meatus, extending superiorly for several centimeters, passing laterally to Hart&[prime]s line and inferiorly 2 cm below the posterior fourchette. Medially the incision passes inferiorly from meatus to hymenal tissue extending 2-3 mm below the hymenal ring. Liposomal bupivacaine is used to hydro-dissect vestibular epithelium off the subcutaneous tissue. The 3 mm deep specimen is sharply dissected en bloc. Reconstruction involves left/right anterior repair to close the dead-space bringing together urethral meatus to vulva. Posterior repair involves developing a vaginal tissue advancement flap with finger dissection of rectovaginal fascia. Anchoring sutures are placed from rectovaginal fascia though vaginal wall. Final repair brings together vagina to vulva. Additional liposomal bupivacaine is placed for post-op pain control. _x000D_ Results 60 patients from 2009-2016 underwent complete vestibulectomy for NPVD with mean operative time 60 minutes, and mean intra-op blood loss 75 ml. There were no anesthesia complications, post-operative infections, flap complications, or acute re-explorations. No patient experienced worsened pain and 80% were pain free at 1 year. Conclusions A safe technique with wide resection for outpatient complete vestibulectomy has been reviewed. Funding none
Authors
Rachel Rubin
Ashley Winter Paulina Plascencia Irwin Goldstein |
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V9-03 |
Randomized Clinical Trial of the No-Flip ShangRing Circumcision for Adolescents and Adults in Africa |
Infertility, ED, and Reconstruction Lower Tract (II) | 17BOS |
Abstract: V9-03 Sources of Funding: The Bill & Melinda Gates Foundation (Global Health Grant Number OPP1084493) to EngenderHealth and Weill Cornell Medicine Introduction Male circumcision (MC) provides a variety of medical benefits, including a 50-60% reduced risk of HIV transmission. The ShangRing is one of two WHO-prequalified MC devices and it comprises a key component of the scale-up of MC services in Africa. The No-Flip ShangRing circumcision technique represents a further simplification of this procedure. The objective of this study was to evaluate the outcomes of this technique in African adults and adolescents with regard to procedure duration, pain, adverse events, healing time, and patient satisfaction. Further, we sought to compare safety, healing rates and patient satisfaction after ring removal at 7 days versus spontaneous detachment. Methods We enrolled patients 10 years of age or older at two study sites in Kenya. All procedures were performed by physicians or nurses trained in the No-Flip ShangRing technique. Patients were randomized in 1:1 fashion to ring removal at 7 days versus spontaneous detachment. Outcomes were assessed weekly until 42 days or complete wound healing. Results 230 patients were enrolled in this study, age ranges 10 to 54. Over 80% of circumcisions were performed by nurses trained in the No-Flip technique. All patients (230/230) were suitable for ShangRing MC regardless of the presence of phimosis or adhesions. On subgroup analysis of patients 10-15 years of age versus >15 years, though more patients in the younger group required a dorsal slit and breaking down of adhesions prior to ring insertion, there was no difference in operative time and all circumcisions were successfully completed (Table 1). There was no difference in pain or adverse events between the age groups, and there was ≥97% patient satisfaction in both groups. Within the group randomized to spontaneous detachment, 72.4% of patients experienced detachment at median 14 days; 27.6% of patients requested ring removal due to pain or discomfort. There were no differences between spontaneous detachment and 7-day removal with regard to healing time, adverse events, or patient satisfaction. Conclusions The No-Flip ShangRing procedure is simple, safe, effective, and acceptable for use in patients 10 years of age or older. Spontaneous detachment is safe and effective, and has the potential to reduce the burden of service provision in resource-poor settings. Funding The Bill & Melinda Gates Foundation (Global Health Grant Number OPP1084493) to EngenderHealth and Weill Cornell Medicine
Authors
Benjamin V Stone
Omar Al Hussein Alawamlh Phil V Bach Ryan Flannigan Quentin Awori Marc Goldstein Mark Barone Philip S Li Richard K Lee |
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V9-04 |
One-stage transvesical laparoendoscopic single-site surgery (T-LESS) for removal of two bladder diverticula in a female patient. |
Infertility, ED, and Reconstruction Lower Tract (II) | 17BOS |
Abstract: V9-04 Sources of Funding: None Introduction Bladder diverticula are usually encountered in males, and they are a rarity in women, especially in the absence of obstruction. Open surgery, as well as laparoscopic or robotic, or single-port surgery have been applied successfully to remove bladder diverticula. To the best of our knowledge, no single-port diverticulectomies have been performed in women. We present the case of using the transvesical laparoendoscopic single-port surgery (T-LESS) for excision of two bladder diverticula in a woman Methods In August 2016, we carried out the T-LESS access on a 67-year old woman to remove two symptomatic bladder diverticula in one session. The patient was placed in the lithotomy position and was under general anesthesia. _x000D_ The procedure was performed transvesically (percutaneous intraluminal approach) with a single-port device (Tri-Port+) via a 1.5-cm incision made 3 cm above the pubic symphysis. Standard 10-mm optic and straight laparoscopic instruments were used. The diverticula were dissected and removed from the bladder with a combination of standard laparoscopic and endoscopic instruments introduced through the TriPort+ or the urethra. The bladder wall openings were closed by running absorbable 2/0 polyglactin sutures. An 18F Foley catheter was left in place for 6 days._x000D_ Results The operation lasted 120 minutes. Blood loss was minimal, and no complications were observed. The postoperative period was uneventful. The patient was discharged within 18 hours of surgery. During a nine-week follow-up, the patient reported the significant improvement in the severity of symptoms. Laboratory examination results were all within the normal range. Conclusions The T-LESS procedure can be considered as a valuable option for diverticulectomies in female patients because of its minimal invasiveness, short hospital stay and fast recovery time Funding None
Authors
Marek Roslan
Maciej Przudzik Michal Borowik Miroslaw ?esiów |
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V9-05 |
Laparoscopic varicocelectomy using intraoperative navigation: indocyanine green angiography and indigo carmine lymphatic dye |
Infertility, ED, and Reconstruction Lower Tract (II) | 17BOS |
Abstract: V9-05 Sources of Funding: None Introduction Varicocelecomy is widely performed to treat of male infertility, scrotal pain, and testicular atrophy. A variety of techniques have been reported. Laparoscopic varicocelectomy is still a commonly used method for varicocele repair. However, the most popular surgery for varicocele uses a microsurgical inguinal or subinguinal approach mainly because of the disadvantages of a retroperitoneal approach including a high incidence of varicocele recurrence and hydrocele formation. Failure is usually caused by preservation of persistent tiny veins and postoperative hydrocele is caused by cutting of lymphatics. On the other hand, a laparoscopic procedure should allow preservation of the testicular artery in a majority of cases and preservation of lymphatics. It is extremely vital to eliminate spermatic venous flow completely to reduce the recurrence rate as much as possible. To facilitate the identification of spermatic vessels and ensure the ligation of veins as well as arterial and lymphatic preservation, we performed laparoendoscopic single-site (LESS) varicocelectomy using intraoperative navigation. Methods An umbilical incision of 25 mm was made. We placed a GelPOINT? Mini Advanced Access Platform (Applied Medical, Rancho Santo Margarita, CA, USA), which has one 12 mm trocar and two 5 mm trocars. After exposing of the spermatic cord, 2 ml of indigo carmine was injected into the space between the tunica vaginalis and tunica albuginea. Then, 1 ml of indocyanine green (ICG, 2.5 mg/ml) was injected intravenously. Spermatic veins were cauterized by bipolar forceps. The spermatic artery and lymphatics were preserved. ICG was injected again to confirm preservation arterial blood flow and that there were no remaining veins. Results A few seconds after injection of indigo carmine, one bundle of lymphatics was stained. About 20 s after injection of ICG, fluorescence of gonadal arterial flow was detected clearly. About 20 s after that, gonadal veins were observed somewhat dully. The artery and lymphatics could be preserved and the veins were cut. Finally, we performed ICG angiography again. Arterial flow was preserved and venous flow was not observed. 3 months later, color Doppler ultrasonography confirmed complete disappearance of the varicocele. Conclusions LESS varicocelectomy using ICG angiography and indigo carmine lymphatic dye facilitates visualization and identification of spermatic vessels. Continued investigation should determine whether it could reduce the disadvantages of laparoscopic varicocelectomy. Funding None
Authors
Keiji Tomita
Eiki Hanada Susumu Kageyama Kazuyoshi Johnin Mitsuhiro Narita Akihiro Kawauchi |
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V9-06 |
Robot Assisted Penile Inversion Vaginoplasty: A Novel Technique |
Infertility, ED, and Reconstruction Lower Tract (II) | 17BOS |
Abstract: V9-06 Sources of Funding: none Introduction Gender confirmation surgery is an essential component in the management of gender identity disorder. However, short vaginal length, vaginal stenosis, or complications in the perineal dissection are significant limitations of current techniques in male to female surgery. Here we describe our technique for the robot assisted penile inversion vaginoplasty that addresses these needs. Methods The patient is prepped and draped in low lithotomy position. The penis is degloved through a circumcision incision. The neurovascular bundle, urethra and corpora cavernosa are dissected out. _x000D_ A six cm bulbar perineal incision is then made, and the dissection is carried to the bulbar urethra. The dissected urethra, neurovascular bundle, glans and corpora are delivered through this incision. The bilateral corpora are transected at their most proximal limit and overswen. The penile skin is inverted and gently retracted to allow a two cm incision above the neovagina for the neoclitoris. Immediately below this, an incision for the neomeatus is made. The urethra is brought through this incision and sutured to the skin. The remaining urethral tissue is used as an inlay onto the incised dorsal epithelial surface of the penile skin. _x000D_ The robotic portion of the surgery uses 4 port incisions: periumbiical Gelport with two pre-placed robotic trocars, right and left lateral ports, and an assistant port in the upper right abdomen. The dissection is from the posterior prostate, staying above Denonviller’s fascia to reach the endopelvic fascia. Under direct vision, the endopelvics are opened sharply from below and opened to a width of two fingerbreadths. The neovagina is passed into robotic field and pexed to the anterior reflection of the posterior peritoneum. The peritoneal reflection is then closed._x000D_ The neoclitoris is fashioned from the glans penis and approximated. Labia majora and minora are fashioned with local skin flaps. A foley catheter is left indwelling as well as a vaginal stent. _x000D_ Results The index case required 7 hours of surgical time with an estimated blood loss of 100 mL. The vaginal length was greater than 15 cm. The patient was discharged home on post-operative day three, with no complications. The patient endorses sensation at the neoclitoris and anterior neovagina, and finds the vaginal depth satisfactory Conclusions Our novel method for robot assisted penile inversion vaginoplasty is an important step in optimizing outcomes for our patients. This technique achieves maximal vaginal length in a safe and reproducible manner. Funding none
Authors
Temitope Rude
Kiranpreet Khurana Aaron Weinberg Jamie Levine Michael Stifelman Lee C. Zhao |
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V9-07 |
Microsurgically-Assisted Inguinal Hernia Repair |
Infertility, ED, and Reconstruction Lower Tract (II) | 17BOS |
Abstract: V9-07 Sources of Funding: Frederick J and Theresa Dow Wallace Fund of the New York Community Trust & the Agency for Healthcare Research and Quality (T32HS00066)_x000D_ _x000D_ This work was supported in part by the Urology Care Foundation Research Scholar Award Program and AUA New York Section Research Scholar Fund Introduction : Inguinal hernia repair is the most commonly performed general surgical procedure, with mesh repair being the favored method. Complications such as chronic pelvic pain and iatrogenic vasal obstruction can occur in up to 19% and 3% of patients, respectively. Better intraoperative visualization of the ilioinguinal nerve has been associated with decreased postoperative pelvic pain. The operating microscope offers the best visualization of inguinal structures and is commonly used in highly precise male infertility procedures. We describe the rationale, technique, and surgical outcomes of microsurgically assisted inguinal hernia repair. Methods We conducted a retrospective review of 252 microsurgically assisted hernia repairs with mesh performed by a single surgeon (M.G.). In all procedures, the vas deferens, deferential vessels and nerves, ilioinguinal nerve, genital branch of the genitofemoral nerve, and spermatic vasculature were identified and preserved under 6-25X magnification. Surgical outcomes and complications were abstracted retrospectively from patient charts. Results Mean follow-up was 26.7 months. Mean patient age was 50.5 years. 196/252 (78%) of patients were symptomatic from their hernias. 215/252 (86%) of patients were undergoing concomitant microsurgical fertility related procedures such as varicocelectomy (56%) and hydrocelectomy (28%). No chronic post-operative pain or vasal injuries were reported. Additionally, no sensory loss or infections were reported. The only complications were one post-operative one hematoma (0.4%) that was managed conservatively and one recurrence (0.4%). Conclusions Operating microscopes have an established record of facilitating extremely difficult male infertility procedures. The application of the operating microscope for inguinal hernia repair resulted in very low complication rates under 1%. Remarkably, there were no instances of chronic post-operative pain or sensory loss, representing significantly improved surgical outcomes compared to those reported in the literature. Funding Frederick J and Theresa Dow Wallace Fund of the New York Community Trust & the Agency for Healthcare Research and Quality (T32HS00066)_x000D_ _x000D_ This work was supported in part by the Urology Care Foundation Research Scholar Award Program and AUA New York Section Research Scholar Fund
Authors
Ryan Flannigan
Brian Dinerman Phil Bach Michael Shulster Philip Li Marc Goldstein |
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V9-08 |
Male Infertility Microsurgery Training – Tricks of the Trade |
Infertility, ED, and Reconstruction Lower Tract (II) | 17BOS |
Abstract: V9-08 Sources of Funding: Supported by The Frederick J. and Theresa Dow Wallace Fund of the New York Community Trust. Introduction Male infertility microsurgery (MIM) is physically, technically and mentally challenging, with surgical outcomes that are heavily dependent on the surgeon&[prime]s skills. MIM training programs that incorporate systematic evaluation protocols offer an excellent platform to teach microsurgical skills while avoiding the acquisition of bad habits. In this report, we describe the most common mistakes made by trainees who attended our MIM training program. Methods We conducted a retrospective review of prospectively collected data from five trainees who attended the MIM training program between July 2015 and December 2015. _x000D_ _x000D_ Briefly, the IRB-approved MIM training program at Weill Cornell Medicine is a two-week training course offered to urologists of all levels that is held in a dedicated MIM training lab. During the first week, trainees are introduced to the operating microscope, microsurgical instruments and sutures, and focus on developing basic microsurgical suturing skills. During the second week, the trainees start to perform live MIM procedures (vasovasostomy and vasoepididymostomy) on a rodent model. Instructors provide intense supervision and continuous evaluation throughout all phases of the training. Trainees are also able to observe surgical cases performed at our institution. Evaluations are conducted four times throughout the training course using a structured score form measuring 18 items, each on a 5-point Likert scale._x000D_ _x000D_ Trainee scores were assessed and compared for improvement over the course of the training course._x000D_ Results The most common mistakes made by our trainees revolved around sitting position, hand tremor, instrument handling, needle control, suture placement, and knot tying. The errors were most prevalent early on and there were statistically significant improvements across all domains by the end of the MIM training course (Table). Conclusions A MIM training program is an effective tool for teaching MIM skills. By incorporating intense supervision and continuous evaluation into an MIM training program, MIM trainees can avoid the development of bad habits that may be difficult to overcome and potentially have a negative impact on surgical outcomes. Funding Supported by The Frederick J. and Theresa Dow Wallace Fund of the New York Community Trust.
Authors
Phil V. Bach
Filipe Neto Ryan Flannigan Benjamin Stone Omar Al Hussein Alawamlh Miriam Feliciano Richard Lee Peter Schlegel Marc Goldstein Philip Li |
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V9-09 |
Robot-assisted Laparoscopic Management of Inflatable Penile Prosthesis Reservoir Migration into Bladder with Utilization of Cryopreserved Amniotic Membrane and Umbilical Tissue |
Infertility, ED, and Reconstruction Lower Tract (II) | 17BOS |
Abstract: V9-09 Sources of Funding: None Introduction At our institution robot assisted laparoscopy has been adopted for many types of exploratory and reconstructive procedures. We have also utilized cryopreserved amniotic membrane and umbilical cord matrix to facilitate healing in hostile tissue environments. Here we present a 70 year old male with a history of inflatable penile prosthesis placement after radiation and salvage prostatectomy who presented with lower urinary tract symptoms. He was discovered to have reservoir migration into the bladder and was offered a robot assisted laparoscopic exploration with prosthesis reservoir explant and reimplant. Methods We performed a robot-assisted laparoscopic exploration and inflatable penile prosthesis reservoir removal and reimplant. We utilized a cryopreserved amniotic membrane and umbilical tissue graft along the suture line to assist in tissue healing. Results Our patient tolerated procedure well and his lower urinary tract symptoms are improved. He has not experienced infection of his prosthesis and it remains functional. Conclusions Robot assisted laparoscopic management of migrated prosthesis reservoirs may be a safe and feasible approach in select patients. We will continue to explore the use of cryopreserved amniotic membrane and umbilical cord matrix in patients with tissue environments hostile to normal healing. Funding None
Authors
Mark Ferretti
Gregory Lovallo Michael Stifelman Mutahar Ahmed |
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V9-10 |
Transurethral resection of ejaculatory ducts: a step-by-step guide |
Infertility, ED, and Reconstruction Lower Tract (II) | 17BOS |
Abstract: V9-10 Sources of Funding: None Introduction Ejaculatory duct obstruction (EDO) is a rare but surgically correctable cause of male infertility. Transurethral resection of the ejaculatory ducts (TURED) serves as an important therapeutic management option for partially and/or completely obstructed ejaculatory ducts (EDs) that may result in significant improvement of semen parameters and pregnancy rate. The aim of this study is to demonstrate the key components for completing a successful TURED. _x000D_ Methods We present a case of a 40-year-old man who presented with primary infertility. His past medical history was otherwise not significant. Physical examination revealed non-tender 14cc testes bilaterally with present and non-tender vas deferens and epididymis. Hormone studies were within the normal range. Semen analysis was abnormal (pH 6.4, volume of 0.7cc, concentration 16 million/cc and 7% motility). A trasnrectal ultrasonography revealed dilated seminal vesicles measuring more than 1.5 cm and seminal vesicle aspiration detected no sperm in the aspirate. _x000D_ We began the procedure by placing the patient in the conventional lithotomy position. Transrectal ultrasonography-guided seminal vesicle puncture was performed and methylene blue was injected into both seminal vesicles. Cystoscopy was performed focusing in the area of the verumontanum to assess for methylene blue drainage in order to more precisely proceed with resection of the ejaculatory ducts._x000D_ Vesiculography was performed by placing a 5 French ureteral into the freshly opened EDs in order to assess for patency and confirm both sides had been opened. Hemostasis was performed carefully in order not to occlude the newly open EDs. _x000D_ Results Patient was discharged home with foley catheter in place with a voiding trial performed one day later. He returned to clinic at 2 weeks for a post-operative evaluation. Semen analysis revealed improved parameters (pH 7.2, volume of 1cc, concentration 20 million/cc and 60% motility). _x000D_ Conclusions The key portions for performing a successful TURED includes seminal vesicle instillation of methylene blue for easier ED identification. Vesiculography is performed near the end of the procedure to ensure both EDs have been opened as well as to assess for passive drainage of the seminal vesicles through the newly open EDs._x000D_ Funding None
Authors
Luis Savio
Joseph Palmer Nachiketh S Prakash Raul Clavijo Desmond Adamu Ranjith Ramasamy |
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V9-11 |
Suprapubic Fat Pad Excision with Simultaneous Placement of Inflatable Penile Prosthesis |
Infertility, ED, and Reconstruction Lower Tract (II) | 17BOS |
Abstract: V9-11 Sources of Funding: None Introduction Many men suffering from erectile dysfunction (ED) are overweight with separate generous suprapubic fat pads, which often contribute to a decrease in visible exophytic phallic length. We present a novel surgical concept of suprapubic fat pad excision with concomitant placement of inflatable penile prosthesis (IPP). Methods A transverse incision is made starting 2 cm inferior and medial to the ASIS and carried across the infrapubic region in a curvilinear fashion, passing approximately one finger breath above the base of the penis. The incision continues in a symmetric fashion to the contralateral side. Dissection is carried down to the lower abdominal anterior fascia, which leads to excision of the suprapubic fat pad. Using this same exposure, the IPP is placed via an infrapubic approach following our standard protocol for prosthetic insertion. The wound is reapproximated and two drains are placed, one subcutaneous in the area of the fat pad excision and the other in the scrotum around the pump. Results A total of eight patients have undergone suprapubic fat pad excision with simultaneous placement of IPP at our institution. Average BMI of our patient cohort is 36.6. One patient required explant secondary to prosthetic infection after inadvertent removal of his JP drains immediately post-op. At last follow up, all other patients have excellent cosmetic and functional outcomes. Conclusions Suprapubic fat pad excision is a safe and reproducible technique that can be performed simultaneously with placement of IPP in appropriately selected patients. Functional outcomes of our initial series have been excellent. This procedure can lead to enhanced patient satisfaction in those with concurrent erectile dysfunction and significant suprapubic fat pad. Funding None
Authors
Adam Baumgarten
Jonathan Beilan Michael Bickell Justin Parker Gerard Henry Rafael Carrion |
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V9-12 |
Fertility recovery after laparoscopic removal of hypertrophic seminal vesicle |
Infertility, ED, and Reconstruction Lower Tract (II) | 17BOS |
Abstract: V9-12 Sources of Funding: None Introduction Zinner syndrome is a rare condition which include unilateral renal agenesis, ipsilateral seminal vesicle cyst and ejaculatory duct obstruction. It is generally diagnosed during the third or the fourth decade of life. While some patients may remain asymptomatic and are discovered incidentally, others present with symptoms related to seminal vesicle cysts or ejaculatory duct obstruction. Invasive treatment should be restricted to symptomatic cases. We present a case of fertility recovery after surgical treatment. Methods A 20-year-old man presented with azoospermia and perineal discomfort. An abdominal ultrasound documented a left kidney agenesis and a MRI confirmed the presence of left seminal vesicle cyst. The patient qualified for laparoscopic removal of the left seminal vesicle cyst because of persistent pain. Results The procedure lasted 145 minutes, with no intra operative complications. The estimated blood loss was 40 mL. The patient was discharged from the hospital on the third postoperative day. Histopathologic examination confirmed the dysgenetic nature of the left seminal vesicle. At the 6-months follow-up the patient was asymptomatic. At the sperm analysis we found a fertility recovery with 1.8 millions sperms with 88% motility. Conclusions Zinner syndrome is uncommon and should be treated only in symptomatic cases. This case suggest that surgical treatment could have a role in fertility recovery, probably due to a contralateral compression of seminal ducts. Our experience confirm that laparoscopic approach is a valid, non-traumatic, safe removal technique. Funding None
Authors
Gaetano Chiapparrone
Giovanni Liguori Nicola Pavan Grazia Bianchi Andrea Lissiani Carlo Trombetta |